Distinguishing Epithelioid Blue Nevus From Blue Nevus-like Cutaneous Melanoma Metastasis Using Fluorescence In Situ Hybridization

Abstract

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.

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

“…21 It could also be useful if it really changes the treatment of patients, for example, with a thickness greater than 1 or 1.5 mm (according to the protocol), leading to interferon treatment or other adjuvant management such as sentinel node biopsy or adjuvant vaccine therapy. Other FISH applications have been reported to facilitate the differential diagnosis between (I) epithelioid blue nevus and cutaneous metastatic melanoma simulating blue nevus 22 or (ii) nevoid melanomas and mitotically active nevi, 23 (iii) conjunctival nevi from melanomas 24 or (iv) intranodal nevus from metastatic melanoma. 25 In conclusion, a single genetic test allowing the differential diagnosis between benign and malignant ambiguous melanocytic lesions does not yet exist.…”

Correlation Between Histologic Assessment and Fluorescence In Situ Hybridization Using MelanoSITE in Evaluation of Histologically Ambiguous Melanocytic Lesions

“…16 The Abbott Molecular melanoma FISH test was also validated in critical differential diagnoses concerning histologically unequivocal benign and malignant blue nevi, nevoid melanoma, dysplastic nevi, desmoplastic melanoma, lentiginous melanoma, nevi with atypical epithelioid cell component, and Spitz nevi. [6][7][8][9][10][11][12]17,19 Obviously, a FISH test is not needed for histologically unequivocal cases. The only current justification for use of this expensive test in a diagnostic setting is to employ it as a diagnostic adjunct to help classify histologically ambiguous lesions.…”

“…6 Several proof-of-principle studies showed potential applications of FISH to solve a variety of diagnostic dilemmas in the evaluation of melanocytic tumors, including differentiating blue nevus-like metastasis from blue nevus, mitotically active nevus from nevoid melanoma, and dysplastic nevus from superficial spreading melanoma. [7][8][9][10][11][12] Fluorescence in situ hybridization test abnormalities characteristic of melanoma were identified in lentiginous melanoma supporting this entity as a variant of melanoma.…”

Comparison between melanoma gene expression score and fluorescence in situ hybridization for the classification of melanocytic lesions

“…6 Numerous subsequent confirmatory 'proof of principle' studies validated the diagnostic utility of FISH in many different diagnostic settings, reporting a 75-100% sensitivity and 89-100% specificity of the assay in differentiating histologically unequivocal melanoma and nevi. 6,[9][10][11][12][13][14][15] However, most of the earliest proof of principle studies utilized histopathologically unambiguous nevi and melanomas to demonstrate the utility of FISH as an ancillary diagnostic test, yet FISH is predominantly deployed in the setting of morphologically ambiguous melanocytic tumors, where ancillary testing most usefully informs the diagnosis. The diagnostic utility of FISH is controversial in the setting of such ambiguous melanocytic lesions, where the overall reported sensitivity lies between 43 and 100% and the specificity between 33 and 83% using clinical behavior or expert histopathologic review as the gold standard.…”