Signet-Ring Cell Carcinoma of the Urinary Bladder: A Review and Update
Authors: Kodzo-Grey Venyo Anthony 
Published: November 2021

Signet-ring cell carcinoma of the urinary bladder is an uncommon histopathology variant of carcinoma of urinary bladder which has been stated to account for 0.5% and 2% of primary malignant tumours of the urinary bladder. Signet-ring cell carcinoma of the urinary bladder is stated to either arise from the wall of the urinary bladder or from remnants of the urachus, or signet-ring cell carcinoma of the urinary bladder could also develop as a metastatic tumour that has ensued a primary signet-ring cell carcinoma that had arisen from a number sites of the body some of which include: the stomach, colon, or breast, the appendix and other organs. It has been iterated that the least common type of signet-ring cell carcinoma is primary signet-ring cell carcinoma and that up to 2013 less than 100 cases had been reported. Signet-ring cell carcinoma of the urinary bladder can affect males as well as females, young individuals or adults. Signet-ring cell carcinoma of the urinary bladder could be diagnosed incidentally or it may present with non-specific symptoms that simulate the symptoms of other urinary bladder tumours including: lower urinary tract symptoms, haematuria, abdominal pain / discomfort or loin pain, retention of urine, feeling unwell, or weight loss. Microscopy examination of the tumour whether it was obtained by means of trans-urethral resection or by cystectomy would tend to demonstrate a tumour that is comprised of signet-ring cells that contain peripherally pushed hyperchromatic nuclei, intra-cytoplasmic mucin, as well as lakes of extracellular mucin. The tumour cells could be arranged in lobules, and separated by fibrovascular septae. There tends to be visualization of mitosis as well as evidence of necrosis. The tumour tends to be seen within the underlying stroma and quite often within the detrusor muscle and up to the extra-vesical fat quite often. Immunohistochemistry staining studies of signet-ring cell carcinoma of the urinary bladder would tend to show tumour cells that exhibit positive staining for: Cytokeratin including cytokeratin 7, CAM 5.2, AE1/3, and 34ßE12; Vimentin; Peanut lectin agglutinin; Ulex europaeus agglutinin. In signet ring cell carcinoma of urinary bladder immunohistochemistry staining of the tumour may also show tumour cells that exhibit positive staining for the following tumour markers: CK, CK7, CK20; CDX2; Villin - There could be a small amount of positive staining for Villin. In signet-ring cell carcinoma of the urinary bladder, immunohistochemistry studies of the tumour may demonstrate tumour cells that do exhibit negative staining for the ensuing tumour markers: Vimentin, (this does show therefore that some tumours would stain positive and others would stain negative); GATA3, and P53. To confirm whether a signet-ring cell carcinoma of the urinary bladder is a pure primary tumour or metastatic tumour does require detailed history taking with evidence of previously treated signet-ring cell carcinoma elsewhere and comparing the pathology features of the tumours, the undertaking of radiology imaging including ultrasound scan, computed tomography scan or magnetic resonance imaging scan of abdomen and pelvis as well as upper gastrointestinal endoscopy and lower gastrointestinal endoscopy to ascertain if there are any lesions within the gastrointestinal tract and taking biopsies of any suspicious lesion found for pathology examination and comparing the features of the lesions with the urinary tract tumours. There is no consensus opinion of the treatment of signet-ring cell carcinomas of the urinary bladder even though it has been realised that primary signet ring cell carcinomas have tended to be more invasive and higher staged as well as associated with very poor prognosis in comparison with the traditional urothelial carcinoma. Treatment options that have been utilized have included: trans-urethral resection of tumour, radical cystectomy alone or radical cystectomy plus adjuvant therapy and despite utilization of radical cystectomy and adjuvant therapy majority of patients tend to die. There are sporadic reports of isolated cases of good short-term, medium-term, and long-term survival usually if the tumour is diagnosed at an early stage. Early diagnosis, aggressive complete surgical excision of primary and metastatic signet-ring cell carcinomas and utilization appropriate combination adjuvant therapies would provide the best treatment of curative intent. Additionally, there is an anecdotal report of an effective treatment of an advanced metastatic primary signet-ring cell carcinoma of the urinary bladder with utilization of docetaxel which resulted in destruction of the tumour cells without an operation which would indicate that some chemotherapy agents could be good enough for the successful treatment of signet-ring cell carcinomas of the bladder including primary and metastatic tumours. Therefore, it is possible that novel treatment options of treatment of signet-ring cell carcinoma of the urinary bladder including an appropriate chemotherapy plus additional non-operative treatments including cryotherapy, radiotherapy, radiofrequency ablation, irreversible electroporation, selective angiography and chemical infusion of chemotherapy agents into the tumour plus immunotherapy could be explored as treatment options. There is a global need for urologists, oncologists, and pharmacotherapy research workers to identify new chemotherapy medicaments that would safely and effectively destroy primary and metastatic signet-ring cell tumours in order to improve upon the outcome of the disease. A global multi-centre trial of various aggressive treatment options should be commenced quickly.