Penis and scrotum
Squamous cell carcinoma and variants
Squamous cell carcinoma - general

Authors: Antonio Cubilla, M.D., Alcides Chaux, M.D. (see Authors page)

Revised: 4 April 2018, last major update April 2010

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

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

See also: Specific variants described separately
Cite this page: Cubilla, A., Chaux, A. Squamous cell carcinoma - general. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/penscrotumcarcinomagen.html. Accessed July 22nd, 2018.
Definition / general
Epidemiology
  • 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-
Sites
  • 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

Images hosted on PathOut server:

Schematic representation of effect of anatomic level of invasion on risk of lymph node metastasis in carcinoma of the glans: each dot represents
an individual case in a series of 51 cases, green representing cases without lymph node metastasis and the red, cases with lymph node metastasis;
note the propensity for the latter cases to spread into the deep corpus spongiosum or corpus cavernosum; the converse is true for the cases
represented by the green dots (lp - lamina propria, scs - superficial corpus spongiosum, dcs - deep corpus spongiosum, cc - corpus cavernosum)


Schematic representation of effect of anatomic depth of invasion on risk of lymph node metastasis in carcinoma arising from the mucosa of the foreskin:
each dot represents an individual case in a series of 20 cases, green dots representing cases without lymph node metastasis and the red dots, cases with
lymph node metastasis; note the tendency for most of the former to invade no deeper than the superficial dartos and the spread to deep dartos or beyond
of all cases with lymph node metastasis (m - mucosa, lp - lamina propria, sd - superficial dartos, dd - deep dartos, dm - dermis, e - epidermis)


Possible sites of resection margin involvement at time of frozen section;
left: possible sites of involvement; purple dots indicate the usual
sites of positive margins (u - urethra, lp - lamina propria, cs - corpus
spongiosum, bf - Buck fascia); right: urethral mucosal involvement



Verruciform lesions:

A: Verrucous carcinoma
B: Papillary carcinoma, NOS
C: Giant condyloma
D: Warty (condylomatous) carcinoma



Frozen section evaluation of surgical margins:

A: Periurethral corpus spongiosum involvement by carcinoma (ca - yellow, u - urethra, cc - corpos cavernosa, fas - Buck fascia)
B: Squamous cell carcinoma involves the corpora cavernosa with the left more involved than the right; urethra (bottom) uninvolved
C: B showing tumor involvement in yellow (ca - carcinoma, a - tunica albuginea, cc - corpus cavernosum, cs - corpus spongiosum, u - urethra)

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)

Metastases:
  • 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
Treatment
Clinical images

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

Scroll to see all images:


Images hosted on PathOut server:

Glans:

Exophytic cauliflower-like mass

Glans extensively
involved by a
multinodular mass
with focal ulceration


Foreskin:

Circumcision specimen shows
a flat, granular and beige
neoplasm involving the mucosa
of the foreskin but not the skin

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; glans to left and the foreskin
to right; nodule to the left is in sulcus,
the one on the right involves foreskin


Verruciform lesions:

Verrucous carcinoma: large,
destructive, cauliflower-like
mass has extensively
replaced the penis



Multiple compartments:

Massive involvement of glans, coronal sulcus and foreskin
with complete effacement of the corpus spongiosum,
sparing the urethra; penis had been destroyed by the
cancer, necessitating an emasculating procedure

Massive involvement has
resulted in autoamputation
Patient had penile lesion for 11
years but declined treatment


4 separate foci of carcinoma are present (red in diagram
on right): the larger neoplasm is located in the ventral glans
(g) and is exophytic; 3 smaller flat lesions involve the glans,
coronal sulcus (cos) and mucosa of the foreskin (f)



Superficial spreading squamous cell carcinoma:

Tumor involves the glans with extension to coronal sulcus; there is an abnormal white to
erythematous abnormality of the glans mucosa, which is extensive squamous cell carcinoma
in situ with a minor foci of invasion of epithelial compartments: mucosa of foreskin (f), glans
(g) and coronal sulcus (cos); urethra (u), meatus (m) and skin of shaft (s) not involved


Tumor is white, involves the mucosa of the foreskin and
coronal sulcus and completely covers the glans; there is
focal superficial infiltration of the corpus spongiosum;
diagram shows (red) widespread involvement



Vertical growth squamous cell carcinoma:

Solid yellow-tan neoplasm in the dorsal half of the glans (top); diagram shows
that the neoplasm (in red) replaces the corpus spongiosum of the dorsal glans
and is present at the interface with the tunica albuginea (a); foreskin (f),
meatus (m), urethra (u) and corpus cavernosum (cc) are not compromised



Mixed low and high grade squamous cell carcinoma:

Neoplasm shows superficial, white, serrated papillary and tan, solid, deeply invasive components; in the diagram, glans surface is completely covered dorsally by a thickened solid tissue (dark blue), which corresponds to the squamous hyperplasia (sh); a papillary exophytic appearance just below the meatus (in mixed blue-red-black colors) 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)



Assessment of depth of invasion:

Penile carcinoma has been transversely sectioned showing differing
depths of invasion of crucial anatomic compartments; note involvement
of corpora cavernosa (central two slices), urethra and periurethral
corpus spongiosum (top) and Buck fascia (top and bottom)

Assessment of depth of invasion
of tumor in resected specimen:
closeup of the bottom portion
of the top specimen is seen



Margin involvement:

Frozen section evaluation of surgical margins; A: periurethral corpus spongiosum involvement by carcinoma
(ca - yellow, u - urethra, cc - corpos cavernosa, fas - Buck fascia); B: squamous cell carcinoma involves the corpora
cavernosa, with the left more involved than the right; urethra (bottom) uninvolved; C: B showing tumor involvement
in yellow (ca - carcinoma, a - tunica albuginea, cc - corpus cavernosum, cs - corpus spongiosum, u - urethra)

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

Grading:
  • 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

Images hosted on PathOut server:

Mucosa is involved
by carcinoma at the
top but epidermis
(bottom) is spared

Invasion of the
lamina propria with
sparing of the corpus
spongiosum (left)



Images hosted on other servers:

Various histologic subtypes

EGFR+

Positive stains
Molecular / cytogenetics description