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Primary malignant melanoma of sinonasal tract is a rare but severe form of melanoma. We retrospectively analyzed 17 cases and focused on the histologic presentation and the expression of c-Kit, epidermal growth factor receptor (EGFR), cyclin D1/Bcl-1, PS100, and HMB45 and searched for BRAF, NRAS, and KIT mutations that are known to be associated with melanoma subtypes, together with amplifications of KIT, cyclin D1, cyclin-dependent kinase 4, MDM2, and microphthalmia-associated transcription factor using quantitative polymerase chain reaction. In most cases (78%), an in situ component was evidenced. Invasive components were composed of diffuse areas of rhabdoid, epithelioid, or spindle cells and, in most cases, lacked inflammatory reaction, suggesting that an immune escape phenomenon probably develops when the disease progresses. EGFR was rarely and weakly expressed in the in situ component of 2 cases. None of the investigated case showed BRAF V600E, but 1 had a D594G mutation. NRAS mutations in exon 2 (G12D or G12A) were found in 3 cases (18%), and a KIT mutation in exon 11 (L576P), in 1, whereas c-Kit was expressed at the protein level in half of the cases. Amplifications of cyclin D1 were evidenced in 5 cases, confirmed in 3 by fluorescence in situ hybridization, but this was not always correlated with protein expression, found in 8 patients (62.5%), 3 having no significant amplification. In conclusion, primary malignant melanoma of sinonasal tract is not associated with BRAF V600E mutations. Instead, NRAS or KIT mutations and cyclin D1 amplification can be found in a proportion of cases, suggesting that primary malignant melanoma of sinonasal tract is heterogeneous at the molecular level and should not be sensitive to therapeutic approaches aiming at BRAF., (Copyright © 2013 Elsevier Inc. All rights reserved.)

A 24-year-old man had a mediastinal embryonal carcinoma containing yolk sac foci. Combination chemotherapy with cisplatin, bleomycin, etoposide, and vinblastine was given, and the residual mass was then resected. Histology showed only necrotic cells. No other treatment was given. Two years later the patient presented with episodes of flushing and syncopes related to a systemicmastocytosis. Bone marrow examination showed a diffuse infiltration with large, atypical mast cells often with multilobulated nuclei. The patient suffered several episodes of cardiovascular collapse and died during one of these episodes, 8 months after the diagnosis of systemic mastocytosis and 40 months after the diagnosis of mediastinal tumor. Autopsy findings included the absence of mediastinal tumor and a diffuse liver and spleen mast cell infiltration. This was the second case with the similar clinicopathologic picture of two rare diseases being associated. This fact supports the hypothesis of a distinct entity, part of the mediastinal germ cell tumor/hematologic malignancy syndrome. The hypothesis of a cytokine secretion induced by mediastinal germ cell tumor supporting mast cell proliferation may be considered.