Urothelial carcinoma

Author: Mikael Häggström
95% of bladder cancers are urothelial carcinoma (also called transitional cell carcinoma).

Contents

Comprehensiveness

On this resource, the following formatting is used for comprehensiveness:

• Minimal depth
• (Moderate depth)
• ((Comprehensive))

Other legend

<< Decision needed between alternatives separated by / signs >>
{{Common findings / In case of findings}}
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Gross processing

Further information: Urinary bladder

Microscopic examination

Low grade urothelial carcinoma.

In contrast, an inverted urothelial papilloma has smooth surface with minimal to absent exophytic component, is well circumscribed with smooth base, and has no obvious infiltration and no/minimal cytologic atypia.

Urothelial carcinoma displays more crowding and layering, and more hyperchromasia and mitoses, than papillomas and papillary urothelial neoplasm of low malignant potential (also included in grading table below for comparison).

Diagnosis

Also consider non-urothelial cancer types (together constituting 5% of urinary bladder cancers): squamous cell carcinomas (Further information: Urothelial versus squamous cell carcinoma ), adenocarcinomas, sarcomas, small cell carcinomas, and secondary deposits from cancers elsewhere in the body.

If urothelial carcinoma, perform grading and staging. Also report any intraepithelial neoplasia of any surrounding urothelium.

Papillary

Urothelial carcinomas are classified as papillary when they have projections with fibrovascular cores.

Grading

By grade, urothelial neoplasms are classified as either:

• Papillary urothelial neoplasm of low malignant potential (PUNLMP)
• Low-grade urothelial carcinoma
• High-grade urothelial carcinoma

Galleries

Papillary urothelial neoplasm of low malignant potential (PUNLMP)

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  PUNLMP - Low magnification: The papillae are discrete and non-fused.

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  PUNLMP -High magnification: Multilayered urothelium with minimal to absent cytologic atypia and preserved cell polarity.

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  Inverted PUNLMP demonstrates inverted (endophytic) growth and resembles inverted papilloma, but in contrast, shows expanded and rounded cords and nests, composed of architecturally and cytologically bland urothelial cells. Inverted PUNLMP also lacks central streaming and peripheral palisading, as typically seen in inverted papilloma.

Low grade

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  Low grade: Urothelium is thickened but only slightly atypical and has maintained polarity.

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  Intermediate magnification.

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  Low magnification, showing papillary architecture.

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  Low grade.

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  Low grade.

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  Low-magnification of the same case, showing inverted growth.

• *'''Complete absence''', lower left: Endometrial serous carcinoma showing complete absence of p53 expression with internal control showing moderate to strong but variable staining. Note, wild-type pattern in normal atrophic glands at 12 and 6 o'clock.
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  In uncertain cases, immunohistochemistry for p53 can help distinguish a PUNLMP from a low-grade urothelial carcinoma:

Overexpression of p53 is seen in 75% of low-grade urothelial carcinomas and only 10% of PUNLMP.

High grade

There should be at least 5% of high grade areas to call the tumor high grade. High-grade areas less than 5% confers a report addition of "focal high-grade features".

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  Low-grade (at left) and high-grade (at right), the latter having more nuclear pleomorphism and prominent nucleoli.

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  High grade, seen as pleomorphism, multiple mitoses, euchromatin and relatively prominent nucleoli, and uneven distribution of nuclei.

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  High grade: Loss of polarity and severe abnormal cytology.

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  Low-magnification of same case, showing papillary architecture.

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  With giant, bizarre, anaplastic cells.

Table

Papillary urothelial neoplasms

		Papillary urothelial neoplasm of low malignant potential	Low grade	High grade
Architecture	Papillae	Delicate Rarely fused	Delicate Occasionally fused	Delicate Fused and branching
	Organization	Normal polarity Cohesive cells	Minimal crowding and loss of polarity Cohesive cells	Crowding Overlapping cells Loss of polarity Often discohesive cells
Nuclei	Size and nuclear/cytoplasmic ratio	Mildly increased	Increased
	Nuclear size variability	No	Some	Marked
	Shape	Elongated Uniform	Elongated—oval—round Slight variability	Pleomorphic
	Chromatin	Fine	Fine with some variability	Frequently coarse with marked variability
	Nucleoli	Absent to inconspicuous	Usually inconspicuous	Prominent Single to multiple
	Mitoses	Rare Basal if present	Infrequent Mostly basal if present	Frequent At any level
Invasion		Non-invasive	Rarely invasive	Invasive

Variants

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  Micropapillary: Micropapillary clusters of tumor cells within lacunae.

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  Cribriform, high magnification.

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  Cribriform, low magnification.

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  Another case of glandular differentiation, showing luminal spaces with proteinaceous secretions.

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  Another case of glandular differentiation.

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  Another case of glandular differentiation.

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  Plasmacytoid: Monotonous discohesive cells with eosinophilic cytoplasm and eccentric nuclei.

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  With inflammatory stromal reaction.

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  With squamous differentiation. Further information: Urothelial versus squamous cell carcinoma

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  Villoglandular: glandular differentiation and villous architecture.

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  Another villoglandular case. Typical papillary urothelial carcinoma is seen on the left.

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  With prominent retraction artifacts.

Staging

In the TNM staging system (AJCC 8th Ed.) for bladder cancer:

T (Primary tumor)

• TX Primary tumor cannot be assessed
• T0 No evidence of primary tumor
• Ta Non-invasive papillary carcinoma
• Tis Carcinoma in situ ('flat tumor')
• T1 Tumor invades subepithelial connective tissue

High grade papillary urothelial carcinoma, with early invasion, showing single cells and irregularly shaped nests of tumor cells infiltrating the underlying stroma (T1). Pointy rather than smooth edges indicate a true invasion rather than a tangential cut of the basal part of carcinoma in situ.

To detect subepithelial invasion, scroll through all areas of subepithelial connective tissue. Distinguish the following:

	Tangentially cut non-invasive tumor	Subepithelial invasion
Nest shapes	Rounded	Irregular
Cells	Similar to non-invasive	Larger and more eosinophilic
At adjacent levels	Fused with non-invasive tumor	Persistently isolated nests

• T2 Tumor invades the detrusor muscle (muscularis propria). In biopsies, muscle areas smaller than 2 mm in size may be regarded as muscularis mucosae (subepithelial connective tissue) whereas areas larger than 4 mm can be regarded as detrusor muscle.

• T2a Tumor invades superficial muscle (inner half of the detrusor muscle)
• T2b Tumor invades deep muscle (outer half of the detrusor muscle)

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  Urothelial carcinoma invading the detrusor muscle (stage pT2), seen as tumor cells among smooth muscle cells. In biopsies, further specification into T2a or T2b is generally not possible.

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  Also look for lymphovascular invasion. However, a micropapillary urothelial carcinoma with retraction artefacts around the tumor cells (imaged) may mimic lymphovascular invasion.

• T3 Tumor invades perivesical tissue:
  • T3a Microscopically
  • T3b Macroscopically (extravesical mass)
• T4a Tumor invades prostate, uterus or vagina
• T4b Tumor invades pelvic wall or abdominal wall

N (Lymph nodes)

• NX Regional lymph nodes cannot be assessed
• N0 No regional lymph node metastasis
• N1 Metastasis in a single lymph node in true pelvis (hypogastric, obturator, external iliac, or presacral nodes)
• N2 Metastasis in multiple lymph nodes in true pelvis (hypogastric, obturator, external iliac, or presacral nodes)
• N3 Metastasis in common iliac lymph nodes

M (Distant metastasis) Can be performed if tissues have been submitted from distant sites.

• MX Distant metastasis cannot be assessed
• M0 No distant metastasis
• M1 Distant metastasis.
  • M1a: The cancer has spread only to lymph nodes outside of the pelvis.
  • M1b: The cancer has spread other parts of the body.

Microscopy report

• Histopathologic type of cancer
• Grade
• Stage. For biopsies, there should be a mention of the presence or absence of the muscularis propria in the sample, and if it is involved.

Template

(Right bladder neck, transurethral resection:) <<Invasive / Non-invasive>> <<Low / high>>-grade {{papillary}} urothelial carcinoma. <<Negative for lamina propria invasion / Carcinoma invades the ___ [[Deepest layer involved]]>>. Muscularis propria is <<present / absent>>. See synoptic report. Synoptic report Procedure: Transurethral resection of bladder (TURBT) Tumor Tumor site: <<Right / left >> bladder <<neck, floor, wall>> Histologic type: Papillary urothelial carcinoma, noninvasive Histologic grade: <<Low / high>>-grade Tumor extension: Noninvasive Muscularis propria presence: Muscularis propria (detrusor muscle) is <<abdent / present in ___ [[location]] Lymphovascular invasion: <<Present / Not identified>> TNM Histopathologic summary: pT__, pN__

Example

High-grade papillary urothelial carcinoma with invasion into subepithelial connective tissue. Synoptic report Procedure:tumor site(s): posterior dome Histologic type: papillary urothelial carcinoma Histologic grade: high-grade TNM tumor stage: Primary tumor (pt): pT1: tumor invading lamina propria Lymph node staging (pN): pNx: lymph nodes not sampled Muscularis propria sampled: present Lymphovascular invasion: absent

  See also: General notes on reporting

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