Cases Of Mycosis Fungoides Research Articles

Cutaneous T-cell lymphoma (Mycosis fungoides)

Cutaneous T cell lymphoma (CTCL) is an uncommon fatal skin condition in which there is an abnormal neoplastic proliferation of T cell lymphocytes [1]. The entity varies considerably in clinical presentation, histological appearance, immunophenotype and prognosis of its variants [2, 3]. Mycosis fungoides (MF) is the commonest subtype of CTCL. It may develop de novo or may persist in one stage for years or slowly progress from patch to plaque stage and later to a nodule. Spread to other organs is most likely in this stage, leading to a rapid, progressive, down hill course [3]. Fatality is usually associated with sepsis. We present two cases of MF.

Immunohistochemical staining for CD45R isoforms in paraffin sections to diagnose mycosis fungoides–type cutaneous T-cell lymphoma

The definitive diagnosis of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL) is difficult because a cumulative set of information is typically required: clinical features, histopathology, and special diagnostic tests (typically immunophenotyping and T-cell receptor gamma [TCRgamma] gene rearrangement). Fresh tissue is not always available for the special tests. We report a simple and readily available procedure evaluating the staining pattern on formalin-fixed, paraffin-embedded skin that can help with the diagnosis of patch/plaque stage MF. We reviewed 92 cases of MF or probable MF that had clinical information, immunophenotyping and TCRgamma gene rearrangement studies and that had been evaluated in our multidisciplinary lymphoma conference. We used antibodies to the isoforms of CD45, CD45RO for mature T cells and CD45RB for subsets of T cells. When atypical CD45RB-positive/CD45RO-negative cells were seen in nonspongiotic epidermis, the individuals had a high cumulative clinical and histologic score for MF. In contrast, 15 cases of known contact dermatitis showed a reactive pattern of both CD45RB- and CD45RO-positive cells in spongiotic epidermis. We compared the epidermal CD45RB-positive/CD45RO-negative staining pattern with CD7 deficiency by immunophenotyping and TCRgamma gene rearrangement, two commonly used methods in the diagnosis of MF. The epidermal CD45RB-positive/CD45RO-negative staining pattern is comparable and may be better in equivocal cases of possible MF. Therefore immunostaining for CD45RB and CD45RO on paraffin sections is a simple, reliable, and convenient modality in the diagnosis of MF.

Mycosis Fungoides in Childhood: Description and Study of Two Siblings

Primary cutaneous T-cell lymphomas are exceedingly rare in children and adolescents. However, mycosis fungoides (MF) is the most frequent primary cutaneous lymphoma diagnosed in childhood. Two cases of MF in siblings (a 14-year-old boy and his 10-year-old sister) are reported. On the basis of clinical features (histopathological and immunophenotypical findings) a diagnosis of MF patch lesions was made in both siblings. Since recent data in the literature have underlined a high frequency of the HLA-DQB1*03 allele in patients with familial MF (including child patients), the HLA profile of the patients was analysed, indicating the presence of a haplotype (HLA-DQB1*03,*03 in the girl, HLA-DQB1*02,*03 in the boy) corresponding with that described in recent literature. Two rare and exceptional cases of MF in siblings are reported, highlighting the presence of a peculiar haplotype.

Retrospective 5‐year review of 131 patients with mycosis fungoides and Sézary syndrome seen at the National Skin Centre, Singapore

A total of 131 new cases of mycosis fungoides and Sézary syndrome were diagnosed clinically and histopathologically at our centre over a 5-year period. There were 87 males and 44 females with a mean age of 36.3 years (range 3-87 years) and no racial predilection. Of the 62 patients (47.3%) with classical mycosis fungoides, the majority were male (male : female = 4.2:1). There was one patient with Sézary syndrome. Patients aged older than 50 years were more likely to present with a longer duration of symptoms and advanced disease. In contrast to classical mycosis fungoides, the 47 patients diagnosed with hypopigmented mycosis fungoides had early stage disease, were younger, and no gender predilection was noted. The mean duration of follow up was 19.7 months (range 0.2-54.8 months). Complete remission was achieved in 24.7% and 53.8% of patients followed up at 1 and 3 years, respectively, using skin-directed and systemic treatment modalities appropriate for the stage of disease. There were five patients with progressive disease and three patients with advanced disease who died from disease-related complications. The most significant prognostic factors for 1-year and 3-year outcomes were the patient's duration of symptoms and stage of disease at presentation.

Association of p53 Arg72Pro polymorphism andβ-catenin accumulation in mycosis fungoides

Aberrant activation of beta-catenin contributes to the onset of a variety of tumours. There are many tumours that display beta-catenin accumulation in the absence of mutations in its gene. Recently, abnormal accumulation of wild-type beta-catenin has been associated with mutational inactivation of the p53 tumour suppressor. To investigate the potential role of p53 and its homologue p63 in beta-catenin deregulation and to correlate this with disease outcome. We analysed a panel of 24 samples of mycosis fungoides (MF), the most frequent manifestation of cutaneous T-cell lymphoma (CTCL), for beta-catenin, p53 and p63 protein expression by immunohistochemistry. Based on the immunostaining results for beta-catenin protein, 11 positive cases were selected for laser microdissection, genomic DNA isolation and subsequent mutation analysis of beta-catenin exon 3 and p53 exons 4-8. Our findings revealed overexpression of beta-catenin, p53 and p63 in 46%, 38% and 17% of cases, respectively. The number of p53-positive cases of MF was significantly higher (P < 0.05) in the beta-catenin-positive group (73%). Sequence analysis demonstrated that wild-type beta-catenin accumulation in MF is not associated with mutational inactivation of the p53 gene and, more importantly, our data provide evidence that a common polymorphic form of p53 (Arg72Pro) is significantly associated with beta-catenin overexpression (P < 0.05). No significant differences in the three genotypes were observed between the CTCL cases and the control group, demonstrating that Arg72Pro polymorphism of the p53 gene is not associated with the risk of developing cutaneous lymphomas (P > 0.05). We found an association of beta-catenin and p53 overexpression without detection of structural alteration in the genes, suggesting that p53 mutation is not an important mechanism for beta-catenin activation in primary CTCL. Additionally, we speculate that the p53 codon 72 polymorphism may influence negative feedback control involving beta-catenin and p53.

Mycosis Fungoides Associated with B-cell Malignancies

Summary Background The coexistence of mycosis fungoides, a peripheral T-cell lymphoma, and B-cell malignancies or Hodgkin's lymphoma in the same patient is unusual. Most descriptions are isolated case reports and case series are strikingly sparse. Objectives To detect cases of mycosis fungoides associated with B-cell malignancies or Hodgkin's lymphoma and to analyse the characteristics of and the interplay between the lymphoproliferative neoplasms. Method Patients with mycosis fungoides who had B-cell malignancies or Hodgkin's lymphoma were selected from among 398 patients either treated or followed up in two tertiary medical centres during a 7-year period. Results Eleven patients with mycosis fungoides and B-cell malignancy were detected (seven of non-Hodgkin's lymphoma, three of chronic lymphocytic leukaemia, one of multiple myeloma). No case of Hodgkin's lymphoma was found. In seven patients the mycosis fungoides preceded the B-cell malignancy whereas in four it was the B-cell malignancy which occurred first. The time elapsed between onset of the two malignancies ranged from 4 to 22 years (average: 12 years). Patients who had mycosis fungoides as the first neoplasm presented with earlier stages of mycosis fungoides (four of seven: IA, three of seven: IB) than those who had mycosis fungoides as their second neoplasm (of four, one: IB, one: folliculotropic, two: IIB). Among the four patients in whom the appearance of mycosis fungoides followed the B-cell malignancy, three had been treated with multiagent chemotherapy. Two patients who presented with early-stage mycosis fungoides (IA) as the first lymphoma developed mycosis fungoides tumours after becoming immunosuppressed. In two patients infiltrates composed of both malignant T- and B-cell populations were found in a single biopsy. One showed two distinct populations of the malignant cells in the skin tumour, thus constituting a classical composite lymphoma of mycosis fungoides and chronic lymphocytic leukaemia, while in the other patient the two malignant populations of marginal B-cell lymphoma and mycosis fungoides (as evidenced by both phenotypic and genotypic findings) were intermingled. Conclusions This case series indicates that while the coexistence of Hodgkin's lymphoma and mycosis fungoides is extremely rare, the association of mycosis fungoides and B-cell malignancies is not as rare as reflected in the literature, with non-Hodgkin's lymphoma constituting the most common associated B-cell malignancy. In this series as well as in the cases reported in the literature mycosis fungoides usually preceded the development of B-cell malignancies, which may be in accordance with previous reports of an increased risk of developing a second haematological neoplasm. The importance of a competent immune system for patients with mycosis fungoides is well demonstrated in these cases. It is suggested that for greater precision the criteria for diagnosis of composite lymphoma of the skin should include both phenotypic and genotypic features.

Mycosis fungoides associated with B-cell malignancies

The coexistence of mycosis fungoides, a peripheral T-cell lymphoma, and B-cell malignancies or Hodgkin's lymphoma in the same patient is unusual. Most descriptions are isolated case reports and case series are strikingly sparse. To detect cases of mycosis fungoides associated with B-cell malignancies or Hodgkin's lymphoma and to analyse the characteristics of and the interplay between the lymphoproliferative neoplasms. Patients with mycosis fungoides who had B-cell malignancies or Hodgkin's lymphoma were selected from among 398 patients either treated or followed up in two tertiary medical centres during a 7-year period. Eleven patients with mycosis fungoides and B-cell malignancy were detected (seven of non-Hodgkin's lymphoma, three of chronic lymphocytic leukaemia, one of multiple myeloma). No case of Hodgkin's lymphoma was found. In seven patients the mycosis fungoides preceded the B-cell malignancy whereas in four it was the B-cell malignancy which occurred first. The time elapsed between onset of the two malignancies ranged from 4 to 22 years (average: 12 years). Patients who had mycosis fungoides as the first neoplasm presented with earlier stages of mycosis fungoides (four of seven: IA, three of seven: IB) than those who had mycosis fungoides as their second neoplasm (of four, one: IB, one: folliculotropic, two: IIB). Among the four patients in whom the appearance of mycosis fungoides followed the B-cell malignancy, three had been treated with multiagent chemotherapy. Two patients who presented with early-stage mycosis fungoides (IA) as the first lymphoma developed mycosis fungoides tumours after becoming immunosuppressed. In two patients infiltrates composed of both malignant T- and B-cell populations were found in a single biopsy. One showed two distinct populations of the malignant cells in the skin tumour, thus constituting a classical composite lymphoma of mycosis fungoides and chronic lymphocytic leukaemia, while in the other patient the two malignant populations of marginal B-cell lymphoma and mycosis fungoides (as evidenced by both phenotypic and genotypic findings) were intermingled. This case series indicates that while the coexistence of Hodgkin's lymphoma and mycosis fungoides is extremely rare, the association of mycosis fungoides and B-cell malignancies is not as rare as reflected in the literature, with non-Hodgkin's lymphoma constituting the most common associated B-cell malignancy. In this series as well as in the cases reported in the literature mycosis fungoides usually preceded the development of B-cell malignancies, which may be in accordance with previous reports of an increased risk of developing a second haematological neoplasm. The importance of a competent immune system for patients with mycosis fungoides is well demonstrated in these cases. It is suggested that for greater precision the criteria for diagnosis of composite lymphoma of the skin should include both phenotypic and genotypic features.

Micose fungóide: estudo epidemiológico de 17 casos e avaliação da resposta terapêutica à PUVA

FUNDAMENTOS: A fotoquimioterapia com PUVA é indicada para tratamento da micose fungóide, empregada como monoterapia em estágios precoces ou combinada a outras drogas nos estágios mais avançados da doença. OBJETIVOS: Avaliação da resposta terapêutica à fotoquimioterapia PUVA em pacientes com micose fungóide. MÉTODOS: Entre janeiro de 1996 e novembro de 2003 avaliaram-se 17 pacientes com micose fungóide no setor de Fototerapia da Clínica Dermatológica da Santa Casa de São Paulo. A terapia com PUVA foi realizada como monoterapia nos estádios iniciais ou como coadjuvante nos estádios avançados da doença. Avaliou-se o resultado do tratamento quanto ao aspecto clínico das lesões e parâmetros histológicos após tratamento. RESULTADOS: Quatorze de 16 pacientes responderam à fotoquimioterapia. Relacionando o estadiamento da doença à resposta terapêutica obteve-se o seguinte: cinco pacientes (um em estágio IA e quatro em IB) com controle total (cura das lesões); quatro (todos IB) com melhora intensa (controle de 70-99%); dois (IIB e IVA) com melhora moderada (de 50 a 69%); três (IA, IB, IIA) com melhora discreta (menos 50%); dois (IB, IIB) inalterados (sem resposta). Um paciente teve de descontinuar o tratamento por apresentar intenso ardor. CONCLUSÃO: Houve resposta à terapia PUVA em 87% dos pacientes, com controle total ou melhora intensa da doença em 56% dos casos. Sua efetividade permitiu regressão das lesões cutâneas, principalmente nos casos precoces. A fotoquimioterapia com PUVA mostrou ser tratamento seguro e efetivo, devendo ser considerado em pacientes com micose fungóide.

Lesions resembling Langerhans cell histiocytosis in association with other lymphoproliferative disorders: a reactive or neoplastic phenomenon?

Langerhans cell histiocytosis (LCH) has been described in association with a variety of neoplasms preceding, after, or synchronous with the other tumor. In some cases, a neoplasm may arise as a complication of therapy for LCH, and in others, the association may be coincidental. Synchronous occurrence has been reported most commonly in association with malignant lymphoma in which discrete proliferations of Langerhans cells (LCs) histologically indistinguishable from LCH are seen. In most cases, these LCs are closely related to or intermingling with the primary pathology. The nature of LCs in this context remains elusive with debate as to whether they represent a true clonal neoplasm or an exaggerated reactive phenomenon. The lack of evidence for LCH progression or disease elsewhere strongly supports the latter. We have encountered 5 examples of LCH-like proliferations occurring in the context of other lymphoproliferative disorders. These include 2 cases of mycosis fungoides and 1 of cutaneous B-cell pseudolymphoma, associations that to our knowledge have not been described before. Two patients were female, and the clonality of the LC proliferation was assessed using laser capture microdissection and the human androgen receptor. The results showed that the LCs forming discrete nodules in a case of cutaneous B-cell pseudolymphoma and a case of Hodgkin's lymphoma were polyclonal. This suggests that, at least in a proportion of cases, the aggregates of LCs occasionally identified within other lymphoproliferative lesions represent a reactive proliferation rather than a potentially aggressive second neoplasm.

Survival of Mycosis Fungoides in Patients in the Southeast of England

Background: Mycosis fungoides (MF) is the most common skin lymphoma. The aetiology of MF remains unknown, and no therapy has to date significantly altered patient survival. Objective: The present study examines trends in survival of MF patients in a well-defined population-based disease group, namely patients registered over a 40-year period at the Thames Cancer Registry, Southeast England. Methods: The Thames Cancer Registry is a population-based registry, covering a population of approximately 14 million people. Data were taken from the Surveillance, Epidemiology and End Results cancer registry programme and the National Centre for Health Statistics. The database was used to identify cases of MF diagnosed between 1961 and 2000. A total of 985 records were identified, 821 (83%) of which had complete information on age, sex, year of diagnosis and area of residence. The observed and relative survivals of patients diagnosed during the periods 1971–1975, 1981–1985 and 1991–1995 were examined over a 5-year period of follow-up, using the relsurv Stata program to perform Cox proportional hazard analysis. Results: A total of 821 MF eligible patients were available with a median follow-up of 4.3 years and a maximum follow-up of 30 years. The overall 5-year relative survival rate was 80%, and there was marked improvement between 1971 and 1981. The prognostic factors leading to a significantly poorer survival were high age, male sex, the presence of the Sézary syndrome, the use of hormone treatment and radiotherapy. Conclusions: A statistically significantly better survival over the last 20 years was found. The prognosis is generally good for most patients but not all. The best survival was seen for the female patients under 45 years of age without the presence of the Sézary syndrome. This difference in survival may be partly due to a difference in the disease stage or different treatment, or to both.

Expression of heat-shock protein-90 in non-Hodgkin's lymphomas

Heat-shock protein-90 (HSP90) inhibitors are currently being used in phase I clinical trials for treating patients with a variety of neoplasms including lymphomas. Using immunohistochemical methods, we assessed for HSP90 expression in 412 cases of non-Hodgkin’s lymphoma. In B-cell lymphomas, HSP90 was moderately to strongly expressed in all cases of Burkitt’s lymphoma (5/5, 100%), and in subsets of follicular lymphoma (17/28, 61%), diffuse large B-cell lymphoma (27/46, 59%), nodal marginal zone B-cell lymphoma (6/16, 38%), plasma cell neoplasms (14/39, 36%), small lymphocytic lymphoma/chronic lymphocytic leukemia (3/9, 33%), mantle cell lymphoma (12/38, 32%) and lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (3/10, 30%). HSP90 was weakly expressed in six of 14 (43%) cases of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. In T-cell lymphomas, HSP90 was moderately to strongly expressed in subsets of anaplastic large-cell lymphoma (14/24, 58%; 9/12 ALK+ and 5/12 ALK−), precursor-T-cell lymphoblastic leukemia/lymphoma (20/65, 31%), unspecified peripheral T-cell lymphoma (8/43, 23%) and angioimmunoblastic T-cell lymphoma (2/17, 12%). HSP90 was weakly expressed in seven of 58 (12%) cases of mycosis fungoides. We conclude that HSP90 is commonly expressed in a subset of many types of B- and T-cell lymphoma. These data suggest that many lymphoma types are suitable targets for modulation of HSP90 activity, and that HSP90 inhibitors are a potential investigational therapy for lymphoma patients.

Mycosis fungoides associated with intestinal mucosa‐associated lymphoid tissue lymphoma

Coexistence of cutaneous T-cell lymphoma (CTCL) and a B-cell malignancy is rare. We report a case of mycosis fungoides (MF) associated with intestinal mucosa-associated lymphoid tissue (MALT) lymphoma, which is a low-grade B-cell lymphoma of marginal cell origin. To the best of our knowledge, there have been only two cases of coexistent CTCL and MALT lymphoma, and this is the first case with typical MF and intestinal MALT lymphoma. The coexistence in our case might be coincidental, but genetic predisposition and the immunoregulatory capacity of neoplastic T lymphocytes may be factors contributing to this association.

Mycosis fungoides with a CD56 + immunophenotype

We report 3 cases of mycosis fungoides (MF) with a CD56+ cytotoxic immunophenotype. Each patient presented with a different clinical phenotype: one exhibited limited poikilodermatous patches (skin stage T1); one, widespread hypopigmented lesions (skin stage T2); and one, poikiloderma with a single cutaneous tumor (skin stage T3). MF was confirmed both histologically and by the presence of a T-cell receptor clone in lesional skin in all cases. CD56 and T-cell intracellular antigen-1 were expressed by the malignant lymphocytes in all patients and two expressed CD8. No sample demonstrated loss of the pan T-cell markers CD2 or CD3. None of the 3 developed systemic disease and T-cell receptor gene analysis of peripheral blood was polyclonal in all cases. Only 3 cases of CD56+ MF have been reported previously, none of which exhibited tumor-stage disease. Currently, the disease in our patients appears to be behaving in a manner similar to that predicted for MF with a normal immunophenotype but the prognosis has to be guarded in view of the rarity of this subtype.

Differential Expression of WT1 Gene Product in Non-Hodgkin Lymphomas

The tumor suppressor gene wt1 (Wilms tumor 1) encodes a zinc finger transcription factor reported to be expressed in many tumors, including mesotheliomas, carcinomas, and acute leukemias. However, WT1 expression in non-Hodgkin lymphomas (NHLs) has not been studied. The authors assessed for WT1 expression in six lymphoma/leukemia cell lines using Western blot methods after subcellular fractionation. We also assessed for WT1 expression in 167 NHLs using immunohistochemical methods. The B-cell NHLs analyzed were 18 diffuse large B-cell lymphomas, 13 marginal zone B-cell lymphomas, 9 small lymphocytic lymphomas, (DLBCLs), 8 follicular lymphomas, 6 mantle cell lymphomas, 5 Burkitt lymphomas, 3 lymphoplasmacytic lymphomas, and 2 B-cell lymphoblastic lymphomas. The T-cell NHLs analyzed were 43 anaplastic large cell lymphomas (ALCLs), 26 peripheral T-cell lymphomas unspecified, 13 angioimmunoblastic T-cell lymphomas, 6 cutaneous ALCLs, 6 cases of mycosis fungoides, 5 extranodal NK/T-cell lymphomas of nasal type, and 4 T-cell lymphoblastic lymphomas. WT1 levels were higher in cytoplasmic extracts than in nuclear extracts of the Karpas 299 and SU-DHL-1 lymphoma cell lines but were higher in nuclear extracts than in the cytoplasmic extracts of the Jurkat, HH, U-937, and K562 leukemia cell lines. In NHLs, WT1 was positive in 4 of 5 (80%) Burkitt lymphomas, 9 of 12 (75%) ALK-positive ALCLs, 3 of 6 (50%) lymphoblastic lymphomas (2 of 4 T-cell, 1 of 2 B-cell), 14 of 31 (45%) ALK-negative ALCLs, 6 of 18 (33%) DLBCLs, and 1 of 6 (17%) cutaneous ALCLs. WT1 was negative in all other NHLs tested. WT1 immunoreactivity was primarily cytoplasmic in all positive NHLs except T-cell lymphoblastic lymphoma. In conclusion, WT1 protein is frequently detected in the cytoplasm of a subset of high-grade NHLs.

Mycosis fongoïde à type d’érythème annulaire centrifuge

Mycosis fungoides is a lymphoma, the classical clinical form of which involves erythematosquamous lesions. However, it can present various atypical aspects: hyper pigmentation or hypo pigmentation, suggestive of pyoderma gangrenosum or ichtyosis. We report a case of mycosis fungoides, unusual in its presentation in the form of centrifugal annular erythema. A 78 year-old man had developed a parapsoriasis in plaques for more than 20 years. In May 2002 he consulted because of the recent infiltration of one of the plaques, without concomitant pruritus. The clinical examination revealed 3 lesions of the popliteal groove of the right groin and the left cheek suggestive of centrifugal annular erythema. Histology, revealing Pautrier microabscesses, was compatible with the diagnosis of mycosis fungoides. Evolution was marked by the spontaneous regression of the plaque on the face and remission of the other two plaques after local treatment with chloromethin and topical corticosteroids. Nevertheless, new plaques appeared despite continued treatment, combined with PUVA therapy sessions. When searching the literature, we only found one other case of mycosis fungoides, the clinical aspect of which was a centrifugal annular erythema, but in which the histological examination confirmed the diagnosis of mycosis fungoides. Our case report is also unusual in the clinical regression of the lesion on the face, without treatment; this has only been reported in two cases. Mycosis fungoides can appear in various clinical forms. The centrifugal annular erythema form is rare, but this diagnosis should be evoked.

Mycosis Fungoides Mimicking Lichen Planus

Introduction: To report an uncommon case of mycosis fungoides in a 62‐year‐old female. Case presentation: A 62‐year‐old Black female presented to our clinic with a wide spread of hyper‐pigmented erythematous grayish plaques on trunk, extremities and face. There were no associated systemic illnesses and laboratory work was otherwise within normal range. Two skin biopsies were taken from the trunk and extremity. Both of the biopsies reveal similar features of coexisting like lichen planus and mycosis fungoides. There was interface dermatitis, vacuolar degeneration, prominent colloid body formation and lichenoid lymphonocytic inflammation through out the dermis. Epidermis was atrophic with overlying hyper and parakeratosis. There were many areas of epidermotrophism with collections of atypical lymphocytes. There was also marked pigmentory incontinence in the dermis. Comment: We present an uncommon case of mycosis fungoides with changes of lichen planus. It is important familiarise oneself with uncommon presentations of mycosis fungoides. It may be worthwhile to look for mycosis fungoides, while reviewing a classical case of lichen planus with clinical presentation of lichen planus.

A Circulating T Cell Clone in Early Mycosis Fungoides Is Not a Negative Prognostic Factor When the Disease Is Treated by a Combination of PUVA + Interferon α.

In patients with early Mycosis Fungoides (MF), a dominant T-cell receptor (TCR) gene rearrangement can be detected in the skin in 50–75% of cases, while in 15–40%, an identical T-cell clone is detectable also in the peripheral blood This may indicate an unfavourable subset of patients.We observed on omogeneus group of early MF patients all receiving the some protocol. The purpuose of this study were: - T-cell receptor gene rearrangement analisys of peropheral blood samples; - evaluation of the prognostic impact of T-cell monoclonality on CR and relapse rate.44 patients diagnosed as having MF at early stage (25 M, 19 F; mean age 58.7 yrs, range 34–77; 11 in stage IA, 28 in stage IB, 5 in stage IIB) and showing a dominant T cell clone in the skin lesions at diagnosis, were included in the present study. Peripheral blood samples were collected for DNA extraction at diagnosis. PCR amplification for TCRγ gene was performed as previously reported by Ashton-Key et al. (1997) in all 44 cases both in peripheral blood and skin and reduplicated: amplification products were visualised by 10% polyacrylamide gel electrophoresis. Peripheral blood samples were considered positive for a circulating T cell clone only if the monoclonal signals in peripheral blood and skin were reproducible and overlapping.All patients received the same treatment, consisting of a combination protocol with low-dose IFNα + PUVA for 14 months, and then followed up. Clinical response to the therapy and further disease recurrences were registered.After a mean time of 6.02 months (range, 1–21), 7 patients failed to respond to combination therapy, while 37 obtained a clinical complete remission (CCR). Among them, 15 experienced a disease recurrence during the follow-up (mean time, 29.8 months, range, 1–77 months).PCR analysis of TCRγ gene showed in the peripheral blood the same T-cell clone detected in the skin in 16 cases (36.4%). Failure to obtain a CCR was found in 3 out of 28 cases without a T cell clone in peripheral blood (10.7%) and in 4 out 16 cases with a circulating T cell clone (25%; c2 test: P=0.41, NS). Disease recurrence was observed in 9 out of 25 cases without a T cell clone in peripheral blood (36%) and in 6 out of 12 cases with a circulating T cell clone (50%; c2 test: P=0.65, NS). Disease-free survival curves plotted by Kaplan-Meier method showed that patients with and without a circulating T cell clone did not behave differently and that half of the patients would have experienced a relapse after a similar period of time (34 and 36 months, respectively, for patients with TCRg+ and − peripheral blood; log rank test, P=0.79).PCR analysis of TCRγ gene rearrangement analysis has allowed us to detect monoclonality in the peripheral blood in 36% of early MF cases with a documented monoclonality in the skin. At this stage of the disease a circulating T cell clone could indicate a subset of patients in which skin-directed therapies are more likely to fail to completely eradicate the malignant cells. Interestingly, our data seems to show that the negative influence of a circulating clone can be bypassed by the combination of a skin-directed therapy like PUVA and the systemic immunoregulatory effects of IFNα.

Fas Gene Mutations in Mycosis fungoides: Analysis of Laser Capture-Microdissected Specimens from Cutaneous Lesions

Fas (APO-1/CD95) is a transmembrane protein which mediates programmed cell death (apoptosis). Cells with a mutated Fas gene are resistant to apoptosis and thus accumulate in lesional tissues. This might provide a basis for the development of neoplasias. Genomic DNA selectively obtained from Pautrier’s microabscesses in 16 cases of mycosis fungoides (MF) using a laser capture microdissection method was analyzed. Fas gene mutations were detected in 3 of 16 cases of MF (18.8%); 1 was silent and 2 were missense mutations located in exon 9. One of the 2 missense mutations involved the death domain of the Fas gene, which is essential for apoptotic signal transduction. The missense mutations resulted in the substitution of Ala with Asp at codon 220 and Ile with Thr at codon 314. Mouse T cell lymphoma cells transfected with mutant genes were resistant to apoptosis induced by the anti-Fas antibody, indicating that the missense mutations found in MF were loss-of-function mutations, thus causing the accumulation of cells in the cutaneous lesions. These findings suggest that the accumulation of lymphoid cells with Fas mutations provides, in part, a basis for the development or maintenance of MF.

Milia in regressing plaques of mycosis fungoides: provoked by topical nitrogen mustard or not?

To report three cases of mycosis fungoides with milia formation in the regressing lesions. Dermatology clinic of a university hospital (referral center). Three patients with mycosis fungoides with body surface involvement of 10% in one case (stage IIb) and exceeding 30% in two cases (stages IIb and III). All patients were treated with photochemotherapy and topical nitrogen mustard ointment in a concentration of 0.01%. After approximately 3 months multiple milia erupted on regressing plaques. The presence of milia was evident and was confirmed by histopathology. Regression of mycosis fungoides was noted in these plaques both clinically and in comparison with the pretreatment histologic appearance. Two of the patients showed a histological picture of follicular mucinosis. We do not know the significance of milia in mycosis fungoides (MF). However, we suggest that follicular rupture or a degenerative process might result in milia formation.

Multilineage progression of genetically unstable tumor subclones in cutaneous T-cell lymphoma.

Molecular analysis of solid malignant tumors has suggested multilineage progression of genetically unstable subclones during early stages of tumorigenesis as a common mechanism of tumor cell evolution. We have investigated whether multilineage progression is a feature of cutaneous T-cell lymphoma (CTCL). To identify individual tumor cell subclones, we determined the pattern of mutations within microsatellite DNA obtained from multiple histomorphologically confined tumor cell nests of mycosis fungoides (MF) and lymphomatoid papulosis (LyP) lesions. Tumor cells were isolated by laser microdissection, and allelotypes were determined at microsatellite markers D6S260, D9S162, D9S171, D10S215, TP53.PCR15, and D18S65. Nine cases of MF and one patient with anaplastic large cell lymphoma (ALCL) originating from LyP were analyzed at 277 different microdissected areas obtained from 31 individual lesions. Three specimens of cutaneous lichen planus microdissected at 26 areas served as the control tissue. Microsatellite instability in microdissected tissue [MSI(md-tissue)] was detected in tumor tissues of all CTCL patients. One hundred and fifty-seven of 469 analyzed polymerase chain reaction (PCR) amplifications contained mutated microsatellite alleles (34%). In lichen planus, MSI(md-tissue) was seen in only four of 76 PCR products (5%) (P < 0.0001). The distribution of allelotypes in tumor cells from different disease stages was consistent with multilineage progression in five MF cases, as well as in the LyP/ALCL patient. Our results suggest that CTCL may evolve by multilineage progression and that tumor subclones in MF can be detected in early disease stages by mutation analysis of microsatellite DNA obtained from multiple microdissected areas.