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PubMed2003

Management of mycosis fungoides: Part 2. Treatment.

Mycosis fungoides is a low-grade lymphoproliferative disorder of skin-homing CD4+ lymphocytes that may produce patches, plaques, tumors, erythroderma, and, ultimately, systemic dissemination. Treatment selection is generally guided by institutional experience, patient preference, and toxicity profile, as data from phase III clinical trials are limited. Effective topical treatments currently include mechlorethamine (Mustargen), carmustine (BCNU, BiCNU), corticosteroids, bexarotene (Targretin, a novel rexinoid), psoralen plus ultraviolet A, ultraviolet B, and total-skin electron-beam radiotherapy. Effective systemic treatments include interferon, retinoids, bexarotene, denileukin diftitox (Ontak), extracorporeal photopheresis, chemotherapy, and high-dose chemotherapy with allogeneic bone marrow transplant. Each of these treatments is discussed in detail, followed by specific recommendations for each stage of mycosis fungoides.

Administration, Topical↗
PubMedDate not supplied

The comparison of expression of cutaneous lymphocyte-associated antigen (CLA), and Th1- and Th2-associated antigens in mycosis fungoides and cutaneous lesions of adult T-cell leukemia/lymphoma.

Mycosis fungoides (MF) is morphologically similar to cutaneous lesions of adult T cell leukemia/lymphoma (ATLL) of human T-cell lymphotropic virus-type I (HTLV-1). In addition, the Th1 or Th2 characteristic of MF and ATLL is still controversial. In the present study, to discriminate MF and cutaneous lesion of ATLL using immunohistochemical markers, and to elucidate Th1 or Th2 dominancy in both disorders, CLA (cutaneous lymphocyte associated antigen) was expressed on epidermotrophic lymphoma cells in all early stage MF. In contrast, all ATLL were negative for CLA. CXCR3 was especially expressed in epidermotropic small lymphoma cells of MF. CCR5 was expressed in both disorders with variable sized lymphoma cells. ST2 was expressed on large transformed lymphoma cells with ATLL, but not in any MF cases. OX40 was expressed in the large transformed cell population in both disorders. These findings suggest that CLA and ST2 could be potentially useful immunohistochemical markers for discrimination of mycosis fungoides and cutaneous lesions of ATLL. And OX40 could be a useful immunohistochemical marker for the histopathological progression of both disorders.

Adult↗
PubMedDate not supplied

Clinical case of the month. A young man with a persistent skin eruption. Mycosis fungoides.

There are many types of skin disease that fit into the classification of cutaneous lymphoma, but mycosis fungoides is by far the most common of this group. It is a non-Hodgkin's lymphoma of T-cell origin that presents in the skin. Mycosis fungoides often evolves for years without a specific diagnosis because it can present as an eczematous or psoriasiform eruption. Patients identified in the early stages and treated appropriately have a normal life expectancy.

Adolescent↗
PubMed1992

State of the art therapy of mycosis fungoides and Sézary syndrome.

Mycosis fungoides and Sézary syndrome are low-grade, non-Hodgkin's lymphomas with initial cutaneous involvement. Early stage patients have a good prognosis and are commonly treated with topical agents. However, most patients eventually develop resistant skin disease or visceral disease, necessitating systemic treatment. Single agent and combination chemotherapy have resulted in high response rates, although these are short lived and not without treatment toxicities. Other modalities that have been tried with promising early results are: interferon, fludarabine, retinoids, cyclosporin, 2'-deoxycoformycin, leukapheresis, photopheresis and monoclonal antibodies (unlabeled, radiolabeled, or toxin labeled). We will discuss the available treatment options, as well as our approach to the patient with mycosis fungoides or the Sézary syndrome.

Antineoplastic Agents↗
PubMed1992

Prognostic implications of evaluation for lymph node involvement by T-cell antigen receptor gene rearrangement in mycosis fungoides.

We investigated the correlation between the detection of clonal rearrangement of the T-cell antigen receptor gene (TCRR) in lymph node tissue with histopathologic lymph node classification in 33 patients with mycosis fungoides with and without the Sezary Syndrome. We analyzed DNA extracted from lymph nodes that were histologically uninvolved (LN1-2), dermatopathic nodes with clusters of atypical cells (LN3), and nodes effaced with lymphoma (LN4) and found TCRR in none of five LN1-2 nodes, 8 of 17 LN3 nodes, and 10 of 11 LN4 nodes. Further, the detection of TCRR correlated with presence of palpable adenopathy (P2 less than .0001) and was associated with a worse survival (P2 = .0024). Within the subgroup of patients with LN3 nodes, there was a trend (P2 = .14) toward inferior survival if nodes were involved by TCRR, irrespective of extent of skin disease. We conclude that detection of TCRR in nodes from mycosis fungoides patients is an objective and reliable means of assessing tumor infiltration of lymph node and is associated with an inferior survival.

Blotting, Southern↗
PubMedDate not supplied

Mycosis fungoides presenting as pigmented purpuric eruption.

A case of pigmented purpuric eruptions evolving to mycosis fungoides during the 4-year follow-up period is described. Clinical manifestation was characterized by petechial lesions with irregular shaped, diffusely pigmented plaques partly sharing morphological similarities with chronic pigmented purpura. Histologically, lymphocytes infiltrated around the capillaries of the superficial dermis with extravasated erythrocytes as well as into the epidermis to form Pautrier microabscesses. Whereas CD4+ cells were observed in the epidermis and upper dermis, CD8+ cells tended to be distributed around the capillaries. Notably, the Rumpel-Leede test revealed extensive punctuate purpura limited to the lesional skin. The aggregation response of platelets was not impaired. Either CD4+ tumor lymphocytes or CD8+ reactive lymphocytes appeared to induce capillary damage resulting in the formation of petechial lesions. Pigmented purpuric eruptions, such as atypical chronic pigmented purpura, is thus an important initial clinical manifestation of mycosis fungoides.

Aged↗
PubMed2005

Efficacy of imiquimod in solitary plaques of mycosis fungoides.

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma. The extent and type of skin involvement (T classification) and presence of lymph node or visceral involvement are important predictors in selecting the type of treatment. Skin directed treatment represents the most appropriate therapy for early stage disease. Current topical treatment including potent topical steroids and nitrogen mustard are associated with adverse effects such as cutaneous atrophy and contact dermatitis. In the present study, we tested the efficacy of imiquimod in mycosis fungoides plaques.

Aminoquinolines↗
PubMedDate not supplied

Expression of HECA-452 in parapsoriasis and mycosis fungoides.

We have investigated the HECA-452 expression in large plaque parapsoriasis (PP) and mycosis fungoides (MF) patients, evaluating the potential role of this biomarker in both cutaneous disorders. Skin specimens from 72 PP and 61 MF patients were selected in this study. We compared their actual histological diagnosis with their previous diagnosis and we found that all 72 PP patients had the same diagnosis as before (stable PP), while 26 out of 61 MF had a previous PP histological diagnosis (evolving PP). Our results show an increased expression of HECA-452 in MF compared to PP (p<0.01). Furthermore, evolving PP showed a significantly higher level of HECA-452 than stable PP (p<0.05). We conclude that HECA-452 expression increases during the natural history of Mycosis Fungoides. HECA-452 could be used as a biomarker for MF and predict which PP evolves to MF.

Antibodies, Monoclonal↗
PubMed2006

Immunogold detection of CD3 and CD4 antigens in patients with Mycosis fungoides.

In this study, we analyzed the distribution of CD3 and CD4 antigens at the ultrastructural level in tissue samples from mycosis fungoides patients using double-immunogold labeling. We observed clusters composed of CD3 and CD4 antigens on the plasma membrane and intracellular. There were also clusters only of one type of the antigen and we could observe more often CD4 than CD3. Labeling of CD3 and CD4 was not found in control cells incubated with non-immune serum. In conclusion, our ultrastructural studies not only visualized pattern distribution and relationship between CD3 and CD4 antigens but might also suggest that the type and form of distribution provides new clues to their possible translocation in mycosis fungoides cells.

CD3 Complex↗
PubMed1990

Differential expression of CD24-related epitopes in mycosis fungoides/Sézary syndrome: a potential marker for circulating Sézary cells.

In the hematopoietic system, the B-cell associated antigen CD24 is expressed at high density on B cells, B-cell precursors, and B-cell malignancies as well as at low density on peripheral blood polymorphonuclear leukocytes. The 42-Kd sialoglycoprotein has not been previously demonstrated to be expressed on T cells, thymocytes, or T-cell malignancies. We identified three patients with mycosis fungoides/Sézary syndrome that showed low density expression of the CD24-related epitope recognized by antibody BA-1 on circulating T cells. All three patients had Sézary cells by morphologic assessment and clonal T-cell populations in the peripheral blood by gene rearrangement studies. In two of these patients, indirect immunofluorescence with a panel of six anti-CD24 monoclonal antibodies demonstrated reactivity for two of six antibodies in one case and only one of six antibodies in the other. The biologic significance of CD24-related epitope expression on circulating T cells in mycosis fungoides/Sézary syndrome is unclear. However, these findings suggest that differential, low density expression of CD24-related epitopes (BA-1+, OKB2-) may be a useful phenotypic marker for identifying circulating Sézary cells.

Antibodies, Monoclonal↗
PubMed2006

Successful treatment of patch type mycosis fungoides with tacrolimus ointment 0.1%.

Cutaneous T cell lymphomas (CTCLs) are a heterogenous group of lymphoproliferative disorders caused by clonally-derived, skin-invasive T cells. A variety of skin-directed and systemic therapies are available to treat mycosis fungoides/Sézary syndrome (MF/SS), the therapeutic choices of which are guided by the stage of disease. A 29-year-old man presented at our clinic with pruritic, erythematous macules located on the sternum and the lower back. Histological findings and immunohistochemistry studies showed patch stage MF. The patient was treated with tacrolimus ointment 0.1% twice daily for one month, achieving complete remission. Three months after the first episode a relapse was successfully treated with the same therapeutic regimen. Tacrolimus is an immunomodulatory macrolide that reduces the stimulatory capacity toward T cells and is therefore worth investigating as a treatment of CTCL. Topical tacrolimus has been related to an unknown effect with the risk for secondary malignancies including CTCL. Also, black box warnings have been proposed by the FDA for the topical calcineurin inhibitors. Nevertheless, our results in the treatment of early stage MF are in agreement with other unpublished data that have observed its efficacy. To our knowledge, there is no other case of patch type mycosis fungoides treated with tacrolimus ointment 0.1% in the medical literature.

Administration, Cutaneous↗
PubMed1991

Observations on the effect of chimeric anti-CD4 monoclonal antibody in patients with mycosis fungoides.

Chimeric (murine/human) anti-CD4 monoclonal antibody was infused into seven patients with mycosis fungoides. Successive patients received doses of 10, 20, 40, and 80 mg of antibody twice a week for 3 consecutive weeks. All patients had some clinical improvement, but responses were of relatively short duration. Serum levels of chimeric antibody varied as a function of dose. At the 80-mg dose level, antibody was readily observed in biopsied skin lesions. Although there was coating by antibody of most CD4 positive cells in the blood, there was no significant depletion of CD4 positive cells. Low-level antibody responses against the mouse Ig variable region and human Ig allotypic constant region determinants were observed in several patients, but none were of clinical significance. All but two patients made primary antibody and T-cell proliferative responses to a simultaneously administered foreign protein test antigen. However, there was marked suppression of the mixed lymphocyte reaction. We conclude that at the dose levels studied, a chimeric anti-CD4 monoclonal antibody (1) had some clinical efficacy against mycosis fungoides; (2) was well tolerated; (3) had a low level of immunogenicity; (4) had immediate immunosuppressive effects; and (5) did not induce tolerance to a co-injected antigen.

Adult↗
PubMed1991

No evidence for HTLV-I infection in 24 cases of French and Portuguese mycosis fungoïdes and Sezary syndrome (as seen in France).

A survey in search of evidence for HTLV-I infection was conducted on French and Portuguese patients residing in France with a diagnosis of mycosis fungoïdes or Sezary syndrome. Methods used in this investigation included serological assays (ELISA, Western blot, particle agglutination, indirect immunofluorescence) and DNA molecular studies (Southern blot and polymerase chain reaction). Cultures of peripheral blood mononuclear cells were performed and checked by electron microscopy and reverse transcriptase assay. The results indicate that neither HTLV-I nor a closely related retrovirus are associated with mycosis fungoïde or Sezary syndrome in the cases studied.

Adult↗
PubMed1978

Kaposi's varicelliform eruption in mycosis fungoides.

Kaposi's varicelliform eruption, caused by herpes simplex type 1, developed in a patient with mycosis fungoides four days after initiation of photochemotherapy with methoxsalen plus long-wave ultraviolet light (PUVA). He had a history of recurrent localized herpes infection. Vidarabine (adenine arabinoside) was used as treatment. Rechallenge with PUVA did not provoke another herpes infection. Kaposi's varicelliform eruption is rare in mycosis fungoides. Vidarabine may prove to be useful in the treatment of widespread herpes simplex.

Humans↗
PubMed1990

[Sea-blue histiocytes in a patient with mycosis fungoides].

The syndrome of the sea-blue histiocyte is a multisystemic infiltration by a special kind of macrophages which contain a ceroid material within its cytoplasm. We report herein a patient with mycosis fungoides, hyperlipidaemia type IIB and sea-blue histiocytes on bone marrow. Moreover, the cutaneous histopathology showed focus of eosinophilic spongiosis, that have not been previously described in mycosis fungoides, as far as we know.

Aged↗
PubMed1990

[A clinico-experimental study of patients with mycosis fungoides and Kaposi's sarcoma].

Twenty-six cultures were prepared by the cultivation method. Continuous cells lines (IK-10 and IK-12) were obtained in two cases, in the rest short-lived cell cultures were prepared. All the isolated cell cultures were studied by transmission electron microscopy. Abnormal lymphoblasts were detected in some cell cultures isolated from the blood and lymph nodes of mycosis fungoides (IJ-137, IK-140, IK-142, IK-143) and Kaposi's sarcoma patients (IK-145). Cell population consisted of small, medium, and large lymphocytes. Electron microscopic examination has revealed retroviruses in IK-143 culture, isolated from the lymph node of a patient with mycosis fungoides. Morphologically these particles were typical of type C oncoviruses, 120-140 nm in diameter, with a spherical core in the center of the virion.

Adolescent↗
PubMed1990

Preliminary observations on the phenotypes of lymphoid cells in mycosis fungoides using anti-human-thymocyte monoclonal antibodies.

The phenotypes of lymphoid cells from twelve patients with mycosis fungoides (including 5 patients in the tumor stage and 7 in the pretumor stage) were determined immunohistochemically using anti-thymocyte monoclonal antibodies (HIT1, HIT2, and Leu 6). The results showed significant differences between the numbers of HIT1 and HIT2 positive cells in tumor and pretumor stage lesions, indicating that these two monoclonal antibodies may be of help in the staging of mycosis fungoides and in making a prognosis. Also, we found that some Leu 6 (+) cells in tumor stage lesions were round or oval in shape without dendritic processes, suggesting that they may be immature lymphocytes.

ADP-ribosyl Cyclase↗
PubMed1990

Autoimmune hemolytic anemia in a patient with mycosis fungoides.

We report a case of autoimmune hemolytic anemia in a patient with mycosis fungoides. We propose that autoimmune hemolytic anemia may be induced by cutaneous lymphoproliferative diseases. Thus, hemolysis should be considered as a mechanism of anemia in patients with mycosis fungoides.

Aged↗