Squamous cell carcinoma and variants
Squamous cell carcinoma - general
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PubMed Search: Squamous cell carcinoma[TI] penis[TI] free full text[sb]
See also: Specific variants described separately
- Malignant epithelial tumor composed of squamous cells; diagnosis often delayed (eMedicine: Urogenital Squamous Cell Carcinoma [Accessed 4 April 2018])
- 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)
- 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
- 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
AFIP images
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)
- 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
- 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
- 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
AFIP images
Tumor at junction of scrotum and penis
Contributed by Dr. S. F. Cramer, Rochester, New York
Large bosselated mass
Images hosted on other servers:
Arising on genital lichen sclerosus
Papillary SCC
Ulcerated SCC on glans
Verrucous carcinoma
- 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
Scroll to see all 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 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)
- 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
AFIP images
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)
Contributed by Dr. A. Cubilla, Paraguay
Scrotum: well, moderately and poorly differentiated tumors
- 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)
