Penis and scrotum - Squamous cell carcinoma

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Penis and scrotum

Squamous cell carcinoma and variants

Squamous cell carcinoma - NOS

Reviewers: Antonio Cubilla, M.D. and Alcides Chaux, M.D. (see Author/Reviewer page)

Revised: 18 November 2010, last major update May 2010

Definition

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● NOS: not otherwise specified; i.e. usual histologic pattern

● Represents 48-65% of all penile squamous cell carcinomas (Anal Quant Cytol Histol 2007;29:185)

● ICD-O: 8070/3

Terminology

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● Also called usual, typical, conventional, classical or epidermoid squamous cell carcinoma

Epidemiology

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● Mean age 58 years

Sites

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● Glans is the preferred site but extension to coronal sulcus and inner foreskin is common

Etiology

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● 25% of cases are HPV+ (Am J Surg Pathol 2010;34:104)

Clinical behavior

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● Inguinal nodal metastases in 28-39% and recurrences in 28% of all cases

● Intermediate mortality rate (20-38%)

Case reports

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● 66 year old man with metastatic disease in pleural effusion (Archives 1992;116:198)

Gross description (Macroscopy)

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● Predominant growth patterns are vertical and superficial spreading

● Gross aspect is non-distinctive and variable

● Mean tumor size varies from 2 cm in low incidence areas to 4-5 cm in high incidence areas

● Cut surface shows tan-white solid irregular tumor with superficial or deep penetration

Gross images

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Red-tan ulcerated tumor Fungating mass

Exophytic cauliflower-like mass has effaced Circumcision specimen shows a flat,

the glans, which is extensively involved by a granular, beige neoplasm involving

multinodular mass with focal ulceration mucosa of the foreskin but not the skin.

Nodular white tumor extensively involves the There is massive involvement of the glans,

sulcus. Cut section shows two discrete coronal sulcus, and foreskin with

nodules of tumor. The glans is to the left complete effacement of the corpus

and the foreskin to the right. The nodule spongiosum. The urethra is spared.

to the left is in the sulcus, the one on the

right involves the foreskin.

Massive involvement has resulted in Massive involvement has caused

autoamputation of the penis. This patient multiple foci of ulceration of the

had a penile lesion for at least 11 years foreskin in an uncircumcised man.

but declined treatment until his penis

had been destroyed by the cancer,

necessitating an emasculating procedure.

The tumor involves the glans with extension to the coronal sulcus. There is an abnormal geographic, white to erythematous abnormality of the glans mucosa which on microscopic examination was extensive squamous cell carcinoma in situ with minor foci of invasion.

The tumor is white and involves the mucosa of foreskin and coronal sulcus, and completely covers the glans. There is focal infiltration of the corpus spongiosum. Deep corpus spongiosum and tunica albuginea are not involved. The diagram shows in red the widespread involvement of epithelial compartments: mucosa of the foreskin (f), glans (g), and coronal sulcus (cos). Urethra (u), meatus (m), and skin of shaft (s) are not involved.

A solid yellow-tan neoplasm in the dorsal half of the glans. The diagram shows that the neoplasm (in red) replaces the corpus spongiosum of the dorsal glands and is present at the interface with the tunica albuginea (a). Foreskin (f), meatus (m), urethra (u), and corpus cavernosum (cc) are not compromised.

Gross picture and diagram of a neoplasm showing superficial, white, serrated papillary and tan, solid, deeply invasive components. In the diagram, the glans surface is completely covered dorsally by a thickened solid tissue (dark blue), which corresponds to squamous hyperplasia (sh); a papillary exophytic appearance just below the meatus (in mixed blue-red-black colors), which corresponds to a low-grade papillary carcinoma (pca); and a serrated benign papillary hyperplasia (ph) (lower part). Most of the corpus spongiosum, including its periurethral and meatal (m) components, is replaced by a high-grade carcinoma (red). Surgical margins are positive ventral to the urethra (u).

Four separate foci of carcinoma are present (red in diagram on right). The larger neoplasm is located in the ventral portion of the glans (g) and is exophytic. Three smaller, flat lesions involve the glans, coronal sulcus (cos), and mucosa of the foreskin (f).

Lateral view of penectomy specimen showing lesion with a cobblestone appearance beneath the corona representing the condyloma (top). More ventrally near the surgical margin is an elevated, reddish, strawberry-like mass representing the carcinoma. Diagrammatic representation in the bottom figure (f-foreskin, cos-coronal sulcus, g-glans, cdl-condyloma, ca-carcinoma.)

Micro description (Histopathology)

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● Usually keratinized with moderate differentiation

● Up to 50% of cases are heterogeneous (more than one histological grade)

● Most cases have differentiated penile intraepithelial neoplasia and squamous hyperplasia

● Tumors composed exclusively of extremely well-differentiated or poorly differentiated areas are uncommon

● In some cases clear glycogenated cells may predominate (but must differentiate from koilocytes)

● Stroma has variable lymphoplasmacytic infiltrate

● Foreign-body type giant cells often seen in highly keratinized tumors

Micro images

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Grade 1 Grade 2 Grade 3

Finger like projections Vascular invasion Measuring depth of invasion

into dermis

Low grade keratinizing (A,B), moderate to high-grade nonkeratinizing (C), high-grade

nonkeratinizing tumor (D), and carcinoma with prominent glycogenated clear cells (E).

Mucosa involved by carcinoma

at the top and uninvolved

epidermis at the bottom

Contributed by Dr. Alcides Chaux and Dr. Antonio Cubilla:

Mixed (hybrid) usual-verrucous carcinoma: a verrucous carcinoma (upper right field) intermingled with a high-grade solid usual squamous cell carcinoma (lower left field)

SQUAMOUS CELL CARCINOMAS, USUAL TYPE:

Well-differentiated (grade 1) usual SCC. Tumor nests are composed of neoplastic cells with minimal basal/parabasal atypia, retained squamous maturation with gradual keratinization, ample and eosinophilic cytoplasm, and well-defined cellular borders. A mild stromal reaction surrounds the tumor nests.

Moderately differentiated (grade 2) usual SCC. Almost all neoplastic cells show evident nuclear atypia with pleomorphism, coarse chromatin, prominent nucleoli and irregular nuclear membranes, but squamous maturation and keratin pearl formation are retained.

Poorly differentiated (grade 3) usual SCC. There is overt nuclear atypia with nuclear pleomorphism, coarse chromatin, prominent nucleoli, and high mitotic/apoptotic rate. Squamous nests and keratin pearl formation are not evident. However, neoplastic cells retain squamous features with ample and eosinophilic cytoplasm and distinct cell boundaries.

Virtual Slides

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Differential Diagnosis

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● Basaloid carcinoma: basophilic cytoplasm, indistinctive cellular borders, mostly HPV positive

● Clear cell carcinoma: exclusively composed of high-grade large polygonal cells with clear PAS+ cytoplasm, extensive areas of geographical necrosis, HPV positive

● Pseudoepitheliomatous hyperplasia: elongated rete ridges, no nuclear atypia, regular epithelial nests with evident peripheral palisading, no stromal reaction

● Urothelial carcinoma: ventral surface of penis, absence of squamous metaplasia, microglandular hyperplasia, lichen sclerosus or penile intraepithelial neoplasia, presence of urothelial carcinoma in situ or history of urothelial CIS or bladder tumor

End of Penis and scrotum > Squamous cell carcinoma and variants > Squamous cell carcinoma NOS

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