Cutaneous marginal zone B-cell lymphoma in the setting of fluoxetine therapy: a hypothesis regarding pathogenesis based on in vitro suppression of T-cell-proliferative response.
BACKGROUND
Drugs may be an important cause of atypical lymphocytic infiltration. Oftentimes, these infiltrates are in the context of pseudolymphomata. We report a patient who developed lymphocytoma cutis temporally associated with initiation of fluoxetine therapy that later went on to develop cutaneous marginal zone B-cell lymphoma. The response of peripheral blood lymphocytes to fluoxetine and other drugs was examined in an attempt to ascertain the potential role for drugs in the propagation of these infiltrates.


METHODS
Routine light microscopic analysis and phenotypic studies were performed on tissue obtained from a skin biopsy. Lymphocyte mitogenic studies were carried out using increasing concentrations of fluoxetine, bupropion, and two anticonvulsants.


RESULTS
An initial biopsy was consistent with lymphocytoma cutis. The patient stopped fluoxetine associated with lesional regression. The lesions recurred despite being off fluoxetine; a repeat biopsy was compatible with marginal zone lymphoma. Lymphocyte proliferation assays revealed a suppressive effect on T-lymphocyte proliferation at physiologic concentrations. Other tested drugs did not have a similar suppressive effect.


CONCLUSIONS
Fluoxetine may be associated with pseudolymphomata and marginal zone lymphoma. The inhibitory effects on T-lymphocyte function and more specifically T-suppressor function may lead to excessive antigen-driven B-cell proliferation.
Breza
Thomas S
TS
College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Zheng
Pan
P
Porcu
Pierluigi
P
Magro
Cynthia M
CM
D000927:Anticonvulsants / Q000494:pharmacology; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects* / Q000494:pharmacology; D016642:Bupropion / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005473:Fluoxetine / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D017403:In Situ Hybridization; D008213:Lymphocyte Activation / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019310:Pseudolymphoma / Q000139:chemically induced / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology
D000927:Anticonvulsants; D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D016642:Bupropion