Our study provides specific information on the clinical characteristics and outcome of this uncommon histological subtype of melanoma. However, the pathogenesis remains unknown. Breslow thickness, male gender and amelanosis were significantly associated with a poorer prognosis.

We found mutations in patients with multifocal CMs associated with AVMs. The phenotype, CM-AVM2, mimics-related CM-AVM1 and also hereditary hemorrhagic telangiectasia. -encoded p120RASGAP is a direct effector of EPHB4. Our data highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS-ERK signaling pathway as a major cause for AVMs.

Our data demonstrate the value of ultradeep NGS for molecular diagnosis of PROS, highlight its substantial allelic heterogeneity, and confirm that optimal diagnosis requires fresh skin or surgical samples from affected regions. Our findings may be of value in guiding future recommendations for genetic testing in PROS and other mosaic conditions.Genet Med advance online publication 02 February 2017.

PurposePIK3CA-related overgrowth spectrum (PROS) encompasses a range of debilitating conditions defined by asymmetric overgrowth caused by mosaic activating PIK3CA variants. PIK3CA encodes the p110α catalytic subunit of phosphatidylinositol-3-kinase (PI3K), a critical transducer of growth factor signaling. As mTOR mediates the growth-promoting actions of PI3K, we hypothesized that the mTOR inhibitor sirolimus would slow pathological overgrowth.MethodsThirty-nine participants with PROS and progressive overgrowth were enrolled into open-label studies across three centers, and results were pooled. For the primary outcome, tissue volumes at affected and unaffected sites were measured by dual energy X-ray absorptiometry during 26 weeks of untreated run-in and 26 weeks of sirolimus therapy.ResultsThirty participants completed the study. Sirolimus led to a change in mean percentage total tissue volume of –7.2% (SD 16.0, p = 0.04) at affected sites, but not at unaffected sites (+1.7%, SD 11.5, p = 0.48) (n = 23 evaluable). Twenty-eight of 39 (72%) participants had ≥1 adverse event related to sirolimus of which 37% were grade 3 or 4 in severity and 7/39 (18%) participants were withdrawn consequently.ConclusionThis study suggests that low-dose sirolimus can modestly reduce overgrowth, but cautions that the side-effect profile is significant, mandating individualized risk–benefit evaluations for sirolimus treatment in PROS.

The presence of a parallel-ridge pattern and/or irregular diffuse pigmentation within the lesion is highly indicative of melanoma on volar skin. An irregular lines pattern is the most prominent dermoscopic feature of pigmented ALM of the nail apparatus. Amelanotic ALM either in volar skin or in nail apparatus is characterized by remnants of pigmentation and a polymorphic vascular pattern.

Conservative surgical management in patients with in situ or minimally invasive SUM is a procedure with good cosmetic and functional outcome and, in our cases as well as in the literature, the prognosis is not changed.

Nail apparatus SCC is often misdiagnosed. Most cases are invasive at the time of diagnosis. Wide surgical excision bears a lower risk of relapse. Micrographic surgery should be considered for a better control in cases treated with limited surgical excision.

This is a detailed pathological study of a large cohort with ALM, an uncommon subtype of melanoma. Mitotic activity appears to be of particular importance in predicting the outcome of ALM.