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.

Extrafacial granuloma faciale: report of a case and response to treatment.

Granuloma faciale (GF) is a rather uncommon form of chronic vasculitis that infrequently involves extrafacial sites. Treatment of this disease is extremely challenging. We report a case of GF with extrafacial lesions and a unique response to treatment. The diseases that are clinical and histologic mimics of this disorder, as well as a review of various treatment modalities, are discussed.

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.

Cutaneous manifestations of alcohol abuse.

Alcohol consumption and abuse can have a variety of cutaneous manifestations. In addition to the well-recognized stigmata of the chronic alcoholic patient, even early abuse can result in distinctive skin changes or exacerbate existing cutaneous disorders. An accurate history of alcohol intake will facilitate recognition of these alcohol-induced cutaneous disorders and treatment resistance of dermatoses such as psoriasis as well as help decrease morbidity in surgical procedures. Familiarization with the spectrum of cutaneous manifestations of alcohol abuse and alcoholic liver disease can also allow for early detection and treatment in an attempt to minimize the medical consequences. We review the medical literature and discuss the spectrum of dermatologic disease associated with the use and abuse of alcohol.

Persistent Sweet's syndrome occurring in a child with a primary immunodeficiency.

Sweet's syndrome (SS) occurs most commonly in association with inflammatory or neoplastic disorders. Only rarely has it been associated with immunodeficiency disorders. We describe a child with a T-cell immunodeficiency who had a persistent neutrophilic dermatosis that was histologically and clinically consistent with SS. SS associated with immunodeficiencies may occur as a reaction to an underlying infection or a defect in immunoregulation. Such patients, however, may not be able to produce the classic fever and neutrophilia associated with SS. They may fail to respond to standard treatment for SS and may suffer a prolonged and persistent course.

Immunologic bullous diseases: blisters without a precipitating event.

Although the overall incidence of immunologic bullous diseases is comparatively low, they are nonetheless potentially lethal dermatologic disorders that occur most commonly in individuals age 55 and older. Thus familiarity with the signs, symptoms, and treatments will be valuable to the primary care physician. For bullous diseases in general, the challenge is to differentiate between those arising from immunologic rather than exogenous causes, such as drug-induced or drug-triggered pemphigus. Treatment goals include screening for associated malignancies, managing the lesions, and minimizing the morbidity and mortality associated with the disease. Collaboration with a dermatologist can aid in achieving these objectives.

Molecular staging of malignant melanoma: correlation with clinical outcome.

CONTEXT: For most solid tumors, the metastatic status of regional lymph nodes is the strongest predictor of relapse and survival. However, routine pathological examination of lymph nodes may underestimate the number of patients with melanoma who have nodal metastases. OBJECTIVE: To determine the clinical significance of a highly sensitive molecular assay for occult nodal metastases for the staging of patients with melanoma. DESIGN: A prospective cohort study of consecutive patients in which lymphatic mapping and sentinel lymph node (SLN) biopsy were performed on 114 melanoma patients with clinical stage I and stage II disease. The SLNs were bivalved, and half of each specimen was submitted for routine pathological examination. The other half was submitted for molecular detection of submicroscopic metastases using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase messenger RNA as a marker for the presence of melanoma cells. Patient follow-up averaged 28 months. SETTING: A major university-based melanoma referral center at a National Cancer Institute-designated cancer center. PATIENTS: A total of 114 patients with newly diagnosed cutaneous malignant melanoma who were at risk for regional nodal metastases. MAIN OUTCOME MEASURE: Melanoma recurrence and overall survival. RESULTS: Twenty-three patients (20%) had pathologically positive SLNs, and all of these patients were also RT-PCR positive. Of the 91 pathologically negative patients, 44 were RT-PCR negative and 47 were RT-PCR positive. There was a recurrence rate among 14 (61%) of the 23 patients who were both pathologically and RT-PCR positive and a recurrence rate among 1 (2%) of 44 patients who were both pathologically and RT-PCR negative. For patients who were upstaged by the molecular assay (pathologically negative, RT-PCR positive), there was a recurrence rate among 6 (13%) of 47 patients. The differences in recurrence rates and overall survival between the pathologically negative, RT-PCR-negative and pathologically negative, RT-PCR-positive patient groups were statistically significant (P= .02 for disease-free survival and for overall survival). In both univariate and multivariate regression analyses, the histological and RT-PCR status of the SLNs were the best predictors of disease-free survival. CONCLUSIONS: The use of an RT-PCR assay for detection of submicroscopic melanoma metastases in SLNs improved the prediction of melanoma recurrence and overall survival over routine pathological examination.

Uses of vitamins A, C, and E and related compounds in dermatology: a review.

Vitamins have been increasingly used as prophylactic and therapeutic agents in the management of skin disorders. The current literature is replete with studies that promote the potential benefits of these compounds and attempt to elucidate their mechanisms of action. We review the literature and discuss the roles, safety, and efficacy of vitamins A, C, and E and related compounds in cutaneous health and disease.

Lymphatic mapping and sentinel node biopsy in the management of high-risk melanoma.

We review sentinel lymph node biopsy in patients with high-risk melanoma. This method of selective lymphadenectomy provides valuable staging information about the regional lymphatics without the need of prophylactic complete lymph node dissection. Only patients with micrometastases are candidates for complete lymph node dissection. This avoids, in nearly 85% of patients, the morbidity of the more extensive procedure. In addition, sentinel lymph node-positive patients may qualify for adjuvant therapy protocols. Whether this surgical approach ultimately results in a survival advantage awaits the results of a National Cancer Institute-sponsored national multicenter trial.

Rosaceous lymphedema: a rare variant of a common disorder.

Rosaceous lymphedema is considered to be a rare and disfiguring variant of acne rosacea. Cases remain difficult to treat and can challenge afflicted patients both cosmetically and psychologically. We describe an unusual presentation of rosaceous lymphedema and review the differential diagnosis of persistent facial edema.

Selective lymphadenectomy in patients with Merkel cell (cutaneous neuroendocrine) carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous tumor with a propensity for local recurrence, regional and distant metastases. There are no well-defined prognostic factors that predict behavior of this tumor, nor are treatment guidelines well established. METHODS: Staging of patients with a new diagnosis of MCC was attempted using selective lymphadenectomy concurrent with primary excision. Preoperative and intraoperative mapping, excision, and thorough histologic evaluation of the first lymph node draining the tumor primary site [sentinel node] was performed. Patients with tumor metastasis in the sentinel node underwent complete resection of the remainder of the lymph node basin. RESULTS: Twelve patients underwent removal of 22 sentinel nodes. Two patients demonstrated metastatic disease in their sentinel lymph nodes, and complete dissection of the involved nodal basin revealed additional positive nodes. The node-negative patients received no further surgical therapy, with no evidence of recurrent local or regional disease at a maximum of 26 months follow-up (median 10.5 months). CONCLUSIONS: While the data are preliminary and initial follow-up is limited, early results suggest that sentinel lymph node mapping and excision may be a useful adjunct in the treatment of MCC. This technique may identify a population of patients who would benefit from further surgical lymph node excision.

Cancer of the skin in the older patient.

This article focuses on the common precancers and skin cancers in the older patient. The hazards of ultraviolet radiation are explained briefly in relation to photoaging and the development of skin cancer. The etiology, clinical appearance, histopathologic diagnosis, treatment, and follow-up for each type of cancer are reviewed thoroughly. It is hoped that early recognition and treatment by geriatric physicians will have a positive impact on the reduction of the morbidity and mortality associated with these cancers in the elderly.

Malignant melanoma: differential diagnosis of pigmented lesions.

The incidence of melanoma is rising globally despite increased awareness. Familiarity with the clinical signs and certain risk factors for melanoma can result in early recognition, and potentially influence outcome. Unfortunately, there are several other cutaneous tumors, both malignant and benign, that resemble melanoma, and may confuse and possibly delay the diagnosis. This paper discusses the clinical characteristics of melanoma and its most common pigmented simulators.

Bleomycin-mediated electrochemotherapy of metastatic melanoma.

BACKGROUND: Electroporation is a new technique that enhances the antitumor effects of chemotherapy by exposing cancerous tissues to pulses of electricity. When used in combination with conventional chemotherapy, the procedure is termed electrochemotherapy (ECT). The electric pulses increase cell membrane permeability and thus intracellular access. Electrochemotherapy has been shown to have potent antitumor activity in a number of in vitro studies, several animal models, and clinical trials with squamous cell carcinomas and basal cell carcinomas. OBJECTIVE: To report the effects of ECT in 5 patients with metastatic malignant melanoma. RESULTS: Twenty-three lesions of metastatic melanoma were treated with intralesional bleomycin sulfate followed by pulses of electricity. Pulses were delivered via caliper or needle electrodes placed around the tumor. Complete responses were observed in 18 tumors (78%) and partial responses were seen in 4 (17%). No responses were seen in lesions treated with either pulses or bleomycin alone. Vital signs were closely monitored during the procedure, and minimal side effects were noted. CONCLUSIONS: This is the first study that documents the antitumor effects of ECT in metastatic melanoma. Although not a cure, it may be an effective alternative to palliative surgery or irradiation in these patients.