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{{Solitary pulmonary nodule}}
{{Solitary pulmonary nodule}}
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==Recommendations for management based on appearance==
==Overview==
===Solid nodules===
 
For response by physicians to lung nodules found on CT scans, the [[clinical practice guideline]]s by the [[American College of Chest Physicians]] (ACCP) recommends<ref name="pmid23649456">{{cite journal| author=Gould MK, Donington J, Lynch WR, Mazzone PJ, Midthun DE, Naidich DP et al.| title=Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. | journal=Chest | year= 2013 | volume= 143 | issue= 5 Suppl | pages= e93S-120S | pmid=23649456 | doi=10.1378/chest.12-2351 | pmc=PMC3749714 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23649456  }} </ref>:
Computed tomography is the method of choice for the diagnosis of solitary pulmonary nodule. On CT, characteristic findings of solitary pulmonary nodules, include: ground-glass opacity, rounded mass, and less than 30mm.<ref name="pmid8190965">{{cite journal |vauthors=Rosado-de-Christenson ML, Templeton PA, Moran CA |title=Bronchogenic carcinoma: radiologic-pathologic correlation |journal=Radiographics |volume=14 |issue=2 |pages=429–46; quiz 447–8 |year=1994 |pmid=8190965 |doi=10.1148/radiographics.14.2.8190965 |url=}}</ref><ref name="pmid19234288">{{cite journal |vauthors=Parker MS, Chasen MH, Paul N |title=Radiologic signs in thoracic imaging: case-based review and self-assessment module |journal=AJR Am J Roentgenol |volume=192 |issue=3 Suppl |pages=S34–48 |year=2009 |pmid=19234288 |doi=10.2214/AJR.07.7081 |url=}}</ref> The evaluation of solitary pulmonary nodule will depend on 7 characteristics: calcification patterns, size, location, size, growth, shape, margins, attenuation, and contrast enhancement.<ref name="pmid19234288">{{cite journal |vauthors=Parker MS, Chasen MH, Paul N |title=Radiologic signs in thoracic imaging: case-based review and self-assessment module |journal=AJR Am J Roentgenol |volume=192 |issue=3 Suppl |pages=S34–48 |year=2009 |pmid=19234288 |doi=10.2214/AJR.07.7081 |url=}}</ref>
* If less than 8 mm, use guidelines in table below by the Fleischner society (see table below).
 
* For nodules greater than 8 mm in diameter, assess the patients risk of complications from thoracic surgery:
==CT==
** If high risk for complications of surgery, obtain non-surgical biopsy
*Computed tomography is the method of choice for the diagnosis of solitary pulmonary nodule
** If low to moderate risk for complications of surgery, assess probability of cancer by a validated calculation. The model developed at the Mayo Clinic has been the most extensively validated<ref name="pmid9129544">{{cite journal| author=Swensen SJ, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES| title=The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. | journal=Arch Intern Med | year= 1997 | volume= 157 | issue= 8 | pages= 849-55 | pmid=9129544 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9129544  }} </ref>. An open-source version is [https://openrules.ocpu.io/home/www/pulmnodule.html available online].
*On CT, characteristic findings of solitary pulmonary nodules, include:
:*Single to multiple intraparenchymal lesion
:*Less than 3 cm in size
:*Rounded or spiculated lesion
[[File: Solitary pul nodule.png|400px|left|thumb| CT scan showing solitary pulmonary nodules (Picture courtesy: [https://openi.nlm.nih.gov/detailedresult?img=PMC4770395_rb-49-01-0035-g05&query=solitary%20pulmonary%20nodules&it=xg&req=4&npos=15 National Library of Medicine])]]
<br style="clear:left">
 
The evaluation of solitary pulmonary nodule will depend on the following characteristics:
 
'''Calcification'''
*Calcification patterns are commonly seen in granulomatous disease and hamartomas
*Calcification patterns are normally a sign of benignancy
*Characteristic benign calcification patterns of pulmonary nodule, include:
:*Diffuse
:*Central
:*Laminated
:*Popcorn
[[File: Calcified lung nodule white arrow.png|400px|left|thumb| CT scan showing a calcified solitary pulmonary nodules (white arrow) (Picture courtesy: [https://openi.nlm.nih.gov/detailedresult?img=PMC3259307_13244_2010_39_Fig6_HTML&query=Calcified%20solitary%20pulmonary%20nodules&it=xg&req=4&npos=2 National Library of Medicine])]]
<br style="clear:left">


{| class="wikitable"
'''Size'''
|+ Fleischner society guidelines for follow-up and management of nodules <8 mm Detected Incidentally at non-screening CT<ref name="pmid16244247">{{cite journal| author=MacMahon H, Austin JH, Gamsu G, Herold CJ, Jett JR, Naidich DP et al.| title=Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. | journal=Radiology | year= 2005 | volume= 237 | issue= 2 | pages= 395-400 | pmid=16244247 | doi=10.1148/radiol.2372041887 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16244247  }} </ref>
*Different types of size ranges for pulmonary nodule, include:
! Nodule Size (mm)
:* Nodules less than 4mm
! Low† risk patients
:* Nodules between 4mm and 7mm
! High‡ risk patients
:* Nodules between 8mm and 20mm
|-
:* Nodules more than 20mm
| <= 4
| No follow-up needed.
| Follow-up at 12 months. If no change, no further imaging needed.
|-
| >4 - 6
| Follow-up at 12 months. If no change, no further imaging needed.
| Initial follow-up CT at 6 -12 months and then at 18 - 24 months if no change.
|-
| >6 - 8
| Initial follow-up CT at 6 -12 months and then at 18 - 24 months if no change.
| Initial follow-up CT at 3 - 6 months and then at 9 -12 and 24 months if no change.
|-
| >8
| Follow-up CTs at around 3, 9, and 24 months. Dynamic contrast enhanced CT, PET, and/or biopsy.
| Same at for low risk patients.
|-
| colspan="3" |† Low risk patients: Minimal or absent history of smoking and of other known risk factors.<br/>‡ High risk patients: History of smoking or of other known risk factors.
|}


===Subsolid nodules===
'''Location'''
The ACCP suggests subsolid nodules may require an extended duration of surveillance for growth or signs of a solid component as these are often premalignant or malignant<ref name="pmid23649456">{{cite journal| author=Gould MK, Donington J, Lynch WR, Mazzone PJ, Midthun DE, Naidich DP et al.| title=Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. | journal=Chest | year= 2013 | volume= 143 | issue= 5 Suppl | pages= e93S-120S | pmid=23649456 | doi=10.1378/chest.12-2351 | pmc=PMC3749714 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23649456  }} </ref>. The Fleischner society has published guidelines for the management of subsolid nodules<ref name="pmid23070270">{{cite journal| author=Naidich DP, Bankier AA, MacMahon H, Schaefer-Prokop CM, Pistolesi M, Goo JM et al.| title=Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society. | journal=Radiology | year= 2013 | volume= 266 | issue= 1 | pages= 304-17 | pmid=23070270 | doi=10.1148/radiol.12120628 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23070270  }} </ref>.
*Locations of pulmonary nodule, include:
:*Perilymphatic
[[File: Perilymphatic solitary pulmonary nodules.jpg |400px|left|thumb| CT scan showing a Perilymphatic solitary pulmonary nodules of [[sarcoidosis]] (Picture courtesy: [https://radiopaedia.org/cases/pulmonary-sarcoidosis?lang=gb Radiopaedia])]]
<br style="clear:left">
:*Perifissural
[[File: Perifissural solitary pulmonary nodules.png|400px|left|thumb| CT scan showing a Perifissural solitary pulmonary nodule (white circle) (Picture courtesy: [https://en.wikipedia.org/wiki/Lung_nodule#/media/File:CT_of_perifissural_nodule.png Wikipedia])]]
<br style="clear:left">
:*Centrilobular
[[File: Centrilobular_solitary_pulmonary_nodule.png |400px|left|thumb| CT scan showing a Centrilobular solitary pulmonary nodule (black arrowheads) (Picture courtesy: [https://openi.nlm.nih.gov/detailedresult?img=PMC2893311_kjr-11-407-g003&query=Centrilobular%20solitary%20pulmonary%20nodule&it=xg&req=4&npos=4 National Library of Medicine])]]
<br style="clear:left">


==Example images==
==CT==


[[Image:Pulmonary AVM as nodule 2.jpg|thumb|center|Thorax CT]]
'''Growth'''
*The growth pattern of the pulmonary nodule plays an important role in the management strategy.<ref name="pmid22156993">{{cite journal |vauthors=Ko JP, Berman EJ, Kaur M, Babb JS, Bomsztyk E, Greenberg AK, Naidich DP, Rusinek H |title=Pulmonary Nodules: growth rate assessment in patients by using serial CT and three-dimensional volumetry |journal=Radiology |volume=262 |issue=2 |pages=662–71 |year=2012 |pmid=22156993 |pmc=3267080 |doi=10.1148/radiol.11100878 |url=}}</ref>
*Nodule growth should be evaluated on a individual basis and based on the risk assessment score
* A 4x growth is associated with a 50% risk of malignancy<ref name="pmid22156993">{{cite journal |vauthors=Ko JP, Berman EJ, Kaur M, Babb JS, Bomsztyk E, Greenberg AK, Naidich DP, Rusinek H |title=Pulmonary Nodules: growth rate assessment in patients by using serial CT and three-dimensional volumetry |journal=Radiology |volume=262 |issue=2 |pages=662–71 |year=2012 |pmid=22156993 |pmc=3267080 |doi=10.1148/radiol.11100878 |url=}}</ref>


<div align="left">
'''Shape'''
<gallery heights="200" widths="200">
*Different types of shape for pulmonary nodule, include:
Image:Pulmonary AVM as nodule 3.jpg|Thorax CT
:*Polygonal
Image:Pulmonary AVM as nodule 4.jpg|Thorax CT
:*Spherical
</gallery>
</div>


'''Margins'''
*Different types of margins for pulmonary nodule, include:
:*Lobulated or scalloped margins
::*Intermediate malignancy probability
:*Smooth margins
:*:Associated with nodule benignancy 
[[File: Pul nodule borders.png|400px|left|thumb| CT scan showing types of solitary pulmonary nodule margins (Picture courtesy: [https://radiologykey.com/pulmonary-neoplasms-4/ Radiologykey])]]
<br style="clear:left">


<div align="left">
'''Attenuation'''
<gallery heights="200" widths="200">
*Different types of attenuation for pulmonary nodule, include:
Image:Pulmonary AVM as nodule 5.jpg|Thorax CT
*Solid pulmonary nodules
Image:Pulmonary AVM as nodule 6.jpg|Thorax CT
:*Malignancy rate of only 7%
</gallery>
*Calcified pulmonary nodules
</div>
*Partly solid pulmonary nodules
:*Malignancy rate of 63%
*Ground glass pulmonary nodules
:*Malignancy rate of 18%


'''Contrast enhancement'''
* Contrast enhancement of pulmonary nodules may be useful to determine benign or malignant features
* Benign pulmonary nodules usually have a contrast enhancement less than 15 HU


<div align="left">
On CT, radiological signs of pulmonary nodule, include:
<gallery heights="200" widths="200">
*'''Corona radiata sign''': highly associated with malignancy
Image:Pulmonary AVM as nodule 7.jpg|Thorax CT
*'''Air bronchogram sign''': airway surrounded by collection in alveolar spaces, non-specific sign
Image:Pulmonary AVM as nodule 8.jpg|Thorax CT
*'''Halo sign''': zone of ground-glass attenuation surrounding a pulmonary nodule or mass on CT images
</gallery>
*'''Tree-in-bud sign''': CT appearance of multiple areas of centrilobular nodules with a linear branching pattern
</div>
*'''Cheerio sign''': pulmonary nodules with a central lucent cavity as seen on CT. It is due to proliferation of (malignant or non-malignant) cells around an airway


====Halo Sign====
==CT Surveillance==


*The halo sign refers to a zone of ground-glass attenuation surrounding a pulmonary nodule or mass on CT images.
According to the [[American College of Chest Physicians]] (ACCP) for the CT surveillance of pulmonary nodules, recommends the following:<ref name="pmid23649456">{{cite journal| author=Gould MK, Donington J, Lynch WR, Mazzone PJ, Midthun DE, Naidich DP et al.| title=Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. | journal=Chest | year= 2013 | volume= 143 | issue= 5 Suppl | pages= e93S-120S | pmid=23649456 | doi=10.1378/chest.12-2351 | pmc=PMC3749714 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23649456  }} </ref>
*The presence of a halo of ground-glass opacity or ground-glass attenuation is usually associated with hemorrhagic nodules.  
* If less than 8 mm, use guidelines by the Fleischner society (see table below).
*In severely neutropenic patients, the halo sign is highly suggestive of infection by an angioinvasive fungus, most commonly [[Aspergillosis | Aspergillus]].  
* For nodules greater than 8 mm in diameter, assess the patients risk of complications from thoracic surgery:
*Vascular invasion by this fungus results in thrombosis of small- to medium-sized vessels, which causes ischemic necrosis.
** If low to moderate risk for complications of surgery, assess probability of cancer by a validated calculation. The model developed at the Mayo Clinic has been the most extensively validated. An open-source version is [https://openrules.ocpu.io/home/www/pulmnodule.html available online].
*At pathologic examination, the nodules represent foci of infarction, and the halo of ground-glass attenuation results from alveolar hemorrhage.  
** If high risk for complications of surgery, assess probability of cancer by a validated calculation. If low to moderate risk of cancer follow up with CT scan surveillance. If moderate to high risk of cancer obtain non-surgical biopsy.<ref name="pmid9129544">{{cite journal| author=Swensen SJ, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES| title=The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules. | journal=Arch Intern Med | year= 1997 | volume= 157 | issue= 8 | pages= 849-55 | pmid=9129544 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9129544  }} </ref>
*Although it is less common, the halo sign may also be observed in nonhemorrhagic nodules, in which case either tumor cells or inflammatory infiltrate account for the halo of ground-glass attenuation.


{| class="wikitable"
|+ Fleischner Society guidelines for follow-up and management of nodules <8 mm <br>Detected incidentally at non-screening CT<ref name="pmid16244247">{{cite journal| author=MacMahon H, Austin JH, Gamsu G, Herold CJ, Jett JR, Naidich DP et al.| title=Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society. | journal=Radiology | year= 2005 | volume= 237 | issue= 2 | pages= 395-400 | pmid=16244247 | doi=10.1148/radiol.2372041887 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16244247  }} </ref>
! Nodule Size (mm)
! Low risk patients†
! High risk patients‡
|-
| <= 4
| No follow-up needed
| Follow-up at 12 months.<br> If no change, no further imaging needed
|-
| > 4 - 6
| Follow-up at 12 months.<br>If no change, no further imaging needed
| Initial follow-up CT at 6 -12 months <br>If no change follow-up CT at 18 - 24 months
|-
| > 6 - 8
| Initial follow-up CT at 6 -12 months<br>If no change follow-up CT at 18 - 24 months
| Initial follow-up CT at 3 - 6 months<br> >If no change follow-up CT at 9 -12 and 24 months
|-
| > 8
| Follow-up CT at around 3, 9, and 24 months<br>Dynamic contrast enhanced CT, PET, and/or biopsy
| Same at for low risk patients
|-
| colspan="3" |† Low risk patients: Minimal or absent history of smoking and of other known risk factors.<br />‡ High risk patients: History of smoking or of other known risk factors
|}


==References==
==References==
{{reflist|2}}
{{reflist|2}}
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[[Category:Disease]]
[[Category:Disease]]
[[Category:Pulmonology]]
[[Category:Pulmonology]]
[[Category:Oncology]]

Latest revision as of 17:56, 22 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2] Joanna Ekabua, M.D. [3]

Overview

Computed tomography is the method of choice for the diagnosis of solitary pulmonary nodule. On CT, characteristic findings of solitary pulmonary nodules, include: ground-glass opacity, rounded mass, and less than 30mm.[1][2] The evaluation of solitary pulmonary nodule will depend on 7 characteristics: calcification patterns, size, location, size, growth, shape, margins, attenuation, and contrast enhancement.[2]

CT

  • Computed tomography is the method of choice for the diagnosis of solitary pulmonary nodule
  • On CT, characteristic findings of solitary pulmonary nodules, include:
  • Single to multiple intraparenchymal lesion
  • Less than 3 cm in size
  • Rounded or spiculated lesion
CT scan showing solitary pulmonary nodules (Picture courtesy: National Library of Medicine)


The evaluation of solitary pulmonary nodule will depend on the following characteristics:

Calcification

  • Calcification patterns are commonly seen in granulomatous disease and hamartomas
  • Calcification patterns are normally a sign of benignancy
  • Characteristic benign calcification patterns of pulmonary nodule, include:
  • Diffuse
  • Central
  • Laminated
  • Popcorn
CT scan showing a calcified solitary pulmonary nodules (white arrow) (Picture courtesy: National Library of Medicine)


Size

  • Different types of size ranges for pulmonary nodule, include:
  • Nodules less than 4mm
  • Nodules between 4mm and 7mm
  • Nodules between 8mm and 20mm
  • Nodules more than 20mm

Location

  • Locations of pulmonary nodule, include:
  • Perilymphatic
CT scan showing a Perilymphatic solitary pulmonary nodules of sarcoidosis (Picture courtesy: Radiopaedia)


  • Perifissural
CT scan showing a Perifissural solitary pulmonary nodule (white circle) (Picture courtesy: Wikipedia)


  • Centrilobular
CT scan showing a Centrilobular solitary pulmonary nodule (black arrowheads) (Picture courtesy: National Library of Medicine)



Growth

  • The growth pattern of the pulmonary nodule plays an important role in the management strategy.[3]
  • Nodule growth should be evaluated on a individual basis and based on the risk assessment score
  • A 4x growth is associated with a 50% risk of malignancy[3]

Shape

  • Different types of shape for pulmonary nodule, include:
  • Polygonal
  • Spherical

Margins

  • Different types of margins for pulmonary nodule, include:
  • Lobulated or scalloped margins
  • Intermediate malignancy probability
  • Smooth margins
    Associated with nodule benignancy
CT scan showing types of solitary pulmonary nodule margins (Picture courtesy: Radiologykey)


Attenuation

  • Different types of attenuation for pulmonary nodule, include:
  • Solid pulmonary nodules
  • Malignancy rate of only 7%
  • Calcified pulmonary nodules
  • Partly solid pulmonary nodules
  • Malignancy rate of 63%
  • Ground glass pulmonary nodules
  • Malignancy rate of 18%

Contrast enhancement

  • Contrast enhancement of pulmonary nodules may be useful to determine benign or malignant features
  • Benign pulmonary nodules usually have a contrast enhancement less than 15 HU

On CT, radiological signs of pulmonary nodule, include:

  • Corona radiata sign: highly associated with malignancy
  • Air bronchogram sign: airway surrounded by collection in alveolar spaces, non-specific sign
  • Halo sign: zone of ground-glass attenuation surrounding a pulmonary nodule or mass on CT images
  • Tree-in-bud sign: CT appearance of multiple areas of centrilobular nodules with a linear branching pattern
  • Cheerio sign: pulmonary nodules with a central lucent cavity as seen on CT. It is due to proliferation of (malignant or non-malignant) cells around an airway

CT Surveillance

According to the American College of Chest Physicians (ACCP) for the CT surveillance of pulmonary nodules, recommends the following:[4]

  • If less than 8 mm, use guidelines by the Fleischner society (see table below).
  • For nodules greater than 8 mm in diameter, assess the patients risk of complications from thoracic surgery:
    • If low to moderate risk for complications of surgery, assess probability of cancer by a validated calculation. The model developed at the Mayo Clinic has been the most extensively validated. An open-source version is available online.
    • If high risk for complications of surgery, assess probability of cancer by a validated calculation. If low to moderate risk of cancer follow up with CT scan surveillance. If moderate to high risk of cancer obtain non-surgical biopsy.[5]
Fleischner Society guidelines for follow-up and management of nodules <8 mm
Detected incidentally at non-screening CT[6]
Nodule Size (mm) Low risk patients† High risk patients‡
<= 4 No follow-up needed Follow-up at 12 months.
If no change, no further imaging needed
> 4 - 6 Follow-up at 12 months.
If no change, no further imaging needed 		Initial follow-up CT at 6 -12 months
If no change follow-up CT at 18 - 24 months
> 6 - 8 Initial follow-up CT at 6 -12 months
If no change follow-up CT at 18 - 24 months 		Initial follow-up CT at 3 - 6 months
>If no change follow-up CT at 9 -12 and 24 months
> 8 Follow-up CT at around 3, 9, and 24 months
Dynamic contrast enhanced CT, PET, and/or biopsy 		Same at for low risk patients
† Low risk patients: Minimal or absent history of smoking and of other known risk factors.
‡ High risk patients: History of smoking or of other known risk factors

References

  1. ↑ Rosado-de-Christenson ML, Templeton PA, Moran CA (1994). "Bronchogenic carcinoma: radiologic-pathologic correlation". Radiographics. 14 (2): 429–46, quiz 447–8. doi:10.1148/radiographics.14.2.8190965. PMID 8190965.
  2. ↑ 2.0 2.1 Parker MS, Chasen MH, Paul N (2009). "Radiologic signs in thoracic imaging: case-based review and self-assessment module". AJR Am J Roentgenol. 192 (3 Suppl): S34–48. doi:10.2214/AJR.07.7081. PMID 19234288.
  3. ↑ 3.0 3.1 Ko JP, Berman EJ, Kaur M, Babb JS, Bomsztyk E, Greenberg AK, Naidich DP, Rusinek H (2012). "Pulmonary Nodules: growth rate assessment in patients by using serial CT and three-dimensional volumetry". Radiology. 262 (2): 662–71. doi:10.1148/radiol.11100878. PMC 3267080. PMID 22156993.
  4. ↑ Gould MK, Donington J, Lynch WR, Mazzone PJ, Midthun DE, Naidich DP; et al. (2013). "Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines". Chest. 143 (5 Suppl): e93S–120S. doi:10.1378/chest.12-2351. PMC 3749714. PMID 23649456.
  5. ↑ Swensen SJ, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES (1997). "The probability of malignancy in solitary pulmonary nodules. Application to small radiologically indeterminate nodules". Arch Intern Med. 157 (8): 849–55. PMID 9129544.
  6. ↑ MacMahon H, Austin JH, Gamsu G, Herold CJ, Jett JR, Naidich DP; et al. (2005). "Guidelines for management of small pulmonary nodules detected on CT scans: a statement from the Fleischner Society". Radiology. 237 (2): 395–400. doi:10.1148/radiol.2372041887. PMID 16244247.

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