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Notes: Differentiation within the nail unit was examined using a range of antikeratin monoclonal antibodies including the recently described antibody LHTric-1, specific to the acidic hair-type keratin Ha1. Keratinocytes of the nail matrix, nail bed and the digit pulp were characterized by different patterns of keratin expression. Nail matrix was the sole site of expression of Ha1, which colocalized in suprabasal matrix epidermis with epidermal keratins K1 and K10. Small amounts of K17 were found at the apex of the matrix in some cases. K6 and K16 were found where the epidermal surface folds forwards to become the ventral aspect of the proximal nail fold. The nail bed was distinguished by the absence of hair-type keratin Ha1 and the absence of markers of cornified epidermis and mucosal differentiation K1/K10 and K4/K13, respectively, while K6, K16 and K17 were detected. The basal keratin conformation marker, LH6, was expressed suprabasally throughout the nail bed. This complement of keratins exists in the nail bed in the absence of notable proliferative activity, and suggests a state of minimally developed differentiation which may be afforded by the physical or biological properties of the overlying nail. Keratins, K6, K16 and K17 were all found in the digit pulp in limited amounts, possibly in association with the epidermal component of the eccrine duct. The simple epithelial keratins, K7, K8 and K18, were found in small amounts in the specimens from younger individuals, mainly in epibasal cells of the apex of the matrix and in putative Merkel cells.

Notes: Epidermodysplasia verruciformis (EV) is a rare inherited condition in which there is widespread infection with human papillomavirus (HPV). Patients have a high risk of developing squamous cell carcinoma and Bowen's disease on sun-exposed sites. We describe a Jatnaican man with the typical clinical and histopathological features of EV. HPV 8·24 and a subtype of HPV 38, along with a novel HPV sequence most closely related to HPV 9 have been detected in his skin lesions. Although skin tumours are rare In black patients with EV and he has lived in a temperate climate most of his life, several of the lesions showed bowenoid atypia and he is at risk of developing invasive cutaneous malignancies.

Notes: Erythrokeratoderma (EK) variabilis is a heterogeneous group of diseases characterized by migratory erythematous patches and hyperkeratotic plaques. Mutations in connexin 31 have recently been found to underlie several cases of EK variabilis. We describe a Japanese girl with extensive lesions that appeared to be a form of EK variabilis, clinically resembling genodermatose en cocardes (Degos). Our patient had characteristic migratory rosette or target-like erythematous keratotic plaques with peripheral scaling in addition to relatively fixed keratotic plaques. Sequencing of the connexin 31 gene did not detect mutations. Skin biopsy showed parakeratotic hyperkeratosis with hypergranulosis. Immunohistochemically, suprabasal keratins, involucrin and profilaggrin were unequivocally expressed, while loricrin expression was greatly diminished and deiminated K1 was undetectable. Our results confirm aetiological heterogeneity in EK. The histological features suggest disruption of keratinocyte terminal differentiation at a very late stage.

Notes: A patient with localised heat urticaria is described. Tolerance of the skin to heat was produced by repeated exposure to hot water and complete symptomatic remission was accomplished.

Notes: The distribution pattern of the basement membrane components type VII collagen and laminin, was studied immunohistochemically in normal human head and neck tissues and in a series of benign and malignant tumours from the same site. Using monoclonal antibodies, a basement membrane containing type VII collagen and laminin could be demonstrated beneath the epithelial cell layer in 16 normal head and neck tissues from different localizations. Unlike type VII collagen, laminin was also abundantly present around blood vessels and muscle fibres.With respect to 42 squamous cell carcinomas studied, type VII collagen and laminin were present in basement membranes surrounding small and large tumour fields, independent of the tumour grade. Type VII collagen was demonstrated in the cytoplasm of tumour cells in 36% of the cases, while the antibody to laminin displayed a basement membrane staining pattern mainly. Both antibodies showed a staining gradient in more than half of the cases, with strong staining in the centre of the tumour and weakening of the staining towards the tumour periphery.In a series of 22 salivary gland tumours consisting of 19 pleomorphic adenomas and three adenoid cystic carcinomas, the distribution pattern of type VII collagen and laminin was very heterogeneous. Laminin was present in 17 and type VII collagen in 10 of 19 cases of pleomorphic adenoma, mostly scattered throughout the tumour fields. In the tumours positive for type VII collagen areas with little or no positivity were also found. A correlation between type VII collagen positivity and the presence of basal cell keratin 14 positivity was noticed in the majority of cases. The three adenoid cystic carcinomas studied displayed random positivity with the laminin antibody, whilst the antibody to type VII collagen showed little positivity in these cases.

Notes: The expression patterns of basement membrane components and keratin intermediate filament proteins were studied in normal human bronchial epithelium and 56 lung carcinomas using monoclonal antibodies to laminin, type VII collagen and the individual keratins 14, 16, 17 and 18. In normal lung, laminin and type VII collagen were present between the epithelium and the lamina propria of bronchi and bronchioles. Keratin 14 was expressed in the basal cells, keratin 17 in the basal and some suprabasal cells and keratin 18 in the columnar cells of the bronchi and bronchioles. Keratin 16 was not present in normal bronchial epithelium. Laminin was found in all subtypes of lung carcinoma, but type VII collagen was present only in squamous cell carcinomas, where it showed a reduction in expression with decreasing differentiation. Type VII collagen was not identified in adenocarcinomas, small cell carcinomas or carcinoids. Antibodies to basal cell keratins 14 and 17 also displayed positivity only in squamous cell carcinomas, although no correlation with the degree of differentiation could be observed. Keratin 16 appeared to be a marker of the squamous phenotype, rather than of hyperproliferation. The keratin 18 marker for columnar epithelial cells showed a reaction pattern opposite to that of the basal cell keratins, being extensively present in adenocarcinomas, small cell carcinomas and carcinoids, with less expression in squamous cell carcinomas. This study shows a correlation between the presence of type VII collagen and the basal cell keratins 14 and 17, and a negative correlation between these components and keratin 18. These findings are likely to be useful in identifying lung cancer subtypes.

Notes: The characteristic expression of keratins by keratinocytes is well documented. A typical ‘hyperproliferative’ profile of epidermal keratin expression occurs in psoriasis, wound healing and warts. This study analyses keratin expression in cutaneous lichen planus to determine abnormalities of differentiation occuring in this inflammatory disorder. Using a panel of monoclonal antibodies 28 samples (20 patients) were studied. The results showed that squamous differentiation was unaffected, with keratins K1 and K10 being expressed normally for the site sampled. The main abnormalities included extension of reactivity of the basal cell marker, LH8, into the suprabasal compartment. Keratin K17, usually restricted to adnexal structures, was variably expressed in the basal and suprabasal layers of the interfollicular epithelium of affected epidermis. Keratins K6 and K16, found suprabasally in hyperproliferative states, were detected both basally and suprabasally in all diseased samples. The keratin profile in lichen planus is analogous to the wound healing response. Suprabasal keratin K17 is found in psoriasis, wound healing and viral warts so the changes in keratin K17 may reflect hyperproliferative changes. It is likely that the changes in epidermal keratin expression are due to up-regulation of specific keratin genes by the production of cytokines and inflammatory mediators from the lymphocytic infiltrate typical of lichen planus.

Notes: Summary We report a large kindred in which a punctate palmoplantar keratoderma (PPK) is associated with malignancy, including Hodgkin's disease, renal, breast, pancreatic and colonic adenocarcinomas. The family was traced through four generations, and over 520 individuals were identified, of whom 49 had punctate PPK. The punctate PPK appeared to be inherited as an autosomal dominant trait with variable penetrance. Ten of the 43 adults (23%) with punctate PPK developed malignancies, and five of these developed before the age of 50. Of the 271 unaffected individuals, six (2%) have developed malignancies, one prior to the age of 50. The association of keratoderma and malignancy is discussed.

Notes: Summary We present a patient with oral lesions consistent with a diagnosis of oral psoriasis and discuss the relationship of oral and skin lesions in psoriasis.

Notes: Summary Keratinocyte differentiation in psoriasis was examined using a panel of monospecific monoclonal antibodies to keratins (K), including two recently dcveloped monoclonal antibodies raised to carboxy terminal peptides of K6 (LL020) and Kl6 (LL025). Keratinocytes from normal skin, untreated psoriatic plaques and non-lesional psoriatic skin, were cultured using multiple in vitro Systems. Timelapse cinephotography was used to measure the intermitotic time of normal and psoriatic keratinocytes in both low calcium-defined and serum-containing media. The intermitotic time did not differ significantly between psoriatic and normal keratinocytes. Keratin expression of psoriatic and normal keratinocytes in vitro was examined by both gel electrophoresis and immunocytochemistry. K6. K16 and Kl7 were detected suprabasally in all culture Systems in vitro, but only in interfollicular psoriatic epidermis in vivo. and not in normal skin. Small subpopulations of keratinocytes expressed simple epithelial keratins K7, K8, Kl8 and K19 in cultures on plastic Substrates, but these keratins were absent in skin equivalents of normal or psoriatic skin. No psoriasis-spesfic pattern of differentiation was found in vitro. As the K6 peptide antibody reacted with basal cells of normal skin. probably due to K5 cross-reactivity. K16 expression determined by LL025 was found to be the most sensitive indicator of the psoriatic state of differentiation. and this antibody is recommended for future work on psoriasis. Kl7 had a distinct pattern of tissue distribution in normal skin: Kl7. but not K16. was present in basal myoepithelial cells in sweat glands. and the dccp outer root shealh. but Kl 7 distribution parallelcd that ol'Klfi in suprabasal psoriatic epidermis. As keratins K6. Kid and Kl 7 are expressed in keratinocyte hyperproliferation. when high Ievels of certain cytokines are also expressed. the role of growth factors and regulalory nuclear transcription factors in the control of K6, K16 and Kl7 cxpression in psoriasis requires further study, in order to provide insight into the relationship between proliferation and differentiation.