Diffuse B giant cell lymphoma associated with fingolimod treatment in Multiple Sclerosis: a case report

Young Investigator
Adriana Casallas Vanegas
Neurologia universidad de la sabana
60
Chia, Colombia

Abstract

Introduction:
Fingolimod, a sphingosine 1-phosphate receptor modulator, is one of the modifying disease therapies approved in the treatment of multiple sclerosis (MS). The immune-modulation effect caused by these agents is associated with an increased risk of secondary malignancies. Here, we present a case of giant B cell lymphoma related to treatment with fingolimod.

Case presentation:
A 65-year-old woman with history of thyroid cancer surgically resected on 2012 and secondary hypothyroidism. The patient had been diagnosed with MS four years prior to first evaluation, when she debuted with sensitive symptoms on the left side of her body. She was initially treated with fingolimod from 2018 to date. Her symptoms started one month ago, with abdominal pain, nausea and emesis. Physical examination demonstrated multiple cervical, axillary and inguinal adenopathies. Initial workup revealed thrombocytopenia and anemia (73,500 platelets, Hb 11.3) in addition to LDH elevation. HIV serology turned out negative. Neck ultrasound was performed with evidence of cervical ganglion conglomerate, highly suspicious for a lymphoproliferative disorder. Cervical ganglion excisional biopsy was performed, reporting inflammatory lymphocytic infiltration, compatible with large cell diffuse B lymphoma. Immunohistochemical studies were performed on block B3 which shown reactivity in the neoplastic cell population for CD20, BcL-2, MUM-1 and focally for BcL-6. Ki67 shows a proliferative activity of 70%. Neoplastic cells do not express Cyclin-D1, CD10,CMy-C, CD138 or CD30, T lymphocyte CD3 was reactive.

Conclusion:
Animal models have shown that fingolimod predisposes to lymphoproliferative disorders by reducing immune surveillance of neoplastic lymphoid clones in the periphery, through modulation of the peripheral T-cell microenvironment. The drug can also, impair antigen presentation by inhibiting Langerhans cell migration to lymph nodes. Several questions remain unanswered regarding the risk of hematological malignancies secondary to immunosupresive/immunomodulatory drugs, but it appears that the suppressed immune surveillance of neoplastic cells is a major factor in its development.

Diffuse B giant cell lymphoma associated with fingolimod treatment in Multiple Sclerosis: a case report

Marco Aurelio Reyes-Guerrero MD, Enrique Gómez-Figueroa MD, Tatiana Rodríguez-Gomez MD, Angela Viviana Navas-Granados. MD, Luisa Fernanda Echavarria-Plata MD, Christian García-Estrada MD, Adriana Casallas-Vanegas MD