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.     

Eccrine sweat gland development and sweat secretion

Eccrine sweat glands help to maintain homoeostasis, primarily by stabilizing body temperature. Derived from embryonic ectoderm, millions of eccrine glands are distributed across human skin and secrete litres of sweat per day. Their easy accessibility has facilitated the start of analyses of their development and function. Mouse genetic models find sweat gland development regulated sequentially by Wnt, Eda and Shh pathways, although precise subpathways and additional regulators require further elucidation. Mature glands have two secretory cell types, clear and dark cells, whose comparative development and functional interactions remain largely unknown. Clear cells have long been known as the major secretory cells, but recent studies suggest that dark cells are also indispensable for sweat secretion. Dark cell‐specific Foxa1 expression was shown to regulate a Ca²⁺‐dependent Best2 anion channel that is the candidate driver for the required ion currents. Overall, it was shown that cholinergic impulses trigger sweat secretion in mature glands through second messengers – for example InsP3 and Ca²⁺ – and downstream ion channels/transporters in the framework of a Na⁺‐K⁺‐Cl^? cotransporter model. Notably, the microenvironment surrounding secretory cells, including acid–base balance, was implicated to be important for proper sweat secretion, which requires further clarification. Furthermore, multiple ion channels have been shown to be expressed in clear and dark cells, but the degree to which various ion channels function redundantly or indispensably also remains to be determined.     

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.     

Neoplasms with sweat gland differentiation express various glycoproteins of the carcinoembryonic antigen (CEA) family

Carcinoembryonic antigen (CEA) is a well-established marker for sweat gland differentiation in adnexal neoplasms. In contrast to previous assumptions, CEA does not represent a single oncofetal antigen but comprises a family of homologous glycoproteins, i.e. the classical CEA-180, biliary glycoprotein (BGP), and non-specific crossreacting antigens (NCA). The aim of the study was to evaluate the distribution of the respective glycoproteins of the CEA family in sweat gland neoplasms, as compared to normal sweat glands. A panel of mono-specific antibodies was applied to a total of 83 samples of hyperplastic and cystic alterations of sweat glands, sweat gland neoplasms, and cutaneous metastases of different origin. Within a single group of neoplasms the immunohistochemical profile was rather consistent. Staining for both CEA-180 and NCA-90 indicated ductal differentiation of both eccrine and apocrine glands. Co-expression of CEA-180, NCA-90, and BGP was consistent with differentiation towards the secretory part of eccrine glands or the transitional portion of proximal ducts. Neoplasms with signs of apocrine secretion showed a preferential immunoreactivity for NCA-90 and BGP. In conclusion, a specification of the members of the CEA family may be of some value in the differential diagnosis of adnexal neoplasms, but not in the discrimination of sweat gland carcinoma from metastatic carcinoma.     

Somatostatin receptors are strongly expressed in palmoplantar sweat glands and ducts: studies of normal and palmoplantar pustulosis skin

Background. The acrosyringium is the target for inflammation in the chronic and intensely inflammatory skin disease palmoplantar pustulosis (PPP). The sweat‐gland apparatus seems to be an immunocompetent structure that probably contributes to skin defence. Furthermore, the sweat gland and duct may be a hitherto unrecognized neuroendocrine organ. Aim. To obtain further information about the neuroendocrine properties of the sweat‐gland apparatus by examining expression of the somatostatin receptors (SSTRs) 1–5 in healthy palmar skin and in PPP skin. Methods. Biopsy specimens were taken from 25 patients with PPP and 25 healthy controls. Immunohistochemical analysis was used to investigate expression of SSTRs 1–5. Results. SSTRs 1–5 were expressed in both epidermal and endothelial structures. The staining intensity of the sweat‐gland apparatus was more pronounced than that of the epidermis. Expression differed significantly between lesional PPP and normal plantar skin, with increased expression of SSTRs 3 and 4 in ducts in epidermis, and decreased expression of SSTR 1 in ducts in both papillary and reticular dermis. In specimens with pronounced inflammation, numerous dendritic cells with strong expression of SSTRs 1, 2 and 4 were seen, especially in the papillary dermis. Conclusions. The presence of SSTRs in palmoplantar skin, and specifically at high density in the sweat glands and ducts, might be of particular importance in skin neuroimmunoendocrinology. Although the relevance of the changes in SSTR expression in PPP skin compared with normal skin is unclear, our hypothesis is that these differences might influence the function of both the neuroendocrine and neuroimmunological properties of palmoplantar skin, especially in the sweat‐gland apparatus.     

Coma-induced bullae and sweat gland necrosis following clobazam

Coma-induced bullae and sweat gland necrosis is a rare clinicopathological entity described in association with a variety of aetiopathological conditions all of which have resulted in an impairment of conscious level. We report the first case observed in association with clobazam, used as adjunctive therapy for resistant epilepsy in a 4-year old. The potential underlying mechanisms and previously reported associations are discussed.     

Immunohistochemical studies of normal sweat glands, sweat gland tumors and extramammary Paget's diseases. II. Immunohistochemical studies of sweat gland tumors and extramammary Paget's diseases

Localizations of 18 antigens were analyzed in 41 cases with benign sweat gland tumors (13 with eccrine acrospiroma, 4 with eccrine spiradenoma, 2 with hidroacanthoma simplex, 9 with chondroid syringoma, 4 with syringocystadenoma papilliferum, 1 with tubular apocrine adenoma, 1 with papillary eccrine adenoma, 1 with apocrine cystadenoma, 1 with cylindroma, 5 with syringoma), 14 with malignant sweat gland tumors (7 with eccrine porocarcinoma, 3 with eccrine duct carcinoma, 3 with apocrine gland carcinoma, 1 with mucinous carcinoma) and 13 with extramammary Paget's disease. The results I obtained were compared with those in the normal sweat glands for determination of a differentiation of each tumor.     

Comparative performance of insulinoma‐associated protein 1 (INSM1) and routine immunohistochemical markers of neuroendocrine differentiation in the diagnosis of endocrine mucin‐producing sweat gland carcinoma

Endocrine mucin‐producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal malignancy with predilection for the eyelids of older adults. It must be distinguished from metastatic adenocarcinomas of extracutaneous origin and from benign adnexal proliferations on partial samples when a solid growth component and mucin production are not evident. Thus, demonstration of neuroendocrine differentiation can help to ensure a correct diagnosis. Insulinoma‐associated protein 1 (INSM1) is a novel neuroendocrine marker that has recently shown greater sensitivity than synaptophysin (SYN) and chromogranin (CHR) in the diagnosis of various neuroendocrine neoplasms. We compared the performance of these three markers across 10 examples of EMPSGC. All EMPSGCs expressed INSM1. Eight of ten were also immunoreactive for SYN; however, INSM1 staining was generally more intense and stained a greater proportion of the tumor cells. CHR staining was weak and focal in most cases. INSM1 staining was present in hidrocystoma‐like components of cystic EMPSGC. These findings suggest that INSM1 may be more sensitive than SYN and CHR and thus valuable for establishing a diagnosis of EMPSGC.     

Transepidermal water loss with and without sweat gland inactivation

The influence of eccrine sweating on transepidermal water loss (TEWL) was investigated. TEWL was simultaneously measured on both forearms, with and without topical inactivation of the eccrine sweat glands by 0.3 ml of 0.5% aqueous scopolamine hydrobromide (HBr), applied under 1 h occlusive patches. The degree of sweat inhibition, after exercise, was measured at 2, 3 and 4 h after patch removal. In 42 out of 44 subjects, complete sweat inhibition (on exercise) was achieved only at 4 h after removal. After a 15-min rest in a room at 20 degrees C, the pre-exercise TEWL values (at 4 h) on the treated and untreated sites were not different (P greater than 0.05), in 38 out of 44 subjects. By this rest period, sweating due to slight physical, thermal or even emotional stimuli may be prevented in most subjects. In the other 6 subjects, the pre-exercise TEWL values (at 4 h) on the untreated site were 1-1.8 g/m2h higher than (P less than 0.001) on the treated site, due to emotional sweating. Thus, accurate baseline TEWL measurements may only be made after anticholinergic suppression of the sweat glands. In this way, accurate TEWL measurements may be made even outside favourable laboratory conditions, at industrial sites etc., where circumstances are far from ideal. The effect of this agent applied to a skin site previously irritated artificially by a 24-h occlusive sodium lauryl sulphate (SLS, 0.3 ml, 0.5% aq.) patch, was also investigated in 17 subjects. In all subjects, 4 h after removal, sweating (on exercise) was completely inhibited on the scopolamine-treated site, pre-irritated with SLS.(ABSTRACT TRUNCATED AT 250 WORDS)     

皮脂腺癌与汗腺癌细胞p53蛋白的定量分析

应用流式细胞免疫技术，对１８例皮脂腺癌及汗腺癌患者细胞的ｐ５３蛋白进行了定量分析。结果表明：癌细胞与正常对照细胞的增殖指数、ＤＮＡ指数及ｐ５３蛋白相对含量之间有显著的差别。癌细胞的异倍体率及ｐ５３蛋白的阳性表达率分别为７２．２２％和１００％，对照细胞的ｐ５３蛋白均为阴性表达。由此可见皮脂腺癌和汗腺癌细胞具有很高的增殖活性及ｐ５３基因的过度表达。     

Comparative cytokeratin analysis of sweat gland ducts and eccrine poromas

Summary Human eccrine sweat gland ducts and benign and malignant eccrine poromas were studied for the expression of various cytokeratins (CK) and vimentin by applying immunoperoxidase and immunofluorescence microscopy to frozen or paraffin-embedded sections, and using two-dimensional gel electrophoresis and immunoblotting. In acrosyringia and dermal eccrine ducts, the luminal cells exhibited intense staining for CKs 1/10/11 and 19. The periluminal cell layers of acrosyringia contained CKs 1/10/11, while CK 5 was absent. In contrast, the basal cell layer of dermal ducts was only positive with the antibody against CK 5, i. e. a pattern resembling that seen in epidermal basal cells. CK 9 was detected only in keratinocytes peripherally surrounding acrosyringia. In benign poromas, gel electrophoresis revealed that CKs 5 and 14 were predominant, with CKs 6, 16 and 17 being minor components. At the immunohistochemical level CKs 1/10/11 and 19 could be further detected with varying frequency in scattered or clustered cells and/or duct-like structures. Occasionally, CK 9-positive cells were observed. Malignant poromas displayed a similar overall gel-electrophoretic pattern. Their immunohistochemical staining patterns were also similar to (albeit rather more variable than) those seen in benign poromas. Our results show that, with respect to their CK expression pattern, the majority of poroma cells resemble the basal cells of both the dermal ducts and the epidermis, while only minor and variable subpopulations acquire features present in ductal/acrosyringial luminal cells that would be indicative of poral differentiation. Thus, the matrix cells of poromas seem to be most closely related to basal cells located at the transition between the glandular epidermal ridge and dermal eccrine duct, being in no way analogous to the cells of the adult acrosyringium above the basal cell level.     

DNA image cytometry in malignant and benign sweat gland tumours

The histopathological differentiation between well‐differentiated carcinomas and atypical adenomas of sweat gland origin may be difficult, even if immunohistochemical methods are used. Therefore, additional techniques may be helpful. We previously demonstrated that DNA image cytometry (ICM‐DNA) can be useful in distinguishing between malignant and benign clear cell hidradenoma. In the present study, a larger series of sweat gland tumours, with a clear‐cut diagnosis as malignant or benign on histopathological criteria, was examined by ICM‐DNA. Enzymatic cell separation specimens were prepared from paraffin‐embedded tissues of 18 sweat gland carcinomas (14 porocarcinomas, one classic eccrine adenocarcinoma, two microcystic adnexal carcinomas and one mostly ductal apocrine carcinoma) and 47 benign sweat gland tumours (three syringocystadenomas, five spiradenomas, 14 cylindromas, three syringomas, seven nodular hidradenomas, 10 cutaneous mixed tumours, four poromas and one apocrine hidrocystoma). Specimens were examined by ICM‐DNA according to the current recommendations of the European Society for Analytical Cellular Pathology with the AutoCyte QUIC‐DNA workstation using mesenchymal cells as an internal reference. DNA aneuploidy was detected by the stemline interpretation according to Böcking and/or at least three 5[c]‐exceeding events. DNA aneuploidy was detected in 16 of 18 (89%) of the sweat gland carcinomas, but in none of the 47 adenomas. These results suggest that the detection of DNA aneuploidy in sweat gland tumours using ICM‐DNA is a clear and specific indicator of prospective malignancy.     

Bullae and sweat gland necrosis after an alcoholic deep slumber

A 37-year-old man developed edematous areas and blisters on the right side of his face, chest, and arm after an alcoholic deep slumber. It was revealed that the affected body parts were those pressed during his alcoholic sleep. Histopathological findings of the patient's skin lesions showed typical sweat gland necrosis. Serum enzyme level studies of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine phosphokinase were characteristic of muscular damage. This case report is an example of the typical findings of the effects of body pressure on soft tissue that can be seen in a dermatology clinic.     

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.