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PubMed1985

Clonal rearrangements of T-cell receptor genes in mycosis fungoides and dermatopathic lymphadenopathy.

Histologic diagnosis of mycosis fungoides may be difficult, especially in lymph nodes that show changes frequently associated with chronic skin disease. As an alternative approach to diagnosis, we have analyzed the configuration of DNA for the beta T-cell receptor genes in biopsy tissues from 14 patients with mycosis fungoides. Clonal rearrangements of these genes were found in each specimen tht contained histologically unambiguous mycosis fungoides. Clonal rearrangements were also found in seven of nine lymph nodes removed from patients with mycosis fungoides and considered histologically to contain only benign lymphadenopathy. Matching rearrangements of beta T-cell receptor genes were detected in benign lymph nodes and histologically involved tissues when paired specimens were available from the same cases. Our findings provide molecular evidence for the clonal T-cell origin of mycosis fungoides and indicate the high incidence of extracutaneous disease in patients with palpable lymphadenopathy. In addition, this study demonstrates that the detection of rearranged T-cell receptor genes can be a sensitive and practical method for the diagnosis and characterization of T-cell neoplasms.

Clone Cells↗
PubMed1975

Management of mycosis fungoides--current status and future prospects.

Current knowledge concerning the course of mycosis fungoides and recognized prognostic factors have been reviewed. Those factors with prognostic significance at the time of biopsy diagnosis include age and the clinical findings of skin tumors, ulceration or palpable lymphadenopathy. During the course of disease, the development of skin tumors, ulceration or palpable lymphadenopathy were each associated with a poor prognosis and median survival was only 12 months if all those clinical parameters were present. Patients who developed overt visceral mycosis fungoides rarely survived more than a few months. Lymphocytopenia and the presence of malignant lymphoma in biopsied lymph nodes were also poor prognostic findings. The various modalities of therapy for proven mycosis fungoides were reviewed. Topical therapy and external irradiation were generally of symptomatic benefit only, but two recent studies have shown that aggressive use of topical nitrogen mustard and electron beam therapy are associated with long-term responses in patients with disease confined to the skin. Single agent chemotherapy often resulted in transient responses in advanced and refractory mycosis fungoides. Future approaches to the management of mycosis fungoides have been suggested. These include a thorough review of the histological features, a thorough and systematic pretreatment evaluation and randomized studies of the various treatment modalities including combination therapy in appropriately staged patients.

Administration, Topical↗
PubMed1998

Mycosis fungoides metastasizing to the brain parenchyma: case report.

OBJECTIVE AND IMPORTANCE: Mycosis fungoides is a rare T-cell lymphoma of the skin that can, in one-half to three-quarters of patients suffering from this disease, involve the viscera in late stages of the disease. Although autopsy series performed more than 2 decades ago showed that the incidence of metastatic mycosis fungoides to the central nervous system is approximately one of seven, a total of only several dozen cases have been reported to date. As compared to meningeal involvement, intraparenchymal metastases are even rarer. We describe a biopsy-proven case of intraparenchymal central nervous system mycosis fungoides in a patient with nonprogressive skin involvement and no detectable visceral involvement, and we present a review of the relevant literature. CLINICAL PRESENTATION: A 68-year-old man, 3 years after the diagnosis of his skin disease, developed fatigue, confusion, and frontal lobe signs without the presence of cerebriform cells in the peripheral blood or any other clinical evidence of visceral involvement. Magnetic resonance imaging revealed a diffuse area of increased T2-weighted signal involving the white matter of both cerebral hemispheres as well as a focal area of T2 abnormality along the body of the corpus callosum. The radiological differential diagnosis was either leukodystrophy caused by chemotherapy, progressive multifocal leukoencephalopathy, or glioma with associated white matter changes. INTERVENTION: A stereotactic serial brain biopsy revealed diffuse perivascular infiltrates of atypical lymphocytes, as well as several large cells with cerebriform nuclei consistent with mycosis fungoides. The cells were immunoreactive for LCA, MT1, UCHL1, and CD3. CONCLUSION: We stress the importance of including mycosis fungoides as part of the differential diagnosis for a brain lesion in patients with cutaneous T-cell lymphoma, because treatments do exist, and we conclude that a serial stereotactic biopsy may be necessary to provide a definitive diagnosis.

Aged↗
PubMed1989

Expression of T-cell receptor antigens in mycosis fungoides and inflammatory skin lesions.

Using immunohistologic methods, we studied the expression of the T-cell receptor (TCR)-associated antigens CD3, TCR-beta, and TCR-delta by cutaneous T cells in mycosis fungoides (MF) (36 patients) and a variety of inflammatory diseases (16 patients). Most T cells in the inflammatory diseases and patch/plaque mycosis fungoides expressed the immunophenotype characteristic of the vast majority of mature peripheral T cells: CD3+ TCR-beta+ TCR-delta-. In contrast, abnormal CD3/TCR-beta antigen expression was seen in 3 of 6 cases (50%) of tumor stage mycosis fungoides. Furthermore, we were able to document its evolution from the normal pattern present in earlier patch/plaque lesions of the two cases in which serial biopsies were available for study. Divergence of epidermal versus dermal CD3/TCR-beta antigen expression was seen in 2 of 34 (6%) of biopsies of patch/plaque mycosis fungoides but not in inflammatory controls. The TCR-delta+ cells were generally rare regardless of diagnosis. We conclude that inflammatory skin diseases and most patch/plaque mycosis fungoides are typically composed of T lymphocytes that resemble mature peripheral T cells in regard to their expression of TCR-associated antigens. In contrast, aberrant patterns of TCR-associated antigen expression can be seen in tumor stage MF, and, more rarely in patch/plaque MF.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1976

Monocytopoiesis in chronic eczematous diseases, psoriasis vulgaris, and mycosis fungoides.

Monocytopoiesis and blood monocytes were examined in 8 patients with disseminated chronic eczematous diseases, 8 patients with disseminated psoriasis vulgaris, and 8 patients with mycosis fungoides in plaque or tumor stage. Monocytopoiesis was moderately stimulated in all these patients. The stimulation manifested itself by: (1) a rise in relative number of promonocytes in bone marrow in all patients with eczema, in 1 out of 8 patients with psoriasis, and in 7 out of 9 examinations in patients with mycosis fungoides; (2) a rise in [3H]thymidine labeling indices of medullar promonocytes (8/8 eczema, 7/7 psoriasis, 8/9 mycosis fungoides); and (3) a rise in the naphthol-AS-D-chloroacetate esterase activity of blood monocytes, indicating premature monocyte marrow egress (3/5 eczema, 7/8 psoriasis, 9/9 mycosis fungoides). In eczema and psoriasis the mean enhancement of monocytopoietic activity was similar but less pronounced than in mycosis fungoides. In the latter disease there was no correlation between measured parameters and visible skin lesions. The results were interpreted as indicative of increased monocyte consumption by pathologic, immunologic, and/or inflammatory processes.

Adult↗
PubMed2007

Mycosis fungoides--a review of the management of 28 patients and of the recent literature.

BACKGROUND: Mycosis fungoides is an uncommon cutaneous T-cell lymphoma characterized by malignant monoclonal proliferation of T-helper lymphocytes. Its course is variable with a potential for lymphatic and hematogenous involvement. We report the investigations, staging, treatment, follow-up, and outcome of 28 patients. This is the first such study reported from Ireland. METHODS: Twenty-eight patients with mycosis fungoides (14 women, 14 men; average age, 52.5 years) were reviewed over 12 years in the dermatology clinic which assesses an average of 4500 patients per year. All mycosis fungoides patients were referred from their family physicians. The diagnosis was made in all cases from a combination of clinical findings, histology, and immunohistochemistry. TNM staging revealed 11 patients at diagnosis stage IA (T1), 12 at stage IB (T2), four at stage IIB (T3), and one at stage III (T4). RESULTS: The usual male preponderance was not found. Eight patients needed multiple biopsies to establish the diagnosis. Detailed investigations were not useful in the early stages. Patients were followed up over a 12-year period. Thirteen patients died as a result of cutaneous lymphoma. Two patients with stage IA disease progressed rapidly and died, a feature reported in only 10% of patients at this stage. Five patients showed unusual features, including a long history prior to presentation, the development of the rarely reported bullous mycosis fungoides, and aggressive disease beginning at a young age. CONCLUSIONS: Mycosis fungoides is rare; we reviewed 28 patients over 12 years. The prognosis is poor at the later stages; 13 patients died. Two patients who died were unusual in that they rapidly progressed from stage IA disease; however, in the majority of patients with this stage, the prognosis is excellent. Detailed investigations were unhelpful in early stage disease. Close clinical follow-up is essential to identify disease progression.

Adult↗
PubMed1977

Lymphoma of the skin. A comparative clinico-pathologic study of 50 cases including mycosis fungoides and primary and secondary cutaneous lymphoma.

A clinico-pathologic study of lymphomas of the skin included 14 cases of mycosis fungoides, 14 of primary lymphoma and 22 of secondary lymphoma. Mycosis fungoides has clinical and histopathologic features which allow for separation from the other groups. In this study, patients with mycosis fungoides had a longer duration of history and presented with papules, plaques, erythroderma or generalized dermatitis but not with tumor nodules ab initio. A confident histologic diagnosis required the presence of the mycosis cell, which was usually present in association with a mixed inflammatory cell infiltrate. Another important histologic feature was the presence of invasion of the epidermis by the mycosis cells singly and/or in nests (Pautrier microabscesses). Primary and secondary lymphomas of the skin presented clinically as multiple tumor nodules and histologically as a monomorphic infiltrate of neoplastic cells confined to the dermis and subcutis. A feature which has not been adequately documented in a large series was the presence of an associated prominent epithelioid cell reaction in several cases from all three groups.

Female↗
PubMed1997

Folliculotropic mycosis fungoides with large-cell transformation presenting as dissecting cellulitis of the scalp.

Follicular mycosis fungoides (MF) is a rare variant of cutaneous T-cell lymphoma (CTCL) in which malignant lymphocytes preferentially infiltrate hair follicles. This report describes a patient with follicular mycosis fungoides presenting in a manner similar to dissecting cellulitis of the scalp with nonhealing, draining nodular lesions. Follicular mucinosis associated with folliculotropic mycosis fungoides resulted in follicular disruption and deep dissecting cellulitis. Large-cell transformation of CTCL was present in the initial diagnostic scalp and axillary lymph node specimens. The patient died from progressive CTCL 9 months following initial diagnosis despite electron beam radiation, topical mechlorethamine, interferon-alpha, and systemic chemotherapy. This case indicates that large-cell transformation of folliculotropic mycosis fungoides is an aggressive form of CTCL, and that folliculotropic mycosis fungoides can give rise to lesions which resemble dissecting cellulitis of the scalp. Upregulation of intercellular adhesion molecule-1 (ICAM-1) on follicular epithelium adjacent to lymphocyte function-associated antigen-1 (LFA-1)-positive folliculotropic lymphoma cells in this report provides insight into lymphocyte homing mechanisms in folliculotropic MF.

Adult↗
PubMed1996

Hodgkin's disease following mycosis fungoides: phenotypic and molecular evidence for different tumour cell clones.

AIMS: (1) To assess the clonality of tumour cells in two patients with mycosis fungoides who subsequently developed Hodgkin's disease; and (2) to determine whether there is a clonal relation between these two disorders. METHODS: Cutaneous tissue samples involved by mycosis fungoides and lymph nodes involved by Hodgkin's disease from both patients were investigated by immunohistochemistry and the polymerase chain reaction. RESULTS: Mycosis fungoides tumour cells in both patients expressed multiple T cell associated antigens; Reed-Sternberg (RS) cells had the null phenotype. T cell receptor gamma chain genes were clonally rearranged in mycosis fungoides cells but not in RS cells, including variants, in both patients. In the patient with intermediate transformation to large cell lymphoma, immunoglobulin heavy chain genes were rearranged in the cutaneous tumour, but not in the lymph node involved by Hodgkin's disease. CONCLUSION: The divergent antigen expression and gene rearrangements observed in these two patients strongly suggest that Hodgkin's disease and mycosis fungoides are not derived from a single tumour cell clone.

Clone Cells↗
PubMed1996

Mycosis fungoides with marked hyperpigmentation.

Pigmentary changes in mycosis fungoides are not rare. Although poikiloderma and hypopigmented skin lesions have often been reported in the literature, there are few cases of mycosis fungoides presenting as a hyperpigmented skin lesion. We present a 57-year-old Japanese male with mycosis fungoides whose skin lesions showed marked hyperpigmentation. The skin lesion initially appeared as an irregularly shaped itchy annular erythema with central pigmentation predominantly on his extremities. During our 5-year follow-up, these skin lesions gradually increased in size and number. The erythema extended peripherally and became elevated with marked hyperpigmentation. Histology revealed extreme elongation of the rete ridges with infiltration of atypical large lymphoid cells characteristic of mycosis fungoides and numerous melanin granules in both the epidermal melanocytes and dermal melanophages. Although the exact mechanism of the marked hyperpigmentation is one of the unique characteristics in mycosis fungoides, especially in non-white individuals.

Humans↗
PubMed1994

Indications of a considerable decrease in the death rate in mycosis fungoides by PUVA treatment.

PUVA therapy has its roots in ancient India and Egypt and began to come into general use in the highly developed countries in the middle of the 1970's (1). The first reports of PUVA treatment of mycosis fungoides were published in 1976 (2); these were followed by several other studies in the two following years (3-7). Some of the early work on PUVA therapy was carried out in Sweden (8,9), and the modality was in general use in most major clinics by 1977. The dramatic effect on mycosis fungoides of PUVA therapy is well known, but whether the death rate is influenced is not known. For ethical reasons no controlled clinical studies have been performed. Sweden is a highly organized country with reliable death statistics at least for diseases as conspicuous as mycosis fungoides. The purpose of the present study was to provide data on the death rate in mycosis fungoides in Sweden from 1961 to 1990, which we think is relevant to the question whether PUVA treatment decreases the death rate in mycosis fungoides.

Humans↗
PubMedDate not supplied

Meningeal mycosis fungoides: cytologic and ultrastructural aspects.

Mycosis cells were identified in the pre-morbid cerebrospinal fluid of a patient with neurological symptoms and mycosis fungoides (MF). Light and electron microscopic examination at autopsy confirmed leptomeningeal involvement by mycosis fungoides. The cellular morphology of the non-cutaneous infiltrates supports the concept that mycosis fungoides retains a unique histopathology in its dissemination to the viscera. The importance of cerebrospinal fluid cytology in patients with mycosis fungoides is emphasized.

Brain Neoplasms↗
PubMed1977

The ultrastructure of mycosis fungoides, of Sezary's syndrome, and of Woringer-Kolopp's disease (pagetoid reticulosis).

Skin lesions of 13 cases of mycosis fungoides, 2 cases of Sézary's syndrome and one case of Woringer-Kolopp's disease were studied. In mycosis fungoides two main cell types were observed: small atypical lymphoid cells, and large atypical lymphoid cells. The small atypical lymphoid cells were characterized by dense nuclei with varying degrees of nuclear lobulation. Normal-appearing lymphocytes and typical mycosis cells were in this cell group. The large atypical lymphoid cells were characterized by large nuclei with little lobulation and by less chromatin condensation, as well as by a more abundant cytoplasm. Their identification is discussed and indications of their possibly being neoplastic or proliferating lymphoblasts are given. In Sézary's syndrome Sézary cells with more lobulated nuclei than in mycosis cells and lymphoblast-like cells as in mycosis fungoides could be found. In Woringer-Kolopp's disease cells similar to Sézary cells aggregated mainly in the epidermis. No interdigitating reticulum cells and no other morphological signs of a specific lymphocyte microenvironment were found in any of the cases.

Dermatitis, Exfoliative↗
PubMed2003

Morphometric study of lymphoid cells in mycosis fungoides and its simulators.

The distinction of early stages of mycosis fungoides from benign lymphoid disorders of skin is difficult by conventional histological techniques. We studied 10 cases of mycosis fungoides, 10 cases of large plaque parapsoriasis, 10 cases of other benign lymphoid disorders of skin and 5 cases of lymph nodes. Nuclear area, perimeter of the nucleus, nuclear contour index, cytoplasmic area, form factor and nuclear cytoplasmic ratio as well as DNA-ploidy were determined by image analysis. There were statistically significant difference (P value < 0.05) between all parameters except nuclear cytoplasmic ratio of the lymphoid cells of Mycosis Fungoides and benign lymphoid disorders of skin. Aneuploidy was found in 50% cases of Mycosis Fungoides. Histopathological parameters like epidermotropism pautrier micro-abscess and atypical lymphocytic infiltrate in both epidermis and dermis were more marked in aneuploid than diploid cases. So, the determination of nuclear contour index and DNA-ploidy is of importance to differentiate between Mycosis Fungoides and benign lymphoid disorders of skin.

Adult↗
PubMed2005

Full clinical recovery after topical acyclovir treatment of Epstein-Barr virus associated cutaneous B-cell lymphoma in patient with mycosis fungoides.

Primary cutaneous T- and B-cell lymphomas are a heterogeneous group of diseases with varied clinical presentations and prognosis. The use of new molecular, histological, and clinical criteria has improved their recognition. Cutaneous B-cell and T-cell lymphomas are seldom found together in the same patient. Here we report a rare case of mycosis fungoides variant of a cutaneous T-cell lymphoma (CTCL) which later developed Epstein-Barr virus (EBV) associated cutaneous B-cell lymphoproliferative disorder. The patient initially presented with generalized erythroderma, extensive plaques, and axillary lymphadenopathy. Histopathology and immunophenotyping of her tumor from the right breast nodule revealed a T-cell lymphoma consistent with mycosis fungoides. She was initially treated with pentostatin, followed by topical mechlorethamine and topical steroids. After progression of her mycosis fungoides with worsening diffuse skin lesions on this regimen, her treatments were changed to oral bexarotene with an initial partial response followed by stable disease. Three years from her initial presentation, she developed ulcerated cauliflower-like nodules on her forehead. Biopsy of these lesions revealed EBV-positive large- and medium-sized pleomorphic B-cells consistent with EBV-driven B-cell lymphoproliferative disorder. She was treated with topical acyclovir cream on the involved skin areas while continuing with oral bexarotene for mycosis fungoides. Skin lesions gradually diminished and totally disappeared after four weeks of topical acyclovir treatment. Bexarotene treatment was continued for another year until the mycosis fungoides progressed and became wide spread causing her death four and a half years after the initial diagnosis. The coexistence of two cutaneous non-Hodgkin lymphomas of different lineage in the same patient and the complete clinical response of EBV-related B-cell cutaneous component to topical acyclovir makes this rare case particularly interesting.

Acyclovir↗
PubMed1979

Gingival involvement in mycosis fungoides: report of case.

A case of mycosis fungoides of the gingiva is reported. Mycosis fungoides is a lymphoproliferative disease that primarily affects the skin. Systemic dissemination is a distinct aspect of the natural course of mycosis fungoides and usually involves the lymph nodes, spleen, and liver. The diagnosis of mycosis fungoides depends on the presence of a variety of atypical cells, including small and large variants of the mycosis cell with an infiltrate of polymorphous inflammatory cells in both the dermis and epidermis. Various modes of treatment have been used. In the current case, remission was achieved with radiation therapy.

Aged↗
PubMed1979

The patch stage of mycosis fungoides. Criteria for histologic diagnosis.

It has long been claimed that a specific histologic diagnosis of mycosis fungoides cannot be made in the premycotic" or "eczematous" (patch) stage of the disease. Indeed, the histologic features of the premycotic lesions were constantly said to be those of "chronic non-specific dermatitis." We studied 46 biopsy specimens of patch lesions from patients in whom mycosis fungoides was unequivocally established by clinical events (i.e., concurrence or later development of typical plaque and/or nodular lesions) and indubitable histologic findings. We divided patch lesions into early nonatrophic patches and late atrophic ones. The early patches are considered to be evolving lesions of mycosis fungoides, whereas late patches represent resolving plaques of the disease. On the basis of this study, we concluded that histologic diagnosis can be made with near certainty in patch lesions of the disease. We found that the critical feature for histologic diagnosis of early and late patch lesions of mycosis fungoides is the presence of an increased number of mononuclear cells distributed singly or in small collections within an epidermis devoid of spongiotic microvesiculation. Other important features are lacunae surrounding intraepidermal mononuclear cells which gives them the appearance of "haloed cells." A sparse infiltrate of mononuclear cells is present around the blood vessels of the superficial, and sometimes the deep, vascular plexus. Atypical mononuclear cells are not necessary for the diagnosis of early patch lesions of mycosis fungoides, but they are found commonly in late patch lesions. Late atrophic patches show a thinned epidermis, loss of the usual configuration between rete ridges and dermal papillae, and coarse collagen throughout a thickened papillary dermis.

Adolescent↗
PubMed1977

Central nervous system involvement in mycosis fungoides: pre mortem diagnosis by light and electron microsocopic study of the spinal fluid.

Involvement of the brain, spinal cord, peripheral nerves, meninges, and cerebrospinal pathways in mycosis fungoides manifests itself, clinically, as an obscure neurologic disturbance, occurring in patients with cutaneous manifestations of that disorder. Neurologic expressions of this particular cutaneous lymphoma are infrequently reported, in spite of the fact that many patients dying in the course of mycosis fungoides have pathologically demonstrable central nervous system, peripheral nervous system, and meningeal involvement. We report here a patient who incurred devastating neurologic illness as one of the initial features of the course of systemic dissemination of mycosis fungoides. Death occurred nine years after the onset of cutaneous illness. In this instance, cerebrospinal fluid cytologic studies established the diagnosis of nervous system involvement. Mycosis fungoides cells shed into the cerebrospinal fluid were studied by special techniques of light and electron microscopy. Brain scan abnormalities were present, which were clinically correlative with foci of brain involvement. The initial response of patient's nervous system illness to therapy was gratifying but unsustained, and she went on to fatal brain and multiple organ involvement with disseminated mycosis fungoides. The techniques of spinal fluid cytologic diagnosis, confirmatory of the etiology of disease in this case, may have practical appications in the diagnosis of otherwise obscure neurologic disorders.

Adult↗