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

Blue nevus (BN)-like cutaneous melanoma metastasis is a well-recognized variant of melanoma metastasis. These lesions may clinically and histologically simulate benign blue nevi. The histologic changes may be indistinguishable from conventional blue nevi or epithelioid blue nevi (EBN), a benign dermal-based melanocytic neoplasm with epithelioid morphology and heavily pigmented cytoplasm. Distinguishing BN-like cutaneous melanoma metastasis from benign conventional or EBN is important for staging and treatment. We evaluated a fluorescence in situ hybridization (FISH) assay using probes targeting 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1), and centromere 6 (Cep6) with previously determined criteria, to distinguish EBN and BN-like melanoma metastasis. Ten BN-like cutaneous melanoma metastatic lesions and 10 EBN were blindly evaluated with the above mentioned FISH probes. FISH enumeration and criteria for diagnosis of melanoma was as previously described. Nine of 10 BN-like cutaneous metastatic lesions showed significant aberrations and met previously established criteria for melanoma. None of the EBN cases showed evidence of significant copy number changes or met FISH criteria for a diagnosis of melanoma. FISH is an important diagnostic adjunct for melanocytic neoplasms. In this study, we show that a FISH assay targeting 6p25, 6q23, 11q13, and centromere 6 can distinguish EBN from BN-like metastatic melanoma with high accuracy. The test and the parameters previously established can perform with high sensitivity and specificity when dealing with this differential diagnosis.
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PMID:Distinguishing epithelioid blue nevus from blue nevus-like cutaneous melanoma metastasis using fluorescence in situ hybridization. 1960 12

Twenty-two surgical biopsy specimens from patients with pigmented skin neoplasms were studied. The patients were divided into 3 groups: 1) 11 patients who had a histological verified diagnosis of melanoma; 2) 10 patients who were diagnosed as having nevi with lentiginous melanocytic dysplasia; 3) 1 patient who had an unclear diagnosis of presumptively, nevus with melanocytic dysplasia. By applying fluorescence in situ hybridization (FISH) by means of a Vysis LSI RREBI/LSI MYB/LSI CCNDI/ CEP 6 probe, the authors employed to test a new probe designed for the genetic diagnosis of melanoma by FISH studies and confirmed in all the 22 patients the diagnosis previously made from the results of the routine histological study and the presumptive diagnosis in 1 patient. Furthermore, it should be noted that multiple genetic disorders were revealed in 3 patients (14% of the total sample and 30% of the sample of patients diagnosed as having nevus with lentiginous melanocytic dysplasia) in the absence of the morphological criteria of melanoma. The patients with such disorders belong to a risk group and need a more meticulous further follow-up.
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PMID:[Molecular biological approaches to differential diagnosis of skin melanoma]. 1993 98

Recently, initial studies describing the use of multicolor fluorescence in situ hybridization (FISH) for classifying melanocytic skin lesions have been published demonstrating a high sensitivity and specificity in discriminating melanomas from nevi. However, the majority of these studies included neither histologically ambiguous lesions nor a clinical long-term follow up. This study was undertaken to validate a special multicolor FISH test in histologically ambiguous melanocytic skin lesions with known clinical long-term follow up. FISH was scored by three independent pathologists in a series of 22 melanocytic skin lesions, including 12 ambiguous cases using four probes targeting chromosome 6p25, centromere 6, 6q23, and 11q13. The FISH results were compared with array comparative genomic hybridization data and correlated to the clinical long-term follow up (mean: 65 months). Pair-wise comparison between the interpretations of the observers showed a moderate to substantial agreement (kappa 0.47-0.61). Comparing the FISH results with the clinical behavior reached an overall sensitivity of 60% and a specificity of 50% (chi(2)=0.25; P=0.61) for later development of metastases. Comparison of array comparative genomic hybridization data with FISH analyses did not yield significant results but array comparative genomic hybridization data demonstrated that melanocytic skin lesions with the development of metastases showed significantly more chromosomal aberrations (P<0.01) compared with melanocytic skin lesions without the development of metastases. The FISH technique with its present composition of locus-specific probes for RREB1/MYB and CCND1 did not achieve a clinically useful sensitivity and specificity. However, a reassessment of the probes and better standardization of the method may lead to a valuable diagnostic tool.
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PMID:Classifying ambiguous melanocytic lesions with FISH and correlation with clinical long-term follow up. 2008 13

A conjunctival melanocytic nevus may on occasion be difficult to distinguish from melanoma both clinically and histopathologically. An unambiguous correct diagnosis is critical because of major differences in management and prognosis. We evaluated a fluorescence in situ hybridization (FISH) assay, which has previously been shown to be of value for the diagnosis of melanocytic nevi and melanomas of the skin, using probes targeting 6p25 (RREB1), 6q23 (MYB), 11q13 (CCND1) and centromere 6 (CEP6), for its potential to assist in the distinction of conjunctival melanocytic nevi from melanomas. Four melanocytic nevi and eight melanomas of the conjunctiva were analyzed. Two of the melanomas were diagnostically problematic because of suboptimal histopathology. None of the conjunctival melanocytic nevi showed a level of chromosomal aberrations that met FISH criteria for a diagnosis of melanoma. All eight conjunctival melanomas (six unequivocal and two suspicious lesions) met FISH criteria for melanoma. Thus, results from FISH assay targeting 6p25, 6q23, 11q13 and centromere 6 correlated well with the histopathologic diagnoses and supported the histopathologic suspicion in two problem cases. The findings encourage further exploration of this technique as an ancillary method for the work-up of conjunctival melanocytic proliferations.
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PMID:Distinction of conjunctival melanocytic nevi from melanomas by fluorescence in situ hybridization. 2010 Jan 76

Twenty samples of benign pigmented neoplasms of the skin, including 9 intradermal nevi and 11 complex ones, were investigated. Fluorescence in situ hybridization was used to detect the copy number of the RREB1 (6p25), MYB (6q23), and CCND1 (11q13) genes. Analysis of the findings revealed no significant changes characteristic of melanoma in the nevi. However, the authors established that there was a direct correlation between the copy number of the MYB and RREB1 genes and that the amount of the MYB gene most frequently deviated from the normal values. In addition, a relationship was found between the number of MYB gene copies and the depth of the epidermal layer. In cases of an intradermal nevus, the copy numbers of the CCND1 and MYB genes were shown to vary more greatly than in cases of a complex nevus.
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PMID:[Molecular genetic study of benign pigmented neoplasms by fluorescence in situ hybridization]. 2108 34

The histopathologic distinction of desmoplastic melanomas from sclerosing (desmoplastic) melanocytic nevi can be difficult, especially when evaluating a partial or superficial biopsy. In the study reported herein, we applied and explored the use of a novel ancillary method, a four-probe fluorescence in situ hybridization (FISH) assay targeting RREB1, MYB, Cep6 and CCND1, to this diagnostic problem. Fifteen sclerosing melanocytic nevi, including desmoplastic Spitz nevi, conventional nevi with prominent stromal sclerosis and sclerotic blue nevi, as well as 15 examples of desmoplastic melanoma, were examined. None of the sclerosing melanocytic nevi showed a level of chromosomal aberrations that met FISH criteria for melanoma. Seven of the 15 desmoplastic melanomas were 'positive' (had documented chromosomal aberrations) by FISH. Thus, a positive FISH test strongly supports the diagnosis of melanoma in this context. However, in this setting a negative FISH test is of limited diagnostic value. Our findings suggest that prior reports about the high sensitivity of the FISH test for melanoma diagnosis need to be adjusted according to melanoma subtype.
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PMID:Fluorescence in situ hybridization as an ancillary method for the distinction of desmoplastic melanomas from sclerosing melanocytic nevi. 2132 20

Pigmented spindle cell nevus (PSCN), also known as Reed nevus, is a distinctive melanocytic tumor that can show worrisome clinical and histologic features mimicking a malignant melanoma. From a series of 46 pigmented spindle cell melanocytic lesions, including 22 PSCN and 24 spindle cell malignant melanomas (SCMMs), we collected clinical and histopathologic characteristics and evaluated cell cycle and apoptosis regulators by immunohistochemistry. Moreover, fluorescence in situ hybridization (FISH) using probes targeting 6p25 (RREB1), 11q13 (CCND1), 6q23 (MYB), and centromere 6 was performed. PSCN presented in younger people, frequently in women, and were small lesions under 7 mm in diameter affecting the lower limbs, whereas SCMMs arose more frequently in the trunk, upper limbs, and head and neck region. Histologically, symmetry, good lateral demarcation, and uniformity of cellular nests were significantly differential features of PSCN, whereas pagetoid and adnexal spread were frequently seen in both tumors. Immunohistochemical markers that significantly differed from melanomas were Ki-67, cyclin D1, and survivin. FISH was positive in 1 of 15 PSCN and was negative in 4 of 15 SCMMs. These results correlated to a sensitivity of 73% and a specificity of 93%. In conclusion, in the evaluation of pigmented spindle cell melanocytic tumors, the integration of clinical and histologic assessment is essential. However, ancillary techniques such as proliferation antigen Ki-67, cyclin D1, survivin, and FISH can be useful as adjunctive tools.
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PMID:Pigmented spindle cell nevus: clues for differentiating it from spindle cell malignant melanoma. A comprehensive survey including clinicopathologic, immunohistochemical, and FISH studies. 2199 94

Melanocytic proliferation constitutes a heterogeneous group of lesions with remarkable differences in their biology and clinical outcome. Thus, accurate histological diagnosis of these cases is mandatory to establish the most appropriate surgical treatment and follow-up. Although histological examination alone is usually sufficient to identify melanomas among the greater number of nevi, the definition of the benign or malignant nature of a subset of melanocytic tumours, exhibiting atypical features, is a challenging task. Novel techniques that may assist in the histopathological diagnosis in difficult cases have been extensively researched over recent years. Fluorescence in-situ hybridization (FISH), performed with a panel of four probes, including three locus-specific identifier (RREB1, MYB, and CCND1) genes, seems to represent a sensitive and specific molecular tool for the diagnosis of non-ambiguous melanocytic lesions. Some studies have agreed that FISH may be an ancillary diagnostic instrument, but cannot replace light microscopy, to distinguish benign nevi from malignant melanomas in daily practice. However, in the context of ambiguous melanocytic tumours, results are still controversial, and additional and substantial work is needed to develop reliable probes that may identify, with high sensitivity, specific subsets of ambiguous melanocytic lesions, including spitzoid proliferation.
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PMID:Fluorescence in-situ hybridization analysis for melanoma diagnosis. 2200 36

The diagnosis of certain melanocytic proliferations remains one of the most challenging areas in pathology. In recent times, fluorescence in situ hybridization (FISH) has emerged as a promising diagnostic aid to conventional microscopy. We previously showed that a 4-probe FISH assay targeting 6p25 (RREB1), 6q23 (MYB), Cep6 (centromere 6), and 11q13 (CCND1) could discriminate between histologically unequivocal melanomas and benign nevi with a sensitivity of 86.7% and specificity of 95.4%. However, the sensitivity of the assay is approximately 70% in melanomas with spitzoid morphology. Furthermore, differentiating true gains from tetraploidy may cause difficulties in interpretation by inexperienced examiners. Here we refine the current probe set to better target spitzoid melanomas and more easily distinguish cells with imbalanced copy number aberrations from tetraploid cells. Using FISH data from 3 training sets of 322 tumors, including 152 melanomas and 170 nevi, we identified 9p21, 6p25, 11q13, and 8q24 as a probe set with improved discriminatory power in differentiating melanomas from nevi. In a validation set of 51 melanomas and 51 nevi this probe set had a sensitivity of 94% and specificity of 98%, compared with the original probe set that had a sensitivity of 75% and specificity of 96% in the same validation cohort. We propose that by incorporating 9p21 into the 4-probe FISH assay, with a new diagnostic algorithm, this new probe set would have improved discriminatory power in melanocytic neoplasms and improved sensitivity for detecting spitzoid melanomas, as demonstrated by our previous studies.
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PMID:A highly specific and discriminatory FISH assay for distinguishing between benign and malignant melanocytic neoplasms. 2315 36

We identified a group of melanocytic lesions with an architectural pattern very similar to that of a junctional nevus: cells mostly grouped in distinct nests, more or less of the same size and shape, and regularly distributed along the dermoepidermal junction. In contrast with these nevus-like features, these neoplasms display additional details which are incompatible with a diagnosis of junctional nevus. These include areas of lentiginous array with focal pagetoid spread of melanocytes above the junction; marked cytological atypia, such as nuclear enlargement, hyperchromasia, nuclear membrane thickening and with a mild degree of cellular pleomorphism. Moreover, these lesions mostly developed on severely sun-damaged skin of old patients. Using a four-probe fluorescence in situ hybridization (FISH) assay targeting RREB1, MYB, Cep6, and CCND1, we found that seven of the eight propositus cases showed chromosomal aberrations consistent with the standardized FISH diagnostic criteria for melanoma. Instead, the five junctional nevi that served as controls were negative in this test. These findings underline the utility of correlating clinical-pathological observations with FISH analysis for diagnosing correctly as melanoma these malignant neoplasms, which closely simulate a junctional nevus.
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PMID:Morphological and molecular characteristics of nested melanoma of the elderly (evolved lentiginous melanoma). 2289 32


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