Answer: Pseudoglandular carcinoma

Histology: The slides show a deeply infiltrating malignant tumor composed of solid nests with extensive central acantholysis. Nonetheless, there is ample variation in the aspect of the tumor, with irregularly shaped nests of different sizes, some showing acantholysis while others depict a more solid appearance.

Discussion: Less than a dozen cases of pseudoglandular, also named acantholytic, penile squamous cell carcinoma (SCC) have been reported. The hallmark of this variant is the pseudogland, a solid tumor nest with extensive central acantholysis simulating a glandular lumen. However, as we can see in the slides, the morphological picture is variegated and solid nests with intracellular edema and prominent bridges are mixed with other showing extensive acantholysis. Lumina are filled with keratin, necrotic debris or micro abscesses. The presence of intracytoplasmic empty vacuoles, either in single cells or adopting a collaret configuration, is a constant feature. Pseudoglandular SCC is a high-grade, deeply infiltrative neoplasm associated with an aggressive biological behavior. It should be distinguished from other tumors showing glandular features (such as adenosquamous, urothelial carcinomas of the distal urethra with glandular features, and true adenocarcinomas of Littre glands) and from the angiosarcomatoid variant of sarcomatoid carcinoma. Penile adenosquamous SCC is also a deeply infiltrating tumor composed of areas with squamous differentiation mixed with others showing true glandular lining. The former areas usually predominate and both components tend to stay segregated with only minimal intermingling; the glandular component is positive for mucin stains and CEA. 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 features and others showing evidence of glandular differentiation (pale, granular and ample cytoplasm with positivity for mucin stains and CEA) without well-defined glandular or ductal structures. 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 problematic cases immunohistochemical markers for urothelial differentiatio may be useful. 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, in the angiosarcomatoid variant of sarcomatoid carcinoma the presence of epitheloid and fusiform neoplastic cells surrounding pseudovascular spaces in an alveolar fashion may simulate an acantholytic pattern of growth; careful examination of the tumor will reveal features of sarcomatoid carcinoma elsewhere.