Cross-sectional associations between cutaneous viral infections and regulatory T lymphocytes in circulation.

BACKGROUND: Cutaneous viral infections and immune suppression are risk factors for some forms of nonmelanoma skin cancer; however, their interrelationship is poorly understood. OBJECTIVES: To examine cross-sectional associations between cutaneous viral infections and circulating forkhead-box P3 (FOXP3)-expressing T-regulatory (Treg) cells, suppressive cells that dampen effective antitumour immunity. MATERIALS AND METHODS: Blood, eyebrow hair (EBH) and skin swab (SSW) samples were collected from 352 patients 60 years and older undergoing skin screening, without prevalent skin cancer, while participating in an ongoing prospective cohort study of cutaneous viral infections and skin cancer. DNA corresponding to 98 cutaneous human papillomavirus (HPV) types and five human polyomaviruses (HPyV) was assessed in EBH and SSW. Distinct classes of circulating Treg-cell subpopulations were defined by flow cytometry including cutaneous lymphocyte antigen (CLA) and CCR4high Treg cells, both previously associated with cutaneous diseases. Age- and sex-adjusted associations between circulating T-cell populations and infection were estimated using logistic regression. RESULTS: Total Treg-cell proportion in peripheral blood was not associated with ß HPV or HPyV infection. However, the proportion of circulating CLA+ Treg cells was inversely associated with γ HPV EBH infection [odds ratio (OR) 0·54, 95% confidence interval (CI) 0·35-0·84]. Interestingly, circulating Treg cells expressing markers indicative of antigen activation (CD27- CD45RA- FOXP3+ CD4+ ) were also inversely associated with γ HPV infection in SSW (OR 0·55, 95% CI 0·30-0·99) and EBH (OR 0·56, 95% CI 0·36-0·86). CONCLUSIONS: Inverse associations between circulating Treg cells and γ HPV infection suggest that localized viral infection may promote immunosuppressive cell migration into skin.

Staged margin control techniques for surgical excision of lentigo maligna.

For melanoma in situ (MIS) arising in chronically photodamaged skin (a.k.a. lentigo maligna, LM), the preferred treatment remains surgical excision. Yet, the standard 5-mm margins of excision recommended for other subtypes of MIS have proven insufficient for LM, due to the its indistinct borders. In this report, authors review specialized surgical techniques for the treatment of LM that focus on meticulous assessment of peripheral margins prior to closure (staged margin control) conducted with analysis of either frozen or permanent histologic sections. Techniques utilizing permanent sections include variations of the ''square'', ''perimeter'', and ''contoured'' excisions, and recurrence rates with these techniques are reportedly low based on short-term follow-up. Similarly, Mohs micrographic surgery (MMS) has been reported to be effective in LM, with recurrence rates generally less than 1% over three-five years of follow-up. In order to simplify margin assessment for MMS, many investigators have begun to rely on intraoperative immunohistochemistry (IHC) to identify melanocytes in frozen sections, and MART-1 is surrently the preferred immunostain for this purpose. Other methods of IHC are currently under investigation. Regardless, surgical methods that employ this degree of margin assessment offer superior cure rates compared to standard excision, and should be seriously considered when encountering patients with LM. Total peripheral margin assessment using staged excisions and analysis of permanent sections appears to be a simple and effective alternative to MMS, especially for institutions that prefer examination of permanent sections to frozen sections.

Sentinel lymph node micrometastasis and other histologic factors that predict outcome in patients with thicker melanomas.

BACKGROUND: In patients with melanoma, lymph node staging information is obtainable by the surgical techniques of lymphatic mapping and sentinel lymph node (SLN) biopsy. Although no survival benefit has been proven for the procedure, the staging information is useful in identifying patients who may benefit from further surgery or adjuvant therapy. Currently, however, it is not being recommended for patients with thick melanomas (> 3-4 mm). The risk of hematogenous dissemination is considered too great in these patients. Recent studies indicate, however, that a surprising number of patients with thick melanomas become long-term survivors, and the lymph node status may be predictive. None of the conventional microscopic features used to gauge prognosis in patients with melanoma have proven helpful in distinguishing the survivors with thick melanoma from those who will die of their disease. OBJECTIVE: Our purpose was to evaluate the influence of SLN histology and other microscopic parameters on survival of patients with thick melanomas. METHODS: A computerized patient database at the Cutaneous Oncology Clinic at H. Lee Moffitt Cancer Center was accessed to obtain records on patients with melanomas thicker than 3.0 mm (AJCC T3b). A retrospective analysis was conducted with attention paid to histologic variables, sentinel node status, and survival. Survival curves were constructed with the Kaplan-Meier method, and a Cox-Mantel rank testing was used to establish statistical significance. RESULTS: Between 1991 and 1999, 201 patients were diagnosed with melanoma thicker than 3.0 mm, and 180 were alive at an average follow-up of 51 months. Of these, 166 were alive without disease. The mean overall and disease-free survival rates were 78% and 66%, respectively. There was a statistically significant difference in disease-free survival (3-year) between SLN-positive and SLN-negative patients (37% vs 73%, respectively; P =.02). The overall survival (3-year) for the SLN-positive patients was less than the node-negative patients (70% vs 82%), but it was not statistically significant (P =.08). The disease-free survival for patients with ulcerated lesions was less than for nonulcerated lesions (77% vs 93%, P =.05). None of the other histologic parameters studied, including Breslow thickness, Clark level, mitotic rate, or regression, had an influence on the overall or disease-free survival in this group of patients with thick tumors. CONCLUSIONS: The results indicate that the SLN node status is predictive of disease-free survival for patients with thick melanomas. A surprising number of patients in the study were free of disease after prolonged follow-up. None of the histologic features of the primary tumor were helpful in predicting outcome, except for ulceration. SLN biopsy appears to be justified for prognostic purposes in patients with thick melanomas.

Purpuric irritant contact dermatitis induced by Agave americana.

The sap of Agave americana, a popular ornamental plant, may cause irritant contact dermatitis. This rare eruption is typically vesiculopapular; however, a new purpuric variant with evidence of leukocytoclastic vasculitis has recently been reported. We report an additional case of a purpuric eruption associated with severe constitutional symptoms further supporting a possible vasculitic component. Both cases resulted from direct exposure to sap propelled by a chainsaw. We speculate that oxalic acid crystals, which are recognized systemic toxins, are embedded in the skin with resulting oxalism, which may result in vascular damage.