Histological Classification of Penile Malignant Tumors

Most tumors affecting the penis are primary carcinomas arising in the epithelium lining glans, coronal sulcus, and inner foreskin.2 Glans tumors represent about 80% of all cases, followed by those exclusive to the foreskin (15%) and coronal sulcus (5%).1,2 Tumors originating in the skin of the shaft are exceedingly uncommon. In almost one-half of all cases, especially in geographical areas of high incidence, tumors extend through multiple anatomical compartments and determination of the

Table 3.1 Pathological classification of penile malignant tumors

Squamous cell carcinoma

Squamous cell carcinoma, usual type

Warty (condylomatous) carcinoma

Verrucous carcinoma

Papillary, not otherwise specified (NOS) carcinoma Basaloid carcinoma Sarcomatoid carcinoma Adenosquamous carcinoma

Pseudoglandular (acantholytic, adenoid) carcinoma

Carcinoma cuniculatum

Pseudohyperplastic carcinoma

Mixed carcinoma

Other malignant epithelial tumors

Clear cell carcinoma

Extramammary Paget's disease

Malignant melanoma

Nonepithelial malignant tumors

Soft-tissue sarcomas (Kaposi's sarcoma, leiomyosarcoma, others) Malignant lymphoma Secondary tumors primary site of origin is not possible.2,9 The vast majority of tumors are squamous cell carcinomas (SCC) although a variegated spectrum of histological subtypes, each one with distinctive clinicopathological features, is observed.2,9,10 Other rare subtypes of penile primary tumors include clear cell carcinoma, basal cell carcinoma, and Paget's disease. Malignant melanocytic lesions and sarcomas can also be observed in the penis and affect the glans or shaft. Finally, the penis can also be involved by meta-static disease, mainly from tumors originating in the genitourinary and lower digestive tract. A selected list of penile malignant tumors is provided in Table 3.1.

About 50-65% of all penile SCC correspond to the usual (classic, typical) subtype.2,9-11 This variant is characterized by infiltrative tumor nests of polygonal neo-plastic cells with distinctive cell borders, ample and eosinophilic cytoplasm, and tendency to squamous maturation and keratin pearl formation (Fig. 3.5a). Nuclear atypia can range from subtle to clearly anaplastic, but most tumors are composed of neoplastic cells with moderate pleomorphism (Fig. 3.5b). Usual SCCs composed entirely of well-differentiated or poorly differentiated neoplasic cells are very uncommon and their presence should raise suspicion about the correct classification. Verruciform carcinomas, representing 19-28% of all penile tumors,9-11 form a distinctive group of penile cancers characterized by an exophytic papillomatous pattern of growth. They are low-grade neoplasms which can sometimes invade deep anatomical levels but are associated with a low metastatic rate and a better prognosis when compared with usual SCC. This group encompasses warty, verrucous, and papillary carcinomas. A recently described SCC variant, the carcinoma cunicula-tum, and a rare HPV-related tumor, the giant condyloma or Buschke-Lowenstein tumor, also belong to this category.12 Morphological features and clues to differential diagnosis will be covered in more detail in the following sections.

Fig. 3.5 Squamous cell carcinoma, usual type. (a) Well-differentiated (grade 1) usual SCC. Tumor nests exhibit minimal cytological atypia, mostly limited to basal/parabasal layers, with ample eosinophilic cytoplasm, distinctive cellular borders, and keratin pearl formation. (b) Moderately differentiated (grade 2) usual SCC with more evident nuclear atypias. Neoplastic cells retain the morphological features of squamous differentiation, although to a lesser degree

Fig. 3.5 Squamous cell carcinoma, usual type. (a) Well-differentiated (grade 1) usual SCC. Tumor nests exhibit minimal cytological atypia, mostly limited to basal/parabasal layers, with ample eosinophilic cytoplasm, distinctive cellular borders, and keratin pearl formation. (b) Moderately differentiated (grade 2) usual SCC with more evident nuclear atypias. Neoplastic cells retain the morphological features of squamous differentiation, although to a lesser degree

Basaloid and sarcomatoid carcinomas correspond to the most aggressive variants of all penile SCC. Basaloid carcinoma, which represents 4-10% of all penile carcinomas, is characterized by highly infiltrative neoplastic nests.9-11,13 Sarcomatoid carcinoma, which accounts for 1-3% of all penile SCC, is also a deeply infiltrative neoplasm which is often associated with necrosis and hemorrhage.9-11,14,15 Most of the tumor is composed of anaplastic spindle cells resembling those of different sarcoma variants. Tumors composed of an admixture of different subtypes of SCC represent up to one-quarter of all penile carcinomas.9,11 The most frequent combination corresponds to tumors in which warty and basaloid components are intermingled, followed by usual carcinomas mixed with other keratinizing SCC variants, especially a combination of verrucous and usual SCCs. Combinations of usual with either warty or basaloid carcinomas are less frequent. In rare occasions adenobasa-loid, mucoepidermoid, or some other polymorphic carcinomas are observed. Some rare variants of penile SCC include adenosquamous, pseudohyperplastic, and pseudoglandular carcinomas.16-18 Several other types of epithelial malignant tumors, such as clear cell carcinomas, basal cell carcinomas, extramammary Paget's disease, and malignant melanomas have been reported but they are uncommon.2 19-23 Penile sarcomas correspond mainly to tumors of vascular and muscular origin.24-28 Malignant lymphomas can also involve the penis, either primary or secondarily.29 Other malignant tumors have been reported affecting primarily the penis but are extremely unusual to warrant detailed descriptions.30-34

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