Case of the Week

2020-45 / November 9

Contributors: Jonathan (Lin) He, Liwei Jia

A man in his 60s presented with right sided abdominal pain. The CT scan of abdomen and pelvis with contrast showed an enhancing plaque-like thickening of the bladder wall. The patient underwent transurethral resection of bladder tumor and subsequent cystectomy, which revealed the lesion shown below.

Click on the below thumbnails to enlarge photos.

Quiz

1. What is the correct diagnosis?

a. Plasmacytoma

b. Urothelial carcinoma, plasmacytoid variant

c. Urothelial carcinoma, sarcomatoid variant

d. Malignant melanoma of the bladder

e. Metastatic invasive lobular carcinoma of male breast

2. Which of the following IHC markers is helpful to differentiate it from other variants of urothelial carcinoma?

a. CD10

b. p63

c. GATA3

d. E-cadherin

e. Her2/neu

3. Which of the following molecular alterations is associated with this entity?

a. Von Hippel-Lindau

b. SDHB

c. CDH1

d. CTNNB1

e. None of them

Plasmacytoid variant of urothelial carcinoma (PUC) is a histologic variant with an aggressive clinical course characterized by a higher pathologic stage at presentation, a higher rate of positive surgical margins, lower overall survival, chemotherapy resistance, frequent local recurrence, and a peritoneal pattern of spread. It is combined with signet ring and diffuse variants in 2016 WHO classification of tumors of the urinary system and male genital organs.

The tumor cells classically exhibit eccentrically located nuclei growing in either diffuse singly scattered and discohesive pattern or loose aggregates forming linear cords with minimal stromal response. These morphologic features raise the differential diagnosis between primary urothelial or spread from the breast or gastrointestinal (GI) tract. In several studies, breast markers, including estrogen receptor and mammaglobin, are usually negative, but progesterone receptor (4-13.3%) and gross cystic disease fluid protein 15 (FCPDFP15, 24.4%) may be positive. Immunostaining for CDX2 is positive in small subset of PUC (15-17.7%). Nuclear beta-catenin is typically negative. CD138 immunostain was reportedly positive in 83% of the cases, which could be another potential pitfall. Therefore, caution should be exercised when these immunostain markers are used to distinguish PUC from metastatic lobular breast carcinoma or GI signet ring cell carcinoma. Loss of E-cadherin by immunohistochemistry has been reported in 57-70% of PUC, in contrast to 11% in conventional UCs. CDH1 loss-of-function mutations or promoter hypermethylation were described in >80% of cases, whereas no CDH1 molecular alterations were seen in conventional UC.

1. Borhan, W.M., Cimino-Mathews, A.M., Montgomery, E.A., Epstein, J.I., 2017. Immunohistochemical differentiation of plasmacytoid urothelial carcinoma from secondary carcinoma involvement of the bladder: The American Journal of Surgical Pathology 41:1570–1575.

2. Kim, D.K., Kim, J.W., Ro, J.Y., Lee, H.S., Park, J.-Y., Ahn, H.K., Lee, J.Y., Cho, K.S., 2020. Plasmacytoid variant urothelial carcinoma of the bladder: a systematic review and meta-analysis of clinicopathological features and survival outcomes. J. Urol. 204:215–223.

3. Lopez-Beltran, A., Henriques, V., Montironi, R., Cimadamore, A., Raspollini, M.R., Cheng, L., 2019. Variants and new entities of bladder cancer. Histopathology 74:77–96.

4. Perrino, C.M., Eble, J, Kao C.S., Whaley, R.D., et al. 2019. Plasmacytoid/diffuse urothelial carcinoma: a single-institution immunohistochemical and molecular study of 69 patients. Human Pathology. 90:27–36

5. Al-Ahamadie, H.A., Iyer, G, Lee, B.H., et al. 2016. Frequent Somatic SDH1 loss-of-function mutations in plasmacytoid variant bladder cancer. Nature Genetics. 48:356-358.

About GUPS

The Genitourinary Pathology Society (GUPS) was formed with the vision of advancing the care of patients with urologic diseases through enhancements of best practices, research, and education in the subspecialty of Urological Pathology.

GUPS is an official Companion Society of the United States and Canadian Academy of Pathology (USCAP).

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