Extracorporeal photochemotherapy in mycosis fungoides

Objectives

Extracorporeal photo-chemotherapy (ECP, photopheresis) is an approved treatment modality for mycosis fungoides (MF). Our aim is to present our ECP data for MF.

Large cell transformation of mycosis fungoides: tetraploidization within skin tumor large cells

Little is known about the molecular or cytogenetic alterations of mycosis fungoides (MF) large cell transformation. We report our findings on chromosomal rearrangement, based on peripheral blood and skin examination before and after cutaneous MF large cell transformation, using both conventional and molecular cytogenetic techniques. Blood cells exhibited a similar hypodiploid karyotype before and after MF transformation. A near-tetraploid karyotype with complex structural rearrangements was established from a skin tumor after MF large cell transformation. Both recurrent chromosome abnormalities and an identical T-cell receptor gamma-chain rearrangement were shared by blood and skin cells, suggesting that MF large cell transformation derived from a common monoclonal ancestor detected at MF stage. A complex hypotetraploid karyotype was established only from the skin tumor, however. MF large cell transformation may be associated with chromosome duplication followed by chromosome losses and interchromosomal rearrangements. Accordingly, additional parallel blood and skin tumor cytogenetic studies are required to further identify the recurrent cytogenetic changes associated with the aggressiveness of the disease after large cell transformation.     

Unusual variants of mycosis fungoides

Conventional presentations of mycosis fungoides may be diagnostically challenging, particularly in light of the controversial boundaries defining the disease. Variant presentations of this cutaneous T-cell lymphoma add a further layer of complexity, requiring a sophisticated and informed perspective when evaluating lymphoid infiltrates in the skin. Herein we discuss well-defined (WHO-EORTC) variants pagetoid reticulosis, granulomatous slack skin and folliculotropic mycosis fungoides as well as less well-defined morphologic/architectural variants, and divergent immunohistochemical presentations of this typically indolent T-cell lymphoproliferative disease.     

miRNA in mycosis fungoides and skin inflammation

In this mini‐review, progress in our understanding of the link between miRNAs and cytokines in inflammatory skin diseases is highlighted with focus on miR‐155 in mycosis fungoides (MF). MF is the most common variant of cutaneous T‐cell lymphoma (CTCL) and is characterized by malignant T‐cell proliferation in a chronic inflammatory environment in affected skin. Recent data show that miR‐155 is expressed in situ by both malignant and non‐malignant T cells, induced via the STAT5 signal pathway and IL‐2Rbeta/gamma cytokines, and thus suggest the importance of miR‐155 in malignant proliferation, clinical diagnosis, and prognosis in CTCL.     

Role of activated T lymphocytes in mycosis fungoides

A patient with mycosis fungoides was treated effectively with the immunosuppressant cyclosporine A. Excretion of urinary neopterin, a marker of activation of the cellular immune system, fell immediately at the start of therapy. This result argues in support of a central role of activated T lymphocytes in this disease as has already been proposed by other authors.     

The immunological profile of mycosis fungoides.

The immune reactivity of 25 patients with mycosis fungoides was studied twice with a 6 month interval using a panel of T lymphocyte surface markers and functional tests. Patients with clinically inactive disease (stage I + II) had normal T lymphocyte biology. Patients with clinically active disease (stage II-IV) had T lymphopenia, alterations in T cell subpopulations (T gamma and T mu) and a reduced lymphocyte reactivity in vitro following mitogen (PHA, Con A, PWM) and antigen (PPD) stimulation. They also had a reduced secretion of immunoglobulin in vitro after PWM stimulation, apparently due to the alterations in their T lymphocyte subpopulations. The observed changes in the peripheral blood T lymphocyte population and the in vitro function of lymphocytes were not shared by lymphocytes from histologically affected lymph nodes. The natural killer cell activity in blood lymphocytes was found to be normal in all patients.     

Chromosome changes in mycosis fungoides in an XYY male

A 32-year-old white male was diagnosed as having mycosis fungoides in 1976; bone marrow biopsy and aspiration in August 1984 revealed infiltration with neoplastic cells. Cytogenetic analysis of the cells from the bone marrow specimen showed that 48 of 50 metaphases contained an extra Y chromosome (i.e., 47,XYY). The remaining two cells were hypotetraploid and hyperpentaploid, respectively, with a common marker derived from chromosome #2. The metaphases obtained by PHA stimulation of peripheral blood cells showed a 47,XYY pattern. An interleukin 2 (IL-2) dependent T-cell line was established from the patient's blood mononuclear cells; all metaphases of this line had an extra Y chromosome. Thus, this case is one of a mycosis fungoides developing in an XYY male.     

Cutaneous expression of Thy-1 in mycosis fungoides.

Dermal dendritic cells from eleven cases of mycosis fungoides (MF) (six patch and five plaque stage), two cases of pre-MF, and five specimens of normal human skin, were characterized immunohistochemically using a panel of antibodies including anti-human Thy-1, intercellular adhesion molecule-1 (ICAM-1; CD54), endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD1a, CD2, CD14, CD18, CD34, MAC387, KP-1, EBM-11, factor XIIIa, factor XIIIs, and S100. Thy-1 expression in normal skin was limited to the microvascular endothelium and perivascular dendritic cells. An extensive interstitial network of Thy-1+ dendritic cells was seen in the papillary dermis of all cases of MF, whereas no epidermal cells were Thy-1+. The mean +/- standard deviation of interstitial Thy-1+ cells per high power field in the dermis was: normal skin, 2.86 +/- 0.34; pre-MF, 15; patch stage MF, 13.4 +/- 7.08; plaque stage MF, 49.96 +/- 21.29. Thy-1+ dendritic cells morphologically resembled the factor XIIIa+ "dermal dendrocyte" (DD) and shared their VCAM-1+, ICAM-1+, CD1a, CD2-, CD14+, CD18+, EMB11+, factor XIIIa+, factor XI-IIs-, S100-, MAC387- and KP-1-immunophenotype in MF. Double labeling studies revealed up to 50% of Thy-1+DD were also factor XIIIa+ in MF. Immediately beneath these cells was a similar network of CD34+, Thy-1-, factor XIIIa- dendritic cells limited to the reticular dermis. Strong microvascular endothelial cell expression of Thy-1 and VCAM-1, and focal vascular ELAM-1 expression were also seen in MF. Distinct cellular compartmentalization (papillary dermis versus reticular dermis versus epidermis) of dendritic cells is demonstrated by the differential expression of Thy-1, factor XIIIa, and CD34 antigens. The extensive number and prominent dermal dendritic network in the papillary dermis juxtaposed between epidermal keratinocytes (KC) and dermal/epidermal T cells, suggests an important pathophysiologic role for this newly recognized and immunophenotypically distinctive cell population in MF.     

Evidence of multiple infectious agents in mycosis fungoides lesions

The etiology of mycosis fungoides (MF) remains to be determined. Several studies have proposed a viral etiology with controversial results.In this case-control study we investigated the presence of Epstein-Barr virus (EBV) and the debated presence of Human T-cell lymphotrophic virus I (HTLV-I) sequences, by polymerase chain reaction on nucleic acid extracts from formalin-fixed paraffin-embedded skin biopsies. Moreover, by a multivariate approach we analyzed in the same case-control study also the contribution of two previously examined pathogens: Hepatitis C virus (HCV) and Borrelia burgdorferi (Bb).Significant differences in the frequency of infectious agents in cases and controls were detected for Bb, HTLV-I and EBV. In MF patients we found the concurrent presence of two or three of these pathogen sequences in 21 out of 83 cases, but only in 1 out of 83 healthy controls.Our results suggest that the persistence of multiple infectious agents may cause a long-term antigenic stimulation contributing to the malignant transformation of T lymphocytes, especially when associated with HTLV-I like sequences. However, these infectious agents do not seem to have effects on disease progression.     

Efficacy of imiquimod in solitary plaques of mycosis fungoides

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma. The extent and type of skin involvement (T classification) and presence of lymph node or visceral involvement are important predictors in selecting the type of treatment. Skin directed treatment represents the most appropriate therapy for early stage disease. Current topical treatment including potent topical steroids and nitrogen mustard are associated with adverse effects such as cutaneous atrophy and contact dermatitis. In the present study, we tested the efficacy of imiquimod in mycosis fungoides plaques.     

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.     

Relative content of cytokines in different tissues in mycosis fungoides

The concentrations of tumor necrosis factor-alpha, interleukin-1beta, interleukin-2, interleukin-4, and the content of antibodies to H1 histone fraction in peripheral blood lymphocytes, epidermis, and serum were evaluated in patients with mycosis fungoides. It was found that as the disease progresses, cytokine synthesis is switched from Th1 to Th2 class and production of proinflammatory cytokines increases, which indirectly promotes the development of the autoimmune reaction.     

Interdigitating reticulum cells in the dermal infiltrate of mycosis fungoides

Summary In order to provide insight into the role of accessory cells in lymphoproliferative neoplasms, 7 cases of mycosis fungoides at various clinical stages - patches, plaques and nodules -were studied ultrastructurally and immunohistochemically. The aim was to establish whether interdigitating reticulum cells are a constant finding in the dermal infiltrate. Their possible relationships with mycosic cells were also investigated. This study revealed that interdigitating reticulum cells were present in all the skin lesions examined, were present in considerable number in the patches and plaques and became sparse in the nodules. Furthermore, in the lesions at various clinical stages these cells showed varying ultrastructural features, probably related to different developmental stages. The close contacts between interdigitating reticulum cells and mycosic cells, the expression of antigenic markers of activation by mycosic cells and the morphological and immunohistochemical signs of progressive de-differentiation of mycosic cells in the more advanced stages suggest that interdigitating reticulum cells are involved in stimulating proliferation and - possibly - neoplastic progression of mycosic cells. A role for the T-cell microenvironment created in the dermis by lymphoid infiltrate in inducing the differentiation of interdigitating reticulum cells from their precursors is proposed.     

Clonal chromosomal abnormalities in hemangiopericytoma

We report the cytogenetic findings in nine hemangiopericytomas studied after short-term culture. Clonal chromosome abnormalities were present in four cases. One case had a simple translocation (12;19)(q13;q13.3) as the sole abnormality whereas complex and multiple chromosomal abnormalities involving almost all chromosomes in the complement characterized tumors from the three other cases.