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Cutaneous gamma-delta (gamma delta) T-cell lymphoma is rare. Eleven cases have been reported to date including four cases of mycosis fungoides (MF), two of pagetoid reticulosis and five of pleomorphic cutaneous T-cell lymphoma (CTCL). We report three further cases of cutaneous gamma delta T-cell lymphoma; one of MF, one of a pleomorphic CTCL and one of a subcutaneous T-cell lymphoma. Combined data suggest that although cutaneous gamma delta T-cell lymphomas do not appear to comprise a single clinicopathological entity, they may be associated with aggressive clinical behaviour and a poor prognosis.

Variegate porphyria (VP) first presenting in old age is uncommon and should raise the possibility of an underlying precipitating cause. This case report documents VP in an elderly woman with a liver tumour.

p53 immunoreactivity was examined in 132 cutaneous non-melanoma tumours from renal transplant recipients and in 114 histologically matched specimens from immunocompetent individuals. Skin lesions examined included 52 viral warts, 50 dysplastic keratoses, 51 intraepidermal carcinomas (IEC), 50 invasive squamous cell carcinomas (SCC) and 43 basal cell carcinomas (BCC). Overall, 51% (51/101) pre-malignant skin lesions and 45% (42/93) non-melanoma skin cancers (NMSC) showed p53 immunoreactivity, with extensive (> 50% cells positive) p53 staining in 27% (27/101) of pre-malignant and 20% (19/93) of malignant lesions. 17% (9/52) viral warts showed p53 immunoreactivity, but this was limited to focal or basal p53 staining. p53 immunoreactivity in all tumours was less in transplant than in non-transplant patients and this reached statistical significance for SCCs (p = 0.03).

Antibody diversification by somatic hypermutation occurs by the introduction of nucleotide substitutions in and around the rearranged Ig V gene segments. Several characteristics of the process suggest that the introduction of mutations is linked to Ig gene transcription. Since there is a connection between mutation and repair with indications that both processes might show linkage to transcription, we asked whether defects in a component of the transcription factor TFIIH which lead to an inability to carry out nucleotide excision repair also affect somatic hypermutation. A PCR strategy was devised that required small samples of peripheral blood and enabled us to monitor hypermutation of a single, abundantly used VH gene. However, the results showed that in xeroderma pigmentosum patients (complementation group D), somatic hypermutaton appears to take place unaffected as regard both extent and distribution.

This double-blind, parallel group study compared a 2-week course of terbinafine 250 mg/day with a 4-week course of itraconazole 100 mg/day. A total of 190 patients were enrolled, of whom 129 were evaluable for efficacy. At week 8, 69% of patients treated with terbinafine were classified as effectively treated (mycological cure, and clinical assessment total score < or = 2) vs. 67% in the itraconazole group. At week 16, however, the rating for effective treatment increased to 71% of the terbinafine group, but decreased to 55% of the itraconazole group. This difference was of borderline statistical significance (P = 0.06). The results of this study demonstrate that both drugs can be used safely, and that 2 weeks' treatment with terbinafine 250 mg daily is as effective as 4 weeks' treatment with itraconazole 100 mg daily, but with fewer long-term relapses.

p53 gene mutation appears to play an important role in the development of systemic lymphoma, and may be associated with tumour progression. Its role in cutaneous lymphoma is currently unknown. We examined p53 expression in 55 biopsies of cutaneous lymphoma, including patch-, plaque- and tumour-stage mycosis fungoides (MF), T- and B-cell lymphoma and lymphomatoid papulosis. Strong, homogeneous p53 expression, thought to correlate most closely with p53 gene mutation, was seen in only three cases; in a plaque and tumour from a patient with tumour-stage MF, in plaque-stage MF in a patient without tumours, and in one case of CD30+ large-cell anaplastic lymphoma. These data suggest that p53 gene mutation is not a critical step in the development of the majority of primary cutaneous lymphomas.

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.

Expression of the p53 tumor suppressor gene product was determined in keratoses and skin cancers associated with psoralen photochemotherapy (PUVA). An immunocytochemical study was employed using CM-1 (polyclonal) and Do-1 (monoclonal) antibodies to human wild-type p53. Thirty-two cutaneous lesions and 20 perilesional PUVA-irradiated skin biopsies were examined from 7 patients, all of whom had received more than 200 PUVA treatments and/or a cumulative UVA dose of greater than 1000J/cm2 as treatment for widespread plaque psoriasis. p53 immunoreactivity was seen in 7 of 15 squamous cell carcinomas (46.7%), 5 of 8 dysplastic keratoses (62.5%) and in no basal cell carcinomas or benign keratoses. The overall prevalence of p53 immunoreactivity in 46.2% of malignant or dysplastic PUVA-associated skin tumors is similar to that previously found by our group in comparable skin tumors from the general population. Most patients with lesions showing positive p53 immunoreactivity had, however, been exposed to additional risk factors before receiving PUVA therapy. p53 gene sequencing of PUVA-associated non-melanoma skin cancer (NMSC) may clarify whether p53 mutation contributes to the development of these tumors and whether this relates to PUVA therapy or prior carcinogen exposure.

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.

Cutaneous necrobiotic xanthogranuloma is rare and closely resembles widespread necrobiosis lipoidica. It is important to recognize this skin disorder because of its strong association with paraproteinemia and, in some cases, with a hematologic malignancy. We describe two patients with necrobiotic xanthogranuloma who are unusual in that they had no periorbital involvement, a feature previously believed to be diagnostic of this condition.

Expression of the tumour suppressor protein, p53, was determined in 77 cutaneous melanocytic lesions, and in five lymph node metastases from malignant melanoma, in an immunohistochemical study employing CM-1, an antiserum raised against recombinant human p53 protein. Because wild-type p53 protein is rapidly degraded in normal cells, p53 immunoreactivity suggests the presence of an abnormally stable p53 protein. This may occur through either post-translational mechanisms or gene mutation. A highly significant correlation was found between p53 immunoreactivity and malignancy in melanocytic lesions (P < 0.0001). Overall, p53 immunoreactivity was observed in 63% of tumour specimens examined, but not in benign melanocytic naevi, although occasional foci of weak nuclear p53 immunoreactivity were observed in a minority of dysplastic naevi and a solitary Spitz naevus. A significant correlation was also found between strong p53 immunoreactivity and malignant melanomas associated with a poor prognosis (P = 0.008). These data suggest an important role for p53 tumour suppressor protein in the biology of human cutaneous malignant melanoma.

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.

It has been suggested that patients with chronic superficial Trichophyton rubrum infection have defective cellular immunity to dermatophyte antigens. This may be due to a selective anergy to dermatophyte antigens or reflect the activity of dermatophyte-derived lymphocyte inhibitory factors. To explore these possibilities, we assessed lymphocyte transformation to a variety of recall antigens, including a cytoplasmic and exoantigen preparation of Trichophyton rubrum in 15 patients with chronic dermatophyte infection and 15 age- and sex-matched positive controls. In a duplicate set of experiments, autologous serum was replaced by heat-inactivated fetal calf serum. In addition, the direct effect of Trichophyton rubrum extracts on lymphoproliferation was assessed in vitro. Comparable lymphocyte transformation to each recall antigen was observed in patients and controls. Moreover, we found no evidence for a circulating dermatophyte-derived lymphocyte inhibitory factor in sera from patients with chronic superficial infection. A direct inhibitory effect of Trichophyton rubrum on lymphocyte proliferation to recall antigens was observed, however, at protein concentrations of > 10 micrograms/ml (exoantigen preparation) and > 25 micrograms/ml (cytoplasmic preparation). This inhibitory effect was rapidly reversible, not associated with loss of cell viability and maximal when added within 24 h of antigen to cultured lymphocytes. Class II MHC antigen HLA-DR, a surface marker of T-cell activation, was observed on inhibited lymphocytes co-cultured with antigen, suggesting the primary target for the inhibitory effect in vitro is the lymphocyte rather than the antigen-presenting cell.(ABSTRACT TRUNCATED AT 250 WORDS)

Cutaneous malignant melanoma was diagnosed in three patients suffering from human immunodeficiency virus (HIV) infection. Staging at presentation inversely correlated with absolute CD4 count. In addition, a notably sparse lymphocytic inflammatory response to the melanoma was observed in two cases. Established data on melanoma in non-HIV immunosuppressed patients suggests a poor prognosis for melanoma in HIV disease.

Seven cases of spontaneous epidural abscess are reviewed. Three patients had posterior abscesses and no evidence of vertebral body osteomyelitis. These patients had excellent outcomes with laminectomies and antibiotics. Because of significant vertebral destruction, two patients with vertebral osteomyelitis required posterior fixation after laminectomy. Two other patients with vertebral osteomyelitis had complete destruction of the vertebral body and required anterior decompression and fusion in addition to posterior fixation. In the four patients with vertebral osteomyelitis, morbidity was high, reflecting their age and significant medical problems. This review supports the contention that medically stable patients with posterior epidural abscesses can be treated with laminectomy and antibiotics with little risk of progressive instability. The proper surgical treatment of anterior epidural abscesses secondary to osteomyelitis requires knowledge about the amount of destruction of the supporting columns, the amount of neural compression secondary to the purulence, and the patient's general medical condition.

Localized granuloma annulare is the commonest form of a granulomatous dermatosis characterized by flesh coloured or violaceous papules often arranged in rings. Several rare atypical variants are also reported including disseminated or generalized, subcutaneous and perforating types. There is a predilection for females and a documented association with diabetes mellitus in some cases. Recently it has been suggested that atypical variants of granuloma annulare might be associated with the acquired immunodeficiency syndrome (AIDS). We describe a patient presenting with extensive generalized granuloma annulare in whom an underlying diagnosis of Human Immunodeficiency Virus (HIV) disease was confirmed.

Two cases are reported of generalized pustular psoriasis complicated by profound alterations in pulmonary capillary permeability. Several features suggest the involvement of cytokines in the pathogenesis of this condition.

The demonstration of HLA-DR on human acrosyringium has led to the suggestion that eccrine epithelium, through its interaction with certain molecules, might play an active role in epidermal immune responses. An immunohistochemical study was undertaken to identify the antigenic profile of acrosyringium in normal skin and following the intradermal administration of a T-lymphocyte-derived cytokine, interferon gamma (IFN-gamma). Acrosyringium in normal skin, in contrast to interappendageal epidermis, was found to lack CD1a+ Langerhans cells. However, antigens CD36 (OKM5) and L1 (MAC387) were uniquely expressed by keratinocytes immediately adjacent to the distal portion of acrosyringium. Constitutive expression of each class II MHC antigen, namely HLA-DR, DP and DQ was observed on luminal acrosyringial cells. EMB11 antigen (CD68), a mononuclear cell determinant, was similarly expressed on acrosyringial epithelium in normal skin. Following intradermal administration of IFN-gamma, intercellular adhesion molecule-1 (ICAM-1) (CD54) was induced on acrosyringial epithelium and the expression of HLA-DR was intensified. A range of other markers including CD3, CD4, CD8, CD11a, CD11b and CD15 were not expressed by acrosyringium either in normal skin or after administration of IFN-gamma. Expression of antigens associated with cell-mediated immune mechanisms on acrosyringium is consistent with the hypothesis that it may have an immunological role in epidermal immune responses.

The development of cutaneous proliferative lesions following renal transplantation has been well documented in the literature. Those lesions most commonly seen include viral warts, actinic keratoses and basal-cell and squamous-cell carcinomata. More recently it has been suggested that melanocyte proliferation, both benign and malignant, may follow renal transplantation, probably as a result of immunosuppression. We report the case of an identical twin who developed numerous benign melanocytic naevi following renal transplantation; no such proliferation of naevi occurred in his identical sibling.

This investigation attempts to determine whether increased survival time seen when the F98 glioma model is treated with boron neutron capture therapy (BNCT) is a result of inhibition of tumor growth caused by radiation-induced alterations in endothelial cells and normal tissue components. This indirect effect of radiation has been called the tumor bed effect. A series of tumor-bearing rats was studied, using a standardized investigational BNCT protocol consisting of 50 mg/kg of Na2B12H11SH injected intravenously 14 to 17 hours before neutron irradiation at 4 x 10(12) n/cm2. Ten rats, serving as controls, received no treatment either before or after tumor implantation. A second group of 10 rats was treated with BNCT 4 days before tumor implantation; these animals received no further treatment. The remaining group of 10 rats received no pretreatment but was treated with BNCT 10 days after implantation. Histological and ultrastructural analyses were performed in 2 animals from each group 17 days after implantation. Survival times of the untreated control animals (mean, 25.8 days) did not differ statistically from the survival times of the rats in the pretreated group (mean, 25.5 days). The rats treated with BNCT after implantation survived significantly longer (P less than 0.02; mean, 33.2 days) than the controls and the preirradiated animals. Tumor size indices calculated from measurements taken at the time of death were similar in all groups. These results indicate that, with this tumor model, BNCT does not cause a tumor bed effect in cerebral tissue. The therapeutic gains observed with BNCT result from direct effects on tumor cells or on the peritumoral neovascularity.

A CD 344 rat glioma model currently used to investigate boron neutron capture therapy (BNCT) was used to demonstrate an increased survival rate after thermal neutron irradiation enhanced by administration of 10B-enriched polyhedral borane, Na2B12H11SH. To investigate the possible effects of BNCT on normal and tumor microvasculature, we subjected animals to sublethal neutron irradiation with and without intravenous injection of 50 mg/kg of enriched 10B and performed histological and ultrastructural analyses. In the rats that did not undergo tumor transplantation, minimal detectable morphological changes in the microvasculature of the central nervous system were observed after treatment, both in the immediate posttreatment phase and at 10 months. Light microscopy of cerebral cortex and caudate nucleus showed normal cytoarchitecture with no evidence of vessel occlusion, hyalinization, thickening, or reactive gliosis. Electron microscopy demonstrated that the junctional complexes of the endothelial cells, the basal lamina, and the perivascular glia were comparable in both treated and control animals. In those animals examined at 18 months, pathological membrane-bound clusters of electron-dense vesicles were seen in pericytes. In the rats implanted with gliomas, vascular proliferation with evidence of breakdown of the blood-brain barrier and vasogenic edema occurred. In the irradiated animals, we noted increased peritumoral edema 3 days after treatment. At seven days, both increased peritumoral edema and necrosis were noted in the rats treated with BNCT. These observations show that the normal microvasculature of the central nervous system tolerates BNCT at the treatment parameters used in our experimental model; the progressive edema and necrosis found in the peritumoral region after BNCT indicate a pathological endothelial response.