Bladder & urothelial tract

• All carcinomas of the bladder are covered by this staging system
• The following topics are not covered: urachal carcinoma, paraganglioma, sarcoma or lymphoma

• pTX: cannot be assessed
• pT0: no evidence of primary tumor
• pTa: noninvasive papillary carcinoma
• pTis: carcinoma in situ
• pT1: invades lamina propria
• pT2a: invades inner half of muscularis propria
• pT2b: invades outer half of muscularis propria
• pT3a: microscopically invades perivesical tissue
• pT3b: macroscopically invades perivesical tissue
• pT4a: directly invades prostatic stroma, seminal vesicles, uterus or vagina
• pT4b: directly invades pelvic wall or abdominal wall

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 (see Histology)
• Has nests, clusters or single tumor cells, sometimes with prominent retraction artifact (mimics lymphovascular invasion)
• Often has desmoplastic or inflammatory stromal response and absent or irregular basement membrane (not seen with noninvasive low grade papillary carcinoma with inverted pattern)
• Tumor cells often have abundant eosinophilic cytoplasm at advancing edge (paradoxical differentiation) but have enlarged, malignant appearing nuclei
• If tumor cells hug the mucosa, they should be more anaplastic than benign mucosal cells
• Pitfalls include tangential sectioning, poor specimen orientation, inflammation, thermal injury, deceptively bland cytology and pseudoinvasive nests of nonneoplastic proliferative urothelial cells (Pathology 2003;35:484)
• Subcategorization of pT1 based on muscularis mucosae is difficult and may not correlate with progression (Mod Pathol 1996;9:1035, Arch Pathol Lab Med 2022;146:1131)
• Other strategies for the subcategorization of pT1 (such as based on depth of invasion) have been proposed but are not a part of AJCC staging (Arch Pathol Lab Med 2022;146:1131)
• pTa cases may actually be invasive when studied by electron microscopy; significance is unclear (Am J Clin Pathol 2003;120:188)
• Invasion of lamina propria (pT1) is not as clinically crucial as invasion of muscularis propria (pT2)

Muscularis propria (pT2)
• Muscularis propria is thick aggregated muscle bundles of detrusor muscle; must distinguish from hypertrophic muscularis mucosae (Am J Surg Pathol 2007;31:1420)
• Muscularis propria presence should be specified in transurethral resections and cold cup biopsies
• Muscularis propria invasion prompts definitive therapy, typically cystectomy with or without neoadjuvant therapy
• Can use muscle markers such as desmin or SMA to highlight muscle and keratins such as AE1 / AE3 to highlight carcinoma in challenging cases
• Difficult to subcategorize as pT2a or pT2b unless the pathologist has full thickness bladder wall and well oriented section such as in a cystectomy specimen and thus would not be documented in biopsy or transurethral resection of bladder tumor (TURBT) specimens

Perivesical fat (pT3)
• Perivesicular 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 classification as pT3 due to tumor infiltration of adipose within the lamina propria, particularly in TURBT specimens (Am J Surg Pathol 2000;24:1286)
• Note that the gross prospector must document the impression of perivesicular adipose invasion to allow for subcategorization as pT3a versus pT3b as pT3b requires macroscopic invasion
• Many cases lack the gross impression of perivesicular adipose invasion and thus cannot be accurately classified (Hum Pathol 2017;61:190)
• Subcategorization into pT3a and pT3b has an uncertain prognostic impact with some studies showing no difference in outcome (Virchows Arch 2012;461:467)

Prostate gland (pT4 versus pT2)
• If carcinoma of the bladder transmurally invades through the bladder wall and into the prostatic stroma, the tumor is designated as pT4a
• If carcinoma of the bladder colonizes the prostatic urethra via in situ spread and then invades the underlying prostatic stroma, it is not pT4a (but can be considered a separate tumor of the prostatic urethra with a pT2 designation; see Staging of the prostatic urethra)
• Survival of patient with pT4 tumors is poor (median: < 1 year; 1.5 year survival: < 15%) (Virchows Arch 2012;461:467)

• pNX: cannot be assessed
• pN0: no regional lymph node metastasis
• pN1: metastasis in 1 true pelvic lymph node
• pN2: metastasis in greater than 1 true pelvic lymph node
• pN3: metastasis in common iliac lymph node

Notes:
• Regional lymph nodes are the true pelvic lymph nodes, which include the following
  • Perivesical
  • Hypogastric / deep obturator / fossa of Marcille / internal iliac
  • Obturator
  • External iliac
  • Presacral / sacral / lateral sacral / sacral promontory
• Be aware that neoadjuvant therapy may result in organ confined tumor or no residual tumor (ypT0 - 2a) yet still harbor lymph node metastases (10% in one study); this phenomenon was not observed in untreated cases (Virchows Arch 2012;461:467)
• Survival of patient with pN1 - 3 tumors is poor (median: < 1 year; 1.5 year survival: 30%) (Virchows Arch 2012;461:467)

• Urothelial carcinoma
  • LG: low grade
  • HG: high grade
• Squamous cell carcinoma and adenocarcinoma
  • GX: cannot be assessed
  • G1: well differentiated
  • G2: moderately differentiated
  • G3: poorly differentiated

Notes:

• Clinical management with respect to intravesicular bacillus Calmette-Guérin (BCG) / chemotherapy and frequency of surveillance differs for high grade versus low grade tumors

Contributed by Debra L. Zynger, M.D.

Contributed by Debra L. Zynger, M.D.

Treatment with cystectomy is typical if there is invasion into which of the following structures?

1. Lamina propria
2. Muscularis mucosae
3. Muscularis propria
4. Urothelium

C. Muscularis propria. Muscularis propria is correct because invasion of the muscularis propria of the bladder is managed via cystectomy if the patient is a surgical candidate. Neoadjuvant chemotherapy can be given prior to surgery for suitable candidates. Answers A, B and D are incorrect because cystectomy is not typical for noninvasive tumors, tumors invading the lamina propria or tumors invading the muscularis mucosae, which is wispy muscle within the lamina propria. However, cystectomy is a management option for BCG refractory tumors that are noninvasive or invade into the lamina propria.

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Reference: Staging-bladder carcinoma