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A 59-year-old Caucasian housewife presented with a 2-year history of marked loss of tissue substance from the finger and toe pulps and the heel pads. There was no clinical evidence or history of urticaria or other inflammatory change. Investigations demonstrated a raised plasma cortisol secondary to a left adrenal adenoma. Skin biopsies showed abnormalities of dermal collagen, but no evidence of elastin destruction. This case presents an unusual variant of the cutaneous atrophy associated with Cushing's syndrome.

An in situ analysis of the mononuclear cell infiltrate found in association with a range of benign, premalignant, and malignant epidermal tumors is described. The predominant cell phenotype was that of the recently described immunoregulatory helper/inducer T lymphocyte. A large number of lymphocytes expressed antigens associated with cellular activation, suggesting an ongoing immunologic response by the host against the tumor, although evidence of in situ proliferation of these cells was lacking. These findings suggest that the infiltrate found in association with cutaneous tumors does not represent passive accumulation of lymphocytes from the circulation but rather an active antitumor response.

The clinical and histopathologic responses to intradermal platelet-activating factor (PAF-acether) in atopic subjects, without evidence of atopic dermatitis are documented. An immediate acute wheal and flare reaction was observed in all volunteers. Histopathologically, the reaction was characterized by a predominantly neutrophilic response, which was seen at 30 minutes and was maximal at 4 hours. Eosinophils were observed in the infiltrate as early as 30 minutes after injection, and were maximal by 12 hours. The specific PAF-acether antagonist BN52063 antagonized the acute flare response to intradermal PAF-acether but had little effect on cellular recruitment at the site of injection.

The antibody G71 is a murine monoclonal antibody directed against an antigen in the basement membrane zone of many human epithelia. Ultrastructurally it is located in the lamina lucida. The epitope is carried on glycoprotein components with molecular weights of 160, 125 and 115 kilodaltons. The authors examined the immunohistochemical expression of G71 antigen, using a standard indirect immunoperoxidase technique, in benign and malignant tumors derived from the epidermis. G71 staining was consistently absent or reduced around basal cell carcinomas (n = 44). In contrast, G71 was present at the basement membrane zone of squamous cell carcinomas (n = 18) and was also frequently expressed within the cytoplasm and on the cell surface of the malignant keratinocytes. The staining pattern of G71 at the basement membrane zone was essentially normal in keratoacanthomas (n = 10), solar keratoses (n = apart from foci of attenuation. In both seborrheic keratoses and intraepidermal squamous 13), seborrheic keratoses (n = 6), and intraepidermal squamous cell carcinomas (n = 8), cell carcinomas cell-surface and cytoplasmic staining were inconstant features. In conclusion, there appears to be a specific defect of G71 antigen expression in basal cell carcinomas.

Alteration in the major histocompatibility complex (MHC) antigen expression by cutaneous tumours may enable them to escape host defence mechanisms and to invade surrounding tissue. Immunohistochemical studies in a wide range of epidermally derived tumours demonstrated expression by keratinocytes of the class II molecule HLA-DR in squamous cell carcinoma (SCC) (2 of 8 cases) and keratoacanthoma (KA) (2 of 7 cases). Additionally, HLA-DP and DQ were expressed by single cases of SCC and KA, although, unlike the widespread distribution of DR, DP and DQ, were only present on keratinocytes adjacent to the inflammatory infiltrate. Therefore, keratinocytes in cutaneous tumours, like carcinoma cells of the colon and breast, may express class II MHC antigens during tumour growth. Beta-2-microglobulin (B2M), an invariant MHC class I marker, was absent in all cases of basal cell carcinoma. Variable loss of B2M was observed in squamous cell carcinoma, Bowen's disease and actinic keratoses, suggesting reduced B2M expression by dysplastic cells. However, the variability in B2M staining both between and within diagnostic categories restricts it's immunodiagnostic usefulness.

In a study of the direct effects of interferon-gamma (IFN-gamma) on normal human skin, healthy adult male volunteers received either 3 micrograms (n = 4) or 30 micrograms (n = 9) of recombinant IFN-gamma administered intradermally over 3 days. Biopsies were taken on day 6 and histopathological examination of fixed paraffin-embedded sections from sites which had received 30 micrograms IFN-gamma revealed a moderate perivascular lymphohistiocytic dermal infiltrate with mast cells. Immunophenotyping of 5 microns cryostat sections demonstrated that 3 micrograms IFN-gamma induced keratinocyte HLA-DR expression in the absence of any significant infiltrate. More intense keratinocyte HLA-DR expression was produced by 30 micrograms IFN-gamma in all specimens, with HLA-DP concurrently expressed in three biopsies. The ratio of CD4:CD8 cells within the infiltrate was approximately 3:1. CD1 + cells within the epidermis were markedly depleted by 30 micrograms IFN-gamma, while CD1-labelled cells were observed in the dermal perivascular infiltrate. Intradermal IFN-gamma induces similar immunopathological changes to those observed in many of the inflammatory dermatoses.

The mononuclear infiltrate found in a variety of inflammatory dermatoses was characterized by a predominance of T helper-inducer lymphocytes (THi), CD4+/CD45RA-/CD45RO+, a population of cells responsible for maintaining and promoting immune reactions. Only small numbers of T-suppressor-inducer lymphocytes (TSi), CD4+/CD45RA+/CD45RO-, cells responsible for inducing CD8 suppressor-effector cells to 'down regulate' immune reactions, were seen. The predominance of CD4+ THi lymphocytes was common to all dermatoses studied and suggests a common final pathway in chronic cutaneous inflammation, irrespective of initial causative factors.

A 31-year-old woman with long-standing renal disease, treated with systemic steroids and azathioprine, developed progressive skin ulceration and subcutaneous nodules. A diagnosis of cryptococcosis was established after histological examination of a cutaneous lesion and confirmed by culture of the organism from the biopsy specimen. A detailed description of the histology and ultrastructure of the cutaneous lesion is presented. Treatment with parenteral amphotericin B and 5-fluorocytosine resulted in dramatic resolution of the skin lesions.

Activity of the enzyme acid alpha-naphthyl acetate esterase (ANAE) in T lymphocytes and histiocytes in cutaneous tissue sections of patients with histologically confirmed lichen planus, chronic discoid eczema and mycosis fungoides was compared with results obtained using an in situ immunohistochemical technique employing an antiserum against the human T lymphocyte surface antigen (HTLA). In lichen planus and chronic discoid eczema, most of the cells in the cutaneous infiltrate exhibited both positive ANAE activity and the presence of HTLA. In mycosis fungoides, cells identified as T lymphocytes by the presence of HTLA often showed no ANAE activity. ANAE activity appears to be a useful marker of T lymphocytes in benign cutaneous infiltrates but is less reliable in labelling abnormal T cells.

A case of malignant bronchial carcinoid with multiple cutaneous metastases is reported. Despite the extremely aggressive behavior of the disease and the presence of multiple hepatic metastases, the patient did not exhibit the usual clinical features of the carcinoid syndrome. The relevance of the finding of elevated 24-hour urinary vanillylmandelic acid levels in patients with carcinoid tumors is discussed.

An ultrastructural study of lesional skin from 4 subjects with hyperkeratosis lenticularis perstans (Flegel's disease) demonstrated variable numbers of lamellar bodies of normal size and architecture within cells of the stratum granulosum and the upper stratum spinosum. Their characteristic lamellate inclusions were frequently observed within the intercellular spaces. These observations suggest that the lamellar bodies are qualitatively normal in Flegel's disease.

Experiments were performed to examine the hypothesis that the surface expression of HLA-DR by keratinocytes in certain disease states is conferred by the activity of gamma-interferon, derived from dermal activated T lymphocytes. In vivo studies revealed a spatial relationship between keratinocyte HLA-DR expression and activated T lymphocytes within the dermal inflammatory infiltrate. In vitro studies confirmed that gamma-interferon can induce keratinocyte synthesis of HLA-DR. These results suggest that, in vivo, gamma-interferon produced by activated T lymphocytes induces keratinocyte HLA-DR synthesis and expression.

Localized persistent pigmented macules and plaques due to a chronic form of pigmented purpuric dermatitis are described in forty-two patients. The designation 'lichen aureus' for this eruption can be justified because of the striking yellowish or bronze-like colour assumed by many of the lesions. The lower legs were the commonest sites but other body regions can be affected also. Histologically lichen aureus differs from other pigmented purpuric dermatoses in the density of the lichenoid tissue reaction and the marked accumulation of pigment-containing macrophages. Recently developed endothelial cell markers have been studied in selected cases.

The presence of natural killer (NK) cells, as defined by reactivity with the monoclonal antibodies Leu 7, Leu 11 and Leu 19 was assessed in the inflammatory infiltrate around epidermal neoplasms and compared with findings in a range of inflammatory dermatoses. HNK-1+ (Leu 7) cells were present in a wide range of malignant, pre-malignant and inflammatory disorders. Cells positive for the more specific NK cell antigens CD16 (Leu 11)/NKH-1 (Leu 19) had a distribution mainly restricted to cases of squamous cell carcinoma (five of nine) and keratacanthoma (three of seven). The variability in distribution between the different antibodies suggests that the majority of cutaneous HNK-1+ cells are not NK cells, but represent cross-reacting T lymphocytes. The qualitatively distinct distribution of CD16+ and NKH-1+ cells around some cases of squamous cell carcinoma and keratoacanthoma is of interest but their absence from a number of such cases calls into question a specific effector role for natural killer cells in these squamoproliferative tumours.

Adrenomedullary function in patients with atopic dermatitis was assessed by measurement of plasma levels of catecholamines (adrenalin and noradrenalin) and cyclic AMP in response to the stimuli of standing after lying supine, and a 5-min infusion of histamine in the standing position (i.e. histamine plus standing). Plasma clearance of adrenalin was examined by measurement of plasma catecholamine and cyclic AMP levels following a 15-min intravenous infusion of adrenalin in the supine position. Resting plasma levels of adrenalin, cyclic AMP and noradrenalin were not statistically different in atopic patients and normal controls. Standing or intravenous infusion of histamine in the standing position caused a rise in plasma catecholamine levels. Plasma adrenalin, cyclic AMP and noradrenalin levels in response to these stimuli and the rate of clearance of exogenous adrenalin from the plasma were not significantly different in patients with atopic dermatitis and in normal subjects.

Immunohistological studies have been performed on tissues from various dermatological conditions using two monoclonal antibodies, RFD1 and NA1/34. These reagents were used to determine whether antigen expression restricted to interdigitating cells (RFD1+) and Langerhans' cells (NA1/34+) in normal tissues might occur together on dendritic cells involved in cutaneous inflammatory reactions. The results presented demonstrate that in psoriasis, allergic contact dermatitis and atopic dermatitis a proportion of the inflammatory dendritic cells express both antigens.

An immunoelectron microscopic method was developed using T6 antiserum in an immunoperoxidase technique to label the dendritic cells of the epidermis in mycosis fungoides (MF). The technique allows simultaneous identification of intracellular Birbeck granules and T6 membrane positivity. Ultrastructural examination of the epidermal infiltrate of MF, using this method, confirmed the T6-positive nature of Langerhans cells and indeterminate cells. All Sézariform and mature lymphocytes were T6-negative and a small population of T6-negative histiocytic cells were also observed.

Tissue from the cutaneous metastases of bronchial carcinoid was examined. Fine argyrophil secretory granules were demonstrated in the cytoplasm of the abnormal cells which showed positive labelling with neuron-specific enolase. Ultrastructural studies revealed numerous electron-dense membrane bound neuro-secretory granules, 50-300 nm in diameter. Other characteristic features included inter-digitating pseudo pod-like processes (up to 2 mu in size) in the cytoplasmic membrane, perinuclear filaments, a well-defined Golgi zone and numerous large mitochondria.

The development of a cutaneous nodule at the site of friction of spectacles has been discussed by several authors. In all but one case the lesion occurred behind the ears. The only previous report of this acquired tumour occurring on the nose is that of Farrell & Wilson (4). It is suggested that this problem is relatively common and most frequently presents when mistaken for basal cell epithelioma or when identified in medical personnel. A further six cases of this neglected tumour occurring on the nose are described.

Two kindreds manifesting an unusual form of pachyonychia congenita are described. Clinical involvement consists of nail dystrophy, which tends to improve with age, and moderate palmoplantar hyperkeratosis. In addition, all affected members show a characteristic pattern of cutaneous hyperpigmentation, which resembles macular amyloidosis around the neck and waist, but which confers a dappled appearance to the axillae, popliteal fossae, thighs, buttocks, and lower aspect of the abdomen. With advancing age the pigmentation fades. Histologic and ultrastructural examination of the hyperpigmented skin has revealed pigmentary incontinence and deposition of amyloid within the papillary dermis. These features appear to constitute a distinct variant of pachyonychia congenita.

An immunoelectronomicroscopic method has been employed to demonstrate in situ the T lymphocyte nature of the dermal and epidermal infiltrates to mycosis fungoides. A specific antiserum to the human T lymphocyte surface antigen (HTLA) was used in an indirect reaction with a peroxidase labeled anti-immunoglobulin. After histochemically revealing the peroxidase activity, T cells were easily identified by the deposition of electron dense material on the cytoplasmic membrane. Counterstaining with uranyl acetate and lead citrate enabled us morphologically to observe the maturity of infiltrating T lymphocytes and to identify Sézary cells and other cells such as eosinophils in the infiltrate. Our results confirm the T cell nature of the dermal infiltrate in mycosis fungoides and show that the epidermal infiltrate of cells forming Pautrier micro-abscesses are predominantly T lymphocytes.

A patient with Pagetoid reticulosis has been investigated using standard transmission electron microscopy and an immunohistochemical technique for identifying T lymphocytes in situ in light and electron microscopy. Our results indicate that the majority of the cells in the underlying dermal infiltrate are T lymphocytes but that only very few T lymphocytes are found in the extensive epidermal infiltrate. Ultrastructurally the majority of the abnormal cells in the epidermis are of histiocytic origin.

The prevalence of lactase deficiency in British adults is unknown. Examination of the distribution of lactase activities in single and multiple biopsies of jejunum indicated that 0.8 U/g wet weight was a suitable cut-off point to separate lactase deficient patients from others. One hundred and fifty white British adults were selected, none of whom had significant intestinal disease and all of whom had normal histopathology of a jejunal biopsy and normal activities of other disaccharidases measured in the biopsy. The prevalence of lactase deficiency in this group was 4.7%. In contrast, 15 of 20 non-white adults were lactase deficient. Lactase deficiency was found in only three of 36 patients investigated because of diarrhoea after gastric surgery, and in 16 of 200 patients with irritable bowel syndrome (8%). As the prevalence of lactase deficiency is no higher in irritable bowel syndrome than in 'normal' individuals, lactase deficiency clearly is not a predisposing factor for irritable bowel syndrome in white British adults although the two conditions may occasionally coexist.

Beta 2-microglobulin (beta 2M) is part of the HLA molecule, and is found on the cell surface of human nucleated cells. In certain skin tumors, malignant change has been associated with a loss of this surface beta 2M, indicating a possible diagnostic value for this marker. At present beta 2M is best identified in paraffin-embedded tissue by means of a triple-layer peroxidase-antiperoxidase technique, using mammalian polyclonal antisera. Recently a polyclonal antiserum against human beta 2M has been produced in chickens. Because of the phylogenetic differences between the species, the resulting antiserum is likely to recognize more epitopes on the beta 2M and show greater sensitivity than antisera raised in mammalian species. To confirm this hypothesis, the avian antiserum was compared to both mammalian polyclonal (rabbit) and monoclonal (mouse) antibody in vitro. beta 2M fixed to plastic surfaces combined with more avian than mammalian antibody. Furthermore, insolubilized chicken antibody could bind more secondary antibody-horseradish peroxidase conjugate than could insolubilized mammalian antibody, thus showing even greater enhancement with this system. Immunohistochemical analysis of these systems confirmed that the chicken strategy has greater sensitivity, and can be used in an indirect system with consequent reduction in nonspecific background activity. It is the most suitable technique for the investigation of the distribution of beta 2M in paraffin-embedded tissue.