Chromosomal copy number changes supporting the classification of lentiginous junctional melanoma of the elderly as a subtype of melanoma

Newman, Marissa; Mirzabeigi, Marjan; Gerami, Pedram

doi:10.1038/modpathol.2009.93

Cited by 54 publications

(30 citation statements)

References 8 publications

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“…However, the impact of thickness on FISH results was not shown by the study by Gerami et al 10 A recent study proved the feasibility of this FISH test for in situ (very thin) melanocytic lesions in the so-called lentiginous junctional melanoma of the elderly. 14 In this study, three out of 19 in situ melanomas were FISH negative. The main difficulty concerning melanocytic lesions is to define the gold standard for malignancy.…”

Section: Discussionmentioning

confidence: 60%

Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases

et al. 2011

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Some melanocytic tumors are ambiguous, so the reproducible histopathological diagnosis of benign or malignant lesion is difficult. This study evaluated the contribution of fluorescence in situ hybridization (FISH) first in 43 non-equivocal melanomas and nevi, and then in 113 ambiguous melanocytic tumors selected by expert pathologists from six different European institutions. We included two groups of ambiguous tumors: patients without recurrence (5-year minimal follow-up) and with metastases. An independent triple-blind histopathological review was performed to classify tumors as 'favor benign' (AÀ) or 'favor malignant' (A þ ). A four-color probe set targeting 6p25, 6q23, 11q13 and CEP6 was used for FISH. In the 43 non-equivocal melanomas and nevi, sensitivity was 85% and specificity 90%. Ninety out of 95 ambiguous melanocytic tumors included were FISH interpretable (67 FISH negative and 23 FISH positive). Of the 90 patients, 69 presented no recurrence and 21/90 exhibited metastases. These ambiguous tumors were mostly spitzoid tumors (45/90). Histopathological reviewers classified these tumors as favor malignant (49/90) and favor benign (32/90), whereas nine cases had a discordant diagnosis. By comparison with outcome, the sensitivity and specificity of histopathological review were 95 and 52%, and the sensitivity and specificity of FISH were 43 and 80%. Compared with histopathological review, the sensitivity and specificity of FISH were 34.5 and 91%. Interestingly, by combining the histopathological diagnosis with FISH results, the diagnosis was optimized, especially by increasing specificity (76% instead of 52% for expert diagnosis alone) and by improving sensitivity compared with FISH alone (90 vs 43% for FISH result alone). The value of this FISH test is to add a reproducible demonstration of malignancy to the histopathological diagnosis, especially in doubtful/ambiguous melanocytic tumors. A positive FISH test reinforces the diagnosis of melanoma, allowing such tumors (particularly thick tumors) to be managed as melanomas.

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Section: Discussionmentioning

confidence: 60%

Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases

et al. 2011

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“…1 Although histological evaluation is a reliable means of accurately classifying melanocytic tumors as benign (nevi) or malignant (melanoma), this distinction can be difficult in a minority of cases. Based on the fact that melanomas are characterized by chromosomal aberrations, molecular genetic tests such as comparative genomic hybridization (CGH) [2][3][4] and fluorescence in situ hybridization [5][6][7][8] have been shown to be useful ancillary techniques, which assist accurate classification of melanocytic tumors. Multiple chromosomal gains and losses are identified with CGH in the majority (495%) of melanomas, whereas melanocytic nevi typically lack chromosomal aberrations.…”

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confidence: 99%

Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests

et al. 2012

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Cutaneous melanomas are characterized by a range of histological appearances, and several morphological variants have been described. In this study, we report a variant of superficial spreading melanoma that is characterized by large, irregular junctional melanocytic nests. The junctional nests varied in shape and size, showed focal tendency to confluence, and were often surrounded by a cuff of epidermal keratinocytes. The melanocytes comprising the nests showed variable cytological atypia. In most of the cases, scant intraepidermal or junctional single melanocytes were seen, and other well-documented diagnostic criteria for melanoma were lacking, and as a result, histological recognition of these tumors as melanoma was difficult. Some cases were associated with an invasive dermal component or showed evidence of sun damage. To provide supporting evidence for malignancy, we analyzed these tumors for genomic aberrations. Using array comparative genomic hybridization (aCGH), we identified multiple genomic aberrations in all analyzed cases. A similar pattern of genomic aberrations was seen in a control group of bona fide superficial spreading melanomas, suggesting that these 'melanomas composed exclusively or predominantly of large nests' are indeed variants of superficial spreading melanoma. Fluorescence in-situ hybridization (FISH) was positive in 40% of the cases. However, using aCGH, the FISH-negative cases showed multiple genomic aberrations in regions that are not covered by FISH. The low sensitivity of the FISH test can be explained by the fact that FISH only evaluates four genomic loci for aberrations, whereas aCGH surveys the entire genome. In summary, we present histological and molecular genetic evidence for a morphological variant of superficial spreading melanoma. Awareness of the histological features will aid in their correct diagnosis as melanoma, and in difficult cases, judicious application of ancillary tests such as aCGH (rather than FISH) will assist accurate diagnosis. Modern Pathology (2012) 25, 838-845; doi:10.1038/modpathol.2012; published online 2 March 2012 Keywords: chromosomal aberrations; comparative genomic hybridization; fluorescence in-situ hybridization; melanocytic tumors; melanoma Cutaneous melanomas are characterized by a diverse range of histological appearances, and several morphological variants have been described. The most common subtypes in histological classification systems are superficial spreading melanoma, nodular melanoma, lentigo maligna melanoma, and acral lentiginous melanoma. 1 Although histological evaluation is a reliable means of accurately classifying melanocytic tumors as benign

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“…Our results seem contradictory to recent studies reporting high sensitivity and specificity of the four FISH probes. 9,10,12 However, these studies did not include histologically ambiguous lesions, and the results of the FISH analysis had been compared with the primary histological diagnosis but not to the clinical long-term follow up, considered the diagnostic gold standard. That said, the development of metastases during the long-term follow up is not conclusive of the malignant potential of the primary melanocytic lesion, and may instead arise from a separate unknown primary elsewhere in the body.…”

Section: Discussionmentioning

confidence: 99%

“…Initial studies analyzing the clinical applicability of such probes have been published, and demonstrated a very high sensitivity and specificity in distinguishing melanomas from nevi. [9][10][11][12] However, most of these studies did not examine ambiguous lesions or address clinical long-term outcomes. This study was undertaken to validate a special multicolor FISH kit in histologically ambiguous melanocytic lesions.…”

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confidence: 99%

Classifying ambiguous melanocytic lesions with FISH and correlation with clinical long-term follow up

et al. 2010

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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 (j 0.47-0.61). Comparing the FISH results with the clinical behavior reached an overall sensitivity of 60% and a specificity of 50% (v 2 ¼ 0.25; P ¼ 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 (Po0.01) 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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Chromosomal copy number changes supporting the classification of lentiginous junctional melanoma of the elderly as a subtype of melanoma

Cited by 54 publications

References 8 publications

Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases

Fluorescence in situ hybridization, a diagnostic aid in ambiguous melanocytic tumors: European study of 113 cases

Histological and genetic evidence for a variant of superficial spreading melanoma composed predominantly of large nests

Classifying ambiguous melanocytic lesions with FISH and correlation with clinical long-term follow up

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