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Southern blot analysis of clonal rearrangements of T-cell receptor gene in plaque lesion of mycosis fungoides.

T-cell populations of 22 plaque lesions from seven mycosis fungoides patients were studied for clonal rearrangement of the beta chain of the T-cell receptor (T beta) gene. All plaque lesions employed in this study showed clinically similar appearance. Histologically, all the biopsy specimens showed epidermotropism and the dermal infiltration of mononuclear cells including atypical cells. Histochemically, the majority of the infiltrated cells had surface markers of helper T cells. DNA extracted from skin lesions, peripheral lymphocytes, and lymph nodes revealed that the monoclonal expansion of T cells was different among patients and lesions. DNA extracted from the two skin lesions of case 1 revealed a clonal expansion of T cells. The rearranged bands persisted for about 1 year. In contrast, all lesions from cases 3-7 showed no rearranged band. Interestingly, three lesions from case 2 showed mixed type results, i.e., the monoclonal expansion of T cells was detected in one lesion but not in the other two lesions. Time course study of case 2 revealed that the same rearranged band became detectable in all three skin lesions and a lymph node about 1 year later. These results suggest that in plaque lesions of mycosis fungoides, there are various stages of detectable monoclonality of infiltrating cells, although the clinical appearance of the plaques was similar, and that the variety of monoclonality may reflect the long clinical course of this disease.

Blotting, Southern↗

Ultrastructural identification of T lymphocytes in tissue sections of mycosis fungoides.

An immunoelectronomicroscopic method has been employed to demonstrate in situ the T lymphocyte nature of the dermal and epidermal infiltrates to mycosis fungoides. A specific antiserum to the human T lymphocyte surface antigen (HTLA) was used in an indirect reaction with a peroxidase labeled anti-immunoglobulin. After histochemically revealing the peroxidase activity, T cells were easily identified by the deposition of electron dense material on the cytoplasmic membrane. Counterstaining with uranyl acetate and lead citrate enabled us morphologically to observe the maturity of infiltrating T lymphocytes and to identify Sézary cells and other cells such as eosinophils in the infiltrate. Our results confirm the T cell nature of the dermal infiltrate in mycosis fungoides and show that the epidermal infiltrate of cells forming Pautrier micro-abscesses are predominantly T lymphocytes.

Adolescent↗

T-cell subsets with a naive phenotype are selectively decreased in the peripheral blood of patients with mycosis fungoides.

Peripheral blood lymphocytes of 33 patients with histopathologic confirmation of mycosis fungoides and 27 healthy controls matched for age and sex were analyzed with a panel of monoclonal antibodies using both single and dual color immunofluorescence. Patients with mycosis fungoides had a significant reduction in the percentage of circulating T cells with a naive phenotype (i.e., CD4+2H4+ and CD4+Leu8+), as well as a significant reduction in the absolute numbers of circulating lymphocytes with the phenotype CD8+Leu8+ compared to the control cohort. The reduction in circulating naive T cells was found to occur irrespective of stage of disease, duration of disease, or mode of treatment. The depletion of circulating naive T cells may reflect increased conversion to memory T cells in the peripheral blood or skin.

Antibodies, Monoclonal↗

Expression of OKM5 antigen on epidermal cells in mycosis fungoides plaque stage.

To characterize and quantitate potential antigen-presenting cell subsets in the epidermis of patients with cutaneous T-cell lymphoma, epidermal cells in suspension were obtained from involved and uninvolved skin. Involved epidermis contained increased numbers of OKT6+HLA-DR+ Langerhans cells and a variable number of OKM5+ epidermal cells (ECs) in all mycosis fungoides (MF) patients tested (N = 14). The OKM5+ EC population from involved epidermis of MF patients were heterogeneous and comprised both OKM5+HLe1- keratinocytes and OKM5+HLe1+ leukocytes. Uninvolved epidermis, in 6 of 14 patients with MF, contained a small number of OKM5+ leukocytes; however, no OKM5+ keratinocytes were detected. Neither OKM5+ leukocytes nor OKM5+ keratinocytes were detected in the epidermis obtained from healthy controls. The increased number of potential antigen-presenting cells, that is, OKT6+HLA-DR+ Langerhans cells and OKM5+HLA-DR+ monocytic leukocytes, in the epidermis of patients with MF may be important for the activation of abnormal T cells contained within the epidermis of these patients. Such activated T cells may release gamma-interferon and induce expression of both HLA-DR and OKM5 antigens on keratinocytes. OKM5+ keratinocytes are present in the epidermis of patients with MF, but not in normal skin, and may thus play a role in the pathogenetic mechanisms of mycosis fungoides by recruitment of immunocompetent cells to the epidermis.

Aged↗

Unilesional (segmental) mycosis fungoides presenting in childhood.

Mycosis fungoides is rare in children, and a unilesional presentation is also rare. A 13-year-old Kuwaiti boy with unilesional mycosis fungoides is described. Clinically he had a single indurated large plaque on the left shoulder with histopathologic features typical of cutaneous T-cell lymphoma. The diagnosis was further supported by the presence of a T-cell clone discovered through molecular biology studies of paraffin-embedded material. No other lesions were detected. The lesion showed a favorable response to local radiotherapy.

Adolescent↗

Treatment of mycosis fungoides with OK-432.

Up to the present no other therapeutic means besides local X-ray or beta-ray irradiation and anticancer drugs for the treatment of patients with mycosis fungoides, especially when the condition has progressed to secondary involvement of the lymph nodes, has been found. A recent clinical trial of OK-432 injected locally into cutaneous tumors of a patient with this disease resulted in a conspicuous contraction not only of the tumors injected but of other tumors as well along with significant regression of lymphadenomas. No serious adverse reaction was observed other than low-grade fever and heavy-headedness. These results suggest host-mediated and direct antitumor effects of OK-432 as the possible underlying mechanisms. The efficacy of OK-432 in reducing the size of the tumors without causing any serious adverse effects indicate the potential usefulness of this drug for the treatment of mycosis fungoides.

Antineoplastic Agents↗

Treatment of a case of mycosis fungoides and one of parapsoriasis en plaque with topical PUVA using a monofunctional furocoumarin derivative, 4,6,4'-trimethylangelicin.

A case of plaque stage mycosis fungoides and one of parapsoriasis en plaque were treated with topical PUVA therapy using a monofunctional furocoumarin derivative, 4,6,4'-trimethylangelicin (TMA). Both patients showed complete clearance of eruptions within 16 treatments. The therapeutic effectiveness of TMA was confirmed by the fact that those eruptions exposed to UVA alone, without TMA application, showed slower and less significant improvement. Histologically, dermal infiltrates of mycosis cells and associated epidermotrophism disappeared almost completely in response to TMA PUVA. No side effects or changes in values in laboratory examinations were observed during treatment.

Administration, Cutaneous↗

Demonstration of histiocytes in the epidermal infiltrate of mycosis fungoides.

The presence of histiocytes in the epidermal and dermal infiltrate of mycosis fungoides was observed histochemically by revealing a diffuse pattern of acid alpha-naphthyl acetate esterase (ANAE) activity in the cytoplasm, and immunohistochemically by demonstrating the presence of histiocyte-specific 'enzymes', lysozyme, alpha-I-antitrypsin and alpha-I-antichymotrypsin. Histiocytes in the infiltrate of mycosis fungoides may be involved in antigen processing and interaction with T lymphocytes.

Histiocytes↗

Establishment of T and B cell lines from patients with mycosis fungoides.

Eighteen patients with mycosis fungoides were studied in order to establish cell lines that might be associated with the human T cell leukaemia-lymphoma virus (HTLV). Three T cell lines were established, two from affected skin and one from a lymph node showing dermatopathic lymphadenopathy. The T cells expressed OKT3 and OKT4 antigens. They temporarily expressed an HTLV p19-like antigen in up to 5% of the cells during culture. None of our patients had lymphocytosis or abnormal lymphocytes, except one patient with Sézary's syndrome. We could not establish T cell lines from peripheral blood, but five B lymphoblastoid cell lines were obtained, all positive for the Epstein-Barr virus nuclear antigen. Our finding that T cell lines can be established from skin biopsies and lymph nodes of patients with mycosis fungoides, but not from the blood, supports the concept of a malignant T lymphocyte primarily localized in the skin. The temporary expression of HTLV p19 antigen may indicate the presence of retrovirus, but further studies are needed.

Adult↗

Skin exudate levels of interleukin 6, interleukin 1 and other cytokines in mycosis fungoides.

The role of locally released cytokines in inducing lymphocyte activation and infiltration in the skin lesions of mycosis fungoides has been investigated. The levels of selected cytokines were measured in chamber fluid samples from lesional and control skin. Biologically active interleukin 6 was significantly elevated in lesional samples and a recombinant form of this cytokine was shown to induce lymphocyte migration in an in vitro assay. Biologically active interleukin 1 was detected in all control chamber fluid samples. Significantly reduced levels of this cytokine were present in lesional samples, which may be the result of the release of preformed material. Interleukin 2 and tumour necrosis factor activity, and gamma interferon and granulocyte macrophage colony-stimulating factor immunoreactivity, were not detectable in any of the samples. Interleukins 1 and 6 may play a role in the pathogenesis of the lesional lymphocyte infiltrates in mycosis fungoides.

Adult↗

A case of classical mycosis fungoides associated with human T-cell lymphotropic virus type I.

A 72-year-old male patient from north-eastern Iran developed the typical clinical and histopathological features of mycosis fungoides with lymphadenopathy, but without any other systemic involvement. Human T-cell lymphotropic virus (HTLV-I) antibodies were detected in the patient's serum by two different ELISAs and by Western blot using purified viral particles from MT-2 culture supernatants. Cultured peripheral blood lymphocytes were positive for labelling with anti-HTLV-I serum. Southern blot hybridization of DNA extracted from a skin tumour and from an involved lymph node revealed integrated proviral DNA with identical restriction patterns. This case supports a relationship between mycosis fungoides and HTLV-I and may indicate a new region of endemic HTLV-I infection.

Aged↗

Molecular detection of clone-specific DNA in hypopigmented lesions of a patient with early evolving mycosis fungoides.

A specific molecular probe for the malignant lymphoid clone of lesions of a patient with mycosis fungoides was developed. As a clone-specific marker the junctional region of rearranged T-cell-receptor-gamma (TCR-gamma) genes was used. An oligonucleotide primer complementary to these sequences was designed. Using this primer and polymerase chain-reaction technology, early hypopigmented lesions of the patient, which were previously unclassifiable by conventional microscopy, were analysed. The study demonstrates, on the molecular level, that these hypopigmented lesions contain tumour clone-specific DNA and may represent early manifestations of mycosis fungoides.

Adult↗

Cutaneous necrosis associated with the antiphospholipid syndrome and mycosis fungoides.

The development of extensive cutaneous necrosis in a patient with tumour-stage mycosis fungoides is described. Skin biopsies showed a lymphomatous infiltrate, and thrombosis of dermal blood vessels. Investigation revealed the presence of anticardiolipin antibodies, a lupus anticoagulant, and low free protein S, which contributed to a prothrombotic state. Antiphospholipid antibodies have been detected in non-Hodgkin's lymphoma, but clinical manifestations are uncommon. Such autoantibodies may be produced by neoplastic lymphoid cells. The frequency with which antiphospholipid antibodies occur in mycosis fungoides is currently unknown.

Antiphospholipid Syndrome↗

HTLV-I-associated lymphoma presenting as mycosis fungoides in an HTLV-I non-endemic area: a viro-molecular study.

Human T-lymphotropic virus type I (HTLV-I) is endemic in the Caribbean region, south-western Japan and Africa, and is associated with tropical spastic paraparesis and adult T-cell leukaemia/lymphoma (ATLL). Cutaneous forms of ATLL are sometimes indistinguishable from other cutaneous T-cell lymphomas (CTCL). We report a woman living in a non-endemic area for HTLV-I, with no risk factors for viral infection, who developed mycosis fungoides-like ATLL. The findings underline the usefulness of molecular biological techniques in distinguishing between mycosis fungoides and ATLL. We emphasize the need to establish the HTLV-I status of patients with CTCL, even in HTLV-I non-endemic areas, not only to establish a preventive policy in these countries, but also to further our knowledge of the lymphoproliferation spectrum associated with human retroviruses.

Aged↗

Hypopigmented mycosis fungoides.

We report the case of a 25-year-old Jamaican woman with hypopigmented mycosis fungoides. She first developed a hypopigmented patch on her arm at the age of 11 years. Further lesions developed on the trunk and limbs over a period of 10 years. The lesions were completely impalpable. Skin biopsy showed an infiltrate of atypical lymphocytes, some with cerebriform nuclei, suggesting a diagnosis of mycosis fungoides. The lesions cleared with PUVA therapy.

Adult↗

The lymph node in mycosis fungoides: a light and electron microscopy and immunohistological study supporting the Langerhans' cell-retrovirus hypothesis.

This paper describes the light and electron microscopy and monoclonal antibody findings in the lymph nodes of nine patients with mycosis fungoides. Four cases showed dermatopathic change characterized by close association between small convoluted T4 lymphocytes and T6 antigen-presenting cells (Langerhans' and indeterminate dendritic cells) in the sinuses and paracortical zones. The T4:T8 ratio was between 3 and 5:1. One case showed dermatopathic change but included large convoluted T4 lymphocytes and occasional T10 lymphocytes. The T4:T8 ratio was 4:1. The antigen-presenting cells were mostly T6 negative (interdigitating reticulum cells). One case showed extensive paracortical expansion by small and large convoluted T4 lymphocytes. The T4:T8 ratio was 20:1. Few B lymphocytes and antigen-presenting cells were present. Two cases showed partial and one case total effacement by atypical lymphoid tissue. This included small and large convoluted T4 lymphocytes and T4 immunoblasts. The T4:T8 ratios were between 30 and 40:1. The changes in their antigen-presenting cell population were complex. Langerhans' cells in one case generally failed to express T6 antigen and in two displayed histiocyte features. In one case, both immature and budding type C retrovirus-like particles were identified in Langerhans cells. One extracellular mature type C virus-like particle was identified in another case. No ultrastructural distinction could be made between similarly sized primary lysosomes and possible intracytoplasmic mature type C retrovirus particles. These findings support the hypothesis that mycosis fungoides may represent an altered dermatonodal cycle resulting from an interaction between retrovirus, Langerhans' cells and lymphocytes.

Adult↗