Resident Program - Case of the Month

Discussion

The diagnosis for this patient is most consistent with metastatic high-grade urothelial carcinoma, plasmacytoid variant, also known as plasmacytoid urothelial carcinoma (PUC). PUC is unique, rare and has been described as a histological variant of urothelial carcinoma and is characterized by tumors cells that exhibit striking resemblance to plasma cells and has immunohistochemical overlap with plasma cells as well. It is characterized by the infiltration of nested or discohesive oval to round tumor cells in a loose or myxoid stroma. The malignant cells can also have occasional vacuoles or form signet ring cells with focal intracytoplasmic mucin.

Variant morphologies consist of approximately 10-25% of invasive urothelial carcinoma, occuring as pure or admixed with conventional urothelial carcinoma. WHO 2016 recognizes many of these variants, and it is important for pathologists to be aware of these variants including PUC which generally has an aggressive course, a poor outcome, high rates of recurrence and death when compared to conventional urothelial carcinoma.

PUC was first described by Sahin et al. in 1991 in a 64-year-old man who presented with metastatic lesions in the ribs and skill that was misdiagnosed as multiple myeloma. Around the same time, Zuckerberg et al also reported a case of invasive urothelial carcinoma that resembled lymphoma. Based on contemporary series from tertiary institutions, PUC is estimated to be 1-4.9% of invasive urothelial carcinoma.   

Epidemiologically PUC is not different from conventional urothelial carcinoma, including a preponderance for older men (mean age 62-66 years) and an association with history of smoking. They tend to be diagnosed at an advanced stage with the most common presenting symptom being hematuria. Cockerill et all reported 83% of patients with PUCs were locally aggressive (>pT2) and 37% had locally advanced (pT4) disease.  PUC may spread within the bladder wall without involving an overlying benign surface urothelial mucosa. It can also spread within the wall and adventitia and can spare the lumen or mucosa.

The immunohistochemistry profile of PUC is also similar conventional urothelial carcinoma. The tumor cells stain with urothelial associated markers GATA3, p63, p63, CK7, CK20, uroplakin II (33%). Majority of the plasmacytoid cells exhibit loss of membranous expression of E-cadherin similar to what has been described in lobular carcinoma of the breast. Interestingly, like plasma cells, the tumors are positive for CD138, however, they consistently stain negative for lymphoid markers. In addition, they stain for GCPDFP-15 (24%), PR (13%), CDX2 (18%), and p-CEA (49%). Therefore, pathologists should practice caution when using stains to differentiate PUC from metastatic lobular carcinoma or gastrointestinal signet ring cell carcinoma.

Knowledge of clinical history such as urothelial carcinoma or plasma cell dyscrasia and if present reviewing prior biopsy is crucial in this case to avoid pitfall, especially during frozen consultation.  Plasma cells express MUM 1, lymphoid cells express CD45, which is observed in PUC.

Metastatic gastrointestinal signet ring cell carcinoma and lobular cell carcinoma can also mimic PUC and distinction at metastatic site may be challenging. GATA 3 and uroplakin II is not expressed in gastrointestinal signet cell carcinoma.

Lastly, the atypical features of these cells make chronic inflammation as the diagnosis unlikely.

References

• Jairajpuri ZS, Rana S, Ali MA, Jetley S. Plasmacytoid variant of urothelial carcinoma: Diagnostic challenges and role of immunohistochemistry. Int J Appl Basic Med Res. 2015;5(3):217-219. doi:10.4103/2229-516X.165368
• Sood S, Paner GP. Plasmacytoid Urothelial Carcinoma: An Unusual Variant That Warrants Aggressive Management and Critical Distinction on Transurethral Resections. Arch Pathol Lab Med. 2019 Dec;143(12):1562-1567. doi: 10.5858/arpa.2018-0139-RS. Epub 2019 Mar 13. PMID: 30865491.
• Gignon DJ, Al-Ahmadie H, Algaba F, et al. Infiltrating urothelial carcinoma. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, eds. WHO Classification of Tumours of the Urinary System and Male Genital Organs. 4th ed. Geneva, Switzerland: WHO Press; 2016:81–98.
• Sahin AA, Myhre M, Ro JY, Sneige N, Dekmezian RH, Ayala AG. Plasmacytoid transitional cell carcinoma: report of a case with initial presentation mimicking multiple myeloma. Acta Cytol. 1991;35(3):277–280.
• Zukerberg LR, Harris NL, Young RH. Carcinomas of the urinary bladder simulating malignant lymphoma: a report of five cases. Am J Surg Pathol. 1991;15(6):569–576.