Answer: Adenosquamous carcinoma

Histology: Slides show a biphasic proliferation of tumors cells showing squamous and glandular differentiation, deeply infiltrating penile erectile tissues. Squamous and glandular structures are found either segregated or in the same tumor nests.

Discussion: Adenosquamous carcinoma is a rare penile SCC variant characterized by the presence of solid squamous tumor nests intermingled with areas of glandular differentiation. About a dozen cases have been reported. The tumor originates in the glans central/perimeatal region and has a tendency for deep infiltration. Most tumors are of high-grade, with frequent vascular and perineural invasion. Metastatic rate is high but cancer-specific mortality remains low. Histologically, areas with squamous differentiation predominate. The glandular component is positive for mucin stains and CEA. The main differential diagnosis is with penile tumors with glandular features, including mucoepidermoid, pseudoglandular, urothelial carcinomas of distal urethra with glandular differentiation and true adenocarcinomas of Littré glands. Mucoepidermoid carcinoma of penis is an exceedingly rare tumor which is histologically similar to its cervical counterpart. Neoplastic population is composed of cell with squamous differentiation and cells showing evidence of glandular differentiation (pale, granular and ample cytoplasm with positivity for mucin stains and CEA) without well-defined glandular or ductal structures. Although more data are needed it seems that mucoepidermoid carcinoma is more aggressive than conventional adenosquamous carcinoma. In pseudoglandular carcinoma the extensive acantholysis can simulate glands lumina but there is no true epithelial lining. Urothelial carcinomas originating in the penile distal urethra or extending from prostate, bladder or even ureter/renal pelvis, can depict glandular features. However, a previous history of urothelial carcinoma elsewhere and the frequent finding of in situ urothelial carcinoma (which is absent in adenosquamous carcinoma) aid in the differential diagnosis. In adenocarcinomas originating in Littré glands there is no true squamous differentiation and tumors tend to be ventrally located with only secondary extension to the perimeatal glans area. Finally, entrapment of Littré’s glans by an otherwise usual SCC can simulate the aspect of an adenosquamous carcinoma. However, the morphology of the glandular component remains bland and admixtures are limited to the periurethral area.