Download Distinguishing Benign from Malignant

Cavitary Lung Lesions:
Are there holes in our approach?
Jonathan Hickle1, MD; Joy Borgaonkar1, MD;
Daria Manos1, MD
1Department
of Diagnostic Radiology, Dalhousie University and Capital District
Health Authority, Halifax, Canada
Objectives
• Review the pathophysiology of pulmonary cavitation.
• Review imaging predictors and features of malignancy and
benignity described in the literature and discuss the limitations of
this approach.
• Application of the described features in pathology or culture
proven cases.
• Provide a suggested algorithm for evaluating cavitary pulmonary
lesions.
• Provide an opportunity to test yourself.
Cavitary Lesion DDX
Malignant
• Bronchogenic carcinoma
• Metastases
Inflammatory
• Sarcoidosis
• Rheumatoid nodules
• Vasculitidies
Infectious
•
•
•
•
Cavitating/necrotizing pneumonia
Septic emboli
Tracheobronchial papillomatosis
Aspergillosis and other fungi
Other
•
•
•
•
Congenital – CPAM, Sequestration
Post traumatic pulmonary laceration
Post pulmonary infarction
Mimics
Pathophysiology of a Cavity
Pulmonary cavitation occurs when nodules or regions of consolidated lung undergo
central necrosis or liquefaction and become air-filled. This is usually through
communication with the bronchial tree, but rarely gas forming organisms can fill a
cavity with gas. Fleischner defines a cavity as a “gas-filled space, seen as a lucency
or low-attenuation area, within pulmonary consolidation, a mass, or a nodule”.
A wall thickness of less than 4mm has been used to
differentiate thin walled cysts from pulmonary cavities, but this
often ignores the underlying pathophysiology of the lesion; it is
not always possible to reliably differentiate cysts from cavities
by imaging. The Fleischner Society defines a cyst as “any round
circumscribed space that is surrounded by an epithelial or
fibrous wall of variable thickness”. Fraser and Paré include
complicated cysts in their definition of a cavitary lesion; in
many cases the pathologist will be required to differentiate the
true cysts from the cavities.
Red and blue boxes: Teaching points
Pulmonary cyst in Lymphangiomyomatosis
CT Features:
A precise description does not equate to a precise prediction
Malignant
Wall thickness
>15mm
Indeterminate
Benign
BEWARE
Irregular internal
margins
Wall thickness 515mm
Air-fluid levels
Wall thickness
<5mm
Surrounding
Ground glass
Spiculated outer
Lobulated outer
Spiculated outer
PET FDG avidity
Associated
Satellite nodules
Prospective
data
correlating
thickness of a cavitary lesion
with
margins
margin,
“notch
margins
bronchial
wallthe
thickening
sign”
likelihood of malignancy is primarily derived from plain film radiography.
Number
lesions rigorous
Location of
lesions show low inter-reader
CT based data is lacking;
theofmore
studies
agreement, significant overlap between benign and malignant features,
and low predictive power. Radiologists should be wary in predicting the
likelihood of malignancy or benignity based on CT features alone.
Linear outer
margin
Features are based on: Lee KH, Lee JS, Lynch DA, Song KS, Lim TH. The radiologic differential diagnosis of diffuse lung diseases characterized by multiple cysts or cavities. J Comput
Assist Tomogr. 2002 Jan-Feb;26(1):5-12.
Malignant
History: 66 year old male with known UIP presents with worsening cough.
Features: Single cavitary lesions with thick, irregular inner walls, lobulated margins, and a “notch” sign.
There is a background of UIP-related changes.
Diagnosis: Squamous cell carcinoma.
Both primary and metastatic
squamous cell carcinoma are
common causes of malignant
cavitation.
Colour Code: Malignant, indeterminate, benign features
Several studies have examined potential
correlations between ILD and development of
malignancy. There is good evidence to suggest that
there is an increased risk of malignancy, (especially
squamous cell carcinoma), in older males who
smoke with a history of UIP.
Malignant
History: 58 year old male presents with general weakness.
Features: Multiple cavitary lesions with thick, irregular walls,
spiculated margins and additional solid nodules. The largest
contains an air-fluid level with surrounding ground glass
Diagnosis: Non-small cell lung cancer with metastases.
Primary and metastatic squamous cell carcinoma is a common cause of
cavitation. The presence of an air-fluid level may indicate superinfection,
which in some cases, may be the presenting complaint. In older patients and
those with risk factors for malignancy, equivocal cases should be followed
closely with a low threshold for more aggressive work-up.
Colour Code: Malignant, indeterminate, benign features
Malignant
History: 61 year old female with a right tonsilar mass.
Features: Two cavitary lesions with thin, irregular walls,
spiculated outer margins. Both lesions demonstrate avid FDG
uptake on PET.
Diagnosis: Metastatic squamous cell carcinoma.
Malignant cavities with little solid component or low FDG
avidity may result in a false negative PET study.
Colour Code: Malignant, indeterminate, benign features
BASELINE
Malignant
2 MONTH
FOLLOWUP
History: 60 year old male presents with flank pain and night sweats. Follow-up CT 2 months after starting
chemotherapy for renal cell carcinoma.
Features: Multiple solid pulmonary lesions have undergone central cavitation. The walls are thin to
moderate thickness, demonstrate smooth contours, and variable solid components. There is an absence
of ground glass. Note the associated right pneumothorax.
Diagnosis: Treated metastatic renal cell carcinoma.
Colour Code: Malignant, indeterminate, benign features
Malignant
History: 44 year old male with scrotal mass.
Features: Multiple cavitary lesions with thin, smooth walls, thin
septations, lobulated outer margins and a “notch sign”, and associated
solid components containing calcium. Large mediastinal nodal mass
containing calcium. Absence of ground glass.
Diagnosis: Metastatic testicular teratoma.
Some metastases cavitate prior to therapy. Fast
growing lesions will often outpace angiogenesis,
leading to central necrosis and cavitation.
Colour Code: Malignant, indeterminate, benign features
Malignant
History: 76 year old male with a history of colon cancer treated with
chemotherapy.
Features: Single cavitary lesion with spiculated outer margins, moderate wall
thickness, irregular inner margins. There is an absence of ground glass.
Diagnosis: Treated metastatic colon adenocarcinoma.
Colour Code: Malignant, indeterminate, benign features
Inflammatory
History: 53 year old male, presents with cough.
Features: Right upper lobe, large, thick walled, cavitary lesion with irregular inner margins,
peripheral spiculations, surrounding ground glass and multiple spiculated satellite nodules.
Diagnosis: Sarcoidosis
Cavitation occurs in approximately 2.2% of cases of
sarcoidosis. Cavities average 2cm in size, and are typically
multiple. A thick wall may reflect superimposed infection.
Colour Code: Malignant, indeterminate, benign features
Inflammatory
History: 17 year old female with history of ulcerative colitis,
pancreatitis, oral ulcers and multisystem vasculitis.
Features: Single cavitary lesion in the right upper lobe with
moderate wall thickness, irregular internal and external margins,
surrounding ground glass. There are discrete pulmonary
nodules, separate regions of subpleural opacity and a right
pleural effusion.
Diagnosis: Pulmonary involvement of Behcet’s syndrome.
With vasculitis, cavitation typically occurs
in areas of hemorrhage and consolidation.
Colour Code: Malignant, indeterminate, benign features
Behcet’s is a complex disorder of multisystem
vasculitis. In addition to areas of hemorrhage, infarct
and occasionally cavitation, the thoracic findings of
Behcet’s include aortic and pulmonary arterial
aneurysms, and pulmonary emboli. Cavities are
thought to result from thrombus-related ischemia due
to Behcet’s involvement of the pulmonary vessels.
Inflammatory
History: 23 year old male with a history of ulcerative colitis,
anemia, lower GI bleed and mild abdominal pain.
Features: Two large pleural based ovoid opacities with focal
irregular areas of central cavitation, smooth outer walls,
surrounding ground glass.
CT for PE was performed 30 months later showing resolution
of the lesions and a new left pleural effusion.
Diagnosis: Granulomatosis with polyangiitis.*
The cavitating nodules and masses in granulomatosis
with polyangiitis result from necrotizing granulomatous
inflammation.
Colour Code: Malignant, indeterminate, benign features
*Formerly known as Wegener’s
Infectious
Both inflammatory and malignant cavitary lesions can be FDG avid; PET is not useful to distinguish
malignant from benign inflammatory cavitary lesions with a malignant CT appearance.
History: 54 year old female with a history of smoking and COPD presents with
hemoptysis, productive cough, fever and chills with general malaise.
Features: Right upper lobe, thin walled, irregular cavitary lesion with
surrounding ground glass and linear margins. PET/CT was performed; SUV max
of 4.
Diagnosis: The patient underwent a lobectomy. Pathology results were
consistent with necrotizing aspergillosis.
Colour Code: Malignant, indeterminate, benign features
Infectious
History: 58 year old male cruise ship staff presents with fever and cough.
Features: Bilateral upper lobe intermediate to thick walled, irregular cavitary lesions with surrounding
ground glass and bronchial thickening. PET/CT demonstrated avidity in the left upper lobe.
Diagnosis: The patient underwent a lobectomy. Culture results were positive for Mycobacterium
tuberculosis.
Colour Code: Malignant, indeterminate, benign features
Infectious
Immunocompromised patients are at higher risk for specific
organisms including mycobacterial, and fungal infections.
Month 0
Month 3
Month 29
History: 54 year old HIV+ male presents with multiple spontaneous pneumothoraces.
Features: Left upper lobe thick walled cavitary lesion with spiculated margins and surrounding
ground glass shows interval worsening before eventual improvement.
Diagnosis: Mycobacterium avium complex diagnosed by bronchial lavage. The patient was
treated with antibiotics and followed by serial CT studies.
Malignant, indeterminate, benign
Infectious
History: 17 year old male with backpain. On steroids for
autoimmune disorder.
Features: Left upper lobe, peripheral, solitary cavitary lesion
with smooth inner and outer margins, mild associated pleural
thickening, mild ground glass and tree-in-bud nodularity. CT and
MRI demonstrates lytic bone lesions with associated enhancing
soft tissue components involving a thoracic vertebral body and
the right sacrum.
Diagnosis: Blastomycosis.
Pulmonary infection by Blastomyces dermatitidis results in cavitation in
15-35% of cases. The fungus is endemic in the Southeastern USA, Great
Lakes region. AKA: “Chicago Disease”.
Colour Code: Malignant, indeterminate, benign features
Infectious
History: 58 year old male with several days of night sweats, fevers and chills.
Features: Single cavitary lesion in the right upper lobe with thick, irregular inner walls and an abundance of
surrounding ground glass.
Diagnosis: Pulmonary abscess.
Colour Code: Malignant, indeterminate, benign features
Pulmonary abscesses should be followed with serial imaging
until resolution. This can usually be accomplished with
radiographs. Complications of cavitating pulmonary abscesses
include bronchopleural fistulae, pneumothorax, empyema.
Infectious
History: 35 year old male IV drug user with known S.
aureus endocarditis. Worsening respiratory status.
Features: Bilateral predominantly peripheral, cavitary
lesions with intermediate wall thickness, air-fluid levels,
variable inner margins and predominantly smooth outer
margins and extensive surrounding ground glass. There
are associated bilateral empyemas and a right sided
pneumothorax.
Diagnosis: S. aureus septic emboli.
Colour Code: Malignant, indeterminate, benign features
Infectious
History: 44 year old male with thigh abscess, weight loss,
night sweats and fevers. Treated with antibiotics.
Features: Bilateral peripheral, cavitary lesions with
variable wall thickness, air-fluid levels, variable inner
margins and predominantly smooth outer margins. No
associated ground glass.
Diagnosis: S. aureus septic emboli.
In contrast to the previous case, there is much less
associated ground glass – likely due to response to
therapy. Like a pulmonary abscess, these lesions have
similar complications and should be followed with
imaging to resolution.
Colour Code: Malignant, indeterminate, benign features
Malignant
Antifungal Therapy
Infectious
Month 0
Month 12
Month 16
History: 69 year old male with a history of chronic cough, and occasional hemoptysis.
Features: Solitary left lower lobe cavitary lesion with thin walls that on a subsequent study is filled
with soft tissue density, has moderate wall thickness and has associated surrounding ground glass.
The patient was treated for presumed fungal infection and the inflammatory changes resolved on a
follow-up study. Spiculated outer margins, irregular inner walls and a thin wall are noted on the
latest study.
Diagnosis: Pathology of the wedge resection was consistent with primary squamous cell carcinoma.
Although there was improvement in the appearance of the lesion after anti-fungal
therapy, persistence of the lesion with some concerning features should alert the
radiologist to potential superinfection of a malignant cavity. Serial imaging and a
multidisciplinary approach lead to the correct diagnosis and treatment in this case.
Colour Code: Malignant, indeterminate, benign features
Other
History: 24 year old male presents after a 6 story fall.
Features: Several large, irregular cavitary lesions with thin walls,
containing air-fluid levels and extensive surrounding ground glass and
consolidation. There is a right sided pneumothorax with rib fractures.
Diagnosis: In the setting of trauma, the findings are consistent with
pulmonary laceration.
Pulmonary laceration presents as spherical, thin walled cavitary
lesions containing varying amount of fluid and air on a
background of parenchymal hemorrhage and contusion. The
appearance of the cavities can change rapidly, usually healing in
less than a month with mild residual scar.
Colour Code: Malignant, indeterminate, benign features
Other
History: 62 year old male presents with pleuritic chest pain despite treatment for pneumonia.
Features: Peripheral cavitary lesion with intermediate wall thickness, irregular internal walls, lobulated
margins, surrounding ground glass. Filling defect in LPA consistent with pulmonary embolus.
Diagnosis: Pulmonary infarct with cavitation.
Colour Code: Malignant, indeterminate, benign features
Cavitation is reported in up to 7% of pulmonary
infarcts. Cavitation is hypothesized to be secondary
to aseptic necrosis or secondary infection. Air-fluid
levels suggest secondary infection.
Other
History: 29 year old male presents with cough.
Features: Multiple cavitary lesions in left lower lobe with thin, smooth walls, airfluid levels. There is some mild surrounding consolidation with an absence of
ground glass. There is focal bronchiectasis and an anomalous feeding artery on CTA.
Diagnosis: Intralobar pulmonary sequestration.
Pulmonary sequestrations are abnormal segments of
lung that have an aberrant arterial supply and do not
communicate with the bronchial tree. Intralobar
sequestrations are located within the visceral pleura
with normal lung; extralobar are external to the
normal visceral pleura.
Colour Code: Malignant, indeterminate, benign features
Pulmonary sequestrations
typically present in late childhood
or in early adulthood.
Other
History: 18 year old female with cough. Returns
3 years later with new cough and fever.
Features: Initially, she has a solitary, thin walled
lesion with tiny septations in the right lower
lobe. Three years later, the lesion demonstrates
thin walls, some internal irregularity, an air-fluid
level and extensive surrounding ground glass.
Diagnosis: Infected congential pulmonary airway
malformation (CPAM).
Colour Code: Malignant, indeterminate, benign features
CPAMs (previously known as CCAMs) are lesions
whose classification and etiology is debated. They
are broadly defined as heterogenous group of
congenital lesions characterized by varying degrees
of cystic and solid components. Infection of these
lesions can result in fluid filling the cystic/cavitary
portion of the lesion.
CTA should be performed to evaluate for an
aberrant feeding vessel which would be suggestive
of a pulmonary sequestration.
Malignant
Baseline
Other
1y 1m
3y 5m
4y 1m
4y 5m
6y 7m
7y 5m
History: 77 year old male with a history of cough and smoking.
Features: Solitary left lower lobe cavitary lesion with thin, irregular walls and associated
ground glass demonstrates an increasingly large solid component over serial studies, until
the cavity is filled with a large, lobulated mass with spiculated margins.
Diagnosis: Pulmonary adenocarcinoma.
Ground glass opacity associated with a cavitary
lesion will typically indicate inflammation. When
there are no other inflammatory findings such as a
thickened cavitary wall and findings persist on
follow up adenocarcinoma should be suspected.
Colour Code: Malignant, indeterminate, benign
This is not a true cavity as defined by Fleischner,
rather, a mass developing around a cyst; this is
included as a cavitary mimic. However, the
pathophysiology of these irregular lung cysts
associated with adenocarcinoma is uncertain.* If the
initial imaging occurred at one of the later time
points, differentiating this from a true cavity would
be impossible.
*Yoshida T., et. al. Lung adenocarcinoma presenting with enlarged and multiloculated cystic lesions over 2 years. Respir Care. 2004 Dec;49(12):1522-4
Other
History: 77 year old male with shortness of breath
Features: Numerous bilateral, thin, smoothly marginated, cystic
lesions with air-fluid levels that communicate with the bronchial
tree.
Diagnosis: Infected cystic bronchiectasis.
Bronchiectasis can mimic pulmonary cavitation, especially
when there is superimposed infection. The air filled spaces
in this case can be followed back to the bronchial tree.
Colour Code: Malignant, indeterminate, benign features
Clinical Correlation Required:
The Radiologist’s Approach
1Age,
smoking, known
primary malignancy,
absence of infectious
features
Cavitary Lung
Lesion
2Fever,
productive cough,
immunocompromise, risk
of aspiration, absence of
clinical features of
malignancy
3Underlying chronic
lung disease, known
vasculitis, trauma
High pretest
probability of
malignancy1
Thoracic surgery
consultation
Biopsy
High pretest
probability of
infection2
Cultures
Therapy and
short interval
follow-up
Specific CT or
clinical features3
Case by case
basis
The non-specific CT features of cavitary lung lesions require the
interpreting radiologist perform detailed clinical correlation to
narrow the differential diagnosis, and suggest appropriate
management. Short interval follow-up in equivocal cases can
minimize the morbidity associated with unnecessary biopsy and
surgery while avoiding the pitfalls of delaying necessary treatment.
Which of these right lung lesions is malignant?
Click on an image or click here for patient history.
60F Cough, nasal congestion
renal dysfunction
47M Cough,
SOB, ↓energy
44M Cough, fever,
dyspnea, advanced sarcoid
Which of these right lung lesions is malignant? Click on an image.
47M 3 weeks cough,
chest pain, syncope
59M Cough, persistent opacity
4 months post stem cell transplant
48F incidental on preoperative
study, 20 pkyrs smoking
Granulomatosis
with polyangiitis
Strep abscess
Aspergilloma
Regrettably, your selection was incorrect. Continue
Strep abscess
Mucor species mycetoma
NSCLCA
Granulomatosis
with polyangiitis
Strep abscess
Aspergilloma
Congratulations! Your selection was correct.
Strep abscess
Mucor species mycetoma
NSCLCA
Teaching Points
• Despite the classic descriptions in the radiology literature, there is
considerable overlap in the CT features of both benign and
malignant cavitary lung lesions.
• The clinical history is often indispensable in narrowing the
differential diagnosis, guiding therapy and follow-up.
• There should be a high index of suspicion for opportunistic and
fungal infections in the immunocompromised patient.
• Suspected infectious or inflammatory cavities should followed with
serial imaging to resolution.
References
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