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PubMed2003

A simple clinical scoring system to improve the sensitivity and standardization of the diagnosis of mycosis fungoides type cutaneous T-cell lymphoma: logistic regression of clinical and laboratory data.

BACKGROUND: The diagnosis of mycosis fungoides (MF) is notoriously difficult to establish because in the early stages, histological features may be nonspecific or merely suggestive. OBJECTIVES: To standardize the diagnosis of MF. METHODS: We studied 138 patients with suspected MF referred over a 7-year period to a university department of a dermatology-based cutaneous lymphoma clinic. Six diagnostic criteria were evaluated: clinical morphology, clinical distribution, skin biopsy T-cell receptor gene rearrangement (TCR-GR), skin biopsy pan T-cell marker loss > or = 2, skin biopsy CD4/CD8 ratio > or = 6, and skin biopsy diffuse epidermal HLA-DR expression. These six clinical and laboratory criteria were compared by logistic regression analysis in patients with histologically diagnosed MF and those with benign disease. RESULTS: Of the 138 patients, 74 had histology of MF, 47 of benign dermatoses and 17 were indeterminate. Close associations were found between a histological diagnosis of MF and TCR-GR (odds ratio 14.4), classical morphology (7.5), classical distribution (2.5) and diffuse epidermal HLA-DR expression (2.8). Logistic regression models were developed depending on the availability of data (either TCR-GR or HLA-DR). Probabilities for correctly diagnosing MF compared with histology as the 'gold standard' were derived from these logistic regression models. A scoring system assigning point values based on these probabilities was then created in order to assist the clinician in making the diagnosis. If using TCR-GR data, a positive TCR-GR = 2.5 points, the presence of classical morphology = 2.0 points, and the presence of classical distribution = 1.5 points. A total score of > or = 3.5 points assigns a high probability (> 85%) of having MF. If using HLA-DR expression, then the presence of classical morphology = 2.5 points, a positive diffuse epidermal HLA-DR expression = 2.0 points, and the presence of classical distribution = 1.5 points. In this case, a total score of > or = 4.0 points assigns a high probability (> 85%) of MF. CONCLUSIONS: The logistic regression models and scoring systems integrate clinical and laboratory assessments, allow rapid probability estimation, and provide a threshold for the diagnosis of MF in an objective, standardized manner.

Biopsy↗
PubMed1997

Mycosis fungoides and Sezary syndrome are not associated with HTLV-I infection: an international study.

Association between mycosis fungoides (MF), its leukaemic variant Sezary syndrome (SS) and the human T-cell lymphotropic virus type-I (HTLV-I) has been controversial, with the reported incidence of infection varying between 0% and nearly 100%. We studied 127 patients (85 MF, 28 SS, five Sezary cell leukaemia, four lymphomatoid papulosis, and five unspecified cutaneous T-cell lymphomas (CTCL)) originating from Europe (France, Spain, U.K., Portugal) or from U.S.A. (California) for the presence of HTLV-I infection markers. HTLV-I and -II serology were performed on 78 patients using standard immunological methods. Reverse transcriptase (RT) assay was also performed in 26 cases using an RT-PCR-based method of high sensitivity. Molecular analyses were performed on 215 DNA samples (121 from fresh PBMCs, 26 from PBMCs after short-term culture and 68 from skin lesions) by PCR amplification using HTLV-I and -II gag, pol, env, pX and LTR specific primers. Immunological tests were negative except for two sera which were indeterminate. PCR with all HTLV-I and -II primer pairs showed negative results in all 215 samples investigated. No RT activity was detected in short-term PBMC cultures of any of the 26 cases studied. The results of this large study from five different countries clearly indicate that MF and SS are not associated with HTLV-I infection.

Blotting, Western↗
PubMed1997

Kaposi's varicelliform eruption in a patient with mycosis fungoides.

A 39-year-old Japanese woman suffering from plaque stage of mycosis fungoides (MF) developed Kaposi's varicelliform eruption (KVE) on her face. KVE appeared 1 month after commencing skin electron beam irradiation (SEBI), when the total irradiation had reached 46 Gy. Natural killer (NK) cell activity in the peripheral blood was abnormally low, but returned to normal after 1 year. However, lymphocyte reactivity to mitogens was persistently low. These facts suggested that the KVE in our patient developed because of abnormally low NK cell reactivity probably induced by radiation therapy.

Adult↗
PubMed2003

Granulomatous mycosis fungoides presenting as an acquired ichthyosis.

We report a case of a 69-year-old gentleman who presented with a 3-month history of unexplained fevers and malaise who developed generalized pruritus, alopecia and an ichthyosiform erythematous eruption on his forearms, legs, chest and back. Skin histology, immunophenotyping and molecular features were consistent with granulomatous mycosis fungoides. He has been successfully treated with twice weekly PUVA photochemotherapy.

Aged↗
PubMed2003

Mycosis fungoides involving the oral mucosa in a child.

Involvement of the oral mucosa in cutaneous T-cell lymphoma is uncommon and is usually associated with a poor prognosis (the majority of patients dying from the disease within 3 years of the diagnosis of oral involvement). We report the first case of intraoral mycosis fungoides occurring in a child. In addition, our patient has had intraoral disease for 3 years and is currently systemically well with no evidence of cutaneous or systemic disease progression.

Child↗
PubMed2003

Assessment of histologic criteria in the diagnosis of mycosis fungoides.

BACKGROUND: The histologic diagnosis of early mycosis fungoides (MF) can be difficult to establish in many instances because the subtle changes observed in patches of MF are also present in many inflammatory dermatoses. METHODS: To assess the frequency and significance of many of these histologic parameters, we retrospectively reviewed 50 slides from patients with documented MF in patch, plaque, and tumor stages. The diagnosis of MF was unequivocally established either by the progression of patients to advanced stages of the disease or by indubitable histologic findings. In the second phase of the study, we compared the histologic parameters observed in 24 patch stage MF patients with those in 24 non-MF patients. The non-MF group were patients whose pathologic pattern was suspicious for MF, but who definitely did not have MF on clinical grounds. The two groups were matched by histologic pattern. Two different observers evaluated the slides and the intensities of 32 histologic parameters were graded on a four-point scale to minimize the subjective variability in the histologic reports. RESULTS: On univariate analysis, the following parameters achieved significance in distinguishing MF from non-MF: Pautrier's microabscesses, haloed lymphocytes, disproportionate epidermotropism, epidermal lymphocytes larger than dermal lymphocytes, hyperconvoluted lymphocytes in the epidermis and dermis, absence of dyskeratosis, and papillary dermal fibrosis. None of these features proved to have additional discriminating power on multivariate analysis. CONCLUSIONS: The efficacy of single histologic features in the diagnosis of early MF is generally poor and, to discriminate MF from its inflammatory simulators, a combination of cytologic and architectural features must be used.

Adolescent↗
PubMed2001

Persistent pigmented purpuric eruption associated with mycosis fungoides: a case report and review of the literature.

A purpuric eruption may be an unusual early manifestation of mycosis fungoides (MF). On the other hand, persistent pigmented purpuric dermatoses (PPPD) may, occasionally, evolve to cutaneous T-cell lymphoma. Coexistence of these two conditions has been reported, but it is extremely rare. We present the case of an elderly woman with a long-standing pruritic, pigmented purpuric eruption. On 1-year follow-up, histological features suggesting early MF were observed and molecular analysis of the rearrangement of T-cell receptor genes revealed clonality. Our patient may represent a case of PPPD evolving to MF, a case of MF clinically featuring PPPD, or an intermediate condition in a nosological continuity extending from PPPD to MF. A persistent pigmented purpuric eruption may rarely be a harbinger of cutaneous T-cell lymphoma. Therefore, vigilant long-term follow-up of PPPD is highly recommended.

Female↗
PubMed2001

Examination of mycosis fungoides for the presence of Epstein-Barr virus and human herpesvirus-6 by polymerase chain reaction.

BACKGROUND: The aetiology of cutaneous T-cell lymphoma (CTCL) remains unknown despite numerous investigations. In recent years, retroviruses and human herpesviruses have been implicated to play a causal part in CTCL. OBJECTIVE: The aim of this study was to elucidate the possible aetiopathogenetic role of human herpesviruses (HHV) in mycosis fungoides (MF). METHODS: Polymerase chain reaction was used to study formalin-fixed, paraffin-embedded lesional skin biopsies from 92 subjects with MF to evidence possible presence of Epstein-Barr virus (EBV) and HHV-6. RESULTS: Biopsy specimens from nine subjects (9.8%) evidenced EBV DNA, whereas all except one of the subjects (1.1%) lacked HHV-6 DNA. CONCLUSIONS: Although these findings do not support a primary aetiological role for EBV and HHV-6 in classical CTCL, the possibility remains that both viruses, particularly EBV, may act as potential cofactors in the development of CTCL.

Adolescent↗
PubMed2002

Mycosis fungoides presenting with extensive pyoderma gangrenosum-like ulcers.

Mycosis fungoides (MF) may present with atypical clinical manifestations. Usually it mimics various chronic dermatoses, with the appearance of ulcers during the tumour stage. Infrequently, cutaneous ulcers are the main or initial sign of lymphoma. We report the case of a man who presented multiple skin lesions that clinically appeared to be pyoderma gangrenosum (PG). However, histological and immunohistochemical examination revealed MF. This case illustrates that PG-like ulcers maybe atypical cutaneous manifestations of MF and exceptionally the presenting sign of this disease.

Biopsy, Needle↗
PubMed2003

Long-term remission of recalcitrant tumour-stage mycosis fungoides following chemotherapy with pegylated liposomal doxorubicin.

Advanced stage mycosis fungoides (MF) generally has a poor prognosis, and currently there is no standard treatment available. Here we report the case of a young woman with recalcitrant tumour-stage MF (T3, stage IIb) whose disease was unresponsive to several therapeutic modalities, but who has showed sustained clinical response to pegylated liposomal doxorubucin. No severe infectious complications have been observed. The use of this drug in tumour-stage MF should be investigated further.

Adult↗
PubMed2003

Mycosis fungoides responding to systemic itraconazole.

Mycosis fungoides is a form of cutaneous lymphoma with a typically indolent course. We describe an unexpected, repeated response to a systemic antifungal agent, itraconazole. The mechanism of action is speculative but itraconazole has marked immunosuppressive activity on T-lymphocyte proliferation in vitro.

Administration, Oral↗
PubMed2000

Microanatomical compartments of clonal and reactive T cells in mycosis fungoides: molecular demonstration by single cell polymerase chain reaction of T cell receptor gene rearrangements.

Mycosis fungoides (MF) is a cutaneous T cell lymphoma, clinically characterized by patches, plaques and tumors occurring in successive stages of the disease. In early MF, an infiltrate consisting of mainly reactive T cells is seen in the papillary dermis while tumor cells are mostly confined to the epidermis. By contrast, later stages show nodular infiltrates formed mostly of tumor cells in the dermis while the epidermis is relatively devoid of tumor cells; however, knowledge of the localization of clonal T cells has been based on histomorphologic features and immunohistochemical stainings visualizing certain V-beta subfamilies of the T cell receptor (TCR). As these techniques do not allow for an unequivocal identification of clonal tumor cells, we used micromanipulation and single cell PCR amplifying the TCR chain gene rearrangement. A total number of 387 single T cells was isolated from six skin biopsies in five patients in patch, plaque, and tumor stages. Of these, 180 T cells were picked from the epidermis and 207 from the dermal infiltrate. The rearranged TCR-gamma DNA could be sequenced from 181 of 387 T cells. In three of six patients representing all three stages, epidermal T cells with a clonal rearrangement could be amplified. In early plaque stage a higher degree of epidermal T lymphocytes was found than in initial patch, later plaque, and tumor stages with an inverse distribution found for reactive T lymphocytes. In two patients a biallelic rearrangement was demonstrated that had not been detected in prior PCR analysis from blood and skin samples. These data show that clonal (neoplastic) and non-clonal (reactive) T lymphocytes in MF preferentially infiltrate different microanatomical compartments of the skin, depending on the stage of disease. The microanatomically distinct localization of reactive and clonal T cells suggests that the absence of direct contact between tumor and host-defense lymphocytes may contribute to tumor persistence and progression in epidermis, peripheral blood, and deep dermal tumor cell nests, respectively.

Aged↗
PubMed2003

Correlations between clinical, histologic, blood, and skin polymerase chain reaction outcome in patients treated for mycosis fungoides.

Little information is currently available regarding post-treatment outcome of TCR-targeted PCR in skin and/or peripheral blood in patients with Mycosis Fungoides (MF) when a dominant gene rearrangement is present at time of diagnosis. To address this matter, a study evaluating the correlations between post-treatment clinical, histological, blood and skin PCR data was conducted in MF patients. Twenty-seven MF patients with dominant gene rearrangement in skin lesions at time of diagnosis were selected. Peripheral blood samples were investigated as well before treatment and post treatment molecular data in skin and blood were compared with clinical and histological outcome. A dominant gene rearrangement was detected before treatment in blood of 16/25 patients. The dominant gene rearrangement disappeared from cutaneous lesions in 8/13 patients displaying complete clinical and histological response whereas skin PCR remained positive in all 10 patients with histologically persistent disease. A dominant gene rearrangement was still present in blood in 10/16 patients after treatment and blood data were not correlated with skin molecular response. This study confirms frequent detection of a dominant gene rearrangement in peripheral blood in MF patients and shows that PCR may remain positive in lesional sites even when skin lesions are successfully treated.

Adult↗
PubMedDate not supplied

Profile and outcome of childhood mycosis fungoides in Singapore.

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma. It usually occurs in middle-aged and elderly persons, although several reports have described its occurrence in young children. The aim of this study was to review the profile and outcome of childhood MF in Singapore from 1989 to 1998. A total of nine patients (six males and three females) were diagnosed with MF before the age of 21 years. There were four Chinese, four Malay, and one Indian. The age at the time of histologic diagnosis ranged from 6 to 20 years (mean 14.3 years). Eight of the nine patients presented with hypopigmented patches and plaques. According to TNM staging, three were in stage 1A and six in stage 1B. The treatment modalities included psoralen plus ultraviolet A (PUVA) (n = 5), UVB (n = 2), and potent topical steroids (n = 2). We found that PUVA induced a faster clinical remission, but maintenance PUVA was required to prolong the relapse-free interval. This study also highlighted the need to consider MF in the differential diagnosis of hypopigmented dermatoses in dark-skinned individuals, especially if they occur on the buttocks.

Administration, Topical↗
PubMed2002

Composite mycosis fungoides and B-cell chronic lymphocytic leukemia.

Concordant or composite mycosis fungoides and B-cell chronic lymphocytic leukemia (B-CLL) is exceedingly rare, with only 10 cases previously described to our knowledge. We report a case of a 64-year-old woman who developed generalized erythroderma 5 years after the diagnosis of early stage B-CLL. Over the next 6 years of her clinical course multiple sequential samples of skin, peripheral blood, and one enlarged lymph node were studied in detail by flow cytometry, immunohistochemistry, molecular diagnostics, and electron microscopy. The progressive cutaneous infiltrates were initially characterized as leukemia cutis, infiltration by B-CLL. Three years later, when she developed worsening skin disease and lymphadenopathy, the cutaneous infiltrates were characterized as cutaneous T-cell lymphoma. At that point, a biopsy of an enlarged lymph node revealed a composite lymphoma of both B-CLL and cutaneous T-cell lymphoma, and the peripheral blood also contained circulating cells of both neoplasms. Herein we summarize the literature on concordant cutaneous T-cell lymphoma and B-CLL, and the literature on concordant T- and B-cell neoplasms in general, with a review of the postulated relationships between these neoplasms.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Constitutive expression of NF-kappa B is a characteristic feature of mycosis fungoides: implications for apoptosis resistance and pathogenesis.

The NF-kappa B family of transcription factors is an important regulator of genes expressed during inflammatory responses, immunoglobulin (Ig) class switching, cellular differentiation, and apoptosis. Recently, members of the NF-kappaB family, including p65(Rel A), have been implicated in promoting survival of various hematopoeitic neoplasms, including T cell malignancies such as adult T cell leukemia-lymphoma. We investigated the expression of active NF-kappa B p65(Rel A) in cases of mycosis fungoides (MF) and the effect of chemical inhibitors of NF-kappa B on apoptosis in cutaneous T cell lymphoma (CTCL) cell lines. Paraffin-embedded tissues from 23 cutaneous lesions and a single lymph node biopsy from patients diagnosed with MF were evaluated for p65(Rel A) expression by using a monoclonal mouse antibody that detects the activated form of p65(Rel A). Apoptosis after treatment with the NF-kappa B inhibitors gliotoxin, MG132, BAY 11-7082, and BAY 11-7085 was quantitatively measured in the CTCL cell lines HuT-78 and HH by propidium iodide (PI)/cell cycle analysis for detection of a hypodiploid (sub-G(0)) population and by determination of increased Annexin V/7-amino-actinomycin D (7-AAD) expression. Nuclear extracts from CTCL cells before and after chemical inhibition were analyzed for NF-kappa B nuclear DNA-binding activity by electrophoretic mobility shift assay (EMSA) with quantitative densitometry. Nuclear expression of p65(Rel A) before and after treatment with the various inhibitory compounds was measured by immunofluorescence staining in each CTCL cell line. Neoplastic T lymphocytes from 22 of 24 cases of MF showed strong nuclear and cytoplasmic expression of active p65(Rel A). Compared with untreated control cells, a marked increase in apoptosis, a significant decrease in NF-kappa B DNA-binding activity, and a marked decrease in nuclear p65(Rel A) expression were seen in cells from both CTCL cell lines after chemical NF-kappa B inhibition. These data show that the active form of NF-kappa B p65(Rel A) is commonly expressed in neoplastic T lymphocytes in patients with MF. In CTCL cell lines, the significant decrease in nuclear NF-kappa B expression and the marked increase in spontaneous apoptosis caused by chemical NF-kappa B inhibition suggest a critical role for NF-kappa B in the pathogenesis and tumor cell maintenance of CTCLs. HUM PATHOL 31:1482-1490.

Anti-Infective Agents↗
PubMed1997

[Cutaneous T-cell lymphoma of the mycosis fungoides type in the area of the eyelid and lacrimal ducts].

PATIENT: A 62-year-old former miner with silicosis of the lungs but otherwise in good general condition presented with a solid nodule in the nasal left lid area for a duration of three months. Because of a central ulceration the reference diagnosis was basalioma. The tumour infiltrated the nasal part of the upper and lower eyelid and the tear ducts so that these were unrinseable. Similar lesions have been present since two years in other skin regions. METHODS: Two cutaneous biopsies confirmed the diagnosis of a Mycosis fungoides without detectable expression of the CD30-antigen. Medical investigation finally revealed hepatosplenomegaly and cervical, inguinal and abdominal lymph node involvement. A lymph node biopsy three months after presentation again showed a T-cell-lymphoma which was CD30-positive now. THERAPY: Systemic polychemotherapy was started. The lid lesions completely resolved, and the tear ducts were rinseable again.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Experience with total skin electron beam therapy in combination with extracorporeal photopheresis in the management of patients with erythrodermic (T4) mycosis fungoides.

OBJECTIVE: We compared the prognosis of patients with erythrodermic mycosis fungoides (MF) administered total skin electron beam radiation (TSEB) plus neoadjuvant, concurrent, and adjuvant extracorporeal photopheresis (ECP) with the prognosis of patients administered only TSEB. Outcomes of clinical interest include disease-free survival (DFS), progression-free survival (PFS), overall survival (OS), and cause-specific survival (CSS). METHODS: This study was a retrospective nonrandomized series. Between 1974 and 1997, a total of 44 patients with erythrodermic MF from the Department of Therapeutic Radiology, Yale University School of Medicine, and the Department of Radiation Oncology, Cancer Care Ontario, Hamilton, Ontario, were collected and analyzed as a group (Hamilton = 15, Yale = 29). These patients received TSEB consisting of 32 to 40 Gy via 4 to 6 MeV. Twenty-one patients at Yale also received ECP treatment 2 days per month for a median of 6 months. Median age was 68 years (range, 29-82 years) at the commencement of TSEB, and 66% were male. Seventy-three percent of patients had received other therapies before TSEB, including 75 courses that failed to control disease (n = 15 systemic therapy, 16 biologicals, and 44 topical therapies). At TSEB, 59% had hematologic involvement (B1), 30% were stage IVA (N3), and 13% were IVB (M1). Median follow-up was 2.2 years (range, 0.3-13.9 years) subsequent to TSEB and 3.7 years from diagnosis (range, 0.8-16.8 years). RESULTS: All patients responded to TSEB within 2 months of completion, with a cutaneous complete response rate of 73%. For the 32 complete responders the 3-year DFS was 63%. It was 49% for those 17 patients who received only TSEB compared with 81% for those 15 patients who received TSEB + ECP. Cox regression analysis demonstrated that ECP was associated with prolonged remission (DFS multivariate P =.024, adjusting for B1 and stage). The 2-year PFS, CSS, and OS for the TSEB group were 36%, 69%, and 63%, respectively, compared with 66%, 100%, and 88% for the TSEB + ECP cohort. Cox regression demonstrated that ECP was associated with CSS (multivariate P =.048, adjusting for B1 and stage). For those who progressed, a total of 49 subsequent courses of therapy were administered (n = 20 chemotherapy, 10 biologicals, and 19 topical therapies). Thirteen patients died from MF-related causes, and 8 died from other causes. Acute and chronic toxicities were consistent with those previously reported. CONCLUSION: ECP given concurrently with, or immediately after, TSEB (32-40 Gy) significantly improves both PFS and CSS for patients with erythrodermic MF compared with TSEB without the addition of ECP.

Adult↗