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 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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  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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  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.
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