Clear-Cell Hyperplasia of Eccrine Sweat Ducts

Kanitakis, Jean MD

American Journal of Dermatopathology: April 2017 - Volume 39 - Issue 4 - p 319–321
doi: 10.1097/DAD.0000000000000648
Letters to the Editor

Laboratory of Dermatopathology, Department of Dermatology, Ed. Herriot Hospital Group, Lyon, France

The author declares no conflicts of interest.

Article Outline

To the Editor:

Eccrine sweat glands in humans consist of a secretory coil (glomerulus) and an excretory duct. The former is composed histologically of 1–2 rows of secretory (clear and dark) cells, lined peripherally by a discontinuous layer of myoepithelial cells. The excretory duct traverses the dermis vertically and enters the epidermis, where it forms an individual, coiled structure (acrosyringium); it is made of a double row of cuboidal, basophilic cells surrounding the lumen of the sweat duct.1 In some people (accounting for about 0.5% of the population at large according to a recent study),2 the secretory coil contains only clear cells, resulting in a characteristic vacuolated/foamy appearance, which has no clear pathological implication. The presence of clear cells in the excretory ducts is an exceptional finding. It has been reported in the so-called “papular eccrine duct hyperplasia (PEDH),” a very rare condition of which 4 cases have been so far reported.3–6 This condition, which is different from clear-cell syringomas,7 was originally described as “eruptive clear cell hamartomas of sweat duct”3 and is characterized microscopically by a hyperplasia of the dermal ducts and the acrosyringium, which contain clear cells. A case similar to PEDH is reported herein, showing prominent clear-cell ductal hyperplasia found incidentally in a skin biopsy. The significance of this rare peculiar pathological finding is discussed.

A 67-year-old white man of Italian origin had a medical history of arthropathic psoriasis since the age of 20 years, for which he had received several therapies, including systemic (Psoralen plus Ultraviolet ray A, retinoids) and local ones (steroids, vitamin D analogs). He was also followed for alcoholic hepatic cirrhosis and for intestinal tubular adenomas with low-grade dysplasia. Increased fasting blood glucose levels were detected on several occasions during his regular follow-up for hepatic cirrhosis. During one of his visits, he presented with an erythematous, circinated, slightly atrophic scapular skin lesion that had reportedly been present for 4 years. A skin biopsy was taken from the lesions and submitted with the clinical suspicion of seborrheic dermatitis or lupus erythematosus. Microscopic examination of routinely stained 5-μm-thick sections cut from formalin-fixed, paraffin-embedded tissue blocks showed dermal capillaries somewhat dilated and surrounded by scarce lymphoid cells. The deep dermis contained eccrine sweat glands whose secretory coils looked normal. Remarkably, the proximal dermal excretory duct contained a peripheral row of cuboidal clear cells and an inner row of more basophilic cells surrounding the lumen (Fig. 1A). The upper dermal excretory duct was hyperplastic, consisting of 2–4 rows of large, polygonal cells with a clear cytoplasm, surrounding a narrow lumen. The clear cells had small basophilic monomorphous nuclei devoid of atypia and mitoses. The corresponding acrosyringium was also made of clear cells, the inner row of which contained small keratohyalin granules (Fig. 1B). Periodic Acid-Schiff staining highlighted the cuticle lining the excretory lumen and very weakly, if at all, some clear cells (Fig. 1C). Alcian blue staining showed normal mucin deposits around the secretory coils. Immunohistochemically, the clear cells of the hyperplastic eccrine ducts expressed membranous reactivity for the epithelial membrane antigen (Fig. 2A), the CD138 antigen (syndecan-1), and more weakly of EGF-R. Their nuclei expressed p63 (Fig. 2B). Cells of the inner row of the clear-cell ducts expressed K19 (Fig. 2C). HLA-DR antigens (revealed with the LN3 monoclonal antibody) were expressed by the inner row of acrosyringeal cells and more weakly by cells of the inner row of the dermal duct. Weak luminal expression of GCDFP-15 was seen, as well as weak expression of keratin 5/6 within basal cells of the hyperplastic ducts. Clear ductal cells did not express Ki67, CD326/epidermal cell-adhesion molecule (Ber-EP4), contrasting with the secretory coil cells that were immunoreactive (Fig. 2D), keratin 7 or 8 (Figs. 2E–F), HPV antigens, or smooth-muscle actin (Fig. 2G). Direct immunofluorescence examination of a frozen skin specimen taken concomitantly with the routine biopsy proved negative. Of note, a skin biopsy that had been taken 5 years before from an erythematous lesion of the patient's back had shown some mild vacuolization of the basal cells of the eccrine ducts, suggesting that the process had been progressive over the years.

PEDH, initially reported as “eruptive clear-cell hamartoma of sweat ducts,”3 is a very rare condition of which 4 cases have been so far reported, all of them in women.3–6 Three of these cases presented clinically as diffuse miliaria-like micropapular lesions3–5 and one was found incidentally, as in our patient, in a biopsy showing scarring changes.6 The case presented here seems histologically very similar, if not identical, with the previously reported cases of PEDH, even though the hyperplasia of sweat ducts was not so prominent as in some of the previous cases.3,6 Immunohistochemically, the affected sweat gland showed a normal phenotype. Remarkably, no Ki67 expression was found in the dermal clear-cell eccrine duct, suggesting that the proliferation rate of the duct was low. As in the case of Izaki et al,3 the clear cells in this patient were Periodic Acid-Schiff negative, suggesting that the clear appearance of cells is not necessarily due to glycogen deposition. Clear-cell changes in keratinocytes can be induced by HPV infection (koilocytosis), but in our patient, immunolabeling for HPV was negative. This patient also differs from all the other hitherto reported cases in that he was male, and from 2 previous cases4,5 in that the clinical appearance was not that of a papular eruption. A biopsy taken from our patient 5 years previously had shown some degree of vacuolar changes but no clear sweat-duct hyperplasia, supporting the contention6 that the process is not hamartomatous (which would imply permanent changes within the sweat ducts). It seems therefore likely that the clear-cell hyperplasia of the ductal cells is a reactive process to some as yet unknown stimulus. Exposure to heat could be one of them, as in 2 cases the lesions became inflamed after heat exposure.3,4 Scarring was present in another case,6 but in our patient, there was no obvious trigger, neither significant periglandular inflammation. The process could have its onset in the dermal duct and spread to the acrosyringium, as the cells of the latter seem to derive from dermal duct cells.8 The reason why not all cases have manifested clinically with papular lesions is unclear. It may be speculated that when the ductal hyperplasia is not pronounced, the process passes clinically unnoticed, but when the hyperplasia becomes sufficiently important, namely, involving the acrosyringium, papular lesions could develop, possibly due to partial obstruction of the sweat ducts, justifying the term “papular” eccrine duct hyperplasia. It can also be hypothesized that the process could be self-regressing if the triggering stimulus disappears.

In conclusion, clear-cell hyperplasia of eccrine ducts is a very rare but distinctive pathologic change of eccrine sweat glands usually observed in diabetic women, although this condition can also be encountered in men and is not necessarily associated with diabetes. The sweat duct clear-cell proliferation may be an incidental pathologic finding or manifest clinically with miliaria-like papular lesions, presumably when the hyperplastic changes are sufficiently severe and involve the acrosyringia. The observation of additional cases will hopefully shed more light on this puzzling eccrine sweat gland disorder.

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