Bladder
Miscellaneous
Staging

Author: Nat Pernick, M.D. (see Authors page)

Revised: 10 August 2016, last major update December 2014

Copyright: (c) 2003-2016, PathologyOutlines.com, Inc.

PubMed Search: Staging bladder[title]
Definition / General
  • 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
  • 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)
  • 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)
    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)
  • M0: No distant metastasis
  • M1: Distant metastasis
Stage groupings and relative 5 year survival
  • 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%)
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