Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278883 (metastatic melanoma)
 6,224 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adoptive immunotherapy with anti-CD3-expanded lymphocytes from lymph nodes draining alloantigen gene-modified autologous tumor vaccines is an effective treatment of poorly immunogenic murine tumors. This phase I/II study was performed to determine the feasibility and toxicity of combining ex vivo gene transfer of autologous tumor cells and adoptive immunotherapy with anti-CD3-expanded tumor vaccine draining lymph node lymphocytes (TVDLN) in patients with metastatic melanoma and renal cell cancer (RCC). To facilitate the generation of tumor-specific lymphocytes in the TVDLN, autologous tumor cells were modified by gene transfer ex vivo to express the alloantigen HLA-B7, a modification that has the potential to enhance the immunogenicity of the tumor cells. After vaccination with gene-modified tumor cells, patients' lymph nodes were harvested; TVDLN lymphocytes were activated and expanded ex vivo with anti-CD3 and interleukin-2 (IL-2), and adoptively transferred to patients in combination with systemic IL-2. Twenty patients, nine with melanoma and 11 with RCC were treated. Tumor was harvested successfully in all 20 patients. Ex vivo gene transfer was performed using lipofection with a lipid: DNA plasmid complex containing the genes for HLA-B7 and beta2-microglobulin. The mean expression of HLA-B7 by autologous tumor cells after gene transfer was 4.53% (range 0.3%-12.1%). Lymph nodes were harvested from all 20 patients with a mean of 53 x 107 and 60 x 107 cells obtained from the gene-modified and unmodified tumor vaccine sites, respectively. Successful expansion of adequate TVDLN was accomplished in 19 of 20 harvests of unmodified vaccines and in 18 of 20 gene-modified vaccines. No major toxicities were noted after vaccination with autologous tumor cells or adoptive transfer of ex vivo activated TVDLN lymphocytes. Typical IL-2-related toxicities were observed in all patients. No objective tumor regressions were observed. MHC class I restricted, tumor-specific cytokine secretion was observed in lymphocytes from TVDLN and the peripheral blood of vaccinated patients.
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PMID:Adoptive cellular therapy with tumor vaccine draining lymph node lymphocytes after vaccination with HLA-B7/beta2-microglobulin gene-modified autologous tumor cells. 1214 59

Accurate staging of patients with primary cutaneous melanoma includes assessment of regional lymph nodes for the presence of micrometastatic disease. Sentinel lymph node biopsy is highly accurate but is an invasive surgical procedure with a 5-10% complication rate, and requires labour-intensive and expensive histological examination to identify disease. A rapid, accurate and cost-effective non-surgical technique able to detect micrometastatic deposits of melanoma in regional lymph nodes would be of great benefit. Fine needle aspiration biopsies and tissue specimens were obtained from lymph nodes from 18 patients undergoing node resection for metastatic melanoma and five patients undergoing radical retropubic prostatectomy. One-dimensional proton magnetic resonance spectroscopy was undertaken at 360 MHz (8.5 T). Lymph nodes were cut into 3 mm thick slices and embedded. Four sequential 5 microm tissue sections were cut from each block and stained, with haematoxylin and eosin, for S100 protein, for HMB45, and again with haematoxylin and eosin, respectively. Proton magnetic resonance spectroscopy distinguished between benign and malignant lymph node tissue (P < 0.001, separate t-test) and benign and malignant lymph node fine needle aspiration biopsy (P < 0.012) based on the ratio of the integrals of resonances from lipid/other metabolites (1.8-2.5 p.p.m. region) and 'choline' (3.1-3.3 p.p.m. region). In conclusion, one-dimensional proton magnetic resonance spectroscopy on a simple fine needle aspiration biopsy can distinguish lymph nodes containing metastatic melanoma from uninvolved nodes, providing a rapid, accurate and cost-effective non-surgical technique to assess regional lymph nodes in patients with melanoma.
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PMID:Rapid detection of metastatic melanoma in lymph nodes using proton magnetic resonance spectroscopy of fine needle aspiration biopsy specimens. 1277 80

Dear Editor, The diagnosis of malignant melanoma accounts for 1-2% of all cancer diagnoses, around 4% of all malignant skin diseases, and 80% of all skin cancer deaths (1). The prognosis depends on several factors including tumor size, Clark level, Breslow thickness, location, ulceration, and presence of metastases. Detection of lymph node metastasis is initially accomplished by clinical examination and by operative evaluation for occult metastasis using sentinel lymph node biopsy (SLNB) when indicated (2). Lymph nodes (LN) with melanoma metastasis may appear normal in early stages, but eventually they become dark, firm, and enlarged (3). In 2017, a 32-year-old female patient was referred to our ward by a dermatologist following a biopsy excision of a nevus under her right breast that tested positive for a cutaneous melanoma grade T2aNx with a Breslow thickness of 1.9 mm, with no sign of ulceration and no history of previous illnesses or chronic diseases. Based on the American Joint Committee on Cancer (AJCC) guidelines, wide excision with a sentinel lymph node (SLN) biopsy was indicated (4). The patient was injected with 0.4 mL CiTc 99m Nanocoll in all four quadrants around the primary scar. A 2 cm wide elliptical excision was performed circumferentially around the scar and to the depth of the muscular fascia of the thorax. With the aid of a gamma probe, a single radioisotope positive lymph node was located in the ipsilateral axilla, but 5 dark pigmented lymph nodes situated behind the SLN were visualized during manual dissection and thought to be consistent with metastatic disease (Figure 1). Due to this new finding, an excisional biopsy of all pigmented nodes was performed. Histology of the excised skin did not demonstrate any further cancerous cells. The size of the SLN was 15 mm, and immunohistochemistry for Melan A was negative for metastatic melanoma. Histological analysis of the darkly pigmented nodes was negative for metastatic melanoma as the pigment was demonstrated to originate from the dermal tattoo on the patient's back that had been removed by dermabrasion 3 years before melanoma development (Figure 2, Figure 3). Dermal tattooing results in initial sloughing of the overlying epidermis, variable dermal inflammation, and gradual assimilation of pigment into macrophages. Much of the pigment is rapidly carried into regional draining LN, which was shown in 2010 on a SKH-1a mouse model, and causes lymphadenopathy which is thought to be a result of local inflammation (6). Importantly, even after removal of the offending cutaneous tattoo the tattoo pigment can persist in draining or distant nodes visible to the naked eye (7). In such cases, LN can mimic metastatic malignant melanoma and may prompt the surgeon to proceed with radical lymph node dissection which may not be necessary. Despite clear guidelines for melanoma treatment in the general population, there are several questions that need to be addressed: firstly, how should a physician approach a patient with unknown history of tattoo removal, a diagnosis of melanoma, and intraoperative darkly pigmented lymph nodes? Secondly, due to the lack of scientific data and treatment protocol, if the SLN is normally colored while other regional nodes are darkly pigmented, what should the treatment plan entail?
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PMID:Tattoo Pigment within Regional Lymph Nodes Mimicking Cutaneous Melanoma Metastasis. 3265 Aug 54

Melanomas with complete histological regression have been seen very infrequently. On the other hand, the diagnosis of metastatic melanoma is based on the histopathology and positivity of markers such as S100, Melan-A, and HMB-45 whose sensitivity is 99%, 82%, and 76%, respectively. It is very rare that metastatic melanomas and even more primary melanoma are negative for all of these markers. In these rare cases, there is usually a known primary. We present the case of a 82-year-old woman with a erythematous mass in the left groin and a 1-cm black-bluish irregular nodule on the skin of the ipsilateral foot. This lesion was clinical and dermoscopically compatible with primary melanoma. In the histological evaluation of the skin, a dermis full of melanophages and hemosiderophages were found in a background of fibrosis, scarce lymphocytic infiltrate, and neovascularization. Any cells expressing melanocytic markers were observed. It was diagnosed as tumoral melanosis. Lymph nodes showed a proliferation of atypical epithelioid cells with eosinophilic cytoplasm. Mitosis was conspicuous. Tumoral cells were vimentin and CD99 positive, and S100, CD34, HMB-45, Melan-A, SOX 10, tyrosinase, C-KIT, CD45, and CKAE1/AE3 negative, and BRAF-V600 mutated was detected. During follow-up, atypical vitiligo-like lesions were discovered, suggesting the diagnosis of metastatic melanoma totally regressed in our patient.
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PMID:Metastatic Melanoma Negative for 5 Melanocytic Markers, Complete Regressed Primary Cutaneous Melanoma, and Melanoma-Associated Leukoderma in the Same Patient. 3280 78