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PubMed1994

Risk of secondary cutaneous malignancies in patients with long-standing mycosis fungoides.

BACKGROUND: Patients with mycosis fungoides (MF) are frequently treated with UV light and psoralen (PUVA), nitrogen mustard, and electron beam irradiation, modalities known to predispose persons to development of cutaneous malignancies. OBJECTIVE: We assessed the relation between these therapeutic modalities and the development of secondary cutaneous malignancies. METHODS: We reviewed the charts of all patients observed during the past year. RESULTS: We found that 7 of 71 patients had cutaneous neoplasms in an average follow-up time of 8.3 years. Orthovoltage radiation was used in five of seven cases and PUVA in four of seven. Five of seven patients had multiple neoplasms. CONCLUSION: The risk of the development of second malignancies from the treatment of MF is relatively small and appears to be related to the type of therapy.

Carcinoma in Situ↗
PubMed1997

Prognostic factors and evaluation of mycosis fungoides and Sézary syndrome.

BACKGROUND: Staging evaluations of patients with mycosis fungoides (MF) and Sézary syndrome (SS) are performed to individualize therapy and to predict survival. OBJECTIVE: Our purpose was to determine the prognostic factors in patients with MF and SS. METHODS: A retrospective study of 101 patients was performed. For inclusion in the study, patients had to have been evaluated for MF or SS within 6 months of the initial definitive histologic diagnosis. The evaluation included physical examination, chest radiograph, peripheral blood smear, lymph node biopsy, bone marrow biopsy, gallium 67 scan, liver-spleen scan and computed tomography (CT) of the chest, abdomen, and pelvis. RESULTS: The type of skin disease present at initial diagnosis was a good prognostic indicator of survival and clinical outcome. Univariate adverse prognostic features included hepatosplenomegaly or adenopathy by CT scan, abnormal liver-spleen scan, abnormal gallium scan, adenopathy, and peripheral blood, bone marrow, and lymph node involvement. Independent prognostic factors in multivariate analysis were the type of skin involvement as well as peripheral blood and visceral involvement. CONCLUSION: Our study confirms previous reports that type of skin and peripheral blood and visceral involvement are important prognostic factors in patients with MF or SS. Our results support the finding that patients with T1 stage disease have an excellent survival outlook and clinical outcome.

Bone Marrow↗
PubMed1997

Mycosis fungoides with onset before 20 years of age.

BACKGROUND: Recent identification of mycosis fungoides (MF) in a man in whom the diagnosis was established at age 22 months prompted us to evaluate our experience with early onset MF. OBJECTIVE: Our purpose was to summarize the clinical characteristics and course of 24 patients in whom MF began by history before age 20 years and was confirmed by biopsy in 13 by that time. METHODS: A retrospective study was conducted. RESULTS: All 24 patients had patch/plaque disease and represented 4.3% of the 557 patients with cutaneous T-cell lymphoma seen by us since 1971. None progressed to a more advanced stage in up to 24 years (median, 12 years) after histologic diagnosis. Five patients (21%) presented with hypopigmentation. CONCLUSION: Early onset MF is not more aggressive than that appearing in adult life. MF should be considered in the differential diagnosis of chronic dermatoses in young persons, particularly in those presenting with hypopigmentation.

Adolescent↗
PubMed1997

Follicular mycosis fungoides: a clinicohistopathologic study.

BACKGROUND: Follicular mycosis fungoides (FMF) is a recently described variant of cutaneous T-cell lymphoma, histopathologically characterized by infiltrates of atypical CD4+ T lymphocytes around and within the epithelium of the hair follicles (folliculotropism). To date, only four cases of FMF have been reported. OBJECTIVE: Our goal was to identify cases of FMF and compare them with those previously reported. METHODS: The clinical and histopathologic features of three cases of FMF were analyzed. In addition, in one case immunohistochemical analysis in paraffin-embedded and frozen tissue as well as genotypic studies were performed. RESULTS: The three reported cases showed typical histologic findings of FMF, namely, perifollicular and intrafollicular infiltrates of atypical lymphocytes, in the absence of either epidermotropism or follicular mucinosis. Clinically, the lesions were similar to classic MF, but also contained follicular papules. Immunohistochemistry and gene rearrangement studies showed findings similar to classic MF. CONCLUSION: FMF is a rare variant of cutaneous T-cell lymphoma. Including our three cases, only seven patients have been reported. We hypothesize that the follicular epithelium in patients with FMF may express increased levels of skin-selective homing receptors and adhesion molecules. These may be involved in the induction of the folliculotropism of atypical lymphocytes.

Female↗
PubMed1998

Immunophenotyping and T-cell receptor gamma gene rearrangement analysis as an adjunct to the histopathologic diagnosis of mycosis fungoides.

BACKGROUND: The histopathologic diagnosis of mycosis fungoides (MF) may be difficult. OBJECTIVE: Our purpose was to evaluate the role of immunophenotyping and T-cell receptor (TCR) gene rearrangement studies as an adjunct to the histopathologic diagnosis of MF. METHODS: Immunohistochemical studies with antibodies to CD4, CD5, CD7, and CD8 and TCR gamma gene rearrangement analysis with a polymerase chain reaction were performed on fresh-frozen material of patients with "classic" histology of MF, "inconclusive" histology, and benign inflammatory dermatoses. RESULTS: Clonal TCR gamma gene rearrangements were found in 11 of 16 (69%) of classic MF cases, in 3 of 19 (16%) of inconclusive cases, and in none of the 12 inflammatory dermatoses cases (P < .05 and P < .001, respectively). Only the mean CD7 counts were statistically significantly different between these 3 groups (MF < inconclusive < inflammatory). CONCLUSION: Inconclusive histology is probably a heterogeneous group in which CD7 counts and TCR gamma gene rearrangement studies might help to differentiate the MF cases from the benign cases.

Adolescent↗
PubMed1998

Mycosis fungoides in young patients: clinical characteristics and outcome.

BACKGROUND: Mycosis fungoides (MF) can begin as early as the first decade of life. Few studies have reviewed MF in younger patients and none has been large enough to assess prognosis and outcome. OBJECTIVE: We reviewed the clinical characteristics, prognosis, factors related to disease progression, and therapy in patients with MF younger than 35 years of age. METHODS: Fifty-eight patients were entered into this retrospective cohort analysis. RESULTS: Significantly fewer patients with MF who are younger than 35 years presented with erythroderma (T4) and more with limited patch/plaque (T1) disease than older patients. Duration of skin disease before diagnosis of MF did not vary between the two groups. The long-term survival of younger patients with MF is significantly decreased when compared with a race-, age-, and sex-matched control population (p < 0.001). Disease-specific survivals (DSS) of younger and older patients are similar, but young patients show a slight but significantly better overall DSS (p < 0.02). However, DSS comparison of generalized patch/plaque (T2) and tumor stage (T3) patients with MF showed no significant difference between young and old patients (p=0.47, p=0.59). Patient age was not a significant predictor of survival when controlled for T-stage. Sixteen of 58 young patients with MF have died, 13 because of MF (22%), compared with 138 of 500 older patients (28%) who died as a result of MF. All younger patients with MF who progressed had at least T2 disease at presentation. Fifty of 56 young patients with MF and T1-T3 disease were treated initially with total skin electron beam or topical nitrogen mustard. The response to therapy was similar in younger and older patients with MF. CONCLUSION: T1 disease is more common and T4 disease is unusual in young patients with MF compared with an older population of patients with MF. Young patients with T1 disease, all of whom were treated with either topical nitrogen mustard or total skin electron beam therapy, or both therapies, showed no disease progression. Overall, young patients with MF showed slightly better DSS, but this was because of differences in stage distribution.

Adolescent↗
PubMed1998

Mycosis fungoides with focal segmental glomerular sclerosis and nephrotic syndrome.

Cutaneous T-cell lymphoma includes mycosis fungoides and the leukemic variant, Sézary syndrome. We report the first two cases of focal segmental glomerulosclerosis in patients with cutaneous T-cell lymphoma, with nephrotic range proteinuria and review the literature on renal disease coexisting with cutaneous T-cell lymphoma. We hypothesize that glomerular injury in cutaneous T-cell lymphoma may be related to interleukin-2.

Biopsy↗
PubMed1999

Epidermotropic cutaneous B-cell lymphoma mimicking mycosis fungoides.

Cutaneous involvement by B-cell lymphoma is often secondary to systemic disease. Primary cutaneous B-cell lymphomas are less common, and patients generally have an excellent prognosis. We present a patient with cutaneous B-cell lymphoma with clinical and histologic features mimicking mycosis fungoides. Although the patient was initially misdiagnosed as having a T-cell lymphoma, immunophenotypic studies demonstrated that this was a B-cell lymphoma.

Aged↗
PubMed1999

Pigmented purpura-like eruption as cutaneous sign of mycosis fungoides with autoimmune purpura.

We describe the clinical and laboratory findings of a young man with mycosis fungoides. The disease was associated, since the early stages, with autoimmune purpura. Interferon alfa (IFN-alpha) administration improved this patient's condition, both the purpuric eruption and patchy cutaneous lesions, thus suggesting T-cell abnormalities may be responsible for the development of the disease.

Adolescent↗
PubMed1994

Mycosis fungoides: expression of C-myc p62 p53, bcl-2 and PCNA proteins and absence of association with Epstein-Barr virus.

The expression of C-myc p62, bcl-2, p53, PCNA and EBV-encoded LMP-1 proteins was studied by immunohistochemistry on paraffin-embedded skin specimens from 14 patients with early stage (premycotic erythema and second stage plaques) mycosis fungoides (MF), 21 patients with advanced stage MF (third stage plaques and tumors), 3 patients with Sezary's syndrome (SS) and 3 patients with pleomorphic medium and large cell cutaneous T-cell lymphomas (PML-CTCL). All 41 cases were also screened for the presence of EBV by using RNA in situ hybridization with EBER 1/2 oligonucleotides. Increased expression of C-myc p62, p53 and PCNA proteins was found in PML-CTCL and advanced stages of MF as compared to early stages of MF. These results suggest a relationship between levels of C-myc p62, p53 and PCNA proteins and aggressiveness of the cutaneous T-cell lymphomas. Furthermore, C-myc p62 and bcl-2 proteins were found to be frequently coexpressed in the present series. In view of the background information from in vitro findings and animal models that cooperation of C-myc and bcl-2 is important for lymphomagenesis, our results suggest that coexpression of these oncogenes may be implicated in the pathogenesis and/or the progression of cutaneous T-cell lymphomas. Neither LMP-1 expression nor EBV EBER l/2 transcripts were detected in our series suggesting that EBV is not involved in the pathogenesis of cutaneous T-cell lymphomas.

Herpesvirus 4, Human↗
PubMed1997

Total skin electron beam therapy followed by adjuvant psoralen/ultraviolet-A light in the management of patients with T1 and T2 cutaneous T-cell lymphoma (mycosis fungoides).

PURPOSE: Patients with mycosis fungoides [cutaneous T-cell lymphoma (CTCL)] may benefit from adjuvant therapy after completing total skin electron beam therapy (TSEBT). We report the results for T1/T2 CTCL patients treated with adjuvant oral psoralen plus ultraviolet light (PUVA) with respect to overall survival (OS), disease-free survival (DFS), salvage of recurrence, and toxicity. METHODS AND MATERIALS: Between 1974 and 1993, TSEBT was administered to a total of 213 patients with CTCL. Records were reviewed retrospectively, and a total of 114 patients were identified as having T1 or T2 disease. Radiotherapy was provided via a 6-MeV linac to a total of 36 Gy, 1 Gy/day, 4 days/week, for 9 weeks. Beginning in 1988, patients were offered adjuvant PUVA within 2 months of completing TSEBT. This was started at 0.5-2 J/m2, 1-2 treatments/week, with a taper over 3-6 months. Therapy then continued once per month. There were 39 T1 and 75 T2 patients. Six T1 (15%) and eight T2 (11%) patients were treated with adjuvant PUVA. A further 49% of the 114 patients received adjuvant systemic therapy, 3% received spot external beam, 4% received adjuvant ECP, 2% received topical nitrogen mustard, 22% received a combination of therapies exclusive of PUVA, and 9% received no adjuvant therapy. Patients were balanced in all subgroups based on pre-TSEBT therapy. The median age of the cohort was 58 (range 20-88), with a median follow-up time of 62 months (range 3-179). RESULTS: Within 1 month after completing of TSEBT, 97% of T1, and 87% of T2 patients had achieved a complete remission. Stratified by adjuvant therapy, none of six T1 and one of eight T2 patients who received adjuvant PUVA failed within the first 3 years after completion of TSEBT. A total of 43% of the T1 and T2 patients receiving other or no adjuvant treatment failed within the same time course. The 5-year OS for the entire cohort was 85%. Those who received PUVA had a 5-year OS of 100% versus a 5-year OS for the non-PUVA group of 82% (p < 0.10). The 5-year DFS for the entire cohort was 53%. Those who received PUVA had a 5-year DFS of 85% versus a 5-year DFS for the non-PUVA group of 50% (p < 0.02). By T stage, those with T1 receiving PUVA exhibited no relapses, whereas those with T1 not treated with PUVA had a crude relapse rate of 36%. Median DFS was not reached at 103 months for the T1 adjuvant PUVA patients versus 66 months for the non-PUVA patients (p < 0.01). For those with T2, crude relapse rates were 25% and 55%, respectively, with DFS of 60 (median DFS not reached) and 20 months (p < 0.03). The 5-year DFS for patients salvaged with PUVA was 50%. Toxicity of adjuvant and salvage PUVA therapy was acceptable, with only two patients requiring a reduction in PUVA dosage. CONCLUSION: PUVA can maintain remissions in patients with CTCL after TSEBT. There is a significant benefit in DFS but no statistically significant improvement in OS. Prospective, randomized data are needed to confirm these results. PUVA is also effective as a salvage therapy after TSEBT in early-stage patients with recurrence, with acceptable toxicity.

Administration, Oral↗
PubMed1998

Utilization of thermoluminescent dosimetry in total skin electron beam radiotherapy of mycosis fungoides.

PURPOSE: The purpose of this report is to discuss the utilization of thermoluminescent dosimetry (TLD) in total skin electron beam (TSEB) radiotherapy to: (a) compare patient dose distributions for similar techniques on different machines, (b) confirm beam calibration and monitor unit calculations, (c) provide data for making clinical decisions, and (d) study reasons for variations in individual dose readings. METHODS AND MATERIALS: We report dosimetric results for 72 cases of mycosis fungoides, using similar irradiation techniques on two different linear accelerators. All patients were treated using a modified Stanford 6-field technique. In vivo TLD was done on all patients, and the data for all patients treated on both machines was collected into a database for analysis. Means and standard deviations (SDs) were computed for all locations. Scatter plots of doses vs. height, weight, and obesity index were generated, and correlation coefficients with these variables were computed. RESULTS: The TLD results show that our current TSEB implementation is dosimetrically equivalent to the previous implementation, and that our beam calibration technique and monitor unit calculation is accurate. Correlations with obesity index were significant at several sites. Individual TLD results allow us to customize the boost treatment for each patient, in addition to revealing patient positioning problems and/or systematic variations in dose caused by patient variability. The data agree well with previously published TLD results for similar TSEB techniques. CONCLUSION: TLD is an important part of the treatment planning and quality assurance programs for TSEB, and routine use of TLD measurements for TSEB is recommended.

Electrons↗
PubMed1998

Mycosis fungoides with involvement of the oral mucosa.

Mycosis fungoides (MF) is a T-cell lymphoma that predominantly affects the skin. Involvement of the oral tissues in MF is rare. A case of MF with involvement of the maxillary gingiva and cervical lymph nodes is presented. Electron-beam radiation with 40 Gy and systemic chemotherapy with vincristine and interferon gamma produced almost complete remission of the oral lesion while the persistent pain was relieved.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Early mycosis fungoides: molecular analysis for its diagnosis and the absence of p53 gene mutations in cases with progression.

The histological diagnosis of initial mycosis fungoides (MF) and the molecular mechanisms that are responsible for its progression and transformation to the more highly malignant variants of MF remain largely unknown. Because of the rare occurrence of these tumours, the need for snap frozen skin biopsy specimens and the difficulty to obtain suitable material for karyotypic and genotypic analysis, specific cytogenetic and molecular lesions have not yet been identified. In particular the role of known oncogenes and tumour suppressor genes, including the p53 gene, in the pathogenesis and clinical progression of MF has not been extensively investigated. The present study was carried out using the polymerase chain reaction (PCR) technique combined with temperature gradient gel electrophoresis (TGGE) to detect mutations of the p53 gene in 58 patients with MF. TGGE analysis was also used in combination with clonality analysis by means of T-cell receptor gamma (TCRG) gene rearrangement studies to distinguish parapsoriasis en plaque and initial MF from patch/plaque stage MF. More than 83% of the diagnoses of initial MF could be confirmed using PCR-TGGE analysis. However, although the sensitive TGGE analysis was used for all exons, p53 gene polymorphisms were found in 4 and p53 gene mutation in only 1 of 58 biopsy specimens. It appears unlikely that p53 gene mutations play a role in either the pathogenesis of parapsoriasis and initial MF or their progression to advanced stages of MF. However, TCRG gene rearrangement studies by means of TCR-TGGE analysis may be useful for distinguishing histologically discordant cases of initial MF.

Biopsy↗
PubMed2003

Viral infection, atopy and mycosis fungoides: a European multicentre case-control study.

Mycosis fungoides (MF) is a rare disease with an unknown aetiology, although it has been suggested that infections may play a role. The present study investigates whether infections, atopic disorders and some other diseases are risk indicators for MF. A European multicentre case-control study involving seven rare cancers, including MF, was conducted from 1995 to 1998. Patients between 35 and 69 years of age diagnosed with MF (n = 140) were recruited, and the diagnoses were verified by a reference pathologist, who classified 83 cases as definitive and 35 cases as possible; 22 cases were not accepted. Of the 118 accepted cases, 104 patients were interviewed (including 76 definitive cases and 28 possible cases). These 76 definitive cases were used for this study. A common set of controls to serve all case groups were interviewed, representing a total of 4574 controls. The latter included 1008 colon cancer patients and 3566 subjects selected from population registers. Information on infections, skin pathology and clinical history 5 years before the diagnosis of MF was used to estimate odds ratios (ORs) derived from logistic regression-modelling, which included gender, age and country. The highest ORs for MF were found in patients who reported a history of psoriasis 5 years before MF was diagnosed (OR 7.2, 95% CI: 3.6-14.5). Urticaria had an OR of 1.4 (95% CI: 0.6-3.6). Infections and atopic diseases were not closely associated with MF. Some diseases correlated to MF. Whether this has a causal background or reflects early diagnostic uncertainty is not known.

Adult↗
PubMed1997

Progression of mycosis fungoides is associated with changes in angiogenesis and expression of the matrix metalloproteinases 2 and 9.

Changes in angiogenesis and expression of extracellular matrix-degrading enzymes have been substantiated during progression of solid tumours, whereas information on haematological tumours remains circumstantial. In this study, 57 biopsies of mycosis fungoides (MF), a haematological tumour of T-cell lineage, were investigated immunohistochemically for the extent of angiogenesis, and by in situ hybridisation for the expression of matrix metalloproteinases 2 (MMP-2, collagenase A) and 9 (MMP-9, collagenase B). The biopsies we grouped according to the stage of progression: patch-->plaque-->nodular (most advanced). The extent of angiogenesis, as microvessel area, of MF lesions as a whole was significantly higher than that of normal uninjured skin, used as a control. When the stages of MF progression were compared, the values of MF patch stage overlapped that of control skin, while values were significantly higher in the plaque stage and even higher in the nodular stage. In these stages, microvessels were widely scattered in the tumour tissue, in close association with tumour cells, and they frequently displayed arborisation and microaneurysmatic dilation. In contrast, in the patch stage microvessels were irregularly distributed around the tumour aggregates, and arborisation or dilated structures were only rarely seen. The expression of MMP-2 and MMP-9 mRNAs underwent significant upregulation in relation to advancing stage. Indeed, the upstaging was significantly associated with higher proportions of lesions positive for each mRNA or for both, and with lesions with the greatest intensity of expression for each mRNA. Besides tumour cells, the MMP-2 mRNA was expressed by microvascular endothelial cells of intratumour and peri-tumour vessels, and by fibroblasts which were especially abundant in the stroma adjacent to the tumour nodules. The MMP-9 mRNA was found to be present in a subset of tissue macrophages which were more frequently located in close vicinity to the tumour nodules. In contrast, in control skin, a weak positivity for the MMP-2 mRNA in very few microvascular endothelial cells and no signal for the MMP-9 mRNA were observed. These in situ data suggest that angiogenesis and degradation of the extracellular matrix occur simultaneously during MF progression. They imply that interaction between tumour cells and their microvasculature are all the more likely to occur during progression, occasionally with the contribution of tumour-associated stromal cells.

Aged↗
PubMed2002

Oliguric acute renal failure in mycosis fungoides with lymphomatous infiltrates in the kidneys.

OBJECTIVE: To present the clinical picture of acute renal failure in patients with mycosis fungoides (MF) and renal lymphomatous infiltrates. To analyze the pathogenesis of renal failure. METHODS: Correlation of clinical picture, urinary findings, imaging reports and autopsy findings in two patients with long-standing MF who died with renal failure. CASE SUMMARIES: Both subjects had sustained oliguria in the last 2 weeks. One patient had persistent hypotension, normal urinalysis, normal renal sonogram, and scarce interstitial lymphomatous infiltrates with preservation of renal parenchymal architecture. He was thought to have ischemic acute renal failure not directly linked to the lymphomatous infiltrates. The second patient developed hypertension one month prior to death, and had moderate proteinuria, hematuria, pyuria, grossly enlarged kidneys with hypoechoic masses, and extensive replacement of the renal parenchyma by lymphomatous infiltrates. This picture is typical of renal failure secondary to lymphomatous replacement of the kidneys. CONCLUSIONS: The development of oliguric renal failure in MF with renal lymphomatous infiltrates may have varying clinical and imaging manifestations and pathogeneses. Potentially reversible pathogenic mechanisms should be systematically investigated, particularly if the overall clinical picture is not characteristic of renal failure secondary to lymphomatous replacement of the parenchyma.

Acute Kidney Injury↗
PubMed2002

Relative content of cytokines in different tissues in mycosis fungoides.

The concentrations of tumor necrosis factor-alpha, interleukin-1beta, interleukin-2, interleukin-4, and the content of antibodies to H1 histone fraction in peripheral blood lymphocytes, epidermis, and serum were evaluated in patients with mycosis fungoides. It was found that as the disease progresses, cytokine synthesis is switched from Th1 to Th2 class and production of proinflammatory cytokines increases, which indirectly promotes the development of the autoimmune reaction.

Case-Control Studies↗