Primary apocrine carcinoma of an unusual site.

Primary apocrine carcinoma is a rare malignancy most commonly occurring in apocrine dense areas like axilla. There are only about 200 cases reported to date. We report a case of primary apocrine carcinoma present at an unusual site, that is, the arm. A wide local excision of the mass was done and was diagnosed as apocrine carcinoma on histopathological examination and was confirmed by immunohistochemistry. Wide local excision is the treatment required.

Diferencia en la población de células cebadas de glándulas apocrinas de sacos anales de perros adultos y seniles / Difference in the population of mast cells of anal sac apocrine glands of adult and senile dogs

Se estudió la población de células cebadas (CC) presentes en sacos anales de perros adultos y seniles mediante su conteo en cortes de tejido procesado con la técnica de inclusión en parafina y teñidos con azul de toluidina. El promedio de CC obtenido para el grupo de perros adultos jóvenes fue de 18,16 +/- 7,58 (n=12 perros) y para el grupos de adultos maduros fue de 73,75 +/- 16,29 (n=12 perros). Al comparar el número de células de ambos grupos con la prueba de U Mann-Withney se encontró que son significativamente diferentes (P< 0,0001), siendo mayor en el grupo de perros seniles. Esta mayor población de CC puede estar relacionada con una mayor susceptibilidad de los perros seniles a reacciones inflamatorias del tejido de los sacos anales causadas por cambios en la dieta, obesidad y diarrea crónica.

We studied the population of mast cells (CC) present in anal sacs of adult and senile dogs by its count in tissue processed with the technique of embedding in paraffin and stained with toluidine blue. The average CC obtained for the group of adult dogs (n=12) was 18.16 +/- 7.58 and for group of senile dogs (n=12) was 73.75 +/- 16.29. When comparing the number of cells in both groups with Mann-Whitney U test were found to be significantly different (P0.0001), being higher in the group of senile dogs. The largest population of CC may be related to an increased susceptibility of senile dogs to inflammatory reactions in the tissue of the anal sacs caused by changes in diet, obesity and chronic diarrhea.

The secretory clear cell of the eccrine sweat gland as the probable source of excess sweat production in hyperhidrosis.

Primary hyperhidrosis is characterized by excessive sweating in palmar, plantar and axillary body regions. Gland hypertrophy and the existence of a third type of sweat gland, the apoeccrine gland, with high fluid transporting capabilities have been suggested as possible causes. This study investigated whether sweat glands were hypertrophied in axillary hyperhidrotic patients and if mechanisms associated with fluid transport were found in all types of axillary sweat glands. The occurrence of apoeccrine sweat glands was also investigated. Axillary skin biopsies from control and hyperhidrosis patients were examined using immunohistochemistry, image analysis and immunofluorescence microscopy. Results showed that glands were not hypertrophied and that only the clear cells in the eccrine glands expressed proteins associated with fluid transport. There was no evidence of the presence of apoeccrine glands in the tissues investigated. Preliminary findings suggest the eccrine gland secretory clear cell as the main source of fluid transport in hyperhidrosis.

Differentiation of papillae and rostral sensory neurons in the larva of the ascidian Botryllus schlosseri (Tunicata).

During the metamorphosis of tunicate ascidians, the swimming larva uses its three anterior papillae to detect the substrate for settlement, reabsorbs its chordate-like tail, and becomes a sessile oozooid. In view of the crucial role played by the anterior structures and their nerve relations, we applied electron microscopy and immunocytochemistry to study the larva of the colonial ascidian Botryllus schlosseri, following differentiation of the anterior epidermis during late embryogenesis, the larval stage, and the onset of metamorphosis. Rudiments of the papillae appear in the early tail-bud stage as ectodermic protrusions, the apexes of which differentiate into central and peripheral bipolar neurons. Axons fasciculate into two nerves direct to the brain. Distally, the long, rod-like dendritic terminations extend during the larval stage, becoming exposed to sea water. After the larva selects and adheres to the substrate, these neurons retract and regress. Adjacent to the papillae, other scattered neurons insinuate dendrites into the tunic and form the net of rostral trunk epidermal neurons (RTENs) which fasciculate together with the papillary neurons. Our data indicate that the papillae are simple and coniform, the papillary neurons are mechanoreceptors, and the RTENs are chemoreceptors. The interpapillary epidermal area, by means of an apocrine secretion, provides sticky material for temporary adhesion of the larva to the substrate.

Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type?

One single-nucleotide polymorphism (SNP), 538G>A (Gly180Arg), in the ABCC11 gene determines the type of earwax. The G/G and G/A genotypes correspond to the wet type of earwax, whereas A/A corresponds to the dry type. Wide ethnic differences exist in the frequencies of those alleles, reflecting global migratory waves of the ancestors of humankind. We herein provide the evidence that this genetic polymorphism has an effect on the N-linked glycosylation of ABCC11, intracellular sorting, and proteasomal degradation of the variant protein. Immunohistochemical studies with cerumen gland-containing tissue specimens revealed that the ABCC11 WT protein was localized in intracellular granules and large vacuoles, as well as at the luminal membrane of secretory cells in the cerumen gland, whereas granular or vacuolar localization was not detected for the SNP (Arg180) variant. This SNP variant lacking N-linked glycosylation is recognized as a misfolded protein in the endoplasmic reticulum and readily undergoes ubiquitination and proteasomal degradation, which determines the dry type of earwax as a mendelian trait with a recessive phenotype. For rapid genetic diagnosis of axillary osmidrosis and potential risk of breast cancer, we developed specific primers for the SmartAmp method that enabled us to clinically genotype the ABCC11 gene within 30 min.

The localization of PMCA1b in epithelial cells and aposomes of the rat coagulating gland is influenced by androgens.

BACKGROUND: Rat coagulating gland epithelial cells export proteins by an apocrine secretion mode within membrane blebs arising from the apical plasma membrane. Using a pan-PMCA antibody, we have recently shown the plasma membrane Ca(2+)-ATPase (PMCA) being part of the apical plasma membrane of epithelial cells and incorporated into the aposomal membrane. The mRNA of PMCA isoforms 1 and 4 respectively, have been detected by RT-PCR in rat coagulating gland. METHODS: In order to identify which PMCA isoform is integrated into aposomes during apocrine secretion and whether or not PMCA export is influenced by androgens RT-PCR, in situ hybridization, Western blotting, and immunofluorescence experiments were performed. RESULTS: PMCA1b is the isoform which is expressed and located in the apical plasma membrane of coagulating gland epithelial cells and is integrated into the aposomal membrane. In contrast, PMCA4 mRNA and protein are restricted to the stroma. Androgen deprivation by castration within 14 days leads to an accumulation of PMCA1b in coagulating gland epithelium, while aposomes are not detected anymore. CONCLUSIONS: We showed for the first time that PMCA isoform 1b is released via aposomes of the epithelial cells of the rat coagulating gland and that the localization of PMCA1b in the epithelial cells is influenced by androgens.

Immunolocalization of defensins and cathelicidin in human glands of Moll.

The human gland of Moll located at the margin of the eyelids is a specialized apocrine gland, the function of which is not exactly known. The presence of antimicrobial proteins was identified in this gland recently, suggesting a function in the external ocular defense barrier against pathogens. In this study, we have demonstrated beta-defensin-1, beta-defensin-2 and cathelicidin (LL-37) in the secretory endpieces of the glands of Moll using immunohistochemical methods. beta-Defensin-1, beta-defensin-2 and cathelicidin (LL-37) showed a weak to moderately intensive staining pattern. The strongest immunolocalization of beta-defensin-1 was observed in the apical protrusions of the gland, which could also be observed but to a lesser extent in the case of beta-defensin-2 and cathelicidin. In active glandular cells, a granular staining pattern could be observed. beta-Defensin-1 and beta-defensin-2 varied in staining intensities, and even within one section strongly and weakly stained cells can coexist side by side. Also cells that, according to morphological criteria, appeared to be inactive still had an apical beta-defensin-1 immunolabeling. We assume that beta-defensin-1, beta-defensin-2 and cathelicidin (LL-37) work together with other antimicrobial peptides and proteins to create a defensive barrier against microbial invasion at the ocular surface.

Use of quantitative analysis as a method for differentiation between canine cutaneous apocrine adenomas and apocrine carcinomas on cytological smears.

Eight canine cutaneous adenomas and eight canine cutaneous carcinomas were analysed by computer-assisted nuclear morphometry in Hemacolor-stained cytological specimens. In each case, the nuclei of at least 100 neoplastic cells were measured, and the mean nuclear area (MNA), mean nuclear perimeter (MNP), mean nuclear diameter (MND) and nuclear roundness (NR) were calculated. The results indicated an increase in the mean values of investigated parameters from canine cutaneous apocrine adenomas (MNA, 75.65+/-2.22; MNP, 31.05+/-0.55; MND, 9.62+/-0.14; NR, 1.10+/-0.009) to canine cutaneous apocrine carcinomas (MNA, 88.78+/-11.29; MNP, 34.38+/-2.43; MND, 10.43+/-0.76; NR, 1.21+/-0.07). The statistical analysis revealed statistically significant differences between benign and malignant neoplastic cells (P<0.01). The statistical differences between investigated parameters (P<0.01) were also found between the metastasizing apocrine carcinomas and all other examined carcinomas. The results indicated that the computerized morphometry could be used as an effective auxiliary tool for differential diagnosis between canine cutaneous adenomas and carcinomas on cytological smears.

The enigmatic nature of apocrine breast lesions.

Epithelial cells of fetal breast glandular structures, at the third trimester of pregnancy (28 weeks), produce GCDFP-15, in the absence of specific apocrine morphology. Apocrine epithelium of the breast may be a normal process of differentiation rather than a result of metaplasia, and it has been demonstrated that it is estrogen-receptor, progesterone-receptor and bcl-2 negative, but androgen-receptor (AR) positive. The significance of AR expression in apocrine epithelium is uncertain. Apocrine epithelium is seen in a wide spectrum of breast entities, ranging from benign lesions to invasive carcinoma. Breast cancer accounts 32% of all cancer cases among women and is the most common type of cancer in women. Little is known about breast carcinogenesis. Widely, it is accepted that breast cancer, like most other type of cancer, is being developed through the accumulation of genetic aberrations. Apocrine epithelium may reflect instability of the breast epithelium, creating an environment favouring further oncogenic alterations. In the last decade, several lines of evidence support the idea that some breast benign epithelial apocrine lesions are clonal lesions and may be considered as truly pre-malignant or precursors of breast carcinoma. Apocrine changes in many cases do not present any diagnostic difficulty; on the other hand, apocrine proliferations with cytologic atypia can be particularly difficult and challenging. The purpose of this study is to collect and highlight the areas of consensus in the literature as well as the controversial areas concerning the apocrine epithelium of the breast.

Disulphide reaction staining for the identification of integumental elastic fibres.

Based on specific methods (Sippel-APM-chromotropic acid technique; IC3-PE-maleimide fluorescence reaction) and skin samples of four domesticated mammals (dog, cattle, horse, pig), disulphide groups were demonstrated in the elastic component of the basement membrane of the epidermis, the elastic fibre system of the dermis, the elastic components of the connective tissue sheath of hair follicles, apocrine tubular glands, and sebaceous glands, and of the connective tissue surrounding the cutaneous muscle. The results are discussed regarding the relation of this reaction staining to the presence of microfibrils (fibrillin) in the elastic fibres.

Aspects of glycoconjugate production and lysozyme- and defensins-expression of the ceruminous glands of the horse (Equus przewalskii f. dom.).

The distribution of complex glycoconjugates and antimicrobial substances in the ceruminous glands of the horse (Equus przewalskii f. dom., type: pony) was studied using carbohydrate histochemical and immunohistochemical methods. The epithelial cells and luminal secretion of these glands exhibited considerable amounts of glycoconjugates with various saccharide residues, such as alpha-D-mannose, alpha-L-fucose, beta-D-galactose, beta-N-acetyl-D-glucosamine and sialic acid, including O-acetylated sialic acid. Several sugars (alpha-D-mannose, alpha-L-fucose, and beta-D-galactose) were also detectable in the secretion of sebaceous glands present. Additionally, lysozyme and the peptide group of beta-defensins are demonstrated as products of the apocrine ceruminous glands and sebaceous glands. The results obtained are discussed with regard to the functional significance of the glandular secretions. It is suggested that the complex carbohydrates, lysozyme and beta-defensins found in the ceruminous gland secretions are involved in the function of cerumen as a general antimicrobial protective agent in the external auditory canal.

Chondroid syringoma. Cytokeratin 20 immunolocalization of Merkel cells and reappraisal of apocrine folliculo-sebaceous differentiation.

CONTEXT: Chondroid syringoma (CS) is a benign cutaneous adnexal tumor with epithelial and stromal components. Epithelial components derived from folliculo-sebaceous-apocrine germ are evident in apocrine but not in eccrine CS. OBJECTIVES: To further characterize pilosebaceous differentiation and to identify the presence of Merkel cells in the areas of follicular differentiation. DESIGN: Histologic type, folliculo-sebaceous differentiation, character of stroma, and presence or absence of Merkel cells by cytokeratin (CK) 20 immunoreactivity were evaluated in 25 CSs (22 apocrine and 3 eccrine) from the surgical pathology files of Henry Ford Hospital (Detroit, Mich). RESULTS: Most CSs occurred in the head and neck region of patients aged 40 years or older. We found no significant difference in sex, age, or location between apocrine and eccrine types. The stroma varied from myxoid (100%) to chondroid (59%), with various amounts of fat (59%) and ossification identified in 2 cases (9%) of apocrine type, but was homogeneously myxoid in the eccrine type. Follicular and sebaceous differentiation was found in 64% and 32% of apocrine CSs, respectively. Only 2 (14%) apocrine CSs with follicular differentiation were positive for CK20 (a few scattered cells in one case and numerous grouped cells in the other in association with follicular epithelium). No correlation was found between type of stroma and the presence of Merkel cells. Scattered Merkel cells were identified in 83% of normal hair follicles and in 33.3% of normal epidermis. CONCLUSION: A high proportion of apocrine CSs show folliculo-sebaceous differentiation. The presence of Merkel cells in foci of follicular differentiation of CS supports the hypothesis that Merkel cells may be an integral constituent of follicles. To our knowledge, the presence of Merkel cells in CS, particularly in proliferative form, has not been described previously in the literature.

Histochemical analysis of glycoconjugates in the ceruminous glands of the North American raccoon (Procyon lotor).

The distribution and selectivities of glycoconjugates in the ceruminous glands of the North American raccoon (Procyon lotor) were studied by light and electron microscopic histochemical methods, particularly lectin histochemistry. In the modified apocrine glands present, the apocrine secretion mode was combined with exocytosis, whereby the secretory epithelium and the luminal secretion of the ceruminous glands exhibited considerable amounts of complex carbohydrates with various terminal sugars (alpha-D-mannose, beta-D-galactose, alpha-L-fucose, alpha-N-acetyl-galactosamine, beta-N-acetyl-D-glucosamine, N-acetyl-neuraminic acid). Alpha-L-fucose and N-acetyl-neuraminic acid were distinctly prominent in secretory granules or within the free surface coat of the plasma membrane of the glandular cells, as well as in the luminal secretion. Several free sugars (alpha-D-mannose, alpha-L-fucose, beta-D-galactose, beta-N-acetyl-D-glucosamine) were also detectable in the secretion of associated sebaceous glands. The ceruminous gland secretion may control viscoelasticity and/or bacterial degradation of the glandular secretion mixture to improve the protection of the external auditory canal against physical damage or microbial contamination.

Apocrine secretory mechanism: recent findings and unresolved problems.

Cell secretion is an important physiological process that ensures smooth metabolic activities, tissue repair and growth and immunological functions in the body. It occurs when the intracellular secretory materials are released to the exterior; these may be in the form of lipids, protein or mucous and may travel through a duct system or via blood to reach the target organ. To date three types of secretory mechanisms have been characterized, they include apocrine, holocrine and exocytosis. Apocrine secretion occurs when the release of secretory materials is accompanied with loss of part of cytoplasm. The secretory materials may be contained in the secretory vesicles or dissolved in the cytoplasm that is lost during secretion. In holocrine secretion, the entire cell is secreted into the glandular lumen, and it is presumed that the intended secretory materials are contained in the cell cytoplasm. Exocytosis is the most commonly occurring type of secretion; here the secretory materials are contained in the secretory vesicles and released without loss of cytoplasm. Apocrine secretory mechanisms have not been properly discussed; for example the biochemical and physiological pathways that regulate apocrine secretory process are not clearly known. Similarly, the plasma membrane dynamics during apocrine secretion has not been researched. In other glands morphological features during apocrine secretion have not been documented. The current paper reviews what is known about apocrine secretion, recent findings and highlights on the unresolved areas for future research.

Cytology of subcutaneous glandular tissues.

This article deals with the cytologic appearance of various glandular tissues located in the subcutaneous tissues. Normal cytologic features are described. In addition, inflammatory, infectious, neoplastic, and hyperplastic changes are discussed. Most of these features are depicted in the 60+ photomicrographs that are distributed throughout the article. Many of the changes are similar in the glands, and it is usually possible to differentiate the gland of origin based on cytologic appearances. Subcutaneous neoplasms that are not associated with a subcutaneous gland, and lymph node cytology are not covered in this article but are addressed elsewhere.

Peroxisomes in the apocrine sweat glands of the human axilla and their putative role in pheromone production.

The products of the human apocrine axillary glands contain volatile steroids which act as pheromones. The steroidal structure of these pheromones implies that the axillary glands should be able to synthesize cholesterol which is the essential precursor of these molecules. Since important steps in cholesterol synthesis are localized within peroxisomes, we investigated the occurrence and the putative role of peroxisomes in the axillary glands at protein and mRNA levels by immunocytochemistry, Western blotting, and RT-PCR. Numerous peroxisomes were localized in the cells of the apocrine glands by immunocytochemistry, and the presence of catalase was confirmed by Western blotting and RT-PCR. Additionally, RT-PCR revealed the presence of mRNAs of two peroxisome-associated enzymes of the cholesterol biosynthetic pathway, mevalonate kinase and farnesyl diphosphate synthase. The results suggest that the peroxisomes in the human apocrine axillary glands may play a pivotal role in the biosynthesis of pheromones.

Enfermedad de Lafora / Lafora's disease

El diagnóstico de enfermedad de Lafora se basa en la sintomatología clínica y en la detección histológica de unas inclusiones intracitoplasmáticos PAS positivas denominadas cuerpos de Lafora. A pesar de que esta entidad no cursa con manifestaciones cutáneas, la participación del dermatólogo y del dermatopatólogo es importante, pues la biopsia de la piel axilar es el procedimiento diagnóstico más rentable. En esta localización los cuerpos de Lafora se detectan principalmente en las células periféricas ductales de los conductos ecrinos y en las células mioepiteliales de las glándulas apocrinas. Presentamos este hallazgo en una mujer de 17 años (AU)

Extramammary Paget disease is characterized by the consistent lack of estrogen and progesterone receptors but frequently expresses androgen receptor.

Extramammary Paget disease (EPD) is an uncommon cutaneous malignant neoplasm that arises in areas rich in apocrine glands (perineum, vulva, and axilla). Apocrine gland origin or apocrine differentiation of cells of EPD has been suggested. Estrongen, progesterone, and androgen hormone receptors have been reported to exhibit a characteristic pattern of expression in mammary apocrine type carcinomas; however, their expression in EPD has not been elucidated fully. By using immunohistochemical methods, we studied the expression of steroid receptors in EPD on formalin-fixed paraffin-embedded tissue samples from 28 patients with EPD without associated visceral malignant neoplasms or adnexal carcinoma. Androgen receptor (AR) was identified in 15 of 28 cases. The proportion of AR-positive cells varied from 1% to more than 75%; 8 cases expressed AR in more than 10% of cells. Strong AR expression also was seen in the invasive carcinoma arising from 1 case of EPD. All cases lacked immunohistochemically detectable estrogen and progesterone receptors. The immunophenotype characteristic of apocrine carcinomas (AR-positive, estrogen receptor-negative, progesterone receptor-negative) was seen in a substantial proportion of EPD cases. Results suggest that AR expression is a factor in pathogenesis of EPD. This may be important for the therapy of recurrent or invasive disease.

Fatty acid synthase is expressed mainly in adult hormone-sensitive cells or cells with high lipid metabolism and in proliferating fetal cells.

Animal fatty acid synthase (FAS) is a homodimer protein which synthesizes long-chain fatty acids and is rich in liver, brain, breast, and lung. However, the precise cellular localization of FAS in human tissues has not been elucidated. Immunohistochemistry with a new antibody to human FAS revealed that in adult human tissues FAS is distributed mainly in cells with high lipid metabolism (adipocytes, corpus luteum, hepatocytes, sebaceous glands, and Type II alveolar cells), in hormone-sensitive cells (anterior pituitary, apocrine gland, breast, endometrium, prostate, seminal vesicle, and adrenal cortex), and in a subset of epithelial cells of duodenum and stomach, colon absorptive cells, cerebral neurons, basket cells of cerebellum, decidua, uroepithelium, and epidymis. In fetal cells at 20 weeks of gestation, FAS was mainly present in proliferative epithelial cells of the digestive and respiratory systems, proximal renal tubules, adrenocortical cells, and mesenchymal and hematolymphoid cells. Staining was significant in nonproliferating cells, as observed in adult, and in sympathetic ganglion cells, Leidig cells of testis, and Langhans cells of chorionic villi. FAS is maintained in hormone-sensitive cells and/or cells active in lipid metabolism in the adult and is expressed in proliferating cells in the fetus, suggesting active fatty acid synthesis for energy utilization or membrane lipids.