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The SWItch Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex is a large multi-subunit protein assembly that orchestrates chromatin compaction and accessibility for gene transcription in an ATP-dependent manner. As a key epigenetic regulator, the SWI/SNF complex coordinates gene expression, cell proliferation and differentiation, and its biologic functions, in part, antagonize the polycomb repressive complex 2. The mammalian SWI/SNF complex consists of 15 subunits encoded by 29 genes, some of which are recurrently mutated in human cancers, in the germline or sporadic setting. Most SWI/SNF-deficient tumors share common "rhabdoid" cytomorphology. SMARCB1 (INI1) is the subunit most frequently inactivated in soft tissue neoplasms. Specifically, SMARCB1 deficiency is observed as the genetic hallmark in virtually all malignant rhabdoid tumors, and most cases of epithelioid sarcoma and poorly differentiated chordoma. In addition, subsets of myoepithelial carcinoma (10-40%), extraskeletal myxoid chondrosarcoma (20%), epithelioid schwannoma (40%), and epithelioid malignant peripheral nerve sheath tumor (70%) demonstrate SMARCB1 loss. The gene encoding the SS18 subunit is involved in the SS18-SSX rearrangement, which is pathognomonic of synovial sarcoma and indirectly inactivates SMARCB1. Finally, undifferentiated SMARCA4-deficient thoracic sarcomas are defined by SMARCA4 subunit inactivation, leading to SMARCA4 and SMARCA2 loss. Rarely, inactivation of alternate but biologically equivalent key regulators can substitute for canonical subunit deficiency, such as SMARCA4 inactivation in cases of SMARCB1-retained epithelioid sarcoma. This review briefly highlights SWI/SNF complex biologic functions and its roles in human cancer and provides a detailed update on recent advances in soft tissue neoplasms with canonical SWI/SNF complex deficiency, correlating morphologic, genomic, and immunohistochemical findings.

Rhabdoid tumor predisposition syndrome (RTPS) is defined as the presence of a SMARCB1 or SMARCA4 genetic aberration in a patient with malignant rhabdoid tumor. Patients with RTPS are more likely to present with synchronous or metachronous rhabdoid tumors. Based on the current state of rhabdoid tumor taxonomy, these diagnoses are based largely on patient demographics, anatomic location of disease, and immunohistochemistry, despite their nearly identical histologic and immunohistochemical profiles. Thus, the true distinction between such tumors remains a diagnostic challenge. Central nervous system atypical teratoid/rhabdoid tumor (AT/RT) is a rare, aggressive, primarily pediatric malignancy with variable histologic features and a well documented association with loss of SMARCB1 expression. Epithelioid sarcoma (ES) is a rare soft tissue tumor arising in patients of all ages and characteristically staining for both mesenchymal and epithelial immunohistochemical markers while usually demonstrating loss of SMARCB1 expression. To our knowledge we herein present the first documented case of a patient with RTPS who presented with metachronous AT/RT and ES.

Objectives: Aberrant expression of neuroendocrine markers has been reported in angiosarcomas and can occasionally result in diagnostic confusion. The aim of this study was to evaluate the expression of insulinoma-associated protein 1 (INSM1), a marker for neuroendocrine differentiation, in angiosarcomas as well as other sarcomas. Methods: Tissue microarrays, including angiosarcoma, Ewing sarcoma, desmoplastic small round cell tumor (DSRCT), clear cell sarcoma, synovial sarcoma, leiomyosarcoma, alveolar soft part sarcoma, epithelioid sarcoma, and undifferentiated pleomorphic sarcoma, were evaluated for expression of INSM1. The extent of immunoreactivity was graded according to the percentage of positive tumor cell nuclei (0, no staining; 1+, Results: INSM1 expression was found in a subset of angiosarcomas (n = 24/94, 26%; majority 5+, weak to moderate), as well as DSRCTs (n = 7/62, 11%; 2+, weak to strong) and rarely synovial sarcomas (n = 3/76, 4%; 2+, moderate to strong). No INSM1 expression was detected in the other sarcomas. Conclusions: Aberrant expression of INSM1 can be seen in a subset of angiosarcomas often with diffuse labeling. Other sarcomas that can rarely demonstrate small cell morphology and focal INSM1 expression include DSRCT and synovial sarcoma.

Epithelioid sarcoma (EpS) is a rare malignant neoplasm that accounts for < 1% of adult soft tissue sarcomas. Primary EpS of the bone is extremely rare and only a few cases have been reported to date. We report a case of primary distal-type EpS of the lumbar vertebra. A 30-year-old man without any history of malignant tumors had complained of lumbago for 3 months before visiting the hospital. Magnetic resonance imaging (MRI) of the lumbar spine showed a high signal intensity on the fat-suppressed T2-weighted image (WI) and a low signal on the T1WI at the L1 vertebral body. The tumor protruded toward the anterior components. Systemic radiological examination revealed no other lesion. A biopsy revealed a primary malignant tumor with epithelioid features. After chemotherapy, total en bloc spondylectomy was performed. Macroscopically, the tumor replaced the entire L1 with necrosis. Histologically, the tumor showed nodules of epithelioid cells that were strongly positive for epithelial markers, but a lack of INI1 expression. Central necrosis in the tumor nodule was also observed. This tumor showed loss of heterozygosity at the SMARCB1 locus but without the SMARCB1 mutation. The result of Foundation One ®CDx showed no actionable mutations. Seven months after surgery, a subcutaneous metastasis to the left cheek and bilateral lung metastasis with pleural dissemination were observed on radiological examination. A final diagnosis of distal-type EpS was made based on these findings. The patient died of the disease 8 months after surgery.

Epithelioid sarcoma (ES) is a rare malignant mesenchymal neoplasm that accounts for less than one percent of all soft-tissue sarcomas. Only two cases of ES involving the adrenal gland were found after a literature review. We report a case of an 82-year-old female initially presenting with right flank pain who was subsequently found to have an incidental left adrenal mass on CT imaging. After appropriate diagnostic workup, the patient underwent surgical resection. A diagnosis of ES was made from the histopathological analysis. The characteristic findings of ES are epithelioid cells with rhabdoid morphology and moderate eosinophilic cytoplasm. Immunohistochemical findings are significant for positive staining for epithelial markers, cytokeratins, vimentin, and CD34, and loss of INI-1 stain. Due to the aggressive nature and limited data of ESs, the standard treatment continues to remain wide surgical excision.

Epithelioid Sarcomas is a rare aggressive subtype of soft tissue sarcomas that is most prevalent in young adult males. It is locally invasive and frequently metastasizes to regional lymph nodes and...

Introduction: Epithelioid sarcoma is a rare soft tissue malignancy that usually presents in the distal extremities along fascial planes, aponeuroses or tendon sheaths. Very rarely, it presents as a primary or metastatic lesion of the head neck. Methods: Chart review and comprehensive literature review using PubMed and Google Scholar. Results: A 17-year-old non-smoker was referred for evaluation of an ulcerative lesion of the right anterior-lateral tongue, progressing over several months. Incisional biopsy was concerning for squamous cell carcinoma. He underwent partial glossectomy and bilateral selective neck dissections, with reconstruction using a radial forearm free flap. Final pathology was consistent with epithelioid sarcoma, proximal type, demonstrating perineural invasion and close margins. Post-operative PET scan showed no persistent nor metastatic disease. He underwent post-operative radiation therapy to a total dose of 56 Gy to the primary site. Conclusion: Epithelioid sarcoma is a rare malignancy usually presenting in the extremities of young adults, which uncommonly presents in the head and neck as a primary or metastatic lesion. The infrequency of these lesions has prevented development of evidence-based treatment recommendations. As with most sarcomas, surgery is the mainstay of therapy for epithelioid sarcoma, while radiation has been used in an adjunctive role. Although a rare lesion, epithelioid sarcoma should be considered in the differential diagnosis for atypical epithelioid lesions of the tongue and oral cavity when patient demographics, gross lesion characteristics, or histopathology are not entirely consistent with more common lesions, such as squamous cell carcinoma.

Introduction As a rare soft tissue malignancy, epithelioid sarcoma (EpS) is infrequently subjected to cytopathologic analysis. With the exception of a few series, the cytology literature regarding EpS is largely limited to single case reports. Our purpose was to evaluate our experience with EpS, and review the literature regarding its cytopathology. Materials and methods A search was made of our cytopathology and surgical pathology databases for cases diagnosed as EpS. Fine-needle aspiration biopsy smears and imprint smears were performed and examined using standard technique. Effusion samples were processed using liquid-based slides. Results Twenty cases of EpS were retrieved from 10 patients (M:F 1:1; mean age = 36 years). One patient had 5, 1 patient had 3, and 3 patients had 2 separate specimens. All patients had prior or subsequent tissue confirmation of EpS; all were of the classic/distal type. Seven were new patient cases, 7 were locally recurrent, and 6 were metastases. Sites included lower extremity (8 cases), upper extremity (4), trunk (4), serous effusion (2), scalp (1), and mediastinum (1). Specific cytologic diagnosis were EpS (13 cases), sarcoma not otherwise specified (5), and malignant neoplasm (2). All cases where cell-block SMARCB-1 staining was used were specifically recognized as EpS. Cytomorphology was composed primarily of epithelioid/plasmacytoid cells having eccentrically positioned nuclei, moderate cytoplasm, and variable nuclear pleomorphism. Conclusion The cytopathology of EpS is somewhat variable, morphologically non-specific, and mimics that of other neoplasms with epithelioid features. Ancillary immunostaining is necessary for a specific diagnosis in newly encountered patients.

Epithelioid sarcoma (ES) is a rarely occurring malignant soft tissue tumor of uncertain histogenesis. It is most common among young males and commonly seen on the forearm, hand, and fingers. ES begins as a small lump or ulcer, and most were painless. ES has a high rate of recurrence and can spread to other parts of the body easily. Hence, physicians should take the necessary steps to ensure proper diagnosis and treatment. We present an interesting case of a 26-year-old male diagnosed with a proximal variant of ES of the shoulder.

Highlights • It is difficult to diagnose cellular variants of Sclerosing epithelioid sarcoma by fine needle aspiration. • If dense areas of tumor cells are collected by FNA, multiple myeloma and myoepithelioma can be different diagnosis. • MUC4 is a very useful immunological marker for diagnosis of Sclerosing epithelioid sarcoma., Introduction Sclerosing epithelioid sarcoma (SEF) is a rare fibroblastic sarcoma. It is classically composed of cords of epithelioid cells embedded in a hyalinized stroma; however, cases of cellular variants also exist. A cellular variants of SEF can mimic Plasmacytoma/Myeloma (PM) and myoepithelioma. Hence, accurate diagnosis of SEF is important for cytologists and pathologists. Presentation of case We present the case of a 75-year-old female patient diagnosed with a cellular variant of SEF occurring in the erector spinal muscle. Immunostaining of MUC4 and fluorescence in situ hybridization of EWSR1 (break-apart signal) were used for diagnosis. Conclusion The cellular variants of SEF presented diagnostic difficulties in fine needle aspiration. Moreover, it could not be distinguished from PM.

In general, patients with neurofibromatosis type I have a higher risk than those with other types of neurofibromatosis of developing soft-tissue sarcomas related to the nervous system. We here present a 42-year-old man with neurofibromatosis type I who developed a protruding mass over only 2 weeks. The histopathological diagnosis was epithelioid sarcoma. Epithelioid sarcomas are rare and, to the best of our knowledge, no epithelioid sarcomas have been reported in patients with neurofibromatosis type I. Radical excision of the primary lesion was performed and postoperative radiotherapy and chemotherapy administered, as is recommended for epithelioid sarcoma. Our case emphasizes that patients with neurofibromatosis type I may develop malignant tumors.

Highlights • The diagnosis of epithelioid sarcoma based on only the clinical manifestation has proven to be difficult. • Thus, the histopathology examination followed by immunohistochemistry is considered as the main modality for the diagnosis. • Better understanding of clinical properties of epithelioid sarcoma will aid in deciding the best treatment for the patient., Introduction Epithelioid sarcoma (ES) is a rare mesenchymal tumor, accounting for less than 1% of all adult soft-tissue sarcomas. The diagnosis of such malignancy is challenging. We reported a 31-year-old male diagnosed with rhabdoid ES that histologically mimicked epithelioid rhabdomyosarcoma in a 31-year-old male. Case presentation A 39-year-old male presented with pain in the left thigh. He had planned for open reduction internal fixation due to left femur fracture. During the surgery, the surgeon found abnormal appearance of the bone and the surrounding tissue. The histopathology examination showed spindle-to-polygonal epithelioid cells arranged in nodular pattern with necrotic areas. Immunohistochemistry examination revealed vimentin and CK positive expression, while myogenin was negative. Further immunostaining using CD34 and HMB45 were also negative. Discussion The diagnosis of ES based on only the clinical manifestation has proven to be difficult. Thus, the histopathology examination followed by immunohistochemistry is considered as the main modality for the diagnosis. Better understanding of clinical properties of ES will aid in deciding the best treatment for the patient.

Epithelioid cell features mimicking carcinomas characterize a variety of histogenetically, phenotypically, and molecularly distinct subsets of mesenchymal neoplasms. In a pathogenetic sense, epithelioid soft tissue tumors basically fall into three main genetic categories: (1) switch/sucrose non-fermenting (SWI/SNF) complex-deficient tumors (with epithelioid sarcoma as their prototype); (2) epithelioid neoplasms driven by specific rare gene fusions (such as sclerosing epithelioid fibrosarcoma with EWSR1 fusions and GLI1-related malignant epithelioid soft tissue neoplasms); and (3) a heterogeneous group encompassing epithelioid variants of diverse other entities. Notably, lesions in the first and third groups may display variable, occasionally prominent, rhabdoid cell morphology, thus further complicating their differential diagnosis. This review summarizes the main clinicopathological, phenotypic, and genotypic features of these diseases and discusses their pertinent differential diagnostic considerations.

Metastatic epithelioid sarcoma to gingiva is extremely rare. One case has only been reported in the literature. We describe our experience for a rare case of female gingival metastasis, which the primary lesion occurred on the volar surface of the forearm and has been treated with wide surgical resection, chemotherapy, and radiotherapy 24 months earlier. Histological and immunohistochemical features of tumor cells led to the diagnosis of epithelioid sarcoma.

Pseudomyogenic hemangioendothelioma (PHE) is an uncommon mesenchymal tumor of intermediate malignant potential with characteristic clinicopathologic and genetic features. Although bone involvement accompanies nearly one-fourth of reported cases of soft tissue PHEs, primary intraosseous PHE is rare. Herein, we report five cases of primary intraosseous PHEs. Male to female ratio was 4:1, with an average age of 28 years (age range, 5–44 years). Radiologically, tumors presented as lytic lesions in the proximal femur (two), diaphysis of the tibia (one), distal radius (one) and vertebrae (one). Multifocal lesions were observed in four cases. Histopathologic examination revealed plump spindle cells and prominent nucleoli. New bone formation was noted in three cases. Immunohistochemically, all tumors were positive for CD31 and negative for CD34. Pan Cytokeratin (CK) (AE1/3) was positively expressed in all, except a single tumor, in which CK7 and Cam5.2 were expressed. INI1/SMARCB1 was completely retained in all tumors. A single patient underwent surgical resection. During follow-up, two cases showed no evidence of disease within two and five years, respectively. Differential diagnosis of a PHE of bone includes osteoblastoma, epithelioid angiosarcoma, metastatic carcinoma, metastatic rhabdomyosarcoma, and epithelioid sarcoma. Caution must be exercised as pan CK (AE1/3) might not be expressed; therefore, the use of other cytokeratins, such as Cam5.2 is recommended. Awareness of such an entity in bone is the key to the diagnosis.

Introduction: Epithelioid sarcoma is a malignant mesenchymal tumor exhibiting epithelioid cytomorphology and epithelial phenotype. Its histogenesis is unknown, but its tumorigenesis may relate to inactivation of hSNF5/SMARCB1/INI1 tumor suppressor gene. This tumor typically affects young adults and older children, but it is uncommon in infants. Case Report: We describe a unique neoplasm in a 15-month-old infant presenting with a heel mass. The tumor was remarkable for retention of SMARCB1/INI1 expression. Conventional cytogenetic analysis revealed trisomy 2 and double minutes, and SNP array analysis confirmed the trisomy 2 and identified segmental amplification of chromosome 11 containing YAP1 and BIRC3; FISH testing proved that the double minutes consisted of BIRC3 and YAP1, potent oncogenes related to tumorigenesis of several types of tumors but not described in epithelioid sarcoma. Conclusion: Our findings expand the spectrum of cytogenetic alterations in this neoplasm, help in better understanding its tumorigenesis, and suggest potential therapeutic targets.

Epithelioid sarcoma of the peripheral nerves is extremely rare. We present a case concerning the median nerve of the right hand in a 35-year-old woman who was treated with radical resection, reconstructive surgery, and chemotherapy. After 2 years of follow-up, there is no evidence of local recurrence or metastatic dissemination.

So-called primary yolk sac tumors of the vulva are very rare and often have an aggressive disease course. Their molecular features have not been previously characterized. There is also a well-documented group of SMARCB1 (INI-1)-deficient vulvar neoplasms, which includes proximal-type epithelioid sarcoma and myoepithelial carcinoma. Until now, "vulvar yolk sac tumors" and SMARCB1-deficient neoplasms were considered unrelated diseases. After reviewing an index case of a vulvar yolk sac tumor with loss of SMARCB1 by immunohistochemistry, we retrospectively identified 2 additional cases diagnosed as vulvar yolk sac tumors. Patient ages were 34, 32, and 25 years old, and 2 tumors were associated with a pregnancy. All 3 cases showed morphology typical of a yolk sac tumor, and by immunohistochemistry all were positive for SALL4, glypican-3, keratins, and lacked CD34 positivity. All tumors also demonstrated loss of SMARCB1 in tumor cells. Targeted molecular profiling was performed in 2 cases and identified 2 copy deletion of SMARCB1, without genomic alterations typically seen in gonadal yolk sac tumors. In the third case, isochromosome 12p was not identified by fluorescence in situ hybridization. All 3 patients had either local recurrences or distant metastases, and 2 died of disease. One patient had progressive disease while receiving the enhancer of zeste homolog 2 inhibitor tazemetostat. Overall, these findings suggest that vulvar tumors with pure yolk sac-like morphology may represent morphologic variants of SMARCB1-deficient tumors and not veritable germ cell neoplasia. This potential reclassification may have both prognostic and treatment implications and warrants study of additional extragonadal yolk sac tumors.

Although soft-tissue masses are common, sarcomas are rare malignant neoplasms showing variable mesenchymal differentiation and can occur at any anatomical site. Limb soft-tissue sarcomas (STS) are rare, but often lethal tumours. Although there are scores of historical pathological subtypes, this article will deal with the commonest: liposarcoma, leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma, myxofibrosarcoma, malignant peripheral nerve sheath tumour (MPNST), epithelioid sarcoma, alveolar rhabdosarcoma, angiosarcoma and radiation-induced sarcoma (RIS). Following a review of >4,000 adult patients with limb sarcoma from our specialist soft-tissue tumour database, we summarise the literature and their imaging findings, with emphasis on radiological hallmarks that can aide in diagnosis and management. Increased awareness of sarcoma when challenged with a new mass in the extremity can ensure timely and appropriate treatment.

AIMS Complete loss of SMARCB1/INI1 in soft-tissue tumours such as malignant rhabdoid tumour, epithelioid sarcoma, myoepithelial tumour of soft tissue and extraskeletal myxoid chondrosarcoma is often associated with high-grade malignancy and poor prognosis. The diagnosis is sometimes challenging, owing to histological similarities, so careful differential diagnosis is required. Therefore, soft-tissue tumours with complete SMARCB1/INI1 loss could potentially include an unknown entity. METHODS AND RESULTS We analysed 160 cases of SMARCB1/INI1-deficient soft-tissue tumour, and found 14 cases that were not classifiable into already existing categories and had common clinical and histological features. These involved two male and 12 female patients, ranging in age from 20 years to 61 years. The tumours were located in the the puboinguinal region (n = 13) and pelvic cavity (n = 1). Histologically, the tumours showed relatively uniform epithelioid to spindle-shaped cells with myxoid stroma. All tumours showed immunoreactivity for brachyury, epithelial membrane antigen, and progesterone receptor, and 12 of 14 cases did so for oestrogen receptor. Variable positive staining for α-smooth muscle actin, S100 and glial fibrillary acidic protein (GFAP) was seen. NR4A3 and EWSR1 gene rearrangements were not detected in 13 and 11 examined cases, respectively. Clinical follow-up data for the 14 patients showed that 13 were alive without disease and one had been lost to follow-up; four patients developed local recurrence and/or metastases. CONCLUSION The designation 'myxoepithelioid tumour with choroid features' (METC) was proposed as a tumour with intermediate malignancy controllable with appropriate treatment, including the entity of myoepithelioma-like tumour of the vulvar region. METC represents a novel and independent subset that is histologically, biologically and clinically distinct from already existing SMARCB1/INI1-deficient soft-tissue tumours.

Epithelioid sarcoma is a rare, slow-growing, malignant tumor with multivariate presentation and a high rate of recurrence following surgery. Diagnosis is often missed or delayed due to its infrequent nature and confusing clinical and pathological presentation. This is compounded by the fact that this tumor is aggressive with a propensity for metastases without being detected. The treatment of this deadly tumor is controversial with no clear-cut consensus. The author presents a case of epithelioid sarcoma in the finger of a young patient with subsequent recurrence after surgery and a review of current literature pertaining to this aggressive tumor. This report would like to stress the importance of a multimodal approach in combatting this tumor as prompt diagnosis and aggressive therapy can significantly reduce the poor outcomes associated with this disease.

Background Soft tissue tumours with epithelioid morphology have many differential diagnoses, which include epithelioid sarcoma, malignant extrarenal rhabdoid tumour, epithelioid malignant peripheral nerve sheath tumour, epithelioid leiomyosarcoma, epithelioid angiosarcoma and sclerosing epithelioid fibrosarcoma. There are other rare entities also. They often express characteristic patterns of immunohistochemical markers that can be used to identify these tumours. Materials and methods This retrospective study comprises 22 cases of malignant soft tissue tumours with epithelioid differentiation diagnosed over a period of four years. Findings regarding clinical presentation, cytological findings, histopathological findings and immunohistochemical profile of the tumours were noted and analyzed. Results A total of 22 cases were included in the study including five cases of epithelioid sarcoma (conventional and proximal), three cases of epithelioid angiosarcoma and epithelioid myxofibrosarcoma, two cases of epithelioid malignant peripheral nerve sheath tumour, epithelioid gastrointestinal stromal tumour and clear cell sarcoma each, one case of epithelioid leiomyosarcoma, sclerosing epithelioid fibrosarcoma, malignant extrarenal rhabdoid tumour, monophasic synovial sarcoma and malignant and malignant perivascular epithelioid cell tumour each. Conclusion Pathologists should be aware of the various differential diagnoses of soft tissue tumours with epithelioid morphology. Over and above the clinical findings and morphological features, ancillary methods like immunohistochemistry help to arrive at a definitive diagnosis in most cases.

Summary:. Epithelioid sarcoma is a rare, high-grade malignant soft tissue tumor that is often misdiagnosed. Classified as a mesenchymal malignancy, it exhibits both mesenchymal and epithelial markers. Occurrence in children under age 10 is extremely rare. This report describes the clinical course and management of a 5-year-old girl who presented with epithelioid sarcoma in the distal extremity. The lesion was initially misdiagnosed and treated for over a year as a common wart.

Herein, we first reported a case of undifferentiated sarcoma with epithelioid features harboring TFE3 amplification. A 66-year-old woman with a history of chronic lymphocytic leukemia and chemotherapy presented with a 4 cm palpable nodule in the left lower leg. Microscopically, the large epithelioid tumor cells with remarkable pleomorphism and the small round tumor cells intermingled with each other in a diffuse sheet or a hemangiopericytoma-like vascular growth pattern. Atypical mitotic figures and lymph node metastasis were found while tumor necrosis was absent. Immunohistochemically, the tumor was positive for vimentin, TFE3, and CD34. TFE3 gene amplification was identified by fluorescence in situ hybridization. The patient was alive and well without recurrence or metastasis for 12 months after tumor resection. The tumor should differentiate from PEComa, alveolar soft part sarcoma, epithelioid sarcoma, epithelioid angiosarcoma, and epithelioid rhabdomyosarcoma.

We present a case (41 years old pregnant female) with epithelioid sarcoma arising in the left external auditory canal. On immunohistochemistry, the tumor cell diffusely expressed cytokeratins and showed patchy expression of ERG and CD34. The neoplastic cells demonstrated uniform loss of INI1-expression. Epithelioid sarcoma arising in the external auditory canal is rare. Awareness that ES may rarely arise at unusual sites is of critical importance in order to apply a broad enough panel in the immunohistochemical study, so a misdiagnosis of carcinoma can be avoided.

The SWI/SNF complexes are major regulators of gene expression and their alterations occur in a large array of cancers both of epithelial and mesenchymal lineages. Malignant rhabdoid tumors were the first malignancies linked to deregulation of these complexes with the involvement of SMARCB1 in their development but genetic alterations affect all subunits in other malignancies. In the chest and lung regions, SMARCA4 (BRG1) is the most frequently altered subunit and is involved in the pathogenesis of two subtypes of tumors, including bona fide carcinomas (SMARCA4-deficient non-small cell lung cancers) but also undifferentiated tumors that harbor an undifferentiated phenotype close to those of malignant rhabdoid tumors (SMARCA4-undifferentiated tumors). Although their histogenesis is yet to be fully understood, these tumors are associated with distinct clinical and pathological features even though some overlapping features have been reported in rare cases. SMARCA4 deficiency is easily asserted by immunohistochemistry that show the loss of nuclear expression of the protein in the nuclei of tumor cells. These tumors are commonly associated with high-grade cytological features, rhabdoid cytomorphology, solid architecture and extensive necrosis. The typical immunohistochemical signature of SMARCA4-UT combines co-inactivation of SMARCA2 (BRM) and the overexpression of SOX2 and SALL4. No specific therapeutic strategies have been so far developed for SMARCA4-deficient neoplasms. SMARCB1 subunit is involved in the development of several SMARCB1-deficient sarcomas on top of malignant rhabdoid tumors that may develop in the thorax. Malignant rhabdoid tumors affect mostly children of less than 5y. The differential diagnosis includes epithelioid sarcomas, malignant myoepithelial tumors or myoepithelial carcinomas, extra-skeletal myxoid chondrosarcomas and synovial sarcomas.

Proliferative fasciitis (PF) and proliferative myositis (PM) are rare benign soft tissue lesions, usually affecting the extremities of middle-aged or older adults. Presenting as poorly circumscribed masses, they histologically show bland spindle cell proliferation in a myxoid to fibrous background and a hallmark component of large epithelioid "ganglion-like" cells in various numbers, which may lead to their misdiagnosis as sarcoma. PF/PM has been long considered as reactive, akin to nodular fasciitis; however, its pathogenesis has remained unknown. In this study, we analyzed the FOS status in 6 PF/PMs (5 PFs and 1 PM). Five PF/PMs occurred in adults, all showing diffuse strong expression of c-FOS primarily in the epithelioid cells, whereas spindle cell components were largely negative. Using fluorescence in situ hybridization (FISH), all 5 c-FOS-immunopositive tumors showed evidence of FOS gene rearrangement in the epithelioid cells. RNA sequencing in 1 case detected a FOS-VIM fusion transcript, which was subsequently validated by reverse transcriptase-polymerase chain reaction, Sanger sequencing, and VIM FISH. The one pediatric PF case lacked c-FOS expression and FOS rearrangement. c-FOS immunohistochemistry was negative in 45 cases of selected mesenchymal tumor types with epithelioid components that may histologically mimic PF/PM, including pleomorphic sarcoma with epithelioid features and epithelioid sarcoma. Recurrent FOS rearrangement and c-FOS overexpression in PF/PM suggested these lesions to be neoplastic. FOS abnormality was largely restricted to the epithelioid cell population, clarifying the histological composition of at least 2 different cell types. c-FOS immunohistochemistry may serve as a useful adjunct to accurately distinguish PF/PM from mimics.

Patient: Male, 65-year-old Final Diagnosis: Epithelioid angiosarcoma Symptoms: Pain Medication: — Clinical Procedure: — Specialty: Oncology • Pathology Objective: Rare disease Background: Epithelioid angiosarcoma is an extremely rare malignant disease of the endothelial cells. Most of the previous reports about this disease were regarding clinical features and radiological findings, with limited descriptions of pathological diagnosis. This report aimed to present a reference to increase understanding of the timely diagnosis of epithelioid angiosarcoma. Case Report: A 65-year-old male was diagnosed with epithelioid angiosarcoma originating from the deep soft tissue of the lower leg. He had a history of 2 months of rapid swelling and painful in the left lower leg, which occurred after a muscle cramp, and was clinically suspicioius for hematoma. Radiological examination revealed a large heterogeneous soft-tissue mass. Histopathology results showed that the mass was malignant, and the differential diagnosis wasa malignant vascular tumor, melanoma, poorly differentiated carcinoma, clear cell sarcoma, epithelioid sarcoma, and anaplastic large-cell lymphoma. Immunohistochemistry findings confirmed that it was an epithelioid angiosarcoma. Conclusions: This case underscores the difficult of diagnosing epithelioid angiosarcoma. It requires careful pathological investigation and immunophenotype labeling.

Pseudomyogenic hemangioendothelioma, an uncommon mesenchymal neoplasm composed of plump spindled and/or epithelioid endothelial cells, may present multicentrically and tends to locally recur but rarely metastasizes. Morphologic resemblance to epithelioid sarcoma and other spindle cell neoplasms may result in diagnostic confusion. Molecular characterization of pseudomyogenic hemangioendothelioma has revealed these neoplasms often harbor a rearrangement of the FOSB gene with SERPINE1 or ACTB as recurrent fusion gene partners. Herein, a case of a fibular pseudomyogenic hemangioendothelioma with minimal extension into the adjacent soft tissue arising in a 17 year-old male is presented. The neoplasm exhibited sheets of epithelioid cells with abundant eosinophilic cytoplasm and variably eccentric nuclei. RNA sequencing revealed a novel CLTC-FOSB fusion transcript that was subsequently confirmed by direct sequencing of reverse transcription-polymerase chain reaction products demonstrating an in-frame fusion between exon 17 of the clathrin heavy chain (CLTC) gene and exon 2 of the FOSB (FosB proto-oncogene, AP-1 transcription factor subunit) gene. CLTC-FOSB fusion has not been described in a neoplasm before.

Primary tumors of the paratesticular region are rare, with sarcomas constituting a major proportion, particularly in the old age. The paratesticular region consists of mesothelial, various epithelial, and mesenchymal cells and may therefore give rise to a variety of tumors. Epithelioid sarcoma usually occurs at the distal extremities of young adults. The proximal-type variant is characterized by a more aggressive course and resistance to treatment. We herein report a case of 32 years male with scrotal swelling diagnosed as proximal-type epithelioid sarcoma of paratesticular region after histopathological examination and immunohistochemistry. To the best of our knowledge, this is only the second case of proximal epithelioid sarcoma of paratesticular region in the English literature. As these tumors are rare, it has been difficult to establish their optimal treatment. Also, these can be easily misdiagnosed as other epithelioid lesions.

Background Epithelioid sarcoma most frequently occurs in the dermal or subcutaneous area of the distal extremities. To date, there have been three cases of primary pulmonary epithelioid sarcoma reported. We report a case of epithelioid sarcoma that is considered a primary lung tumor. Case presentation A 65-year-old asymptomatic Asian male patient underwent chest radiography during a routine health examination, and an abnormal mass was detected. His past medical history was unremarkable. He smoked 40 cigarettes every day and had slightly obstructive impairment on spirometry. He worked as an employee of a company and had no history of asbestos exposure. He underwent partial resection of the right lung by thoracoscopy. A histological examination of the tumor revealed a cellular nodule of epithelioid and spindle-shaped cells. Some of the tumor cells displayed rhabdoid features and reticular arrangement in a myxomatous stroma. Immunohistochemically, the tumor cells were positive for vimentin, smooth muscle actin (SMA), CD34, and epithelial membrane antigen (EMA); loss of the BAF47/INI1 protein in the tumor cells was also confirmed. A diagnosis of epithelioid sarcoma was established. Careful screening by whole-body positron emission tomography for another primary lesion after surgery did not detect any possible lesion. He had no cutaneous disease. Conclusion To our knowledge, this is the fourth case of a proximal-type epithelioid sarcoma considered as a primary lung tumor.

Introduction: Epithelioid sarcoma is a malignant mesenchymal neoplasm with evidence of epithelial differentiation. All the cases reported in the solid organs are of “proximal type” occurring in adu...

BACKGROUND Epithelioid sarcoma (ES) is a rare mesenchymal tumor that is divided into 2 types: classic and proximal. To the authors' knowledge, ES has been poorly studied in cytology, with fewer than 50 cases reported to date. The objective of the current study was to analyze the cytological and immunohistochemical information regarding 5 cases of ES. METHODS Five cases of ES were analyzed: 4 of proximal type and 1 of classic type. The cases were taken from 4 female patients and 1 male patient. The patients ranged in age from 10 to 75 years. RESULTS All smears obtained from the proximal type of ES were found to be hypercellular with a necrotic and inflammatory background. Smears from classic-type ES were hypocellular with a hemorrhagic background. Large, dispersed epithelioid cells and loosely cohesive groups of cells were most frequently noted in all cases. All cases of proximal-type ES demonstrated rhabdoid cells and marked nuclear atypia, but in only one case were rhabdoid cells found to be dominant. ES diagnoses were confirmed by immunohistochemistry in histological material. In 4 cases, epithelial marker expression was noted, whereas CD34 was found to be positive in only the classic type of ES. In 2 cases, total loss of SMARCB1/INI1 nuclear expression was observed. In the 2 SMARCB1/INI1-positive cases, loss of SMARCA2/BRM expression was observed in one case and partial loss was observed in the other case. CONCLUSIONS The proximal type of ES differs from the classic type by the presence of rhabdoid cells and marked nuclear atypia. A specific immunohistochemical profile demonstrating loss of SMARCB1/INI1 or other proteins from the SWI/SNF complex also may be indicative of this diagnosis.

Background & objective:Primary pleural neoplasms are rare entities compared with the pleural involvement by metastatic carcinoma. The current study aimed at investigating the complete spectrum of pleural neoplasms and differentiating between them with the aid of immunohistochemistry (IHC). Methods: Consecutive pleural biopsy specimens positive for a neoplasm, both primary and metastatic, were included in the study. Diagnosis or a differential diagnosis was suggested on histopathology confirmed by a panel of IHC markers such ascytokeratin (AE1/AE3), epithelial membrane antigen (EMA), vimentin, calretinin, CD34, CD99, SMA, bcl2, S100, CK7,CK20,TTF1,GCDFP, HMB45, LCA, synaptophysin, chromogranin, and naspsin. Results: A total of 35 cases of pleural neoplasms included 15 (42.9%) primary pleural neoplasms and 20 (57.1%) metastatic carcinoma. Synovial sarcoma, malignant mesothelioma (MM), and solitary fibrous tumor (SFT) accounted for 14.2%, 11.4%, and 8.5% of metastatic cases, respectively. Epithelioid sarcoma (ES), neuroendocrine carcinoma, and inflammatory myofibroblastic tumor were less common, each contributing to 2.9% of pleural neoplasms. Among the 20 cases of metastatic carcinoma, 13 were from the lung and 7 from the breast. Lung neoplasms metastasizing to the pleura were adenocarcinoma (n=12) and atypical carcinoid (n=1). Conclusion: Analysis of histopathological pattern along with a panel of appropriate IHC markers distinguished the rare entities of pleural neoplasms essential to determine the prognosis and treatment modality.

Objective To ascertain the effectiveness of IHC markers of vascular origin like CD31, CD34, FLI1 and ERG in vascular soft tissue sarcomas including angiosarcomas, Kaposi sarcomas, epithelioid hemangioendothelioma and a non-vascular soft tissue sarcoma (Epithelioid sarcoma). Study design Descriptive study. Place and duration of study Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from 2011 to 2017. Methodology Diagnosed cases of angiosarcomas (n=48), epithelioid hemangioendothelioma (n=9), Kaposi sarcoma (n=9) and epithelioid sarcoma (n=20) were selected. Immunohistochemical staining as performed on formalin fixed paraffin embedded sections. The sections were stained for the following markers: CD34 (VENTANA clone Q Bend 10), CD31 (Leica clone 1 A 10), FLI1 (CELL MARQUE clone MRQ-1) and ERG (CELL MARQUE clone EP111). Results A complete panel of CD34, CD31 and ERG was applied on 8/48 cases of angiosarcomas with triple positivity in 6 cases. Eight cases showed positivity for only CD31 and ERG and 2 cases showed positivity for only ERG. A complete panel of CD34, CD31 and ERG was applied on 3/9 cases of epithelioid hemangioendothelioma with positivity for all markers in 2 cases. Combined positivity for ERG and CD34 was seen in 2 cases and on 4 cases only CD31 immunohistochemical was solely applied with 100% positivity. FLI1 was not applied on any case. Among 9 cases of Kaposi sarcoma, ERG, CD34 and CD31 in combination were applied on only 1 case with triple positivity. Remaining cases show positivity for either CD34, CD31 or FLI1. Majority of cases of epithelioid sarcomas were diagnosed on the basis of cytokeratin and CD34 positivity with loss of INI1. The other vascular markers showed negativity in all cases. Conclusion Among these four markers, ERG immunohistochemical stain is highly effective for endothelial differentiation due to its specific nuclear staining pattern in normal blood vessel endothelial cells (internal control) as well as neoplastic cells of vascular tumors and lack of background staining.