mart-1-antigen and Soft-Tissue-Neoplasms

Undifferentiated melanoma should be considered in the differential diagnosis of sarcomatoid cutaneous malignancies to ensure that patients receive the correct treatment. Dermatopathologists should recognize the pitfalls of relying too heavily on immunohistochemistry to establish this diagnosis and consider ancillary tests, including single-nucleotide polymorphism (SNP) copy number arrays and targeted next-generation sequencing (NGS), when a definitive diagnosis cannot be rendered on a primary or metastatic tumor. This technology can also help to exclude a collision of melanoma and sarcoma when both differentiated and undifferentiated components are juxtaposed. We describe an exceedingly rare, illustrative example of undifferentiated sarcomatoid melanoma presenting as a pedunculated nodule. The clinical context and presence of a small differentiated component helped to establish the diagnosis; however, the transition from differentiated to undifferentiated melanoma was accompanied by an abrupt loss of S100, Sox10, MITF, MelanA, and HMB45 with gain of CD10 and p63 staining. SNP copy number array and NGS revealed shared chromosomal copy number changes and overlapping mutations with additional aberrances detected exclusively in the sarcomatoid component, thereby excluding a collision tumor and confirming our putative impression of melanoma with progression to an undifferentiated sarcomatoid phenotype.

Topics: Aftercare; Aged; Antibodies, Monoclonal, Humanized; Biomarkers, Tumor; Diagnosis, Differential; gp100 Melanoma Antigen; Humans; Lymphadenopathy; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Membrane Proteins; Microphthalmia-Associated Transcription Factor; Mutation; Neprilysin; Polymorphism, Single Nucleotide; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms; SOXE Transcription Factors; Treatment Outcome

Clear cell sarcoma is a rare cancer primarily of tendons, fascia, and aponeuroses that can be difficult to discern from primary cutaneous malignant melanoma. The two cancers share several histological markers, with most cases of both cancers staining positively for S-100, HMB-45, and melanin. Primary therapy of both cancers involves wide local excision, but while systemic therapy has proven benefit for malignant melanoma, it has not been established for clear cell sarcoma.We report the case of a 58 year old woman with a large, ulcerated, fungating mass on her left lower leg. Frozen section of the mass showed a malignant epithelioid and spindle cell tumor confined to the subcutaneous tissue. A provisional diagnosis of soft-tissue sarcoma was made. Through in-depth study of initial biopsy with immunohistochemistry for S-100, HMB-45, MART-1, and MITF, along with karyotyping and FISH analysis for EWS gene rearrangement, the diagnosis of amelanotic malignant melanoma was confirmed. The patient then underwent systemic treatment with ipilimumab upon recurrence with good response.. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1989338475107348.

Topics: Antibodies, Monoclonal; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Ipilimumab; MART-1 Antigen; Melanoma; Microphthalmia-Associated Transcription Factor; Middle Aged; Proto-Oncogene Proteins B-raf; Sarcoma, Clear Cell; Skin Neoplasms; Soft Tissue Neoplasms; Treatment Outcome

We present the unusual case of a perivascular epithelioid cell tumor (PEComa) occurring within the cheek of a 32-year-old woman. PEComa is a rare, recently described, family of tumors with diverse clinicopathologic expression and which express melanocytic and muscle markers. It mainly affects the abdominopelvic region and rarely occurs in somatic soft tissue or skin. To our knowledge, this is the first reported case of PEComa occurring in the facial cutaneous tissues. Other possible diagnoses considered included benign mesenchymal tumors of smooth muscle or neural origin. However, the cytomorphologic and immunohistochemical profile were most suggestive of PEComa. The tumor was completely excised, but in view of uncertainty as to how this entity would behave in an unusual location, lifelong follow up is recommended. After complete excision, there was no recurrence in 4 years.

Topics: Actins; Adult; Antigens, Neoplasm; Arterioles; Cheek; Diagnosis, Differential; Epithelioid Cells; Facial Neoplasms; Female; Follow-Up Studies; Humans; MART-1 Antigen; Muscle, Smooth, Vascular; Neoplasm Proteins; Perivascular Epithelioid Cell Neoplasms; Soft Tissue Neoplasms

Topics: Adipose Tissue; Adolescent; Antigens, Neoplasm; Biomarkers, Tumor; Female; Fibroma; Humans; Lipoma; MART-1 Antigen; Neoplasm Proteins; Pigmentation; S100 Proteins; Soft Tissue Neoplasms; Treatment Outcome

Clear cell sarcoma (CCS) of soft tissue is a rare sarcoma with morphologic similarities to malignant melanoma but a distinct genetic background including a chromosomal translocation, t(12;22)(q13;q12), or a resultant EWSR1-ATF1 fusion gene. In addition, the tumors occurring in the gastrointestinal tract may have a variant fusion gene EWSR1-CREB1. This study analyzed the clinicopathologic and molecular genetic features of 33 CCSs of soft tissue. The patients' ages ranged from 13 to 73 years (median, 30 y), and there was a male predominance (20 males, 13 females). The tumors were located in the deep soft tissues of the extremities (N=25) or in the trunk or limb girdles (N=8). The median tumor size was 4 cm (range, 1 to 15 cm). The tumor cells were either spindle or epithelioid, and they were arranged predominantly in a short fascicular (N=19) or a solid sheetlike growth pattern (N=14). Minor histologic variations included the existence of rhabdoid cells (N=8), bizarre pleomorphic cells (N=6), alveolar structures due to loss of cellular cohesion (N=3), and a seminomalike pattern (N=2). Tumor necrosis was evident in 14 tumors, and the mitotic activity ranged from 0 to 43 mitotic figures (MF)/10 high-power fields (HPF) (mean: 4 MF/10 HPF). Immunohistochemically, the tumors were consistently positive for S-100 protein (33/33) and variably or focally for HMB45 (32/33), microphthalmia transcription factor (26/32), Melan A (23/32), CD57 (25/33), bcl-2 (30/32), synaptophysin (14/32), CD56 (7/32), epithelial membrane antigen (12/33), cytokeratin (AE1/AE3) (1/32), CD34 (3/32), c-erbB-2 (10/32), c-kit (5/32), and c-met (5/32). alpha-Smooth muscle actin, desmin, and cytokeratin (CAM5.2) were negative. Reverse transcription-polymerase chain reaction using RNA extracted from formalin-fixed, paraffin-embedded tissues demonstrated transcripts of the EWSR1-ATF1 (31/33) or EWSR1-CREB1 fusion gene (2/33). In 26 cases with available clinical information, local recurrences and metastases developed in 2 and 15 patients, respectively. Ten patients were dead of the disease, and the overall survival rate was 63% at 5 years. However, no clinicopathologic or molecular variables associated with the patients' prognosis were identified. This study confirms that CCS is an aggressive soft tissue tumor with a melanocytic phenotype and wider morphologic variations than had been generally considered. In cases with unusual histologic findings, molecular detection of the EWSR1-ATF1/CREB1 fusio

Topics: Adolescent; Adult; Aged; Antigens, CD34; Antigens, Neoplasm; Calmodulin-Binding Proteins; CD57 Antigens; Cyclic AMP Response Element-Binding Protein; Female; Gene Fusion; Genes, bcl-2; Histocytochemistry; Humans; Immunohistochemistry; Keratins; Male; MART-1 Antigen; Melanoma-Specific Antigens; Microphthalmia-Associated Transcription Factor; Middle Aged; Mucin-1; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Proteins; Proto-Oncogene Proteins c-kit; Proto-Oncogene Proteins c-met; Receptor, ErbB-2; RNA-Binding Protein EWS; RNA-Binding Proteins; S100 Proteins; Sarcoma, Clear Cell; Soft Tissue Neoplasms; Survival Rate; Synaptophysin; Translocation, Genetic

PEComa is a rare tumour developing from perivascular epithelioid cells (PEC) and is characterised by positive immunoreactivity for HMB45. Since PEComas are tumours having both a spindle cell component and an epithelioid and giant cell component, as seen in many sarcomas, as well as having a wide distribution in various organs and soft tissue, we reviewed cases originally diagnosed as sarcomas of the soft tissue in our institution and screened them by immunostaining for HMB45.. Consecutive soft tissue sarcomas (31 tumours) retrieved from the Surgical Pathology file at our institution for a period of 3 years were submitted for immunostaining for HMB45. Cases with positive HMB45 immunostaining were submitted for further immunostaining for MART1, CD68, S100 protein, cytokeratin AE1/3, EMA, vimentin, MSA and CD117.. Of 31 sarcomas, three tumours in the group of 11 malignant fibrous histiocytomas (MFH) and unclassified sarcomas showed positive immunoreactivity for HMB45 and MART1 in 1-25% of tumour cells. The three tumours were located in the lower extremities and measured 8, 11 and 12 cm in diameter. Patient gender male:female was 2:1 and ages were 46, 56 and 60 years. Microscopically, the tumours were composed of a variable proportion of spindled cells, multinucleated cells and epithelioid cells disposed in diffuse sheets or nests. Mitotic figures and necrosis were frequent. The immunoreactivity was diffuse for CD68, focal for AE3 and EMA, negative or focal for MSA and CD117, and negative for S100 and AE1. All three patients developed lymph node or distant metastases and died of the disease within 1-2 years.. PEComa re-screened from the group of high grade sarcomas without definite differentiation range from pleomorphic to monomorphic cytohistopathological features. Immunostaining for HMB45 of unclassified sarcomas is useful for the classification of these tumours. They occur preferentially in the lower extremities and have a high malignant potential when associated with large size, tumoural necrosis and high mitotic activity.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Epithelioid Cells; Fatal Outcome; Female; Humans; Immunohistochemistry; Lung Neoplasms; Male; MART-1 Antigen; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Sarcoma; Soft Tissue Neoplasms

Clear cell sarcoma is a rare soft-tissue tumor presenting typically in the extremities of young adults. It has been also known as malignant melanoma of the soft parts because of the presence of melanin and cytoplasmic melanosomes. However, clear cell sarcoma is, at present, usually considered as a unique lesion because the t(12;22)(q13;q12) translocation is present only in clear cell sarcoma. Myxoid malignant melanoma is now a well-recognized morphologic variant of malignant melanoma. However, a myxoid variant of clear cell sarcoma has not been well described yet. We report a case of myxoid clear cell sarcoma occurring on the heel in a 22-year-old man. The tumor was composed of nests and fascicles of oval to fusiform cells with clear to pale eosinophilic cytoplasm, often separated by fibrous septa. The tumor cells were reactive for S-100 protein, HMB-45, and MART-1. Variably sized cysts lined by one or several layers of tumor cells were observed. Alcian blue and mucicarmine stains demonstrated prominent mucin deposition in the tumor stroma and especially in the lumen of the cysts. Fluorescence in situ hybridization for the Ewing sarcoma gene showed rearrangement in nearly all of the neoplastic cells.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; DNA, Neoplasm; Humans; Immunoenzyme Techniques; In Situ Hybridization, Fluorescence; Male; MART-1 Antigen; Melanoma-Specific Antigens; Mucins; Myxosarcoma; Neoplasm Proteins; RNA-Binding Protein EWS; S100 Proteins; Sarcoma, Clear Cell; Soft Tissue Neoplasms

Topics: Adult; Antigens, Neoplasm; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Male; MART-1 Antigen; Neoplasm Proteins; Osteoclasts; S100 Proteins; Sarcoma, Clear Cell; Soft Tissue Neoplasms

Six cases are reported of an osteoclast-rich tumor of the gastrointestinal tract that should be segregated from GIST. Five of the cases were located in the small bowel and one in the stomach. The age of the patients ranged from 13 to 37 years. The tumors behaved aggressively, with metastases to regional lymph nodes, liver, and other intra-abdominal sites. Microscopically, the tumor cells were medium-sized, predominantly oval, relatively monomorphic, diffusely immunoreactive for S-100-protein, and negative for CD117, CD34, HMB-45, and Mart-1. They were admixed with scattered osteoclast-like, multinucleated giant cells which were S-100-protein negative and KP1-positive. One case studied cytogenetically had the karyotype 46XX t(12;22)(q13;q12). The cases here reported are interpreted as examples of a distinctive type of gastrointestinal neoplasm which shares some features with clear cell sarcoma of soft parts (melanoma of soft parts), including in one case the chromosomal translocation that is characteristically associated with that entity.

Topics: Adolescent; Adult; Antigens, CD34; Antigens, Neoplasm; Biomarkers, Tumor; Diagnosis, Differential; Female; Gastrointestinal Neoplasms; Giant Cells; Humans; Immunohistochemistry; Karyotyping; Lymphatic Metastasis; Male; MART-1 Antigen; Melanoma-Specific Antigens; Microscopy, Electron; Neoplasm Proteins; Osteoclasts; Proto-Oncogene Proteins c-kit; S100 Proteins; Sarcoma, Clear Cell; Soft Tissue Neoplasms

Osteocartilaginous metaplasia is known to occur rarely in melanomas, particularly in subungual melanomas. We present a case of a calcified subungual soft tissue tumour in which biopsy of the lesion showed malignant round and spindle-shaped tumour cells, many of which were associated with the formation of cartilage and osteoid-like material. Subsequent resection showed clear histological evidence of a subungual melanoma. Tumour cells expressed S100, melan-A and neurone-specific enolase but were negative for HMB45. Diagnostic radiological and histological features and the nature of the osteocartilaginous differentiation within this lesion is discussed.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Biopsy; Bone Neoplasms; Cartilage; Diagnosis, Differential; Fingers; Humans; Magnetic Resonance Imaging; Male; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Middle Aged; Neoplasm Proteins; Osteochondroma; Osteosarcoma; Phosphopyruvate Hydratase; Soft Tissue Neoplasms; Tomography, X-Ray Computed

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Cartilage; Diagnosis, Differential; Epithelioid Cells; Humans; MART-1 Antigen; Melanoma-Specific Antigens; Melanoma, Amelanotic; Neoplasm Proteins; Nerve Sheath Neoplasms; Neurilemmoma; Soft Tissue Neoplasms

Clear cell sarcoma (CCS), malignant melanoma of soft parts, is a rare malignant tumor with a poor prognosis. In this study, a CCS cell line, designated MP-CCS-SY, was established from a metastatic tumor of a 17-year-old Japanese girl that originated in the left Achilles tendon. A small number of melanosomes were detected in the cytoplasm by electron microscopy. The melanosomes immunoreacted with two melanoma-associated antibodies, HMB45 and Melan-A. A Western blot demonstrated the existence of a Melan-A antigen in this cell line. Although a t(12;22)(q13;q12), which is characteristic of CCS, was not identified by a chromosomal analysis with conventional banding techniques, fluorescence in situ hybridization analysis with painting probes of chromosomes 12 and 22 revealed the insertion of a chromosome 12 fragment into one of the long arms of chromosome 22. The chimeric EWS/ATF1 transcript was detected by the reverse transcriptase polymerase chain reaction. Extra copies and structural abnormalities of chromosome 8 were observed. Overexpression of c-myc mRNA was detected by Northern blot analysis and may have a role in malignant progression of CCS. The availability of this MP-CCS-SY cell line will help to understand the molecular biology of this malignancy and should be useful as a tool for developing an immunotherapy.

Topics: Achilles Tendon; Adolescent; Antigens, Neoplasm; Chromosomes, Human, Pair 12; Chromosomes, Human, Pair 22; Chromosomes, Human, Pair 8; Disease Progression; Fatal Outcome; Female; Gene Expression Regulation, Neoplastic; Genes, myc; Humans; In Situ Hybridization, Fluorescence; MART-1 Antigen; Melanosomes; Mutagenesis, Insertional; Neoplasm Proteins; Oncogene Proteins, Fusion; Proto-Oncogene Proteins c-myc; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Sarcoma, Clear Cell; Soft Tissue Neoplasms; Transcription Factors; Tumor Cells, Cultured

HMB-45, an antibody directed against a premelanosome glycoprotein, has thus far been considered the most specific antibody for the immunocytochemical substantiation of the diagnosis of malignant melanoma (MM). A recently described antigen, MART-1, is a transmembrane protein that is present in normal melanocytes and widely expressed in MM. Antibodies to MART-1 have recently become commercially available. Both HMB-45 and MART-1 form the basis of ongoing immunotherapy protocols at the National Institutes of Health/National Cancer Institute.. The authors evaluated 207 lesions from 160 patients with metastatic MM procured via fine-needle aspiration (FNA) for expression of MART-1 (clone M2-7C10) and HMB-45 prior to commencement of immunotherapy. FNAs were performed on subcutaneous soft tissue masses (190 lesions), lung (8 lesions), liver (5 lesions), pancreas (3 lesions), and brain (1 lesion). To test the specificity of the monoclonal antibody directed against MART-1, the authors evaluated its reactivity in normal tissues as well as in various nonpigmented neoplasms that are often included in the differential diagnosis of MM.. Of all lesions tested, 13 (6%) were negative for both MART-1 and HMB-45. Of all patients tested, 20% had 1 or more lesions that were non-immunoreactive with HMB-45, whereas only 10% had 1 or more lesions that were nonimmunoreactive for MART-1. Eight percent of the lesions tested were negative for MART-1 only, whereas 16% of lesions tested were negative for HMB-45 only. In 35% of the lesions, MART-1 stained more cells than HMB-45. In 13%, MART-1 stained fewer cells than HMB-45, and in 52% both antibodies stained an equivalent number of cells. All samples of normal tissue were negative for staining with MART-1, as were the nonpigmented lesions tested. Melanocytes in normal skin samples stained positively for MART-1.. The MART-1 antibody is a superior immunohistochemical marker for the diagnosis of MM. It has the potential to become the preferred antibody over HMB-45 for the diagnosis of metastatic MM in FNA material, as MART-1 stains a higher percentage of lesions in a higher percentage of patients than does HMB-45.

Topics: Antibodies, Monoclonal; Antibodies, Neoplasm; Antigens, Neoplasm; Biopsy, Needle; Diagnosis, Differential; Humans; Immunoenzyme Techniques; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Neoplasm Proteins; Paraffin Embedding; Sensitivity and Specificity; Soft Tissue Neoplasms

The purpose of this study was to test different malignant non-melanocytic tumours with the commercially available antibody Melan-A to examine its diagnostic specificity and to compare the S100, Melan-A and HMB-45 reactivity in various melanocytic lesions.. Seventy-three benign and malignant melanocytic lesions and 31 cases of non-melanocytic tumours, sarcomas, carcinomas and carcinoids, were selected. Immunohistochemical staining of paraffin sections, following a high temperature antigen unmasking technique, was performed. Melan-A stains junctional and dermal melanocytes in all benign melanocytic lesions with the exception of neuro-naevoid areas. The epithelioid and the spindle cells in malignant melanomas did not show considerable difference in their Melan-A reactivity. The predominantly spindle cell type mucosal melanomas contained more Melan-A-positive cells than HMB-45-positive cells and similar results were observed in metastatic malignant melanomas. In desmoplastic melanomas the positivity of Melan-A was not consistent. None of the sarcomas, carcinomas and carcinoids expressed Melan-A. Almost all soft tissue tumours, except for two malignant gastrointestinal stromal tumours, were unreactive for HMB-45. These two cases did not react with Melan-A antibody.. Melan-A is a useful additional marker to differentiate non-melanocytic tumours from primary or metastatic melanoma. In melanocytic lesions the Melan-A staining pattern is similar to S100, but seems to be more specific. In desmoplastic melanomas, however, the variable Melan-A staining further necessitated detailed histological examination and the use of the S100 reaction.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Carcinoid Tumor; Carcinoma; Humans; Immunohistochemistry; MART-1 Antigen; Melanoma; Melanoma-Specific Antigens; Neoplasm Proteins; S100 Proteins; Sarcoma; Skin Neoplasms; Soft Tissue Neoplasms