CD30-positive Lymphoproliferative Disorders Research Articles

Cutaneous T-cell lymphoproliferative disorders: approach for the surgical pathologist: recent advances and clarification of confused issues.

Cutaneous T-cell lymphoproliferative disorders (CTCLs) remain a subject of confusion and controversy. In this review, the authors discuss diagnostic criteria and classification, including the role of immunohistochemistry and gene rearrangement studies. In addition, cutaneous T-cell pseudolymphomas, the current status of parapsoriasis and other premalignant syndromes, and the clinicopathological variants of mycosis fungoides are discussed. CD30-positive lymphoproliferative disorders and a number of rare variants of CTCL including granulamatous slack skin, subcutaneous (panniculitic) T-cell lymphoma, gamma-delta cutaneous lymphoma, NK/NK-like T-cell lymphoma, and primary cutaneous CD8-positive epidermotropic cytotoxic T-cell lymphoma are also considered.

Therapeutic use of interferon-? for lymphomatoid papulosis

Lymphomatoid papulosis is a primary cutaneous, CD30 positive lymphoproliferative disorder with the potential to transform into systemic, malignant lymphoma. Therapeutic strategies for patients with lymphomatoid papulosis have been designed to prevent transformation but have proved to be either inefficacious or limited by side effects. The authors compared the clinical, histologic, and immunohistochemical features from a group of five patients receiving interferon-alpha (IFN-alpha) subcutaneously three times per week with the same features from a group of six patients receiving conventional therapy, including photochemotherapy, antibiotics, topical corticosteroids, or surgery, in an open trial. In the IFN-alpha group, four patients showed a complete remission, and one patient showed a partial remission within a time period of 6 weeks. Two patients developed disease recurrences after discontinuation of short term IFN-alpha therapy (5-7 months). Thereof, one patient went into stable remission after long term IFN-alpha therapy (17 months), and one patient remains in partial remission. In the control group, one patient went into spontaneous remission, two patients showed partial remission, of which one patient developed progressive disease at a later time point, whereas three patients have recurrent disease despite of treatment. The current results indicate that the treatment with IFN-alpha of patients with lymphomatoid papulosis alters the clinical course of the disease with fewer side effects than previous regimens; however, short term treatment does not induce stable remission. Therefore, prolonged treatment appears to be warranted for these patients.

Immunohistochemical Analysis of CD30-Positive Lymphoproliferative Disorders for Expression of CD95 and CD95L

Primary cutaneous (PC) CD30-positive large cell lymphoma and lymphomatoid papulosis (LyP) represent the spectrum of PC CD30-positive lymphoproliferative disorders (LPDs) associated with a favorable prognosis. Noncutaneous CD30-positive anaplastic large cell lymphoma (ALCL), although morphologically similar to PC CD30-positive LPDs, seems to be a biologically distinct entity. Cell lines derived from noncutaneous ALCL express CD95 and undergo CD95-induced apoptosis. Little is known about expression or function of CD95/CD95L in cutaneous lesions. We examined a series of PC CD30-positive LPDs and noncutaneous ALCL for expression of CD95/CD95L to investigate possible differences between these histologically similar but biologically distinct entities.Paraffin-embedded, formalin-fixed tissue sections from 25 cases of CD30-positive LPDs (10 noncutaneous ALCL, 15 PC CD30-positive LPDs) were immunostained for CD3, CD20 (L26), CD43 (Leu22), CD30 (BerH2), anaplastic lymphoma kinase (ALK-1), CD95, and CD95L (C-33). One hundred large atypical cells and 100 small lymphocytes were counted to determine the percentage of CD95/CD95L-positive cells. Statistical analysis using the Mann-Whitney U test was performed.CD95 expression was slightly higher in the large atypical cells of noncutaneous ALCL compared with PC CD30-positive LPDs (median, 100% versus 94%; P =.003) because of the lower expression of CD95 in LyP. CD95L expression was higher in the surrounding small lymphocytes in PC CD30-positive LPDs (median, 3% versus 13%; P =.002). Expression of CD95 in the small lymphocytes and CD95L in the large atypical cells was not significantly different.These results support the biologic distinction between cutaneous and noncutaneous CD30-positive LPDs and may have implications in the differing clinical behavior of these entities. Further study of expression and function of apoptosis-related proteins in these entities is warranted.

Clinical evidence of transfer of contact dermatitis to mycosis fungoides

MUM1 is a member of the interferon regulatory factor family of transcription factors. It is normally expressed in plasma cells, late B cells, and activated T cells, and has been described in several B-cell malignancies. Although its expression has been reported in some T-cell neoplasms, the full range and character of expression have not been explored. We studied 58 cases of T-cell lymphoproliferative lesions, including systemic and cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis (LyP), mycosis fungoides (MF), MF with large cell transformation, and Sézary syndrome (SS). Nearly all cutaneous (5/5) and systemic anaplastic large cell lymphomas (4/5) were positive for MUM1, mainly in the large cell population. Similarly, 12 of 16 types A and C LyP showed MUM1 reactivity in greater than 50% of the large cells. Focal MUM1 staining was seen in 3 type B LyP, mostly in reactive lymphoid cells. All 9 MF with large cell transformation expressed MUM1 in large cells, where it paralleled CD30 expression. In comparison, most MF (11/12) were MUM1 negative. Interestingly, all SS cases (8/8) were MUM1 positive, 3 of which demonstrated diffuse staining. There was a significant difference in MUM1 expression between MF and SS groups as well as between MF and large cell transformation of MF groups (P < .001 for both). In summary, MUM1 is not helpful in separating different types of CD30-positive lymphoproliferative disorders. Potentially, MUM1 could serve as an adjunct marker for SS and/or large cell transformation of MF.

Th2 Cytokine mRNA Expression in Primary Cutaneous CD30-Positive Lymphoproliferative Disorders: Successful Treatment With Recombinant Interferon-γ

Primary cutaneous CD30 (Ki-1)+ large cell lymphoma (KiL) and lymphomatoid papulosis (LyP) type A are collectively termed as primary cutaneous CD30-positive lymphoproliferative disorders. We examined the cytokine profile of skin-infiltrating cells and the therapeutic efficacy of recombinant interferon-gamma (rIFN-gamma) in primary cutaneous KiL and LyP type A. By reverse transcriptase-polymerase chain reaction, mRNAs for interleukin-4 (IL-4) and IL-10 were detected in the dermis of skin lesions in all cases (three cases of KiL and four cases of LyP). In addition, tissue from one KiL patient transcribed IL-2 and IFN-gamma messages, and one LyP patient showed IL-2 mRNA. In contrast, normal skin from ten healthy donors contained mRNA for IL-2 or IFN-gamma, or both, but not for IL-4. Before the therapeutic trial of rIFN-gamma, the response of skin lesions was assessed by a predictive skin test with local injection of rIFN-gamma (0.5 x 10(6) Japan Reference Units [JRU; 1 JRU roughly corresponds to 4 NIH units]) for 3 consecutive days in two KiL and two LyP patients. Numbers of skin-infiltrating CD30+ cells were decreased, and transcription of mRNA for IL-4 and IL-10 was downregulated after the skin test in one KiL and two LyP cases. One KiL patient showed no histologic response or change in mRNA expression. In the therapeutic trial, rIFN-gamma (total doses of 1.2-4.0 x 10(7) JRU) was administered intravenously (n = 2) or locally (n = 2). In three patients who responded to the skin test, the lesions were objectively improved and the numbers of skin-infiltrating CD30+ cells were markedly decreased after the therapeutic trial. No improvement was observed in one KiL patient who did not respond to the skin test. These findings suggest that the skin-infiltrating CD30+ cells in KiL and LyP have a Th2 cytokine profile and raise the possibility that the administration of rIFN-gamma improves the conditions by inhibiting cytokine mRNA transcription and proliferation of CD30+ cells.

Methotrexate is effective therapy for lymphomatoid papulosis and other primary cutaneous CD30-positive lymphoproliferative disorders

Background: The spectrum of primary cutaneous CD30 + lymphoproliferative disease consists of lymphomatoid papulosis (LyP) at one extreme and CD30+ peripheral T-cell lymphoma (Ki-1 + lymphoma) presenting in the skin at the other extreme. Methotrexate has been reported to be effective in LyP, but the experience has been limited to single case reports or small series. Objective: The objective was to determine the effectiveness of methotrexate in the treatment of primary cutaneous CD30 + lymphoproliferative disease. Methods: We reviewed our 20-year experience with the use of methotrexate in 45 patients with relatively severe LyP, Ki-1 + lymphoma, and interface presentations. Results: During induction of methotrexate therapy patients received maximum doses ranging from 10 to 60 mg/week (median, 20 mg/week). Clinical improvement usually occurred quickly, typically at doses of 15 to 20 mg weekly, and satisfactory long-term control was achieved in 39 patients (87%) with maintenance doses given at 10- to 14-day intervals (range, 7 to 28 days). After methotrexate was discontinued, 10 patients remained free of CD30 + lesions from more than 24 months to more than 227 months (median, more than 127 months). The median total duration of methotrexate therapy for all patients exceeded 39 months (range, 2 to 205 months). Adverse effects were generally mild and transient and included fatigue (47%), nausea (22%), weight loss (13%), diarrhea or gastrointestinal cramping (10%), increased serum hepatic transaminase levels (27%), anemia (11%), or leukopenia (9%). Early hepatic fibrosis was found in 5 of 10 patients, all of whom had been treated for more than 3 years (range, 38 to 111 months). Conclusion: Low-dose methotrexate (25 mg or less given at 1- to 4-week intervals) is an effective and well-tolerated treatment of selected patients with primary cutaneous CD30 + lymphoproliferative disease.