View source for Lung tumours

'''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.

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

==Lung tumours overview==
===Schematic overview of lung cancer (clinical)===
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*NSCLC = non-small cell lung cancer.
*SCLS = small cell lung cancer.

===Basic pathologic approach to lung cancer===
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{{familytree | B | |C | |D | |E |B=Adenocarcinoma|C=Squamous<br>cell carcinoma|D=SCLC|E=LCLC}}
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*LCLC = large cell lung cancer.
*SCLS = small cell lung cancer.

Notes:
*Most lung cancer fits into one of the above categories.  
*All types may be metastatic.  Pathologists usually don't have to sort this out, as the clinican often knows whether a given lesion is metastatic (when correlated with radiology).
*Lung cancers may have a mixed morphology, e.g. SCLS may have squamous component.<ref name=pmid17684766>{{cite journal |author=Righi L, Volante M, Rapa I, Scagliotti GV, Papotti M |title=Neuro-endocrine tumours of the lung. A review of relevant pathological and molecular data |journal=Virchows Arch. |volume=451 Suppl 1 |issue= |pages=S51–9 |year=2007 |month=August |pmid=17684766 |doi=10.1007/s00428-007-0445-0 |url=}}</ref>
*Categorization as ''non-small cell lung cancer'' (NSCLC) should be avoided, as treatment is now somewhat dependent on subcategorization.<ref>URL: [http://www.nature.com/modpathol/journal/v21/n2s/full/3801018a.html http://www.nature.com/modpathol/journal/v21/n2s/full/3801018a.html]. Accessed on: 8 September 2010.</ref>

===Major types (primary)=== 
Mnemonic ''ASSL'':
*[[Adenocarcinoma]].
*[[Squamous cell carcinoma]].
*[[Small cell carcinoma]] (SCLC).
*Large cell carcinoma (LCLC).

===Epidemiology===
*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.

===Distribution===
*Distribution - think about the location of letters in mnemonic ''ASSL''.
**Adenocarcinoma is usually periperal, i.e. smaller airways.
**Squamous cell carcinoma and small cell carcinoma are typically central.

===Management of primary lung cancer===
Management is currently determined by categorization into:
*Small cell cancer.
*Non-small cell cancer (includes adenocarcinoma, squamous cell carcinoma, large cell carcinoma).

==Microscopic features overview==
===Adenocarcinoma===
*Glands or cytoplasm with mucin.

===Squamous cell carcinoma===
*Distinct cell borders with intercellular bridges.
*Eosinophilic cytoplasm.

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

==IHC==
There is a great review paper by ''Jagirdar''.<ref name=pmid18318581>{{cite journal |author=Jagirdar J |title=Application of immunohistochemistry to the diagnosis of primary and metastatic carcinoma to the lung |journal=Arch. Pathol. Lab. Med. |volume=132 |issue=3 |pages=384-96 |year=2008 |month=March |pmid=18318581 |doi= |url=http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=132&page=384}}</ref>

===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>
*CK7 -ve, CK20 -ve.

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>
===Squamous cell carcinoma===
*CK7 -ve, CK20 -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>

===Primary vs. secondary===
*TTF-1 is considered useful.<ref name=pmid18318581/> 
**75% +ve adenocarcinoma
**11% +ve SSC
**50% +ve large cell carcinoma
**0% +ve mesothelioma
**significant rates of +ve in some metastatic tumours -- see article by ''Jagirdar''.

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>
**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)].

==Primary adenocarcinoma==
===General===
Treatment:
*Lung adenocarcinoma may be treated with EGFR inhibitors (e.g. gefitinib (Iressa), erlotinib (Tarceva)).<ref>{{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==
===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>
*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>

===Classification===
The grouping can be divided into four types:<ref name=cancerorg_car>URL: [http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_lung_carcinoid_tumor_56.asp http://www.cancer.org/docroot/CRI/content/CRI_2_4_1X_What_is_lung_carcinoid_tumor_56.asp]. Accessed on: 16 February 2011.</ref>
*Small cell carcinoma.
*Large cell neuroendocrine carcinoma. 
*Typical carcinoid.
*Atypical carcinoid.

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

Notes:<ref name=cancerorg_car/>
*''Large cell'' and ''small cell'' tumours behave in a similar fashion; ''large cell'' can be considered a morphological variant of ''small cell''.
*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''.

==Mesothelioma==
===Locations===
*Lung.
*Primary peritoneal.

===Epidemiology===
*Associated with asbestos exposure.

===Microscopy===
*''Ferruginous body'' (AKA ''asbestos body'').<ref>[http://medical-dictionary.thefreedictionary.com/asbestos+body http://medical-dictionary.thefreedictionary.com/asbestos+body]</ref>
** Made of asbestos fiber. 
** Looks like a (twirling) baton.

Images: 
*[http://commons.wikimedia.org/wiki/File:Ferruginous_body.jpg Ferruginous body (wikimedia.org)].
*[http://www.pathconsultddx.com/images/S1559867506708488/gr2-sml.jpg Ferruginous body (pathconsultddx.com)].

===IHC===
*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>
**Usually two carcinoma markers + two mesothelial markers.

Panel:<ref name=pmid18318582/>
*Mesothelial markers:
**Calretin.
**WT-1.
**D2-40.
**CK5/6.
*Carcinoma markers:
**CEA.
**TTF-1.

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

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

[[Category:Pulmonary pathology]]