Tumours of cutaneous sweat glands are uncommon, with a wide histological spectrum, complex classification and many different terms often used to describe the same tumour. Furthermore, many eccrine/apocrine lesions coexist within hamartomas or within lesions with composite/mixed differentiation. In addition to the eccrine and apocrine glands, two other skin sweat glands have recently been described: the apoeccrine and the mammary-like glands of the anogenital area. In this review (the second of two articles on skin adnexal neoplasms), common as well as important benign and malignant lesions of cutaneous sweat glands are described, and a summary for differentiating primary adnexal neoplasms from metastatic carcinoma is outlined, striving to maintain a common and acceptable terminology in this complex subject. Composite/mixed adnexal tumours are also discussed briefly.

Skin adnexal neoplasms comprise a wide spectrum of benign and malignant tumours that exhibit morphological differentiation towards one or more types of adnexal structures found in normal skin. Most adnexal neoplasms are relatively uncommonly encountered in routine practice, and pathologists can recognise a limited number of frequently encountered tumours. In this review, the first of two, the normal histology of the skin adnexal structures is reviewed, and the histological features of selected but important benign and malignant tumours and tumour-like lesions of pilosebaceous origin discussed, with emphasis on the diagnostic approach and pitfalls in histological diagnosis.

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Tumorigenesis results from dysregulation of oncogenes and tumor suppressors that influence cellular proliferation, differentiation, apoptosis, and/or senescence. Many gene products involved in these processes are substrates of the E3 ubiquitin ligase Mule/Huwe1/Arf-BP1 (Mule), but whether Mule acts as an oncogene or tumor suppressor in vivo remains controversial. We generated K14Cre;Mule flox/flox(y) (Mule kKO) mice and subjected them to DMBA/PMAinduced skin carcinogenesis, which depends on oncogenic Ras signaling. Mule deficiency resulted in increased penetrance, number, and severity of skin tumors, which could be reversed by concomitant genetic knockout of c-Myc but not by knockout of p53 or p19Arf. Notably, in the absence of Mule, c-Myc/Miz1 transcriptional complexes accumulated, and levels of p21CDKN1A (p21) and p15INK4B (p15) were down-regulated. In vitro, Muledeficient primary keratinocytes exhibited increased proliferation that could be reversed by Miz1 knockdown. Transfer of Mule-deficient transformed cells to nude mice resulted in enhanced tumor growth that again could be abrogated by Miz1 knockdown. Our data demonstrate in vivo that Mule suppresses Ras-mediated tumorigenesis by preventing an accumulation of c-Myc/Miz1 complexes that mediates p21 and p15 down-regulation.