On December 14, 2017, a 51-year-old man visited our General Internal Medicine department for finding a hepatic mass without any discomfort during health examination. The entire process of diagnosis and treatment is briefly depicted in Figure 1. The patient claimed no history of hepatitis or TB and no family history of liver cancer. Physical examination was unremarkable. Detailed laboratory examination data are presented in Table 1. Contrast-enhanced abdominal computed tomography (CT) showed a hypodense lesion with mild to moderate enhancement in the right hepatic lobe near hepatic hilar, which indicated the possibility of cholangiocellular carcinoma; in addition, a soft tissue density lesion with heterogeneous enhancement in the left posterior mediastinum suggested the possibility of neurogenic tumor (Figures 1A,B).
In the following 2 years, he had visited several hospitals and had underwent a huge number of blood tests, CT scans, and magnetic resonance imaging (MRI) examinations. Mantoux test was positive (24 x22 mm). The results of T-SPOT.TB tests elevated progressively from 14 to 84 pg/ml. Repeated sputum smear examinations for acid-fast bacilli (AFB) were all negative. Chest CT displayed multiple small lung nodules and a left posterior mediastinal mass. 18F-fluorodeoxyglucose positron emission tomography (F-18 FDG-PET)/CT showed intense accumulation of FDG in the right hepatic lobe, right abdomen, lower left lung, left hilar, and lower mediastinal lymph nodes, suggesting the possibility of malignancy. MRI showed multiple cystic nodules in the prostate. Histopathological examinations of specimens obtained by fine-needle aspiration biopsy from the liver mass, mediastinal mass, and prostatic nodules suggested granulomatous inflammation, and special stains including acid-fast staining, Grocott's methenamine silver (GMS), Periodic acid-Schiff (PAS), and gram were all negative. The diagnosis remained unclear.
On December 18, 2019, the patient was admitted to our hospital again with backache for 50 days. MRI of thoracic spine demonstrated multiple bone destructions at T3/T4 and T7/T8 with surrounding soft tissue lesions, suggesting spinal TB with cold abscesses (Figures 1C-E). Radionuclide bone scan demonstrated that the metabolism of vertebral bodies of T4 and T8 was abnormal, and metastatic bone tumors were considered (Figure 1F). He underwent a thoracic spinal operation. Considering the possibility of TB, the surgical specimens were subjected to both mNGS and histopathological examination. The process of mNGS is provided in the Supplementary Material. The mNGS revealed 25 total reads of MTB complex (Table 2). Significantly, because of the high internal homology and relatively insufficient coverage, the species within the MTB complex was not determined. Meanwhile, histopathological examination showed caseous necrosis with a significant number of inflammatory cells and multinucleate giant cells (Figure 1G). Therefore, the patient was diagnosed with spinal TB and immediately treated with anti-TB drugs including isoniazid, rifampicin, ethambutol, and pyrazinamide.
On March 1, 2020, the patient presented to our hospital for the third time due to coughing for a week. His bronchoalveolar lavage fluid (BALF) was obtained by fiberoptic bronchoscopy for mNGS and Xpert MTB/RIF assay. The process of Xpert MTB/RIF is provided in the Supplementary Material. MTB complex was successfully detected by mNGS. In addition, the result of Xpert MTB/RIF was positive for MTB gene and negative for rifampicin resistance. Based on the available evidence, it was eventually considered that the patient suffered from disseminated TB with systemic multi-organ involvement, including the lung, spine, mediastinum, liver, and prostate. To enhance the treatment effect, moxifloxacin was added to the original anti-TB treatment regimen.
According to the national laws and regulations, the patient was subsequently referred to the TB designated hospital for systematic treatment because of intrapulmonary TB. Through telephone follow-up, we learned that pyrazinamide was discontinued because of hyperuricemia shortly after the referral, and then the patient received anti-TB treatment with isoniazid, rifampicin, ethambutol, levofloxacin, and linezolid for 1 year. Diammonium glycyrrhizinate, which protects the liver, was continuous in the course of anti-TB therapy. The anti-TB drug regimen was well-tolerated and achieved a remarkable effect. At the latest follow-up, the patient reported significant reduction in the size of the lesions on imaging tests, reconfirming the diagnosis of TB, and started receiving anti-TB treatment with isoniazid, rifampicin, and ethambutol. He thanked us for our contribution to the diagnosis.