A fatal case of spinal tuberculosis mistaken for metastatic lung cancer: recalling ancient Pott's disease
Annals of Clinical Microbiology and Antimicrobials
A fatal case of spinal tuberculosis mistaken for metastatic lung cancer: recalling ancient Pott's disease
0 Institute of Pathology, Ruhr-University Bochum , Germany
1 Department of Medicine , Spital Bulach, Bulach , Switzerland
2 Department of Medicine III, Pneumology, Allergology and Sleep Medicine, University Hospital Bergmannsheil, Ruhr-University Bochum , Germany
3 Institute of Diagnostic Radiology, Interventional Radiology and Nuclear Medicine, University Hospital Bergmannsheil, Ruhr-University Bochum , Germany
Background: Tuberculous spondylitis (Pott's disease) is an ancient human disease. Because it is rare in high-income, tuberculosis (TB) low incidence countries, misdiagnoses occur as sufficient clinical experience is lacking. Case presentation: We describe a fatal case of a patient with spinal TB, who was mistakenly irradiated for suspected metastatic lung cancer of the spine in the presence of a solitary pulmonary nodule of the left upper lobe. Subsequently, the patient progressed to central nervous system TB, and finally, disseminated TB before the accurate diagnosis was established. Isolation and antimycobacterial chemotherapy were initiated after an in-hospital course of approximately three months including numerous health care related contacts and procedures. Conclusion: The rapid diagnosis of spinal TB demands a high index of suspicion and expertise regarding the appropriate diagnostic procedures. Due to the devastating consequences of a missed diagnosis, Mycobacterium tuberculosis should be considered early in every case of spondylitis, intraspinal or paravertebral abscess. The presence of certain alarm signals like a prolonged history of progressive back pain, constitutional symptoms or pulmonary nodules on a chest radiograph, particularly in the upper lobes, may guide the clinical suspicion.
In 2007, one-fifth of 5,020 tuberculosis (TB) cases
reported to the responsible German authority (Robert
Koch Institute) were extrapulmonary, mainly lymphatic
(9.1%) disease manifestations, but only 0.8% of all adult
TB cases were spinal TB . Even though spinal TB is
scarce in countries with a low incidence of TB, it is an
ancient human disease. While the characteristic clinical
features of tuberculous spondylitis were first described in
the medical literature by Sir Percivall Pott in 1779 (Pott's
disease) , spinal TB has been identified in Egyptian
mummies dating back to 3000 B. C. by typical skeletal
lesions and consecutive DNA analysis . A delay in
diagnosis and timely initiation of treatment of aggressive TB
manifestations like central nervous system (CNS) TB or
vertebral TB may cause severe and irreversible neurologic
sequelae including paraplegia, even if antimycobacterial
chemotherapy is available [4,5]. Moreover, as evidence of
either previous or current pulmonary TB is found in
approximately half the reported patients, a delay in
diagnosis may lead to further significant exposure of contacts,
particularly endangering health care workers and thus
highlighting TB's potential as a nosocomial and
occupational disease .
We report a fatal case of a patient with Pott's disease, who
was misdiagnosed and irradiated for metastatic lung
cancer of the spine. Subsequently, the patient progressed to
CNS TB, and finally, disseminated TB before the accurate
diagnosis was established after an in-hospital course of
approximately three months including numerous health
care related contacts and procedures .
A 67-year old Caucasian male of German descent
presented to the emergency department of an external
hospital at December 8th 2006 due to severe upper back pain.
His past medical history was unremarkable. He had no
history of previous TB or TB exposure. His complaints had
emerged over the past six month and were accompanied
by slight night sweats and a moderate weight loss.
Physical examination and routine laboratory studies on
admission including hemoglobin, white blood count and
Creactive protein (CRP) were within normal range.
Conventional radiographs of the chest and the thoracic spine
revealed a compression fracture of the third thoracic
vertebra (Th3) and a solitary pulmonary nodule of the left
upper lobe (Figure 1). On the basis of this coincidence, a
pathological vertebral fracture secondary to metastatic
lung cancer was suspected. The further work-up included
a computed tomography (CT) scan of the chest and of the
spine, which confirmed the thoracic vertebral
compression fracture. Moreover, it revealed lytic destructions of
the posterior margins of both adjacent vertebral bodies
and showed an intraspinal soft tissue mass expanding
between Th2 and Th5. Additionally, a tumorous lesion of
the ventral left upper lobe was observed. Apparent
mediastinal lymphadenopathy was interpreted as metastatic
disease of the mediastinal lymph nodes (Figure 2). Bone
scintigraphy was not suggestive of malignancy and
detected only minor degenerative alterations of the upper
spine. Both repeated transbronchial biopsies, which had
been obtained by flexible bronchoscopy, and repeated
CT-guided transthoracic needle biopsies of the pulmonary
nodule failed to establish a specific histological diagnosis,
oFCniogniunvrieteinatl1ioprneaslernatdaiotigornaphs of the thoracic spine and the chest
Conventional radiographs of the thoracic spine and
the chest on initial presentation. (A) Compression
fracture of the third thoracic vertebra (arrows). (B) Solitary
pulmonary nodule of 2.5 cm in diameter of the left upper lobe
(arrow), in posterior-anterior and lateral projection,
Given the progressive back pain and supposed spinal
instability, the patient was referred to another external
hospital, where a palliative irradiation of the upper
thoracic spine was initiated and a cumulative dose of 36 Gy
was applied over three consecutive weeks. However, the
patient's condition deteriorated and he soon developed
paresthesia and paralysis of both lower limbs. At this
point, magnetic resonance imaging (MRI) of the spine
revealed an extensive intraspinal abscess, which resulted
in compression of the upper thoracic spinal cord. Hence,
the patient was immediately referred to the
neurotraumatological service of our university hospital for surgical
Upon arrival at our institution on January 10th 2007 the
patient presented with incomplete paraplegia at the level
of Th3. Promptly, spinal decompression surgery including
laminectomy of Th2 to Th4, revision of vertebra Th3, and
thoracic spondylodesis from Th1 to Th6 was performed.
The histology of the removed intraspinal soft tissue mass
was read as an unspecific chronic inflammatory and
granulating process. No malignancy or specificity was evident.
Routine cerebrospinal fluid (CSF) cultures were sterile.
No further CSF analyses were performed. Soon, after an
initial post-operative improvement, the patient
deteriorated again and developed a persistent dorsal swelling,
reddening, and fluid collection that was suggestive of a
paravertebral abscess (Figure 3). Thus, surgical revision
was repeated. Again, routine CSF cultures grew no
microorganisms and no further CSF analyses were prompted.
Nevertheless, temperatures >38.0C persisted despite the
use of various antimicrobial regimes. Repeated routine
FCiTguscraen2s of the spine and the chest
CT scans of the spine and the chest. The sagittal
reconstruction of the native CT scan of the spine (A) confirms a
compression fracture of the third thoracic vertebra with lytic
destructions of posterior margins of both adjacent vertebral
bodies (arrow). The axial reconstruction of the contrast
enhanced CT scan of the chest (B) suggests a tumorous
lesion of the ventral left upper lobe (large arrow) with
accompanying mediastinal lymphadenopathy (small arrows).
blood cultures remained sterile and infectious
endocarditis was ruled out by transesophageal echocardiography. A
CT scan of the brain, which was performed due to
persistent headaches, showed no abnormalities, while a
followup CT scan of the chest showed multiple novel opacities
with tree-in-bud sign (Figure 4).
When the patient was finally referred to the pulmonary
department for further evaluation of the initially
sustFMioiRgnIu)oreft3he thoracic spine (T2-weighted, sagittal
reconstrucMRI of the thoracic spine (T2-weighted, sagittal
reconstruction). The dorsal fluid collection suggests a
paravertebral abscess (large arrow) just above the fractured and
operated third thoracic vertebra (small arrow).
pected metastatic lung cancer on February 28th 2007, he
had developed a new brachiofacially accentuated,
rightsided hemiparalysis and aphasia. Now, MRI of the brain
revealed multiple fresh ischemic bihemispheric and
pontine lesions. Again, infectious endocarditis was ruled out.
The patient was febrile with a temperature of 39.3C
despite an antimicrobial regime consisting of Imipeneme/
Cilastatin, Vancomycin, Ciprofloxacin, and
Metronidazole, which had been administered for the past two weeks.
At this time, the major findings on physical examination
included cachexia, signs of respiratory distress (a
respiratory rate of 25/min, productive cough, but insufficiently
coughing up), moderate fluid overload (bilateral basal
pulmonary rales, peripheral edema), and a dorsal
paravertebral reddish and fluctuating swelling at the site of prior
surgery, but no meningeal signs. Furthermore, we
observed oral candidiasis and a unilateral segmental
herpes zoster rash at the lower back that both indicated
relevant immunosuppression. Now, routine laboratory
studies showed markedly increased inflammatory activity
(CRP 22 mg/dL), but a normal white blood count of
4,900/L. HIV serology was negative. Remarkably, the
FFoiglluorwe-u4p contrast enhanced CT scan of the chest
Follow-up contrast enhanced CT scan of the chest.
The axial CT reconstructions in craniocaudal sequence
(AD) show exudative pulmonary tuberculosis with multiple
novel opacities and tree-in-bud sign (arrows). Secondary
findings: post-specific scarring (A), tuberculoma (B) of the left
upper lobe, and small bilateral pleural effusions (B-D).
interferon- release assay QuantiFERON-TB Gold
InTube was negative (IFN 0.189 IU/mL).
However, complicated and disseminated TB with bone,
soft tissue, CNS, and pulmonary involvement was
suspected by thoroughly reviewing the patient's previous
history and medical course. We immediately prompted
retrospective polymerase chain reaction (PCR) analysis of
the surgically resected tissue regarding the presence of
Mycobacterium-tuberculosis-(MTB)-complex DNA and
initiated microbiological sampling for the confirmation
of the suspected diagnosis. Aspirates of the dorsal fluid
collection suggested an abscess (purulent appearance, low
glucose concentration of 0.3 mmol/L), but no CSF fistula
(low -trace-protein of 3.8 mg/L). No microorganisms
were detected on gram stain or acid-fast bacilli (AFB)
smear. CSF was obtained by lumbar puncture and showed
signs of purulent meningitis (800/L predominantly
polymorphonuclear cells, low glucose concentration of 0.8
mmol/L, elevated protein level of 1.5 g/L). CSF
microscopy (gram stain and AFB smear), routine cultures, and
PCR for MTB-complex DNA were negative. As the patient
was suffering from severe respiratory distress,
bronchoscopy was considered potentially harmful and therefore
abandoned. Instead, repeated morning fasting gastric acid
aspirates, which may be considered as swallowed
respiratory secretions according to the German authorities ,
were obtained for TB cultures in order to evaluate for the
dissemination of viable mycobacteria via the respiratory
route. AFB smears of repeated gastric acid aspirates were
negative. Subsequently, both PCR results of the resected
intraspinal tumor tissue and the aspirate of the
paravertebral abscess indicated the presence of MTB-complex DNA.
After two weeks TB cultures grew MTB from both the
abscess and gastric acid aspirates and after six weeks from
CSF, too. The MTB isolate was fully susceptible to all first
line antimycobacterial drugs. All samples had been
negative on AFB smears with both auramine and Ziehl-Neelsen
staining (Table 1).
On March 7th 2007, a total of 57 days after referral to our
hospital, and three months after the first presentation to
the external hospital, isolation and antimycobacterial
treatment with rifampicine, isoniazide, pyrazinamide,
and streptomycin were initiated. Due to apparent
meningitis, extensive cerebral vasculitis, and suspected
arachnoiditis, an adjuvant treatment with oral corticosteroids
was administered and tapered after three weeks .
Lumbar puncture was repeated one week after treatment
initiation and showed clearly improved findings (290/L
mixed mono- and polymorphonuclear cells, negative AFB
smear, negative TB cultures after eight weeks). Within the
following weeks the patient's general and neurological
condition gradually improved. Isolation was terminated
and mobilization into a wheel chair was achieved after
four weeks of treatment due to intensive physical therapy
NA positive positive positive
*PCR amplified gene fragments specific for Mycobacterium-tuberculosis-complex mycobacteria (insertion sequence IS6110). Cultures grew
Mycobacterium tuberculosis fully susceptible for all first line antituberculous drugs; Morning fasting gastric acid was considered as swallowed
respiratory secretions according to the German authorities . AFB = acid-fast bacilli; NA = not assessed; PCR = polymerase chain reaction; TB =
(See additional file 1: Table S1 - Summary of the patient's
diagnostic and therapeutic in-hospital course).
Unfortunately, at April 12th 2007 the patient died due to a lethal
episode of ventricular fibrillation with cardiac arrest.
Autopsy confirmed all clinically suspected TB-related
diagnoses: spinal TB (Pott's disease) with subsequent
tuberculous meningoencephalitis, extensive cerebral
vasculitis (Figure 5), spinal arachnoiditis, paravertrebral
tuberculous abscess, miliary pulmonary TB (Figure 6),
and a tuberculoma of the ventral left upper lobe (Figure
7). Death occurred secondary to CNS dysregulation with
elevated intracranial pressure (Figure 8).
There are some important lessons this fatal case teaches.
The clinical diagnosis of TB, particularly extrapulmonary
TB, requires a certain extent of clinical suspicion and
expertise regarding the adequate diagnostic tests. Along
with Staphylococcus aureus and a few other bacteria, MTB
is still an important cause of spondylitis, intraspinal or
paravertebral abscess. In TB low incidence countries
spinal TB is mainly a disease of the elderly, resulting from
endogenous reactivation of infectious foci that spread
during the initial bacteremia. Pott's disease most often
affects the lower thoracic and lumbar spine, while disease
of the upper thoracic and cervical spine is potentially
more disabling [4,9,10]. The most common cause of delay
in the diagnosis of Pott's disease is failure to consider the
diagnosis. Hence, skeletal TB should always be considered
in patients with focal bony abnormalities and a chest
radiograph compatible with prior or active TB.
PFuiglmuorena6ry tuberculosis (hematoxylin and eosin stain)
Pulmonary tuberculosis (hematoxylin and eosin
stain). Miliary foci with partially active necrotizing epitheloid
granulomas (A) besides postspecific scarring with irregular
traction emphysema and bronchiolectasia (B).
Our patient showed a combination of alarm signals
(progressive back pain over several months, presence of a
pulmonary nodule of the left upper lobe, night sweats and
weight loss), which should have prompted further
workup in order to enforce a definite diagnosis. Back pain is the
typical presenting symptom of early Pott's disease, but
signs or symptoms of systemic infection are often missing.
Constitutional symptoms, fever, and weight loss are
unspecific and present in less than 40% of spinal TB cases.
Due to the subtle nature of symptoms, diagnostic
evaluations are often not initiated until the process is advanced.
However, establishing the correct diagnosis is challenging
and misdiagnoses may occur in up to 41% of cases .
Hence, a significant proportion of patients present with
neurological impairment in advanced stages of disease
[4,12]. The early changes of spinal TB are particularly
difficult to detect by routine radiographs of the spine. CT and
sTFtuiagbinue)recu5lous meningoencephalitis (hematoxylin and eosin
Tuberculous meningoencephalitis (hematoxylin and
eosin stain). High-grade active and chronic lymphocytic and
granulomatous cerebral vasculitis (arrow).
FMiagcurroesc7opic preparation of the left lung
Macroscopic preparation of the left lung. Tuberculoma
of the left upper lobe (2.5 cm in diameter, arrow).
cFMeiagrceurbroresacl8oepdiecmpareparation of the brain demonstrating final
Macroscopic preparation of the brain demonstrating
final cerebral edema. The arrows indicate a lower
cerebral incarceration secondary to increased intracranial
pressure, which caused CNS regulation disturbance, and finally,
resulted in ventricular fibrillation and cardiac arrest.
MRI scans of the spine are considerably more sensitive
and should be obtained whenever an infectious process is
CT-guided percutaneous biopsy of the vertebral body is an
effective and safe diagnostic procedure for spinal lesions
of unclear origin [14,15]. The consecutive microbiological
and histological work-up including PCR may help to
establish a rapid diagnosis as PCR results are usually
available within one or two working days. In this context, PCR
is an extremely useful tool for the guidance of further
diagnostic steps and treatment decisions, particularly if
the initiation of antimicrobial chemotherapy is crucial.
Nevertheless, it should be mentioned that PCR has a
limited sensitivity, particularly in AFB smear negative
specimens, and that TB culture of clinical specimens remains
the gold standard for the confirmation of active TB
infection and the assessment of mycobacterial resistance .
Combining radical surgery with a standard triple or
quadruple antimycobacterial chemotherapy produces the most
favourable outcomes and a more rapid neurological
recovery [4,10], while a conservative, nonsurgical
approach may be warranted in patients without advanced
neurological deficits [9,17].
IGRAs were developed as immunological diagnostics for
the diagnosis of TB infection rather than TB disease, and
data on the sensitivity of these assays in critically ill
patients and patients with severe immunosuppression
and advanced or disseminated active TB is sparse .
There were important implications of the delayed
diagnosis for the health care workers (HCWs) at our institution.
Two-hundred and two HCWs were evaluated, 158
subjects were screened for the nosocomial transmission of TB,
and 143 subjects were eventually analyzed within a
recently published contact investigation . However,
this study concluded that, fortunately, major nosocomial
TB transmission from the source case did not occur.
Nevertheless, the present case illustrates the increased risk of
occupational TB transmission in health care [6,19].
Finally, the following basic implications for the general
clinical practice emerge from this fatal case: a) whenever
possible, aim at establishing a definite diagnosis before
initiating treatment, particularly if cancer is suspected,
and immediate or extensive therapeutic implications
arise; b) easily treatable causes of disease should always be
thoroughly considered and regularly re-evaluated, if
applicable; c) copying and pasting medical diagnoses
without critical reflection endangers patients and should
therefore be strictly rejected.
Awareness is the key point of diagnosing Pott's disease, an
ancient but nowadays rare manifestation of
extrapulmonary TB. Due to the devastating consequences of a missed
diagnosis, MTB should be considered early in every case of
spondylitis, intraspinal or paravertebral abscess. The
presence of certain alarm signals like a prolonged history of
progressive back pain, constitution symptoms or
pulmonary nodules on a chest radiograph, particularly in the
upper lobes, may guide the clinical suspicion. CT-guided
percutaneous biopsy of the affected vertebral body and
the consecutive microbiological and histological work-up
including PCR may contribute to rapidly establishing the
Written informed consent was obtained from the patient's
widow for publication of this case report and any
accompanying images. A copy of the written consent is available
for review by the Editor-in-Chief of this journal.
The authors declare that they have no competing interests.
Furthermore, our case emphasizes that IGRAs are of
limited value in the context of severely ill patients, where false
negative results occur secondary to the host's anergy.
FCR took clinical care of the patient and drafted the
manuscript. AT, AW and VN conducted and interpreted the
pathological and radiological studies, respectively, and
revised the manuscript critically for important intellectual
content. HWD, GSW and GR took clinical care of the
patient and revised the manuscript critically for important
intellectual content. All authors read and approved the
Additional file 1
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