The classification of cutaneous sweat gland lesions is very complex (table 1), as these lesions have a wide histological spectrum, and the pathogenesis and exact origin of many lesions is still under investigation and not clear.1,2
Many different terms are often used to describe the same tumour (table 2), making this subject more difficult for pathologists to reach a uniform terminology for the diagnosis of these lesions. Furthermore, the issue is complicated by the coexistence of eccrine and/or apocrine lesions within cutaneous hamartomas or within adnexal lesions with composite/mixed differentiation, which also includes those with follicular and sebaceous differentiation. A detailed practical approach to different skin adnexal lesions has been illustrated in the first review article of this series.3
Nonetheless, some important general features of sweat glands are reviewed here.
Table 1Classification of cutaneous sweat gland adnexal lesions according to the current concept of the predominant “accepted” origin
Table 2Cutaneous sweat gland lesions and their synonyms
Eccrine sweat glands are widely distributed almost everywhere in the skin. The cells in the excretory coil express positivity for low molecular weight keratin (LMWK), epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA), as well as S100 protein in the basal layer only. The myoepithelial cell layer may be highlighted by smooth muscle actin (SMA), p63 and calponin. Acrosyringeal cells (intraepidermal portion) stain for high molecular weight keratin (HMWK) and cytokeratin (CK) 14. A subpopulation of cells also expresses positivity to bcl‐2. Skin tumours with eccrine differentiation often also express positive immunohistochemical staining for oestrogen and progesterone receptors.4
The positivity of some eccrine carcinomas to oestrogen receptors has important clinical implications, as affected patients may be partially treated with hormonal therapy.5
Unfortunately, positivity for oestrogen receptors and progesterone receptors does not distinguish cutaneous eccrine tumours from cutaneous metastases of breast carcinoma,6
in which case clinical and radiological correlation is critical.
Apocrine lesions of the skin are rare and are found mainly in body folds including the axillary, groin and anogenital regions, where apocrine glands are most concentrated, as well as in the umbilicus, eyelid (Moll's glands), areola and in external auditory meatus. They also occur as heterotopic lesions elsewhere in the body, exemplified by tubular apocrine adenoma and within hamartomatous adnexal lesions such as in nevus sebaceous of Jadassohn (NSJ) in the scalp. In lesions of apocrine origin, the cells have abundant eosinophilic cytoplasm and eccentric, basally located nuclei. In addition, there is usually evidence of decapitation secretion in the luminal cells, and the tumour cells contain periodic acid Schiff (PAS)‐positive diastase‐resistant granules, and iron pigment (best illustrated with Prussian blue stain). The luminal cells are immunoreactive to CEA and EMA. The secretory cells are positive for LMWK, and the glandular epithelium often also expresses gross cystic disease fluid protein 15 (GCDFP‐15) and androgen receptors, which may be useful in the assessment of lesions suspicious of apocrine carcinoma. However, oestrogen receptors/progesterone/bcl‐2 negativity is more consistent, and is considered more helpful to confirm the diagnosis of apocrine carcinoma than GCDFP‐15/androgen receptor positivity.7
Apoeccrine glands are mostly found in the axillary region, and within lesions of NSJ.8
Their presence helps to explain the existence of some adnexal lesions that have both eccrine and apocrine components, including syringocystadenoma papilliferum (SCAP)1
and Fox–Fordyce disease.9
believe that these glands are synonymous with cutaneous mammary‐like glands (MLG), which are now recognised to be a normal component of the skin in the anogenital region, including the perianal skin.11
MLG are unique in having features of apocrine, eccrine and mammary glands. The previous assumption that these glands represent ectopic/accessory breast tissue lying along the milk line (mammary ridge) is now believed to be incorrect.12
Many adnexal lesions of the anogenital area are now recognised to be of MLG origin, including “apocrine” adenoma/fibroadenoma, hidrocystoma, hidradenoma papilliferum, extramammary Paget's disease and adenocarcinoma.11,12,13,14
These lesions often have papillary/cribriform growth pattern and a fibrous stroma reminiscent of fibroepithelial lesions of the breast. A helpful feature in attributing MLG origin to an adnexal tumour is the presence of normal MLG in the deep dermis and subcutaneous fatty tissue, in the vicinity of the lesion of interest,13
with a transition zone between benign and lesional areas.12
Tumours of pure apocrine origin appear to be much less common than those of eccrine origin, by virtue of the localisation of apocrine glands in the body. However, it is important to mention at the outset of this review that many of the sweat gland tumours traditionally assumed to have an eccrine origin are now recognised to have apocrine counterparts as well, as evidence of apocrine differentiation has been elucidated in many of them. These tumours include hidrocystoma, poroma, cylindroma, spiradenoma and chondroid syringoma. In addition, many sweat gland lesions have both eccrine and apocrine differentiation (as well as pilosebaceous occasionally) within the same tumour. Examples of this are the many composite/mixed adnexal tumours and hamartomas that continually appear in the literature. Therefore, it was felt necessary in this review to drop the prefix “eccrine” from many of these terms.
This review will concentrate on common and/or important benign as well as malignant tumours of cutaneous sweat glands (tables 3 and 4, respectively), with emphasis on a diagnostic approach. Many benign sweat gland tumours have malignant counterparts, which are discussed under the same subheading. Some entities are referred to only in the tables, but not considered in the text. After reading this review, the practising pathologist will be able to diagnose most of the entities considered herein. However, when a tumour is difficult to classify, it is more important to differentiate between benign and malignant lesions, and in that setting it may be sufficient to describe the tumour as a benign or malignant cutaneous sweat gland tumour, with predominant eccrine or apocrine differentiation. Furthermore, complete excision of all skin adnexal lesions is always advisable. The differentiation of sweat gland tumours from metastatic carcinomas is discussed where appropriate.
Table 3Morphological approach to benign cutaneous sweat gland lesions
Table 4Malignant cutaneous sweat gland tumours that have relatively constant identifiable features (discussed in text)