Non-small cell lung carcinoma

Non-small cell lung carcinoma
Diagnosis in short
Synonyms	large cell carcinoma (term discouraged in the context of biopsies & FNAs)
LM DDx	lung adenocarcinoma, lung squamous carcinoma, lung small cell carcinoma, poorly differentiated metastatic carcinoma
IHC	pankeratin +ve, CD56 -ve, chromogranin A -ve, synaptophysin -ve
Staging	lung cancer staging
Site	lung - see lung tumours
Clinical history	typically no history of malignancy
Prevalence	uncommon
Radiology	not suggestive of metastatic disease
Prognosis	usually poor
Clin. DDx	other lung tumours
Treatment	surgery if feasible

Non-small cell lung carcinoma, abbreviated NSCLC, is a malignant epithelial neoplasm of the lung that is not small cell carcinoma of the lung.

It is umbrella term that includes squamous cell carcinoma of lung, adenocarcinoma of the lung and adenosquamous carcinoma of the lung.

It is also known as large cell carcinoma; however, usage of large cell carcinoma is discouraged in the context of lung biopsies and lung cytopathology specimens.

In the clinical context, it is usually referred to as non-small cell lung cancer; this ignores the fact that not all non-small cell lung cancer fits into the carcinoma category.

Poorly differentiated carcinoma of the lung and poorly differentiated lung carcinoma redirect to this article.

General

• Non-small cell lung carcinoma can be considered a waffle diagnosis and as such its use should be limited.
  • It is preferable to be more specific if this is possible, i.e. call adenocarcinoma or squamous cell carcinoma.
• Historically, it was sufficient to differentiate between small cell and non-small cell carcinomas, as the treatment for all non-small cell lung carcinomas was the same.
• Small cell carcinoma is typically considered non-surgical disease; thus, non-small cell carcinoma or poorly differentiated carcinoma, as a diagnosis, is less likely to exclude surgery as an option.

Clinical:

• Radiologic findings should not be suggestive of a metastasis.

Microscopic

Features:

• Typically large cells with abundant cytoplasm.
• +/-Nucleoli.
• No stippled chromatin.

DDx:

• Squamous cell carcinoma of the lung.
• Adenocarcinoma of the lung.
• Small cell carcinoma of the lung.
• Large cell variant of small cell carcinoma of the lung.
• Lung metastasis - imaging suggestive of a metastasis or a history of malignancy.

IHC

Features:

• Lack of staining with neuroendocrine markers (chromogranin A -ve, synaptophysin -ve, CD56 -ve).
• Keratins +ve.

Note:

• Immunostains should not favour adenocarcinoma or squamous cell carcinoma - see Sloan-Kettering algorithm below.

Adenocarcinoma versus squamous carcinoma

Sloan-Kettering algorithm - Rekhtman et al.:

TTF-1\p63	p63 -ve (0% of cells)	p63 +ve <50% of cells	p63 +ve >=50% of cells
TTF-1 +ve >=50% of cells	Adenocarcinoma	Adenocarcinoma	Adenocarcinoma
TTF-1 +ve <50% of cells	Adenocarcinoma	Adenocarcinoma	Squamous carcinoma
TTF-1 -ve (0% of cells)	Adenocarcinoma	CK5/6 to determine	Squamous carcinoma

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Consensus terminology from Travis et al.:

Diagnosis	Morphology	Stains
Non-small cell carcinoma, favour adenocarcinoma	undifferentiated morphology	TTF-1 +ve
Non-small cell carcinoma, favour squamous cell carcinoma	undifferentiated morphology	p40 or p63 +ve
Non-small cell carcinoma-not otherwise specified	undifferentiated morphology	-ve NE stains, -ve SCC stains, -ve adenoca stains

Lung, Left Lower Lobe, Core Biopsy: 
- NON-SMALL CELL CARCINOMA-NOT OTHERWISE SPECIFIED, see comment. 

COMMENT: 
The tumour stains as follows: 
POSITIVE: EMA, AE1/AE3. 
NEGATIVE: TTF-1, chromogranin A, synaptophysin, CD56, CD45, CK5/6, p63.

The morphology would be compatible with small cell carcinoma or basaloid 
squamous cell carcinoma.  

The neuroendocrine markers (chromogranin A, synaptophysin, CD56) and the squamous 
markers (p63, CK5/6) are negative; thus, the tumour is not further classified. 

See also

• Lung tumours.
• SUV.
• Sarcomatoid carcinoma of the lung.