Penis & scrotum

Squamous cell carcinoma and variants

Squamous cell carcinoma-general

Topic Completed: 1 April 2010

Minor changes: 29 October 2020

Copyright: 2002-2021,, Inc.

PubMed Search: Squamous cell carcinoma[TI] penis[TI] free full text[sb]

See also: Specific variants described separately

Alcides Chaux, M.D.
Antonio L. Cubilla, M.D.
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Cite this page: Chaux A, Cubilla AL. Squamous cell carcinoma-general. website. Accessed October 23rd, 2021.
Definition / general
  • Most penile neoplasms are squamous cell carcinoma
  • Rare in U.S.; < 1% of carcinomas in men (Cancer 2008;113:2883) vs. 10 - 20% in Asia (excluding Japan), Africa and South America
  • Usually age 40 - 70 years, median age 58 years
  • Incidence is 0.29 per 100,000 in U.S. whites vs. 4.2 per 100,000 in Paraguay vs. 4.4 per 100,000 in Uganda
  • Rare if circumcision at birth, more common if late circumcision (after age 10)
  • More prevalent in populations with lower education and higher poverty (Cancer 2008;113:2910)
  • More common in Hispanic and black men
  • Familial cases have occasionally been reported
  • Patients from high risk areas tend to be younger and present with a higher stage disease
  • Rarely associated with genital piercing (J Sex Med 2010;7:2280)
Risk factors
HPV related squamous cell carcinoma
  • HPV present in 40 - 50% of penile carcinomas (lower rate in Japanese, Pathol Int 2008;58:477) but frequency varies by histologic type (Am J Surg Pathol 2010;34:104)
  • Usually HPV 16 or 18 (J Clin Pathol 2009;62:870)
  • HPV related tumors include basaloid, warty and warty basaloid carcinomas
  • HPV is rarely found in papillary and sarcomatoid carcinomas
  • Verrucous, pseudohyperplastic and cuniculatum carcinomas are consistently HPV-
  • Most tumors arise from glans or inner foreskin near coronal sulcus as a slow growing, irregular mass
  • In high incidence areas, tumors involve multiple anatomical compartments in up to 50% of cases
Diagrams / tables

AFIP images

Schematic representation of effect of anatomic depth of invasion on risk of lymph node metastasis in carcinoma

Possible sites of
resection margin
involvement at time
of frozen section

Verruciform lesions

Frozen section evaluation of surgical margins

Clinical features and outcome
  • Patients occasionally present with inguinal nodal metastases with occult penile cancer due to severe phimosis or very small primary tumor
  • Local recurrence in 1/3 is due to insufficient surgery or positive margins, which also increases risk of regional inguinal and pelvic nodal metastases
  • 10 year survival rate of 82% (J Urol 2009;182:528)
  • Histologic subtypes have similar frequency in Paraguay and U.S. (Int J Surg Pathol 2010;18:268)

  • 5% have metastases at diagnosis
  • Common sites are inguinal and pelvic lymph nodes, liver, lung, heart or bone (Int J Surg Pathol 2011;19:164)
  • Nodes are often enlarged at clinical presentation due to infection, not metastases
  • 5 year survival is related to nodal involvement: 66% (not involved) vs. 27% (involved)

Low grade:
High grade:
  • Deep invasion (8 - 10 mm) into corpus spongiosum, dartos or corpora cavernosa is associated with 80% rate of metastases
  • Intermediate / high grade with invasion of 5 - 10 mm have 15% risk of metastases
Poor prognostic factors

Prognostic index score:
  • Combines histologic grade, anatomical level of tumor infiltration and perineural invasion to predict the likelihood of inguinal nodal involvement (Am J Surg Pathol 2009;33:1049)
  • Useful for risk group stratification and clinical management
  • Appropriate for surgical specimens, not for biopsies
  • Score is sum of points for histologic grade (grade 1: 1, grade 2: 2, grade 3: 3), anatomical level of maximum tumor infiltration (lamina propria: 1, corpus spongiosum / dartos: 2, corpus cavernosum / preputial skin: 3) and perineural invasion (absent: 0, present: 1)
  • Low risk: score of 2 - 3, intermediate risk: score of 4, high risk: score of 5 - 7
Clinical images

Contributed by Stewart F. Cramer, M.D.

Large bosselated mass

AFIP images

Tumor at junction of scrotum and penis

Images hosted on other servers:

Arising on genital lichen sclerosus

Papillary SCC

Ulcerated SCC on glans

Verrucous carcinoma

Gross description
  • Grossly noted growth patterns may have prognostic implications (Am J Surg Pathol 1993;17:753, World J Urol 2009;27:169)
  • Superficial spreading: tumors are limited to lamina propria or superficial corpus spongiosum and usually extend horizontally through multiple anatomical compartments
  • Vertical growth: tumors invade deep anatomical levels, surface is nonverruciform and frequently ulcerated
  • Verruciform: tumors are exophytic and papillomatous with a cauliflower-like aspect, may be limited to surface (verrucous) or invade deep anatomical levels (cuniculatum)
  • Mixed patterns: observed in 10 - 15% of all cases
  • In some cases, multicentric tumors (2 or more independent foci of carcinomas) are identified
Gross images

AFIP images


Exophytic cauliflower-like mass

Glans extensively
involved by a
multinodular mass
with focal ulceration


specimen shows a
flat, granular and
beige neoplasm

Massive involvement
has caused multiple
foci of ulceration

Coronal sulcus:

Nodular white
tumor extensively
involves the sulcus

Cut section
shows two
discrete nodules
of tumor

Verruciform lesions:


Multiple compartments:

Massive involvement
of glans, coronal
sulcus and foreskin

Massive involvement
has resulted in

4 separate
foci of
are present

Superficial spreading (SCC):

Tumor involves
the glans with
extension to
coronal sulcus

Tumor is white,
involves the mucosa
of the foreskin
and coronal sulcus

Assessment of depth of invasion:

Penile carcinoma has
been transversely

Assessment of
depth of invasion
of tumor in
resected specimen

Vertical growth (SCC):

Solid yellow-tan
neoplasm in
the dorsal half
of the glans

Mixed low and high grade (SCC):

Neoplasm shows
superficial, white,
serrated papillary

Margin involvement:

Frozen section evaluation of surgical margins

Microscopic (histologic) description
  • Most histologic subtypes resemble those in vulva, anus or buccal mucosa
  • 48 - 65% are usual squamous cell carcinoma
  • Verruciform tumors are verrucous, warty, papillary or cuniculatum carcinomas
  • Basaloid and sarcomatoid carcinomas usually have a vertical growth pattern
  • Often undifferentiated (bowenoid) penile intraepithelial neoplasia and lichen sclerosis (J Am Acad Dermatol 2010;62:284)
  • Features to report: depth of invasion measured from deepest malignant cells to highest overlying dermal papilla; resection margins

  • Grade 1: well differentiated cells, almost undistinguishable from normal squamous cells except for the presence of minimal basal / parabasal cell atypia
  • Grade 2: all tumors not fitting into criteria for grade 1 or 3 (Am J Surg Pathol 2009;33:1042)
  • Grade 3: any anaplastic cells
Microscopic (histologic) images

AFIP images

Mucosa is involved
by carcinoma
but epidermis
is spared

Invasion of the
lamina propria with
sparing of the
corpus spongiosum

Contributed by Antonio L. Cubilla, M.D.

Scrotum: well, moderately and poorly differentiated tumors

Positive stains
Molecular / cytogenetics description
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