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PubMed2000

p16(INK4a) gene alterations are frequent in lesions of mycosis fungoides.

Mycosis fungoides is usually an indolent disease that, after a variable period of time in a stable phase, evolves into a tumoral form with aggressive behavior. The molecular events that mark this progression remain essentially unknown to date, and this prompted us to investigate the hypothetical role of p16(INK4a) silencing in mycosis fungoides progression. We analyzed the three most frequent mechanisms of inactivation of the p16(INK4a) gene (deletion, promoter hypermethylation, and mutation) in nine cases with patch/plaque and tumoral lesions of mycosis fungoides. The existence of alterations was investigated by microsatellite analysis, methylation-specific polymerase chain reaction, and direct sequencing. Alterations of the p16(INK4a) gene were found in four of nine of the plaque lesions (hypermethylation in three samples and allelic loss in one sample) and seven of nine in the tumor lesions (hypermethylation in five samples and allelic loss in three samples). No case presented point mutations. Although a higher incidence of p16(INK4a) hypermethylation was observed in the cases that failed to achieve a complete remission, the limited size of our series prompted us to evaluate this finding cautiously. The results of this study therefore showed a common genetic alteration that is found more frequently in tumoral lesions than it is in plaque lesions of mycosis fungoides. It also offers data that could suggest a relationship between p16(INK4a) hypermethylation and unfavorable clinical outcome. Broader studies are needed to confirm both relationships.

Adult↗
PubMed2005

[Hypopigmented mycosis fungoides].

INTRODUCTION: Hypopigmented mycosis fungoides is a rare clinical form of the disease, first described in 1978. Since then, only a hundred odd cases have been documented. CASE REPORT: A young 19 year-old African woman had presented with hypochromatic macules since the age of 9 and for which the diagnostic enquiry had finally concluded in hypopigmented mycosis fungoides. DISCUSSION: The particularities of this form of mycosis fungoides, grade I according to the TNM classification, are principally its onset in black-skinned persons or of Asian origin, and the age of early onset with a predominance of pediatric cases. Its course is indolent for several years and thus source of delayed diagnosis. The differential diagnoses to be evoked are basically vitiligo, achromate eczematides and parapsoriasisis. The post-inflammatory depigmentation, frequent in black-skinned subjects, is only an eliminating diagnosis. Its treatment is that of classical Grade I mycosis fungoides: topical mechlorethamine, phototherapy and topical corticosteroids.

Adult↗
PubMed2005

[Mycosis fungoides with predominant periorificial and mucous involvement].

INTRODUCTION: Specific involvement of the mucous membranes is possible during the course of mycosis fungoides but has seldom been reported, except in postmortem series. A single mucous membrane is most often involved, mainly in the mouth. Such mucous lesions are generally ominous with regard to the general outcome of the disease. OBSERVATION: A 74 year-old woman was investigated for mycosis fungoides complicated with lesions around the mouth and of the mucosa, involving the tongue and esophagus, featuring ulcerated nodules with specific chorion infiltration and epidermotropism. This progression was rapidly followed by a fatal outcome, in spite of various systemic treatments. DISCUSSION: This case report of mycosis fungoides displaying multiple and predominant oral and mucosal involvement of mycosis fungoides is unique. The rapidly unfavorable outcome confirms the ominous prognosis of mucous lesions, whereas no patent visceral extension was detected. The mechanisms underlying the mucous membranes involvement is discussed.

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PubMed1986

Disseminated pagetoid reticulosis associated with mycosis fungoides: immunomorphologic study.

We report a 77-year-old woman with erythrosquamous plaques on the legs for 10 years. Biopsies taken 4 years ago revealed a pagetoid reticulosis with a massive epidermal cell infiltrate. She has now also developed a typical tumor of mycosis fungoides. The epidermal infiltrate of the two types of lesions bore the surface membrane marker for T lymphocytes rich in both T helper and T cytotoxic-suppressor subsets (ratio, 1.8). Both lesions also showed dendritic OKT6-positive Langerhans cells, and staining of the intercellular material with the DR locus of human lymphocyte antigen was positive. A dense dermal infiltrate was evident only in the mycosis fungoides lesions, and it was similar to that in the epidermis. Electron microscopy of the two lesions showed the atypical cells described in mycosis fungoides and the Sézary syndrome. These observations suggest that disseminated pagetoid reticulosis probably is a variant of mycosis fungoides.

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PubMed1986

Cutaneous malignancies and metastatic squamous cell carcinoma following topical therapies for mycosis fungoides.

Specific treatments for mycosis fungoides, including electron beam irradiation, topical mechlorethamine, and psoralen plus ultraviolet A (PUVA) may be associated with the development of skin cancers after a variable latency period. Because these treatments are often not curative, topical therapies for mycosis fungoides, administered sequentially or concomitantly, are being used increasingly in order to control recurrent disease. This report documents the development of multiple cutaneous tumors, including squamous cell carcinoma, basal cell carcinoma, actinic keratoses, keratoacanthomas, and one case of lentigo maligna, in seven patients who received topical therapies for mycosis fungoides. In contrast to the usual latency period between ionizing radiation therapy and the development of skin cancer, two of our patients who had received prior PUVA therapy developed multiple skin tumors upon completion of electron beam irradiation. The development of metastatic squamous cell carcinoma in two of the other seven patients with multiple cutaneous neoplasms suggests that this potential hazard must be considered in the evaluation and treatment of patients with mycosis fungoides.

Administration, Topical↗
PubMed1986

Epidermal mucinosis in mycosis fungoides.

In many cases of mycosis fungoides there is widening of the epidermal intercellular spaces (i.e., spongiosis) and papillary dermal fibrosis with minimal papillary dermal edema. Twenty biopsies of mycosis fungoides, stained with a modified colloidal iron procedure, were analyzed to substantiate the notion that the spongiosis resulted from the formation of an osmotic gradient because of intercellular acidic mucopolysaccharide deposition. In nineteen of twenty cases of patch-plaque mycosis fungoides, there was positive intercellular deposition of acidic mucopolysaccharides. In addition to the contribution of acidic mucopolysaccharides to the process of spongiosis, the biologic significance of epidermal mucin deposition is discussed. Mycosis fungoides should be added to the growing list of diseases in which there is epidermal mucinosis.

Adult↗
PubMed1987

Diffuse, progressive hyperpigmentation: an unusual skin manifestation of mycosis fungoides.

Pigmentary changes in mycosis fungoides usually occur in association with poikiloderma atrophicans vasculare or following therapy and regression of lesions. Several cases of hypopigmented mycosis fungoides have also been reported. We present the case report of a patient who developed pruritic, diffuse macular hyperpigmentation of the skin. Biopsy specimens from hyperpigmented skin revealed histologic and ultrastructural features typical of mycosis fungoides. Giant melanin granules were found in the tumor cells, as well as in keratinocytes and Langerhans cells. As far as we know, this is the first report of cutaneous hyperpigmentation as a single presenting sign of mycosis fungoides.

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PubMed1996

Mycosis fungoides presenting as an acquired ichthyosis.

A 25-year-old patient with an acquired ichthyosis-like condition is described. Histologic and molecular biologic examination of the fine, whitish, scaling skin lesions suggested the diagnosis of mycosis fungoides. Typical lesions of mycosis fungoides, such as patches, plaques, or tumors, were not present. To the best of our knowledge, this is the first case of mycosis fungoides presenting solely with the clinical features of acquired ichthyosis. The sudden appearance of ichthyosiform skin changes in adults must be taken seriously and the underlying cause must be evaluated. A skin biopsy should be performed in all cases of acquired ichthyosis to rule out mycosis fungoides.

Adult↗
PubMed1997

Spontaneous regression of granulomatous mycosis fungoides in an HIV positive patient.

The development of mycosis fungoides in HIV-positive patients is uncommon. We describe the granulomatous type of mycosis fungoides in an HIV-positive patient whose cutaneous lesions regressed without treatment. In addition to HIV seropositivity and mycosis fungoides, he had a long history of pulmonary sarcoidosis. Immunophenotyping of the cutaneous lymphoid infiltrates revealed a predominance of CD4+ T cells, and monoclonality was demonstrated by T-cell gene rearrangement studies. The regression of mycosis fungoides in this patient was associated with a falling peripheral blood CD4 T-cell count.

Adult↗
PubMed1998

Radiotherapy for unilesional mycosis fungoides.

PURPOSE: To evaluate the treatment outcome and natural history of patients with the diagnosis of unilesional mycosis fungoides, treated according to a prospective radiotherapy protocol in our institution since July 1975. METHODS AND MATERIALS: A total of 325 patients with the diagnosis of mycosis fungoides have been referred to the Department of Radiation Oncology at Allegheny University of Health Sciences from July 1975 through September 1996. Of these, 18 patients (5%) were classified as having unilesional mycosis fungoides and were irradiated with a curative intent using local electron fields. One patient received 22 Gy; 1 patient received 40 Gy, and the rest of the patients 30.6 Gy. Daily fractions ranged from 1.8 to 2.0 Gy. Treatments prior to radiation consisted of topical steroids and/or antifungal creams in the majority of patients, with temporary partial responses. One patient had received 2 years of topical mechlorethamine (HN2) and another patient had received topical carmustine solution (BCNU) without response prior to irradiation. RESULTS: The responses were measured clinically; posttreatment skin biopsy was not performed routinely unless there was clinical evidence of disease persistence. Complete response rate was 100%; all treated lesions cleared completely within 4 to 8 weeks after the completion of radiation. With a median follow-up of 43 months (range 12 to 240 months), 2 relapses have occurred, 2 and 71 months after the completion of radiation. Both relapses were confined to the skin and were remote from the original site. Both relapses responded to topical application of HN2. There have been no recurrences in the irradiated field nor systemic dissemination. No long-term side effects were found related to treatment, and all the patients are currently alive and without evidence of disease. Actuarial relapse-free and overall survival at 10 years are, respectively, 86.2% and 100%. CONCLUSION: Unilesional mycosis fungoides has a long natural history, is possibly the earliest manifestation of a malignant process, and local treatments, including local radiotherapy, result in long-term disease-free intervals and, possibly, cure. Total skin electron beam radiotherapy is not indicated for this disease entity.

Adult↗
PubMed2000

Failure of detection of mucin in the clear halos around the epidermotropic lymphocytes in mycosis fungoides.

Epidermotropic lymphocytes in mycosis fungoides typically reside in clear lacunae. The material forming this space is unknown. Thirty specimens from 30 patients with mycosis fungoides were stained with alcian blue, modified Mowry's colloidal iron and mucicarmine to determine if some form of mucin could be identified. Using these stains, no form of mucin was noted in the lacunae surrounding the epidermotropic lymphocytes of mycosis fungoides. The cause of the clear spaces around epidermotropic lymphocytes in mycosis fungoides remains unexplained, but is unlikely to represent mucin deposition.

Alcian Blue↗
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↗
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↗
PubMed2002

Mycosis fungoides causing severe lower eyelid ulceration.

Mycosis fungoides is a form of cutaneous malignant T-cell lymphoma initially confined to the skin. A range of ophthalmic manifestations has been described; these usually appear in advanced disease. Lid involvement is most common and ranges from ectropion, usually cicatricial, to diffuse thickening and placoid tumours. A case of a 72-year-old man presenting with progressive, full thickness, lower eyelid ulceration is presented. The patient had a long history of placoid skin lesions, previously diagnosed as discoid lupus. Repeat biopsies of these lesions including the eyelid eventually revealed mycosis fungoides. The ulceration progressed to destroy most of the lower lid before the correct diagnosis was made. This type of eyelid involvement has not previously been reported in mycosis fungoides. This case also highlights the diagnostic difficulties encountered in the early phases of mycosis fungoides. If suspected, multiple biopsies are essential to establish the diagnosis.

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PubMed2000

Granulomatous mycosis fungoides. Report of two cases and review of the literature.

BACKGROUND: Granulomatous mycosis fungoides is an extremely rare type of cutaneous T-cell lymphoma. Two cases are described and checked for clinical, histological and therapeutic differences to other variants of mycosis fungoides. CASE REPORTS: Case 1: a 52-year-old patient with livid plaques covering the whole integument. Histological findings showed granulomas with multinuclear giant cells in addition to a malignant lymphohistiocytic infiltrate (monodonal T-cell receptor (TCR)-gamma rearrangement). Despite various chemotherapeutic regimens, progression to tumour stage was observed. Case 2: an 88-year-old man with plaques and ulcerating tumours on the trunk and head. Histological findings showed malignant T-lymphocyte infiltrate (monoclonal TCR-gamma rearrangement) and granulomas with multinuclear foreign-body giant cells. Complete regression of all lesions was achieved using both local psoralen-ultraviolet A and electron radiotherapy. CONCLUSIONS: The diagnosis of a granulomatous mycosis fungoides depends exclusively on the histological demonstration of granulomas. Distinct clinical characteristics are not present. Apart from granuloma formation, no other noticeable histological features are evident. The presence of granulomas in mycosis fungoides does not have prognostic implications, as cases with aggressive, but also with a prolonged course have been described.

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PubMed1999

Expression of the CD4+ cell-specific chemoattractant interleukin-16 in mycosis fungoides.

Interleukin-16 is a soluble ligand to the CD4 molecule with chemotactic properties for CD4+ cells and a competence growth factor for CD4+ T cells, upregulating HLA-DR and the interleukin-2 receptor CD25. There is also evidence for a synergistic effect of interleukin-16 and interleukin-2 on the activation of CD4+ T cells. The infiltrate in mycosis fungoides, the most common cutaneous T cell lymphoma, is typically CD4+. We tested the possibility that interleukin-16 is involved in the formation and progression of these lesions. By reverse transcription-polymerase chain reaction, interleukin-16 mRNA was detected in 18 of 18 mycosis fungoides lesions investigated. By competitive reverse transcription-polymerase chain reaction, interleukin-16 mRNA expression increased with disease stage. Secreted interleukin-16 was detected by enzyme-linked immunosorbent assay in both Th1- and Th2-like T cell clones (as characterized by their production of interferon-gamma and interleukin-4) grown from lesional dermis and epidermis. By immunohistochemistry and in situ hybridization, infiltrating lymphocytes were the main producers of interleukin-16 whereas keratinocytes and endothelial cells remained negative. Atypical cells with convoluted nuclei were also positive. In advanced mycosis fungoides stages, many blast-like cells were positive, but some larger blasts remained negative. Interleukin-16 expression correlated positively with the expression of interleukin-2 and its receptor CD25 in individual skin lesions. Interleukin-2 expression, however, was weak or absent in samples from uninvolved skin, healthy controls and lesional psoriasis. Given the biologic properties of interleukin-16 and the parallel activation of the interleukin-2/CD25 pathway, interleukin-16 might be involved in the recruitment and stimulation of CD4+ lymphocytes in mycosis fungoides lesions and therefore contribute to the perpetuation of the associated cutaneous inflammation.

CD4-Positive T-Lymphocytes↗
PubMed2000

Detection of a peripheral blood T cell clone is an independent prognostic marker in mycosis fungoides.

UNLABELLED: T cell receptor gene analysis is a sensitive method for assessment of peripheral blood involvement in mycosis fungoides. This study uses polymerase chain reaction/single-strand conformational polymorphism (PCR/SSCP) analysis of the T cell receptor gamma gene and relates the results to skin stage and outcome in mycosis fungoides. Seventy-five peripheral blood samples from 66 patients were obtained from 1990 onwards and subjected to PCR/SSCP. Both Southern blot analysis and PCR/SSCP analysis were performed on 63 samples from 56 patients. Fourteen patients had T1 disease (12 IA, two IIA), 20 T2 (14 IB, five IIA, one IVA), 29 T3 (24 IIB, two IVA, three IVB, two patients tested at both T2 and T3), and five T4 (all III). The percentage of positive samples was higher with PCR/SSCP than with Southern blot analysis (29 of 63 vs eight of 63 samples, p < 0.001), and the percentage of positive samples increased with each stage (21% at T1, 35% at T2, 58% at T3, and 71% at T4). Proportional hazards analysis corrected for age, skin, and lymph node stage showed that the presence of a peripheral blood clone is associated with a worse outcome (p = 0.03, CI 1.1-6.03). These results indicate that the presence of a peripheral blood clone is an independent prognostic variable in patients with mycosis fungoides after correcting for age, skin, and lymph node stage, and that peripheral blood involvement is present in a large proportion of patients with early stage mycosis fungoides. KEYWORDS: polymerase chain reaction/single-strand conformational polymorphism/T cell receptor gene rearrangement. J Invest Dermatol 114:117-121, 2000

Biomarkers↗
PubMed2001

Mycosis fungoides bullosa: report of a case and review of the literature.

Mycosis fungoides, the most common type of cutaneous T-cell lymphoma, can manifest in a variety of clinical and histologic forms. Presentation with vesiculobullous lesions is extremely rare. We report the ninth documented case of mycosis fungoides bullosa in which other concomitant autoimmune blistering diseases were ruled out by negative immunofluorescence. All previously reported cases in the world literature since the first in 1887 are reviewed. We recommend the following defining criteria for the disease: (1) clinically apparent vesiculobullous lesions, with or without typical mycosis fungoides lesions (patches, plaques, tumors); (2) typical histologic features of mycosis fungoides (atypical lyphoid cells, epidermotropism, Pautrier's microabscesses) with intraepidermal or subepidermal blisters; (3) negative immunofluorescence (both direct and indirect, if possible) to rule out concomitant autoimmune bullous diseases; (4) negative evaluation for other possible causes of vesiculobullous lesions (eg, medications, bacterial or viral infection, porphyria, phototherapy).

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