Low Frequency of Cytogenetic Abnormality, BRAF and NRAS Mutations in Borderline Melanocytic Tumors Arising in Deep Penetrating Nevi
Ruifeng Guo, Shibo Li, Cynthia Magro, A Neil Crowson. University of Oklahoma Health Sciences Center, Oklahoma City, OK; University of Oklahoma and Regional Medical Laboratory, St. John Medical Center, Tulsa, OK; Weill Medical College of Cornell University, New York, NY
Background: A borderline melanocytic tumor arising in deep penetrating nevus (B-DPN) has histologic features consistent with a conventional deep penetrating nevus (C-DPN), superimposed upon which are cytologic atypia, deep mitosis and an expansile nodular growth pattern. A recent study has shown a high incidence of regional lymph node deposits of melanocytes in B-DPN patients. Cytogenetic analysis of B-DPN may provide valuable information in predicting a risk of aggressive biological behavior.
Design: Oligo-array comparative genomic hybridization (aCGH) assay was applied for cytogenetics analysis. Sanger sequencing was performed to detect the Codon 598-601 point mutation of BRAF gene and the Codon 61 point mutation of NRAS gene. A total 10 cases of C-DPN and 22 cases of B-DPN were studied.
Results: The aCGH assay was successfully performed on 7 cases of C-DPN and 13 cases of B-DPN. The CGH patterns of the C-DPN cases did not show abnormalities. In the B-DPN cases, a significant cytogenetic abnormality was only identified in 1 patient, despite the fact that the other 12 B-DPN cases also showed severe atypia, including 2 of which developed subsequent lymph node metastases. One B-DPN case without obvious cytogenetic abnormality progressed to a lethal metastatic plexiform melanoma a few years later accompanied by an abnormal aCGH pattern at that time. The BRAF mutation analysis was successfully performed on 29 cases, and showed low frequency in both C-DPN (2/11) and B-DPN (2/18) cases with mostly mosaic and heterozygous patterns. The NRAS mutation analysis was successfully performed on 28 cases, and also showed low frequency in both C-DPN (0/10) and B-DPN (1/18) cases with heterozygous patterns.
|Conventional DPN||Borderline DPN|