Adenosquamous carcinoma is composed of an adenocarcinoma and squamous cell carcinoma component comprising at least 10% of the whole tumor.^1,2,3 Various hypotheses for the pathogenesis of adenosquamous carcinomas include primarily adenocarcinomas with squamous differentiation, collision tumors, a variant of high-grade mucoepidermoid carcinoma, or tumors of pluripotential undifferentiated cell origin.⁴

Adenosquamous carcinomas represent between 1.1% and 2.2% of resected lung cancers.^5,6,7,8

There is a male predominance of 2 to 4:1. The mean age at presentation is 60 to 70 years, and about 80% are smokers.^5,7,9 The rate of smoking is lower in patients with a well-differentiated adenocarcinoma component.¹⁰

Adenosquamous carcinomas form ill-defined (38%), lobulated (32%), or spiculated (19%) masses. Fewer than 10% show ground-glass areas.⁸ Pleural indentation indicative of likely pleural invasion is seen in onethird of tumors.⁸

Adenosquamous carcinomas are generally larger than adenocarcinomas or squamous carcinomas and are solid, irregular masses with variable necrosis.⁹ About four of five tumors are peripheral.¹¹

Adenosquamous cell carcinoma morphologically shows two distinct cell population. The adenocarcinoma is acinar, papillary, or lepidic or a combination of these, in ˜75% of tumors (Fig. 83.1). In about 25% of cases, the adenocarcinoma is solid comprised of only large cells or cribriform. If entirely solid, it is confirmed as adenocarcinoma by immunohistochemical staining for TTF-1.¹⁰ By definition, the squamous component shows keratinization or intercellular bridges.

Adenosquamous carcinomas are more likely than other non-small cell carcinomas to have lymphatic, blood vessel, and visceral pleural invasion (11%, 20%, and 30%, respectively).⁹

Immunohistochemistry is not necessary if the two population of cells, adenocarcinoma and squamous cell carcinoma, are morphologically recognizable by regular H&E. But in cases where the adenocarcinoma component is solid and the squamous cell carcinoma nonkeratinizing and higher grade, performing TTF-1 and p40 assists with the diagnosis. As with morphology, the immunoprofile reveals two distinct population of cells, one that is TTF-1 positive and a separate that is p40 positive. Rarely, TTF-1-positive cells may be seen in squamous cell carcinoma and p40 in adenocarcinoma. This does not constitute an adenosquamous cell carcinoma (Fig. 83.2).