Adenocarcinoma of the lung

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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 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.
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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  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.
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  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.
  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: 3.4.0.0. URL: http://www.cap.org/ShowProperty?nodePath=/UCMCon/Contribution%20Folders/WebContent/pdf/cp-lung-16protocol-3400.pdf. Accessed on: March 23, 2016.
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  19. 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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