Activating cysteinyl leukotriene receptor 2 (CYSLTR2) mutations in blue nevi.

Blue nevi are common melanocytic tumors arising in the dermal layer of the skin. Similar to uveal melanomas, blue nevi frequently harbor GNAQ and GNA11 mutations. Recently, recurrent CYSLTR2 and PLCB4 mutations were identified in uveal melanomas not harboring GNAQ or GNA11 mutations. All four genes (GNAQ, GNA11, CYSLTR2, and PLCB4) code for proteins involved in the same signaling pathway, which is activated by mutations in these genes. Given the related functional consequences of these mutations and the known genetic similarities between uveal melanoma and blue nevi, we analyzed a cohort of blue nevi to investigate whether CYSLTR2 and PLCB4 mutations occur in tumors lacking GNAQ or GNA11 mutations (as in uveal melanoma). A targeted next-generation sequencing assay covering known activating mutations in GNAQ, GNA11, CYSLTR2, PLCB4, KIT, NRAS, and BRAF was applied to 103 blue nevi. As previously reported, most blue nevi were found to harbor activating mutations in GNAQ (59%, n=61), followed by less frequent mutations in GNA11 (16%, n=17). Additionally, one BRAF (1%) and three NRAS (3%) mutations were detected. In three tumors (3%) harboring none of the aforementioned gene alterations, CYSLTR2 mutations were identified. All three CYSLTR2 mutations were the same c.386T>A, L129Q mutation previously identified in uveal melanoma that has been shown to lead to increased receptor activation and signaling. In summary, our study identifies CYSLTR2 L129Q alterations as a previously unrecognized activating mutation in blue nevi, occuring in a mutually exclusive fashion with known GNAQ and GNA11 mutations. Similar to GNAQ and GNA11 mutations, CYSLTR2 mutations, when present, are likely defining pathogenetic events in blue nevi.

Childhood mycosis fungoides with a CD8+ CD56+ cytotoxic immunophenotype.

Primary cutaneous T-cell lymphomas mostly occur in patients of middle and higher age. Their rarity and an oftentimes atypical clinical presentation in childhood as well as the reluctance of taking biopsies in children are reasons for a delayed diagnosis. We report the case of an 11-year-old boy with a 7-year history of slowly progressive CD8+CD56+ mycosis fungoides of the cytotoxic immunophenotype. His trunk and extremities were affected by extensive pale-erythematous patches and plaques with fine scaling. In addition, several poikilodermatous lesions were present on his thighs. Improvement was achieved by topical mometasone furoate treatment. On the basis of our observation, a brief review on cutaneous T-cell lymphomas in childhood and on CD8+ subtypes in particular is given. Clinicopathological correlation is crucial for establishing the correct diagnosis and for estimation of the prognosis.