You are here: Urology Textbook > Bladder > Bladder cancer Pathology

Bladder cancer (2/7): Tumor Stages and Pathology

Review Literature: EAU guidelines superficial bladder cancer. EAU guidelines of muscle-invasive and metastatic bladder cancer. German S3 guidelines bladder carcinoma Harnblasenkarzinom.

• Bladder carcinoma: Definition, Epidemiology and Etiology
• Bladder carcinoma: Pathology and TNM tumor stages
• Bladder carcinoma: Symptoms and Diagnosis
• Bladder carcinoma: Surgical Treatment
• Bladder carcinoma: Chemotherapy and Immunotherapy of Metastases

TNM Tumor Staging of Bladder Cancer

Superficial bladder carcinoma:

• Ta: noninvasive papillary tumor
• Tis: flat high-grade tumor without polarity and without invasion
• T1: Tumor with infiltration of the subepithelial connective tissue (lamina submucosa)

T2: Tumor invades muscle (tunica muscularis).

• T2a: infiltration of the inner half of the lamina muscularis
• T2b: infiltration of the outer half of the lamina muscularis

T3: Tumor invades perivesical tissue.

• T3a: microscopic perivesical infiltration
• T3b: macroscopic perivesical infiltration

T4: Tumor invades adjacent organs.

• T4a: infiltration of prostate, uterus or vagina
• T4b: infiltration of the pelvic or abdominal wall

N: Lymph node involvement.

• N0: no regional lymph node metastasis
• N1: solitary regional lymph node metastasis (in the true pelvis hypogastric, obturator, external iliac, or presacral).
• N2: multiple regional lymph node metastases (in the true pelvis hypogastric, obturator, external iliac, or presacral).
• N3: metastases in common iliac lymph node(s).

M: Distant metastasis.

• M0: no distant metastasis
• M1a: metastases in non-regional lymph nodes
• M1b: other distant metastases

G: Grading.

• Low-grade bladder cancer: corresponding to G1 (well differentiated) and partly to G2 (intermediate differentiated) of the WHO 1973 classification
• High-grade bladder cancer: corresponding to partly G2 and G3 (poor to undifferentiated) of the WHO 1973 classification

Macroscopic Pathology of Bladder Cancer

Localization:

Bladder cancer most commonly begins at the side walls or posterior wall in 70%. Less common locations are bladder neck and trigone (20%) or anterior wall in 10%. 50% are multifocal tumors.

Growth pattern:

The initial growth pattern is either flat or exophytic. In advanced disease, the tumor infiltrates the detrusor muscle and adjacent organs [Fig. advanced bladder cancer].

Lymph node metastasis:

Lymphogenic metastases may affect the iliac, obturator, presacral, and aortic lymph node groups. The probability of lymph node metastasis is 5% for pT1 tumors, 30% for pT2, and 60% for pT3b tumors. The tumor manifestation at the bladder trigone is associated with a higher risk of lymph node metastases (HR 1.83) and increased mortality (HR 1.68).

Distant metastases:

Bone, liver, lung, peritoneum, and brain. The risk for distant metastasis is 50% for locally advanced tumors (≥ stage pT3b).

Microscopic Pathology (Histology)

Over 95% of bladder cancers are urothelial carcinomas (synonym: transitional cell carcinoma), 2% are squamous cell carcinomas and 1% are adenocarcinomas. Urothelial carcinoma is differentiated in the current WHO classification (2016) into infiltrative tumors and non-invasive tumors (Humphrey et al., 2016). The reproducibility of the pathological staging has been shown to be highly variable in comparative studies: T-stage 50–80% agreement, grading 60–75% agreement (Meijden et al., 2000).

Infiltrative urothelial carcinoma:

Over 95% of infiltrative tumors are high-grade lesions. Up to 33% of the infiltrative tumors show additional growth patterns in addition to the "normal type": nested variant, microcystic, micropapillary, lymphoepithelioma-like, plasmacytoid, seal-ring cell, sacromatoid, giant cell, lipid-rich, clear cell or low differentiated.

Non-invasive urothelial carcinoma:

Non-invasive urothelial carcinoma can be divided into flat and papillary lesions, both types can exhibit a wide spectrum of atypia (from reactive to highly malignant).

• Urothelial dysplasia: flat atypical epithelial with mild loss of polarity, normal thickness, benign.
• Urothelial papilloma: papillary tumor with normal thickness urothelium, sharply defined and intact superficial umbrella layer, no mitotic activity. Benign lesion.
• Inverted urothelial papilloma: see above, the papillary tumor growth into deeper bladder wall layer, benign.
• Papillary urothelial neoplasm of low malignant potential (PUNLMP): increasingly nuclear atypia, interupted superficial umbrella layer, increased urothelial cell layers. A recurrence of a PUNLMP lesion is possible, but the risk of tumor progression is low.
• Papillary urothelial carcinoma: palisading predominantly present, less or more nuclear atypia depends on grading (low-grade or high-grade), superficial umbrella layer often not present, increased urothelial cell layers. Malignant lesion.
• Carcinoma in situ: prominent nuclear atypia (high-grade lesion), disorders of polarity, mitotic activity, high proliferation (MIB-1). Malignant.

Rare Carcinomas of the Urinary Bladder

2% of bladder carcinoma are squamous cell carcinoma and 1% are adenocarcinoma, other types are infrequent.

Squamous cell carcinoma:

Risk factors for squamous cell carcinoma are chronic infections, schistosomiasis, or chronic indwelling bladder catheter. Prognosis is comparable to transitional cell carcinoma.

Adenocarcinoma:

Either primary adenocarcinoma from the bladder, often from the urachus. Secondary adenocarcinoma from urinary diversion with bowel segments or from bladder metastasis.

Neoplasms of the urachus:

Neoplasms of the urachus are located at the bladder roof or arise from the extravesical part of the urachus. Adenocarcinoma is the most common type of this rare neoplasia, but transitional cell carcinoma or sarcoma is also possible.

Small-cell carcinoma of the bladder:

The bladder is the most common extrapulmonary manifestation of small-cell carcinoma. The prognosis is poor.

Other rare cancers:

Hepatoid adenocarcinoma, lymphoepithelial carcinoma, carcinoid tumors (neuroendocrine tumors), and germ cell tumors.

Nonepithelial tumors of the urinary bladder

Benign, nonepithelial tumors:

Leiomyoma, rhabdomyoma, hemangioma, lipoma, and neurofibroma.

Sarcomas:

Please see section sarcoma of the bladder

Primary malignant lymphoma:

Primary bladder lymphoma arises from the mucosa-associated lymphoid tissue (MALT) and is associated with an excellent prognosis. Secondary bladder lymphoma is found in patients with a history of malignant lymphoma.

Pheochromocytoma:

Pheochromocytoma of the bladder are tumors from the paravesical ganglia. Paroxysmal hypertension may be associated with micturition.

Metastasis of the urinary bladder

Infiltrative growth of tumors into the bladder wall from female genital organs, prostate, or colon is more common than distant metastases caused by malignant melanoma, gastric cancer, breast cancer, or lung cancer.

References

Abol-Enein, H. Infection: is it a cause of bladder cancer?
Scand J Urol Nephrol Suppl, 2008, 79-84.

Amin und Young 1997 AMIN, M. B. ; YOUNG, R. H.: Primary carcinomas of the urethra.
In: Semin Diagn Pathol
14 (1997), Nr. 2, S. 147–60

Babjuk, M.; Burger, M.; Compérat, E.; Gonter, P.; Mostafid, A.; Palou, J.; van Rhijn, B.; Rouprêt, M.; Shariata, S.; Sylvester, R. & Zigeuner, R.
Non-muscle-invasive Bladder CancerEAU Guidelines, 2020 https://uroweb.org/guidelines/non-muscle-invasive-bladder-cancer/

Brinkman, M. & Zeegers, M. P. Nutrition, total fluid and bladder cancer.
Scand J Urol Nephrol Suppl, 2008, 25-36.

Cohn, J. A.; Vekhter, B.; Lyttle, C.; Steinberg, G. D. & Large, M. C. Sex disparities in diagnosis of bladder cancer after initial presentation with hematuria: a nationwide claims-based investigation.
Cancer, 2014, 120, 555-561

DGU; DKG; DKG & Leitlinienprogramm Onkologie S3-Leitlinie (Langfassung): Früherkennung, Diagnose, Therapie und Nachsorge des Harnblasenkarzinoms. https://www.leitlinienprogramm-onkologie.de/leitlinien/harnblasenkarzinom/

Helpap und Kollermann 2000 HELPAP, B. ; KOLLERMANN, J.: [Revisions in the WHO histological classification of urothelial bladder tumors and flat urothelial lesions].
In: Pathologe
21 (2000), Nr. 3, S. 211–7

IARC (2004) Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 83. Tobacco Smoke and Involuntary Smoking. World Health Organization.

Kalble 2001 KALBLE, T.: [Etiopathology, risk factors, environmental influences and epidemiology of bladder cancer].
In: Urologe A
40 (2001), Nr. 6, S. 447–50

Kataja und Pavlidis 2005 KATAJA, V. V. ; PAVLIDIS, N.: ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of invasive bladder cancer.
In: Ann Oncol
16 Suppl 1 (2005), S. i43–4

Krieg und Hoffman 1999 KRIEG, R. ; HOFFMAN, R.: Current management of unusual genitourinary cancers. Part 2: Urethral cancer.
In: Oncology (Williston Park)
13 (1999), Nr. 11, S. 1511–7, 1520; discussion 1523–4

Lammers, R. J. M.; Witjes, W. P. J.; Hendricksen, K.; Caris, C. T. M.; Janzing-Pastors, M. H. C. & Witjes, J. A. Smoking status is a risk factor for recurrence after transurethral resection of non-muscle-invasive bladder cancer.
Eur Urol, 2011, 60, 713-720

Lampel und Thuroff 1998a LAMPEL, A. ; THUROFF, J. W.: [Bladder carcinoma 1: Radical cystectomy, neoadjuvant and adjuvant therapy modalities].
In: Urologe A
37 (1998), Nr. 1, S. 93–101

Lampel und Thuroff 1998b LAMPEL, A. ; THUROFF, J. W.: [Bladder carcinoma. 2: Urinary diversion].
In: Urologe A
37 (1998), Nr. 2, S. W207–20

Leppert u.a. 2006 LEPPERT, J. T. ; SHVARTS, O. ; KAWAOKA, K. ; LIEBERMAN, R. ; BELLDEGRUN, A. S. ; PANTUCK, A. J.: Prevention of bladder cancer: a review.
In: Eur Urol
49 (2006), Nr. 2, S. 226–34

Liu, S.; Yang, T.; Na, R.; Hu, M.; Zhang, L.; Fu, Y.; Jiang, H. & Ding, Q.
The impact of female gender on bladder cancer-specific death risk after radical cystectomy: a meta-analysis of 27,912 patients. International urology and nephrology, 2015, 47, 951-958

Michaud u.a. 1999 MICHAUD, D. S. ; SPIEGELMAN, D. ; CLINTON, S. K. ; RIMM, E. B. ; CURHAN, G. C. ; WILLETT, W. C. ; GIOVANNUCCI, E. L.: Fluid intake and the risk of bladder cancer in men.
In: N Engl J Med
340 (1999), Nr. 18, S. 1390–7

Plna und Hemminki 2001 PLNA, K. ; HEMMINKI, K.: Familial bladder cancer in the National Swedish Family Cancer Database.
In: J Urol
166 (2001), Nr. 6, S. 2129–33

Rajan u.a. 1993 RAJAN, N. ; TUCCI, P. ; MALLOUH, C. ; CHOUDHURY, M.: Carcinoma in female urethral diverticulum: case reports and review of management.
In: J Urol
150 (1993), Nr. 6, S. 1911–4

Robert-Koch-Institut (2015) Krebs in Deutschland 2011/2012. www.krebsdaten.de

Stein u.a. 2001 STEIN, J. P. ; LIESKOVSKY, G. ; COTE, R. ; GROSHEN, S. ; FENG, A. C. ; BOYD, S. ; SKINNER, E. ; BOCHNER, B. ; THANGATHURAI, D. ; MIKHAIL, M. ; RAGHAVAN, D. ; SKINNER, D. G.: Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1054 patients.
In: J Clin Oncol
19 (2001), Nr. 3, S. 666–75

Weissbach 2001 WEISSBACH, L.: [Palliation of urothelial carcinoma of the bladder].
In: Urologe A
40 (2001), Nr. 6, S. 475–9

Witjes, J.; Compérat, E.; Cowan, N.; Gakis, G.; Hernánde, V.; Lebret, T.; Lorch, A.; van der Heijden, A. & Ribal, M. Muscle-invasive and Metastatic Bladder Cancer
EAU Guidelines, 2020 https://uroweb.org/guidelines/bladder-cancer-muscle-invasive-and-metastatic/

  Deutsche Version: Pathologie und TNM Tumor Staging des Harnblasenkarzinoms