Search

Ectodysplasin receptor EDAR is seen as a typical Tumor Necrosis Factor receptor (TNFR) family member known to interact with its ligand Eda-A1, and signaling mainly through the nuclear factor-kappaB (NF-κB) and c-jun N-terminal kinases pathways. Mutations in genes that encode proteins involved in EDAR transduction cascade cause anhidrotic ectodermal dysplasia. Here, we report an unexpected pro-apoptotic activity of EDAR when unbound to its ligand Eda-A1, which is independent of NF-κB pathway. Contrarily to other death receptors, EDAR does recruit caspase-8 to trigger apoptosis but solely upon ligand withdrawal, thereby behaving as the so-called dependence receptors. We propose that pro-apoptotic activity of unbound EDAR confers it a tumor suppressive activity. Along this line, we identified loss-of-pro-apoptotic function mutations in EDAR gene in human melanoma. Moreover, we show that the invalidation of EDAR in mice promotes melanoma progression in a B-Raf mutant background. Together, these data support the view that EDAR constrains melanoma progression by acting as a dependence receptor.

Background Trichoblastic carcinoma (or malignant trichoblastoma) is a rare malignant cancer of adnexal structures with morphological features that in some cases are reminiscent of a trichoblastoma. Trichoblastic carcinoma is underdiagnosed as it is a rather recent entity which is still not recognized as such by all pathologists. The differential diagnosis with basal cell carcinoma is often difficult to make and the optimal treatment has not yet been established.Case report We report the case of a 43-year-old patient who underwent surgical excision and adjuvant radiotherapy for a growing mass of 40 × 48 mm located in the lumbar right paraspinal skin. The pathological findings demonstrated a trichoblastic carcinoma. The clinicopathological profile, the histogenesis, and the difficulties related to the histopathological diagnosis and treatment of this rare entity are discussed in this article.Conclusion Although the published reports on this disease are few, surgery should be considered the standard therapeutic approach for trichoblastic carcinomas. Selected cases presenting clinical features of local aggressiveness can safely be treated with adjuvant irradiation to improve local control. However, acute and particularly late toxicities need to be taken into account in the decision.

Fine needle aspiration (FNA) is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. Recently use of molecular biomarkers was proposed to improve pathologic accuracy. We evaluated feasibility and performance of molecular analysis in liquid-based FNA (LB-FNA) with indeterminate cytology. Mutation profiling of NRAS, HRAS and BRAF was performed on residual material from LB-FNA of 215 cases including 83 atypia of undetermined significance (AUS), 72 follicular neoplasms (FN), 46 suspicious for malignancy (SM), and 14 malignant (M). Forty-eight (22%) cases were mutated. Twenty-four cases presented a RAS mutation (19 NRAS and 5 HRAS) (11 AUS, 6 FN, and 7 SM) and 24 were carrying a BRAF mutation (1FN, 11 SM, and 12M). Surgical samples were available for 38 cases: 3 AUS, 14 FN, 13 SM and 8M. In the AUS category, 1 was a papillary carcinoma (PC) with NRAS mutation and 2 were benign (1 with NRAS mutation). In the FN category, 3 were malignant (1 with BRAF and 1 with HRAS mutation) and 11 benign (1 with HRAS and 1 with NRAS mutation). In the SM group, 10 were PC (3 with NRAS mutation and 5 with BRAF mutation) and 3 benign (no mutation). In the M group, all were PC with BRAF mutation. In conclusion, mutation profiling of BRAF and RAS can be successfully performed on residual material of thyroid LB-FNA and could improve the diagnostic accuracy of FNA.