Mycosis Fungoides: A chronic, malignant T-cell lymphoma of the skin. In the late stages, the LYMPH NODES and viscera are affected.Sezary Syndrome: A form of cutaneous T-cell lymphoma manifested by generalized exfoliative ERYTHRODERMA; PRURITUS; peripheral lymphadenopathy, and abnormal hyperchromatic mononuclear (cerebriform) cells in the skin, LYMPH NODES, and peripheral blood (Sezary cells).Skin Neoplasms: Tumors or cancer of the SKIN.Lymphoma, T-Cell, Cutaneous: A group of lymphomas exhibiting clonal expansion of malignant T-lymphocytes arrested at varying stages of differentiation as well as malignant infiltration of the skin. MYCOSIS FUNGOIDES; SEZARY SYNDROME; LYMPHOMATOID PAPULOSIS; and PRIMARY CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA are the best characterized of these disorders.Parapsoriasis: The term applied to a group of relatively uncommon inflammatory, maculopapular, scaly eruptions of unknown etiology and resistant to conventional treatment. Eruptions are both psoriatic and lichenoid in appearance, but the diseases are distinct from psoriasis, lichen planus, or other recognized dermatoses. Proposed nomenclature divides parapsoriasis into two distinct subgroups, PITYRIASIS LICHENOIDES and parapsoriasis en plaques (small- and large-plaque parapsoriasis).PUVA Therapy: Photochemotherapy using PSORALENS as the photosensitizing agent and ultraviolet light type A (UVA).Mucinosis, Follicular: A disease of the pilosebaceous unit, presenting clinically as grouped follicular papules or plaques with associated hair loss. It is caused by mucinous infiltration of tissues, and usually involving the scalp, face, and neck. It may be primary (idiopathic) or secondary to mycosis fungoides or reticulosis.Ultraviolet Therapy: The use of ultraviolet electromagnetic radiation in the treatment of disease, usually of the skin. This is the part of the sun's spectrum that causes sunburn and tanning. Ultraviolet A, used in PUVA, is closer to visible light and less damaging than Ultraviolet B, which is ionizing.Skin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Acitretin: An oral retinoid effective in the treatment of psoriasis. It is the major metabolite of ETRETINATE with the advantage of a much shorter half-life when compared with etretinate.Hypopigmentation: A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections.Antigens, CD7: Differentiation antigens expressed on pluripotential hematopoietic cells, most human thymocytes, and a major subset of peripheral blood T-lymphocytes. They have been implicated in integrin-mediated cellular adhesion and as signalling receptors on T-cells.Lymphomatoid Papulosis: Clinically benign, histologically malignant, recurrent cutaneous T-cell lymphoproliferative disorder characterized by an infiltration of large atypical cells surrounded by inflammatory cells. The atypical cells resemble REED-STERNBERG CELLS of HODGKIN DISEASE or the malignant cells of CUTANEOUS T-CELL LYMPHOMA. In some cases, lymphomatoid papulosis progresses to lymphomatous conditions including MYCOSIS FUNGOIDES; HODGKIN DISEASE; CUTANEOUS T-CELL LYMPHOMA; or ANAPLASTIC LARGE-CELL LYMPHOMA.Skin DiseasesVitiligo: A disorder consisting of areas of macular depigmentation, commonly on extensor aspects of extremities, on the face or neck, and in skin folds. Age of onset is often in young adulthood and the condition tends to progress gradually with lesions enlarging and extending until a quiescent state is reached.Methoxsalen: A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA ADDUCTS in the presence of ultraviolet A irradiation.Dermatitis, Exfoliative: The widespread involvement of the skin by a scaly, erythematous dermatitis occurring either as a secondary or reactive process to an underlying cutaneous disorder (e.g., atopic dermatitis, psoriasis, etc.), or as a primary or idiopathic disease. It is often associated with the loss of hair and nails, hyperkeratosis of the palms and soles, and pruritus. (From Dorland, 27th ed)Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor: Ordered rearrangement of T-cell variable gene regions coding for the gamma-chain of antigen receptors.Mechlorethamine: A biologic alkylating agent that exerts its cytotoxic effects by forming DNA ADDUCTS and DNA interstrand crosslinks, thereby inhibiting rapidly proliferating cells. The hydrochloride is an antineoplastic agent used to treat HODGKIN DISEASE and LYMPHOMA.Radiotherapy, High-Energy: Radiotherapy using high-energy (megavolt or higher) ionizing radiation. Types of radiation include gamma rays, produced by a radioisotope within a teletherapy unit; x-rays, electrons, protons, alpha particles (helium ions) and heavy charged ions, produced by particle acceleration; and neutrons and pi-mesons (pions), produced as secondary particles following bombardment of a target with a primary particle.Lymphoma, T-Cell: A group of heterogeneous lymphoid tumors representing malignant transformations of T-lymphocytes.Gene Rearrangement, T-Lymphocyte: Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.Telangiectasis: Permanent dilation of preexisting blood vessels (CAPILLARIES; ARTERIOLES; VENULES) creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders.Antigens, CD30: A member of the tumor necrosis factor receptor superfamily that may play a role in the regulation of NF-KAPPA B and APOPTOSIS. They are found on activated T-LYMPHOCYTES; B-LYMPHOCYTES; NEUTROPHILS; EOSINOPHILS; MAST CELLS and NK CELLS. Overexpression of CD30 antigen in hematopoietic malignancies make the antigen clinically useful as a biological tumor marker. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Lymphatic Diseases: Diseases of LYMPH; LYMPH NODES; or LYMPHATIC VESSELS.Immunophenotyping: Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.Occlusive Dressings: Material, usually gauze or absorbent cotton, used to cover and protect wounds, to seal them from contact with air or bacteria. (From Dorland, 27th ed)Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.
Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma is a cutaneous condition that usually presents as solitary or generalized plaques, nodules, or tumors of short duration.Cutaneous lymphoma: There are two classes of lymphomas that affect the skin:Large plaque parapsoriasisPUVA-induced acrobullous dermatosis: PUVA-induced acrobullous dermatosis is a cutaneous condition characterized by the sudden occurrence of tense blisters, usually on the distal extremities, during long-term PUVA therapyUrticaria-like follicular mucinosis: Urticaria-like follicular mucinosis is a rare cutaneous disorder that occurs primarily in middle-aged men.Ultraviolet light therapyDermal equivalent: The dermal equivalent is an in vitro model of the dermal layer of skin. It is constructed by seeding dermal fibroblasts into a collagen gel.AcitretinProgressive macular hypomelanosis: Progressive macular hypomelanosis is a common skin condition, a disorder, observed more frequently in young women with darkly pigmented skin who originate from or reside in tropical climates.Vitiligo Research FoundationBergaptenErythrodermaMegavoltage X-raysT-cell receptor excision circles: T-cell receptor excision circles (TRECs) are small circles of DNA created in T-cells during their passage through the thymus as they rearrange their TCR genes.http://allergycases.Telangiectasia macularis eruptiva perstans: Telangiectasia macularis eruptiva perstans is persistent, pigmented, asymptomatic eruption of macules usually less than 0.5 cm in diameter with a slightly reddish-brown tinge.Brentuximab vedotinDermatopathic lymphadenopathyImmunophenotyping: Immunophenotyping is a technique used to study the protein expressed by cells. This technique is commonly used in basic science research and laboratory diagnostic purpose.Brain biopsyPMHC cellular microarray: PMHC cellular microarrays are a type of cellular microarray that has been spotted with pMHC complexes peptide-MHC class I or peptide-MHC class II.World Lymphoma Awareness Day: World Lymphoma Awareness Day (WLAD) is held on September 15 every year and is a day dedicated to raising awareness of lymphoma, an increasingly common form of cancer. It is a global initiative hosted by the Lymphoma Coalition (LC), a non-profit network organisation of 63 lymphoma patient groups from 44 countries around the world.
(1/348) Expression of cytotoxic proteins by neoplastic T cells in mycosis fungoides increases with progression from plaque stage to tumor stage disease.
Granzyme B (GrB) and T-cell-restricted intracellular antigen (TIA-1) are cytotoxic proteins that are specifically expressed by cytotoxic CD4 or CD8 positive T cells and natural killer cells. Recent studies demonstrated frequent expression of GrB and TIA-1 by neoplastic cells in primary cutaneous CD30(+) large T-cell lymphomas and lymphomatoid papulosis but not in CD30(-) large T-cell lymphomas. In the present study, 74 biopsies from 54 patients with mycosis fungoides (MF) were investigated for the expression of GrB and TIA-1 using immunohistochemistry on paraffin sections. Staining of more than 10% of the neoplastic T cells for GrB or TIA-1 was considered positive. All but two follow-up biopsies had been obtained from patients without extracutaneous disease at the time of biopsy. Expression of TIA-1 and GrB was found in 33 (45%) and 14 (19%) of 74 MF biopsies, respectively. Comparison of biopsies from T3NoMo-stage MF (n = 27) and T2NoMo-stage MF (n = 45) showed increased expression of TIA-1 (55 versus 37%) and GrB (33 versus 9%) in T3NoMo-stage MF. Evaluation of multiple sequential biopsies from successive stages of MF also revealed an increase in the GrB/TIA-1 expression with tumor progression in five of eight cases. A clearcut relation between the expression of TIA-1 and/or GrB and the type of skin lesion biopsied was found. Considering all 74 biopsies, expression of TIA-1 and GrB was found in 18 of 50 (35%) and 5 of 50 (10%) patches or plaques, 9 of 16 (55%) and 3 of 16 (20%) tumors without blastic transformation, and 6 of 8 (75%) and 6 of 8 (75%) tumors with blastic transformation (defined as >50% blast cells). Correlation between GrB/TIA-1 expression in first diagnostic biopsies from patches or plaques from 40 patients with T2NoMo-stage MF and clinical follow-up data did not reveal differences in clinical behavior and survival between patients with (n = 14) or without (n = 26) expression of cytotoxic proteins, indicating that MF expressing cytotoxic proteins should not be considered as a separate group. (+info)
(2/348) Prognostic factors in primary cutaneous lymphomas other than mycosis fungoides and the Sezary syndrome. The French Study Group on Cutaneous Lymphomas.
Prognostic studies of primary cutaneous lymphomas (PCL) other than mycosis fungoides (MF) and the Sezary syndrome (SS; non-MF/SS PCL) have been mainly performed on subgroups or on small numbers of patients by using univariate analyses. Our aim was to identify independent prognostic factors in a large series of patients with non-MF/SS PCL. We evaluated 158 patients who were registered in the French Study Group on Cutaneous Lymphomas database from January 1, 1986 to March 1, 1997. Variables analyzed for prognostic value were: age; sex; type of clinical lesions; maximum diameter, location, and number of skin lesions; cutaneous distribution (ie, local, regional, or generalized); prognostic group according to the European Organization for Research and Treatment of Cancer (EORTC) classification for PCL; B- or T-cell phenotype; serum lactate dehydrogenase (LDH) level; and B symptoms. Univariate and multivariate analyses were performed using a model of relative survival. Forty-nine patients (31%) died. The median relative survival time was 81 months. In univariate analysis, EORTC prognostic group, serum LDH level, B symptoms, and variables related to tumor extension (ie, distribution, maximum diameter, and number of skin lesions) were significantly associated with survival. When these variables were considered together in a multivariate analysis, EORTC prognostic group and distribution of skin lesions remained statistically significant, independent prognostic factors. This study confirms the good predictive value of the EORTC classification for PCL and shows that the distribution of skin lesions at initial evaluation is an important prognostic indicator. (+info)
(3/348) Ophthalmic abnormalities in patients with cutaneous T-cell lymphoma.
PURPOSE: To determine the frequency of ophthalmic abnormalities in patients with cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome) and T-cell lymphoma involving the skin and to describe the clinical course of the disease with selected examples. METHODS: A computerized diagnostic retrieval system was used to identify all patients with T-cell lymphoma involving the skin who were examined at the Mayo Clinic (Rochester, Minnesota) between January 1, 1976 and December 31, 1990. The medical records of affected patients were reviewed. RESULTS: During the 15-year interval from 1976 through 1990, cutaneous T-cell lymphoma was diagnosed in 2,155 patients. Of these 2,155 patients, 42 (1.95%; 26 male and 16 female) had at least 1 ophthalmic abnormality attributable to the disease. The diagnoses in these 42 patients were mycosis fungoides in 19, clinical variants of T-cell lymphoma of the skin (most commonly, peripheral T-cell lymphoma) in 11, and Sezary syndrome in 12. Cicatricial eyelid ectropion was the most common finding, affecting 17 (40.4%) of the 42 patients. Thirty-seven patients had findings that, although probably not a direct consequence of cutaneous T-cell lymphoma, have been cataloged in previous studies. CONCLUSION: Although ophthalmic abnormalities in patients with cutaneous T-cell lymphoma are relatively uncommon, the manifestations of the disease are diverse and frequently difficult to treat. (+info)
(4/348) Twenty-year trends in the reported incidence of mycosis fungoides and associated mortality.
OBJECTIVES: Patterns of mycosis fungoides incidence and associated mortality in the United States were evaluated. METHODS: Data were taken from the Surveillance, Epidemiology, and End Results cancer registry program and the National Center for Health Statistics. RESULTS: The incidence rate from 1973 through 1992 was 0.36/10(5) person-years. The age-adjusted incidence rate ratio of Blacks to Whites was 1.7; that of Asians to Whites was 0.6. There was no evidence of increasing incidence rates during the period 1983 through 1992. Mortality rates declined steadily from 1979 to 1991 and were less heterogeneous geographically than incidence rates. Mortality rate patterns with age, sex, and race were similar to the corresponding incidence patterns. CONCLUSIONS: The incidence rate of mycosis fungoides has stabilized and the mortality rate has declined. For unknown reasons, the disorder varies greatly among demographic and geographic subgroups. (+info)
(5/348) O6-alkylguanine-DNA alkyltransferase in cutaneous T-cell lymphoma: implications for treatment with alkylating agents.
Mycosis fungoides is a low-grade cutaneous T-cell lymphoma. Early treatment often involves the use of topical chemotherapy such as mechlorethamine or carmustine although single-agent oral chemotherapy with alkylators is common for advanced disease. Recently, in a Phase I study of the new alkylating agent temozolomide, two mycosis fungoides patients experienced a complete response. The mechanism of resistance to alkylating drugs such as temozolomide is thought to be due to the presence in tumor cells of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT). The protein mediates a reaction with the O6-position of guanine in DNA, removing the lesion and leaving guanine intact. We, therefore, examined the levels of AGT in CD4+ T lymphocytes obtained by negative antibody selection from the blood of noncancerous individuals and mycosis fungoides patients, and in paraffin-embedded sections from mycosis fungoides patch, plaque, or tumor lesions and cells from involved lymph nodes. AGT protein levels were measured by quantitative immunofluorescence microscopy using a monoclonal antibody against human AGT. Using this approach, the mean level of our positive control (AGT-expressing cells) was 84,807 molecules/nucleus; values below 5,000 molecules/nucleus are considered very low. The mean AGT level in CD4+ T lymphocytes from noncancerous and cancerous individuals was 18,618 (n = 12) and 8,593 (n = 5), respectively. The mean fraction of outliers in circulating CD4+ T lymphocytes from mycosis fungoides patients was statistically significantly lower than T cells in lymph nodes. AGT molecules/nucleus from lymph node biopsies from 8 of 10 patients showed low (< 10,000 molecules/nucleus) or undetectable levels (n = 5) of AGT. The mean AGT level from samples of mycosis fungoides patch/plaque and tumor was also low at 221 (n = 4) and 2,363 (n = 6), respectively. Surprisingly, Hut78, a mycosis fungoides T-cell lymphoma cell line, was positive for AGT activity (median: 77,700 molecules/nucleus), and Hut102--another mycosis fungoides cell line--was low (median: 5,990 molecules/nucleus). Because AGT is a primary means of cell resistance to alkylating agents, the low level of AGT in neoplastic T lymphocytes from patients with mycosis fungoides suggests that treatment with alkylating agents producing O6-alkylguanine adducts, such as carmustine or temozolomide, may produce improved clinical outcomes. (+info)
(6/348) Low dose interferon-alpha2b combined with PUVA is an effective treatment of early stage mycosis fungoides: results of a multicenter study. Cutaneous-T Cell Lymphoma Multicenter Study Group.
BACKGROUND AND OBJECTIVE: The early stages of mycosis fungoides (MF) can be treated but not cured by photochemotherapy (PUVA) alone; some recent studies of the effect of a combination of human interferon-alpha (IFN(alpha)) and PUVA reported a high degree of response. The aim of our study was to evaluate the activity of a low dose of IFN-alpha2b combined with PUVA. DESIGN AND METHODS: Twenty-five patients were included: 16 men and 9 women aged between 23-80 years; 19 patients ahd stage I and 6 stage II disease. In the induction phase, the dose of IFNalpha was gradually raised over 6-8 weeks to the target dose of 18 MU/week; in the maintenance phase, the combination with PUVA allowed IFNalpha to be reduced to a maximum dose of 6 MU/week; in this way the cumulative administration of IFNalpha and PUVA was considerably lower than in similar combination protocols. Treatment success was analyzed in terms of freedom from treatment failure (FFTF). RESULTS: After the induction phase 9/25 patients (36%) achieved complete remission (CR) and 15/25 (56%) achieved partial remission (PR). One to five months from the beginning of the maintenance phase, a CR was recorded in 19/25 patients (76%) and a PR in 5/25 patients (20%) accounting for an overall response rate of 96%. The median of FFTF was not reached; probability of FFTF was 82% at 12 months and 62% at 24 months. Disease free survival projected to 48 months was 75%. INTERPRETATION AND CONCLUSIONS: Even with low doses of IFNalpha plus PUVA it is possible to achieve excellent clinical responses,many of which are long-lasting, in patients with early MF. (+info)
(7/348) A novel Epstein-Barr virus-like virus, HV(MNE), in a Macaca nemestrina with mycosis fungoides.
Epstein-Barr virus (EBV) infection of humans has been associated with the development of lymphoid malignancies mainly of B-cell lineage, although occasionally T-cell lymphomas have been reported. We describe here the characterization of a novel EBV-like virus (HV(MNE)) isolated from a simian T-cell lymphotropic virus type I/II (STLV-I/II) seronegative pigtailed macaque (Macaca nemestrina) with a cutaneous T-cell lymphoma. Immunohistochemistry studies on the skin lesions demonstrated that the infiltrating cells were of the CD3(+)/CD8(+) phenotype. Two primary transformed CD8(+) T-cell lines were obtained from cultures of peripheral blood mononuclear cells (PBMC) and skin, and, with time, both cell lines became interleukin-2-independent and acquired the constitutive activation of STAT proteins. Polymerase chain reaction analysis of the DNA from the cell lines and tissues from the lymphomatous animal demonstrated the presence of a 536-bp DNA fragment that was 90% identical to EBV polymerase gene sequences, whereas the same DNA was consistently negative for STLV-I/II sequences. Electron microscopy performed on both cell lines, after sodium butyrate treatment, showed the presence of a herpes-like virus that was designated HV(MNE) according to the existing nomenclature. In situ hybridization studies using EBV Epstein-Barr viral-encoded RNA probes showed viral RNA expression in both CD8(+) T-cell lines as well as in the infiltrating CD8(+) T cells of skin-tissue biopsies. Phylogenetic analysis of a 465-bp fragment from the polymerase gene of HV(MNE) placed this virus within the Lymphocryptovirus genus and demonstrated that HV(MNE) is a distinct virus, clearly related to human EBV and other EBV-like herpesviruses found in nonhuman primates. (+info)
(8/348) 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. (+info)
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