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“A 71 y/o Woman with Dysuria”
California Tumor Tissue Registry’s
Case of the Month
CTTR COTM www.cttr.org Vol 8(11), 2006
A 71 year old woman with a previous history of breast cancer presented with dysuria and
bleeding and was found to have a urethral diverticulum. At surgery, however, a partially
obstructing papillary tumor was discovered within the diverticulum. Subsequent CXR
and abdominal CT scans were negative. A post-resection cystoscopy with biopsies failed
to reveal residual tumor.
The neoplasm was exophytic, papillary (Fig. 1), and partially obstructed the urethra (Fig.
2). The lining cells were mostly tall columnar with pleomorphic nuclei, prominent
nucleoli, and numerous mitotic figures. Varying degrees of dysplasia were present (Fig.
3). There were regions where the cells showed cytoplasmic vacuolations and mucin
droplets (“goblet cells”) reminiscent of intestinal mucosal epithelium (Fig. 4). Some
regions had unequivocal carcinomatous change (Fig. 5). In-situ tumor was present in the
peri-urethral glands making evaluation of invasion most difficult. Immunostains were
positive for CK7 and negative for CK20, prostatic specific antigen, estrogen receptors
and progesterone receptors.
Diagnosis: “Well differentiated papillary adenocarcinoma of the urethra, developing in
a diverticulum”
Angie Pham, M.D. and Donald R. Chase, M.D.
Loma Linda University Medical Center, and
The California Tumor Tissue Registry
Adenocarcinoma of the urethra is a very rare malignancy with a female preponderance
approximating 3-4:1. It typically presents in the post-menopausal period and has no race
predilection. Symptoms include vaginal or urethral bleeding, frequency, incontinence,
dysuria, urinary tract infection, perineal or introital mass, or urinary obstruction. It can
clinically be mistaken for urethral polyps, prolapse, or caruncles.
Urethral carcinomas in women are markedly different clinically and pathologically than
in men. This is attributed to the anatomic and histologic differences of the sexes. On
average the female urethra is 2.5 to 4 cm in length, from bladder to vulva. Its epithelial
lining varies from transitional (proximal one third) to stratified squamous epithelium
(distal two thirds). There are also occasional patches of pseudostratified columnar
epithelium and several accessory glands which connect to the urethral lumen. Tumors
which arise correlate histologically with the type of epithelium that is normally present.
For instance squamous cell carcinomas more often occurs in the distal urethra, and
adenocarcinomas and transitional cell carcinomas tend to occur in the proximal urethra.
CTTR’s Case of the Month
August, 2006
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Squamous cell carcinoma is the most common (~70%), transitional cell carcinomas is
next (~20%) and adenocarcinoma is the rarest (~10%).
Adenocarcinomas often present as large infiltrative or expansile neoplasms with variable
exophytic areas and a mucinous, gelatinous or cystic consistency. They have two
patterns:
 non-clear cell adenocarcinoma (~60%), and
 clear cell adenocarcinoma (~40%)
Non-clear cell adenocarcinomas show tubular or tubulopapillary architecture with interanastomosing glands. The lining cell are usually columnar and mucin producing. The
nuclei are round to oval, mildly pleomorphic with variably prominent nucleoli. The
cytoplasm is eosinophilic to amphophilic and often vacuolated. Most tumors show
abundant mucin production and even occasional mucin-filled cells resembling goblet
cells. A diversity of patterns frequently coexists including enteric, mucinous, signet ring
or adenocarcinoma NOS, in fact some tumors bear a striking resemblance to colonic or
endometrial adenocarcinoma. Less differentiated neoplasms may consist of solid sheets
of undifferentiated tumor cells.
Clear cell adenocarcinomas are lined by flat, cuboidal, or hobnail cells with moderate to
abundant clear to finely granular eosinophilic cytoplasm. Mild to moderate nuclear
pleomorphism and large nucleoli are characteristic. The cytologic features may range
from low to high grade (most frequently). There are numerous mitoses. Necrosis and
extensive infiltration are common. They also exhibit a variety of patterns including
tubular, papillary, tubulocystic, or diffuse.
Although some studies suggest that clear-cell adenocarcinoma may behave less
aggressively than the non-clear cell types, female urethral adenocarcinomas, overall,
share a relatively poor prognosis. The most important prognostic factors are the tumor
location and stage. A tumor located in the distal one third of the urethra or the meatus is
more likely to be adequately surgically treated and have a more favorable outcome. But
tumors involving the proximal two thirds or the entire urethra require more radical
surgery with have a poorer prognosis. Metastasis at presentation is found in
approximately 18 to 50% of women. The overall survival for distal or meatus tumors is
51% as compared to only 6% survival for proximal tumors.
Studies have implicated human papilloma as a possible cause, particularly in the
squamous cell and transitional cell types. There is also an association with
adenocarcinoma.
Because the prognosis is poor, many therapeutic regimens have been tried. Most
patients, however, are managed with extirpative surgery including cystourethrectomy and
urinary diversion. Others have been treated with multimodal therapy or even by radiation
therapy alone. To date, however, the tumor remains difficult to diagnose early and even
more difficult to treat.
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Suggested Reading:
Amin MB, Young RH: Primary Carcinomas of the Urethra. Seminars in Diagnostic
Pathology 14:147-160, 1997.
Grabstald H, Hilaris B, Henschke U, Whitmore WF Jr. Cancers of the female urethra?
JAMA 197:113-120, 1966.
Grabstald H: Tumors of the Urethra in Men and Women. Cancer 32:1236-1255, 1973.
Meis JM, Ayala AG, Johnson DE: Adenocarcinoma of the urethra in women. Cancer
60:1038-1052, 1987.
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