Urethral carcinoma

Author: Jesus A. Chavez, M.D. (see Authors page)
Editor: Debra L. Zynger, M.D.

Revised: 23 August 2016, last major update April 2016

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Urethral carcinoma[title]
Definition / General
  • Rare primary neoplasm of epithelial origin
  • Secondary involvement by urothelial carcinoma of the bladder is much more common than a primary (Eur Urol 2013;64:823)
Essential Features
  • Urethral carcinoma is usually due to secondary involvement
  • Primary urethral carcinoma is rare and the most frequent histologic types are urothelial carcinoma, squamous cell carcinoma and adenocarcinoma (not otherwise specified, clear cell)
  • Type depends on sex and location:
    • Male urethra divided into four anatomic regions: prostatic, membranous, bulbous and penile
    • Female urethra divided in proximal 2/3 and distal 1/3
      • Proximal 2/3 usually urothelial carcinoma
      • Distal 1/3 usually squamous cell carcinoma (BJU Int 2014;114:25)
      • Frequently initially misdiagnosed as caruncle
    • Adenocarcinoma present in both sexes; may originate anywhere along the urethra
  • Predisposing factors include:
Clinical Features
  • Most patients present with symptoms associated with locally advanced disease (Eur Urol 2013;64:823)
    • Gross hematuria or bloody urethral discharge, dysuria, extraurethral mass
    • Bladder outlet obstruction, pelvic pain, urethrocutaneous fistula
    • Abscess formation, dyspareunia
  • Approximately 1/3 of men and women present with involved regional lymph nodes
  • Clinical examination with palpation of external genitalia for suspicious indurations and pelvic exam in women (Eur Urol 2013;64:823)
  • Urinary cytology
  • Diagnostic urethroscopy and biopsy
Radiology Description
  • Aims to assess local extent and detect lymphatic and distant metastatic spread
  • Magnetic resonance imaging for evaluating extent of tumor and monitoring response to neoadjuvant chemotherapy (Eur Urol 2013;64:823)
Prognostic Factors
Case Reports
Gross Images

Images hosted on PathOut server:

Contributed by Dr. Jesus Chavez and Dr. Debra Zynger, The Ohio State University / Wexner Medical Center (USA):

Female, invasive squamous cell carcinoma
involving urethra and periurethral tissue

Invasive squamous cell carcinoma of
penile urethra with periurethral involvement

Micro Description
  • Urothelial carcinoma
  • Squamous Cell Carcinoma
    • Sheets of large, pleomorphic tumor cells with focal or abundant keratinization (depending of grade of differentiation), ample cytoplasm, intercellular bridges, high mitotic activity, prominent nuclear atypia
  • Adenocarcinoma
  • Clear Cell Adenocarcinoma
    • May have glandular, tubulocystic, solid/diffuse, papillary or micropapillary growth patterns
    • Cuboidal, variably sized cells with abundant clear or eosinophilic cytoplasm and cytoplasmic vacuoles
    • Nuclei that are hyperchromatic, pleomorphic and have prominent nucleoli
    • Hobnail changes and extracellular mucoid material may be present
    • Mitoses and necrosis are often seen
Micro Images

Scroll to see all images.

Images hosted on PathOut server:

Contributed by Dr. Jesus Chavez and Dr. Debra Zynger, The Ohio State University / Wexner Medical Center (USA):

Low power of a noninvasive
papillary urothelial
carcinoma, low grade,
in a male

High power of a noninvasive
papillary urothelia
carcinoma, low grade, with
bland monomorphic nuclei

Noninvasive high grade
urothelial carcinoma
in a female

Invasive high grade
urothelial carcinoma
in a female

Male penile urethra,
squamous cell carcinoma
in situ within
periurethral glands

Male penile urethra, HPV+
high risk ISH in squamous
cell carcinoma in situ
within periurethral glands

Primary urethral squamous
cell carcinoma with necrosis
and keratinization

Elderly female: metastatic
squamous cell carcinoma
of urethral origin

Female, low power,
prominent necrosis and
overlying normal epithelium

With tubules and small
glands that can mimic
nephrogenic metaplasia

With hobnailing

With prominent clear cells
and diffuse, sheet-like growth

Positive Stains
Negative Stains
Differential Diagnosis