A 27‐Year‐Old Female with Multiple Intracranial Lesions

Clinical History

A 27‐year‐old female patient, presented with left hemiparesis. Brain MRI showed multiple cystic ring‐enhancing lesions involving the cerebrum and cerebellum (Figure 1A). She has received anti‐tuberculous treatment for a recent diagnosis with pulmonary tuberculosis, however, the brain lesions showed with no response. Investigations revealed no other medical conditions. She underwent craniotomy and one of the lesions was excised from the left parietal lobe. It consisted of an oval white to gray soft tissue mass with solid white cut surface measuring 1.2 × 0.8 × 0.9 cm (Figure 1B).

Figure 1.

Microscopic Pathology

Microscopic examination revealed a well‐defined lesion (Figure 1C H&E ×4) that consisted of well‐defined chronic granulomatous inflammation (Figure 1D,E, H&E ×10, ×20) located at the periphery surrounding a large center of necrosis (Figure 1F, H&E ×40). No evidence of parasitic microorganisms could be seen. Special stains including PAS (Figure 1G, ×40) and Ziehl–Neelsen (Figure 1H, ×100) were performed. What is your diagnosis?”

Diagnosis

Multiple intracranial tuberculomas.

Discussion

Tuberculosis (TB) continues to be one of the important infectious disease worldwide, with more than 2 billion people affected 1, 3. Besides the pulmonary system, TB affects nearly every system in the body, including the lymph nodes, central nervous system (CNS) and others. CNS TB remains one of the most severe manifestations of the disease 3. It can present in many forms, one of which is intracranial tuberculomas (ICT) which develop in 16%–40% of affected patients 4.

An extensive literature review on 291 cases showed that more than half of the reported cases came from Asia (n = 155, 53.2%) (Graph 1; Graph 2). A complete bibliography with 102 citations can be found at: http://path.upmc.edu/divisions/neuropath/bpath/cases/case367.html

The male (n = 136) and female (n = 140) were affected almost equally with a male to female ratio of 1:1.03. The average age at diagnosis was 30.25 years, and around two thirds of the cases (n = 192, 65%) were reported in the first four decades. Twenty percent of cases occurred in the 20–29 age group; the most common age group affected. Pediatric patients (0–19 years of age) constituted one third of the affected individuals (n = 95, 33.8%). Females were more likely to be affected in second and third decades, while males were more likely to be affected in later decades.

Symptoms of increased intracranial pressure were the most common presenting manifestations, with headache (n = 108, 37.1%), and fever (n = 83, 28.5%) as the most common presentations. Radiologically; enhancing multiple lesions was the most common pattern (n = 288, 99%). The lesions were mostly seen in the cerebrum involving the frontal lobe in 50(17.2%) cases, the parietal lobe in 41 (14%), the temporal lobe in 34 (11.7%) and the occipital lobe in 22 (7.6%). In the cerebellum there were 97 (33.3%) cases, followed by the brain stem in 22 (7%), including the pons in 16 (5%), thalamus in 22 (7%) and the basal ganglia in 12 (4%). Leptomeningeal enhancement was seen in 14(5%) cases only. Spinal involvement was reported in only a minority of cases (n = 23, 8%). Concurrent or previous pulmonary involvement was reported in around a third of cases (n = 106, 36%).

Predisposing conditions were reported in another quarter of cases (n = 64, 22.6%) These conditions included HIV (n =10), use of immunosuppressant agents (n = 10), malignancies (n = 8), diabetes mellitus (n = 4), alcoholism (n = 4), systemic lupus erythematosus (SLE; n = 3), liver cirrhosis (n = 3) and malnutrition (n = 2). Interestingly pregnancy was reported in 6 cases. History of contact with tuberculosis patients (n = 21) was also a potential important predisposing condition. Diagnosis was confirmed by a tissue biopsy in 41% (n = 118) of cases, including postmortem tissue diagnosis (n = 3) as well as abscess aspiration (n = 12). Granulomatous inflammation either caseating or non‐caseating was seen. The ZN special stain was performed in 131 (45%) cases and was positive in 70 (53%) cases, while it was negative in 61 (47%). The PCR was performed in 57 (19%) cases, and was positive in 30 (52.6%) cases, while it was negative in 27 (47.4%).Treatment was documented in only 220 (75.0%). Of these anti‐tuberculous medication was used alone in 79% (n = 174), medication and surgery in 18% (n = 40) and surgical alone in 3% (n = 6). The outcome was reported in 212 (72.8%) cases (Table 1).

Table 1.

Outcome reported	212 Cases (78.8%)
Cured	192 Cases (91%)
Expired	15 Cases (7%)
Lost to follow up	5 Cases (2%)

Metastatic malignancy remains the most common cause for multiple IC ring‐enhancing lesions. However, in developing countries infectious diseases appear to be encountered more frequently 2, and remains an important consideration, especially in young individuals. While tuberculosis remains the most common infectious pathology, neurocysticercosis and toxoplasmosis should be ruled out.