Adenocarcinoma of the lung

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).
• Adenocarcinoma is the non-smoker tumour - SCLC and squamous are more strongly associated with smoking.
• Lung adenocarcinoma is the most common brain metastasis.

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.

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:

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

DDx:

• Atypical adenomatous hyperplasia of the lung - spaced hobnail cells, mild-to-moderate nuclear atypia, small lesion (< 5 mm).
• Adenocarcinoma in situ.
• Squamous cell carcinoma of the lung.
• Small cell carcinoma of the lung.
• Non-small cell lung carcinoma - diagnosis should be avoided if possible.
• Malignant mesothelioma.
• Metastatic adenocarcinoma.
  • Colorectal adenocarcinoma.
  • Breast adenocarcinoma.
    • Invasive ductal carcinoma of the breast.
    • Invasive lobular carcinoma.
  • Other carcinomas.
• Carcinomas of the bronchial glands, e.g. adenoid cystic carcinoma.

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:

• BAC mucinous type adjacent to benign (pathpedia.com).
• BAC mucinous and nonmucinous (cancergrace.org).
• Lepidic adenocarcinoma with invasive (flickr.com/Yale Rosen).
• Lepidic adenocarcinoma (flickr.com/Yale Rosen).
• Mucinous adenocarcinoma (pathlabmed.typepad.com).
• Non-mucinous adenocarcinoma in situ (flickr.com/Yale Rosen).
• Non-mucinous adenocarcinoma in situ (flickr.com/Yale Rosen).
• Acinar adenocarcinoma (flickr.com/Yale Rosen).
• Acinar adenocarcinoma (flickr.com/Yale Rosen).

Classification

Classification based on extent:

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.
2. Minimally invasive adenocarcinoma (MIA).
   • Lepidic growth with up to 5 mm of invasion.
   • Subtypes: nonmucinous (most common), mucinous (uncommon), mixed (mucinous/nonmucinous).
   • Should not have lymphovascular invasion.^{[citation needed]}
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):

• 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.

IHC

Primary versus metastatic:

• TTF-1 +ve.
• CK7 +ve.
• CK20 -ve.

Panel for adenocarcinoma versus SCC:

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

Others:

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

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.

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.
  • Do not occur with EGRF mutations or KRAS mutations.

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Biopsy

Consensus recommendations:

• 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.

Staging note

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

See also

• Lung tumours.
• Adenocarcinoma.
• Metastasis.

External links

• Lung cancer staging (cancer.org).
• Thoracic lymph node stations (nucmedresource.com).