Unusual Presentations of Eccrine Porocarcinomas.

Eccrine porocarcinomas (EPCs) are rare tumours, albeit the most common malignant adnexal tumours of the skin. They can present with very heterogeneous clinical and dermoscopic features, rendering diagnosis limited to histopathological examination alone. We share 2 cases of EPCs, one of which arose in a patient with a prior diagnosis of cutaneous squamous cell carcinoma (SCC) and another whose EPC was likely a malignant transformation of an existing poroma. An occurrence of porocarcinoma after the diagnosis of SCC may suggest the possibility of unknown risk factors for both. Positivity to androgen, oestrogen, and epidermal growth factor receptors was seen in a proportion of porocarcinomas, and this may prompt further research on combination therapy between conventional treatment modalities with hormone receptor antagonists. Malignant change of a poroma may be a more common phenomenon than we would expect based on the current literature.

Progressive expression of PPARGC1α is associated with hair miniaturization in androgenetic alopecia.

Current opinion views androgens as the pathogenic driver in the miniaturization of hair follicles of androgenetic alopecia by interfering with the dermal papilla. This cannot be the sole cause and therefore it is important for therapeutic and diagnostic purposes to identify additional pathways. Comparative full transcriptome profile analysis of the hair bulb region of normal and miniaturized hair follicles from vertex and occipital region in males with and without androgenetic alopecia revealed that next to the androgen receptor as well the retinoid receptor and particularly the PPAR pathway is involved in progressive hair miniaturization. We demonstrate the concurrent up-regulation of PPARGC1a in the epithelial compartment and androgen receptor in the dermal papilla of miniaturized hair. Dynamic Ppargc1a expression in the mouse hair cycle suggests a possible role in regulating hair growth and differentiation. This is supported by reduced proliferation of human dermal papilla and predominantly epithelial keratinocytes after incubation with AICAR, the agonist for AMPK signaling which activates PPARGC1a and serves as co-activator of PPARγ. In addition, miRNA profiling shows enrichment of miRNA-targeted genes in retinoid receptors and PPARGC1α/PPARγ signaling, and antigen presentation pathways.

Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation.

Squamous cell carcinoma (SCC) is a common and important primary cutaneous malignancy. On skin biopsies, SCC is characterized by significant squamous cell atypia, abnormal keratinization, and invasive features. Diagnostic challenges may occasionally arise, especially in the setting of small punch biopsies or superficial shave biopsies, where only part of the lesion may be assessable by the pathologist. Benign mimics of SCC include pseudoepitheliomatous hyperplasia, eccrine squamous syringometaplasia, inverted follicular keratosis, and keratoacanthoma, while malignant mimics of SCC include basal cell carcinoma, melanoma, and metastatic carcinoma. The careful application of time-honored diagnostic criteria, close clinicopathological correlation and a selective request for a further, deeper, or wider biopsy remain the most useful strategies to clinch the correct diagnosis. This review aims to present the key differential diagnoses of SCC, to discuss common diagnostic pitfalls, and to recommend ways to deal with diagnostically challenging cases.

Tamoxifen-induced eccrine squamous syringometaplasia.

A 74-year-old woman had carcinoma of her right breast for which surgery was performed. Four weeks following the start of tamoxifen therapy, she developed papules and plaques over her face, trunk and limbs. A skin biopsy showed perivascular and periadnexal mixed inflammatory cellular infiltrate with fibroplasia. Notably, the dermis also showed squamous epithelial islands, which in foci were noted to be closely associated with eccrine epithelium. This was confirmed with double peroxidase - alkaline phosphatase immunohistochemistry - the eccrine lumina highlighted with carcinoembryonic antigen (polyclonal) and the squamous metaplasia positive for cytokeratin 5/6. Eccrine squamous syringometaplasia was diagnosed. With close clinicopathological correlation, the cutaneous eruption was attributed to tamoxifen. Following discontinuation of the drug, the eruption resolved. Eccrine squamous syringometaplasia has been reported to occur in association with diverse conditions, including skin ulcers, burns and as a cutaneous adverse drug reaction, most commonly to chemotherapeutic drugs. This is believed to be the first report involving tamoxifen.