Aberrant Immunostaining of Breast Carcinoma by MRQ-50 PAX8 Antibody.

melanoma. The tumor did not present BRAFV600 mutations but did have a NRAS mutation in codon 61, Q61R (nucleotide change c.182A>G). The previously excised lentigo maligna melanoma was reviewed and compared with the ankle melanoma. This tumor presented a higher atypia degree and 1 mitosis per square millimeter was found. The 4-probe FISH assay showed gains of 11q13 (CCND1). The tumor also failed to show a BRAFV600 mutation, but a different NRAS mutation was detected on codon 61, Q61K (nucleotide change c.181C>A). The melanoma of the ankle was finally diagnosed as nonulcerated nevoid melanoma (Breslow 2.5mm). Two months after the excision of the lesion the patient presented systemic progression of the melanoma and eventually died. Although histopathologic study is the gold standard for the diagnosis of melanoma, the biological behavior of some melanocytic lesions can be extremely difficult to accurately predict on the basis of the histopathologic features, even for expert dermatopathologists.3 To address these difficulties, immunohistochemistry and molecular techniques have been developed as adjunctive tools. In our case, the histopathology and immunohistochemical results were concerning but the commercially available FISH panel did not give abnormalities. This 4-color probe set FISH identifies the most recurrent genomic aberrations in cutaneous melanomas, including copy number increases of 6p25 (RREB1) and 11q13 (CCND1) and deletion of 6q23 (MYB). It has shown to be useful in the differential diagnosis between nevus and melanoma in different settings, including the diagnosis of ambiguous melanocytic lesions4 and nevoid melanomas.5 We were finally able to confirm the diagnosis of melanoma by the study of the genomic copy number array. Several chromosomal abnormalities were observed in loci that are not tested with FISH, being concordant with the diagnosis of melanoma. The arraybased test for DNA copy number aberration analyses the entire genome in a single assay, thereby having a higher sensitivity than FISH for the diagnosis of challenging melanocytic lesions.6 In conclusion, the diagnosis of nevoid melanomas can be challenging and can require the molecular exploration of the tumor. These molecular studies are also useful to differentiate primary from metastatic tumors.

[1]  R. Røge,et al.  NordiQC Assessments of PAX8 Immunoassays. , 2018, Applied immunohistochemistry & molecular morphology (Print).

[2]  A. Husain,et al.  PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma , 2017, The American journal of surgical pathology.

[3]  D. Elston,et al.  Nevoid melanoma: A study of 43 cases with emphasis on growth pattern. , 2015, Journal of the American Academy of Dermatology.

[4]  Jaime Prat,et al.  Simultaneous Carcinomas of the Breast and Ovary: Utility of Pax-8, WT-1, and GATA3 for Distinguishing Independent Primary Tumors from Metastases , 2015, International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists.

[5]  A. Viale,et al.  A genome-wide high-resolution array-CGH analysis of cutaneous melanoma and comparison of array-CGH to FISH in diagnostic evaluation. , 2013, The Journal of molecular diagnostics : JMD.

[6]  D. Elder,et al.  Melanocytic Tumors of Uncertain Malignant Potential: Results of a Tutorial Held at the XXIX Symposium of the International Society of Dermatopathology in Graz, October 2008 , 2010, The American journal of surgical pathology.

[7]  Yu Fang,et al.  Fluorescence in Situ Hybridization for Distinguishing Nevoid Melanomas From Mitotically Active Nevi , 2009, The American journal of surgical pathology.

[8]  A. D. Dei Tos,et al.  Morphological Analysis of Nevoid Melanoma: A Study of 20 Cases With A Review of the Literature , 2001, The American Journal of dermatopathology.