Peripheral T cell lymphoma not otherwise specified induced by fingolimod treatment for multiple sclerosis

Abstract

Abstract Introduction Fingolimod is a sphingosine-1-phosphate (S1P) receptor modulator that prevents B and T lymphocyte egress from the lymph nodes, and reduces peripheral lymphocyte counts and entry of lymphocytes into the central nervous system. In 2010, the Food and Drug Administration (FDA) approved it for the treatment of relapsing-remitting multiple sclerosis (MS). It has been reported that Fingolimod treatment causes cutaneous side-effects such as opportunistic skin infections and cutaneous malignancies. We herein report the first case of peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) induced by Fingolimod. Case report A 63-year-old man was diagnosed with MS at 33 years of age. Due to repeated MS relapses, the administration of Fingolimod was started at 61 years of age. After 2 years, skin rash appeared in the abdominal and right femoral regions. Computed tomography showed swelling of the left cervical, mesenteric and bilateral inguinal lymph nodes and cutaneous tumors in the abdominal and right femoral regions. He was diagnosed with PTCL-NOS based on biopsies of the skin in right femoral region and right inguinal lymph nodes. Immunohistochemistry was positive for CD3, CD4, CD5, CD7, and negative for CD8, CD25 and CD30. He was treated with methylprednisolone (500 mg/day) for 3 days followed by prednisolone. His skin tumors and lymph node swelling did not progress. Discussion Among 10 reported cases of malignant lymphoma induced by fingolimod, 7 had a T-cell lineage and 8 cases occurred in the cutaneous region. Fingolimod should be stopped if lymphomatous lesions are found. However, the treatment of the MS patients with lymphoma is very troublesome. There are few alternatives to fingolimod for the treatment of relapsing MS. Additionally, the performance status of the patients with relapsing MS is not usually good enough to undergo standard therapies. Further analyses are required to reveal the lymphomagenesis in patients undergoing fingolimod treatment.