Immunohistochemical demonstration of keratins 8 and 14 in benign tumours of the skin appendage

Summary The expression of keratins 8 and 14 was investigated immunohistochemically by the avidin-biotin-peroxidase (ABC) method using formalin-fixed paraffinembedded specimens from 42 tumours of human skin appendages. Results were compared with the staining of 34 specimens from normal skin and skin appendages adjacent to the tumours. Keratin 14 was detected by the monoclonal antibody (mAb) 312C8-1, and was found in the basal cells of the epidermis, the outer root sheaths of hair follicles, and the peripheral cells of sebaceous glands. It was also detected in the inner and outer layers of cells in the ductal portion and the myoepithelial cells in the secretory portion of apocrine and eccrine sweat glands. Keratin 8 was detected by mAb 35BH11, and was present in the secretory cells of eccrine and apocrine sweat glands but not in myoepithelial or ductal cells. The pilosebaceous apparatus and the epidermis were uniformly negative. In benign skin appendage tumours, the staining patterns for both keratins generally resembled their distribution in the corresponding normal tissues. The demonstration of keratins 8 and 14 may be useful in the recognition, classification and diagnosis of skin appendage tumours.     

Clear cell hidradenoma of the eyelid: a case report

Sweat gland tumours are extremely rare in the eyelids. We report a case of a clear cell hidradenoma (nodular hidradenoma) in an elderly female, who had presented with a nodular swelling in a eyelid. Clear cell hidradenomas arise as intradermal nodules from eccrine sweat glands. Ultrastructural and enzyme histochemical studies have shown nodular hidradenomas to be intermediate between eccrine poroma and eccrine spiradenoma. No apocrine differentiation has ever been observed in these tumours. Malignant forms are distinctly unusual. This case is being documented for the extremely uncommon presentation of this tumour as an eyelid mass. Complete primary excision is advocated and local steroid preparations should bot be used.     

Vimentin expression in sweat gland tumours.

Immunohistochemical localization of vimentin was studied in 93 cases of sweat gland tumours using a monoclonal anti-vimentin antibody. A strong immunoreactivity of vimentin was observed in modified myoepithelial or neoplastic myoepithelial cells of mixed tumour of the skin, syringoma, and sweat gland adenoma. Tumour cells in outer layers of tubular, ductal, and duct-like structures usually showed positive staining for vimentin, which coincided with modified myoepithelial cells. All tumour cells of clear cell hydroadenoma showed positive vimentin staining. Tumour cells of the luminal border of tubulo-ductal structures of mixed tumours were rarely immunoreactive for vimentin. Positive vimentin staining of tumour cells in the outer zone of tubulo-ductal structures in sweat gland tumours may be related to reactive proliferation of modified myoepithelial cells and simultaneous growth of luminal tumour cells.     

Immunohistochemical analysis of keratin distribution in eccrine poroma.

Although eccrine poroma has been thought of as a neoplasm of the intradermal eccrine duct, this interpretation has not been entirely confirmed. In this study, twenty-five cases of eccrine poroma were retrieved and analyzed by immunohistochemical techniques, using various kinds of monoclonal antikeratin antibodies. Comparative immunohistochemical observations of eccrine poroma and normal eccrine glands revealed that the poroma cells expressed immunophenotypes similar to those of the basal cells of dermal eccrine ducts. Sweat-ductlike structures showed similar staining patterns to those observed in the inner cells of dermal eccrine ducts. Some cystic spaces were similar to those observed in the secretory cells of eccrine glands. Eccrine poroma is, therefore, speculated to originate via the proliferation and expansion of the basal cells of eccrine ducts, although it is very difficult to prove the histogenesis. Some tumor cells may differentiate toward inner cells of the eccrine ducts, forming ductal lumina, whereas other tumor cells differentiate toward eccrine secretory regions, forming some cystic spaces.     

Immunohistochemical study of carbonic anhydrase in mixed tumours from major salivary glands and skin

Summary Immunohistochemical distribution of carbonic anhydrase isoenzyme I and II was studied in mixed tumours of major salivary glands and skin. The normal salivary glands displayed strong carbonic anhydrase activity in both ductal epithelium and serous acinar cells and the serous demilune cells in the submandibular glands, including the eccrine ducts. Pleomorphic adenoma salivary gland origin exhibited positive staining in the innerlayer of epithelial cells of tubular, duct-like and glandular structures. No enzymatic staining was noted in the outer layer of tumour cells in these structures. Spindle tumour cells or the fibroblast-like cells with long cytoplasmic processes identified in the adjacent hyalin and myxomatous stroma were rarely positive, while chondroidal and osteo-chondroidal cells were highly reactive. Mixed tumours of eccrine gland origin showed the most reactive staining cells scattered throughout neoplastic epithelium in all tissues examined. Immunohistochemical stainability was usually higher for carbonic anhydrase II than I for both normal and tumour tissues. The biological roles of the distribution profiles of carbonic anhydrase are discussed.This investigation was supported partially from Miyata Research fund     

Isoantigens A, B, H in normal skin and tumors of the epidermal appendages.

Isoantigens A, B, H(O) in biopsy specimens of 26 normal skin and in 35 adnexal tumors were studied by the red cell adherence (RCA) test of Davidsohn. Isoantigens were detected in the stratum corneum, stratum granulosum, stratum spinosum, acrosyringium, keratogenous zone of hair follicle, eccrine duct, and eccrine gland. The apocrine gland and duct consistently had negative test results for isoantigens. Seventy percent of all tumors tested contained isoantigens and included syringoma, hidrocystoma, syringocystadenoma papilliferum, spiradenoma, eccrine poroma, dermal duct tumor, clear cell hidradenoma, and cylindroma. We interpreted the presence of isoantigens in adnexal tumors as being evidence of immunologic maturity with differentiation toward eccrine structures. The RCA test is a new, sensitive, immunologic technique that can complement enzyme histochemical stains and electron microscopy in the study of the histogenesis of adnexal skin tumors.     

Skin adnexal neoplasms--part 2: an approach to tumours of cutaneous sweat glands

Tumours of cutaneous sweat glands are uncommon, with a wide histological spectrum, complex classification and many different terms often used to describe the same tumour. Furthermore, many eccrine/apocrine lesions coexist within hamartomas or within lesions with composite/mixed differentiation. In addition to the eccrine and apocrine glands, two other skin sweat glands have recently been described: the apoeccrine and the mammary-like glands of the anogenital area. In this review (the second of two articles on skin adnexal neoplasms), common as well as important benign and malignant lesions of cutaneous sweat glands are described, and a summary for differentiating primary adnexal neoplasms from metastatic carcinoma is outlined, striving to maintain a common and acceptable terminology in this complex subject. Composite/mixed adnexal tumours are also discussed briefly.     

Distribution of glycoconjugates in human skin appendages

The purpose of this paper is to describe the occurrence and distribution of glycoconjugates in normal human epidermis and skin appendages (pilosebaceous unit, eccrine sweat gland) by means of FITC-labelled lectins (ConA, WGA, UEA I). Both the outer hair root and the follicular ostium-epithel disclosed a glycoconjugate expression with close homology to interfollicular epidermis. The acinar epithelium of sebaceous glands and the inner layers of hair follicles showed a more or less distinct staining pattern. Lectin binding of eccrine sweat glands revealed marked differences between ducts and secretory coils. The epithelial distribution of glycoconjugates indicates a relatively independent differentiation pathway of eccrine sweat glands compared with other specialized epithelia of the human skin.     

Localization of Ca2+-binding S100 proteins in epithelial tumours of the skin

 The Ca²⁺-binding proteins S100A1, S100A2, S100A4, S100A6 and S100B were evaluated immunohistochemically in normal skin and skin appendage tumours. Epidermal basal cells, epithelial cells of sebaceous glands, hair follicle sheet epithelia and eccrine duct reacted strongly with an antiserum against human S100A2 but were nonreactive or weakly reactive to S100A1, S100A4, S100A6 and S100B. Varying types of skin appendage tumours and most peripheral cells in tumour nests of basal cell carcinoma and squamous cell carcinoma showed positive S100A2 immunoreactivity in neoplastic cells corresponding to basal cells but were nonreactive or faintly reactive for other S100 proteins. Langerhan’s cells and melanocytes were labelled by S100B. Basophilic cells of calcifying epithelioma were occasionally stained with S100A2 antiserum. Eccrine poroma did not react with any S100 antiserum. Mixed tumours of the skin containing neoplastic myoepithelial cells stained strongly for S100A2 and S100B but only faintly for S100A1, S100A4, S100A6. This is the first report on selective evaluation of different S100 proteins in normal skin. These antibodies are valuable tools for better characterization of skin appendage tumours. Received: 12 March 1997 / Accepted: 26 May 1997     

Hautadnex- und Speicheldrüsentumoren

Benign and malignant skin adnexal neoplasms, especially glandular lesions, show morphologically striking similarities to salivary gland tumors. On the other hand, histological and clinical differences are evident, and knowledge of their existence is important for adequate treatment and reliable prognostication. In this review similarities and differences of selected entities are briefly described and discussed. The following entities are reviewed: cylindroma (vs. membranous variant of basal cell adenoma), sebaceoma (vs. sebaceous adenoma), syringocystadenoma papilliferum (vs. sialadenoma papilliferum), chondroid syringoma (vs. pleomorphic adenoma), cutaneous myoepithelioma (vs. myoepithelioma of salivary glands), cutaneous malignant myoepithelioma (vs. malignant myoepithelioma of salivary glands), cutaneous adenoid cystic carcinoma (vs. adenoid cystic carcinoma of salivary glands), and mucinous eccrine carcinoma (vs. mucous carcinoma of salivary glands).     

Malignant eccrine poroma: report of three cases

The characteristic clinical and histological features of three cases of malignant eccrine poroma are discussed, in addition to the metastatic disease that had occurred in two cases. These cases were compared with previously reported cases of malignant eccrine poroma that had metastasised, and it is suggested that a strict classification of malignant eccrine sweat gland tumours should be made.     

Non-epithelial cellular components in eccrine spiradenoma: a histological and immunohistochemical study of 20 cases

In this study, 20 cases of eccrine spiradenoma have been examined using monoclonal antibodies to identify the nature of the epithelial, as well as the non-epithelial, cellular components of this tumour. The results indicate that there is striking similarity between the epithelial cells of eccrine spiradenoma and the normal cells lining eccrine apparatus. An interesting finding was the presence of abundant T-lymphocytes and Langerhans' cells within the tumour lobules. Additionally, endothelial-lined vascular channels and neurofibrils were prominent in larger lesions.     

Human eccrine sweat glands--a histochemical approach.

Histogenesis of eccrine sweat glands is incompletely understood. Histochemistry of the human eccrine sweat gland of adult skin by the use of lectins as well as antibodies to neuroglandular antigen (NGA) and urokinase was in favour of a relative independent differentiation from interfollicular epidermis. Expression of NGA by sweat glands is a feature unique among skin appendages. The possible impact of our findings for sweat gland histogenesis is briefly discussed.     

Das apokrine Porom

Poromas were originally classified as eccrine tumors which predominantly consist of poroid ductal cells and differentiate in the direction of sweat gland ducts. However, there have now been many reports on poromas with additional differential characteristics differentiating in the direction of sebaceous and/or apocrine glands and/or hair follicles. These tumors have been termed apocrine poromas. Multilineage differentiation within a poroma can be explained by the embryological association of the sweat duct with the so-called folliculo-sebaceous-apocrine unit. The clinical and histopathological features of apocrine poromas are reviewed in comparison to classical eccrine poromas by taking into account seven own cases of apocrine poroma and a review of the literature. It is important for histopathologists not to confuse apocrine poroma with other tumors with multilineage differentiation. Apocrine poroma needs to be distinguished from sebaceoma and from basal cell carcinoma with sebaceous differentiation, in particular, because these tumors have therapeutic consequences for the patient. The main histopathological differences between apocrine poroma, sebaceoma and basal cell carcinoma with sebaceous differentiation are explained.     

Mixed tumours of the skin: a histopathological, enzyme-histochemical and immunohistochemical study

Twenty-eight cases of mixed tumour of the skin were studied and subclassified into three types: eccrine (1 case), indeterminate (7), and apocrine type (20). The indeterminate type was defined as mixed tumours having tubulo-alveolar patterns with two layers of epithelium, but without apocrine secretion or pilosebaceous differentiation. Enzyme-histochemical studies were performed on four cases (one indeterminate, three apocrine): in the indeterminate type the tubular epithelial cells showed eccrine differentiation while in the apocrine type tubules were found showing the direction of differentiation to be toward the apocrine gland, but tubules with eccrine differentiation were intermingled in all three. Immunohistochemically, no differences were observed between the indeterminate and the apocrine type: hints of eccrine features were observed in both groups. Thus, the indeterminate type could be an eccrine tumour and the apocrine type showed direction of differentiation toward both eccrine and apocrine glands. It is concluded that mixed tumours of the skin are fundamentally eccrine neoplasmas, and that the apocrine features may represent apocrine metaplasia.     

Merkel cell differentiation in trichoblastoma

 Four cases of trichoblastoma rich in Merkel cells (MCs) are reported. They occurred in two men and two women, with ages ranging from 58 to 76 years (mean 67.5 years). MCs were detected immunohistochemically with antibodies to keratin 20, chromogranin A and neuron-specific enolase (NSE). In an attempt at better definition of the nature and role of MCs in trichoblastoma, the distribution of MCs in normal adult and fetal skins obtained at autopsy was studied. In addition, ten cases of sebaceous naevus of Jadassohn (NSJ) were evaluated along similar lines. MCs made up 2–20% of the tumour cells in trichoblastomas; they were present in normal fetal skin and were rare in normal adult skin. All but one of the cases of NSJ showed numerous positive cells in the epidermal component of the lesion with all three antibodies. Six basal cell carcinomas and one syringocystadenoma papilliferum associated with NSJ were negative with keratin 20, chromogranin A and NSE antibodies, whereas a minute trichoblastoma arising against the same background was positive for these markers. Hair follicle cell tumours may recapitulate the skin embryogenesis, as numerous MCs are present in fetal follicles, but only occasional such cells are seen in adult skin. Received: 26 February 1998 / Accepted: 22 April 1998     

Matrigel‐Induced Tubular Morphogenesis of Human Eccrine Sweat Gland Epithelial Cells

Human eccrine sweat glands are tubule‐structured glands of the skin that are vital in thermoregulation, secretion, and excretion of water and electrolytes. A study of tubular morphogenesis in vitro would facilitate the development of a tissue engineering model for eccrine sweat glands and other tubule‐structured glands. Matrigel, a basement membrane matrix, has been shown to promote differentiation and morphogenesis of many different cell types, including tubular cells. This study investigated the growth, differentiation, and tubular morphogenesis of human eccrine sweat gland epithelial cells cultured in Matrigel. Human eccrine gland epithelial cells were isolated and cultured in vitro. The cell growth in Matrigel was evidenced by the formation of cell clusters, which were observed under an inverted microscope. The internal structure of the cell clusters was further investigated by hematoxylin–eosin (HE) staining and confocal laser scanning microscopy (CLSM) of propidium iodide‐stained nuclei. The results demonstrated that although on a plastic surface or in a collagen gel the cells could not form tubular structures, they formed tubular structures when cultured in Matrigel. Consequently, we conclude that Matrigel can promote tubular morphogenesis of human eccrine sweat gland epithelial cells. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.     

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.     

Tenascin expression in normal human adult skin and skin appendage tumours

The expression and distribution of tenascin, an extracellular matrix glycoprotein, was investigated immunohistochemically using an anti-human tenascin monoclonal antibody (RCB 1) in formalin-fixed paraffin-embedded tissues obtained from 79 patients with skin appendage tumours, and compared with adjacent normal skin. Tissue specimens were pretreated with actinase and processed by the labelled streptavidin-biotin method. In normal skin, tenascin immunoreactivity was consistently found around the ductal portion of the sweat glands, around the lower part of the hair follicle and hair bulbs, and around or within blood vessels. Immunoreactivity was also observed variably around secretory coils of the sweat glands, and below the epidermis. No immunoreactivity was seen around the sebaceous glands. Tumours originating from sweat glands and hair follicles expressed tenascin around the tumour cells nests, while sebaceous gland tumours were immunonegative. Thus, tenascin expression in skin appendage tumours generally resembled that in corresponding normal tissue.     

Vasoactive intestinal polypeptide receptor-like immunoreactivity in human sweat glands

Human sweat and sebaceous glands were studied immunohistochemically with a monoclonal antibody recognizing a vasoactive intestinal polypeptide (VIP) receptor. The staining pattern correlated well with the known distribution of sympathetic VIP-containing nerves in the human skin. The luminal cell layer of the sweat gland ducts and some acinar cells of the secretory coil of eccrine sweat glands were the major sites of VIP receptor-like immunoreactivity. From these findings and the known pharmacological actions of VIP it is concluded that a major role of VIP released from sympathetic nerves in the skin is to regulate chloride reabsorption from the primary sweat at the ductal segment.