Presence of K-ras Mutations and Distinct Age-Associated Variations in Pilomatricoma
Anna C Harris, A John Iafrate, Farin Kamangar, Thomas J Flotte, Alireza Sepehr. Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Massachusetts General Hospital and Harvard Medical School, Boston, MA; Morgan State University, Baltimore, MD; Mayo Clinic, Rochester, MN
Background: Previous reports suggested a bimodal age distribution and 4 morphologic developmental stages in pilomatricomas. CTNNB1 mutations have been suggested as a causative event, but up to 39% of cases may not have this mutation. The association of β-catenin immunohistochemistry (IHC) with mutation status is controversial. We performed a comparative morphologic analysis in various age groups, assessed β-catenin IHC patterns, and examined CTNNB1 and K-ras mutations.
Design: Clinical data, H&E slides, β-catenin IHC, CTNNB1 and K-ras mutation status were assessed. A logistic regression analysis was performed to assess any association between variables.
Results: 611 cases were included (male: 51%; mean age 29.4 yrs, range: 1-87 yrs; mean size: 13 mm). A trimodal age distribution was observed with peaks in the 1st, 4th, and 7th decades. Head and neck was the most common site, followed by the extremities and trunk. H&E slides on 142 cases were evaluated for four previously described developmental patterns: proliferative, fully developed, early regressive (38%; most common) and late regressive. The presence of the following morphologic variables was significantly lower in the older patients: histiocytic reaction, myxoid changes, ossification, cartilage, calcification, and melanin pigment (p<0.05). Only 8% of examined cases (n=82) had a predominantly nuclear pattern for β-catenin IHC while most cases had either predominantly cytoplasmic (47%) or membranous staining (45%). There was no correlation between β-catenin IHC pattern and clinical data, morphology, or mutation status. Only 41% of tested cases (n=34) harbored CTNNB1 mutation, but of cases tested for K-ras mutations (n=48), 35% were positive. The patients with β-catenin mutation were relatively younger (mean age: 24.7 yrs) compared to patients with K-ras mutation (mean age: 36.4 yrs).
Conclusions: There are significant morphologic variations between age groups in pilomatricomas. β-catenin IHC pattern is more frequently cytoplasmic/membranous rather than nuclear, suggesting involvement in cell-cell adhesion rather than the nuclear Wnt pathway of tumorigenesis. K-ras mutations are reported for the first time in pilomatricomas and they may play a distinct role in the development of this tumor.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 110, Tuesday Morning