Familial cylindromatosis

Familial cylindromatosis: we report a daughter with turban tumor and her mother with cylindromatosis. The dermal eccrine cylindroma arose as small, solitary lesions on the head of the mother when she was 28 years old. The following years other tumors became apparent. She was operated on several times. The first lesions appeared on the frontal part of the scalp of the daughter when she was 23 years old. Other tumors grew on the scalp. Histopathological examination of the excised tumors showed the same lesions in both the mother and the daughter: dermal eccrine cylindromata. Family history showed that the daughter's maternal aunt had a few tumors. Dermal eccrine cylindroma should be differentiated from malignant syndromes such as basal naevoid carcinoma or metastases and from neurofibromata. The gene of familial cylindromatosis was localised to chromosome 16q12-q13 and it was proposed that this gene is a tumor supressor gene.     

The evolution of sweat glands

Mammals have two kinds of sweat glands, apocrine and eccrine, which provide for thermal cooling. In this paper we describe the distribution and characteristics of these glands in selected mammals, especially primates, and reject the suggested development of the eccrine gland from the apocrine gland during the Tertiary geological period. The evidence strongly suggests that the two glands, depending on the presence or absence of fur, have equal and similar functions among mammals; apocrine glands are not primitive. However, there is a unique and remarkable thermal eccrine system in humans; we suggest that this system evolved in concert with bipedalism and a smooth hairless skin.Iowa Quaternary Studies Contribution No. 47     

Benign dermal eccrine cylindroma. A pitfall in the cytologic diagnosis of adenoid cystic carcinoma

Aspiration cytology from four benign dermal eccrine cylindromas and five adenoid cystic carcinomas were compared. These two lesions were found to have so much in common morphologically that they may be indistinguishable on a purely cytologic basis. Accordingly, we recommend a restricted excision to obtain a histopathologic diagnosis before more extensive surgery is performed whenever a lesion is cytologically consistent with adenoid cystic carcinoma but clinically shows a picture that does not exclude dermal eccrine cylindroma.     

Cytologic features of pleural effusion in apocrine sweat gland carcinoma. A case report

BACKGROUND: Carcinoma arising in the apocrine sweat glands is very rare, and there are few reports of the cytologic features. We encountered a case of metastatic apocrine carcinoma in a pleural effusion. CASE: A 46-year-old male had a dark reddish nodule in the right axillary region that was diagnosed as apocrine carcinoma of skin appendage origin. Three years after wide resection and chemotherapy, widespread metastases developed with a massive pleural effusion. Needle aspiration fluid cytology contained clusters of adenocarcinoma. Some tumor cells had abundant cytoplasm or periodic acid-Schiff-positive, coarse granules. Decapitation secretion was occasionally found on the cell surface. Immunohistochemically, the tumor cells were often positive for BRST-2 and BRST-3. CONCLUSION: Cytologic features of metastatic apocrine sweat gland carcinoma show some characteristics of adenocarcinoma. Moreover, its definitive diagnosis in a pleural effusion can be made because of retaining the characteristics of apocrine sweat gland.     

Immunoelectron microscopic localization of epidermal growth factor in the eccrine and apocrine sweat glands.

We studied the localization of the epidermal growth factor (EGF) in eccrine and apocrine sweat glands with light microscopic and electron microscopic immunohistochemistry. Anti-human EGF (anti-hEGF) polyclonal antiserum and anti-hEGF monoclonal antibody (MAb) were used for the study. Light microscopic immunohistochemistry with monoclonal and polyclonal antibodies showed that hEGF-like immunoreactivity was strongly positive in the myoepithelial cells and weakly positive in the secretory cells of eccrine sweat glands. In apocrine sweat glands, it was strongly positive in the secretory cells as well as in the myoepithelial cells. Immunoelectron microscopy with polyclonal antibody showed that hEGF-like immunoreactivity was present in secretory granules of apocrine secretory cells. These granules had mitochondrion-like internal structure. No reactivity was observed on the eccrine secretory cells by immunoelectron microscopy. Neither dark cell granules nor mitochondria in eccrine secretory cells were labeled with anti-hEGF antibody. In both eccrine and apocrine sweat glands, hEGF-like immunoreactivity was diffusely present in the cytoplasm of myoepithelial cells. However, nuclei and mitochondria of myoepithelial cells were devoid of immunoreactivity for hEGF. Our observations indicate that apocrine sweat glands may secrete more hEGF in the sweat than eccrine sweat glands.     

Immunohistochemical localization of activated EGF receptor in human eccrine and apocrine sweat glands.

Epidermal growth factor (EGF) is secreted into sweat from secretory cells of human sweat glands. The function of EGF in sweat is poorly understood. The biological function of EGF is exerted by the binding of EGF to the receptor (EGFR) and its activation. Therefore, we immunohistochemically localized the activated form of EGFR in human eccrine and apocrine sweat glands to assess the functional importance of the EGF-EGFR system in human sweat glands. Frozen sections of human skin were stained with a monoclonal antibody (MAb) specific for tyrosine-phosphorylated (activated) EGFR and with an MAb that stains both activated and non-activated EGFR. In the secretory portion of eccrine sweat glands, nuclei of the secretory cells were stained with the anti-activated EGFR MAb. In coiled and straight portions of eccrine sweat ducts, nuclei of luminal and peripheral cells were stained with the antibody specific for activated EGFR. Luminal cell membranes and luminal cytoplasm of inner ductal cells possessed non-activated EGFR. In the secretory portion of apocrine sweat glands, activated EGFRs were present in cytoplasm and nuclei of secretory cells. These data suggest that EGF, already known to be present in the cytoplasm of secretory cells in eccrine and apocrine sweat glands, activates EGFR in the nuclei of secretory cells themselves in an intracrine manner. Because ductal cells do not express EGF, EGF in the sweat secreted from the secretory cells should activate EGFR in the ductal cells in a paracrine manner. (J Histochem Cytochem 49:597-601, 2001)     

Localization of gamma-glutamyl transpeptidase in human sweat glands: an immunohistochemical study using a monoclonal antibody

We studied the distribution of gamma-glutamyl transpeptidase (gamma-GT) by use of a monoclonal antibody (MAb) against human kidney gamma-GT in human sweat glands. In the eccrine sweat gland, the enzyme was localized along the luminal membrane and small apocrine extrusions of the superficial cells of the secretory portion. The intercellular canaliculi between basal cells were occasionally immunoreactive. In the secretory portion of the apocrine gland, luminal membrane and apocrine extrusions of various sizes and stages at the apices of the secretory cells exhibited positive reactions. Immunoreaction was also seen in the Golgi area of the cuboidal secretory cells. No positive reaction was observed in the myoepithelial cells of either gland or in the excretory duct cells.     

Evolutionary origins of the mammary gland

Because the mammary gland has no known homologue among the extant reptiles, attempts to reconstruct its evolution must focus on evidence from living mammals. Of the numerous structures that have been hypothesized to have given rise to the mammary gland, only three remain as plausible progenitors: sebaceous glands, eccrine glands and apocrine glands. Ancestral mammary glands are usually assumed to have produced a copious watery secretion like that of human eccrine sweat glands. However, in terms of anatomy, physiology, development and topographical distribution, mammary glands are more similar to apocrine and sebaceous glands than to typical eccrine glands. Nevertheless, each of the three populations of cutaneous glands exhibit specializations unlikely to be primitive for the mammary gland. The mammary gland either predated full differentiation of mammalian cutaneous glands or, more probably, evolved as a neomorphic mosaic that combined the properties of apocrine and sebaceous glands. Consequently, ancestral, prototypic lacteal glands may have had the capacity to synthesize and secrete small amounts of organic substances, as do sebaceous and apocrine glands of living mammals.     

Different keratin polypeptides in epidermis and other epithelia of human skin: a specific cytokeratin of molecular weight 46,000 in epithelia of the pilosebaceous tract and basal cell epitheliomas

Cytokeratin polypeptides of human epidermis, of epithelia microdissected from various zones of the pilosebaceous tract (outer root-sheath of hair follicle, sebaceous gland), and of eccrine sweat-glands have been separated by one- and two-dimensional gel electrophoresis and characterized by binding of cytokeratin antibodies and by peptide mapping. The epithelium of the pilosebaceous tract has three major keratin polypeptides in common with interfollicular epidermis (two basic components of mol wts 58,000 and 56,000 and one acidic polypeptide of mol wt 50,000); however, it lacks basic keratin polypeptides in the mol wt range of 64,000-68,000 and two acidic keratin-polypeptides of mol wts 56,000 and 56,500 and contains an additional characteristic acidic cytokeratin of mol wt 46,000. Another cytokeratin polypeptide of mol wt 48,000 that is prominent in hair-follicle epithelium is also found in nonfollicular epidermis of foot sole. Both epidermis and pilosebaceous tract are different from eccrine sweat-gland epithelium, which also contains two major cytokeratins of mol wts 52,500 and 54,000 (isoelectric at pH 5.8-6.1) and a more acidic cytokeratin of mol wt 40,000. A striking similarity between the cytokeratins of human basal-cell epitheliomas and those of the pilosebaceous tract has been found: all three major cytokeratins (mol wts 58,000; 50,000; 46,000) of the tumor cells are also expressed in hair-follicle epithelium. The cytokeratin of mol wt 46,000, which is the most prominent acidic cytokeratin in this tumor, is related, by immunological and peptide map criteria, to the acidic keratin-polypeptides of mol wts 48,000 and 50,000, but represents a distinct keratin that is also found in other human tumor cells such as in solid adamantinomas and in cultured HeLa cells. The results show that the various epithelia present in skin, albeit in physical and ontogenic continuity, can be distinguished by their specific cytokeratin-polypeptide patterns and that the cytoskeleton of basal-cell epitheliomas is related to that of cells of the pilosebaceous tract.     

Fine needle aspiration cytology of breast cylindroma in a woman with familial cylindromatosis: a case report

BACKGROUND: That sweat gland type tumors occur occasionally in the breast is not surprising, as the breast and cutaneous sweat glands are embryologically related. Cylindromas present most commonly as solitary and sporadic dermal nodules on the face and scalp. Cases of multiple cylindromas are dominantly inherited, and the neoplasms are referred to as "turban tumors" when multiple lesions cover the scalp. Primary cylindroma of the breast has been reported once in the past. To the best of our knowledge, the fine needle aspiration cytology of primary breast cylindroma and its occurrence in the setting of familial cylindromatosis have not previously been reported. CASE: A 59-year-old woman presented with an ill-defined left breast mass. She had a personal and family history of dermal cylindromas on the head and face. Fine needle aspiration cytology demonstrated small, uniform cells with oval nuclei and finely granular cytoplasm, with some cells arranged around conspicuous cylinders of dense, acellular material. Excisional biopsy was recommended to exclude adenoid cystic carcinoma. Tissue biopsy revealed a benign cylindroma arising in breast parenchyma. CONCLUSION: Fine needle aspiration cytology of cylindroma very closely mimics that of adenoid cystic carcinoma. Although extremely rare, primary breast cylindroma is another entity to be included in the cytologic differential diagnosis of bland, basaloid cells associated with globular, extracellular material, a finding most commonly associated with adenoid cystic carcinoma.     

Multipotent Nestin-Positive Stem Cells Reside in the Stroma of Human Eccrine and Apocrine Sweat Glands and Can Be Propagated Robustly In Vitro

Human skin harbours multiple different stem cell populations. In contrast to the relatively well-characterized niches of epidermal and hair follicle stem cells, the localization and niches of stem cells in other human skin compartments are as yet insufficiently investigated. Previously, we had shown in a pilot study that human sweat gland stroma contains Nestin-positive stem cells. Isolated sweat gland stroma-derived stem cells (SGSCs) proliferated in vitro and expressed Nestin in 80% of the cells. In this study, we were able to determine the precise localization of Nestin-positive cells in both eccrine and apocrine sweat glands of human axillary skin. We established a reproducible isolation procedure and characterized the spontaneous, long-lasting multipotent differentiation capacity of SGSCs. Thereby, a pronounced ectodermal differentiation was observed. Moreover, the secretion of prominent cytokines demonstrated the immunological potential of SGSCs. The comparison to human adult epidermal stem cells (EpiSCs) and bone marrow stem cells (BMSCs) revealed differences in protein expression and differentiation capacity. Furthermore, we found a coexpression of the stem cell markers Nestin and Iα6 within SGSCs and human sweat gland stroma. In conclusion the initial results of the pilot study were confirmed, indicating that human sweat glands are a new source of unique stem cells with multilineage differentiation potential, high proliferation capacity and remarkable self renewal. With regard to the easy accessibility of skin tissue biopsies, an autologous application of SGSCs in clinical therapies appears promising.     

Histomorphology of preorbital gland in territorial and non-territorial male blackbuck Antelope cervicapra, a critically endangered species

The preorbital gland is a specialized dermal gland of antelopes which plays an important role in territorial marking behavior and pheromonal communication. To our knowledge, there is little information available on the role of preorbital gland marks in Indian antelopes (blackbucks). Males are seen averting the gland during behavioural display and territorial marking but the functional aspect of this gland has not been examined. Hence, the aim of this study was to describe the histomorphology of the preorbital gland in territorial and non-territorial male blackbucks to determine its morphology and secretory function. The results showed that the preorbital gland is composed of modified sebaceous and apocrine glands. The apocrine gland is lined by simple cuboidal epithelial cells; the serous parts of the secretory products are often seen in the apical portions of the cells. The myoepithelial cells contain actin filaments lying on the basal membranes of the apocrine gland. There are some considerable histological changes in the presence of the sebaceous and apocrine glands in territorial males in comparison to non-territorial males. The following histological changes associated with occurrence of the sebaceous and apocrine glands have been observed in territorial and non-territorial male blackbucks: (1) increase of size of sebaceous and apocrine glands and (2) increase in density of sebaceous and apocrine glands in territorial males compared to non-territorial males. It is suggested that the higher development (i.e., size) and density of sebaceous and apocrine glands in territorial males could depend on hormone production (i.e., testosterone). Based on the histological observation and the role of sebaceous and apocrine glands in the preorbital gland supported by literature, it is possible to conclude that both territorial and non-territorial blackbuck males may produce pheromonal substances through preorbital gland (secretion) for olfactory communication.     

The skin of primates. XXXVI. The skin of the pigmy marmoset--Callithrix (Cebuella) pygmae

The pigmy marmoset — Callithrix (= Cebuella) pygmaea Spix — is the second detailed study of the members of the family Callithricidae. It is closely allied to the red-mantled tamarin — Saguinus (=Tamarinus) fuscicollis illigeri Spix — and shares some of its characteristics with both Prosimii and Anthropoidea. The epidermis and dermis contain moderate numbers of concurrent, melanotic melanocytes. The dermis is rich in elastin. Hair follicles grow in groups of three or four over the general body surface, and one apocrine gland is associated with each grouping. Arrectores pilorum muscles are well developed. On the ventral ulnar wrist are sinus hairs associated with apocrine glands. Most hair follicles have nerve end-organs around them that are reactive for acetylcholinesterase and alkaline phosphatase. There is a large aggregation of sebaceous glands in the suprapubic region. The large sebaceous glands in the eyelid, face, and external genitalia are surrounded by cholinesterasereactive nerves. Apocrine glands are found over most of the hairy skin except the brow, scalp and back; a large grouping of them is present in the sternal region. Only the secretory coils of apocrine glands in the external genitalia are invested with butyrylcholinesterase-rich nerves. Eccrine glands are confined to the volar surfaces of the pes and manus. They have dark cells with abundant glycogen and clear cells with neither glycogen nor PAS-reactive material. The nerves around the eccrine secretory coil are reactive only for acetylcholinesterase.     

Localization of sex steroid receptors in human skin

Sex steroid hormones are involved in regulation of skin development and functions as well as in some skin pathological events. To determine the sites of action of estrogens, androgens and progestins, studies have been performed during the recent years to accurately localize receptors for each steroid hormone in human skin. Androgen receptors (AR) have been localized in most keratinocytes in epidermis. In the dermis, AR was detected in about 10% of fibroblasts. In sebaceous glands, AR was observed in both basal cells and sebocytes. In hair follicles, AR expression was restricted to dermal papillar cells. In eccrine sweat glands, only few secretory cells were observed to express AR. Estrogen receptor (ER) alpha was poorly expressing, being restricted to sebocytes. In contrast, ERbeta was found to be highly expressed in the epidermis, sebaceous glands (basal cells and sebocytes) and eccrine sweat glands. In the hair follicle, ERbeta is widely expressed with strong nuclear staining in dermal papilla cells, inner sheath cells, matrix cells and outer sheath cells including the buldge region. Progesterone receptors (PR) staining was found in nuclei of some keratinocytes and in nuclei of basal cells and sebocytes in sebaceous glands. PR nuclear staining was also observed in dermal papilla cells of hair follicles and in eccrine sweat glands. This information on the differential localization of sex steroid receptors in human skin should be of great help for future investigation on the specific role of each steroid on skin and its appendages.     

The skin of primates. XXXIV. The skin of the golden spider monkey (Ateles geoffroyi)

The skin of the golden spider monkey (Ateles geoffroyi) has many histological and histochemical similarities to that of the woolly monkey (Lagothrix lagotricha) and howler monkey (Alouatta caraya); however, this monkey possesses certain peculiar properties such as large sebaceous glands, a combined distributional pattern of eccrine and apocrine sweat glands, and abundant alkaline phosphatase in the sebaceous glands, apocrine and eccrine sweat glands. In brief, the anatomical and histochemical properties of the skin of this animal are more similar to those of the howler monkey than to the woolly monkey. In addition, the skin of these three Ceboids falls phylogenetically between that of the Cercopithecoidea and Pithecoidea.     

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.     

Protein gene product 9.5-immunoreactive nerve fibres and cells in human skin

Summary Sections of human skin were processed according to the indirect immunofluorescence technique with a rabbit antiserum against human protein gene product 9.5 (PGP 9.5). Immunoreactivity was detected in intraepidermal and dermal nerve fibres and cells. The intraepidermal nerves were varicose or smooth with different diameters, running as single processes or branched, straight or bent, projecting in various directions and terminating in the stratum basale, spinosum or granulosum. The density of the intraepidermal nerves varied between the different skin areas investigated. PGP 9.5-containing axons of the lower dermis were found in large bundles. They separated into smaller axon bundles within the upper dermis, entering this portion of the skin perpendicular to the surface. Then they branched into fibres mainly arranged parallel to the epidermal-dermal junctional zone. However, the fibres en route to the epidermis traversed the upper dermis more or less perpendicularly. Furthermore, immunoreactive dermal nerve fibres were found in the Meissner corpuscles, the arrector pili muscles, hair follicles, around the eccrine and apocrine sweat glands and around certain blood vessels. Such fibres were also observed around most subcutaneous blood vessels, sometimes heavily innervating these structures. Numerous weakly-to-strongly PGP 9.5-immunoreactive cells were found both in the epidermis and in the dermis.     

Dermal cylindroma (turban tumor). Case report.

We present an unusual case of massive dermal cylindroma (turban tumor), occupying the entire scalpand forehead. It was treated by a total scalping procedure and skin grafting in two stages. Additional tumors of the face, neck, chest, shoulders, and back were excised and closed. The nose was treated by shoving and dermabrasion, similar to a rhinophyma. The lip was treated by dermabrasion. There has been no evidence of recurrence in the scalp which was treated by excision and grafting. There is now a papular quality of the skin over the nose and on the uppler lip, indicating that regrowth may occur. The etiology, pathology, and a review of the literature are presented.     

Effects of subepithelial fibroblasts on epithelial differentiation in human skin and oral mucosa: heterotypically recombined organotypic culture model

The stratified squamous epithelia differ regionally in their patterns of morphogenesis and differentiation. Although some reports suggested that the adult epithelial phenotype is an intrinsic property of the epithelium, there is increasing evidence that subepithelial connective tissue can modify the phenotypic expression of the epithelium. The aim of this study was to elucidate whether the differentiation of cutaneous and oral epithelia is influenced by underlying mesenchymal tissues. Three normal skin samples and three normal buccal mucosa samples were used for the experiments. Skin equivalents were constructed in four ways, depending on the combinations of keratinocytes (cutaneous or mucosal keratinocytes) and fibroblasts (dermal or mucosal fibroblasts), and the effects of subepithelial fibroblasts on the differentiation of oral and cutaneous keratinocytes were studied with histological examinations and immunohistochemical analyses with anti-cytokeratin (keratins 10 and 13) antibodies. For each experiment, three paired skin equivalents were constructed by using single parent keratinocyte and fibroblast sources for each group; consequently, nine (3 x 3) organotypic cultures per group were constructed and studied. The oral and cutaneous epithelial cells maintained their intrinsic keratin expression. The keratin expression patterns in oral and cutaneous epithelia of skin equivalents were generally similar to their original patterns but were partly modified exogenously by the topologically different fibroblasts. The mucosal keratinocytes were more differentiated and expressed keratin 10 when cocultured with dermal fibroblasts, and the expression patterns of keratin 13 in cutaneous keratinocytes cocultured with mucosal fibroblasts were different from those in keratinocytes cocultured with cutaneous fibroblasts. The results suggested that the epithelial phenotype and keratin expression could be extrinsically modified by mesenchymal fibroblasts. In epithelial differentiation, however, the intrinsic control by epithelial cells may still be stronger than extrinsic regulation by mesenchymal fibroblasts.     

Ultrastructural and immunocytochemical detection of keratins and extracellular matrix proteins in lizard skin cultured in vitro

The present study shows the localization of epidermal and dermal proteins produced in lizard skin cultivated in vitro. Cells from the skin have been cultured for up to one month to detect the expression of keratins, actin, vimentin and extracellular matrix proteins (fibronectin, chondroitin sulphate proteoglycan, elastin and collagen I). Keratinocytes and dermal cells weakly immunoreact for Pan-Cytokeratin but not with the K17-antibody at the beginning of the cell culture when numerous keratin bundles are present in keratinocyte cytoplasm. The dense keratin network disappears after 7-12 days in culture, and K17 becomes detectable in both keratinocytes and mesenchymal cells isolated from the dermis. While most epidermal cells are lost after 2 weeks of in vitro cultivation dermal cells proliferate and form a pellicle of variable thickness made of 3-8 cell layers. The fibroblasts of this dermal equivalent produces an extracellular matrix containing chondroitin sulphate proteoglycan, collagen I, elastic fibers and fibronectin, explaining the attachment of the pellicle to the substratum. The study indicates that after improving keratinocyte survival a skin equivalent for lizard epidermis would be feasible as a useful tool to analyze the influence of the dermis on the process of epidermal differentiation and the control of the shedding cycle in squamates.