Clear Cell Sarcoma-like Tumor with Osteoclast-like Giant Cells in the Small Bowel: Further Evidence for a New Tumor Entity

Friedrichs, Nicolaus; Testi, Maria Adele; Moiraghi, Luisa; Modena, Piergiorgio; Paggen, Ellen; Plötner, Andreas; Wiechmann, Volker; Mantovani-Löffler, Luisa; Merkelbach‐Bruse, Sabine; Buettner, Reinhard; Wardelmann, Eva

doi:10.1177/106689690501300402

Cited by 61 publications

(47 citation statements)

References 12 publications

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“…In spite of the negativity for melanocytic markers, the morphologic appearance coupled with the t(12;22) translocation supports a diagnosis of CCS in such cases. Although all three of our EWS-CREB1-positive CCS lacked melanocytic expression by immunohistochemistry, this was also noted in four of eight previously reported EWS-ATF1-positive CCS of the gastrointestinal tract (9,21,23,24), suggesting that gastrointestinal location rather than the fusion transcript type might determine the lack of melanocytic differentiation. Furthermore, two additional gastrointestinal CCS from our files (not previously reported, see Supplementary Table S1), showing either EWS-ATF1 by RT-PCR or EWS rearrangement by FISH lacked evidence of melanocytic differentiation by immunohistochemistry.…”

Section: Discussionmentioning

confidence: 74%

“…Microscopically, the predominant pattern is of nested or solid growth of small epithelioid cells with amphophilic or clear cytoplasm and uniform nuclei with conspicuous nucleoli. However, certain cases contain somewhat distinctive morphologic features, due to a component of admixed reactive, KP1-positive, and osteoclast-type giant cells (9,23). One of our cases showed a similar, although very minor, component of osteoclast-type giant cells.…”

Section: Discussionmentioning

confidence: 87%

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EWS-CREB1: A Recurrent Variant Fusion in Clear Cell Sarcoma—Association with Gastrointestinal Location and Absence of Melanocytic Differentiation

Antonescu

Nafa²,

Segal³

et al. 2006

Clinical Cancer Research

301

267

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Purpose: Clear cell sarcoma (CCS) usually arises in the lower extremities of young adults and is typically associated with a t(12;22) translocation resulting in the fusion of EWS (EWSR1) with ATF1, a gene encoding a member of the cyclic AMP^responsive element binding protein (CREB) family of transcription factors. CCS arising in the gastrointestinal tract is rare and its pathologic and molecular features are not well defined. Experimental Design: We report a novel variant fusion of EWS to CREB1, a gene at 2q32 encoding another CREB family member highly related to ATF1, detected in three women with gastrointestinal CCS. All three cases contained an identical EWS-CREB1 fusion transcript that was shown by reverse transcription-PCR. In two of the cases tested, EWS gene rearrangement was also confirmed by fluorescence in situ hybridization and the EWS-CREB1 genomic junction fragments were isolated by long-range DNA PCR. Results: Morphologically, all three tumors lacked melanin pigmentation. By immunohistochemistry, there was a strong and diffuse S100 protein reactivity, whereas all melanocytic markers were negative. Ultrastructurally, two of the cases lacked melanosomes. The melanocyte-specific transcript of MITF was absent in two cases, and only weakly expressed in the third case. The Affymetrix gene expression data available in one case showed lower expression of the melanocytic genes MITF, TYR, and TYRP1, compared with four EWS-ATF1-positive CCSs of non-gastrointestinal origin. Conclusions: EWS-CREB1 may define a novel subset of CCS that occurs preferentially in the gastrointestinal tract and shows little or no melanocytic differentiation. Thus, evidence of melanocytic lineage or differentiation is not a necessary feature of sarcomas with gene fusions involving CREB family members.Clear cell sarcoma (CCS), also known as melanoma of soft parts, typically presents in the deep soft tissues of the lower extremity, in close proximity to tendons, fascia, or aponeuroses. Young adults are preferentially affected and the clinical course is often marked by regional and distant metastases. Most CCS show immunoreactivity for melanoma markers, such as HMB45, and contain melanosomes. Indeed, most CCS share a melanocytic gene expression signature with melanomas (1). However, CCS are also genetically distinct from melanomas, as they lack BRAF mutations (2) and show, in most cases, a recurrent chromosomal translocation t(12;22)(q13;q12), resulting in the fusion of the EWS gene (also known as EWSR1) on 22q12 with the activating transcription factor-1 gene (ATF1) on 12q13 (3 -6).Primary CCSs of the gastrointestinal tract are rare (7,8). Gastrointestinal CCS includes a histologic variant rich in osteoclast-type giant cells which uniformly express S100 protein, but lack melanocytic differentiation by immunohistochemistry, being negative for HMB45 and Mart-1 (9). As a result of its rarity in the gastrointestinal tract, the differential diagnosis of CCS in this site includes more common mesenchymal or neuroectodermal neoplasms,...

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 87%

EWS-CREB1: A Recurrent Variant Fusion in Clear Cell Sarcoma—Association with Gastrointestinal Location and Absence of Melanocytic Differentiation

Antonescu

Nafa²,

Segal³

et al. 2006

Clinical Cancer Research

301

267

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“…Nucleoli are most often small and inconspicuous, although occasionally there are macronucleoli. Spindling of cells is a rarer feature, as are large epithelioid cells 5 and pleomorphism (Figure 3), 19 which can also occur in gastrointestinal CCS with EWSR1-ATF1 fusion transcripts. 20 Architecturally, cells are most often arranged in diffuse sheets or more ill-defined nests (Figures 2 through 4), without the well-formed nests typical of CCS.…”

Section: Pathologic Features Of Ccslgt Morphologymentioning

confidence: 99%

“…S100 protein positivity has been seen in all 38 CCSLGTs where it was performed, whereas the melanocyte-specific markers were negative in all CCSLGTs studied. 1,2,[5][6][7][8][9][10][11][12][13][14] This is in contrast to conventional-type CCSs occurring in the gastrointestinal tract, most of which are positive for S100 protein as well as melanocyte-specific antigens. There is now increasing evidence that many CCSLGTs also express neuroendocrine markers ( Figure 9).…”

Section: Ancillary Studies Immunohistochemistry and Electron Microscopymentioning

confidence: 99%

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

Wang

Thway

2015

Archives of Pathology &Amp; Laboratory Medicine

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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 melanocytespecific 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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“…This latter site is extremely rare. To date, 15 genetically confirmed cases of gastrointestinal CCS have been reported, of which seven where located in the ileum [1,2,4,5,9,10,13,17,22,[27][28][29]. In this study, we report an adjunctive case of CCS arising in the ileum and discuss the tumor diagnosis approach, the importance of molecular genetics in tumor diagnostics, along with a review of the literature on the clinicopathological characters of this rare tumor.…”

Section: Introductionmentioning

confidence: 81%

Clear cell sarcoma of the ileum: report of a case and review of literature

et al. 2007

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Clear cell sarcoma (CCS) is a high grade soft tissue sarcoma with a distinct molecular profile and with morphological features resembling those of melanoma. CCS has been rarely described in other locations other than the soft tissues, including the gastrointestinal tract. In this study, we report a case of CCS arising in the ileum of a 31-year-old woman. Histologically, the tumor involved the entire thickness of the intestinal wall. Tumor cells were polygonal or fusiform, with clear or eosinophilic cytoplasm, arranged in a uniform nested to fascicular growth pattern. Immunohistochemical studies revealed strong positivity for vimentin and S-100 protein. HMB-45, Melan-A, tyrosinase, cytokeratins, EMA, smooth muscle actin, CD34, CD31, CD117, CD99, synaptophysin, chromogranin A, CD56, and NSE were negative. Fluorescence in situ hybridization analysis demonstrated the presence of a t(12;22)(q13;q12) translocation, the diagnostic hallmark of CCS of soft parts. The present case, together with a detailed review of the literature on this topic, demonstrates that the gastrointestinal tract is a possible site of CCS of soft tissues and that making a reliable diagnosis of this tumor requires cytogenetic or molecular diagnostic investigations.

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Clear Cell Sarcoma-like Tumor with Osteoclast-like Giant Cells in the Small Bowel: Further Evidence for a New Tumor Entity

Cited by 61 publications

References 12 publications

EWS-CREB1: A Recurrent Variant Fusion in Clear Cell Sarcoma—Association with Gastrointestinal Location and Absence of Melanocytic Differentiation

EWS-CREB1: A Recurrent Variant Fusion in Clear Cell Sarcoma—Association with Gastrointestinal Location and Absence of Melanocytic Differentiation

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

Clear cell sarcoma of the ileum: report of a case and review of literature

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