[470] 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.

Brief Summary
 Conventional DPNBorderline DPN
CGH Abnormality0%(0/7)7.69%(1/13)
BRAF Mutation18.18%(2/11)11.11%(2/18)
NRAS Mutation0%(0/10)5.56%(1/18)

Conclusions: The above findings suggest that B-DPN may represent a group of melanocytic lesions with high heterogeneity and low BRAF and NRAS mutation rates. The current modality of comparative genomic hybridization does not appear to be a valid tool in predicting risk of aggressive behavior in these lesions.
Category: Dermatopathology

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 65, Monday Morning


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