Lung cancer Diagnostic study of choice: Difference between revisions

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__NOTOC__
__NOTOC__
{{Lung cancer}}
{{Lung cancer}}
{{CMG}}; {{AE}}
{{CMG}}; {{AE}} {{SH}}{{KSH}}, {{CZ}}. {{Rim}}, [[User:Michael Maddaleni|Michael Maddaleni, B.S.]]
==Overview==
==Overview==
Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include, a solitary [[pulmonary nodule]], centrally located [[Tumor|masses]], [[Mediastinum|mediastinal]] invasion
[[Chest]] [[Computed tomography|CT scan]] is the modality of choice in the [[diagnosis]] of lung cancer. Findings on [[Computed tomography|CT scan]] suggestive of lung cancer include a [[pulmonary nodule|solitary pulmonary nodule]], centrally located [[Tumor|masses]], [[Mediastinum|mediastinal]] [[Invasive (medical)|invasion]]
CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sights of metastases: adrenal glands, liver, and brain. CT scans diagnose lung cancer by providing anatomical detail to locate the [[tumor]], demonstrating proximity to nearby structures, and deciphering whether [[lymph nodes]] are enlarged in the [[mediastinum]].
[[Computed tomography|CT scans]] help [[Cancer staging|stage]] the lung cancer. A [[Computed tomography|CT scan]] of the [[abdomen]] and [[brain]] can help visualize the common sights of [[Metastasis|metastases]] such as [[Adrenal gland|adrenal glands]], [[liver]], and [[brain]]. [[Computed tomography|CT scans]] [[Diagnosis|diagnose]] lung cancer by providing [[anatomical]] detail to locate the [[tumor]], demonstrating proximity to the nearby structures, and deciphering whether [[lymph nodes]] are enlarged in the [[mediastinum]].


== CT Scan ==
== Diagnostic Study of Choice ==
Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include:<ref name="PurandareRangarajan2015">{{cite journal|last1=Purandare|first1=NilenduC|last2=Rangarajan|first2=Venkatesh|title=Imaging of lung cancer: Implications on staging and management|journal=Indian Journal of Radiology and Imaging|volume=25|issue=2|year=2015|pages=109|issn=0971-3026|doi=10.4103/0971-3026.155831}}</ref>
 
*Solitary [[pulmonary nodule]]
=== Study of Choice ===
[[Chest]] [[Computed tomography|CT scan]] is the modality of choice in the [[diagnosis]] of lung cancer. Findings on [[Computed tomography|CT scan]] suggestive of lung cancer include:<ref name="PurandareRangarajan2015">{{cite journal|last1=Purandare|first1=NilenduC|last2=Rangarajan|first2=Venkatesh|title=Imaging of lung cancer: Implications on staging and management|journal=Indian Journal of Radiology and Imaging|volume=25|issue=2|year=2015|pages=109|issn=0971-3026|doi=10.4103/0971-3026.155831}}</ref>
 
*[[pulmonary nodule|Solitary pulmonary nodule]]
*Centrally located [[Tumor|masses]]
*Centrally located [[Tumor|masses]]
*[[Mediastinum|Mediastinal]] invasion
*[[Mediastinum|Mediastinal]] [[Invasive (medical)|invasion]]
*Peripherally situated [[Lesion|lesions]] invading the [[Thoracic cavity|chest wall]]
*Peripherally situated [[Lesion|lesions]] invading the [[Thoracic cavity|chest wall]]
*A [[Ground glass opacification on CT|ground-glass opacity]]
*A [[Ground glass opacification on CT|ground-glass opacity]]
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== Spiral CT perfusion imaging ==
==== Spiral CT perfusion imaging ====
 
*Spiral CT perfusion study can be used as a diagnostic method for peripheral pulmonary nodules.
*Spiral CT perfusion study can be used as a diagnostic method for peripheral pulmonary nodules.
*Spiral CT perfusion study provides non-invasive method of quantitative assessment about the blood flow patterns of peripheral pulmonary nodules.
*Spiral CT perfusion study provides non-invasive method of quantitative assessment about the blood flow patterns of peripheral pulmonary nodules.
*Spiral CT perfusion imaging is analyzed and evaluated for:.<ref name="MaLe2008">{{cite journal|last1=Ma|first1=Shu-Hua|last2=Le|first2=Hong-Bo|last3=Jia|first3=Bao-hui|last4=Wang|first4=Zhao-Xin|last5=Xiao|first5=Zhuang-Wei|last6=Cheng|first6=Xiao-Ling|last7=Mei|first7=Wei|last8=Wu|first8=Min|last9=Hu|first9=Zhi-Guo|last10=Li|first10=Yu-Guang|title=Peripheral pulmonary nodules: Relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression|journal=BMC Cancer|volume=8|issue=1|year=2008|issn=1471-2407|doi=10.1186/1471-2407-8-186}}</ref>]]
*Spiral CT perfusion imaging is analyzed and evaluated for:.<ref name="MaLe2008">{{cite journal|last1=Ma|first1=Shu-Hua|last2=Le|first2=Hong-Bo|last3=Jia|first3=Bao-hui|last4=Wang|first4=Zhao-Xin|last5=Xiao|first5=Zhuang-Wei|last6=Cheng|first6=Xiao-Ling|last7=Mei|first7=Wei|last8=Wu|first8=Min|last9=Hu|first9=Zhi-Guo|last10=Li|first10=Yu-Guang|title=Peripheral pulmonary nodules: Relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression|journal=BMC Cancer|volume=8|issue=1|year=2008|issn=1471-2407|doi=10.1186/1471-2407-8-186}}</ref>]]
**TDC (time density curve)
**TDC (time density curve)
**Perfusion parametric maps
**Perfusion parametric maps
**The respective perfusion parameters.  
**The respective perfusion parameters.
**Immunohistochemical findings of microvessel density (MVD) measurement  
**Immunohistochemical findings of microvessel density (MVD) measurement
**VEGF expression
**VEGF expression
{| class="wikitable"
{| class="wikitable"
|[[Image:Peripheral pulmonary nodules1.jpg|thumb|300px|(A-H) Poorly differentiated adenocarcinoma found in the apicoposterior segment of superior lobe of the left lung of a 56 year-old male. (A) Time density curve. (B-F) (original image, BF, BV, MTT, PS) typeI parametric maps, PS value is higher (30.883). (G) CD34 staining shows many immature tumor microvessels (× 200). (H) VEGF expression is strong positive (× 400) via, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474637/figure/F6/.<ref name="MaLe2008">{{cite journal|last1=Ma|first1=Shu-Hua|last2=Le|first2=Hong-Bo|last3=Jia|first3=Bao-hui|last4=Wang|first4=Zhao-Xin|last5=Xiao|first5=Zhuang-Wei|last6=Cheng|first6=Xiao-Ling|last7=Mei|first7=Wei|last8=Wu|first8=Min|last9=Hu|first9=Zhi-Guo|last10=Li|first10=Yu-Guang|title=Peripheral pulmonary nodules: Relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression|journal=BMC Cancer|volume=8|issue=1|year=2008|issn=1471-2407|doi=10.1186/1471-2407-8-186}}</ref>]]
|[[Image:Peripheral pulmonary nodules1.jpg|thumb|300px|(A-H) Poorly differentiated adenocarcinoma found in the apicoposterior segment of superior lobe of the left lung of a 56 year-old male. (A) Time density curve. (B-F) (original image, BF, BV, MTT, PS) typeI parametric maps, PS value is higher (30.883). (G) CD34 staining shows many immature tumor microvessels (× 200). (H) VEGF expression is strong positive (× 400) via, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474637/figure/F6/.<ref name="MaLe2008">{{cite journal|last1=Ma|first1=Shu-Hua|last2=Le|first2=Hong-Bo|last3=Jia|first3=Bao-hui|last4=Wang|first4=Zhao-Xin|last5=Xiao|first5=Zhuang-Wei|last6=Cheng|first6=Xiao-Ling|last7=Mei|first7=Wei|last8=Wu|first8=Min|last9=Hu|first9=Zhi-Guo|last10=Li|first10=Yu-Guang|title=Peripheral pulmonary nodules: Relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression|journal=BMC Cancer|volume=8|issue=1|year=2008|issn=1471-2407|doi=10.1186/1471-2407-8-186}}</ref>]]
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== CT Findings of Metastatic disease ==
==== CT Findings of Metastatic disease ====
 
*CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sights of metastases: adrenal glands, liver, and brain.
*CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sights of metastases: adrenal glands, liver, and brain.
*The benefits of CT Scans in lung cancer patients are the following:<ref name="Silvestri">Gerard A. Silvestri, Lynn T. Tanoue, Mitchell L. Margolis, John Barker, Frank Detterbeck.11/30/11.The Noninvasive Staging of Non Small-cell Lung Cancer. Chestpubs. http://chestjournal.chestpubs.org/content/123/1_suppl/147S.full/</ref>
*The benefits of CT Scans in lung cancer patients are the following:<ref name="Silvestri">Gerard A. Silvestri, Lynn T. Tanoue, Mitchell L. Margolis, John Barker, Frank Detterbeck.11/30/11.The Noninvasive Staging of Non Small-cell Lung Cancer. Chestpubs. http://chestjournal.chestpubs.org/content/123/1_suppl/147S.full/</ref>
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**Demonstrates proximity to nearby structures
**Demonstrates proximity to nearby structures
**Deciphers whether [[lymph nodes]] are enlarged in the [[mediastinum]]
**Deciphers whether [[lymph nodes]] are enlarged in the [[mediastinum]]
{| class="wikitable"
{| class="wikitable"
|[[Image:IJRI-25-109-g010.jpg|thumb|300px|Metastatic disease. Bilateral pleural effusions-M1a (arrow, A), lung metastases-M1a (arrows, B), adrenal metastasis-M1b (arrow, C), vertebral metastasis-M1b (arrow, D), brain metastasis-M1b (arrow, E), liver metastases-M1b (arrows, F)via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F10/>This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.<ref name="PurandareRangarajan2015">{{cite journal|last1=Purandare|first1=NilenduC|last2=Rangarajan|first2=Venkatesh|title=Imaging of lung cancer: Implications on staging and management|journal=Indian Journal of Radiology and Imaging|volume=25|issue=2|year=2015|pages=109|issn=0971-3026|doi=10.4103/0971-3026.155831}}</ref>]]
|[[Image:IJRI-25-109-g010.jpg|thumb|300px|Metastatic disease. Bilateral pleural effusions-M1a (arrow, A), lung metastases-M1a (arrows, B), adrenal metastasis-M1b (arrow, C), vertebral metastasis-M1b (arrow, D), brain metastasis-M1b (arrow, E), liver metastases-M1b (arrows, F)via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F10/>This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.<ref name="PurandareRangarajan2015">{{cite journal|last1=Purandare|first1=NilenduC|last2=Rangarajan|first2=Venkatesh|title=Imaging of lung cancer: Implications on staging and management|journal=Indian Journal of Radiology and Imaging|volume=25|issue=2|year=2015|pages=109|issn=0971-3026|doi=10.4103/0971-3026.155831}}</ref>]]
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*Unfortunately, research has shown that there are a number of false positives associated with CT scanning because a CT scan on its own cannot determine [[malignancy]].  
*Unfortunately, research has shown that there are a number of false positives associated with CT scanning because a CT scan on its own cannot determine [[malignancy]].  
*A positive result for a tumor using a CT scan is typically followed up with a [[biopsy]] for confirmation.
*A positive result for a tumor using a CT scan is typically followed up with a [[biopsy]] for confirmation.
=== Staging ===
The following is 2017 TNM classification of lung cancer.<ref>{{cite book | last =Mountain | first =CF | authorlink = | coauthors =Libshitz HI, Hermes KE | title =A Handbook for Staging, Imaging, and Lymph Node Classification | publisher =Charles P Young Company | date =2003 | url =http://www.ctsnet.org/book/mountain/index.html | accessdate =2007-09-01 }}</ref><ref name="Collins">{{cite journal | last = Collins | first = LG | coauthors = Haines C, Perkel R, Enck RE | title = Lung cancer: diagnosis and management | journal = American Family Physician | volume = 75 | issue = 1 | pages = 56–63 | publisher = American Academy of Family Physicians | date = Jan 2007 | url= http://www.aafp.org/afp/20070101/56.html | pmid =17225705 | accessdate =2007-08-10 }}</ref><ref name="HarmsKriegsmann2017">{{cite journal|last1=Harms|first1=A.|last2=Kriegsmann|first2=M.|last3=Fink|first3=L.|last4=Länger|first4=F.|last5=Warth|first5=A.|title=Die neue TNM-Klassifikation für Lungentumoren|journal=Der Pathologe|volume=38|issue=1|year=2017|pages=11–20|issn=0172-8113|doi=10.1007/s00292-017-0268-y}}</ref>
====T: Primary Tumor====
{|
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''T'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="center" |'''Description'''
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |TX || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Primary tumor cannot be assessed.<br> OR <br>Tumor is demonstrated by the presence of malignant cells in bronchial washings or [[sputum]], but is not visualized by imaging or [[bronchoscopy]].
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" | T0 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |There is no evidence of primary tumor.
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Tis || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Carcinoma in situ
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |The tumor has the following characteristics:
* T1a: tumor ≤1 cm in the largest diameter.
* T1b: tumor> 1 cm, but ≤2 cm in the largest diameter.
* T1c: tumor> 2 cm, but ≤3 cm in the largest diameter.<br> AND <br>The tumor is surrounded by lung or [[visceral pleura]]<br> AND <br>The tumor does not extend to the main bronchus as demonstrated by the absence of bronchoscopic evidence of invasion more proximal than the lobar bronchus.
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |The tumor has the following characteristics:
* T2a: tumor> 3 cm, but ≤4 cm in the largest diameter.
* T2b: Tumor> 4 cm, but ≤5 cm in the largest diameter.<br>The tumor involves the main bronchus, 2 cm or more distal to the [[carina]]. <br> OR <br>The tumor invades the [[visceral pleura]]. <br> OR <br>There is evidence of [[atelectasis]] or obstructive [[pneumonitis]] that extends to the hilar region without the involvement of the entire lung.
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Tumor > 5 cm, but ≤ 7 cm in size.
AND
It directly invades any of the following: [[chest wall]] (including superior sulcus tumors), [[diaphragm]], mediastinal pleura, parietal [[pericardium]].<br> OR <br>The tumor is localized in the main bronchus at a distance less than 2 cm distal to the [[carina]] but without the involvement of the [[carina]].<br> OR <br>There is evidence of associated [[atelectasis]] or obstructive [[pneumonitis]] of the entire lung.
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T4 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Tumor > 7 cm in size.
The tumor invades any of the following: [[mediastinum]], [[heart]], great vessels, [[trachea]], [[esophagus]], [[vertebral body]], [[carina]]<br> OR <br>There is/are separate tumor nodule(s) in the same lobe. <br> OR
The tumor is associated with malignant [[pleural effusion]].
|}
====N:Regional Lymph Nodes====
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''T'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="center" |'''Description'''
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |NX || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |the regional [[lymph node]]s cannot be assessed.
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N0 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |There is no evidence of regional lymph node metastasis.
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N1 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |[[Metastasis]] in [[Anatomical terms of location|ipsilateral]] peribronchial and/or [[Anatomical terms of location|ipsilateral]] [[Hilar lymphadenopathy|hilum]] or intrapulmonary [[Lymph node|lymph nodes]]
N1a - A [[lymph node]] invasion.
N1b - > 1 [[lymph node]] affected.
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |There is [[metastasis]] in ipsilateral [[Mediastinum|mediastinal]] and/or subcarinal [[Lymph node|lymph node(s).]]
N2a1 - One lymph node infested without lymph node involvement of an N1-defined lymph node station.
N2a2 - One lymph node infested with a lymph node of an N1-defined lymph node station
N2b - > 1 lymph node affected
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |There is [[metastasis]] in [[Anatomical terms of location|contralateral]] [[Mediastinum|mediastinal]], contralateral [[Hilum|hilar]], [[Anatomical terms of location|ipsilateral]] or [[Anatomical terms of location|contralateral]] scalene, or supraclavicular [[Lymph node|lymph node(s).]]
|}
====M: Distant Metastasis====
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF; width: 10%" align="center" |'''T'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="center" |'''Description'''
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |MX || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Distant metastasis cannot be assessed.
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |There is no evidence of distant [[metastasis]].
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M1 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |There is evidence of [[distant]] metastasis which includes the presence of separate tumor nodule(s) in a different lobe (ipsilateral or contralateral).
M1a - Tumor foci separated from the primary tumor in a contralateral lung lobe; Tumor with pleural metastases or malignant pleural or pericardial effusion
M1b - Simple metastases in an organ
M1c - Multiple metastases in one organ or one or more metastases in more than one organ
|}
===Classification of Lung Cancer by Staging===
{| style="cellpadding=0; cellspacing= 0; width: 600px;"
|-
| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="center" |'''Stage'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="center" |'''T'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="center" |'''N'''|| style="padding: 0 5px; font-size: 100%; background: #4682B4; color: #FFFFFF" align="center" |'''M'''
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Occult carcinoma''' || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |TX|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N0|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Stage 0''' || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Tis || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" | N0 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Stage IA1''' || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1(mi)/T1a || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N0 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Stage IA2''' || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1b || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N0 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" | M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" | '''Stage IA3'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1c || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N0 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" | M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Stage IB''' || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2a || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N0 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" | M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Stage IIA''' || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2b || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N0 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| rowspan="5" style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Stage IIB''' || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1a || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N1 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" | M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1c || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N1 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2a || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N1 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2b || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N1 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N0 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| rowspan="13" style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Stage IIIA''' || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1a
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1b || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1c || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2a || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2b || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1a || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1b || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1c || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2a || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2b || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N1 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T4 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N0 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T4|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N1 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| rowspan="12" style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Stage IIIB''' || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1a|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1b || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1c || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2a || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2b || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1a || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1b || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T1c || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2a || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T2b || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T4 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N2 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| rowspan="2"  style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Stage IIIC'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |T4 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |N3 || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M0
|-
| rowspan="2" style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Stage IVA'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Any T || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Any N || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M1a
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Any T || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Any N || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M1b
|-
| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |'''Stage IVB'''|| style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Any T || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |Any N || style="font-size: 100; padding: 0 5px; background: #B8B8B8" align="left" |M1c
|}
===Procedures for Staging Lung Cancer===
There are currently multiple different procedures available to stage lung cancer.
* They can be broken down into two overarching categories, [[invasive]] and minimally invasive.
** The [[Invasive (medical)|invasive procedures]] are:
*** [[EUS-NA]] ([[esophageal]] [[endoscopic]] [[ultrasound]] with needle [[aspiration]])
*** [[TBNA]] ([[TBNA|transbronchial needle aspiration]])
*** [[EBUS-NA|EBUS-NA (endobronchial ultrasound with needle aspiration)]]
*** [[TTNA]] ([[transthoracic needle aspiration]])
*** [[Thoracoscopy|VATS staging (video assisted thoracic surgery)]] ''aka'' [[thoracoscopy]]
*** [[Mediastinoscopy|Extended cervical mediastinoscopy]]
*** [[Chamberlain procedure]]
** The [[Minimally invasive procedure|minimally invasive procedures]] are:
*** [[EBUS-NA|EBUS-FNA]] ([[Endoscopic ultrasound|endobronchial ultrasound]] guided [[Needle aspiration biopsy|fine needle aspiration)]]
*** [[EUS-NA|EUS-FNA]] ([[esophageal endoscopic ultrasound]] guided [[Needle aspiration biopsy|fine needle aspiration)]]


==References==
==References==

Latest revision as of 19:04, 4 July 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dildar Hussain, MBBS [2]Kim-Son H. Nguyen M.D., Cafer Zorkun, M.D., Ph.D. [3]. Rim Halaby, M.D. [4], Michael Maddaleni, B.S.

Overview

Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include a solitary pulmonary nodule, centrally located masses, mediastinal invasion CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sights of metastases such as adrenal glands, liver, and brain. CT scans diagnose lung cancer by providing anatomical detail to locate the tumor, demonstrating proximity to the nearby structures, and deciphering whether lymph nodes are enlarged in the mediastinum.

Diagnostic Study of Choice

Study of Choice

Chest CT scan is the modality of choice in the diagnosis of lung cancer. Findings on CT scan suggestive of lung cancer include:[1]

Common radiological appearances of lung cancer. Centrally located mass with mediastinal invasion (arrow, A), peripherally situated mass abutting the pleura (arrow, B), mass with smooth, lobulated margins (arrow, C) and with spiculated, irregular margins (arrow, D), via <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F1/>[1]
Lung cancers with atypical radiological pattern. Squamous cell cancer presenting as a cavitating mass (arrow, A). Adenocarcinoma presenting as dense consolidation (arrow, B). Bronchoalveolar carcinoma (adenocarcinoma in situ) presenting as ground-glass opacity (arrow, C) and mixed density, solid (arrow), and ground-glass nodules (arrowhead) in D via <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F2/>[1]
Stage T1 and T2 tumors. Stage T1 tumor due to size <3 cm (arrow, A). Stage T2 endobronchial tumor (arrowhead) causing pneumonitis restricted to the upper lobe (arrow) in B. T2a tumor >3 cm but <5 cm (arrow, C). T2b tumor >5 cm but <7 cm (arrow in D) via <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F3/>[1]
Stage T3 tumors. T3 tumor due to size >7 cm in size (arrow, A), eroding the ribs (arrow, B), infiltrating the mediastinal pleura but not the vessels (arrow, C), and causing atelectasis of the entire lung (arrowhead, D via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F4/>.[1]
Stage T4 tumors. T4 tumor due to invasion of pulmonary artery (arrow, A), descending aorta (arrow, B), vertebral body (arrow, C), superior vena cava with thrombus (arrow, D)via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F5/>[1]
Superior sulcus tumor. Axial (A) and coronal (B) CT scans show a large mass in the apex of the right lung causing destruction of the first and second ribs (arrows) with erosion of the right half of the vertebral body (arrowheads) suggestive of a superior sulcus tumor, via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F16/>[1]

Spiral CT perfusion imaging

  • Spiral CT perfusion study can be used as a diagnostic method for peripheral pulmonary nodules.
  • Spiral CT perfusion study provides non-invasive method of quantitative assessment about the blood flow patterns of peripheral pulmonary nodules.
  • Spiral CT perfusion imaging is analyzed and evaluated for:.[2]]]
    • TDC (time density curve)
    • Perfusion parametric maps
    • The respective perfusion parameters.
    • Immunohistochemical findings of microvessel density (MVD) measurement
    • VEGF expression
(A-H) Poorly differentiated adenocarcinoma found in the apicoposterior segment of superior lobe of the left lung of a 56 year-old male. (A) Time density curve. (B-F) (original image, BF, BV, MTT, PS) typeI parametric maps, PS value is higher (30.883). (G) CD34 staining shows many immature tumor microvessels (× 200). (H) VEGF expression is strong positive (× 400) via, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474637/figure/F6/.[2]
(A-H) (A-H) Well differentiated squamous cell carcinoma found in the posterior basal segment of inferior lobe of the right lung of a 61-year-old male. (A) Time density curve. (B-F) (original image, BF, BV, MTT, PS) TypeII parametric maps, PS value is higher (27.051). (G) CD34 staining shows many immature tumor microvessels (× 200). (H) VEGF expression is strong positive (× 400). via, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474637/figure/F3/.[2]

CT Findings of Metastatic disease

  • CT scans help stage the lung cancer. A CT scan of the abdomen and brain can help visualize the common sights of metastases: adrenal glands, liver, and brain.
  • The benefits of CT Scans in lung cancer patients are the following:[3]
    • Provides anatomical detail to locate the tumor
    • Demonstrates proximity to nearby structures
    • Deciphers whether lymph nodes are enlarged in the mediastinum
Metastatic disease. Bilateral pleural effusions-M1a (arrow, A), lung metastases-M1a (arrows, B), adrenal metastasis-M1b (arrow, C), vertebral metastasis-M1b (arrow, D), brain metastasis-M1b (arrow, E), liver metastases-M1b (arrows, F)via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F10/>This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.[1]
Adrenal adenoma versus metastasis. Enhancing solid adrenal nodule on CT scan in a case of lung cancer (arrow, A) suggestive of metastatic deposit. Unenhanced CT scan shows fatty attenuation within the nodule with an HU value of 0 suggesting the possibility of an adenoma (arrow, B). FDG PET/CT shows no tracer concentration in the nodule, confirming the diagnosis of adenoma. Enhancing solid adrenal nodule on CT scan in another patient of lung cancer (arrow, D), which is indeterminate in nature. FDG PET/CT shows abnormal focal tracer concentration in the nodule (arrow, E) highly suggestive of a metastatic deposit via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F11/>[1]
Brain metastases in asymptomatic patient, CT scan versus MRI. MRI brain in a patient of lung cancer shows multiple tiny enhancing foci scattered in the parenchyma bilaterally (arrows in A and B) suggestive of metastatic lesions. Corresponding contrast CT scan sections of the brain show no obvious lesions (C and D). Note the beam hardening effects due to bone, leading to a loss of resolution on the CT images (C and D)via<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419420/figure/F12/>[1]
  • Unfortunately, research has shown that there are a number of false positives associated with CT scanning because a CT scan on its own cannot determine malignancy.
  • A positive result for a tumor using a CT scan is typically followed up with a biopsy for confirmation.

Staging

The following is 2017 TNM classification of lung cancer.[4][5][6]

T: Primary Tumor

T Description
TX Primary tumor cannot be assessed.
OR
Tumor is demonstrated by the presence of malignant cells in bronchial washings or sputum, but is not visualized by imaging or bronchoscopy.
T0 There is no evidence of primary tumor.
Tis Carcinoma in situ
T1 The tumor has the following characteristics:
  • T1a: tumor ≤1 cm in the largest diameter.
  • T1b: tumor> 1 cm, but ≤2 cm in the largest diameter.
  • T1c: tumor> 2 cm, but ≤3 cm in the largest diameter.
    AND
    The tumor is surrounded by lung or visceral pleura
    AND
    The tumor does not extend to the main bronchus as demonstrated by the absence of bronchoscopic evidence of invasion more proximal than the lobar bronchus.
T2 The tumor has the following characteristics:
  • T2a: tumor> 3 cm, but ≤4 cm in the largest diameter.
  • T2b: Tumor> 4 cm, but ≤5 cm in the largest diameter.
    The tumor involves the main bronchus, 2 cm or more distal to the carina.
    OR
    The tumor invades the visceral pleura.
    OR
    There is evidence of atelectasis or obstructive pneumonitis that extends to the hilar region without the involvement of the entire lung.
T3 Tumor > 5 cm, but ≤ 7 cm in size.

AND

It directly invades any of the following: chest wall (including superior sulcus tumors), diaphragm, mediastinal pleura, parietal pericardium.
OR
The tumor is localized in the main bronchus at a distance less than 2 cm distal to the carina but without the involvement of the carina.
OR
There is evidence of associated atelectasis or obstructive pneumonitis of the entire lung.

T4 Tumor > 7 cm in size.

The tumor invades any of the following: mediastinum, heart, great vessels, trachea, esophagus, vertebral body, carina
OR
There is/are separate tumor nodule(s) in the same lobe.
OR The tumor is associated with malignant pleural effusion.

N:Regional Lymph Nodes

T Description
NX the regional lymph nodes cannot be assessed.
N0 There is no evidence of regional lymph node metastasis.
N1 Metastasis in ipsilateral peribronchial and/or ipsilateral hilum or intrapulmonary lymph nodes

N1a - A lymph node invasion.

N1b - > 1 lymph node affected.

N2 There is metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s).

N2a1 - One lymph node infested without lymph node involvement of an N1-defined lymph node station.

N2a2 - One lymph node infested with a lymph node of an N1-defined lymph node station

N2b - > 1 lymph node affected

N3 There is metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s).

M: Distant Metastasis

T Description
MX Distant metastasis cannot be assessed.
M0 There is no evidence of distant metastasis.
M1 There is evidence of distant metastasis which includes the presence of separate tumor nodule(s) in a different lobe (ipsilateral or contralateral).

M1a - Tumor foci separated from the primary tumor in a contralateral lung lobe; Tumor with pleural metastases or malignant pleural or pericardial effusion

M1b - Simple metastases in an organ

M1c - Multiple metastases in one organ or one or more metastases in more than one organ

Classification of Lung Cancer by Staging

Stage T N M
Occult carcinoma TX N0 M0
Stage 0 Tis N0 M0
Stage IA1 T1(mi)/T1a N0 M0
Stage IA2 T1b N0 M0
Stage IA3 T1c N0 M0
Stage IB T2a N0 M0
Stage IIA T2b N0 M0
Stage IIB T1a N1 M0
T1c N1 M0
T2a N1 M0
T2b N1 M0
T3 N0 M0
Stage IIIA T1a N2 M0
T1b N2 M0
T1c N2 M0
T2a N2 M0
T2b N2 M0
T1a N2 M0
T1b N2 M0
T1c N2 M0
T2a N2 M0
T2b N2 M0
T3 N1 M0
T4 N0 M0
T4 N1 M0
Stage IIIB T1a N3 M0
T1b N3 M0
T1c N3 M0
T2a N3 M0
T2b N3 M0
T1a N3 M0
T1b N3 M0
T1c N3 M0
T2a N3 M0
T2b N3 M0
T3 N2 M0
T4 N2 M0
Stage IIIC T3 N3 M0
T4 N3 M0
Stage IVA Any T Any N M1a
Any T Any N M1b
Stage IVB Any T Any N M1c

Procedures for Staging Lung Cancer

There are currently multiple different procedures available to stage lung cancer.


References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 Purandare, NilenduC; Rangarajan, Venkatesh (2015). "Imaging of lung cancer: Implications on staging and management". Indian Journal of Radiology and Imaging. 25 (2): 109. doi:10.4103/0971-3026.155831. ISSN 0971-3026.
  2. ↑ 2.0 2.1 2.2 Ma, Shu-Hua; Le, Hong-Bo; Jia, Bao-hui; Wang, Zhao-Xin; Xiao, Zhuang-Wei; Cheng, Xiao-Ling; Mei, Wei; Wu, Min; Hu, Zhi-Guo; Li, Yu-Guang (2008). "Peripheral pulmonary nodules: Relationship between multi-slice spiral CT perfusion imaging and tumor angiogenesis and VEGF expression". BMC Cancer. 8 (1). doi:10.1186/1471-2407-8-186. ISSN 1471-2407.
  3. ↑ Gerard A. Silvestri, Lynn T. Tanoue, Mitchell L. Margolis, John Barker, Frank Detterbeck.11/30/11.The Noninvasive Staging of Non Small-cell Lung Cancer. Chestpubs. http://chestjournal.chestpubs.org/content/123/1_suppl/147S.full/
  4. ↑ Mountain, CF (2003). A Handbook for Staging, Imaging, and Lymph Node Classification. Charles P Young Company. Retrieved 2007-09-01. Unknown parameter |coauthors= ignored (help)
  5. ↑ Collins, LG (Jan 2007). "Lung cancer: diagnosis and management". American Family Physician. American Academy of Family Physicians. 75 (1): 56–63. PMID 17225705. Retrieved 2007-08-10. Unknown parameter |coauthors= ignored (help)
  6. ↑ Harms, A.; Kriegsmann, M.; Fink, L.; Länger, F.; Warth, A. (2017). "Die neue TNM-Klassifikation für Lungentumoren". Der Pathologe. 38 (1): 11–20. doi:10.1007/s00292-017-0268-y. ISSN 0172-8113.

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