Penis & scrotum
Squamous cell carcinoma and variants
Squamous cell carcinoma-general
Authors: Alcides Chaux, M.D., Antonio L. Cubilla, M.D.
Topic Completed: 1 April 2010
Minor changes: 29 October 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: Squamous cell carcinoma[TI] penis[TI] free full text[sb]
See also: Specific variants described separately
Table of Contents
Definition / general | Epidemiology | Risk factors | HPV related squamous cell carcinoma | Sites | Diagrams / tables | Clinical features and outcome | Poor prognostic factors | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Molecular / cytogenetics descriptionCite this page: Chaux A, Cubilla AL. Squamous cell carcinoma-general. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/penscrotumcarcinomagen.html. Accessed April 15th, 2021.
Definition / general
- Malignant epithelial tumor composed of squamous cells; diagnosis often delayed (eMedicine: Urogenital Squamous Cell Carcinoma [Accessed 4 April 2018])
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
- Phimosis and long foreskin, paraphimosis (Am J Surg Pathol 2003;27:994)
- Genital warts (6x increased risk, J Natl Cancer Inst 1993;85:19); also HPV infection in general, particularly HPV 16 and related risk factors (Cancer Epidemiol Biomarkers Prev 2008;17:2683)
- 1/3 of non-HPV cases are associated with lichen sclerosus (balanitis xerotica obliterans, Am J Surg Pathol 2003;27:1448)
- Penile injury, tears and chronic balanitis
- Smoking, psoriasis patients treated with UVB radiation, penile rash > 1 month, immunosuppression and radiation therapy
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
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)
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:
- Usually no regional metastases if only superficial invasion of 6 mm or less (Mod Pathol 2001;14:963)
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
- High stage
- High histologic grade (Am J Surg Pathol 2008;32:974, J Surg Oncol 2008;97:487)
- Deeper invasion (anatomic levels are epithelium, lamina propria, corpus spongiosum and corpus cavernosum) but anatomic variations exist (corpus cavernosum may not be located in glans in 25% of cases, Am J Surg Pathol 2001;25:1091)
- Angiolymphatic invasion (J Urol 2008;180:1354)
- Perineural invasion (World J Urol 2009;27:169)
- Anaplastic, basaloid, pseudoglandular, sarcomatoid or solid subtypes
- Lymph node density in one study (J Urol 2009;182:2721)
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
- Local resection, partial / total penectomy (NIH: Skin Cancer Treatment [Accessed 4 April 2018])
- Local excision and partial penectomy are inadequate for sarcomatoid and basaloid carcinomas (Am J Surg Pathol 2009;33:1299); poor outcomes with metastatic disease (Ann Surg Oncol 2007;14:3614)
- Higher risk for recurrence if node positive or partial penectomy (Eur Urol 2008;54:161)
- Possibly brachytherapy for tumors confined to glans (Int J Radiat Oncol Biol Phys 2009;74:1150)
- Criteria for inguinal lymphadenopathy are controversial, as palpable nodes may be reactive (Can Urol Assoc J 2008;2:525)
- Patients with prognostic index scores of 2 - 3 may not need inguinal nodal dissection
- Patients with prognostic index scores of 5 - 7 may benefit from prophylactic groin dissection
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
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
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:
Verrucous
carcinoma
Multiple compartments:
Massive involvement
of glans, coronal
sulcus and foreskin
Massive involvement
has resulted in
autoamputation
4 separate
foci of
carcinoma
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
sectioned
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
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
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
- Mutations in PIK3CA, HRAS or KRAS genes in 39% (J Urol 2008;179:2030)
- Epigenetic silencing (by methylation) of FHIT gene in 92% (Virchows Arch 2008;452:377)
