Difference between revisions of "Adenocarcinoma of the lung"

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{{ Infobox diagnosis
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Name      = {{PAGENAME}}
| Image      = Bronchioloalveolar carcinoma, mucinous type.jpg
| Image      = Acinar pattern adenocarcinoma of lung -- low mag.jpg
| Width      =
| Width      =
| Caption    = Lung adenocarcinoma, mucinous. [[H&E stain]].
| Caption    = Invasive adenocarcinoma, acinar pattern (right of image) and benign lung (left of image). [[H&E stain]].
| Synonyms  =
| Synonyms  =
| Micro      = +/-nuclear atypia (may be absent in mucinous tumours), eccentrically placed nuclei, usu. abundant cytoplasm (classically with mucin vacuoles), often conspicuous [[nucleoli]], +/-[[nuclear pseudoinclusions]]
| Micro      = +/-nuclear atypia (may be absent in mucinous tumours), eccentrically placed nuclei, usu. abundant cytoplasm (classically with mucin vacuoles), often conspicuous [[nucleoli]], +/-[[nuclear pseudoinclusions]]
Line 9: Line 9:
| LMDDx      = [[atypical adenomatous hyperplasia of the lung]], adenocarcinoma in situ, [[squamous cell carcinoma of the lung]], [[small cell carcinoma of the lung]], [[non-small cell lung carcinoma]], [[malignant mesothelioma]], [[Metastasis|metastatic]] [[adenocarcinoma]] (esp. [[colorectal adenocarcinoma]], breast adenocarcinoma ([[invasive ductal carcinoma of the breast]], [[invasive lobular carcinoma]]))
| LMDDx      = [[atypical adenomatous hyperplasia of the lung]], adenocarcinoma in situ, [[squamous cell carcinoma of the lung]], [[small cell carcinoma of the lung]], [[non-small cell lung carcinoma]], [[malignant mesothelioma]], [[Metastasis|metastatic]] [[adenocarcinoma]] (esp. [[colorectal adenocarcinoma]], breast adenocarcinoma ([[invasive ductal carcinoma of the breast]], [[invasive lobular carcinoma]]))
| Stains    =
| Stains    =
| IHC        = CK7 +ve, TTF-1 +ve, CK20 -ve, p40 -ve, p63 -ve (usually)
| IHC        = [[CK7]] +ve, [[TTF-1]] +ve, CK20 -ve, [[p40]] -ve, p63 -ve (usually)
| EM        =
| EM        =
| Molecular  = +/-EGFR mutations, +/-ALK [[chromosomal translocation]] (inv(2)(p21p23) -- EML4-ALK fusion)
| Molecular  = +/-KRAS mutations, +/-EGFR mutations, +/-ALK [[chromosomal translocation]] (inv(2)(p21p23) -- EML4-ALK fusion), +/-ROS1 rearrangements, +/-RET rearrangements
| IF        =
| IF        =
| Gross      =  
| Gross      =  
| Grossing  =
| Grossing  =
| Staging    = [[lung cancer staging]]
| Site      = [[lung]] - see ''[[lung tumours]]''
| Site      = [[lung]] - see ''[[lung tumours]]''
| Assdx      =
| Assdx      =
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===Image===
===Image===
<gallery>
<gallery>  
Image:Adenocarcinoma (3950819000).jpg | Lung adenocarcinoma. (WC/Rosen)
Image:Adenocarcinoma (3950819000).jpg | Lung adenocarcinoma. (WC/Rosen)
</gallery>
</gallery>
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DDx:
DDx:
*[[Atypical adenomatous hyperplasia of the lung]] - spaced hobnail cells, mild-to-moderate nuclear atypia, small lesion (< 5 mm).
*[[Atypical adenomatous hyperplasia of the lung]] - spaced [[hobnail]] cells, mild-to-moderate nuclear atypia, small lesion (must be <5 mm).
*Adenocarcinoma in situ.
*Adenocarcinoma in situ.
*[[Papillary thyroid carcinoma|Papillary carcinoma of thyroid]].
*[[Squamous cell carcinoma of the lung]].
*[[Squamous cell carcinoma of the lung]].
*[[Small cell carcinoma of the lung]].
*[[Small cell carcinoma of the lung]].
*[[Adenoid cystic carcinoma]].
*[[Non-small cell lung carcinoma]] - diagnosis should be avoided if possible.
*[[Non-small cell lung carcinoma]] - diagnosis should be avoided if possible.
*[[Malignant mesothelioma]].
*[[Malignant mesothelioma]].
Line 90: Line 93:
***[[Invasive ductal carcinoma of the breast]].
***[[Invasive ductal carcinoma of the breast]].
***[[Invasive lobular carcinoma]].
***[[Invasive lobular carcinoma]].
***[[Bronchiolar metaplasia]].
**Other carcinomas.
**Other carcinomas.
*Carcinomas of the bronchial glands, e.g. [[adenoid cystic carcinoma]].
*Carcinomas of the bronchial glands, e.g. [[adenoid cystic carcinoma]].


===Images===
===Images===
=====Acinar adenocarcinoma=====
<gallery>
Image: Acinar pattern adenocarcinoma of lung -- low mag.jpg | Acinar LA - low mag.
Image: Acinar pattern adenocarcinoma of lung -- intermed mag.jpg | Acinar LA - intermed. mag.
Image: Acinar pattern adenocarcinoma of lung -- high mag.jpg | Acinar LA - high mag.
Image: Acinar pattern adenocarcinoma of lung -- very high mag.jpg | Acinar LA - very high mag.
Image: Acinar pattern adenocarcinoma of lung - alt -- very high mag.jpg | Acinar LA - very high mag.
</gallery>
<gallery>
<gallery>
Image:Adenocarcinoma, acinar subtype (3923397562).jpg | Acinar adenocarcinoma. (WC/Yale Rosen)
Image:Adenocarcinoma,_acinar_subtype_(4420421886).jpg | Acinar adenocarcinoma. (WC/Yale Rosen)
</gallery>
=====Mucinous adenocarcinoma=====
<gallery>
Image: Mucinous adenocarcinoma of the lung -- low mag.jpg | MAL - low mag.
Image: Mucinous adenocarcinoma of the lung -- intermed mag.jpg | MAL - intermed. mag.
Image: Mucinous adenocarcinoma of the lung -- high mag.jpg | MAL - high mag.
Image: Mucinous adenocarcinoma of the lung -- very high mag.jpg | MAL - very high mag.
</gallery>
<gallery>
Image: Mucinous lung adenocarcinoma -- low mag.jpg | MAL - low mag.
Image: Mucinous lung adenocarcinoma -- intermed mag.jpg | MAL - intermed. mag.
Image: Mucinous lung adenocarcinoma -- high mag.jpg | MAL - high mag.
Image: Mucinous lung adenocarcinoma and airway -- intermed mag.jpg | MAL - intermed. mag.
Image: Mucinous lung adenocarcinoma and airway -- high mag.jpg | MAL - high mag.
Image: Mucinous lung adenocarcinoma and airway - alt -- high mag.jpg | MAL - high mag.
</gallery>
<gallery>
Image:Bronchioloalveolar carcinoma, mucinous type 2.jpg |BAC - mucinous type - low mag. (WC/Yale Rosen)
Image:Bronchioloalveolar carcinoma, mucinous type 2.jpg |BAC - mucinous type - low mag. (WC/Yale Rosen)
Image:Bronchioloalveolar carcinoma, mucinous type.jpg | BAC - mucinous type - high mag. (WC/Yale Rosen)
Image:Bronchioloalveolar carcinoma, mucinous type.jpg | BAC - mucinous type - high mag. (WC/Yale Rosen)
Image:Adenocarcinoma, acinar subtype (3923397562).jpg | Acinar adenocarcinoma. (WC/Yale Rosen)
Image:Adenocarcinoma,_acinar_subtype_(4420421886).jpg | Acinar adenocarcinoma. (WC/Yale Rosen)
</gallery>
</gallery>
www:
 
=====Papillary adenocarcinoma=====
<gallery>
Image: Papillary adenocarcinoma of the lung -- very low mag.jpg | PAL - very low mag. (WC/Nephron)
Image: Papillary adenocarcinoma of the lung -- low mag.jpg | PAL - low mag. (WC/Nephron)
Image: Papillary adenocarcinoma of the lung -- intermed mag.jpg | PAL - intermed. mag. (WC/Nephron)
Image: Papillary adenocarcinoma of the lung -- high mag.jpg | PAL - high mag. (WC/Nephron)
</gallery>
 
====Fetal adenocarcinoma====
<gallery>
Image: Fetal adenocarcinoma of the lung -- very low mag.jpg | FAL - very low mag. (WC)
Image: Fetal adenocarcinoma of the lung - alt2 -- very low mag.jpg | FAL - very low mag. (WC)
Image: Fetal adenocarcinoma of the lung -- low mag.jpg | FAL - low mag. (WC)
Image: Fetal adenocarcinoma of the lung -- intermed mag.jpg | FAL - intermed. mag. (WC)
Image: Fetal adenocarcinoma of the lung -- high mag.jpg | FAL - high mag. (WC)
</gallery>
 
====www====
*[http://www.pathpedia.com/education/eatlas/histopathology/lung_and_bronchi/bronchioloalveolar_carcinoma_mucinous.aspx BAC mucinous type adjacent to benign (pathpedia.com)].
*[http://www.pathpedia.com/education/eatlas/histopathology/lung_and_bronchi/bronchioloalveolar_carcinoma_mucinous.aspx BAC mucinous type adjacent to benign (pathpedia.com)].
*[http://cancergrace.org/wp-content/uploads/2007/05/mucinous-vs-nonmucinous-bac-histology.jpg BAC mucinous and nonmucinous (cancergrace.org)].<ref>URL: [http://cancergrace.org/lung/2007/05/14/bac-mucinous-and-non-mucinous/ http://cancergrace.org/lung/2007/05/14/bac-mucinous-and-non-mucinous/]. Accessed on: 8 August 2013.</ref>
*[http://cancergrace.org/wp-content/uploads/2007/05/mucinous-vs-nonmucinous-bac-histology.jpg BAC mucinous and nonmucinous (cancergrace.org)].<ref>URL: [http://cancergrace.org/lung/2007/05/14/bac-mucinous-and-non-mucinous/ http://cancergrace.org/lung/2007/05/14/bac-mucinous-and-non-mucinous/]. Accessed on: 8 August 2013.</ref>
*[https://www.flickr.com/photos/pulmonary_pathology/7589291672/ Lepidic adenocarcinoma with invasive (flickr.com/Yale Rosen)].
*[https://www.flickr.com/photos/pulmonary_pathology/7589291672/ Lepidic adenocarcinoma with invasive (flickr.com/Yale Rosen)].
*[https://www.flickr.com/photos/pulmonary_pathology/7589292214/in/photostream/ Lepidic adenocarcinoma (flickr.com/Yale Rosen)].
*[https://www.flickr.com/photos/pulmonary_pathology/7589292214/in/photostream/ Lepidic adenocarcinoma (flickr.com/Yale Rosen)].
*[http://www.rosaicollection.org/searchresults.cfm/ Lepidic adenocarcinoma (rosaicollection.org/index.cfm)].
*[http://pathlabmed.typepad.com/surgical_pathology_and_la/2010/09/digital-case-challenge-non-mucinous-bronchioloalveolar-adenocarcinoma.html Mucinous adenocarcinoma (pathlabmed.typepad.com)].
*[http://pathlabmed.typepad.com/surgical_pathology_and_la/2010/09/digital-case-challenge-non-mucinous-bronchioloalveolar-adenocarcinoma.html Mucinous adenocarcinoma (pathlabmed.typepad.com)].
*[https://www.flickr.com/photos/pulmonary_pathology/7589292780/in/photostream/ Non-mucinous adenocarcinoma in situ (flickr.com/Yale Rosen)].
*[https://www.flickr.com/photos/pulmonary_pathology/7589292780/in/photostream/ Non-mucinous adenocarcinoma in situ (flickr.com/Yale Rosen)].
Line 113: Line 161:
===Classification===
===Classification===
Classification based on 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>
Classification based on 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) - previously known as [[BAC]].
#Adenocarcinoma in situ (AIS) - previously known as ''bronchioloalveolar carcinoma'' (abbreviated [[BAC]]).
#*Subtypes: nonmucinous, mucinous, mixed mucinous/nonmucinous.
#*Subtypes: nonmucinous, mucinous, mixed mucinous/nonmucinous.
#*Definition: lack of invasion into the stroma, vascular spaces and pleura.
#*Definition: lack of invasion into the stroma, vascular spaces and pleura.
Line 125: Line 173:


====Grading====
====Grading====
Graded G1-G4 - as per CAP protocol (version 3.3.0.0):<ref>CAP Lung protocol. Version: 3.3.0.0. URL: [http://www.cap.org/ShowProperty?nodePath=/UCMCon/Contribution Folders/WebContent/doc/lung-13protocol-3300.doc http://www.cap.org/ShowProperty?nodePath=/UCMCon/Contribution Folders/WebContent/doc/lung-13protocol-3300.doc]. Accessed on: August 14, 2015.</ref>
Graded G1-G4 - as per CAP protocol (version 3.4.0.0):<ref name=cap_protocol>CAP Lung protocol. Version: 3.4.0.0. URL: [http://www.cap.org/ShowProperty?nodePath=/UCMCon/Contribution%20Folders/WebContent/pdf/cp-lung-16protocol-3400.pdf http://www.cap.org/ShowProperty?nodePath=/UCMCon/Contribution%20Folders/WebContent/pdf/cp-lung-16protocol-3400.pdf]. Accessed on: March 23, 2016.</ref>
*G1 = lepidic.
*G1 = lepidic.
*G2 = acinar and papillary.
*G2 = acinar, papillary, cribriform.
*G3 = micropapillary, solid, mucinous.
*G3 = micropapillary, solid, mucinous, colloid.
*G4 = undifferentiated.
*G4 = undifferentiated - '''not''' used for lung adenocarcinoma; it used for small cell carcinoma and large cell carcinoma.


Note:
Note:
*There is no consensus currently on grading - as per the international consensus guidelines of 2011.<ref name=pmid21252716>{{Cite journal | last1 = Travis | first1 = WD. | last2 = Brambilla | first2 = E. | last3 = Noguchi | first3 = M. | last4 = Nicholson | first4 = AG. | last5 = Geisinger | first5 = KR. | last6 = Yatabe | first6 = Y. | last7 = Beer | first7 = DG. | last8 = Powell | first8 = CA. | last9 = Riely | first9 = GJ. | 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 | month = Feb | year = 2011 | doi = 10.1097/JTO.0b013e318206a221 | PMID = 21252716 }}</ref>
*There is no consensus currently on grading - as per the international consensus guidelines of 2011.<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>
 
==Special stains==
*[[Mucicarmine]] +ve, cytoplasmic.
*[[PAS-diastase]] +ve, cytoplasmic.


==IHC==
==IHC==
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Panel for adenocarcinoma versus SCC:
Panel for adenocarcinoma versus SCC:
*TTF-1 +ve.
*TTF-1 +ve.
*Napsin A +ve.
*[[Napsin]] A +ve.
*p40 -ve.<ref name=pmid22056955>{{Cite journal  | last1 = Bishop | first1 = JA. | last2 = Teruya-Feldstein | first2 = J. | last3 = Westra | first3 = WH. | last4 = Pelosi | first4 = G. | last5 = Travis | first5 = WD. | last6 = Rekhtman | first6 = N. | title = p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. | journal = Mod Pathol | volume = 25 | issue = 3 | pages = 405-15 | month = Mar | year = 2012 | doi = 10.1038/modpathol.2011.173 | PMID = 22056955 }}</ref>
*[[p40]] -ve.<ref name=pmid22056955>{{Cite journal  | last1 = Bishop | first1 = JA. | last2 = Teruya-Feldstein | first2 = J. | last3 = Westra | first3 = WH. | last4 = Pelosi | first4 = G. | last5 = Travis | first5 = WD. | last6 = Rekhtman | first6 = N. | title = p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma. | journal = Mod Pathol | volume = 25 | issue = 3 | pages = 405-15 | month = Mar | year = 2012 | doi = 10.1038/modpathol.2011.173 | PMID = 22056955 }}</ref>
*CK5/6 -ve.
*CK5/6 -ve.


Line 150: Line 202:
*Vimentin -ve/+ve (+ve relatively common).
*Vimentin -ve/+ve (+ve relatively common).
**Poor prognosticator.<ref>{{Cite journal  | last1 = Dauphin | first1 = M. | last2 = Barbe | first2 = C. | last3 = Lemaire | first3 = S. | last4 = Nawrocki-Raby | first4 = B. | last5 = Lagonotte | first5 = E. | last6 = Delepine | first6 = G. | last7 = Birembaut | first7 = P. | last8 = Gilles | first8 = C. | last9 = Polette | first9 = M. | title = Vimentin expression predicts the occurrence of metastases in non small cell lung carcinomas. | journal = Lung Cancer | volume = 81 | issue = 1 | pages = 117-22 | month = Jul | year = 2013 | doi = 10.1016/j.lungcan.2013.03.011 | PMID = 23562674 }}</ref>
**Poor prognosticator.<ref>{{Cite journal  | last1 = Dauphin | first1 = M. | last2 = Barbe | first2 = C. | last3 = Lemaire | first3 = S. | last4 = Nawrocki-Raby | first4 = B. | last5 = Lagonotte | first5 = E. | last6 = Delepine | first6 = G. | last7 = Birembaut | first7 = P. | last8 = Gilles | first8 = C. | last9 = Polette | first9 = M. | title = Vimentin expression predicts the occurrence of metastases in non small cell lung carcinomas. | journal = Lung Cancer | volume = 81 | issue = 1 | pages = 117-22 | month = Jul | year = 2013 | doi = 10.1016/j.lungcan.2013.03.011 | PMID = 23562674 }}</ref>
Note:
*In mucinous adenocarcinoma of the lung TTF-1 is usu. -ve (46% +ve) and napsin is usu. -ve (36% +ve).
**Positive staining is unusual but useful if present, as metastatic disease is uniformily negative for both.<ref name=pmid24651909>{{Cite journal  | last1 = Rossi | first1 = G. | last2 = Cavazza | first2 = A. | last3 = Righi | first3 = L. | last4 = Sartori | first4 = G. | last5 = Bisagni | first5 = A. | last6 = Longo | first6 = L. | last7 = Pelosi | first7 = G. | last8 = Papotti | first8 = M. | title = Napsin-A, TTF-1, EGFR, and ALK Status Determination in Lung Primary and Metastatic Mucin-Producing Adenocarcinomas. | journal = Int J Surg Pathol | volume = 22 | issue = 5 | pages = 401-7 | month = Aug | year = 2014 | doi = 10.1177/1066896914527609 | PMID = 24651909 }}
</ref>


==Molecular==
==Molecular==
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**See ''[[lung carcinoma with ALK rearrangement]].
**See ''[[lung carcinoma with ALK rearrangement]].
**Do ''not'' occur with EGRF mutations ''or'' KRAS mutations.<ref name=pmid23729361>{{Cite journal  | last1 = Gainor | first1 = JF. | last2 = Varghese | first2 = AM. | last3 = Ou | first3 = SH. | last4 = Kabraji | first4 = S. | last5 = Awad | first5 = MM. | last6 = Katayama | first6 = R. | last7 = Pawlak | first7 = A. | last8 = Mino-Kenudson | first8 = M. | last9 = Yeap | first9 = BY. | title = ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. | journal = Clin Cancer Res | volume = 19 | issue = 15 | pages = 4273-81 | month = Aug | year = 2013 | doi = 10.1158/1078-0432.CCR-13-0318 | PMID = 23729361 }}</ref>
**Do ''not'' occur with EGRF mutations ''or'' KRAS mutations.<ref name=pmid23729361>{{Cite journal  | last1 = Gainor | first1 = JF. | last2 = Varghese | first2 = AM. | last3 = Ou | first3 = SH. | last4 = Kabraji | first4 = S. | last5 = Awad | first5 = MM. | last6 = Katayama | first6 = R. | last7 = Pawlak | first7 = A. | last8 = Mino-Kenudson | first8 = M. | last9 = Yeap | first9 = BY. | title = ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. | journal = Clin Cancer Res | volume = 19 | issue = 15 | pages = 4273-81 | month = Aug | year = 2013 | doi = 10.1158/1078-0432.CCR-13-0318 | PMID = 23729361 }}</ref>
*ROS1 - good response to crizotinib.<ref name=pmid25264305>{{Cite journal  | last1 = Shaw | first1 = AT. | last2 = Ou | first2 = SH. | last3 = Bang | first3 = YJ. | last4 = Camidge | first4 = DR. | last5 = Solomon | first5 = BJ. | last6 = Salgia | first6 = R. | last7 = Riely | first7 = GJ. | last8 = Varella-Garcia | first8 = M. | last9 = Shapiro | first9 = GI. | title = Crizotinib in ROS1-rearranged non-small-cell lung cancer. | journal = N Engl J Med | volume = 371 | issue = 21 | pages = 1963-71 | month = Nov | year = 2014 | doi = 10.1056/NEJMoa1406766 | PMID = 25264305 }}</ref>
**Approximately 1% of NSCLC.<ref name=pmid25409376>{{Cite journal  | last1 = Gold | first1 = KA. | title = ROS1--targeting the one percent in lung cancer. | journal = N Engl J Med | volume = 371 | issue = 21 | pages = 2030-1 | month = Nov | year = 2014 | doi = 10.1056/NEJMe1411319 | PMID = 25409376 }}</ref>


==Sign out==
==Sign out==
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Comment:
Comment:
The tumour is positive for TTF-1 and napsin. EGFR/ALK testing was ordered.
The adenocarcinoma is positive for TTF-1 and napsin. EGFR/ALK testing was ordered.
</pre>
 
====Lepidic pattern on biopsy====
Important note: lesion '''''must''''' be >=5 mm ''and'' <=30 mm.
<pre>
Lung, Left Upper Lobe, Core Biopsy:
    - ADENOCARCINOMA, lepidic pattern.
 
Comment:
The tumour is stains as follows:
POSITIVE: TTF-1, napsin A, CK7.
NEGATIVE: p40.
 
The findings are in keeping with lepidic pattern adenocarcinoma; the differential diagnosis includes: (1) adenocarcinoma in situ, (2) minimally invasive adenocarcinoma, and (3) invasive adenocarcinoma.
 
Lung biomarkers (EGFR, ALK, PDL1, ROS1) have been ordered.
</pre>
 
 
=====Mucinous adenocarcinoma with noncontributory stains=====
<pre>
Lung, Right Upper Lobe, Core Biopsy:
- ADENOCARCINOMA, MUCINOUS, see comment.
 
Comment:
The adenocarcinoma is negative for both napsin and TTF-1. EGFR/ALK testing was ordered.
 
The findings are compatible with a primary or secondary adenocarcinoma; clinical and
radiologic correlation is required.
</pre>
</pre>


====Block letters===
====Block letters====
<pre>
<pre>
LUNG, LEFT, BIOPSY:
LUNG, LEFT, BIOPSY:
Line 262: Line 351:
</pre>
</pre>


===Staging note===
====Mucinous====
*Two small tumours in one lobe is pT3.
The sections show cores with well-formed glands composed of foveolar-like columnar cells with a relatively bland cytomorphology. Mitotic activity is not readily apparent. A small amount of non-lesional lung parenchyma is present.
*Visceral pleural involvement upgrades small tumours.
 
===Lung cancer staging===
{{Main|Lung cancer staging}}


==See also==
==See also==
Line 270: Line 361:
*[[Adenocarcinoma]].
*[[Adenocarcinoma]].
*[[Metastasis]].
*[[Metastasis]].
*[[Lung carcinoma with ALK rearrangement]].
*[[SMARCA4-deficient adenocarcinoma of the lung]].


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
==External links==
*[http://www.cancer.org/cancer/lungcancer-non-smallcell/detailedguide/non-small-cell-lung-cancer-staging Lung cancer staging (cancer.org)].
*[http://www.nucmedresource.com/thoracic-nodal-stations.html Thoracic lymph node stations (nucmedresource.com)].


[[Category:Diagnosis]]
[[Category:Diagnosis]]
[[Category:Lung tumours]]
[[Category:Lung tumours]]

Latest revision as of 21:54, 11 January 2022

Adenocarcinoma of the lung
Diagnosis in short

Invasive adenocarcinoma, acinar pattern (right of image) and benign lung (left of image). H&E stain.

LM +/-nuclear atypia (may be absent in mucinous tumours), eccentrically placed nuclei, usu. abundant cytoplasm (classically with mucin vacuoles), often conspicuous nucleoli, +/-nuclear pseudoinclusions
LM DDx atypical adenomatous hyperplasia of the lung, adenocarcinoma in situ, squamous cell carcinoma of the lung, small cell carcinoma of the lung, non-small cell lung carcinoma, malignant mesothelioma, metastatic adenocarcinoma (esp. colorectal adenocarcinoma, breast adenocarcinoma (invasive ductal carcinoma of the breast, invasive lobular carcinoma))
IHC CK7 +ve, TTF-1 +ve, CK20 -ve, p40 -ve, p63 -ve (usually)
Molecular +/-KRAS mutations, +/-EGFR mutations, +/-ALK chromosomal translocation (inv(2)(p21p23) -- EML4-ALK fusion), +/-ROS1 rearrangements, +/-RET rearrangements
Staging lung cancer staging
Site lung - see lung tumours

Prevalence most common primary lung tumour
Radiology lung mass - typically peripheral lesion (distant from large airways), may be multifocal
Prognosis dependent on stage (minimally invasive and noninvasive: very good; invasive: moderate)
Clin. DDx other lung tumours - primary and metastatic
Treatment surgical resection if feasible

Adenocarcinoma of the lung, also lung adenocarcinoma, is common malignant lung tumour.

General

  • Adenocarcinoma is the most common (primary lung cancer).[1]
  • Adenocarcinoma is the non-smoker tumour - SCLC and squamous are more strongly associated with smoking.
  • Lung adenocarcinoma is the most common brain metastasis.[2]

Treatment:

  • Lung adenocarcinoma may be treated with EGFR inhibitors (e.g. gefitinib (Iressa), erlotinib (Tarceva)).[3]

Patients that receive EGFR inhibitors classically are:[4]

  • Non-smokers.
  • Female.
  • Asian.
    • Caucasians also benefit.[5]

Gross

  • Classically peripheral lesions.
  • May be multifocal.

Image

Microscopic

Features:

  • +/-Nuclear atypia - important.
    • May be absent in mucinous tumours - may look similar to foveolar epithelium.
  • Eccentrically placed nuclei.
  • Abundant cytoplasm - classically with mucin vacuoles.
  • Often conspicuous nucleoli.
  • +/-Nuclear pseudoinclusions.

Negatives:

  • Lack of intercellular bridges.

Patterns:[6]

  • Lepidic - tumour grows long the alveolar wall; means scaly covering.[7] At lower power, the shapes should still resemble lung acini.
  • Acinar - berry-shaped glands, smaller than lung acini.
  • Papillary - fibrovascular cores.
  • Micropapillary - nipple shaped projections without fibrovascular cores.
  • Solid - sheet of cells.

Notes:

  • Lymphovascular invasion is common.
  • Micropapillary predominant pattern and tumours with any amount of the lepidic pattern are associated with EGFR mutations.[8]

DDx:

Images

Acinar adenocarcinoma
Mucinous adenocarcinoma
Papillary adenocarcinoma

Fetal adenocarcinoma

www

Classification

Classification based on extent:[6]

  1. Adenocarcinoma in situ (AIS) - previously known as bronchioloalveolar carcinoma (abbreviated BAC).
    • Subtypes: nonmucinous, mucinous, mixed mucinous/nonmucinous.
    • Definition: lack of invasion into the stroma, vascular spaces and pleura.
    • Must have a lepidic growth pattern.[10]
  2. Minimally invasive adenocarcinoma (MIA).
  3. Invasive adenocarcinoma:
    • Subtypes: micropapillary, mucinous (previously mucinous BAC), colloid, fetal, enteric.

Grading

Graded G1-G4 - as per CAP protocol (version 3.4.0.0):[11]

  • G1 = lepidic.
  • G2 = acinar, papillary, cribriform.
  • G3 = micropapillary, solid, mucinous, colloid.
  • G4 = undifferentiated - not used for lung adenocarcinoma; it used for small cell carcinoma and large cell carcinoma.

Note:

  • There is no consensus currently on grading - as per the international consensus guidelines of 2011.[6]

Special stains

IHC

Primary versus metastatic:

  • TTF-1 +ve.
  • CK7 +ve.
  • CK20 -ve.

Panel for adenocarcinoma versus SCC:

Others:

  • p63 -ve -- occasionally +ve.
  • Vimentin -ve/+ve (+ve relatively common).
    • Poor prognosticator.[13]

Note:

  • In mucinous adenocarcinoma of the lung TTF-1 is usu. -ve (46% +ve) and napsin is usu. -ve (36% +ve).
    • Positive staining is unusual but useful if present, as metastatic disease is uniformily negative for both.[14]

Molecular

  • EGFR mutations (typically assessed by PCR) - respond to TKIs (e.g. gefitinib, erlotinib) if:[15]
    • Exon 19 deletion.
    • Exon 21 L858R.
      • Natural history of mutation is suspected to have a better prognosis vs. wild-type.[16]
    • KRAS mutations are absent, i.e. wild-type KRAS.[17]
  • ROS1 - good response to crizotinib.[21]
    • Approximately 1% of NSCLC.[22]

Sign out

Biopsy

Consensus recommendations:[6]

  • Adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma should not be used in the reporting of small biopsies and cytology.
    • Tumours with a non-invasive pattern are referred to by their pattern, e.g. lepidic growth, not as AIS.
Lung, Right Upper Lobe, Core Biopsy:
- INVASIVE ADENOCARCINOMA, NON-MUCINOUS.

Comment:
The adenocarcinoma is positive for TTF-1 and napsin. EGFR/ALK testing was ordered.

Lepidic pattern on biopsy

Important note: lesion must be >=5 mm and <=30 mm.

Lung, Left Upper Lobe, Core Biopsy:
     - ADENOCARCINOMA, lepidic pattern.

Comment:
The tumour is stains as follows:
POSITIVE: TTF-1, napsin A, CK7. 
NEGATIVE: p40.

The findings are in keeping with lepidic pattern adenocarcinoma; the differential diagnosis includes: (1) adenocarcinoma in situ, (2) minimally invasive adenocarcinoma, and (3) invasive adenocarcinoma.

Lung biomarkers (EGFR, ALK, PDL1, ROS1) have been ordered.


Mucinous adenocarcinoma with noncontributory stains
Lung, Right Upper Lobe, Core Biopsy:
- ADENOCARCINOMA, MUCINOUS, see comment.

Comment:
The adenocarcinoma is negative for both napsin and TTF-1. EGFR/ALK testing was ordered.

The findings are compatible with a primary or secondary adenocarcinoma; clinical and 
radiologic correlation is required.

Block letters

LUNG, LEFT, BIOPSY:
- ADENOCARCINOMA, LEPIDIC GROWTH; INVASION CANNOT BE EXCLUDED IN THIS SMALL SPECIMEN.
LUNG, RIGHT UPPER LOBE, NEEDLE BIOPSY:
- INVASIVE ADENOCARCINOMA, NON-MUCINOUS.

COMMENT:
The tumour stains as follows:
POSITIVE: TTF-1.
NEGATIVE: p40.

The immunoprofile is compatible with lung adenocarcinoma.
MASS, LEFT LOWER LOBE OF LUNG, BIOPSY:
- INVASIVE ADENOCARCINOMA.

COMMENT:
The tumour is positive for TTF-1.

Tissue will be sent for molecular testing and the results reported as an addendum.

Resection

LUNG, LEFT UPPER LOBE, LOBECTOMY:
- ADENOCARCINOMA WITH AN ACINAR PATTERN, SOLID PATTERN, MICROPAPILLARY PATTERN 
  AND LEPIDIC PATTERN -- PATTERNS IN ORDER OF PREVALENCE.
- MARGINS NEGATIVE FOR MALIGNANCY.
- THREE LYMPH NODES NEGATIVE FOR MALIGNANCY (0 POSITIVE/3).
- PLEASE SEE TUMOUR SUMMARY.
LUNG, RIGHT UPPER LOBE, LOBECTOMY:
- MULTIPLE ADENOCARCINOMAS (x2) WITH AN ACINAR PATTERN, SOLID PATTERN, MICROPAPILLARY PATTERN 
  AND LEPIDIC PATTERN -- PATTERNS IN ORDER OF PREVALENCE.
- MARGINS NEGATIVE FOR MALIGNANCY.
- FOUR LYMPH NODES NEGATIVE FOR MALIGNANCY (0 POSITIVE/4).
- LYMPHOVASCULAR INVASION PRESENT.
- PLEASE SEE TUMOUR SUMMARY AND COMMENT.

COMMENT:
The histology of the two adenocarcinomas resemble one another and lymphovascular
invasion is present.  These findings favour that the smaller tumor is a metastasis, rather
than a synchronous primary.

Micro

Size (tissue): scant tissue (<0.5 cm).
Gland formation: focal, poorly formed.
Cell size: large.
Cytoplasm: moderate-to-abundant, grey-eosinophilic.
Nucleus location: eccentric.
Nuclear pleomorphism: moderate.
Nuclear moulding: absent.
Nucleoli: present, prominent.
Nuclear pseudoinclusions: present.
Number of cores: 3.
Length of cores (total): 2.0 cm.

Gland formation: present.
Cell size: large.
Cytoplasm: moderate, grey-eosinophilic.
Necrosis: none apparent.
Mucin: none.

Nucleus location: eccentric.
Nuclear pleomorphism: moderate.
Nuclear moulding: absent.
Nuclear pseudoinclusions: absent.
Nuclear shape/arrangment: cigar-like/pseudostratified.
Nucleoli: present.

Mucinous

The sections show cores with well-formed glands composed of foveolar-like columnar cells with a relatively bland cytomorphology. Mitotic activity is not readily apparent. A small amount of non-lesional lung parenchyma is present.

Lung cancer staging

See also

References

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