Novel gene mutations in Chédiak–Higashi syndrome with hyperpigmentation

angiosarcoma, he was referred to our hospital in April 2018. At the first visit, we examined the purpuric pigmentation spreading from his forehead to right eyelids (Fig. 1a). A biopsy specimen from the purpuric macules showed lumen structures proliferating in the upper dermis. The endothelial cells of the lumen had cell atypia with a doublet nucleus and protruded into the lumen (Fig. 1b). Immunohistochemistry revealed the partially positivity of the lumen wall for CD31, CD34 and D2-40 (Fig. 1c). In addition, melanin deposition was confirmed by Fontana-Masson staining, and abundant hemosiderin leakage from the microvessels was detected by Berlin-blue staining (Fig. 1d). Although the initial diagnosis was angiosarcoma, the possibility of minocycline-induced hyperpigmentation or subcutaneous hemorrhage needed to be considered. Because he had already quit oral minocycline 2 weeks before the first consultation, we decided to follow up the patient with observation. The purpuric pigmentations gradually improved over 2 months and had almost disappeared by 5 months (Fig. 1e). Taken together with the history of no recurrence during 1-year observation, we excluded the possibility of natural regression of angiosarcoma. Skin pigmentation is a well-recognized adverse effect of minocycline; the incidence ranges 2.4–14.8% in limited longitudinal studies. Minocycline-induced cutaneous hyperpigmentation has been classified into three different types: type I, blue-black pigmentation limited to sites of scarring or inflammation on the face; type II, blue-gray circumscribed pigmentation of the normal skin of the limbs; and type III, diffuse muddy brown pigmentation of the normal skin on sun-exposed areas. Histopathological examinations of type I and type II cases are characteristically positive for both iron and melanin. In contrast, only increased basal melanosis and dermal melanophage infiltration are observed without iron in type III. While the staining pattern in the present case was compatible with type I or type II, the scar formation was unexpectedly obscure. Because the pigmentation occurred on sun-exposed areas, it is thought to represent a case of type III pigmentation coexisting with microbleeding induced by aspirin. To our knowledge, no other cases of minocycline-associated microvascular hyperproliferation with a similar appearance to angiosarcoma have been reported. Minocycline was suggested to induce morphological changes in the endothelial cells. Minocycline leads not only to endothelial cell vacuolation but also to growth inhibition in a concentration-dependent manner in vitro. The microvascular proliferation observed in the present case might have resulted from a compensation effect after cell growth inhibition by minocycline. Angiosarcoma is a life-threatening skin malignancy; thus, it shouldbepreciselydiagnosedbasedon itsclinicalandhistopathological features. Given the present rare case mimicking angiosarcoma, the importance of the differential diagnosis of angiosarcomaneedstobere-recognizedbydermato-oncologists.