LAUSR

To the Editor: The malignant variant of pilomatricoma, pilomatrix carcinoma, is a rare tumor. Approximately 90 cases of pilomatrix carcinoma have been reported in the English literature. Pilomatrical carcinosarcoma is another much rarer malignant counterpart of pilomatricoma, with only three cases documented in the literature. Lazar et al. reported that pilomatrix carcinoma and pilomatricoma harbored mutations in exon 3 of CTNNB1, the gene encoding beta-catenin, a downstream effector of the Wnt signaling pathway, and they proposed beta-catenin as a useful marker for the precise diagnosis of pilomatrical neoplasms by immunohistochemistry. We report here a fourth case of pilomatrical carcinosarcoma and describe for the first time the investigation of both beta-catenin expression and the mutational status of exon 3 of CTNNB1 by immunohistochemistry and DNA sequencing, respectively, in pilomatrical carcinosarcoma. The patient was a 73-year-old Japanese man, who presented with an erythematous tumor that had developed in the left preauricular region in the preceding 6 months. The first examination revealed an erythematous tumor (20 20mm in size) on the left cheek (Fig. 1a). The tumor was resected marginally and diagnosed as malignant by pathological examination. Additional resection was conducted with a 10mm margin from the scar, and no residual tumor was found in the specimen. No metastasis was identified from computed tomography of the whole body or cervical ultrasonography. No evidence of recurrence has been seen in the 8 months since the initial surgery. Microscopically, the tumor cells had infiltrated into the dermis, with nests of basaloid tumor cells comprising of anaplastic cells with numerous mitoses and a central part showing transition of matrical cells into pilomatrical ghost cells (Fig. 1b). The basophilic cells also showed keratinization and transformation to necrotic tissue. The stromal component surrounding the epithelial cell nests revealed mitotically active spindle cells with nuclear atypia (Fig. 1c). Spindle cells were also seen around and very close to the basaloid tumor cells. In the spindle cell component, many spindle cells were sarcomatous with bizarre nuclei and some spindle cells showed focal keratinization similar to the basaloid cells. The component composed of basaloid cells occupied half of the total tumor, and the spindle cells had spread to the residual area. The basaloid parts were well circumscribed and composed of epithelial islands embedded in the stromal component. The tumor grew upward, and the border was occupied by the spindle cells. Immunohistochemical staining of the resected specimen was performed using antibodies to pancytokeratin (AE1/ AE3), CK5/6, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), CAM5.2, vimentin, alphasmooth muscle actin (alpha-SMA), desmin, CD31, CD34, neuron-specific enolase (NSE), S-100 protein, Ki-67 (MIB1), and beta-catenin (Table S1). The basaloid component stained positive for AE1/AE3 (Fig. S1a), CK5/6, EMA, and beta-catenin, and negative for CEA, CAM5.2, vimentin (Fig. S1b), alph-SMA, desmin, CD31, CD34, NSE and S-100, although CEA was expressed in the keratinized cells. The spindle cell component was positive for vimentin and alpha-SMA, as well as partially positive for beta-catenin and NSE. It was also negative for AE1/AE3, CK5/6, EMA, CEA, CAM5.2, desmin, CD31, CD34, and S-100, although the keratinized parts were positive for CK5/6 and CEA. Thus, these results along with the morphological aspect indicated that the spindle cell component had sarcomatous feature. Ki-67 staining indicated that the basaloid cells were highly proliferative, with more than 40% of their nuclei showing positive staining, as compared to around 20% of sarcomatous cells. Staining for beta-catenin showed positive staining in both the nuclei and the cytoplasm of many basaloid cells and in the nuclei of some spindle cells (Fig. 1d). Although the spindle cells were mostly negative for pancytokeratin, they showed positive staining for CEA and CK5/6 in the focal keratinized areas as in the basaloid cells. Genomic DNA was extracted from formalin-fixed paraffinembedded specimen using the QIAamp DNA Mini Kit (QIAGEN KK, Tokyo, Japan), and exon 3 of CTNNB1 was amplified by polymerase chain reaction using the method of Lazar et al. DNA sequencing analysis was performed, but no mutation in exon 3 of CTNNB1 was identified (data not shown). Pilomatrical carcinosarcoma is extremely rare, with only three previously documented cases. This pathology was first described in 1994. According to two of the three previously reported cases, its behavior is aggressive, often with local invasion and distant metastases. Thus, the prognosis of our patient was assumed to be poor and strict follow-up was needed. Surgical resection, irradiation, and