Proximal-type Epithelioid Sarcoma Research Articles

Proximal-type epithelioid sarcoma: A new case report

Epithelioid sarcoma (ES) is a rare high-grade soft tissue sarcoma, first described by Enzinger in 1970, classically presenting as a subcutaneous or deep dermal mass in the distal extremities of adolescents and young adults. In 1997, Guillou et al. described the proximal-type epithelioid sarcoma, which is found mostly in the pelvic, perineal regions, and genital tracts of young to middle-aged adults. Epithelioid sarcoma is characterized by a proliferation of epithelioid-like cells with rhabdoid features and the absence of a granuloma-like pattern. We present, in this paper, a case of proximal-type epithelioid sarcoma of abdominal wall, with an aggressive clinical course, including distant metastasis and death one month after diagnosis. In this particular case, the location is infrequent, and it had not previously been described.

Soft tissue tumours of the penis. The 30-year Istituto Nazionale Tumori di Milano experience.

Small series and individual cases of penile soft tissue tumours are reported in the literature: these are rare tumours that represent less than 5% of all penile tumours. Penile soft tissue tumours were collected from the archive of the Department of Pathology at the Istituto Nazionale dei Tumori of Milan between January 1990 and October 2021. All available medical records were retrieved and reviewed to obtain clinical information. Our series refers to the 30-year experience of highlighting the heterogeneity in the presentation and microscopic features of these rare sarcomas. 18 penile soft tissue tumours are described, 4 benign and 14 malignant. The mean age at diagnosis was 58.2 years (range 24-96 years) and 53.6 years among malignancies (range 24-89). The most frequent histotype was Kaposi's sarcoma (nr = 4) and very unusual histotypes were observed, namely low-grade fibromyxoid sarcoma, synovial sarcoma, proximal type epithelioid sarcoma and the first reported case of dedifferentiated liposarcoma of the penis. Among sarcomas of the genitourinary tract, tumours of the soft tissues of the penis are the rarest. Penile sarcomas can present at a young age. Kaposi's sarcoma in HIV-negative patients has a favorable outcome, while deep sarcomas have an aggressive behavior and poor prognosis.

Primary Epithelioid Sarcoma of Frontotemporal Scalp: a Rare Case Report with Recent Literature Review

Epithelioid sarcoma (ES) is a very rare and aggressive mesenchymal sarcoma subtype which represents less than 1% of soft tissue sarcomas (STS). According to the origin of the site, there are two types of ES: distal-type epithelioid sarcoma and proximal-type epithelioid sarcoma. The clinical diagnosis of ES mainly is confirmed by histopathology examination followed by immunohistochemistry. Radical excisional surgery is the best treatment option for epithelioid sarcoma. According to TNM staging, the treatment option will vary from surgery to surgery accompanied with radiotherapy and chemotherapy. Here in, we presented a 36-year-old man had non-healing ulcer in left frontotemporal scalp extending to involve left orbit. Histopathological confirmed epithelioid sarcoma. Magnetic Resonance Imaging (MRI) of Head and Neck revealed that there was mass in left frontotemporal scalp measuring 6.7 X 5.7 X 2.6 cm extending to zygomatic region and left orbit D/D malignant mass/sarcoma with bilateral (B/L) sinusitis. After that patient undergone for Wide Local excision (WLE) surgery on 11th September 2022. Adjuvant Radiation Therapy (RT) 6000 cGy radiation dose in 30 fractions (#) which was 200 cGy per fraction (#) were given during 22nd September to 10th November 2022 due to local advancement of disease. Patient was asked to follow up after 6 weeks after completion of RT. After 6 weeks of surgery, the patient was undergone for MRI and report revealed normal study.

Proximal epithelioid sarcoma of the vulva. A rare neoplasm. A clinicopathological case

Epithelioid sarcoma is a rare aggressive soft tissue sarcoma, which can be distal or proximal types. The classic form (distal-type) of epithelioid sarcoma mainly occurs in teenagers and young adults. A rarer form, called large-cell (proximal-type) epithelioid sarcoma, tends to be more aggressive and mainly affects adults. The proximal subtype mostly arises from the proximal pelvis, limbs, and genital tract. We report a case of a 59 -year-old female, presented with a progressively growing mass in the left labia majora. Gynecologic examination revealed a 2 cm mobile and painless mass that was not attached to deep planes. The histological study showed a multinodular tumor was seen comprising sheets of oval to polygonal cells with moderate amount of cytoplasm. Interspersed were larger, rhabdoid cells with abundant eosinophilic cytoplasm and prominent nucleoli. On IHC, the tumor cells showed positivity for EMA and CKAE1/AE3 and do not expressed INI-1 in the nucleus. All tumor cells were negative for S-100 protein and CD34. The histopathological diagnosis was soft tissue of the vulvar region with proximal epithelioid sarcoma. The patient received adjuvant external pelvic radiotherapy and brachytherapy in the vulvar bed. Currently, 3 years after diagnosis, the patient does not present signs of tumor recurrence in her controls. Due to its low incidence, there are no evidence-based diagnostic algorithms or published recommendations for treatment. The prognosis is generally poor. A wide excision with clear margins is imperative with options of post-operative CT/RT in individual cases during a close follow-upbehavior, as seen in our case.

Young Woman With Vulvar Mass.

A 20-year-old woman presented to the emergency department with a 2-month history of a left groin mass, which slowly grew after mild blunt trauma. The mass became painful 2 days ago, but she denied vaginal discharge, pain, abnormal bleeding, or dysuria. Physical examination revealed an asymmetric, indurated, tender mass over the left lateral aspect of the mons pubis extending through the labia and inguinal area. (Figure 1) Bedside ultrasound evaluation showed a complex lesion without obvious fluid collection or Doppler flow (Figure 2), and computed tomography confirmed (Figure 3) a 9-centimeter soft tissue density.Figure 2Bedside ultrasound showed heterogenous mass without fluid collection or Doppler flow.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Computed tomography of pelvis with contrast demonstrated a peripherally enhancing 9 cm soft tissue density in the left inguinal region (arrow).View Large Image Figure ViewerDownload Hi-res image Download (PPT) Epithelioid sarcoma. After surveillance imaging results of the abdomen and thorax were negative, surgeons performed a core biopsy to confirm the diagnosis. The patient underwent neoadjuvant chemotherapy with prophylactic salpingectomy and planned resection. Soft tissue sarcomas represent an eclectic group of rare neoplasms, and epithelioid sarcoma is an aggressive subtype more commonly affecting young men, typically as a firm, painless distal extremity lesion that is notably associated with slow growth after trauma.1Popovich J.R. Kashyap S. Cassaro S. Sarcoma StatPearls [Internet]. StatPearls Publishing, Treasure Island (FL)2022 Janhttps://www.ncbi.nlm.nih.gov/books/NBK519533/Date accessed: March 7, 2022Google Scholar, 2Sobanko J.F. Meijer L. Nigra T.P. Epithelioid sarcoma: a review and update.J Clin Aesthet Dermatol. 2009 May; 2: 49-54PubMed Google Scholar, 3Enzinger F.M. Epitheloid sarcoma. A sarcoma simulating a granuloma or a carcinoma.Cancer. 1970; 26: 1029-1041Crossref PubMed Google Scholar, 4Andrisani A. Serena A. Ambrosini G. Capobianco G. Chiarelli S. Proximal-type epithelioid sarcoma of the mons pubis: report of a case.Eur J Gynaecol Oncol. 2011; 32: 339-342PubMed Google Scholar A lesion of the mons pubis is rare. Prognosis is generally poor as epithelioid sarcoma has a propensity for local recurrence and distant metastases.2Sobanko J.F. Meijer L. Nigra T.P. Epithelioid sarcoma: a review and update.J Clin Aesthet Dermatol. 2009 May; 2: 49-54PubMed Google Scholar,5Patrizi L. Corrado G. Saltari M. et al.Vulvar “proximal-type” epithelioid sarcoma: report of a case and review of the literature.Diagn Pathol. 2013; 8: 122Crossref PubMed Google Scholar Benign etiologies such as cysts, abscesses, or lipomas are clinically similar.

Metastatic proximal-type epithelioid sarcoma presenting as a chest lesion with a pathological fracture of the humeral neck

Introduction: Proximal-type epithelioid sarcoma is a rare soft tissue neoplasm which occurs mostly in young males and is much rarer than classic distal sub type. A young male, with a known diagnosis of neurofibromatosis type 1 (NF1) presenting with metastatic proximal-type epithelioid sarcoma is reported. Case Report: A 30-year-old male with known NF1, hypothyroidism, epilepsy, presented with a right shoulder pain of two weeks duration. Plain radiographs revealed an expansile lytic lesion, an aggressive periosteal reaction in right humeral head with an underlying pathological fracture. A well-defined extrapulmonary mass with a lobulated margin in upper zone of right hemithorax with inferior rib erosion of 3rd rib and the 3rd intercostal space widening were also observed. Contrast-enhanced computed tomography (CECT) chest and abdomen confirmed peripherally located poorly enhancing soft tissue mass with lobulated margins arising from posterior chest wall along with a subdiaphragmatic deposit. Multiple lytic lesions in right head of humerus with an underlying pathological fracture of surgical neck, T2, T6, and L3 vertebral bodies, and pelvic bones were observed too. Diagnosis of malignant peripheral nerve sheath tumor with metastases was made and ultrasound-guided biopsy of chest wall lesion was performed. Histology and immunohistochemistry (IHC) revealed a proximal type epithelioid sarcoma. The patient was managed with palliative surgery and oncological follow-up. Conclusion: Presentation of proximal-type epithelioid sarcoma with disseminated metastases in a patient with NF1 masquerading malignant peripheral nerve sheath tumor (MPNST) and the challenges of diagnosis on clinical, radiological, and histopathology as well as IHC perspectives of this rare disease entity is highlighted.

Primary pulmonary epithelioid sarcoma: a case report

BackgroundEpithelioid 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 presentationA 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.ConclusionTo our knowledge, this is the fourth case of a proximal-type epithelioid sarcoma considered as a primary lung tumor.

Epitheliod sarcoma: Molecular insights into proximal versus classic variant.

e23552 Background: Epithelioid sarcoma (ES) is an ultra-rare sarcoma with distinctive pathologic and clinical features, marked by the loss of the expression of the SWI/SNF chromatin remodeling complex subunit SMARCB1. The current WHO classification recognizes two ES subtypes, different by morphology, clinical behavior and outcome: the “classic-type” and “proximal-type” ES. This study is aimed to better understand the molecular grounds sustaining this difference, and to identify new potential treatment targets to personalize therapy in this rare disease. Methods: RNA sequencing profiling was conducted on FFPE samples. Functional annotation enrichment was evaluated through over representation and gene set enrichment analyses (GSEA). Inference of immune contexture was obtained through deconvolution and single sample GSEA (ssGSEA) approaches. Results: Twelve samples from 5 proximal-type ES and 7 classic-type ES were profiled, 10 naïve and 2 pre-treated with chemotherapy. Proximal variant samples featured an overepresentation of MYC activity signatures and of other signatures impacting on cell cycle, protein synthesis and chromatin metabolism. Pathways enriched in the classic variant included NOTCH/HEDGEHOG and immune system regulation (e.g. inflammatory, interferon alpha and interferon gamma). Accordingly, deconvolution and ssGSEA approaches predicted an increased immune infiltration in classic subtype samples, essentially involving T cells, as well as increased expression of HLA class I molecules. Conclusions: Different regulatory networks seem to contribute to the different biologic and clinical behavior of proximal and classic ES. These preliminary data suggest a potential greater sensitivity of proximal type ES to drugs targeting the cell cycle, whilst immune checkpoint inhibitors might have some activity in classic variant ES. Further studies are ongoing to validate these preliminary observations.

The natural history of epithelioid sarcoma. A retrospective multicentre case-series within the Italian Sarcoma Group

IntroductionThis case-series is aimed to describe the natural history of epithelioid sarcoma (ES) and to provide insights into the differential clinical behaviour of its two variants (“classic-type” and “proximal-type”). The value of a subtype-adapted grading system based on pathological features is explored. MethodsData from consecutive, primary, localised, INI1-deleted ES operated at three Italian sarcoma reference centres (1995–2015) were included. Centralised pathological review was performed. Classic-type ES was broken down into “high-grade” and “low-grade”, according to number of mitoses, evidence of necrosis and nuclear atypia. Five- and 10-year overall survival (OS) and crude cumulative incidence (CCI) of local recurrence (LR) and distant metastasis (DM) were estimated. ResultsFifty-two patients were included. 5- and 10-year OS estimates were 70% and 47% in the whole series, 57% and 37% in patients with proximal-type ES, 77% and 54% in patients with classic-type ES (P = 0.02). In classic-type ES, 5- and 10-year OS was higher for low-grade (95% and 72%, respectively) than high-grade tumours (P = 0.002). 5- and 10-year CCI estimates for LR were 21% and 33% in the whole series. 5- and 10-year CCI estimates for DM were 35% and 39% in the whole series, both 28% in classic-type ES, 47% and 59% in proximal-type ES (P = 0.03). ConclusionsSuffering from a proximal- or a classic-type is the stronger predictor of outcome in patients with localised ES, with proximal-type ES patients having lower survival due to a higher tendency toward metastatic spreading. However, the “high-grade” classic-type ES was associated with outcomes close to proximal-type ES.

Perineal mass in a 50-year-old man

A man in his fifties presented with a lump in his left anal/perineal region, which was clinically thought to be a lipoma and was excised. No preoperative imaging was available....

Comparative Assessment of Antitumor Effects and Autophagy Induction as a Resistance Mechanism by Cytotoxics and EZH2 Inhibition in INI1-Negative Epithelioid Sarcoma Patient-Derived Xenograft.

Epithelioid sarcoma (ES) is a rare mesenchymal malignancy marked by SMARCB1/INI1 deficiency. Retrospective clinical data report on the activity of anthracycline- and gemcitabine-based regimens. EZH2 inhibitors are currently being tested in clinical trials. Since comparisons of these agents are unlikely to be prospectively evaluated in the clinics, we took advantage of an INI1-deficient proximal-type ES patient-derived xenograft (PDX ES-1) to comparatively assess its preclinical antitumor activity. Mice were treated with doxorubicin and ifosfamide, singly or in combination, gemcitabine, and the EZH2 inhibitor EPZ-011989. Comparable antitumor activity (max tumor volume inhibition: ~90%) was caused by gemcitabine, EPZ-011989, and the doxorubicin–ifosfamide combination. The integration of RNAseq data, generated on tumors obtained from untreated and EPZ-011989-treated mice, and results from functional studies, carried out on the PDX-derived ES-1 cell line, revealed autophagy induction as a possible survival mechanism in residual tumor cells following EPZ-011989 treatment and identified HMGA2 as a main player in this process. Our data support the clinical use of gemcitabine and the doxorubicin–ifosfamide combination, confirm EZH2 as a therapeutic target in proximal-type ES, and suggest autophagy as a cytoprotective mechanism against EZH2 inhibition.

FNA of epithelioid sarcoma: Curie Institute experience and critical review of the literature

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. 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. 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. 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.

Ultrasonography findings of proximal-type epithelioid sarcoma of the vulva: A case report.

Proximal-type epithelioid sarcoma (PES) of the vulva is an exceedingly rare malignant soft tissue tumor. We herein present the case of a 41-year-old female patient who presented to our hospital with complaints of a painless mass in the right mons pubis that she had first noticed 3 years prior. Ultrasonographic (US) and color Doppler ultrasonographic (CDUS) examination revealed a solid mass with well-defined, homogeneous hypoechoic structure and quite hypervascular on CDUS. The results of the immunohistochemical examination confirmed the diagnosis of vulvar PES (myxoid variant). The patient was treated with wide local excision and remained recurrence- and metastasis-free at 9 months postoperatively. Although cases of PES in the pelvic region had been previously reported, to the best of our knowledge, the US or CDUS findings of PES of the vulva have not been described to date.

Immunohistochemical Biomarkers of Mesenchymal Neoplasms in Endocrine Organs: Diagnostic Pitfalls and Recent Discoveries.

Mesenchymal neoplasms rarely present in or adjacent to endocrine organs. In this context, the recognition of these rare tumor types can be challenging, with significant potential for misdiagnosis as sarcomatoid carcinomas (i.e., anaplastic thyroid carcinoma and sarcomatoid adrenal cortical carcinoma) or neuroendocrine carcinomas, depending upon the dominant histologic patterns. In this review, we address potential pitfalls in diagnosing selected mesenchymal neoplasms arising within or near endocrine organs, including dedifferentiated liposarcoma, synovial sarcoma, angiosarcoma, PEComa, proximal-type epithelioid sarcoma, Ewing sarcoma, and neuroblastoma. For each of these tumor types, we review clinical and pathologic features, histologic clues to distinguish them from endocrine neoplasms, and recently developed immunohistochemical markers that can be particularly useful for establishing the correct diagnosis.

Proximal-Type Epithelioid Sarcoma in Skull Base: a Pathological Diagnosis Challenge with Other Intracranial Tumors

Proximal-type ES (PES) is a rare and aggressive sarcoma originated from soft tissues with uncertain differentiation. It mainly affects middle-aged patients and often locates in proximal extremity and deep-seated tissues. Only one case of PES located in the skull base has been reported to date. Herein, we report two cases of PES occurred in the middle cranial fossa in two middle-aged Chinese women. Microscopically, the tumors were consisted of epithelial-like cells with or without rhabdoid cells. And frequent mitotic activity and coagulation necrosis were present. Immunohistochemically, tumor cells in the two cases were positive for vimentin, AE1/AE3, epithelial membrane antigen (EMA), CD34, and synaptophysin. A few number of tumor cells expressed CD56. They were completely negative for integrase interactor-1 (INI1). Besides, TP53 positive cells were observed (>50%) in the two cases. The MIB-1 proliferation index was high up to 50-70%. Fluorescence in situ hybridization showed the monoallelic deletions of INI1. Intracranial PES is needed to identify with other mimic tumors, especially rhabdoid meningioma, epithelioid MPNST and adult AT/RT. The prognosis of the two patients was very poor. They died respectively less than a month and half a month after surgery. Tumor grew rapidly and was easy to infiltrate into the surrounding tissues. It may suggest that the prognosis of PES occurred at the base of skull was worse than in other sites.

Secondary EWSR1 gene abnormalities in SMARCB1-deficient tumors with 22q11-12 regional deletions: Potential pitfalls in interpreting EWSR1 FISH results.

SMARCB1 inactivation occurs in a variety of tumors, being caused by various genetic mechanisms. Since SMARCB1 and EWSR1 genes are located close to each other on chromosome 22, larger SMARCB1 deletions may encompass the EWSR1 locus. Herein, we report four cases with SMARCB1-deletions showing concurrent EWSR1 gene abnormalities by FISH, which lead initially to misinterpretations as EWSR1-rearranged tumors. Our study group included various morphologies: a poorly differentiated chordoma, an extrarenal rhabdoid tumor, a myoepithelial carcinoma, and a proximal-type epithelioid sarcoma. All cases showed loss of SMARCB1 (INI1) by immunohistochemistry (IHC) and displayed characteristic histologic features for the diagnoses. The SMARCB1 FISH revealed homozygous or heterozygous deletions in three and one case, respectively. The co-hybridized EWSR1 probes demonstrated either unbalanced split signals or heterozygous deletion in two cases each. The former suggested bona fide rearrangement, while the latter resembled an unbalanced translocation. However, all the FISH patterns were quite complex and distinct from the simple and uniform split signals seen in typical EWSR1 rearrangements. We conclude that in the context of 22q11-12 regional alterations present in SMARCB1-deleted tumors, simultaneous EWSR1 involvement may be misinterpreted as equivalent to EWSR1 rearrangement. A detailed clinicopathologic correlation and supplementing the EWSR1 FISH assay with complementary methodology is mandatory for correct diagnosis. © 2016 Wiley Periodicals, Inc.

Proximal-type epithelioid sarcoma: a new case report and literature review

Proximal-type epithelioid sarcoma is a rare soft tissue neoplasm which arises from the more proximal part of body and occurs more often in young people; the definite diagnosis depends mainly on the pathological examination; early detection and complete excision remain the foundation of treatment. Due to its aggressive behavior, high capacity of recurrence and the great ability to metastasize, a careful clinical long-term monitoring is required. We report a new case of a 20 years old girl, presented with proximal-type epithelioid sarcoma in her right scapular region, confirmed by pathological examination and removed surgically without recurrence or metastasis at eighteen months of follow-up.

Epithelioid Sarcoma: Diagnostic Features and Genetics.

Epithelioid sarcoma (ES) is a rare, aggressive soft-tissue neoplasm of uncertain differentiation, characterized by nodular aggregates of epithelioid cells, which are immunoreactive to cytokeratins (CKs) and epithelial membrane antigen, and often for CD34. It has a propensity for multifocal disease at presentation, local recurrence, and regional metastasis. These are aggressive neoplasms with particularly poor prognosis after regional or distant metastatic disease, for which surgical resection is still the mainstay of treatment, and options for patients with metastatic disease remain undefined. There are 2 distinct variants: classic ES, which typically presents as a subcutaneous or deep dermal mass in the distal extremities of young adults and comprises nodular distributions of relatively uniform epithelioid cells with central necrosis, and the proximal variant, which has a predilection for proximal limbs and limb girdles and the midline of the trunk, which is composed of sheets of larger, more atypical cells with variable rhabdoid morphology. Both classic and proximal-type ESs are associated with the loss of SMARCB1/INI1 protein expression, but appear otherwise molecularly relatively heterogeneous. We review classic and proximal-type ES, discussing morphology, immunohistochemical and genetic findings, the differential diagnosis, and the future potential for targeted therapies.

Diagnosis and treatment of epithelioid sarcoma

To analyze the clinical features, diagnosis, treatment, and prognosis of epithelioid sarcoma (ES). The clinical data of 13 cases with epithelioid sarcoma in the Tianjin Medical University Cancer Institute and Hospital from March 1995 to December 2009 were collected and analyzed. There were 10 males and 3 females in the group, with an average age of 41.5 years (range: 13 to 68 years). Nine patients had classic ES and 4 had proximal-type ES. Surgery was the mainstay of treatment. After the operation, four patients received radiotherapy, five received chemotherapy, and one received chemoradiotherapy. Of the 13 cases, only 1 had multi-locus lesion. The average tumor size was (6.07 ± 1.34) cm. The lymph node involvement was found in 46.2% of the patients. Local and distant failure occurred in 50% and 30% patients, respectively. The most common site for dissemination was the lung. Four cases died within 3 years after initial operation. The 1-, 2-, 5-, 10-year overall survival rates of the 11 cases were 72.7%, 54.5%, 27.3% and 9.1%, respectively, with a median survival time of 27 months. Epithelioid sarcoma is a rare disease. The prognosis for patients with epithelioid sarcoma is poor because of a high propensity for local recurrence, lymph node metastases, and/or distant metastases. The definite diagnosis depends mainly on the pathologic examination. Wide surgical excision is the mainstay treatment, and radiation and chemotherapy have been used occasionally as adjuvant therapy but have had limited success.

SMARCB1-deficient Vulvar Neoplasms: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 14 Cases.

Loss of expression of the SMARCB1 (INI1/BAF47/SNF5) tumor-suppressor protein, originally identified in pediatric malignant rhabdoid tumors, has been noted in significant percentages of epithelioid sarcomas of classical and proximal-type and in myoepithelial carcinomas. Epithelioid sarcoma and myoepithelial carcinoma are very rare in the vulvar region, and few of these cases have been evaluated for SMARCB1 protein loss by immunohistochemistry (IHC) or for SMARCB1 gene alterations by molecular genetic techniques. We studied the clinicopathologic, IHC, and molecular genetic features of 14 SMARCB1-deficient vulvar neoplasms. All available routinely stained sections were reexamined, and IHC analysis for wide-spectrum cytokeratins, high-molecular weight cytokeratins, epithelial membrane antigen, S100 protein, CD34, smooth muscle actin, desmin, and SMARCB1 was performed. Multiplex ligation-dependent probe amplification and DNA sequencing of the SMARCB1 gene was performed on 12 cases with sufficient available tissue. The 14 vulvar tumors occurred in adult women (mean age 46 y, range 22 to 62 y) and measured 1.1 to 8.8 cm in size (mean 4.7 cm). Tumors were classified as classical-type epithelioid sarcoma (N=1), proximal-type epithelioid sarcoma (N=6), myoepithelial carcinoma (N=4), and "SMARCB1-deficient vulvar sarcoma, not otherwise specified" (N=3) on the basis of combined histopathologic and IHC findings. One myoepithelial carcinoma showed divergent rhabdomyoblastic differentiation. All tested cases showed partial or complete SMARCB1 deletions (homozygous: 9 cases; heterozygous: 3 cases). One case with a heterozygous deletion also showed a c.528delC mutation in exon 5. Fluorescence in situ hybridization for EWSR1 rearrangement was performed for 3 cases classified as myoepithelial carcinoma and was negative. Follow-up (13 patients, range 5 to 72 mo, mean 31 mo) data showed 3 patients dead of disease, 1 alive with unresectable metastatic disease, 1 alive with radiographic evidence of extensive lymph nodal disease, and 8 alive without disease. We conclude that SMARCB1-deficient vulvar neoplasms chiefly comprise epithelioid sarcoma and myoepithelial carcinoma, although some defy easy classification. No association was seen between clinical behavior and the type of SMARCB1 alteration.