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Lung tumours (view source)

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'''Lung tumours''' comes to pathology to get diagnosed.  This article basically deals with core biopsies.  Pulmonary cytopathology is dealt with in the ''[[pulmonary cytopathology]]'' article.
[[Image:Small cell carcinoma (3931938372).jpg|right|thumb|300px|A lung tumour ([[small cell carcinoma of the lung]]) - centre of image. (WC/Rosen)]]
'''[[Lung]] tumours''' comes to pathology to get diagnosed.   
 
This article deals with the surgical pathology (core biopsies, lung resections).  Pulmonary cytopathology is dealt with in the ''[[pulmonary cytopathology]]'' article.


An introduction to lung pathology is found in the ''[[pulmonary pathology]]'' article.
An introduction to lung pathology is found in the ''[[pulmonary pathology]]'' article.


==Lung tumours overview==
=Lung tumours overview=
===Schematic overview of lung cancer (clinical)===
===Schematic overview of lung cancer (clinical)===
{{familytree/start}}
{{familytree/start}}
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*Adenocarcinoma is the most common (primary lung cancer).<ref>{{cite journal |author=Lutschg JH |title=Lung cancer |journal=N. Engl. J. Med. |volume=360 |issue=1 |pages=87-8; author reply 88 |year=2009 |month=January |pmid=19118313 |doi=10.1056/NEJMc082208 |url=}}</ref>
*Adenocarcinoma is the most common (primary lung cancer).<ref>{{cite journal |author=Lutschg JH |title=Lung cancer |journal=N. Engl. J. Med. |volume=360 |issue=1 |pages=87-8; author reply 88 |year=2009 |month=January |pmid=19118313 |doi=10.1056/NEJMc082208 |url=}}</ref>
*Adenocarcinoma is the non-smoker tumour - SCLC and squamous are more strongly associated with [[smoking]].
*Adenocarcinoma is the non-smoker tumour - SCLC and squamous are more strongly associated with [[smoking]].
Children:
*Most common lung tumour in children: metastasis (80-85% of lung tumours in children<ref name=pmid>{{Cite journal  | last1 = Dishop | first1 = MK. | last2 = Kuruvilla | first2 = S. | title = Primary and metastatic lung tumors in the pediatric population: a review and 25-year experience at a large children's hospital. | journal = Arch Pathol Lab Med | volume = 132 | issue = 7 | pages = 1079-103 | month = Jul | year = 2008 | doi = 10.1043/1543-2165(2008)132[1079:PAMLTI]2.0.CO;2 | PMID = 18605764 }}</ref>
**Most common primary tumours in children: [[inflammatory myofibroblastic tumour]], [[pleuropulmonary blastoma]], [[lung carcinoid]].<ref name=pmid26971789>{{Cite journal  | last1 = Giuseppucci | first1 = C. | last2 = Reusmann | first2 = A. | last3 = Giubergia | first3 = V. | last4 = Barrias | first4 = C. | last5 = Krüger | first5 = A. | last6 = Siminovich | first6 = M. | last7 = Botto | first7 = H. | last8 = Cadario | first8 = M. | last9 = Boglione | first9 = M. | title = Primary lung tumors in children: 24 years of experience at a referral center. | journal = Pediatr Surg Int | volume = 32 | issue = 5 | pages = 451-7 | month = May | year = 2016 | doi = 10.1007/s00383-016-3884-3 | PMID = 26971789 }}</ref>


===Distribution===
===Distribution===
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**Adenocarcinoma is usually periperal, i.e. smaller airways.
**Adenocarcinoma is usually periperal, i.e. smaller airways.
**Squamous cell carcinoma and small cell carcinoma are typically central.
**Squamous cell carcinoma and small cell carcinoma are typically central.
===Margins in lung===
Margin in pneumonectomy specimens include:
*Vessels (artery, vein).
*Airway (bronchus).
*Soft tissue (lymphatics, fibrous tissue and lymph nodes).<ref name=pmid21129810>{{Cite journal  | last1 = Sakai | first1 = Y. | last2 = Ohbayashi | first2 = C. | last3 = Kanomata | first3 = N. | last4 = Kajimoto | first4 = K. | last5 = Sakuma | first5 = T. | last6 = Maniwa | first6 = Y. | last7 = Nishio | first7 = W. | last8 = Tauchi | first8 = S. | last9 = Uchino | first9 = K. | title = Significance of microscopic invasion into hilar peribronchovascular soft tissue in resection specimens of primary non-small cell lung cancer. | journal = Lung Cancer | volume = 73 | issue = 1 | pages = 89-95 | month = Jul | year = 2011 | doi = 10.1016/j.lungcan.2010.11.002 | PMID = 21129810 }}</ref>
Notes:
*The traditional teaching is there are only hollow structure margins (artery, vein, airway) - yet the bronchial margin has been divided into mucosal and extramucosal.<ref>{{Cite journal  | last1 = Kaiser | first1 = LR. | last2 = Fleshner | first2 = P. | last3 = Keller | first3 = S. | last4 = Martini | first4 = N. | title = Significance of extramucosal residual tumor at the bronchial resection margin. | journal = Ann Thorac Surg | volume = 47 | issue = 2 | pages = 265-9 | month = Feb | year = 1989 | doi =  | PMID = 2537610 }}</ref>
*Peribronchovascular soft tissue involvement is a poor prognosticator but not an independent predictor if considered within the [[TNM staging]].<ref name=pmid21129810/>


===Management of primary lung cancer===
===Management of primary lung cancer===
Management is currently determined by categorization into:
Management in the past was determined by categorization into:
*Small cell cancer.
*Small cell cancer.
*Non-small cell cancer (includes adenocarcinoma, squamous cell carcinoma, large cell carcinoma).
*Non-small cell cancer (includes adenocarcinoma, squamous cell carcinoma, large cell carcinoma).
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==Microscopic features overview==
==Microscopic features overview==
===Adenocarcinoma===
===Adenocarcinoma===
{{Main|Adenocarcinoma of the lung}}
*Glands or cytoplasm with mucin.
*Glands or cytoplasm with mucin.


===Squamous cell carcinoma===
===Squamous cell carcinoma===
{{Main|Squamous cell carcinoma of the lung}}
*Distinct cell borders with intercellular bridges.
*Distinct cell borders with intercellular bridges.
*Eosinophilic cytoplasm.
*Eosinophilic cytoplasm.


===Small cell carcinoma===
===Small cell carcinoma===
{{Main|Small cell carcinoma of the lung}}
*Very cellular.
*Very cellular.
*Large NC ratio - very small amount of cytoplasm.
*Large [[NC ratio]] - very small amount of cytoplasm.
*Cells fragile - they tend to look "smudged" ([[Azzopardi phenomenon]]).
*Cells fragile - they tend to look "smudged" ([[Azzopardi phenomenon]]).


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===Small cell carcinoma===
===Small cell carcinoma===
*CD56 +ve - sensitive.<ref name=pmid16862075>{{cite journal |author=Hiroshima K, Iyoda A, Shida T, ''et al'' |title=Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis |journal=Mod. Pathol. |volume=19 |issue=10 |pages=1358-68 |year=2006 |month=October |pmid=16862075 |doi=10.1038/modpathol.3800659 |url=}}</ref>
*[[TTF-1]] +ve.
*CK7 -ve, CK20 -ve.
*[[CD56]] +ve - sensitive.<ref name=pmid16862075>{{cite journal |author=Hiroshima K, Iyoda A, Shida T, ''et al'' |title=Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis |journal=Mod. Pathol. |volume=19 |issue=10 |pages=1358-68 |year=2006 |month=October |pmid=16862075 |doi=10.1038/modpathol.3800659 |url=}}</ref>
*[[CK7]] -ve, [[CK20]] -ve.


Note:
Note:
*CD56 - cytoplasmic.<ref>URL: [http://jcp.bmjjournals.com/content/58/9/978.full http://jcp.bmjjournals.com/content/58/9/978.full]. Accessed: 11 February 2010.</ref>
*CD56 - cytoplasmic.<ref>URL: [http://jcp.bmjjournals.com/content/58/9/978.full http://jcp.bmjjournals.com/content/58/9/978.full]. Accessed: 11 February 2010.</ref>
===Adenocarcinoma===
*[[TTF-1]] +ve.
*[[Napsin]] +ve - sensitive.<ref name=pmid22288963>{{cite journal |author=Turner BM, Cagle PT,Fukuoka J, ''et al'' |title=Napsin A, a New Marker for Lung Adenocarcinoma, Is Complementary and More Sensitive and Specific Than Thyroid Transcription Factor 1 in the Differential Diagnosis of Primary Pulmonary Carcinoma: Evaluation of 1674 Cases by Tissue Microarray |journal=Arch Pathol Lab Med. |volume=136 |issue=10 |pages=163-71 |year=2012 |month=February|pmid=22288963 |doi: 10.5858/arpa.2011-0320-OA|url=}}</ref>
*[[CK7]] +ve, [[CK20]] -ve.
===Squamous cell carcinoma===
===Squamous cell carcinoma===
*CK7 -ve, CK20 -ve.
*[[CK7]] -ve, CK20 -ve.
*HMWK +ve.
*HMWK +ve.
*Usually TTF-1 -ve.<ref>{{cite journal |author=Al-Zahrani IH |title=The value of immunohistochemical expression of TTF-1, CK7 and CK20 in the diagnosis of primary and secondary lung carcinomas |journal=Saudi Med J |volume=29 |issue=7 |pages=957-61 |year=2008 |month=July |pmid=18626520 |doi= |url=}}</ref>
*Usually TTF-1 -ve.<ref>{{cite journal |author=Al-Zahrani IH |title=The value of immunohistochemical expression of TTF-1, CK7 and CK20 in the diagnosis of primary and secondary lung carcinomas |journal=Saudi Med J |volume=29 |issue=7 |pages=957-61 |year=2008 |month=July |pmid=18626520 |doi= |url=}}</ref>
*[[p40]] +ve.


===Primary vs. secondary===
===Primary vs. secondary===
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Note:
Note:
*TTF-1 - should be nuclear staining; cytoplasmic staining is non-specific.<ref name=pmid15861215>{{cite journal |author=Compérat E, Zhang F, Perrotin C, ''et al.'' |title=Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin |journal=Mod. Pathol. |volume=18 |issue=10 |pages=1371–6 |year=2005 |month=October |pmid=15861215 |doi=10.1038/modpathol.3800422 |url=http://www.nature.com/modpathol/journal/v18/n10/full/3800422a.html}}</ref>
*TTF-1 - should be nuclear staining; cytoplasmic staining is non-specific.<ref name=pmid15861215>{{cite journal |author=Compérat E, Zhang F, Perrotin C, ''et al.'' |title=Variable sensitivity and specificity of TTF-1 antibodies in lung metastatic adenocarcinoma of colorectal origin |journal=Mod. Pathol. |volume=18 |issue=10 |pages=1371–6 |year=2005 |month=October |pmid=15861215 |doi=10.1038/modpathol.3800422 |url=http://www.nature.com/modpathol/journal/v18/n10/full/3800422a.html}}</ref>
**Image: [http://commons.wikimedia.org/w/index.php?title=File:Lung_adenocarcinoma_-_TTF-1_-_high_mag.jpg Nuclear staining with TTF-1 in a metastatic lung adenocarcinoma (WC)].
**Image: [http://commons.wikimedia.org/w/index.php?title=File:Lung_adenocarcinoma_-_TTF-1_-_high_mag.jpg Nuclear staining with TTF-1 in a primary lung adenocarcinoma (WC)].
 
==Lung adenocarcinoma==
===General===
Treatment:
*Lung adenocarcinoma may be treated with [[EGFR inhibitors]] (e.g. gefitinib (Iressa), erlotinib (Tarceva)).<ref name=pmid20855837>{{cite journal |author=Sun Y, Ren Y, Fang Z, ''et al.'' |title=Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases |journal=J. Clin. Oncol. |volume=28 |issue=30 |pages=4616–20 |year=2010 |month=October |pmid=20855837 |doi=10.1200/JCO.2010.29.6038 |url=}}</ref>
 
Patients that receive EGFR inhibitors classically are:<ref>{{cite journal |author=Job B, Bernheim A, Beau-Faller M, ''et al.'' |title=Genomic Aberrations in Lung Adenocarcinoma in Never Smokers |journal=PLoS One |volume=5 |issue=12 |pages=e15145 |year=2010 |pmid=21151896 |pmc=2997777 |doi=10.1371/journal.pone.0015145 |url=}}</ref>
*Non-smokers.
*Female.
*Asian. (???)
 
===Microscopic===
Features:
*Nuclear atypia.
*Eccentrically placed nuclei.
*Abundant cytoplasm - classically with mucin vacuoles.
 
Negatives:
*Lack of intercellular bridges.
 
Patterns:<ref name=pmid21252716>{{cite journal |author=Travis WD, Brambilla E, Noguchi M, ''et al.'' |title=International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma |journal=J Thorac Oncol |volume=6 |issue=2 |pages=244–85 |year=2011 |month=February |pmid=21252716 |doi=10.1097/JTO.0b013e318206a221 |url=}}</ref>
*Lepidic.
*Acinar.
*Papillary.
*Solid.
 
====Classification====
Extent:<ref name=pmid21252716>{{cite journal |author=Travis WD, Brambilla E, Noguchi M, ''et al.'' |title=International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma |journal=J Thorac Oncol |volume=6 |issue=2 |pages=244–85 |year=2011 |month=February |pmid=21252716 |doi=10.1097/JTO.0b013e318206a221 |url=}}</ref>
*Adenocarcinoma in situ (AIS).
*Minimally invasive adenocarcinoma (MIA).
**Have lepidic growth (AIS), upto 5 mm of invasion.
**Usually nonmucinous.
 
Subtypes of invasive adenocarcinoma:
*Micropapillary
*Mucinous.
*Colloid.
*Fetal.
*Enteric.


==Neuroendocrine tumours==
==Neuroendocrine tumours==
{{Main|Neuroendocrine tumours}}
===Overview===
===Overview===
*This is a group of tumours that has benign (e.g. [[carcinoid]] tumour of the lung) to malignant (e.g. small cell lung carcinoma) behaviour.<ref>URL: [http://emedicine.medscape.com/article/426400-overview http://emedicine.medscape.com/article/426400-overview]. Accessed on: 20 January 2010.</ref>
*This is a group of tumours that has benign (e.g. [[carcinoid]] tumour of the lung) to malignant (e.g. small cell lung carcinoma) behaviour.<ref>URL: [http://emedicine.medscape.com/article/426400-overview http://emedicine.medscape.com/article/426400-overview]. Accessed on: 20 January 2010.</ref>
*They are thought to arise from [[pulmonary neuroendocrine cell]]s.<ref>{{cite journal |author=Chong S, Lee KS, Chung MJ, Han J, Kwon OJ, Kim TS |title=Neuroendocrine tumors of the lung: clinical, pathologic, and imaging findings |journal=Radiographics |volume=26 |issue=1 |pages=41–57; discussion 57–8 |year=2006 |pmid=16418242 |doi=10.1148/rg.261055057 |url=}}</ref>
*They are thought to arise from ''pulmonary neuroendocrine cells''.<ref>{{cite journal |author=Chong S, Lee KS, Chung MJ, Han J, Kwon OJ, Kim TS |title=Neuroendocrine tumors of the lung: clinical, pathologic, and imaging findings |journal=Radiographics |volume=26 |issue=1 |pages=41–57; discussion 57–8 |year=2006 |pmid=16418242 |doi=10.1148/rg.261055057 |url=}}</ref>


===Classification===
===Classification===
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*Typical carcinoid.
*Typical carcinoid.
*Atypical carcinoid.
*Atypical carcinoid.
Notes:
*[[Typical carcinoid]]-like lesions <5 mm are called [[carcinoid tumourlet]]s.


===Cytologic features===
===Cytologic features===
Cytologic features useful for differentiation:
Cytologic features useful for differentiation:
*Small cell carcinoma: necrosis, scant cytoplasm, mitoses.
*Small cell carcinoma: necrosis, scant cytoplasm, mitoses.
*Typical carcinoid: often more cytoplasm, no necrosis, low mitotic rate (MIB-1: scant staining).
*Typical carcinoid: often more cytoplasm, no necrosis, low mitotic rate (MIB1: scant staining).
*Atypical carcinoid: higher mitotic rate/MIB-1 than ''typical carcinoid'',<ref>WG. February 2010.</ref> no necrosis.
*Atypical carcinoid: higher mitotic rate/MIB1 than ''typical carcinoid'',<ref>Geddie, W. February 2010.</ref> no [[necrosis]].


Notes:<ref name=cancerorg_car/>
Notes:<ref name=cancerorg_car/>
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*9/10 of carcinoids are ''typical'' and usually have a good prognosis, i.e. do not metastasize.
*9/10 of carcinoids are ''typical'' and usually have a good prognosis, i.e. do not metastasize.
**Central location (vis-a-vis peripheral location) tends favours ''typical carcinoid'' over ''atypical carcinoid''.
**Central location (vis-a-vis peripheral location) tends favours ''typical carcinoid'' over ''atypical carcinoid''.
=Malignant tumours=
==Adenocarcinoma of the lung==
*[[AKA]] ''lung adenocarcinoma''.
{{Main|Adenocarcinoma of the lung}}
==Bronchioloalveolar carcinoma==
:Abbreviated ''BAC''.
'''The term is no longer used''' in the new classification;<ref name=pmid21926387>{{Cite journal  | last1 = Travis | first1 = WD. | last2 = Brambilla | first2 = E. | last3 = Noguchi | first3 = M. | last4 = Nicholson | first4 = AG. | last5 = Geisinger | first5 = K. | last6 = Yatabe | first6 = Y. | last7 = Powell | first7 = CA. | last8 = Beer | first8 = D. | last9 = Riely | first9 = G. | title = International association for the study of lung cancer/American Thoracic Society/European Respiratory Society: international multidisciplinary classification of lung adenocarcinoma: executive summary. | journal = Proc Am Thorac Soc | volume = 8 | issue = 5 | pages = 381-5 | month = Sep | year = 2011 | doi = 10.1513/pats.201107-042ST | PMID = 21926387 |URL = http://iaslc.org/assets/Documents/lung-adenocarcinoma-classification.pdf }}</ref> it is now "adenocarcinoma in situ" - see ''[[lung adenocarcinoma]]''.
==Squamous cell carcinoma of the lung==
{{Main|Squamous cell carcinoma of the lung}}
==Small cell carcinoma of the lung==
*[[AKA]] ''small cell lung carcinoma'', abbreviated ''SCLC''.<ref name=pmid20943645>{{Cite journal  | last1 = Travis | first1 = WD. | title = Advances in neuroendocrine lung tumors. | journal = Ann Oncol | volume = 21 Suppl 7 | issue =  | pages = vii65-71 | month = Oct | year = 2010 | doi = 10.1093/annonc/mdq380 | PMID = 20943645 }}</ref>
{{Main|Small cell carcinoma of the lung}}


==Malignant mesothelioma==
==Malignant mesothelioma==
*[[AKA]] ''mesothelioma''.
:Should '''not''' be confused with ''[[benign multicystic mesothelioma]]'' and ''[[benign papillary mesothelioma]]''.
===General===
{{Main|Malignant mesothelioma}}
*Prognosis sucks.
 
==Non-small cell lung carcinoma==
*[[AKA]] ''poorly differentiated carcinoma of the lung''.
{{Main|Non-small cell lung carcinoma}}
 
==Adenosquamous carcinoma of the lung==
{{Main|Adenosquamous carcinoma of the lung}}
 
==Lung metastasis==
*[[AKA]] ''pulmonary metastasis''.
{{Main|Lung metastasis}}
 
=Malignant potential=
==Atypical alveolar hyperplasia==
*Abbreviated ''AAH''.
*[[AKA]] ''atypical adenomatous hyperplasia of the lung''.<ref name=pmid11235908>{{Cite journal  | last1 = Mori | first1 = M. | last2 = Rao | first2 = SK. | last3 = Popper | first3 = HH. | last4 = Cagle | first4 = PT. | last5 = Fraire | first5 = AE. | title = Atypical adenomatous hyperplasia of the lung: a probable forerunner in the development of adenocarcinoma of the lung. | journal = Mod Pathol | volume = 14 | issue = 2 | pages = 72-84 | month = Feb | year = 2001 | doi = 10.1038/modpathol.3880259 | PMID = 11235908 }}</ref>
{{Main|Atypical adenomatous hyperplasia of the lung}}


Locations:
==Atypical carcinoid lung tumour==
*Lung.
*[[AKA]] ''atypical carcinoid tumour of the lung''.
*Primary peritoneal.
{{Main|Atypical lung carcinoid tumour}}


Epidemiology:
==Solitary fibrous tumour of the pleura==
*Associated with asbestos exposure.
{{Main|Solitary fibrous tumour of the pleura}}


===Microscopic===
=Benign tumours=
Features:
==Pulmonary apical cap==
*+/-''Ferruginous body'' ([[AKA]] ''asbestos body'') - '''diagnostic'''.<ref>URL: [http://medical-dictionary.thefreedictionary.com/asbestos+body http://medical-dictionary.thefreedictionary.com/asbestos+body]. Accessed on: 4 November 2011.</ref>
{{Main|Pulmonary apical cap}}
** Made of asbestos fiber.
A lesion that can mimic a lung neoplasm.
** Looks like a (twirling) baton.
*+/-Atypical glands formed from epithelial cells.


Images:
==Pulmonary carcinoid tumourlet==
*[http://commons.wikimedia.org/wiki/File:Ferruginous_body.jpg Ferruginous body (wikimedia.org)].
*[[AKA]] ''carcinoid tumourlet''.
*[http://www.pathconsultddx.com/images/S1559867506708488/gr2-sml.jpg Ferruginous body (pathconsultddx.com)].
{{Main|Pulmonary carcinoid tumourlet}}


===IHC===
==Typical carcinoid lung tumour==
*Several panel exists - ''no agreed upon best panel''.<ref name=pmid18318582>{{cite journal |author=Marchevsky AM |title=Application of immunohistochemistry to the diagnosis of malignant mesothelioma |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=3 |pages=397-401 |year=2008 |month=March |pmid=18318582 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=397}}</ref>
*[[AKA]] ''carcinoid tumour of the lung''.
**Usually two carcinoma markers + two mesothelial markers.
*[[AKA]] ''lung carcinoid''.
{{Main|Typical carcinoid lung tumour}}


Panel:<ref name=pmid18318582/>
==Clear cell sugar tumour of the lung==
*Mesothelial markers:
*[[AKA]] ''clear cell sugar tumour''.
**Calretinin.
**Abbreviated ''CCST''.
**WT-1.
{{Main|Clear cell sugar tumour of the lung}}
**D2-40.
**CK5/6.
*Carcinoma markers:
**CEA (monoclonal and polyclonal).
**TTF-1.
**Ber-EP4.
**MOC-31.


==See also==
=See also=
*[[Lung]] - introduction to the lung, includes a basic approach.
*[[Lung]] - introduction to the lung, includes a basic approach.
*[[Medical lung disease]].
*[[Medical lung disease]].
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*[[Basics]].
*[[Basics]].
*[[Heart]].
*[[Heart]].
*[[Missed endobronchial biopsy]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


[[Category:Pulmonary pathology]]
[[Category:Pulmonary pathology]]
Michael
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