Immunohistochemical studies of normal sweat glands, sweat gland tumors and extramammary Paget's disease. I. Immunohistochemical studies of normal sweat glands

Localizations of 18 antigens in normal sweat glands were analyzed. The antigens were roughly classified into 8 antigens: 1) distributed throughout the epithelial cells; 2) localized in whole sweat glands; 3) localized only in the secretory portion of sweat glands; 4) localized only in the inner cells of ductal portion of sweat glands; 5) localized in the myoepithelial cells; 6) localized only in the outer cells of dermal ducts of eccrine glands; 7) localized only seen in some of apocrine glands; 8) seen in the inflamed sweat glands. Based on these findings, I discussed about the forms and meanings of localization of those antigens.     

Triple extramammary Paget's disease. Immunohistochemical studies

A 75-year-old man developed three lesions of Paget's disease which involved the pubic area and both axillae. Histologically, there was no invasion into the dermis in any of the three lesions. Various kinds of histochemical and immunohistochemical studies including those for carcinoembryonic antigen showed that both genital and axillary lesions were identical in nature. Cases with triple involvement of Paget's disease are thought to be extremely rare in the literature.     

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.     

Immunohistochemical markers of sweat gland tumors

Using immunoperoxidase methods, normal sweat glands, 44 benign and 4 malignant sweat gland tumors were tested for the presence of carcinoembryonic antigen (CEA), pregnancy-specific-B1-glycoprotein (SP1) and actin (ACT). CEA and SP1 stained the secretory and duct-lining cells of normal eccrine glands. Among benign tumors, 74% were positive for CEA and 44% for SP1. The staining reaction was found mainly in luminal secretions and surrounding cells. Staining by SP1 was reduced, but not suppressed, after absorption with the purified antigen. ACT was found in myoepithelial cells of the secretory tract of normal glands and in basal cells of all cases of hidradenoma papilliferum. Only 3 sweat gland carcinomas reacted for CEA. In a malignant chondroid syringoma, no ACT-positive cells were seen in the myxochondroid stroma. The potential value of CEA, SP1 and ACT in the diagnosis of sweat gland tumors is discussed.     

Immunohistochemical stains in extramammary Paget's disease.

The histologic and immunohistochemical characteristics of 49 skin biopsy specimens from 49 patients with extramammary Paget's disease were studied. Patients with extramammary Paget's disease with and without underlying malignant disease were identified. Associated malignant lesions, present in 16 patients (33%), were transitional cell carcinoma of the bladder (n = 8), adenocarcinoma underlying the skin (n = 3), adenocarcinoma of the anus (n = 1), adenocarcinoma of the vulva (n = 1), apocrine carcinoma (n = 1), prostate carcinoma (n = 1), and carcinoma metastatic to the lung (n = 1). The main histologic feature was the presence of Paget's cells, predominantly at the base of the epidermis. In 6% of the cases, well-defined nests of large Paget's cells mimicked melanocytic nests. Carcinoembryonic antigen and Cam 5.2 (a monoclonal antibody that stains 40-kDa, 45-kDa, and 52.5-kDa low molecular weight keratins) were localized to the Paget's cells in 42 of 45 (93%) and 29 of 41 cases (71%), respectively. Forty-four of 46 lesions (96%) were mucin positive, as determined by Hale's colloidal iron stain. Absence of staining for colloidal iron and carcinoembryonic antigen occurred somewhat more frequently in patients with underlying malignant disease than in patients without tumors (13% vs. 0% mucin negative and 13% vs. 3% carcinoembryonic antigen negative, respectively). Although immunohistochemical staining for low molecular weight keratin may be used to confirm the diagnosis of extramammary Paget's disease, Cam 5.2 is not as sensitive as the colloidal iron or carcinoembryonic antigen stain.     

Immunohistochemical demonstration of ferritin in sweat gland and sweat gland neoplasms

Using a rabbit anti-human liver ferritin antibody, we examined the binding patterns of this reagent in normal skin and observed a unique binding pattern limited to the outermost layer of the eccrine duct. Examination of a variety of sweat gland neoplasms revealed 2 distinct patterns. One was the binding of this antibody to the outermost layer of cells in the epithelial cords of syringoma, producing a characteristic ring when seen in cross-section. This pattern of binding did not occur in other neoplasms known to be related to the eccrine duct such as dermal duct tumor and eccrine poroma. Only sparse sporadic binding occurred in other eccrine and apocrine neoplasms. A second characteristic binding pattern, not related to that noted in syringoma and diffuse in pattern, was seen in acrospiroma and in a number of adnexal carcinomas. Diffuse ferritin expression has been described in malignant neoplasms in tissues other than skin. Diffuse ferritin staining of certain sweat gland neoplasms may be an indication of biologic activity and potential aggressivity of these neoplasms.     

Immunohistochemical study of angiotensin receptors in normal human sweat glands and eccrine poroma

BACKGROUND: Angiotensin II exerts its actions through its specific receptors. However, expression of these receptors has not been determined in sweat glands. OBJECTIVES: To clarify the expression and localization of the angiotensin receptors in normal human sweat glands and eccrine poroma. METHODS: Expression of angiotensin type 1 (AT1) and type 2 (AT2) receptors in normal human eccrine and apocrine sweat glands and 12 cases of eccrine poroma was studied using immunohistochemistry. RESULTS: In eccrine sweat glands, the acrosyringium and the inner surfaces and luminal cells of the intradermal duct showed positive staining with AT1. In apocrine sweat glands, the intraepithelial duct and luminal cells of the intradermal duct showed positive staining with AT1. In 12 cases of eccrine poroma, some of the tumour cells in the tumour strands and cells surrounding the luminal structures stained positively. There were no positive findings with AT2. CONCLUSIONS: Studying AT1 distribution may be useful in understanding the pathophysiology of sweat glands and sweat gland tumours.     

Immunohistochemical detection of carcinoembryonic antigen and protein S-100 in sweat gland tumors

Carcinoembryonic antigen (CEA) and S 100 protein (S 100) have been demonstrated in formalin-fixed paraffin sections of eccrine and apocrine sweat glands, and tumors of the sweat glands, as well as, for comparison, in a variety of tumors deriving from epidermal and follicular structures using the peroxidase-antiperoxidase technique. CEA is detectable, as a membrane antigen, in the normal coil of eccrine sweat glands and in the cytoplasm of luminal cells in eccrine and apocrine sweat ducts up to the horny layer. Nearly all tumors of the sweat glands contain variable amounts of CEA. S 100 is localized in the cytoplasm of eccrine coils and secreted with the sweat. Apparently it is only found in tumors derived from the eccrine and apocrine sweat gland coils. Immunohistochemical demonstration of CEA and S 100 thus facilitates the diagnosis of tumors of the sweat glands and their differentiation from epidermal and follicular tumors.     

Immunohistochemical demonstration of peptidylarginine deiminase in human sweat glands.

Human skin is known to contain protein-bound citrulline. This is the product of enzymatic deimination of arginine residues catalyzed by peptidylarginine deiminase. We probed frozen sections of human skin with a rabbit antiserum raised to rat skeletal muscle peptidylarginine deiminase using the avidin-biotin-peroxidase complex technique. This led us to interesting findings. No staining was observed in epidermis, inner root sheaths of hair follicles, sebaceous glands, and hair erector muscle. However, we noticed specific staining of the cytoplasm of secretory and myoepithelial cells of both eccrine and apocrine sweat glands. The procedure also stained neoplastic cells present in specimens dissected from extramammary Paget's disease. The data mean that peptidylarginine deiminase may be used as a new marker in the classification of skin neoplasms showing sweat gland differentiation. Possible localization of multiple types of peptidylarginine deiminases in human skin is discussed.     

乳房外Paget病中汗腺病理及免疫组化分析

目的：分析乳房外Paget病(EMPD)中汗腺上皮组织CK7和CEA的表达及临床意义。方法：应用免疫组化SP法对15例EMPD皮损和周边正常皮肤CK7和CEA的表达进行检测。结果：15例中有8例在汗腺腺体及导管部见CK7和CEA呈阳性，其中仅5例发现汗腺上皮细胞呈异常改变。结论：免疫组化方法在诊断和鉴别诊断EMPD中汗腺上皮细胞的不典型增生具有一定价值。     

Immunohistochemical analysis of human milk fat globulin expression in extramammary Paget's disease

Primary extramammary Paget's disease is thought to be an intraepidermal carcinoma indicating apocrine secretory differentiation. In addition to expression in breast tissue, human milk fat globulin (HMFG) is expressed in the normal apocrine glands and tumours with apocrine differentiation. In this study HMFG expression in extramammary Paget's disease was analysed immunohistochemically in 18 cases of primary extramammary Paget's disease and two cases of secondary extramammary Paget's disease. The proportion and staining pattern of positive tumour cells with the anti-HMFG antibody was variable in each case. Cytoplasmic staining was observed frequently in dermal invasion and metastasis of Paget cells. The variabilities were thought to be due to modulation of the cellular localization of the cell surface component, HMFG, according to changes in cellular differentiation or malignant potency.     

Extramammary Paget's cells: further evidence of sweat gland derivation

Tissue from a 66-year-old male patient with extramammary Paget's disease of the right side of the scrotum and the right groin was studied for the presence of several antigens with the immunoperoxidase technic. Adenokeratin (cytokeratin No. 18) and carcinoembryonic antigens were positive in Paget's cells, whereas squamokeratin (cytokeratin No. 10) was expressed only in normal epidermal cells. Langerhans cells were decreased in the region of the tumor. Many transferrin receptors were present on the tumor cells, indicating a high cellular proliferation rate. Enzyme histochemical studies of the extramammary Paget's cells showed positive reactions for several enzymes typical of sweat glands, except for leucine aminopeptidase, which was negative. A comparison with three other cases showed that these enzyme reactions varied greatly from case to case. Both immunohistochemical and enzyme histochemical findings provide further evidence that extramammary Paget's cells are related to sweat gland epithelial cells, with variable expression of cellular characteristics.     

Immunohistochemical staining properties of keratin type intermediate filaments in mammary and extramammary Paget's disease

Utilizing three different anti-keratin antibodies and the avidin-biotin peroxidase complex system on sections of formalin-fixed paraffin-embedded tissues and on cryostat sections, immunohistochemical localization of keratin type intermediate filaments in mammary Paget's disease and extramammary Paget's disease was investigated. Anti-keratin antibodies EAB-903 and EAB-904, which recognize 66K and 57K dalton keratin peptides, did not decorate any Paget's cells in either mammary or extramammary Paget's disease. On the other hand, anti-keratin antibody MAK-6, which recognizes 52.5K, 50K, 48K, 45K and 40K daltons keratin peptides, did decorate Paget's cells in both Paget's diseases. These staining properties of Paget's cells were the same as those of secretory cells in normal human sweat glands and mammary glands. Anti-keratin antibody MAK-6 is thought to be useful in the diagnosis of mammary and extramammary Paget's diseases.