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.     

Mycosis fungoides. The importance of pulmonary cytology in the diagnosis of a case with systemic involvement

A patient with cutaneous mycosis fungoides developed pulmonary lesions while under radiation therapy. Bronchial cytologic specimens demonstrated malignant lymphocytes, which open lung biopsy confirmed to be mycosis cells. We believe this is the first report to document pulmonary involvement of mycosis fungoides by the use of bronchial cytology.     

Further evidence for the T-cell nature of the atypical mononuclear cells in mycosis fungoides

It is well known that in some cases of mycosis fungoides the lymph nodes contain atypical mononuclear cells with a characteristic electron-microscopic morphology, first described in skin lesions of mycosis fungoides. Because it has been shown, that these cells have T-cell membrane characteristics the question can be raised, if these cells have other properties of T cells. One of these is a preferential localization in the T-cell dependent regions (paracortical areas) of the lymph node. In this paper we present a study of dermatopathic lymph nodes from four patients with mycosis fungoides (plaque stage). The lymph nodes of these patients contained atypical mono nuclear cells in the paracortical areas only, and not in the follicles or medulla. In one of the patients we could demonstrate the migration of these cells through the epitheloid venules into the paracortical area.     

Mycosis fungoides with pulmonary involvement. Cytopathologic findings

In order to define the cytologic features of pulmonary involvement by mycosis fungoides, 15 respiratory cytology specimens from four patients with biopsy-proven pulmonary mycosis fungoides were reviewed. The presence in sputum smears of occasional small or large cerebriform mononucleated cells against a background of numerous atypical lymphocytic cells permitted an antemortem cytologic diagnosis of probable or definite dissemination of mycosis fungoides with pulmonary involvement. Similar cells were seen in aspiration smears. The lymphocytic infiltrates were similar to those in corresponding skin biopsies in each case. The distinctive cytologic findings in these cases may therefore help to determine the underlying etiology of pulmonary lesions and may contribute to the antemortem diagnosis of visceral dissemination of mycosis fungoides.     

Mycosis fungoides cells in sputum. A case report

Atypical lymphoid cells were identified in the sputum of a patient known to have mycosis fungoides. Although the lungs are the second most common organ to be affected when there is extracutaneous dissemination of mycosis fungoides, this is the first report of pulmonary involvement diagnosed by the cytologic identification of "mycosis cells" in the sputum.     

Clinical results of the total skin electron irradiation of the mycosis fungoides in adults. Conventional fractionation and low dose schemes

Background

Mycosis fungoides (MF) is a rare skin condition, effectively treated by irradiation. Since 1951, different methods of total skin irradiation have been developed. Although dose–response effect has been demonstrated in many publications, controversies about low dose treatment still exist.

Aim

The analysis of results of the total skin electron irradiation (TSEI), especially low dose TSEI in comparison with standard dose treatment is the subject of this review. Also, acute and late side effects of radiotherapy in MF are discussed.

Materials and methods

Medline search and analysis of studies published between 1995 and 2012, containing key words: mycosis fungoides, standard dose TSEI, low dose TSEI, total skin electron beam therapy (TSEBT).

Results

Detailed analysis of relevant studies demonstrated that standard dose radiotherapy 30–36 Gy is the most effective treatment used in clinical practice. Objective response rate (ORR) is high, especially for less advanced stages of disease. Complete response rate (CR), although slightly lower, is still relatively high.For more advanced MF, TSEI serves as a very good method of palliative treatment and relief of symptoms, like pruritus, pain or desquamation.There is no consensus regarding low dose TSEI; the method is widely accepted as a palliative treatment or in case of reirradiation.

Conclusions

Standard dose TSEI is an effective method of MF treatment for radical and palliative treatment, producing high rate of ORR and reasonably long time to progression (TTP). Acute and late side effect of treatment are mostly mild and easy to manage. Low dose TSEI is still in the phase of clinical studies.     

Subpopulations of human T lymphocytes. IV. Quantitation and distribution in patients with mycosis fungoides and Sézary syndrome.

T cell subpopulations (Tμ and Tγ cells) were examined in the peripheral blood from fourteen patients with mycosis fungoides and Sézary syndrome. One patient with Sézary syndrome having low lymphocyte count had higher proportions of Tγ cells when compared to controls while the other with high lymphocyte count (75% Sézary cells) lacked Tγ cells and had normal proportions of Tμ cells. T cells from a third patient with Sézary syndrome having high lymphocyte count (95% Sézary cells) lacked almost completely both Tμ and Tγ cells. Three of eleven patients with mycosis fungoides had a high proportion of Tγ cells and one had a high proportion of Tμ cells. Study of T cells in the peripheral blood, lymph nodes, and bone marrow from two patients with mycosis fungoides demonstrated that the quantitative abnormality of tμ and Tγ cells is shared by the peripheral blood and bone marrow and not by the lymph nodes. Heterogeneity of T cells subsets in mycosis fungoides appears to be in non-malignant T cells. However, in Sézary syndrome malignant Sézary T cells demonstrate heterogeneity with regard to receptors for IgM (Tμ) and IgG (Tγ).     

Locomotion of T cells from patients with cutaneous T-cell lymphoma (Sezary syndrome and mycosis fungoides)

Peripheral blood T cells from eight patients with cutaneous lymphoma (four each with Sezary syndrome or mycosis fungoides) and T cells from skin tumor of one patient each with Sezary syndrome or mycosis fungoides were studied for their locomotor responses to the chemoattractant, casein. Nonmalignant peripheral blood T cells from each patient with mycosis fungoides moved normally. Malignant T cells from skin tumor of patients with mycosis fungoides or Sezary syndrome did not move in the presence of casein. Peripheral blood malignant T cells (Sezary cells) from three of four patients with Sezary syndrome either moved very poorly or did not move at all. The circulating Sezary cells from the fourth patient with Sezary syndrome responded moderately to the chemoattractant, casein. Two of three patients with Sezary syndrome with poor or no locomotor response of T cells underwent therapeutic leukopheresis without any demonstrable effect on their skin infiltration. The patient whose malignant T cells demonstrated moderate locomotor response to casein had a leukemic blast crisis and at that time her skin became free of malignant cells. A repeat study of her circulating T cells at that time demonstrated almost normal locomotor response to casein. These results demonstrate that the locomotor properties of malignant T cells in patients with Sezary syndrome may have prognostic significance.     

Lymphoblastomas in childhood; cutaneous manifestations

The lymphoblastomas occurring in childhood are divided for purposes of discussion into lymphocytoma cutis, mycosis fungoides, lymphosarcoma, Hodgkin's disease, and leukemia. The cutaneous lesions may be either specific (as a result of the infiltration of the skin with specific cells of the conditions) or toxic (non-specific). With the possible exception of mycosis fungoides, the cutaneous manifestations are not diagnostic. The final diagnosis depends upon microscopic examination of the specific tissue involved and the coordination of the clinical and microscopic findings.     

LYMPHOBLASTOMAS IN CHILDHOOD—Cutaneous Manifestations

The lymphoblastomas occurring in childhood are divided for purposes of discussion into lymphocytoma cutis, mycosis fungoides, lymphosarcoma, Hodgkin''s disease, and leukemia. The cutaneous lesions may be either specific (as a result of the infiltration of the skin with specific cells of the conditions) or toxic (non-specific). With the possible exception of mycosis fungoides, the cutaneous manifestations are not diagnostic. The final diagnosis depends upon microscopic examination of the specific tissue involved and the coordination of the clinical and microscopic findings.     

Molecular cytogenetics in the study of cutaneous T-cell lymphomas (CTCL)

The etiology of primary cutaneous T-cell lymphomas (CTCL) has been poorly understood. CTCL patients show a large variety of non-clonal and clonal chromosome aberrations, but no specific aberration has been found until recently. This review describes cytogenetic and molecular cytogenetic findings and their relevance to diagnostics and etiology in two of the most common forms of CTCL, mycosis fungoides (MF) and the leukemic CTCL, Sézary syndrome (SS).     

The results of clinical trials and the prospects of using the Soviet preparation of human recombinant interferon alpha-2 (reaferon) in medical practice

The results of the clinical trials of human recombinant interferon alpha-2 (reaferon) make it possible to come to the conclusion that the preparation is well-tolerated and produces a pronounced therapeutic effect in a number of viral and oncological diseases. The Pharmacological Committee of the USSR has recommended reaferon for use in acute hepatitis B, hairy cell leukemia, renal cancer at stage IV, disseminated sclerosis, ocular herpes. The use of reaferon has been found to be promising in the treatment of papillomatosis of the larynx, Kaposi's sarcoma, mycosis fungoides, chronic myeloleukemia.     

Literature review of clinical results of total skin electron irradiation (TSEBT) of mycosis fungoides in adults

Background

Mycosis fungoides (MF) is an extranodal, indolent non-Hodgkin lymphoma of T cell origin. Even with the establishment of MF staging, the initial treatment strategy often remains unclear.

Aim

The aim of this study was to review the clinical results of total skin electron beam therapy (TSEBT) for MF in adults published in English language scientific journals searched in Pubmed/Medline database until December 2012.

Results

MF is very sensitive to radiation therapy (RT) delivered either by photons or by electrons. In limited patches and/or plaques local electron beam irradiation results in good outcomes besides the fact of not being superior to other modalities. For extensive patches and/or plaques data suggest that TSEBT shows superior response rates. The cutaneous disease presentation is favorably managed with radiotherapy due to its ability to treat the full thickness of deeply infiltrated skin. For generalized erythroderma presentation, TSEBT seems to be an appropriate initial therapy. For advanced disease, palliation, or recurrence after the first radiotherapy treatment course, TSEBT may still be beneficial, with acceptable toxicity. Recommended dose is 30–36 Gy delivered in 6–10 weeks.

Conclusion

TSEBT can be used to treat any stage of MF. It also presents good tumor response with symptoms of relief and a palliative effect on MF, either after previous irradiation or failure of other treatment strategies.     

The supramolecular organization of the keratinocyte cytoskeleton and extracellular matrix in human skin revealed by freezing-deep etching with rotary platinum-carbon shadow-casting

The supramolecular organization of the keratinocyte cytoskeleton, the basal lamina and of the dermal extracellular matrix in the whole human skin revealed by freeze-deep etching with Pt/C rotary shadowing is presented. The routine equipment for this method and sample preparation are described. The resolution of the method is sufficient to visualize individual cytoskeleton elements and extracellular matrix. The presented cytoskeleton organization is very similar to the meshwork of strands or "microtrabeculae" seen in the cytoplasm of the whole cells by high voltage electron microscopy. Besides, the ultrathin section pattern of epidermis in human skin from patients with mycosis fungoides is described.     

Bleomycin in the Reticuloses

Bleomycin alone was used in the treatment of 54 patients with Hodgkin''s disease in its later stages, 17 with generalized lymphosarcoma, 22 with reticulum cell sarcoma, and 7 with mycosis fungoides. The patients had had radiotherapy and full courses of conventional chemotherapy. Bleomycin was given in doses of 30 mg weekly to an average total dosage of 200 mg, though up to 800 mg could be given because of its marrow-sparing properties. Sixteen (29%) of the patients with Hodgkin''s disease remitted, most of them achieving only a partial remission, and similar results were obtained in the other three reticuloses. Bleomycin would seem to have some beneficial action in the late stages of Hodgkin''s disease, though it is less effective than some drug regimens recently introduced. Nevertheless it may be useful when there is diminished bone marrow reserve. It would be a suitable drug to use in combination therapy of these four reticuloses.     

Expression of HECA-452 antigen correlates with disease relapse in mycosis fungoides

OBJECTIVE: To determine the expression of HECA-452 epitope in mycosis fungoides (MF), assess whether its expression increases in relapsed MF compared with nonrelapsed MF and determine the potential prognostic relevance of HECA-452 expression. STUDY DESIGN: HECA-452 expression was evaluated by immunohistochemistry in a consecutive series of 20 MF. In all patients we evaluated the disease-free survival rate according to HECA-452 expression in a univariate analysis. RESULTS: We found a low expression in 5 MF (25%), a moderate expression in 8 MF (40%) and a high expression in 7 MF (35%) in the intraepidermal area. All patients were disease-free after appropriate therapy. Four of 20 patients (20%) relapsed within 2 years. HECA-452 expression significantly correlated with disease relapse in these patients. In fact, among the 7 patients whose lesions had a high expression, 4 had a disease recurrence (57%), whereas 0 of 13 (0%) with a low or moderate expression relapsed (p < 0.05). CONCLUSION: HECA-452 expression correlates with disease relapse in MF. Correlation with disease progression suggests that HECA-452 could be of prognostic relevance in the early stage of mycosis fungoides.     

Evaluation of T-cell receptor gene rearrangements in patients with recurrent patch/plaque (T2) CTCL (mycosis fungoides)

Cutaneous T-cell lymphoma is typically a clonal neoplasm of epidermotropic CD4+ T-lymphocytes that includes the entity mycosis fungoides (MF). After identification of patients with recurrent MF treated with total skin electron beam therapy (TSEBT) at the Yale University School of Medicine, this study attempted to compare T-cell receptor (TCR) gamma gene rearrangements via polymerase chain reaction (PCR) in both original and recurrent skin biopsies from these patients. Between 1974 and 1996, a total of 95 T2 MF patients were treated with TSEB, and four of these were identified for the study. Slides and tissue samples of both primary and recurrent skin biopsies for each patient were confirmed as being consistent with ME DNA for PCR was isolated from paraffin-embedded tissue samples. Using consensus primers that hybridize with conserved regions of the TCR gene, these regions of the genome were amplified. The PCR products were then analyzed by acrylamide gel electrophoresis. Of the primary and recurrent samples from four patients with a median disease-free interval (DFI) of 1222 days, only two showed evidence of a dominant TCR clone. A number of factors, including lack of sequence homology between the primers and the gene segments, the existence of multiple neoplastic cell lines, DNA degradation in the archival samples, and the presence of reactive as well as malignant lymphocytes, may have prevented the detection of dominant TCR rearranged clones in the samples. Despite the results of this study, TCR analysis via PCR and gel electrophoresis continues to be of utility in the evaluation of patients with MF when used in conjunction with other diagnostic modalities and in cases with nonspecific clinical, histopathological, and immunophenotyping findings.     

Lck is involved in interleukin-2 induced proliferation but not cell survival in human T cells through a MAP kinase-independent pathway

The role of Lck in IL-2-induced proliferation and cell survival is still controversial. Here, we show that the Src family kinase inhibitor, PP1, reduced the IL-2-induced proliferation of human T cells significantly without inhibiting the anti-apoptotic effect of IL-2. As Lck is the only Src family kinase activated upon IL-2 stimulation in T cells, this indicates that Lck is involved in IL-2-induced proliferation but not survival. IL-2-induced MAP kinase activation was only slightly inhibited by PP1, suggesting that Lck is not essential for IL-2-induced MAP kinase activation in human T cells. We found that an IL-2-sensitive, human mycosis fungoides-derived tumor T cell line is Lck negative, and that the IL-2-induced MAP kinase activation is comparable to non-cancerous T cells, although a little delayed in kinetics. An Lck expressing clone was established by transfecting Lck into mycosis fungoides tumor T cells, but Lck had no influence on the delayed kinetics of MAP kinase activation, indicating that Lck is not essential for MAP kinase activation in mycosis fungoides tumor T cells or in non-cancerous T cells. Taken together, this indicates that Lck is involved in IL-2-induced proliferation, but not cell survival, through a pathway not involving MAP kinase.