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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The melanosome is a secretory organelle unique to the melanocyte and its neoplastic counterpart, malignant melanoma. The synthesis and assembly of these intracytoplasmic organelles is not yet fully understood. We have developed a murine monoclonal antibody (MoAb) against melanosomes isolated from human melanocytes (newborn foreskin) cultured in the presence of 12-O tetradecanoyl phorbol-13-acetate (TPA). This MoAb, designated HMSA-5 (Human Melanosome-Specific Antigen-5) (IgG1), recognised a cytoplasmic antigen in both normal human melanocytes and neoplastic cells, such as common and dysplastic melanocytic nevi, and malignant melanoma. None of the carcinoma or sarcoma specimens tested showed positive reactivity with MoAb HMSA-5. Under immunoelectron microscopy, immuno-gold deposition was seen on microvesicles associated with melanosomes, and a portion of the ER-Golgi complexes. Radioimmunoprecipitation analysis showed that the HMSA-5 reactive antigen was a glycoprotein of M(r) 69 to 73 kDa. A pulse-chase time course study showed that the amount of antigen detected by MoAb HMSA-5 decreased over a 24 h period without significant expression on the cell surface, or corresponding appearance of the antigen in the culture supernatant. This glycoprotein appears to play a role in the early stages of melanosomal development, and the HMSA-5 reactive epitope may be lost during subsequent maturation processes. Importantly, HMSA-5 can be identified in all forms of human melanocytes, hence it can be considered a new common melanocytic marker even on routine paraffin sections.
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PMID:A murine monoclonal antibody, MoAb HMSA-5, against a melanosomal component highly expressed in early stages, and common to normal and neoplastic melanocytes. 767 81

The vast majority of cutaneous malignant melanomas (CMM) develop from a proliferation of intraepidermal melanocytes that may progress through radial (including in situ and microinvasive stages) and vertical growth phases (VGP). The currently accepted classification of melanoma is based on the presence (eg, superficial spreading, lentigo maligna, or acral lentiginous melanoma) or absence of a radial growth phase (nodular melanoma). Although not standardized, melanoma may also be classified as to the nature of the VGP, eg, as expansile nodules composed of epithelioid cells, spindle cells, or smaller nevus-like cells supervening on one of the radial growth components previously mentioned, or developing de novo. Less common variants of the VGP include desmoplastic and neurotropic melanomas (often arising with lentiginous melanomas), and the controversial (and perhaps mainly conceptual) entity, minimal deviation melanoma. Other unusual or rare forms of melanoma are malignant blue nevus, balloon cell melanoma, and clear cell sarcoma. An extensive discussion of the differential diagnosis of the various types of melanoma is provided.
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PMID:The histopathology of cutaneous malignant melanoma. 850 17

Six rodent cell lines (36B10 rat glioma cells, 9L rat gliosarcoma cells, V79 Chinese hamster lung fibroblasts, EMT6/UW and EMT6/Ro mouse mammary sarcoma cells, and RIF-1 mouse fibrosarcoma cells) were tested for growth in cylindrical threads of Matrigel. These cells grew in the threads with doubling times of 17-23 h, reaching maximum cell densities on the order of 10(8) cells/ml. Histological sections of these threads showed a heterogeneous cell distribution: cells grew to confluence at the thread surface and at somewhat lower cell densities in the thread core. [H-3]thymidine labeling index and radiation sensitivity were measured for 9L and EMT6/UW cells in Matrigel threads. For both cell types, the labeling index in Matrigel was lower than observed in cell monolayers, with higher labeling indexes at the thread periphery than in the thread core. When these threads were grown in stirred medium, lower thread diameters, higher cell yields per thread, and higher labeling indices were obtained. EMT6 cell monolayers coated with Matrigel were less radiosensitive than cells in uncoated monolayers. This protective effect was eliminated by irradiating in the presence of 1 mg/ml misonidazole. EMT6 cells consume nearly three times as much oxygen (mole/cm3-sec) as do 9L cells, which are equally radiosensitive in monolayers with or without a Matrigel coating. The radiation sensitivity of EMT6/UW cells in Matrigel threads was similar to that for monolayers of plateau phase cells, whereas for 9L cells, the response in threads was more similar to exponentially growing cells. We conclude that Matrigel threads provide an alternative in vitro model for studying the radiation response of cells in a three-dimensional geometry.
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PMID:Growth rate, labeling index, and radiation survival of cells grown in the Matrigel thread in vitro tumor model. 852 12

We report a patient who developed malignant transformation of a cellular blue nevus. At the age of 19 years the congenital, pigmented tumor on the left buttock was histopathologically diagnosed as cellular blue nevus. Thirty years later the tumor dramatically increased in size, involving the entire left buttock within several months. Multiple biopsies revealed the presence of a cellular blue nevus within the papillary dermis and an invasive, pleomorphic pigmented sarcoma in the depth of the tissue spreading into subcutis and skeletal muscle. Both benign and malignant cells were S100+, vimentin+ and HMB-45+, but only the malignant tumor cells stained positive for the proliferating cell nuclear antigen. General examination disclosed multiple metastases in the paraaortal lymph nodes and the retroperitoneum as well as a single brain metastasis. Despite palliative therapy with ionizing radiation and chemotherapy, the patient developed generalized metastases and died within weeks. This case clearly confirms that cellular blue nevi have the potential for malignant transformation and that the malignant variant may behave aggressively just as a malignant melanoma.
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PMID:[Malignant blue nevus with metastasis to lymph nodes and brain]. 899 29

This series presents six cases of a rare variant of dermatofibroma, characterized by marked clear cell change. All lesions occurred on the lower extremities of middle-aged adults (four women, two men), mostly with the clinical diagnosis of fibrohistiocytic lesion. Histological examination revealed well circumscribed, faintly stained dermal to subcutaneous lesions which were due to the overwhelming presence of clear cells (> 90%), some with prominent PAS-positive cytoplasmic granulation. Overlying epidermal hyperplasia as well as storiform arrangement of spindle cells, sclerotic collagen and some interspersed lympho-histiocytic infiltrate at the periphery of the lesion indicated the fibrohistiocytic origin. Individual histopathological peculiarities included: bizarre giant cells in two cases, perifollicular arrangement and haemangiopericytoma-like features with iron deposition in one case each. Immunohistochemically three of four lesions showed moderate reactivity for factor XIIIa and two of four with an anti-metallothionen marker E9, but were otherwise negative with a broad panel of markers. Electronmicroscopy in two cases revealed large pools of glycogen beside focal, prominent endoplasmic reticulum and lysosomes in some granular cells, but only optically translucent cells in cases of clear cells. Recognition of clear cell dermatofibroma is important as the differential diagnosis includes some entities with more serious outcome/considerations such as metastases of renal cell carcinoma, xanthogranulomatous reactions, balloon cell naevus/melanoma and clear cell sarcoma.
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PMID:Clear cell dermatofibroma. 902 59

Desmoplastic/spindle cell melanoma is a rare variant of melanoma. A number of factors complicate the diagnosis of desmoplastic/spindle cell melanoma, including the variable absence of a lentiginous component, its spindle cell morphology, and its many morphologic mimics, including scars, malignant peripheral nerve sheath tumor, neurofibroma, atypical fibroxanthoma, and spindled carcinoma. The immunohistochemical confirmation of desmoplastic/spindle cell melanoma may also be difficult, because the majority of tumors are negative for specific melanocytic markers such as HMB-45 and Melan-A, despite their usual expression of S-100 protein. Two new and potentially promising melanocytic markers, microphthalmia transcription factor (MiTF) and melanoma cell adhesion molecule (Mel-CAM), have been shown to be sensitive markers of epithelioid melanoma, but have not been tested in desmoplastic/spindle cell melanoma or in other rare melanocytic neuroectodermal tumors such as clear cell sarcoma. We immunostained 79 tumors (20 desmoplastic/spindle cell melanomas, 10 scars, 10 neurofibromas, 12 malignant peripheral nerve sheath tumors, 10 atypical fibroxanthomas, 10 clear cell sarcomas, 3 melanotic schwannomas, and 4 cellular blue nevi) for MiTF and Mel-CAM. MiTF expression was seen in 11 of 20 desmoplastic/spindle cell melanomas, 0 of 10 scars, 2 of 10 neurofibromas, 0 of 12 malignant peripheral nerve sheath tumors, 1 of 10 atypical fibroxanthomas, 7 of 10 clear cell sarcomas, 3 of 3 melanotic schwannomas, and 3 of 4 cellular blue nevi. Mel-CAM expression was present in 14 of 17 desmoplastic/spindle cell melanomas, 0 of 10 scars, 4 of 10 neurofibromas, 3 of 11 malignant peripheral nerve sheath tumors, 0 of 10 atypical fibroxanthomas, 9 of 10 clear cell sarcomas, 3 of 3 melanotic schwannomas, and 0 of 4 cellular blue nevi. MiTF and Mel-CAM were coexpressed in 6 of 17 desmoplastic/spindle cell melanomas and in no other tumor. Regarding desmoplastic/spindle cell melanoma, scar, neurofibroma, malignant peripheral nerve sheath tumor, and atypical fibroxanthoma, the sensitivity and specificity of MiTF for desmoplastic/spindle cell melanoma were 55% and 91%, respectively. For this same group of tumors, Mel-CAM had a sensitivity of 82% and a specificity of 83%. We conclude that the sensitivity and specificity of MiTF for desmoplastic melanoma equals or exceeds that of such markers as HMB-45 or Melan-A, and that MiTF should be part of the initial immunohistochemical panel for the work-up of such cases. Mel-CAM, while very sensitive, is relatively nonspecific, because it is also expressed in a variety of mesenchymal tumors and carcinomas. Mel-CAM is best reserved for cases morphologically suspected to be desmoplastic/ spindle cell melanoma, in which S-100 is positive and MiTF and other melanocytic markers are negative. These markers may also be helpful in certain other differential diagnoses, such as distinguishing clear cell sarcomas from epithelioid malignant peripheral nerve sheath tumors.
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PMID:Microphthalmia transcription factor and melanoma cell adhesion molecule expression distinguish desmoplastic/spindle cell melanoma from morphologic mimics. 1114 52

The diagnosis of mast cell lesions of the skin can occasionally be challenging. Calretinin, a 29 kD neuron-specific calcium-binding protein found mostly in the CNS and retina, has been shown to be a positive marker for mesotheliomas, and is also expressed in mast cells. We studied the diagnostic value of calretinin and compared our results to other established ancillary studies used to identify mast cells, such as Toluidine blue and the Leder stain. Sixty-three cases were studied, including 45 mast cell lesions (22 urticaria pigmentosum, 17 mastocytomas, and six telangiectasia macularis eruptiva perstans [TMEP]), seven nevi, three melanomas, four granular cell minors of the skin, three cutaneous lymphomas, and one granulocytic sarcoma. Patients ranged in age from less than 1 to 85 years with a median age of 29 years. The group consisted of 36 females and 27 males. Calretinin was expressed in all 45 mast cell lesions. Negative staining for calretinin was seen in all skin lesions that potentially could be considered in the differential diagnosis of mast cell lesions such as nevi, melanomas, lymphomas, and the granulocytic sarcoma. However, calretinin expression was noted in four/four granular cell tumors. Leder and Toluidine blue stains were positive in all 45 mast cell lesions, and all nonmast cell lesions were negative with these stains. In conclusion, our study demonstrated that calretinin is a sensitive and specific marker of mast cells and can be an aid in distinguishing mast cell lesions from other skin lesions considered in the differential diagnosis. Calretinin may be more sensitive than the currently used special stains utilized to diagnose mast cell lesions having few diagnostic mast cells such as TMEP. However, this immunoperoxidase stain does not add significant diagnostic information in most cases, when compared with the currently used less expensive special stains and, therefore, is not cost-effective. Int J Surg Pathol 8(2):119-122, 2000
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PMID:Diagnostic Value of Calretinin in Mast Cell Lesions of the Skin. 1149 76

Connective tissue consists of collagen, elastic fibers and ground substances produced by fibrocytes. These cells are usually spindle-shaped with slender nuclei and bipolar cytoplasmic extensions. Apart from labeling for vimentin and variable reactivity for factor XIIIa and CD34, fibrocytes are immunonegative. Electron microscopy reveals prominent endoplasmic reticulum, but is otherwise indistinct. Lesions with fibrocytic differentiation can be divided into five categories: scars, keloids, dermatofibromas, nodular fasciitis, and superficial fibromatoses are inflammatory lesions. Thereby, dermatofibromas and their subcutaneous/deep soft tissue counterpart nodular fasciitis can present with a wide variety of clinicopathologic variants which may be misinterpreted as malignancies. Prurigo nodularis, chondrodermatitis nodularis helicis, acanthoma fissuratum, and knuckle pads are hyperplasias; fibroma molle, fibrous papules, connective tissue nevi, and elastofibroma are hamartomas; and fibroma of tendon sheath, pleomorphic fibroma, and giant cell tumor of tendon sheath are benign neoplasms. Deep fibromatoses, dermatofibrosarcoma protuberans, giant cell fibroblastoma, giant cell angiofibroma, hyalinizing spindle cell tumor with giant rosettes, solitary fibrous tumor, myxofibrosarcoma, low-grade fibromyxoid sarcoma, acral myxoinflammatory fibroblastic sarcoma, and classical fibrosarcoma, are malignant neoplasms, that is fibrosarcomas of variable malignant potential. Lesions dominated by myocytes/ myofibroblasts, e.g. cutaneous myofibroma/infantile myofibromatosis, or by macrophages, e.g. xanthogranulomas, are not part of this chapter.
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PMID:Connective tissue tumors. 1207 32

In 1897, Reis was the first to describe benign nevus inclusions in the lymph node of patients undergoing surgery for genital neoplasia. These inclusions are very rarely encountered and can be misleading in the absence of careful analysis. We report on two cases of nevus cell inclusions in axillary and inguinal lymph nodes dissected in the context of breast cancer and thigh sarcoma respectively. Cautious morphological analysis should be compared with histochemistry and immunohistochemistry data to avoid erroneous diagnosis of metastasis. We also should bare in mind the possible occurrance of primitive lymph node melanoma.
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PMID:[Begnin naevus cell inclusions in two patients treated for cancer]. 1241 Jan 56

We report the production of a new monoclonal antibody, PNL2, directed against a fixative resistant melanocyte antigen. The analysis of PNL2 immunostaining on a broad range of normal or malignant human tissues and on various melanocytic lesions revealed its high specificity. PNL2 gave a strong cytoplasmic staining of skin and oral mucosae melanocytes, and staining of granulocytes when used at high concentration. PNL2 stained all intra-epidermal nevi irrespective of their histologic type, but common intradermal nevi and the dermal component of compound nevi were largely non-reactive as only scattered nevus cells in the papillary dermis were labeled. PNL2 labeled more than 70% of the neoplastic cells in all primary melanomas irrespective of their histologic type. However, PNL2 did not label desmoplastic melanomas. All metastatic melanomas were also stained but the percentage of labeled cells was occasionally lower than the primary tumor. PNL2, as anti-Melan A and HMB-45 antibodies, stained most of the clear cell sarcoma cells, and a few cells in angiomyolipomas and lymphangioleiomyomatosis. None of the other non-melanocytic lesions tested were labeled. Proteomic approaches showed that the immunoaffinity purified PNL2-binding complexes isolated from melanoma cell lines comprise at least TAP1, Clathrin 17 and prealbumin proteins, but not the gp100 recognized by HMB-45. In conclusion, this new monoclonal antibody, PNL2, is directed against a new fixative resistant melanocyte associated antigen. This antigen is chemically resistant and thus allows immunostaining after melanin bleaching or decalcification. We also demonstrate that it is different from Melan A and from gp100, even if PNL2 and HMB-45 staining patterns are sometimes similar.
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PMID:PNL2, a new monoclonal antibody directed against a fixative-resistant melanocyte antigen. 1274 55


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