Adenocarcinoma of the lung

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

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

General

• Adenocarcinoma is the most common (primary lung cancer).
• 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)).

Patients that receive EGFR inhibitors classically are:

• Non-smokers.
• Female.
• Asian.
  • Caucasians also benefit.

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:

• Lepidic - tumour grows long the alveolar wall; means scaly covering.
• 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.

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:

• BAC mucinous type adjacent to benign (pathpedia.com).
• BAC mucinous and nonmucinous (cancergrace.org).

Classification

Classification based on extent:

1. Adenocarcinoma in situ (AIS) - previously known as BAC.
   • Subtypes: nonmucinous, mucinous, mixed mucinous/nonmucinous.
2. Minimally invasive adenocarcinoma (MIA).
   • Lepidic growth with up to 5 mm of invasion.
   • Subtypes: nonmucinous (most common), mucinous, mixed mucinous/nonmucinous.
3. 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.
• p63 -ve -- occasionally +ve.

Molecular

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

• ALK chromosomal translocation (inv(2)(p21p23) -- EML4-ALK fusion).
  • Associated with a poor prognosis.
  • 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.

See also

• Lung tumours.
• Adenocarcinoma.
• Metastasis.