Penile Carcinomas with Glandular Features

Adenosquamous carcinoma is a rare SCC variant characterized by the presence of solid squamous tumor nests intermingled with areas of glandular differentiation. About a dozen cases have been reported.9 16,60-64 The tumor originates in the glans

Penile Cancer

Fig. 3.17 Carcinomas with glandular features. (a) In adenosquamous carcinoma areas of glandular differentiation are intermingled with squamous features. Tumor is highly infiltrative and squamous areas are of high grade. (b) The pseudogland, a structure formed by a solid tumor nest with extensive central acantholysis, is the hallmark of pseudoglandular carcinoma. Pseudolumina are filled with necrotic debris, desquamated cells, neutrophils, and an amorphous eosinophilic material. Stromal reaction is intense

Fig. 3.17 Carcinomas with glandular features. (a) In adenosquamous carcinoma areas of glandular differentiation are intermingled with squamous features. Tumor is highly infiltrative and squamous areas are of high grade. (b) The pseudogland, a structure formed by a solid tumor nest with extensive central acantholysis, is the hallmark of pseudoglandular carcinoma. Pseudolumina are filled with necrotic debris, desquamated cells, neutrophils, and an amorphous eosinophilic material. Stromal reaction is intense 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 and both components tend to stay segregated with only minimal intermingling (Fig. 3.17a). 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 the distal urethra with glandular differentiation and true adenocarcinomas of Littre glands.

Mucoepidermoid carcinoma of the penis is an exceedingly rare tumor which is histologically similar to its cervical counterpart.65,66 The neoplastic population is composed of cells 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 appears that mucoepidermoid carcinoma is more aggressive than conventional adenosquamous carcinoma.66 In pseudoglandular carcinoma the extensive acan-tholysis can simulate glands lumina but there is no true epithelial lining (see below).

Urothelial carcinomas originating in the distal penile urethra or extending from the prostate, bladder, or even ureter/renal pelvis, can depict glandular features.16 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 immunohistochemi-cal markers for urothelial differentiation, such as uroplakin III and thrombomodulin, may be useful.67,68 In adenocarcinomas originating in Littre 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 Littre's glands 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.

About ten cases of pseudoglandular penile carcinoma have been reported. 1 8,69 The hallmark of this variant is the pseudogland, a solid tumor nest with extensive central acantholysis simulating a glandular lumen (Fig. 3.17b). However, the morphological picture is variegated and solid nests with intracellular edema and prominent bridges are mixed with others showing extensive acantholysis. Lumina are filled with keratin, necrotic debris, or micro abscesses. The presence of intracyto-plasmic empty vacuoles, either in single cells or adopting a collaret configuration, is a constant feature. Pseudoglandular carcinoma is a high-grade deeply infiltrative neoplasm associated with an aggressive biological behavior. It should be distinguished from other tumors showing glandular features and from the angiosarcoma-toid variant of sarcomatoid carcinoma. In the latter the presence of epitheloid and fusiform neoplastic cells surrounding pseudovascular spaces in an alveolar fashion may simulate an acantholytic pattern of growth. i 518,57 Careful examination of the tumor will reveal features of sarcomatoid carcinoma elsewhere.

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