Non-small cell lung carcinoma

Non-small cell lung carcinoma
	Diagnosis in short
	; Non-small cell lung carcinoma. H&E stain.
Synonyms	large cell carcinoma (term discouraged in the context of biopsies & FNAs)
Subtypes	NSCC favour adenocarcinoma, NSCC favour squamous cell carcinoma, NSCC-not otherwise specified
LM DDx	lung adenocarcinoma, lung squamous carcinoma, lung small cell carcinoma, poorly differentiated metastatic carcinoma, other poorly differentiated neoplasms
IHC	pankeratin +ve, CD56 -ve, chromogranin A -ve, synaptophysin -ve, TTF-1 +ve/-ve, p63 +ve/-ve
Staging	lung cancer staging
Site	lung - see lung tumours
Clinical history	no history of malignancy or no suspicion of recurrence
Symptoms	+/-hemopytsis, +/-dyspnea
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.^[1]

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.^[2]

In the clinical context, it is often 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.
No history of malignancy or no suspicion of recurrence.
+/-Hemopytsis.
+/-Dyspnea.

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.
Malignant melanoma.
Other poorly differentiated neoplasms

Grading

NSCC-NOS, NSCC-favour adenocarcinoma, NSCC-favour SCC are grade 4.

Note:

In a large series of patients, there is no statistical difference in survival been grade 3 and grade 4.^[3]

Images

NSCLC - low mag. (WC)
NSCLC - intermed mag. (WC)
NSCLC - high mag. (WC)
NSCLC - very high mag. (WC)
NSCLC - very high mag. (WC)

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

Memorial Sloan-Kettering algorithm - Rekhtman et al.:^[4]

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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International consensus terminology - Travis et al.:^[2]

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

Not otherwise specified

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.

Favour squamous

Lung, Left Upper Lobe, Core Biopsy:
- NON-SMALL CELL CARCINOMA, favour squamous cell carcinoma, see comment.

Comment:
The tumour stains as follows: 
POSITIVE: AE1/AE3, CK5/6, CK7.
NEGATIVE: TTF-1, napsin A, p63, CDX2, CK20, S-100.

EGFR/ALK testing has been ordered.

The immunostains favour squamous cell carcinoma.

References

↑ Song, Z.; Lin, B.; Shao, L.; Zhang, Y. (Sep 2013). "Therapeutic efficacy of gefitinib and erlotinib in patients with advanced lung adenosquamous carcinoma.". J Chin Med Assoc 76 (9): 481-5. doi:10.1016/j.jcma.2013.05.007. PMID 23769878.
↑ ^2.0 ^2.1 Travis, WD.; Brambilla, E.; Noguchi, M.; Nicholson, AG.; Geisinger, K.; Yatabe, Y.; Ishikawa, Y.; Wistuba, I. et al. (May 2013). "Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification.". Arch Pathol Lab Med 137 (5): 668-84. doi:10.5858/arpa.2012-0263-RA. PMID 22970842.
↑ Sun, Z.; Aubry, MC.; Deschamps, C.; Marks, RS.; Okuno, SH.; Williams, BA.; Sugimura, H.; Pankratz, VS. et al. (May 2006). "Histologic grade is an independent prognostic factor for survival in non-small cell lung cancer: an analysis of 5018 hospital- and 712 population-based cases.". J Thorac Cardiovasc Surg 131 (5): 1014-20. doi:10.1016/j.jtcvs.2005.12.057. PMID 16678584.
↑ Rekhtman, N.; Ang, DC.; Sima, CS.; Travis, WD.; Moreira, AL. (Oct 2011). "Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens.". Mod Pathol 24 (10): 1348-59. doi:10.1038/modpathol.2011.92. PMID 21623384.

[1] Song, Z.; Lin, B.; Shao, L.; Zhang, Y. (Sep 2013). "Therapeutic efficacy of gefitinib and erlotinib in patients with advanced lung adenosquamous carcinoma.". J Chin Med Assoc 76 (9): 481-5. doi:10.1016/j.jcma.2013.05.007. PMID 23769878.

[pmid22970842-2] 2.0 ^2.1 Travis, WD.; Brambilla, E.; Noguchi, M.; Nicholson, AG.; Geisinger, K.; Yatabe, Y.; Ishikawa, Y.; Wistuba, I. et al. (May 2013). "Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification.". Arch Pathol Lab Med 137 (5): 668-84. doi:10.5858/arpa.2012-0263-RA. PMID 22970842.

[pmid16678584-3] Sun, Z.; Aubry, MC.; Deschamps, C.; Marks, RS.; Okuno, SH.; Williams, BA.; Sugimura, H.; Pankratz, VS. et al. (May 2006). "Histologic grade is an independent prognostic factor for survival in non-small cell lung cancer: an analysis of 5018 hospital- and 712 population-based cases.". J Thorac Cardiovasc Surg 131 (5): 1014-20. doi:10.1016/j.jtcvs.2005.12.057. PMID 16678584.

[pmid21623384-4] Rekhtman, N.; Ang, DC.; Sima, CS.; Travis, WD.; Moreira, AL. (Oct 2011). "Immunohistochemical algorithm for differentiation of lung adenocarcinoma and squamous cell carcinoma based on large series of whole-tissue sections with validation in small specimens.". Mod Pathol 24 (10): 1348-59. doi:10.1038/modpathol.2011.92. PMID 21623384.

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