To the Editor: Tumor-associated dystrophic calcification has been predominantly reported in benign adnexal neoplasms, such as pilomatricoma (1), trichoepithelioma (2), and trichilemmal cysts (3), as well as malignant tumors, such as proliferating tricholemmal cystic squamouscell carcinoma (4) and basal cell carcinoma (BCC) (5). Dystrophic calcification in squamous cell carcinoma (SCC) is exceptional (5). In most calcified BCCs/SCCs calcification occurred in a keratin-filled cyst, invagination or epidermoid cyst. To our knowledge, miliary calcification in a horn overlying SCC has not been reported. Herein we report a case of SCC with horn displaying miliary calcification. The tumor was a long-standing 1.6 cm wide plaque on the lateral aspect of the foot of an elderly woman. Biopsy specimen showed a well differentiated, 1.6 mm thick SCC—the tumor showed conspicuous acanthosis rather than infiltrative undersurface. It displayed a digitated pattern, focal adenoid features, ie mucin pools, and an extensively microcalcified cutaneous horn (Fig. 1). This low-grade neoplasm showed some features of adnexal differentiation but the histopathologic findings were not those of trichilemmal or adenosquamous carcinoma.FIG. 1.: Well-differentiated squamous cell carcinoma with cutaneous horn. The horn shows miliary calcification and a few mucin pools (hematoxylin-eosin stain).Alcian blue stain showed pools of mucin in the malpighian and granular layers and the horn. Carcinoembryonic antigen and epithelial membrane antigen were positive focally (strongly and weakly respectively). Von Kossa stain showed numerous calcospherites (microcalcifications) in the horn. Solid or granular mineralization was visualized on the corneocytes with high-power microscopy (Fig. 2). The microcalcifications were seen in individual corneocytes and not in or adjacent mucin pools. There was no spatial relationship between mucin pools and microcalcifications, which makes it unlikely that the calcified corneocytes were previously mucinotic. Serum calcium levels were within normal limits, and there was no evidence of vascular calcification in the biopsy.FIG. 2.: High-power photomicrograph shows cutaneous horn with microcalcifications. Individual corneocytes show granular or solid mineralization (von Kossa stain).The pathogenesis of dystrophic calcification in skin tumors has been poorly understood. In most calcified BCCs, calcium deposits were located in keratin-filled cysts that were thought to represent abortive hair follicles (5). It was, therefore, suggested that a calcium-binding protein is expressed in the follicularly-derived keratin. Skin calcium-binding protein has been localized to the cytoplasm of basal cells, outer root sheath of the hair follicle, sweat glands and malpighian mucosa in rabbits (6). In humans, calcium-binding protein has been localized to the cytoplasm of basal epidermal cells (7). Skin calcium-binding protein has been detected in undifferentiated but not in mature keratinocytes (8). Squamous cell carcinomas may have a relatively low rate of calcification because they arise from more mature and differentiated keratinocytes that do not express this binding protein. Nevertheless, it has been shown that differentiated keratinocytes may express other calcium-binding proteins, such as calmodulin and annexins (lipocortins). Squamous cell carcinoma cells have shown increased levels of calmodulin (9), a protein that increases the resistance of SCC cells to growth arrest, and may play a role in the early events of tumor growth. Furthermore, annexin AS-1 was found in differentiated SCC whereas undifferentiated SCC and BCC were negative (10). Studies examining the expression of calcium-binding proteins in skin tumors may shed more light in the pathogenesis of dystrophic calcification in these neoplasms. In our case, miliary calcification was seen predominantly in corneocytes and may result from the expression of a calcium-binding protein by keratinocytes, which reach a high level of cellular differentiation. Aldo González-Serva, M.D. George Kroumpouzos, M.D., Ph.D.