An incisional biopsy specimen of the scalp nodule revealed a

An incisional biopsy specimen of the scalp nodule revealed a diffuse infiltrate extending into the subcutis (B). In the upper dermis, many S-100 positive spindle order nicergoline exhibited neuroid structures mixed together with adipocytes. These slender spindle cells possessed wavy nuclei and showed a haphazard and fascicular pattern in a fibromyxoid matrix reminiscent of a neurofibroma (C). Numerous nested pigmented melanocytes were located in the deep dermis and perifollicular area (D). The elements in the upper dermis were stained with S-100 but were negative for melan-A, indicating neural differentiation (A and B). The nested pigmented cells were highlighted with melan-A stain (C). Epithelial membrane antigen-positive slender perineural cells were present in both the upper and middle dermis (D). The whole dermis and superficial subcutis were infiltrated by these various neural and melanocytic components, thus supporting a neurocristic hamartoma (NCH) diagnosis. A total excision was suggested but the patient was reluctant to undergo immediate extensive surgery. She has been followed for 1 year post diagnosis without change. NCH is a rare hamartomatous proliferation of melanocytic, neuroid, and mesenchymal tissues. The development of this condition may be attributed to the aberrant development of neural crest cells, especially in the cephalic regions. Clinically they are congenital or acquired lesions presenting as pigmented macules, papules or nodules with or without alopecia. Dermis or subcutaneous tissues are frequently affected, and folliculocentric lesions may be observed. Most NCHs have a predilection for the scalp, but they have also been reported to occur on the trunk and extremities. NCH shares many histological features with blue and congenital nevi, and histopathological analysis is essential to differentiate it from other dermal melanocytoses. Key NCH indicators include distribution of various cells, morphology and depth of dermal melanocytes, stromal components, and presence of neuroid differentiation. It usually consists of a combination of dermal melanocytes, spindle cells, pigmented dendritic cells, and Schwannian cells in different proportions. Other features include perivascular pseudorosettes, tactoid bodies, and prominent collections of melanocytes around hair follicles, eccrine glands, nerves, and blood vessels. Tumor growth may involve the subcutaneous fascia, and deep infiltration into the skeletal muscle without overt malignancy has also been described. Immunohistochemical stains are helpful in distinguishing NCH from other dermal melanocytoses or nerve sheath tumors. The melanocytic elements stain positive for S-100 protein, melan-A, and HMB-45. The neuroid cell elements are positive for S-100 protein but negative for melan-A and HMB-45, whereas the epithelial membrane antigen stain may highlight perineural cells. Spindle cells within the mucinous stroma commonly stain positive for CD34, indicating proliferation of perifollicular fibrous tissue. Congenital nevi with a neuroid component and plaque-type blue nevus usually do not have stromal CD34 staining or perineural cell markers. NCH identification is clinically important to avoid confusion with other dermal melanocytoses and because of its malignancy potential. Although its course is generally indolent, long-standing NCH has been reported to give rise to cutaneous malignant melanocytic neurocristic tumors. Therefore, it is important to correctly differentiate NCH from other benign dermal melanocytoses, due to the possibility of malignant transformation. Malignant NCH consists of a poorly circumscribed mass arising from the dermis without elements in the overlying epidermis, and pathologists should be aware of this cytological atypia. In previous reports, mitotic activity did not correlate with poor prognosis. It seems that malignant NCH shows a less aggressive behavior than melanoma, and patients may experience multiple recurrences and hematogenous metastasis in the latter phase. Its malignant potential is similar to a low-grade mesenchymal tumor. In a recent study of three malignant NCH cases, no , , , or mutations were found, suggesting that malignant NCH may be distinct from conventional melanoma.