Apocrine Chromhidrosis.

Apocrine chromhidrosis is a rare diagnosis that occurs due to colored sweat being secreted from the apocrine glands, which are located in the axillae, anogenital skin, and areolae and over the skin of the trunk, face, and scalp. We present the case of a 65-year-old woman who presented with a sudden onset of pink sweating affecting mainly her axillae but also her pelvis, causing staining of clothing and bed sheets. There was nil to note on examination and histology with immunostaining demonstrated focally prominent yellow-brown lipofuscin granules in the cytoplasm of the apocrine secretory cells confirming the diagnosis. The disease can have a significant psychosocial impact, and treatment remains challenging. Our case is unique because the red and pink coloring of sweat is less common in cases of apocrine chromhidrosis, which is often in favor of darker colored sweat, and the distribution involved the inguinal canal, which is also less often seen.

Clinical and Molecular Evidence of ABCC11 Protein Expression in Axillary Apocrine Glands of Patients with Axillary Osmidrosis.

Accumulating evidence suggests that the risk of axillary osmidrosis is governed by a non-synonymous single nucleotide polymorphism (SNP) 538G>A in human ATP-binding cassette C11 (ABCC11) gene. However, little data are available for the expression of ABCC11 protein in human axillary apocrine glands that produce apocrine sweat-a source of odor from the armpits. To determine the effect of the non-synonymous SNP ABCC11 538G>A (G180R) on the ABCC11 in vivo, we generated transiently ABCC11-expressing transgenic mice with adenovirus vector, and examined the protein levels of each ABCC11 in the mice with immunoblotting using an anti-ABCC11 antibody we have generated in the present study. Furthermore, we examined the expression of ABCC11 protein in human axillary apocrine glands extracted from axillary osmidrosis patients carrying each ABCC11 genotype: 538GG, GA, and AA. Analyses of transiently ABCC11-expressing transgenic mice showed that ABCC11 538G>A diminishes the ABCC11 protein levels in vivo. Consistently, ABCC11 protein was detected in the human axillary apocrine glands of the 538GG homozygote or 538GA heterozygote, not in the 538AA homozygote. These findings would contribute to a better understanding of the molecular basis of axillary osmidrosis.

Immunohistological Expression of p16INK4a is Commonly Present Both in Benign and Malignant Sweat Gland Neoplasias.

The expression of p16INK4a has been reported to be a significant marker for malignant transformation of epidermal tumors. However, little is known about sweat gland tumors. We examined the immunohistological expression of p16INK4a in benign and malignant sweat gland tumors. The ductal and acrosyringial portion of normal eccrine glands were positively stained with p16INK4a while it was negative in the normal epidermis. Moderate to strong expression of p16INK4a was found in 16 of 17 eccrine poromas, 4 of 5 hidradenomas, 3 of 3 syringocystadenoma papilliferums, 2 of 2 mixed tumors, and 3 of 3 syringomas. The p16INK4a expression was observed focally or diffusely in 4 of 4 porocarcinomas, 4 of 4 apocrine carcinomas and 12 of 17 extramammary Paget's diseases. We conclude that the p16INK4a expression is not a good marker for dictating malignant transformation of sweat gland tumors.

Eccrine squamous syringometaplasia secondary to cutaneous extravasation of docetaxel: report of three cases.

Eccrine squamous syringometaplasia is characterized by the metaplasia of cuboidal epithelial cells of the eccrine sweat ducts into squamous epithelial cells. It has been associated with several conditions including chemotherapy-related bilateral dermatitis, an entity that can take place in body areas rich in eccrine glands, as well as in acral erythema related to chemotherapy. Only a few cases because of cutaneous extravasation of chemotherapy have been previously reported. We report three cases of eccrine squamous syringometaplasia secondary to extravasation of docetaxel.

Correlation of axillary osmidrosis to a SNP in the ABCC11 gene determined by the Smart Amplification Process (SmartAmp) method.

Axillary osmidrosis (AO) is caused by apocrine glands secretions that are converted to odouriferous compounds by bacteria. A potential link between AO and wet earwax type has been implicated by phenotype-based analysis. Recently, a non-synonymous single nucleotide polymorphism (SNP) 538G> A (Gly180Arg) in the human adenosine triphosphate (ATP)-binding cassette (ABC) transporter ABCC11 gene was found to determine the type of earwax. In this context, we examined a relationship between the degree of AO and the ABCC11 genotype. We have genotyped the SNP 538G> A in a total of 82 Japanese individuals (68 volunteers and 14 AO patients) by both DNA sequencing and the recently developed Smart Amplification Process (SmartAmp). The degree of AO in Japanese subjects was associated with the genotype of the ABCC11 gene as well as wet earwax type. In most AO patients investigated in this study, the G/G and G/A genotypes well correlated with the degree of AO, whereas A/A did not. The specific SmartAmp assays developed for this study provided genotypes within 30 min directly from blood samples. In East Asian countries, AO is rather infrequent. Although the judgement of the degree of AO prevalence is subjective, the SNP 538G> A in ABCC11 is a good genetic biomarker for screening for AO. The SmartAmp method-based genotyping of the ABCC11 gene would provide an accurate and practical tool for guidance of appropriate treatment and psychological management for patients.

Reduction in QSART and vasoactive intestinal polypeptide expression in the skin of Parkinson's disease patients and its relation to dyshidrosis.

BACKGROUND: With regards to dyshidrosis in Parkinson's disease (PD), there is no established and consistent view on the occurrence sites, frequency and etiology, although there have been several reports on hypohidrosis of the limbs and sudoresis on the face/cervical region. METHODS: Hydrosis in the forearms of PD patients and healthy individuals were compared by quantitative sudomotor axon reflex test (QSART). The expression of various neuropeptides and alpha-synuclein was examined with immunohistochemical staining. RESULTS: There was a significant reduction in QSART of PD patients but not of healthy controls. Reduced expression of vasoactive intestinal polypeptide (VIP) was also detected in the sweat glands of PD patients. CONCLUSION: Reduction in QSART and VIP expression in the sweat glands might be involved in the dyshidrosis of PD patients.

Eccrine angiomatous hamartoma with features resembling verrucous hemangioma.

Eccrine angiomatous hamartoma (EAH) is a benign malformation characterized by a proliferation of eccrine glands and capillary vessels in the dermis. Hyperplasia of other dermal constituents, such as fat, nerve fibers, pilar structures and dermal mucin, has been reported. EAH typically presents as a painful lesion on the extremities of children or young adults and may be associated with local hyperhidrosis. We report a case of a 7-year-old boy with a keratotic lesion on the ankle, present since birth. Histologically, there was a nodular proliferation of eccrine glands intimately admixed with numerous small vessels in the dermis. In addition, there was marked epidermal hyperplasia associated with increased numbers of dilated, thin-walled vessels in the superficial and mid-dermis. The vessels were negative for glucose transporter-1 protein (GLUT-1), supporting the impression of hamartoma over that of hemangioma. EAH has been described in association with spindle cell hemangioma and arteriovenous malformation; overlying verrucous epidermal features have been noted in rare cases. However, changes resembling verrucous hemangioma associated with EAH, as seen in this case, have not been emphasized in the literature. The findings are unusual and expand the histological spectrum of this hamartoma.

Late-onset eccrine angiomatous hamartoma: clinical, histological and imaging findings.

Eccrine angiomatous hamartoma (EAH) is an exceedingly rare benign tumor-like lesion prevalent in childhood which may produce pain and marked sweating. Although an aggressive treatment is not generally indicated, surgery may be considered in severe cases. In this report we present novel morphological findings by immunophenotyping, document the first MRI findings in EAH and emphasize the importance of preoperative imaging of such lesions.

Grover's disease (transient acantholytic dermatosis): relationship of acantholysis to acrosyringia.

Transient acantholytic dermatosis is often associated with excessive sweating, fever, and bed confinement. The pathogenesis of this disease has been postulated to be poral occlusion of damaged eccrine intraepidermal ducts. Histological and immunohistochemical and ultrastructural studies were performed on 10 biopsies from 10 patients with transient acantholytic dermatosis. Immunoreactions for carcinoembryonic antigen and cytokeratin-7 to identify eccrine duct epithelium were performed on all 11 biopsies. In addition, 5 of the biopsies were immunoreacted for cytokeratin 8. All immunoreactions were reviewed independently by two observers to determine extent of reactivity and whether it correlated with areas of epidermal acantholysis. Among the 11 biopsies, 8 showed acantholysis not associated with eccrine duct outflow tracts. In 2 biopsies the acantholysis was consistently associated with acrosyringea; in one case acantholysis was inconsistently associated with eccrine outflow tracts. Epidermal acantholysis in patients with Grover's disease is associated with the outflow tracts of eccrine ducts in a subgroup of patients. Although leakage of sweat from occluded sweat ducts in acrosyringia may be the mechanism operating in a subgroup of patients with Grover's disease, this does not appear to be the subgroup of patients in whom Grover's disease develops in the setting of being bedridden and/or sweating.

Eccrine angiomatous hamartoma (nevus): immunohistochemical findings and review of the literature.

Eccrine angiomatous hamartoma (nevus) is a rare form of congenital tumorous malformation with proliferation of eccrine secretory coils and ducts, surrounding capillary angiomatous channels and occasionally other minor elements. To date, there have been only about 24 cases reported in the literature. We report an additional case with more detailed description of the microscopic findings, including immunohistochemical observations. The patient was a 28-year-old female who presented with painless, flesh- to reddish brown-colored, violaceous or bluish subcutaneous nodules on the extremities and trunk. The tumors did not show sweating following exertion. The histologic features were comparable to the previously reported cases. The hamartomatous eccrine sweat glands and ducts and a few apocrine glands demonstrated qualitatively diminished antigens commonly found in the eccrine sweat apparatuses, such as carcinoembryonic antigen (CEA) and S-100 protein. The findings of CD34, CD44, human nerve growth factor receptor and Ulex europaeus antigens have not been previously reported. The histologic features suggested a "hamartomatous" growth rather than a true neoplastic process.

Androgen metabolism by isolated human axillary apocrine glands in hidradenitis suppurativa.

Androgen metabolism was investigated in normal human apocrine glands and in those isolated from age-matched patients with hidradenitis suppurativa. Axillary glands were isolated by shearing and androgen interconverting enzyme activities were measured in cell-free homogenates by incubation with [3H] dehydroepiandrosterone, [3H] androstenedione and [3H] testosterone. The activities (pmol/mg protein/min: mean + SEM) of 3 beta-hydroxysteroid dehydrogenase delta 4-5-isomerase (10.0 +/- 1.2 vs. 5.3 +/- 0.5: n = 5) and 17 beta-hydroxysteroid dehydrogenase (58.1 +/- 4.5 vs. 35.7 +/- 5.2: n = 5) were significantly lower (P less than 0.005) in hidradenitis suppurativa, whereas 5 alpha-reductase activity (12.5 +/- 2.3 vs. 12.5 +/- 2.0: n = 5) was similar. This report suggests that hidradenitis suppurativa cannot be attributed to exaggerated activities of end-organ androgen interconverting enzymes.

Zinc alpha-2 glycoprotein levels in serum and breast fluids: a potential marker of apocrine activity.

Zinc alpha-2 glycoprotein (ZnGP) was measured in human breast microcysts, breast secretions, breast cyst fluid and serum. Detectable amounts of ZnGP were found in all fluids but the highest levels were found in microcysts. Apocrine macrocysts had a higher ZnGP level than flattened macrocysts. In both cysts and secretions levels of ZnGP correlated with those of dehydroepiandrosterone sulphate. Levels were significantly higher in cyst fluids from women who developed further cysts during follow-up compared with those in fluid from women who did not. Concentrations of ZnGP in serum from breast cancer patients were significantly higher than controls but not women with breast cysts. Women with node positive breast cancer had higher serum levels compared with those in node negative patients. Women with more advanced breast cancer had higher serum ZnGP levels than those with earlier disease. ZnGP is a serum and breast marker of apocrine activity and may prove to be a useful prognostic marker in breast cancer.

Immunocytochemical demonstration of intermediate filament proteins, S-100 protein and CEA in apocrine sweat glands and apocrine gland derived lesions of the dog.

The presence of carcinoembryonic antigen (CEA), intermediate filament proteins and S-100 protein in normal and pathological canine apocrine sweat glands was investigated, using a standard immunoperoxidase technique. The normal apocrine sweat glands showed a constant immunoreactivity in all the cases studied. The cells of the acini and of the ducts only reacted with the antikeratin antibody. The myoepithelial cells reacted positively with the antisera antikeratin and anti protein S-100. Epithelial cells of apocrine cysts, sweat gland adenomas and sweat gland carcinomas showed the same immunoreaction than normal apocrine cells. Proliferating myoepithelial cells were also positive for vimentin. In two out of three adenocarcinomas a positive reaction with the anti CEA could be detected in the glandular cells. This can be due to the presence in glandular cells of CEA or of Nonspecific Crossreacting Antigen (NCA). These findings indicate that demonstration of keratin is a useful aid in the detection of apocrine gland derived lesions in the dog. Similarly, S-100 protein is a marker for myoepithelial cells. Further research is necessary to investigate the expression of CEA in canine tumours.

Intranuclear androgen and cytosolic receptor concentrations in the axillary skin of osmidrosis.

5 alpha-Dihydrotestosterone (DHT) and testosterone were measured by radioimmunoassay in the crude nuclear and cytoplasmic fractions of the axillary skin of both male and female patients with osmidrosis and the levels compared with those of nongenital skin. The intranuclear levels of DHT were 1.44 +/- 0.22 and 1.77 +/- 0.38 pg/micrograms DNA in men and women, respectively. Those of testosterone were about 10% of DHT levels. In the skin of nontarget regions nuclear DHT was much scarcer or undetectable. Cytosolic androgen receptors in isolated apocrine glands were also measured using 3H-R1881 as a ligand. Typical androgen receptors were present in all of eight patients (KD = 1.32 +/- 0.24 X 10(-9)M, Bmax = 10.3 +/- 0.51 fmol/mg protein). Neither the intranuclear androgen concentrations nor the cytosolic androgen receptor levels were significantly different between the two sexes. These data indicate clearly that the apocrine gland of patients with osmidrosis is a typical androgen target organ, irrespective of sex, and suggest that nuclear DHT in the axillary skin of women is derived from not only testosterone but also other precursors, especially in consideration of the very low serum concentrations of testosterone in females.