Our case report is unique because it describes a novel case of fever of unknown origin secondary to isolated secondary CNS lymphoma without an associated systemic lymphoma relapse.
Review of the literature reveals only two similar cases. The first case, described in 2001, was in a patient that presented with pituitary lymphoma and fever was thought to be a localized effect of the lymphoma, in this case secondary to extrasellar leakage of blood. [citation 8]. The second case, described in 2009 by Salih, Saeed, et al, described a patient that presented with intraparenchymal primary CNS lymphoma without other cause. [citation 9].
The mechanism of fever among patients with systemic lymphoma is not entirely understood, but is believed to be secondary to elevated levels of IL-6 and IL-10, with higher levels of IL-6 among patients with B-symptoms. [citation 7] Elevated serum levels of IL-6 and IL-10 have not been reported in the literature among patients with isolated PCNSL. Instead, the elevated levels of IL-6 and IL-10 are found in higher concentration in CSF. [citation 10] We theorize that, in the majority of cases of CNS lymphoma, the localization of the inflammatory interleukins to CSF may preclude the same systemic inflammation leading to fevers in patients with PCNSL or isolated SCNSL compared to those with systemic DLBCL.
However, for reasons not yet understood, our case and that reported by Salih, Saeed, et al, describe cases in which the patient’s localized CNS lymphoma led to activation of the inflammatory cascade and B-symptoms typically only seen in systemic lymphoma. Based on our experiences, CNS lymphoma remains a possible diagnosis for patients that present with FUO. For all comers that present with FUO, we recommend typical work up for infectious sources. However, in patients with a history of DLBCL that present with persistent fever of unknown origin, we recommend evaluation for CNS recurrence in addition to evaluation for systemic recurrence and infectious sources.