Diagnosis of human bovine tuberculosis aided by PET/CT scanning and EBUS-TBNA

Abstract

Human bovine tuberculosis is a rare zoonotic infection in developed countries which has been achieved predominantly by effective eradication programmes in cattle. The principal modes of transmission are consumption of unpasteurised dairy products and close contact with infected cattle. The clinical and radiological presentation is indistinguishable from tuberculosis caused by Mycobacterium tuberculosis. The diagnosis should be considered in individuals with relevant risk factors who present with intra/extrathoracic pathology. We describe and discuss a case of bovine tuberculosis with a synchronous primary bronchus carcinoma in an immunocompetent individual who presented with a solitary pulmonary nodule and contralateral mediastinal lymphadenopathy on CT imaging. The diagnosis of M. bovis infectionwas aided by 18F-fluorodeoxyglucose positron emission tomography/CT imaging and endobronchial ultrasound-guided mediastinal lymph node sampling.

Background

The performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) after positron emission tomography (PET)/CT scan resulted in the diagnosis of dual pathology. EBUS-TBNA excluded neoplastic involvement of the mediatinal lymph nodes, upgraded the staging of the primary bronchus carcinoma in the LLL (diagnosed by CT scan-guided biopsy) and thereby influenced treatment of the tumour and patient survival.

The submission of lymph node samples at EBUS-TBNA for microbiological culture is important but often omitted where the likelihood of malignancy is assumed to be high.

EBUS-guided mediastinal lymph node sampling is increasingly used for the diagnosis of mycobacterial/granulomatous intrathoracic lymph node disease and largely replaced mediastinoscopy in the developed world.

A review and comparison of epidemiology related to Mycobacterium bovis infection in low-income and developed countries is discussed.

The treatment of human M. bovis infection is largely based on expert opinion and longer in duration than for pulmonary tuberculosis.

Case presentation

A 75-year-old Caucasian woman was referred to the Respiratory Medicine service with an abnormal chest radiograph for further investigation. She was asymptomatic at the time. Medical history included chronic obstructive pulmonary disease, aortic stenosis, atrial fibrillation and hypertension. There was no significant family or occupational history and no BCG vaccination scar was evident. She had no recollection of ingesting unpasteurised dairy products or exposure to farm animals and was an ex-smoker with a 30 pack-year history of cigarette smoking.

Clinical examination of the respiratory and lymphatic systems was unremarkable.

Investigations

Chest radiography demonstrated a 2 cm left mid-zone pulmonary opacity. Contrast-enhanced CT scan of the thorax revealed a cavitating 22 mm pulmonary nodule in the LLL and enlarged partially calcified right paratracheal and hilar lymph nodes (figure 1; arrow). Primary bronchus carcinoma was considered as the most likely diagnosis.

Figure 1.

Axial thorax CT image. Enlarged right paratracheal lymph nodes with small area of calcification (arrow).

18F-fluorodeoxyglucose (18F-FDG) PET/CT imaging was performed after multidisciplinary discussion of the case. The right paratracheal lymph nodes demonstrated high FDG avidity and the pulmonary nodule moderate FDG avidity (figure 2A,B; arrows). Histology and immunoprofiling performed on a CT scan-guided biopsy of the nodule was consistent with adenocarcinoma of the lung. EBUS-TBNA sampling of the 4R mediastinal lymph node station revealed few epithelioid granulomata and Ziehl-Neelsen and fungal stains were reported negative. Tissue was sent for mycobacterial and fungal staining and culture.

Figure 2.

Coronal 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT images. (A) High FDG uptake in right paratracheal lymph nodes (arrow) and (B) moderate FDG uptake in left lower lobe pulmonary nodule (arrow).

Mycobacterial staining was reported negative but liquid culture positive for M. bovis. Drug sensitivity testing revealed a pyrazinamide-resistant isolate.

Differential diagnosis

1. Primary bronchus carcinoma with N3 lymph node involvement

2. Granulomatous lung disease

3. Pulmonary mycobacterial infection

Treatment

The patient was commenced on an antimycobacterial drug regimen that consisted of isoniazid (INH) 300 mg daily, rifampicin (RIF) 600 mg daily and ethambutol (EMB) 900 mg daily for the first 2 months (intensive phase) followed by 7 months of INH and RIF (maintenance phase).

Outcome and follow-up

The antimycobacterial therapy was well tolerated and the patient completed treatment within 9 months. There was a significant reduction in the size of the right paratracheal lymph node after antimycobacterial therapy (figure 3; arrow).

Figure 3.

Axial thorax CT image. Significant reduction in size of right paratracheal lymph nodes after 9 months of antimycobacterial therapy (arrow).

The LLL nodule regressed completely with stereotactic ablative radiotherapy and the patient remains asymptomatic.

Discussion

Human bovine tuberculosis is caused by M. bovis, a predominantly zoonotic pathogen and member of the M. tuberculosis (MTB) complex. Transmission to humans occurs via ingestion of unpasteurised dairy products, close contact with infected cattle and infrequently via aerosolised droplet nuclei.¹ Human-to-human transmission of M. bovis infection is rare.

M. bovis infection is rarely seen in high-income countries as a result of major eradication programmes in the early and middle parts of the last century and ongoing disease surveillance and control efforts. It remains prevalent in low/middle-income countries however where up to 30% of all tuberculosis cases are due to M. bovis.²

M. bovis infection in UK, according to recent surveillance studies, accounts for approximately 1.1% of cases presenting with tuberculosis.³ The number of cases of human M. bovis infection in the UK has remained static despite a relatively high incidence of tuberculosis in cattle. Recognised risk factors in the UK include ingestion of unpasteurised dairy products, UK-born individuals, age greater than 65 years and occupations with an animal–human interface.

The clinical, radiological and pathological presentation of M. bovis infection is identical to that of MTB. The frequency of extrapulmonary disease is higher due to mode of transmission.

M. bovis is genotypically resistant to pyrazinamide.⁴ The drug is critical for the killing of non-replicating or ‘persistent’ bacilli. This unique action of pyrazinamide has allowed shortening of the treatment period for tuberculosis from 9 to 12 months to 6 months. Expert opinion and literature review recommend a 2-month intensive treatment phase consisting of INH, RIF and EMB (15 mg/kg) followed by a 7-month maintenance phase of INH and RIF.^5–7

Although granulomatous pathology including mycobacterial infection may be associated with increased 18F-FDG avidity on PET imaging, it is difficult to differentiate from neoplastic pathology. PET/CT imaging may be useful to detect extrapulmonary involvement of mycobacterial disease and guide diagnostic procedures.⁸

EBUS sampling of mediastinal lymph nodes or EBUS-TBNA has largely superseded surgical techniques. It is a minimally invasive, same-day procedure, performed under conscious sedation and safer. Its role has extended to the diagnosis of mycobacterial disease over the past few years. It has a high sensitivity and specificity for this purpose in areas with low to intermediate prevalence rates of MTB.^{9 10} Tissue sampling by EBUS-TBNA enables histological assessment, mycobacterial staining and culture and the utilisation of MTB PCR testing for rapid diagnosis and exclusion of multidrug-resistant tuberculosis.^{11 12}

Learning points.

• The decision-making and indications for performing endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA) sampling of mediastinal lymph nodes.

• The importance of submitting lymph node samples obtained from EBUS-TBNA for microbiological analysis.

• The role of positron emission tomography/CT scanning and EBUS-guided mediastinal lymph node sampling in the diagnosis of mycobacterial/granulomatous intrathoracic disease.

• The pathogen is usually resistant to pyrazinamide and treatment of Mycobacterium bovis infection is longer than that for tuberculosis.