Malignant neurocristic hamartoma: a tumor distinct from conventional melanoma and malignant blue nevus.

Neurocristic hamartomas are rare pigmented lesions comprised of melanocytes, Schwann cells, and pigmented dendritic spindle cells that involve the skin and soft tissue. Malignant transformation can rarely arise within neurocristic hamartomas. Up to date, there has been only 1 series of 7 cases of malignant neurocristic hamartomas (MNHs), with 3 cases that developed metastases. We present the histology and clinical course of 3 additional cases of MNH, 2 of which were metastatic. CD117 was strongly positive in all cases with available archival materials--the tumors and background neurocristic hamartoma of 3 cases, and 1 lymph node metastasis; however, KIT sequencing for exons 11, 13, 17, and 18 was negative. Mutational analyses of recurrent mutations of 17 cancer genes, including BRAF and KIT, were also negative. Although our series is small, KIT overexpression in MNH does not seem to correlate with gene mutation. The lack of BRAF, NRAS, GNAQ, and KIT mutations seems to support the notion that MNH may be distinct from conventional melanoma and from other dermal melanomas, such as malignant blue nevi and melanoma arising in congenital nevi.

Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin.

Distinction of primary skin adnexal carcinomas from cutaneous metastasis of adenocarcinomas is challenging. In this study, we evaluated podoplanin immunoreactivity in a series of primary skin adnexal tumors and adenocarcinomas metastatic to skin using a D2-40 antibody. The initial test series were composed of a total of 93 cases including 32 primary skin adnexal carcinomas, 46 benign primary adnexal tumors, and 15 cutaneous metastatic adenocarcinomas. We found that variable D2-40 reactivity was seen in all of the primary cutaneous carcinomas including sebaceous carcinomas (10/10), squamous cell carcinomas (10/10), porocarcinomas (4/4), trichilemmal carcinomas (4/4), skin adnexal carcinomas not otherwise specified (4/4), and in the majority of benign skin adnexal tumors. In contrast, no podoplanin immunoreactivity was seen in any of the 15 (0/15) cutaneous metastases. To confirm the initial findings and to further explore the utility of podoplanin reactivity in the distinction of these tumors, we also examined a test set of 35 unknown cases, including 21 adenocarcinomas metastatic to skin and 14 primary adnexal tumors, in a blinded fashion. In this test set of cases, podoplanin was negative in 22 cases and positive in 13 cases. Of the 22 podoplanin negative cases, 20 were proven to be metastatic adenocarcinoma. Of the 13 D2-40 positive cases, 12 were proven to be primary adnexal tumors. Our results suggest that podoplanin can be a useful tool to distinguish primary skin adnexal carcinomas form adenocarcinomas metastatic to skin with high sensitivity (94.5%) and specificity (97.2%).

Cellular nodules in congenital pattern nevi.

BACKGROUND: The diagnosis of 'cellular dermal nodule in melanocytic nevi' is challenging, as it can simulate invasive and tumorigenic melanoma. Because cellular nodules are presumed benign, it is essential to differentiate them from true malignant melanoma arising within a nevus, which portends a poor prognosis. Although presumed benign, to date, no published long-term follow-up studies have proved the benignity of this lesion. METHODS: To better understand the clinical behavior and histological features of these lesions, we present a clinical pathological study of a cohort of 26 cases, for which we obtained clinical follow up by chart review and questionnaires. RESULTS: Clinical follow up was obtained on 16 out of 26 patients (61.5%) and ranged from 12 to 132 months (average 62.3 months). The cellular nodules in congenital pattern nevi, reported here, had an invariably benign clinical course. CONCLUSIONS: Features useful in differentiating cellular nodule from melanoma include: (1) lack of high-grade uniform cellular atypia; (2) lack of necrosis within the nodule; (3) rarity of mitoses; (4) evidence of maturation in the form of blending or transitional forms between the cells in the nodule and the adjacent nevus cells; (5) lack of pagetoid spread into the overlying epidermis; and (6) no destructive expansile growth. The difference between cellular nodule and melanoma arising from nevus can be very subtle, and it is important to emphasize that these lesions must be assessed on an individual case-by-case basis.