Proliferative Nodule Arising within Congenital Melanocytic Nevus: Histologic, Immunohistochemical and Molecular Analyses of 43 Cases.
Pushkar A Phadke, Dinesh Rakheja, Long P Le, M Angelica Selim, Payal Kapur, Amy Davis, Martin C Mihm, Mai P Hoang. Massachusetts General Hospital/Harvard Medical School, Boston; University of Texas Southwestern Medical Center, Dallas; Duke University Medical Center, Durham, NC
Background: The histopathologic interpretation of proliferative nodules (PN) in congenital melanocytic nevi (CMN) can present significant challenges since some PN may exhibit atypical features which make the histologic distinction from melanoma difficult.
Design: We compared histologic features, Ki-67%, PHH3 (number of positive cells per 10 high power fields), and CD117% expression by immunohistochemistry (IHC) in 18 benign and 25 atypical PN (from 41 patients) to that of background CMN (of these 43 cases), 10 CMN and 3 dermal melanomas (MM). In addition, we evaluated the presence of NRAS, BRAF, KRAS, HRAS, and GNAQ mutations in all groups using the SNaPshot® Multiplex System.
Results: Follow-up was available on 19 patients (9 benign PN, 10 atypical PN) (range: 2 to 19 years; median: 8 years) and all were alive with no evidence of disease. Specific histologic features of atypical PN: sharp demarcation, expansile growth, epidermal effacement, pleomorphism, and increased mitoses differed significantly from benign PN using Fisher's exact test. Comparison of the IHC expression in the 5 groups was performed by analysis of variance, with Holm-Sidak post-hoc test. Immunohistochemical results (Table 1) showed that Ki-67% and PHH3 scores, but not CD117% expression, were statistically different (P < 0.05) for benign PN vs. atypical PN and MM; but not atypical PN vs. MM. Molecular analysis (Table 1), revealed no significant difference in mutation frequency although BRAF and NRAS mutations were common.
|CMN||Background CMN||Benign PN||Atypical PN||MM|
|Ki-67%||Mean±SD||0.2±0.03 (n=10)||0.09±0.03 (n=37)||1.01±0.28 (n=13)||7.23±1.45 (n=22)||5.87±3.3 (n=3)|
|PHH3||Median (range 25-75%)||1 (1-1.25) (n=18)||5 (2-8) (n=25)||10 (6.25-11.5) (n=3)|
|BRAF||Positive mutation/Number of samples||1/5||10/35||4/16||7/19||0/3|
|NRAS||Positive mutation/Number of samples||-||13/27||5/11||6/14||1/3|