Cases reported "Mycosis Fungoides"

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1/10. 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.
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2/10. Establishment of two continuous T-cell strains from a single plaque of a patient with mycosis fungoides.

    From a plaque biopsy of a patient with mycosis fungoides, two different continuous cell lines were established by including both IL-2 and IL-4 in the culture medium. Both continuous cell lines appeared with characteristic chromosome markers after approximately 40 cell population doublings. The initial karyotype recognized in T cells from the skin biopsy was 46,XY and the karyotypes of the continuous cell strains were 46,XY, -18, i(18q) and another with multiple chromosome aberrations as described in Sezary T-cell leukemia. Phenotyping with monoclonal antibodies and T-cell receptor analysis indicates that the latter cell strain represents a minority of T-cells in the plaque. Due to its many chromosomal aberrations it probably represents the malignant cell, which may be a central cell in the immune stimulation taking place in the skin.
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3/10. A case of classical mycosis fungoides associated with human T-cell lymphotropic virus type I.

    A 72-year-old male patient from north-eastern iran developed the typical clinical and histopathological features of mycosis fungoides with lymphadenopathy, but without any other systemic involvement. Human T-cell lymphotropic virus (HTLV-I) antibodies were detected in the patient's serum by two different ELISAs and by Western blot using purified viral particles from MT-2 culture supernatants. Cultured peripheral blood lymphocytes were positive for labelling with anti-HTLV-I serum. Southern blot hybridization of dna extracted from a skin tumour and from an involved lymph node revealed integrated proviral dna with identical restriction patterns. This case supports a relationship between mycosis fungoides and HTLV-I and may indicate a new region of endemic HTLV-I infection.
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4/10. Phenotypic and functional characterization of tumor infiltrating lymphocytes in mycosis fungoides: continuous growth of CD4 CD45R T-cell clones with suppressor-inducer activity.

    Tumor-infiltrating lymphocytes (TIL) were obtained by mechanical release from a solitary rapidly grown tumor of a patient with mycosis fungoides. The preparations separated by density gradient centrifugation contained a major portion of CD3 CD8 WT31 CD5- large T-cell blasts and a minor portion of non-blastic TIL predominantly of the CD3 CD4 phenotype. Using cDNA-probes for the constant region of the T-cell receptor beta-genes, the large cell fraction was identified as tumor by its distinct monoclonal rearrangement. TIL were expanded by culture in recombinant interleukin 2 and cloned by limiting dilution. Phenotypic analysis of expanded TIL and two clones further analyzed in more detail showed CD3 , CD4 , CD8-, and 2H4 (CD45R ) expression. Cloned and uncloned TIL showed no NK and LAK activity, no proliferative response, and no cytotoxic activity against autologous tumor cells. These cells were unable to suppress the proliferative response of alloreactive T-cell clones stimulated by B-lymphoblastoid cell lines (i.e., they had no suppressor-effector activity), but strongly suppressed proliferation responses in allogeneic mixed lymphocyte culture (i.e., they most likely had suppressor-inducer activity). This was not the case when irradiated tumor cells were added. The present results demonstrate continuous in vitro growth of CD4 and 2H4 T-cell clones with suppressor-inducer activity obtained from TIL, and indicate that a subpopulation of TIL may down-regulate immune responses which may lead to suppression of antitumor immunity.
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5/10. Functional properties in Sezary cells with an unusual phenotype.

    The immunological and functional characteristics of Sezary cells with an unusual phenotype are reported. The clinical, histologic, and hematologic picture was typical for sezary syndrome. Studies with monoclonal antibodies showed that 80% Sezary cells had an CD3 , CD4 , CD5 , CD7-, CD8-, Leu-7 , Leu-8-, Leu-11-, OKM1- phenotype. By two-color immunofluorescence assay 80% FACS-sorted Leu-7 cells coexpressed CD4 antigen and did not express the myeloid antigen OKM1, CD8, and antigens characteristic of immature T cells. The cells had no NK activity but did display a high helper activity. Unseparated and FACS-sorted Leu-7 and Leu-7- Sezary cells did not respond to mitogens but were able to grow in the presence of exogenous IL-2. FACS sorted Leu-7- cells, cultured for 7 days in the presence of 20% IL-2, acquired the receptors for Leu-7. IL-2 and IFN-gamma production was studied in unseparated Leu-7 and Leu-7- FACS-sorted Sezary cells. IL-2 production was lower than in normal cells. The addition of PHA or PHA plus TPA led to an increase in IL-2 production. Also IFN-gamma production was marked lower than in normal controls but increased after 7-day culture in exogenous IL-2. In conclusion in this case the Sezary cells may represent a neoplastic expansion of the CD3 , CD4 , CD5 , Leu-7 , Leu-11- subpopulation which is equivalent to the 2-4% of the Leu-7 population in normal lymphocytes.
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6/10. Subpopulations of T lymphocytes in a patient with fulminant mycosis fungoides.

    A patient with fulminant mycosis fungoides was found to have a very high percentage of T lymphocytes with Fc receptors for IgG and a low percentage of T lymphocytes with Fc receptors for IgM. The total number of T lymphocytes was normal, but the in vitro function of the lymphocytes was depressed in short-term cultures, though not in cultures of 5 days' duration. T lymphocytes with Fc receptors for IgG are considered to have suppressor functions, and the immunological changes in this patient may be explained by an increased suppressor cell activity. Other investigators have proposed that the abnormal lymphocytes in mycosis fungoides are T helper cells. After treatment with electron beam and transfer factor, our patient developed uraemia due to uric acid crystallization in the kidneys. This complication to the treatment given seems not to have been reported before.
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7/10. Skeletal manifestations in cutaneous T-cell lymphomas.

    The clinical course of three patients with cutaneous T-cell lymphoma (CTCL) in whom skeletal disease developed is presented and the literature on skeletal involvement in these disorders is reviewed. Three separate types of skeletal manifestations occurred: (1) osteolytic lesions, (2) osteoblastic lesions, and (3) diffuse osteoporosis. hypercalcemia was present in two cases. Tumor cells from two patients in short-term culture secreted osteoclast-activating factor(s). Both of these patients had pathologic evidence of osteoclast activation in bone sections. Thus, the tumor cells in certain patients with CTCL may derive from a monoclonal proliferation of a T-cell subset capable of producing humoral bone-resorbing factor(s) similar to those demonstrated in cultures of mitogen- and antigen-activated normal lymphocytes. Since skeletal lesions are unusual, it would follow that other T-cell subsets account for pathologic cell proliferation in most patients with CTCL.
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8/10. Widespread cutaneous candidiasis and tinea infection masking mycosis fungoides.

    A 71-year-old female with a widespread double mycotic infection caused by C. Albicans and T. rubrum was discovered to be suffering from mycosis fungoides. Clinically she was found to have large, polycyclic erythematous plaques with scaly, slightly infiltrated borders, covering almost all areas of the glabrous skin, and also involving the scalp (with no hair penetration), the soles and palms, toe-webs, finger and toe nails; there was also perleche and oral thrush. Cultures yielded C. albicans from most of the skin lesions, from the scalp, mouth, finger nails and urine and stool specimens, and T. rubrum from intermingled skin specimens, from the palms and soles and toe-nails. blood culture was negative as were intracutaneous tests with fungal antigens and tuberculin. Histological examination confirmed the fungal invasion of the horny layer and at the same time revealed an underlying pathologic picture of mycosis fungoides, the lesions having been masked by the mycotic eruption. Intensive cytostatic and antifungal therapy led to a transient improvement but shortly thereafter there was a relapse of the fungal and lymphoproliferative manifestations and the patient died in septic shock.
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9/10. Banding studies of chromosomes in a patient with mycosis fungoides.

    chromosomes from a patient with mycosis fungoides were examined in detail with banding techniques. Hyperdiploid cells from a lymph node had common anomalies of certain chromosomes which formed three similar clones. The abnormalities involved chromosomes No. 1, 2, 5, 8, 9, 10, 14, and 18, in addition to an unkwown small metacentric marker (M3). Although there were a number of mitotic cells in peripheral blood cultured both with and without PHA, none of the few cells with abnormal karyotypes was similar to the clonal cells of the lymph node. One of the abnormalities in the lymph node was a 14q rearrangement, which could be the result of a translocation of Nos. 8 and 14 involving a third chromosome, No. 2. An abnormality in the blood resulted from a translocation between the long arms of Nos. 1 and 14. These findings could be useful for studies in which mycosis fungoides is compared with the sezary syndrome and other lymphoid malignancies.
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10/10. An unusual and fatal case of disseminated cutaneous herpes simplex. infection in a patient with cutaneous T cell lymphoma (mycosis fungoides).

    A patient with plaque stage mycosis fungoides (MF) developed an atypical disseminated cutaneous herpes simplex virus (HSV) infection manifested by polycyclic cutaneous ulcers. Although Tzanck preparations and serial antibody titers to herpes virus were negative, the diagnosis was readily established by viral culture and histologic examination of the skin lesions. Following adenine arabinoside therapy, the viral cultures of the ulcers became negative and the spread of virus-induced ulcerations ceased. In an immunocompromised host with rapidly advancing, sharply punched-out polycyclic cutaneous ulcerations, herpes simplex infection should be considered even though the classical vesicular lesions are absent.
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