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Bladder

Miscellaneous

Staging


Reviewer: Nat Pernick, M.D., PathologyOutlines.com, Inc. (see Reviewers page)
Revised: 30 June 2011, last major update June 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.

General
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● Clinical staging is based on bimanual examination under anesthesia, imaging, biochemical and isotopic tests for metastases
● Pathologic staging is based on review of TURBT (transurethral resection of bladder tumor), partial cystectomy or radical cystectomy specimens
● Pathological stage is the most important determinant of treatment and prognosis for bladder cancer (Cancer 2000;88:2326)
● Lamina propria invasion may be difficult to determine due to fragmentation, cautery, tangential sectioning and poorly oriented specimens
● Muscularis propria invasion can be difficult to determine if there are insufficient muscle bundles to distinguish between hypertrophic muscularis mucosae and true muscularis propria
An accurate pathological stage can be assigned to TURBO (transurethral resection in one piece) specimens in most bladder cancer patients (Int J Urol 2010;17:708)

Changes in AJCC 7th Edition from 6th Edition
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● T4 disease includes prostatic stromal invasion directly from bladder cancer, but does not include subepithelial invasion of prostatic urethra
● Common iliac nodes are defined as regional nodes (secondary drainage region) and not metastatic disease
● N staging has been changed as indicated below (size is no longer relevant)
● Tumors are graded with the low grade / high grade designation of the WHO/ISUP, replacing the previous 3 and 4 four grade systems

Primary Tumor (pT)
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● pTX: Primary tumor cannot be assessed
● pT0: No evidence of primary tumor (example: no residual disease in cystectomy specimen after TURBT or biopsy)
● pTa: Noninvasive papillary carcinoma; i.e. confined to urothelium with no lamina propria invasion
● pTis: Carcinoma in situ
● pT1: Invasive, into lamina propria (subepithelial connective tissue)
● pT2: Invasive, into muscularis propria
● pT2a: Invasive, into inner half (superficial) muscularis propria
● pT2b: Invasive, into outer half (deep) muscularis propria
● pT3: Invasive, into perivesical tissue
● pT3a: Invasive into perivesical tissue - microscopic
● pT3b: Invasive into perivesical tissue - macroscopic (extravesicular mass)
● pT4: Tumor invades prostatic stroma, seminal vesicles, uterus, vagina, pelvic wall or abdominal wall (excludes in situ invasion of prostatic ducts)
● pT4a: Tumor invades prostatic stroma, uterus or vagina
● pT4b: Tumor invades pelvic wall or abdominal wall

References: AJCC 7th edition, US National Cancer Institute

General staging notes:
● Clinical management with respect to intravesicular BCG/chemotherapy and frequency of surveillance differs for high grade versus low grade tumors
● Designation as low vs. high grade does predict stage, although tumors are often understaged by TURBT (Am J Clin Pathol 2000;113:275, Int Braz J Urol 2007;33:25)
● Hyperplastic muscular mucosa may resemble muscularis propria (Am J Surg Pathol 2007;31:1420)
● Adipose tissue often is present within deep lamina propria, usually as small localized aggregates, and is always found within muscularis propria (superficial and deep); beware of inappropriate staging as pT3 due to tumor infiltration of adipose tissue, particularly in TURBT specimens (Am J Surg Pathol 2000;24:1286)

Lamina propria (pT1):
● Lamina propria contains connective tissues between urothelium and detrusor muscle (muscularis propria), made of loose stroma, variably sized blood vessels and thin muscle bands of muscularis mucosae
● pTa cases may actually be invasive when studied by electron microscopy, significance unclear (Am J Clin Pathol 2003;120:188); invasion of lamina propria can be subjective and is not as clinically crucial as invasion of muscularis propria (pT2)
● Has nests, clusters or single tumor cells, sometimes with prominent retraction artifact (does not represent lymphovascular invasion)
● Often has desmoplastic or inflammatory stromal response and absent or irregular basement membrane, not seen with low grade papillary carcinomas with inverted pattern
● Tumor cells often have abundant eosinophilic cytoplasm at advancing edge (“paradoxical differentiation”)
● If tumor cells hug the mucosa, they should be more anaplastic than mucosa cells
● Pitfalls in diagnosis include tangential sectioning, poor specimen orientation, inflammation, thermal injury, deceptively bland cytology and pseudoinvasive nests of benign proliferative urothelial cells (Pathology 2003;35:484)
● Substaging of pT1 based on muscularis mucosa is technically difficult and not reproducible (Mod Pathol 1996;9:1035)
● 50% recur

Muscularis propria (pT2):
● Muscularis propria is thick aggregated muscle bundles of detrusor muscle; must distinguish from muscularis mucosa
● Assessment of muscularis propria invasion is very important (pTa/pT1 vs. pT2)
● Mention whether muscularis propria is present in biopsies and if invasion is present
● Don’t confuse occasionally prominent fascicles of muscularis mucosa that is part of lamina propria (more common in women) with muscularis propria invasion (hypertrophic muscularis mucosa)
● Cannot substage pT2 as pT2a or pT2b unless have full thickness and well oriented biopsy of bladder
● Muscularis propria invasion implies tumor infiltrating thick smooth muscle bundles
● Can use trichrome or HHF to highlight all smooth muscle tissue to determine if muscularis mucosa or muscularis propria is invaded
● Smoothelin antibody may be useful to distinguish muscularis propria from muscularis mucosa (but see Virchows Arch 2011;458:665)
● Tumor cells should “carve out” the muscle bundles, often desmoplastic response should be present
● Can assess presence but not depth of muscularis propria invasion in TURBT specimen

Perivesical fat (pT3):
● Perivesical adipose tissue is deep to muscularis propria, but is also present within deep lamina propria, usually as small localized aggregates, and within muscularis propria (superficial and deep)
● Beware of inappropriate staging as pT3 due to tumor infiltration of adipose tissue, particularly in TURBT specimens (Am J Surg Pathol 2000;24:1286)
● For node positive radical cystectomy patients with meticulous lymph node dissection and thorough histologic examination, extracapsular extension has prognostic value, but N1 vs. N2 does not (Am J Surg Pathol 2005;29:89)
● Metastases to lymph nodes in 25% of invasive tumors; also to lung, liver, bone and CNS
● Often dysplasia or carcinoma in situ elsewhere in bladder; also in ureters, bladder neck, urethra, prostatic ducts and seminal vesicle
● 10 year survival only 40% for high grade tumors

Regional Lymph Nodes (pN)
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Regional lymph nodes are those within the true pelvis (hypogastric, iliac/external iliac, obturator/deep obturator, perivesical pelvic, presacral/sacral, fossa of Marcille) or common iliac lymph nodes

● NX: Lymph nodes cannot be assessed
● N0: No lymph node metastases
● N1: Single regional lymph node metastasis in the true pelvis (hypogastric, obturator, external iliac or presacral lymph node)
● N2: Multiple regional lymph node metastases in the true pelvis (hypogastric, obturator, external iliac or presacral lymph node)
● N3: Lymph node metastasis to the common iliac lymph nodes

Notes
● For node positive radical cystectomy patients with meticulous lymph node dissection and thorough histologic examination, extracapsular extension has prognostic value, but N1 vs. N2 based on size (AJCC-6th edition classification) does not (Am J Surg Pathol 2005;29:89)

Distant Metastasis (pM)
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● M0: No distant metastasis
● M1: Distant metastasis

Stage groupings and relative 5 year survival
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● 0a: Ta N0 M0 (98%)
● 0is: Tis N0 M0
● I: T1N0M0 (88%)
● II: T2a or T2b N0 M0 (63%)
● III: T3a or T3b or T4a N0 M0 (46%)
● IV: T4bN0M0 or any T, N1-N3 or M1 (15%)

Micro images
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Diagrams of cancer staging

Staging diagram


Adipose in lamina propria or muscularis mucosa

   

Tis


Involvement of von Brunn’s nests, but no stromal invasion


Urothelial CIS with microinvasion

   

pT1 tumors: lamina propria invasion


pT1 tumors: various invasive patterns


pT1 urothelial carcinoma


pT1 tumors: retraction artifact


pT1 tumors: paradoxical differentiation


pT1 tumors: invasion of muscularis mucosa but not muscularis propria

   

pT2 urothelial carcinoma


pT3 urothelial carcinoma


pT4a urothelial carcinoma


Extranodal tumor extension

Virtual slides
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pT1 bladder cancer

Additional references
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Mod Pathol 2009;22 Suppl 2:S70

End of Bladder > Miscellaneous > Staging


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