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Combination chemotherapy for mycosis fungoides with cyclophosphamide, vincristine, methotrexate, and prednisone.

Seven patients with stage IV mycosis fungoides [TNM classification] have been treated with combination chemotherapy consisting of cyclophosphamide, vincristine, methotrexate, and prednisone [COMP]. A complete response rate of 57% was produced with an overall response of 100% in patients having limited prior steroid and/or chemotherapy. Complete responses range from 4+ to 20 months [median, 11 months]. Overall survival ranges from 2 to 40+ months [median, 12+ months]. The protocol was well tolerated except for one treatment-related death. Combination chemotherapy can produce effective remissions in patients with advanced mycosis fungoides. TNM classification should be considered in staging patients with mycosis fungoides for comparison of different treatment regimens.

Adult↗

Gallium-67 uptake in cutaneous lesions of mycosis fungoides.

The literature on gallium imaging in mycosis fungoides is limited and conflicting. A case of mycosis fungoides with increased uptake of Ga-67 in clinically noninfected skin lesions is reported. The literature regarding mycosis fungoides and gallium imaging is reviewed.

Aged↗

Mycosis fungoides of thyroid diagnosed by fine needle aspiration.

Fine needle aspiration of a poorly defined thyroid nodule in a patient with mycosis fungoides revealed convoluted mononuclear cells consistent with involvement by mycosis fungoides. I have briefly reviewed the literature on extracutaneous involvement, and discussed the potential usefulness of fine needle aspiration studies in diagnosing visceral or lymphatic mycosis fungoides.

Biopsy, Needle↗

Early mycosis fungoides: can the diagnosis be made reliably?

The diagnosis of early mycosis fungoides is often regarded as difficult or impossible due to the lack of clear-cut histopathologic criteria. Many authors have published observations of histologic features seen in biopsies of patients with mycosis fungoides and have offered parameters that may be helpful in diagnosis. In the study, undertaken by members of the EORTC Cutaneous Lymphoma Study Group, the proposed histologic features are tested for sensitivity and specificity. This commentary discusses some of the historical issues and the value of the EORTC study pertaining to the diagnosis of early mycosis fungoides.

Cytodiagnosis↗

Ulcerative keratitis in mycosis fungoides.

PURPOSE: To present a case of ulcerative keratitis and impending corneal perforation in a patient with mycosis fungoides (cutaneous T-cell lymphoma) that developed eyelid involvement. METHODS: Case report analysis. Cultures and biopsies of the right cornea, conjunctiva, and eyelids were obtained. Biopsy tissue was examined with histologic and immunohistologic stains. RESULTS: This patient with mycosis fungoides involving the eyelids developed corneal exposure and bacterial keratitis with impending corneal perforation. Lamellar keratoplasty and permanent tarsorrhaphy were performed to protect the globe from perforation. DISCUSSION: Mycosis fungoides involving the eyelids is capable of causing severe ocular tissue injury without direct infiltration of the malignant lymphocytes. Preventative medical and surgical measures must be taken to protect the globe.

Anti-Infective Agents↗

Detection of low-level tumor cells in allergic contact dermatitis induced by mechlorethamine in patients with mycosis fungoides.

Two patients with histologically proven mycosis fungoides, a malignancy of phenotypically mature T cells, received a topical challenge with mechlorethamine to areas of clinically uninvolved skin to exclude possible hypersensitivity reactions to this chemotherapeutic agent. In both patients, allergic contact dermatitis (ACD) developed at the sites of the application and resolved completely after withdrawal of mechlorethamine. The lesions were biopsied and analyzed for the presence of clonal T-cell receptor (TCR)-gamma gene rearrangements using two polymerase chain reaction (PCR)-based assays involving denaturing gradient gel electrophoresis (PCR/DGGE) and ribonuclease protection analysis (PCR/RPA). The former method has a clonal detection threshold of 10(-3)-10(-2), while the latter has a sensitivity of 10(-5). In both cases, the ACD lesions were polyclonal by PCR/DGGE. In contrast, PCR/RPA detected tumor-specific TCR-gamma gene rearrangements in these same lesions. This indicates that the ACD lesions contained tumor cells at a density within the 10(-5)-10(-2) range. Analysis of peripheral blood mononuclear cells from both patients failed to detect the malignant clone and showed the same result as blood from four normal individuals. The normal skin from one skin patient also lacked detectable TCR-gamma gene rearrangements. These results indicate that mycosis fungoides tumor are present within ACD lesions induced in mycosis fungoides patients and that this phenomenon does not appear to be due to the ubiquitous presence of detectable levels of these tumor cells in the blood or skin. These findings might be explained by nonspecific recruitment of malignant T cells to sites of local inflammation mediated by non-neoplastic antigen-specific T cells. Alternatively, they might be due to the local proliferation of very rare tumor cells in apparently normal skin in response to cytokines generated during the ACD reaction. In either case, the present study offers evidence that the malignant cells in myosis fungoides retain at least some capability of responding in vivo to physiologic stimuli.

Adult↗

E-rosette inhibitory factor in sera from patients with mycosis fungoides.

Peripheral blood lymphocytes from some of patients with mycosis fungoides disease showed decreased ability to form rosettes with sheep erythrocytes. This decreased percentage of E-rosette forming cells could be normalized when those cells were incubated in culture for 20 hr. Since these data led us to considering a possible inhibitory factor present in patients' sera, we tested their ability to inhibit E-rosetting by T lymphocytes from normal donors, and found that sera from mycosis fungoides patients with low levels of E-rosetting blood lymphocytes showed greater inhibitory effect on E-rosette formation by normal T cells when compared to those either from normal donors or from mycosis patients who had almost normal levels of E-rosetting blood lymphocyte number. The E-rosette inhibitory factor was sensitive to 2-mercaptoethanol treatment and was copurified with serum IgM by ammonium sulfate precipitation and by sequential gel filtrations, suggesting that it might be an anti-T lymphocyte antibody naturally occurring during the disease process.

Adult↗

DNA-cytophotometry of lymph node imprints from patients with mycosis fungoides.

To obtain objective criteria for early diagnosis of lymph node involvement in patients with mycosis fundoides, Feulgen DNA-cytophotometry was carried out in lymph node imprints from patients with mycosis fungoides. The lymph nodes of 3 patients with lymph nodes, showing partial or total replacement by atypical lymphoreticular tissue histologically, showed a polyploid and aneuploid DNA distribution. Eleven out of 22 patients with dermatopathic lymphadenopathy both with or without early involvement histologically had an abnormal DNA histogram with hypertetraploid DNA values. Four of these 11 died, 5 had a partial remission in response to therapy and 2 had sustained remission during the follow-up period of 5 yr. The other 11 patients had a normal DNA distribution. Of these 11, one died and 10 achieved sustained remission after therapy. There is a good correlation between the DNA-cytophotometric results and histology of the lymph nodes. On the basis of these results DNA-cytophotometry may be considered an additional and objective aid in the diagnosis of lymph node involvement in mycosis fungoides.

Adult↗

Surface markers and mitogen response of cells harvested from cutaneous infiltrates in mycosis fungoides and Sézary's syndrome.

It was the purpose of this study to characterize the proliferating cells in skin lesion of Sézary's syndrome and of mycosis fungoides by means of their surface markers and their response to Phytohemagglutinine mitogen stimulation. Viable infiltrating cells were freed from skin biopsy specimens by means of a disaggregating homogenizer and the cells yielded were tested with heterologius polyvalent anti-human Ig and with anti-human T-cell globulin, as well as for spontaneous rosette formation with sheep red blood cells (SRBC) and for their response to stimulation with Phytohemagglutinine. Most of the infiltrating cells in skin lesions of mycosis fungoides and Sézary's syndrome lack receptors for anti-human Ig but form spontaneous rosettes with SRBC and have receptors for anti-T-cell globulin, indicating the T-lymphocyte nature of the infiltrating cells; however, their response to Phytohemagglutinine is weak. The results indicate the atypical, presumably neoplastic, nature of T-lymphocytes proliferating in skin lesions of mycosis fungoides and Sézary's syndrome.

B-Lymphocytes↗

T-cell membrane characteristics of "mycosis cells" in the skin and lymph node.

In some patients with mycosis fungoides atypical cells ("mycosis cells") are found in the blood. Recently the T-cell membrane characteristics of these atypical cells have been described. In this paper the results of a study of the atypical cells isolated from the lymph nodes and the skin lesions of three patients with mycosis fungoides are presented. Using electron microscopy, it could be demonstrated that the atypical cells formed rosettes with uncoated sheep red blood cells, but not with antibody-complement-coated sheep erythrocytes, indicating the T-cell membrane characteristics of the atypical cells.

Aged↗

Effect of serum of mycosis fungoides patients on lymphocyte transformation.

In vitro transformation of peripheral lymphocytes by PHA was usually impaired in mycosis fungoides patients in the infiltrative plaque and tumor stages, while not being significantly impaired in the premycotic stage. A serum factor, reducing transformation by PHA, was demonstrated in 2 of 5 patients in the premycotic stage as well as in 2 and probably 3 of 4 patients in the infiltrative plaque or tumor stage. This serum factor affected both autologous (mycosis fungoides) and normal lymphocytes. The factor tended to be present in patients whose lymphocytes were impaired rather than in those whose lymphocytes were not significantly impaired. The degree of the reduction by mycosis fungoides serum seemed to correlate with the serum concentration of gamma-globulin rather than that of alpha2-globulin. The possible nature and clinical significance of this factor are discussed.

Humans↗

Skin-infiltrating lymphocytes in normal and disordered skin: activation signals and functional roles in psoriasis and mycosis fungoides-type cutaneous T cell lymphoma.

T lymphocytes recruited into the skin can experience several different outcomes. On the one hand, they may be recruited by adhesion molecules and chemoattractants to enter the perivascular space, but never undergo activation. Other T cells undergo activation and further differentiation under the influence of the cutaneous milieu. These activated lymphocytes then coordinate specific and non-specific immune responses characteristic of inflamed tissue. We have explored two models for studying the activation and function of skin infiltrating T lymphocytes (SIL's). In the first model, we have identified a family of Langerhans cell-related professional dendritic antigen presenting cells that exist in the epidermis and dermis of normal skin, atopic skin, and mycosis fungoides skin. These have APC abilities to activate freshly recruited resting blood T cells that are distinct from another family of macrophage-related cells abnormally present in sunburned or psoriatic skin. In the second model, we examined the function of cells that have already been recruited into the skin of patients with psoriasis and mycosis fungoides. Lesional psoriasis and mycosis fungoides T cells exhibited a variety of T cell receptor gene rearrangements, conclusively demonstrating that heterogeneous populations of T lymphocytes exist in inflamed human skin. From psoriasis, clones were identified that were particularly effective at inducing normal keratinocytes to assume "psoriatic" phenotypic features and functions. Thus, lesional psoriatic SIL's could induce HLA-DR, ICAM, and CDw60 on normal keratinocytes. In addition, psoriatic SIL's induced increased keratinocyte proliferation and cytokine profile changes characteristic of psoriatic epidermis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Presenting Cells↗

Clinical significance of serum adenosine deaminase activity in patients with mycosis fungoides.

Adenosine deaminase is one of the key enzymes in purine nucleotide degradation. This enzyme exists in most of the human tissues and the activity is high in lymphatic tissues, especially in T lymphocytes. Elevated adenosine deaminase activity in T cell leukemia has been reported, and its inhibitor, deoxycoformycin, has been developed as an antitumor agent. In some types of leukemia, serum adenosine deaminase activity increases in accordance with the severity of the disease. Although mycosis fungoides rarely involves peripheral blood, tumor cells do invade the skin. In order to evaluate the clinical significance of adenosine deaminase in mycosis fungoides, adenosine deaminase activity was measured in sera of 15 patients with mycosis fungoides at various stages. The mean enzyme activity was 23.2 IU/l, which was high with statistical significance compared with healthy controls (P < 0.001). Nine of twelve patients in the plaque stage (T2N0M0, IB) showed higher adenosine deaminase activity than did the normal population. The mean adenosine deaminase activity in sera in the patients in the plaque stage (T2N0M0, IB) was as high as 19.0 IU/l (range 13.7-21.4) with statistical significance compared with healthy control (P < 0.001). Three tumor stage patients without visceral involvement (T3N0M0, IIB) showed higher levels of adenosine deaminase activity (19.7, 21.5, 24.4 IU/l). An erythrodermic patient (T4N0M0, III) also had a high adenosine deaminase activity 28.4 IU/l. Two tumor stage patients with organ involvement (T3N0M1, IVB) exhibited extremely high adenosine deaminase activity (60.9, 32.2 IU/l). The adenosine deaminase activity in sera showed a tendency to become higher with the extension of the stages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase↗

The effects of non-interval PUVA therapy on the plaque stage of mycosis fungoides.

The effectiveness of non-interval topical PUVA treatment was studied in four patients with mycosis fungoides at the plaque stage. Five regions of each patient were exposed to UVA immediately, 30 minutes, 60 minutes, 90 minutes, and 120 minutes, after topical application of 8-methoxypsoralen, respectively. The effects of these treatments were evaluated by clinical appearance and histological findings after the 20th treatment. All five regions were more improved clinically and histologically than the control region, which was not given PUVA therapy. There were no clear differences clinically among these five regions. Biopsy specimens from each region revealed the disappearance of epidermotropism and a marked decrease in atypical mononuclear cell infiltrations in the dermis. From these data, we concluded that there were no clear differences between these five treatments clinically or histologically and that non-interval PUVA therapy is useful for the early stages of mycosis fungoides. To our knowledge, this is the first report of non-interval PUVA therapy for mycosis fungoides.

Adult↗

Ultraviolet-B phototherapy is successful in Japanese patients with early-stage mycosis fungoides.

UVB phototherapy is widely used for the treatment of psoriasis and atopic dermatitis, however, only limited reports evaluate its usefulness in the treatment of mycosis fungoides. We introduced UVB phototherapy to five patients with early-stage mycosis fungoides. All of them were classified as stage IB (erythematous stage), and none had obtained a satisfactory response to other therapies. After initial treatment with UVB phototherapy, all the patients obtained significant improvement in their skin lesions leaving pigmentary changes. After this satisfactory response was achieved, the same dose of UVB was administrated as a maintenance therapy with longer intervals between exposures. Histopathological examination of three patients revealed decreased numbers of inflammatory cells in both the epidermis and the dermis after the treatment. Immunohistochemical study showed that CD1a+/HLA-DR+ dendritic cells were present throughout the lesional epidermis before the treatment. In contrast, after the treatment, the dendritic cells in the epidermis were CD1a+/HLA-DR-. Although it remains unclear why only the expression of HLA-DR antigen was eliminated after treatment, we presume that this loss of HLA-DR antigen expression by epidermal Langerhans cells was, in part, responsible for the improvement of skin lesions. This preliminary study suggests that UVB phototherapy is an effective treatment for patients with early-stage mycosis fungoides.

Adult↗

Lymphocyte abnormalities in mycosis fungoides.

Fourteen patients with clinical and histological evidence of mycosis fungoides have undergone a series of immunological tests. Significant findings include the presence of low numbers of E and EAC rosette-forming cells in the peripheral circulation of the mycosis fungoides patients. Elevated levels of IgE were seen in five of the mycosis fungoides patients, and the mean IgE level was significantly higher than in the control series. Possible explanations of these findings are considered.

Adult↗

Demethylchlortetracycline and griseofulvin as examples of specific treatment for mycosis fungoides.

Long-term control of mycosis fungoides in the tumour stage was achieved in one patient by daily demethylchlortetracycline therapy. On two occasions widespread nodules and tumours completely involuted within 1 month of initiating this therapy. A second patient showed complete resolution of his plaque stage mycosis fungoides after the institution of oral griseofulvin therapy for a chronic fungus infection. The disease reappeared upon stopping the griseofulvin and involuted upon its resumption. The observations are interpreted as evidence that reduction or eradication of a persistent bacterial or fungal antigen may have a remarkable ameliorative effect in selected mycosis fungoides patients.

Demeclocycline↗

Hypopigmented mycosis fungoides: report of five cases with ultrastructural observations.

Five dark-skinned individuals presented with widespread well-demarcated hypopigmented lesions, biopsy of which revealed the histopathological features of mycosis fungoides. Ultrastructural studies showed focal invasion of the epidermis by mycosis cells with degenerative changes in adjacent melanocytes and keratinocytes. The majority of melanocytes exhibited swelling of cytoplasmic organelles and disordered melanogenesis with production of spherical incompletely melanized melanosomes. In addition disintegrating melanocytes were occasionally seen. Perifollicular repigmentation within hypopigmented areas occurred in two patients following clearing of the epidermal infiltrate with PUVA therapy. Mycosis fungoides may present with areas of cutaneous hypopigmentation.

Adolescent↗