Bladder & urothelial tract

Urothelial carcinoma - invasive


Last author update: 23 December 2021
Last staff update: 5 January 2022

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PubMed Search: Plasmacytoid urothelial carcinoma [TI]

Timothy Isaac Miller, M.D., M.A.
Maria Tretiakova, M.D., Ph.D.
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Cite this page: Miller TI, Tretiakova M. Plasmacytoid. website. Accessed February 26th, 2024.
Definition / general
  • Aggressive variant of urothelial carcinoma (UC) characterized by single infiltrating cells with eccentrically placed nuclei and abundant eosinophilic cytoplasm similar to plasmacytes or resembling signet ring cells due to intracytoplasmic vacuoles
Essential features
  • Uncommon histologic variant of UC (~1 - 3%) with plasmacytoid morphology
  • Discohesive infiltrating tumor cells can spread extensively along tissue planes and peritoneal surfaces
  • Plasmacytoid tumor cells are often positive for CD138, which can result in a misdiagnosis for a plasma cell neoplasm; must use other immunohistochemistry markers to differentiate
  • Often has loss of membranous E-cadherin due to mutations in CDH1, similar to lobular breast carcinoma
  • More likely to be diagnosed at an advanced stage compared with conventional UC resulting in a poorer prognosis
  • PUC (plasmacytoid urothelial carcinoma)
  • Plasmacytoid variant (PCV)
  • Signet ring cell variant
ICD coding
  • ICD-O: 8120/3 - transitional cell carcinoma, NOS
Clinical features
  • Clinical symptoms prompt cystoscopy, which then results in a transurethral biopsy or resection of tumor
  • Imaging may show focal mass in bladder wall or diffuse bladder wall thickening, which results in cystoscopy with biopsy
Radiology description
  • On CT / MRI, PUC case series demonstrated focal bladder mass in 68% of cases and diffuse mural thickening in 32% of cases (Can Urol Assoc J 2017;11:E50)
  • On CT / MRI, imaging specific to PUC compared with conventional UC may be discontinuous thick sheets of tissue extending along fascial pelvic planes (Can Urol Assoc J 2017;11:E50)
Radiology images

Images hosted on other servers:

MRI of PUC with bladder muscle invasion

MRI and CT of PUC with peritoneal spread

CT of PUC with
peritoneal spread
and bladder wall

Prognostic factors
Case reports
  • 33 year old woman presenting with macroscopic hematuria and a solid lesion (Urol J 2019;16:86)
  • 53 year old man with plasmacytoid urothelial carcinoma metastatic to the duodenum (Case Rep Pathol 2017;2017:5209059)
  • 57 year old man presenting with renal colic and a solid lesion (Urol J 2019;16:86)
  • 60 year old man with a small bowel obstruction and an obstructive ureteric mass on CT scan (Am J Case Rep 2018;19:158)
  • 69 year old woman with a history of bilateral hydronephrosis, presenting with weight loss and vaginal spotting (Case of the Month #510)
  • 71 year old man with incidental plasmacytoid bladder cancer causing bilateral ureteral obstruction, hydroureteronephrosis and renal failure (Urol Case Rep 2020;33:101415)
  • More likely to receive neoadjuvant chemotherapy compared with conventional UC because it is discovered at a higher stage (J Urol 2020;204:215)
    • Literature review found overall pathological complete response to neoadjuvant chemotherapy to be 21% (J Urol 2020;204:215)
  • Same treatment for urothelial carcinoma of the same stage (Eur Urol Focus 2020;6:653)
  • Role of neoadjuvant therapy before cystectomy has been questioned for PUC
Gross description
Gross images

Contributed by Timothy Isaac Miller, M.D., M.A. and Maria Tretiakova, M.D., Ph.D.

Bladder with plasmacytoid urothelial carcinoma

Frozen section description
Microscopic (histologic) description
  • Discohesive single cells with eccentrically placed nuclei and abundant eosinophilic cytoplasm
  • Often deeply infiltrative but with minimal stromal reaction (Eur Urol Focus 2020;6:653)
  • Further subclassified into classic, pleomorphic and desmoplastic subtypes:
    • Classic: signet ring-like morphology, singly scattered and discohesive in loose aggregates forming cords (Hum Pathol 2019;90:27)
    • Pleomorphic: similar to classic but with pleomorphic nuclei and more atypia; can be rhabdoid and bizarre appearing (Hum Pathol 2019;90:27)
    • Desmoplastic: plasmacytoid neoplastic cells with a surrounding desmoplastic stromal response (Hum Pathol 2019;90:27)
  • Associated with sarcomatoid variant in 31% of cases (Hum Pathol 2019;90:27)
  • Often mixed with other histologic subtypes; in 1 case series, 53% of PUC had mixed histologic subtypes (Am J Clin Pathol 2017;147:500)
  • Despite resemblance to signet ring carcinoma cells, notably lack extracellular mucin, contrasting to signet ring adenocarcinoma (Acta Cytol 1991;35:277, Am J Surg Pathol 1991;15:569)
Microscopic (histologic) images

Contributed by Timothy Isaac Miller, M.D., M.A., Nicole K. Andeen, M.D. and Maria Tretiakova, M.D., Ph.D.

PUC with carcinoma in situ

Muscularis propria involvement

Diffuse growth

Pleomorphic subvariant

Desmoplastic subvariant

Signet ring and classic morphologies

Lymphovascular invasion

Perineural invasion

PUC in bladder wall

PUC at urethral margin

AE1 / AE3


Contributed by Lisa Han, M.D. and Ricardo Lastra, M.D. (Case #510)

Urothelial carcinoma, plasmacytoid variant

Cytology description
Cytology images

Images hosted on other servers:

Bladder washing with PUC (Papanicolau stain, x400)

Immunohistochemical panels
Molecular / cytogenetics description

Plasmacytoid variant histology in bladder cancer

Sample pathology report
  • Bladder, transurethral resection:
    • Urothelial carcinoma, high grade
      • Histologic component: plasmacytoid (90%)
      • Adjacent flat CIS: absent
      • Angiolymphatic invasion: absent
      • Muscularis propria: present, invaded by carcinoma
      • pT: invasive of muscularis propria (pT2)
  • Bladder, cystectomy:
    • Invasive high grade urothelial carcinoma, plasmacytoid variant (see synoptic report)
Differential diagnosis
Board review style question #1

Which of the following is true regarding the histologic variant of urothelial carcinoma shown above?

  1. Neoplastic cells usually express CD138
  2. Mutations / loss of CDH1 are uncommon
  3. Patients are less likely to present at an advanced stage compared with conventional urothelial carcinoma
  4. Primary ureteral carcinoma of this variant is common
  5. Neoplastic cells are usually positive for mucin
Board review style answer #1
A. Neoplastic cells usually express CD138. The histologic variant of urothelial carcinoma shown above is the plasmacytoid variant, consisting of discohesive cells with eccentrically placed nuclei and abundant cytoplasm. The neoplastic cells are usually positive for CD138 (making choice A the correct answer). Choice B is false, as truncating CDH1 mutations are common, causing loss of E-cadherin. Choice C is false, as these patients are generally diagnosed at an advanced stage and thus, have a worse prognosis. Choice D is incorrect because the primary ureteral of the variant has rarely been reported. Choice E is false since the cells do not express mucin, making it possible to distinguish from metastatic signet ring cell adenocarcinoma. (Hum Pathol 2019;90:27, Int J Clin Exp Pathol 2012;5:601, Nat Genet 2016;48:356, Eur Urol Focus 2019;5:104, Urology 2017;102:143, Bladder Cancer 2020;6:71, Am J Case Rep 2018;19:158, Am J Surg Pathol 2008;32:752).

Comment Here

Reference: Plasmacytoid
Board review style question #2
Which of the following immunoprofiles would be most helpful to differentiate primary plasmacytoid urothelial carcinoma of the bladder from metastatic lobular breast carcinoma?

  1. CK7, E-cadherin
  2. E-cadherin, uroplakin II
  3. GATA3, CK7
  4. GATA3, GCDFP-15
  5. Uroplakin II, ER
Board review style answer #2
E. Uroplakin II, ER. Membranous loss of E-cadherin will be seen in both lobular breast carcinoma and plasmacytoid UC. GATA3 and CK7 are usually expressed by both. GCDFP-15 can be positive in some cases of plasmacytoid UC (~25% in 1 study) and also positive in lobular breast carcinoma. ER is positive in most cases of lobular breast carcinoma and negative in plasmacytoid UC. Uroplakin II is negative in lobular breast carcinoma and may be positive in plasmacytoid UC. Overall, given these patterns, the immunoprofile most likely to discriminate between the 2 are uroplakin II and ER (choice E). (Breast Cancer Res 2015;17:12, Hum Pathol 2019;90:27, BMC Urol 2020;20:72, Ann Diagn Pathol 2015;19:6, Am J Surg Pathol 2017;41:1570, Cancers (Basel) 2021;13:3695, BMC Cancer 2014;14:546, Am J Clin Pathol 2017;147:500).

Comment Here

Reference: Plasmacytoid
Board review style question #3
Which panel of immunohistochemical stains would be most helpful to distinguish plasmacytoid urothelial carcinoma from its mimickers at other primary sites?

  1. CD138, CK20, CK7, ER, PR
  2. CD138, CK20, CDX2, GCDFP-15
  3. p63, GATA3, E-cadherin
  4. GATA3, mammaglobin, ER, Uroplakin II
Board review style answer #3
D. GATA3, mammaglobin, ER, Uroplakin II. A panel including GATA3, mammaglobin, ER and uroplakin II would be helpful. GATA3, more so than p63, is positive in plasmacytoid urothelial carcinoma (PUC) and while it does not differentiate between breast and urothelial origin, is helpful in ruling out gastrointestinal metastases. Mammaglobin and ER are consistently negative in PUC, which helps differentiate PUC from breast metastasis, particularly lobular carcinoma, which is more often ER positive. UroplakinII is helpful as it is negative in nonurothelial mimickers. CD138 has been reported to be positive in PUC although it is nonspecific with expression reported in squamous cell carcinoma, normal urothelium and other epithelial and lymphoid malignancies (Int J Surg Pathol 2016;24:614). E-cadherin expression is typically abnormal in both PUC and breast lobular carcinoma, which includes complete absence of staining or aberrant cytoplasmic staining. Of note, E-cadherin staining was normal in 27% of PUC cases in a recent study (Hum Pathol 2020;102:54).

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Reference: Plasmacytoid
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