PubNeph papers Free papers Chemokine Receptor CXCR4 Is a Novel Marker for the Progression of Cutaneous Malignant Melanomas. Acta Histochem Cytochem 2012; 45 (5): 293-9
The CXCR4/CXCL12 pathway has recently been reported to be involved in stimulating the metastasis of many different neoplasms, in which CXCR4 activates various phenomena such as chemotaxis, invasion, angiogenesis and proliferation. The purpose of this study was to analyze a possible association between the expression of chemokine receptors CXCR4, CCR6 and CCR7 with the clinicopathological features of cutaneous malignant melanoma, and to assess the usefulness of these chemokine receptors for diagnosis and prognosis. In our study, a percentage of immunoexpression of both CXCR4 and its ligands CXCL12 was associated with high clinical risk. In contrast, the patients with a low immunoexpression of CXCR4 and CXCL12 had low clinical risk. CCR6 and CCR7 immunoexpressions were also correlated with some clinical parameters, but seemed no more useful than CXCR4. These data suggest that the assessment of CXCR4 immunoexpression is a novel tool for predicting tumor aggressiveness in malignant melanomas, and in particular, a high immunoexpression percentage of CXCR4 and CXCL12 might be a sign of a poor prognosis.
*23209338* 23209338 Immunohistochemical Analysis of CXCR4 Expression in Fibrohistiocytic Tumors. Acta Histochem Cytochem 2010; 43 (2): 45-50
Functional chemokine receptors are expressed in many malignant tumors. These receptors promote tumor growth and metastasis in response to endogenous chemokines. We analyzed the expression of CXCR4, CCR6 and CCR7 in fibrohistiocytic tumors, including dermatofibrosarcoma protuberance (DFSP), malignant fibrous histiocytoma (MFH), dermatofibroma (DF) using immunohistochemistry. We also investigated the relationship between CXCR4 and CD34, the latter of which is an immunohistochemical marker for DFSP. We observed a higher expression of CXCR4 in DFSP and MFH as compared with DF. Interestingly, a significantly higher expression of CXCR4 was detected in relapsed DFSP than in non-relapsed DFSP, but no significant differences were detected between non-relapsed DFSP and DFSP with CD34 immunostaining. Moreover, MFH had strong immunoreactivity for CXCR4, CCR6 and CCR7. These findings suggest that the assessment of CXCR4 immunoreactivity in fibrohistiocytic tumors is a useful tool for predicting tumor aggressiveness.
*20514291* 20514291 Pathology of Peripheral Nerve Sheath Tumors: Diagnostic Overview and Update on Selected Diagnostic Problems. Acta Neuropathol 2012; 123 (3): 295-319
Peripheral nerve sheath tumors are common neoplasms, with classic identifiable features, but on occasion, they are diagnostically challenging. Although well defined subtypes of peripheral nerve sheath tumors were described early in the history of surgical pathology, controversies regarding the classification and grading of these tumors persist. Advances in molecular biology have provided new insights into the nature of the various peripheral nerve sheath tumors, and have begun to suggest novel targeted therapeutic approaches. In this review we discuss current concepts and problematic areas in the pathology of peripheral nerve sheath tumors. Diagnostic criteria and differential diagnosis for the major categories of nerve sheath tumors are proposed, including neurofibroma, schwannoma, and perineurioma. Diagnostically challenging variants, including plexiform, cellular and melanotic schwannomas are highlighted. A subset of these affects the childhood population, and has historically been interpreted as malignant, although current evidence and outcome data suggests they represent benign entities. The growing current literature and the authors experience with difficult to classify borderline or ?hybrid tumors? are discussed and illustrated. Some of these classification gray zones occur with frequency in the gastrointestinal tract, an anatomical compartment that must always be entertained when examining these neoplasms. Other growing recent areas of interest include the heterogeneous group of pseudoneoplastic lesions involving peripheral nerve composed of mature adipose tissue and/or skeletal muscle, such as the enigmatic neuromuscular choristoma. Malignant peripheral nerve sheath tumors (MPNST) represent a diagnostically controversial group; difficulties in grading and guidelines to separate ?atypical neurofibroma? from MPNST are provided. There is an increasing literature of MPNST mimics which neuropathologists must be aware of, including synovial sarcoma and ossifying fibromyxoid tumor. Finally, we discuss entities that are lacking from the section on cranial and paraspinal nerves in the current WHO classification, and that may warrant inclusion in future classifications. In summary, although the diagnosis and classification of most conventional peripheral nerve sheath tumors are relatively straightforward for the experienced observer, borderline and difficult to classify neoplasms continue to be problematic. In the current review, we attempt to provide some useful guidelines for the surgical neuropathologist to help navigate these persistent, challenging problems.
*22327363* 22327363 ALDH1 is an immunohistochemical diagnostic marker for solitary fibrous tumours and haemangiopericytomas of the meninges emerging from gene profiling study. Acta Neuropathol Commun 2013; 1 (ä): 10
Background: Solitary Fibrous Tumours (SFT) and haemangiopericytomas (HPC) are rare meningeal tumours that have to be distinguished from meningiomas and more rarely from synovial sarcomas. We recently found that ALDH1A1 was overexpressed in SFT and HPC as compared to soft tissue sarcomas. Using whole-genome DNA microarrays, we defined the gene expression profiles of 16 SFT/HPC (9 HPC and 7 SFT). Expression profiles were compared to publicly available expression profiles of additional SFT or HPC, meningiomas and synovial sarcomas. We also performed an immunohistochemical (IHC) study with anti-ALDH1 and anti-CD34 antibodies on Tissue Micro-Arrays including 38 SFT (25 meningeal and 13 extrameningeal), 55 meningeal haemangiopericytomas (24 grade II, 31 grade III), 163 meningiomas (86 grade I, 62 grade II, 15 grade III) and 98 genetically confirmed synovial sarcomas. Results: ALDH1A1 gene was overexpressed in SFT/HPC, as compared to meningiomas and synovial sarcomas. These findings were confirmed at the protein level. 84% of the SFT and 85.4% of the HPC were positive with anti-ALDH1 antibody, while only 7.1% of synovial sarcomas and 1.2% of meningiomas showed consistent expression. Positivity was usually more diffuse in SFT/HPC compared to other tumours with more than 50% of tumour cells immunostained in 32% of SFT and 50.8% of HPC. ALDH1 was a sensitive and specific marker for the diagnosis of SFT (SE?=?84%, SP?=?98.8%) and HPC (SE?=?84.5%, SP?=?98.7%) of the meninges. In association with CD34, ALDH1 expression had a specificity and positive predictive value of 100%. Conclusion: We show that ALDH1, a stem cell marker, is an accurate diagnostic marker for SFT and HPC, which improves the diagnostic value of CD34. ALDH1 could also be a new therapeutic target for these tumours which are not sensitive to conventional chemotherapy.
*24252471* 24252471 Improved prognosis in soft-tissue sarcoma of extremity and trunk wall: Comparison of patients diagnosed during 1998?2001 and 2005?2010 in Finland. Acta Orthop 2017; 88 (1): 116-20
Background and purpose ? Soft-tissue sarcoma (STS) is rare, with challenging individualized treatment, so diagnostics and treatment should be centralized. Historical controls are sometimes used for investigation of whether new diagnostic or therapeutic tools affect patient outcome. However, as yet unknown factors may affect the outcome. We investigated prognostic factors and prognosis in 2 nationwide cohorts of patients diagnosed with a local STS during the periods 1998?2001 and 2005?2010, with special interest in finding factors lying behind possible improvement of prognosis.Patients and methods ? 2 cohorts of patients with STS of the extremities or trunk diagnosed during the periods 1998?2001 and 2005?2010 were retrieved from the nationwide Finnish Cancer Registry. Detailed information was gathered from patient files.Results ? Compared to first cohort, a larger proportion of patients with inadequate surgery in the second cohort received radiation therapy, and both the local control rate and the sarcoma-specific survival rate improved in the second cohort. For sarcoma-specific survival, cohort (HR =0.6, 95% CI: 0.5?0.9), age, depth, grade, and margin were significant factors in multivariate analysis. For local control, cohort (HR =0.6, 95% CI: 0.5?0.9), age, and margin were significant in multivariate analysis.Interpretation ? Known prognostic factors including type of treatment did not entirely explain the secular trend of continuous improvement in prognosis in STS. This illustrates the danger of using historical controls for investigation of whether new diagnostic or therapeutic tools have an effect on patient outcome.
*27321676* 27321676 Subcutaneous benign fibrous histiocytoma of the cheek. Case report and review of the literature. Acta Otorhinolaryngol Ital 2007; 27 (2): 90-3
Fibrous histiocytoma is a benign tumour composed of a mixture of fibroblastic and histiocytic cells. Based on the location of this tumour, fibrous histiocytoma are usually divided into cutaneous types and those involving deep tissues. These lesions most often arise on the skin, but may rarely occur in soft deep tissues. The diagnosis of fibrous histiocytoma may be clinically difficult when the lesion is located in the deep tissues, and is frequently confirmed after local excision. The most important diagnostic distinction is the separation of this tumour from aggressive forms of fibrohistiocytic neoplasms, including dermatofibrosarcoma protuberans and malignant fibrous histiocytoma. A 19-year-old male presented with a painless swelling on the right cheek. Detailed clinical and laboratory examinations were performed. The lesion had been totally excised under local anaesthesia, and histopathology revealed a benign fibrous histiocytoma. The diagnosis, location, treatment and prognosis of fibrous histiocytoma are also discussed.
*17608138* 17608138 Malignant peripheral nerve sheath tumor of the distal phalanx of the fifth toe: a case report. Acta Radiol Short Rep 2014; 3 (1): ä
Malignant peripheral nerve sheath tumor (MPNST) involving bone is rare. We report a case of MPNST of the fifth toe. The lesion was located in the distal phalanx of the right fifth toe and extended into surrounding subcutaneous tissues. Findings on magnetic resonance imaging and histological features of the case are described and the literature is briefly reviewed.
*24778799* 24778799 Epigenetic alterations in bone and soft tissue tumors. Adv Anat Pathol 2017; 24 (6): 362-71
Human malignancies are driven by heritable alterations that lead to unchecked cellular proliferation, invasive growth and distant spread. Heritable changes can arise from changes in DNA sequence, or, alternatively, through altered gene expression rooted in epigenetic mechanisms. In recent years, high-throughput sequencing of tumor genomes has revealed a central role for mutations in epigenetic regulatory complexes in oncogenic processes.1?3 Through interactions with or direct modifications of chromatin, these proteins help control the accessibility of genes, and thus the transcriptional profile of a cell. Dysfunction in these proteins can lead to activation of oncogenic pathways or silencing of tumor suppressors.While epigenetic regulators are altered across a broad spectrum of human malignancies, they play a particularly central role in tumors of mesenchymal and neuroectodermal origin (table 1). This review will focus on recent advances in the understanding of the molecular pathogenesis of a subset of tumors in which alterations in the polycomb family of chromatin modifying complexes, the SWI/SNF family of nucleosome remodelers, and histones play a central role in disease pathogenesis. While this review will focus predominantly on the molecular mechanisms underlying these tumors, each section will also highlight areas in which an understanding of the molecular pathogenesis of these diseases has led to the adoption of novel immunohistochemical and molecular markers.
*28885261* 28885261 New Therapeutic Targets in Soft Tissue Sarcoma. Adv Anat Pathol 2012; 19 (3): 170-80
Soft tissue sarcomas are an uncommon and diverse group of more than 50 mesenchymal malignancies. The pathogenesis of many of these is poorly understood, but others have begun to reveal the secrets of their inner workings. With considerable effort over recent years, soft tissue sarcomas have increasingly been classified on the basis of underlying molecular alterations. In turn, this has allowed the development and application of targeted agents in several specific, molecularly defined, sarcoma subtypes. This review will focus the rationale for targeted therapy in sarcoma, with emphasis on the relevance of specific molecular factors and pathways in both translocation-associated sarcomas and in genetically complex tumors. In addition, we will address some of the early successes in sarcoma targeted therapy as well as a few challenges and disappointments in this field. Finally we will discuss several possible opportunities represented by poorly understood, but potentially promising new therapeutic targets, as well as several novel biologic agents currently in preclinical and early phase I/II trials. This will provide the reader with context for understanding the current state this field and a sense of where it may be headed in the coming years.
*22498582* 22498582 Phase 1 trial of preoperative image guided intensity modulated proton radiation therapy with simultaneously integrated boost to the high risk margin for retroperitoneal sarcomas. Adv Radiat Oncol 2017; 2 (1): 85-93
Purpose: To conduct phase 1 and 2 trials with photon intensity modulated radiation therapy and intensity modulated proton therapy (IMPT) arms to selectively escalate the retroperitoneal sarcoma preoperative radiation dose to tumor volume (clinical target volume [CTV] 2) that is judged to be at a high risk for positive margins and aim to reduce local recurrence. We report on the IMPT study arm in phase 1. Methods and materials: Patients aged ?18 years with primary or locally recurrent retroperitoneal sarcoma were treated with preoperative IMPT, 50.4 GyRBE in 28 fractions, to CTV1 (gross tumor volume and adjacent tissues at risk of subclinical disease) with a simultaneous integrated boost to CTV2 to doses of 60.2, 61.6, and 63.0 GyRBE in 28 fractions of 2.15, 2.20, and 2.25 GyRBE, respectively. The primary objective of the phase 1 study was to determine the maximum tolerated dose to CTV2, which will be further tested in the phase 2 study. Results: Eleven patients showed increasing IMPT dose levels without acute dose limiting toxicities that prevented dose escalation to maximum tolerated dose. Acute toxicity was generally mild with no radiation interruptions. No unexpected perioperative morbidity was noted. Eight months postoperatively, one patient developed hydronephrosis that was treated by stent with ureter dissected off tumor and received 57.5 GyRBE. Retained ureter(s) was (were) subsequently constrained to 50.4 GyRBE without further problem. With an 18-month median follow-up, there were no local recurrences. Conclusions: IMPT dose escalation to CTV2 to 63 GyRBE was achieved without acute dose limiting toxicities. The phase 2 study of IMPT will accrue patients to that dose. Parallel intensity modulated radiation therapy phase 1 arm is currently accruing at the initial dose level. Ureters that undergo a high dose radiation and/or surgery are at risk for late hydro-ureter. Future studies will constrain retained ureters to 50.4 GyRBE to avoid ureteral stricture.
*28740917* 28740917 Principles in Management of Soft Tissue Sarcoma. Adv Surg 2015; 49 (1): 107-22 *26299493* 26299493 The Use of Integra Dermal Regeneration Template Versus Flaps for Reconstruction of Full-Thickness Scalp Defects Involving the Calvaria: A Cost?Benefit Analysis. Aesthetic Plast Surg 2016; 40 (6): 901-7
Background: INTEGRA® Dermal Regeneration Template is a well-known and widely used acellular dermal matrix. Although it helps to solve many challenging problems in reconstructive surgery, the product cost may make it an expensive alternative compared to other reconstruction procedures. This retrospective study aims at comparing INTEGRA-based treatment to flap surgery in terms of cost and benefit. Patients and Methods: We considered only patients treated for scalp defects with bone exposure in order to obtain two groups as homogeneous as possible. We identified two groups of patients: 17 patients treated with INTEGRA and 18 patients treated with flaps. All patients were admitted in our institution between 2004 and 2010, and presented a defect of the scalp following trauma or surgery for cancer, causing a loss of the soft tissues of the scalp with bone exposure without pericranium. To calculate the cost in constant euros of each treatment, three parameters were evaluated for each patient: cost of the surgical procedure (number of doctors and nurses involved, surgery duration, anesthesia, material used for surgery), hospitalization cost (hospitalization duration, dressings, drugs, topical agents), and outpatient cost (number of dressing changes, personnel cost, dressings type, anti-infective agents). The statistical test used in this study was the Wilcoxon Mann?Whitney (? = 0.05). Results: No significant difference was characterized between the two groups for gender, age, presence of diabetes, mean defect size, and number of surgical procedures. All patients healed with good quality and durable closure. The median total cost per patient was ?11,121 (interquartile range (IQR) 8327?15,571) for the INTEGRA group and ?7259 (IQR 1852?24,443) for the flap group (p = 0.34). A subgroup of patients (six patients in the INTEGRA group and five patients in the flap group) showing defects larger than 100 cm2 were considered in a second analysis. Median total cost was ?11,825 (IQR 10,695?15,751) for the INTEGRA group and ?23,244 (IQR 17,348?26,942) for the flap group. Conclusion: Both treatments led to a good healing of the lesions with formation of soft and resistant tissue. No significant difference was characterized between the two groups for days of hospitalization and costs. In cases of patients with defects larger than 100 cm2 for whom major surgery is needed, the treatment with INTEGRA seemed to be less expensive than the treatment with free flaps or pedicle flaps. Level of Evidence V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the A5 online Instructions to Authors.www.springer.com/00266.
*27699461* 27699461 Aromatherapy as an Adjuvant Treatment in Cancer Care ? A Descriptive Systematic Review. Afr J Tradit Complement Altern Med 2012; 9 (4): 503-18
Claims of benefits of aromatherapy for cancer patients include reduced anxiety levels and relief of emotional stress, pain, muscular tension and fatigue. The objective of this paper is to provide an updated descriptive, systematic review of evidence from pre-clinical and clinical trials assessing the benefits and safety of aromatherapy for cancer patients. Literature databases such as Medline (via Ovid), the Cochrane database of systematic reviews, Cochrane Central were searched from their inception until October 2010. Only studies on cancer cells or cancer patients were included. There is no long lasting effect of aromatherapy massage, while short term improvements were reported for general well being, anxiety and depression up to 8 weeks after treatment. The reviewed studies indicate short-term effects of aromatherapy on depression, anxiety and overall wellbeing. Specifically, some clinical trials found an increase in patient-identified symptom relief, psychological wellbeing and improved sleep. Furthermore, some found a short-term improvement (up to 2 weeks after treatment) in anxiety and depression scores and better pain control. Although essential oils have generally shown minimal adverse effects, potential risks include ingesting large amounts (intentional misuse); local skin irritation, especially with prolonged skin contact; allergic contact dermatitis; and phototoxicity from reaction to sunlight (some oils). Repeated topical administration of lavender and tea tree oil was associated with reversible prepubertal gynecomastia.
*23983386* 23983386 An Overview on Ashwagandha: A Rasayana (Rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med 2011; 8 (5 Suppl): 208-13
Withania somnifera (Ashawagandha) is very revered herb of the Indian Ayurvedic system of medicine as a Rasayana (tonic). It is used for various kinds of disease processes and specially as a nervine tonic. Considering these facts many scientific studies were carried out and its adaptogenic / anti-stress activities were studied in detail. In experimental models it increases the stamina of rats during swimming endurance test and prevented adrenal gland changes of ascorbic acid and cortisol content produce by swimming stress. Pretreatment with Withania somnifera (WS) showed significance protection against stress induced gastric ulcers. WS have anti-tumor effect on Chinese Hamster Ovary (CHO) cell carcinoma. It was also found effective against urethane induced lung-adenoma in mice. In some cases of uterine fibroids, dermatosarcoma, long term treatment with WS controlled the condition. It has a Cognition Promoting Effect and was useful in children with memory deficit and in old age people loss of memory. It was also found useful in neurodegenerative diseases such as Parkinson s, Huntington s and Alzeimer s diseases. It has GABA mimetic effect and was shown to promote formation of dendrites. It has anxiolytic effect and improves energy levels and mitochondrial health. It is an anti-inflammatory and anti-arthritic agent and was found useful in clinical cases of Rheumatoid and Osteoarthritis. Large scale studies are needed to prove its clinical efficacy in stress related disorders, neuronal disorders and cancers.
*22754076* 22754076 Platelet-derived growth factor B induces senescence and transformation in normal human fibroblasts. Aging (Albany NY) 2013; 5 (7): 531-8
Normal cells enter a senescent state upon aberrant oncogenic signals and this response inhibits tumor initiation and progression. It is now well admitted that intracellular and membrane localized oncogenes can illicit oncogene induced senescence. However, the effect of mitogenic growth factor on cellular senescence is so far largely unknown. Here we show that normal human dermal fibroblasts display a complex response to Platelet derived growth factor B (PDGFB) expression. Indeed, PDGFB expression induces, in the same cell population, both senescence and cellular transformation. Remarkably both populations are sustained with passages suggesting that transformed cells eventually enter a senescent state. This senescence state is p53 dependent as inhibiting the p53 pathway blocks the ability of PDGFB to induce senescence and results in strong cellular transformation increase upon PDGFB expression. The relevance of these observations is supported by the fact that human dermatofibrosarcoma protuberans, skin tumors arising from constitutive PDGFB production with little aggressiveness, also display some senescence hallmarks. Together these data support the view that PDGFB, a mitogenic growth factor, has a limited ability to induce senescence. We propose that this low level of senescence might decrease the transforming ability of this factor without totally abolishing it.
*23934686* 23934686 Complications of Targeted Drug Therapies for Solid Malignancies: Manifestations and Mechanisms. AJR Am J Roentgenol 2013; 200 (3): 475-83
OBJECTIVE: This article reviews important complications of targeted drug therapies for solid malignancies that can be identified on diagnostic imaging. Wherever possible, known or proposed mechanistic explanations for drug complications are emphasized. CONCLUSION: Familiarity with the toxicity profiles of different targeted cancer therapies is important for identifying drug-related complications and for differentiating drug effects from disease progression. A mechanistic understanding may be useful for associating individual drugs with their complications and for predicting the complications of emerging agents.
*23436834* 23436834 Platelet-derived growth factors and their receptors in normal and malignant hematopoiesis. Am J Blood Res 2012; 2 (1): 44-56
Platelet-derived growth factors (PDGF) bind to two closely related receptor tyrosine kinases, PDGF receptor ? and ?, which are encoded by the PDGFRA and PDGFRB genes. Aberrant activation of PDGF receptors occurs in myeloid malignancies associated with hypereosinophilia, due to chromosomal alterations that produce fusion genes, such as ETV6-PDGFRB or FIP1L1-PDGFRA. Most patients are males and respond to low dose imatinib, which is particularly effective against PDGF receptor kinase activity. Recently, activating point mutations in PDGFRA were also described in hypereosinophilia. In addition, autocrine loops have been identified in large granular lymphocyte leukemia and HTLV-transformed lymphocytes, suggesting new possible indications for tyrosine kinase inhibitor therapy. Although PDGF was initially purified from platelets more than 30 years ago, its physiological role in the hematopoietic system remains unclear. Hematopoietic defects in PDGF-deficient mice have been reported but appear to be secondary to cardiovascular and placental abnormalities. Nevertheless, PDGF acts directly on several hematopoietic cell types in vitro, such as megakaryocytes, platelets, activated macrophages and, possibly, certain lymphocyte subsets and eosinophils. The relevance of these observations for normal human hematopoiesis remains to be established.
*22432087* 22432087 Multiple gene dysfunctions lead to high cancer-susceptibility: evidences from a whole-exome sequencing study. Am J Cancer Res 2011; 1 (4): 562-73
A total of $275 million has been launched to The Cancer Genome Atlas Project for genomic mapping of more than 20 types of cancers. The major challenge is to develop high throughput and cost-effective techniques for human genome sequencing. We developed a targeted exome sequencing technology to routinely determine human exome sequence. As a proof-of-concept, we chose a unique patient, who underwent three high mortalities cancers, i.e., breast, gallbladder and lung cancers, to reveal the genetic cause of high-cancer-susceptibility. Total 24,545 SNPs were detected. 10,868 (44.27%) SNPs were within coding regions, and 1,077 (4.38%) located in the UTRs. 3367 genes were hit by 4480 non-sysnonymous mutations in CDS with truncation of 30 proteins; and 10 mutations occurred at the splice sites that would generate different protein isoforms. Substitutions or premature terminations occurred in 132 proteins encoded by cancer-associated genes. CARD8 was completely loss; ANAPC1 was pre-translationally terminated from the transcripts of one allele. On the Ras-MAPK pathway, 18 genes were homozygously mutated. 15 growth factors/cytokines and their receptors, 9 transcription factors, 6 proteins on WNT signaling pathway, and 16 cell surface and extracellular proteins may be dysfunctioned. Exome sequencing made it possible for individualized cancer therapy.
*21984973* 21984973 Oral Spindle Cell Lipoma in a Rare Location: A Differential Diagnosis. Am J Case Rep 2015; 16 (ä): 844-8
Patient: Male, 56Final Diagnosis: Spindle cell lipomaSymptoms: AsymptomaticMedication: Not applicableClinical Procedure: Excisional biopsySpecialty: Oral and Maxillofacial Surgery ? Oral and Maxillofacial PathologyObjective:: Rare disease Background:: Spindle cell lipoma (SCL) is an uncommon and histologically distinct variant of lipoma. It usually occurs as a solitary, subcutaneous, and well-circumscribed lesion in the posterior neck, shoulders, and back of older men. SCL of the oral cavity is rare. We present the clinical-pathologic features of the third case of SCL located on the hard palate and discuss the histological differential diagnosis with other fusiform neoplasms. Case Report:: A 56-year-old man was evaluated for an asymptomatic swelling on the right side of the hard palate. The intra-oral examination showed a 25×20 mm sessile and circumscribed tumor, underlying an apparently healthy mucosa of normal color. The lesion revealed a floating consistency during palpation. Excisional biopsy was carried out based on a clinical diagnosis of lipoma or a benign minor salivary gland tumor. The histopathology demonstrated a well-circumscribed but unencapsulated proliferation of bland spindle cells admixed with mature adipocytes in a collagenous/myxoid stroma. The spindle cells were uniform, exhibiting elongated nuclei and narrow cytoplasmic processes without atypia. They were positive to CD34 and negative to factor VIII, alpha-smooth muscle actin, S100, cytokeratin, and actin. Mitotic activity was low, as confirmed by Ki-67 immunostaining. No lipoblastic activity was found. The diagnosis of SCL was therefore established. Conclusions:: Oral spindle cell lipoma is a rare benign lipomatous tumor. The histologic picture shows a range of variations and the observation of morphological features is important to distinguish this lesion from other fusiform tumors. Immunohistochemistry should be helpful in this differentiation.
*26615969* 26615969 EXTENSIVE SURVEY OF STAT6 EXPRESSION IN A LARGE SERIES OF MESENCHYMAL TUMORS. Am J Clin Pathol 2015; 143 (5): 672-82
Objectives: Expression of strong nuclear STAT6 is thought to be a specific marker for solitary fibrous tumors (SFT). Little is known about subtle expression patterns in other mesenchymal lesions. Methods: We performed immunohistochemical studies against the C-terminus of STAT6 in tissue microarrays and whole sections, comprising 2366 mesenchymal lesions. Results: Strong nuclear STAT6 was expressed in 285/2021 tumors, including 206/240 SFT, 49/408 well/dedifferentiated liposarcomas, 8/65 unclassified sarcomas, and 14/184 desmoids, among others. Expression in SFT was predominately limited to the nucleus. Other positive tumors typically expressed both nuclear and cytoplasmic STAT6. Complete absence of STAT6 was most common in pleomorphic liposarcoma and alveolar soft part sarcoma (60% and 72% cases negative, respectively). Conclusions: Strong nuclear STAT6 is largely specific for SFT. Physiologic low-level cytoplasmic/nuclear expression is common in mesenchymal neoplasia, and is of uncertain significance.
*25873501* 25873501 Viral Drug Sensitivity Testing Using Quantitative PCR Effect of Tyrosine Kinase Inhibitors on Polyomavirus BK Replication. Am J Clin Pathol 2010; 134 (6): 916-20
Our objective was to determine whether quantitative polymerase chain reaction (PCR) can be used to measure the effect of tyrosine kinase (TK) inhibition on polyomavirus BK (BKV) replication. The BKV was grown in a cell culture system. The rate of viral replication in the presence or absence of the drug being tested was assessed by amplifying the viral genome using primers directed against the viral capsid 1 protein.Dasatinib, erlotinib, gefitinib, imatinib, sunitinib, and sorafenib all showed antiviral activity at micromolar concentrations. The 50% effective concentration for erlotinib and sorafenib was within blood concentrations readily achieved in human subjects.Quantitative PCR is a convenient method for viral drug sensitivity testing for slow-growing viruses that do not readily produce cytopathic effect. TK inhibitors deserve further consideration as a potential therapeutic option for BKV-associated nephropathy and hemorrhagic cystitis.
*21088155* 21088155 A dermatofibrosarcoma protuberans-like tumor with COL1A1 copy number gain in the absence of t(17;22). Am J Dermatopathol 2017; 39 (4): 304-9
A 57 year-old woman presented with a three year history of a progressive firm plaque on the right cheek. Skin biopsies revealed a bland, storiform, spindle cell proliferation involving the deep dermis and subcutaneous fat. By immunohistochemistry the tumor cells were diffusely positive for CD34 and caldesmon with multifocal reactivity for EMA and focal, weak staining for SMA. Retinoblastoma protein expression was not detectable in tumor cells by immunohistochemistry. An interphase FISH analysis for PDGFB gene rearrangement was negative. A SNP-array study detected 1) a gain of chromosome segment 17q21.33-q25.3 which overlapped the entire COL1A1 gene with a breakpoint at 17q21.33, approximately 250 Kb centromeric to the 3? end of COL1A1 gene, 2) several segmental gains on chromosome 11 and 3) an RB1 gene locus with normal copy number and allele frequency. While the current case resembles DFSP, it is unique in that it demonstrates a copy number gain of chromosome 17q in the absence of fusion of COL1A1 and PDGFB genes and an unusual immunohistochemical staining profile. The morphologic and molecular findings suggest a novel molecular variant of DFSP not detectable with standard FISH for PDGFB rearrangement. This variant appears to respond to imatinib after 9 months of follow-up.
*27984233* 27984233 Founding BRCA1 mutations in hereditary breast and ovarian cancer in southern Sweden. Am J Hum Genet 1996; 58 (3): 441-50
Nine different germ-line mutations in the BRCA1 breast and ovarian cancer susceptibility gene were identified in 15 of 47 kindreds from southern Sweden, by use of SSCP and heteroduplex analysis of all exons and flanking intron region and by a protein-truncation test for exon 11, followed by direct sequencing. All but one of the mutations are predicted to give rise to premature translation termination and include seven frameshift insertions or deletions, a nonsense mutation, and a splice acceptor site mutation. The remaining mutation is a missense mutation (Cys61Gly) in the zinc-binding motif. Four novel Swedish founding mutations were identified: the nucleotide 2595 deletion A was found in five families, the C 1806 T nonsense mutation in three families, the 3166 insertion TGAGA in three families, and the nucleotide 1201 deletion 11 in two families. Analysis of the intragenic polymorphism D17S855 supports common origins of the mutations. Eleven of the 15 kindreds manifesting BRCA1 mutations were breast-ovarian cancer families, several of them with a predominant ovarian cancer phenotype. The set of 32 families in which no BRCA1 alterations were detected included 1 breast-ovarian cancer kindred manifesting clear linkage to the BRCA1 region and loss of the wild-type chromosome in associated tumors. Other tumor types found in BRCA1 mutation/haplotype carriers included prostatic, pancreas, skin, and lung cancer, a malignant melanoma, an oligodendroglioma, and a carcinosarcoma. In all, 12 of 16 kindreds manifesting BRCA1 mutation or linkage contained ovarian cancer, as compared with only 6 of the remaining 31 families (P<.001). The present study confirms the involvement of BRCA1 in disease predisposition for a subset of hereditary breast cancer families often characterized by ovarian cancers.Images: Figure 1aFigure 1b
*8644702* 8644702 Poster Presentations. Am J Hum Genet 1995; 57 (Suppl): A59-A106 *C1801572* C1801572 Rare Inherited A2BP1 Deletion In A Proband With Autism And Developmental Hemiparesis. Am J Med Genet A 2012; 0 (7): 1654-61 *22678932* 22678932 Altered Dermal Fibroblasts in Systemic Sclerosis Display Podoplanin and CD90. Am J Pathol 2016; 186 (10): 2650-64
Tissue injury triggers the activation and differentiation of multiple cell types to minimize damage and initiate repair processes. In systemic sclerosis, these repair processes appear to run unchecked, leading to aberrant remodeling and fibrosis of the skin and multiple internal organs, yet the fundamental pathological defect remains unknown. We describe herein a transition wherein the abundant CD34+ dermal fibroblasts present in healthy human skin disappear in the skin of systemic sclerosis patients, and CD34?, podoplanin+, and CD90+ fibroblasts appear. This transition is limited to the upper dermis in several inflammatory skin diseases, yet in systemic sclerosis, it can occur in all regions of the dermis. In vitro, primary dermal fibroblasts readily express podoplanin in response to the inflammatory stimuli tumor necrosis factor and IL-1?. Furthermore, we show that on acute skin injury in both human and murine settings, this transition occurs quickly, consistent with a response to inflammatory signaling. Transitioned fibroblasts partially resemble the cells that form the reticular networks in organized lymphoid tissues, potentially linking two areas of fibroblast research. These results allow for the visualization and quantification of a basic stage of fibroblast differentiation in inflammatory and fibrotic diseases in the skin.
*27565038* 27565038 CD137 Is Expressed in Follicular Dendritic Cell Tumors and in Classical Hodgkin and T-Cell Lymphomas: Diagnostic and Therapeutic Implications. Am J Pathol 2012; 181 (3): 795-803
CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy.
*22901750* 22901750 Local Mesenchymal Stem/Progenitor Cells Are a Preferential Target for Initiation of Adult Soft Tissue Sarcomas Associated with p53 and Rb Deficiency. Am J Pathol 2010; 177 (5): 2645-58
The cell of origin and pathogenesis of the majority of adult soft tissue sarcomas (STS) remains poorly understood. Because mutations in both the P53 and RB tumor suppressor genes are frequent in STS in humans, we inactivated these genes by Cre-loxP?mediated recombination in mice with floxed p53 and Rb. Ninety-three percent of mice developed spindle cell/pleomorphic sarcomas after a single subcutaneous injection of adenovirus carrying Cre-recombinase. Similar to human STS, these sarcomas overexpress Cxcr4, which contributes to their invasive properties. Using irradiation chimeras generated by transplanting bone marrow cells from mice carrying either the Rosa26StoploxPLacZ or the Z/EG reporter, as well as the floxed p53 and Rb genes, into irradiated p53loxP/loxPRbloxP/loxP mice, it was determined that sarcomas do not originate from bone marrow?derived cells, such as macrophages, but arise from the local resident cells. At the same time, dermal mesenchymal stem cells isolated by strict plastic adherence and low levels of Sca-1 expression (Sca-1low, CD31negCD45neg) have shown enhanced potential for malignant transformation according to soft agar, invasion, and tumorigenicity assays, after the conditional inactivation of both p53 and Rb. Sarcomas formed after transplantation of these cells have features typical for undifferentiated high-grade pleomorphic sarcomas. Taken together, our studies indicate that local Sca-1low dermal mesenchymal stem/progenitor cells are preferential targets for malignant transformation associated with deficiencies in both p53 and Rb.
*20864684* 20864684 Prognostic Significance of Stromal Platelet-Derived Growth Factor ?-Receptor Expression in Human Breast Cancer. Am J Pathol 2009; 175 (1): 334-41
This study systematically analyzes platelet-derived growth factor (PDGF) receptor expression in six types of common tumors as well as examines associations between PDGF ?-receptor status and clinicopathological characteristics in breast cancer. PDGF receptor expression was determined by immunohistochemistry on tumor tissue microarrays. Breast tumor data were combined with prognostic factors and related to outcome endpoints. PDGF ?- and ?-receptors were independently expressed, at variable frequencies, in the tumor stroma of all tested tumor types. There was a significant association between PDGF ?-receptor expression on fibroblasts and perivascular cells in individual colon and prostate tumors. In breast cancer, high stromal PDGF ?-receptor expression was significantly associated with high histopathological grade, estrogen receptor negativity, and high HER2 expression. High stromal PDGF ?-receptor expression was correlated with significantly shorter recurrence-free and breast cancer-specific survival. The prognostic significance of stromal PDGF ?-receptor expression was particularly prominent in tumors from premenopausal women. Stromal PDGF ?- and ?-receptor expression is a common, but variable and independent, property of solid tumors. In breast cancer, stromal PDGF ?-receptor expression significantly correlates with less favorable clinicopathological parameters and shorter survival. These findings highlight the prognostic significance of stromal markers and should be considered in ongoing clinical development of PDGF receptor inhibitors.
*19498003* 19498003 Coordinate Expression of Colony-Stimulating Factor-1 and Colony-Stimulating Factor-1-Related Proteins Is Associated with Poor Prognosis in Gynecological and Nongynecological Leiomyosarcoma. Am J Pathol 2009; 174 (6): 2347-56
Previously, we showed that the presence of high numbers of macrophages correlates with poor prognosis in nongynecological leiomyosarcoma (LMS). In gynecological LMS, a similar trend was noted but did not reach statistical significance. Colony-stimulating factor-1 (CSF1) is a major chemoattractant for macrophages. Here we show that in a subset of LMS cases, CSF1 is expressed by the malignant cells. Previously, we found that CSF1 is translocated and highly expressed in tenosynovial giant cell tumors (TGCTs), and this observation allowed us to identify genes that showed a coordinate expression with CSF1. Here, we evaluated the expression of CSF1 and TGCT-associated proteins in 149 cases of LMS. The coordinate expression of CSF1 and three TGCT-associated proteins (CD163, FCGR3a, and CTSL1) identified cases with poor prognosis in both gynecological LMS (P = 0.00006) and nongynecological LMS (P = 0.03). In gynecological LMS, the coordinate expression of these four markers was the only independent prognosticator in multivariate analysis (hazard ratio, 4.2; 95% CI, 1.12 to 16; P = 0.03). Our findings indicate that CSF1 may play an important role in the clinical behavior of LMS that may open a window for new therapeutic reagents.
*19443701* 19443701 Oncogenic Regulators and Substrates of the Anaphase Promoting Complex/Cyclosome Are Frequently Overexpressed in Malignant Tumors. Am J Pathol 2007; 170 (5): 1793-805
The fidelity of cell division is dependent on the accumulation and ordered destruction of critical protein regulators. By triggering the appropriately timed, ubiquitin-dependent proteolysis of the mitotic regulatory proteins securin, cyclin B, aurora A kinase, and polo-like kinase 1, the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase plays an essential role in maintaining genomic stability. Misexpression of these APC/C substrates, individually, has been implicated in genomic instability and cancer. However, no comprehensive survey of the extent of their misregulation in tumors has been performed. Here, we analyzed more than 1600 benign and malignant tumors by immunohistochemical staining of tissue microarrays and found frequent overexpression of securin, polo-like kinase 1, aurora A, and Skp2 in malignant tumors. Positive and negative APC/C regulators, Cdh1 and Emi1, respectively, were also more strongly expressed in malignant versus benign tumors. Clustering and statistical analysis supports the finding that malignant tumors generally show broad misregulation of mitotic APC/C substrates not seen in benign tumors, suggesting that a ?mitotic profile? in tumors may result from misregulation of the APC/C destruction pathway. This profile of misregulated mitotic APC/C substrates and regulators in malignant tumors suggests that analysis of this pathway may be diagnostically useful and represent a potentially important therapeutic target.
*17456782* 17456782 Association of Platelet-Derived Growth Factor-B Chain with Simian Human Immunodeficiency Virus Encephalitis. Am J Pathol 2004; 165 (3): 815-24
Chemokines and cytokines play a critical role in HIV infection, serving both to modulate virus replication and to recruit target cells to the site of infection. Platelet-derived growth factor (PDGF), a mitogen and chemoattractant for a wide variety of cells, is secreted by macrophages. Since macrophages are the target cells for lentiviral infection in the brain and PDGF is a known inducer of macrophage chemoattractant protein-1 (MCP)-1, a potent chemokine closely associated with HIV encephalitis, we investigated the association of PDGF-B chain (PDGF-B) with encephalitis in macaques caused by simian human immunodeficiency virus (SHIV), a chimera of HIV and SIV. Northern blot analysis confirmed elevated expression of PDGF-B chain mRNA in the brains from encephalitic macaques. Validation of these in vivo studies was confirmed in rhesus macrophage cultures infected with SHIVKU2 in which we demonstrated heightened expression of PDGF-B chain mRNA. Nuclear run-off analysis established transcriptional up-regulation of PDGF-B chain in virus-inoculated macrophage cultures. Reciprocally, addition of exogenous PDGF enhanced virus replication and MCP-1 expression in these cells. Inhibition of virus replication by tyrosine kinase inhibitor, STI-571, and by PDGF-B antisense oligonucleotides confirmed the specificity of the PDGF effect. Relevance of these findings was confirmed by analysis of archival brain tissue from SHIV encephalitic and non-encephalitic macaques for PDGF-B chain expression. PDGF-B chain protein expression was observed in the virus-infected cells in microglial nodules in the brains of SHIV-encephalitic macaques.
*15331406* 15331406 Activation of the GLI Oncogene through Fusion with the ?-Actin Gene (ACTB) in a Group of Distinctive Pericytic Neoplasms: Pericytoma with t(7;12). Am J Pathol 2004; 164 (5): 1645-53
Activation of the GLI oncogene is an important step in the sonic hedgehog signaling pathway, and leads to, eg, tissue-specific cell proliferation during embryogenesis. GLI activity in adult tissues is restricted, but has been identified in various neoplasms, as a result of mutations in the PTCH (patched) or SMOH (smoothened) genes, encoding components of the sonic hedgehog pathway, or by amplification of GLI. Herein, we present a new mechanism of GLI activation through fusion with the ?-actin gene (ACTB) in five histologically distinctive soft tissue tumors showing a t(7;12)(p21-22;q13-15) and a pericytic phenotype. Each was composed of a perivascular proliferation of monomorphic short spindle cells that stained positively for smooth muscle actin and laminin and that showed pericytic features by electron microscopy. To date, with a median follow-up of 24 months, none has behaved in an aggressive manner. Molecular genetic analysis showed that the translocation in all cases resulted in a fusion transcript including the 5?-part of ACTB and the 3?-part of GLI. The DNA-binding zinc finger domains of GLI were retained in the fusion transcripts and it is likely that the replacement of the promoter region of GLI with that of the ubiquitously expressed ACTB gene leads to deregulation of GLI expression and its downstream target genes.
*15111311* 15111311 Gene Expression Patterns and Gene Copy Number Changes in Dermatofibrosarcoma Protuberans. Am J Pathol 2003; 163 (6): 2383-95
Dermatofibrosarcoma protuberans (DFSP) is an aggressive spindle cell neoplasm. It is associated with the chromosomal translocation, t(17:22), which fuses the COL1A1 and PDGF? genes. We determined the characteristic gene expression profile of DFSP and characterized DNA copy number changes in DFSP by array-based comparative genomic hybridization (array CGH). Fresh frozen and formalin-fixed, paraffin-embedded samples of DFSP were analyzed by array CGH (four cases) and DNA microarray analysis of global gene expression (nine cases). The nine DFSPs were readily distinguished from 27 other diverse soft tissue tumors based on their gene expression patterns. Genes characteristically expressed in the DFSPs included PDGF? and its receptor, PDGFRB, APOD, MEOX1, PLA2R, and PRKCA. Array CGH of DNA extracted either from frozen tumor samples or from paraffin blocks yielded equivalent results. Large areas of chromosomes 17q and 22q, bounded by COL1A1 and PDGF?, respectively, were amplified in DFSP. Expression of genes in the amplified regions was significantly elevated. Our data shows that: 1) DFSP has a distinctive gene expression profile; 2) array CGH can be applied successfully to frozen or formalin-fixed, paraffin-embedded tumor samples; 3) a characteristic amplification of sequences from chromosomes 17q and 22q, demarcated by the COL1A1 and PDGF? genes, respectively, was associated with elevated expression of the amplified genes.
*14633610* 14633610 High-Throughput Copy Number Analysis of 17q23 in 3520 Tissue Specimens by Fluorescence in Situ Hybridization to Tissue Microarrays. Am J Pathol 2002; 161 (1): 73-9
The chromosomal region 17q23 has been shown to be commonly amplified in breast tumors, especially those with poor prognosis. In addition to breast cancer, studies by comparative genomic hybridization have implicated the involvement of 17q23 in other tumor types as well. Here we performed a large-scale survey on the distribution and frequency of the 17q23 copy number increases across different tumor types using fluorescence in situ hybridization on tissue microarrays containing 4788 specimens. A total of 4429 tumor samples representing 166 different tumor categories and 359 normal tissue samples from 40 different tissue categories were analyzed. Successful hybridizations were observed in 3520 of the 4788 specimens (74%). Increased 17q23 copy number was detected in 15% of the evaluable specimens with tumors originating from the lung, mammary gland, and soft tissue being most frequently affected. Interestingly, high-level amplification was detected only in 2% of the tumors and was generally restricted to mammary tumors. In addition, we observed an association between the frequency of increased 17q23 copy number and tumor progression in various tumor types. These results indicate that increased 17q23 copy number occurs frequently in several different tumor types suggesting that increased dosage of genes in this region might play a role in development and progression of many tumor types.
*12107091* 12107091 Translocations in Malignant Tumors. Am J Pathol 2001; 159 (6): 1979-80 *11733346* 11733346 Matriptase and HAI-1 Are Expressed by Normal and Malignant Epithelial Cells in Vitro and in Vivo. Am J Pathol 2001; 158 (4): 1301-11
Matriptase and its cognate, Kunitz-type serine protease inhibitor, HAI-1, comprise a newly characterized extracellular matrix-degrading protease system that may function as an epithelial membrane activator for other proteases and latent growth factors. Both enzyme and inhibitor have been detected in breast cancer cells, immortalized mammary epithelial cells, and human milk, but not in cultured fibroblasts nor in fibrosarcoma cells. To test the hypothesis that this system is expressed by normal breast epithelium, invasive breast cancers, and other cancers of an epithelial origin (carcinomas) but not in cancers of a mesenchymal origin, we have expanded our expression analysis of matriptase and HAI-1 in vitro and in vivo. Matriptase and HAI-1 were detected at the protein and mRNA levels both in hormone-dependent and hormone-independent cultured breast cancer cells, and this expression correlated with the expression of the epithelial markers E-cadherin or ZO-1. However, none of the breast cancer cell lines tested that express the mesenchymal marker vimentin express matriptase or HAI-1, consistent with an epithelial-selective expression of this system. Expression of matriptase, as determined by Western blot analysis, was observed in primary human breast, gynecological, and colon carcinomas, but not in stromal-derived ovarian tumors and human sarcomas of various origins and histological grades. The epithelial-selective expression of matriptase and HAI-1 was further confirmed in human breast cancers by immunohistochemistry and in situ hybridization, where the expression of the protease and the inhibitor were found in the carcinoma cells and in surrounding normal breast epithelia. The expression of the matriptase/HAI-1 system by malignant epithelial cells in vivo suggests a possible role for this protease in multiple aspects of the pathophysiology of epithelial malignancy, including invasion and metastasis.
*11290548* 11290548 A Novel, Nuclear Pore-Associated, Widely Distributed Molecule Overexpressed in Oncogenesis and Development. Am J Pathol 2000; 157 (5): 1605-13
Nuclear pore complexes are large, elaborate macromolecular structures that mediate the bidirectional nucleocytoplasmic traffic. In vertebrates, nuclear pore complexes comprise 50 to 100 proteins termed nucleoporins (Nup). An 88-kd nucleoporin (Nup88) has been recently cloned and characterized, and found to be associated in a dynamic subcomplex with the oncogenic nucleoporin CAN/Nup 214. We have produced a polyclonal antiserum to Nup88, and found that it immunoreacts convincingly in conventional tissue sections of 214 samples of malignant tumors of many types. All carcinomas were stained irrespective of site or line of differentiation; the majority of cases reacted strongly and extensively. In situ carcinomas and highly dysplastic epithelia were similarly reactive. Samples of malignant mesotheliomas, gliomas, sarcomas, and lymphoreticular tumors were also stained. Substantial reactions were also found in certain fetal tissues. Focal reactions were noted in some reactive-proliferative processes. Most benign epithelial and mesenchymal tumors and hyperplasias, and normal adult tissues reacted weakly and sporadically or not at all. Immunoblot analysis of selected samples strongly corroborated those findings. If further substantiated, our findings indicate that Nup88 could be regarded as a selective yet broadly based proliferation marker of potential significance in the histological evaluation and diagnosis of malignant transformation. Its ready applicability on conventional paraffin sections and on cytological preparations may broaden its clinical and investigative significance.
*11073820* 11073820 Gastrointestinal Stromal Tumors May Originate from a Subset of CD34-Positive Interstitial Cells of Cajal. Am J Pathol 2000; 156 (4): 1157-63
Most gastrointestinal stromal tumors (GISTs), a subgroup of mesenchymal neoplasms of the gut wall, express both Kit (CD117) and CD34 proteins. It has been suggested that GISTs originate from or differentiate into interstitial cells of Cajal (ICC), after several reports indicated that ICC are likely the only cells in the gut which express both Kit and CD34. ICC are among the few cell types resident in the gut which express Kit, together with mast cells. However, the question whether or not ICC express CD34 is currently disputed. Using single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) on cultured murine intestinal cells, single ICC were selected by morphology and tested for the expression of c-kit and CD34 mRNA. Most ICC were only c-kit-positive, however a subset (7 out of 43) were double positive for both c-kit and CD34. In the human small intestine, sequential immunohistochemical staining for Kit and CD34 proteins on the same 3-?m sections showed that some of the ICC surrounding Auerbach?s plexus and ICC within the circular muscle layer of the small intestine were positive for both Kit and CD34. In addition, CD34+Kit? cells were seen adjacent to ICC. These data from two different techniques indicate that ICC can be double positive for Kit and CD34. Thus, GISTs with the Kit+CD34+ phenotype may arise from a subpopulation of CD34+ Kit+ ICC.
*10751339* 10751339 Overexpression of the Hepatocyte Growth Factor (HGF) Receptor (Met) and Presence of a Truncated and Activated Intracellular HGF Receptor Fragment in Locally Aggressive/Malignant Human Musculoskeletal Tumors. Am J Pathol 2000; 156 (3): 821-9
Enhanced hepatocyte growth factor (HGF) receptor (Met) signaling has been suggested to play an important role in the development and progression of various epithelial and nonepithelial tumors. N-terminally truncated forms of the HGF receptor have been shown to be constitutively activated and tumorigenic in animal experiments. In the present study, 102 benign and malignant human musculoskeletal tumors were examined for expression of the HGF receptor by Western blotting and/or immunohistochemistry. A clear predominance of HGF receptor expression was seen in malignant as compared to benign tumors (Western blotting, P < 0.001; immunohistochemistry, P < 0.02). For the first time we show HGF receptor expression in the following four tumor types: dermatofibrosarcoma protuberans, clear cell sarcoma of tendons, malignant primitive neuroectodermal tumor, and benign fibrous histiocytoma. In three cases of sarcoma with high HGF receptor expression by Western blotting, we found indications of a short 85-kd N-terminally truncated HGF receptor that was tyrosine phosphorylated and located in the cytoplasm. Although fragments of this length were seen in 18 of 65 tumors, most were not tyrosine-phosphorylated. Northern blotting revealed only the 7.5-kb full-length HGF receptor transcript, suggesting that the 85-kd fragment is generated by an alternative initiation of translation or by proteolytic cleavage. Southern blotting detected no amplification of the Hgfr/Met gene in the 35 tumors examined, in contrast to our recent report of Hgfr/Met gene amplification in 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat sarcomas. The present data suggest that the locally aggressive and malignant properties of human mesenchymal tumors maybe related, in part, to high levels of full-length HGF receptors, and in some cases to the occurrence of N-terminally truncated HGF receptors, activated independently of HGF.
*10702398* 10702398 Immunoblot Analysis of CD34 Expression in Histologically Diverse Neoplasms. Am J Pathol 2000; 156 (1): 21-7
CD34 is a heavily glycosylated transmembrane protein of ?110 kd whose function is essentially uncharacterized. First identified in a myeloid leukemia cell line, immunohistological reactivity with anti-CD34 antibodies is also encountered in a histologically diverse subset of nonhematolymphoid neoplasms including angiosarcoma, solitary fibrous tumors, epithelioid sarcomas, spindle cell lipomas, dermatofibrosarcoma protuberans, and myofibroblastomas. Immunohistological reactivity for CD34 in hematopoietic stem cells and endothelial cells has been shown to correspond to the expression of the CD34 protein. With the exception of gastrointestinal stromal tumors, CD34 protein expression has not been investigated in other CD34 immunohistologically reactive nonhematolymphoid neoplasms. We undertook this study to examine whether the observed reactivity for anti-CD34 antibodies in apparently unrelated tumors is due to the expression of the same protein or whether shared epitopes elaborated by other proteins could account for this reactivity. Immunoblot analyses with anti-CD34 antibodies of six different CD34 immunohistologically reactive lesions show the same ?110-kd molecular weight protein. In addition, two cases of dermatofibrosarcoma protuberans show double bands at ?110 kd. Laser-capture microdissection of CD34 immunohistologically reactive epithelioid sarcoma and nonreactive epidermal cells illustrates that this reactivity is specific to tumor cells. These results show that the observed immunohistological reactivity with anti-CD34 antibodies is due to the expression of the CD34 protein and not to shared epitopes on unrelated proteins.
*10623649* 10623649 Correlation between Clinicopathological Features and Karyotype in Spindle Cell Sarcomas : A Report of 130 Cases from the CHAMP Study Group. Am J Pathol 1999; 154 (6): 1841-7
Soft-tissue tumors have proved to be a fruitful area for the identification of reproducible cytogenetic aberrations, especially among pediatric round-cell sarcomas and lipomatous tumors. Thus far, however, data regarding sarcomas of monomorphic spindle cell type have been limited and somewhat disappointing, with the notable exception of synovial sarcoma. As part of an ongoing international collaborative study, 130 karyotyped spindle-cell sarcomas were reviewed and classified histologically, without knowledge of the clinical and karyotypic data, with the aim of identifying objective correlations between morphology, karyotype, and clinical parameters. Clonal chromosomal abnormalities were identified in 82 cases studied (63%), but only in the group of synovial sarcomas was there clear correlation between the cytogenetic findings, in the form of a consistent t(X;18)(p11;q11), and morphology. Among leiomyosarcomas (41 cases) and malignant peripheral nerve sheath tumors (MPNSTs; 27 cases) as well as in individual examples of rarer entities, there was a general tendency for karyotypic complexity associated with frequent loss or rearrangement of chromosome arms 1p, 10p, 11q, 12q, 17p, and 22q. Rearrangements of 17q (the region of the NF1 gene) were seen in 9/27 (33%) of MPNSTs. Among nine cases of solitary fibrous tumor (in which previous cytogenetic data are very limited) no consistent aberrations were identified. We conclude that, with the exception of synovial sarcoma, most spindle-cell sarcomas share with pleomorphic sarcomas the tendency for karyotypic complexity. There was no indication (in most of these lesions) that detectable cytogenetic aberrations could either facilitate their diagnosis or help to determine prognosis. There is a clear need to further study and understand the significance of multiple chromosomal abnormalities in this group of mesenchymal neoplasms with the particular goal of determining their role in the process of tumor development.
*10362810* 10362810 Trisomies 8 and 20 Characterize a Subgroup of Benign Fibrous Lesions Arising in Both Soft Tissue and Bone. Am J Pathol 1999; 154 (3): 729-33
Trisomy 8 and trisomy 20 are nonrandom aberrations in desmoid tumors. The presence of these trisomies in related benign fibrous lesions of bone has not been previously addressed. In this study, 22 specimens from 19 patients diagnosed with desmoid tumor, desmoplastic fibroma, periosteal desmoid tumor, osteofibrous dysplasia, or fibrous dysplasia were examined by cytogenetic analysis of short-term cultures and bi-color fluorescence in situ hybridization of cytological touch preparations or paraffin-embedded tissue with centromeric probes for chromosomes 8 and 20. Trisomy 8 and trisomy 20 were detected by molecular cytogenetic methodologies in 15 specimens, including 10 primary bone lesions. Traditional cytogenetic analysis revealed trisomy 8 in two cases of osteofibrous dysplasia. Our findings demonstrate that trisomy 8 and trisomy 20 are also nonrandom aberrations in histologically similar, but clinically distinct, benign fibrous lesions of bone.
*10079250* 10079250 Congenital Mesoblastic Nephroma t(12;15) Is Associated with ETV6-NTRK3 Gene Fusion : Cytogenetic and Molecular Relationship to Congenital (Infantile) Fibrosarcoma. Am J Pathol 1998; 153 (5): 1451-8
Morphological, cytogenetic, and biological evidence supports a relationship between congenital (infantile) fibrosarcoma (CFS) and congenital mesoblastic nephroma (CMN). These tumors have a very similar histological appearance, and they are both associated with polysomies for chromosomes 8, 11, 17, and 20. Recently, CFS was shown to contain a novel t(12;15)(p13;q25) translocation resulting in ETV6-NTRK3 gene fusion. The aims of this study were to determine whether congenital mesoblastic nephroma contains the t(12;15)(p13;q25) translocation and ETV6-NTRK3 gene fusion and whether ETV6-NTRK3 fusions, in CMN and CFS, antedate acquisition of nonrandom chromosome polysomies. To address these aims, we evaluated 1) ETV6-NTRK3 fusion transcripts by reverse transcriptase polymerase chain reaction and sequence analysis, 2) genomic ETV6-region chromosomal rearrangement by fluorescence in situ hybridization, and 3) chromosomal polysomies by karyotyping and fluorescence in situ hybridization. We report ETV6-NTRK3 fusion transcripts and/or ETV6-region rearrangement in five of six CMNs and in five of five CFSs. The ETV6-NTRK3 fusion transcripts and/or ETV-region chromosome rearrangements were demonstrated in two CMNs and one CFS that lacked chromosome polysomies. These findings demonstrate that t(12;15) translocation, and the associated ETV6-NTRK3 fusion, can antedate acquisition of chromosome polysomies in CMN and CFS. CMN and CFS are pathogenetically related, and it is likely that they represent a single neoplastic entity, arising in either renal or soft tissue locations.
*9811336* 9811336 Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 1998; 152 (5): 1259-69
The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach s ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor.Images: Figure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9
*9588894* 9588894 Ring chromosomes in dermatofibrosarcoma protuberans are composed of interspersed sequences from chromosomes 17 and 22. Am J Pathol 1995; 147 (6): 1553-8
Ring chromosomes are found in most dermatofibrosarcoma protuberans (DFSPs), and recent reports demonstrate that portions of the DFSP ring chromosomes derive from chromosome 17. In this study we characterized ring chromosomes in three DFSPs using a combined approach of karyotyping, chromosome painting, and comparative genomic hybridization. Chromosome painting demonstrated that the ring chromosomes in each DFSP were composed of discontinuous, interwoven sequences from chromosomes 17 and 22. Amplification of chromosomes 17 and 22 sequences was confirmed in each of these cases by comparative genomic hybridization, and over-representation of chromosomes 17 and 22 sequences was also demonstrated by comparative genomic hybridization in 1 of 2 cytogenetically unremarkable DFSPs. We conclude that amplification of chromosomes 17 and 22 sequences, in ring form, is a characteristic aberration in DFSP.Images: Figure 1Figure 2
*7495279* 7495279 Ultraviolet-induced p53 mutations in atypical fibroxanthoma. Am J Pathol 1994; 145 (1): 11-7
Atypical fibroxanthoma (AFX) is an uncommon neoplasm of the superficial soft tissue occurring in actinically damaged skin of elderly patients. Sun-exposed skin also represents the main site of squamous and basal cell carcinomas and malignant melanoma, and a key role for ultraviolet (UV) radiation in their pathogenesis has long been suspected. UV-related mutations of the p53 gene have been identified in human skin cancers. To verify whether the pathogenesis of AFX is related to the effect of sunlight, p53 protein and gene status have been investigated in a series of 10 cases of AFX. Seven of 10 showed p53 immunoreactivity in most of the neoplastic cells. Molecular analysis of the p53 gene revealed an abnormal single strand conformation polymorphism pattern in all the p53 positive cases. Polymerase chain reaction direct sequencing revealed that all the mutations involved cytosine bases. Four cases showed C to T transitions (including two CC-TT double base substitutions) and two cases showed C to G transversion. All but one mutation took place at dipyrimidine sites. These findings provide the first objective evidence for the central role of UV radiation in the development of AFX and also represent the first in vivo demonstration of solar UV-induced mutations in a human mesenchymal neoplasm.Images: Figure 1Figure 2Figure 3
*8030743* 8030743 PG-M1: A New Monoclonal Antibody Directed against a Fixative-Resistant Epitope on the Macrophage-Restricted Form of the CD68 Molecule. Am J Pathol 1993; 142 (5): 1359-72
A new anti-macrophage monoclonal antibody (PG-M1) was produced by immunizing BALB/c mice with fresh spleen cells from a patient with Gaucher s disease. PG-M1 reacts strongly with a fixative-resistant epitope of an intracytoplasmic molecule, selectively expressed by virtually all macrophages of the human body. Although attempts to immunoprecipitate the molecule recognized by PG-M1 have failed so far, the reactivity of the antibody with COS-1 and WOP cells transfected with a human complementary DNA clone encoding for the CD68 antigen suggests that PG-M1 is a new member of the CD68 cluster. However, unlike other CD68 antibodies (KP1, EBM11, etc.), which react with both macrophages and myeloid cells, PG-M1 detects a fixative-resistant epitope on the macrophage-restricted form of the CD68 antigen. In 957 routinely fixed, paraffin-embedded samples, PG-M1 showed a more restricted reactivity with elements of the monocyte/macrophage lineage than the previously described monoclonal antibodies MAC-387 (anti-calgranulins), KP1 (CD68) and Ki-M1P. Among hematological malignancies, PG-M1 only labels acute leukemias of M4 and M5 type and rare examples of malignant histiocytosis/true histiocytic sarcoma. In contrast, acute leukemias of the M1, M2, M3, M6, M7, and L1-L3 types, non-Hodgkin s lymphomas, and Hodgkin and Reed-Sternberg cells of Hodgkin s disease are consistently PG-M1-negative. In the daily diagnostic practice, PG-M1 seems to be particularly valuable for the diagnosis of myelomonocytic or monocytic leukemia and neoplasms of true histiocytic origin in routine paraffin sections.Images: Figure 1Figure 2Figure 1Figure 2
*7684194* 7684194 Inducible expression of MS-1 high-molecular-weight protein by endothelial cells of continuous origin and by dendritic cells/macrophages in vivo and in vitro. Am J Pathol 1993; 142 (5): 1409-22
Recently, we have described a monoclonal antibody, named MS-1, which identifies a novel high-molecular-weight protein expressed by noncontinuous, sinusoidal endothelia and by interstitial dendritic cells in certain normal human organs (S Goerdt, LJ Walsh, GF Murphy, JS Pober, J Cell Biol 1991, 113:1425-1437; and LJ Walsh, S Goerdt, JS Pober, H Sueki, GF Murphy, Lab Invest 1991, 65: 732-741). In this report, we demonstrate in studying a variety of skin lesions that MS-1 antigen can also be expressed by endothelia of continuous origin under certain pathological conditions. Among the skin lesions tested, MS-1 antigen expression by endothelial cells of continuous origin is frequently observed in wound healing tissue, in cutaneous T-cell lymphoma, in psoriasis, and in melanoma metastasis, ie, in 100%, 80%, 71%, and 71% of cases, respectively. In contrast, endothelial MS-1 antigen expression rarely occurred in other skin lesions, including vascular tumors, six of which were Kaposi s sarcomas (13% and 0% of cases with vascular MS-1 expression, respectively). The percentage of cases with MS-1+ vessels is only marginally different in malignant versus benign lesions (55% versus 31%); when melanocytic nevi, primary melanomas, and melanoma metastases are compared, however, an increase in the percentage of cases with MS-1+ vessels is seen (31%, 50%, and 71%, respectively). Apart from wound healing, the relative number of MS-1+ vessels in a given lesion amounts to less than 5% compared with the number of continuous type vessels stained by monoclonal antibody 1F10 (S Goerdt, F Steckel, K Schulze-Osthoff, H-H Hagemeier, E Macher, C Sorg, Exp Cell Biol 1989, 57: 185-192). In addition, the occurrence of MS-1+ vessels is not related to the overall vascularity of a given lesion. Thus, the conditions for MS-1 antigen expression by endothelia of continuous origin cannot as yet be exactly defined. Furthermore, we have noticed that the number of MS-1+ dendritic cells varies considerably in skin lesions; in the early patch lesions of Kaposi s sarcoma and in juvenile xanthogranuloma MS-1+ cells even constitute the major cell type. This prompted us to investigate MS-1 antigen expression and its regulation in cultured human monocytes/macrophages. Expression of MS-1 antigen by these cells regularly starts at day 3 of culture and reaches its maximal value at day 9, after which it declines.(ABSTRACT TRUNCATED AT 400 WORDS)Images: Figure 1Figure 2Figure 3
*8494045* 8494045 Distribution of VLA integrins in solid tumors. Emergence of tumor-type-related expression. Patterns in carcinomas and sarcomas. Am J Pathol 1993; 142 (4): 1009-18
Integrins form a family of membrane-spanning cell-surface proteins that promote cell-cell or cell-matrix adhesion and integrate the pericellular matrix to the cytoskeleton. Integrins are believed to be involved in the differentiation of tissues during development. They are involved in the relationship of tumor cells to the matrix and may on the other hand reflect the differentiation status of cells. In this study, we evaluated immunohistochemically the distribution of VLA integrins (alpha 1 to alpha 6 chains of beta 1 integrins) in a representative selection of normal tissues and 110 solid tumors. In simple epithelia, VLA2 and VLA3 were usually uniformly present in epithelial cells, whereas in ductal and stratified epithelia they were seen predominantly in the basal/myoepithelial cells. VLA6 was seen in the basal aspect of epithelia in a polar manner. In carcinomas, VLA2 and VLA3 were variably expressed, showing either basal distribution in cellular islands or generalized widespread distribution or rarely being absent. VLA2 and VLA3 were also seen in epithelial components of epitheliomesenchymal tumors. VLA1 and VLA5 were widely distributed in benign and malignant mesenchymal tumors and in the desmoplastic stroma of carcinomas. They were usually not seen in epithelia, except that VLA1 was present in myoepithelia of the breast and VLA5 occasionally in poorly differentiated carcinoma cells. Mesenchymal cell/tumor types had characteristic patterns of VLA integrins; for example, smooth muscle and its benign tumors showed VLA1, 3, and 5, whereas schwannomas showed VLA1, 2, 3 and 6. Endothelial cells and angiosarcomas showed multiple VLA-types: VLA1, 2, 3, 5, and 6 in a similar manner. In malignant schwannomas and leiomyosarcomas, moderate to extensive reduction of expression of VLA2, 3, and 6 and of VLA3 and 5, respectively, occurred. The results show that VLA (beta 1) integrins show characteristic cell lineage-dependent distribution patterns in solid tumors and are a potentially useful tool in tumor typing.Images: Figure 1Figure 2Figure 3
*7682756* 7682756 Expression of platelet-derived growth factor and its receptors in proliferative disorders of fibroblastic origin. Am J Pathol 1992; 140 (3): 639-48
Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of connective tissue-derived cells in vitro. Less is known about its functions in vivo, and the role of PDGF in the development of human tumors has not been clarified. The authors have investigated the occurrence of PDGF and PDGF receptors in a series of proliferative disorders of fibroblastic origin using immunohistochemical and in situ hybridization techniques. High expression of PDGF beta-receptor mRNA and protein was found in the malignant tumors, and also in some benign lesions, such as dermatofibroma. In all these cases, benign as well as malignant, the PDGF B-chain mRNA, and less clearly, the PDGF A-chain mRNA, were coexpressed with the beta-receptor. In contrast, high expression of PDGF alpha-receptor mRNA was only found in fully malignant lesions, i.e., malignant fibrous histiocytoma. These data indicate that an autocrine growth stimulation via the PDGF beta-receptor could occur in an early phase of tumorigenesis, and may be a necessary but insufficient event for the progression into fully malignant human connective tissue lesions.Images: Figure 1Figure 2Figure 3Figure 4Figure 5
*1372158* 1372158 Keratin subsets in spindle cell sarcomas. Keratins are widespread but synovial sarcoma contains a distinctive keratin polypeptide pattern and desmoplakins. Am J Pathol 1991; 138 (2): 505-13
The presence of individual keratin polypeptides and desmoplakins was immunohistochemically studied in 25 spindle cell sarcomas of different types using acetone-fixed frozen sections. Results revealed that keratins 8 and 18 were present in a high number of tumors: 9 of 9 synovial sarcomas, 5 of 7 leiomyosarcomas, 5 of 5 malignant schwannomas, and 1 of 4 undifferentiated spindle cell sarcomas. In addition to keratins 8 and 18, the glandular component of synovial sarcoma showed prominent reactivity with antibodies to keratins 7 and 19. Also the glandular epithelial cells in synovial sarcoma showed desmoplakin immunoreactivity preferentially in a luminal distribution, but desmoplakin was absent in other spindle cell sarcomas. Furthermore keratin 13 was seen focally in 4 of 9 synovial sarcomas. In contrast, keratins 7, 13, and 19 were practically absent in leiomyosarcomas, malignant schwannomas, and undifferentiated spindle cell sarcomas. The widespread presence of keratins 8 and 18 in various spindle cell sarcomas may reflect aberrant keratin expression in mesenchymal cells, previously described in cultured transformed fibroblasts. The presence of keratins 7 and 19 and desmoplakin is highly associated with morphologically observable epithelial differentiation restricted to synovial sarcoma among spindle cell sarcomas.Images: Figure 1Figure 2Figure 3
*1704194* 1704194 Proliferation markers Ki-67 and p105 in soft-tissue lesions. Correlation with DNA flow cytometric characteristics. Am J Pathol 1990; 137 (6): 1491-500
Frozen tissue immunoreactivity with Ki-67, a monoclonal antibody that recognizes a nuclear antigen in nonresting or proliferating cells, was compared to DNA flow cytometry results (from fresh tissue) in a diverse group of 60 soft-tissue lesions. Both DNA index and Ki-67 score were independently reported to be associated with grade and prognosis in sarcomas, but no direct comparison of these two variables was made. It was attempted to measure proliferative activity in fixed paraffin-embedded tissues immunohistochemically in a subset of lesions using an antibody to another nuclear proliferation antigen, p105. Lesions were given a grade according to lesion category (reactive, 1; benign, 2; low-grade malignant, 3; and high-grade malignant, 4). Ki-67 reactivity correlated relatively well with this grading system (r = 0.59); benign lesions usually exhibited a low Ki-67 score and malignant lesions usually but not always exhibited a high score. For example, some malignant fibrous histiocytomas contained only rare positive cells. Some disparity between Ki-67 score and grade and within histologic types indicates some independence from these features, a fact that may be important when correlation with prognosis is performed. However Ki-67 did not correlate well with flow data such as percentage S phase (r = 0.30), percentage S + G2M phases (r = 0.37), or DNA index (r = 0.39). This probably is due to the fact that Ki-67 also marks cells in the G1 phase, whereas these are excluded in flow data analyses. Anti-p105 highlighted almost all nuclei in all cases tested, including fibromatosis, and did not correlate with Ki-67 score, histologic grade or DNA flow cytometric data. Results with p105 could not be favorably affected by titration experiments. It is reasonable to conclude that the Ki-67 score is a variable related to but independent of histologic grade, histologic type, and DNA flow values. Whether it is prognostically important in human sarcomas, as has been suggested, awaits further clinicopathologic study.Images: Figure 1Figure 2Figure 3
*1979714* 1979714 The spindle-shaped cells in cutaneous Kaposi s sarcoma. Histologic simulators include factor XIIIa dermal dendrocytes. Am J Pathol 1989; 135 (5): 793-800
Kaposi s sarcoma is a neoplasm that develops as multifocal lesions, often involving the skin, characterized by a complex histologic picture including numerous vascular spaces, perivascular and interstitial spindle-shaped cells, and extravasated erythrocytes, lymphocytes, and plasma cells. Using an antibody against factor XIIIa, which identifies dermal dendrocytes, numerous factor XIIIa-positive dermal dendrocytes were detected among the spindle-shaped cells in 12 acquired immune deficiency syndrome (AIDS)-associated, and five non-AIDS-associated Kaposi s sarcoma lesions. The factor XIIIa-positive dermal dendrocytes were also increased in histologic simulators of Kaposi s sarcoma such as dermatofibroma, angiomatoid malignant fibrous histiocytoma, granuloma annulare, and early wound healing, but were absent in keloids. The increased number of dermal dendrocytes, which are often in an angiocentric configuration and which also express CD4, lymphocyte function associated antigen-1 (LFA-1), and Leu M3 in Kaposi s sarcoma, may be important to the angioproliferative response. The results suggested that the spindle-shaped cells that are present in a variety of cutaneous lesions are dermal dendrocytes and belong to the reticuloendothelial system, unlike other mesenchymal cell types such as the endothelial cell. Apparently a diverse array of stimuli, including human immunodeficiency virus type-1 (HIV-1) infection and trauma, can stimulate the accumulation of factor XIIIa expressing dermal dendrocytes in the skin. These cells can then participate in different stages of a variety of cutaneous alterations including Kaposi s sarcoma, dermatofibroma, granuloma annulare, and early wound healing. Thus, the factor XIIIa-positive dermal dendrocyte is a common cellular denominator among diverse clinical entities that share some histologic features.Images: Figure 1Figure 2Figure 3p797-a
*2573283* 2573283 Monoclonal antibody to a human pancreatic carcinoma cell line recognizes gastrointestinal neoplasms. Am J Pathol 1989; 134 (3): 641-9
A monoclonal antibody designated RWP1.1 was produced against a human pancreatic carcinoma cell line RWP1. This antibody was shown to recognize an epitope of carcinoembryonic antigen. The reactivity of the antibody was evaluated on formalin-fixed normal tissues, 86 malignant neoplasms, 10 colonic polyps, and 6 cases of chronic pancreatitis using the peroxidase anti-peroxidase technique. RWP1.1 did not react with normal tissues apart from weak staining of fetal pancreatic ducts. This antibody preferentially reacted with primary and metastatic adenocarcinomas of the colon, stomach, pancreas, and colonic polyps but not with most adenocarcinomas from other sites nor with other types of tumors or cases of chronic pancreatitis. It also reacted with colon adenocarcinomas on frozen sections. The restricted specificity of this antibody could be used in differentiating gastrointestinal adenocarcinomas from other types of tumors including adenocarcinomas from other sites and most pancreatic adenocarcinomas from chronic pancreatitis.Images: Figure 1Figure 2Figure 3Figure 4Figure 5
*2466406* 2466406 Antibody specific to muscle actins in the diagnosis and classification of soft tissue tumors. Am J Pathol 1988; 130 (1): 205-15
A series of soft tissue tumors, melanomas, carcinomas, and lymphomas were studied immunohistochemically for the presence of muscle actins (MA) with the monoclonal antibody HHF-35, and for the presence of desmin for comparison. In nonneoplastic tissues, MA immunoreactivity was present in skeletal and smooth muscle cells, in the pericytes of small vessels, and in the myoepithelial cells. Desmin immunoreactivity had a similar distribution, except that the pericytes of small vessels and myoepithelial cells were negative. All 17 rhabdomyosarcomas were positive for both MA and desmin. Of leiomyosarcomas, 31/32 were positive for MA, and 29/32 for desmin. In pleomorphic undifferentiated sarcomas (malignant fibrous histiocytomas) MA and desmin-positive cells were present in 9/35 and 5/35 cases, respectively. Three of five pleomorphic liposarcomas showed MA-positive tumor cells, which were also desmin-positive in one case. Desmoid tumors often showed a moderate number of both desmin- and MA-positive cells. Hemangiopericytoma, Kaposi s sarcoma, and endometrial stromal sarcoma showed MA-positive staining only in the pericytes and not in the neoplastic cells. In various types of carcinomas, melanomas, and lymphomas, MA- or desmin-positive neoplastic cells were not identified. MA, but not desmin, was present in the desmoplastic stroma in many carcinomas. Both MA and desmin are good markers for muscle differentiation and especially serve to identify rhabdomyosarcomas and leiomyosarcomas. These markers are also present in some sarcomas currently regarded as nonmuscle tumors. This may suggest that some of these tumors have differentiation properties related to true myosarcomas. The absence of muscle actin, a pericytic marker, in hemangiopericytoma does not confirm the concept of pericytic nature of this tumor.Images: Figure 2Figure 1Figure 3Figure 4Figure 5Figure 6
*3276210* 3276210 Malignant fibrous histiocytoma. Expression of monocyte/macrophage differentiation antigens detected with monoclonal antibodies. Am J Pathol 1986; 124 (2): 303-9
Monoclonal antibodies were used in an investigation of the histogenesis of malignant fibrous histiocytoma (MFH), a neoplasm with morphologic features of both fibroblastic and histiocytic differentiation. In 4 cases of MFH studied, the tumor cells were found to react uniformly with antibodies to determinants expressed on monocyte macrophages (T-200, Ia, MoS-1, MoS-39, MoR-17). Both spindle and histiocyte-like tumor cells expressed these markers. In contrast, in 8 non-MFH soft tissue tumors, tumor cell reactivity was not observed. The reactivity of the spindle cells of MFH for determinants of monocyte/macrophages favors their origin from tissue histiocytes (facultative fibroblasts). The results support the view that MFH is a tumor of the mononuclear phagocyte system.Images: Figure 1Figure 2Figure 3
*2426951* 2426951 A primary lymph node malignancy with features suggestive of dendritic reticulum cell differentiation. A report of 4 cases. Am J Pathol 1986; 122 (3): 562-72
Four cases are described of a nonlymphomatous primary lymph node malignancy characterized by the proliferation of oval and spindle cells, occasionally multinucleated, and arranged in a nesting, swirling, and storiform pattern. The combination of light-microscopic, ultrastructural, and immunohistochemical features suggests that these tumors might be derived from dendritic reticulum cells.Images: Figure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7Figure 8Figure 9Figure 10Figure 11
*2420185* 2420185 S-100 protein in soft-tissue tumors derived from Schwann cells and melanocytes. Am J Pathol 1982; 106 (2): 261-8
In soft tissues outside the central nervous system, S-100 protein is found normally only in Schwann cells. Using the peroxidase-antiperoxidase immunohistochemical method S-100 was also found in tumors derived from Schwann cells and melanocytes, including neurofibromas, neurilemomas, granular cell myoblastomas, cutaneous nevi, and malignant melanomas. S-100 was not detected in malignant Schwannomas, neuroblastomas, oat cell carcinomas, medullary carcinomas of the thyroid, paragangliomas, or meningiomas. S-100 was also absent from neoplasms of soft tissues not usually considered to arise from cells of neural crest origin. S-100 appears to be a useful marker for identifying neoplasms derived from Schwann cells and melanocytes.Images: Figure 1Figure 2Figure 3Figure 4Figure 5Figure 6
*6278936* 6278936 Ultrastructure of Sclerosing Hemangioma. Am J Pathol 1974; 77 (3): 377-86
Specimens from 9 patients with the varying histopathologic patterns of sclerosing hemangioma were studied by electron microscopy. Not only were there numerous identifiable vascular spaces, but many of the cells had the ultrastructural characteristics of endothelial cells whether they were lining vascular spaces, forming organoid structures or were isolated. The Weibel-Palade bodies served as a marker for endothelial cells. They are rod-shaped, with a length up to 2 ? and a diameter up to .1 ?, and contain a tubular substructure, the diameter of the individual tubules being 150 [unk]. Our findings clearly support Gross and Wolbach s theory that this group of lesions is of endothelial origin.Images: Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6Fig 7
*4372890* 4372890 Spontaneous Tumors in the Rochester Strain of the Wistar Rat. Am J Pathol 1958; 34 (2): 311-35
Images: Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10Fig. 11Fig. 12Fig. 13Fig. 14Fig. 15Fig. 16Fig. 17Fig. 18Fig. 19Fig. 20Fig. 21Fig. 22Fig. 23Fig. 24
*13520911* 13520911 The Occurrence and Distribution of Glycogen in Hemangioma, Dermatofibrosarcoma Protuberans, Hemangiopericytoma, and Kaposi s Sarcoma. Am J Pathol 1952; 28 (6): 1027-33
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*12985832* 12985832 Pathophysiology of gadolinium-associated systemic fibrosis. Am J Physiol Renal Physiol 2016; 311 (1): F1-F11
Systemic fibrosis from gadolinium-based magnetic resonance imaging contrast is a scourge for the afflicted. Although gadolinium-associated systemic fibrosis is a rare condition, the threat of litigation has vastly altered clinical practice. Most theories concerning the etiology of the fibrosis are grounded in case reports rather than experiment. This has led to the widely accepted conjecture that the relative affinity of certain contrast agents for the gadolinium ion inversely correlates with the risk of succumbing to the disease. How gadolinium-containing contrast agents trigger widespread and site-specific systemic fibrosis and how chronicity is maintained are largely unknown. This review highlights experimentally-derived information from our laboratory and others that pertain to our understanding of the pathophysiology of gadolinium-associated systemic fibrosis.
*27147669* 27147669 The accuracy of siblings family history reports of thyroid and other cancers. Am J Public Health 1995; 85 (3): 408-9 *7892930* 7892930 Criteria for Risk Stratification of Vulvar and Vaginal Smooth Muscle Tumors: An Evaluation of 71 Cases Comparing Proposed Classification Systems. Am J Surg Pathol 2018; 42 (1): 84-94
Accurate risk stratification of smooth muscle tumors is essential for appropriate patient management. Yet, the rarity of smooth muscle tumors of the vagina and vulva makes development of a prognostically meaningful classification system challenging. While 2 classification methods for vulvar smooth muscle tumors and 1 for vaginal smooth muscle tumors have been proposed, it is our experience that many pathologists tend to apply criteria for uterine smooth muscle tumors when evaluating vulvovaginal tumors.We retrospectively reviewed a large cohort of vulvovaginal smooth muscle tumors with clinical follow up and evaluated which method most accurately classified tumors according to patient outcome. A total of 71 tumors, 53 vaginal (75%) and 18 vulvar (25%), from 71 patients were identified. All tumors were centrally examined for degree of cytologic atypia, morphology (spindled, epithelioid, myxoid), mitotic index per 10 high power fields, atypical mitotic figures, tumor cell necrosis, ischemic necrosis, tumor interface (circumscribed or infiltrative) and margin status. Clinical features were recorded for each patient. Follow up was available for 63 patients (89%), and ranged from 1 to 234 months (median 64 months). While site-specific and uterine criteria showed equally excellent sensitivity in classifying smooth muscle neoplasms as leiomyosarcoma according to patient outcome, uterine criteria showed improved specificity relatively to site-specific methods in classifying non-sarcoma tumors according to patient outcome. We recommend that uterine smooth muscle tumor criteria and nomenclature be adopted for evaluation and classification of vulvovaginal smooth muscle tumors.
*28786880* 28786880 The Surveillance, Epidemiology and End Results (SEER) Program and Pathology: Towards Strengthening the Critical Relationship. Am J Surg Pathol 2016; 40 (12): e94-e102
The Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute collects data on cancer diagnoses, treatment and survival for approximately 30% of the United States (U.S.) population. To reflect advances in research and oncology practice, approaches to cancer control are evolving from simply enumerating the development of cancers by organ sites in populations to include monitoring of cancer occurrence by histopathologic and molecular subtype, as defined by driver mutations and other alterations. SEER is an important population-based resource for understanding the implications of pathology diagnoses across demographic groups, geographic regions, and time, and provides unique insights into the practice of oncology in the U.S that are not attainable from other sources. It provides incidence, survival and mortality data for histopathologic cancer subtypes, and data by molecular subtyping is expanding. The program is developing systems to capture additional biomarker data, results from special populations, and expand bio-specimen banking to enable cutting edge cancer research that can improve oncology practice. Pathology has always been central and critical to the effectiveness of SEER, and strengthening this relationship in this modern era of cancer diagnosis could be mutually beneficial. Achieving this goal requires close interactions between pathologists and the SEER program. This review provides a brief overview of SEER, focuses on facets relevant to pathology practice and research, and highlights the opportunities and challenges for pathologists to benefit from and enhance the value of SEER data.
*27740970* 27740970 Recurrent NTRK1 Gene Fusions Define A Novel Subset Of Locally Aggressive Lipofibromatosis-Like Neural Tumors. Am J Surg Pathol 2016; 40 (10): 1407-16
The family of pediatric fibroblastic and myofibroblastic proliferations encompasses a wide spectrum of pathologic entities with overlapping morphologies and ill-defined genetic abnormalities. Among the superficial lesions, lipofibromatosis (LPF), composed of an admixture of adipose tissue and fibroblastic elements, in the past has been variously classified as infantile fibromatosis or fibrous hamartoma of infancy. In this regard, we have recently encountered a group of superficial soft tissue tumors occurring in children and young adults, with a notably infiltrative growth pattern reminiscent of LPF, variable cytologic atypia and a distinct immunoprofile of S100 protein and CD34 reactivity, suggestive of neural differentiation. SOX10 and melanocytic markers were negative in all cases tested. In contrast, a control group of classic LPF displayed bland, monomorphic histology and lacked S100 protein immunoreactivity. In order to define the pathogenetic abnormalities in these seemingly distinctive groups, we performed RNA sequencing for fusion gene discovery in 2 cases each, followed by screening for any novel alterations identified in a larger cohort representing both entities. The 2 index LPF-like neural tumors (LPF-NT) showed TPR-NTRK1 and TPM3-NTRK1 gene fusions, which were further validated by FISH and RT-PCR. Subsequent FISH screening of 14 LPF-NT identified recurrent NTRK1 gene rearrangements in 10 (71%) cases. Of the NTRK1 negative LPF-NT cases, one case each showed ROS1 and ALK gene rearrangements. In contrast none of the 25 classic LPF showed NTRK1 gene rearrangements, although regional abnormalities were noted in the 1q21?22 region by FISH in a majority of cases. Furthermore, NTRK1 immunostaining was positive only in NTRK1-rearranged S100 positive LPF-NT, but negative in classic LPF. These results suggest that NTRK1 oncogenic activation through gene fusion defines a novel and distinct subset of soft tissue tumors resembling LPF, but displaying cytologic atypia and a neural immunophenotype, provisionally named LPF-like neural tumors.
*27259011* 27259011 Sox10 ? A marker for not only Schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue. A systematic analysis of 5134 tumors. Am J Surg Pathol 2015; 39 (6): 826-35
Sox10 transcription factor is expressed in Schwannian and melanocytic lineages and is important in their development and can be used as a marker for corresponding tumors. Additionally, it has been reported in subsets of myoepithelial/basal cell epithelial neoplasms, but its expression remains incompletely characterized. In this study, we examined Sox10 express-ion in 5134 human neoplasms spanning a wide spectrum of neuroectodermal, mesenchymal, lymphoid, and epithelial tumors. A new rabbit monoclonal antibody (clone EP268) and Leica Bond Max automation were used on multitumor block libraries containing 30?70 cases per slide. Sox10 was consistently expressed in benign Schwann cell tumors of soft tissue and the GI-tract and metastatic melanoma, and was variably present in malignant peripheral nerve sheath tumors. In contrast, Sox10 was absent in many potential mimics of nerve sheath tumors such as cellular neurothekeoma, meningioma, gastrointestinal stromal tumors, PEComa, and a variety of fibroblastic-myofibroblastic tumors. Sox10 was virtually absent in mesenchymal tumors but occasionally seen in alveolar rhabdomyosarcoma. In epithelial tumors of soft tissue, Sox10 was expressed only in myoepitheliomas, although often absent in malignant variants. Carcinomas, other than basal cell type breast cancers, were only rarely positive but included rare squamous carcinomas of head and neck and pulmonary small cell carcinomas. Furthermore, Sox10 was often focally expressed in embryonal carcinoma reflecting a primitive Sox10-positive phenotype or neuroectodermal differentiation. Expression of Sox10 in entrapped non-neoplastic Schwann cells or melanocytes in various neoplasms has to be considered in diagnosing Sox10-positive tumors. The Sox10 antibody belongs in a modern immunohistochemical panel for the diagnosis of soft tissue and epithelial tumors.
*25724000* 25724000 Cutaneous Syncytial Myoepithelioma: Clinicopathologic Characterization in a Series of 38 Cases. Am J Surg Pathol 2013; 37 (5): 710-8
Cutaneous myoepithelial tumors demonstrate heterogeneous morphologic and immunophenotypic features. We previously described, in brief, seven cases of cutaneous myoepithelioma showing solid syncytial growth of ovoid, spindled or histiocytoid cells. We now present the clinicopathologic features in a series of 38 cases of this distinctive syncytial variant, which were diagnosed between 1997?2012 (mostly seen in consultation). There were 27 men and 11 women, with a median age of 39 years (range 2 months to 74 years). Primary anatomic sites were upper extremity (11, including 2 on the hand), upper limb girdle (3), lower extremity (14; 3 on the foot), back (6), face (2), chest (1), and buttock (1); the typical presentation was as either a polypoid or papular lesion. Tumors were well-circumscribed and centered in the dermis and ranged in size from 0.3 to 2.7 cm (median 0.8 cm). Microscopically all tumors showed a solid sheet-like growth of uniformly sized ovoid to spindled or histiocytoid cells with palely eosinophilic syncytial cytoplasm. Nuclei were vesicular with fine chromatin and small or inconspicuous nucleoli, and exhibited minimal to no atypia. Mitoses ranged from 0 to 4 per 10 HPF; 28 tumors showed no mitoses. Necrosis and lymphovascular invasion were consistently absent. Adipocytic metaplasia, appearing as superficial fat entrapped within the tumor, was seen in 12 cases. Chondro-osseous differentiation was seen in one tumor. All tumors examined were diffusely positive for EMA, and the majority showed diffuse staining for S-100 protein (5 showing focal staining). Keratin staining was focal in 1 of 33 tumors and seen in rare cells in 3 other cases. There was also positivity for GFAP (14/33), SMA (9/13), and p63 (6/11). Most lesions were treated by local excision. The majority of tumors tested (14/17; 82%) were positive by fluorescence in situ hybridization for EWSR1 gene rearrangement; testing for potential fusion partners (PBX1, ZNF444, POU5F1, DUX4, ATF1, CREB1, NR4A3, DDIT3, and NFATc2) was negative in all EWSR1-rearranged tumors. No FUS gene rearrangement was detected in two tumors lacking EWSR1 rearrangement. Follow-up information is available for 21 patients (mean follow-up 15 months). One patient with a positive deep margin developed a local recurrence 51 months after initial biopsy. All other patients with known follow-up, including 11 who had positive deep margins, are alive with no evidence of disease and no reported metastases. In summary, cutaneous syncytial myoepithelioma is a morphologically distinct variant that more frequently affects men, occurs over a wide age range, and usually presents on the extremities. Tumors are positive for S-100 protein and EMA, and unlike most myoepithelial neoplasms, keratin staining is infrequent. EWSR1 gene rearrangement is present in nearly all tumors tested, and likely involves a novel fusion partner. Prior reports describe some risk of recurrence and metastasis for cutaneous myoepithelial tumors; however, the syncytial variant appears to behave in a benign fashion and only rarely recurs locally.
*23588365* 23588365 Ossifying Fibromyxoid Tumor of Soft Parts: A Clinicopathologic, Proteomic and Genomic Study. Am J Surg Pathol 2011; 35 (11): 1615-25
Ossifying fibromyxoid tumor of soft parts (OFMT) is a rare soft tissue and bone tumor of borderline malignancy displaying an uncertain line of differentiation. The existence of fully malignant OFMT is controversial. In order to better understand the natural history and line of differentiation taken by OFMT, we studied 46 cases by light microscopic, immunohistochemical (IHC), genomic, proteomic, and fluorescent in situ hybridization (FISH) methods. Cases were classified according to the 2003 Folpe and Weiss system. Clinical and follow-up information was obtained. IHC for S-100 protein, desmin, epithelial membrane antigen (EMA), cytokeratins, smooth muscle actin (SMA), INI-1, neurofilament protein (NFP), CD56d excitatory amino acid transporter-4 (EAAT4), and MUC4 was performed on formalin-fixed, paraffin-embedded (FFPE) tissues. Gene expression profiling and proteomic studies were performed on FFPE tissues from 13 and 5 cases, respectively. FISH for INI-1 was performed on 10 cases. The 46 tumors arose in 29 males and 17 females (median age 52 years, range 39-63 years) and involved the proximal (N=17) and distal extremities (N=13), head and neck (N=9) and trunk (N=5). Median tumor size was 5.4 cm (range 1.0-21.0 cm). Cases were classified as typical OFMT (26 of 46, 57%), atypical OFMT (5 of 46, 11%) and malignant OFMT (15 of 46 cases, 32%). Clinical follow-up (27 cases, median 55 months duration) showed all patients with typical and atypical OFMT to be alive without disease. Adverse events, including 3 local recurrences, 3 metastases, and 3 deaths, were seen only in malignant OFMT. IHC results were: S100 protein (30/41, 73%), desmin (15/39, 38%), cytokeratin (4/35 11%), EMA (5/32, 16%), SMA (2/34, 6%), INI-1 (lost in mosaic pattern in 14/19, 74%), EAAT4 (31/39, 80%), MUC4 (3/14, 21%), NFP (8/10, 80%) and CD56 (6/14, 43%). Gene expression profiling showed typical and malignant OFMT to cluster together, distinct from schwannian tumors. Proteomic study showed expression of various collagens, S100 protein, and neuron-related proteins. FISH showed INI-1 deletion in 5/7 (71%) cases. We conclude that malignant OFMT exist, and may be recognized by the previously proposed criteria of Folpe and Weiss. Expression of neuron-related, in addition to Schwann cell and cartilage-associated markers, suggests a ?scrambled? phenotype in OFMT. Loss of INI-1 or other genes on 22q are likely important in the pathogenesis of these rare tumors.
*21997683* 21997683 CD39 is a promising therapeutic antibody target for the treatment of soft tissue sarcoma. Am J Transl Res 2015; 7 (6): 1181-8
Soft tissue sarcoma (STS) is a heterogenous tumor arising from the embryonic mesoderm represented by approximately 50 histological subtypes. Effective therapeutic intervention is lacking for recurrent, late stage and metastatic disease. CD39, a cell-surface ectonucleotidase, has previously been shown to be upregulated in hematological malignancies and various epithelial tumors, but not in STS. Here, we show by mass spectrometry and immunohistochemistry that CD39 is highly expressed in primary patient sarcoma samples. Moreover, CD39 nucleotidase activity is enhanced in fibrosarcoma compared with normal control cells. We demonstrate that an inhibitory monoclonal anti-CD39 antibody, abrogates CD39 enzymatic activity significantly and prolongs survival in a lethal metastatic patient-derived sarcoma model. Taken together, the data suggest CD39 is a novel therapeutic target for the treatment of STS.
*26279761* 26279761 Single institution outcome experience using AlloDerm® as temporary coverage or definitive reconstruction for cutaneous and soft tissue malignancy defects. Am Surg 2013; 79 (5): 476-82
Introduction: Definitive reconstruction after excision of cutaneous and soft tissue malignancies is sometimes limited due to lack of native tissue coverage options, patient comorbidities or pending permanent margin analysis. Acellular dermis (AlloDerm®) reconstruction offers an excellent coverage alternative to autologous reconstruction in these situations. We describe our experience using AlloDerm for coverage of skin and soft tissue defects. Methods: An IRB approved review of patients undergoing skin and soft tissue reconstruction or coverage with AlloDerm from 2006-2012 was performed. Clinicopathologic variables, early post-operative findings and subjective final cosmetic outcome were analyzed. Results: Sixty-seven patients underwent resection with AlloDerm reconstruction (median age 72 years (33-95 years). Melanoma (67%) was the most frequent diagnosis. The median defect size was 42 cm2 (2-340 cm2), involving the lower extremity in 45%, head & neck in 32%. AlloDerm was intended for use as a temporary biologic dressing in 64% (43/60) and permanent coverage in 24 (36%). Ten patients required re-excision for positive margins. Twenty-five (37%) underwent STSG or flap coverage after AlloDerm placement. Radiation was administered to 16 patients (24%) after AlloDerm reconstruction within a median of 53 days after surgery (range, 18-118 days). At first post-operative examination (median 11 days after surgery), 85% had evidence of healthy AlloDerm incorporation. Cellulitis was the most frequent complication (13%) all resolving with oral antibiotics. Conclusions: AlloDerm reconstruction after skin and soft tissue resection offers a suitable coverage alternative and may serve as a bridge to permanent reconstruction or as a permanent biologic dressing of complex surgical defects. In situations where adjuvant radiation is needed, AlloDerm can be used without major complications.
*23635582* 23635582 An unusual variant of atrophic dermatofibrosarcoma protuberans. An Bras Dermatol 2018; 93 (2): 282-4
Dermatofibrosarcoma protuberans is an uncommon neoplasm that is most often seen in young adults. The most common clinical presentation is the protruding form; however, other subtypes are known, such as the atrophic. In 2012 there were only 33 reports of this variant in the literature. Many cases of Dermatofibrosarcoma protuberans in children are only discovered in adulthood because they were not diagnosed early. Due the high morbidity, we raise the need for attention from the dermatologist to recognize uncommon neoplasms in the clinical practice. We report a case of a 15-year-old patient diagnosed with atrophic Dermatofibrosarcoma protuberans on the back.
*29723383* 29723383 Lobomycosis: a therapeutic challenge. An Bras Dermatol 2018; 93 (2): 279-81
Lobomycosis or lacaziosis is a chronic granulomatous fungal infection caused by Lacazia loboi. Most cases are restricted to tropical regions. Transmission is believed to occur through traumatic inoculation in the skin, mainly in exposed areas. It is characterized by keloid-like nodules. There are only a few hundred cases reported. The differential diagnoses include many skin conditions, and treatment is difficult. The reported case, initially diagnosed as keloid, proved to be refractory to surgical treatment alone. It was subsequently approached with extensive surgery, cryotherapy every three months and a combination of itraconazole and clofazimine for two years. No signs of clinical and histopathological activity were detected during follow-up.
*29723380* 29723380 Multiple dermatomyofibromas. An Bras Dermatol 2018; 93 (2): 268-70
This study describes a case of a 19-year-old patient with seven asymptomatic lesions on the chest, measuring between 0.5 to 1cm in diameter, with no history of trauma in the region. The immunohistochemical evaluation was positive for vimentin and smooth muscle actin, determining Dermatomyofibroma as definitive diagnosis. Dermatomyofibroma is a benign skin tumor, with a myofibroblastic origin, prevalent in young women. It usually presents as a single lesion, with very few reports of multiple lesions.
*29723353* 29723353 Cutaneous leiomyosarcoma on the face. An Bras Dermatol 2018; 93 (2): 262-4
Leiomyosarcoma is a rare skin tumor, most common in white men in the fifth to eighth decades of life. Primary tumors are classified in dermal or subcutaneous, that differ by clinical and prognostic features. They may appear on any site of the body, but are rare on the face. A 54-year-old female was admitted with a 5cm exophytic nodular lesion of 8 months duration on the right cheek, site of previous chronic radiodermatitis. Histopathology revealed spindle-shaped cell neoplasia, positive for smooth muscle actin on immunohistochemistry. Cutaneous leiomyosarcomas on the face are rare and may occur in previously irradiated areas. Immunohistochemistry is mandatory for an accurate diagnosis. Its similarity with other tumors may complicate the diagnosis, with delay expansion of the tumor.
*29723357* 29723357 Undifferentiated pleomorphic sarcoma. An Bras Dermatol 2018; 93 (1): 154-5 *29641724* 29641724 Periorbital leiomyosarcoma treated by means of conventional surgery and frontal myocutaneous flap. An Bras Dermatol 2017; 92 (5 Suppl 1): 118-20
Cutaneous leiomyosarcoma is a rare neoplasia, and its periorbital presentation is rather uncommon. We present a case of a male patient who was surgically treated, with the reconstruction performed with a frontal myocutaneous flap. The patient has been followed up for one year with adequate oncologic control and good aesthetic outcome.
*29267467* 29267467 Dermatomyofibroma. An Bras Dermatol 2017; 92 (1): 101-3
We report a case of dermatomyofibroma that, to our knowledge, is the second case reported in Brazil. About 100 cases have been reported worldwide. Dermatomyofibroma represents a rare, benign mesenchymal neoplasm of fibroblastic/myofibroblastic differentiation, with prolonged evolution and little or no symptoms. It most commonly occurs in young women and male children. Dermatomyofibroma can be easily confused with other clinical entities, which could lead to unnecessary treatments. Therefore, it is important that dermatologists and pediatricians suspect and start to consider this hypothesis in their diagnostic exercises.
*28225965* 28225965 Dermatofibrosarcoma protuberans with fibrosarcomatous transformation. An Bras Dermatol 2016; 91 (5): 700-1 *27828659* 27828659 Indication guidelines for Mohs micrographic surgery in skin tumors. An Bras Dermatol 2016; 91 (5): 621-7
Mohs micrographic surgery is a technique used to excise skin tumors based on comprehensive surgical mapping, in which the surgeon removes the tumor, followed by a complete histological evaluation of the tumor s margins. The correlation of the presence of a tumor in histological examinations and its precise location on the surgical map result in a complete removal of the tumor with maximum normal tissue preservation. The present article seeks to provide general practitioners and healthcare specialists with guidelines regarding recommendations for Mohs micrographic surgery to treat skin tumors, based on the most reliable evidence available in medical literature on the subject. This bibliographic review of scientific articles in this line of research was conducted based on data collected from MEDLINE/PubMed. The search strategy used in this study was based on structured questions in the Patient, Intervention, Control, and Outcome (PICO) format. MeSH terms were used as descriptors. The indications of this technique are related to recurrence, histology, size, definition of tumor margins, and location of tumors. These guidelines attempt to establish the indications of Mohs surgery for different types of skin tumors.
*27828636* 27828636 Two friends with eroded nodules on the ears: atypical fibroxanthoma case report. An Bras Dermatol 2015; 90 (4): 577-9
Atypical fibroxanthoma is an uncommon mesenchymal tumor that manifests clinically as a reddish papule or nodule in sun-exposed areas of the body. The clinical presentation is not specific and histology and immunohistochemistry are both necessary for a correct diagnosis. Surgery is the gold standard of therapy. Recurrence and metastasis should be excluded with a follow-up at 6 months, since this tumor should nowadays be considered a medium-grade neoplasm, rather than low-grade as previously believed. We report the case of two friends who came to our hospital during the same period, complaining of very similar lesions. After biopsy and immunohistochemical examination, a diagnosis of atypical fibroxanthoma in both cases was formulated.
*26375231* 26375231 Cutaneous metastasis from gastrointestinal adenocarcinoma of unknown primary origin. An Bras Dermatol 2015; 90 (4): 564-6
Cutaneous metastasis is a rare manifestation of visceral malignancies that indicates primarily advanced disease. Due to its low incidence and similarity to other cutaneous lesions, it is not uncommon to have a delayed diagnosis and a shortened prognosis. We describe the case of a patient who presented with a cutaneous nodule in the sternal region as a first sign of malignancy.
*26375228* 26375228 Case for diagnosis. An Bras Dermatol 2014; 89 (3): 519-20
We report the case of an 11-year-old male patient with a histopathological and immunohistochemical diagnosis of dermatofibroma with an atypical clinical presentation on the right forearm. Although dermatofibroma is considered a benign skin tumor, some of its differential diagnoses, such as dermatofibrosarcoma protuberans and malignant fibrous histiocytoma, are truly aggressive. Lesions with atypical clinical aspects and topology associated with specific histopathological variants are some of the criteria for complete tumor excision.
*24937835* 24937835 Variants of dermatofibroma - a histopathological study. An Bras Dermatol 2014; 89 (3): 472-7
Several variants of dermatofibroma have been described. They are essentially distinguished by their clinical and histopathological features. To review the mainfeaturesof these variants, a retrospective study of skin biopsies and tissue excisions of dermatofibromasperformed in the dermatology and venereology service at the Hospital Garcia de Orta between May 2007 and April 2012 was carried out. During that period, 192 dermatofibromas were diagnosed in 181 patients, the lesions being more common in women. Median age of the study population was 48 years. The most common lesion site was the limbs (74% of patients). The histopathological types found were common fibrous histiocytoma (80%) and the aneurysmal (5.7%),hemosiderotic (5.7%), epithelioid (2.6%), cellular (2.1%), lipidized (2.1%), atrophic (1.0) and clear cell (0.5%) variants. Based on these findings, this review focuses on the clinical and histological features of the various variants of dermatofibroma in terms of their clinical presentation, distinct histopathological features, differential diagnosis and prognosis.
*24937822* 24937822 Case for diagnosis. An Bras Dermatol 2014; 89 (2): 357-8
Dermatofibrosarcoma protuberans is a fibrohistiocytic tumor of intermediate malignancy with aggressive localized growth, high recurrence rate, but low metastatic potential. It appears as a hardened plaque, with slow growth, upon which the development of nodules occurs. It predominates in the trunk and is unusual in acral locations. Histopathology reveals spindle cells with storiform pattern and cartwheel-like or whirlwind-like aspect. Immunohistochemistry shows positivity for CD34. The treatment is surgical. We report a case of long evolution, with an unusual location, that relapsed after surgery, to emphasize the importance of early diagnosis and proper treatment, avoiding aggressive resections with increased morbidity.
*24770523* 24770523 Superficial Acral Fibromyxoma involving the nail s apparatus. Case report and literature review. An Bras Dermatol 2014; 89 (1): 147-9
Superficial Acral Fibromyxoma is a rare tumor of soft tissues. It is a relatively new entity described in 2001 by Fetsch et al. It probably represents a fibrohistiocytic tumor with less than 170 described cases. We bring a new case of SAF on the 5th toe of the right foot, in a 43-year-old woman. After surgical excision with safety margins which included the nail apparatus, it has not recurred (22 months of follow up). We carried out a review of the location of all SAF published up to the present day.
*24626661* 24626661 Case for diagnosis. An Bras Dermatol 2013; 88 (6): 997-9
The chondroid syringoma is a rare benign tumor, also called mixed cutaneous tumor by the presence of epithelial and mesenchymal components, consisting of sweat elements in cartilaginous, collagenous, myxoid or osseous stroma, among others. It mainly affects middle-aged men and is characterized by asymptomatic and slowgrowing, dermal or subcutaneous nodules. The most common locations are the head and neck. It is rare on the extremities. There are reports of malignant variants predominantly in women, located on the extremities. We report a case of a female patient with a lesion on the toe, with excellent outcome after surgical treatment.
*24474117* 24474117 Nodular fasciitis on the zygomatic region: a rare presentation. An Bras Dermatol 2013; 88 (6 Suppl 1): 89-92
Nodular fasciitis is a benign tumor, resulting from reactive proliferation composed of fibroblastic/myofibroblastic cells. Due to its rapid growth and high cellularity it may be mistaken for sarcoma. Despite the possibility of spontaneous regression, excision is the treatment of choice. A 24-year-old female patient presented with a nodule on the zygomatic region with 3 months of evolution. Excisional biopsy was performed. Histopathological examination associated with immunohistochemical markers HHF35, AML and Ki-67 allowed diagnostic confirmation. The main relevance of the case presented is its rare location, suggesting its inclusion among the differential diagnoses of tumor lesions on the face.
*24346889* 24346889 Atrophic dermatofibroma. An Bras Dermatol 2013; 88 (5): 793-5
Dermatofibroma is a benign fibrohistiocytic tumor, common and easily diagnosed when classical clinicopathologic features are present. The atrophic variant of dermatofibroma is of uncertain origin. This lesion is characterized clinically by a flat or atrophic and depressible surface. Histopathological features show reduction of the thickness of the dermis and elastic fibers. We report a typical case of this uncommon and probably underdiagnosed variant.
*24173186* 24173186 Case for diagnosis. An Bras Dermatol 2013; 88 (3): 469-71
Granular cell tumor (Abrikossoff s tumor) is a rare benign disease that preferentially affects the cervicofacial segment. It is usually a solitary nodule that may ulcerate and present pearly infiltration on the borders, while keeping a clean background and a hyperchromic halo. This paper describes the case of an ulcerated granular cell tumor on an unusual location, which reinforces the necessity of including this tumor in the differential diagnosis of nodular-ulcerative skin lesions.
*23793211* 23793211 Acute Peritonitis Caused by a Fibrosarcoma of the Transverse Colon in an Adult. Ann Coloproctol 2014; 30 (6): 280-4
A fibrosarcoma is a malignant mesenchymal tumor derived from fibrous connective tissue. It usually develops in the deep soft tissues of the extremities, as well as the trunk, head, and neck. In extremely rare cases, a fibrosarcoma may occur in the gastrointestinal tract. Most cases of fibrosarcoma in the gastrointestinal tract have been observed in the pediatric age group while only a few cases have been reported in adults. A 61-year-old male presented with pain in the entire abdominal region. Chest radiography showed free air in the subphrenic space. After an emergency operation, we found a solid mass around the transverse colon and performed a segmental resection with a lymphatic dissection of the transverse colon, including the mass. A pathologic examination showed a fibrosarcoma with a perforation. There was no perioperative complication. The patient was discharged on postoperative day 11 and had follow-ups for 1 year without any recurrence.
*25580415* 25580415 A Case-Control Study of Skin Cancer and Exposure of Toxic Heavy Metals. Ann Dermatol 2018; 30 (2): 238-40 *29606828* 29606828 Recurrent Dermatofibrosarcoma Protuberans of Scalp in a Distant Location 10 Years after Primary Excision. Ann Dermatol 2018; 30 (2): 226-8
Dermatofibrosarcoma protuberans (DFSP) is a slow growing low-grade cutaneous sarcoma. Local recurrence after excision is common due to the poorly defined periphery that renders histological control of surgical margin difficult, Mohs micrographic surgery is the optimal method for treatment. A 41 years old male patient, who had a previous history of DFSP, came to our dermatology clinic for evaluation of an asymptomatic firm flesh-colored nodule on the forehead. Total excision biopsy was done and the mass was histologically proved as DFSP. Wide excision with reconstruction was performed and showed no sign of recurrence till 18-month follow up. Local recurrence is known to be common for DFSP but a new visible lesion distant from the initial site may be confused as a de novo lesion or a benign neoplasm especially in scalp area, and thus interrupt early detection of DFSP. Herein, we report a case of recurrent DFSP of scalp which recurred distant from the original lesion.
*29606823* 29606823 Arborizing Vessels on Dermoscopy in Various Skin Diseases Other Than Basal Cell Carcinoma. Ann Dermatol 2017; 29 (3): 288-94
Background: Arborizing vessels (AVs) are dermoscopically defined as telangiectasias with distinct treelike branching, and are a characteristic feature of basal cell carcinoma (BCC). However, AVs are observed in various conditions other than BCC. Objective: The aim of this study was to investigate skin diseases showing AV and investigates dermoscopic differences between BCC and non-BCC. Methods: Dermoscopic images showing AV were prospectively collected and classified into BCC/non-BCC. Non-BCC was further classified into tumors (benign cystic, benign non-cystic, premalignant, and malignant) and non-tumors. We compared AV focusing, widest diameter of stem vessels, widest diameter ratio of stem vessel to first branch, and number of ramifications between groups. Results: Among 124 images, 54.0% were BCC and 46.0% were non-BCC. Non-BCC included epidermal cysts, hypertrophic scars/keloids, intradermal nevi, actinic keratoses, etc. The proportion of focused AV in BCC was significantly higher and the proportion of unfocused AV in BCC was lower than that of premalignant and malignant non-BCC. The widest diameter ratio of stem vessel to first branch was higher in non-BCC. Number of ramifications was significantly less in benign cystic non-BCC than BCC. Conclusion: Various skin diseases showed AV, so that diagnoses other than BCC should be considered. The findings in this study could help discriminate BCC from non-BCC.
*28566904* 28566904 Case of Pleomorphic Dermal Sarcoma of the Eyelid Treated with Micrographic Surgery and Secondary Intention Healing. Ann Dermatol 2016; 28 (5): 632-6
Pleomorphic dermal sarcoma (PDS) is a rare mesenchymal neoplasm sharing histopathological features with atypical fibroxanthoma (AFX), but has additional features of deep invasion of the superficial subcutis, tumor necrosis and vascular/perineural invasion. It is not well documented in the literature because of its rarity, and its clinical course has been debated due to the lack of homogenous criteria. We describe here the case of a 91-year-old female with a 6-month history of a solitary, asymptomatic, well-defined, 3.4-cm-sized, reddish, hard, protruding mass on the lateral aspect of the right upper eyelid. On the basis of initial punch biopsy results, storiform cellular infiltrate of pleomorphic spindle and polygonal cells with frequent atypical mitoses, the lesion was identified as AFX. Following the initial biopsy, micrographic surgery was performed and a tumor-free margin was confirmed. Considering the conservation of the periocular function and the advanced age of the patient, we planned secondary intention healing rather than primary suturing. After surgery, skeletal muscle infiltration was found and the diagnosis was revised to PDS by a pathologist based on the currently accepted criteria for PDS. There has been no evidence of recurrence or periocular functional defects during a 2-year follow-up without adjuvant therapy. Although the PDS is highly malignant, complete excision under micrographic surgery can prevent recurrence without adjuvant therapy. Also, the secondary intention healing is an effective method for closure of large defects on the face.
*27746645* 27746645 Pedunculated Nodules as a Variant of Dermatofibrosarcoma Protuberans. Ann Dermatol 2016; 28 (5): 629-31
Dermatofibrosarcoma protuberans (DFSP) is a rare disease of dermal fibroblastic origin that accounts for less than 5% of all soft tissue sarcomas in adults. DFSP grows slowly and is an asymptomatic lesion at the initial diagnosis. Herein, we report a case of multiple pedunculated nodules as a variant of DFSP. A 47-year-old man presented with a 7-month history of multiple well-circumscribed, firm, pedunculated nodules on the inguinal area. Histopathologic examination results showed densely packed uniform spindle cells with a storiform and cartwheel pattern, and positivity for CD34. Wide excision and skin graft were performed and at the 6-month follow-up, there was no evidence of recurrence or metastasis.
*27746644* 27746644 A Unique Cutaneous Presentation of Breast Cancer: A Red Apple Stuck in the Breast. Ann Dermatol 2016; 28 (4): 499-501 *27489436* 27489436 Treatment of Nodular Fasciitis Occurring on the Face. Ann Dermatol 2015; 27 (6): 694-701
Background: Surgical excision is generally recommended for the treatment of nodular fasciitis (NF) to rule out sarcoma. However, in cases of NF occurring on the face, the reported recurrence rate is higher and the surgical approach may result in considerable aesthetic concern. Objective: To describe our experience with NF occurring on the face and evaluate the outcomes of surgical and nonsurgical methods of treatment. Methods: We performed a retrospective review of 16 patients with NF on the face. The patients were treated with surgical excision or nonsurgical methods such as triamcinolone intralesional injection (TA ILI) and pinhole method with a carbon dioxide (CO2) laser. Results: Among the 16 patients, surgical treatment was performed in 9 and recurrence occurred in 7 of these 9 patients (77.8%). The recurred lesions showed regression after repeated TA ILI. On the other hand, five patients underwent nonsurgical treatment after the histologic exclusion of malignancy. Their lesions showed regression after repeated pinhole treatment and TA ILI. In one case, NF spontaneously regressed. On a visual analogue scale, the nonsurgical approach showed superior results. However, the values were not statistically significant (6.90±1.56 vs. 5.61±1.36; p=0.163). The satisfaction level was lower in patients who experienced recurrence after surgical excision. Conclusion: Surgical treatment for NF on the face showed a noticeable recurrence rate and resulted in scarring. Therefore, considering the possibility of spontaneous regression, the nonsurgical method can be considered as an alternative treatment option for NF on the face.
*26719638* 26719638 A Giant, Deep, Benign Fibrous Histiocytoma with a Palisading Pattern. Ann Dermatol 2015; 27 (5): 643-5 *26512193* 26512193 Congenital Dermatofibrosarcoma Protuberans: A Case Report and Literature Review. Ann Dermatol 2015; 27 (5): 597-600
Congenital dermatofibrosarcoma protuberans (DFSP) is an extremely rare skin tumor that is commonly misdiagnosed, or is often diagnosed long after the initial presentation. Although many cases of DFSP are diagnosed in adulthood, there are some differences between adult DFSP and congenital DFSP. We report a case of congenital DFSP that was initially misdiagnosed as a simple vascular lesion. The delay in diagnosis led to the considerable growth of the lesion, such that a huge scar was left after the surgical treatment. The major differences between adult and congenital DFSP are discussed through a literature review. Clinicians should be aware of the characteristics of congenital DFSP, to reduce misdiagnosis and the delay of diagnosis from the initial presentation.
*26512174* 26512174 A Rare Case of Multiple Spindle Cell Lipomas. Ann Dermatol 2015; 27 (4): 472-3 *26273175* 26273175 Diagnostic Pitfalls of Differentiating Cellular Digital Fibroma from Superficial Acral Fibromyxoma. Ann Dermatol 2015; 27 (4): 462-4 *26273171* 26273171 Cutaneous Metastatic Undifferentiated Pleomorphic Sarcoma from a Mediastinal Sarcoma. Ann Dermatol 2015; 27 (3): 310-4
Undifferentiated pleomorphic sarcoma, known as malignant fibrous histiocytoma, is a malignant neoplasm that arises in both soft tissue and bones. In 2002, the World Health Organization declassified malignant fibrous histocytoma as a formal diagnostic entity and renamed it undifferentiated pleomorphic sarcoma not otherwise specified. It most commonly occurs in the lower extremities and rarely metastasizes cutaneously. We report a case of cutaneous metastatic undifferentiated pleomorphic sarcoma of the buttocks occurring in a 73-year-old man diagnosed with mediastinal sarcoma 4 years previously. He first noticed the mass approximately 2 months previously. Histological findings with immunomarkers led to a final diagnosis of cutaneous metastatic sarcoma from mediastinal undifferentiated pleomorphic sarcoma.
*26082589* 26082589 Identification of Leukocyte-Specific Protein 1-Positive Cells: A Clue to the Cell of Origin and a Marker for the Diagnosis of Dermatofibroma. Ann Dermatol 2015; 27 (2): 157-62
Background: Dermatofibroma (DF) comprises a heterogeneous group of mesenchymal tumors, with fibroblastic and histiocytic elements present in varying proportions. The cell of origin of DF has been investigated, but remains unclear. Objective: The present study attempted to investigate the expression of leukocyte-specific protein 1 (LSP1), a marker of fibrocytes, in DF. Additionally, we evaluated the effectiveness of LSP1 in the differential diagnosis of DF from dermatofibrosarcoma protuberans (DFSP). Methods: Immunohistochemical staining was performed on 20 cases of DF using antibodies against LSP1, CD68, and factor XIIIa (FXIIIa). In addition, the expression of LSP1 and FXIIIa was evaluated in 20 cases of DFSP. Results: Eighteen of 20 cases (90%) of DF stained positive for LSP1, with variation in the intensity of expression. CD68 was positive in 10 cases (50%), and FXIIIa was expressed in all cases of DF. There were differences between the regional expression patterns of the three markers in individual tumors. In contrast, only 2 of 20 cases of DFSP expressed LSP1, and none of DFSP cases stained positive for FXIIIa. Conclusion: The LSP1-positive cells in DF could potentially be fibrocyte-like cells. FXIIIa and CD68 expression suggests that dermal dendritic cells and histiocytes are constituent cells of DF. It is known that fibrocytes, dermal dendritic cells and histiocytes are all derived from CD14+ monocytes. Therefore, we suggest that DF may originate from CD14+ monocytes. Additionally, the LSP1 immunohistochemical stain could be useful in distinguishing between DF and DFSP.
*25834354* 25834354 Dermatofibrosarcoma Protuberans on the Chest with a Variety of Clinical Features Masquerading as a Keloid: Is the Disease Really Protuberant? Ann Dermatol 2014; 26 (5): 643-5 *25324663* 25324663 Superficial Acral Fibromyxoma on the Palm. Ann Dermatol 2014; 26 (1): 123-4 *24648703* 24648703 Medallion-Like Dermal Dendrocyte Hamartoma: Differential Diagnosis with Congenital Atrophic Dermatofibrosarcoma Protuberans. Ann Dermatol 2013; 25 (3): 382-4 *24003290* 24003290 A Case of Eccrine Porocarcinoma: Usefulness of Immunostain for S-100 Protein in the Diagnoses of Recurrent and Metastatic Dedifferentiated Lesions. Ann Dermatol 2013; 25 (3): 348-51
Eccrine porocarcinoma is a rare malignant tumor. Immunostain for S-100 protein, in addition to epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), is described to be useful in the diagnosis. Herein, we report a case of eccrine porocarcinoma with immunostain for S-100 protein which was useful in diagnoses of recurrent and metastatic lesions. The primary lesion in the left inguinal region was excised, but it recurred on the same site 14 months after the resection. The recurrent lesion showed epithelioid melanocytic findings. Three months later, metastasis to the lungs was found. Since these recurrent and metastatic lesions were dedifferentiated, typical histologic findings of eccrine porocarcinoma disappeared in biopsied specimens. Nevertheless, scattered immunoreactive cells for S-100 protein were maintained in these dedifferentiated lesions. S-100 protein positive cells could be an aid to diagnose, even if histologic findings of recurrent and metastatic lesions have changed by dedifferentiation.
*24003279* 24003279 Rapid Growing Superficial Cutaneous Leiomyosarcoma of the Face. Ann Dermatol 2013; 25 (2): 237-41
Leiomyosarcomas are uncommon malignant smooth muscle tumors, mainly derived from vessels or viscera. Superficial leiomyosarcomas are a rare soft tissue sarcoma arising from the dermis or subcutaneous tissue in the skin. According to tumor origin and location, they are divided into cutaneous and subcutaneous leiomyosarcoma. They have distinctly different histologic and prognostic features from each other. Superficial leiomyosarcomas show a predilection for the proximal extremities and tend to be slow growing. We report one rare case of superficial cutaneous leiomyosarcoma on the right temporal area of face, which showed an extremely rapid growing mass within 3 months.
*23717020* 23717020 The Diagnostic Significance of Infiltration Pattern and Perilesional Lymphoid Cell Infiltrate in Dermatofibroma. Ann Dermatol 2012; 24 (2): 228-9 *22577281* 22577281 Deep Penetrating Benign Fibrous Histiocytoma of the Foot Associated with Throbbing Pain. Ann Dermatol 2011; 23 (Suppl 2): S239-42
Compared to cutaneous benign fibrous histiocytoma (BFH), deep-seated BFH is very rare and poorly recognized. Both cutaneous and deep-seated BFH are usually asymptomatic. We herein report a 25 year-old woman who presented with a painful mass in her foot that was poorly controlled by analgesics and associated with walking difficulty. After preoperative ultrasonographic evaluation, the mass was completely excised and histologic exam showed spindle cells loosely arranged in storiform architecture, with CD34-, desmin-, S-100-, focal CD68+, vimentin+, smooth muscle actin+, and factor XIIIa+. The patient was diagnosed with deep-seated BFH based on the histologic, radiologic and intraoperative findings.
*22148060* 22148060 Acral-type Malignant Acanthosis Nigricans Associated with Gastric Adenocarcinoma. Ann Dermatol 2011; 23 (Suppl 2): S208-10
Acanthosis nigricans is a symmetric eruption characterized by the presence of a hyperpigmented, velvety cutaneous thickening, that can develop on any part of the body, but characteristically affects the flexural areas of the body. The velvety hyperkeratotic lesions can be located on the dorsum of the hands and feet in dark-skinned people in the form of a variant of acanthosis nigricans called as acral acanthotic anomaly or acral type acanthosis nigricans. Although acanthosis nigricans is associated with malignant tumors, particularly gastric carcinoma, acral type acanthosis nigricans has never been reported to be associated with gastric adenocarcinoma. In our present study, we describe a case of 58-year-old man with acral type acanthosis nigricans and its association with carcinoma of the stomach; a marked improvement was seen in the skin condition of the patient with chemotherapy.
*22148052* 22148052 Development of Dermatomyofibroma in a Male Infant. Ann Dermatol 2011; 23 (Suppl 1): S72-4
Dermatomyofibroma is a rare benign cutaneous mesenchymal neoplasm of the fibroblasts and myofibroblasts. The majority of dermatomyofibromas present as red-brown discolored plaques or nodules, commonly located on the shoulder, upper arm, axilla, neck, and/or upper trunk. These lesions develop most frequently in young female patients at a mean of 28-years-of-age. Herein, a case of dermatomyofibroma is reported that developed in an infant. A 4-month-old boy presented with an ill-defined bluish firm plaque on the trunk that developed 1 month after birth. Histopathologically, there was proliferation of bland-looking spindle cells with fascicular arrangement in the dermis and subcutaneous tissue. Immunohistochemistry showed that most of the tumor cells expressed diffuse positivity for vimentin and smooth muscle actin, but were negative for S-100 protein, desmin, and CD34.
*22028578* 22028578 A Case of Myxoid Dermatofibrosarcoma Protuberans. Ann Dermatol 2011; 23 (3): 379-81
Dermatofibrosarcoma protuberans (DFSP) is a slowly growing dermal spindle cell tumor and its myxoid variant, a rare type of DFSP, is characterized by extensive myxoid degeneration. We present the case of a 69-year-old woman with a multinodular reddish plaque on her trunk. Histopathologically, the tumor was located in the dermis and consisted of uniform spindle-shaped cells, showing strongly positive reaction for CD34, and negative for both S-100 and desmin. In addition to the typical storiform pattern, prominent myxoid stromal changes were demonstrated. Herein, we report an interesting case of myxoid DFSP, rarely reported in the dermatology literature.
*21909213* 21909213 Subcutaneous Dermatofibroma. Ann Dermatol 2011; 23 (2): 254-7
Dermatofibroma (DF) is usually confined to the dermis and the overlying epidermis is usually hyperplastic. Although DF with deep subcutaneous extension is commonly encountered, purely subcutaneous DF is uncommon. In this review, we describe a case of a 41-year-old male patient who presented with a painless, subcutaneous, hard papule on the left thigh. After the skin had been incised the lesion was totally removed, and histopathology revealed a subcutaneous dermatofibroma.
*21747634* 21747634 A Clinical and Histopathological Study of 122 Cases of Dermatofibroma (Benign Fibrous Histiocytoma). Ann Dermatol 2011; 23 (2): 185-92
Background: Many variants of dermatofibromas have been described, and being aware of the variants of dermatofibromas is important to avoid misdiagnosis. Objective: We wanted to evaluate the clinical and pathologic characteristics of 122 cases of dermatofibromas. Methods: We retrospectively reviewed the medical records and 122 biopsy specimens of 92 patients who were diagnosed with dermatofibroma in the Department of Dermatology at Eulji Hospital of Eulji University between January 2000 and March 2010. Results: Nearly 80% of the cases occurred between the ages of 20 and 49 years, with an overall predominance of females. Over 70% of the lesions were found on the extremities. The most common histologic variant was a fibrocollagenous dermatofibroma (40.1%). Other variants included histiocytic (13.1%), cellular (11.5%), aneurysmal (7.4%), angiomatous (6.5%), sclerotic (6.5%), monster (4.9%), palisading (1.6%) and keloidal dermatofibromas (0.8%). There were 9 dermatofibromas (7.3%) that were the mixed type with two co-dominant histologic features. Conclusion: The results of this study are consistent with previous reports on the clinical features of dermatofibromas. However, we observed several characteristic subtypes of dermatofibroma and we compared the frequency of the histologic subtypes.
*21747617* 21747617 A Case of Dermatofibroma of the Upper Lip. Ann Dermatol 2010; 22 (3): 333-6
Dermatofibroma (DF) is a common benign mesenchymal tumor composed of fibroblastic and histiocytic cells. It occurs anywhere on the body surface but has a propensity for the extremities. To our knowledge, DF arising in the oral cavity, especially on the lip, is quite rare. DFs of the head and neck region have been known to be most often of the cellular type and frequently recur, so a wider initial excision is recommended. Herein we report a case of DF in a 41-year-old female who presented with a deep-seated nodule on her upper lip.
*20711274* 20711274 A Case of Cutaneous Inflammatory Myofibroblastic Tumor. Ann Dermatol 2010; 22 (1): 91-5
Pseudo-inflammatory tumors are also known as plasma cell granuloma, inflammatory pseudo-tumor and inflammatory myofibroblastic tumor, and these tumors are a group of highly variable proliferations of myofibroblastic cells that are associated with a prominent inflammatory infiltrate. This tumor is known to most commonly occur in the lungs, bladder and gastrointestinal system with only a few cases having been reported in the skin. A previously healthy 26-year-old man presented with a 6-year history of an intermittently pruritic lesion on his back. On the histologic examination, there were spindle cells in fascicles and a mixed inflammatory cellular infiltrate of plasma cells and lymphocytes. A diagnosis of inflammatory fibroblastic tumor was made and the nodule was surgically removed. We report here on an additional case of this rare cutaneous entity, and it is probably the first such report from Korea.
*20548893* 20548893 A Case of Recurrent Superficial Acral Fibromyxoma. Ann Dermatol 2010; 22 (1): 110-3
Superficial acral fibromyxoma (SAFM) is a rare myxoid tumor that was first described in 2001. The presence of a very slow growing solitary tender mass in the subungual area is the typical clinical feature at presentation. Histopathologically, SAFM is composed of stellate cells in a myxocollagenous matrix with a poorly circumscribed margin. This tumor is thought to be benign, but its natural course is not fully understood. We describe a 15-year-old patient with recurrent SAFM and discuss the proper treatment and follow up.
*20548898* 20548898 Dermatofibrosarcoma Protuberans Arising from a Burn Scar. Ann Dermatol 2009; 21 (4): 416-8
Malignant neoplasms arising in burn scars are well known. In previous literature, 25 cases of burn scar sarcomas were reported. However, dermatofibrosarcoma protuberans is very rare and only two cases have been reported. A 43-year-old Korean man presented with multiple erythematous clustered plaques and nodules and a skin-colored subcutaneous mass on the chest after a severe burn injury at the age of 8 years. A biopsy specimen revealed dermatofibrosarcoma protuberans. The tumor was excised widely to include the surrounding burn scar. Herein, we report this third case of dermatofibrosarcoma protuberans arising from a burn scar.
*20523837* 20523837 Coexistence of Amelanotic Melanoma and Liposarcoma. Ann Dermatol 2009; 21 (4): 409-12
An amelanotic malignant melanoma is characterized by little or no pigment. It is frequently misdiagnosed because it is a rare entity in general, and because of its unusual clinical features. Liposarcoma is one of the most common adult soft tissue sarcomas. We encountered a case of amelanotic melanoma with a concurrent liposarcoma. A 68-year-old man presented with a single, 1.5×1.5 cm round erythematous, eroded nodule on the left heel. A biopsy specimen showed atypical, pleomorphic tumor cells with little melanin pigment. The tumor cells were positive for S-100, HMB-45 and negative for cytokeratins. These findings were consistent with amelanotic melanoma. On positron emission tomography/computed tomography (PET/CT), a hypermetabolic lesion was found in the left buttock. This lesion was excised and diagnosed as a well-differentiated liposarcoma. An association between sarcomas and other primary malignancies has been reported. However, an association between melanoma and liposarcoma is rare.
*20523835* 20523835 Aneurysmal Benign Fibrous Histiocytoma with Atrophic Features. Ann Dermatol 2009; 21 (1): 42-5
Aneurysmal benign fibrous histiocytoma is an uncommon pathologic variant of dermatofibroma. In addition to the features of a typical dermatofibroma, it has large cleft-like or cavernous blood-filled spaces with numerous hemosiderin pigments. It should be differentiated from angiomatoid malignant fibrous histiocytoma, malignant melanoma, and vascular tumors such as Kaposi s sarcoma and angiosarcoma. Atrophic dermatofibroma is also a rare variant of dermatofibroma, and the combination of aneurysmal and atrophic features is rarer still. We report a case of aneurysmal benign fibrous histiocytoma with atrophic features in a 27-year-old male who had a grayish-brown atrophic patchy lesion on his back for 2 years.
*20548854* 20548854 Surgical Tip: The Double-Bladed Scalpel in Mohs Micrographic Surgery. Ann Dermatol 2008; 20 (2): 86-9
Mohs micrographic surgery is applied as the primary method of treatment for various cutaneous neoplasms. Many other methods that are modified applications of Mohs micrographic surgery have also been suggested. We introduce a technique, which is a modified vertical method of Mohs micrographic surgery using the double-bladed scalpel.
*27303167* 27303167 Repurposing medicinal compounds for blood cancer treatment. Ann Hematol 2015; 94 (8): 1267-76
Drug development is being continuously scrutinised for its lack of productivity. Novel drug development is associated with high costs, high failure rates and lengthy development process. These downfalls combined with a huge demand in blood cancer for new therapeutic treatments have led many to consider the method of drug repurposing. Finding new therapeutic indications for already established drug substances is known as redirecting, repositioning, reprofiling, or repurposing of drugs. Off-patent and on-patent drugs can be screened for additional targets and new indications thus bringing them to clinical trials at a faster pace. This approach offers smaller research groups, such as those that are academic based, into the drug development industry. Drug repurposing can make use of previously published data concerning dosage, toxicology and mechanism of activity.
*26048243* 26048243 A phase II study of tivozanib in patients with metastatic and nonresectable soft-tissue sarcomas. Ann Oncol 2017; 28 (1): 121-7
Background: Soft tissue sarcomas (STSs) overexpress vascular endothelial growth factors (VEGF) and VEGF-receptors (VEGFR) activation have been associated with tumor aggressiveness. Tivozanib is a potent small molecule tyrosine kinase inhibitor against VEGFR1-3, with activity against PDGFR?/? and cKIT. The primary endpoint of this study was progression free survival (PFS) rate at 16 weeks. Secondary end points were overall survival (OS), response rate, safety and correlative studies. Patients and methods: A Simon two-stage phase II trial was performed using tivozanib given orally at 1.5?mg daily, 3 week on 1 week off on a 28?day cycle until disease progression or intolerable toxicity. Results: Fifty-eight patients were enrolled and treated with tivozanib. Leiomyosarcoma was the most common STS histological type in our cohort (47%) and 27 patients (46%) had received at least 3 lines of therapy prior to study entry. Up to 24 patients (41%) had prior VEGF targeted therapies. Partial response and stable disease were observed in 2 (3.6%) and 30 (54.5%) patients. The 16 week PFS rate was 36.4% [95% confidence interval (CI) 23.7?49.1] and a median PFS of 3.5 months (95% CI 1.8?3). Median OS observed was 12.2 months (95% CI 8.1?16.8). The most frequent all grade toxicities were fatigue (48.3%), hypertension (43.1%), nausea (31%) and diarrhea (27.6%). The most common grade three toxicity was hypertension (22.4%). Correlative studies demonstrate no correlation between the expression of VEGFR 1, 2 or 3, PDGFR?/? or FGF, and activity of tivozanib. Conclusion: Tivozanib was well tolerated and showed antitumor activity with a promising median PFS and PFS rate at 4 months in a heavily pretreated population of metastatic STSs. Our results support further studies to assess the clinical efficacy of tivozanib in STS. Clinical Trial Number: NCT01782313
*27771610* 27771610 Adherence to consensus-based diagnosis and treatment guidelines in adult soft-tissue sarcoma patients: a French prospective population-based study?. Ann Oncol 2014; 25 (1): 225-31
The present patient-based prospective study evaluates soft-tissue sarcoma care management. Adherence to clinical guidelines was assessed through 23 criteria defined by consensus. Although practices were found to be relatively compliant overall, initial diagnosis and treatment across all stages need improving, particularly outside specialized centers. Standardized incidence rates are also reported.
*24285018* 24285018 Sarcoma: concordance between initial diagnosis and centralized expert review in a population-based study within three European regions. Ann Oncol 2012; 23 (9): 2442-9
Background: Sarcomas represent a heterogeneous group of tumors. Accurate determination of histological diagnosis and prognostic factors is critical for the delineation of treatment strategies. The contribution of second opinion (SO) to improve diagnostic accuracy has been suggested for sarcoma but has never been established in population-based studies. Methods: Histological data of patients diagnosed with sarcoma in Rhone-Alpes (France), Veneto (Italy) and Aquitaine (France) over a 2-year period were collected. Initial diagnoses were systematically compared with SO from regional and national experts. Results: Of 2016 selected patients, 1463 (73%) matched the inclusion criteria and were analyzed. Full concordance between primary diagnosis and SO (the first pathologist and the expert reached identical conclusions) was observed in 824 (56%) cases, partial concordance (identical diagnosis of connective tumor but different grade or histological subtype) in 518 (35%) cases and complete discordance (benign versus malignant, different histological type or invalidation of the diagnosis of sarcoma) in 121 (8%) cases. The major discrepancies were related to histological grade (n = 274, 43%), histological type (n = 144, 24%), subtype (n = 18, 3%) and grade plus subtype or grade plus histological type (n = 178, 29%). Conclusion: More than 40% of first histological diagnoses were modified at second reading, possibly resulting in different treatment decisions.
*22331640* 22331640 Treatment of cancer with oral drugs: a position statement by the Spanish Society of Medical Oncology (SEOM). Ann Oncol 2010; 21 (2): 195-8 *20110291* 20110291 Colossal pilomatrixoma. Ann R Coll Surg Engl 2018; 100 (2): e38-40
We describe the largest reported case of pilomatrixoma in the literature. While pilomatrixomas typically present as small soft-tissue nodules of the head, neck and upper extremities, they can also present as much larger masses in atypical locations. When they present in their usual size, pilomatrixomas have typical imaging features and can be correctly diagnosed with imaging studies before histological confirmation. Their clinical and imaging diagnosis become challenging when they are very large, as in our case. A giant pilomatrixoma should also be considered for paediatric patients presenting with a large subcutaneous soft-tissue mass.
*29182000* 29182000 Does the two-week rule pathway improve the diagnosis of soft tissue sarcoma? A retrospective review of referral patterns and outcomes over five years in a regional sarcoma centre. Ann R Coll Surg Engl 2010; 92 (5): 417-21
INTRODUCTION: The NHS Cancer Plan was introduced in 2000 and included guidelines for the rapid assessment and referral of cases of suspected malignancy. We wished to assess the efficiency and appropriateness of patients referred under the Department of Health s general practitioner referral guidelines implemented for sarcomas in December 2000. PATIENTS AND METHODS: A retrospective case-note review was performed of all patients referred to our regional soft tissue sarcoma unit between 1 January 2004 and 31 December 2008. Patients referred under the two-week guidelines and all patients referred routinely were analysed. The main outcome measures were the total number of patients referred on the basis of the two-week guidelines and the proportion they constitute of all referrals. The referring criteria were noted and compared to the observed criteria recorded. The final histo-logical diagnosis of patients referred on the basis of the two-week guidelines are documented. RESULTS: A total of 2746 referrals for suspected sarcoma were made from January 2004 to December 2008. Of these, 154 referrals were made under the two-week rule of which 102 were referred purely on the clinical criteria for suspected soft tissue sarcoma. The remaining patients were referred after non-urgent special investigations indicated the possibility of sarcoma. Twelve patients referred under the two-week rule were proved to have sarcoma, nine after specific investigations including imaging or histological diagnosis. Of the 102 patients referred on clinical suspicion of a sarcoma, two patients had proven soft tissue sarcomas and one patient a cutaneous sarcoma. Between 2004 and 2008, the number of 2-week referrals rose 25-fold but accounted for an increase of less than 1% of the sarcomas treated in this unit. CONCLUSIONS: The numbers of all referrals for suspected sarcoma are increasing; however, the rate of increase of 2-week referrals is increasing faster than routine referrals and will exceed it in 2012 if current trends continue. There has not been a commensurate rise in the detection of sarcoma or, more specifically, diagnosis of the deep sarcomas associated with worse prognosis. Current clinical guidelines have essentially had no impact on the early diagnosis and treatment of soft tissue sarcoma, and may negatively impact on the treatment of patients with proven sarcoma by delaying treatment within a regional centre because of redirection of a large number of patients with benign abnormalities to such centres.
*20487596* 20487596 Soft tissue sarcoma of the extremity. Ann R Coll Surg Engl 1996; 78 (5): 453-6
A retrospective review of 33 cases of soft tissue sarcoma of the extremity presenting over a 10 year period was undertaken. The history, patterns of referral, diagnostic investigations, procedures undertaken and outcomes were studied. We found there was a frequent delay in diagnosis and sometimes misinterpretation of biopsy specimens. Patients were seen by a variety of specialists from disciplines such as general surgery, plastic surgery, orthopaedic surgery and rheumatology. Considerable progress has been made in the treatment of soft tissue sarcomas, often allowing local control of the tumour without amputation. We believe there should be early referral of patients having these tumours to a centre where a combined multidisciplinary approach can be undertaken.
*8881731* 8881731 The diagnosis of soft tissue tumours. Ann R Coll Surg Engl 1992; 74 (4): 277-80
We prospectively analysed methods of diagnosis in 118 patients referred for definitive treatment with documented or presumed soft tissue sarcoma (STS). Of 65 patients with primary STS, 54 were biopsied before referral. Of these, 5 (9%) were biopsied by Tru-cut biopsy, 17 (32%) by incisional biopsy and 32 (59%) by excisional biopsy. The remaining 11 patients with primary STS, referred without biopsy, were all diagnosed by Tru-cut biopsy. An additional eight patients suspected of having STS were referred without biopsy and were found to have malignant tumours other than STS involving soft tissue by Tru-cut biopsy. Nineteen patients were proved to have benign soft tissue tumours; in 13 presumed to have STS, the diagnosis was unknown at referral. In four of these, biopsy was inappropriate. Of nine submitted to Tru-cut biopsy, an unequivocal diagnosis was made in 5 (56%) and incisional biopsy was required in the other four. Therefore, paradoxically, benign soft tissue tumours may be more difficult to diagnose with Tru-cut biopsy than malignant tumours. This study confirms the high degree of accuracy of Tru-cut biopsy in diagnosing malignant soft tissue tumours and highlights the disadvantages of open biopsy techniques.
*1416683* 1416683 Skin malignancy and the reconstructive plastic surgeon. Ann R Coll Surg Engl 1989; 71 (3): 150-8
Skin malignancy represents at least 25% of the plastic surgeon s workload. The commonest tumour, the basal cell carcinoma, usually arises in the skin of elderly patients who are frequently managed by surgery under local anaesthetic, often as outpatients. The recurrent basal cell carcinoma poses a difficult problem regardless of the primary therapy. Skin repair with direct closure or skin grafts is usually simple, but skin flaps will be needed when bone, cartilage or major neurovascular structures are exposed, or where tissue vascularity has been reduced by irradiation fibrosis. Squamous cell carcinomas of lip, ear and hand may recur as lymph node metastases despite clinical and histological clearance. Malignant melanoma continues to present as advanced disease (thick tumours) in this country, and this largely dictates prognosis, since tumour thickness is recognised as the single most important dominant prognostic variable. Incisional biopsy compromises histological microstaging and should be avoided. Indirect evidence from narrow margin excision of invasive head and neck cutaneous melanomas suggests no detriment, and narrow margin excision of melanomas is increasingly being practised.Images: fig. 1fig. 2fig. 3fig. 4fig. 5fig. 6fig. 7FIG. 8fig. 9fig. 10fig. 11fig. 12fig. 13
*2589782* 2589782 Jonathan Hutchinson FRCS. Ann R Coll Surg Engl 1975; 57 (6): 296-308
Images: Fig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6
*813554* 813554 The influence of anti-TNF therapy upon incidence of keratinocyte skin cancer in patients with rheumatoid arthritis: longitudinal results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis 2012; 71 (6): 869-74
Objectives: To compare the risk of keratinoctye skin cancer (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)) in patients treated for rheumatoid arthritis (RA) compared with the general population, and to determine whether anti-tumour necrosis factor (TNF) therapy exacerbates this risk. Methods: Patients with RA enrolled in the British Society for Rheumatology Biologics Register, a prospective national cohort established in 2001 to monitor the safety of anti-TNF, were followed until 2008. 11 881 patients treated with anti-TNF were compared with 3629 patients receiving non-biological disease-modifying antirheumatic drugs (nbDMARD). Standardised incidence ratios (SIR) were calculated for each cohort and rates between cohorts were compared using Cox proportional HR, adjusted using inverse probability of treatment weighting. Results: SIR for skin cancer was increased in both cohorts compared with the English population: SIR 1.72 (95% CI 1.43 to 2.04) anti-TNF; 1.83 (95% CI 1.30 to 2.50) nbDMARD only. In patients without previous skin cancer, BCC incidence per 100 000 patient-years was 342 (95% CI 290 to 402) after anti-TNF and 407 (95% CI 288 to 558) after nbDMARD. HR after anti-TNF adjusted for treatment weighting was 0.95 (95% CI 0.53 to 1.71). SCC incidence per 100 000 patient-years: anti-TNF 53 (95% CI 33 to 79); nbDMARD 43 (95% CI 12 to 110); adjusted HR 1.16 (95% CI 0.35 to 3.84). Conclusions: Skin cancers were increased among treated patients with RA. No evidence was found that anti-TNF therapy exacerbates the risk of BCC or SCC but this cannot be excluded. Patients with RA should use sun protection and be monitored for skin cancer.
*22241900* 22241900 A Postoperative Nomogram for Local Recurrence Risk in Extremity Soft Tissue Sarcomas after Limb-Sparing Surgery Without Adjuvant Radiation. Ann Surg 2012; 255 (2): 343-7
Purpose: To develop a nomogram based on clinicopathologic factors to quantify the risk of local recurrence (LR) after limb-sparing surgery without adjuvant radiation (RT). Methods: Review of our prospective sarcoma database identified 684 patients with primary, nonmetastatic, extremity STS treated with limb-sparing surgery alone between 6/1982?12/2006. No patient received adjuvant radiation or chemotherapy. Age, sex, grade, depth, size, site, margin status and histology were analyzed for prognostic significance with respect to local recurrence rates using Gray?s test. Variables which were significant in univariate analysis at the 0.05 level were entered into a multivariate competing risk regression model. Based upon the multivariate analysis, a nomogram for predicting the 3- and 5-year risk of LR was developed using R libraries cmprsk and QHScrnomo. Concordance index (C-index) was calculated to evaluate the discriminatory power of the prognostic model. Results: With a median follow-up of 58 months for censored patients (73 months for all patients), the overall 3- and 5-year actuarial local recurrence rates were 11% and 13%, respectively. Factors included in the nomogram were age (?50 vs >50), size (?5 vs >5cm), margin status (negative vs positive), grade (low vs high), and histology (atypical lipomatous tumor/well differentiated liposarcoma vs other). The STS nomogram predicted the local recurrence rate with a C-index of 0.73. Conclusions: A nomogram for extremity STS that includes age, size, margin status, grade of tumor, and histology predicts the 3- and 5-year risk of local recurrence after limb-sparing surgery in the absence of adjuvant RT.
*22143203* 22143203 Effect of Reresection in Extremity Soft Tissue Sarcoma. Ann Surg 2000; 231 (5): 655-63
Objective: To determine whether reresection affects survival in patients with inadequately resected, primary extremity soft tissue sarcoma. This study correlates reresection with local recurrence-free survival, metastasis-free survival, and disease-free survival. Summary Background Data: Soft tissue sarcomas are rare neoplasms, with an incidence of approximately 6,000 per year in the United States. Because these tumors are rare and benign soft tissue tumors are common, many are initially thought to be benign and are excised without wide margins. Methods: Patients who underwent treatment for primary tumors from July 1982 to June 1999 at a single institution were the subject of study. Two groups of patients were analyzed: those who underwent one definitive resection (one operation) and those whose tumors were previously resected and who were then referred for subsequent reresection (two operations). Patients were given adjuvant radiation or chemotherapy according to the standard of care. Results: Of 1,092 patients with primary extremity soft tissue sarcoma underwent resection, 685 underwent definitive radical resection and 407 underwent reresection after undergoing excisional resection elsewhere. Median follow-up was 4.8 years. The 5-year disease-free survival rate of the definitive resection (one operation) group was 70%; that of the reresection (two operations) group was 88%. On multivariate analysis, reresection was adjusted and controlled for age, grade, depth, size, histology, and margins. Reresection remained a significant predictor of improved disease-free survival, even after these adjustments. To determine whether this difference was stage- or referral-biased, the patient population was divided by AJCC stage. In all stages there was a trend toward improved outcome; this was most marked for those with stage III disease (>5 cm, high-grade, and deep). Conclusions: Patients with extremity soft tissue sarcoma who undergo reresection with two ?primary? operations have an improved survival compared with those who undergo one operation. The most plausible explanation, referral and selection bias, is questionable given the significance of reresection as a variable after adjusting for stage and other risk factors. This suggests that where indicated and possible, reresection should be liberally applied in patients with primary extremity soft tissue sarcoma.
*10767786* 10767786 Preoperative chemotherapy for soft-tissue sarcomas of the extremities. Ann Surg 1990; 211 (4): 476-81
Forty-six patients with extremity soft-tissue sarcomas were treated with a mean of 4.4 cycles of preoperative adriamycin-based combination chemotherapy, followed by definitive local surgery and radiotherapy. All tumors were larger than 5 cm and of histologic type having significant risk of metastasis. Eighteen patients (40%) had an objective clinical response to the chemotherapy, while 27 patients (60%) did not respond. Patients with tumors responsive to chemotherapy had significantly improved overall survival (median 60 + months versus 32.7 months; p = 0.02), continuous disease-free survival (median 60 + months versus 15.1 months; p = 0.04), and distant metastasis-free survival (median 60+ months versus 28.5 months; p = 0.006) compared to the nonresponding patients. Tumor response to preoperative chemotherapy provides strong prognostic information and identifies a subgroup of patients most likely to benefit from chemotherapy.
*2157378* 2157378 Treatment of dermatofibrosarcoma protuberans with Mohs micrographic surgery. Ann Surg 1988; 208 (5): 669 *3190295* 3190295 Letters to the Editor. Ann Surg 1988; 208 (5): 669 *C1493763* C1493763 Treatment of dermatofibrosarcoma protuberans with Mohs micrographic surgery. Ann Surg 1988; 207 (1): 102-7
Ten patients with dermatofibrosarcoma protuberans, all of whom had been treated previously by conventional excisional surgery without success, were treated with Mohs micrographic surgery. A team approach utilizing margin control by Mohs-trained physicians and reconstruction by surgical specialists was employed. Average follow-up exceeds 3 1/2 years, with no recurrences. Microscopically controlled excision appears to be the treatment of choice for dermatofibrosarcoma protuberans.Images: Fig. 2.Fig. 3.Fig. 8.
*3337558* 3337558 The ubiquitous fibroblast. Multiple oncogenic potentials with illustrative cases. Ann Surg 1987; 205 (5): 445-55
The wide range of oncogenic proliferative potentials of the fibroblast is demonstrated with a series of eight patients. Diagnoses included infantile digital fibromatosis, "aggressive fibromatosis," aggressive fibromatosis progressing to poorly differentiated sarcoma, infantile myofibromatosis, recurrent desmoid tumor, fibrosarcoma arising in a keloid, dermatofibrosarcoma protuberans, and malignant fibrous histiocytoma of left atrium. Still other types of fibroblastic tumefactions might have been included. Oncogenic factors that may have been operative in the causation of the lesions presented include: genetic factors, sex-linked factors, hormonal factors, numerous growth factors, and certain viruses, especially retroviruses. Certain fibromatoses in children are commonly self-limited and need only be monitored carefully as the process regresses. Aggressive fibromatosis, on the other hand, can prove fatal if the lesion is not completely resected with a wide margin and, occasionally, the process may become frankly malignant, with metastases. The standard triad of excisional surgery, radiotherapy, and chemotherapy has been used to treat frankly malignant fibrous tumors with variable results.Images: Fig. 5.Fig. 6.Fig. 4.Fig. 9.Fig. 11.Fig. 12.Fig. 14.
*3034175* 3034175 The role of electron microscopy in the management of surgical patients. Ann Surg 1982; 195 (1): 1-11
This report records a 12-month experience with 49 neoplasms submitted to the hospital pathologists for electron microscopic (EM) diagnosis as a part of routine clinical surgical practice. Twenty-five specimens were from a private community hospital and 24 from a university hospital. In 40 of 49 cases (82%), EM confirmed a tentative light microscopic (LM) diagnosis. In 11 of these 40 cases, EM provided a more specific histogenetic diagnosis than was possible by LM. In three cases (6%), EM corrected the original LM diagnosis. In two cases EM did resolve a diagnostic dilemma. EM is a beneficial adjunct to the correct diagnosis of selected tumors. Although in general EM does not help differentiate benign from malignant tumors, it is helpful in identifying the cell of origin of poorly differentiated neoplasma. A more precise histogenetic diagnosis was judged to be clinically helpful in 56% of th cases studied in this experience. EM is a relatively inexpensive ($115-250) and prompt (three to five days) adjunct to surgical care. It should be routinely available to the practicing surgeon for help in determining the cell type of confusing tumors. EM is no longer simply a research tool.Images: Fig. 1a.Fig. 1b.Fig. 2a.Fig. 2b.Fig. 3a.Fig. 3b.Fig. 4a.Fig. 4b.Fig. 5a.Fig. 5b.Fig. 6a.Fig. 6b.Fig. 7a.Fig. 7b.
*7055377* 7055377 Analysis of staging and management of patients with sarcoma: a ten-year experience. Ann Surg 1980; 191 (4): 488-93
Over ten years, 70 patients with soft tissue sarcoma were treated for their primary tumors at the hospital of The Fox Chase Cancer Center. The clinical characteristics of these tumors are correlated with the outcome of various management efforts. The results of these evaluations identify three groups that can provide the basis for future treatment decisions and stratification for randomized studies of management options. The first group of patients, those with small well differentiated tumors, have no systemic spread regardless of the treatment modality used. The second group, those with large (greater than 5 cm) tumors that are moderately or poorly differentiated, do uniformly poorly despite the management techniques used. An intermediate group, those with high grade or large size but not both, have outcomes which may be correlated to treatment modalities.
*7369814* 7369814 Sweat gland carcinoma: a clinico-pathologic study of 83 patients. Ann Surg 1971; 173 (2): 270-4 *5100098* 5100098 Solitary malignant schwannoma. Ann Surg 1970; 171 (3): 419-28
Images: Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 7.Fig. 8.Fig. 9.Fig. 11.Fig. 12.
*5416584* 5416584 Extra-abdominal desmoids: a clinicopathological study. Ann Surg 1969; 170 (1): 109-21
Images: Fig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8.Fig. 10.Fig. 11.Fig. 12.Fig. 13.Fig. 14.Fig. 15.Fig. 16.Fig. 17.
*5789523* 5789523 Dermatofibrosarcoma protuberans: an analysis of 86 cases--five with metastasis. Ann Surg 1967; 166 (5): 803-16
Images: Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8.Fig. 9.Fig. 10.Fig. 12.
*4964386* 4964386 Endemic and Morphologic Similarities Existing Between Spontaneous Colonic Neoplasms in Man and 3:2?-Dimethyl-4-Aminobiphenyl Induced Colonic Neoplasms in Rats. Ann Surg 1965; 161 (2): 309-24
Images: Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6.Fig. 7.Fig. 8.
*14260828* 14260828 Beyond PubMed : called unfree