Eccrine ductal and acrosyringeal metaplasia in breast carcinomas: report of eight cases.

Eccrine ductal and acrosyringeal metaplasia was described in 2006 as the presence of tumor structures that resemble the epithelium of the eccrine skin ducts and their opening within the epidermis, the acrosyringeum. Here, we report the clinical, morphological, and phenotypic characteristics of eight breast carcinomas that we collected over the past years showing this metaplasia. Unlike squamous metaplasia, acrosyringeal and eccrine ductal metaplasia are luminated structures comprising cells with eosinophilic cytoplasm that are easily detectable in routine histological slides. These lesions invariably appeared in triple-negative carcinomas, but the cases differed in their clinical, radiological, and histological manifestations. Correct interpretation of these changes may facilitate identification of some metaplastic carcinomas.

Eccrine Sweat as a Biofluid for Profiling Immune Biomarkers.

PURPOSE: Sweat is a relatively unexplored biofluid for diagnosis and monitoring of disease states. In this study, the proteomic profiling of immune-related biomarkers from healthy individuals are presented. EXPERIMENTAL DESIGN: Eccrine sweat samples are collected from 50 healthy individuals. LC-MS/MS is performed on two pools of sweat samples from five male and female participants. Individual sweat samples are analyzed by antibody isotyping microarrays (n = 49), human cytokine arrays (n = 30), and quantitative ELISAs for interleukin-1α (n = 16), epidermal growth factor (n = 6), and angiogenin (n = 7). RESULTS: In sweat, 220 unique proteins are identified by shotgun analysis. Detectable antibody isotypes include IgA (100% positive; median 1230 ± 28 700 pg mL-1 ), IgD (18%; 22.0 ± 119 pg mL-1 ), IgG1 (96%; 1640 ± 6750 pg mL-1 ), IgG2 (37%; 292 ± 6810 pg mL-1 ), IgG3 (71%; 74.0 ± 119 pg mL-1 ), IgG4 (69%; 43.0 ± 42.0 pg mL-1 ), and IgM (41%; 69.0 ± 1630 pg mL-1 ). Of 42 cytokines, three are readily detected in all sweat samples (p < 0.01). The median concentration for interleukin-1α is 352 ± 521 pg mL-1 , epidermal growth factor is 86.5 ± 147 pg mL-1 , and angiogenin is 38.3 ± 96.3 pg mL-1 . Multiple other cytokines are detected at lower levels. CONCLUSIONS AND CLINICAL RELEVANCE: Sweat can be used for profiling antibodies and innate immune biomarkers.

The evolution of eccrine sweat glands in human and nonhuman primates.

Sweating is an unusual thermoregulatory strategy for most mammals, yet is critical for humans. This trait is commonly hypothesized to result from human ancestors moving from a forest to a warmer and drier open environment. As soft tissue traits do not typically fossilize, this idea has been difficult to test. Therefore, we used a comparative approach to examine 15 eccrine gland traits from 35 primate species. For each trait we measured phylogenetic signal, tested three evolutionary models to explain trait variation, and used phylogenetic models to examine how traits varied in response to climate variables. Phylogenetic signal in traits varied substantially, with the two traits exhibiting the highest values being gland distribution on the body and percent eccrine vs. apocrine glands on the body. Variation in most traits was best explained by an Ornstein-Uhlenbeck model suggesting the importance of natural selection. Two traits were strongly predicted by climate. First, species with high eccrine gland glycogen content were associated with habitats exhibiting warm temperatures and low rainfall. Second, species with increased capillarization were associated with high temperature. Glycogen is a primary energy substrate powering sweat production and sodium reabsorption in the eccrine gland, and increased capillarization permits greater oxygen, glucose and electrolyte delivery. Thus, our results are evidence of natural selection for increased sweating capacity in primate species with body surface eccrine glands living in hot and dry climates. We suggest that selection for increased glycogen content and capillarization may have been part of initial increases in hominin thermoregulatory sweating capacity.

Expression of S100A2 and S100P in human eccrine sweat glands and their application in differentiating secretory coil-like from duct-like structures in the 3D reconstituted eccrine sweat spheroids.

Secretory coils and ducts are two components of eccrine sweat glands with different structures and functions. In our previous study, we combined keratins and α-SMA to distinguish between secretory coils and ducts. However, the key deficiency of the method was that none of the antibodies used was specific for ducts. In this study, we first examined the co-localization of K5/K7, α-SMA/K14, K7/S100P and α-SMA/S100A2 by double-immunofluorescence staining to confirm the localization of S100P and S100A2 in native human eccrine sweat glands, and second we identified secretory coil-like and duct-like structures in the 3D reconstituted eccrine sweat gland spheroids by double-immunofluorescence staining for K7/S100P and α-SMA/S100A2. In native human eccrine sweat glands, S100A2 immunoreactivity was confined to the outer layer and S100P to the inner layer of the duct. In 12-week Matrigel plugs containing eccrine sweat gland cells, double-immunofluorescence staining for K7/S100P and α-SMA/S100A2 could easily distinguish duct-like structures from secretory coil-like structures. We conclude that S100A2 and S100P can be used as specific duct markers in eccrine sweat glands, and combined use of S100P or S100A2 with keratins enables easy to distinction between secretory coils and ducts.

Identification of a new sweat gland progenitor population in mice and the role of their niche in tissue development.

Sweat gland cells are responsible for the regulation of body temperature and are critical for wound repair. Furthermore, they have the regenerative potential in response to injury, and show a substantial turnover during both wound healing and homeostasis. However, as a usual research model of sweat gland, mice have not too much glandular cells for experiments. In this study, we identify previously unreported sweat gland progenitor population in mice and characterize them. The progenitor characteristics of sweat gland were confirmed using cellular immunofluorescence assay and quantitative real-time PCR assay. K8 and K18 expression was barely detected in the early stage of skin development (Embryo 17.5d) and increased to a high level at P5d (postnatal 5d), then showed reduction at adult stage (P28d). Further investigation of K8 and K18 positive cells using tissue immunofluorescence revealed the presence of sweat gland progenitors in back epidermis of mice at early stage of sweat gland development and continuous reduction during the developmental process. In vivo transplantation assay with animal models elucidated that sweat gland specific niche in paw pads was critical for the development of sweat gland cells. Although the relationship between new sweat gland progenitors and their niche still needs to be further investigated, the presence of these cells implicates that there is more source ascribed to sweat glands in addition to serving as progenitors in mice.

[Eccrine angiomatous hamartoma: a clinicalopathologic analysis of 4 cases].

OBJECTIVE: To investigate the clinical and histopathologic features, diagnosis and differential diagnosis of eccrine angiomatous hamartoma(EAH). METHODS: Four cases of eccrine angiomatous hamartoma were studied by light microscopy and immunohistochemical staining along with review of the literature. RESULTS: There were 3 male and 1 female patients at diagnosis in age of 4 months, 3.5 years, 5.5 years and 14.0 years, respectively. Tumor sites included the left little finger (1 case), right index finger (1 case), lower back (1 case) and knee (1 case). Clinically, most cases presented as a solitary, flesh or reddish papule, plaque or nodule with size of 0.4-6.0 cm in diameter. The skin lesions in 3 cases enlarged commensurate with the growth of the patients, and local hyperhidrosis in one case. Histologically, EAH was characterized by proliferation of well-differentiated eccrine secretory and ductal elements closely associated with thin-walled angiomatous channels in the middle or deep dermis and subcutaneous tissue. By immunohistochemistry, the vascular components were positive for CD31, CD34 and factor Ⅷ related antigen while the eccrine glands were positive for S-100 protein, CEA, EMA, CAM5.2 and GCDFP15. Local surgical resection was performed in 4 cases and follow-up data (0.5 to 4.5 years) showed no recurrence. CONCLUSION: EAH is a rare, benign cutaneous hamartoma. Combination of clinical manifestations, histological changes and immunohistochemical findings is useful for the diagnosis and differential diagnosis.

Autofluorescence of eccrine sweat glands.

BACKGROUND/PURPOSE: The monitoring of autofluorescence in skin tissue samples can have diagnostic and therapy significance. In this study, we are the first to describe autofluorescence of eccrine sweat glands, which is important and helpful for the diagnosis and therapy of diseases that involve the eccrine sweat glands. METHODS: Eccrine sweat gland autofluorescence in haematoxylin-eosin (HE) stained skin tissue sections was observed under a fluorescence microscope, which was compared to the immunofluorescence of keratin 19 and 15 in the skin tissue sections. The single eccrine sweat glands from five volunteers including three males and two females were isolated and also observed under a fluorescence microscope. The autofluorescence intensity of the single eccrine sweat gland was measured using a laser confocal scanning microscope system. RESULTS: Eccrine sweat gland autofluorescence in HE stained skin tissue sections appears green under GFP fliter system (470/40 nm) and red under N2.1 fliter system (515-560 nm). Furthermore, the single eccrine sweat gland showed various autofluorescence colours, including green under wide blue and red under wide green. The autofluorescence intensity of the single eccrine sweat gland was measured. The spectrum excited at 488 nm exhibited two peaks located at approximately 530 nm (11.54 ± 4.66) and 590 nm (10.38 ± 4.33). The results suggest flavin and lipopigment as the endogenous fluorophores. CONCLUSION: The autofluorescence of the HE stained eccrine sweat gland sections is simple and helpful for easily determining the structure of eccrine sweat glands. The autofluorescence of the single eccrine sweat gland may be due to the existence of flavin and lipopigment.

Preferential expression of OVOL1 in inner root sheath of hair, sebaceous gland, eccrine duct and their neoplasms in human skin.

OVOL1 is an important transcription factor for epidermal keratinization, which suppresses proliferation and switches on the differentiation of keratinocytes. A recent genome-wide association study has revealed that OVOL1 is one of the genes associated with susceptibility to atopic dermatitis. Although it is known to be expressed in murine skin and hair follicles, no investigations have focused on its localization in human skin. In the present study, we thus immunolocalized the expression of OVOL1 in normal and diseased human skin. In normal human skin, OVOL1 was preferentially expressed in the suprabasal layer of the epidermis, inner root sheath of hair, mature sebocytes and the ductal portion of the eccrine glands. Compared to this, no remarkable change in the expression of OVOL1 was observed among inflammatory skin diseases. The expression of OVOL1 was evident in eccrine poroma and hidradenoma. Moreover, it was overexpressed in Bowen's disease and sebaceous adenoma, in sharp contrast to its downregulation in their more malignant counterparts, squamous cell carcinoma and sebaceous carcinoma. OVOL1 may play an important role in human skin morphogenesis and tumorigenesis.

Cutaneous ciliated cyst of the scalp: a case report of a cutaneous ciliated eccrine cyst and a brief review of the literature.

Cutaneous ciliated cysts (CCC) are rare benign cysts known to occur in the lower extremities of females of reproductive age. Currently, there are 2 theories that attempt to explain the histogenesis of this rare entity. The theory of Mullerian heterotopia provides a plausible histogenetic explanation for the vast majority of CCC. A proposed alternative theory is the ciliated metaplasia of eccrine glands. We believe that previously reported cases of CCC include 2 distinct entities. We report, herein, the first case reported in the literature of a cutaneous ciliated eccrine cyst occurring on the scalp.

Markers of epidermal stem cell subpopulations in adult mammalian skin.

The epidermis is the outermost layer of mammalian skin and comprises a multilayered epithelium, the interfollicular epidermis, with associated hair follicles, sebaceous glands, and eccrine sweat glands. As in other epithelia, adult stem cells within the epidermis maintain tissue homeostasis and contribute to repair of tissue damage. The bulge of hair follicles, where DNA-label-retaining cells reside, was traditionally regarded as the sole epidermal stem cell compartment. However, in recent years multiple stem cell populations have been identified. In this review, we discuss the different stem cell compartments of adult murine and human epidermis, the markers that they express, and the assays that are used to characterize epidermal stem cell properties.

5α-Androst-16-en-3α-ol ß-D-glucuronide, precursor of 5α-androst-16-en-3α-ol in human sweat.

5α-Androst-16-en-3α-ol (α-androstenol) is an important contributor to human axilla sweat odor. It is assumed that α-andostenol is excreted from the apocrine glands via a H2 O-soluble conjugate, and this precursor was formally characterized in this study for the first time in human sweat. The possible H2 O-soluble precursors, sulfate and glucuronide derivatives, were synthesized as analytical standards, i.e., α-androstenol, ß-androstenol sulfates, 5α-androsta-5,16-dien-3ß-ol (ß-androstadienol) sulfate, α-androstenol ß-glucuronide, α-androstenol α-glucuronide, ß-androstadienol ß-glucuronide, and α-androstenol ß-glucuronide furanose. The occurrence of α-androstenol ß-glucuronide was established by ultra performance liquid chromatography (UPLC)/MS (heated electrospray ionization (HESI)) in negative-ion mode in pooled human sweat, containing eccrine and apocrine secretions and collected from 25 female and 24 male underarms. Its concentration was of 79 ng/ml in female secretions and 241 ng/ml in male secretions. The release of α-androstenol was observed after incubation of the sterile human sweat or α-androstenol ß-glucuronide with a commercial glucuronidase enzyme, the urine-isolated bacteria Streptococcus agalactiae, and the skin bacteria Staphylococcus warneri DSM 20316, Staphylococcus haemolyticus DSM 20263, and Propionibacterium acnes ATCC 6919, reported to have ß-glucuronidase activities. We demonstrated that if α- and ß-androstenols and androstadienol sulfates were present in human sweat, their concentrations would be too low to be considered as potential precursors of malodors; therefore, the H2 O-soluble precursor of α-androstenol in apocrine secretion should be a ß-glucuronide.

Eccrine angiomatous hamartoma is a lymphatic proliferation.

BACKGROUND: Eccrine angiomatous hamartoma (EAH) is recognized as a vascular hamartoma composed of abnormal proliferation of blood vessels and eccrine glands. OBJECTIVE: We sought to investigate the immunohistochemical results of D2-40 and Prox1 in EAH in order to gain further insight into its histogenesis. MATERIALS AND METHODS: We collected 21 cases of EAH diagnosed in a dermatology department. Immunohistochemical staining of D2-40 and Prox1 was performed on all cases. RESULTS: Prox1 was universally positive in the endothelial cells of proliferated vessels in all cases. D2-40 was universally positive in the endothelial cells of proliferated vessels in 3 cases, focally positive in 18 cases. CONCLUSION: EAH is a lymphatic proliferation and therefore we suggest the name of eccrine lymphangiomatous hamartoma.

Immunohistochemical sweat gland profiles.

BACKGROUND: Human sweat glands are heterogeneous in their structures and functions. Accordingly, eccrine, apocrine, and apoeccrine glands are distinguished. AIMS: Some immunohistochemical markers are expected to distinguish the sweat gland types in their secretory and excretory parts. METHODS: This study used two sets of antibodies. The first panel was composed of antibodies directed to well-defined sweat gland structures. The molecular targets included the low-molecular-weight cytokeratins CAM 5.2, the S100-B protein, the epithelial membrane antigen (EMA), the carcinoembryonic antigen (CEA), and the lectin Ulex europaeus agglutinin-1 (UEA-1). A second exploratory panel of antibodies targeted syndecan-1 (CD138), NKI-C3 (CD63), and CD68. They were used to disclose some undescribed antigen expressions in human sweat glands. RESULTS: The first set of antibodies confirmed previous findings. The immunoreactivities of the three sweat gland types were similar in the excretory ducts. By contrast, they were distinguished in the deeper coiled secretory portions of the glands. CONCLUSION: Clues supporting their distinction and probably their functional activity were obtained by immunohistochemistry using the S100-B protein, CEA and CD63 antibodies. The immunoreactivity to the S100-B protein, CEA and CD63 possibly help identifying apoeccrine sweat glands or a peculiar functional activity of eccrine sweat glands.

Three-dimensional culture and identification of human eccrine sweat glands in matrigel basement membrane matrix.

Interactions between the extracellular matrix (ECM) and epithelial cells are necessary for the proper organization and function of the epithelium. In the present study, we show that human eccrine sweat gland epithelial cells cultured in matrigel, a representation of ECM components, constitute a good model for studying three-dimensional reconstruction, wound repair and regeneration and differentiation of the human eccrine sweat gland. In matrigel, epithelial cells from the human eccrine sweat gland form tubular-like structures and then the tubular-like structures coil into sphere-like shapes that structurally resemble human eccrine sweat glands in vivo. One sphere-like shape can be linked to another sphere-like shape or to a cell monolayer via tubular-like structures. Hematoxylin and eosin staining has revealed that the tubular-like structures have a single layer or stratified epithelial cells located peripherally and a lumen at the center, similar to the secretory part or duct part, respectively, of the eccrine sweat gland in sections of skin tissue. Immunohistochemical analysis of the cultures has demonstrated that the cells express CK7, CK19, epithelial membrane antigen and actin. Thus, matrigel promotes the organization and differentiation of epithelial cells from the human eccrine sweat gland into eccrine sweat gland tissues.

Microbiological and biochemical origins of human axillary odour.

The generation of malodour on various sites of the human body is caused by the microbial biotransformation of odourless natural secretions into volatile odorous molecules. On the skin surface, distinctive odours emanate, in particular, from the underarm (axilla), where a large and permanent population of microorganisms thrives on secretions from the eccrine, apocrine and sebaceous glands. Traditional culture-based microbiological studies inform us that this resident microbiota consists mainly of Gram-positive bacteria of the genera Staphylococcus, Micrococcus, Corynebacterium and Propionibacterium. Among the molecular classes that have been implicated in axillary malodour are short- and medium-chain volatile fatty acids, 16-androstene steroids and, most recently, thioalcohols. Most of the available evidence suggests that members of the Corynebacterium genus are the primary causal agents of axillary odour, with the key malodour substrates believed to originate from the apocrine gland. In this article, we examine, in detail, the microbiology and biochemistry of malodour formation on axillary skin, focussing on precursor-product relationships, odour-forming enzymes and metabolic pathways and causal organisms. As well as reviewing the literature, some relevant new data are presented and considered alongside that already available in the public domain to reach an informed view on the current state-of-the-art, as well as future perspectives.

Cytochemistry of sialoglycoconjugates, lysozyme, and ß-defensin in eccrine glands of porcine snout skin as studied by electron microscopy.

In most mammals except for humanoid primates, eccrine glands are confined to the skin of a series of specific body regions. Sialic acids and antimicrobial substances exhibit various functional properties and serve as a component of nonspecific defense against micro-organisms, respectively. In this study, the distribution of these moieties was studied by electron microscopic histochemical methods. The eccrine glandular acini consisted of two types of dark cells as well as clear cells. The secretory granules and Golgi apparatus of both types of dark cells contained sialic acid residues linked to α2-6Gal/GalNAc. On the other hand, sialoglycoconjugates with Siα2-3Galß1-4GlcNAc sequence were confined to those of the Type II dark cells. In addition, lysozyme and ß-defensin were mainly detected in the secretory granules of the Type II dark cells. These secretory products may create a defensive barrier against microbial invasion and play an essential role in preservation of the integrity of porcine snout skin as a sensory organ.

Immunohistochemical study of calretinin in normal skin and cutaneous adnexal proliferations.

Calretinin is a calcium-binding protein member of the EF-hand family. The presence of calretinin has been demonstrated in certain stages of the cellular cycle in a wide variety of normal and neoplastic tissues. The main aims of our study were (1) to investigate what structures of the normal skin and cutaneous adnexal proliferations express immunoreactivity for calretinin and (2) to determine the value of immunohistochemical expression for calretinin as a marker for follicular, sebaceous, apocrine, and eccrine differentiation in cutaneous adnexal proliferations. We studied 139 biopsy specimens, including 10 cases of normal skin of different locations and 129 benign and malignant cutaneous adnexal proliferations. In normal skin, we found that calretinin is expressed in the innermost cell layer of the outer root sheath in anagen hair follicle, in both the duct and sebolemma of the sebaceous gland, in the secretory portion of eccrine glands, and in mast cells of the stroma. In cutaneous adnexal proliferations, we found strong immunoreactivity for calretinin in tricholemmal cysts, tricholemmomas/inverted follicular keratoses, tumors of follicular infundibulum, and in some basal cell carcinomas. Focal positivity was also seen in trichoadenomas, trichoblastomas/trichoepitheliomas, pilomatricomas, proliferating tricholemmal tumors, pilar sheath acanthomas, trichofolliculomas, follicular hybrid cysts, cutaneous mixed tumors, steatocystomas, sebaceous hyperplasias, and sebaceomas. These results demonstrate that immunohistochemical study for calretinin may be helpful to identify the innermost cell layer of the outer root sheath in anagen hair follicle and the cutaneous adnexal proliferations showing differentiation toward this structure. Calretinin immunoreactivity supports eccrine differentiation in some sweat gland neoplasms, and it is also useful in identifying neoplasms with ductal sebaceous differentiation.