Lymphomatoid Granulomatosis Treated Successfully with Rituximab in a Renal Transplant Patient

Abstract

Lymphomatoid granulomatosis (LYG) in renal transplant recipients is rare multisystemic angiocentric lymphoproliferative disorder with significant malignant potential. Here, we describe LYG in a 70-year-old renal allograft recipient who, 4 years after transplantation, on tacrolimus and mycophenolate mofetil and prednisone maintenance immunosuppression, complained of low-grade fever, persistent headache and gait disturbance. The MRI of the brain revealed diffuse periventricular cerebral and cerebellar contrast-enhanced lesions. The CT scan of the thorax showed multiple pulmonary nodular opacities in both lung fields. The patient was diagnosed LYG based on the cerebral biopsy showing perivascular infiltration of CD20-positive B-lymphocytes with granulomatous lesions and immunofluorescence staining with anti-EBV antibodies. With careful reduction of the immunossuppression combined with the use of rituximab, our patient showed a complete disappearance of LYG, and she is clinically well more than 4 years after the diagnosis, with good kidney function. No recurrence has been observed by radiological imaging until now. This is the first report of a durable (>4 years) complete remission of LYG after treatment with rituximab in renal transplantation.

Lymphomatoid Granulomatosis

“…Available data, however, for the use of rituximab as a single agent in LYG are currently restricted to expert anecdotes and case reports, as there are currently no published studies on its response rate or duration of remission. 16,17 One case report describes a dramatic response to therapy in a patient who died of fatal pulmonary hemorrhage only a month after therapy. 18 Research done at the US National Cancer Institute (NCI) uses a risk-adapted approach to the management of LYG with promising results.…”

Primary Cerebral Lymphomatoid Granulomatosis Progressing to Methotrexate-associated Lymphoproliferative Disease Under Immunosuppressive Therapy

“…In a large case series of LYG reported prior to the rituximab era, systemic LYG with CNS involvement was found to typically correlate with a poor prognosis, with a mortality rate of 86% at 14 months (compared with 66% among the patients without CNS involvement) (5). Rituximab was recently used to treat LYG patients, with a favorable toxicity profile (15)(16)(17)(18), and has been reported to be effective against CNS lesions (18). In addition, a retrospective study of rituximab-containing chemotherapy for high-grade LYG documented a progressionfree survival of 40% at a median follow-up of 28 months (6).…”

Fatal lymphomatoid granulomatosis with primary CNS-involvement in an immunocompetent 80-year-old woman

“…In our patient, such an aggressive approach did not appear feasible as there was a need for invasive critical care, including mechanical ventilation and external CSF drainage. There have been reports suggesting rituximab alone3 16–18 or in combination with temozolomide as a successful treatment option for LYG and also for lymphomas of the central nervous system 19–21. Nonetheless, failure of treatment with rituximab monotherapy has been reported 22.…”

“…The lungs are usually affected at diagnosis of LYG, but involvement of the kidneys, the central and peripheral nervous system, and the skin, along with constitutional symptoms, are also reported 1. While LYG is mainly seen in immunocompromised patients suffering from AIDS, cases of solid-organ transplantation and in others,2 3 there are reports on LYG in immunocompetent persons as well 4 5. Presentation of LYG with initial CNS symptoms is rare.…”