Bladder, ureter & renal pelvis

Urothelial carcinoma - invasive

With trophoblastic differentiation

Last author update: 2 March 2022
Last staff update: 1 December 2022

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PubMed Search: Urothelial carcinoma with trophoblastic differentiation

Mohammed Alghamdi, M.B.B.S.
Judy Sarungbam, M.D.
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Page views in 2023 to date: 1,332
Cite this page: Alghamdi M, Sarungbam S. With trophoblastic differentiation. website. Accessed September 21st, 2023.
Definition / general
  • Urothelial carcinoma with focal or diffuse trophoblastic / syncytiotrophoblastic morphology or beta hCG immunoreactivity
Essential features
  • Carries a worse prognosis compared to conventional urothelial carcinoma
  • Multinucleated giant cells admixed with urothelial carcinoma is the most commonly encountered pattern
  • Beta hCG immunohistochemical stain highlights cells with trophoblastic differentiation
  • Reporting the presence of this element is recommended
  • Urothelial carcinoma with choriocarcinomatous differentiation
ICD coding
  • ICD-O:
    • 8120/3 - urothelial carcinoma, NOS
    • 8130/3 - papillary urothelial carcinoma
  • ICD-10: C67.9 - malignant neoplasm of bladder, NOS
  • Can be seen along the entire urothelial tract, including urinary bladder, prostatic urethra and upper urothelial tract (Urol Oncol 2021;39:732.e17)
  • Some reports consider it as metaplastic / retrodifferentiation from urothelial to trophoblastic differentiation (Acta Cytol 1992;36:176)
Clinical features
  • Transurethral resection for bladder tumors
  • Cystoscopic biopsy
  • Serum beta hCG can be elevated (Br J Urol 1986;58:143)
  • Elevation of serum beta hCG is not uncommon in high grade invasive urothelial carcinoma even without obvious trophoblastic differentiation (J Urol 1986;136:403)
Prognostic factors
Case reports
  • Depending on the stage of the disease, modalities include transurethral resection, intravesical therapies, chemotherapy, radiotherapy or cystectomy
Microscopic (histologic) description
  • Wide spectrum of trophoblastic differentiation, ranging from scattered isolated cells with trophoblastic differentiation to pure choriocarcinoma
  • Often admixed with conventional urothelial carcinoma or other variants / subtypes
  • When present as scattered isolated cells, they can be in the form of cytotrophoblasts (usually indistinguishable from high grade urothelial carcinoma or syncytiotrophoblast (recognizable by their multinucleated giant cells)
  • Resembles choriocarcinoma in other organs
Microscopic (histologic) images

Contributed by Anuradha Gopalan, M.D., Victor Reuter, M.D. and AFIP images
Multinucleated giant cells Multinucleated giant cells Multinucleated giant cells

Multinucleated giant cells





Cytology description
  • Mixture of mononuclear and multinucleated giant cells with marginal indistinct vacuole-like cytoplasmic inclusions, which stains positively for human placental lactogen (HPL) (Cytopathology 2013;24:405)
Molecular / cytogenetics description
  • Losses of chromosomes 10, 11p12-p14 and 13q22-qter and gains of chromosomes 1q and 12p12-p13
  • High level amplification at 12q14-q21 (Hum Pathol 2002;33:1234)
Sample pathology report
  • Bladder, tumor, transurethral resection:
    • Invasive urothelial carcinoma, high grade, with trophoblastic differentiation (5%), invasive to lamina propria (see comment)
    • Comment: Muscularis propria is identified and is non-involved. Immunohistochemical studies reveal that a subset of tumor cells are positive for beta hCG and GATA3 supporting the presence of trophoblastic differentiation.
Differential diagnosis
Board review style question #1
Which immunohistochemical stain is useful to confirm the trophoblastic differentiation on a bladder biopsy with multinucleated giant cells?

  1. Beta hCG
  2. CD68
  3. CK7
  4. OCT4
Board review style answer #1
Board review style question #2

Which histology should be considered in the urothelial carcinoma shown in the photomicrograph?

  1. Glandular
  2. Plasmacytoid
  3. Sarcomatoid
  4. Trophoblastic
Board review style answer #2
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