Primary cutaneous follicle center lymphoma in the setting of chronic lymphocytic leukemia.

Primary cutaneous malignancies arising in association with chronic lymphocytic leukemia (CLL) are notable for their atypical clinical and histological presentation. We report a 69-year-old man with a 17-year history of CLL who presented for evaluation of a well-defined red to violaceous nodule with a central depressed scar on the left lower extremity. Microscopic examination of a punch biopsy revealed an infiltrate of predominantly small lymphocytes with scattered large, atypical epithelioid cells. Immunohistochemical stains revealed diffuse positive staining of the lesional cells with CD20+ and bcl-6+ and focal positive staining with bcl-2+ (negative CD10 and CD23), findings which, in conjunction with the histology, were most compatible with a diagnosis of primary cutaneous follicle center lymphoma (PCFCL). A review of the clinical charts revealed several prior biopsies with varied diagnoses. In light of the most recent biopsy findings, all previous biopsies were re-reviewed and interpreted as PCFCL arising in the setting of CLL. Features contributing to the diagnostic conundrum in this case included an atypical clinical and histological presentation, lack of pertinent clinical history and multiple presentations at different institutions.

Biological correlates of acute hypersensitivity events with DAB(389)IL-2 (denileukin diftitox, ONTAK) in cutaneous T-cell lymphoma: decreased frequency and severity with steroid premedication.

DAB(389)IL-2 (denileukin diftitox, ONTAK) is a cytokine-targeted fusion protein that delivers the catalytic domain of diphtheria toxin to lymphoma cells expressing the interleukin-2 receptor (IL-2R). In phase I and phase III studies of DAB(389)IL-2 in patients with cutaneous T-cell lymphoma (CTCL), non-Hodgkin's lymphoma, and Hodgkin's disease in which premedications were limited to diphenhydramine and acetaminophen, acute infusion-related hypersensitivity reactions occurred in 70% of patients and vascular leak syndrome (VLS) in 27%, resulting in discontinuation of therapy in 29% of patients. There was no correlation between the dose or half-life of DAB(389)IL-2 and the occurrence of hypersensitivity events or VLS. To explore whether steroid premedication would improve the tolerability of DAB(389)IL-2, we treated 15 patients with CTCL with either dexamethasone or prednisone prior to each dose of DAB(389)IL-2. The incidence of acute infusion events was significantly decreased, with only three patients experiencing acute infusion events (one grade 4) and only two patients developing clinically apparent VLS. Grade 3 skin rash occurred in two patients and moderately severe asthenia in nine patients. A significantly improved response rate of 60% was noted with the use of steroid premedication compared to prior studies in which steroids were prohibited. We conclude that steroid premedication significantly improves the tolerability of DAB(389)IL-2 without compromising the clinical response.

A phase III, randomized, double-blind, placebo-controlled study of peldesine (BCX-34) cream as topical therapy for cutaneous T-cell lymphoma.

BACKGROUND: The purine nucleoside phosphorylase inhibitor peldesine is a new agent being evaluated as a T-cell inhibitor. OBJECTIVE: We attempted to determine the efficacy of peldesine (BCX-34) in a 1% dermal cream formulation as a treatment for cutaneous T-cell lymphoma (CTCL). METHODS: Ninety patients with patch and plaque phase CTCL, histologically confirmed by a referee dermatopathologist, were enrolled in a randomized, double-blind, placebo-controlled study. BCX-34 dermal cream 1% or the vehicle cream (as a placebo control) was applied twice daily to the entire skin surface for up to 24 weeks. Efficacy of the topical therapy was assessed in terms of complete or partial (> or = 50%) clearing of patches and plaques. RESULTS: Of the 89 patients able to be examined, 43 received BCX-34 and 46 received the placebo vehicle cream. One patient withdrew early and was not analyzed. The two groups were well balanced for potential prognostic factors. A total of 28% (12/43) of the patients treated with BCX-34 showed a response, but 24% (11/46) of patients who received vehicle also responded (P =.677). CONCLUSION: Although BCX-34 dermal cream 1% was not significantly better than the control as therapy for patch and plaque-phase CTCL, this appears to be the first published placebo-controlled trial evaluating treatment for CTCL. Whether the vehicle cream has more than a placebo therapeutic effect is unclear. The relatively high (24%) placebo response rate should be kept in mind in assessing other treatments for early-stage CTCL.

Hypopigmented mycosis fungoides: case reports and literature review.

BACKGROUND: Hypopigmented mycosis fungoides is a rare variant of mycosis fungoides (MF) that usually has a predilection for young individuals with dark complexion. OBJECTIVE: The aim is to describe new cases of hypopigmented MF with confirmed T-cell receptor gene rearrangement analysis. METHODS: This article includes case reports and a literature review. RESULTS: Three out of four hypopigmented MF patients had a positive TCR gene rearrangement. A fifth patient is reported who had hypopigmented mycosis fungoides and classical Pautrier microabscesses, for whom no TCR gene rearrangement analysis was performed. CONCLUSION: Although hypopigmented MF has a predilection for dark-complexioned populations, it can also affect Caucasian patients. In challenging cases, polymerase chain reaction can be a useful method for detecting early cases of hypopigmented MF.

Rapidly progressing mycosis fungoides presenting as follicular mucinosis.

Follicular mucinosis can occur as a primary idiopathic disorder or can arise in association with benign or malignant disease, most notably mycosis fungoides. We describe a patient with an aggressive folliculotropic variant of mycosis fungoides that initially presented as follicular mucinosis with alopecia. One month after the diagnosis of follicular mucinosis, a diagnosis of mycosis fungoides was made, and 3 months later inguinal lymph node involvement with mycosis fungoides developed. A skin biopsy specimen demonstrated prominent follicular mucinosis with folliculotropism of atypical cells and intrafollicular Pautrier's microabscesses. As demonstrated in this case, follicular mucinosis can be a presenting sign of rapidly progressive mycosis fungoides. In our review of follicular mucinosis and its association with mycosis fungoides, we found that the folliculotropic variant of mycosis fungoides appears more commonly to have an aggressive course than classic mycosis fungoides.

Advances in specific immunotherapy of malignant melanoma.

UNLABELLED: Management of malignant melanoma continues to present a challenge to dermatologists, particularly in advanced cases. In light of the steady increase in the worldwide incidence and mortality rates for melanoma, better understanding of the immune mechanisms regulating melanoma progression and interaction with the host's immune system seems eminently important. New studies on the role of immune mechanisms in the pathogenesis and clinical course of melanoma have recently been published. We review the immune mechanisms involved in tumor progression and ways in which these mechanisms may be applied toward immunotherapeutic management of malignant melanoma. LEARNING OBJECTIVE: After the completion of this learning activity, participants should be familiar with (1) the immune mechanisms involved in host-tumor interaction and tumor rejection, (2) factors allowing the escape of melanoma cells from immune recognition, and (3) the current rationale for the different types of specific immunotherapy in melanoma. Better understanding of basic mechanisms in tumor immunology should raise awareness of future immunotherapeutic approaches in patients with melanoma, particularly in those who are at high risk of recurrence or who present with advanced disease.

Cancer skills laboratories for medical students: a promising approach for cancer education.

BACKGROUND: Most medical students graduate without the skills necessary to assist patients in cancer control. To address this problem, the authors developed a cancer skills laboratory for second-year medical students. METHODS: The skills laboratory consists of two hours of training, with 15 minutes allotted per station (six to eight students assigned per station). Faculty and fellows lead the stations on prostate cancer, breast cancer, colorectal cancer, skin cancer, counseling for smoking cessation, and a discussion of anti-tobacco advertisements. Students completed pre- and post-laboratory surveys consisting of ten brief questions. RESULTS: Overall, 94% of eligible students in 1997 and 1998 completed the surveys. Using a five-point scale, self-rated skill level increased from 2.12 to 3.83 when all modalities were averaged (p < .001). CONCLUSIONS: Cancer skills laboratories are a promising new means for cancer education.

Public knowledge, awareness, and perceptions of the association between skin aging and smoking.

BACKGROUND: Although the tobacco industry promotes images of glamour, 2 decades of epidemiologic research have concluded the opposite: smokers have enhanced facial aging and skin wrinkling compared with nonsmokers. OBJECTIVE: The purpose of this study was to obtain information on the public's awareness of the association between cigarette smoking and skin aging. METHODS: In the spring of 1994, the Maine-wide Cooperative Telephone Survey conducted telephone interviews in 678 randomly selected, nonseasonal dwelling units in Maine. From each dwelling unit, one randomly selected adult resident was interviewed to assess awareness of the association of skin aging with smoking. RESULTS: Fifty-eight percent of those persons interviewed had smoked at least 100 cigarettes, and among them, 24% were current smokers (28% men, 21% women). After adjusting for sex, age, and education, current smokers remained less likely to be aware of this association compared with former (prevalence ratio, 0.78; 95% confidence interval, 0.64-0.95) and never smokers (prevalence ratio, 0.87; 95% confidence interval, 0.70-1.07). However, nearly one fourth of smokers in this study believed that most or some smokers would consider this information in their decision to quit, with slightly higher findings in young smokers. CONCLUSION: These findings are of public health importance. While strategies for framing messages about the association between smoking and facial aging await further study, this association deserves to be considered in all tobacco control and counter-advertising campaigns.

Early detection of cutaneous lymphoma.

Cutaneous lymphomas comprise a spectrum of diseases characterized by infiltration of the skin by malignant lymphocytes. The clinical manifestations of cutaneous lymphomas vary, and they can mimic benign dermatoses, as well as nodal or visceral malignancies with cutaneous spread. Cutaneous lymphomas are divided into T-cell lymphomas and B-cell lymphomas. Cutaneous T-cell lymphomas include mycosis fungoides, Sézary syndrome, lymphomatoid papulosis, CD30+ large cell lymphoma, and adult T-cell leukemia/lymphoma. The extent and severity of skin manifestations in cutaneous T-cell lymphomas are prognostic indicators of extracutaneous involvement. Primary cutaneous B-cell lymphomas comprise 10% to 25% of all primary cutaneous non-Hodgkin's lymphomas and are classified according to their cell of origin. Most cutaneous B-cell lymphomas have an indolent course and excellent prognosis when compared to their nodal counterparts. Many factors have been implicated in the etiology of cutaneous lymphomas, including chemical and drug exposures, as well as microbial agents, such as the Epstein-Barr virus (EBV), human T-lymphocyte virus-1 (HTLV-1), and Borrelia burgdorferi. Immunohistochemistry and lymphocyte-receptor gene rearrangement studies are useful in distinguishing malignant from benign conditions.

Adjuvant therapy for cutaneous malignant melanoma.

We discuss the current status of adjuvant therapy for melanoma by first reviewing the rationale and goals of adjuvant therapy and then analyzing the results of published randomized trials. We pay particular attention to adjuvant interferon trials that raise many challenging issues in the management of patients with melanoma at high risk of recurrence. Past adjuvant trials have used immunotherapeutic approaches, chemotherapy, radiation therapy, as well as hormonal and retinoid therapy. We also summarize ongoing adjuvant trials.

Is it lymphoma or lymphomatoid papulosis?

Distinguishing malignancy from premalignant conditions can be difficult. Controversy surrounds both the clinical and histologic criteria used to distinguish lymphomatoid papulosis, a benign disorder, from CD30+ anaplastic large-cell lymphoma. Three case histories illustrate important points in categorizing different lymphoproliferative disorders as benign or malignant. We emphasize a multidisciplinary approach to improve diagnosis and patient management.

Proceedings of the International Consensus Conference on Cutaneous T-cell Lymphoma (CTCL) Treatment Recommendations. Boston, Massachusetts, Oct. 1 and 2, 1994.

At the International Consensus Conference for Cutaneous T-Cell Lymphoma (CTCL) Treatment Recommendations (held in Boston, Massachusetts, Oct. 1 and 2, 1994), international experts were asked to assess where consensus existed and to identify areas that required clinical research. We review the epidemiology, pathology, and immunology of CTCL, summarize the important areas in which consensus exists, and discuss newer targeted therapies.