Intra-abdominal EWSR1/FUS-CREM-rearranged malignant epithelioid neoplasms: two cases of an emerging aggressive entity with emphasis on misleading immunophenotype

AbstractCREB family (CREB1, ATF1, and CREM) gene fusions are defining markers in diverse mesenchymal neoplasms (clear cell sarcoma, angiomatoid fibrous histiocytoma, and others). However, neoplasms harboring EWSR1-CREM/FUS-CREM fusions are rare and poorly characterized. We describe two cases (55-year-old male with 7.5 cm renal mass and 32-year-old female with 5.5 cm mesenteric mass) illustrating their misleading immunophenotypes. Histologically, both showed eosinophilic and focally clear epithelioid cells arranged into sheets, nests, and trabeculae. Immunohistochemistry showed ALK, EMA, and AE1/AE3 immunoreactivity suggesting ALK-rearranged renal cell carcinoma (Case 1) and coexpression of keratin, EMA, synaptophysin, and chromogranin-A, suggesting neuroendocrine neoplasm (Case 2). Targeted RNA sequencing revealed EWSR1-CREM (Case 1) and FUS-CREM (Case 2) fusions. These cases add to the spectrum of CREM fusion-positive intra-abdominal epithelioid neoplasms. Their unusual immunophenotype and unexpected sites represent major pitfalls, underline a wide differential diagnosis, and emphasize the value of molecular testing in correctly diagnosing them.

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Clear Cell Sarcoma–like Tumor of the Gastrointestinal Tract: An Evolving Entity

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2013-0547-rs ◽

2015 ◽

Vol 139 (3) ◽

pp. 407-412 ◽

Cited By ~ 34

Author(s):

Jayson Wang ◽

Khin Thway

Keyword(s):

Gastrointestinal Tract ◽

Clear Cell ◽

S100 Protein ◽

Malignant Neoplasm ◽

Clear Cell Sarcoma ◽

Current Status ◽

Gene Fusions ◽

Epithelioid Cells ◽

Cell Sarcoma ◽

Clear Cytoplasm

Clear cell sarcoma–like tumor of the gastrointestinal tract (CCSLGT) is a rare malignant neoplasm that occurs in the wall of the small bowel, stomach, or large bowel, predominantly in young adults. It is an aggressive neoplasm that frequently presents with metastatic disease and has a high mortality rate. Histologically, it is usually composed of medium-sized primitive ovoid or epithelioid cells with pale or clear cytoplasm that are arranged in sheets or in papillary or alveolar architectures. Clear cell sarcoma–like tumor of the gastrointestinal tract is positive for S100 protein, invariably negative for melanocyte-specific markers and is often also positive for neuroendocrine markers. The etiology of CCSLGT is unknown, but many studies have shown associations with EWSR1-CREB1 gene fusions and, less frequently, with EWSR1-ATF1 fusions. Here, we discuss the current status of CCSLGT, including histologic, immunophenotypic, and molecular findings.

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Utilization of Fluorescence In Situ Hybridization in the Diagnosis of 230 Mesenchymal Neoplasms: An Institutional Experience

Archives of Pathology & Laboratory Medicine ◽

10.5858/2009-0571-oar.1 ◽

2010 ◽

Vol 134 (12) ◽

pp. 1797-1803 ◽

Cited By ~ 2

Author(s):

Munir R. Tanas ◽

Brian P. Rubin ◽

Raymond R. Tubbs ◽

Steven D. Billings ◽

Erinn Downs-Kelly ◽

...

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Clear Cell ◽

Clear Cell Sarcoma ◽

Low Grade ◽

Nerve Sheath Tumor ◽

High Grade ◽

Round Cell ◽

Mesenchymal Neoplasms

Abstract Context—Mesenchymal neoplasms harbor characteristic translocations and amplification of gene regions amenable to evaluation by fluorescence in situ hybridization (FISH). Objective—To determine the utility of FISH in the diagnosis of mesenchymal neoplasms. Design—Two hundred thirty soft tissue cases analyzed by FISH were reviewed retrospectively. Results—Morphologic patterns where FISH was used included high-grade round cell sarcomas (n = 67), nonmyogenic spindle cell sarcomas (n = 40), low-grade myxoid neoplasms (n = 34), adipocytic neoplasms (n = 20), and melanocytic neoplasms (n = 19). Fifty cases did not fit into the previously mentioned categories. SYT FISH (96% of monophasic synovial sarcomas were positive; 0% of malignant peripheral nerve sheath tumor were positive) and DDIT3 FISH (100% of myxoid/round cell liposarcomas; no other neoplasm positive) were very sensitive and specific. EWSR1 FISH was very sensitive and specific in the differential diagnosis of melanocytic neoplasms (88% of clear cell sarcomas were positive; all melanomas were negative). EWSR1 FISH was sensitive among high-grade round cell sarcomas (positive in 100% of desmoplastic small round cell tumors and 96% of Ewing sarcoma/primitive neuroectodermal tumors) but not specific because clear cell sarcoma, extraskeletal myxoid chondrosarcoma, and a subset of round cell liposarcomas also harbor rearrangements of EWSR1. FUS FISH was very sensitive in detecting low-grade fibromyxoid sarcomas (91% positive) but not specific because most myxoid/round cell liposarcomas also contain rearrangements of FUS. All atypical lipomatous tumors were positive for amplification of MDM2, whereas all lipomas were negative. FOXO1A FISH was positive in ∼70% of cases of alveolar rhabdomyosarcoma. Conclusion—FISH is a useful adjunct in the diagnosis of mesenchymal neoplasms.

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Simultaneous Clear Cell Sarcomas of the Duodenum and Jejunum

Case Reports in Medicine ◽

10.1155/2016/1534029 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Maitham A. Moslim ◽

Gavin A. Falk ◽

Michael Cruise ◽

Gareth Morris-Stiff

Keyword(s):

Clear Cell ◽

Mass Effect ◽

Clear Cell Sarcoma ◽

Gastrointestinal Tumor ◽

Epithelioid Cells ◽

Microscopic Evaluation ◽

Resection Specimen ◽

The Subject ◽

Disease Free

Clear cell sarcoma (CCS) is an uncommon tumor that usually presents as an extremity mass but can rarely manifest as a gastrointestinal tumor with a diverse spectrum of symptoms, most commonly related to a mass effect or ulceration. Herein we report a case in which two separate tumors, one in the duodenum and the other in the jejunum, present concurrently. The subject presented with symptomatic anemia and underwent imaging and endoscopic studies that culminated in the discovery of the two lesions. He subsequently underwent operative treatment with resection of both tumors and made an unremarkable recovery. The resection specimen consisted of two separate clear cell sarcomas with negative margins. Under microscopic evaluation, they demonstrated nested growths of epithelioid cells with scattered spindled cells infiltrating the enteric wall. The neoplastic cells were positive for S100 with scattered expression of Melan A. Florescence in situ hybridization revealed a translocation at the EWRS1 locus. He was disease-free for 30 months following the procedure; then he developed a rapidly progressing metastatic disease with subsequent death 4 months later.

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Malignant tumours of soft tissues

10.1093/med/9780199550647.003.002004 ◽

2011 ◽

Author(s):

Rej S. Bhumbra ◽

Panagiotis D. Gikas ◽

Sammy Hanna ◽

Jakub Jagiello ◽

Stephen R. Cannon

Keyword(s):

Soft Tissue ◽

Peripheral Nerve ◽

Soft Tissues ◽

Clear Cell ◽

Fibrous Histiocytoma ◽

Epithelioid Sarcoma ◽

Clear Cell Sarcoma ◽

Malignant Tumours ◽

Cell Sarcoma ◽

Nerve Sheath

♦ Malignant vascular tumours of soft tissue♦ Synovial sarcoma♦ Malignant peripheral nerve sheath tumours♦ Rhabdomyosarcoma♦ Leiomyosarcoma♦ Epithelioid sarcoma♦ Clear cell sarcoma♦ Malignant fibrous histiocytoma♦ Chordoma.

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