Benign glandular schwannomas are rare and should be distinguished from malignant peripheral nerve sheath tumors with similar divergent tissue differentiation. The authors present a benign glandular schwannoma with ancient change that developed in the subcutis of a 46-year-old man's posterior calf. He lacked stigmata of neurofibromatosis type 1 (NF1). The glandular elements stained positively for epithelial membrane antigen and pancytokeratin. The spindled cells stained positively for SOX10 and S100 protein, supporting schwannian (neural crest) differentiation. The tumor's location and histopathology suggest that the pathogenesis stems from entrapment of sweat glands. Finally, it must be recognized that ancient change may mimic malignancy in these neoplasms as the malignant counterparts have a greater association with NF1 and a poorer prognosis.

Cutaneous meningiomas (CM) are a small subset of meningiomas, further classified into three subtypes. The authors present a 15-year-old male with a symptomatic congenital type I CM and describe the histopathological and immunohistochemical findings. To the authors' knowledge, this is the first report of an extraspinal lumbar type I CM with intradural attachment to the phylum terminale.

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Relapsing linear acantholytic dermatosis (RLAD) is a rare disease that manifests as recurring episodes of crusted and vesicular lesions distributed in a Blaschkoid pattern with histology resembling Hailey-Hailey disease. RLAD, in the presence of generalized disease, has been shown to be a type 2 mosaic form of Hailey-Hailey disease. RLAD, without systemic disease, has been hypothesized to be type 1 mosaic Hailey-Hailey disease, but this assertion has lacked genetic conformation. To determine the genetic abnormalities causing RLAD, we performed exome sequencing of affected tissue and blood in one patient. Exome sequencing of a punch biopsy revealed a c.238A>T, p.(Lys80*) variant in ATP2C1 found in 26% of the reads from lesional skin but absent in germline DNA. This somatic variant causes a truncated protein that would likely result in loss of function. Our findings indicate that, in this patient, RLAD is a clinical presentation of type 1 segmental Hailey-Hailey disease.

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The autosomal dominant presentation of trichilemmal cysts is one of the most common single gene familial diseases in humans. However, the genetic basis for the inheritance and genesis of these lesions has remained unknown. We first studied patients with multiple trichilemmal cysts using exome and Sanger sequencing. Remarkably, 21 of 21 trichilemmal cysts from 16 subjects all harbored a somatic p.S745L (c.2234 G > A) mutation in phospholipase C delta 1 (PLCD1), a proposed tumor suppressor gene. In addition to this specific somatic mutation in their tumors, 16 of the 17 subjects with multiple trichilemmal cysts were also heterozygous for a p.S460L (c.1379 G > A) germline variant in PLCD1 which is normally present in only about 6% of this population. The one patient of 17 that did not show the p.S460L germline variant had a germline p.E455K (c.1363 C > T) mutation in the same exon of PLCD1. Among 15 additional subjects, with a history suggesting a single sporadic trichilemmal cyst, six were likely familial due to the presence of the p.S460L germline variant. Of the remaining truly sporadic trichilemmal cysts that could be sequenced, only half showed the p.S745L somatic mutation in contrast to 100% of the familial cysts. Surprisingly, in contrast to Knudsen's two hit hypothesis, the p.S745L somatic mutation was always on the same chromosome as the p.S460L germline variant. Our results indicate that familial trichilemmal cysts is an autosomal dominant tumor syndrome resulting from two hits to the same allele of PLCD1 tumor suppressor gene. The c.1379 G > A base change and neighboring bases are consistent with a mutation caused by ultraviolet radiation. Our findings also indicate that approximately one-third of apparently sporadic trichilemmal cysts are actually familial with incomplete penetrance. Sequencing data suggests that the remaining, apparently sporadic, trichilemmal cysts are genetically distinct from familial cysts due to a lack of the germline mutations that underlie familial cysts and a decreased prevalence of the p.S745L somatic mutation relative to familial trichilemmal cysts.

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3.Fuji S, Inoue Y, Utsunomiya A, et al. Pretransplantation anti-ccr4 antibody mogamulizumab against adult t-cell leukemia/lymphoma is associated with significantly increased risks of severe and corticosteroid-refractory graft-versus-host disease, nonrelapse mortality, and overall mortality.