Primary Cutaneous Follicular Helper T-cell Lymphoma A New Subtype of Cutaneous T-cell Lymphoma Reported in a Series of 5 Cases

Background: Peripheral nodal follicular T-cell lymphomas expressing follicular helper T-cell (T-FH) markers have recently been identified. Such lymphomas are characterized by a nodal neoplastic T-cell proliferation accompanied by numerous reactive B cells and demonstrate some overlap with nodal angioimmunoblastic T-cell lymphoma (AITL). We identified 5 cases of cutaneous T-cell lymphoma with a peculiar pathologic aspect and expression of T-FH markers. Observations: The mean age of the patients was 61 years (range, 33-78 years). Four patients had multiple papules, plaques, and nodules predominating on the trunk and the head. One had a nodular plaque on the face. Lesional T-cell clonality was found in all 5 patients, and blood T-cell clonality in 4 of the 5. Nodal involvement was never found. Patients had no systemic symptoms and no biological signs of AITL. In 3 cases, findings from skin biopsy specimens were initially misdiagnosed as primary cutaneous follicle B-cell lymphoma due to major B-cell infiltrate and CD10 positivity. Rituximab-containing therapies were ineffective in these cases, and biopsy specimens after treatment with rituximab showed medium- to large-sized atypical T-cell skin infiltrate expressing T-FH markers (CD10, Bcl-6, PD-1, CXCL13, and ICOS). The final diagnosis proposed for all patients was cutaneous T-FH lymphoma. The patient with localized disease was successfully treated with radiotherapy. Patients with diffuse disease showed marked resistance to treatments, with only 1 case of complete remission after allogeneic hematopoietic stem cell transplantation followed by bortezomib and donor-lymphocyte infusion. Bexarotene, methotrexate, thalidomide, interferon alfa, gemcitabine, liposomal doxorubicin, or multiagent chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) were either ineffective or induced transitory partial remission. Conclusions: We describe an original clinicopathologic series of primary cutaneous lymphomas with T-FH phenotype, suggesting the existence of a new entity among cutaneous T-cell lymphomas. Relations of these lymphomas with the provisional entity of primary cutaneous small to medium CD4(+) pleomorphic T-cell lymphoma need to be further addressed.