S p e c i a l A r t i c l e P i c t o r i a l E s s ay

Tan et al.
Radiologic Patterns in Tuberculosis

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Special Article
Pictorial Essay

Tuberculosis: A Benign Impostor

Cher H. Tan1
Dimitrios P. Kontoyiannis 2
Chitra Viswanathan1
Revathy B. Iyer 1

OBJECTIVE. The purpose of this article is to illustrate the overlapping radiologic patterns in proven tuberculosis cases in patients initially referred to our cancer center for presumed malignancy.
CONCLUSION. Tuberculosis can simulate malignancy both clinically and radiologically, especially in its extrapulmonary form.

Tan CH, Kontoyiannis DP, Viswanathan C, Iyer RB

Keywords: malignancy, tuberculosis

DOI:10.2214/AJR.09.3055
Received May 15, 2009; accepted after revision
August 18, 2009.
1
Department of Diagnostic Radiology, The University of
Texas M. D. Anderson Cancer Center, 1515 Holcombe
Blvd., Unit 368, Houston, TX 77030-4009. Address
correspondence to R. B. Iyer.
2
Department of Infectious Diseases, The University of
Texas M.D. Anderson Cancer Center, Houston, TX.

AJR 2010; 194:555561

0361803X/10/1943555
American Roentgen Ray Society

AJR:194, March 2010

total of 9.2 million cases of tuberculosis were reported worldwide

in 2006 [1], and the disease continues to be a common health
problem worldwide despite efforts at eradication and control. Although the incidence of tuberculosis and tuberculosis-related mortality
has been on the decline in the United States,
with an incidence rate of 4.6 per 100,000 people, it remains a problem among the migrant
and HIV-infected populations [2].
The causative pathogen is Mycobacterium
tuberculosis, an aerobic, non-spore-forming
bacillus. Its mechanism of destruction lies in
the development of cell-mediated hypersensitivity, leading to the formation of caseous
granulomas. The lungs are the primary organ of spread, accounting for approximately
70% of cases [2]. Extrapulmonary infection
generally occurs as a result of hematogenous
dissemination from a clinically occult pulmonary focus. Tuberculosis granulomata, especially in extrapulmonary disease, may be
confused with neoplasm. Accurate diagnosis
is important so that appropriate therapy can
be administered. Although steroids form a
cornerstone of treatment of many malignancies, their use may be contraindicated in the
setting of tuberculosis [3].
Lung
Pulmonary involvement is the major cause
of tuberculosis morbidity and mortality. The
Ghon focus is the hallmark of pulmonary infection and may either enlarge to form an
area of consolidation or show healing with
central caseous necrosis. On imaging, pri-

mary tuberculosis typically manifests as parenchymal consolidation that can occur in

any pulmonary lobe or segment, often with
associated lymphadenopathy. In the postprimary form, there is a predilection for the superior segments of the lungs. Cavitation of
the lesion occurs as the tubercle erodes into
and discharges its contents into the airways
(Fig. 1). Endobronchial and miliary (hematogenous) dissemination are other features of the disease.
Tuberculosis may account for one quarter
of the cases of lung infection initially presumed to be lung cancer [4]. Benign-type
(diffuse, central, or lamellar) calcifications
may be clues to the imaging diagnosis of tuberculosis over malignancy. However, tuberculomas can appear masslike and tend to be
mistaken for malignancy if typical characteristics, such as upper lobe involvement and
calcification, are absent [5]. Furthermore, tuberculomas may be hypermetabolic on 18FFDG PET (Figs. 1 and 2), showing significant overlap of standardized uptake values
with malignant nodules [6]. Even when there
are characteristic features, such as the treein-bud appearance of endobronchial spread
on CT, neoplastic, inflammatory, or other infectious conditions cannot be totally excluded [7]. When the combination of clinical, laboratory, and imaging findings does not help
to exclude malignancy, transthoracic needle
biopsy can to lead to a timely diagnosis.
Cervical Lymph Nodes
Lymphatic involvement is the most common form of extrapulmonary tuberculosis

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Tan et al.
and accounts for 43% of cases [2]. Tuberculosis infection in the otolaryngic region often presents as cervical lymphadenitis. It can
result through direct extension or hematogenous spread. A history of tuberculous infection need not always be present and was seen
in only 16.1% of cases in one series [8].
At ultrasound, the nodes may be anechoic
or hypoechoic, with or without septations, and
often surrounded by a thick capsule (Fig. 3).
Rim-enhancing nodal lesions with central low
attenuation on CT are characteristic for tuberculosis (Fig. 4). However, these findings are
not pathognomonic, and one should always
consider lymphoma and metastatic lymphadenopathy from head and neck primary lesions
as possible differential diagnoses. Biopsy usually provides a definitive diagnosis.
Bones
Appendicular Skeleton
The clinical presentation of tuberculosis
osteomyelitis is often subtle and insidious.
This disease is less common than tuberculosis of the spine and joints, and failure to consider it among the differential diagnoses may
lead to a delay in treatment. The disease usually spreads hematogenously through large
areas of the medullary cavity, causing extensive necrosis. The cystic variant is more
commonly seen in children (Fig. 5). At imaging, it initially presents as a nonspecific
area of osteolysis that could be mistaken for
malignancy. CT and MRI are useful to show
the extent of bone destruction and to evaluate
for associated soft-tissue extension (Fig. 6).
Multifocal involvement can mimic disseminated malignancies [9] such as lymphoma,
leukemia, multiple myeloma, and metastasis
(Fig. 7).
Vertebra
Spondylitis is the most common form of
skeletal tuberculosis infection, accounting
for 60% of cases [10]. The disease typically involves the anterior vertebral body. Subligamentous spread to contiguous vertebrae
with diskitis is characteristic. Involvement of
the posterior elements is useful as a distinguishing feature but with the advent of CT
and MRI, has been increasingly seen in tuberculosis spondylitis and therefore is not
useful as a finding on its own [11] (Fig. 8).
Typically, osteolysis, compression fractures,
and varying degrees of sclerosis will be seen.
Paraspinal and extradural disease that is occult
on radiography can lead to cord compression, a complication that can be accurately

556

depicted by MRI. Changes of edema and enhancement within the vertebral bodies are
not specific for infection and can be seen in
lymphoma, multiple myeloma, and chordoma
as well as metastatic disease.
Brain
Involvement of the CNS is the most clinically significant type of systemic tuberculosis because of its high mortality rate and
possible neurologic sequelae. Clinical presentation is often subtle and secondary to the
mass effect from perilesional edema. Granulomas are the most common parenchymal
manifestation. Like metastatic lesions, they
tend to occur in the corticomedullary junctions of the parietal and frontal lobes. After
treatment with antituberculous agents, there
may be transient enlargement of the lesion
secondary to an inflammatory response.
On CT or MRI, solid or ring enhancement
of the lesions may be seen, depending on the
degree of central necrosis and age of the lesion. Diffusion-weighted MRI, which typically shows restricted diffusion, as well as
MR spectroscopy, is commonly inconclusive in tuberculosis and may not distinguish
it from a brain tumor (Fig. 9). Therefore,
the diagnosis is usually established through
brain biopsy [12].

large omental masses, matted loops of bowel, and nodular thickening of the mesentery
(Fig. 11). Nodal morphology, nodal distribution, mesenteric nodularity, and omental
caking are not useful to distinguish between
tuberculosis and peritoneal carcinomatosis
because of considerable overlap [13].
In particular, the combination of ascites,
elevated CA-125 levels, and pelvic and peritoneal masses found in tuberculosis can be
easily mistaken for coelomic spread of ovarian cancer [14] (Fig. 12). Peritoneal tuberculosis can also be hypermetabolic on FDG
PET, further mimicking peritoneal carcinomatosis [15]. Definitive diagnosis is made
with tissue or fluid analysis and culture.
Conclusion
Tuberculosis frequently mimics malignancy both radiologically and clinically despite the use of the most sophisticated imaging techniques available. In these cases, the
correct diagnoses can be made with certainty only with biopsy.
Acknowledgment
The authors thank Camilla T. Ramagli of
The M. D. Anderson Cancer Center for her
help with the illustrations.
References

Bowel
Because of the abundance of lymphoid tissue, the ileocecal region is most commonly affected in tuberculosis [10] (Fig. 10). Involvement of other regions of the gastrointestinal
tract has been reported but is less common
[10]. Pathologically, the disease comes in three
macroscopic forms: ulcerative, hypertrophic,
and ulcerohypertrophic. In the less-common
hypertrophic form, there is an extensive inflammatory response resulting in a thickened
multinodular mucosa. On CT, the cecum and
terminal ileum are often concentrically thickened, with associated ileocecal valve enlargement and mesenteric lymphadenopathy [10].
Endoscopic biopsy is performed to exclude
lymphoma and primary adenocarcinoma.
Peritoneal Involvement
Peritoneal involvement in tuberculosis is
present in 5% of cases [2] and is usually associated with widespread abdominal disease
involving the lymph nodes or bowel. There
are three main types of tuberculous peritoneal involvement (wet, fibroticfixed, and dry
plastic). Among them, the fibroticfixed type
most resembles malignancy. It manifests as

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HIV activities through publicprivate mix and
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February 2008. whqlibdoc.who.int/hq/2008/
WHO_HTM_TB_2008.408_eng.pdf. Accessed
February 27, 2009
2. Centers for Disease Control and Prevention Website. Reported tuberculosis in the United States,
2006. www.cdc.gov/tb/surv/surv2006/pdf/FullReport.pdf. Accessed February 27, 2009
3. De La Rosa GR, Jacobson KL, Rolston KV, et al.
Mycobacterium tuberculosis at a comprehensive
cancer centre: active disease in patients with underlying malignancy during 19902000. Clin Microbiol Infect 2004; 10:749752
4. Rolston KV, Rodriguez S, Dholakia N, et al. Pulmonary infections mimicking cancer: a retrospective, three-year review. Support Care Cancer
1997; 5:9093
5. Cherian MJ, Dahniya MH, al-Marzouk NF, et al.
Pulmonary tuberculosis presenting as mass lesions and simulating neoplasms in adults. Australas Radiol 1998; 42:303308
6. Goo JM, Im JG, Do KH, et al. Pulmonary tuberculoma evaluated by means of FDG PET: findings
in 10 cases. Radiology 2000; 216:117121

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Radiologic Patterns in Tuberculosis

7. Rossi SE, Franquet T, Volpacchio M, et al. Treein-bud pattern at thin-section CT of the lungs: radiologicpathologic overview. RadioGraphics
2005; 25:789801
8. Kanlikama M, Mumbu S, Bayazit Y, et al. Management strategy of mycobacterial cervical lymphadenitis. J Laryngol Otol 2000; 114:274278
9. Chang DS, Rafii M, McGuinness G, et al. Primary multifocal tuberculous osteomyelitis with involvement of the ribs. Skeletal Radiol 1998;
27:641645

10. Harisinghani MG, McLoud TC, Shepard JA, et al.

Tuberculosis from head to toe. RadioGraphics
2000; 20:449470
11. Gupta RK, Agarwal P, Rastogi H. Problems in
distinguishing spinal tuberculosis from neoplasia
on MRI. Neuroradiology 1996; 38[suppl 1]:S97
S104
12. Omuro AM, Leite CC, Mokhtari K, et al. Pitfalls
in the diagnosis of brain tumours. Lancet Neurol
2006; 5:937948
13. Ha HK, Jung JI, Lee MS, et al. CT differentiation

of tuberculous peritonitis and peritoneal carcinomatosis. AJR 1996; 167:743748

14. Bilgin T, Karabay A, Dolar E, et al. Peritoneal tuberculosis with pelvic abdominal mass, ascites
and elevated CA 125 mimicking advanced ovarian carcinoma: a series of 10 cases. Int J Gynecol
Cancer 2001; 11:290294
15. Chen CJ, Yao WJ, Chou CY, et al. Peritoneal tuberculosis with elevated serum CA125 mimicking
peritoneal carcinomatosis on F-18 FDG-PET/CT.
Ann Nucl Med 2008; 22:525527

Fig. 163-year-old man initially diagnosed with squamous cell carcinoma of right lung, but subsequent repeat
biopsies were negative for malignancy.
A, Axial CT image in lung window setting shows single cavitary mass involving right upper lobe (arrow). There
was no associated lymphadenopathy.
B, In 18F-FDG PET image obtained 2 weeks after A, lesion is shown to be hypermetabolic (arrow). CT-guided
percutaneous core needle biopsy of lesion confirmed diagnosis of tuberculosis, and patient was started on
antituberculosis drug regimen.
C, Follow-up axial CT image obtained 14 months after A shows marked improvement of mass (arrow) with
residual scarring.

Fig. 254-year-old man with history of heavy smoking and recent weight loss who was referred for suspected lung cancer.
A, Axial CT image in lung window setting shows single spiculated mass (arrow) in superior segment of left upper lobe. There was no
associated lymphadenopathy.
B, Mass (arrow) with maximum standard uptake value of 17 is seen on 18F-FDG PET image. This finding was highly suspicious for malignancy.
Bronchoscopy showed acute fibrinous pneumonitis but no evidence of neoplasm. Subsequent percutaneous CT-guided core needle
biopsy showed necrosis and granulomatous inflammation. Cultures were positive for tuberculosis. Patient was returned to his community
infectious disease physician for appropriate treatment.

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Tan et al.

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Fig. 335-year-old woman who presented with lump

in her neck.
A, Real-time ultrasound Doppler image shows
heterogeneously hypoechoic nodal mass (arrow)
with surrounding vascularity located in right lower
jugular chain.
B, CT scan of neck and chest shows multiple enlarged
mediastinal lymph nodes (arrow) with necrotic
centers. Differential diagnosis at that time was
lymphoma. Dominant necrotic node in neck was
biopsied and culture was positive for tuberculosis.

Fig. 439-year-old man who presented with large

right neck lump.
A, Axial contrast-enhanced CT of neck shows large
necrotic right internal jugular lymph node (arrow)
with irregular borders.
B, Frontal chest radiograph shows extensive bilateral
nodules against background of miliary opacities.
Metastatic disease from head and neck primary
malignancy was considered. Cultures were positive
for tuberculosis.

Fig. 53.5-year-old boy who presented with refusal to walk over 2 months, without fever or elevated WBC.
A, Anteroposterior radiograph of right knee shows lytic lesion (arrow) in medial distal metaphyseal region of right femur. Absence of periosteal reaction and lack of
permeative pattern were clues to benign nature. However, presence of associated soft-tissue mass led to consideration of Ewing sarcoma and lymphoma.
B, Axial CT scan of right femur in bone window setting shows lytic, intramedullary lesion (arrow) with relative sparing of cortex. Adjacent soft-tissue mass was of fluid
attenuation. CT-guided biopsy of lesion was performed at same sitting and was positive for tuberculosis. He was started on appropriate antituberculosis medications.
C, Follow-up anteroposterior radiograph of right knee obtained 1 year later shows interval decrease in size of lytic lesion (arrow) but increased sclerosis compatible with
healing. There has also been resolution of accompanying soft-tissue swelling.

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Radiologic Patterns in Tuberculosis

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Fig. 652-year-old woman with history of left hip

mass who was referred for evaluation of possible
malignancy.
A, Axial contrast-enhanced CT scan of pelvis
shows well-circumscribed rim-enhancing fluid
collection (arrow) in contiguity with lytic lesion of
greater trochanter of left femur. Myxoid variant of
low-grade sarcoma can present as cystic mass, but
focal destruction of adjacent bone, as seen in this
case, would be highly unusual. Patient underwent
biopsy of lytic lesion in proximal left femur as well
as ultrasound-guided needle biopsy of fluid-filled
mass. Cultures were positive for tuberculosis, and
appropriate therapy was initiated.
B, Follow-up axial contrast-enhanced CT scan of
same region obtained 1 year later shows marked
improvement, with new bone formation within lytic
lesion (arrow).

B
Fig. 741-year-old man diagnosed with
acute myeloid leukemia. His second course
of chemotherapy was complicated by active
tuberculosis with miliary dissemination.
A, Axial T2-weighted image of pelvis reveals
disseminated lesions, including sacrum and bilateral
iliac bones. Most pronounced lesion in left iliac bone
contains small central fluid collection (arrow). There
is extension through bony cortex into superior aspect
of left gluteus medius muscle, with surrounding
edema.
B, Sagittal contrast-enhanced T1-weighted fatsaturated image of lumbar spine shows diffuse
replacement of L1 vertebral body with epidural
extension (arrow). Abnormal leptomeningeal
enhancement was also present. It was uncertain
whether these findings represented infection or
underlying tumor. CSF analysis was positive for
acute leukemic blast cells. However, biopsy of L1 was
positive for tuberculosis instead.

Fig. 846-year-old woman who presented with 3 months of lower back pain.
A, Sagittal T2-weighted MR image shows enhancing mass (arrow) involving posterior T11 vertebra.
B, Axial contrast-enhanced fat-saturated T1-weighted image shows right-sided epidural extension (arrow) resulting in 50% central spinal canal stenosis and
narrowing of adjacent neural foramen. Differential diagnoses included tuberculosis, lymphoma, and metastatic disease. CT-guided biopsy of right T11 pedicle showed
granulomatous inflammation. She was started on empirical antituberculous therapy. Spinal biopsy culture was positive for tuberculosis.
C, Axial contrast-enhanced fat-saturated T1-weighted image obtained 2 months after A and B shows interval decrease in size of enhancing focus (arrow), consistent
with positive treatment response.

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Tan et al.

Fig. 935-year-old woman who presented with 7-month history of worsening headaches and vague visual symptoms.
A, Axial contrast-enhanced CT scan of brain shows left occipitoparietal mass (arrow), with perilesional vasogenic edema.
B, Axial T2-weighted image shows heterogeneous, hyperintense mass (arrow) with marked perilesional edema. Metastases, lymphoma, and glioblastoma multiforme
could have similar appearance.
C, Single-voxel MR spectroscopy performed over lesion in left parietooccipital region shows high choline peak (arrow) and depressed N-acetylaspartate peak,
suspicious for tumor. Gross total excision of lesion revealed granulomatous disease and cultures were positive for tuberculosis.

Fig. 1055-year-old gravida 4, para 3, postmenopausal woman who experienced intermittent lower abdominal pain. CA-125 was noted to be significantly elevated (492
mol/L), hence malignancy had to be ruled out.
A, Axial contrast-enhanced CT image shows marked thickening of cecum (arrow), with multiple enlarged ileocolic lymph nodes. There is associated stranding and
thickening of greater omentum. This may be mistaken for locally advanced cecal carcinoma.
B, Axial contrast-enhanced CT image shows low-attenuation mass located within uterus (arrow), later confirmed to represent degenerating fibroid. Incidental right
ovarian dermoid cyst is present. Examination under anesthesia, total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and peritoneal biopsies were
performed in one sitting. At histology, multiple granulomas were present on peritoneal and bilateral ovarian surfaces, consistent with tuberculosis.

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Radiologic Patterns in Tuberculosis

Fig. 1151-year-old man who presented with right lower quadrant abdominal pain.
A, Axial contrast-enhanced CT image shows stranding and nodularity throughout greater omentum (arrow), associated with ascites.
B, Axial unenhanced CT image shows enlarged right anterior diaphragmatic lymph node (arrow). Findings were initially thought to represent peritoneal carcinomatosis
with metastasis to anterior diaphragmatic node. Biopsy of lymph node showed granulomatous lymphadenitis. Purified protein derivative test was positive. Patient was
started on appropriate antituberculosis medications.
C, Repeat CT obtained 21 months after A and B shows complete resolution of ascites and omental disease.

Fig. 1263-year-old gravida 3, para 3, postmenopausal woman who first presented with abdominal distention due to ascites after cystocele repair. Initial abdominal
paracentesis was negative for malignancy. However, CA-125 was found to be elevated (207.3 mol/L). Patient underwent exploratory laparotomy, total abdominal
hysterectomy and bilateral salpingo-oophorectomy, and peritoneal biopsies. Diagnosis of intraperitoneal tuberculosis was made.
A, Axial contrast-enhanced CT image shows marked soft-tissue thickening and fat stranding in right adnexa. There is questionable 1.5-cm cystic lesion (arrow) to right of
uterus. It was uncertain if this represented primary lesion.
B, Axial image from same study shows large amount of intraabdominal ascites with enhancement of peritoneum (arrow), suggestive of peritoneal implants.
C, Additional axial CT image shows right adrenal mass (arrow), concerning for metastatic disease.

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