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Background: Diagnosis of the underlying dermatosis in erythroderma is often difficult. The cause of increased mortality in erythroderma, particularly in relation to infection, is incompletely understood., Objective: We investigated the potential diagnostic use of circulating intercellular adhesion molecule-1 (cICAM-1), vascular cell adhesion molecule-1 (cVCAM-1), and E-selectin (cE-selectin) levels in erythroderma., Methods: cICAM-1, cVCAM-1, and cE-selectin were measured by enzyme-linked immunosorbent assay in 14 patients with erythroderma of known cause and in 17 control subjects. Levels were correlated with other markers of the inflammatory response., Results: In erythroderma median cICAM-1, cVCAM-1, and cE-selectin levels were significantly elevated, but no difference was found between values in patients with eczema and values in those with psoriasis. Circulating adhesion molecule levels did not correlate with erythrocyte sedimentation rate or total white blood cell count., Conclusion: cICAM-1, cVCAM-1, and cE-selectin were detectable in patients with erythroderma but were not differential diagnostic use in this study. Because in vitro these molecules may interfere with normal cell adhesion mechanisms, we speculate that they may contribute to the immunosuppressive state in these patients.

Background: Loss of p53 tumor suppressor function is a critical step in the development of diverse malignancies, including skin cancers in nonimmunosuppressed patients where UV-specific p53 gene mutations have been identified. In tumors associated with human papillomavirus (HPV), such as cervical carcinoma, p53 may be inactivated instead by binding to a viral oncoprotein., Objective: Our purpose was to examine the hypothesis that HPV may play an analogous role in the development of posttransplant skin cancer., Methods: p53 Immunoreactivity, suggestive of p53 gene mutation, was examined by immunocytochemistry. Oncogenic HPV DNA was detected by polymerase chain reaction., Results: Comparable p53 immunoreactivity was seen in skin tumors from both transplant and nontransplant patients. HPV DNA was not demonstrated in any tumor specimen., Conclusion: Our data do not implicate oncogenic HPV in posttransplant skin cancer. p53 Gene mutation, rather than HPV-induced p53 degradation, may be more significant in the development of these tumors.

Background: Posttransplant lymphoma is closely associated with Epstein-Barr virus (EBV) infection and appears to have a predilection for extranodal sites. We describe four cases of primary cutaneous posttransplant lymphoma., Objective: Our aim was to determine cell lineage and any possible association with EBV in each case of cutaneous lymphoma., Methods: Tumor tissue was examined by light microscopy, immunohistochemistry, nonisotopic in situ hybridization and polymerase chain reaction., Results: The data were consistent with a diagnosis of EBV-associated cutaneous B-cell lymphoma in three cases and cutaneous T-cell lymphoma not associated with EBV in one case. No patient with B-cell lymphoma had extracutaneous involvement during a mean follow-up of 3.9 years. The patient with cutaneous T-cell lymphoma died of cerebral involvement 9 months after initial presentation., Conclusion: These data suggest a possible role for EBV infection in the origin of cutaneous B-cell lymphoma in immunosuppressed patients.

Background: Vascular cell adhesion molecule-1 (VCAM-1) is an endothelial protein with adhesive properties for inflammatory cells including lymphocytes. Its role in skin disease and regulation in vivo are uncertain., Objective: Our purpose was to determine expression of VCAM-1 in normal and inflamed skin and the effect on this of the T-cell-derived cytokine interferon gamma (IFN-gamma)., Methods: VCAM-1 was detected immunohistochemically in frozen-section biopsy specimens of inflammatory dermatoses and skin tumors. Volunteers received intradermal IFN-gamma and underwent biopsy 2 hours to 6 days later., Results: In normal skin, VCAM-1 was present on perivascular dendritic cells and some follicular keratinocytes. In allergic contact dermatitis, atopic dermatitis, and psoriasis, VCAM-1 was variably upregulated on dermal endothelium and dendritic cells, but was most pronounced in lichen planus. IFN-gamma led to marked upregulation of endothelial and dermal dendritic cell VCAM-1., Conclusion: VCAM-1 may be involved in the pathogenesis of various skin diseases and in vivo, IFN-gamma is a potent modulator of its expression.

Background: Renal allograft transplantation is associated with an increased incidence of malignant melanoma. The development of excess melanocytic nevi may be an indicator of this risk., Objective: This study determines the prevalence of melanocytic nevi in children who have received renal allografts., Methods: Total and regional melanocytic nevi counts were made in 38 children (27 boys, 11 girls) with a renal allograft and in 38 individually age- and sex-matched healthy controls; counts were related to age, sex, skin type, and duration of immunosuppression., Results: There was a significant increase in the total number of nevi in the renal transplant group compared with the control group (p < 0.05), with most marked increases occurring on the back and at acral sites. A strong positive correlation between nevi count and duration of immunosuppression independent of age was observed (p < 0.005)., Conclusion: Excess numbers of melanocytic nevi occur in children with renal allografts. These patients constitute a risk group for malignant melanoma and require continued assessment.

Background: Epidermal dendritic cells (DCs) isolated from psoriasis possess greatly enhanced T lymphocyte-activating properties compared with DCs from normal skin, suggesting that DCs in psoriasis express surface antigens crucial for antigen presentation. These include beta 2-integrins and intercellular adhesion molecule (ICAM)-1., Objective: Our purpose was to determine DC phenotype in psoriatic compared with normal epidermis with respect to these molecules., Methods: Tissue sections were single labeled with a peroxidase antiperoxidase (PAP) immunohistochemical technique and double labeled where necessary with a combination of a PAP and an alkaline phosphatase-anti-alkaline phosphatase technique., Results: In psoriatic compared with normal skin, decreased numbers of DCs expressed CD1a (p less than 0.05), whereas increased numbers of DCs expressed class II major histocompatibility antigens (p less than 0.05). In normal skin positive staining for CD18 was not observed, whereas in psoriasis both CD1a+ and CD1a- DCs expressed beta 2-integrins, LFA-1 (CD11a/CD18), and gp 150/95 (CD11c/CD18). DCs in atopic dermatitis and lichen planus were also found to express beta 2-integrins. Neither MAC 1 (CD11b/CD18) nor ICAM-1 was observed on DCs., Conclusion: These data are consistent with either migration of dendritic antigen-presenting cells into the epidermis or in situ cytokine modulation of Langerhans cell phenotype in inflamed skin. Furthermore, they indicate that epidermal DCs in psoriasis and other cutaneous inflammatory diseases express molecules that are known to be crucial for Langerhans cell-driven T-cell activation in vitro.

We report the clinical and histopathologic features of 17 patients with orf or milkers' nodule infection. The majority were male, 12 to 65 years of age, and gave a history of contact with farm animals. Most lesions affected the hands or arms, ranged in size from 1 to 3 cm, and occurred on average 3 weeks after presumed exposure. On low-power examination the epidermis showed endophytic strandlike proliferations and the dermal papillae were distended by intense edema. There was massive capillary proliferation and dilation and a dense inflammatory infiltrate. High-power examination revealed epidermal viral cytopathic changes with inclusion bodies, clumping of keratohyalin, and cytoplasmic vacuolation that had a distinctive "spongiform" appearance within follicular structures. We conclude that orf and milkers' nodule infection have distinctive histopathologic features, and, in contrast to some previous reports, viral changes may frequently be found.

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.

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.

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.

A detailed examination of material from 10 cases of cutaneous endometriosis revealed a range of histopathologic features similar to those found within the uterine endometrium at each of the main phases of the menstrual cycle. However, there appeared to be a poor correlation between histologic appearance and menstrual stage. Recognition of these cyclic variations is important for the accurate diagnosis of cutaneous endometriomas.

Epidermal patterns of class II human lymphocyte antigen (HLA) expression in atopic and allergic contact dermatitis have been compared, using monoclonal antibodies recognizing each subregion. Expression of class II human lymphocyte antigens on keratinocytes has been confirmed in allergic contact dermatitis, while we have found them to be absent in atopic dermatitis. This finding argues that cell-mediated immune responses, possibly to epicutaneous contact with allergen, are not implicated in the pathogenesis of atopic dermatitis.

In this paper we look at the regional variation of Langerhans cell (LC) numbers in tissue sections between different sites in the same individual and identical sites in different individuals. We also looked at the reproducibility of identification of LC in tissue sections by their OKT6 reactivity. In this way we could assess the validity of comparative enumeration in random tissue sections. Stepped sections were obtained and stained by the OKT6 method. The slides were projected, the cells counted, and an image analysis system used to measure the length of basement membrane. In this way we could calculate the number of LC per millimeter of basement membrane. Our subjects were six age- and sex-matched volunteers. We found that the number of LC on the trunk was significantly lower than on any of the limbs. However, each individual had significant site variation of LC that was different for each one. This makes direct comparison of individual sections invalid and suggests that the most suitable control, when counting LC in lesional skin, is adjacent normal skin.

Aberrant expression of class II major histocompatibility complex (MHC) subregion antigens by keratinocytes was examined immunohistochemically in a range of cutaneous disorders. Although cell surface expression of human lymphocyte antigen (HLA)-DR was observed, HLA-DQ and HLA-DP were not expressed in any disorder investigated except for allergic contact dermatitis. Epidermal Langerhans cells expressed antigens of all three subregions on the cell surface. Differential expression of class II MHC subregion antigens may be related to tissue levels of gamma-interferon or to different functions of each subregion.

A technique involving modification of the routine paraffin embedding procedure that allows immunohistochemical examination of extracellular antigens by light microscopy is described. The method is thus suitable for routine diagnostic immunofluorescence studies, permitting reliable, reproducible immunolabeling of immunoglobulins and complement components usually not preserved by routine processing procedures. Immunoreactivity as measured by direct immunofluorescence and immunoenzymatic (peroxidase-antiperoxidase) histochemistry is comparable to results with fresh-frozen cryostat sections. Morphologic preservation is superior, however, and the processed material is suitable for routine hematoxylin-eosin staining.

Four highly sensitive monoclonal antibodies were assessed for their use in an immunoperoxidase technic on cutaneous sections. Three, B2, C23, and 2A1, were found to discriminate basal cell carcinomas (BCCs) from benign proliferative disorders of skin, and 2A1, a monoclonal antibody against the heavy chain component of class 1 human leukocyte antigens (HLA) for the first time directly demonstrated the absence of this structure from the malignant cell membrane. However, the deeper portions of hair follicles were also found to be unlabeled, and further study of benign follicular tumors which may histologically mimic basal cell carcinomas is suggested.