Differential antigen expression between human eccrine sweat glands and hair follicles/pilosebaceous units.

Eccrine sweat glands and hair follicles are two primary skin appendages that serve different functions. Although the two appendages exhibit unique morphological patterns in adults, it is difficult to distinguish them morphologically in the early stages of development and regeneration. To research and compare the development, differentiation and regeneration between eccrine sweat glands and hair follicles/pilosebaceous units, specific antigen markers must be found first. Human skin samples were fixed, paraffin-embedded, and cut. The expression of K5, K7, K8, K14, K27, K31, K73, AE13, α-smooth muscle actin (α-SMA), epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Na+/K+-ATPase α and Na+-K+-2Cl cotransporter 1 (NKCC1) in eccrine sweat glands, hair follicles and sebaceous glands was detected by immunofluorescence staining. The results showed that eccrine sweat glands expressed K5, K7, K8, K14, K31, α-SMA, CEA, EMA, Na+/K+-ATPase α and NKCC1, but did not express K27, K73 or K31. Hair follicles expressed K5, K8, K14, K27, K31, K73, α-SMA and AE13, but did not express K7, CEA, Na+/K+-ATPase α or NKCC1. Sebaceous glands expressed K5, K14, K73, and EMA, but did not express K7, K8, K31, α-SMA, CEA, EMA, Na+/K+-ATPase α or NKCC1. We concluded that K7, CEA, Na+/K+-ATPase and NKCC1 can be used as specific markers for eccrine sweat glands, K27 and AE13 can be used as specific markers for hair follicles, and K73 can be used as a specific marker for pilosebaceous unit. These specific markers may contribute to differentiate between eccrine sweat glands and hair follicle/pilosebaceous units.

Lichen striatus with syringotropism and hyperplasia of eccrine gland cells: a rare phenomenon that should not be confused with syringotropic mycosis fungoides.

BACKGROUND: Syringotropism is characterized by lymphocyte infiltration in the eccrine gland and is usually associated with various degrees of hyperplasia of eccrine gland cells. This phenomenon has been reported in rare cases of mycosis fungoides, which are also called as syringotropic mycosis fungoides. METHODS: We studied seven cases of lichen striatus associated with syringotropism and hyperplasia of eccrine gland cells, diagnosed at our dermatology department in the past 5 years. The hematoxylin and eosin-stained slides from these cases were analyzed, and immunohistochemical and T-cell receptor gene rearrangement studies were performed. RESULTS: Of the seven cases, two showed prominent and five showed subtle syringotropism and hyperplasia of eccrine gland cells. Immunohistochemical study showed mixed infiltration by T-cells and B-cells around the eccrine glands. The T-cells were composed of CD4 and CD8-positive cells. T-cell receptor gene rearrangement study showed negative results in all the cases. CONCLUSION: Syringotropism and hyperplasia of eccrine gland cells is a rare phenomenon in lichen striatus. Dermatopathologists should be aware of this to avoid misdiagnosis as syringotropic mycosis fungoides.

Perniosis: clinical and histopathological analysis.

Perniosis are inflammatory cutaneous lesions, located on acral skin, which present in association with cold exposure. They can appear as an idiopathic dermatosis or with an underlying autoimmune disease. The use of cutaneous biopsy to distinguish between both types is controversial. We analyze the histological findings in 9 cases of idiopathic perniosis (IP) and compare them with those obtained from 11 cases of perniosis associated with an autoimmune disease (autoimmune perniosis). The most frequent histopathological features observed in cases of IP were a lymphocytic infiltrate with perivascular (8 cases, 89%) and perieccrine distribution (6 cases, 66%), dermal edema (5 cases, 55%), and necrotic keratinocytes (5 cases, 55%), whereas those found in perniosis associated with an autoimmune disease were lymphocytic infiltrate with perivascular distribution (11 cases, 100%) but without perieccrine distribution (3 cases, 27%), vacuolation of the basal layer (7 cases, 63%), and necrotic keratinocytes (5 cases, 45%). The only significant difference between both groups was the perieccrine distribution of the lymphocytic infiltrate in cases of IP, which, as mentioned in previous studies, could be considered a histopathological clue to differentiate both types of perniosis.

Eccrine porocarcinoma: a case with an obscure primary tumor diagnosed from lymph node metastasis.

Eccrine porocarcinoma (EPC), a rare malignant epidermal appendage tumor, is mainly seen in elderly patients. A long history is one of its main characteristics. Two types of EPC are known: juxtaepidermal and dermal. The juxtaepidermal type usually has a more aggressive behavior. Lymph node metastasis and high mitotic activity are associated with poor prognosis. A case of EPC with a long-standing but indolent primary site diagnosed from lymph node metastasis is presented here. There was also accompanying chronic dermatitis as a paraneoplastic syndrome. Diagnosing EPC prior to the regional lymph node involvement is the most valuable factor for a successful treatment. Persistent examinations and attempts to find the primary site(s) have to be made in such cases.

Expression of CD1d in human scalp skin and hair follicles: hair cycle related alterations.

BACKGROUND: CD1d belongs to a family of antigen presenting molecules that are structurally and distantly related to the classic major histocompatibility complex class I (MHC I) proteins. However, unlike MHC I molecules, which bind protein antigens, CD1d binds to lipid and glycolipid antigens. CD1d is expressed by cells of lymphoid and myeloid origin, and by cells outside of the lymphoid and myeloid lineages, such as human keratinocytes of psoriatic skin. AIMS: To investigate whether CD1d is also expressed in sun exposed skin and in the immuno-privileged anagen hair follicle. MATERIALS/METHODS: CD1d immunoreactivity was studied in human scalp skin and hair follicles of healthy women in situ by immunofluorescent and light microscopic immunohistology. Skin biopsies were obtained from normal human scalp containing mainly anagen VI hair follicles from women (age, 53-57 years) undergoing elective plastic surgery. RESULTS: CD1d showed strong immunostaining in human scalp skin epidermis, pilosebaceous units, and eccrine glands. In the epidermis, CD1d was strongly expressed by basal and granular keratinocytes. In hair follicles, CD1d was expressed in the epithelial compartment and showed hair cycle related alterations, with an increase in the anagen and a reduction in the catagen and telogen phases. CONCLUSIONS: These results suggest that CD1d plays a role in human scalp skin immunology and protection against lipid antigen rich infectious microbes. They also raise the question of whether keratinocytes of the immuno-privileged anagen hair follicle can present lipid antigens to natural killer T cells. These data could help provide new strategies for the manipulation of hair related disorders.

Structure and function of human sweat glands studied with histochemistry and cytochemistry.

The basic structure and the physiological function of human sweat glands were reviewed. Histochemical and cytochemical techniques greatly contributed the elucidation of the ionic mechanism of sweat secretion. X-ray microanalysis using freeze-dried cryosections clarified the level of Na, K, and Cl in each secretory cell of the human sweat gland. Enzyme cytochemistry, immunohistochemistry and autoradiography elucidated the localization of Na,K-ATPase. These data supported the idea that human eccrine sweat is produced by the model of N-K-2Cl cotransport. Cationic colloidal gold localizes anionic sites on histological sections. Human eccrine and apocrine sweat glands showed completely different localization and enzyme sensitivity of anionic sites studied with cationic gold. Human sweat glands have many immunohistochemical markers. Some of them are specific to apocrine sweat glands, although many of them stain both eccrine and apocrine sweat glands. Histochemical techniques, especially immunohistochemistry using a confocal laser scanning microscope and in situ hybridization, will further clarify the relationship of the structure and function in human sweat glands.

Chemotherapy-induced acral erythema: report of a case and immunohistochemical findings.

Chemotherapy-induced acral erythema (CAE) is an uncommon and distinct reaction seen in patients receiving high-dose chemotherapy. The exact pathogenic mechanisms of this disorder are still unknown. We report a 27-year-old woman who presented with red, swollen and painful macules on both palms, clinically consistent with this disease. Histological examination demonstrated vacuolar degeneration of the basal cell layer and spongiotic blisters in the epidermis, especially in the atrophied eccrine ducts and papillary oedema with mild perivascular infiltration of mononuclear and hypersegmented neutrophils. Immunohistochemistry showed that the infiltrating mononuclear cells were CD3-CD16+CD56+ leucocyte function antigen-1+, possibly natural killer cells. The eccrine ducts expressed HLA-DR and intracellular adhesion molecule-1 (ICAM-1). Our findings suggest that cell-to-cell interaction between NK cells and keratinocytes in the eccrine apparatus may induce CAE and may be involved in the pathogenesis of the skin reaction in our patient and possibly in this disease.

Staining of eccrine and apocrine neoplasms and metastatic adenocarcinoma with IKH-4, a monoclonal antibody specific for the eccrine gland.

The histogenesis of apocrine and eccrine neoplasms has always interested dermatopathologists. In addition, the histologic differential diagnosis of eccrine carcinoma from metastatic adenocarcinoma is of practical importance. We describe a novel monoclonal antibody IKH-4 which stains the eccrine secretory coil, but not the apocrine secretory segment. Positive staining was observed in eccrine hidradenoma, eccrine poroma, eccrine spiradenoma, papillary eccrine adenoma, eccrine hidrocystoma, syringoma, eccrine carcinoma, and in 1 case of syringocystadenoma papilliferum. Negative staining was observed in apocrine adenocarcinoma, hidradenoma papilliferum, erosive adenomatosis of the nipple, and primary and metastatic adenocarcinomas. IKH-4 antibody was useful in differentiating eccrine from apocrine neoplasms and in differentiating eccrine carcinoma from metastatic adenocarcinomas.

CD44 standard and variant isoform expression in normal human skin appendages and epidermis.

CD44 isoforms have been implicated in tumor progression and metastasis formation. This study presents a thorough immunohistochemical analysis of CD44 standard and isoform expression in normal human skin appendages and epidermis applying monoclonal antibodies against CD44s, CD44v3, -v4, -v5, -v6, and -v9. An improved immunohistochemical protocol with microwave-based antigen retrieval in paraffin sections and heavy metal amplification of the diaminobenzidine reaction product provided enhanced resolution and sensitivity as compared to studies on frozen sections. The hair follicle, the seborrheic and eccrine sweat glands were strongly positive for all CD44 isoforms studied. In the latter, the clear cells but not the dark (intercalated) cells were positive. the sudoriferous ducts adjacent to the glands were weakly positive for all CD44 isoforms and strongly positive near the skin surface. In the apocrine glands, the basal cells showed only a moderate positivity. The myoepithelial cells expressed only CD44s. In the epidermis, all CD44 isoforms were detectable, with strongest CD44 immunostaining in the lower third of the stratum spinosum and weaker staining in the stratum basale and the upper two-thirds of the stratum granulosum. The stratum granulosum and corneum were unreactive. Thus, a regional and cell type-specific CD44 expression was revealed.

A simple method for measuring the amount of immunoglobulin A secreted onto the skin surface.

We developed a simple method for measuring the amount of the secretory form of immunoglobulin A (sIgA) present in sweat. A small disk (10 x 10 mm) made of cellulose membrane was attached to the skin surface for periods of 1 to 24 h. SIgA was absorbed to the membrane and accumulated during the period of application. Enzyme immunoassay using anti-sIgA and antisecretory component (SC) antibodies revealed distinct dots on the disk that corresponded to the eccrine excretory ducts. A densitograph was used to determine the number and density of the dots, thus obtaining the amount of sIgA excreted to the surface of the skin (per mm2). The amount of skin sIgA excreted differed inter-individually as well as intra-individually. That is, it varied according to the region of the skin, and its distribution roughly reflected that of the sweat ducts. SIgA excretion was maintained at a certain level, regardless of the increased sweating produced by either heat or exercise, which raised the output of sweat 3- to 15-fold. Immunohistochemical studies revealed that fewer glandular cells expressed SC in their cytoplasm as the amount of sIgA decreased. Such an independence of the excretion of sIgA from that of sweat may be necessary to the local immune defenses of the skin.

Eccrine differentiation in basal cell carcinoma.

Eccrine differentiation according to histologic and immunohistochemical criteria was demonstrated in 16 of 66 basal cell carcinomas. The possibility of origin of these neoplasms from the eccrine duct, including the acrosyringium, is discussed in relation to the differences in site distribution and etiology between basal cell carcinoma and squamous cell carcinoma.

Distribution of complement regulators (CD46, CD55 and CD59) in skin appendages, and in benign and malignant skin neoplasms.

Immunohistochemical studies were performed to establish the distribution of membrane cofactor protein (MCP; CD46), decay-accelerating (DAF; CD55) and homologous restriction factor (HRF20; CD59), in normal skin appendages, and in benign and malignant skin neoplasms. At least two of these regulators were detected on normal eccrine glands, apocrine glands and sebaceous glands. They were also found in cellular naevi (CN), seborrhoeic keratoses (SK), basal cell carcinoma (BCC), Bowen's disease (BD), squamous cell carcinoma (SCC) and Paget's disease (PD). Although there were slight differences in their distribution, these regulators were found in all the cells examined, indicating that they are essential factors in human skin as well as other organs, and in neoplasms, in preventing autologous complement attack.

Antigenic profile of human acrosyringium.

The demonstration of HLA-DR on human acrosyringium has led to the suggestion that eccrine epithelium, through its interaction with certain molecules, might play an active role in epidermal immune responses. An immunohistochemical study was undertaken to identify the antigenic profile of acrosyringium in normal skin and following the intradermal administration of a T-lymphocyte-derived cytokine, interferon gamma (IFN-gamma). Acrosyringium in normal skin, in contrast to interappendageal epidermis, was found to lack CD1a+ Langerhans cells. However, antigens CD36 (OKM5) and L1 (MAC387) were uniquely expressed by keratinocytes immediately adjacent to the distal portion of acrosyringium. Constitutive expression of each class II MHC antigen, namely HLA-DR, DP and DQ was observed on luminal acrosyringial cells. EMB11 antigen (CD68), a mononuclear cell determinant, was similarly expressed on acrosyringial epithelium in normal skin. Following intradermal administration of IFN-gamma, intercellular adhesion molecule-1 (ICAM-1) (CD54) was induced on acrosyringial epithelium and the expression of HLA-DR was intensified. A range of other markers including CD3, CD4, CD8, CD11a, CD11b and CD15 were not expressed by acrosyringium either in normal skin or after administration of IFN-gamma. Expression of antigens associated with cell-mediated immune mechanisms on acrosyringium is consistent with the hypothesis that it may have an immunological role in epidermal immune responses.

Distribution of epithelial membrane antigen in eccrine poroma.

Using immunohistochemical methods, we investigated the distribution of epithelial membrane antigen (EMA) on the normal eccrine gland, eccrine poroma and hidroacanthoma simplex. Granular membrane-associated reaction of EMA was detected on the outer cells of both the intraepidermal and the upper portion of intradermal eccrine ducts, as well as on the luminal surfaces and intercellular canaliculi of eccrine glands. Clear immunolabeling was also present in the tumor cells of eccrine poroma and hidroacanthoma simplex. Thus, it is suggested that the constituent cells of these tumors originate from the outer cells of the intraepidermal and/or the upper portion of the intradermal eccrine ducts. There was no immunolabeling for EMA on the tumor cells of seborrheic keratosis and basal cell carcinoma. Immunohistochemical staining for EMA is a useful tool for the diagnosis of skin appendage tumors.

Ultrastructural immunocytochemical studies of blood group substances in human eccrine glands.

We investigated the ultrastructure of blood group antigens A, B, and H in human eccrine glands by means of the immunogold labeling technique. Blood group antigens A, B, and H were found in the Golgi apparatus, secretory granules, and over the apical and basolateral cell membranes of dark cells of eccrine glands depending on the blood group phenotype of the donors. Both A and B antigens were found in the dark cells of AB donors. The labeling pattern of the Golgi stacks seemed to have a polarity whereby the anti-blood group A antibody labeled all the stacks, whereas anti-blood groups B and H bound to the trans side of the Golgi complex. These observations suggest that the blood group substances are secreted into the lumen after being processed through the Golgi apparatus and the immature and mature granules in the dark cells of human eccrine glands.

Immunohistochemical staining of normal sweat glands.

Sweat glands from normal skin obtained at autopsy or as routine biopsies were examined using a panel of immunoperoxidase-linked antibodies. The results indicate that such a panel of antibodies defines all known functional regions of the eccrine sweat gland and provides a reliable distinction from all other skin elements.

Reactivity pattern of anti-CD1 and anti-HLA class II monoclonal antibodies with human eccrine sweat glands.

The known cross-reactivity of monoclonal antibodies prepared against CD1 and HLA-DR antigens with skin components prompted us to study the reactivity pattern of human eccrine sweat glands with a panel of monoclonal antibodies directed against CD1 antigens (OKT6, BL6, D-47) and against HLA-class II antigens (anti-DR, BL2, LEU-10, IV-D12, MAJA-7). The labelling pattern of eccrine glands with the panel of monoclonal antibodies used in this study permits to establish three different antigenic compartments on eccrine glands: 1) acrosyringium and distal part of dermal duct anti-DR+, BL2+, LEU-10+, IV-D12+; 2) proximal part of dermal duct MAJA-7+; 3) secretory part D-47+. The immunological markers used in this work provide a useful tool for investigation of eccrine gland differentiation and human eccrine glandular pathology.