Unraveling the masquerade: Decoding mimics of spinal tuberculosis

Non-tubercular infectious spondylodiscitis

Pyogenic spondylodiscitis usually presents as a result of hematogenous dissemination from a septic focus [Figure 1]. There has been an increasing incidence of spondylodiscitis in recent years due to increasing numbers of older patients with chronic diseases such as diabetes mellitus and renal failure, steroid and other immunosuppressive therapies, sickle cell disease (SCD), HIV infection, and other immunocompromised states, and intravenous drug abuse.^[6,7] Escherichia coli and methicillin-resistant Staphylococcus aureus are isolated from blood cultures in most of the patients of pyogenic spondylodiscitis.^[8] Bacterial infections, particularly from S. aureus, are the most common cause of vertebral osteomyelitis, accounting for 40–67% of cases.^[9] Although most of these Staphylococcus infections respond to methicillin, Methicillin-resistant S. aureus strains are becoming more prevalent.^[10] Other common bacterial culprits include Gram-negative bacteria such as E. coli, Pseudomonas, and Proteus species.^[11] Certain conditions increase the risk of specific infections: Streptococcus is more common in patients with infectious endocarditis, while Salmonella is a frequent cause in individuals with SCD. An isolated psoas abscess is often caused by bacteria such as S. aureus, rather than TB.^[12] Common risk factors for the same include immunocompromised states such as diabetes or intravenous drug use, and the infection can spread from intra-abdominal sources. Due to the endemicity of TB, radiologists and clinicians often tend to misdiagnose it as TB even when there is no obvious evidence of Pott’s spine.

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Figure 1:

Pyogenic spondylodiscitis. (a) Sagittal T1-weighted and (b) short tau inversion recovery magnetic resonance images demonstrate edema involving the L1-L2 as well as the L4-L5 intervertebral discs and the adjacent vertebral bodies, suggesting infective spondylodiscitis. This was reported as Pott’s spine, and the patient started on ATT with inadequate clinical response after 2 months. (c and d) Axial computed tomography images show the transpedicular biopsy of the affected vertebra. Cultures were positive for Escherichia coli with no histopathological or microbiological evidence of tuberculosis. ATT: Anti-tubercular therapy

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Approximately 30% of cases are caused by M. tuberculosis in non-endemic countries,^[9] whereas in endemic countries, TB constitutes a staggering 80% cases of all infective spondylodiscitis.^[2] Other bacterial infections cause most remaining cases, and a definitive organism is never identified in 21–34% of cases.^[13] The closest imaging mimicker for tubercular spondylodiscitis would be spinal brucellosis, in a relevant clinical scenario, and thus needs to be differentiated intricately. It should be considered in patients from rural or endemic regions with occupational or dietary exposure to livestock or unpasteurized dairy products presenting with prolonged fever and musculoskeletal symptoms.^[14] While spinal TB tends to affect the thoracic or thoracolumbar junction, brucellosis shows a distinct predilection for the lumbar spine [Figure 2]. Brucellosis primarily affects the anterior aspect of the vertebral endplates, leading to a characteristic serrated or irregular outline. The vertebral body itself is often relatively preserved. In contrast, TB frequently causes significant, widespread destruction of the vertebral bodies, often leading to their collapse. The rarity of large paravertebral abscesses and the absence of extensive subligamentous spread and multi-level contiguous vertebral involvement in brucellosis are a few hallmark features that can differentiate it from tubercular spondylodiscitis.

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Figure 2:

Spinal Brucellosis. (a) Lateral radiograph of the lumbar spine in a 34-year-old female with backache for about 3 months, shows reduced L3-L4 disc space with erosion of the inferior endplate of L3. (b) Sagittal T1-weighted, (c) T2-weighted, and (d) coronal short tau inversion recovery magnetic resonance images demonstrate fluid signal in the L3-L4 intervertebral disc and adjacent endplate erosions (white arrows in d), suggesting infective spondylodiscitis. The patient also had lesions in the lungs and liver. Based on imaging, empirical anti-tubercular therapy was given with inadequate clinical response after 2 months. (e) A biopsy was performed from the liver lesion, and the high-power photomicrograph (hematoxylin & eosin, ×400) shows the presence of non-caseating granulomas. Enzyme-linked immunosorbent assay immunoglobulin G for Brucella was positive in this patient, which confirmed the diagnosis.

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Fungal infections are rare, making up only about 0.5% of cases, and viral and parasitic causes are even less common. However, when fungal infections do occur, they most often affect the vertebrae. Of these, about a third are due to Aspergillus and another third are due to Candida.^[15,16]

Multiple contiguous vertebral body involvement with subligamentous, intraosseous, and paraspinal abscesses is a hallmark feature of tubercular spondylodiscitis,^[17] which characteristically differentiates it from pyogenic spondylodiscitis, which often shows affection of a single vertebral body with absence of subligamentous and intraosseous abscesses. However, sometimes involvement of multiple contiguous vertebral bodies can also be seen in bacterial spondylodiscitis. In such a scenario, other corroborative findings, such as small, non-loculated abscesses with thick shaggy walls of pyogenic spondylodiscitis as compared to thin-walled, smooth, large, loculated abscesses in tubercular spine, should be given importance.^[18] A diagnosis is easily confirmed when a patient’s blood cultures are positive. However, if they are negative, an image-guided biopsy is essential [Figure 3].

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Figure 3:

Flowchart for workup of suspected infective spondylodiscitis.

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The emerging role of quantitative magnetic resonance imaging (MRI) techniques, such as T2 mapping, offers a powerful, novel dimension. The T2 value of the involved vertebra in bacterial etiology was found to be markedly higher than that in Pott’s spine.^[19] The different inflammatory processes, such as a caseating granuloma in TB versus an acute, suppurative infection in pyogenic spondylodiscitis, result in different fluid and tissue micromilieu within the affected vertebrae, affecting the T2 relaxation time.

Axial spondyloarthropathy (AS)

Inflammatory arthritic conditions such as ankylosing spondylitis/AS can present diagnostic challenges when differentiating from spinal TB [Figure 4]. Elevated inflammatory markers, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), add complexity to the diagnostic process, as they can be seen in both. Sacroiliitis, which is the hallmark of ankylosing spondylitis, may also resemble tuberculous infection patterns. When sacroiliac joint inflammation is associated with spinal changes consistent with infection, ankylosing spondylitis and other seronegative spondyloarthropathies should be considered.

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Figure 4:

Axial spondyloarthropathy (AS). (a) Sagittal and (b) coronal magnetic resonance images in a 28-year-old male with backache for 2–3 months showed intense edema in the left-sided posterior elements in the lumbar region (dashed circles in a and b). Repeat imaging after 6 months of anti-tubercular therapy was done in view of inadequate clinical response and to assess treatment response. Follow-up sagittal images of (c) thoracic and (d) lumbar spine revealed new areas of edema at the posterior corners of the thoracic spine (white arrows in c) with resolution of signal abnormalities in the lumbar spine (dashed circle in d). (e) Dedicated coronal T1-weighted and (f) short tau inversion recovery (STIR) images of the sacro-iliac joints demonstrate changes of chronic bilateral sacroiliitis (yellow circles in e) with active edema on the left (block arrow in f). Re-assessment of the earlier images revealed that these changes could be seen on the coronal STIR image (dashed arrow in b) with fatty metaplasia and edema in the SI joints. Further work-up confirmed AS with positive HLA-B27.

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These patients typically demonstrate hypointensity in subchondral bone on T1-weighted imaging and hyperintensity on T2-weighted sequences, resembling paradiscal TB. Andersson lesions may also mimic tuberculous discitis, as they exhibit bright signals on T2 sequences.^[20] When ankylosing spondylitis affects multiple spinal levels, it can be mistaken for disseminated TB.

Several distinguishing features that can aid in accurate diagnosis include the absence of paravertebral abscesses and the presence of syndesmophytes in ankylosing spondylitis. Andersson lesions characteristically affect all three spinal columns, which serves as another differentiating factor. Sacroiliitis is usually bilateral in inflammatory conditions, although affliction may be asymmetrical. In the sacroiliac joints, active lesions are characterized by bone marrow edema, synovitis, capsulitis, and enthesitis, all of which present as high-signal intensity on short tau inversion recovery (STIR) sequences.^[21] Symmetrical edema in the lower and posterior joint sections is typical, while unilateral edema may suggest an infectious cause. In the spine, active inflammation includes spondylitis, which appears as high-signal intensity at the vertebral corners (Romanus lesions), and spondylodiscitis (Andersson lesions), which affects the cortical plates and intervertebral discs. Other active lesions include arthritis in the facet joints and costovertebral joints, and enthesitis of the spinal ligaments.

Beyond active inflammation, MRI can also reveal features of long-standing damage. In the sacroiliac joints, this includes low-signal intensity areas representing subchondral sclerosis, bony defects from erosions, and bony fusion (ankylosis). Fat depositions, which appear as high-signal intensity, are also a sign of past inflammation. Similarly, chronic changes in the spine are characterized by new bone formation at the vertebral corners, known as syndesmophytes, and bony bridging, or ankylosis, both of which show low-signal intensity.^[22] Fat deposits on the vertebral corners are also considered a sign of previous inflammation and are a predictor of future syndesmophyte formation.

Joint effusion and extra-articular fluid collections/abscesses (e.g., extracapsular fluid collections, periarticular muscle edema) are significantly more common in infective sacroiliitis on MRI compared to inflammatory sacroiliitis. These findings help distinguish infection from spondyloarthropathy-related sacroiliitis. In contrast, inflammatory sacroiliitis due to seronegative spondyloarthropathy typically shows bone marrow edema and capsulitis without pronounced fluid collections extending into the surrounding soft tissues.^[23]

Paget’s disease

Paget’s disease can present as a hypointense lesion on T1-weighted images and a hyperintense lesion on T2-weighted images, which can be confused with spinal TB. However, hematological parameters and the characteristic absence of soft-tissue components in Paget’s disease can offer additional clues to differentiate between them. In the rare instance where vertebrae are affected by the lytic phase of Paget’s disease, radiographs reveal a marked reduction in bone density, leading to a “ghost vertebra” appearance. This can be challenging to distinguish from other causes of osteolysis and vertebral collapse, such as TB of the spine.^[24] However, computed tomography scans can confirm the diagnosis by demonstrating classic features of Paget’s disease, such as cortical thickening, trabecular hypertrophy, and vertebral expansion, findings that are typically absent in tubercular spondylitis. Another presentation of Paget’s disease, which often can mimic Pott’s spine, is “ivory vertebra.” It presents as a diffusely sclerotic vertebral body on radiograph and non-contrast computed tomography, with a corresponding hypointense lesion on T1- and T2-weighted images. While positron emission tomography and bone scans can aid in diagnosis, a histopathological examination remains the definitive mode to diagnose Paget’s disease.^[25]

Degenerative changes

Type 1 modic changes, characterized by hypo-intense lesions on T1-weighted MRI and hyper-intense lesions on T2-weighted MRI, can present a diagnostic dilemma due to their potential to involve paraspinal soft-tissue changes [Figure 5]. This similarity often leads to confusion with spinal TB. Asymmetric disc space narrowing with dehydrated disc, presence of osteophytes, and preserved end plates point toward a diagnosis of degenerative spine. Diffusion-weighted and T2-weighted/fluid-sensitive sequences are instrumental in differentiating infectious/inflammatory processes from degenerative spondylosis. Osteomyelitis, discitis, and abscess reveal hyperintensity on T2-weighted and fluid-sensitive sequences, which can be critical to clinch a diagnosis. The presence of a characteristic “claw sign” on sagittal diffusion-weighted images is a hallmark of degenerative spine disease [Figure 6]. It appears as well-defined, linear, and often paired areas of high-signal intensity located at the margins of adjacent vertebral bodies, near the affected disc.^[26] Recognition of this sign is instrumental in avoiding unnecessary biopsies in these patients. Believed to represent a physiological reactive response, this sign is particularly useful for distinguishing a degenerative condition with Modic type I changes from an infection.^[27]

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Figure 5:

(a-d) Degenerative spondylosis. (a and d) Sagittal T1 and (b and e) sagittal short tau inversion recovery (STIR) and (c and f) coronal STIR magnetic resonance (MR) images in a 49-year-old female with backache. (a-c) Initial MR images at the time of presentation show intense edema adjoining the L2, L3 vertebral end-plates, predominantly on the right side, with subtle adjacent soft-tissue edema. The intervening disc shows fluid signal intensity (white arrow in b). This was reported as Pott’s spine, and the patient started on empirical anti-tubercular therapy. (d-f) Follow-up imaging after 9 months shows subsidence of edema and loss of intervertebral disc space on the right with increased scoliosis. However, the prominent marginal osteophytes are clearly visualized (dashed circle in f), favoring degenerative etiology. Furthermore, there is an absence of end-plate erosions/osseous destruction, bony ankylosis, or paravertebral collections, which would be expected in a tubercular disease. Degenerative edema would also be expected to subside on conservative management.

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Figure 6:

Degenerative spondylosis. (a) Sagittal T1 and (b) sagittal T2, and (c) diffusion-weighted imaging (DWI) magnetic resonance images in a 47-year-old male with backache for few months and low-grade fever for 15 days. Reduced L5-S1 intervertebral disc height is seen with mixed signal within the disc (white arrow in b). Mild marrow edema is present at the adjoining end-plates. Note that the rest of the intervertebral discs appear normal in morphology (black stars in a and b). The involvement of a single disc and a history of fever raised suspicion of a low-grade infection. DWI (c) showed well-defined paired bands of hyperintensity at the margins of vascularized and normal marrow (black arrows), suggesting the presence of “claw-sign.” This was managed as a case of degenerative spondylosis.

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The presence of a vacuum phenomenon on CT is highly suggestive of a degenerated rather than infected disc. The end-plate changes in degeneration appear more irregular with the presence of end-plate sclerosis, whereas end-plate destruction or erosion favors infection.^[28] However, the presence of gas does not rule out infection, and in the appropriate clinical context, this may be well seen in more severe cases of infective spondylodiscitis, as was shown by Schömig et al.^[29]

While constitutional symptoms and hematological markers such as ESR and CRP can offer supportive evidence to help differentiate between degenerative spine and spinal TB, none of these indicators are definitive.

The patient’s age may be an important criterion, as degenerative spine disease is less likely in the younger patient. However, in older patients, differentiation is often challenging and therefore, a short imaging follow-up is recommended for excluding spinal TB in equivocal cases.

Metastasis

Metastasis in the spine can be difficult to distinguish from central spinal TB, as both can present with similar symptoms such as pain, weight loss, and appetite loss. The presence of a soft-tissue mass further complicates differentiation. Metastatic deposits typically spare the disc space and end plates, while spinal TB often shows irregular endplates. Furthermore, involvement of the posterior elements and pedicles is more indicative of a malignant process and is rarely seen in infective spondylodiscitis. Contrast-enhanced MRI is useful for differentiating between an abscess (peripheral rim enhancement), which is more common in TB, and a solid soft-tissue mass (homogenous enhancement) seen in metastasis.^[30]

This should be given consideration even in patients with a history of TB and/or presence of mediastinal lymphadenopathy [Figure 8]. The role of image-guided biopsy and histopathological evaluation cannot be overemphasized in such scenarios.

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Figure 8:

Spinal metastasis. A 47-year-old male with a past history of anti-tubercular therapy intake for pulmonary Koch’s 7 years ago, presenting with backache after a trivial trauma. (a) Sagittal T1, (b) short tau inversion recovery (STIR) and (c) post-contrast T1 fat-suppressed magnetic resonance images reveal contiguous involvement of mid dorsal vertebral bodies (dashed circle in a-c) as well as posterior elements (white arrows in a-c). Prevertebral soft tissue is evident (white star in b and c). (d) Coronal STIR and (e) post-contrast images show the presence of extensive conglomerated necrotic mediastinal lymphadenopathy (dashed white arrows). With the given clinical history, tuberculosis was given as a likely diagnosis. Biopsy from the supraclavicular lymph node, however, confirmed metastatic disease from small cell neuroendocrine carcinoma of the lung with nodal as well as spinal metastasis.

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Primary tumors-benign

Osteoid osteoma, a benign bone tumor, can be mistaken for spinal TB because it often presents with significant surrounding inflammation in MRI^[31] [Figure 9]. When located eccentrically within a vertebral body, it can appear as an abscess-like lesion. Several clues can help distinguish osteoid osteoma from TB. A key indicator for osteoid osteoma is the presence of pain that worsens at night, which typically responds well to nonsteroidal anti-inflammatory drugs. A CT scan is usually diagnostic, revealing a characteristic nidus surrounded by a sclerotic rim. Osteoblastoma is similar to osteoid osteoma but with a larger nidus (>1.5cm). These have a propensity to occur in posterior elements, which is a less favored location for TB.^[32]

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Figure 9:

Osteoid osteoma. (a) Short tau inversion recovery coronal and (b) sagittal magnetic resonance images in a 21-year-old male with severe back pain, show edema in the left transverse process and costo-transverse joint (white solid arrow in a and b), and a suspicious round hypointensity (dashed arrow in b). (c) Axial computed tomography image shows a characteristic nidus (white arrow) surrounded by a sclerotic rim (black arrow), pathognomonic of osteoid osteoma.

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Hence, the presence of unilateral edema on MRI, especially in an unusual location like posterior elements, accompanied by normal ESR and CRP levels, which are typically elevated in infections like TB, should raise suspicion for osteoid osteoma or osteoblastoma instead, and further imaging with CT should always be performed. CT usually clinches the diagnosis and can be used to guide ablation of the nidus as well.^[33]

An extremely important differential in the pediatric population that should always be considered is Langerhans cell histiocytosis (LCH). Involvement of the vertebra is known to occur in 10–18% of pediatric LCH.^[34] Collapsed vertebral body-vertebra plana can be found in both TB of the spine and LCH [Figure 10].^[35,36] However, the absence of paravertebral soft-tissue favors LCH. Nonetheless, biopsy should always be performed as a thumb rule in children to rule out LCH, for better survival and prognosis.

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Figure 10:

Langerhans cell histiocytosis (LCH). (a) Lateral cervical spine lateral radiograph in an 8-year-old male with neck pain and restricted movement demonstrates complete collapse of C4 vertebral body- vertebra plana (white arrow in a-c). (b) Sagittal T2-weighted, (c) T1-weighted and (d) T1-weighted fat saturation contrast-enhanced magnetic resonance images show complete collapse of the solitary cervical vertebral body with anterior epidural enhancement (dashed arrow in d). Biopsy proved it to be LCH.

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Primary tumors-malignant

Primary malignant spinal tumors of the spine, such as myeloma and plasmacytoma, lymphoma, and Ewing’s sarcoma, can also mimic spinal TB, owing to hyperintensity on T2-weighted imaging and hypointensity on T1-weighted imaging [Figures 11 and 12].^[37] Primary malignancy of the spine can mimic central TB. Spondylitis without discitis, flattened vertebra with sclerosis, or lesions within the spinal canal and epidural space are seen in tumors more often than TB. However, the presence of paravertebral abscesses with subligamentous spread, sparing of the posterior elements of the vertebra, and presence of skip lesions often favor the diagnosis of spinal TB over primary malignancy.^[38,39]

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Figure 11:

Spinal lymphoma. (a) Sagittal and (b) coronal short tau inversion recovery magnetic resonance images in a 44-year-old male who was referred from another centre with large paravertebral soft-tissue collections along with marrow edema involving multiple vertebral bodies as well as posterior elements. (c) Intraoperative image shows large paravertebral soft tissues, which proved to be lymphomatous deposits.

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Figure 12:

Plasmacytoma. (a) Sagittal T2-weighted and (b) T1-weighted Magnetic resonance images in a 44-year-old male with a history of pain over the lower back for 3 months, show vertebral body destruction, with serpiginous intraosseous soft tissue with herniation of disc into the L4 vertebra (white arrow in a and b). (c) C-arm-guided vertebral biopsy was done. (d) High power (hematoxylin & eosin, ×400) photomicrograph shows diffuse sheets of mature and atypical plasma cells with eccentric nuclei, coarse “clock-face” chromatin, prominent nucleoli, and perinuclear hof, consistent with plasmacytoma.

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However, misdiagnosis is still common in areas that lack experienced radiologists, scenarios being complicated by the fact that endemicity of TB may induce a cognitive bias in misinterpretation. Delayed diagnosis in these cases can lead to disease progression and poorer patient outcomes. This further highlights the importance of a timely biopsy for accurate characterization of indeterminate lesions. Table 1 summarises the common mimickers of Pott’s spine and radiological clues for differentiating these.