CT of lung nodules - Revision history

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|author1=[[User:Mikael Häggström|Mikael Häggström]]
|author2=Authors of integrated Creative Commons article<ref name=Snoeckx2017>{{cite journal|last1=Snoeckx|first1=Annemie|last2=Reyntiens|first2=Pieter|last3=Desbuquoit|first3=Damien|last4=Spinhoven|first4=Maarten J.|last5=Van Schil|first5=Paul E.|last6=van Meerbeeck|first6=Jan P.|last7=Parizel|first7=Paul M.|title=Evaluation of the solitary pulmonary nodule: size matters, but do not ignore the power of morphology|journal=Insights into Imaging|volume=9|issue=1|year=2017|pages=73–86|issn=1869-4101|doi=10.1007/s13244-017-0581-2}}</ref>
|author3=
}}

A '''lung nodule''' or '''pulmonary nodule''' is a relatively small focal density in the [[lung]]. This article deals with the presence a '''solitary pulmonary nodule''' ('''SPN''') or '''coin lesion''', which is a mass in the lung smaller than 3 centimeters in diameter.<ref>{{cite web |url=https://radiopaedia.org/articles/coin-lesion-lung?lang=gb|title=Coin lesion (Lung)}}</ref>

==Scope==
The content may be applied to the presence of a few '''solitary pulmonary nodules''', each of which is defined as a single lesion in the lung completely surrounded by functional lung tissue with a diameter less than 3 cm, and without associated [[pneumonia]], [[atelectasis]] (lung collapse) or [[lymphadenopathy|lymphadenopathies]].<ref name="pmid12527568">{{cite journal |author=Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD |title=The solitary pulmonary nodule |journal=Chest |volume=123 |issue=1 Suppl |pages=89S–96S |date=January 2003 |pmid=12527568 |doi=10.1378/chest.123.1_suppl.89S |url=http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=12527568 |archive-url=https://archive.is/20130112232936/http://www.chestjournal.org/cgi/pmidlookup?view=long&pmid=12527568 |dead-url=yes |archive-date=2013-01-12 |last2=Flaherty |last3=Kazerooni |last4=Iannettoni |author5=American College of Chest Physicians }}</ref><ref name="Radiology2006">{{cite journal |author=Winer-Muram HT |title=The solitary pulmonary nodule |journal=Radiology |volume=239 |issue=1 |pages=34–49 |date=April 2006 |pmid=16567482 |doi=10.1148/radiol.2391050343 |url=http://radiology.rsnajnls.org/cgi/pmidlookup?view=long&pmid=16567482}}</ref>

==Planning==
{{Lung nodule - choice of investigation}}

==Evaluation==
Always evaluate the following:
*'''Size''': larger size confers a higher risk of cancer<ref name="MacMahonNaidich2017">{{cite journal|last1=MacMahon|first1=Heber|last2=Naidich|first2=David P.|last3=Goo|first3=Jin Mo|last4=Lee|first4=Kyung Soo|last5=Leung|first5=Ann N. C.|last6=Mayo|first6=John R.|last7=Mehta|first7=Atul C.|last8=Ohno|first8=Yoshiharu|last9=Powell|first9=Charles A.|last10=Prokop|first10=Mathias|last11=Rubin|first11=Geoffrey D.|last12=Schaefer-Prokop|first12=Cornelia M.|last13=Travis|first13=William D.|last14=Van Schil|first14=Paul E.|last15=Bankier|first15=Alexander A.|title=Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017|journal=Radiology|volume=284|issue=1|year=2017|pages=228–243|issn=0033-8419|doi=10.1148/radiol.2017161659}}</ref>
[[File:CT of a subpleural nodule.png|thumb|subpleural nodule.<ref name=Snoeckx2017/>]]
*'''Location''': Upper lobe location is a risk factor for cancer, while a location close to a [[lung fissure|fissure]] or the [[pleura]] indicates a benign lymph node,<ref name="MacMahonNaidich2017"/> especially if having a triangular shape.<ref name=Snoeckx2017/>
*'''Margin''' morphology: a [[Spiculated mass|spiculated]] margin is a risk factor for cancer.<ref name="MacMahonNaidich2017"/> Benign causes tend to have a well defined border, whereas lobulated lesions or those with an irregular margin extending into the neighbouring tissue tend to be malignant.<ref name="Radiology2006"/> In particular, spiculations are highly predictive of malignancy with a positive predictive value up to 90%.<ref name=Snoeckx2017/> Also, a "notch sign", which is an abrupt indentation of the nodule, increases the risk of cancer, but may also be found in granulomatous diseases.<ref name=Snoeckx2017/>
<gallery mode=packed heights=190>
File:CT of a round well-delineated solid lung nodule with smooth border.jpg|Round well-delineated solid lung nodule with smooth border.<ref name=Snoeckx2017/>
File:CT of a lobulated lung nodule.png|Lobulated nodule.<ref name=Snoeckx2017/>
File:CT of a spiculated lung nodule.png|Spiculated lung nodule.<ref name=Snoeckx2017/>
File:CT of a lung nodule with a notch sign.png|A "notch sign".<ref name=Snoeckx2017/>
File:CT of perifissural nodule.png|A triangular perifissural node can be diagnosed as a benign lymph node.<ref name=Snoeckx2017/>
</gallery>
*'''Multiplicity''': Where the presence of up to an additional 3 nodules has been found to increase the risk of cancer, but decrease in case of 4 or more additional ones, likely because it indicates a previous granulomatous infection rather than cancer.<ref name="MacMahonNaidich2017"/>
*Presence of '''[[emphysema]]''' and/or '''[[lung fibrosis]]''', which are risk factors for cancer.<ref name="MacMahonNaidich2017"/>
*'''Attenuation''': A solitary nodule with a density below 15 [[Hounsfield unit]]s on [[computed tomography]] tends to be benign, whereas malignant tumors often measure more than 20 Hounsfield units. Fatty tissue inside hamartomas will have a strongly negative value on the [[Hounsfield scale]]. However, oly about 50% of hamartomas are fat containing.<ref name=Snoeckx2017/>

If previous exams are available, also evaluate:
*'''Growth''' rate: solid cancers generally doubles in volume over between 100 to 400 days, while subsolid cancers (generally representing adenocarcinomas) generally doubles in volume over 3 to 5 years.<ref name="MacMahonNaidich2017"/> One volume doubling equals approximately a 26% increase in diameter.<ref name="MacMahonNaidich2017"/> In comparison, the typical size doubling are less than 20 days for infections, and more than 400 days for benign nodules.<ref>{{cite journal|last1=Truong, MD|first1=Mylene T.|last2=Ko, MD|first2=Jane P.|last3=Rossi, MD|first3=Santiago E.|last4=Rossi, MD|first4=Ignacio|last5=Viswanathan, MD|first5=Chitra|last6=Bruzzi, MBBCh|first6=John F.|last7=Marom, MD|first7=Edith M.|last8=Erasmus, MD|first8=Jeremy J.|title=Update in the Evaluation of the Solitary Pulmonary Nodule|journal=Radiological Society of North America|date=2014|volume=34|issue=6|pages=1658–1679|doi=10.1148/rg.346130092|pmid=25310422}}</ref>

Preferably also look for the following signs:
*If there is a '''central cavity''', then a thin wall points to a benign cause whereas a thick wall is associated with malignancy (especially 4 mm or less versus 16 mm or more).<ref name="Radiology2006"/>
<gallery>
File:CT of a fat containing hamartoma.png|Low attenuating nodule (in this case a fat containing hamartoma).<ref name=Snoeckx2017/>
File:CT of an aspergilloma.png|Cavitation with relatively thick wall, in this case [[aspergilloma]]).<ref name=Snoeckx2017/>
</gallery>
[[File:CT of a hamartoma.png|thumb|Calcifications and popcorn-like appearance, conferring a diagnosis of hamartoma.<ref name=Snoeckx2017/>]]
*In case of '''calcifications''', a popcorn-like appearance indicates a hamartoma, which is benign.<ref name="NEJM-cp"/>
*In case of '''subsolid''' nodules, being part solid has a higher risk of cancer than being purely [[ground glass opacity]].
<gallery mode=packed heights=190>
File:CT of part solid lung nodule.png|Part solid nodule.<ref name=Snoeckx2017/>
File:CT of ground glass lung nodule.png|[[Ground glass opacity]] nodule.<ref name=Snoeckx2017/>
</gallery>
*'''Pleural retraction''' is far more common in cancers.<ref name=Snoeckx2017/> It is the pulling of visceral pleura towards the nodule.<ref name=Snoeckx2017/>
<gallery mode=packed heights=190>
File:CT of a lung nodule with pleural retraction.png|Nodule with pleural retraction.<ref name=Snoeckx2017/>
File:CT of a subpleural nodule with pleural retraction.png|In this case, pleural retraction is seen as a triangular fat component.<ref name=Snoeckx2017/>
</gallery>
[[File:CT of a lung nodule abutting a cystic airspace.png|thumb|180px|Lung nodule abutting a pulmonary cyst.<ref name=Snoeckx2017/>]]
*A lung nodule '''abutting a [[pulmonary cyst]]''' is a rare finding, yet indicating cancer.<ref name=Snoeckx2017/>
*'''Bubble-like lucencies''' in the nodule indicate cancer:<ref name=Snoeckx2017/>
<gallery mode=packed heights=190>
File:CT of spiculated lung nodule with bubble-like lucencies.png
File:CT of lung nodule with bubble-like lucencies.png
</gallery>
[[File:CT of lung nodule with vascular convergence (crop).png|thumb|Thin slice and [[maximal intensity projection]] of a lung nodule, the latter better visualizing vascular convergence.<ref name=Snoeckx2017/>]]
*'''Vascular convergence''' is where vessels converge to a nodule without adjoining or contacting the edge of the nodule, and is mainly seen in peripheral subsolid lung cancers.<ref name=Snoeckx2017/> It reflects [[angiogenesis]].<ref name=Snoeckx2017/>

[[Air bronchogram]]s is defined as a pattern of air-filled bronchi on a background of airless lung, and may be seen in both benign and malignant nodules, but certain patterns thereof may help in risk stratification.<ref name=Snoeckx2017/> {{Further|Air bronchogram}}

===Further management===
Further management depends largely on an overall radiologic classification of a nodule as low or high cancer risk, which is rather subjective. Furthermore, it generally also requires knowledge of general risk factors of cancer (such as exposure to tobacco smoking or other carcinogens such as asbestos, previously diagnosed cancer, respiratory infections, or chronic obstructive pulmonary disease.<ref name=Zhan2013>{{cite journal|last1=Zhan|first1=Ping|last2=Xie|first2=Haiyan|last3=Xu|first3=Chunhua|last4=Hao|first4=Keke|last5=Hou|first5=Zhibo|last6=Song|first6=Yong|title=Management strategy of solitary pulmonary nodules|journal=Journal of Thoracic Disease|date=2013|volume=5|issue=6|pages=824–829|doi=10.3978/j.issn.2072-1439.2013.12.13|pmid=24409361|pmc=3886686}}</ref>). For incidentally detected nodules on CT scan, Fleischner Society guidelines are given in table below. For multiple nodes, management is based on the most suspicious node.<ref name="MacMahonNaidich2017"/> These guidelines do not apply in lung cancer screening, in patients with immunosuppression, or in patients with known primary cancer.<ref name="MacMahonNaidich2017"/>

{|class="wikitable"
|+Solid nodules<ref name="MacMahonNaidich2017"/>
|-
!colspan=2| !! <6 mm (<100mm3) !! 6-8mm (100-250mm3) !! >8mm (>250mm3)
|-
!rowspan=2| Single nodule !! Low risk
| No routine follow-up || CT after 6-12 months, then consider CT after 18-24 months ||rowspan=2| Consider CT at 3 months, [[PET-CT]] or biopsy
|-
! High risk
| Optionally, CT after 12 months || CT after 6-12 months, then after 18-24 months
|-
!rowspan=2| Multiple nodules !! Low risk
| No routine follow-up ||colspan=2 align=center| CT after 3-6 months, then consider CT after 18-24 months
|-
! High risk
| Optionally CT after 12 months ||colspan=2 align=center| CT after 3-6 months, then after 18-24 months
|}

{|class="wikitable"
|+Subsolid nodules<ref name="MacMahonNaidich2017"/>
|-
!colspan=2| !! Total size <6 mm (<100mm3) !! Total size >6mm (>1003)
|-
!rowspan=2| Single nodule !! [[Ground glass opacity]]
| No routine follow-up || CT after 6-12 months to check if persistent, then after 2 years and then another 2 years
|-
! Part solid
| No routine follow-up || CT after 6-12 months:
*If unchanged and solid component remains <6mm: Annual CT for 5 years.
*Solid component ≥6mm: highly suspicious
|
|-
!colspan=2| Multiple nodules
| CT after 3-6 months. If stable, consider CT after 2 and then another 2 years. || CT after 3-6 months, then after 18-24 months
|}

More frequent CT scans than what is recommended has not been shown to improve outcomes but will increase radiation exposure and the [[unnecessary health care]] can be expected to make the patient anxious and uncertain.<ref name="ACCPandATSfive-1b">{{Cite journal|author1 = American College of Chest Physicians |author1-link = American College of Chest Physicians |author2 = American Thoracic Society |author2-link = American Thoracic Society |date = September 2013 |title = Five Things Physicians and Patients Should Question |publisher = American College of Chest Physicians and American Thoracic Society |journal = Choosing Wisely: An Initiative of the ABIM Foundation |page = |url = http://www.choosingwisely.org/doctor-patient-lists/american-college-of-chest-physicians-and-american-thoracic-society/ |accessdate = 6 January 2013|postscript = {{inconsistent citations}} }}, which cites
*{{cite journal|last1=Smith-Bindman|first1=R|last2=Lipson|first2=J|last3=Marcus|first3=R|last4=Kim|first4=KP|last5=Mahesh|first5=M|last6=Gould|first6=R|last7=Berrington de González|first7=A|last8=Miglioretti|first8=DL|title=Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer.|journal=Archives of Internal Medicine|date=Dec 14, 2009|volume=169|issue=22|pages=2078–86|pmid=20008690|doi=10.1001/archinternmed.2009.427|pmc=4635397}}
*{{cite journal|last1=Wiener|first1=RS|last2=Gould|first2=MK|last3=Woloshin|first3=S|last4=Schwartz|first4=LM|last5=Clark|first5=JA|title=What do you mean, a spot?: A qualitative analysis of patients' reactions to discussions with their physicians about pulmonary nodules.|journal=Chest|date=Mar 2013|volume=143|issue=3|pages=672–7|pmid=22814873|doi=10.1378/chest.12-1095|pmc=3590883}}</ref>

;PET scan
[[Image:FDG-PET initial study solitary pulmonary nodule Non-Hodgkin lymphoma.jpg|thumb|[[FDG-PET]] study of a 71-year-old woman with a solitary pulmonary nodule (''thin arrow'') in the left lower lobe near the heart. The scan also revealed abnormal increased activity at the [[gastro-esophageal junction]] (''thick arrow''). The final diagnosis was [[non-Hodgkin lymphoma]] at both sites.]]
If there is an intermediate risk of malignancy, further imaging with positron emission tomography (PET scan) is appropriate (if available). It can be done as a [[PET-CT]]. Around 95% of patients with a malignant nodule will have an abnormal PET scan, while around 78% of patients with a benign nodule will look normal on PET (this is the test sensitivity and specificity).<ref name="JAMA-2001">{{cite journal |author=Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK |title=Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis |journal=JAMA |volume=285 |issue=7 |pages=914–24 |date=February 2001 |pmid=11180735 |doi=10.1001/jama.285.7.914 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=11180735 |archive-url=https://archive.is/20090425182659/http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=11180735 |dead-url=yes |archive-date=2009-04-25 |last2=MacLean |last3=Kuschner |last4=Rydzak |last5=Owens }}</ref> Thus, an abnormal PET scan will reliably pick up cancer, but several other types of nodules (inflammatory or infectious, for example) will also show up on a PET scan. If the nodule has a diameter of less than one centimeter, PET scans are often avoided because of an increased risk of [[false-negative|falsely normal]] results.<ref name="JAMA-2001"/><ref name="pmid17412254">{{cite journal |author=Khan A |title=ACR Appropriateness Criteria on solitary pulmonary nodule |journal=J Am Coll Radiol |volume=4 |issue=3 |pages=152–5 |date=March 2007 |pmid=17412254 |doi=10.1016/j.jacr.2006.12.003 |url=http://linkinghub.elsevier.com/retrieve/pii/S1546-1440(06)00694-6}}</ref><ref name="pmid17409830">{{cite journal |author=Vansteenkiste JF, Stroobants SS |title=PET scan in lung cancer: current recommendations and innovation |journal=J Thorac Oncol |volume=1 |issue=1 |pages=71–3 |date=January 2006 |pmid=17409830 |doi= 10.1097/01243894-200601000-00014|url=|last2=Stroobants }}</ref> Cancerous lesions usually have a high [[metabolism]] on PET, as demonstrated by their high uptake of [[fluorodeoxyglucose|FDG]] (a radioactive sugar).
<gallery>
File:PET-CT of a tuberculoma.png|PET-CT of a tuberculoma.
</gallery>
{{Bottom}}

@@ Line 27: / Line 27: @@
 *'''Multiplicity''': Where the presence of up to an additional 3 nodules has been found to increase the risk of cancer, but decrease in case of 4 or more additional ones, likely because it indicates a previous granulomatous infection rather than cancer.<ref name="MacMahonNaidich2017"/>
 *Presence of '''[[emphysema]]''' and/or '''[[lung fibrosis]]''', which are risk factors for cancer.<ref name="MacMahonNaidich2017"/>
-*'''Attenuation''': A solitary nodule with a density below 15 [[Hounsfield unit]]s on [[computed tomography]] tends to be benign, whereas malignant tumors often measure more than 20 Hounsfield units. Fatty tissue inside hamartomas will have a strongly negative value on the [[Hounsfield scale]]. However, oly about 50% of hamartomas are fat containing.<ref name=Snoeckx2017/>
+*'''Enhancement''': If the exam is done as a combined non-contrast and [[contrast CT]], a solitary nodule with an enhancement off less than 15 [[Hounsfield unit]]s (HU), whereas a higher enhancement indicates a malignant tumor (with a [[sensitivity and specificity|sensitivity]] estimated at 98%).<ref name=Medscape>{{cite web|url=https://emedicine.medscape.com/article/358090-overview#a3|title=Lung Metastases Imaging|author=Tanay Patel|website=[[Medscape]]}} Updated: Sep 30, 2018</ref>
 If previous exams are available, also evaluate:
@@ Line 35: / Line 37: @@
 *If there is a '''central cavity''', then a thin wall points to a benign cause whereas a thick wall is associated with malignancy (especially 4&nbsp;mm or less versus 16&nbsp;mm or more).<ref name="Radiology2006"/>
 <gallery>
 File:CT of an aspergilloma.png|Cavitation with relatively thick wall, in this case [[aspergilloma]]).<ref name=Snoeckx2017/>
 </gallery>
@@ Line 61: / Line 62: @@
 [[Air bronchogram]]s is defined as a pattern of air-filled bronchi on a background of airless lung, and may be seen in both benign and malignant nodules, but certain patterns thereof may help in risk stratification.<ref name=Snoeckx2017/> {{Further|Air bronchogram}}
 ===Further management===

@@ Line 12: / Line 12: @@
 ==Planning==
 {{Lung nodule - choice of investigation}}
 ==Evaluation==
 Always evaluate the following:

@@ Line 41: / Line 41: @@
 </gallery>
 [[File:CT of a hamartoma.png|thumb|Calcifications and popcorn-like appearance, conferring a diagnosis of hamartoma.<ref name=Snoeckx2017/>]]
-*In case of '''calcifications''', a popcorn-like appearance indicates a hamartoma, which is benign.<ref name="NEJM-cp"/>
+*In case of '''calcifications''', a popcorn-like appearance indicates a hamartoma, which is benign.<ref name="NEJM-cp">{{cite journal |author=Ost D, Fein AM, Feinsilver SH |title=Clinical practice. The solitary pulmonary nodule |journal=N. Engl. J. Med. |volume=348 |issue=25 |pages=2535–42 |date=June 2003 |pmid=12815140 |doi=10.1056/NEJMcp012290 |last2=Fein |last3=Feinsilver }}</ref>
 *In case of '''subsolid''' nodules, being part solid has a higher risk of cancer than being purely [[ground glass opacity]].
 <gallery mode=packed heights=190>