Herschel S. Zackheim

Granulomatous variants of cutaneous T-cell lymphoma : the histopathology of granulomatous mycosis fungoides and granulomatous slack skin

Granulomatous mycosis fungoides is an unusual histologic variant of mycosis fungoides, a condition that is ordinarily indolent. Granulomatous slack skin, like granulomatous mycosis fungoides, shows epidermotropism, granulomatous inflammation, a clonal T-helper cell population, and progression to systemic lymphoma in some cases. Unlike granulomatous mycosis fungoides, it is characterized clinically by bulky, pendulous skin folds. The similarities between the two conditions prompted us to compare the histologic features. We reviewed 24 biopsies from 10 patients with granulomatous mycosis fungoides. These showed several distinct histologic patterns, including three cases that mimicked granuloma annulare. We also reviewed biopsy specimens from four patients with granulomatous slack skin. These specimens had a more stereotypic appearance, with permeation of the entire dermis and subcutis by lymphocytes, marked epidermotropism, and a more even distribution of granulomas and giant cells within the infiltrate. Biopsies of fully developed lesions of granulomatous slack skin showed elastolysis involving the full thickness of the dermis—a feature not seen in any of our granulomatous mycosis fungoides cases. Biopsy specimens from granulomatous mycosis fungoides and granulomatous slack skin may be mistaken for nonneoplastic granulomatous dermatitides, but they can usually be distinguished from these by the presence of epidermotropism or atypical lymphocytes. Because several of our patients with granulomatous mycosis fungoides died after courses of unremarkable length, it seems unlikely that the presence of granulomas is invariably correlated with a more benign course than nongranulomatous mycosis fungoides.

Topical carmustine (BCNU) for cutaneous T cell lymphoma: A 15-year experience in 143 patients

One hundred forty-three patients with cutaneous T cell lymphoma were treated with topical carmustine (BCNU). A complete response was obtained in 86% of those with limited extent (less than 10%) plaques (T1 stage), in 48% of those with extensive (greater than or equal to 10%) plaques (T2 stage), and in 21% of those with erythroderma. The median time to achieve complete response was 11.5 weeks. Favorable results were obtained in patients with less than 5% involvement treated locally. Mild hematopoietic depression occurred in less than 10% of patients. Erythematous reactions were common, but no secondary cutaneous malignancies occurred. Differences in freedom from relapse or in survival between T2-stage patients with and those without clinical adenopathy were not statistically significant. The 5-year overall survival rate was 77%; the median survival time was 9.4 years.

Low-dose methotrexate to treat erythrodermic cutaneous T-cell lymphoma: results in twenty-nine patients.

BACKGROUND Most patients with erythrodermic cutaneous T-cell lymphoma (CTCL) have intense, generalized, refractory pruritus. In some large series the median survival was approximately 3 years. OBJECTIVE Our purpose was to review our experience with methotrexate in the treatment of 29 patients with erythrodermic CTCL observed for up to 129 months. METHODS This is a retrospective study. Data are presented in terms of response rates, freedom from treatment failure, and overall survival. RESULTS Twelve patients (41%) achieved complete remission, and five (17%) achieved partial remission for a total response rate of 58%. The median freedom from treatment failure was 31 months, and the median survival was 8.4 years. Side effects caused treatment failure in only two patients. CONCLUSION Low-dose methotrexate is a valuable first-line treatment for the majority of patients with early to intermediate-stage erythordermic CTCL.

Low-dose methotrexate to treat mycosis fungoides: A retrospective study in 69 patients

BACKGROUND Although low-dose methotrexate has been used to treat mycosis fungoides for many years, documentation is very limited. OBJECTIVE Our purpose was to review our experience with methotrexate in the treatment of 69 patients with patch/plaque and tumor stage mycosis fungoides observed for up to 201 months. METHODS This was a retrospective study. Data are presented in terms of response rates and time to treatment failure. RESULTS The greatest number of patients (60) had patch/plaque stage T2 disease (>/=10% skin involved). Of these, 7 (12%) achieved complete remission and 13 (22%) achieved partial remission for a total response rate of 20 of 60 (33%). The median time to treatment failure was 15 months. Only 1 of 7 patients with tumor stage disease responded. Side effects caused treatment failure in 6 (9%) of the total cohort of 69 patients. CONCLUSION Low-dose methotrexate may be of value in the treatment of a subset of patients with patch/plaque mycosis fungoides resistant to other therapies.

Mycosis fungoides with onset before 20 years of age

BACKGROUND Recent identification of mycosis fungoides (MF) in a man in whom the diagnosis was established at age 22 months prompted us to evaluate our experience with early onset MF. OBJECTIVE Our purpose was to summarize the clinical characteristics and course of 24 patients in whom MF began by history before age 20 years and was confirmed by biopsy in 13 by that time. METHODS A retrospective study was conducted. RESULTS All 24 patients had patch/plaque disease and represented 4.3% of the 557 patients with cutaneous T-cell lymphoma seen by us since 1971. None progressed to a more advanced stage in up to 24 years (median, 12 years) after histologic diagnosis. Five patients (21%) presented with hypopigmentation. CONCLUSION Early onset MF is not more aggressive than that appearing in adult life. MF should be considered in the differential diagnosis of chronic dermatoses in young persons, particularly in those presenting with hypopigmentation.

Low-dose methotrexate for the Sézary syndrome

Seventeen patients with Sézary syndrome were treated with low-dose methotrexate for periods of up to 5 years (median follow-up 22 months). Seven patients (41%) achieved a complete response, and six patients (35%) achieved a partial response (more than 50% improvement). As of their latest evaluation, 10 of 17 (59%) were in a state of either complete or partial response. The estimated 5-year survival rate was 71% (standard error 13%). Toxicity was minor and self-limiting in only one patient. Clinical improvement was accompanied by a decrease in the circulating Sézary cell count.

Mycosis fungoides beginning in childhood and adolescence

Mycosis fungoides is a form of cutaneous T cell lymphoma usually occurring in mid to late adulthood. We report 12 patients with mycosis fungoides whose eruption began before age 20 years, including one patient with histologic documentation at 5 years of age. The onset of mycosis fungoides during the first two decades may be more common than is generally recognized and should be included in the differential diagnosis of chronic dermatoses in children and adolescents.

Lymphomatoid papulosis associated with mycosis fungoides: a study of 21 patients including analyses for clonality

BACKGROUND Although an association of lymphomatoid papulosis (LyP) with mycosis fungoides (MF) is recognized, our understanding of this relation is limited. OBJECTIVE We sought to document the clinical experience at the University of California, San Francisco, in 21 patients who had both LyP and MF and to do clonality studies in 7 of those patients in whom this was possible. METHODS We conducted chart review of the 21 patients and analysis for T-cell receptor-gamma gene rearrangements by the polymerase chain reaction. RESULTS Of 54 patients, 21 (39%) with LyP had associated MF. LyP preceded MF in 14 (67%), MF preceded LyP in 4 (19%), and there was concurrent appearance in 3 (14%). Of the 21 patients, 20 (95%) were type A and only 1 (5%) was type B. An identical clone was found in lesions of both LyP and MF in all 7 patients in whom analysis was possible. CONCLUSION Findings of this study strengthen the idea that LyP and MF are related T-cell lymphoproliferative disorders.

The use of methotrexate for treatment of psoriasis in patients with HIV infection

The use of methotrexate (MTX) has been contraindicated for treatment of severe psoriasis in HIV infection on the basis of six previously reported cases in which MTX appeared to potentiate opportunistic infections and accelerate HIV disease. We describe three HIV-infected patients who were given MTX for severe psoriatic arthritis. In two patients opportunistic infections did not develop. On the basis of survival data, it is not clear that use of MTX adversely affected the natural course of their HIV disease.

6-Thioguanine treatment of psoriasis: Experience in 81 patients

BACKGROUND Despite recent innovations a considerable number of patients with psoriasis cannot be successfully treated by current therapies. OBJECTIVE Our purpose was to summarize our 18-year experience with the antimetabolite 6-thioguanine in the management of patients with psoriasis. METHODS We retrospectively studied 81 patients who were treated with 6-thioguanine. A variety of schedules were used to find the optimal schedule. Forty-eight percent of the patients either had been treated with methotrexate or were excluded from receiving methotrexate because of liver or kidney disease. RESULTS Forty-nine percent of patients with plaques were effectively maintained with 6-thioguanine for a median of 33 months. Four of five patients with palmoplantar pustular psoriasis experienced substantial benefit. The most common side effect was myelosuppression. CONCLUSION 6-Thioguanine is an effective therapy for psoriasis and should be considered for patients who have failed to respond to other systemic agents.