Adenocarcinoma of the lung

Adenocarcinoma of the lung
	Diagnosis in short
	; Lung adenocarcinoma, mucinous. H&E stain.
LM	nuclear atypia, eccentrically placed nuclei, usu. abundant cytoplasm (classically with mucin vacuoles), often conspicuous nucleoli, +/-nuclear pseudoinclusions
IHC	CK7 +ve, TTF-1 +ve, CK20 -ve, p40 -ve, p63 -ve (usually)
Molecular	+/-EGFR mutations, +/-ALK chromosomal translocation (inv(2)(p21p23) -- EML4-ALK fusion)
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	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.

Treatment:

Lung adenocarcinoma may be treated with EGFR inhibitors (e.g. gefitinib (Iressa), erlotinib (Tarceva)).^[2]

Patients that receive EGFR inhibitors classically are:^[3]

Non-smokers.
Female.
Asian.
- Caucasians also benefit.^[4]

Gross

Classically peripheral lesions.
May be multifocal.

Microscopic

Features:

Nuclear atypia.
Eccentrically placed nuclei.
Abundant cytoplasm - classically with mucin vacuoles.
Often conspicuous nucleoli.
+/-Nuclear pseudoinclusions.

Negatives:

Lack of intercellular bridges.

Patterns:^[5]

Lepidic - tumour grows long the alveolar wall; means scaly covering.^[6]
Acinar - berry-shaped glands.
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.^[7]

DDx:

Metastatic adenocarcinoma.
- Colorectal adenocarcinoma.
- Breast adenocarcinoma.
  - Invasive ductal carcinoma of the breast.
  - Invasive lobular carcinoma.
Squamous cell carcinoma of the lung.
Non-small cell lung carcinoma - diagnosis should be avoid if possible.
Malignant mesothelioma.
Small cell carcinoma of the lung.
Adenocarcinoma in situ.

Images

BAC - mucinous type - low mag. (WC/Yale Rosen)
BAC - mucinous type - high mag. (WC/Yale Rosen)

www:

Classification

Classification based on extent:^[5]

Adenocarcinoma in situ (AIS) - previously known as BAC.
- Subtypes: nonmucinous, mucinous, mixed mucinous/nonmucinous.
Minimally invasive adenocarcinoma (MIA).
- Lepidic growth with up to 5 mm of invasion.
- Subtypes: nonmucinous (most common), mucinous, mixed mucinous/nonmucinous.
Invasive adenocarcinoma:
- Subtypes: micropapillary, mucinous (previously mucinous BAC), colloid, fetal, enteric.

IHC

Primary versus metastatic:

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

Adenocarcinoma versus SCC:

TTF-1 +ve.
p40 -ve.^[9]
p63 -ve -- occasionally +ve.

Molecular

EGFR mutations (typically assessed by PCR) - respond to TKIs (e.g. gefitinib, erlotinib) if:^[10]
- Exon 19 deletion.
- Exon 21 L858R.
  - Natural history of mutation is suspected to have a better prognosis vs. wild-type.^[11]
- KRAS mutations are absent, i.e. wild-type KRAS.^[12]

ALK chromosomal translocation (inv(2)(p21p23) -- EML4-ALK fusion).^[13]
- Associated with a poor prognosis.^[14]
- Amenable to treatment with TKI.
- See lung carcinoma with ALK rearrangement.

Sign out

Biopsy

LUNG, LEFT, BIOPSY:
- ADENOCARCINOMA, LEPIDIC GROWTH; INVASION CANNOT BE EXCLUDED IN THIS SMALL SPECIMEN.

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 (3 POSITIVE/4).
- 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

Adequacy: 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.

Staging note

Two small tumours in one lobe is pT3.
Visceral pleural involvement upgrades small tumours.

References

↑ Lutschg JH (January 2009). "Lung cancer". N. Engl. J. Med. 360 (1): 87-8; author reply 88. doi:10.1056/NEJMc082208. PMID 19118313.
↑ Sun Y, Ren Y, Fang Z, et al. (October 2010). "Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases". J. Clin. Oncol. 28 (30): 4616–20. doi:10.1200/JCO.2010.29.6038. PMID 20855837.
↑ Job B, Bernheim A, Beau-Faller M, et al. (2010). "Genomic Aberrations in Lung Adenocarcinoma in Never Smokers". PLoS One 5 (12): e15145. doi:10.1371/journal.pone.0015145. PMC 2997777. PMID 21151896. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997777/.
↑ Rosell, R.; Moran, T.; Cardenal, F.; Porta, R.; Viteri, S.; Molina, MA.; Benlloch, S.; Taron, M. (Oct 2010). "Predictive biomarkers in the management of EGFR mutant lung cancer.". Ann N Y Acad Sci 1210: 45-52. doi:10.1111/j.1749-6632.2010.05775.x. PMID 20973798.
↑ ^5.0 ^5.1 Travis WD, Brambilla E, Noguchi M, et al. (February 2011). "International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma". J Thorac Oncol 6 (2): 244–85. doi:10.1097/JTO.0b013e318206a221. PMID 21252716.
↑ URL: http://medical-dictionary.thefreedictionary.com/lepidic. Accessed on: 8 August 2013.
↑ Shim, HS.; Lee, da H.; Park, EJ.; Kim, SH. (Oct 2011). "Histopathologic characteristics of lung adenocarcinomas with epidermal growth factor receptor mutations in the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification.". Arch Pathol Lab Med 135 (10): 1329-34. doi:10.5858/arpa.2010-0493-OA. PMID 21970488.
↑ URL: http://cancergrace.org/lung/2007/05/14/bac-mucinous-and-non-mucinous/. Accessed on: 8 August 2013.
↑ Bishop, JA.; Teruya-Feldstein, J.; Westra, WH.; Pelosi, G.; Travis, WD.; Rekhtman, N. (Mar 2012). "p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma.". Mod Pathol 25 (3): 405-15. doi:10.1038/modpathol.2011.173. PMID 22056955.
↑ John, T.; Liu, G.; Tsao, MS. (Aug 2009). "Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors.". Oncogene 28 Suppl 1: S14-23. doi:10.1038/onc.2009.197. PMID 19680292.
↑ URL: http://www.mycancergenome.org/mutation.php?dz=nsclc&gene=egfr&code=l858r. Accessed on: 27 April 2012.
↑ Pao, W.; Wang, TY.; Riely, GJ.; Miller, VA.; Pan, Q.; Ladanyi, M.; Zakowski, MF.; Heelan, RT. et al. (Jan 2005). "KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib.". PLoS Med 2 (1): e17. doi:10.1371/journal.pmed.0020017. PMID 15696205.
↑ Li, Y.; Ye, X.; Liu, J.; Zha, J.; Pei, L. (Jan 2011). "Evaluation of EML4-ALK fusion proteins in non-small cell lung cancer using small molecule inhibitors.". Neoplasia 13 (1): 1-11. PMID 21245935.
↑ Yang, P.; Kulig, K.; Boland, JM.; Erickson-Johnson, MR.; Oliveira, AM.; Wampfler, J.; Jatoi, A.; Deschamps, C. et al. (Jan 2012). "Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma.". J Thorac Oncol 7 (1): 90-7. doi:10.1097/JTO.0b013e31823c5c32. PMID 22134072.

[pmid19118313-1] Lutschg JH (January 2009). "Lung cancer". N. Engl. J. Med. 360 (1): 87-8; author reply 88. doi:10.1056/NEJMc082208. PMID 19118313.

[pmid20855837-2] Sun Y, Ren Y, Fang Z, et al. (October 2010). "Lung adenocarcinoma from East Asian never-smokers is a disease largely defined by targetable oncogenic mutant kinases". J. Clin. Oncol. 28 (30): 4616–20. doi:10.1200/JCO.2010.29.6038. PMID 20855837.

[pmid21151896-3] Job B, Bernheim A, Beau-Faller M, et al. (2010). "Genomic Aberrations in Lung Adenocarcinoma in Never Smokers". PLoS One 5 (12): e15145. doi:10.1371/journal.pone.0015145. PMC 2997777. PMID 21151896. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997777/.

[pmid20973798-4] Rosell, R.; Moran, T.; Cardenal, F.; Porta, R.; Viteri, S.; Molina, MA.; Benlloch, S.; Taron, M. (Oct 2010). "Predictive biomarkers in the management of EGFR mutant lung cancer.". Ann N Y Acad Sci 1210: 45-52. doi:10.1111/j.1749-6632.2010.05775.x. PMID 20973798.

[pmid21252716-5] 5.0 ^5.1 Travis WD, Brambilla E, Noguchi M, et al. (February 2011). "International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma". J Thorac Oncol 6 (2): 244–85. doi:10.1097/JTO.0b013e318206a221. PMID 21252716.

[6] URL: http://medical-dictionary.thefreedictionary.com/lepidic. Accessed on: 8 August 2013.

[pmid21970488-7] Shim, HS.; Lee, da H.; Park, EJ.; Kim, SH. (Oct 2011). "Histopathologic characteristics of lung adenocarcinomas with epidermal growth factor receptor mutations in the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification.". Arch Pathol Lab Med 135 (10): 1329-34. doi:10.5858/arpa.2010-0493-OA. PMID 21970488.

[8] URL: http://cancergrace.org/lung/2007/05/14/bac-mucinous-and-non-mucinous/. Accessed on: 8 August 2013.

[pmid22056955-9] Bishop, JA.; Teruya-Feldstein, J.; Westra, WH.; Pelosi, G.; Travis, WD.; Rekhtman, N. (Mar 2012). "p40 (ΔNp63) is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma.". Mod Pathol 25 (3): 405-15. doi:10.1038/modpathol.2011.173. PMID 22056955.

[pmid19680292-10] John, T.; Liu, G.; Tsao, MS. (Aug 2009). "Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors.". Oncogene 28 Suppl 1: S14-23. doi:10.1038/onc.2009.197. PMID 19680292.

[11] URL: http://www.mycancergenome.org/mutation.php?dz=nsclc&gene=egfr&code=l858r. Accessed on: 27 April 2012.

[12] Pao, W.; Wang, TY.; Riely, GJ.; Miller, VA.; Pan, Q.; Ladanyi, M.; Zakowski, MF.; Heelan, RT. et al. (Jan 2005). "KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib.". PLoS Med 2 (1): e17. doi:10.1371/journal.pmed.0020017. PMID 15696205.

[pmid21245935-13] Li, Y.; Ye, X.; Liu, J.; Zha, J.; Pei, L. (Jan 2011). "Evaluation of EML4-ALK fusion proteins in non-small cell lung cancer using small molecule inhibitors.". Neoplasia 13 (1): 1-11. PMID 21245935.

[pmid22134072-14] Yang, P.; Kulig, K.; Boland, JM.; Erickson-Johnson, MR.; Oliveira, AM.; Wampfler, J.; Jatoi, A.; Deschamps, C. et al. (Jan 2012). "Worse disease-free survival in never-smokers with ALK+ lung adenocarcinoma.". J Thorac Oncol 7 (1): 90-7. doi:10.1097/JTO.0b013e31823c5c32. PMID 22134072.

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