Spiradenoma and cylindroma are distinctive skin adnexal tumors with sweat gland differentiation and potential for malignant transformation and aggressive behaviour. We present the genomic analysis of 75 samples from 57 representative patients including 15 cylindromas, 17 spiradenomas, 2 cylindroma–spiradenoma hybrid tumors, and 24 low- and high-grade spiradenocarcinoma cases, together with morphologically benign precursor regions of these cancers. We reveal somatic or germline alterations of the CYLD gene in 15/15 cylindromas and 5/17 spiradenomas, yet only 2/24 spiradenocarcinomas. Notably, we find a recurrent missense mutation in the kinase domain of the ALPK1 gene in spiradenomas and spiradenocarcinomas, which is mutually exclusive from mutation of CYLD and can activate the NF-κB pathway in reporter assays. In addition, we show that high-grade spiradenocarcinomas carry loss-of-function TP53 mutations, while cylindromas may have disruptive mutations in DNMT3A . Thus, we reveal the genomic landscape of adnexal tumors and therapeutic targets.

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Parathyroid carcinoma is a rare disease, which accounts for less than 1% of all case of primary hyperparathyroidism and is usually not detected until the time of surgery or thereafter. For most patients preoperative staging is not available. A radical excision remains the standard management; the place of adjuvant radiotherapy is not well established yet. Local recurrence and/or the metastases are unfortunately frequent. The present paper presents an up to date review of the literature illustrated by three clinical cases.

This study further illustrates that CA of the vulva has distinct clinical and pathologic features that set it apart from the other soft tissue conditions involving this area. However, like many soft tissue neoplasms, this tumor also exhibits some variation in its histological or immunohistochemical features.