The differential diagnosis of ring enhancing lesions of the brain includes but is not limited to the following:
The somewhat smooth appearing contrast enhancing lesion and significant edema would put primary neoplasm and abscess higher in the differential (1). Given that this patient had a prior transplant and was currently on immunosuppressive therapy, the primary medical and infectious disease teams suspected an infectious cause specifically Toxoplasma gondii given the patient's exposure history (reported handling of cats in the months prior to diagnosis). Toxoplasma gondii is a protozoan parasite that infects a multitude of warm-blooded animals; however, domestic cats are the only known definitive hosts (see Figure 1). Oocytes from cat feces can be ingested by other animals including humans via consumption of contaminated food or water. These oocytes transform into tachyzoites, a rapidly dividing crescent-shaped, approximately 2 by 6 μm, form, which can localize to neural and muscle tissue. Within those tissues, tachyzoites develop into bradyzoites, cyst forms (2,3). Humans may also be infected through blood transfusion or transplacentally from mother to fetus (2,4,5).
Figure 1. This is an illustration depicting the life cycle of the protozoa, Toxoplasma gondii, the causal agent for toxoplasmosis. Credit: CDC/ Alexander J. da Silva, PhD; Melanie Moser (https://phil.cdc.gov/Details.aspx?pid=3421). Please refer the CDC website regarding Toxoplasmosis (https://www.cdc.gov/parasites/toxoplasmosis/biology.html) link for additional information regarding the Toxoplasma gondii life cycle.
In immunocompetent patients, Toxoplasma species infection may result in flu-like myalgia but can be asymptomatic in up to 50% of patients. In immunocompromised patients, such as this case where the patient was on immunosuppressive therapy after transplant, toxoplasmosis is associated but not limited to the following clinical manifestations: reactivation lymphadenopathy with atypical lymphocytosis and hepatic dysfunction, fever, meningoencephalitis, chorientinitis, myocarditis, pneumonitis, myositis and myelitis (2, 4-6). Typically serology tests are performed to diagnose toxoplasmosis. However, in this case, peripheral and CSF levels of only anti-Toxoplasma IgG were elevated not anti-Toxoplasma IgM which could be indicative of past infection and does not definitively support recent/current infection (2,6).
On smear preparation during intraoperative consultation, the neuropathology team could only definitively appreciate the bradyzoites in cysts (see below, arrows highlight tissue cysts).
However, on permanent sections immunohistochemistry against Toxoplasma spp. antigen was performed demonstrating both the tissue cysts as well as tachyzoites (see below, full arrow highlights cyst, dotted arrow highlights putative tachyzoites).
The patient was placed on appropriate antimicrobial therapy but still experiences sequelae of the infection with seizures post-treatment.
Contributed by Tanner Freeman MD, PhD and Scott Kulich MD, PhD