Background: Primary cutaneous cribriform carcinoma (PCCC) is a rare and under‐recognized variant of sweat gland carcinoma, characterized by anastomosing tubules and solid nests producing a sieve‐like appearance.Methods: Six cases of PCCC were clinically, histopathologically and immunophenotypically studied.Results: All cases showed an unencapsulated, nodular dermal tumor composed of solid and cribriform nests, cords and tubules embedded within a desmoplastic stroma. Some tubules showed micropapillary projections reminiscent of tubular adenoma, and intraluminal thin bridges resembling adenomatoid tumor. One case showed a predominantly solid component. Only two cases showed very focal decapitation secretion. Tumor cells expressed CK7, CK5/6, EMA, CEA, S‐100, BerEP4 and c‐kit and were negative for cytokeratin 20, estrogen receptor/progesterone receptor (ER/PR), androgen receptor and GCDFP‐15. Calponin, p63 and smooth muscle actin (SMA) showed absence of a myoepithelial layer.Conclusions: Contrary to the original reports, our series shows that PCCC may be predominantly solid with only a minor cribriform component, and expresses c‐kit and S‐100 which may potentially lead to the misdiagnosis of adenoid cystic carcinoma. Immunohistochemical stains may aid in distinction from tubular adenoma. Current data suggest a favorable outcome, as metastatic disease has not been reported to date.

Cutaneous melanoma remains the most lethal skin cancer, and ranks third among all malignancies in terms of years of life lost. Despite the advent of immune checkpoint and targeted therapies, only roughly half of patients with advanced melanoma achieve a durable remission. Sirtuin 5 (SIRT5) is a member of the sirtuin family of protein deacylases that regulates metabolism and other biological processes. Germline Sirt5 deficiency is associated with mild phenotypes in mice. Here we showed that SIRT5 was required for proliferation and survival across all cutaneous melanoma genotypes tested, as well as uveal melanoma, a genetically distinct melanoma subtype that arises in the eye and is incurable once metastatic. Likewise, SIRT5 was required for efficient tumor formation by melanoma xenografts and in an autochthonous mouse Braf Pten–driven melanoma model. Via metabolite and transcriptomic analyses, we found that SIRT5 was required to maintain histone acetylation and methylation levels in melanoma cells, thereby promoting proper gene expression. SIRT5-dependent genes notably included MITF, a key lineage-specific survival oncogene in melanoma, and the c-MYC proto-oncogene. SIRT5 may represent a druggable genotype-independent addiction in melanoma.