Introduction

Tuberculosis (TB) remains a global health issue, endemic among developing countries and increasingly prevalent in developed ones [1]. In the World Health Organization Global Tuberculosis Report 2020, it is estimated that up to 10 million people were afflicted with the infection in 2019. Mycobacterium tuberculosis, the pathogen involved in TB, typically affects the lung. Extrapulmonary manifestations are less common, such as skeletal TB which accounts for about 5–20% of all TB infections, of which 50% of cases affect the spine [2,3,4]. Multifocal skeletal TB is defined as the involvement of two or more non-contiguous locations in the skeletal system. It is an extremely rare clinical entity and only accounts for about 5% of all skeletal TB cases [4].

TB is often labeled as the great mimicker—its varied and often non-specific presentation, as well as radiologic manifestations, can mimic various diseases across different organ systems. Diagnosis of TB in such cases remains a challenge but is imperative as treatment strategies for TB differ greatly from other conditions.

This article reports a rare case of disseminated mycobacterium tuberculous infection affecting the skeletal system, mimicking widespread bony and spinal metastasis.

Case presentation

The patient was a 28-year-old male of Southeast-Asian descent, with no significant past medical history and no travel history over the past few years. He presented to the orthopedics clinic with worsening lower back pain of 6 months duration, with significant symptoms of rest pain and night pain. He denied any prior falls or trauma, and did not have any fever, cough or constitutional symptoms. Clinical examination did not show any midline or paravertebral spinal tenderness, with intact upper and lower limb neurology. Initial plain radiographs reviewed T11 vertebra fracture with patchy lucencies seen over T10 and T11 vertebra (Fig. 1). Chest radiographs were normal.

Fig. 1: Initial anteroposterior (AP) and lateral plain radiographs of the thoracolumbar spine.
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The radiographs show T11 pathological vertebra fracture (red arrow) with patchy lucencies over T10 and T11 vertebral bodies.

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Biochemical investigations for this patient revealed normal cell counts on complete blood count, normal liver and kidney function tests, negative myeloma panel, mildly elevated erythrocyte sedimentation rate (ESR) level of 21 mm/h and negative HIV tests. Magnetic resonance imaging (MRI) of the thoracolumbar spine showed pathological T11 vertebra burst fracture with posterior retropulsion indenting the spinal cord (Fig. 2), with multiple foci of marrow infiltrative process involving thoracic vertebra (T5, T7–T11), lumbar vertebra (L1, L4, L5), sacrum and left iliac bone (Fig. 3). There was also an epidural soft tissue lesion at T10/T11 foramina surrounding the left nerve roots. Subsequent bone scintigraphy with technetium 99m-methyl diphosphonate (Tc-99m MDP) reviewed heterogeneous tracer uptake involving T7 to L5 vertebrae, manubrium, sternum, iliac bones, and sacrum (Fig. 4). These findings were consistent with bony metastasis. Computed tomography (CT) imaging of the thorax, abdomen and pelvis was then performed that revealed right upper lung lobe nodularity (Fig. 5) and enlarged lymph nodes involving the left supraclavicular station, celiac axis and porta hepatis station. There were no mass lesions or obvious tumors demonstrated in the chest, abdomen or pelvis.

Fig. 2: MRI imaging of the thoracic spine.
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Sagittal and coronal T1 fat-suppressed contrasted MRI scans showing the pathological burst fracture of T11 vertebra (red arrow), with abnormal marrow infiltration involving the vertebral body and posterior elements.

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Fig. 3: MRI imaging of the thoracic and lumbosacral spine.
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Sagittal T1 fat-suppressed contrasted MRI scans showing multiple non-contiguous foci of marrow infiltration involving the thoracic vertebra (T5, T7–T11), lumbar vertebra (L1, L4–L5), and sacrum.

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Fig. 4: Bone scintigraphy (Tc-99m MDP) scan.
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The scan shows heterogeneous tracer uptake involving T7 to L5 vertebrae, manubrium, sternum, iliac bones, and sacrum.

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Fig. 5: CT thorax done pre-operatively.
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Coronal and axial cuts of CT thorax showing right upper lobe nodularity and scarring suggestive of prior infection.

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The patient underwent T9–T12 posterior instrumentation, left T10/T11 facetectomy and biopsy. Surgery was conducted under general anesthesia, with the patient in the prone position. Pedicle screws were inserted for T9 and T12 segments under O-arm navigation, and biopsy of T10 and T11 vertebral bodies was performed via the left pedicular approach. Left T10/11 facetectomy was performed under microscopy, and left T10/T11 foramina tissue was sent for histology and culture. Histology came back showing necrotizing granulomatous inflammation composed of epithelioid histiocytes forming discrete granulomas with central necrosis. There was no evidence of malignancy or metastatic disease. Ziehl–Neelsen stain was negative for acid-fast bacilli. Aerobic and anaerobic cultures were negative for bacterial infection.

An infection disease specialist was consulted and a subsequent CT-guided biopsy of the sacrum was performed to obtain more tissue samples for testing to guide treatment. Histology again showed florid necrotizing granulomatous inflammation, this time positive for acid-fast bacilli (rare) on the Ziehl–Neelsen stain (Fig. 6). Acid-fast bacilli cultures subsequently came back positive for drug-susceptible M. tuberculosis (Fig. 7).

Fig. 6: Histopathological slides taken from the CT-guided sacrum biopsy.
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a Granulomatous inflammation composing of epithelioid histiocytes with central necrosis. b Acid-fast bacilli (black arrow) seen after Ziehl–Neelsen staining.

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Fig. 7: AFB culture report taken from the CT-guided sacrum biopsy.
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The cultures came back positive for drug-susceptible Mycobacterium tuberculosis.

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The patient was diagnosed with multifocal skeletal M. tuberculosis infection and was treated with rifampicin, ethambutol, pyrazinamide and isoniazid for 2 months, followed by rifampicin and isoniazid for 10 months. Follow-up after treatment completion showed full clinical recovery with stable implant positions on check radiographs (Fig. 8).

Fig. 8: AP and lateral plain radiographs of the thoracic spine taken on follow-up review.
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The radiographs were taken after completion of antituberculosis treatment demonstrating stable T9–T12 posterior instrumentation.

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Discussion

TB remains a major worldwide healthcare burden with increasing incidence due to immigration, immunosuppression due to HIV infections and diabetes, and the emergence of multidrug-resistant TB. Skeletal TB is an uncommon manifestation but can result in significant bone destruction, deformities and neurological compromise [2,3,4,5]. Multifocal skeletal TB is an extremely rare clinical entity, accounting for approximately 5% of skeletal TB cases [4]. The diagnosis is often delayed due to its rarity and non-specific insidious symptoms [4, 6, 7]. In particular, it is difficult to distinguish between multifocal skeletal TB against bony metastasis as both entities can have similar presentations and radiological findings. Biochemical tests such as ESR, C-reactive protein, T-SPOT tests are not useful for diagnosis [3].

Typical features for plain radiographs in skeletal TB affecting the spine can show rarefaction of vertebral endplates, anterior vertebral wedging, loss of vertebral height, bony destruction and development of paraspinal soft tissue abscess [4, 8]. In our case, there was a pathological fracture at T11 with bony destruction and osteolytic lesions seen in the T10/T11 vertebral bodies.

Typical MRI features of skeletal spine TB infections include marrow edema, endplate erosions, paravertebral collections with subligamentous or epidural extension, contiguous vertebra body involvement and intraosseous abscess [8]. Interesting MRI findings noted for our patient included the involvement of posterior spinal elements, non-contiguous lesions and sacral involvement—all of which are rare findings of skeletal spine TB [9,10,11].

There have been a few reported cases of multifocal skeletal TB mimicking widespread bony metastasis in literature till date [2,3,4, 12,13,14,15]. These cases were shown to demonstrate radiographic features on various imaging modalities such as MRI, bone scintigraphy (Tc-99m MDP) and fluorodeoxyglucose (FDG) positron emission tomography (PET)–CT strongly suggestive of bony metastasis initially before the diagnosis of multifocal skeletal TB was ultimately established after analyzing tissue biopsy results.

While bone scans are a useful and common tool used for staging cancers and surveillance of bony metastasis, there are limitations. It has low specificity and has increased sensitivity towards increased bone remodeling from both benign and malignant causes. Benign osteolytic lesions such as TB infections can have a similar appearance to bony metastasis [16]. Similarly, TB infections can resemble bone metastasis in FDG PET–CT scans. FDG tracer accumulates in tumor tissue, but active TB lesions can also exhibit increased glucose metabolism and intense FDF uptake [2, 3]. Liu et al. reported a case of disseminated TB infection showing up on PET–CT scan as multiple FDG avid lymph nodes, with hypermetabolic destruction involving rib, scapula and L5 vertebral bones, mimicking bony metastasis [2]. Meiping et al. similarly reported a case of multifocal skeletal TB presenting with MRI and PET–CT scan findings strongly suggestive of bony metastasis leading to delayed TB diagnosis. For cases with an already established diagnosis of multifocal skeletal TB, it is proposed that PET–CT can be a useful follow-up tool to decide the endpoint of treatment [4, 8]. Shankar et al. suggest that CT perfusion scans can potentially help with the differentiation of the two conditions. They reported that TB infected tissues had low relative blood flow and volume while neoplastic lesions had high relative blood flow and volume which potentially allows for differentiation [17].

Tissue biopsy for histopathology and microbiology is the cornerstone for diagnosis. Key histological features for tissues with TB infection include a granulomatous reaction with epithelioid histiocytes, giant cells, and caseous necrosis. M. tuberculosis bacteria can be found inside the granuloma with Ziehl–Neelsen staining. There is however low bacterial loads in spine TB cases, and the TB bacteria can only be identified in less than 50% of cases [18]. This was seen in the first biopsy report of our patient from the spine surgery that came back negative for TB, and only came back positive on repeat CT-guided sacrum biopsy.

Treatment of multifocal skeletal TB involves a culture-directed anti-TB drug regimen with consideration of surgical interventions. Surgery may be indicated in cases of severe joint or bone deformities, unstable pathological fractures, neurological compromise, cold abscess or necrotic debris [4, 19]. Outcomes are generally good, with multiple authors reporting resolution of TB infection and symptoms following treatment [4, 14, 15, 19].

This case highlights the importance for clinicians to consider multifocal skeletal TB as a differential diagnosis for patients who present with multiple bony lesions picked up on radiographic modalities. Whilst TB infections remain less common in developed countries, they can still cause significant morbidity.

Conclusion

Multifocal skeletal tuberculous infections can resemble spinal or bony metastasis on various imaging modalities. Care must be taken when interpreting such imaging results, with histopathology and mycobacterial cultures remaining the gold standard to determine the presence of active TB infections.