Cases reported "Melanoma"

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1/17. Animal type melanoma: a report of a case with balloon-cell change and sentinel lymph node metastasis.

    Animal type melanoma is a rare histopathologic variant of melanoma characterized by sheets and nodules of heavily pigmented epithelioid melanocytes that involve the entire thickness of the dermis. This human neoplasm mimics melanocytic neoplasms seen in gray horses and laboratory animals; thus, is termed animal type melanoma. It is quite rare and, with only a few reported cases, its biological behavior is not well understood. We report an example of animal type melanoma on the back of a 27-year-old man. The lesion showed areas of melanoma in situ, which ruled out the possibility of metastatic melanoma. Features of regression were also seen at dermo-epidermal junction and papillary dermis. In some areas, neoplastic melanocytes exhibited a balloon-cell appearance; in others the neoplasm was composed of sheets and fascicles of heavily pigmented epithelioid melanocytes that permeated the entire dermis and extended into the dermal-subcutaneous interface, mimicking a cellular blue nevus. Epithelioid melanocytes in deeper areas showed abundant, heavily pigmented cytoplasm and pleomorphic nuclei with prominent eosinophilic nucleoli and some mitotic figures. The neoplastic cells did not show evidence of maturation in deeper areas of the lesion. In some sections, a nodule of heavily pigmented epithelioid melanocytes was seen far from the main bulk of the lesion, at the dermal-subcutaneous interface, raising the possibility of a satellite lesion. A lymphoscintigraphy showed a sentinel lymph node in the right axilla and a subsequent axillary lymphadenectomy demonstrated that the architecture of the sentinel lymph node was effaced by metastatic melanoma. The patient received adjuvant chemotherapy with inteferon alfa-2b and four months after this treatment the patient is alive and well, without evidence of recurrences or additional metastases.
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2/17. melanoma with prominent pigment synthesis (animal-type melanoma): a case report with ultrastructural studies.

    melanoma with prominent pigment synthesis or animal-type melanoma (ATM) is a very rare type of melanoma. Its histogenesis has not been elucidated and ultrastructural features have not been described in human beings. We present an additional case of ATM in a 28-year-old woman with positive sentinel node biopsy and provide the results of electron microscopic studies. Histopathologically, the skin lesion was composed of heavily pigmented neoplastic cells mostly arranged as large sheets, focally also in a nodular growth pattern. After bleaching, the neoplastic cells demonstrated round nuclei with 1 or rarely 2 conspicuous nucleoli and a prominent nuclear membrane and abundant, gray, slate-like cytoplasm. Some cells demonstrated round cytoplasmic inclusions. There was no nuclear pleomorphism, and only a few mitotic figures could be found after extensive search. Multiple areas of necrosis en masse of tumor cells were seen. The lymph node biopsy revealed a complete effacement of the lymph node architecture by the extensive proliferation of hyperpigmented cells in the parenchyma. Immunohistochemically, the same pattern of staining was seen on the bleached and unbleached slides both in the skin and in the lymph node. The neoplastic cells stained positively with MiTF (nuclei), NSE, NKI/C3, tyrosinase (weak), p53, and CD68. S-100 protein, HMB45, Melan A, Mac367, and lysozyme reacted negatively. Occasional cells (<1%) reacted with MIB-1. Ultra-structural studies revealed that the neoplastic cells possessed a large, indented nucleus with a prominent nuclear membrane, a single (para) centrally located nucleolus, and peripherally marginated chromatin. The cytoplasm was abundant and contained numerous single melanosomes and rare compound melanosomes. The melanosomes were in stages II to IV of maturation, with a marked predominance of stage II and stage III melanosomes. There was a high number of aberrant melanosomes with a wide variety of configurations. Melanophages were a minor component of the lesion. Our ultrastructural studies provide unequivocal evidence that ATM is a neoplasm of melanosome-producing cells. We also review the literature on ATM.
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3/17. Cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma: a new cause of uveitis.

    Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4) is an important costimultory receptor expressed on activated T cells. CTLA-4 blockade using a monoclonal antibody (mAb) in conjunction with tumor vaccines has improved tumor responses in animal models and enhanced numerous models of T cell-associated autoimmune diseases. Two patients with stage IV metastatic melanoma vaccinated with the gp 100 melanocyte/melanoma differentiation antigen either before or during anti-CTLA-4 mAb therapy developed uveitis. This is the first report of autoimmune disease involving the eye in patients treated with anti-CTLA-4 mAb. This suggests that CTLA-4 is an important regulatory molecule for maintenance of tolerance to melanosomal antigens and prevention of uveitis.
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4/17. Pigmented epithelioid melanocytoma: two case reports.

    Because of indolent course without mortality, the term "pigmented epithelioid melanocytoma" has been suggested as a replacement for "equine" or "animal-type" melanoma and for the epithelioid blue nevus of the Carney type, from which they are histologically indistinguishable. This report reviews this concept and recounts in detail two of eighteen cases occurring in residents of the Central Coast of california. This paper also contains clinical photographs of pigmented epithelioid melanocytoma, unlike prior reports.
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5/17. Intraepidermal animal-type melanoma.

    Animal-type melanoma is a rare variant of melanoma in humans.1 Its name is derived from its histological appearance, which is similar to that described in melanomas occurring in white or gray horses.2 All tumors are dermally located, and characterized by a proliferation of deeply pigmented elongated or rounded cells, showing moderate atypia and a low mitotic rate. In some tumors, secondary infiltration of the epidermis has been noted. More than half of the patients are younger than 30 years, and prognosis seems to be much better than that expected for a superficial spreading or nodular melanoma of the same size. We report the first case of animal-type melanoma in situ.
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6/17. Phase I study of 2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP), an oral interferon inducer, in cancer patients.

    2-Amino-5-bromo-6-phenyl-4(3H)-pyrimidinone (ABPP) was given to 59 patients in a Phase I study. The agent was selected because it is an interferon inducer and an immunotherapeutic agent in animal tumor models. The study was conducted in two phases. In the first phase, the drug was administered as a single oral dose of 25-2,000 mg/m2. In the second part, the highest tolerated dose reached during part one was used as the initial dose in a multiple-dose scheme of treatment. patients were treated weekly. The dose was escalated each week, starting with a dose of 2 g/m2 and escalating to 3, 4, and 5 g/m2. No cardiac, hematologic, hepatic, or renal toxicity was observed. The most common toxicity was nausea and vomiting, which occurred in 18% of the patients; others were headache (8%), abdominal pain (8%), and diarrhea (6%). No consistent induction of interferon and no major modification of host defense parameters occurred. One patient with malignant melanoma showed evidence of tumor regression. Pharmacologic studies demonstrated a significant decrease in the bioavailability of the drug as it was administered in this study. Further studies of ABPP with a preparation that has good availability are indicated to determine the potential antitumor activity of this agent or this class of agents in humans.
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7/17. Human excimer laser keratectomy. Short-term histopathology.

    The first human trial utilizing the argon fluoride excimer laser at 193 nm to produce a superficial keratectomy in the initial three of 10 human eyes has been described with the clinical appearance and short-term (less than 14 days) histopathologic evaluation of these three eyes. The process of laser superficial keratectomy has proved one of the promising areas of surgical intervention for reconstructive or refractive keratoplasty in the future. Intensive investigations of corneal wound healing following laser ablation as well as the nature and long-term stability of the corneal excisions or induced refractive corrections are needed. It is essential that the optimal laser parameters be established for the various refractive corrections and other corneal surgical techniques and that pathophysiologic and histopathologic changes that have been induced by the excimer laser-corneal tissue interaction in animals and humans be critically and extensively analysed.
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8/17. Endolymphatic isotope and BCG in the management of malignant melanoma.

    Endolymphatic isotope therapy had such promising early clinical results that the M.R.C. (Medical research Council) U.K. set up a clinical trial in 1966. This was to compare the effect of endolymphatic isotope therapy with the results of standard methods in the treatment of lower limb malignant melanoma. The interim report had three groups for analysis: Standard methods (S); Endolymphatic Satisfactory (ES); and Endolymphatic Unsatisfactory (EU). This third group was a subdivision, as a significant number of patients did not have the correct endolymphatic treatment. The five-year survival figures expressed as actuarial percentages were ES=78.8%; S=82.3%; and EU=57.3%. Lymph node recurrence showed a significant difference: ES=2.3%; EU=12%; and S=19%. The conclusions were that endolymphatic isotope therapy was justified in specialized centres where good results could be obtained. Further animal experiments using the VX2 tumour in rabbits indicated that BCG given intracutaneously or intravenously had no therapeutic effect, whereas when applied by intralymphatic injection BCG was successful in treating lymph node metastases. Nineteen patients with poor-prognosis malignant melanoma have received endolymphatic BCG. The clinical results are recorded in this paper and are sufficiently encouraging to warrant its continued use.
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9/17. Histopathologic effects of ultrasonically induced hyperthermia in intraocular malignant melanoma.

    Four cases of human intraocular malignant melanoma were treated with ultrasonically induced hyperthermia immediately before enucleation. Tumors were treated in two regimens: 30 minutes at 43 degrees to 45 degrees C and 5 minutes at greater than 50 degrees C. Temperatures were estimated from applied power levels, based on empirical data and mathematical models. Histopathologic changes observed in human tumors were compared with changes seen in malignant melanoma xenografts in athymic nude mice which were treated with ultrasonically induced hyperthermia for 30 minutes at 42 degrees to 46 degrees C. The effects of treatment were similar to changes seen in the animal model treated under analogous conditions: increased intercellular spacing, cytoplasmic vacuole formation, clumping of chromatin, breaks in cell membranes, and swelling and collapse of cells. Perivascular and peripheral zones sometimes showed decreased damage levels. The high temperature (greater than 50 degrees C) technique is presently being used as a means of "sterilizing" tumors before planned enucleation. The moderate temperature (43 degrees-45 degrees C) technique has been used in combination with radiotherapy to treat tumors when vision can be salvaged.
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10/17. Active immunotherapy of human melanoma exploiting the immunopotentiating effects of cyclophosphamide.

    Malignant tumors may escape rejection by the immune system because they induce a state of immunological tolerance mediated by tumor antigen-specific suppressor T cells. In animal systems, cyclophosphamide can reverse the tolerance and thereby facilitate immunologically mediated tumor destruction. We have applied these concepts to the immunotherapy of human malignant melanoma. Forty-three patients with metastatic disease were treated with a whole cell vaccine 3 days after intravenous administration of cyclophosphamide, 300 mg/m2. The vaccine consisted of cryopreserved, irradiated autologous melanoma cells, obtained from metastatic masses by dissociation with collagenase and DNAse, mixed with bacillus Calmette-Guerin (BCG) and injected intradermally. The cyclophosphamide (CY) vaccine combination was repeated every 28 days. Delayed-type hypersensitivity (DTH) was tested by injecting 1 x 10(6) melanoma cells intradermally and measuring the diameter of induration at 48 h. Most patients had minimal pretreatment DTH responses to melanoma cells (mean /- SE, mm = 2.4 /- 0.5). After two vaccine treatments, the responses increased significantly (mean increase /- SE = 12.1 /- 1.6 p less than .001) and that level of response was maintained after 4, 6, and 8 treatments. The patients were also skin-tested with a mixture of the enzymes used to dissociate the tumors. No patients exhibited DTH to collagenase DNAse prior to vaccine injection, but every patient developed DTH to the mixture following two treatments (mean, mm = 26.4 /- 3.9). Although extracting viable cells from tumor tissue without the use of enzymes proved difficult, we were able to test DTH to mechanically dissociated tumor cells in 23 patients. After two vaccine treatments, there was a significant increase in DTH to enzyme-free autologous melanoma cells (mean DTH /- SE, mm: 5.4 /- 1.0, p less than .01). Whereas 5 of 23 patients had positive DTH responses (5 mm induration or greater) before treatment, 11 of 23 were positive after two treatments. Further significant increases in DTH enzyme-free cells were observed after 6 and 8 treatments. Thus, it appears that patients receiving CY vaccine developed DTH to tumor-associated antigens as well as to residual collagenase and DNAse on the cell surface. Thirty-three patients could be evaluated for antitumor effects of cyclophosphamide vaccine. There were 3 complete remissions, 1 partial remission, and 2 minor responses. Two complete responders remain alive and free of disease after 57 and 12 months, respectively, and the third died after 39 months. The partial remission consisted of 75% regression of a pulmonary metastasis.(ABSTRACT TRUNCATED AT 400 WORDS)
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