Mariela R. Pow-Sang, MD, Victor Benavente, MD, Julio E. Pow-Sang, MD, Carlos Morante, MD, Luis Meza, MD, Mark Baker, MD, and Julio M. Pow-Sang, MD

Disclosures

Cancer Control. 2002;9(4) 

In This Article

Pathology

Malignancies of the penis are divided into primary malignancies (ie, those that originate from either the soft tissues, urethral mucosa, or covering epithelium) and secondary malignancies (ie, those that represent metastatic disease and often affect the corpus cavernosum). The first step in the histological diagnosis of malignancy is the confirmation of the diagnosis and assessment of depth of invasion by microscopic examination of a biopsy specimen. A dorsal slit is often necessary to gain adequate exposure to the lesion.[18]

Secondary malignancies (metastatic tumors) should be suspected in patients with a known diagnosis of cancer and who also present with new-onset priapism (involvement of the corpora cavernosum) or an unusual penile lesion. Metastatic lesions are often multiple, palpable, painless nodules that may mimic syphilitic chancres. The primary malignancy is most often prostate, followed by bladder, rectosigmoid colon, and kidney, and it is spread most commonly by retrograde venous dissemination.[19,20,21]

Primary, nonsquamous malignancies comprise less than 5% of penile cancers. Sarcomas are the most frequent nonsquamous penile cancers, followed by melanomas, basal cell carcinomas, and lymphomas.[18] Kaposi's sarcoma, once isolated only in elderly men, has increased in frequency with the onset of AIDS. The lesion presents as a well-marginated red nodule, often isolated to the glans, and represents the initial site of presentation in 3% of patients.[22]

Many penile lesions have been identified as premalignant to the development of invasive squamous cell carcinoma, including leukoplakia, balanitis xerotica obliterans (BXO), Bowen's disease, erythroplasia of Queyrat, and giant condyloma acuminatum. Leukoplakia represents a rare lesion more frequently arising in individuals with diabetes, most likely as a result of their susceptibility to chronic infections. Histologically, leukoplakia is characterized by hyperkeratosis, parakeratosis, and acanthosis. Grossly, plaques appear as one or more whitish patches that cannot be wiped away and are usually around or involving the meatus. If ulceration or fissuring is present, the lesion poses a high likelihood of malignant degeneration.[23,24]

BXO, the penile equivalent of lichen sclerosis et atrophicus, is typically limited to the glans and prepuce. BXO appears as a thin, scaly, dry lesion possibly with ulcerations or fissures and often causing pruritus and pain. Histologically, the epidermis is atrophic, with the dermis showing edema, fibrosis, and lymphocytic infiltrates of the reticular dermis.[23,24,25] The lesion is typically benign; 12 cases of squamous cell carcinoma associated with BXO have been reported in the past 30 years.[26]

Carcinoma in situ (CIS) reflects the full thickness alteration in the epithelium with loss of polarity, multiple atypical mitoses, and increased hyperchromatic cells and multinucleated cells isolated strictly to the epithelium and with an intact basement membrane. Erythroplasia of Queyrat refers to CIS involving the glans penis, prepuce, or shaft, whereas Bowen's disease refers to CIS involving the remainder of the genitalia or perineal region.[27] A third, histologically identical lesion, bowenoid papulosis, has a clinically benign course and often presents in young men (mean age of 29.5) who are sexually active and circumcised. Bowenoid papulosis appears as multiple, pigmented red to brown papular lesions that can spontaneously regress in a number of cases yet poses no risk of malignant degeneration. [28,29]

Bowen's disease usually presents within the 5th to 6th decade as a solitary, thickened, gray-to-white plaque with crusting and oozing. Multiple biopsies are warranted to confirm that the dermal-epidermal border is sharply delineated by an intact basement membrane. Ulceration and erosion usually signify the development of invasive carcinoma. Bowen's disease has been reported to degenerate into invasive carcinoma in 5% to 10% of cases.[24] Conversely, erythroplasia of Queyrat has been noted to transform to invasive carcinoma more commonly, in approximately 10% to 33% of cases.[23,27] Erythroplasia of Queyrat usually presents as a red, velvety, well-marginated lesion that is often nontender. As in Bowen's disease, the lesion presents more commonly in noncircumcised men (approximately 80% to 90% of cases), yet the increased likelihood of malignant degeneration may be secondary to its mucosal location.[30]

The majority of squamous cell carcinomas arise de novo. Jensen et al[31] presented a series of 511 patients with penile squamous cell carcinoma. Only 39 (7.6%) had a history of previous or concomitant penile lesions. Squamous cell carcinoma is diagnosed by the histological confirmation on biopsy of invasion through the basement membrane. At presentation, squamous cell carcinoma is found on the glans in 48% of cases, the prepuce in 21%, glans and prepuce in 9%, coronal sulcus in 6%, and shaft in <2%.[32] The histopathologic grading is based on the Broder's Classification System (I-IV).[18] In this system, grade I consists of cells well differentiated with keratinization, prominent intercellular bridges, and keratin pearls. Grade II to III includes greater nuclear atypia, increased mitotic activity, and decreased keratin pearls. Grade IV cells are deeply invasive and consist of marked nuclear pleomorphism, nuclear mitoses, necrosis, lymphatic and perineural invasion, and no keratin pearls.

Half of lesions presenting on the penile shaft are poorly differentiated, whereas only 10% of lesions on the prepuce are well differentiatied.[33] Cubilla and group[34] associated the morphology of the primary lesion to disease progression. Superficially spreading squamous cell cancers occur most frequently and present with lymph nodes positive for metastatic disease in 42% of cases. Lesions with a deeper vertical growth present with positive lymph nodes in 82% of cases. Multicentric lesions have positive nodes in 33%, whereas verrucous lesions rarely present with metastasis to lymph nodes.[34] Differences between exophytic and ulcerative lesions have also been described. Patients with ulceration have a higher likelihood of node-positive disease.[35]

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