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PubMed1995

Detection of clonal T-cell receptor gamma gene rearrangements with the use of the polymerase chain reaction in cutaneous lesions of mycosis fungoides and Sézary syndrome.

BACKGROUND AND DESIGN: We used the amplification of junctional V (variable)-J joining sequences of the rearranged T-cell receptor gamma (TCR gamma) genes by polymerase chain reaction for rapid and sensitive detection of a clonal T-cell population in a total of 51 skin specimens obtained from 45 patients with mycosis fungoides, five patients with Sézary syndrome, and 29 patients with chronic inflammatory dermatoses. RESULTS: A clonal TCR gamma gene rearrangement was present in all tumors (3/3, 100%) and in most infiltrated plaques (16/22, 73%) and erythrodermas (10/12, 83%). In the patch stage, a clonal subset was found in more than half of the cases (8/14, 57%), whereas no clonality was observed in the controls. We also amplified the V-J sequences of the Igh locus coding for the heavy chain of immunoglobulins, without evidence of clonal rearrangement. These data were compared with those from in situ immunophenotypic analysis. Moreover, by using the same assay with successive dilutions of standard clonal T-cell DNA, a semiquantitative study of the T-cell clone was carried out in some cases. The highest ratios of clonal DNA were observed in advanced stages. CONCLUSIONS: These data validate polymerase chain reaction V gamma-J gamma as a rapid, sensitive tool that can be used in the routine analysis of clonality in cutaneous lesions of mycosis fungoides and in the early diagnosis of mycosis fungoides and Sézary syndrome. Semiquantitative studies suggest that the malignant T-cell clone follows a selective process during the course of the progressive form of mycosis fungoides.

Clone Cells↗
PubMed1999

Radiotherapy in the management of mycosis fungoides: indications, results, prognosis. Twenty years experience.

PURPOSE: To determine the role of total skin electron beam therapy (TSEBT) and the prognosis of patients with mycosis fungoides. MATERIALS AND METHODS: From 1978 to 1996, 66 consecutive patients with mycosis fungoides received 30 Gy TSEBT delivered in 12 fractions over 40 days as treatment of their relapsed after topical or/and systemic therapy. All patients were staged as follows: stage A, superficial lesions covering less than 50% of the body surface; stage B, superficial lesions covering more than 50% of the body surface; Stage C. tumors involving the skin, lymph nodes and/or visceral organs. RESULTS: The median age was 50 years (ranging from 13-78 years). There were 39 males and 27 females. The minimum follow-up was 12 months (range 12-192 months). There were 24 (36%) stage A patients, 22 (33%) stage B patients, and 20 (30%) stage C patients. The overall survival at 5 years for our series was as follows: 93% for stage A; 79% for stage B, and 44% for stage C disease (P = 0.002). For the entire cohort, the complete remission rate was 65%, the progression-free survival (PFS) at 5 years and 10 years was 30 and 18% respectively. For the group A, PFS was 62% at 5 years and 46% at 10 years; for group B, PFS was 19% at 5 years. CONCLUSIONS: This study suggests that TSEBT gives good results for relapsed stage A disease. Total skin electron beam therapy combined with local fields irradiation or other local treatment (puvatherapy or topical nitrogen mustard) might further improve permanent complete response for stage B patients. The most advanced stages of mycosis fungoides are not controlled by TSEBT, but the radiation therapy offers good palliation results.

Adolescent↗
PubMed2002

Frequent abnormalities of the p15 and p16 genes in mycosis fungoides and sezary syndrome.

There are few data on the molecular pathogenesis of cutaneous T cell lymphomas. A recent allelotyping study by our group identified frequent allelic loss on 9p, 10q, and 17p including losses on 9p21 in 16% of patients with mycosis fungoides and 46% with Sezary syndrome. The P15 and P16 genes are intricately linked on 9p21 and can be inactivated in melanoma and non-Hodgkin's lymphoma. We have therefore studied 76 patients with either mycosis fungoides or Sezary syndrome for abnormalities of these genes. DNA samples were analyzed for loss of heterozygosity, homozygous deletion, intragenic mutations, and promoter methylation. In addition P15 and P16 protein expression was assessed. Microsatellite analysis was informative in 73 of 76 cases: allelic loss on 9p21 was identified in 18 patients (25%), including 12 of 57 with mycosis fungoides (21%) and six of 16 with Sezary syndrome (37%). Single strand conformation polymorphism analysis of the entire coding regions of both genes did not identify any mutations, although two polymorphisms were identified including C613A, which has not previously been described. P15 and P16 gene promoter methylation was found in 45% and 29% of patients, respectively. Furthermore aberrant P15 protein expression was detected in 85% of patients analyzed with P15 gene abnormalities and abnormal P16 expression in 59% with P16 gene abnormalities. These abnormalities were not dependent on cutaneous stage of disease. This study suggests that abnormalities of the P15 and P16 genes are common in both early and advanced stages of mycosis fungoides and Sezary syndrome and that these genes may be inactivated by allelic loss and aberrant promoter methylation.

Cell Cycle Proteins↗
PubMed2000

Monoclonality of intraepidermal T lymphocytes in early mycosis fungoides detected by molecular analysis after laser-beam-based microdissection.

The identification of neoplastic lymphocytes in early lesions of mycosis fungoides is difficult because of the scarcity of the infiltrate and the presence of reactive T lymphocytes admixed with neoplastic cells. Molecular analysis of the T cell receptor gene rearrangement using the polymerase chain reaction technique demonstrates monoclonality only in a proportion of these cases. The exact location of the malignant clone is unknown, and at present it is not clear whether neoplastic cells in early lesions reside within the epidermis, the superficial dermis, or both. We analyzed skin lesions from five patients with early mycosis fungoides using the polymerase chain reaction technique after microdissection of the specimens. In each case the epidermis was separated from the dermis using a laser-beam microdissection technique. Three samples were prepared from each lesion: one containing only the epidermis, one only the superficial dermis, and one the entire specimen. A distinct band could be observed in the epidermal sample in four cases, indicating the presence of an intraepidermal monoclonal population of T lymphocytes. The dermal sample revealed a monoclonal pattern in two cases (both of them showing clonality also within the epidermis). Analysis of the entire specimen revealed a monoclonal pattern only in two cases. Our results demonstrate that intraepidermal lymphocytes in early mycosis fungoides often show a monoclonal pattern of T cell receptor gene rearrangement. Microdissection of biopsy specimens may enhance the sensitivity of the polymerase chain reaction technique.

Actins↗
PubMed1982

Demonstration of histiocytes in the epidermal infiltrate of mycosis fungoides.

The presence of histiocytes in the epidermal and dermal infiltrate of mycosis fungoides was observed histochemically by revealing a diffuse pattern of acid alpha-naphthyl acetate esterase (ANAE) activity in the cytoplasm, and immunohistochemically by demonstrating the presence of histiocyte-specific 'enzymes', lysozyme, alpha-I-antitrypsin and alpha-I-antichymotrypsin. Histiocytes in the infiltrate of mycosis fungoides may be involved in antigen processing and interaction with T lymphocytes.

Histiocytes↗
PubMed2005

Cytokine gene polymorphisms in patch-stage mycosis fungoides.

Cytokine production is under genetic control and certain allelic variants of cytokine genes are associated with lower or higher cytokine production in vitro and in vivo. The general concept is that a shift from a Th1 to a Th2 cytokine profile accompanies disease progression from patch-stage mycosis fungoides to tumour stage, although the results of the studies carried out have not been entirely conclusive. We aimed to investigate whether certain cytokine polymorphisms might represent a risk factor for developing patch-stage mycosis fungoides. Genotyping for IFN-gamma (Th1 cytokine), IL-6, IL-10 (Th2 cytokines), TNF-alpha and TGF-beta 1 was undertaken for 33 patients with patch-stage mycosis fungoides and the results were compared with those in a control group. Genotype distribution showed no significant differences between the patients and the controls for any of the five cytokines studied. Our study suggests that patch-stage mycosis fungoides is not determined by a specific genotype polymorphism. However, further studies on larger numbers of cases are needed before definite conclusions can be drawn.

Adolescent↗
PubMed1982

Central nervous system involvement in mycosis fungoides: diagnosis, treatment and literature review.

A 58-year-old man with mycosis fungoides developed headache, back pain, and dorsal column signs. A diagnosis of central nervous system (CNS) involvement by mycosis fungoides was made on examination of his spinal fluid. In this patient, cranial and local radiotherapy and aggressive treatment with intrathecal methotrexate cleared the leukemic cells from his CNS, and maintenance therapy with intrathecal methotrexate has resulted in an 18-month remission.

Brain Neoplasms↗
PubMed1983

Simultaneous occurrence of mycosis fungoides and Hodgkin disease: clinical and histologic correlations in three cases with ultrastructural studies in two.

We present three patients who manifested both Hodgkin disease and mycosis fungoides. Ages ranged from 39 to 66 and two were male. Skin lesions were present from 3 to 40 years before the diagnosis of Hodgkin disease. In all cases, mycosis fungoides was confirmed histologically by skin biopsy; the clinical course of the mycosis fungoides was indolent in all cases. Hodgkin disease was confirmed histologically in three, and confirmed by electron microscopy in two. All three patients responded to appropriate treatment for Hodgkin disease and are alive and well at the present time.

Adult↗
PubMed1995

[A case of mycosis fungoides with pulmonary involvement: effect of etoposide and prednisolone].

Persistent coughing and bloody sputum developed in a 75-year-old man with mycosis fungoides. Chest X-ray films on admission showed combined patterns of alveolar and interstitial shadows in both lung fields. Histological examination of the transbronchial lung biopsy specimen revealed patchy infiltration of mycosis fungoides cells in alveolar septa. VEPA chemotherapy was ineffective against skin lesions and caused bacterial pneumonia, but combined treatment with etoposide (200 mg, once a week) and prednisolone (30 mg, 3 days per week) resulted in remission. The patient has been taking oral etoposide and prednisolone regularly, and has been free of skin and pulmonary lesions for two years. Combined therapy with low-dose etoposide and prednisolone may be worth trying in cases of advanced mycosis fungoides with pulmonary involvement.

Aged↗
PubMed1977

The role of total skin irradiation with electrons in the management of mycosis fungoides.

The study presents a group of 176 patients with biopsy proven mycosis fungoides treated with total skin irradiation with electrons. The treatment resulted in a complete disappearance of all cutaneous lesions in 117/176 (66 percent) of the patients. The rate of complete remission was dose-dependent and was inversely dependent on the extent of the disease. Nineteen patients have been continuously free of any evidence of mycosis fungoides 4-14 years following a single course of treatment and may be considered as cured. Most of the patients presenting with significant peripheral lymphadenopathy (Stage II) eventually relapsed with cutaneous lesions and 37 percent of these patients developed extra-cutaneous dissemination. The prognosis of patients with extracutaneous involvement was poor and no patients in this series survived for more than three years after the histological diagnosis of extractaneous dissemination. The role of total skin irradiation with electrons in the management of each stage of the disease, given either alone or in combination with other treatment modalities, is discussed.

Electrons↗
PubMed2003

Mycosis fungoides associated with malignant melanoma and dysplastic nevus syndrome.

BACKGROUND: The increased risk of second malignancies, including nonmelanoma skin cancers, in cutaneous T-cell lymphoma (CTCL) patients has been well documented. However, relatively few studies of malignant melanoma in CTCL patients have been reported. METHODS: A database of 250 CTCL patients registered over a 3-year period was searched to identify patients with diagnoses of both mycosis fungoides (MF) and malignant melanoma. RESULTS: We identified six cases of MF associated with malignant melanoma and one associated with dysplastic nevus syndrome, which is a marker of increased risk of melanoma. In four patients, melanoma was diagnosed along with or before MF. In the remaining two patients, MF was diagnosed prior to melanoma, although dysplastic nevi were noted at the time MF was diagnosed. These two patients received treatment for their MF (one with topical nitrogen mustard and another with radiation therapy and nitrogen mustard) prior to the histologic confirmation of melanoma. Six patients had early stages of MF (IA or IB), while one patient presented with simultaneous erythrodermic mycosis fungoides involving the lymph nodes as well as melanoma metastatic to the lymph nodes from an unknown primary. CONCLUSION: There is an elevated prevalence of malignant melanoma in MF patients compared to the general US population (P < 0.00001) with a relative risk of 15.3 for observing malignant melanoma in MF patients (95% confidence interval 7.0-33.8). Possible pathologic links between the two diagnoses include effects of mycosis fungoides therapies, immunosuppression secondary to mycosis fungoides, and genetic alterations in the p16 tumor suppressor protein.

Adult↗
PubMed1975

Treatment of mycosis fungoides with topical nitrosourea compounds: Further studies.

Twenty-six patients with mycosis fungoides were treated topically with three nitrosourea compounds: carmustine (BCNU), lomustine (CCNU), and 1-methyl-1-nitrosourea. A high percentage experienced good to excellent results. Remissions following treatment of individual lesions varied from one month to at least three years. Remissions following total body surface treatment varied from two weeks to at least four months. Two of 13 patients treated over the entire body suffered temporary bone marrow depression, indluding one with severe pancytopenia. This toxic effect was attributed to lomustine and was not seen in patients treated with carmustine alone. Thirteen patients highly allergic to mechlorethamine hydrochloride showed no cross-sensitivity to nitrosourea compounds. A primary irritant dermatitis occurred in about one half of the patients and telangiectasia in two. Two patients developed hypersensitivity to nitrosourea compounds. Carmustine is the preferred nitrosourea compound for topical therapy of mycosis fungoides.

Administration, Topical↗
PubMed1981

Effectiveness of once weekly total skin electron beam therapy in mycosis fungoides and Sezary syndrome.

During the past eight years, 137 patients with mycosis fungoides were given total skin electron beam therapy (TSEB) using 2.5 to 4 MeV electrons. A single treatment delivers 400 rads to the entire skin surface, and patients are treated once a week for six to eight consecutive weeks. All have been followed for a median of 18 months (range 6-103 months). Although approximately 80 to 90% of the total population were in the advanced stages of the disease and had been previously treated elsewhere, cutaneous lesions and associated symptoms were effectively controlled. The remission lasted 6 to 103 months (median 19 months) after beginning the therapy for 109 mycosis fungoides patients, who were at risk for 12-103 months (median 24 months). Erythroderma and circulating Sezary cells adversely affected the duration of remission and indicate extracutaneous dissemination. Lymphocyte responsiveness to various mitogens and antigens correlated well with duration of the remission that was obtained from a course of TSEB.

Adult↗
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↗