A year old Japanese female presented with a tumor

A 19-year-old Japanese female presented with a tumor grown within 7 months on her right breast. The tumor was dark red, exophytic, and a firm mass with a diameter of 8 cm×7 cm (A and 1B). Breast carcinoma was suspected and total resection was performed. On the cut appearance, the tumor was well circumscribed with central necrosis (C). Histologically, the tumor was surrounded by fibrotic connective tissue and composed of peripheral basophilic order isradipine and central necrosis (D). Oval-shaped basophilic cells and anucleated eosinophilic shadow cells were observed continually (E). Nuclear atypia was scarcely noted in basophilic cells. In the outer side, a foci of the tumor nest composed of differentiated keratinocytes with pleomorphic nuclei and keratinization, which looked like squamous cell carcinoma (SCC), was observed (F). Immunohistochemically, β-catenin displayed marked expression and nuclear staining (A). Ki-67 positive ratio was over 50%, suggesting its high proliferation. Although the present case showed histological findings of necrosis and keratinization reminiscent of SCC, we diagnosed this case as GPM from the well circumscribed structure without infiltrative growth and lack of the nuclear atypia. More than 2 years after the operation, there were no signs of recurrence or metastasis. GPM is a rare condition. In the review of past literatures, only 32 cases have been reported including our case (figure legends listed in Supplementary References). From its clinicopathological features, there is occasionally some difficulty in differentiating GPM from pilomatrical carcinoma (PMCa), the malignant counterpart of PM. Several histological findings have been reported to be useful in distinguishing GPM from PMCa, and include necrosis, keratinization, infiltrative growth, and cellular atypia. Presence of the multiple findings of these will support the diagnosis of PMCa. However, keratinization of tumor cells showing SCC-like features and necrosis have been reported to be present in GPM. In the review of past literatures with histological description, 10 out of 32 GPM cases (31.2%) showed SCC-like features, suggesting that basophilic cells have differentiating potency. Necrotic change in GPM was reported in three out of 32 cases (9.4%), which is a relatively high frequency for a benign tumor. In further analysis of 10 rapidly grown cases which developed within 1 year, four (40%) showed SCC-like features and two (20%) showed necrosis, suggesting that rapidly grown GPM tends to display histological findings suggesting the possibility of malignancy. From the characteristic clinical course showing rapid growth, we hypothesized that pathogenic factors, other than the activation of Wnt β-catenin signaling, contributed to the pathogenesis of the present case. We made further immunohistochemical analysis of the specimen and c-KIT (B and 2C) showed diffuse positive staining in the basophilic tumor cells, whereas the staining was focally positive or mostly negative in six common PM cases (D–2F). c-KIT is a receptor for platelet-derived growth factor, colony-stimulating factor 1, and flt-3 ligand. Activation of c-KIT signaling has been found to mediate cell survival and proliferation. Although c-KIT expression has not been reported in GPM, Goto reported four c-KIT positive PM cases, one of which showed focally positive staining. In our analysis, three out of six cases showed focally positive staining, most of which tend to be positive in undifferentiated basophilic cells, but become negative in accordance with differentiation (D and 2E). These results suggest that c-KIT will be a marker of undifferentiated basophilic cells. As c-KIT stained diffusely positive in almost all basophilic cells in the present case, we are speculating that most of the basophilic cells remained undifferentiated and continue to proliferate, leading to GPM. Further accumulation of the cases is necessary to reveal the etiology of this characteristic condition.