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Langerhans cells and mycosis fungoides--a critical overview of their pathogenic role in the disease.

Skin biopsies from seven patients with mycosis fungoides in various clinical stages (patches, plaques, nodules) were studied immunohistochemically and ultrastructurally, with the aim of investigating and quantifying the distribution of Langerhans cells and their relationships to mycosis cells. Our findings have revealed that in patches and plaques both Langerhans cells and mycosis cells were numerous in the epidermis. Notwithstanding this, in all the specimens examined, only one Langerhans cell forming close contact with a mycosis cell was detected. In the nodules, Langerhans cells and mycosis cells were sparse in the epidermis and no contacts were seen between them. Moreover, in all the patients studied, only a single Langerhans cell was found in the dermal infiltrate without any closely related mycosis cells. Conversely, numerous interdigitating cells have been found in the dermis of patches and plaques, often tightly adhering to mycosis cells. In the nodule, a few scattered interdigitating cells were seen, but often these had close contacts with neoplastic lymphoid cells. These findings indicate that close apposition between Langerhans cells and mycosis cells, which led previous authors to hypothesize a persistent stimulatory action of Langerhans cells on T lymphocytes, eventually leading to the malignant transformation of the latter, is unusual in mycosis fungoides. Therefore, if such a pathogenic role may be attributed to accessory cells in mycosis fungoides it is more probably exerted by dermal interdigitating cells and not by Langerhans cells, as previously proposed.

Humans↗

Combination chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) in TNM-classified stage IV mycosis fungoides.

Nine patients with stage IV mycosis fungoides (MF), according to TNM classification, were treated with cyclophosphamide, vincristine, and prednisone (CVP). CVP induced a 66% overall objective response rate and a 44% complete response rate, which is the highest reported in the literature. CVP is an effective regimen in MF and could be employed in combination with total skin or total lymphoid radiotherapy. TNM classification should be used for all patients with MF, because it makes the evaluation and comparison of treatments more reliable.

Adult↗

An unusual and fatal case of disseminated cutaneous herpes simplex. Infection in a patient with cutaneous T cell lymphoma (mycosis fungoides).

A patient with plaque stage mycosis fungoides (MF) developed an atypical disseminated cutaneous herpes simplex virus (HSV) infection manifested by polycyclic cutaneous ulcers. Although Tzanck preparations and serial antibody titers to herpes virus were negative, the diagnosis was readily established by viral culture and histologic examination of the skin lesions. Following adenine arabinoside therapy, the viral cultures of the ulcers became negative and the spread of virus-induced ulcerations ceased. In an immunocompromised host with rapidly advancing, sharply punched-out polycyclic cutaneous ulcerations, herpes simplex infection should be considered even though the classical vesicular lesions are absent.

Female↗

Total skin electron beam therapy in mycosis fungoides.

Thirty-nine patients with mycosis fungoides were treated with total skin electron beam irradiation from 1971 to 1976, and all received minimum follow-up of 12 months. Details of treatment technique and dosimetry are given. Sixteen patients cleared completely. Seven patients are in long-term remission (1 1/2 to 4 1/2 years). Eleven patients died. Those who failed are now being treated with topical therapy with varying degrees of control. Some have been retreated with local irradiation. Most of the patients had extensive disease; for this group, total skin electron beam therapy was especially useful, as many of those who failed developed only minimal disease that was well controlled by topical measures.

Administration, Topical↗

Demonstration of OKT 6-reactive cells in mycosis fungoides.

Infiltrates of five cases of mycosis fungoides (MF) were studied for the presence of cells reactive with a monoclonal antibody, OKT 6, which detects an antigen present on relatively immature thymocytes and Langerhans cells. In situ immunohistochemical staining was used for their demonstration. OKT 6-reactive cells formed a definite component of the dermal infiltrates of all patients examined. In three patients who showed numerous Pautrier microabscesses on routine histologic examination, OKT 6-positive cells were found to form a component of these abscesses. OKT 6-reactive cells have also recently been shown to be present in varying numbers in the dermal infiltrates of large plaque (atrophic) parapsoriasis (LPAP), a condition which may terminate in MF. The significance of these findings is discussed.

Antibodies, Monoclonal↗

Vitiligo-like leucoderma during photochemotherapy for mycosis fungoides.

We describe four patients with mycosis fungoides (MF) in whom depigmentation, and also leucotrichia in one, occurred following the resolution of the eruption during phototherapy (psoralen plus ultraviolet A treatment in three patients, climatotherapy in one). In all cases, the depigmentation was localized to the area of the pre-existing MF lesions. There was no clinically obvious phototoxicity. Biopsy study including S100 staining in all cases, and electron microscopy in one case, demonstrated the total absence of melanocytes, with no evidence of MF. It is suggested that the phototherapy may have activated a cell-mediated immunity leading to destruction of the melanocytes. We recommend that vitiligo-like leucoderma be added to the list of untoward effects of phototherapy in MF.

Adolescent↗

Mycosis fungoides and sezary syndrome: an update.

Mycosis fungoides (MF), and the associated leukemic variant Sezary Syndrome (SS), are the most common group of cutaneous T-cell lymphomas. MF/SS is a non-Hodgkin's lymphoma of mature, skin-homing, clonal, malignant T lymphocytes that initially presents in the skin as patches, plaques, tumors, or generalized erythema (erythroderma) and can involve the lymph nodes and peripheral blood. Much progress has been made in recent years in understanding the origin of the malignant T cell in MF/SS and the pathophysiology and immunology of the disease. This recent work has made a great impact on diagnosis, prognostication, and treatment. In this review, we survey the MF/SS published literature over the past year and highlight some of the important advances.

Combined Modality Therapy↗

Mycosis fungoides: clinical course and cellular abnormalities.

Mycosis fungoides is a lymphoma that appears to begin in skin. Although variable in its clinical course, it tends to affect middle-aged people, is present for a median of 4 yr before diagnosis, and generally results in death of the patient 4 to 5 yr after diagnosis. Cutaneous tumors and palpably enlarged lymph nodes are associated with shortened survival, and each of these frequently is accompanied by extracutaneous dissemination of the disease. The malignant cells are T lymphocytes with highly infolded nuclei, and they frequently express a helper cell function. Their chromosome complement has been found to be abnormal in karyotyping studies, and measurement of the amount of DNA by cytophotometry may permit diagnosis of the disease before the histological characteristics are detectable by light microscopy.

Adult↗

PUVA treatment of erythrodermic and plaque type mycosis fungoides.

Five patients with plaque type mycosis fungoides (MF) and five patients with erythrodermic MF responded favorably to oral psoralen photochemotherapy (PUVA). The mean total UVA irradiation dose was less for erythrodermic than for plaque type MF, but the mean number of treatments to achieve clearing was greater in the erythrodermic patients. Histologic examination at clearing revealed persistence of an inflammatory infiltrate in the lower dermis in most cases. Subsequent recurrent lesions in five patients revealed a more extensive dermal inflammatory infiltrate, although findings were not always diagnostic of MF due to a lack of epidermal involvement. Resumption of more intensive PUVA therapy again resulted in clinical clearing in all five patients. The follow-up period for six patients who received long-term PUVA maintenance ranged from 1 1/2 to 3 1/2 years. During PUVA therapy, five of ten patients developed epithelial malignancies or premalignancies, and one patient developed a malignant fibrous histiocytoma. Most of these patients had received prior treatment with electron beam and topical nitrogen mustard.

Adult↗

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↗

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

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

Adolescent↗

Follicular mycosis fungoides: a clinicohistopathologic study.

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

Female↗

Narrowband TL-01 phototherapy for patch-stage mycosis fungoides.

BACKGROUND: Although patch-stage mycosis fungoides (MF) has a generally good prognosis, and long-term survival rates with current therapies (UV-B, photochemotherapy, topical nitrogen mustards, electron-beam therapy) are similar, there is concern regarding their potential adverse effects. Narrowband or TL-01 UV-B phototherapy (311 nm), in use for more than 10 years, is more effective than broadband UV-B for the treatment of psoriasis, with an efficacy approaching that of psoralen UV-A. This open study assesses TL-01 as an alternative therapy for patch-stage MF. OBSERVATIONS: Eight white patients (4 men, 4 women; age range, 66-83 years) with histologically proven patch-stage MF received TL-01 phototherapy 3 times weekly using a standard protocol. Complete clearance of MF was achieved in 6 cases in a mean of 9 weeks or 26 treatments (range, 20-37 weeks) and 4 patients have had prolonged remissions. Mean duration of clinical improvement has been 20 months (range, 11-40 months). Partial response to TL-01 or poor histologic improvement was associated with rapid relapse. CONCLUSIONS: TL-01 is an effective, convenient therapy that may have less risk of long-term adverse effects than current alternatives. Although larger prospective studies are necessary, for some patients intermittent courses of TL-01 may offer effective long-term therapy.

Aged↗

Mycosis fungoides: review of epidemiological observations.

BACKGROUND: Mycosis fungoides (MF) is a chronic cutaneous T-cell lymphoma characterized by small cells with cerebriform nuclei that usually express a mature peripheral T-helper cell (CD4+) immunophenotype. Its evolution is typically quite slow, with years between the first manifestations and development of advanced stages of disease. OBJECTIVE: The purpose of the present paper is to contribute to the material about MF already present in the literature. The review articles that have appeared to date fundamentally address the morphological characteristics, diagnostic criteria and treatment of the disease; in contrast, the present study centers on the evolution of the incidence of MF and on the knowledge of the possible risk factors implicated in its development. METHODS: Review of published papers about MF epidemiology. RESULTS: The evidence suggests that the incidence is increasing, but this may be artifactual due to improved diagnostic techniques. The risk of MF is limited to gender and race, being higher in males and in blacks. Survival is highly stage dependent, but 90% of patients survive 15 years with only 10% of cutaneous involvement. Few risk factors have been identified, but several studies have found an association with industrial exposure, particularly to oils. CONCLUSION: MF is a rare disease and its risk factors have not been studied in any great detail. A European case-control study in progress will substantially increase the evidence available and progress towards identifying a prevention strategy.

Adult↗

Clinicopathologic and immunologic features associated with transformation of mycosis fungoides to large-cell lymphoma.

Mycosis fungoides (MF) can progress to a large-cell malignant lymphoma (LCL). This transformation is associated with a more aggressive biologic behavior and course. We reviewed cutaneous tumors of 36 MF patients and divided them into two groups, one showing histologic evidence of transformation into LCL, another characterized by infiltrates of small- to medium-sized cerebriform cells (nontransformed cases). Biopsies of patches or plaques from early MF stages were available from 34 patients. Twenty of the 36 cases (55.6%) showed transformation to a large-cell variant: nine tumor-stage (T) medium-sized and large-cell pleomorphic, five T immunoblastic, two T large-cell anaplastic, and four unclassified T LCL. Sixteen cases represented nontransformed tumor stage MF. In 23 cases, including both nontransformed (n = 6) and LCL (n = 17) groups, immunohistochemical investigations revealed aberrant patterns of antigen expression (partial loss of one or more T cell-associated antigens) and the presence of activation- and proliferation-associated antigens. Clusters of B-lymphocytes formed a distinctive component of the infiltrate in two nontransformed and nine LCL biopsies. Although survival rates after tumor onset did not significantly differ between the two groups (5-year survival rate 23% for nontransformed patients, 11.1% for LCL patients, p greater than 0.05), overall survival from first biopsy diagnostic of MF showed a statistically significant difference between patients with nontransformed tumor stage MF compared with LCL patients (10-year survival rate 46.6% and 11.2%, respectively, p less than 0.02). The recognition of transformation to LCL in MF should provide a better assessment of future therapeutic approaches.

Adult↗

Progression of pigmented purpura-like eruptions to mycosis fungoides: report of three cases.

The cases of three relatively young male patients with pigmented purpura-like eruptions evolving to mycosis fungoides are described. Initially, the eruptions, both clinically and histologically, very closely resembled pigmented purpuric dermatitis. After a follow-up period averaging 8.4 years, diagnostic histologic changes of mycosis fungoides were observed. Although uncommon, mycosis fungoides should be considered in the differential diagnosis of pigmented purpuric eruptions.

Adolescent↗

Human T-cell lymphotropic virus type 1 provirus and phylogenetic analysis in patients with mycosis fungoides and their family relatives.

BACKGROUND: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma of unknown aetiology. A pathogenic role of human T-cell lymphotropic virus type 1 (HTLV-1) has been suggested but remains controversial. To determine whether MF is linked to HTLV-1. METHODS: Blood samples were collected from 60 patients, 15 family relatives of patients with MF (MFRs), 20 healthy controls and 10 patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The presence of HTLV-1 antibodies in serum was tested by the Western blot rp21e-enhanced test. DNA was extracted from the blood with the Qiagen blood kit. We used 500 ng of DNA either in conventional HTLV-1-specific polymerase chain reaction (PCR) or in real-time PCR using primers sk43 and sk44 together with a tax-specific fluorescent probe. RESULTS: In Western blot, antibodies against three to four HTLV-1 antigens were detected in 52% of patients with MF. All of the patients with HAM/TSP were positive, while only 7% of the MFRs and none of the 20 healthy controls reacted with HTLV-1 antigens in Western blot. One of 60 patients with MF and one of 15 MFRs were positive in HTLV-1 PCR. These two PCR-positive samples which were quantified in real-time PCR showed that fewer than five in 10(6) cells were HTLV-1 infected. We succeeded in amplifying and sequencing the 5' end of the provirus from the blood of the PCR-positive MFR by seminested PCR. A positive result was also obtained in this test. Phylogenetic tree analyses revealed a high homology of this sequence with other HTLV-1 sequences from the Middle East. The above PCR-positive MFR was the brother of a PCR-negative patient with MF. CONCLUSIONS: These findings demonstrate that HTLV-1 is probably not the aetiological agent of MF. However, it may play a role in immunosuppression and in the spreading of the disease.

Adult↗

The effects of non-interval PUVA therapy on the plaque stage of mycosis fungoides.

The effectiveness of non-interval topical PUVA treatment was studied in four patients with mycosis fungoides at the plaque stage. Five regions of each patient were exposed to UVA immediately, 30 minutes, 60 minutes, 90 minutes, and 120 minutes, after topical application of 8-methoxypsoralen, respectively. The effects of these treatments were evaluated by clinical appearance and histological findings after the 20th treatment. All five regions were more improved clinically and histologically than the control region, which was not given PUVA therapy. There were no clear differences clinically among these five regions. Biopsy specimens from each region revealed the disappearance of epidermotropism and a marked decrease in atypical mononuclear cell infiltrations in the dermis. From these data, we concluded that there were no clear differences between these five treatments clinically or histologically and that non-interval PUVA therapy is useful for the early stages of mycosis fungoides. To our knowledge, this is the first report of non-interval PUVA therapy for mycosis fungoides.

Adult↗