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Differential localization of ICAM-1 and HLA-DR expression on epidermal basal surface in mycosis fungoides and lichenoid reaction.

Scanning electron microscopy with immunogold labeling revealed that epidermal keratinocytes expressed ICAM-1 (intercellular adhesion molecule-1) and HLA-DR molecules on their surfaces in patterns that differed in mycosis fungoides (MF) and lichenoid reaction (LR). ICAM-1 molecules, visualized as deposits of gold particle, were visualized as clusters adjacent to the junctions interconnecting the keratinocytes of MF lesions. LFA-1 (leukocyte function-associated antigen-1) molecules were seen as granules on the surfaces of all infiltrates, most of which also expressed ICAM-1. HLA-DR molecules were seen continuously along the borders of the individual keratinocytes, thus producing a cobblestone appearance on the epidermal undersurface. In contrast, ICAM-1 and HLA-DR were found only sparsely on the undersurface of the epidermis from LR. These findings may help to explain the differing histological features of MF and LR: ICAM-1 molecules present on the intercellular junctions of MF epidermis lead the LFA-1-bearing cells to migrate into the interspaces, thus producing epidermotropism. These cells aggregate by means of co-expressed ICAM-1 to thus produce Pautrier's microabscess. In LR, the minimal expression of ICAm-1 on the epidermal undersurface leaves most infiltrates within the dermis, thus producing a band-like infiltrate.

Adult↗

Ag-NOR staining and satellite association in bone marrow cells from patients with mycosis fungoides.

Silver staining of nucleolus organizing regions (Ag-NORs) of acrocentric chromosomes and the frequency of satellite association (SA) in bone marrow (BM) cells from 7 patients with mycosis fungoides (MF), were studied. BM samples of 7 normal healthy individuals were taken as controls. The mean number of Ag-NORs per metaphase was increased in patients (7.20 +/- 0.25) compared with controls (5.40 +/- 0.16) (p < 0.002), related with the increase of the D group. Moreover, a significant higher percentage of Ag-NOR positive cells in patients (71.7 +/- 3.9) than controls (48.0 +/- 7.8) (p < 0.02), was seen. The analysis of SA revealed a significant increase in the percentage of cells with 1-2 association pairs (ASPs) in patients with respect to their controls (p < 0.05), and a trend to a decrease in the percentage of cells without ASPs. Furthermore, a correlation between the number of Ag-NORs and the mean of ASPs per cell was also found for patients (rk = 0.65; p < 0.05). These results may be associated with a certain degree of immaturity, a high proliferative activity and modifications of the growth rate of BM cells in MF patients.

Adolescent↗

Epitheliotropic lymphoma (mycosis fungoides) presenting as blepharoconjunctivitis in an Irish setter.

An 11-year-old neutered female Irish setter was presented with a six-week history of blepharoconjunctivitis affecting the right eye. A conjunctival biopsy was taken and histopathological examination revealed a heavy cellular infiltrate involving the epithelial and subepithelial tissues. Immunohistochemical staining showed the intraepithelial cell population to uniformly have the phenotype CD3 (T-cell specific marker). A diagnosis of epitheliotropic lymphoma (mycosis fungoides) was made. The use of a synthetic retinoid and topical prednisolone in the management of the case is discussed.

Administration, Topical↗

Ocular involvement in mycosis fungoides.

A case of mycosis fungoides with bilateral intraocular involvement is reported. The diagnosis was established with the aid of a vitreous biopsy. Intraocular involvement, though rare, may be an early sign of extracutaneous disease.

Eye Neoplasms↗

Transition of Sézary syndrome into mycosis fungoides after complete clinical and molecular remission under extracorporeal photophoresis.

Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common clinical variants of cutaneous T cell lymphoma. Although thought to be closely related to mature T helper cells, the relation between the neoplastic cells in MF and SS is still not fully clarified. This report describes a patient with complete remission of SS under treatment with extracorporeal photophoresis (ECP), who subsequently developed typical plaques of MF and large cell lymphoma (LCL). Serial polymerase chain reaction analyses confirmed identical T cell receptor beta and gamma gene rearrangements in SS, MF, and LCL, and complete disappearance of the circulating malignant T cell clone from the peripheral blood after ECP. These findings indicate that the neoplastic cells in SS, MF, and LCL are derived from a common precursor T cell, despite the change in clinical phenotype.

Aged↗

Severe cutaneous reactions to captopril and enalapril; histological study and comparison with early mycosis fungoides.

A severe non-dose related skin eruption attributable to treatment with captopril was recently reported: this is distinct from the dose related rashes that have been widely described. Ultrastructural and immunohistochemical studies were carried out to determine in detail the histological features of this eruption: the histological appearances were similar to those found in early mycosis fungoides, so that this disease was erroneously diagnosed in one case. Unlike most other complications resulting from treatment with Captopril, an indistinguishable rash can result from treatment with enalapril, a newer angiotensin converting enzyme inhibitor.

Captopril↗

Density of neoplastic lymphoid infiltrate, CD8+ T cells, and CD1a+ dendritic cells in mycosis fungoides.

BACKGROUND/AIMS: CD8+ T cells and epidermal/dermal dendritic cells expressing CD1a are found among neoplastic CD4+ T cells in mycosis fungoides (MF) lesions. This study analysed the relation of CD8+ tumour infiltrating lymphocytes (TILs), CD1a+ epidermal Langerhan's cells (LCs), and dermal dendritic cells (DDCs) to clinicopathological parameters in 46 MF cases. METHODS: Pretreatment diagnostic biopsy specimens of 46 MF cases were submitted to histological analysis and immunohistochemistry. Four histological grades were defined based on the density of the neoplastic infiltrate: grade 1 (mild superficial perivascular infiltrate), grade 2 (moderate superficial perivascular infiltrate with some tendency to confluence), grade 3 (pronounced superficial band-like infiltrate), and grade 4 (deep nodular infiltrate). Epidermotropism was scored as low, moderate, or high. Numbers of CD8+ T cells and of dermal and epidermal CD1a+ cells were scored as 1 (low), 2 (moderate), and 3 (high). Correlations between these parameters and clinical data (age, sex, clinical type of lesions, stage, response to treatment, and recurrence) were analysed by the chi(2) test. RESULTS: Numbers of TILs and DDCs were associated with subepidermal infiltrates, being lower in less dense infiltrates, whereas there was no association between epidermal CD1a+ cells and the analysed parameters. Complete remission in treated patients was related to subepidermal infiltrates but not to TILs, LCs, or DDCs. CONCLUSIONS: These results support the notion that CD8+ cells and dermal CD1a+ cells are active against tumour cells. MF with low numbers of TILs could represent an early stage of the disease, before TILs are activated against tumour specific antigens.

Adult↗

Dose-time fractionation study in patients with mycosis fungoides and lymphoma cutis.

Single and multiple dose-time fractionation schemes were investigated in patients with mycosis fungoides and lymphoma cutis. The single dose response shows that the disease-free interval is dose dependent. Remission rates are similar when the same total dose is given in either single treatments or multiple daily fractions. Weekly dose fractionation schemes are superior to daily regimes for lymphoma cutis. Changes in tumor volume reduction following single doses to lymphoma cutis indicate that the mean lethal dose (DO) is 90 rads and the extrapolation number (N) is less than 2. These findings are discussed in relation to the reoxygenation process and the cell cycle distribution of the tumor cell population.

Dose-Response Relationship, Radiation↗

Whole body surface electron irradiation in the treatment of mycosis fungoides. An evaluation of 200 patients.

The records of 200 patients with generalized cutaneous mycosis fungoides treated with whole body surface electron irradiation were reviewed. Type of skin lesion appeared to be the most important factor with respect to both survival and generalized skin disease-free interval. High-dose irradiation did not seem to influence prognosis significantly compared with a relatively conservative dose. The "cure" rate for the entire group was 7%. For a more homogeneous dose distribution, the eight-field technique is now used instead of the original four-field method. A new formula is proposed to standardize the reporting of doses.

Adolescent↗

Presence of circulating CCR10+ T cells and elevated serum CTACK/CCL27 in the early stage of mycosis fungoides.

PURPOSE: Mycosis fungoides (MF), a common type of cutaneous T cell lymphoma with an indolent clinical course, has the characteristic that malignant T cell clones are recruited into the skin from the early disease stages. The mechanisms of recruitment have been suggested from our knowledge of various chemokine-chemokine receptor interactions. Recently, CCR10 and CTACK/CCL27 were proposed to play a role in the recruitment of other types of cutaneous T cell lymphoma. We examined the expression of CCR10 in peripheral blood and serum CTACK/CCL27 levels in patients with MF. EXPERIMENTAL DESIGN: Eighteen patients with MF, six patients with atopic dermatitis, and nine healthy volunteers were enrolled in our investigation. We investigated the differences in CCR10+ CD4+ expression in peripheral blood mononuclear cells by flow cytometry. Serum CTACK/CCL27 levels were determined using a CTACK/CCL27 ELISA assay kit. RESULTS: The number of circulating CCR10+ CD4+ cells was significantly higher in MF peripheral blood than in controls, even during the early stages. In lesional MF skin, infiltrating tumor cells also showed extensive expression of CCR10. The serum level of CTACK/CCL27 was higher in patients with MF than normal controls, but no statistical difference was found compared with atopic dermatitis patients. CONCLUSIONS: CCR10-CTACK/CCL27 interactions between circulating T cells and keratinocytes would seem to play an important role in the pathophysiology of MF from the early disease stages.

Adult↗

Alteration of cytokine genes and bcl-2 expression following immunotherapy with intralesional IFN-gamma in a patient with tumor-stage mycosis fungoides.

BACKGROUND: Interferon-gamma (IFN-gamma) is used in the treatment of tumor stage mycosis fungoides (MF), whereas its mechanism is still unknown. We have previously shown that treatment with intralesional IFN-gamma induced tumor regression. OBJECTIVE: To explore the possibility that IFN-gamma may alter the cytokine expression by tumor cells, we studied cytokine gene expression in a tumor nodule of MF. METHODS: By using the reverse transcriptase-polymerase chain reaction, Th1- and Th2-type cytokine mRNA expression was examined before and after intralesional IFN-gamma therapy. Additionally, we examined bel-2 protein expression on tumor cells. RESULTS: We found weak mRNA expression of interleukin-4 (IL-4) and IL-5, and strong expression of IL-6, IL-10 and IFN-gamma before therapy. After successful treatment of intralesional IFN-gamma, mRNA expression of IL-5, IL-6 and IL-10 were significantly reduced and IL-2 mRNA was mildly induced. Culture for 24 h of tumor cells with IFN-gamma showed upregulation of IL-2 mRNA and downregulation of IL-6 mRNA expression. bcl-2 expression was significantly decreased after successful intralesional IFN-gamma therapy, photochemotherapy (PUVA) and radiation therapy. CONCLUSION: These data suggest that IFN-gamma induces tumor regression by affecting cytokine gene expression in MF tumor lesions. The reduced bcl-2 expression did not seem to be induced by a direct immunological affect of IFN-gamma, but to represent a nonspecific result of tumor regression after successful treatment.

Cytokines↗

Mycosis fungoides in patients under 20 years of age: report of 7 cases, review of the literature and study of the clinical course.

BACKGROUND: Mycosis fungoides (MF) is rare in young patients. Its clinical behavior is still uncertain, as some reports have suggested that it has a more aggressive course than does the adult-onset type. AIM: To ascertain if early-onset MF represents a heterogeneous group of cutaneous T cell lymphomas. MATERIALS AND METHODS: Clinical, immunohistopathological and follow-up data of early-onset (<20 years of age) MF cases reported in the literature (n = 42) plus 7 described herein were compared with those of a cohort of adult-onset MF patients (n = 252) diagnosed at our institution since 1975. RESULTS: The majority of the 49 early-onset MF patients had patch-plaque stage disease at diagnosis. Ten had hypopigmented lesions. The predominant phenotype was CD3+ CD4+CD7-CD8-. Seven patients had a stage progression, 6 with extracutaneous involvement. Five- and 10-year survival rates were 93 and 74%, respectively. CONCLUSIONS: No statistically significant differences were found in the disease course between early- and adult-onset MF.

Adolescent↗

Unilesional follicular mycosis fungoides.

Follicular mycosis fungoides (FMF) is an unusual clinical and histological variant of MF, characterized by selective involvement of hair follicles by atypical lymphocytes. We describe a female patient who had follicular papules located only on the medial aspect of her right thigh. To the best of our knowledge, this patient represents the first reported case of unilesional FMF.

Diagnosis, Differential↗

Interferon-alpha-associated development of bullous lesions in mycosis fungoides.

We report a 67-year-old woman with mycosis fungoides (MF) who was receiving subcutaneous injections of recombinant interferon alpha-2b (IFN-alpha). After 2 months of IFN-alpha treatment, bullous lesions appeared on her trunk and extremities. A skin biopsy specimen from the trunk revealed histopathologic features of bullous MF. Bullous lesions with specific infiltrates of MF are very rare; to the best of our knowledge, this is the first case showing specific bullous lesions of MF developed under IFN-alpha treatment.

Aged↗

Generalized granuloma annulare associated with granulomatous mycosis fungoides.

We describe a 68-year-old man with plaque stage mycosis fungoides (MF) for 8 years. He developed tumorous lesions of granulomatous MF (GrMF) and generalized granuloma annulare (GA) after a previously indolent clinical course. Since then, the clinical course was aggressive with involvement of the bone marrow and lymph nodes, and leukemic change occurred. Systemic chemotherapy was given, but the patient died 9 months later due to neutropenic fever and septic shock. GA in malignant lymphoma has been reported most frequently in association with Hodgkin's disease. To the best of our knowledge, GA associated with GrMF has never been reported in the English language literature. The prognostic significance of the association of granulomatous inflammation and malignancy is reviewed.

Aged↗

Exposure at home to airborne concentrations of nitrogen mustard during topical application for the treatment of mycosis fungoides: a case study.

BACKGROUND: Although effective at treating mycosis fungoides (MF), nitrogen mustard (HN(2)) creates potential exposure risks to those who administer it, including health care workers and family members. OBJECTIVE: The main objective was to examine the potential for nontarget individuals to be exposed to HN(2) vapors during and shortly after treatment with HN(2) in a home environment. METHODS: Air concentrations of HN(2) were measured during the topical treatment of MF in a patients home. RESULTS: The results demonstrate that eye and mucous membrane irritation may occur at HN(2) levels commonly encountered during the treatment of MF in the home, hospital or health clinic. Because no exposure thresholds have been developed for HN(2), the exposure thresholds of a surrogate chemical (sulfur mustard) were used. CONCLUSIONS: The study findings show that eye and mucous membrane irritation may occur at HN(2) levels below the exposure thresholds of the surrogate chemical. Recommendations for controlling exposures to HN(2) in the home are given.

Administration, Topical↗

Mycosis fungoides: review of epidemiological observations.

BACKGROUND: Mycosis fungoides (MF) is a chronic cutaneous T-cell lymphoma characterized by small cells with cerebriform nuclei that usually express a mature peripheral T-helper cell (CD4+) immunophenotype. Its evolution is typically quite slow, with years between the first manifestations and development of advanced stages of disease. OBJECTIVE: The purpose of the present paper is to contribute to the material about MF already present in the literature. The review articles that have appeared to date fundamentally address the morphological characteristics, diagnostic criteria and treatment of the disease; in contrast, the present study centers on the evolution of the incidence of MF and on the knowledge of the possible risk factors implicated in its development. METHODS: Review of published papers about MF epidemiology. RESULTS: The evidence suggests that the incidence is increasing, but this may be artifactual due to improved diagnostic techniques. The risk of MF is limited to gender and race, being higher in males and in blacks. Survival is highly stage dependent, but 90% of patients survive 15 years with only 10% of cutaneous involvement. Few risk factors have been identified, but several studies have found an association with industrial exposure, particularly to oils. CONCLUSION: MF is a rare disease and its risk factors have not been studied in any great detail. A European case-control study in progress will substantially increase the evidence available and progress towards identifying a prevention strategy.

Adult↗

Gab2 is phosphorylated on tyrosine upon interleukin-2/interleukin-15 stimulation in mycosis-fungoides-derived tumor T cells and associates inducibly with SHP-2 and Stat5a.

Cutaneous T cell lymphomas (CTCLs) often show abnormal interleukin-2 (IL-2) receptor signaling. In this study, we investigated the role of Gab2, a recently identified adaptor molecule involved in IL-2 receptor signaling in CTCLs. We show that Gab2 was transiently phosphorylated by tyrosine in human mycosis fungoides (MF) tumor T cells upon IL-2 stimulation and that SHP2 as well as Stat5a associated inducibly with Gab2. IL-15, but not IL-4, also induced tyrosine phosphorylation of Gab2, suggesting that the IL-2 receptor beta-chain is important for IL-2-induced Gab2 phosphorylation. Preincubation of cells with the Src family kinase inhibitor, PP1, surprisingly increased the IL-2- and IL-15-induced tyrosine phosphorylation of Gab2, indicating that an Src family kinase member negatively regulates IL-2 receptor signaling in MF T cells. Thus, although Gab2 seems to function normally in MF T cells compared to normal T cells, Gab2 itself might be abnormally regulated by an Src family kinase.

Adaptor Proteins, Signal Transducing↗