Bladder, ureter & renal pelvis

Urothelial carcinoma - invasive

Invasive urothelial carcinoma



Topic Completed: 13 May 2021

Minor changes: 23 August 2021

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PubMed Search: Invasive urothelial carcinoma [TI] pathology "free full text" [SB]

Lindsey Durowoju, M.D.
Maria Tretiakova, M.D., Ph.D.
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Cite this page: Durowoju L, Tretiakova M. Invasive urothelial carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bladderurothelialinvasivegen.html. Accessed October 15th, 2021.
Definition / general
  • Urothelial carcinoma that has penetrated the basement membrane and invaded into the lamina propria or deeper
Essential features
  • Histologic characterization and depth of invasion are the most important factors for determining prognosis (Adv Anat Pathol 2015;22:102)
  • Urothelial carcinoma is morphologically heterogenous with many variants and subtypes (Surg Pathol Clin 2018;11:713)
  • Invasive urothelial carcinoma involving the lamina propria (T1) is often treated with conservative intravesical therapy and mucosal resection (Ann Diagn Pathol 2007;11:395)
  • Invasive urothelial carcinoma involving the muscularis propria (T2) is often treated with radical cystectomy (Ann Diagn Pathol 2007;11:395)
Terminology
  • Invasive transitional cell carcinoma (historical term)
  • WHO classification 2016:
    • Infiltrating urothelial carcinoma
    • Urothelial carcinoma with divergent differentiation
      • With squamous differentiation
      • With glandular differentiation
      • With trophoblastic differentiation
    • Nested urothelial carcinoma
      • Including large nested variant
    • Microcystic urothelial carcinoma
    • Micropapillary urothelial carcinoma
    • Lymphoepithelioma-like urothelial carcinoma
    • Plasmacytoid / signet ring / diffuse urothelial carcinoma
    • Sarcomatoid urothelial carcinoma
    • Giant cell urothelial carcinoma
    • Poorly differentiated urothelial carcinoma
    • Lipid rich urothelial carcinoma
    • Clear cell (glycogen rich) urothelial carcinoma
ICD coding
  • ICD-O:
    • 8120/3 - infiltrating urothelial carcinoma
    • 8131/3 - micropapillary urothelial carcinoma
    • 8082/3 - lymphoepithelioma-like urothelial carcinoma
    • 8122/3 - sarcomatoid urothelial carcinoma
    • 8031/3 - giant cell urothelial carcinoma
    • 8020/3 - poorly differentiated urothelial carcinoma
  • ICD-10: C67.9 - malignant neoplasm of bladder, unspecified
Epidemiology
  • Fourth most common malignancy in U.S. men
  • Eight most common malignancy associated with death in U.S. men
  • Median age: 69 years in men and 71 years in women (Adv Anat Pathol 2015;22:102)
  • Incidence:
    • 4x higher in men than women
    • 2x higher in white men than in black men
Sites
Pathophysiology
  • Smoking or other chemical exposures start the process of carcinogenesis by altering the DNA of the bladder mucosa; these genetic alterations lead to unregulated cell growth (Adv Anat Pathol 2019;26:251)
Etiology
Clinical features
  • Hematuria, irritation / pain during urination, increased urinary frequency or urgency (Urology 2006;67:3)
Diagnosis
Radiology description
  • CT image findings include urothelial thickening / hyperenhancement, asymmetric collecting duct system, urothelial calcifications or the presence of a nodule / mass (Urol Clin North Am 2018;45:389)
  • MRI T2 weighted images demonstrate hypointense thickening of bladder wall (Abdom Radiol (NY) 2019;44:3858)
Radiology images

Images hosted on other servers:
CT with bladder thickening

CT with bladder thickening

CT and MRI urothelial carcinoma

Bladder tumor and lung metastasis

Retrograde pyelogram

Retrograde pyelogram

Pyeloureteral transitional cell

Pyeloureteral transitional cell

Prognostic factors
Case reports
Treatment
Clinical images

Images hosted on other servers:
Cystoscopy pedunculated tumor

Cystoscopy: pedunculated
tumor (PDF Fig 3)

Gross description
Gross images

Contributed by Debra L. Zynger, M.D., Nicole K. Andeen, M.D. and Maria Tretiakova, M.D.
Muscularis propria invasion (pT2b) Muscularis propria invasion (pT2b)

Muscularis propria invasion (pT2b)

Prostatic invasion (pT4a)

Prostatic invasion (pT4a)

Renal pelvic and peripelvic fat invasion (pT3)

Renal pelvic and peripelvic fat invasion (pT3)

Friable, exophytic papillary mass, renal pelvis

Friable, exophytic
papillary mass,
renal pelvis

Frozen section description
  • Positive margin is defined by the presence of in situ or invasive urothelial carcinoma on frozen section (Ann Diagn Pathol 2015;19:107)
  • Ureteric intraoperative frozen sections have significant clinical limitations due to skip lesions, which often occur in multifocal urothelial carcinoma in situ (J Clin Pathol 2010;63:475)
Frozen section images

Images hosted on other servers:
Urothelial carcinoma in situ in frozen section

Urothelial carcinoma in situ in frozen section

Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Maria Tretiakova, M.D., Ph.D., Andrey Bychkov, M.D., Ph.D. and Nicole K. Andeen, M.D.
Invasive high grade urothelial carcinoma

Invasive high grade urothelial carcinoma

Extensive invasion into lamina propria

Extensive invasion into lamina propria

Invasive urothelial carcinoma with comedo necrosis

Invasive urothelial
carcinoma with
comedo necrosis

Lymphovascular invasion

Lymphovascular invasion


Muscularis propria invasion Muscularis propria invasion Muscularis propria invasion

Muscularis propria invasion

IHC profile

IHC profile


Subepithelial invasion characterized by jagged, irregular nests and a desmoplastic response (pT1)

Subepithelial invasion (pT1)

Invasion into muscularis (pT2)

Invasion into muscularis (pT2)

Invasion of renal parenchyma (pT3) Invasion of renal parenchyma (pT3)

Invasion of renal parenchyma (pT3)

Cytology description
Cytology images

Contributed by Bonnie Choy, M.D.
High grade urothelial carcinoma High grade urothelial carcinoma High grade urothelial carcinoma High grade urothelial carcinoma High grade urothelial carcinoma

High grade urothelial carcinoma



Contributed by Nicole K. Andeen, M.D. and Maria Tretiakova, M.D.
Highly atypical cells

Highly atypical cells

Large nuclei with high nuclear to cytoplasmic ratios, coarse chromatin and irregular nuclear contours (Papanicolaou and DiffQuik) Large nuclei with high nuclear to cytoplasmic ratios, coarse chromatin and irregular nuclear contours (Papanicolaou and DiffQuik) Large nuclei with high nuclear to cytoplasmic ratios, coarse chromatin and irregular nuclear contours (Papanicolaou and DiffQuik)

Large nuclei with high nuclear to cytoplasmic ratios, coarse chromatin and irregular nuclear contours (Papanicolaou and DiffQuik)

Positive stains
Molecular / cytogenetics description
  • Most commonly mutated genes are associated with cell cycle progression, including TP53, PIK3CA, RB1 and FGFR3 (Nature 2014;507:315)
  • UroVysion is an FDA approved fluorescent in situ hybridization (FISH) that detects aneuploidy in chromosomes 3, 7 and 17 and loss of 9p21 locus (72% sensitivity and 83% specificity) (BJU Int 2013;112:E372, Curr Opin Urol 2019;29:203)
  • Nuclear matrix proteins (NMP22): group of proteins produced by cancerous cells
    • NMP22 BladderChek test is an FDA approved qualitative assay for surveillance and detection of bladder cancer (50% sensitivity and 87% specificity) (Curr Opin Urol 2019;29:203)
  • Bladder tumor antigen (BTA): antigen produced by cancerous cells
    • BTA Trak (quantitative) and BTA Stat (qualitative) are FDA approved assays for surveillance (68 - 77.5% sensitivity and 50 - 75% specificity) (Curr Opin Urol 2019;29:203)
Molecular / cytogenetics images
Contributed by Nikole K. Andeen, M.D. and Maria Tretiakova, M.D.
FISH, loss of 9p, normal disomy chromosomes 3, 7, 17

FISH, loss of 9p, normal disomy chromosomes 3, 7, 17

FISH, polyploidy chromosomes 3, 7, 17; 9p preserved

FISH, polyploidy chromosomes 3, 7, 17; 9p preserved

Sample pathology report
  • Bladder, TURB:
    • Urothelial carcinoma, high grade (see comment)
    • Type / grade comment: micropapillary (20%)
    • Associated lesions: carcinoma in situ
    • Extent: lamina propria invasion, extensive (pT1)
    • Angiolymphatic invasion: present
    • Muscularis propria: present, uninvolved
Differential diagnosis
Board review style question #1
A 76 year old man with gross hematuria was found to have invasive urothelial carcinoma on transurethral biopsy. Which of the following is not a risk factor for urothelial carcinoma but is a risk factor for developing squamous cell carcinoma?

  1. Tobacco smoke
  2. Polycyclic aromatic hydrocarbon exposure
  3. Benzidine exposure
  4. Indwelling catheter
Board review style answer #1
D. Indwelling catheter

Comment Here

Reference: Invasive urothelial carcinoma
Board review style question #2
Which of the following histopathologic subtypes of urothelial carcinoma is most likely to be associated with a worse prognosis?

  1. Clear cell urothelial carcinoma
  2. Microcystic urothelial carcinoma
  3. Conventional high grade urothelial carcinoma
  4. Plasmacytoid urothelial carcinoma
Board review style answer #2
D. Plasmacytoid urothelial carcinoma

Comment Here

Reference: Invasive urothelial carcinoma
Board review style question #3

An 85 year old man has a mass involving the prostate and bladder shown above. Which of the following findings is most supportive of invasive urothelial carcinoma over prostatic adenocarcinoma?

  1. Sheets of monotonous cells with amphiphilic cytoplasm and prominent nucleoli
  2. Negative for PSA and CK7
  3. Positive for GATA3 and HMWCK
  4. Focus of squamous differentiation
Board review style answer #3
C. Positive for GATA3 and HMWCK immunohistochemical stains

Comment Here

Reference: Invasive urothelial carcinoma
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