Visceral Clear Cell Sarcoma of Soft Tissue with Confirmation by EWS-ATF1 Fusion Detection

Abstract

Clear cell sarcoma of soft tissue (CCS-ST) is a rare malignant neoplasm characterized by a tumor-defining translocation [t(12;22) (q13;q12)], resulting in the EWS-ATF1 gene fusion. An extremely limited number of visceral CCS-ST cases have been reported in the literature. Here the authors report a visceral CCS-ST in a Hispanic adolescent male with a large infiltrative mass involving the small bowel. The tumor was evaluated by light microscopy, immunocytochemistry, electron microscopy, cytogenetics, and molecular genetics. The tumor cells were strongly positive for S-100 protein, but negative for HMB-45. Rare premelanosomes were identified only after an extensive search with electron microscopy. Cytogenetics showed a characteristic t(12;22)(q13;q12) for CCS-ST with isochromosome 18q and trisomy 22. An EWS exon 8 sense primer and an antisense ATF1 primer were employed for detection of the CCS-ST tumor-defining EWS-ATF1 translocation, using reverse transcriptase-polymerase chain reaction techniques (RT-PCR), and the fusion gene breakpoint underwent DNA sequencing. This tumor is exceptional, because it is the first visceral CCS-ST that has been confirmed by RT-PCR and DNA sequencing. This case also illustrates the necessity of a multimodal approach to tumor diagnosis, and the utility of cytogenetics and molecular pathology in confirming the diagnosis of CCS-ST and eliminating conventional metastatic or primary visceral malignant melanoma as a consideration.

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

“…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).…”

“…No melanosomes or melanosome-like structures have been identified, although premelanosomes were very occasionally seen in one case. 7 Stockman et al 13 performed electron microscopy on 5 CCSLGTs, of which 4 contained dense-core secretory granules, consistent with neuroendocrine differentiation. Some also showed synapselike structures, and one showed neuroaxonal and Schwannian-like features.…”

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

“…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.…”

“…The nuclei are typically vescicular with prominent nucleoli. Within genetically confirmed CCSs, the presence of CD68-positive osteoclast-like multinucleated giant cells has been reported in four [2,9,13,29] of 16 cases, whereas multinucleated HMB-45-positive tumor cells, which are commonly seen in soft tissue CCS, were described only in one case [4]. At this point, it is worthwhile to mention the description of a major number of gastrointestinal neoplasms containing CD68-positive osteoclast-like multinucleated giant cells with morphological features resembling those of CCS lacking molecular confirmation.…”

Clear Cell Sarcoma of Soft Tissue: Diagnostic Dilemma in Cytologic Appearance

“…There have been a few articles in the medical literature reporting on possible errors in microscopic observation. 2,3 We report the presence of 2 structures ( Figure 1A) found in a routine sputum smear stained by the Papanicolaou method in a 58-year-old man with chronic cough and episodes of hemoptysis. Initially, the structures observed on the smear were considered to be contaminants, but, because of the structures' shape and size, the possibility of the presence of helminth eggs (Toxocara spp.)…”