Showing papers on "Clear-cell sarcoma published in 2017"

EWSR1 Fusions With CREB Family Transcription Factors Define a Novel Myxoid Mesenchymal Tumor With Predilection for Intracranial Location

Abstract: Recurrent gene fusions involving EWSR1 with members of the cAMP response element binding protein (CREB) family (ATF1 and CREB1) have been reported in a diverse group of tumors including angiomatoid fibrous histiocytoma (AFH), soft tissue and gastrointestinal clear cell sarcoma, primary pulmonary myxoid sarcoma, and hyalinizing clear cell carcinoma of salivary gland. We have recently encountered a group of 5 myxoid mesenchymal tumors positive for EWSR1 fusions with one of the CREB family member (ATF1, CREB1, and CREM), with histologic features distinct from any of the previously described pathologic entities. Tumors occurred in children or young adults (12 to 23 y; mean, 18 y), with equal sex distribution. All except 1 were intracranial (intra-axial, 2; meningeal, 2), whereas 1 was perirectal. Histologically, the tumors were well circumscribed, often lobulated, composed of uniform ovoid to round cells, and arranged in cord-like or reticular structures in a myxoid background. All except 1 displayed unique sunburst amianthoid fibers. Immunohistochemically, tumors were positive for epithelial membrane antigen (5/5; 4 focal, 1 diffuse) and desmin (3/5). A novel EWSR1-CREM fusion was identified by RNA sequencing in the perirectal tumor, which was further confirmed by fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). A second case with similar EWSR1-CREM fusion was identified by RT-PCR and FISH in a meningeal tumor. The remaining cases studied by FISH showed the presence of EWSR1-CREB1 fusion in 2 cases and EWSR1-ATF1 in 1. In conclusion, we report a distinct group of myxoid mesenchymal neoplasms occurring in children or young adults with a predilection for intracranial locations. Although the immunoprofile [epithelial membrane antigen (EMA), desmin] and the fusion type raise the possibility of a myxoid AFH, none of the typical histologic findings of AFH were present, suggesting a novel entity.

Primary Renal Sarcomas With BCOR-CCNB3 Gene Fusion: A Report of 2 Cases Showing Histologic Overlap With Clear Cell Sarcoma of Kidney, Suggesting Further Link Between BCOR-related Sarcomas of the Kidney and Soft Tissues.

Abstract: We report 2 primary renal sarcomas demonstrating BCOR-CCNB3 gene fusions that have recently been identified in undifferentiated round cell sarcomas of bone and soft tissue. These neoplasms occurred in male children aged 11 and 12 years, and both were cystic as a result of entrapment and dilatation of native renal tubules. Both cases were composed of variably cellular bland spindle cells with fine chromatin set in myxoid stroma and separated by a branching capillary vasculature. Both neoplasms demonstrated immunoreactivity for BCOR, cyclin D1, TLE1, and SATB2 in the spindle neoplastic cells and negativity in the prominent capillary vasculature. One case was extensively cystic and had hypocellular areas that simulated cystic nephroma; this neoplasm recurred 3 years later as a solid, highly cellular spindle cell sarcoma in the abdominal cavity. The morphology and immunoprofile of these renal neoplasms was compared with a control group of other sarcomas with BCOR genetic abnormalities, including clear cell sarcoma of the kidney (CCSK), infantile undifferentiated round cell sarcomas of soft tissue/primitive myxoid mesenchymal tumor of infancy, and bone/soft tissue sarcomas with BCOR-CCNB3 gene fusion; along with primary renal synovial sarcoma. Our findings show that the renal sarcomas with BCOR-CCNB3 gene fusion overlap with CCSK. These results are in keeping with a "BCOR-alteration family" of renal and extrarenal neoplasms which includes CCSK and undifferentiated round cell sarcomas of soft tissue/primitive myxoid mesenchymal tumor of infancy (which typically harbor BCOR internal tandem duplication), and BCOR-CCNB3 sarcomas, all of which are primarily driven by BCOR overexpression and have overlapping (but not identical) clinicopathologic features.

The spectrum of EWSR1 -rearranged neoplasms at a tertiary sarcoma centre; assessing 772 tumour specimens and the value of current ancillary molecular diagnostic modalities

Abstract: EWSR1 rearrangements were first identified in Ewing sarcoma, but the spectrum of EWSR1-rearranged neoplasms now includes many soft tissue tumour subtypes including desmoplastic small round cell tumour (DSRCT), myxoid liposarcoma (MLPS), extraskeletal myxoid chondrosarcoma (EMC), angiomatoid fibrous histiocytoma (AFH), clear cell sarcoma (CCS) and myoepithelial neoplasms. We analysed the spectrum of EWSR1-rearranged soft tissue neoplasms at our tertiary sarcoma centre, by assessing ancillary molecular diagnostic modalities identifying EWSR1-rearranged tumours and reviewing the results in light of our current knowledge of these and other Ewing sarcoma-like neoplasms. We retrospectively analysed all specimens tested for EWSR1 rearrangements by fluorescence in situ hybridisation (FISH) and/or reverse transcription–PCR (RT–PCR) over a 7-year period. There was a total of 772 specimens. FISH was performed more often than RT–PCR (n=753, 97.5% vs n=445, 57.6%). In total, 210 (27.9%) specimens were FISH-positive for EWSR1 rearrangement compared to 111 (14.4%) that showed EWSR1 fusion transcripts with RT–PCR. Failure rates for FISH and RT–PCR were 2.5% and 18.0%. Of 109 round cell tumours with pathology consistent with Ewing sarcoma, 15 (13.8 %) cases were FISH-positive without an identifiable EWSR1 fusion transcript, 4 (3.7%) were FISH-negative but RT–PCR positive and 4 (3.7%) were negative for both. FISH positivity for DSRCT, MLPS, EMC, AFH and CCS was 86.3%, 4.3%, 58.5%, 60.0% and 87.9%, respectively. A positive FISH result led to diagnostic change in 40 (19.0%) EWSR1-rearranged cases. 13 FISH-positive cases remained unclassifiable. FISH is more sensitive for identifying EWSR1 rearrangements than RT–PCR. However, there can be significant morphologic and immunohistochemical overlap between groups of EWSR1-rearranged neoplasms, with important prognostic and therapeutic implications. FISH and RT–PCR should be used as complementary modalities in diagnosing EWSR1-rearranged neoplasms, but as tumour groups harbouring EWSR1 rearrangements are increasingly characterised and because given translocations involving EWSR1 and its partner genes are not always specific for tumour types, it is critical that these are evaluated by specialist soft tissue surgical pathologists noting the morphologic and immunohistochemical context. As RT–PCR using commercial primers is limited to only the most prevalent EWSR1 fusion transcripts, the incorporation of high-throughput sequencing technologies into the standard diagnostic repertoire to assess for multiple molecular abnormalities of soft tissue tumours in parallel (including detection of newly characterised Ewing sarcoma-like tumours) might be the most effective and efficient means of ancillary diagnosis in future.

Cutaneous Melanocytoma With CRTC1-TRIM11 Fusion: Report of 5 Cases Resembling Clear Cell Sarcoma.

Abstract: We report 5 cases of primary intradermal nodular unpigmented tumors with a melanocytic immunophenotype associated with a novel CRTC1-TRIM11 fusion. Clinically, the cutaneous nodules were slowly growing in 3 women and 2 men (25 to 82 y old, median, 28 y) with no specific topography. Lesion size ranged from 4 to 12 mm (median, 5 mm). The tumors were strictly located in the dermis with a nodular pattern. The cells were arranged in confluent nests and fascicules. Central fibronecrotic areas were present in 2 cases. Cells were medium to large, sometimes multinucleated, and presented a spindled and epithelioid cytology with prominent nucleoli. Cytonuclear atypia was constant, and mitotic activity in hotspot areas ranged from 1 to 5/mm². Immunohistochemistry found a constant positivity with S100, MiTF, and Sox10, and a heterogenous staining by MelanA or HMB45. NTRK1 was strongly positive in 3 cases. In all cases, RNA sequencing found an invariable CRTC1(e1)-TRIM11(e2) fusion, confirmed by fluorescent in situ hybridization techniques with a TRIM11 break-apart probe. In 4/4 cases, nuclear TRIM11 expression was positive by immunohistochemistry. Fluorescent in situ hybridization techniques showed no rearrangement of NTRK1 or EWSR1, and array-comparative genomic hybridization displayed no alteration (1 case) or only a whole chromosome 7 gain (2 cases) when performed. No relapse or metastatic event was observed during follow-up [3 to 72 months (median, 14 mo)]. Cutaneous clear cell sarcoma was the main differential diagnosis. Overlapping morphologic features previously described in primary dermal melanomas and paraganglioma-like melanocytic tumors were present. The CRTC1-TRIM11 fusion appears to be specific of an unpigmented nodular tumor combining a melanocytic phenotype and low-grade tumor behavior.

Clinical benefit of antiangiogenic therapy in advanced and metastatic chondrosarcoma

Abstract: Chondrosarcoma is the most common bone sarcoma in adults. Conventional chondrosarcoma, the commonest histological subtype, is largely resistant to anthracycline-based chemotherapy. There have been anecdotal reports of durable clinical benefit with antiangiogenic agents in this disease. A retrospective search of patients treated at three sarcoma referral centers was performed to identify patients with advanced chondrosarcoma treated with antiangiogenic agents. The aim of this study was to evaluate the efficacy and safety of antiangiogenic agents in advanced chondrosarcoma. Ten patients were identified; seven with conventional, one each with clear cell, extraskeletal mesenchymal chondrosarcoma and extraskeletal myxoid chondrosarcoma. The median progression-free survival for patients with conventional and clear cell sarcoma was 22.6 months. Median overall survival has not been met. Antiangiogenic therapy was well tolerated in this series of patients. Our retrospective data suggest that antiangiogenic therapy can provide prolonged clinical benefit in advanced chondrosarcoma patients. Further prospective trials are required to precisely define the role of this class of agent in advanced chondrosarcoma.

Malignant gastrointestinal neuroectodermal tumor: a case report and review of the literature.

Abstract: Malignant gastrointestinal neuroectodermal tumor (GNET) is an extremely rare entity that was first described by Zambrano et al. in 2003 as “Clear cell sarcoma-like tumor of the gastrointestinal tract”. It shares some of the histological features of clear cell sarcoma (CCS) but lacks the immunohistochemical reactivity for melanocytic markers. We report a case of GNET that was initially misdiagnosed as gastrointestinal stromal tumor (GIST). Recognizing this entity is important to avoid misdiagnosis. A case of an 18-year-old male presented with a small intestinal tumor. Histologically it was characterized by polygonal cells arranged in pseudoalveolar pattern and situated in the muscularis propria. Scattered osteoclast-like multinucleated giant cells were also noted. The neoplastic cells were positive for S-100 protein and negative for HMB-45, Melan A, smooth muscle actin, desmin and CD117. EWSR1 gene rearrangement was detected by fluorescence in situ hybridization (FISH) analysis. The patient returned with recurrence after 36 months’ management by surgical resection and died one year later. GNET can be mistaken histologically for other non-epithelial gastrointestinal tumors. Awareness of its existence and diagnostic criteria by the pathologist is necessary to avoid misdiagnosis, particularly as GIST, CCS or malignant peripheral nerve sheath tumor (MPNST).

Malignant tumours of the foot and ankle

Abstract: Most of tumours of the foot are tumour-like (synovial cyst, foreign body reactions and epidermal inclusion cyst) or benign conditions (tenosynovial giant cells tumours, planta fibromatosis). Malignant tumours of the soft-tissue and skeleton are very rare in the foot and their diagnosis is often delayed with referral to specialised teams after initial inappropriate procedures or unplanned excisions. The adverse effect of these misdiagnosed tumours is the increasing rate of amputation or local recurrences in the involved patients. In every lump, imaging should be discussed before any local treatment. Every lesion which is not an obvious synovial cyst or plantar fibromatosis should have a biopsy performed.After the age of 40 years, chondrosarcoma is the most usual malignant tumour of the foot. In young patients bone tumours such as osteosarcoma or Ewing's sarcoma, are very unusually located in the foot. Synovial sarcoma is the most frequent histological diagnosis in soft tissues. Epithelioid sarcoma or clear cell sarcoma, involve more frequently the foot and ankle than other sites. The classic local treatment of malignant conditions of the foot and ankle was below-knee amputation at different levels. Nowadays, with the development of adjuvant therapies, some patients may benefit from conservative surgery or partial amputation after multidisciplinary team discussions.The prognosis of foot malignancy is not different from that at other locations, except perhaps in chondrosarcoma, which seems to be less aggressive in the foot. The anatomy of the foot is very complex with many bony and soft tissue structures in a relatively small space making large resections and conservative treatments difficult to achieve. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160078. Originally published online at www.efortopenreviews.org.

Programmed Death Ligand 1 (PD-L1) Expression in Malignant Mesenchymal Tumors.

Abstract: Objective Programmed death ligand 1 (PD-L1) found on tumor cells has recently been reported to have a key role in the development and dissemination of many tumors, such as lung and breast carcinomas. In this study, we retrospectively analyzed PD-L1 expression among different types of sarcomas. Material and method Tissue microarrays of 3-4 mm diameter were composed from paraffin blocks of 222 various sarcomas. Slides prepared from microarrays were stained for PD-L1 antibody (Cell Signaling, E1L3N®) using Leica Bond Autostainer. Any membranous staining over 5% of the cells was regarded as positive. Quantitative real-time PCR with TaqMan gene expression assays for PDL1 was performed using whole sections from FFPE tissue of PD-L1 positive cases, by normalizing absolute values to β-actin. Relative expression level of mRNA of PDL1 was calculated and scored using Log102(threshold cycle of b-actin - threshold cycle of PDL1). Results Immunohistochemically, PD-L1 expression was present in 34 of 222 (15%) sarcomas. 5/13 (39%) undifferentiated pleomorphic sarcomas, 6/18 (33%) malignant peripheral nerve sheath tumors, 5/16 (31%) dedifferentiated liposarcomas, 4/19 (21%) rhabdomyosarcomas, 2/16 (13%) epithelioid sarcomas, 2/15 (13%) leiomyosarcomas, 3/26 (12%) synovial sarcomas, 1/18 (6%) myxoid liposarcoma, 1/2 (50%) extraskeletal myxoid chondrosarcoma, 1/3 (33%) alveolar soft part sarcoma, 1/3 (33%) parachordoma/myoepithelioma, 1/5 (20%) pleomorphic liposarcoma, 1/7 (14%) angiosarcoma, 1/8 (13%) Ewing sarcoma showed PD-L1 expression. Cases of solitary fibrous tumor/hemangiopericytoma (18), desmoplastic round cell tumor (14), Ewing-like sarcoma (6), epithelioid hemangioendothelioma (5), clear cell sarcoma (4), myxofibrosarcoma (4), low grade fibromyxoid sarcoma (2) were all negative. Tumor-infiltrating hematopoietic cells were positive for PD-L1 in 32 cases (15%) with only 2 cases overlapping with PD-L1 staining in tumoral cells. Sixteen of 34 (47%) immunohistochemically PD-L1 positive cases showed significant but low-level PD-L1 mRNA overexpression. Conclusion We have shown PD-L1 expression in a subset of sarcomas, both at the protein and mRNA level. High-grade pleomorphic sarcomas tend to show more frequent PD-L1 expression. Clinical trials are necessary to further assess the effect of anti PD-L1 drugs on sarcomas showing PD-L1 expression.

Unusual Signal Patterns of Break-apart FISH Probes Used in the Diagnosis of Soft Tissue Sarcomas.

Abstract: Break-apart FISH probes are the most popular and reliable type of FISH probes used to confirm certain pathological diagnoses. The interpretation is usually easy, however, in some instances it is not so unequivocal. Our aim was to reveal and elucidate the problems occurring in the process of evaluation of the break-apart probe results. Altogether 301 soft tissue sarcomas with confirmed molecular tests using break-apart probes were assessed to reveal the frequency and type of unusual signal pattern. Among 89 synovial sarcoma (SS18) 11%, 12 alveolar rhabdomyosarcoma (FOXO1) 50%, 53 myxoid liposarcoma (DDIT3) 7.5%, 6 low grade fibromyxoid sarcoma (FUS) 67%, 93 Ewing sarcoma (EWSR1) 3%, 12 clear cell sarcoma (EWSR1) 8%, 5 desmoplastic small round cell tumor (EWSR1) 0%, 9 extraskeletal myxoid chondrosarcoma (EWSR1) 0%, 2 myoepithelial carcinoma (EWSR1) 50%, 14 dermatofibrosarcoma protuberans (COL1A1) 86% and 6 nodular fasciitis (USP6) 17% atypical break-apart signals were detected. Despite the unusual signal pattern type, the fusion genes were detected using either metaphase FISH, interphase FISH with translocation/TriCheck probe or RT-PCR methods. Although the interpretation problems in the process to evaluate the break-apart probe results is well known from sporadic case reports, a systemic overview to detect their frequency has not been performed so far. In our work we highlighted the relative frequency of this problem and pinpointed those signal-patterns which, despite their unusual appearance, can still confirm the diagnosis.

Complete response of mediastinal clear cell sarcoma to pembrolizumab with radiotherapy

Abstract: Clear cell sarcoma (CCS) is a rare, aggressive soft tissue sarcoma thought to derive from neural crest and characterized by a 12;22 translocation. The resulting fusion protein directly activates expression of the melanocyte master transcription factor and drives the same down-stream pathways in CCS and melanoma leading to significant clinical parallels between these malignancies. Striking success of immune checkpoint blockade in melanoma has promoted interest in immunotherapy of CCS. We report the first complete clinical response of a bulky chest wall recurrence of mediastinal CCS in a young woman to anti-PD1 checkpoint blockade with pembrolizumab combined with standard fractionation radiotherapy to enhance regional control and potentially boost the systemic immune response. The treatment was well tolerated with grade 2 skin toxicity within the range expected with radiation alone. Significant reduction in tumor bulk occurred after only 2 radiation fractions and complete response was achieved at 50 Gray. The complete clinical response observed in our patient suggests synergy between concurrent radiotherapy and PD1 blockade in CCS. This case and the striking parallels between CCS and melanoma indicate the need for prospective trials of immune checkpoint blockade combined with radiotherapy in this rare malignancy.

Implications of Lymph Node Evaluation in the Management of Resectable Soft Tissue Sarcoma

Abstract: The rate of lymph node (LN) metastasis is rare in soft tissue sarcoma, but there are histologic subtypes that metastasize via the lymphatics The prognostic value of LN evaluation in these high-risk histologies is unknown Resected soft-tissue sarcoma patients with clear cell sarcoma, epithelioid sarcoma, rhabdomyosarcoma, or angiosarcoma (n = 2993) were identified in the National Cancer Data Base (2004–2013) Cox regression evaluated the association of omission of LN assessment (NX) and overall survival (OS) Subjects who underwent surgical resection with or without regional LN evaluation were matched (1:1) by propensity scores based on the likelihood of NX or survival hazard on Cox modeling OS was compared by Kaplan–Meier estimates A total of 637 (213%) underwent LN evaluation and 176 (59%) were found to have nodal metastasis Omission of nodal evaluation was significantly associated with risk of death (reference: N0; N+: hazard ratio [HR] 146, 95% confidence interval [CI] 111–191; NX: OR 118, 95% CI 100–140) After propensity score matching, there was a significant difference in median OS following pathologic identification of nodal disease for epithelioid sarcoma (N0: not reached vs N+: 559 months vs NX: not reached, p = 0001) and clear cell sarcoma (N0: not reached vs N+: 200 months vs NX: 950 months, p < 0001) These data support more standardized approaches to regional lymph node examination for patients with epithelioid and possibly clear cell sarcoma and provide compelling evidence that nodal evaluation can be considered a quality measure in the delivery of cancer care for certain sarcoma subtypes

Primary Clear Cell Sarcoma of the Dermis Mimicking Malignant Melanoma.

Abstract: Background: Clear cell sarcoma is a rare malignant soft tissue neoplasm that typically involves tendons and aponeurosis. Clear cell sarcoma in the dermis is an extremely rare occurrence, and it is difficult to differentiate between this neoplasm and dermal malignant melanoma because they have similar morphologic and immunohistochemical features. Although rare, clear cell sarcoma of the skin typically occurs in the extremities. To our knowledge, there are no reported cases of primary clear cell sarcoma of the skin occurring in the neck. Here, we report an unusual case of clear cell sarcoma arising in the skin of the neck.Case Report: A 43-year-old female presented with a right neck lesion. Histologic sections of the lesion showed a nodular proliferation of spindle cells with pale cytoplasm with epithelioid features involving the entire dermis with no epidermal component. The tumour cells were positive for melanocytic markers, including S100 and Human Melanoma Black 45, which led to an initial diagnosis of malignant melanoma. Fluorescence in situ hybridization showed a rearrangement of the EWSR1 gene on chromosome 22q12, which led to a diagnosis of primary clear cell sarcoma in the skin.Conclusion: Because the treatments for clear cell sarcoma and conventional melanoma are different, fluorescence in situ hybridization for EWSR1 should be performed in any dermal lesions with melanocytic features that do not have an in situ component.

Clear cell sarcoma of kidney involving a horseshoe kidney and harboring EGFR internal tandem duplication.

Abstract: Clear cell sarcoma of kidney (CCSK) is a rare renal malignancy, previously unreported in horseshoe kidney (HSK). B-cell lymphoma 6 corepressor (BCOR) gene internal tandem duplication (ITD) was identified as a recurrent somatic alteration in approximately 85% of CCSKs. This and the YWHAE–NUTM2B/E fusion, the second most common recurrent molecular alteration in CCSK (10%), are considered to be mutually exclusive. However, there is a subset of CCSKs that do not harbor either the BCOR-ITD or YWHAE–NUTM2 translocation and lack known molecular alterations. Herein, we report the first case of CCSK arising in HSK and harboring epidermal growth factor receptor ITD.

Metastasis of soft tissue sarcomas in lymph node: A cytomorphological study.

Abstract: Background Soft-tissue sarcoma (STS) rarely metastasizes to lymph node compared to carcinoma Fine-needle aspiration cytology (FNAC) carries a pivotal role in diagnosis of metastatic tumor to lymph node This study highlights the role of FNAC in diagnosis of STS metastasis to lymph node Method A retrospective study over a period by 4 years carried out FNAC of enlarged lymph node was performed in patients with STS Cytology smears were examined in conjunction with clinical details Histopathology and Immunohistochemistry (IHC) were correlated in synchronous cases Results Out of 326 patients, 21 with STS had enlarged lymph nodes, of which 19 cases showed involvement (58%) Sixteen cases were metachronous and 3 cases showed synchronous involvement Fifteen cases had regional lymph nodes while 4 cases had distal lymph node involvement Head and neck and lower extremities were the most common primary sites of STS Rhabdomyosarcoma was the most common sarcoma metastasing to the lymph nodes followed by synovial sarcoma, malignant peripheral nerve sheath tumor, and clear cell sarcoma Other rare tumors included leiomyosarcoma, epitheloid sarcoma, liposarcoma, malignant fibrous histiocytoma, and Ewing's sarcoma/peripheral neuroectodermal tumor We had a case of dermatofibrosarcoma protuberance (DFSP) of scalp with cervical lymph node metastasis Very unusual about this case was its rare primary site and the rarer lymph node metastasis Conclusion FNAC plays an important role in the diagnosis of lymph node metastasis in cases of STS

Trabectedin is a promising antitumor agent potentially inducing melanocytic differentiation for clear cell sarcoma.

Abstract: Clear cell sarcoma is an aggressive soft tissue sarcoma and highly resistant to conventional chemotherapy and radiation therapy. This devastating disease is defined by EWSR1-ATF1 fusion gene resulting from chromosomal translocation t(12;22)(q13;q12) and characterized by melanocytic differentiation. A marine-derived antineoplastic agent, trabectedin, inhibits the growth of myxoid liposarcoma and Ewing sarcoma by causing adipogenic differentiation and neural differentiation, respectively. In this study, we examined the antitumor effects and mechanism of action of trabectedin on human clear cell sarcoma cell lines. We showed that trabectedin decreased the cell proliferation of five clear cell sarcoma cell lines in a dose-dependent manner in vitro and reduced tumor growth of two mouse xenograft models. Flow cytometry and immunoblot analyses in vitro and immunohistochemical analysis in vivo revealed that trabectedin-induced G2/M cell cycle arrest and apoptosis. Furthermore, trabectedin increased the expression of melanocytic differentiation markers along with downregulation of ERK activity in vitro and the rate of melanin-positive cells in vivo. These results suggest that trabectedin has potent antitumor activity against clear cell sarcoma cells by inducing cell cycle arrest, apoptosis, and, in part, by promoting melanocytic differentiation through inactivation of ERK signaling. Our present study indicates that trabectedin is a promising differentiation-inducing agent for clear cell sarcoma.

Clear cell sarcoma‐like tumor of the gastrointestinal tract: A clinicopathological review

Abstract: To the Editor: Clear cell sarcoma of soft parts (CCS) is a rare melaninproducing soft tissue sarcoma that was originally reported by Enzinger in 1968. Morphological and immunohistochemical features of CCS are similar to those of malignant melanoma. However, CCS is genetically distinct from melanoma as it lacks BRAF mutations, and has EWSR1/ ATF1 or EWSR1/CREB1 fusion transcripts. In 1993, Ekfors et al. reported a case of clear cell sarcoma of the duodenum, which was the first visceral case reported. Following this report, several clear cell sarcomas of visceral cases were reported with a variety of names (including malignant gastrointestinal neuroectodermal tumor, an osteoclast-rich tumor of the gastrointestinal tract with features resembling those of clear cell sarcoma of soft parts). Clear cell sarcoma in the gastrointestinal tract is classified as a poor prognostic subtype of CCS in the World Health Organization Classification of Tumors-Tumors of Soft Tissue and Bone 4th edition. In contrast, it is classified as an independent disease, clear cell sarcoma-like tumor in gastrointestinal tract (CCSLGT) because of its different histological features, immunohistochemical expression, and poor prognosis, as described in Enzinger & Weiss's Soft Tissue Tumors 6th edition. To the best of our knowledge, tumors belonging to the CCSLGT category have been reported in 58 cases in the English literature and in one case in the Japanese literature. Herein, we report our CCSLGT case and review 60 cases. The patient was a 32-year-old woman who had no history of malignancy. She visited the hospital because of fever and was diagnosed with anemia. She underwent gastrointestinal endoscopy. Lower gastrointestinal endoscopy revealed a tumor of the transverse colon. On admission, tumor marker levels (CA 19–9, <2.0U/mL; carcinoembryonic antigen [CEA], 1.6 ng/mL) were not elevated. Contrast-enhanced computed tomography showed a poorly enhanced tumor in the transverse colon and lymphadenopathy around the colon. Substantial organ metastasis was not found. Positron emission tomography showed that the tumor had an abnormal accumulation (standard uptake value: 13.7). There was no other abnormal accumulation, except in the lymph nodes. Tumor biopsy showed round to oval cells that were growing in solid sheets. The neoplastic cells contained clear to lightly eosinophilic cytoplasm. The nuclei had small nucleoli. Mitotic activity was brisk. Because the tumor was diagnosed as malignant using biopsy, the patient underwent transverse colon resection and lymphadenectomy. The resected specimen showed a well-circumscribed mass with ulcer formation, having a diameter of 65 40 25mm. On cut section, the tumor was a multinodular tan-gray mass. Pathological analysis showed round to oval cells with a high nucleus to cytoplasm ratio; the cells had grown in solid sheets with an area of short spindle cell proliferation. Some osteoclast-like multinucleated giant cells were identified (Fig. 1a–c). There was no pleomorphism or necrosis. Fifteen mitotic figures were noted per 10 high-power fields (HPFs). There were lymph node metastases around the intestinal tract (6/57). Immunohistochemical staining showed that the tumor cells were positive for S100 protein, vimentin, BCL2, and synaptophysin, focally positive for chromogranin A, CD56, and epithelial membrane antigen (EMA), and negative for AE1/AE3, CAM5.2, leukocyte common antigen, CD34, glial fibrillary acidic protein, c-kit, a-smooth muscle actin, desmin, transducer-like enhancer of split 1, CD99, melan A, human melanoma black 45 (HMB45), and neuron-specific enolase (Fig. 1d). The Ki-67 index was approximately 30%. Fluorescence in situ hybridization (FISH) using a Ewing sarcoma breakpoint region (EWSR) 1 probe showed split signals in 76% of tumor cells. The tumor cells contained EWSR1-ATF1 fusions with exon 11 of EWSR1 fused to exon 5 of ATF1, which were detected using reverse transcription polymerase chain reaction (RTPCR). Therefore, our case was finally diagnosed as clear cell sarcoma-like tumor of the colon. The patient received postoperative adjuvant chemotherapy (ifosfamide and doxorubicin). Recurrence was confirmed as liver metastasis 38 months after resection, and we are currently considering the possibility of further chemotherapy. We reviewed 60 cases that were classified into the CCSLGT category (Table S1). There were 32 male and 28 female patients, with ages ranging from 10 to 85 years (median, 40 years). In terms of clinical findings, abdominal pain, anemia and weight loss were reported in many cases. The tumors ranged from 15 to 150mm (median, 53mm). CCSLGT occurs everywhere in the gastrointestinal tract, but is most frequent in the small intestine (70%). Only seven patients survived for longer than 3 years, including our case, but there are insufficient cases to conclude that CCSLGT have a worse prognosis than CCS (Fig. S1). The frequency of lymph node metastases at the time of diagnosis of CCSLGT was 62% in comparison with 4% for CCS.

Imprint cytology of clear cell sarcoma-like tumor of the gastrointestinal tract in the small intestine: A case report.

Abstract: Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is an extremely rare malignant neoplasm in the digestive tract. Its cytomorphologic features have never previously been reported. Here, we describe a case of CCSLGT, including its cytologic examination findings. A 47-year-old woman presented with a mass in the small intestine, which was resected and sent for imprint cytology. Imprint smears revealed tumor cells with light eosinophilic or clear cytoplasm in a necrotic background. Many of the tumor cells were arranged in a perivascular growth with a pseudopapillary formation, and there were some non-neoplastic osteoclast-like giant cells. Histological examination revealed solid nests and a pseudopapillary pattern of the tumor cells with clear or pale eosinophilic cytoplasm and large nuclei with small nucleoli. Immunohistochemistry showed positive for vimentin, S-100, and SOX-10, and negative for SMA, c-KIT, cytokeratin, HMB-45, and MelanA. The EWSR1 gene split signal was detected by reverse transcriptase fluorescence in situ hybridization, and EWSR1-CREB1 gene fusion was indicated by reverse transcriptase polymerase chain reaction analysis. From these findings, we diagnosed the tumor as CCSLGT. To best of our knowledge, this is the first description of the imprint cytology features of CCSLGT.

Primary mediastinal clear cell sarcoma: a case report and review of the literature.

Abstract: Clear cell sarcoma (CCS) is a rare malignant soft-tissue neoplasm that displays melanocytic markers and exhibits striking histopathological features. The tumour has a predilection for the lower extremities and rarely presents in the mediastinum. We present a case of primary mediastinal CCS in a 57-year-old man. Computer tomography (CT) revealed a 12 × 12 × 7.5 cm mass in the anterior mediastinum. Microscopically, the tumour mainly consisted of epithelioid cells with oval vesicular nuclei and eosinophilic cytoplasm. Immunohistochemically, the tumour was positive for human melanoma black 45 (HMB-45) and vimentin but negative for S-100 and Melan-A. Fluorescence in situ hybridisation (FISH) showed a translocation involving the EWSR1 gene region. This report will illustrate that the mediastinum is a potential site for primary CCS and FISH plays an important role in making a conclusive diagnosis.

Renal Clear Cell Sarcoma - Anaplastic Variant: A Rare Entity.

Abstract: Clear Cell Sarcoma of Kidney (CCSK) is known for its morphologic diversity, aggressive behaviour, tendency to recur and metastasis to bone. Amongst the various morphologic subtypes, anaplastic CCSK is associated with worse prognosis. Here, we report a case of this rare variant of CCSK. A five-year-old boy presented with history of lump and pain in abdomen since one week. The Computed Tomography (CT) scan revealed a large mass occupying the middle and inferior pole of right kidney. The clinical impression was Wilms tumour. Nephrectomy specimen was received and the diagnosis of CCSK anaplastic variant was offered only after excluding the differentials and after performing ancillary tests such as Immunohistochemistry (IHC). Thus, this case emphasizes the diagnostic challenges on morphology and the essential role of IHC in arriving at a definitive diagnosis, because failure to do so may deprive the child from optimal treatment.

Renal clear cell sarcoma presenting as a spontaneous renal hematoma: A rare presentation.

Abstract: Clear cell sarcoma of the kidney (CCSK) is an uncommon renal neoplasm of childhood It represents between 2% and 9% of all pediatric renal tumors, and generally arises before the age of 5 years It often mimics other pediatric renal tumors Presently described is the case of a 7-year-old girl who presented with complaints of vomiting and abdominal pain Abdominal ultrasonography revealed a right renal mass, and the patient developed a renal hematoma a few hours after admission The patient underwent a nephroureterectomy with a provisional diagnosis of Wilms tumor; however, histopathological examination of a specimen revealed CCSK CCSK is similar to Wilms tumor in terms of the typical age of appearance and clinical and histopathological features, but the treatment method and prognosis are different Therefore, the differential diagnosis is very important This case was presented to draw attention to a rare presentation of clear cell sarcoma CCSK should be kept in mind in the differential diagnosis of a renal mass

Dual tumor - Clear cell sarcoma of kidney with differentiating neuroblastoma: A rare case with review of literature.

Abstract: Occurrence of two distinct synchronous primary tumors is a rare event in children as well as in adults. Here, we report an extremely rare case of an infant found to have two synchronous Tumours namely clear cell sarcoma of kidney(CCSK) and differentiating neuroblastoma of preaortic region. To our knowledge, this may be the first case of synchronous CCSK and differentiating neuroblastoma being reported.

Brain metastasis from gastrointestinal clear cell sarcoma.

Abstract: Clear cell sarcoma (CCS) of the gastrointestinal tract presents a diagnostic challenge to the pathologist due to its morphological and immunohistochemical similarity to melanoma. It usually metastasizes to regional lymph nodes, liver, and lungs. Herein, we report the first known metastasis of a gastrointestinal CCS to the central nervous system. Cytogenetic testing showed the t(12,22) translocation corresponding to the presence of the EWS/ATF1 hybrid consistent with CCS. The literature that compares melanoma to CCS is reviewed in the context of this rare presentation to differentiate between the two diseases. .

Clear cell sarcoma of the scalp: A case report.

Abstract: Dear Editor, Clear cell sarcoma (CCS), malignant melanoma (MM) of soft parts, is a rare tumor that typically arises in the deep tissues of the foot and ankle region of young individuals. A number of case reports of CCS have been published, but primary head and neck CCS is rare. Here, we report a case of CCS that arose in the scalp. A 24-year-old Japanese woman was referred to our hospital because of a reddish nodule on the scalp that had first appeared approximately 5 years previously and had since gradually increased in size. The physical examination revealed a 15-mm, reddish and movable nodule on the back of the head (Fig. 1a). Her personal and family histories were unremarkable. The nodule was excised. Histopathologically, the tumor was composed of nests and fascicles of spindle or epithelioid cells with clear cytoplasm in the dermis spreading to subcutis (Fig. 1b). The nuclei were large and vesicular, with prominent nucleoli (Fig. 1c). The immunohistochemical staining revealed that the tumor cells were positive for S100 (Fig. 1d) and HMB-45, and partially positive for Melan-A. EWSR1–ATF1 fusion transcripts were shown by fluorescence in situ hybridization (Fig. 1e). The histological, immunohistochemical and molecular findings were consistent with a diagnosis of CCS. Sentinel lymph node biopsy (SLNB) was performed, which resulted in failure. No sign of recurrence or metastasis has appeared during a 2-year follow up. Clear cell sarcoma usually occurs in the deep tissues, in association with the fascia, tendons or aponeuroses. More than 95% of CCS involve the extremities. Approximately 40% of CCS arise in the foot and ankle, followed by the knee, thigh, forearm, elbow, shoulder, neck and trunk. Only two cases of CCS of the scalp have been previously reported. One case was that of a 33-year-old man who received wide local excision and radiotherapy and had no recurrence during a 23-month follow up. The other case was that of a 20-year-old woman for whom the treatment details are not available and who developed local recurrence and metastasis, resulting in death 120 months later. EWSR1 gene rearrangements were shown in the former case

FNAC aided diagnosis of clear cell sarcoma of kidney: Report of two cases in infants

Abstract: Clear cell sarcoma of kidney (CCSK) is a rare aggressive malignant renal neoplasm with a high metastatic potential. Its outcome has however, improved with the advent of doxorubicin based neoadjuvant chemotherapy. Here, we present two cases of CCSK in infants diagnosed on cytology followed by nephrectomy. The first case presented in the neonatal period and had the unusual histological finding of islands of cartilage. The second case presented at the age of eight months. The possibility of CCSK should, therefore, be considered in the differential diagnoses of renal masses in infants as well as neonates. Diagn. Cytopathol. 2017;45:761-765. © 2017 Wiley Periodicals, Inc.