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 January 16th, 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
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
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:
Foreskin:
Coronal sulcus:
Multiple compartments:
Superficial spreading (SCC):
Assessment of depth of invasion:
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
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)