Primary Clear Cell Sarcoma Research Articles

Unusual Clinical Presentation of Clear Cell Sarcoma Masquerading as Cutaneous Lymphoma, in a Young Male

Background: Clear cell sarcoma of soft tissue is an exceedingly rare tumor that originates from the neural crest cells. These tumors are histologically characterized by the presence of clear cells that contain accumulated glycogen. Clear cell sarcomas share histological and immunohistochemical features with malignant melanoma. They commonly arise from tendinous sheaths and aponeuroses, with the lower limbs, particularly around the ankles, being the most common site. Tumors arising in the upper extremities are rare, and very few primary clear cell sarcoma cases have been described in the chest wall and scapular soft tissues. They usually present as a solitary mass. Materials and Methods: Here we are reporting a case of clear cell sarcoma in a young boy, presenting with multifocal lesions involving the trunk, both upper and lower extremities, lymph nodes, bone marrow, and many internal viscera. Results: The case described an unusual presentation of clear cell sarcoma with multifocal involvement, which is rare compared to the typical presentation as a solitary mass. Conclusion: The reported case demonstrates a very unusual presentation of clear cell sarcoma involving multiple sites, highlighting the importance of considering a wide differential diagnosis when encountering multifocal soft tissue lesions.

Primary clear cell sarcoma of the femur: a unique case with RT-PCR and direct sequencing confirmation of EWSR1/ATF1 fusion gene

BackgroundIt is very rare for clear cell sarcomas (CCS) to arise in the bone. During diagnosis, it is important to distinguish primary CCS of bone from bone metastasis of melanoma because this difference fundamentally changes the therapeutic options. Recently, characteristic fusion genes of CCS have been detected using reverse transcription polymerase chain reaction (RT-PCR) or direct sequencing which allowed to distinguish CCS from melanoma. However, there was no study applying these analyses with positive results. In this case, we describe the use of fusion gene analysis to diagnose a primary CCS of the bone.Case presentationA 36-year-old male presented with a four-months history of left knee pain. Magnetic resonance imaging showed a lesion in the left femoral medial epicondyle. Histological examination of the biopsy specimen revealed proliferating oval or rounded cells. These cells had clear cytoplasm arranged in fascicles or compact nests with frequent deposits of brown pigment. Furthermore, immunohistochemistry analysis revealed that tumor cells were positive for S-100 protein, HMB-45, Melan-A, and SOX10. It stained negative for CD34 and BRAF v600e. Conclusively, detection of the EWSR1/ATF1 fusion gene using RT-PCR and direct sequencing confirmed that the lesion was a primary CCS of the bone. Wide-margin resection and reconstruction with a tumor endoprosthesis were performed.ConclusionsHerein, we diagnosed a rare case of primary CCS of the bone by detecting EWSR1/ATF1 fusion gene using RT-PCR and direct sequencing. Since fluorescence-in situ hybridization (FISH) and RT-PCR could show false positive by mainly due to technical problems, it is better to perform direct sequencing to confidently diagnose the tumor as a primary CCS especially at very rare site such as bone.

Primary Clear Cell Sarcoma of the Breast: A Case Report

Abstract Casestudy: Clear cell sarcoma (CCS), also known as malignant melanoma of soft parts, is a primary soft tissue neoplasm exhibiting evidence of melanocytic differentiation. It is an uncommon aggressive tumor that arises in tendons and aponeuroses of the distal extremities. Here, we report the first case of primary CCS of the breast. The patient was a 43-year-old female who presented with a left breast mass and underwent surgical resection at an outside hospital. No history of melanoma or any other malignancies was reported. Grossly, it was described as a 2 x 1.5 x 1.5 cm, well-demarcated, white nodular mass. Microscopic examination showed a malignant neoplasm composed of short spindle cells with ill-defined, eosinophilic cytoplasm and ovoid nuclei with finely stippled chromatin and exhibiting moderate pleomorphism. The lesional cells were arranged in short interlacing fascicles with abundant collagen, with brisk mitotic activity (>15/10 HPF). The differential diagnosis included spindle cell carcinoma, myoepithelial carcinoma and melanocytic neoplasm. The tumor cells were immunoreactive for S-100 protein, SOX10, Mart-1, HMB45 and MiTF, but negative for multiple cytokeratins (including high and low molecular weight keratins), p63, EMA, CEA, Caldesmon, smooth muscle myosin, calponin, desmin, ERG, and CD31, thus confirming melanocytic origin. EWSR1 gene rearrangement was detected by fluorescence in situ hybridization analysis using break-apart probes. Overall, the histomorphology combined with the immunophenotype and cytogenetic characteristics, was most consistent with a CCS. To our knowledge, no primary CCS of the breast has been previously reported in the English language literature.

Primary Clear Cell Sarcoma of Bone: Report of a Case Arising from Distal Femur in a Pediatric Patient and Review of the Literature

Clear cell sarcoma is a rare mesenchymal tumor with melanocytic differentiation, firstly described by Enziger in 1965. It accounts for less than 1% of all soft tissue sarcomas and occurs predominantly in the extremities of adults. Primary clear cell sarcoma of bone is even rarer; current literature consists of only 13 cases with a mean age of presentation of 45-year-old, ranging from 18 to 81. Because of the overlapping expression of melanocytic markers, the differential diagnosis should be addressed with metastatic malignant melanoma and metastasis from clear cell sarcoma of soft parts. Essential for the diagnosis is the evidence of translocations t (12;22) or t (2;22) resulting respectively in EWSR1/ATF1 and EWSR1-CREB1 gene fusion. Clinical history and radiological assessment could help discriminate between bone or soft parts origin. We report an unusual case of clear cell sarcoma of distal femur involving a 13-year-old patient. Histological sections showed a malignant neoplasm composed of nests of uniform cells separated by fibrous septa, showing strong immunoreactivity for melanoma triple cocktail. Real Time-Polymerase Chain Reaction revealed the presence of the fusion product EWSR1-ATF1, confirming the diagnosis of clear cell sarcoma of bone. Our purpose was to revise the current literature in order to find common clinicalradiological features to this rare entity. To the best of our knowledge, our case is the first bone clear cell sarcoma arising from the distal femur in a pediatric patient described in the literature: it highlights the importance of considering this rare entity in the differential diagnosis of primary bone tumor, although extremely rare and of the use of molecular means to confirm the diagnosis.

Primary Cutaneous Clear Cell Sarcoma, Clinical Outcome With Sentinel Lymph Nodes Status

Primary cutaneous clear cell sarcoma (PCS) is a rare malignancy and difficult to differentiate from melanoma. We investigated factors influencing survival and recurrence. An institutional cancer registry and literature search were used for a retrospective study. Only clear cell sarcoma cases with a primary site of skin and subcutaneous tissue were included. Kaplan-Meier and Cox regression analyses were used to assess survival time and hazard ratios. Three eligible cases were identified at our institution. In addition, the PubMed and Google Scholar reviews identified 1,878 items, with 23 patients with PCS. The median age was 25 years with 62% female. The tumors ranged in size from 0.4 to 4.5 cm. Cytogenetics showed t(12;22)(q13;q12) in all cases and a unique variant of t(2;22)(q32.3;q12) in one case. Surgery was the most common treatment, followed by chemotherapy/radiation. PCS recurred in 46% of patients with a median relapse-free survival time of 15 months. Only two known PCS-related mortalities were recorded, at 38 and 60 months following initial diagnosis. Smaller tumor size and negative sentinel lymph node biopsy (SLNB) status were significantly associated with a better disease-free survival. Tumor size and SLNB status influence PCS survival and recurrence. More research is needed due to the rarity of this disease.

Intra-Extracranial Primary Clear Cell Sarcoma: The First Report and Review of the Literature

Clear cell sarcoma (CCS) is a rare malignant soft tissue tumor with poor prognosis owing to metastasis and insensitive response to chemotherapy and radiotherapy. We first searched PubMed and Embase using the terms "clear cell sarcoma," "malignant melanoma of soft tissue," "head," and "neck." In the 15 articles selected for literature review, only 27% (4/15) of patients were diagnosed with primary CCS of the head. Pathologically, those tumors arose from either the scalp or the superficial temporal fascia, but none invaded the skull and brain. Next, the search was performed in the same database using the terms "clear cell sarcoma," "malignant melanoma of soft tissue," and "bone," and only 24 articles were selected. In the case reported here, a 36-year-old woman was found to have a palpable mass located at the left temporal-occipital region, and surgical finding confirmed the invasion into the skull and the brain. The diagnosis of primary CCS was made because of the detection of t(12;22)(q13;q12) in >50% of tumor cells by fluorescence in situ hybridization, and metastasis to the lymph nodes and lungs was discovered by postoperative positron emission tomography-computed tomography. To the best of our knowledge, this is the first case of primary central nervous system CCS. Primary CCS may involve the skull and should be one of the differential diagnoses for intra-extracranial communicating tumors. Further research on biological characteristics and molecular targeted therapy of CCS are needed to improve its poor prognosis.

Primary clear cell sarcoma of the tongue: report of a case

软组织透明细胞肉瘤（CCS）是一种具有黑色素细胞分化的软组织恶性肿瘤，具有相对特征性病理学特征，具有t（12，22）（q13；q12）易位，产生EWS（22q12）/ATFl（12q13）融合基因，主要发生于软组织，发生于舌十分罕见，我们收集1例2017年4月就诊于福建省立医院病理科的舌部软组织CCS患者资料，分析其临床病理学特征，为治疗及预后提供依据。.

Primary clear cell sarcoma of the tongue and surgical reconstruction: About a rare case report

Clear cell sarcomas (SCC), also called "soft-tissue melanoma", are rare and aggressive tumors that preferentially affect the lower limbs (tendons and fasciae) and which have also been described in head and neck localizations. Their clinical and immunohistochemical mimicry with melanoma makes it difficult to diagnose sarcomas. SCC treatment is mainly focused on large-scale resection surgery with adjuvant radiotherapy because of their low chemo-sensitivity and extreme lymphophilia. In case of head and neck localization, these treatments may lead to function and aesthetic sequelae thus requiring the use of modern techniques of reconstructive surgery. The authors describe the diagnosis, treatment and follow-up of large lingual SCC case using a DIEP free flap reconstruction according to an original technique developed in the department. Given the characteristics of patients with SCC (a high proportion of women between 20 and 40 years old) and its inherent qualities (low morbidity of the donor site, volume delivered and excellent plasticity), the fascio-cutaneous free flap type "DIEP" "taken according to the design of the" Cathedral triptych seems to be a viable choice among the range of reconstruction solutions.

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

BackgroundClear 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.Case presentationWe 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.ConclusionThis report will illustrate that the mediastinum is a potential site for primary CCS and FISH plays an important role in making a conclusive diagnosis.

Primary clear cell sarcoma of small intestine: report of a case

Primary clear cell sarcoma of small intestine: report of a case

Primary Clear Cell Sarcoma of the Tongue

Clear cell sarcoma shares features with melanoma, but frequently shows EWSR1 rearrangements. It is an aggressive tumor typically occurring in the soft tissues of the extremities, with a gastrointestinal variant with less consistent melanocytic differentiation. It is extremely rare in the head and neck region, with no reported cases in the oral cavity. We report a case of an 82-year-old woman with a clear cell sarcoma arising in the tongue, with cervical lymph node metastases. Histologically, the tumor showed some features of gastrointestinal clear cell sarcoma. No osteoclast-type giant cells were present. The tumor cells were positive for S100 protein and negative for other melanocytic markers. Fluorescence in situ hybridization showed rearrangements of EWSR1 and ATF1. This case expands the spectrum of clear cell sarcoma with a gastrointestinal-like variant in a novel site, emphasizing the need to consider it as a differential diagnosis to melanoma in mucosal sites.

Clear cell sarcoma originating in the anterior mediastinum

A 34-year-old man with intermittent chest pain had a 60-mm mass in the anterior mediastinum. A CT-guided needle biopsy revealed that the tumor was composed of atypical small cells and was positive for HMB-45 without cytoplasmic melanin pigmentation. These results suggested a diagnosis of malignant melanoma (MM) or clear cell sarcoma (CCS). EWS gene rearrangement was detected by fluorescence in situ hybridization, resulting in the definite diagnosis of CCS. Sarcomas originating in the mediastinum account for only 1 % of all sarcoma cases. CCS is a rare soft tissue sarcoma, which usually occurs in the tendons and aponeuroses and is often misdiagnosed as MM because of similar immunophenotypes. There is only one reported case of a primary CCS of the mediastinum. There is no standard treatment for CCS, but for metastatic MM, dacarbazine, ipilimumab, and BRAF-inhibitors can be treatments of choice. Thus, differential diagnoses are important to determine treatment strategies. Meticulous observation of skin lesions and pathological and molecular diagnoses, including EWS gene rearrangement, is recommended in cases with mediastinal tumors suspected of MM or CCS.

A rare case of primary clear cell sarcoma of the pubic bone resembling small round cell tumor: an unusual morphological variant

BackgroundClear cell sarcoma (CCS) and malignant melanoma share overlapping immunohistochemistry with regard to the melanocytic markers HMB45, S100, and Melan-A. However, the translocation t(12; 22)(q13; q12) is specific to CCS. Therefore, although these neoplasms are closely related, they are now considered to be distinct entities. However, the translocation is apparently detectable only in 50%–70% of CCS cases. Therefore, the absence of a detectable EWS/AFT1 rearrangement may occasionally lead to erroneous exclusion of a translocation-negative CCS. Therefore, histological assessment is essential for the correct diagnosis of CCS. Primary CCS of the bone is exceedingly rare. Only a few cases of primary CCS arising in the ulna, metatarsals, ribs, radius, sacrum, and humerus have been reported, and primary CCS arising in the pubic bone has not been reported till date.Case presentationWe present the case of an 81-year-old man with primary CCS of the pubic bone. Histological examination of the pubic bone revealed monomorphic small-sized cells arranged predominantly as a diffuse sheet with round, hyperchromatic nuclei and inconspicuous nucleoli. The cells had scant cytoplasm, and the biopsy findings indicated small round cell tumor (SRCT). Immunohistochemical staining revealed the tumor cells to be positive for HMB45, S100, and Melan-A but negative for cytokeratin (AE1/AE3) and epithelial membrane antigen. To the best of our knowledge, this is the first case report of primary CCS of the pubic bone resembling SRCT. This ambiguous appearance underscores the difficulties encountered during the histological diagnosis of this rare variant of CCS.ConclusionAwareness of primary CCS of the bone is clinically important for accurate diagnosis and management when the tumor is located in unusual locations such as the pubic bone and when the translocation t(12; 22)(q13; q12) is absent.

Co-Expression and Multiple Cytokines and Their Receptors in Primary Clear Cell Sarcoma of the Pubic Bone with Features of a Small round Cell Tumor

We present the case of an 81-year-old man with primary clear cell sarcoma (CCS) of the pubic bone with an associated aggressive clinical course. The patient's laboratory tests showed marked leukocytosis, elevated levels of C-reactive protein and multiple cytokines, including interleukin-6 (IL-6) and granulocyte colony-stimulating factor (G-CSF). Histological examination showed monomorphic small cells predominantly arranged as a diffuse sheet with morphological features of a small round cell tumor (SRCT). Immunohistochemical staining indicated that the tumor cells were positive for HMB45, S100, Melan A, IL-6, IL-6 receptor, G-CSF, and G-CSF receptor and negative for cytokeratin (AE1/AE3) and epithelial membrane antigen. To the best of our knowledge, this is the first case report of aggressive primary CCS of the pubic bone with features of SRCT showing the production and co-expression of multiple cytokines and their receptors. Thus, we suggest that proliferation through an IL-6- and G-CSF-associated autocrine mechanism may play an important role in the aggressive clinical course and poor prognosis of some CCSs showing features of SRCT.

Cutaneous Clear Cell Sarcoma: A Rare Aggressive Tumor with Potential Diagnostic Challenge

Clear cell sarcoma is a deep-seated, exceedingly rare aggressive tumor, typically involving the tendons and aponeuroses with melanocytic differentiation and a distinct genetic background. A primary dermal location is rarer. It exhibits histological, immunohistochemical, and ultrastructural similarities with the more common primary (or metastatic) malignant melanoma causing major diagnostic confusion. We describe a case of primary cutaneous clear cell sarcoma arising in the right lower extremity of a 40-year-old male patient.

Primary clear cell sarcoma of humerus: case report

We report a case of primary clear cell sarcoma occurring in the humerus. A 20 year old girl was referred to our hospital two years ago with painless swelling of the soft tissue surrounding the proximal right humerus. The conventional radiographic image showed an ill-defined, aggressive, osteolytic lesion associated with a partial cortical defect of the proximal right humerus. Magnetic resonance imaging found an irregularly shaped extraosseous mass extending from the proximal shaft of the right humerus, penetrating through the destroyed bone and invading the biceps brachii. After preoperative chemotherapy, a total tumor resection, internal fixation and bone cement implantation were performed. Histological studies of the resected tumor found that fibrous septa divided into well-defined nests and polygonal and fusiform cells with clear cytoplasm. Immunohistochemical studies demonstrated strong positive cytoplasmic staining with S-100 and scattered positivity with HMB-45. These findings led to a final, definitive diagnosis of clear cell sarcoma of the humerus. After routine postoperative chemotherapy, a 2-year follow-up showed no metastasis. Our findings in this report point out that primary clear cell sarcoma can originate from within the humerus and that limb salvage surgery can obtain a good result.

Selected Unusual Tumors of the Stomach

Several unusual stomach tumors have been recently described. In addition, some tumors that are often encountered in other sites may rarely occur as primary gastric tumors. The diagnostic surgical pathologist needs to be aware of some of these lesions to prevent misdiagnosis. This overview discusses the key clinical features, pathology, immunohistochemistry, and relevant molecular findings of multiple minute gastrointestinal stromal tumors and interstitial cell of Cajal hyperplasia, nerve sheath tumors (schwannoma and perineurioma), gastroblastoma, granular cell tumor, glomus tumor, plexiform angiomyxoid myofibroblastic tumor, and primary clear cell sarcoma of the gastrointestinal tract that occur as primary gastric neoplasms.

Primary clear cell sarcoma of the sacrum: a case report

Clear cell sarcoma, first described by Enzinger in 1965, is an uncommon malignant soft tissue neoplasm that displays melanocytic differentiation. It occurs predominantly in the soft tissue of the extremities in young adults or children. Primary clear cell sarcoma of the bone is extremely rare, only seven cases have been reported to our knowledge. We present here a case of a huge primary clear cell sarcoma of the sacrum arising in a 25-year-old man. The average percentage of melanin content in the tumor was 9.25 ± 6.71%, which resulted in hypointense signal in T2-weighted and heterogeneous hyperintense signal in T1-wieghted images of magnetic resonance imaging (MRI). The patient was treated with curettage of the mass and neither further radiotherapy nor chemotherapy had been provided. The patient had local regrowth of tumor at 9 months after surgery. To our knowledge, this is the first case of CCS in the axial skeleton documented in English literature.

Cutaneous Clear Cell Sarcoma: A Clinicopathologic, Immunohistochemical, and Molecular Analysis of 12 Cases Emphasizing its Distinction from Dermal Melanoma

Clear cell sarcoma (CCS) of tendons and aponeuroses/malignant melanoma (MM) of soft parts is a rare tumor and in the majority of cases presents a characteristic reciprocal translocation t(12;22)(q13;q12) that results in fusion of the EWS and ATF1 genes. Although the melanocytic differentiation of CCS is indisputable, its precise lineage remains unclear. Typically, the slowly growing tumor affects the extremities of adolescents or young adults, especially around the ankle and foot. CCS is classically regarded as a deep soft tissue tumor associated with tendons or aponeuroses. This traditional view is put into perspective by the description of primary CCS of the gastrointestinal tract that may have a variant fusion gene EWSR1-CREB1. We describe 12 cases of cutaneous CCS and discuss the differential diagnoses. These 12 cases share an identical immunohistochemical profile with MM and thus can easily be confused with a dermal variant of spindle cell MM or metastasis of MM. The patients' ages ranged from 6 to 74 years (median: 25 y), and there was a female predominance (10 females, 2 males). Most tumors (n = 9) were located on the extremities, 2 tumors arose on the back, and 1 on the abdomen. The mean tumor size was 0.97 cm (range, 0.4 to 1.7 cm). Six cases showed invasion of the subcutis, the other 6 cases were entirely dermal. Tumor necrosis was evident in 2 cases, melanin pigment in 2 cases, and ulceration in 1 tumor. All cases showed uniform nests and fascicles of pale spindled or slightly epitheloid cells with finely granular eosinophilic or clear cytoplasm. There was fair pleomorphism with plump spindled nuclei and significantly prominent nucleoli. Multinucleated wreath-like tumor giant cells were observed in two-thirds of cases, but were usually present only focally. The dense cellular aggregates were encased by delicate fibrous septa. The stroma showed a sclerotic reticulated pattern. Partly, the nests of spindle cells bordered the epidermis, prima vista mimicking junctional nests of melanocytes. The specific translocation pattern was confirmed in all cases by fluorescence in situ hybridization. Local recurrences and metastases developed in 2 and 3 patients, respectively, and 1 patient died of the disease.

Primary Giant Clear Cell Sarcoma (Soft Tissue Malignant Melanoma) of the Sternum

One case of a primary clear cell sarcoma of the sternum (also called soft tissue melanoma) is reported. This neoplasm represents a rare occurrence, and as a rule, differential diagnosis with melanoma often requires detailed immunohistochemistry and cytogenetic analysis (ie, rearrangement of EWS gene localized on 22q12 chromosome). Because wide resection is recommended, chest wall reconstruction may pose challenging technical issues. In our patient, we elected not to proceed to clavicular stabilization. Nevertheless, acceptable shoulder girdle mobility was observed after surgery.