Showing papers on "Clear-cell sarcoma published in 2015"

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

Abstract: 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.

Biologic Activity of Autologous, Granulocyte–Macrophage Colony-Stimulating Factor Secreting Alveolar Soft-Part Sarcoma and Clear Cell Sarcoma Vaccines

Abstract: Purpose: Alveolar soft parts sarcoma (ASPS) and clear cell sarcoma (CCS) are rare mesenchymal malignancies driven by chromosomal translocations that activate members of the microphthalmia transcription factor (MITF) family. However, in contrast to malignant melanoma, little is known about their immunogenicity. To learn more about the host response to ASPS and CCS, we conducted a phase I clinical trial of vaccination with irradiated, autologous sarcoma cells engineered by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor (GM-CSF). Experimental Design: Metastatic tumors from ASPS and CCS patients were resected, processed to single cell suspensions, transduced with a replication defective adenoviral vector encoding GM-CSF, and irradiated. Immunizations were administered subcutaneously and intradermally weekly times three and then every other week. Results: Vaccines were successfully manufactured for 11 of the 12 enrolled patients. Eleven subjects received from 3 to 13 immunizations. Toxicities were restricted to grade 1-2 skin reactions at inoculation sites. Vaccination elicited local dendritic cell infiltrates and stimulated T cell mediated delayed type-hypersensitivity reactions to irradiated, autologous tumor cells. Antibody responses to tissue-type plasminogen activator (tTPA) and angiopoietins-1/2 were detected. Tumor biopsies showed programmed death-1 (PD-1) positive CD8+ T cells in association with PD ligand-1 (PD-L1) expressing sarcoma cells. No tumor regressions were observed. Conclusions: Vaccination with irradiated, GM-CSF secreting autologous sarcoma cell vaccines is feasible, safe, and biologically active. Concurrent targeting of angiogenic cytokines and antagonism of the PD-1 negative regulatory pathway might intensify immune-mediated tumor destruction.

BRAF-mutated clear cell sarcoma is sensitive to vemurafenib treatment

Abstract: We report a patient with a metastatic relapse of clear cell sarcoma, whose tumor harbored BRAF V600E mutation. Standard chemotherapy with doxorubicin and ifosfamide failed to slow the disease progression. Subsequent administration of vemurafenib (960 mg twice a day) resulted in complete tumor response after 8 weeks of treatment. Literature data on the use of vemurafenib and dabrafenib in non-melanoma BRAF-mutated tumors are reviewed.

An unusual association of malignant gastrointestinal neuroectodermal tumor (clear cell sarcoma-like) and Ewing sarcoma.

Abstract: Very recently a new designation of "Malignant Neuroectodermal Gastrointestinal Tumor" has been proposed for an aggressive form of neuroectodermal tumor with features similar to that of Clear Cell Sarcoma of Soft Tissue, however without a melanocytic differentiation. Also known as "clear cell sarcoma-like tumors of the gastrointestinal tract", these tumors show some features strongly suggesting an origin from a gastrointestinal neuroectodermal precursor cell unable to differentiate along the melanocytic lineage. They occur mainly in young and middle-aged adults, and have a poor prognosis with a high rate of liver and lymphnode metastases. Histologically they are composed of epithelioid or oval-to spindle cells with a sheet-like or nested pattern of growth, strongly positive for neural markers (S-100, SOX10, and vimentin) and negative for the melanocytic ones. EWSR1 gene rearrangements including EWSR1-ATF1 or EWSR1-CREB1 GENE fusions are typically assessed in these tumors. Here we report a case of malignant neuroectodermal gastrointestinal tumor which immunophenotypically unusually expressed FLI-1, occurring in a 29-year-old man with a previous medical history of Ewing sarcoma. We finally suggest that this case might be a further evidence of a link between these two entities.

Clear Cell Sarcoma–Like Tumor of the Gastrointestinal Tract A Case Report and Review of the Literature

Abstract: Clear cell sarcoma is a rare tumor classically associated with tendons and aponeuroses of lower extremities of young adults and has a distinctive histopathologic and molecular profile. It has been rarely described in other locations other than soft tissues, including the gastrointestinal tract. Herein we report a case of clear cell sarcoma of gastrointestinal tract arising in the ileum, which is rich in osteoclast-like giant cells with a review of the literature.

Melan-A/MART-1 immunity in a EWS-ATF1 translocated clear cell sarcoma patient treated with sunitinib: a case report

Abstract: Clear cell sarcoma (CCS), initially named malignant melanoma of soft parts, is an aggressive soft tissue sarcoma (STS) that, due to MITF activation, shares with melanoma the expression of melanocyte differentiation antigens. CCS is poorly sensitive to chemotherapy. Multi-kinase inhibitors have been used as therapeutic agents. In the case we report here, treatment with sunitinib induced a long-lasting clinical response that was associated with an immune activation directed against Melan-A/MART-1 antigen. A 28 years old female patient with an advanced molecularly confirmed CCS resistant to conventional chemotherapy was started in January 2012 on sunitinib, 37.5 mg/day, with evidence of radiologic and metabolic response at the primary and metastatic sites of disease. Pathologic response and loss of the Melan-A/MART-1 antigen were evidenced on residual tumor removed in April 2012. Immunological monitoring performed on patient’s blood during pharmacological treatment revealed a systemic, Melan-A/MART-1 specific immunity and a low frequency of immunosuppressive cells. Sunitinib was restarted in May 2012, with a new response, and continued for 11 months although with repeatedly interruptions due to toxicity. Disease progression and new responses were documented at each treatment interruption and restart. Sunitinib was definitively interrupted in April 2013 for disease progression. The analysis of this case proves that antigens expressed by CCS, as for melanoma, can be immunogenic in vivo and that tumor-antigen specific T cells may exert anti-tumor activity in CCS patient. Thus, manipulation of the immune response may have therapeutic potential for this STS subtype and immunotherapy approaches, can be promising therapeutic options for these patients.

Esophageal subepithelial lesion diagnosed as malignant gastrointestinal neuroectodermal tumor

Abstract: A 21-year-old male visited our hospital with a complaint of aggravating dysphagia and odynophagia for a few days. Esophagogastroduodenoscopy showed huge bulging mucosa with an intact surface causing luminal narrowing at 35 cm from the incisor teeth. Endoscopic ultrasonography showed an about 35 mm sized irregular margined in-homogenous hypoechoic lesion with an obscure layer of origin. Endoscopic ultrasonography fine needle aspiration revealed spindle cell proliferation without immunoreactivity for CD117, SMA, and cytokeratin. The patient underwent excision of the subepithelial lesion at the distal esophagus. On pathologic examination of the specimen, the tumor was composed of short fascicles of oval to spindle cells with eosinophilic and clear cytoplasm and vesicular nuclei. The tumor cells were positive for S-100 and SOX10 and negative for CD117, SMA, HMB-45, melan-A, cytokeratin, and CD99. The split-apart signal was detected in EWSR1 on FISH, suggesting a malignant gastrointestinal neuroectodermal tumor. At the time of writing, the patient is on radiation therapy at the operated site of esophagus and doing well, with no recurrence for three months. Malignant gastrointestinal neuroectodermal tumor is a rare gastrointestinal tumor with features of clear cell sarcoma, without melanocytic differentiation, and shows a poor prognosis. This is the first reported case of malignant gastrointestinal neuroectodermal tumor arising as subepithelial lesion in the esophagus.

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

Abstract: Clear cell sarcoma (CCS), is an uncommon malignant soft tissue neoplasm that displays melanocytic differentiation with a distinct molecular profile. It is very rarely localized in gastrointestinal tract. We reported the first case of a primary CCS arising in pancreas. A 36-year-old man presented with jaundice for one month. A preoperative abdominal computer tomography showed a low-density mass in the head of pancreas. Whipple procedure was performed and the tumor was resected. Pathological examination showed polygonal or fusiform cells arranged in a uniform nested to fascicular growth pattern with thin fibrous septa. Immunohistochemical studies revealed positivity for HMB-45, Melan A, S-100, MiTF and vimentin protein. Fluorescence in situ hybridization on paraffin section showed a translocation involving the EWSR1 gene region. No BRAF and NRAS mutation was detected. The patient underwent transcatheter arterial chemoembolization (TACE) six times and eventually died of diffuse liver metastasis 10 months later. This case illustrates that the pancreas is a potential site for primary clear cell sarcoma and molecular studies play an important role in making a conclusive diagnosis.

Bone-patellar tendon-bone allograft reconstruction for peri-patellar tendon sarcomas: case series.

Abstract: Reconstruction after wide resection for a sarcoma involving the knee extensor mechanism is challenging even if the tumor is small. We report on four consecutive peri-patellar tendon sarcomas treated similarly at a single institution. Histological diagnoses were synovial sarcoma (two cases), clear cell sarcoma and extraskeletal Ewing’s sarcoma (one case each). Follow-up periods after surgery were 18–67 months. All cases underwent pre-operative radiotherapy and subsequent surgery. After preoperative radiotherapy and wide resection including the patellar tendon, bone-patellar tendon-bone allograft was fixed to the residual patella and tibial tuberosity with screws and a cable wire. Soft tissue and skin defect over allograft was covered by free antero-lateral thigh flap. Post-operatively, the operated knee was splinted straight for at least 6 weeks, and then range-of-motion exercise was gradually introduced. Except for one case with a proximal tibial stress fracture 5 months post-operatively, no complication was observed. Both bone–bone junctions between allograft and residual bones were united within 1 year after surgery. At the latest clinical follow-up, all the patients had satisfactory functions with Musculoskeletal Tumor Society score of 28–30 out of 30 points and virtually full range of motion. This case series is the first to report bone-patellar tendon-bone allograft for reconstruction after tumor resection with joint preservation and with satisfactory clinical outcomes. Bone-patellar tendon-bone allograft reconstruction with vascularized flap reconstruction is a viable option for peri-patella tendon sarcomas.

Clear cell sarcoma of soft tissue in right parapharyngeal region: report of a rare case

Abstract: Clear cell sarcoma (CCS), initially named malignant melanoma of soft parts, is a rare malignant neoplasm typically involving deep soft tissue of the extremities, in close proximity to tendons and aponeuroses. Here we describe a case of clear cell sarcoma of the right parapharyngeal region in a young female aged 20 years. MRI detected a mass about 4.4 cm×3.4 cm×3.0 cm, located in the right parapharyngeal area and between the external pterygoid and the medial pterygoid. Microscopically, most of the tumor cells were epithelioid with palely eocinophilic cytoplasm arranged in sheets. Pleophorism of tumor cells were not marked. Immunohistochemical analysis shows that the tumor cells were positive for vimentin, S-100, HMB45 and MelanA, and negative for AE1/AE3, actin-sm, desmin, CD117, TFE-3, and P63. Ki67 index was about 5%.

Renal tumor in developing countries: 142 cases from a single institution at Shanghai, China.

Abstract: Background The clinical management of children with renal tumors including Wilms’ tumor, clear cell sarcoma, rhabdoid tumor and other renal tumors in our center was designed according to the National Wilms’ Tumor Study Group protocols.

Activity of crizotinib (C) in patients (pts) with clear cell sarcoma (CCSA) in EORTC phase II trial 90101 "CREATE".

Abstract: 10542 Background: This phase II trial assesses the safety and activity of the ALK/MET inhibitor C in 6 different ALK- or MET-driven tumor types including CCSA, an orphan, treatment-refractory malig...

Unusual Clinical Presentation of Gastrointestinal Clear Cell Sarcoma.

Abstract: Background: Use of molecular assays is gradually becoming a mandatory part of the clinical management of soft tissue tumors, however the choice and the interpretation of these tests may present a challenge. Summary: This report demonstrates an unusual presentation of sarcoma, which was initially diagnosed as a tumor of unknown primary site. Given the presence of vimentin, Fli-1, CD99 and S100 markers, lack of immunostaining for melan A, HMB45, MITF, synaptophysin, CD56, myf4, CKAE1/3 and WT-1, as well as the presence of EWSR1 translocation determined by a break-apart FISH assay, Ewing's sarcoma (ES) diagnosis seemed to be well justified. However, polymerase chain reaction testing for ES-specific rearrangements (EWSR1/FLI1, EWSR1/ERG, EWSR1/ETV1, EWSR1/ETV4, EWS/FEV) failed to confirm the ES origin of the neoplastic tissue. We further considered clinical, morphological, immunohistochemical and molecular diagnostic features of other types of EWSR1-rearranged sarcomas and performed molecular testing for gastrointestinal clear cell sarcoma. The polymerase chain reaction assay revealed EWSR1ex7/ATF1ex5 fusion, thus confirming the latter diagnosis. Subsequent high-precision computed tomography of the abdominal cavity revealed a 5-cm tumor of the small bowel, which was subjected to surgical resection. Key Message: This report exemplifies that the use of anonymous cytogenetic assays, such as break-apart FISH EWSR1 testing, may not be sufficient even in case of a perfect match with relevant morphological and immunohistochemical tumor features. Practical Implications: Explicit identification of the translocation gene partners is indeed important for proper sarcoma diagnosis management.

Clear cell sarcoma of the penis: a case report

Abstract: Clear cell sarcoma of the penis is exceedingly rare with only one prior case involving the penis reported in the literature. We present the case of a 32 year old male who presented with an infiltrative neoplasm at the base of the penis as well as extensive metastatic disease to the lymph nodes and bone. Morphologic, immunohistochemical and cytogenetic findings established the diagnosis of clear cell sarcoma. Despite chemotherapy the patient’s disease was rapidly progressive and the patient died of disease within 8 months of diagnosis.

Clear cell sarcoma: a case report from clinic to cytogenetic studies.

Abstract: In 1965, Franz M. Enzinger reported a series of 21 cases of a malignant tumor, which was named clear cell sarcoma of tendons and aponeuroses. Since then, a little over 300 cases have been reported, corresponding to 1% of all soft tissue sarcomas. Clear cell sarcoma is an anaplastic rare tumor of soft tissues, originating from neural crest cells derived from melanoblasts. It affects 30to 40-year-old adults, primarily Caucasian, with no sex predilection. Most of the tumors are located close to the tendons and aponeuroses of the extremities: feet, ankles, plantar aponeurosis, hands, and forearms. They present as a swelling or non-fluctuating mass and are typically painless, mobile, and non-pigmented, with sluggish growth and a variable size with average diameter of 4 cm. Histologically, nests and fascicles are located in the deep dermis and subcutis, almost always associated with tendons and aponeurosis. The epidermis and dermal–epidermal junction are generally not involved. Occasionally, organized, uniform neoplastic cells interspersed with connective tissue tendons are seen, as are fascia and aponeuroses, forming lobes with septa of varying thickness. The cells are polygonal or spindle-shaped with pale eosinophilic cytoplasm, a round or oval central nucleus, and a prominent basophilic nucleolus. Few mitoses are found, which is in accordance with the slow growth of the tumor. Some giant cells may also be present. In clear cell sarcoma, immunohistochemical studies are positive for antigens associated with the synthesis of melanin, such as human melanoma black-45 (HMB-45), S-100 protein, Melan-A, and microphthalmia-associated transcription factor. In melanocytic lesions, such as nevi and melanoma, these markers are also positive. S-100 protein is positive in almost 95% of primary cutaneous melanoma, HMB-45 is highly specific for melanocytic differentiation, and microphthalmia-associated transcription factor is a nuclear protein involved with melanocytogenesis and melanogenesis. The positivity of these stains and their patterns are used to diagnose and differentiate melanoma from benign pigmented lesions of the skin. Vimentin and cytoketarins are usually negatives in clear cell sarcoma cases. To confirm the diagnosis, it is often necessary to perform cytogenetic studies and verify the presence of reciprocal chromosomal translocation t(12, 22):(q13, q12). This is also demonstrable via the Ewing’s sarcoma breakpoint region 1 (EWSR1) gene on 22q12 using fluorescent in situ hybridization (FISH). The FISH method uses specific DNA probes and can detect chromosomal aberrations in formalin-fixed, paraffin wax-embedded tissue.

Case of clear cell sarcoma in the left buttock in which serum neuron‐specific enolase was a useful marker for monitoring disease progression

Abstract: We report a case of clear cell sarcoma (CCS) in the left buttock in which serum neuron-specific enolase (NSE) was useful as a biomarker of CCS progression. A 40-year-old man had a subcutaneous tumor, 1.7 cm in diameter, in the left buttock. Histopathology revealed that the tumor consisted of nests of polygonal or spindle-shaped cells with abundant clear cytoplasm delineated by fibrous septa in the subcutaneous tissue. There was cellular atypia but no melanin deposits. Immunohistochemically, the tumor cells were positive for HMB-45, Melan-A, S-100 protein and NSE. Reverse transcription polymerase chain reaction demonstrated Ewing's sarcoma oncogene-activating transcription factor 1 fusion transcripts in the tumor cells. CCS was diagnosed. There was no metastasis to the lymph nodes and viscera, and the patient was treated by surgical wide resection. The serum NSE levels increased before detection of distant metastasis and further increased in parallel with the expansion of metastasis. The present case suggests that serum NSE could be used as a biochemical marker in the clinical follow up of patients with CCS.

Malignant Extragastrointestinal Neuroectodermal Tumor Located at Right Cervical Region

Abstract: Malignant Gastrointestinal Neuroectodermal Tumor (GNET) is a recently described rare malignant neoplasm, resembling “clear cell sarcoma of tendons and aponeuroses” morphologically, immunohistochemically and molecular pathologically. We will describe a case of soft tissue sarcoma located at right cervical region of a 9-year-old male patient, mimicking malignant GNET, which can be considered as extragastrointestinal counterpart of this tumor. These tumors have poor prognosis. This is unique, possibly the first case of a soft tissue sarcoma resembling GNET.

Clear cell sarcoma of the kidney with calcification and a novel chromosomal abnormality: a case report.

Abstract: A 9-year-old male presented with a renal tumor that showed a cystic structure with calcification on computed tomography. A pathological analysis of the resected tumor suggested clear cell sarcoma of the kidney (CCSK). Thus, this patient suffered atypical CCSK with significant calcification and gross necrosis. A novel chromosomal abnormality was also identified in the tumor.

Clear cell sarcoma of kidney in an adult: an extremely rare case

Abstract: Clear cell sarcoma of kidney is extremely rare in adults. It is a very malignant tumor, with a high tendency for relapse and a propensity for skeletal metastases, particularly skull. Treatment of clear cell sarcoma of kidney generally involves surgical intervention coupled with radiation and chemotherapy. This paper reports a case of adult clear cell sarcoma of kidney.

Tumeur neuroectodermique gastro-intestinale (GNET) : à propos d’un cas de tumeur du grêle avec métastases hépatiques

Abstract: The gastro-intestinal neuroectodermal tumor (GNET) is a rare sarcoma of the digestive tract, which was recently recognised. The knowledge of the morphological, immunohistochemical and molecular diagnostic criteria is necessary to not mistake it for the metastasis of a melanoma or for another sarcoma of the digestive tract as the gastro-intestinal clear cells sarcoma or the malignant peripheral nervous system tumor (MPNST). We report the case of a 41-year-old patient with a GNET of the small intestine with hepatic metastasis. The histological examination showed a diffuse proliferation of epithelioid cells, which only express PS100. The presence EWSR1-ATF1 gene fusions with any melanocytic differentiation leads to the diagnosis of GNET.

[Small cell type (Ewing-like) clear cell sarcoma of soft parts: a case report].

Abstract: The authors present a unique case of small cell variant of clear cell sarcoma of soft parts in a 42-year old woman. The tumor originally arose in the right flank of the soft tissues and ultimately developed both a local recurrence and multiple distant skin metastases two years and ten months thereafter. Nonspecific morphology of small blue round cell tumor was preserved at all microscopically verified sites and initially led to the spectrum of erroneous diagnoses such as an extraskeletal myxoid chondrosarcoma, Ewing sarcoma as well as malignant melanoma. The distinctive features of clear cell sarcoma such as fascicular nested growth pattern, spindling, clear cell change and/or eosinophilic cytoplasm were not disclosed even by extensive sampling. Immunohistochemically, the tumor expressed only S100protein and HMB45; all other markers (CD99, FLI1, cytokeratins, EMA) were completely negative. The molecular analysis carried out in one of the cutaneous metastases revealed translocation t(12;22) (EWSR1-ATF1) and ultimately led to the correct diagnosis of unusual Ewing-like clear cell sarcoma. Discussed is the implementation of molecular tests in routine diagnostics considering the existence of both histologically and biologically different tumors with an identical pathogenic molecular background.

Renal Tumors and Tumor-Like Conditions

Abstract: Chapter 1 presents main clinical and pathologic characteristics of tumors and tumor-like conditions arising in the kidney. Emphasis is placed on rare and recently described entities. Diagnostic pathologic and immunohistochemical features useful in differential diagnosis are key characteristics described in text and tables. Representative images illustrate both common and rare tumors and tumor-like conditions of the kidney

Clear Cell Sarcoma of Soft Tissue (Malignant Melanoma of Soft Tissue)

Abstract: Clear cell sarcoma (CCS) of the soft tissue is an exceedingly rare sarcoma with melanocyte differentiation and a distinct genetic background whose precise lineage remains unclear. Usually, it is a tumor of deep soft tissue, but a primitive cutaneous localization has been described by Hantschke et al. in 2010 (cutaneous clear cell sarcoma).

Atypical amplification of chromosome region 22q12 in melanoma: A case report

Abstract: Morphological, ultrastructural and immunohistochemical characteristics of clear cell sarcoma (CCS) of the soft tissue frequently overlap with those of malignant melanoma. Thus, the differential diagnosis between the two lesions represents an important diagnostic dilemma. However, a number of genetic factors can be used to differentiate the two tumors; in particular, the t(12;22)(q13;q12) chromosomal translocation is typical of CCS, resulting in fusion of the EWSR1 gene on chromosome 22q12 and the ATF1 gene on chromosome 12q13. The detection of this molecular alteration has proved useful in the differential diagnosis of the two lesions. The present study reports the case of a 71-year-old male patient with a suspicious lymph node mass. Immunohistochemical analysis of the lesion indicated a diagnosis of metastatic melanoma, however, cytogenetic analysis using fluorescence in situ hybridization was additionally performed to investigate the chromosomal rearrangements of the 22q12 region and completely exclude the possibility of CCS. The current case did not demonstrate the presence of the translocation, supporting the diagnosis of melanoma. However, a clear orange amplification signal was observed relative to an ~500-kb region adjacent to the EWSR1 gene in the centromeric direction of chromosome 22q12. To the best of our knowledge, this is the first description of a 22q12 chromosomal alteration in melanoma. Furthermore, despite the presence of numerous genes in this region, their amplification has not previously been associated with the pathogenesis of melanoma.