Cutaneous T cell lymphoma: update on treatment

Background Cutaneous T-cell lymphoma (CTCL) is a myeloproliferative disease with pronounced epidermotropism. The major subtypes of CTCL are mycosis fungoides and Sézary syndrome. Survival is dependent on the histological subtype and clinical stage. Early CTCL has a normal life expectancy, therefore early disease recognition and stage adapted treatment might help to ensure a good prognosis. Methods This is a review of recent advances in CTCL treatment based on literature review. Results Skin targeted therapies are useful for patch and limited plaque disease with phototherapy as the cornerstone of such treatments. More advanced disease will benefit from systemic mono- or combined treatments including drug therapy, extracorporeal photopheresis, and radiotherapy. In practice combined treatments may reduce adverse events and improve response rates. For selected younger patients, stem cell transplantation seems a third-line option. Conclusions The therapeutic spectrum for CTCL has been advanced during the last years, providing the opportunity of tailored treatment for patients.     

Primary hyperparathyroidism and cutaneous T-cell lymphoma: fortuitous association?

This is the third report of an association between T-cell cutaneous lymphoma (mycosis fungoides) and primary hyperparathyroidism (adenoma). Some studies support the concept that hyperparathyroidism may have promotional activity for the development of certain malignant tumors. A high risk for successive or concurrent neoplasms has been reported in patients with parathyroid adenomas. Primary hyperparathyroidism in a neoplastic context may be underreported. Patients with tumor-associated hypercalcemia should be evaluated for the possibility of primary hyperparathyroidism.     

Relapsing polychondritis and malignant lymphoma: is polychondritis paraneoplastic?

BACKGROUND: Relapsing polychondritis (RP) is associated with other rheumatic or autoimmune disease in about 30% of cases; however, an association with malignancy is rare with the exception of myelodysplastic syndrome (MDS). Observation Herein we report the first case, to our knowledge, of RP following splenic non-Hodgkin lymphoma (NHL), and we have reviewed all the previous well-documented reports that described the cases of RP associated with malignant lymphoma (ML). CONCLUSIONS: Our case and the review of reported cases showed that RP preceded ML in 2 cases, RP occurred after diagnosis and treatment of ML in 2 cases, and RP and ML occurred simultaneously in 1 case. The types of ML encountered were Hodgkin lymphoma, orbital mucosa associated lymphoid tissue type lymphoma, nodal NHL, and splenic NHL. From the frequent association of RP with MDS and, less frequently, with ML, we speculate that some RP cases may occur as a paraneoplastic condition of the concurrent hematological malignancies.     

Systemic Hodgkin's lymphoma in a patient with Sézary syndrome

We report a case of a 71-year-old male with Sézary syndrome diagnosed in 1996 who subsequently developed systemic Hodgkin's lymphoma. His only past treatment was bath psoralen plus ultraviolet A. He has since been treated with multiagent chemotherapy (ChlVPP/PABLOE) which induced a remission in his Hodgkin's disease. Eighteen months later he remains in remission from Hodgkin's disease but the Sézary syndrome remains active. He has also developed a squamous cell carcinoma on the upper lip. Sézary syndrome is a primary cutaneous T-cell lymphoma characterized by a malignant proliferation of CD4-positive cells in the skin and peripheral circulation. The CD4 count may be markedly elevated but this results from expansion of a neoplastic T-cell clone and there is a relative lymphopenia of normal T cells leading to a degree of immunoparesis. Immunosuppression is known to be associated with an increased rate of malignancies and this may account for the occurrence of Hodgkin's disease and squamous cell carcinoma in this patient with Sézary syndrome.     

Is there truly a risk of lymphoma from biologic therapies?

The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept. Biologics are generally safe and well tolerated. However, there has been concern over the risk of lymphoma with use of these agents because of their immunosuppressive properties. This review summarizes the current evidence in regards to lymphoma risk with biologic therapy obtained from case reports and case series, observational studies, clinical trials, and meta-analyses. The majority of data for T-cell inhibitors comes from case reports and relatively small, short-term clinical trials. In addition to published case reports and case series, TNF-α inhibitors have also been studied extensively in large cohort studies and meta-analyses of clinical trials derived primarily from the rheumatoid arthritis population. Current data are neither sufficient to completely rule out an increased risk of lymphoma associated with biologics, nor to firmly establish a causal relationship between biologics and lymphoma. Short- to intermediate-term treatment with biologics (e.g., up to 4 years) appears to be very safe with respect to lymphoma risk, especially with TNF-α inhibitors in which their potential risks appear to be well defined. Continued vigilance is warranted; however, in the appropriate patient, the risk-to-benefit profile of psoriasis treatment with respect to lymphoma risk appears highly favorable.     

Systemic sarcoidosis and cutaneous lymphoma: is the association fortuitous?

The association of systemic sarcoidosis and malignant lymphoma is known as the 'sarcoidosis-lymphoma syndrome'. Cutaneous involvement is rare in this syndrome. We report a 52-year-old woman who was diagnosed as having tumour-stage mycosis fungoides. Complete remission was achieved by combination therapy consisting of isotretinoin, interferon (IFN) alpha, electron beam irradiation, photochemotherapy and topical corticosteroids. Three years later, the patient developed systemic sarcoidosis characterized by yellowish papules on the abdominal wall and the eyelids that histologically revealed non-caseating granulomas, multiple fine-nodular interstitial pulmonary infiltrates on chest X-ray, hilar lymphadenopathy, decreased vital capacity and increased lymphocyte count in bronchoalveloar lavage fluid. As opposed to most of the reported cases, in our patient the manifestation of cutaneous lymphoma preceded the diagnosis of systemic sarcoidosis. We review the cases reported in the literature and discuss a possible causal and temporal relationship as well as the role of IFN alpha in the development of sarcoidosis.     

Psoriasis, lymphoma and etanercept: is there a correlation?

Psoriasis is a chronic inflammatory disease that can affect skin and joints. Their treatment varies depending on the severity and includes topical and systemic. Among the latter are the immunobiological that target the T cell We report a case that demonstrates the close relationship between psoriasis, lymphoma and biologic therapies.     

Primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma with a chronic and indolent course. Is this different from peripheral T cell lymphoma?

Cutaneous T cell lymphomas most commonly have a CD4+ memory T cell phenotype and exhibit a relatively indolent course, but may in rare cases present with a CD8+ cytotoxic phenotype with a strikingly more aggressive clinical behavior. Primary cutaneous aggressive epidermotropic CD8+ T cell lymphoma is an extremely rare entity with distinct clinicopatological features. The clinical features and prognosis of the recently-described CD8+ peripheral lymphoma are very different from cytotoxic CD8+ epidermotropic lymphoma, but the histological and phenotypic characteristics are very similar. We report a new case of CD8+ epidermotropic lymphoma with a chronic course and suggest the possibility of an overlap between these two types of lymphoma.     

Lymphomatoid papulosis: is a second lymphoma commoner among East Asians?

Background. Lymphomatoid papulosis (LyP) is a low‐grade cutaneous lymphoma, which lies within the spectrum of primary cutaneous CD30‐positive lymphoproliferative disorders. Around 10–20% of LyP cases are associated with a second lymphoma. Aim. To analyse a cohort of Asian patients with LyP, diagnosed from 1987 to 2007 at the National Skin Centre (NSC), Singapore, in terms of epidemiology, treatment and association with a second lymphoma. Methods. Patients were identified through the NSC clinical and histological databases. Results. During this period, 13 patients were diagnosed with LyP based on clinicopathological criteria. The mean age at diagnosis was 41 years, the male : female ratio was 2.3 : 1, and 92% of the patients were Chinese. Recurrent papulonecrotic lesions were present for a mean of 3 years before diagnosis. Treatment of LyP comprised monotherapy (n = 4) or combination therapy (n = 9) using corticosteroids, oral antibiotics, methotrexate and/or phototherapy. Mean duration of follow‐up was 6.4 years. Eight patients (61.5%) were diagnosed with a second lymphoma, either before (n = 2), concurrently with (n = 1) or after (n = 5) the diagnosis of LyP. Mycosis fungoides (MF) was the commonest lymphoma (78%, n = 7), followed by primary cutaneous anaplastic large‐cell lymphoma (12%, n = 2). There was one death (mortality rate 7.7%), which occurred in a patient who had developed stage IIA MF after LyP, which subsequently progressed to systemic T‐cell lymphoma. Conclusions. LyP is a chronic, relapsing disease with considerable morbidity, but an overall good prognosis. A strikingly large proportion of our Asian patients (61.5%) had a second lymphoma, compared with previous studies. This emphasizes the importance of regular lifetime surveillance for associated lymphomas in all patients with LyP.     

Fibromucinous T-cell lymphoma: a new clinicopathologic variant of mycosis fungoides?

We report a case of mycosis fungoides associated with extensive dermal fibrosis and mucin deposition. The patient developed indurated plaques with diffuse tightening of the skin reminiscent of the sclerosing disorder scleromyxedema, which was later associated with nodules and lymphadenopathy. Skin biopsies showed diffusely thickened collagen bundles in the dermis and mucin deposition with a dense infiltrate of atypical lymphocytes with an immunophenotypic pattern indicative of mycosis fungoides. In our opinion, these clinical and histopathologic features are unusual for mycosis fungoides and can be construed as a distinct fibromucinous variant. Alternatively, this may represent a fibrosing reaction pattern similar to that described with systemic T- and B-cell lymphomas or a variety of inflammatory disorders.     

Cutaneous lymphoplasmacytoid lymphoma (immunocytoma) with Waldenström's macroglobulinemia mimicking rosacea

A 50-year-old woman presented with a 2-year history of facial lesions that were resistant to rosacea therapy. Evaluation of histology, immunohistochemistry, gene rearrangement study, bone-marrow biopsy specimen, and systemic workup revealed the findings of lymphoplasmacytoid lymphoma (immunocytoma) in both the skin lesions and bone marrow, and IgM kappa paraprotein. Lesions cleared after chemotherapy.     

Febrile ulceronecrotic Mucha-Habermann disease with clonality: a cutaneous T-cell lymphoma entity?

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a severe variant of pityriasis lichenoides et varioliformis acuta (PLEVA). PLEVA patients only very rarely have systemic signs; the cutaneous lesions are usually asymptomatic, but may be pruritic and may heal with scarring. FUMHD often starts out as classic PLEVA, but goes on to develop widespread ulceronecrotic lesions and is associated with a high mortality rate. Whether Pityriasis lichenoides chronica (PLC) and PLEVA form a spectrum rather than single entities of clonal lymphoproliferative diseases has been discussed. Recently, it has been proposed that FUMHD, too, is a clonal lymphoproliferative disorder. Here, we report two cases of FUMHD with monoclonal T-cell population, as detected by Southern blot analysis. We propose that clonal FUMHD represents a cutaneous T-cell lymphoma entity.     

Anaplastic lymphoma kinase-positive primary cutaneous anaplastic large cell lymphoma--is it a new variant?

Anaplastic large cell cutaneous lymphomas are clinically and pathologically heterogeneous, CD30 + (Ki-1) lymphoproliferative disorders. The importance of anaplastic lymphoma kinase (ALK) positivity is well known in the prognosis of primary systemic anaplastic large cell cutaneous lymphomas; however, the same in primary cutaneous anaplastic large cell cutaneous lymphomas is not much clear. Herein we report a 65-year-old male with an 18-month history of minimally pruritic localized nodulo-plaque lesion over lower back. Histology revealed cutaneous large cell lymphoma and immunohistochemical staining showed positivity for CD30, CD3 and ALK. The role of ALK positivity in pcALCL is discussed in this article.     

Cutaneous T‐cell lymphoma and atopy: is there an association?

BACKGROUND: Case reports have suggested a relationship between atopic diatheses and Sézary syndrome, pre-Sézary syndrome or mycosis fungoides. However, Sézary and pre-Sézary syndromes are rare entities, and this association has never been analysed in greater detail for specific subtypes of cutaneous T-cell lymphoma (CTCL). OBJECTIVES: To evaluate the prevalence of atopy in subjects with Sézary syndrome, pre-Sézary syndrome or mycosis fungoides, and to compare the rates with the reported prevalence of atopy in the general population. METHODS: We retrospectively reviewed the records of 157 patients with the diagnosis of Sézary or pre-Sézary syndrome seen between 1965 and 2000, and 102 patients with the diagnosis of mycosis fungoides evaluated from 1994 to 2000 at Mayo Clinic. RESULTS: Of 157 subjects with Sézary or pre-Sézary syndrome and 102 subjects with mycosis fungoides, 18 and 12, respectively, were identified as having a history of atopic dermatitis, asthma or allergic rhinitis. The prevalence rates of atopy in Sézary or pre-Sézary syndrome and mycosis fungoides were 11.5% (95% confidence interval 6.9-17.5%) and 11.8% (6.2-19.7%), respectively. CONCLUSIONS: No significant difference exists in the prevalence of atopy in Sézary or pre-Sézary syndrome compared with that in mycosis fungoides (chi2-test, P = 1.00). Furthermore, the rates of atopy in Sézary or pre-Sézary syndrome and mycosis fungoides are not significantly different from the prevalence of atopy in the general population (17-40%). On the basis of these observations, no evidence currently implicates a causal association of CTCL with atopy.