Protocol for the Examination of Cystectomy Specimens From

Patients With Carcinoma of the Urinary Bladder

Version: Urinary Bladder Resection 4.0.2.0 Protocol Posting Date: February 2020

CAP Laboratory Accreditation Program Protocol Required Use Date: November 2020

Includes pTNM requirements from the 8th Edition, AJCC Staging Manual

For accreditation purposes, this protocol should be used for the following procedures AND tumor types:
Procedure Description
Cystectomy Includes specimens designated partial, total or radical cystectomy,
radical cystoprostatectomy (for bladder cancer), and anterior
exenterations
Tumor Type Description
Carcinomas Includes invasive carcinomas of the urinary tract, including urothelial
carcinoma, its morphological variants, and other carcinoma (squamous
cell carcinoma, adenocarcinoma, Mϋllerian carcinoma, neuroendocrine
carcinoma, and sarcomatoid carcinoma)#
# This protocol is recommended for reporting noninvasive urothelial tumors (papillary and flat), but it is not required for
accreditation purposes.

This protocol is NOT required for accreditation purposes for the following:
Procedure
Biopsy, transurethral resection of the bladder tumor# (TURBT), or enucleations (consider Urinary
Bladder Biopsy protocol)
Primary resection specimen with no residual cancer (eg, following neoadjuvant therapy)
Cytologic specimens
#Transurethral resection of a bladder tumor is NOT considered to be the definitive resection specimen, even though the entire
cancer may be removed.

The following tumor types should NOT be reported using this protocol:
Tumor Type
Urachal Carcinoma
Lymphoma (consider the Hodgkin or non-Hodgkin Lymphoma protocols)
Sarcoma (consider the Soft Tissue protocol)

Authors
Gladell P. Paner, MD*; Ming Zhou, MD, PhD*; John R. Srigley, MD*; Mahul B. Amin, MD; Robert Allan, MD; Brett
Delahunt, MD; Bernard H. Bochner, MD; Jonathan I. Epstein, MD; David J. Grignon, MD; Peter A. Humphrey, MD,
PhD; Rodolfo Montironi, MD; Jason Pettus, MD; Victor E. Reuter, MD

With guidance from the CAP Cancer and CAP Pathology Electronic Reporting Committees.
* Denotes primary author. All other contributing authors are listed alphabetically.

© 2020 College of American Pathologists (CAP). All rights reserved.

For Terms of Use please visit www.cap.org/cancerprotocols.
 Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

Accreditation Requirements
This protocol can be utilized for a variety of procedures and tumor types for clinical care purposes. For
accreditation purposes, only the definitive primary cancer resection specimen is required to have the core and
conditional data elements reported in a synoptic format.
• Core data elements are required in reports to adequately describe appropriate malignancies. For
accreditation purposes, essential data elements must be reported in all instances, even if the response is
“not applicable” or “cannot be determined.”
• Conditional data elements are only required to be reported if applicable as delineated in the protocol. For
instance, the total number of lymph nodes examined must be reported, but only if nodes are present in the
specimen.
• Optional data elements are identified with “+” and although not required for CAP accreditation purposes,
may be considered for reporting as determined by local practice standards.
The use of this protocol is not required for recurrent tumors or for metastatic tumors that are resected at a
different time than the primary tumor. Use of this protocol is also not required for pathology reviews performed at
a second institution (ie, secondary consultation, second opinion, or review of outside case at second institution).

Synoptic Reporting
All core and conditionally required data elements outlined on the surgical case summary from this cancer protocol
must be displayed in synoptic report format. Synoptic format is defined as:
• Data element: followed by its answer (response), outline format without the paired "Data element:
Response" format is NOT considered synoptic.
• The data element should be represented in the report as it is listed in the case summary. The response for
any data element may be modified from those listed in the case summary, including “Cannot be
determined” if appropriate.
• Each diagnostic parameter pair (Data element: Response) is listed on a separate line or in a tabular format
to achieve visual separation. The following exceptions are allowed to be listed on one line:
o Anatomic site or specimen, laterality, and procedure
o Pathologic Stage Classification (pTNM) elements
o Negative margins, as long as all negative margins are specifically enumerated where applicable
• The synoptic portion of the report can appear in the diagnosis section of the pathology report, at the end of
the report or in a separate section, but all Data element: Responses must be listed together in one location
Organizations and pathologists may choose to list the required elements in any order, use additional methods in
order to enhance or achieve visual separation, or add optional items within the synoptic report. The report may
have required elements in a summary format elsewhere in the report IN ADDITION TO but not as replacement for
the synoptic report i.e. all required elements must be in the synoptic portion of the report in the format defined
above.

Summary of Changes
Version 4.0.2.0
Modified Histologic Type (Squamous cell carcinoma)

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CAP Approved Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

Surgical Pathology Cancer Case Summary

Protocol posting date: February 2020

URINARY BLADDER: Cystectomy and Anterior Exenteration

Select a single response unless otherwise indicated.

Procedure (Note A)
___ Partial cystectomy
___ Radical cystectomy (total cystectomy)
___ Radical cystoprostatectomy
___ Anterior exenteration
___ Other (specify): ____________________________
___ Cannot be determined

Tumor Site (select all that apply)

___ Trigone
___ Right lateral wall
___ Left lateral wall
___ Anterior wall
___ Posterior wall
___ Dome
___ Other (specify): ____________________________
___ Cannot be determined

Tumor Size
Greatest dimension (centimeters): ___ cm
+ Additional dimensions (centimeters): ___ x ___ cm
___ Cannot be determined (explain): __________________________

Histologic Type (select all that apply) (Note B)

Urothelial
___ Papillary urothelial carcinoma, noninvasive
___ Papillary urothelial carcinoma, invasive
___ Urothelial carcinoma in situ
___ Urothelial carcinoma, invasive
___ Urothelial carcinoma, nested (including large nested) variant
___ Urothelial carcinoma, microcystic variant
___ Urothelial carcinoma, micropapillary variant
___ Urothelial carcinoma, lymphoepithelioma-like variant
___ Urothelial carcinoma, plasmacytoid / signet ring / diffuse variant
___ Urothelial carcinoma, sarcomatoid variant
___ Urothelial carcinoma, giant cell variant
___ Urothelial carcinoma, poorly differentiated variant
___ Urothelial carcinoma, lipid-rich variant
___ Urothelial carcinoma, clear cell variant
___ Urothelial carcinoma with squamous differentiation
+ Specify percentage of squamous differentiation: _____%
___ Urothelial carcinoma with glandular differentiation
+ Specify percentage of glandular differentiation: _____%
___ Urothelial carcinoma with trophoblastic differentiation
+ Specify percentage of trophoblastic differentiation: _____%
___ Urothelial carcinoma with Mϋllerian differentiation

+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 3
clinically important but are not yet validated or regularly used in patient management.
CAP Approved Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

+ Specify percentage of Mϋllerian differentiation: _____%

Squamous
___ Squamous cell carcinoma
___ Verrucous carcinoma
___ Squamous cell carcinoma in situ (no invasive carcinoma identified)

Glandular
___ Adenocarcinoma
___ Adenocarcinoma, enteric
___ Adenocarcinoma, mucinous
___ Adenocarcinoma, mixed
___ Adenocarcinoma in situ (no invasive carcinoma identified)

Tumors of Mϋllerian Type

___ Clear cell carcinoma
___ Endometrioid carcinoma

Neuroendocrine Tumors
___ Small cell neuroendocrine carcinoma
+ Specify percentage of small cell neuroendocrine component: _____%
___ Large cell neuroendocrine carcinoma
+ Specify percentage of large cell neuroendocrine component: _____%
___ Well-differentiated neuroendocrine carcinoma
+ Specify percentage of well-differentiated neuroendocrine component: _____%

___ Other histologic type not listed (specify): ____________________________

+ Associated Epithelial Lesions (select all that apply) (Note C)

+ ___ None identified
+ ___ Urothelial papilloma
+ ___ Urothelial papilloma, inverted type
+ ___ Papillary urothelial neoplasm, low malignant potential (PUNLMP)
+ ___ Urothelial proliferation of uncertain malignant potential
+ ___ Urothelial dysplasia
+ ___ Cannot be determined

Histologic Grade (Note C)

For urothelial carcinoma, other variants, or divergent differentiation

___ Low grade
___ High grade
___ Other (specify): ____________________________

For squamous cell carcinoma or adenocarcinoma

___ G1: Well differentiated
___ G2: Moderately differentiated
___ G3: Poorly differentiated
___ GX: Cannot be assessed

___ Other (specify): ____________________________

___ Not applicable
___ Cannot be assessed

+ Tumor Configuration (select all that apply)

+ ___ Papillary

+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 4
clinically important but are not yet validated or regularly used in patient management.
CAP Approved Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

+ ___ Solid/nodule
+ ___ Flat
+ ___ Ulcerated
+ ___ Cannot be determined
+ ___ Other (specify): ___________________________

Tumor Extension (select all that apply) (Note D)

___ No evidence of primary tumor
___ Noninvasive papillary carcinoma
___ Urothelial carcinoma in situ
___ Tumor invades lamina propria (subepithelial connective tissue)
___ Tumor invades muscularis propria
___ Tumor invades superficial muscularis propria (inner half)
___ Tumor invades deep muscularis propria (outer half)
___ Tumor invades perivesical soft tissue
___ Microscopically
___ Macroscopically (extravesical mass)
___ Tumor invades adjacent structures#
___ Prostate (transmural invasion from the bladder tumor)##
___ Seminal vesicles
___ Uterus
___ Vagina
___ Adnexae
___ Pelvis wall
___ Abdominal wall
___ Rectum
___ Other (specify): ______________________________
___ Cannot be assessed
#Note: Use the Urethral protocol for tumors that involve the urethral mucosa without invasion, tumors that involve the urethral
mucosa with invasion of subepithelial connective tissue/prostate stroma, or tumors that involve prostatic ducts and acini with or
without stromal invasion.
## See Note D, Figure 1.

Margins (select all that apply) (Note E)

___ Cannot be assessed
___ Uninvolved by invasive carcinoma and carcinoma in situ/ noninvasive urothelial carcinoma
___ Uninvolved by invasive carcinoma
___ Involved by invasive carcinoma
___ Right ureteral margin
___ Left ureteral margin
___ Urethral margin
___ Soft tissue margin
___ Other margin(s) (specify)#: _______________________
___ Involved by carcinoma in situ/noninvasive high-grade urothelial carcinoma
___ Right ureteral margin
___ Left ureteral margin
___ Urethral margin
___ Soft tissue margin
___ Other margin(s) (specify)#: _______________________
___ Involved by noninvasive low-grade urothelial carcinoma/urothelial dysplasia
___ Right ureteral margin
___ Left ureteral margin
___ Urethral margin
___ Soft tissue margin
___ Other margin(s) (specify)#: _______________________

+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 5
clinically important but are not yet validated or regularly used in patient management.
CAP Approved Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

#Note: For partial cystectomies, if the specimen is received unoriented precluding identification of specific margins, it should
be denoted here.

Lymphovascular Invasion (Note F)

___ Not identified
___ Present
___ Cannot be determined

Regional Lymph Nodes

___ No lymph nodes submitted or found

Lymph Node Examination (required only if lymph nodes are present in the specimen)

Number of Lymph Nodes Involved: _____

Lymph Node Metastasis

+ Size of Largest Metastatic Deposit (centimeters): ___ cm

+ Specify Site: _________

+ Size of Largest Lymph Node Involved (centimeters): ___ cm

+ Specify Site: _________

+ Extranodal Extension
+ ___ Not identified
+ ___ Present
+ ___ Cannot be determined

Number of Lymph Nodes Examined: _____

Pathologic Stage Classification (pTNM, AJCC 8th Edition) (Note G)

Note: Reporting of pT, pN, and (when applicable) pM categories is based on information available to the pathologist at the time
the report is issued. Only the applicable T, N, or M category is required for reporting; their definitions need not be included in
the report. The categories (with modifiers when applicable) can be listed on 1 line or more than 1 line.

TNM Descriptors (required only if applicable) (select all that apply)

___ m (multiple primary tumors)
___ r (recurrent)
___ y (posttreatment)

Primary Tumor (pT)

___ pTX: Primary tumor cannot be assessed
___ pT0: No evidence of primary tumor
___ pTa: Noninvasive papillary carcinoma
___ pTis: Urothelial carcinoma in situ: “flat tumor”
___ pT1: Tumor invades lamina propria (subepithelial connective tissue)
___ pT2: Tumor invades muscularis propria
___ pT2a: Tumor invades superficial muscularis propria (inner half)
___ pT2b: Tumor invades deep muscularis propria (outer half)
___ pT3: Tumor invades perivesical soft tissue
___ pT3a: Tumor invades perivesical soft tissue microscopically
___ pT3b: Tumor invades perivesical soft tissue macroscopically (extravesical mass)
___ pT4: Extravesical tumor directly invades any of the following: prostatic stroma, seminal vesicles, uterus,
vagina, pelvic wall, abdominal wall
___ pT4a: Extravesical tumor invades directly into prostatic stroma, uterus, or vagina
___ pT4b: Extravesical tumor invades pelvic wall, abdominal wall

+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 6
clinically important but are not yet validated or regularly used in patient management.
CAP Approved Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

Regional Lymph Nodes (pN)

___ pNX: Lymph nodes cannot be assessed
___ pN0: No lymph node metastasis
___ pN1: Single regional lymph node metastasis in the true pelvis (perivesical, obturator, internal and external
iliac or sacral lymph node)
___ pN2: Multiple regional lymph node metastasis in the true pelvis (perivesical, obturator, internal and external
iliac or sacral lymph node metastasis)
___ pN3: Lymph node metastasis to the common iliac lymph nodes

Distant Metastasis (pM) (required only if confirmed pathologically in this case)

___ pM1: Distant metastasis
___ pM1a: Distant metastasis limited to lymph nodes beyond the common iliacs
___ pM1b: Non-lymph node distant metastases

Specify site(s), if known: ____________________________

+ Additional Pathologic Findings (select all that apply)

+ ___ Urothelial dysplasia
+ ___ Adenocarcinoma of prostate (use protocol for carcinoma of prostate)
+ ___ Inflammation/regenerative changes
+ ___ Therapy-related changes (specify): _________________
+ ___ Cystitis cystica et glandularis
+ ___ Keratinizing squamous metaplasia
+ ___ Intestinal metaplasia
+ ___ Other (specify): ____________________________

+ Comment(s)

+ Data elements preceded by this symbol are not required for accreditation purposes. These optional elements may be 7
clinically important but are not yet validated or regularly used in patient management.
Background Documentation Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

Explanatory Notes

A. Sections for Microscopic Evaluation

Bladder
Sections of bladder for microscopic evaluation for cystectomy specimens, several representative sections of the
tumor, including the macroscopically deepest penetration, should be sampled. Submit several sections of the
mucosa remote from the carcinoma, especially if abnormal, including the lateral wall(s), dome, and trigone.
Submit one section of ureteral margin, unless submitted separately as frozen section specimens, and 1 section of
urethral margin. If a long segment of the ureter(s) is present, then additional sections from the mid-portion may be
necessary, as urothelial cancer often is multifocal.

Prostate and Prostatic Urethra

Prostatic urethral involvement should be carefully investigated in cystectomy specimens. Sections should include
the prostatic urethra, including at the margin and with the surrounding prostatic parenchyma. Representative
sections of the peripheral zone, central zone, and seminal vesicles should be included. Close gross examination
may help target sampling of selective abnormal-appearing areas.

Lymph Nodes
Submit one section from each grossly positive lymph node. All other lymph nodes should be entirely submitted, as
presence of nodal disease may be used as an indication for adjuvant therapy. Lymph nodes may be grossly or
microscopically detected in the perivesical fat.

Other Tissues
Submit one or more sections of uterus (as indicated) and one or more sections of vagina, seminal vesicles, and
other organs (as indicated). If the tumor grossly appears to invade the prostate, uterus, or vagina, sections should
be targeted, such that the relationship of the infiltrating tumor in the bladder wall and the adjacent viscus is clearly
demonstrable.

B. Histologic Type
The vast majority (more than 95%) of carcinomas of the urinary bladder, renal pelvis, and ureter are urothelial cell
in origin. The most recent 2016 World Health Organization (WHO) classification of tumors of the urothelial tract,
including urethra, urinary bladder, ureter, and renal pelvis, is provided in this note. Benign tumors are included in
this classification because, within the same patient, a spectrum of differentiation from benign to malignant tumors
may be seen in the bladder, either at the same time or over the clinical course of the disease. Also, clinicians
stage most tumors irrespective of histologic grade.1-9 The distinction between a urothelial carcinoma with
divergent squamous, glandular, or Müllerian differentiation and a pure squamous cell carcinoma, adenocarcinoma
or Müllerian is rather arbitrary. Most authorities, including the 2016 WHO classification, require a pure histology of
squamous cell carcinoma, adenocarcinoma or Müllerian to designate a tumor as such, all others with
recognizable papillary, invasive, or flat carcinoma in situ (CIS) urothelial component being considered as
urothelial carcinoma with divergent differentiation. A malignant neoplasm with small cell neuroendocrine
carcinoma component arising in the urinary tract is designated as small cell carcinoma.

2016 WHO Classification of Tumors of the Urothelial Tract

Urothelial tumors
Infiltrating urothelial carcinoma
Nested, including large nested
Microcystic
Micropapillary
Lymphoepithelioma-like
Plasmacytoid/signet ring cell/diffuse
Sarcomatoid
Giant cell
Poorly differentiated

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Background Documentation Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

Noninvasive urothelial lesions

Urothelial carcinoma in situ
Noninvasive papillary urothelial carcinoma, low grade
Noninvasive papillary urothelial carcinoma, high grade
Papillary urothelial neoplasm of low malignant potential
Urothelial papilloma
Inverted urothelial papilloma
Urothelial proliferation of uncertain malignant potential
Urothelial dysplasia

Squamous cell neoplasms

Squamous cell carcinoma
Verrucous carcinoma
Squamous cell papilloma

Glandular neoplasms
Adenocarcinoma, NOS
Enteric
Mucinous
Mixed
Villous adenoma

Urachal carcinoma

Tumors of Mullerian type

Clear cell carcinoma
Endometrioid carcinoma

Neuroendocrine tumors
Small cell neuroendocrine carcinoma
Large cell neuroendocrine carcinoma
Well-differentiated neuroendocrine tumor
Paraganglioma

References:
1. Amin MB, Murphy WM, Reuter VE, et al. Controversies in the pathology of transitional cell carcinoma of the
urinary bladder. In: Rosen PP, Fechner RE, eds. Reviews of Pathology. Vol. 1. Chicago, IL: ASCP Press;
1996.
2. Reuter VE. The urothelial tract: renal pelvis, ureter, urinary bladder, and urethra. In: Mills Se, Carter D,
Greenson JK, Oberman HA, Reuter V, Stoler MH, eds. Sternberg’s Diagnostic Surgical Pathology. 4th ed.
Philadelphia, PA: Lippincott Williams and Wilkins; 2004.
3. Amin MB, Young RH. Intraepithelial lesions of the urinary bladder with a discussion of the histogenesis of
urothelial neoplasia. Semin Diagn Pathol. 1997;14(2):84-97.
4. Eble JN, Young RH. Carcinoma of the urinary bladder: a review of its diverse morphology. Semin Diagn
Pathol. 1997;14(2):98-108.
5. Mostofi FK, Davis CJ, Sesterhenn IA. Histologic typing of urinary bladder tumors. In: World Health
Organization International Histologic Classification of Tumours. 2nd ed. Heidelberg, Germany: Springer-
Verlag, Berlin; 1999.
6. Eble JN, Sauter G, Epstein JI, Sesterhenn IA. Tumors of the urinary system. In: World Health Organization
Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital
Organs. Lyon, France: IARC Press; 2004.
7. Moch H, Humphrey PA, Ulbright TM, Reuter VE. WHO Classification of Tumours of the Urinary System and
Male Genital Organs. Geneva, Switzerland: WHO Press; 2016.
8. Murphy WM, Grignon DJ, Perlman EJ. Tumors of the urinary bladder. In: Tumors of the Kidney, Bladder, and
Related Urinary Structures. AFIP Atlas of Tumor Pathology Series 4. Washington, DC: American Registry of
Pathology; 2004.

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Background Documentation Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

9. Epstein JI, Amin MB, Reuter VR, Mostofi FK, the Bladder Consensus Conference Committee. The World
Health Organization/ International Society of Urological Pathology Consensus classification of urothelial
(transitional cell) neoplasms of the urinary bladder. Am J Surg Pathol. 1998;22:1435-1448.

C. Histologic Grade
Flat intraepithelial lesions and papillary and invasive lesions are graded separately.1-8 There has been significant
controversy in the classification of these lesions. Flat lesions were graded as mild, moderate, and severe
dysplasia and carcinoma in situ; or atypical hyperplasia and carcinoma in situ; or dysplasia and carcinoma in
situ.9,10 Papillary lesions were classified as papillomas (grade 0) and transitional cell carcinomas, grades I, II and
III; or as papillomas, low-grade and high-grade transitional cell carcinomas.4-6 Due to variable classification
systems and the need for a universally acceptable system, the World Health Organization/International Society of
Urological Pathology (WHO/ISUP) consensus classification was proposed.4 This system is adopted in the WHO
2004 classification1 and 2004 Armed Forces Institute of Pathology (AFIP) fascicle,3 and has been validated by
many studies to be prognostically significant. The 2016 WHO system used essentially the same classification with
minor modification.2 Other systems (that were being used previously) may still be used according to institutional
preference. Tumor grade according to both the WHO/ISUP (1998)4 / WHO (2004)1 system and the older WHO
(1973)6 system may be concurrently used.

2004 WHO / ISUP Consensus Classification for Urothelial Lesions

Normal
Normal#
Hyperplasia
Flat hyperplasia
Papillary hyperplasia
Flat Lesions with Atypia
Reactive (inflammatory) atypia
Atypia of unknown significance
Dysplasia (low-grade intraurothelial neoplasia)#
Carcinoma in situ (high-grade intraurothelial neoplasia)##
Papillary Neoplasms
Papilloma
Inverted papilloma
Papillary neoplasm of low malignant potential
Papillary carcinoma, low-grade
Papillary carcinoma, high-grade###
Invasive Neoplasms
Lamina propria invasion
Muscularis propria (detrusor muscle) invasion
# May include cases formerly diagnosed as “mild dysplasia.”
## Includes cases with “severe dysplasia.”
### Option exists to add comment as to the presence of marked anaplasia.

Flat and papillary urothelial hyperplasia has been renamed as “urothelial proliferation of uncertain malignant
potential” in the 2016 WHO classification.

Squamous carcinomas and adenocarcinomas may be graded as well-differentiated, moderately differentiated,

and poorly differentiated.

References:
1. Eble JN, Sauter G, Epstein JI, Sesterhenn IA. Tumors of the urinary system. In: World Health Organization
Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital
Organs. Lyon, France: IARC Press; 2004.
2. Moch H, Humphrey PA, Ulbright TM, Reuter VE. WHO Classification of Tumours of the Urinary System and
Male Genital Organs. Geneva, Switzerland: WHO Press; 2016.

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Background Documentation Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

3. Murphy WM, Grignon DJ, Perlman EJ. Tumors of the urinary bladder. In: Tumors of the Kidney, Bladder, and
Related Urinary Structures. AFIP Atlas of Tumor Pathology Series 4. Washington, DC: American Registry of
Pathology; 2004.
4. Epstein JI, Amin MB, Reuter VR, Mostofi FK, the Bladder Consensus Conference Committee. The World
Health Organization/ International Society of Urological Pathology Consensus classification of urothelial
(transitional cell) neoplasms of the urinary bladder. Am J Surg Pathol. 1998;22:1435-1448.
5. Murphy WM, Beckwith JB, Farrow GM. Tumors of the kidney, bladder, and related urinary structures. In:
Atlas of Tumor Pathology. 3rd series. Fascicle 11. Washington, DC: Armed Forces Institute of Pathology;
1994.
6. Mostofi FK. Histological typing of urinary bladder tumours. In: WHO Histological Classification of Tumours.
No. 10. Geneva, Switzerland: World Health Organization; 1973.
7. Bergkvist A, Ljungqvist A, Moberger G. Classification of bladder tumors based on the cellular pattern. Acta
Chir Scand. 1965;130:371-378.
8. Friedell GH, Bell JR, Burney SW, Soto EA, Tiltman AJ. Histopathology and classification of urinary bladder
carcinoma. Urol Clin North Am. 1976;3:265-227.
9. Amin MB, Murphy WM, Reuter VE, et al. Controversies in the pathology of transitional cell carcinoma of the
urinary bladder. In: Rosen PP, Fechner RE, eds. Reviews of Pathology. Vol. 1. Chicago, IL: ASCP Press;
1996.
10. Amin MB, Young RH. Intraepithelial lesions of the urinary bladder with a discussion of the histogenesis of
urothelial neoplasia. Semin Diagn Pathol. 1997;14(2):84-97.

D. Extent of Invasion
A critical role of the surgical pathologist is to diagnose the depth and extent of invasion into the subepithelial
connective tissue/lamina propria/submucosa (pT1), muscularis propria (pT2), or beyond (pT3 or pT4).1-3 In
papillary tumors, invasion occurs most often at the base of the tumor and very infrequently in the stalk. In the
urinary bladder, a tumor infiltrating the lamina propria (pT1) is sometimes overdiagnosed as vascular invasion;
hence, caution should be exercised when diagnosing this feature, which in some cases may be supported by
performing immunohistochemical studies for endothelial markers.4
Involvement of the prostate gland may occur in several different patterns. Tumors (flat carcinoma in situ, papillary
or invasive carcinoma) can first spread along the prostatic urethral mucosa and prostate glands and subsequently
invade prostatic stroma (transurethral mucosal route) (Figure 1, B). Tumors may also invade through the bladder
wall and the base of the prostate directly into the prostate gland (Figure 1, A, straight arrow).11 Tumors can also
invade into extravesical fat and then extend back into the prostate gland (Figure 1, B, curved arrow). The latter
two routes are considered direct transmural invasion. The American Joint Committee on Cancer (AJCC) 8th
edition staging manual defines direct extension of urinary bladder cancer into the prostate gland as T4 disease
and excludes transurethral mucosal prostatic stroma invasion from the pT4a staging status. However, there is
limited data on the best methodology to stage urothelial carcinoma that concurrently involves the urinary bladder
and the prostatic urethra. In patients who have a large urinary bladder carcinoma that has invaded through the full
thickness of the bladder wall and thereby secondarily involves the prostatic stroma, a T4 stage should be
assigned per urinary bladder staging. In other circumstances in which involvement by urothelial carcinoma is seen
in both sites, separate urinary bladder and prostatic urethral staging should be assigned. Transmucosal route into
prostatic stroma from a bladder cancer without transmural prostatic stromal invasion is now categorized as pT2
per urethral cancer staging, and the concomitant bladder proper cancer is given a separate stage category
according to the bladder cancer staging.

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Background Documentation Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

Figure 1. Prostatic invasion from urinary bladder cancer via direct transmural and extravesical route (A) and transurethral
invasion (B). From: Patel AR, Cohn JA, El Latif AA, et al. Validation of new AJCC exclusion criteria for subepithelial prostatic
stroma invasion from pT4a bladder urothelial carcinoma. J Urol. 2013;189:53-58. Reproduced with permission.

References:
1. Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th Ed. New York: Springer; 2017.
2. Brierley JD, Gospodarowicz MK, Wittekind C, et al, eds. TNM Classification of Malignant Tumours. 8th ed.
Oxford, UK: Wiley; 2016.
3. Jimenez RE, Keane TE, Hardy HT, Amin MB. pT1 urothelial carcinoma of the bladder: criteria for diagnosis,
pitfalls, and clinical implications. Adv Anat Pathol. 2000;7(1):13-25.
4. Amin MB, Murphy WM, Reuter VE, et al. Controversies in the pathology of transitional cell carcinoma of the
urinary bladder. Part II, Chapter 5. In: Rosen PP, Fechner RE, eds. Reviews of Pathology. Vol. 2. Chicago,
IL: ASCP Press; 1997:71-110.
5. Eble JN, Sauter G, Epstein JI, Sesterhenn IA. Tumors of the urinary system. In: World Health Organization
Classification of Tumours: Pathology and Genetics of Tumours of the Urinary System and Male Genital
Organs. Lyon, France: IARC Press; 2004.
6. Epstein JI, Amin MB, Reuter VR, Mostofi FK, the Bladder Consensus Conference Committee. The World
Health Organization/ International Society of Urological Pathology Consensus classification of urothelial
(transitional cell) neoplasms of the urinary bladder. Am J Surg Pathol. 1998;22:1435-1448.
7. Ro JY, Ayala AG, El-Naggar A. Muscularis mucosa of urinary bladder: importance for staging and treatment.
Am J Surg Pathol. 1983;136:265-271.
8. Paner GP, Ro JY, Wojcik EM, Venkataraman G, Data MW, Amin MB. Further characterization of the muscle
layers and lamina propria of the urinary bladder by systematic histologic mapping: implications for pathologic
staging of invasive urothelial carcinoma. Am J Surg Pathol. 2007;31:1420-1429.
9. Murphy WM. ASCP survey on pathology examination of the urinary bladder. Am J Clin Pathol.
1994;102:715-723.
10. Philip AT, Amin MB, Tamboli P, Lee TJ, Hill CE, Ro JY. Intravesical adipose tissue: a quantitative study of its
presence and location with implications for therapy and prognosis. Am J Surg Pathol. 2000;24:1286-1290.
11. Patel AR, Cohn JA, El Latif AA, et al. Validation of new AJCC exclusion criteria for subepithelial prostatic
stroma invasion from pT4a bladder urothelial carcinoma. J Urol. 2013; 189:53-58.

E. Margins
Resection margins, including those mentioned in Note A, should be carefully specified. Statements about deep
soft tissue margins should specify whether peritoneal surfaces are involved by tumor. In cases of urachal
adenocarcinoma in which partial cystectomy with excision of the urachal tract and umbilicus is performed, the
margins of the urachal tract, ie, the soft tissue surrounding the urachus and the skin around the umbilical margin,
should be specified.

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Background Documentation Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

F. Lymphovascular Invasion
Urothelial carcinoma may invade blood vessels or lymphatic channels. Lymphovascular invasion has been shown
to be an independent predictor of recurrence and decreased overall survival. In suspicious cases, blood vessels
can be highlighted by immunohistochemical staining for factor VIII-related antigen, CD31 or CD34. Staining will
not resolve the problem of differentiating lymphatic versus artifactual space entrapment by tumor cells, and as
mentioned, this is frequently seen in urothelial tumors invading the lamina propria. Retraction artifact is also
prominent in the “micropapillary variant” of urothelial carcinoma.2

References:
1. Lotan Y, Gupta A, Shariat SF, et al. Lymphovascular invasion is independently associated with overall
survival, cause-specific survival, and local and distant recurrence in patients with negative lymph nodes at
radical cystectomy. J Clin Oncol. 2005;23:6533-6539.
2. Amin MB, Young RH. Intraepithelial lesions of the urinary bladder with a discussion of the histogenesis of
urothelial neoplasia. Semin Diagn Pathol. 1997;14(2):84-97.

G. TNM and Stage Groupings

The TNM Staging System for carcinomas of the urinary bladder of the AJCC is recommended.1
A cystoprostatectomy specimen may contain three separate primaries: carcinoma of the urinary bladder,
carcinoma of the prostate and carcinoma of the urethra. Depending on the pathology in a given case, the number
of protocols to be used in a cystoprostatectomy specimen will vary.

By AJCC convention, the designation “T” refers to a primary tumor that has not been previously treated. The
symbol “p” refers to the pathologic classification of the TNM, as opposed to the clinical classification, and is based
on gross and microscopic examination. pT entails a resection of the primary tumor or biopsy adequate to evaluate
the highest pT category, pN entails removal of nodes adequate to validate lymph node metastasis, and pM
implies microscopic examination of distant lesions. Clinical classification (cTNM) is usually carried out by the
referring physician before treatment during initial evaluation of the patient or when pathologic classification is not
possible. Pathologic staging is usually performed after surgical resection of the primary tumor. Pathologic staging
depends on pathologic documentation of the anatomic extent of disease, whether or not the primary tumor has
been completely removed. If a biopsied tumor is not resected for any reason (eg, when technically unfeasible)
and if the highest T and N categories or the M1 category of the tumor can be confirmed microscopically, the
criteria for pathologic classification and staging have been satisfied without total removal of the primary cancer.

Primary Tumor (T) (Figure 2)

The suffix “m” should be added to the appropriate T category to indicate multiple tumors. The suffix “is” may be
added to any T to indicate the presence of associated carcinoma in situ.

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Background Documentation Urinary Tract • Urinary Bladder • Resection • 4.0.2.0

Figure 2. Extent of Tis, Ta, T1, and T3. From: Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th
ed. New York, NY: Springer; 2017. Reproduced with permission.

TNM Descriptors
For identification of special cases of TNM or pTNM classifications, the “m” suffix and “y” and “r” prefixes are used.
Although they do not affect the stage grouping, they indicate cases needing separate analysis.

The “m” suffix indicates the presence of multiple primary tumors in a single site and is recorded in parentheses:
pT(m)NM.

The “y” prefix indicates those cases in which classification is performed during or following initial multimodality
therapy (ie, neoadjuvant chemotherapy, radiation therapy, or both chemotherapy and radiation therapy). The
cTNM or pTNM category is identified by a “y” prefix. The ycTNM or ypTNM categorizes the extent of tumor
actually present at the time of that examination. The “y” categorization is not an estimate of tumor prior to
multimodality therapy (ie, before initiation of neoadjuvant therapy).

The “r” prefix indicates a recurrent tumor when staged after a documented disease-free interval, and is identified
by the “r” prefix: rTNM.

Additional Descriptors
Residual Tumor (R)
Tumor remaining in a patient after therapy with curative intent (eg, surgical resection for cure) is categorized by a
system known as R classification, shown below.

RX Presence of residual tumor cannot be assessed

R0 No residual tumor
R1 Microscopic residual tumor
R2 Macroscopic residual tumor

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For the surgeon, the R classification may be useful to indicate the known or assumed status of the completeness
of a surgical excision. For the pathologist, the R classification is relevant to the status of the margins of a surgical
resection specimen. That is, tumor involving the resection margin on pathologic examination may be assumed to
correspond to residual tumor in the patient and may be classified as macroscopic or microscopic according to the
findings at the specimen margin(s).

References:
1. Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th Ed. New York: Springer; 2017.

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