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Intraoral sebaceous hyperplasia. Diagnostic criteria.

Surprisingly little is understood about the physiologic and pathologic processes that involve intraoral sebaceous glands. Neoplasms are rare. Hyperplasia of these glands is undoubtedly more common, but criteria for the diagnosis of intraoral sebaceous hyperplasia have not been established. These lesions are too often misdiagnosed as large "Fordyce granules" or, when very large, as sebaceous adenomas. On the basis of a series of 31 nonneoplastic sebaceous lesions and on published data, the following definition is proposed: intraoral sebaceous hyperplasia occurs when a lesion, judged clinically to be a distinct abnormality that requires biopsy for diagnosis or confirmation of clinical impression, has histologic features of one or more well-differentiated sebaceous glands that exhibit no fewer than 15 lobules per gland. Sebaceous glands with fewer than 15 lobules that form an apparently distinct clinical lesion on the buccal mucosa are considered normal, whereas similar lesions of other intraoral sites are considered ectopic sebaceous glands. Sebaceous adenomas are less differentiated than sebaceous hyperplasia.

Adenoma↗

Skin retinoid concentrations are modulated by CYP26AI expression restricted to basal keratinocytes in normal human skin and differentiated 3D skin models.

Cellular levels of all-trans retinoic acid (RA) are meticulously regulated utilizing an array of systems to balance uptake, biosynthesis, catabolism, and efflux transport. Metabolic transformation of all-trans RA to 4-hydroxylated RA appears to be primarily catalyzed by the cytochrome P450 (CYP) 26AI. Analysis of monolayer cultures of normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts by quantitative real-time PCR and reverse transcription-PCR revealed no basal levels of CYP26AI mRNA expression, whereas specific transcripts were detectable following addition of 10(-6) M all-trans RA. Immunofluorescence and Western blot analysis showed a weak expression of CYP26AI in NHEK, which was increased by stimulation with all-trans RA. Using a newly developed peptide antibody, we further examined the localization of CYP26AI expression in normal skin and three-dimensional (3D) skin models. In contrast to cell culture monolayers where CYP26AI was only weakly detectable, strong constitutive expression of CYP26AI in vivo and in organotypic culture was found to be restricted to basal epidermal keratinocytes, as well as eccrine sweat glands and sebaceous glands. These studies verify the capacity of human skin to metabolize RA, although substantial differences exist in CYP expression between normal skin and 3D skin models compared to monolayer cultures. Complex metabolic processes that maintain retinoid homeostasis may therefore be better studied in model systems more closely resembling in vivo skin. In light of our prior studies documenting the functional activity of RA metabolites, expression of CYP26 in the sebaceous gland epithelium supports the suggestion that altered RA metabolism may be involved in the pathogenesis of acne.

Blotting, Western↗

[Muir-Torre syndrome. Diagnostic criteria and review of the literature].

We report on a 63-year-old female patient with Muir-Torre syndrome (MTS). In the course of this disease two carcinomas of the colon, a kerato-acanthoma and multiple sebaceous gland tumours, including four sebaceous carcinomas, appeared. This case is thought to be a hereditary form as one of daughters was also found to have a sebaceous epithelioma. MTS is a mostly autosomal-dominant disease with the association of sebaceous gland tumours and internal carcinomas. As the malignant tumours only show slight aggressiveness the prognosis is quite favourable. Oral isotretinoin therapy was successfully used for the inhibition of sebaceous gland proliferation. A narrower definition is presented and an updated survey of the published cases is given. Furthermore, the histopathologic peculiarities of sebaceous gland tumours, especially of sebaceous gland carcinomas, are discussed and compared to sebaceous gland tumours not connected with MTS. A total number of 100 of the 135 published cases of MTS were included and analysed regarding sebaceous gland tumours and other skin tumours. The data on internal carcinomas were taken from the work of Cohen et al. (1991) and 11 current cases were added.

Adenocarcinoma↗

Loss of p21(WAF1) compartmentalisation in sebaceous carcinoma compared with sebaceous hyperplasia and sebaceous adenoma.

AIMS: Regulation of cell cycle progression is a fundamental control process, linked to cellular differentiation and apoptosis in normal tissues. p21(WAF1) is a nuclear protein that regulates cell cycle progression. p21(WAF1) can be transcriptionally upregulated by p53, but may be activated independently of p53-for example, during terminal differentiation. Loss of topological control of p21(WAF1) expression is an early feature of malignancy in the colorectal system. Similar to the colonic mucosa, sebaceous glands contain cells that are constantly going through a process of cell division, differentiation, and cell death. This study investigated the expression of p53, p21(WAF1), and the proliferation marker Ki67 in normal sebaceous glands, sebaceous adenoma, sebaceoma, and sebaceous carcinoma. METHODS: Serial sections were stained with monoclonal antibodies to p21(WAF1), p53, and Ki67 (MIB1) using standard immunohistochemical techniques. RESULTS: In normal sebaceous glands, p21(WAF1) positive cells were only seen within the differentiating compartment, which was spatially distinct from the cycling peripheral Ki67 positive cells. In sebaceous adenoma and sebaceoma, topological control was maintained, with the distribution of markers being similar to that seen in normal sebaceous glands. Loss of topological control of markers of cellular control was seen in sebaceous carcinoma only. This contrasts with colonic tumours, in which loss of p21 compartmentalisation is seen in adenomas at an early stage of tumour progression. CONCLUSION: This work confirms the hypothesis that the dysregulation of cell cycle progression is an important process in the development of malignancy within sebaceous glands, although loss of topological control was seen only in sebaceous carcinoma.

Adenocarcinoma, Sebaceous↗

Benign lymphoepithelial lesion of the parotid gland with sebaceous differentiation.

The salivary duct system in the setting of chronic sialadenitis is predisposed to undergo a variety of cellular modifications. This report documents a rare type of metaplasia of a parotid benign lymphoepithelial lesion. Epimyoepithelial islands showing focal sebaceous differentiation and pure sebaceous cell nests in addition to their usual histologic appearance were noted throughout the lesion. The possible pathogenesis is discussed through a review of the literature.

Adult↗

Dimorphic immunohistochemical staining in ocular sebaceous neoplasms: a useful diagnostic aid.

PURPOSE: We studied whether patterns of immunostaining in formalin-fixed, paraffin-embedded tissue could help to distinguish between sebaceous neoplasms of the eyelid and other eyelid neoplasms. METHODS: We applied antibodies to human milk fat globule-1 (HMFG1), cytokeratins (PKK1 and MNF116), epithelial membrane antigen (EMA) and carcino-embryonic antigen (CEA) to normal eyelid tissue and to a range of sebaceous lesions of the eyelid; these included sebaceous hyperplasia, sebaceous adenoma and sebaceous epithelioma, in addition to well to poorly differentiated sebaceous carcinoma. RESULTS: The central and peripheral cellular components of normal sebaceous glands and neoplastic sebaceous lesions showed a distinctive dimorphic staining pattern with the antibody panel used. The central foamy 'sebaceous' cells expressed HMFG1 and EMA, but not PKK1 or MNF116, whereas the smaller, peripheral basal and ductal cells expressed PKK1 or MNF116 but not HMFG1 or EMA. CEA expression in sebaceous cells was unhelpful diagnostically. CONCLUSION: Normal sebaceous glands and all sebaceous neoplasms show a dimorphic cell population that can be identified using a small panel of antibodies on formalin-fixed, paraffin-embedded tissue. This distinctive staining pattern can be assessed retrospectively, even in small biopsies, and largely removes the need for fat stains on frozen sections to differentiate sebaceous lesions from other ocular neoplasms. The results also support the suggestion that ocular sebaceous neoplasms arise from a common stem cell, rather than from either sebaceous or basal/ductal cells.

Adenocarcinoma, Sebaceous↗

Immunohistochemical staining for androgen receptors: a sensitive marker of sebaceous differentiation.

Androgen receptors (AR) are present in normal skin being localized to the basal and differentiating cells of the sebaceous gland, and as such, sebaceous glands are androgen sensitive tissue. Androgen receptor expression was examined in 43 sebaceous neoplasms including 8 sebaceous carcinomas, 22 sebaceous adenomas, 12 specimens showing sebaceous hyperplasia, and 1 sebaceous epithelioma, as well as in 14 squamous cell carcinomas, 2 clear cell acanthomas, and 35 basal cell carcinomas. Epithelial membrane antigen (EMA) expression was also examined in all of the sebaceous neoplasms. All specimens were fixed in formalin and embedded in paraffin. Diffuse positive nuclear androgen receptor antibody immunohistochemical staining was observed in all samples of sebaceous neoplasms, whereas approximately 60% of basal cell carcinomas showed only focal positivity for nuclear androgen receptor immunoreactivity. Clear cell acanthomas and squamous cell carcinomas were uniformly negative. Whereas all sebaceous neoplasms exhibited immunoreactivity for androgen receptors, the staining pattern was more marked in the nuclei of seboblasts and differentiating sebocytes in the adenomatous, hyperplastic, and epitheliomatous lesions than in the nuclei of the less differentiated sebaceous carcinoma cells. All the sebaceous neoplasms except for sebaceous carcinomas exhibited immunoreactivity for EMA. In the sebaceous carcinomas, EMA staining was absent in the most poorly differentiated specimen, but with increasing differentiation, the carcinomas became immunoreactive to EMA. We have shown that the nuclei of sebaceous neoplasms, including sebaceous gland carcinomas, show immunoreactivity for androgen receptors (AR), that immunohistochemical staining for the presence of AR may be a reliable marker of sebaceous differentiation, and that the AR may be a better marker of sebaceous differentiation than EMA, particularly in poorly differentiated sebaceous carcinomas.

Biomarkers↗

Demodicosis of ophthalmic concern.

Hair-follicle mites are the only metazoan organism commonly found in the pilosebaceous components of the eyelid of man. Our study showed that Demodex folliculorum in all stages is found in the small hair follicles and the eyelash hair follicles. This species, in adult and immature forms, consumes epithelial cells, produces follicular distension and hyperplasia, and increases keratinization leading, in eyelashes, to cuffing consisting of keratin and lipid moieties. Demodex brevis (in all stages) is present in the eyelash sebaceous glands, small hair sebaceous glands, and in the lobules of the meibomian glands. Adults and immature forms consume the gland cells in all of these loci and, when infestations are heavy, can affect the formation of the superficial lipid layer of the tear film coacervate. Comparative studies of demodicids from man and other mammals suggest that keratinization, hyperplasia, distension, and melanocyte aggregation may be even more extensive if large populations of D. folliculorum build up in the follicles of the eyelid. Large populations of D. brevis may destroy the glandular cells, produce granuloma in the eyelid, and plug the ducts of the meibomian or sebaceous glands. Further studies may incriminate either or both species, in conjunction with microorganisms, as transfer agents or synergists, or both, in producing ocular disease in man. Prevention and control of these mites must await experimental studies with infested laboratory animals (such as the squirrel monkey, Saimiri sciureus). These mites are probably most vulnerable during transfer stages, when they leave their glandular or follicular habitats.

Eyelashes↗

Morphology of the intermandibular gland of the Lesser mouse deer, Tragulus javanicus.

The morphology of the intermandibular gland of the Lesser mouse deer (Tragulus javanicus), which plays an important function in marking area and territory and in the reproductive behaviour of the animal, was examined using immunohistochemistry, lectin histochemistry and scanning electron microscopy. The gland was composed of sebaceous and apocrine glandular material. Sebaceous glands occupied a greater area of the total gland and consisted of many large lobules with polyhedral cells having a pale cytoplasm. The sebaceous gland, being holocrine, possessed no special secretory ducts. The apocrine gland was lined by cuboid cells and the secretory products were often seen in the apical portions of the cells. Myoepithelial cells contained actin filaments lining the basal membranes of the apocrine gland and were surrounded by nerve fibres which immunostained with protein gene product 9.5. The secretion of the gland appears to be a mixture of larger amounts of lipid material from sebaceous glands, and glycoconjugates secreted by both sebaceous and apocrine glands. Lectin histochemistry detected these as galactose, N-acetyl-D-galactosamine, N-acetyl-D-glucosamine, D-mannose and D-glucose. The male gland was larger in size and contained more N-acetyl galactosamine and N-acetyl glucosamine in its secretion than the gland of the female. This implied the presence of sexual differences in secretions in the intermandibular gland of the Lesser mouse deer.

Animals↗

Steatocystoma multiplex: anatomic reevaluation, electron microscopy, and autoradiography.

Histologic and electron-microscopic features of steatocystoma multiplex were investigated. Specimens from 25 patients (8 females, 17 males) were serially cut and three-dimensional drawings constructed. Steatocystoma multiplex is a nevoid sebaceous duct and sebaceous gland tumor, originating from sebaceous follicles, but is not a dermoid tumor. One pilary unit continuously produces vellus hairs, which are trapped in the cystic cavity or in the pilary canal (trichostasis). Steatocystoma multiplex is connected to the epidermis by a straight or meandering epithelial cord, the remnant of the follicular infundibulum. This infundibulum is a more or less solid strand, often containing sebocytes or sebaceous lobulelike structures. A lumen, partly present in a few areas of the cord, is filled with cellular debris of keratinocytes, corneocytes, sebocytes, or trapped hairs. Steatocystoma multiplex has electron-microscopical features similar to the sebaceous duct and sebaceous glands of sebaceous follicles. The 3H-thymidine labeling index of the cyst wall with or without sebaceous acini is lower than in sebaceous follicles. Steatocystoma multiplex suppurativum, characterized by spontaneous rupture of the cyst, inflammation and scarring, mimics acne conglobata with hidradenitis-suppurativa-like lesions as seen in the acne triade or tetrade.

Adolescent↗

Meibomian keratoconjunctivitis.

We evaluated, dermatologically and ophthalmologically, 26 patients who had chronic blepharitis (meibomitis); we also investigated 26 age- and sex-matched controls. All of the blepharitic patients had an abnormality of sebaceous gland function ranging from seborrhea sicca to seborrheic dermatitis or acne rosacea, suggesting a generalized sebaceous gland dysfunction that included the meibomian glands. Sebaceous gland abnormalities most frequently involved the cool areas of the face or scalp. Stagnation of the meibomian glands presumably caused a defect in the tear lipid layer; this resulted in an unstable tear film that produced superficial punctate keratopathy. The break-up time was much lower in these patients than in controls. The break-up time returned to normal or super-normal levels when fresh meibomian secretions were expressed into the tear film. The superficial punctate keratopathy had the characteristics of those seen in conditions with a known unstable tear film and not of those experimentally produced by staphylococcus toxin.

Adult↗

Sebaceous adenitis in the Akita: clinical observations, histopathology and heredity.

Ninety-seven pure-bred Akitas were examined clinically and histologically for sebaceous adenitis. The diagnosis was established histologically in 23 Akitas by demonstrating an inflammatory reaction targeted against the sebaceous glands or a reduction in the number of glands. The clinical course of sebaceous adenitis in the Akita was similar to that seen in other breeds. The first skin lesions occurred mainly on the dorsal midline and ears. Compared with the Poodle, the age at first onset of the disease was more variable and the hair loss affected mainly the undercoat. The progression of sebaceous gland destruction varied between dogs and was not seen in all cases. Because bud-like sebaceous gland proliferation could be identified, it seems that regeneration of the sebaceous glands may occur. An autosomal recessive inheritance appears to be possible. Apart from a genetic background, immune-mediated factors possibly influence the onset and course of sebaceous adenitis.

Animals↗

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.

Antigens, CD↗

The presence of nitric oxide synthase in the mammary glands of lactating rats.

Our objective was to show the presence of nitric oxide synthase (NOS) in the mammary glands of lactating rats and to determine the role that nitric oxide plays in lactation of humans. We used the nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase reaction and immunostaining on fresh frozen breast tissue obtained from lactating Wistar rats (13-18 wk old, 320-380 g, 3-4 d after parturition, first pregnancy). The breast tissues positive for NADPH diaphorase staining were the mammary gland, muscle, sebaceous gland, epidermis, and endothelium of the lactiferous ducts and blood vessels. These findings corresponded to tissues that were NOS-immunoreactive. The NOS detected in the mammary glands was the constitutive NOS. The finding of positive anti-NOS immunoreactivity and of positive NADPH diaphorase activity in the cells of the rat mammary glands leads us to conclude that nitric oxide is synthesized in mammary glands of rats. The high nitric oxide activity in the human breast was previously reported by measuring the total concentration of nitrite plus nitrate, biopterin, and neopterin in human milk. These results suggest that nitric oxide plays a role in the secretion of human breast milk.

Animals↗

Is sebosuppression by cimetidine an antiandrogenic effect?

By using the Syrian hamster ear model it is shown that cimetidine inhibits cell proliferation in the sebaceous gland. Furthermore, the S phase of sebaceous gland cells is lengthened and the number of labelled cells still in contact with the basal lamina of the sebaceous gland 6 days after isotope application related to the total number of labelled sebaceous gland cells is reduced. The effect of cimetidine is absolutely identical with that of cyproterone acetate, but is quite different from that of the nonhormonal sebosuppressive agent benzoyl peroxide.

Androgen Antagonists↗

[Ectodermal dysplasia: a heterogenic deviation].

The 'problem' of ectodermal dysplasia is discussed in conjunction with a case report and a review of the literature. In a range of hereditary disorders all ectodermal structures can be effected in a variable way: reduction of the amount of hair, sweat glands and sebaceous glands, and a complete or partial anodontia of the deciduous and permanent dentition with malformation of the erupted teeth.

Adult↗

Disulphide reaction staining for the identification of integumental elastic fibres.

Based on specific methods (Sippel-APM-chromotropic acid technique; IC3-PE-maleimide fluorescence reaction) and skin samples of four domesticated mammals (dog, cattle, horse, pig), disulphide groups were demonstrated in the elastic component of the basement membrane of the epidermis, the elastic fibre system of the dermis, the elastic components of the connective tissue sheath of hair follicles, apocrine tubular glands, and sebaceous glands, and of the connective tissue surrounding the cutaneous muscle. The results are discussed regarding the relation of this reaction staining to the presence of microfibrils (fibrillin) in the elastic fibres.

Animals↗

Inherited systemic amyloidosis (Finnish type): ultrastructure of the skin.

Ultrastructural study of skin biopsies from two patients suffering from inherited systemic amyloidosis (Finnish type) showed amyloid deposits between epidermal basal cells and dermal fibroblasts. Amyloid was seen on the epithelial side of the fibroblasts, and material resembling basal laminae was embedded in the aggregates of amyloid. Also amyloid deposits were found adjacent to other cells with a basal lamina such as epithelial cells of the sweat glands or sebaceous glands, Schwann cells, capillary endothelial cells, and even smooth muscle cells in the dermis. Amyloidogenetic interaction of cells with a basal lamina and fibroblasts is suggested and the potential role of structural glycoproteins in the genesis of amyloid is discussed.

Adult↗