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

A 40-yr-old woman with an asymptomatic sinonasal rhabdomyosarcoma (RMS) initially presented with submental nodal metastasis. The fine-needle aspiration (FNA) and the subsequent biopsy of the nodal metastasis were misinterpreted as metastatic carcinoma because the primary tumor was occult, the tumor cells were exclusively round cells with a nested arrangement, and rhabdomyoblasts were absent. The correct diagnosis of metastatic RMS became apparent when the primary sinonasal tumor, detected in a CT, was biopsy proven to be an alveolar RMS. Retrospectively, there were helpful clues to the correct diagnosis in the nodal FNA and biopsy. When FNA cytology or biopsy histology of a lymph node suggests metastatic carcinoma but the tumor cells are nonimmunoreactive to carcinoma markers, the differential diagnosis should be expanded to include not only metastatic melanoma but also metastatic sarcoma and lymphoma. Cytologically, the presence of multinucleated giant tumor cells, including the rosette forms, in the FNA smears should alert the cytopathologist to the possibilities of sarcoma and anaplastic large cell lymphoma.
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PMID:Rhabdomyosarcoma in an adult presenting with nodal metastasis: a pitfall in fine-needle aspiration cytology of lymph nodes. 1583 Mar 59

We describe the computed tomography and F-18 FDG PET findings of a patient with extensive mediastinal nodal enlargement resulting from histoplasmosis. This patient with known metastatic melanoma presenting for restaging was initially considered to have widespread mediastinal and cervical metastases on the basis of the imaging findings. Bronchoalveolar lavage fluid and transbronchial lymph node biopsy were consistent with histoplasmosis. The imaging findings improved after treatment with antifungal medication. A relatively small area of pulmonary involvement proved to be the clue in the imaging studies that the disease was inflammatory rather than neoplastic.
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PMID:Mediastinal histoplasmosis: F-18 FDG PET and CT findings simulating malignant disease. 1610 Apr 91

The diagnosis of epidermotropic metastatic malignant melanoma (EMMM) can be extremely challenging for both clinicians and pathologists. The diffculties include distinguishing metastatic lesions with an epidermal component from residual incompletely excised primary melanoma, and multiple primary melanomas. This has great prognostic significance as the current American Joint Committee on Cancer guidelines consider localized metastatic disease such as satellites and intransits in the nodal (N) category of N2C or stage IIIB disease. In this report, we present a case of EMMM with angiotropism. Additionally, we discuss in detail the differential diagnosis for recurrence of malignant melanoma with an epidermal component within the scar. Angiotropism may be seen in lesions of EMMM and the current literature suggests that angiotropism is highly suggestive of metastatic melanoma. The differential diagnosis of locally recurrent melanoma with an epidermal component can be extremely challenging and the presence of angiotropism may be a clue to the diagnosis of EMMM.
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PMID:Angiotropism in epidermotropic metastatic melanoma: another clue to the diagnosis. 1701 20

HSP-70, C-myc and HLA-DR were examined in patients with cutaneous malignant melanoma metastatic to lymph nodes. Lymph-nodal fine-needle aspiration biopsies (FNABs) were analyzed and the results were correlated to other variables, such as the gender of the patients, Clark level and Breslow thickness of the primary tumor. Thirty cases of metastatic melanoma in lymph nodes from 30 patients with cutaneous malignant melanoma were studied. All patients (100%) had microscopic regional nodal metastasis and a recurrence of the lesion during the first two years. The HSP-70, C-myc and HLA-DR expressions were investigated immunocytologically, using the APAAP (alkaline phosphatase) method on the FNAB samples. The immunocytochemical expressions of HSP-70 protein, C-myc oncogene, and HLA-DR antigen were found in 18 cases (60%), in 14 cases (43.3%) and in 12 cases (40%), respectively. Clark levels were significantly associated with HSP-70 protein (< 0.01), C-myc oncogene expression (< 0.05) and HLA-DR antigen (< 0.01) expression. The HLA-DR antigen was also found to be related (< 0.05) to higher Breslow thickness (> 1.5 mm). The clinical course of malignant cutaneous melanoma is related to the expression of these indices, which seem to play a significant role in the metastasis and prognosis of this aggressive tumor. The immunocytochemical expression of HSP-70 in the malignant melanoma tumor could be of particular value in the identification of patients with poor prognosis.
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PMID:HSP-70, C-myc and HLA-DR expression in patients with cutaneous malignant melanoma metastatic in lymph nodes. 1709 81

Sentinel lymph node evaluation has enabled identification of patients with cutaneous melanoma who might benefit from elective regional lymph node dissection. Sentinel nodes are currently assessed by histologic and reverse transcription polymerase chain reaction (RT-PCR) evaluation for melanocyte-specific markers. The clinical significance of positive findings by RT-PCR in the absence of histologic evidence of metastasis (HIS(NEG)/PCR(POS)) remains unclear. Examination of 264 lymph nodes from 139 patients revealed histopathologic positivity in 34 patients (24.5%), in which 26 also demonstrated simultaneous RT-PCR positivity (HIS(POS)/PCR(POS)). Of 35 HIS(NEG)/PCR(POS) patients (25.2%), five also had nodal capsular nevi. In total, capsular nevi were detected in 13 patients (9.4%). A total of 70 patients (50.4%) had negative sentinel nodes by both histopathology and RT-PCR (HIS(NEG)/PCR(NEG)). Over a median follow-up of 25 months, local and/or systemic recurrence developed in 31 patients (22.3%). Recurrence rates were similar among patients with histopathologic evidence of sentinel lymph node metastasis, irrespective of RT-PCR status (HIS(POS)/PCR(POS) 62%; HIS(POS)/PCR(NEG) 75%). In contrast, only 10% of HIS(NEG)/PCR(NEG) patients developed recurrence, significantly less than those in either HIS(POS) group (P<0.0001). Recurrence in the HIS(NEG)/PCR(POS)/CN(NEG) group (7.7%) was comparable to that in HIS(NEG)/PCR(NEG) patients and significantly lower than that in either HIS(POS) group (P<0.0001). The only independent prognostic factors identified by multivariate analysis were the Breslow thickness of the primary tumour and histopathologic positivity of sentinel nodes. Our findings support previous observations that histopathologic evidence of metastatic melanoma in sentinel lymph nodes is an independent predictor of disease recurrence. In contrast, detection of tyrosinase mRNA by RT-PCR alone does not appear to increase the likelihood of short-term disease recurrence.
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PMID:Detection of tyrosinase mRNA in the sentinel lymph nodes of melanoma patients is not a predictor of short-term disease recurrence. 1733 54

Cytoreductive surgery represents a therapeutic attempt to improve patient outcomes by reducing overall tumor burden to render postsurgical therapy effective or at least increase its effectiveness. The intent of cytoreduction differs from palliative or curative-intent surgery for oligometastatic melanoma. Both palliative surgery and attempted curative resection have important roles to play in the management of patients with melanoma that has spread beyond the regional nodes or recurred "in transit" between the primary and the regional nodal basin. To date, however, no evidence shows that cytoreductive surgery offers any meaningful benefit to patients with metastatic melanoma, and, outside of a clinical trial, there is no role for cytoreductive surgery in melanoma. To date, adjuvant vaccine therapy after complete resection of metastatic melanoma has not proved to be efficacious in clinical trials, so there is little reason to believe that the use of currently available immunotherapy strategies will be enhanced after incomplete tumor resections.
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PMID:Cytoreductive surgery for melanoma. 1760 1

The highest quality gray-scale ultrasound images are obtained with high-frequency transducers; however, such high frequencies do not penetrate more than a few centimeters into body tissue. Fortunately, in patients with melanoma, the structures of interest are close to the skin surface, making them ideal targets for examination with high-resolution ultrasound. These include primary cutaneous melanomas, uveal melanomas and the regional lymph nodes draining the skin that lie in the axilla, groin, neck and other locations. Although ultrasound study of primary melanomas arising in the skin and eye has provided some insights, a major role for ultrasound has evolved recently, to provide early detection of metastatic melanoma in regional lymph nodes. Ultrasound is clearly superior to clinical palpation of the nodes during follow-up and, when combined with guided fine-needle biopsy, allows the earliest possible surgical intervention for regional nodal metastases. In the future the use of ultrasound contrast agents may improve the sensitivity of ultrasound in the detection of very small metastatic deposits.
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PMID:The utility of ultrasound in patients with melanoma. 1802 Sep 29

The primary cutaneous melanoma initially migrates to the regional lymph nodes (LNs). Human melanoma overexpresses gangliosides, the sialylglycosphingolipids. The ganglioside signatures may differ between primary and LN melanomas owing to the differences in the tumor microenvironments. The melanoma cells obtained from the primary and LN of the same patient might be useful to evaluate the above hypothesis. For this purpose, the cryopreserved cell lines from a primary cutaneous melanoma (IGR-39) and its nodal metastasis (IGR-37) from the same patient were used. We have also compared the ganglioside signatures of freshly obtained melanoma cells from primary, LN and organ metastases from different patients. Gangliosides were extracted, purified and identified by resorcinol and specific murine monoclonal antibodies. Comparison of the primary cell line with the nodal metastatic line obtained from the same patient distinctly showed the following features: (i) an increased production of gangliosides, (ii) O-acetylation of GM2 and GD3, (iii) an increased and altered O-acetylation of GD2 and (iv) possibly de-N-acetylation of GD3. These findings suggest that the nodal microenvironment might favor activation of O-acetyl-transferases capable of O-acetylating both alpha2, 3 and alpha2, 8 sialic acids of gangliosides. Supporting this, the primary melanoma cells obtained from different patients, showed no O-acetylation of GD3 or GD2. The cell line from groin LN showed the presence of O-acetyl (O-Ac)GD3. The cell lines from thyroid, spleen and jejunum expressed O-AcGD2. In all metastatic melanoma cell lines GD1a is more prevalent than GD3, suggesting that GD1a may be a major melanoma-ganglioside.
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PMID:Ganglioside signatures of primary and nodal metastatic melanoma cell lines from the same patient. 1822 8

CCN3/nephroblastoma overexpressed belongs to the CCN family of genes that encode secreted proteins associated with the extracellular matrix (ECM) and exert regulatory effects at the cellular level. Overexpression of CCN3 was shown in metastatic melanoma cells compared with cells of the primary tumor from the same patient. Analysis of short-term cultures from 50 primary and metastatic melanomas revealed a heterogeneous expression pattern of both the 46-kDa full-length cytoplasmic/secreted protein and the 32-kDa nuclear-truncated form. The different protein expression patterns were not associated with gene alterations or polymorphisms. Like the metastatic cells expressing high levels of the 46-kDa CCN3, cells transfected to overexpress CCN3 showed increased adhesion to ECM proteins, whereas inhibition of CCN3 expression by small interfering RNA decreased adhesion to laminin and vitronectin. CCN3 overexpression induced increased expression of laminin and vitronectin integrin receptors alpha 7 beta 1 and alpha v beta 5 by increasing their mRNA production. Moreover, CCN3 secreted by melanoma cells acted as an adhesion matrix protein for melanoma cells themselves. Analysis of CCN3 protein expression with respect to melanoma progression detected the protein in all visceral metastases tested and in most nodal metastases from relapsing patients but in only a few nodal metastases from nonrelapsing patients and cutaneous metastases. Consistently, xenotransplantation in immunodeficient mice showed a higher metastatic potential of melanoma cells overexpressing CCN3. Together, these data indicate a role for CCN3 in melanoma cell interaction with the ECM by regulating integrin expression, resulting in altered cell adhesion and leading melanoma progression to aggressive disease.
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PMID:CCN3/nephroblastoma overexpressed matricellular protein regulates integrin expression, adhesion, and dissemination in melanoma. 1824 71

Elective pelvic lymphadenectomy is one of the enduring controversies in the management of Stage III melanoma of the groin. It can provide valuable staging information but concerns remain over the possibility of increased morbidity without the benefit of increased survival. Endoscopic lymphadenectomy of the pelvic nodes is an established procedure in the management of urological and gynaecological malignancy but is relatively novel in the management of metastatic melanoma. An endoscopic approach reduces the risks suggested to be associated with the open procedure while still providing the clinician with the benefit of improved staging information. The authors present their experience of a combined procedure in a series of eight patients undertaken between January 2005 and May 2006 at the Exeter Melanoma Unit. One patient was discovered to harbour occult pelvic nodal metastases, despite a negative pre-operative CT scan. While no complications were directly attributable to the endoscopic procedure, the only major complication was post-operative lymphoedema which occurred in one case. The authors' experience suggests a combined procedure is both feasible and safe in the Plastic Surgery Department setting for the management of Stage III melanoma of the groin. This is the first documented UK experience of this technique.
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PMID:Inguinal lymphadenectomy combined with staging endoscopic pelvic node sampling for stage III melanoma. 1848 94


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