Calcifications associated with basal cell carcinoma: prevalence, characteristics, and correlations

Carcinoma-associated calcifications (Ca(2+)) are a common phenomenon. In the skin, basal cell carcinomas (BCC) can be associated with Ca(2+).

To examine the prevalence, characteristics, and clinicopathologic correlations of BCC associated with Ca(2+).

Eighty-three BCC with Ca(2+) were retrieved, 27 (11.1%) of which were identified from a review of 243 consecutive BCC. Ca(2+) were classified into 4 types: type 1, Ca(2+) within BCC epithelium; type 2, Ca(2+) in BCC keratocysts; type 3, BCC tumor necrosis with Ca(2+); and type 4, free Ca(2+) adjacent to BCC. Clinical and pathologic features were assessed and compared with BCC without Ca(2+). Expression of hair-associated proteins (hair keratins (K31, K32, and K35) and matrical transcription factors (LEF1, HOXC13, and β-catenin) were examined in a subset of BCC with Ca(2+) and compared with matched controls without Ca(2+).

Compared with BCC without Ca(2+), BCC with Ca(2+) were significantly more likely to show a nodular keratinizing phenotype with keratocyst formation, background solar elastosis, active regression, and areas of tumor necrosis (all P ≤ 0.03). Comparing all BCC, high-risk BCC (mostly infiltrative) had significantly higher frequency of Ca(2+) than low-risk (mostly nodular) BCC (44% vs. 25%; P = 0.009). The median and mean number of Ca(2+) deposits per specimen were 2 and 3 ± 4, range 1-30. In decreasing frequency, type 2 Ca(2+) (58%), type 4 (53%), type 3 (14%), and type 1 (10%) were found. In 9 cases (11%), type 2 and type 4 Ca(2+) were linearly arranged, ostensibly after a follicular or eccrine duct tract. In 5 cases (6%), initial histologic sections showed type 4 dermal Ca(2+) without evidence of BCC; level sections revealed BCC in the adjacent tissue. Neither BCC with nor BCC without Ca(2+) showed evidence of matrical differentiation by immunophenotypic analysis.

A minority of BCC exhibits Ca(2+) that are associated with BCC-related keratin and/or necrosis. Like other follicular-derived tumors (trichilemmal cyst, pilomatricoma, and trichoepithelioma), BCC produce keratins that are ostensibly predisposed to calcification but are not related to matrical differentiation (mature hair keratin formation). Either due to transtumor elimination or due to tumor regression, Ca(2+) are frequently found free in solar elastotic or fibrotic dermis: a histologic clue in sun-damaged skin to the presence of BCC in the surrounding dermis.