Pseudocarcinomatous hyperplasia involving the ear from gout: a diagnostic pitfall.

The ear is a characteristic location for deposition of uric acid in patients with gout. Pseudocarcinomatous hyperplasia has not been described in this location. We report three patients with tophaceous gout on the ear whose biopsies exhibited epidermal hyperplasia mimicking squamous cell carcinoma, in order to call attention to this potential diagnostic pitfall.

Histopathology of the red lunula: new histologic features and clinical correlations of a rare type of erythronychia.

The lunula is the semi-lunar shaped area seen at the proximal aspect of the nail unit. It is the most distal aspect of the nail matrix that can be visualized through the transparent nail plate. The term red lunula describes erythema that partially or completely replaces the normal white color of the lunula. Red lunulae have been associated with a number of dermatologic and systemic conditions. However, the etiology and histopathology of the red lunula have not been characterized. We report a case of red lunulae of the fingernails in an adult male. Histopathologic examination revealed an increased density of benign-appearing and mildly dilated vascular channels present in the superficial papillary dermis of the nail matrix. To our knowledge, this is the first report of distinct pathologic findings seen on histologic examination of a red lunula. The increased vascularity of the lunula seen microscopically correlates with the clinically observed red color. These findings raise the possibility that systemic or local factors are responsible for angiogenesis within the nail unit in disorders associated with the red lunula.

Improvement in peripheral blood disease burden in patients with Sézary syndrome and leukemic mycosis fungoides after total skin electron beam therapy.

BACKGROUND: There is a paucity of effective therapies for patients with Sézary syndrome and advanced mycosis fungoides with peripheral blood involvement. Total skin electron beam (TSEB) radiation therapy is an extremely effective skin-directed therapy for these patients, but, until recently, it was thought not to signifcantly affect the peripheral blood malignant T-cell population. OBJECTIVE: We conducted this study to determine if TSEB has therapeutic effect on the peripheral blood in patients with advanced mycosis fungoides and Sézary syndrome. METHODS: All patients on stable medication regimens seen in our photopheresis facility who received TSEB therapy between January 2008 and October 2011 at Temple University Hospital, Philadelphia, PA, were analyzed retrospectively for improvement in the peripheral blood, as documented by flow cytometry. RESULTS: Six of 11 patients achieved 50% or greater decrease in their peripheral blood malignant T-cell population after TSEB therapy, for an overall response rate of 55%. Within the group of patients who had a response in the skin, 67% also had a response in the peripheral blood. LIMITATIONS: This analysis is limited in 3 ways. First, the sample described is small. Second, the results may be confounded by the fact that each patient was on other systemic therapies in addition to TSEB, albeit stable pre-existing regimens. The time interval between completion of TSEB therapy and repetition of flow cytometry was not standardized among patients, which may result in an underestimation of the overall response to TSEB therapy. CONCLUSION: In patients with advanced mycosis fungoides and Sézary syndrome, the peripheral blood tumor burden may improve after treatment with TSEB.

Inhibition of cell-mediated immunity by the histone deacetylase inhibitor vorinostat: implications for therapy of cutaneous T-cell lymphoma.

Several histone deacetylase inhibitors (HDACi), including vorinostat, have been approved for the therapy of cutaneous T-cell lymphoma (CTCL). Emerging data suggest that HDACi may exert immune suppressive effects which would be disadvantageous for therapy of CTCL. We describe a patient with Sezary syndrome who was monitored for drug-induced immunosuppression while undergoing treatment with vorinostat. Analysis of the patient's natural killer cell function before and after initiation of treatment confirmed inhibition of this important cell-mediated immune function. In addition, the in vitro effects of vorinostat on the immunity of healthy volunteers confirmed that this class of drug can profoundly suppress multiple arms of the cellular immune response. These findings raise concerns of increased susceptibility to infection in this high-risk population.

High clinical response rate of Sezary syndrome to immunomodulatory therapies: prognostic markers of response.

OBJECTIVES: To quantify response rates of Sézary syndrome (SS) to multimodality immunomodulatory therapy and to identify the important prognostic parameters that affect overall response to treatment. DESIGN: Retrospective cohort study. SETTING: Cutaneous T-cell lymphoma clinic at The Hospital at the University of Pennsylvania. PARTICIPANTS: Ninety-eight patients who met the revised International Society for Cutaneous Lymphomas (ISCL) and the European Organization of Research and Treatment of Cancer (EORTC) criteria for the diagnosis of SS and were seen over a 25-year period at the University of Pennsylvania. Intervention Patients were treated with at least 3 months of extracorporeal photopheresis and 1 or more systemic immunostimulatory agents. MAIN OUTCOME MEASURES: Overall response to treatment was the main measurement of outcome. RESULTS: A total of 73 patients had significant improvement with multimodality therapy: 30% had complete response, with clearing of all disease (n = 29), and 45% had partial response (n = 44). At baseline, the complete response group had a lower CD4/CD8 ratio than the nonresponse group (13.2 vs 44.2) (P = .04) and a lower median percentage of CD4(+)/CD26(-) cells (27.4% vs 57.2%) (P = .01) and CD4(+)/CD7(-) cells (20.0% vs 41.3%) (P < .01). Median monocyte percentage at baseline was higher for patients who had a complete response than for nonresponders (9.5% vs 7.3%) (P = .02). The partial response group did not have any statistically significant variables compared with the nonresponse group. CONCLUSIONS: In this large cohort study of patients with SS, a high clinical response rate was achieved using multiple immunomodulatory therapies. A lower CD4/CD8 ratio, a higher percentage of monocytes, and lower numbers of circulating abnormal T cells at baseline were the strongest predictive factors for complete response compared with nonresponse and warrant further examination in a larger cohort.

Photodynamic therapy with the silicon phthalocyanine pc 4 induces apoptosis in mycosis fungoides and sezary syndrome.

Our current focus on the effects of Photodynamic Therapy (PDT) using silicon phthalocyanine Pc 4 photosensitizer on malignant T lymphocytes arose due to preclinical observations that Jurkat cells, common surrogate for human T cell lymphoma, were more sensitive to Pc 4-PDT-induced killing than epidermoid carcinoma A431 cells. Mycosis fungoides (MF) as well as Sezary syndrome (SS) are variants of cutaneous T-cell lymphoma (CTCL) in which malignant T-cells invade the epidermis. In this study, we investigated the cytotoxicity of Pc 4-PDT in peripheral blood cells obtained from patients with SS and in skin biopsies of patients with MF. Our data suggest that Pc 4-PDT preferentially induces apoptosis of CD4(+)CD7(-) malignant T-lymphocytes in the blood relative to CD11b(+) monocytes and nonmalignant T-cells. In vivo Pc 4-PDT of MF skin also photodamages the antiapoptotic protein Bcl-2.