Adenocarcinoma of the lung

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Adenocarcinoma of the lung
Diagnosis in short

Lung adenocarcinoma, mucinous. 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 +/-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 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

  • Lung adenocarcinoma. (WC/Rosen)

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

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

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

  • Acinar adenocarcinoma. (WC/Yale Rosen)

  • Acinar adenocarcinoma. (WC/Yale Rosen)

www:

Classification

Classification based on extent:[6]

  1. Adenocarcinoma in situ (AIS) - previously known as 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 3.3.0.0):[11]

  • G1 = lepidic.
  • G2 = acinar and papillary.
  • G3 = micropapillary, solid, mucinous.
  • G4 = undifferentiated.

Note:

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

IHC

Primary versus metastatic:

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

Panel for adenocarcinoma versus SCC:

  • TTF-1 +ve.
  • Napsin A +ve.
  • p40 -ve.[12]
  • CK5/6 -ve.

Others:

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

Molecular

  • EGFR mutations (typically assessed by PCR) - respond to TKIs (e.g. gefitinib, erlotinib) if:[14]
    • Exon 19 deletion.
    • Exon 21 L858R.
      • Natural history of mutation is suspected to have a better prognosis vs. wild-type.[15]
    • KRAS mutations are absent, i.e. wild-type KRAS.[16]

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 tumour is positive for TTF-1 and napsin. EGFR/ALK testing was ordered.

=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.

Staging note

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

See also

References

  1. ↑ Lutschg JH (January 2009). "Lung cancer". N. Engl. J. Med. 360 (1): 87-8; author reply 88. doi:10.1056/NEJMc082208. PMID 19118313.
  2. ↑ Nayak, L.; Lee, EQ.; Wen, PY. (Feb 2012). "Epidemiology of brain metastases.". Curr Oncol Rep 14 (1): 48-54. doi:10.1007/s11912-011-0203-y. PMID 22012633.
  3. ↑ 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.
  4. ↑ 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/.
  5. ↑ 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.
  6. ↑ 6.0 6.1 6.2 6.3 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. Cite error: Invalid <ref> tag; name "pmid21252716" defined multiple times with different content Cite error: Invalid <ref> tag; name "pmid21252716" defined multiple times with different content
  7. ↑ URL: http://medical-dictionary.thefreedictionary.com/lepidic. Accessed on: 8 August 2013.
  8. ↑ 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.
  9. ↑ URL: http://cancergrace.org/lung/2007/05/14/bac-mucinous-and-non-mucinous/. Accessed on: 8 August 2013.
  10. ↑ Borczuk, AC. (Jan 2012). "Assessment of invasion in lung adenocarcinoma classification, including adenocarcinoma in situ and minimally invasive adenocarcinoma.". Mod Pathol 25 Suppl 1: S1-10. doi:10.1038/modpathol.2011.151. PMID 22214965.
  11. ↑ CAP Lung protocol. Version: 3.3.0.0. URL: 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.
  12. ↑ 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.
  13. ↑ Dauphin, M.; Barbe, C.; Lemaire, S.; Nawrocki-Raby, B.; Lagonotte, E.; Delepine, G.; Birembaut, P.; Gilles, C. et al. (Jul 2013). "Vimentin expression predicts the occurrence of metastases in non small cell lung carcinomas.". Lung Cancer 81 (1): 117-22. doi:10.1016/j.lungcan.2013.03.011. PMID 23562674.
  14. ↑ 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.
  15. ↑ URL: http://www.mycancergenome.org/mutation.php?dz=nsclc&gene=egfr&code=l858r. Accessed on: 27 April 2012.
  16. ↑ 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.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ Gainor, JF.; Varghese, AM.; Ou, SH.; Kabraji, S.; Awad, MM.; Katayama, R.; Pawlak, A.; Mino-Kenudson, M. et al. (Aug 2013). "ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer.". Clin Cancer Res 19 (15): 4273-81. doi:10.1158/1078-0432.CCR-13-0318. PMID 23729361.
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