Melanoma FISH Test

We are pleased to announce that we now offer fluorescent in situ hybridization (FISH) testing as a diagnostic tool to aid in the classification of histologically ambiguous melanocytic lesions. The test is offered through our molecular pathology/cytogenetics division, Delta MDx (

The vast majority of benign nevi can be distinguished from malignant melanoma on the basis of standard histologic criteria. However, a subset of melanocytic lesions presents a diagnostic challenge due to conflicting or overlapping histologic features. Some examples have features that may preclude a definitive consensus diagnosis even among the most expert dermatopathologists (Corona, Mele et al. 1996). This may result in the under- or over-diagnosis of malignant melanoma.

Over 95% of primary malignant melanomas demonstrate a high rate of chromosomal aberrations as compared to benign nevi (Bastain, Olshen et al. 2003; Curtin, Fridlyand et al. 2005). Based on this information, FISH probes on chromosomes 6 and 11 were developed and have been validated to be useful in the diagnosis of melanoma in histologically ambiguous cases (Gerami, Jewell et al. 2009; Newman, Lertsburapa et al. 2009; Gerami, Mafee et al. 2010).

In a large series of over 300 cases, 4 FISH probes [RREB1 (6p25), centromere 6, MYB (6q23), and CCND1 (11q13)], distinguished melanoma from benign nevi with a high sensitivity and specificity (Gerami, Jewell et al. 2009). Over 380 primary melanomas, 44 metastatic melanomas, and 366 nevi have been validated in the literature using this FISH test. The overall sensitivity and specificity have been estimated to be approximately 82% and 95% respectively. Based on more recent data we will be running a panel composed of 4 FISH probes [chromosome 6 centromere, 6q/MYB, CDKN2A 9p21 and CCND1 (11q13)].

Given the utility of this test in ambiguous melanocytic lesions, Delta Dermatopathologists will begin ordering the test in appropriate cases in an attempt to improve diagnostic accuracy. The test is performed on routinely processed formalin fixed paraffin-embedded tissue and utilizes DNA probe hybridization, fluorescence microscopy, and cytogenetic interpretation.

All tests are performed through our Molecular Pathology Division, MDx ( All tests are interpreted by experienced FISH technicians under the direction of board certified dermatopathologists and our Director of Molecular Pathology, Mary Lowery-Nordberg, PhD.

Clinical Implications
Diagnostically ambiguous melanocytic lesions are typically completely excised regardless, but a greater degree of certainty about the diagnosis would be helpful in the direction of therapy and in prognosis. The sensitivity and specificity of the FISH test is high and felt to be diagnostically useful in many cases. However, it should be cautioned that, as with any test, false negative and false positive results may occur and individual cases may remain diagnostically ambiguous.

Similar to other diagnostic tests, the FISH test is typically reimbursed by government and third party payers. Thus, your patients should not realize any additional out of pocket costs, apart from the usual co-pays and deductibles, as part of the total pathology charge.

References: Bastian BC, Olshen AB, et al. Classifying melanocytic tumors based on DNA copy number changes. Am J Pathol 2003;163(5):1765-1770.
Corona R, Mele A, et al. Interobserver variability on the histologic diagnosis of cutaneous melanoma and other pigmented skin lesions. J Clin Oncol 1996;14(4):1218-1223.
Curtin JA, Fridlyand J, et al. Distinct sets of genetic alterations in melanoma. N Engl J Med 2005;353(20):2135-2147.
Gerami P, Jewell SS, et al. Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma. Am J Surg Pathol 2009;33(8):1146-1156.
Gerami P, Mafee M, et al. Sensitivity of fluorescence in situ hybridization for melanoma diagnosis using RREB1, MYB, Cep6, and 11q13 probes in melanoma subtypes. AQrch Dermatol 2010;146(3):273-278.
Newman MD, Lertsburapa T, et al. Fluorescence in situ hybridization as a tool for microstaging in malignant melanoma. Mod Pathol 2009;22(8):989-995.