Primary Signet Ring Cell Carcinoma of the Urinary Bladder

Primary signet ring cell carcinoma of the urinary bladder is a relatively rare subtype of adenocarcinoma and comprises only 0.5-2% of all primary cancers of the urinary bladder.2 Since its initial description by Saphir1 in 1955, approximately 70 cases have been reported worldwide,3 and 3 have been reported in the Korean literature.4, 5

Bladder adenocarcinoma may be very difficult to rule out because it has the same histologic and immunohistochemical features as urachal carcinoma. Signet ring cells can also be found in adenocarcinomas of urachal origin. Several criteria for classifying a tumor as urachal in origin have been suggested. Johnson et al proposed the following criteria6: 1) tumor in the bladder (dome), 2) a sharp demarcation between the tumor and the surface epithelium, and 3) exclusion of primary adenocarcinoma located elsewhere that spread secondarily to the bladder. The present cases showed intestinal metaplasia in surface epithelium in case 2 cystitis glandularis in case 1. There were no sharp demarcations between the tumor and the surface epithelium. Thus, we can exclude a urachal tumor in origin, although the tumors occurred in the anterior wall to dome.

The histogenesis of primary nonurachal mucin-producing adenocarcinomas including signet ring cell carcinomas remains unclear, because the normal bladder contains neither columnar nor mucus-secreting glandular epithelium. Such adenocarcinomas are considered to arise directly from the totipotent cells of the transitional epithelium,3 but stepwise development from preexisting transitional cell carcinomas by a metaplastic process is assumed to occur more frequently.7

Primary signet ring cell carcinoma of the urinary bladder generally occurs in middle age and is usually diagnosed at an advanced stage, usually demonstrating a subsequently poor prognosis.2 In our cases, both patients were initially diagnosed as having bladder cancer with perivesical invasion (T3b). The usual clinical presentation does not differ significantly from that of other bladder malignancies.2 Hematuria and irritation on voiding are the most common presenting complaints. In addition, the patient in case 1 developed the tumor in the fourth decade of life, a relatively young age compared with the conventional age of incidence of bladder cancer.

Cystoscopic findings of signet ring cell carcinoma are usually no obvious mucosal lesion. The mucosal surface is described as simply edematous, bullous, and erythematous. When a mass lesion is recognizable, it is described as pedunculated, polypoid, sessile, and ulceroinfiltrative.8 Both of our cases had a huge, sessile mass that could be detected grossly by cystoscopy.

Primary signet ring cell carcinoma of the urinary bladder has the same histology as that of the gastrointestinal tract, breast, lung, gallbladder, and prostate; therefore, further evaluations for other primary sites are mandatory to exclude metastasis. In our cases, the gastrointestinal evaluation included esophagogastroduodenoscopy and colonoscopy. But we found no other tumor lesions. Although there is no established serum marker of primary signet ring cell carcinoma of the urinary bladder, elevated CEA has often been reported. Yamamoto et al9 reported that the serum level of CEA is normalized postoperatively and gradually increases as the disease progresses. Therefore, they have suggested that CEA might be used for determining malignant potential and for monitoring signet ring cell carcinoma. In both of our cases, CEA elevation was not noted.

Treatment modalities for signet ring cell carcinomas include surgery, radiotherapy, and chemotherapy. Surgical options range from transurethral resection to radical cystectomy with urinary diversion. Most of the reported cases have undergone radical cystectomy with urinary diversion. But because most of these cancers were diagnosed at an advanced stage, the prognosis was very poor.2 In the present case 2, partial cystectomy and adjuvant chemotherapy were planned because of the peritoneal metastasis at diagnosis. Radiotherapy and chemotherapy alone have had limited success and are usually used as adjuvant therapy after surgery. Recently, Hirano et al10 reported successful treatment with intra-arterial chemotherapy alone for invasive primary signet ring cell carcinoma of the urinary bladder. However, the appropriate chemotherapy regimen and the method of injection have not yet been established.

To improve the prognosis of primary signet ring cell carcinoma of the urinary bladder, early diagnosis and establishment of the more effective chemotherapy regimen would be necessary.