Squamous cell carcinoma of lung

Definition

A tumour arising from bronchial epithelium showing keratinisation or intercellular bridges.

Epidemiology

Squamous cell carcinoma accounts for about 45% of primary lung carcinomas in men, 25% in women. More than 90% of squamous cell carcinomas of lung occur in cigarette smokers.

Squamous cell carcinomas can be subdivided into central and peripheral. The peripheral tumours present in older patients, at a lower stage, with less lymph node involvement: they have variably been reported to have a similar⁶ or better²² prognosis when compared to central tumours.

Radiology

Squamous cell carcinoma is the most frequent type to cavitate. Spiral CT reveals two to four times as many cancers as does plain chest x-ray¹⁸. CT and MRI have limited sensitivity in the imaging of mediastinal nodes for staging. FDG-PET gives greater accuracy in assessing both nodes⁵^,18,23 and distant metastases²³.

Macroscopic appearances

A minority of T1 tumours are endobronchial and exophytic: they do not have a better prognosis than other T1N0 squamous carcinomas of lung⁸.

Histopathology

There is keratinisation and/or intercellular bridges are seen.

Variants:

Papillary variant of squamous cell carcinoma. This variant includes verrucous carcinoma, rare in the lung.
Clear cell variant of squamous cell carcinoma^9,10. The differential includes primary large cell carcinoma, primary adenocarcinoma and metastatic renal cell carcinoma.
Small cell variant of squamous cell carcinoma¹¹. The differential includes pure small cell carcinoma and combined small cell / squamous cell carcinoma. Small cell variant of squamous cell carcinoma tends to have coarser chromatin and more prominent nucleoli than does true small cell carcinoma. Immunohistochemistry is invaluable.
Basaloid variant^3,12: there is prominent peripheral nuclear palisading. If lacking squamous differentiation, should be classified as basaloid variant of large cell carcinoma.
Alveolar space-filling peripheral variant; this subtype appears to have a better prognosis⁶.
Transitional cell carcinoma: rare

Immunohistochemistry

See immunohistochemistry of malignant epithelial tumours of lung.

34bE12

positive

CK5/6

positive¹³

CEA

positive

35bH11

often positive

TTF-1

usually negative

CK7

usually negative

Transcription factor E2F1

2/11³⁶

Cytogenetics and molecular genetics

Numerous somatic mutations are implicated in the pathogenesis of lung cancer¹⁴. Gains in 3q are more common in squamous carcinomas than in adenocarcinomas^15,16,20. Losses on 3p have also been reported^19,20,24. The FHiT (fragile histidine triad) gene^21,34 and RASSF1A²⁶ are two genes on 3p that may be of importance in the pathogenesis of lung cancer, particularly squamous carcinoma. Certain deletions may be associated with metastatic potential²⁰. Epidermal growth factor receptor overexpression is ubiquitous in squamous cell carcinoma²⁵, occurs in about 65% of adenocarcinomas and large cell carcinomas but is not a feature of small cell carcinomas.¹⁷

Ultrastructure

Differential diagnosis

Large cell carcinoma: lacks squamous differentiation
Adenosquamous carcinoma may be mimicked by entrapped pneumocytes.
Thymic squamous carcinoma
Squamous metaplasia with atypia in diffuse alveolar damage.
Pseudovascular adenoid squamous cell carcinoma closely mimics angiosarcoma but is positive for cytokeratins and EMA, negative for CD31, CD34 and Ulex europaeus I lectin^1,2.

Prognosis

Stage I five year survival is 70%.
Epidermoid carcinomas are the non-small cell carcinomas of lung most prone to give rise to isolated local recurrences⁷.
Basaloid carcinoma is reported to have a prognosis inferior to that of poorly differentiated squamous cell carcinoma^4,12.
pRb2/p130 is a member of the retinoblastoma gene family; loss may correlate with poor overall survival and is demonstrable by immunohistochemistry²⁸. Immunohistochemical demonstration of abnormal expression of p27(KIP1)²⁹, loss of expression of the fragile histidine triad gene^27,34, p16³⁰ or p21³³, or overexpression of cyclin E^31,32 may predict poor survival. Nuclear, as opposed to cytoplasmic, expression of the transcription factor Y-box binding protein (YB-1) correlates with poor prognosis³⁵.