2021-06 / February 08
Contributors: Aditi Dewan, Sambit K. Mohanty

A man in his mid-60s presented with lower abdominal pain and hematuria. Cystoscopy revealed ulceration of the entire urinary bladder mucosa along with a thickened bladder wall. A transurethral resection of the bladder tumor was performed and submitted for histopathological examination.


1. What is the correct diagnosis?

a. Plasmacytoma

b. Rhabdomyosarcoma

c. Lymphoma

d. Signet ring cell carcinoma

e. Plasmacytoid urothelial carcinoma


2. Mutations in which gene are most commonly encountered in the above entity?

a. TP53


c. CDH1



1. e
2. c

1. Plasmacytoid urothelial carcinoma

Histopathologic examination revealed infiltration of the bladder wall by a tumor arranged in diffuse sheets and nest, as well as in single cell files and cords. Individual cells displayed mild to moderate nuclear pleomorphism with polygonal cell outlines, round to oval eccentric nuclei, vesicular chromatin, inconspicuous nucleoli, and moderate amount of eosinophilic cytoplasm. Intracytoplasmic vacuolation was observed at some foci. The tumor invades the muscularis propria. The tumor cells expressed pancytokeratin (CK), CD138, GATA3, EMA, and uroplakin-2 and were negative for NKX3.1 and CDX2. E-cadherin showed loss of membranous staining. A diagnosis of plasmacytoid urothelial carcinoma (PUCa) was rendered.

Several morphologic variants of UCa have been described with differences in prognosis, clinical behavior, and management strategies. The PUCa was first described by Sahin et al in 1991. This variant is more common in elderly male patients with a mean age at diagnosis of 60 years. It constitutes around 1% to 3% of muscle invasive UCa. Clinically, these patients have a poor prognosis and present at an advanced stage with a higher incidence of metastatic and extravesical disease compared to non-PUCa muscle invasive UCa. The loss of E-cadherin expression in PUCa cells may contribute to the tumor’s characteristic discohesion and diffusely infiltrative growth pattern. Most PUCas lack expression of the RB gene, suggesting that the abnormal function of the RB gene plays an important role in the tumorigenesis. Additionally, truncating somatic mutations of the cadherin1 (CDH1), the gene encoding E-cadherin, are identified in PUCa, whereas no CDH1-truncating mutations are identified in conventional UCa. The differential diagnoses include benign conditions such as chronic cystitis with prominent plasma cell infiltrate to malignant conditions such as plasmacytoma and signet ring cell carcinoma (primary as well as metastatic). Unlike plasmacytoma, PUCa typically lacks perinuclear hof/halo and bi- or multinucleation. The presence of focal signet ring cell morphology in the present case can also lead to confusion with a signet ring cell carcinoma. Although the nuclei were eccentrically placed, the classical peripherally compressed nuclei seen in signet ring cell carcinoma were not seen. The other differential diagnoses include lymphoma, metastatic carcinoma (particularly lobular carcinoma of the breast), malignant melanoma, and rhabdomyosarcoma. These may be differentiated by immunohistochemistry.

PUCa is an aggressive variant of UCa. An appropriate diagnosis by cystoscopy and biopsy supported by immunostains may aid in early treatment in these patients. IHC plays a pivotal role in differentiating this neoplasm from its morphologic mimics.

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Aditi Dewan
CORE Diagnostics, India.

Sambit K. Mohanty
CORE Diagnostics and Advanced Medical Research Institute, India.


Plasmacytoid; urothelial; bladder; immunohistochemistry.