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Bladder cancer differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shanshan Cen, M.D. [2]

Overview

Bladder cancer must be differentiated from renal cancer, renal stones, prostate cancer, and cystitis.

Differential Diagnosis

The most common presentation of bladder cancer is hematuria; however in the advanced cases, the presentation can be bladder mass.

Bladder cancer must be differentiated from other causes of hematuria as in the below table:

Diseases Clinical manifestations Para-clinical findings Gold standard
Symptoms Physical examina
Lab Findings Diagnosi
Low back pain Fever Nausea/

Vomiting

Urinary symptoms Hypertension Pitting edema Other
Dysuria Frequency Oliguria
Glomerular diseases IgA nephropathy[1][2] (Berger nephropathy) + – – – + + + – – Biopsy:

IgA deposited in a diffuse granular pattern in the mesangium

Biopsy
    Hereditary nephritis[3][4] (Alport syndrome) – – – – – – + –
    • Cataract
    • Hearing loss
    		 Biopsy: Genetic analysis
    Post-streptococcal glomerulonephritis[5][6] +/- + – – + + + +

    Biopsy

    		Biopsy
    Focal segmental glomerular sclerosis[7][8][9] – – – – – – + + Biopsy
    • Segmental solidification in the perihilar region and peripheral areas, especially the tubular pole
    • Coarsely granular deposits -of IgM and C3
    		 Biopsy
    Rapidly progressive glomerulonephritis[10][11][12] + + + – – – + – Biopsy: Biopsy
    Lupus nephritis[13][14] – + – – – – + +
    • Foamy dark urine
    • Weight gain
    		 Biopsy,
    • Different pathologies, CLICK HERE for more information.
    		 Biopsy
    Fabry disease – – – – – – + + – Biopsy Biopsy
    Disease Low back pain Fever Nausea/

    Vomiting

    		Dysuria Frequency Oliguria Hypertension Pitting edema Other Lab Findings Diagnosis method Gold standard
    Tubulointerstitial diseases[15][16][17] + + + – – – – – Rash Biopsy: Renal biopsy
    Nephrolithiasis[18][19] + ± + ± ± ± – –
    • Radiating pain to groin
    		 Abdominal CT scan without contrast
    Reflux nephropathy (hydronephrosis) + + – – – – – + –
    Malignancy Renal cell carcinoma (RCC)[20][21] – – – – – – ± ± –
    Nephroblastoma (Wilms tumor)[22][23] – – – – – – – –

    Biopsy:

    		Biopsy
    Bladder cancer[27][28][29] – – – – ± ± – – Suprapubic pain Ultrasound, CT scan, Biopsy Biopsy
    Prostate cancer[30][31] ± – – – ± ± – – – Ultrasound, CT scan, Biopsy Biopsy
    Disease Low back pain Fever Nausea/

    Vomiting

    		Dysuria Frequency Oliguria Hypertension Pitting edema Other Lab Findings Diagnosis method Gold standard
    Familial diseases Polycystic kidney disease[32][33] + – – – – – + + Ultrasound:
    • Unilateral or bilateral cysts

    CT:

    • Hyperdense appearance,
    • Septations
    • Calcifications

    Genetic testing demonstrates:

    • Frame insertions/deletions
    • Non-canonical splice site alterations
    • Combined missense changes

    Biopsy:

    • Interstitial fibrosis
    • Tubular atrophy
    • Thickening and lamellation of tubular basement membranes
    		 Ultrasound
    Vascular diseases Renal vein thrombosis[34][35] + + + – – – – – Renal venography: Gold standard
    Wegner’s granulomatosis polyangiitis[36][37][38][39] – – – – – +/- + + CT chest:

    Biopsy:

    		Biopsy
    Henoch-Schönlein purpura[40][41] – – – – – +/- +/- + Biopsy:

    IgA deposited in a diffuse granular pattern in the mesangium

    		Renal biopsy, and clinical syndrome
    Disease Low back pain Fever Nausea/

    Vomiting

    		Dysuria Frequency Oliguria Hypertension Pitting edema Other Lab Findings Diagnosis method Gold standard
    Lower urinary tract diseases Benign prostatic hyperplasia +/- – – + + – – –
    • Nocturia
    • Other voiding symptoms
      • Slow urinary stream
      • Splitting or spraying of the urinary stream
      • Intermittent urinary stream
      • Hesitancy
      • Straining to void
      • Terminal dribbling
    • Urinalysis to rule out UTI
    • Elevated BUN/Cr
    • High PSA values
    • Urine cytology to screen for bladder cancer
    • Biopsy to rule out cancer
    		 Biopsy
    Urolithiasis[42][43][44] + +/- + + + + – – Abdominppelvic CT scan without contrast Abdominppelvic CT scan without contrast
    Disease Low back pain Fever Nausea/

    Vomiting

    		Dysuria Frequency Oliguria Hypertension Pitting edema Other Lab Findings Diagnosis method Gold standard
    Infectious diseases Pyelonephritis[45][46] + + + + + + – – CT and ultrasound: –
    Cystitis[47][48] – – – + + + – – Ultrasound:
    • Presence of gas in the bladder wall.
    • Also, help to detect the presence of a tumor or a stone.
    		 Urine culture
    Prostatitis[49][50] – + – + + + – –
    • Body aches
    		 Ultrasound:
    • Focal hypoechoic region located in the peripheral part of the prostate

    CT scan:

    		–
    Urethritis[51][52] -/- + – + + + – –

    CT scan:

    • Diffuse, circumferential urothelial wall thickening and contrast-enhancement
    • Periureteric or perinephric fat stranding.
    		 Urine culture
    Urogenital trauma Inserted bladder or ureteral catheters – – – + + + – –
    • Retrograde urethrogram (RUG)
    • Retrograde urethrogram (RUG)

    Lower abdominal mass can be classified to the gynecological and non-gynecological causes. Bladder cancer in the advanced cases can present as a bladder mass. Below table discusses lower abdominal mass causes:

    References

    1. ↑ Donadio JV, Grande JP (2002). “IgA nephropathy”. N Engl J Med. 347 (10): 738–48. doi:10.1056/NEJMra020109. PMID 12213946.
    2. ↑ Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB; et al. (2011). “The pathophysiology of IgA nephropathy”. J Am Soc Nephrol. 22 (10): 1795–803. doi:10.1681/ASN.2011050464. PMID 21949093.
    3. ↑ McCarthy PA, Maino DM (2000). “Alport syndrome: a review”. Clin Eye Vis Care. 12 (3–4): 139–150. PMID 11137428.
    4. ↑ Bodziak KA, Hammond WS, Molitoris BA (1994). “Inherited diseases of the glomerular basement membrane”. Am J Kidney Dis. 23 (4): 605–18. PMID 8154501.
    5. ↑ Yoshizawa N, Yamakami K, Fujino M, Oda T, Tamura K, Matsumoto K, Sugisaki T, Boyle MD (July 2004). “Nephritis-associated plasmin receptor and acute poststreptococcal glomerulonephritis: characterization of the antigen and associated immune response”. J. Am. Soc. Nephrol. 15 (7): 1785–93. PMID 15213266.
    6. ↑ Oda T, Yoshizawa N, Yamakami K, Tamura K, Kuroki A, Sugisaki T, Sawanobori E, Higashida K, Ohtomo Y, Hotta O, Kumagai H, Miura S (September 2010). “Localization of nephritis-associated plasmin receptor in acute poststreptococcal glomerulonephritis”. Hum. Pathol. 41 (9): 1276–85. doi:10.1016/j.humpath.2010.02.006. PMID 20708459.
    7. ↑ Kwoh C, Shannon MB, Miner JH, Shaw A (2006). “Pathogenesis of nonimmune glomerulopathies”. Annu Rev Pathol. 1: 349–74. doi:10.1146/annurev.pathol.1.110304.100119. PMID 18039119.
    8. ↑ Reidy K, Kaskel FJ (March 2007). “Pathophysiology of focal segmental glomerulosclerosis”. Pediatr. Nephrol. 22 (3): 350–4. doi:10.1007/s00467-006-0357-2. PMC 1794138. PMID 17216262.
    9. ↑ D’Agati VD, Fogo AB, Bruijn JA, Jennette JC (2004). “Pathologic classification of focal segmental glomerulosclerosis: a working proposal”. Am J Kidney Dis. 43 (2): 368–82. PMID 14750104.
    10. ↑ Couser WG (1998). “Pathogenesis of glomerular damage in glomerulonephritis”. Nephrol Dial Transplant. 13 Suppl 1: 10–5. PMID 9507491.
    11. ↑ Atkins RC, Nikolic-Paterson DJ, Song Q, Lan HY (1996). “Modulators of crescentic glomerulonephritis”. J Am Soc Nephrol. 7 (11): 2271–8. PMID 8959617.
    12. ↑ Jennette JC (March 2003). “Rapidly progressive crescentic glomerulonephritis”. Kidney Int. 63 (3): 1164–77. doi:10.1046/j.1523-1755.2003.00843.x. PMID 12631105.
    13. ↑ Schwartz N, Goilav B, Putterman C (September 2014). “The pathogenesis, diagnosis and treatment of lupus nephritis”. Curr Opin Rheumatol. 26 (5): 502–9. doi:10.1097/BOR.0000000000000089. PMC 4221732. PMID 25014039.
    14. ↑ Giannico G, Fogo AB (2013). “Lupus nephritis: is the kidney biopsy currently necessary in the management of lupus nephritis?”. Clin J Am Soc Nephrol. 8 (1): 138–45. doi:10.2215/CJN.03400412. PMID 22977215.
    15. ↑ Baker, R. J.; Pusey, C. D. (2004). “The changing profile of acute tubulointerstitial nephritis”. Nephrology Dialysis Transplantation. 19 (1): 8–11. doi:10.1093/ndt/gfg464. ISSN 0931-0509.
    16. ↑ Kelly C, Tomaszewski J, Neilson E. Immunopathogenic mechanisms of tubulointerstitial injury. In: Tisher C, Brenner B, eds, Renal Pathology: With Clinical and Functional Correlations, 2nd Edn., Vol. 1. J. B. Lippincott & Co, Philadelphia, PA, 1994; 699–722
    17. ↑ Dharmarajan TS, Yoo J, Russell RO, Boateng YA. Acute post streptococcal interstitial nephritis in an adult and review of the literature. Int Urol Nephrol 1999; 31:145
    18. ↑ Hochreiter W, Knoll T, Hess B (February 2003). “[Pathophysiology, diagnosis and conservative therapy of non-calcium kidney calculi]”. Ther Umsch (in German). 60 (2): 89–97. doi:10.1024/0040-5930.60.2.89. PMID 12649987.
    19. ↑ Trinchieri A (February 2013). “Diet and renal stone formation”. Minerva Med. 104 (1): 41–54. PMID 23392537.
    20. ↑ Cohen HT, McGovern FJ (2005). “Renal-cell carcinoma”. N Engl J Med. 353 (23): 2477–90. doi:10.1056/NEJMra043172. PMID 16339096.
    21. ↑ Leveridge MJ, Bostrom PJ, Koulouris G, Finelli A, Lawrentschuk N (June 2010). “Imaging renal cell carcinoma with ultrasonography, CT and MRI”. Nat Rev Urol. 7 (6): 311–25. doi:10.1038/nrurol.2010.63. PMID 20479778.
    22. ↑ Jolly RD, Stellwagen E, Babul J, Vodkaĭlo LV, Titov VL, Moldomusaev DM, Maianskiĭ AN (November 1975). “Mannosidosis of Angus Cattle: a prototype control program for some genetic diseases”. Adv Vet Sci Comp Med. 19 (23): 1–21. PMID 1978.
    23. ↑ Stefanowicz J, Sierota D, Balcerska A, Stoba C (2004). “[Wilms’ tumour of unfavorable histology–results of treatment with the SIOP 93-01 protocol at the Gdańsk centre. Preliminary report]”. Med Wieku Rozwoj (in Polish). 8 (2 Pt 1): 197–200. PMID 15738594.
    24. ↑ Hartman DS, Sanders RC (April 1982). “Wilms’ tumor versus neuroblastoma: usefulness of ultrasound in differentiation”. J Ultrasound Med. 1 (3): 117–22. PMID 6152936.
    25. ↑ De Campo JF (1986). “Ultrasound of Wilms’ tumor”. Pediatr Radiol. 16 (1): 21–4. PMID 3003660.
    26. ↑ Cahan LD (1985). “Failure of encephalo-duro-arterio-synangiosis procedure in moyamoya disease”. Pediatr Neurosci. 12 (1): 58–62. PMID 4080660.
    27. ↑ Pons F, Orsola A, Morote J, Bellmunt J (2011). “Variant forms of bladder cancer: basic considerations on treatment approaches”. Curr Oncol Rep. 13 (3): 216–21. doi:10.1007/s11912-011-0161-4. PMID 21360040.
    28. ↑ Metts MC, Metts JC, Milito SJ, Thomas CR (June 2000). “Bladder cancer: a review of diagnosis and management”. J Natl Med Assoc. 92 (6): 285–94. PMC 2640522. PMID 10918764.
    29. ↑ Rom M, Kuehhas FE, Djavan B (2007). “New findings in bladder and prostate cancer: highlights of the 22nd annual congress of the European association of urology, march 21-24, 2007, berlin, Germany”. Rev Urol. 9 (4): 214–9. PMC 2199502. PMID 18231618.
    30. ↑ Chung SD, Liu SP, Lin HC (2013). “Association between prostate cancer and urinary calculi: a population-based study”. PLoS ONE. 8 (2): e57743. doi:10.1371/journal.pone.0057743. PMC 3581486. PMID 23451265.
    31. ↑ Rom M, Kuehhas FE, Djavan B (2007). “New findings in bladder and prostate cancer: highlights of the 22nd annual congress of the European association of urology, march 21-24, 2007, berlin, Germany”. Rev Urol. 9 (4): 214–9. PMC 2199502. PMID 18231618.
    32. ↑ Gabow PA (July 1993). “Autosomal dominant polycystic kidney disease”. N. Engl. J. Med. 329 (5): 332–42. doi:10.1056/NEJM199307293290508. PMID 8321262.
    33. ↑ Adeva M, El-Youssef M, Rossetti S, Kamath PS, Kubly V, Consugar MB, Milliner DM, King BF, Torres VE, Harris PC (January 2006). “Clinical and molecular characterization defines a broadened spectrum of autosomal recessive polycystic kidney disease (ARPKD)”. Medicine (Baltimore). 85 (1): 1–21. doi:10.1097/01.md.0000200165.90373.9a. PMID 16523049.
    34. ↑ U. Kuhlmann, J. Steurer, A. Bollinger, G. Pouliadis, J. Briner & W. Siegenthaler (1981). “[Incidence and clinical significance of thromboses and thrombo-embolic complications in nephrotic syndrome patients]”. Schweizerische medizinische Wochenschrift. 111 (27–28): 1034–1040. PMID 7268357. Unknown parameter |month= ignored (help)
    35. ↑ F. Llach, S. Papper & S. G. Massry (1980). “The clinical spectrum of renal vein thrombosis: acute and chronic”. The American journal of medicine. 69 (6): 819–827. PMID 7446547. Unknown parameter |month= ignored (help)
    36. ↑ Pagnoux C (2016). “Updates in ANCA-associated vasculitis”. Eur J Rheumatol. 3 (3): 122–133. doi:10.5152/eurjrheum.2015.0043. PMID 27733943.
    37. ↑ Lee KS, Kim TS, Fujimoto K, Moriya H, Watanabe H, Tateishi U, Ashizawa K, Johkoh T, Kim EA, Kwon OJ (2003). “Thoracic manifestation of Wegener’s granulomatosis: CT findings in 30 patients”. Eur Radiol. 13 (1): 43–51. doi:10.1007/s00330-002-1422-2. PMID 12541109.
    38. ↑ Kallenberg CG, Heeringa P, Stegeman CA (2006). “Mechanisms of Disease: pathogenesis and treatment of ANCA-associated vasculitides”. Nat Clin Pract Rheumatol. 2 (12): 661–70. doi:10.1038/ncprheum0355. PMID 17133251.
    39. ↑ Jennette JC, Falk RJ (November 1997). “Small-vessel vasculitis”. N. Engl. J. Med. 337 (21): 1512–23. doi:10.1056/NEJM199711203372106. PMID 9366584.
    40. ↑ Jennette JC, Falk RJ (November 1997). “Small-vessel vasculitis”. N. Engl. J. Med. 337 (21): 1512–23. doi:10.1056/NEJM199711203372106. PMID 9366584.
    41. ↑ Chen JY, Mao JH (February 2015). “Henoch-Schönlein purpura nephritis in children: incidence, pathogenesis and management”. World J Pediatr. 11 (1): 29–34. doi:10.1007/s12519-014-0534-5. PMID 25557596.
    42. ↑ Hochreiter W, Knoll T, Hess B (February 2003). “[Pathophysiology, diagnosis and conservative therapy of non-calcium kidney calculi]”. Ther Umsch (in German). 60 (2): 89–97. doi:10.1024/0040-5930.60.2.89. PMID 12649987.
    43. ↑ Flannigan R, Choy WH, Chew B, Lange D (June 2014). “Renal struvite stones–pathogenesis, microbiology, and management strategies”. Nat Rev Urol. 11 (6): 333–41. doi:10.1038/nrurol.2014.99. PMID 24818849.
    44. ↑ Pereira DJ, Schoolwerth AC, Pais VM (March 2015). “Cystinuria: current concepts and future directions”. Clin. Nephrol. 83 (3): 138–46. PMID 25685869.
    45. ↑ Pereira DJ, Schoolwerth AC, Pais VM (March 2015). “Cystinuria: current concepts and future directions”. Clin. Nephrol. 83 (3): 138–46. PMID 25685869.
    46. ↑ Rosen DA, Hooton TM, Stamm WE, Humphrey PA, Hultgren SJ (2007). “Detection of intracellular bacterial communities in human urinary tract infection”. PLoS Med. 4 (12): e329. doi:10.1371/journal.pmed.0040329. PMC 2140087. PMID 18092884.
    47. ↑ Franco AV (2005). “Recurrent urinary tract infections”. Best Pract Res Clin Obstet Gynaecol. 19 (6): 861–73. doi:10.1016/j.bpobgyn.2005.08.003. PMID 16298166.
    48. ↑ Franco AV (2005). “Recurrent urinary tract infections”. Best Pract Res Clin Obstet Gynaecol. 19 (6): 861–73. doi:10.1016/j.bpobgyn.2005.08.003. PMID 16298166.
    49. ↑ John N. Krieger, Ulrich Dobrindt, Donald E. Riley & Eric Oswald (2011). “Acute Escherichia coli prostatitis in previously health young men: bacterial virulence factors, antimicrobial resistance, and clinical outcomes”. Urology. 77 (6): 1420–1425. doi:10.1016/j.urology.2010.12.059. PMID 21459419. Unknown parameter |month= ignored (help)
    50. ↑ Sharp VJ, Takacs EB, Powell CR (2010). “Prostatitis: diagnosis and treatment”. Am Fam Physician. 82 (4): 397–406. PMID 20704171.
    51. ↑ McNagny SE, Parker RM, Zenilman JM, Lewis JS (1992). “Urinary leukocyte esterase test: a screening method for the detection of asymptomatic chlamydial and gonococcal infections in men”. J. Infect. Dis. 165 (3): 573–6. PMID 1538163.
    52. ↑ Brill JR (2010). “Diagnosis and treatment of urethritis in men”. Am Fam Physician. 81 (7): 873–8. PMID 20353145.

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