Mycosis fungoides/Sézary syndrome: report of an unusual case

Introduction: Sézary syndrome (SS) is an uncommon form of cutaneous T cell lymphoma (CTCL) with a classical triad of lymphadenopathy, characteristic circulating lymphoma cells (Sézary cells) and erythrodermatous skin involvement with classical mycosis fungoides (MF)‐like histological picture. Case report: A 32‐year‐old woman presented with this classical triad; however, her skin involvement, histologically, was in the form of folliculotropic MF, rather than the usual classical form of MF. Conclusions: In the vast majority of cases, the cutaneous involvement in SS resembles conventional MF, histologically. One case of CD30‐positive CTCL with pilotropic MF has been reported. However, English literature does not describe any case of SS with folliculotropic MF with typical immunophenotype of SS thus far. We presume that this case represents the first report of SS with folliculotropic MF histologically, displaying the typical CD30‐negative immunophenotype.     

Expression pattern of chemokine receptors and chemokine release in inflammatory erythroderma and Sézary syndrome

BACKGROUND: Erythroderma can be caused by inflammatory dermatoses or cutaneous T-cell lymphoma. Even if chemokines and their receptors are involved in the skin-selective lymphocyte recruitment, their role in inflammatory erythroderma is yet unclear. OBJECTIVE: To evaluate the chemokine release (TARC, MDC, IP-10) and to define the expression pattern of Th1- (CCR5, CXCR3) and Th2-related (CCR4) chemokine receptors in inflammatory erythroderma and Sézary syndrome (SS). MATERIALS AND METHODS: Flow cytometry has been carried out on both circulating and skin-infiltrating T lymphocytes; serum chemokine levels have been evaluated using ELISA techniques. RESULTS: CCR4, CCR5 and CXCR3 were expressed on about 40% of peripheral blood lymphocytes and on the majority of skin-infiltrating lymphocytes in the inflammatory erythroderma patients, whereas the leukemic CD4+CD26- subpopulation in SS was characterized by a high CCR4 expression without a concurrent increase in CCR5 or CXCR3. TARC, MDC and IP-10 serum levels were significantly increased in both erythrodermic and SS patients. CONCLUSIONS: Our results confirm that SS is a Th2 disorder with a selective expression of CCR4, whereas inflammatory erythroderma shares an overexpression of both Th1- and Th2-related chemokine receptors, suggesting an activation of different pathways driving reactive lymphocytes to the skin.     

Mycosis fungoides and Sézary syndrome: focus on the current treatment scenario

Cutaneous T-cell lymphomas are a heterogeneous group of lymphoproliferative disorders, characterized by infiltration of the skin by mature malignant T cells. Mycosis fungoides is the most common form of cutaneous T-cell lymphoma, accounting for more than 60% of cases. Mycosis fungoides in the early-stage is generally an indolent disease, progressing slowly from some patches or plaques to more widespread skin involvement. However, 20% to 25% of patients progress to advanced stages, with the development of skin tumors, extracutaneous spread and poor prognosis. Treatment modalities can be divided into two groups: skin-directed therapies and systemic therapies. Therapies targeting the skin include topical agents, phototherapy and radiotherapy. Systemic therapies include biological response modifiers, immunotherapies and chemotherapeutic agents. For early-stage mycosis fungoides, skin-directed therapies are preferred, to control the disease, improve symptoms and quality of life. When refractory or in advanced-stage disease, systemic treatment is necessary. In this article, the authors present a compilation of current treatment options for mycosis fungoides and Sézary syndrome.     

Mycosis fungoides and Sézary syndrome: clinical,histopathological and immunohistochemical review and update

This paper reviews the diagnostic and classificatory concepts of mycosis fungoidesand Sézary syndrome in light of the latest normative publications. Itdescribes the great variability of the clinical expression of mycosis fungoides inits early stages as well as the histopathological and immunohistochemical aspectsthat help with diagnosis. The diagnostic criteria required for characterizingSézary syndrome and the staging system used for both mycosis fungoides andSézary syndrome are described.     

Systemic chemotherapy for the treatment of mycosis fungoides and Sézary syndrome

The treatment of mycosis fungoides and Sézary syndrome is unique. The treatments of choice are highly stage-and practitioner-dependent. For early stage patients, treatment with palliative topical therapies is often adequate to yield excellent, high-quality and durable responses. For the more advanced stages, systemic approaches are more appropriate, either alone or in combination, to palliate patients. There is still little convincing evidence from randomized trials that any single approach is favorable for improving survival. Many practitioners believe the disease can be controlled with the host immune system, but there again is little scientific support for this conclusion. It has been hypothesized that some of our therapies work through this mechanism, such as photopheresis and perhaps even psoralen and ultraviolet A. Unfortunately, even the use of biologic response modifiers, such as interferon and the interleukins, is not absolutely supportive of an active role for immune surveillance since these agents have been shown to have cytotoxic and differentiating effects. Because of the above, many practitioners have actively discouraged the use of chemotherapy because it may impair the host immune system; certainly, the purine analogs would fall into this category. However, there is little evidence supporting significant immune effects for other chemotherapeutics, and clearly, the responses seen would support their use in appropriate patients. As the present authors will detail in this paper, the advances in understanding cancer biology and mechanisms of resistance should, in the future, lead to optimal selection of agents that are predicted to be optimally active, limiting the toxicity and waste associated with ineffective drug usage.     

Prognosis of 100 Japanese patients with mycosis fungoides and Sézary syndrome

BackgroundSurvival analysis of a large series of patients with mycosis fungoides (MF) and Sézary syndrome (SS) has not been performed in Japan. Revision to the staging system for MF and SS was recently published.ObjectiveTo determine the long-term prognosis of Japanese patients with MF and SS, to identify factors predictive of survival, and to evaluate the prognostic significance of the revised staging system.MethodsWe performed a retrospective cohort study of 100 Japanese patients with MF and SS managed at the dermatology division of Niigata University Hospital between April 1, 1982 and March 31, 2006. We estimated survival according to the patient's clinical characteristics including the stages, and assessed their prognostic significance.ResultsSurvival rates of Japanese patients with MF and SS were similar to those shown in previous studies conducted in the United States and Europe. Prognosis of patients with skin tumor (stage IIB) and extracutaneous involvement (stage IV) was significantly worse than that of those with early-stage disease (stages IA–IIA), but erythrodermic MF patients without blood involvement (stage IIIA) showed excellent survival. Independent prognostic factors in multivariate analyses were higher age and the presence of skin tumor and extracutaneous disease.ConclusionPatient age and stage are the most important clinical prognostic factors in Japanese patients with MF and SS. The revised staging system is useful for predicting survival of the patients, but at least a subpopulation of stage IIIA patients may have a favorable prognosis.     

Follicular mucinosis: a critical reappraisal of clinicopathologic features and association with mycosis fungoides and Sézary syndrome

CONTEXT: Beginning in 1957, patients have been described with localized alopecia characterized histopathologically by mucin deposition within hair follicles (follicular mucinosis [FM]). At least 2 distinct diagnostic entities have been proposed: one occurring in children and young adults without association with other diseases ("idiopathic" FM), the other occurring in elderly patients and associated with mycosis fungoides or Sézary syndrome ("lymphoma-associated" FM). OBJECTIVE: To determine whether idiopathic and lymphoma-associated FM are distinct or related entities. DESIGN: Case series. SETTING: Department of Dermatology, University of Graz, Graz, Austria. PATIENTS: Forty-four patients with FM were divided into 2 groups. Group 1 comprised 16 patients (mean age, 37.5 years) with no associated mycosis fungoides or Sézary syndrome; group 2 was made up of the other 28 (mean age, 52.2 years), who had clinicopathologic evidence of cutaneous T-cell lymphoma. RESULTS: Mean age was lower in patients with idiopathic FM, but a considerable overlapping among the 2 groups was present. Location on the head and neck region was common in both groups, but most patients with lymphoma-associated FM had lesions also on other body sites. In fact, solitary lesions at presentation were common in patients with idiopathic FM (11 [68.8%] of 16 patients), but uncommon in those with lymphoma-associated FM (2 [7.1%] of 28 patients). Histopathologic findings did not allow clear-cut differentiation of the 2 groups. Finally, a monoclonal rearrangement of the T-cell receptor gamma gene was demonstrated by polymerase chain reaction analysis in about 50% of tested cases from each group. CONCLUSIONS: Criteria previously reported to differentiate idiopathic from lymphoma-associated FM proved ineffective. In analogy to localized pagetoid reticulosis (Woringer-Kolopp disease), small-plaque parapsoriasis, and so-called solitary mycosis fungoides, idiopathic FM may represent a form of localized cutaneous T-cell lymphoma.     

Bexarotene treatment of late-stage mycosis fungoides and Sézary syndrome: development of extracutaneous lymphoma in 6 patients

Bexarotene is a retinoid drug that is approved for the treatment of cutaneous T-cell lymphoma. We report 6 cases in which the initiation of bexarotene therapy for cutaneous T-cell lymphoma was temporally associated with the progression of internal disease despite improvement in cutaneous signs and symptoms. It is possible that bexarotene contributed to this progression. Although bexarotene therapy may alleviate symptoms and signs of cutaneous T-cell lymphoma, careful surveillance of lymph nodes and solid organs during treatment is advised.     

Prevalence and treatment of Staphylococcus aureus colonization in patients with mycosis fungoides and Sézary syndrome

Background  Mycosis fungoides (MF) and Sézary syndrome (SS), variants of cutaneous T-cell lymphoma, may arise from antigen-driven clonal expansion and accumulation of helper-memory T cells. Superantigens from Staphylococcus aureus can stimulate T cells.
Objectives  (i) To determine the prevalence of S. aureus carriage in nares and skin in patients with MF/SS compared with historical rates in other conditions. (ii) To determine whether eradication of S. aureus carriage is associated with clinical improvement.
Methods  Skin and nares cultures were performed prospectively. Patients with positive nares and skin cultures were treated with oral antibiotics and intranasal mupirocin 2% and samples were taken for reculturing at 3 days, 4 weeks and 8 weeks. An exact binomial test was used to compare the carriage rates among different groups.
Results  Among 106 patients with MF/SS, 67 (63%) had skin colonization and 57 (54%) had nasal colonization. Staphylococcus aureus was isolated from 44 patients, 33 (31%) each from skin and nares. Colonization was highest in erythrodermic SS (48%), similar to atopic dermatitis (64%), and lowest in MF without erythroderma (26%), psoriasis (21%), and the general population (10%). Oral and topical antibiotics eradicated S. aureus colonization in nares in 28 of 33 (85%) patients and in MF skin lesions in 30 of 33 (91%) patients at 4–8 weeks, with rapid clinical improvement seen in 58% of S. aureus -colonized patients.
Conclusions  Staphylococcal carriage in nares and skin lesions of patients with MF is similar to that in atopic dermatitis. Eradication of staphylococci from the skin is possible with treatment and was associated with clinical improvement.     

Sustained remission of Sézary syndrome

Sézary syndrome, an aggressive form of cutaneous T-cell lymphoma, is a devastating, highly symptomatic form of non-Hodgkin lymphoma. Malignant clones of mature helper CD4 T cells containing large, convoluted nuclei known as Sézary cells circulate in the blood and infiltrate the skin. Clinical features include exfoliative erythroderma, generalized lymphadenopathy, alopecia, onychodystrophy, palmoplantar hyperkeratosis, and ectropion. Patients often have severe pruritus, burning sensations, pain, bleeding from excoriations, and disfigurement. Extracorporeal photopheresis, an immunomodulatory therapy, has become a primary therapy for these patients. This pheresis-based therapy uses psoralen and ultraviolet A radiation-mediated photochemotherapy to induce immune responses. The effects of extracorporeal photopheresis vary considerably. We report sustained remission (2 years) in a patient with Sézary syndrome. Previously he had received extracorporeal photopheresis and interferon alfa-2b injections. He is the only one of 55 patients with Sézary syndrome treated at Mayo Clinic (Rochester, Minnesota, USA) to achieve sustained remission on extracorporeal photopheresis alone.     

Increased serum immunoglobulin levels are common in mycosis fungoides and Sézary syndrome

BACKGROUND: Patients with cutaneous T-cell lymphoma (CTCL; mycosis fungoides [MF] and Sézary syndrome [SS]) acquire immunodeficiency and opportunistic infections. OBJECTIVE: We attempted to determine whether abnormalities of humoral immunoglobulin levels are present. METHODS: A retrospective analysis of serum immunoglobulin levels in patients with CTCL at baseline evaluation at a cancer center was compared to levels in patients with leukemias and levels in healthy control subjects. RESULTS: A total of 254 of 650 patients with CTCL evaluated between 1987 and 2001 had baseline quantitative immunoglobulin levels. Mean IgG, IgA, and IgM levels were similar among all MF/SS patients versus controls. The percentages of MF/SS patients with elevated levels of each immunoglobulin class were higher than percentages in healthy controls, and elevated IgA levels occurred among late versus early patients (P =.043). CONCLUSION: High immunoglobulin levels are more frequent in patients with MF and SS than in healthy controls, patients with chronic lymphocytic leukemia, and patients with hairy cell leukemia. High IgA levels are more frequent in late stage MF/SS.     

Toll-like receptors 2, 4 and 9 expression in cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome)

The aim of this work was to study Toll-like receptors (TLRs) 2, 4 and 9 expression patterns in parapsoriasis and in cutaneous T-cell lymphoma (CTCL): Mycosis fungoides (MF) and Sézary syndrome (SS) at different stages of the illness. The expression of TLRs was examined by immunohistochemistry on paraffin-embedded biopsies. Normal skin, atopic dermatitis and psoriasis, were used as controls. In cutaneous lesions of inflammatory diseases (atopic dermatitis, psoriasis) the expression of TLR2, TLR4 and TLR9 was low compared to normal skin. In parapsoriasis the expression of the three TLRs was similar to control. By contrast, in MF skin we observed a strong intensity of labelling with the three TLRs in the epidermis. Concerning SS, the expression of TLR2, TLR4 and TLR9 was intermediate between inflammatory lesions and MF. Thus, the development of skin lesions in MF appears associated with an increase of TLR2, TLR4 and TLR9 expression by keratinocytes in cutaneous lesions, which could play a role in the chronic activation of T lymphocytes in the skin.