Poorly Differentiated Adenocarcinoma with Signet Ring Cell Features, Consistent with Rectal Primary
Loyola University Medical Center
A 70-year-old man presented with hematuria, hesitancy, urgency, and nocturia. Imaging studies showed bilateral hydronephrosis. He had a past medical history significant for partial nephrectomy, prostatic hypertrophy with obstruction, and hyperlipidemia. A cystoscopy and bladder barbotage was performed.
Diagnosis: Poorly differentiated adenocarcinoma with signet ring cell
features, consistent with rectal primary
Poorly differentiated carcinoma with signet ring cell
Poorly differentiated adenocarcinoma with signet
ring cell features, consistent with rectal primary (Bladder biopsy).
The ThinPrep smear shows loosely cohesive clusters and single cells with cytoplasmic vacuolization,
and intracytoplasmic mucin. The nuclei are hyperchromatic and eccentrically located. Prominent nucleoli
could be observed in some of the cells. Especially cells in clusters show high N:C ratio and nuclear
hyperchromasia. A background of necrotic debris is evident.
Adenocarcinoma of the urinary bladder can be primary (arising from the bladder wall or urachal
remnants) or metastatic (from tumors originating in the stomach, colon, or breast). Primary
adenocarcinoma of the bladder is rare, accounting for 0.5-2% of all malignant tumors of the bladder. It
is more common in males with a peak incidence at 60 years of age. Patients typically present with
hematuria, dysuria and rarely mucusuria. There are two types of adenocarcinomas arising in the bladder:
primary bladder adenocarcinoma (more common, accounting for two thirds of the cases) and urachal
carcinoma (less common). Outcomes for patients with bladder adenocarcinoma are generally poor, with
increased pathologic stage significantly correlating with worsened overall survival in several studies.
Although some series have reported that adenocarcinomas of urachal origin may demonstrate more favorable
long-term outcomes, this finding has been controversial and may be associated with the younger age at
presentation of urachal adenocarcinomas.
There are multiple subtypes of bladder adenocarcinoma including colonic-type adenocarcinoma, mucinous
adenocarcinoma, signet-ring cell carcinoma, clear cell carcinoma, hepatoid carcinoma, and adenocarcinoma
not otherwise specified, as well as mixed forms. The signet ring cell carcinoma is a rare variant of
mucus-producing adenocarcinoma. It is recognized as an entity for two reasons: its morphology is
distinctive, and it follows a highly malignant course. The reported cases of this neoplasm were
discovered in advanced stages with dismal outcome. In a recent study, Thomas et al., showed that signet
ring cells were found in 76% of the bladder adenocarcinomas (67% in urachal and 79% in nonurachal
adenocarcinomas). In their study the volume of signet ring cell differentiation ranged between 5-100%.
However, most tumors showed 60% signet ring cell differentiation, and the percentage of signet ring cells
correlated with adverse outcome (defined as unresectable primary tumor or lymph node involvement).
When a signet-ring tumor is diagnosed in the bladder, it is most likely a primary. However, a
metastatic disease from a GI primary (gastric or colon) is possible, and should be taken into
consideration. Therefore, in spite of this rare manifestation, a gastroscopy and possibly a colonoscopy
may be considered in the diagnostic work up. This may influence the type of therapy because cystectomy
must be considered in the light of poor sensitivity to radiotherapy or chemotherapy of a primary bladder
tumor of signet-ring cell histology.
The distinction between primary adenocarcinomas of the bladder and those secondarily involving the
bladder either by direct extension or metastatic spread has been the focus of numerous studies.
Specifically, most markers examined have concentrated on the differentiation between colon carcinoma and
colonic type bladder adenocarcinoma. For this purpose many markers have been examined, including
cytokeratin (CK) 7, CK20, villin-1, CDX-2 and β-catenin. Unfortunately, studies have shown that
none of these markers are quite reliable in differentiating these entities. In addition, signet ring
carcinomas have been shown to have decreased expression of a subset of immunohistochemical markers,
making it difficult to distinguish the origin of the neoplasm. See the table for differential staining
patterns of adenocarcinoma in the bladder (modified from Bostwick et al, and Thomas et al.).
In conclusion, signet-ring cell adenocarcinoma of the bladder is a rare lesion which may present as
either a primary or metastatic tumor. The co-presence of squamous or urothelial carcinoma cells would
suggest a primary tumor. A history of previous cancer should raise the possibility of metastatic
disease. Occasionally, the bladder may be the first manifestation of an occult primary, usually of GI
origin. Searching for such a primary, despite its rarity may have significant clinical and prognostic
implications, and should therefore be considered.
Table: Immunohistochemical Differentiation of Adenocarcinoma in the Urinary Bladder.
| ||HMWCK ||CK 7 ||CK 20 ||PSA ||CDX 2 ||VILLIN|
|PBA, colonic type ||+ ||+/- ||+/- ||- ||+ ||+/-|
|PBA, signet ring cell type ||+ ||+/- ||+ ||- ||+/- ||+/-|
|Colorectal Adenocarcinoma ||- ||- ||+ ||- ||+ ||+|
|Gastric Adenocarcinoma ||- ||+/- ||+/- ||- ||+/- ||+/-|
|Prostatic Adenocarcinoma ||- ||- ||+/- ||+ ||- ||-|
PBA= Primary Bladder Adenocarcinoma; + usually positive, - usually negative, +/- variable staining
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