18F-fludeoxyglucose positron emission tomography computed tomography-guided diagnosis of prostatic and leptomeningeal tuberculosis.

Genitourinary tuberculosis contributes to 10%-14% of extrapulmonary TB. Prostate tuberculosis is rare and usually found incidentally following transurethral resection of the prostate for benign prostatic hyperplasia. We report a case of an immunocompetent patient with pyrexia of unknown origin, on evaluation with whole-body 18F-fludeoxyglucose positron emission tomography computed tomography scan found to have suspicious prostatic primary, with hypermetabolic abnormalities involving the brain. Histopathological diagnosis was established as multifocal tuberculosis involving prostate, meninges, and intracranial tuberculomas.

INTRODUCTION

Extrapulmonary tuberculosis (EPTB) has variable clinical presentation depending on the site of involvement and the aggressiveness of disease. Granulomatous prostatitis, as part of genitor-urinary tuberculosis (GUTB), mimics prostatic neoplasm and is usually found incidentally following transurethral resection. Urine polymerase chain reaction has good sensitivity (95.5%) and specificity (98.12%).[1] Imaging techniques such as transrectal ultrasound and magnetic resonance imaging (MRI) allow lesion characterization. 18F-fludeoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT) scan provides real time assessment of the active TB because FDG accumulates in inflammatory cells such as neutrophils and activated macrophages.[2] 18F-FDG PET/CT is significantly more efficient as compared to CT, for the identification of sites of EPTB. The authors report an unusual case of simultaneous prostate and intracranial tuberculosis (TB) detected on 18F-FDG PET/CT scan in an immunocompetent patient.

CASE REPORT

A 54-year old man presented with persistent fever and weight loss of 5–6 kg over 1 month. There was no demonstrable abnormality on clinical examination. Complete blood counts, liver and renal function tests, and blood culture for common pathogens as well as Mycobacteria were unremarkable. Chest radiography and ultrasonography of abdomen and pelvis were normal. Erythrocyte sedimentation rate was raised (35 mm/h) and C-reactive protein was normal. In view of persistent generalized symptoms, the absence of localizing symptoms, with no obvious anatomical and biochemical abnormality, he was referred for whole body F-18 FDG PET-CECT, to detect an occult pathology. It was performed as standard guidelines from head to mid-thigh [Figure 1a]. There was focal intense FDG uptake seen in the right lobe of prostate gland (standardized uptake value [SUVmax] 20.7) [Figure 1b] and asymmetric heterogeneous FDG uptake in left frontal lobe peripherally (SUVmax 13.4) [Figure 2]. Overall scan findings raised possibilities of suspicious prostate infection or neoplasm. In view of left frontal lobe abnormality, an MRI brain was advised.

Figure 1

(a) Fludeoxyglucose positron emission tomography computed tomography scan maximum intensity projection images: focal intense flfludeoxyglucose uptake in the right lobe of prostate gland. (b) Axial fused, positron emission tomography, and computed tomography images: Focal intense fludeoxyglucose uptake seen in right lobe of prostate gland

Figure 2

Axial fused positron emission tomography and computed tomography images: Heterogeneous flfludeoxyglucose uptake in left frontal lobe peripherally

Regional MRI pelvis revealed T2 hypointensity in peripheral zone of the right half of prostrate with contrast enhancement, without any extracapsular extension, and crossing midline [Figure 3a], favoring neoplastic etiology. On digital rectal examination, the prostate was found to be hard and nodular. Serum total prostate-specific antigen (PSA) level was within normal range (2.4 ng/ml). Urine sample was negative for acid fast bacilli. Transrectal ultrasound-guided biopsy (TRUS)-guided biopsy was performed with sampling from base, mid zone, and apex of the right lobe of prostate. Histopathology revealed multiple caseous epithelioid granulomas containing giant cells and central amorphous, eosinophilic necrotic material [Figure 3a]. The diagnosis was prostatic TB. Anti-tubercular therapy (ATT) was started with isoniazid, rifampicin, pyrazinamide, and ethambutol. However, before the patient could undergo MRI brain as scheduled, he developed sudden altered mental state, with delirium and slurred speech, which lasted for few minutes. The provisional diagnosis was Ethambutol and Isoniazid induced psychosis. MRI brain with gadolinium contrast demonstrated asymmetrical exaggerated irregular leptomeningeal enhancement in the left frontal region with enhancing granulomas in the supra and infratentorial brain parenchyma [Figure 4]. Overall findings represented intracranial TB. The patient was continued on ATT under monitoring. Clinical improvement was witnessed within 2 months, with subsided fever and normalized ESR. Serum PSA after 3 months was 2 ng/ml. There were no further neurological episodes.

Figure 3

(a) Magnetic resonance axial T2 and contrast enhance images: T2 hypointensity in peripheral zone of right half of prostrate with enhancement on postcontrast images, extending to the capsule without any obvious extension beyond the capsule, and was also crossing midline. (b) Magnetic resonance axial T2 and contrast enhance images: asymmetrical exaggerated irregular and nodular leptomeningeal enhancement in left frontal region with nodular enhancing foci/granulomas in the supra and infratentorial brain parenchyma with no significant mass effect

Figure 4

Histopathology slides of prostate biopsy: granulomatous inflammation with multiple caseous epithelioid granulomas containing Langhans' and foreign body type giant cells and central amorphous, eosinophilic necrotic material

DISCUSSION

Definition of PUO includes (i) temperature >38.3°C on multiple occasions; (ii) duration of illness of more than 3 weeks; and (iii) exclusion of patients who are currently immune-compromised. Causes are infection (16%), neoplasm (7%), inflammatory (22%), and miscellaneous causes (4%). In the rest, no diagnosis can be made.[2] Baseline blood panel would include inflammatory markers, such as ESR and CRP, and a full blood count with differential white cell count, creatinine, electrolytes, LFTs, rheumatoid factor, antinuclear antibodies, serum protein electrophoresis, and three blood cultures from separate venepunctures. Second-line investigations include HIV testing, lactate dehydrogenase, ferritin, thyroid function test, and infectious diseases testing appropriate for any specific risk factors, such as tuberculosis in South Asian countries.[2]

If the diagnosis is not established with initial workup, invasive investigations can be considered. Traditionally, contrast-enhanced CT scan has been the imaging modality of choice; however, recent evidence suggests a higher sensitivity with FDG-PET/CT. In meta-analysis performed by Hao et al., pooled sensitivity of FDG PET-CT in detecting, or guiding toward the cause of PUO was 85%.[3] TB is the most common cause in developing countries. In one study of 25 patients of PUO undergoing FDG PET-CT scan, 8 patients were diagnosed with TB. The same study reported a sensitivity of 90.9% and PPV of 95.2% for FDG PET-CT in cases of PUO.[4]

GUTB constitutes a major urological problem in India and found in around <0.5% of EPTB. The prostate is the least affected organ in GUTB. Its involvement is usually secondary to upper GU tract TB, by direct intracanalicular extension, or by hematogenous spread. Frequently, prostatic TB is associated with epididymal involvement. Hence, such patients usually present with localizing symptoms such as pyuria, hemospermia, and lower abdominal pain. Solitary prostate TB is extremely rare with most of the cases reported on autopsy, as they may not present with characteristic symptoms.[5]

Due to biological heterogeneity in prostate cancer, FDG PET-CT cannot differentiate it from prostate TB on the basis of uptake indices. However, well-differentiated prostate adenocarcinoma demonstrates low glycolysis rates and lower FDG uptake.[5] In a meta-analysis of incidental FDG-avid prostate lesions, SUV max of prostate cancer varied between 3.1 and 10.[5] In our case, very high SUVmax of 20.7 with normal PSA helped us suspecting an infective etiology.

In conclusion, in our case of PUO, 18F-FDG PET-CT pointed out the probable active pathology of extremely rare solitary prostate involvement as a part of GUTB, guided biopsy, and directed the diagnosis of CNS involvement. Prostate tuberculosis is one of the differentials of high-grade FDG-avidity. The need of inclusion of brain acquisition during 18F-FDG PET-CT scan in cases of PUO is also highlighted.

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Conflicts of interest

There are no conflicts of interest.