Pathology of Urothelial Malignancies of the Upper Urinary Tract

  • Sabina Hajiyeva
  • Minghao ZhongEmail author


Summary: The upper urinary tract includes renal pelvis and ureter which are muscular conduits lined by urothelium. The upper urinary tract may be involved by distinct entities which have different prognosis and diverse treatment options. Here, we focus on noninvasive urothelial carcinoma: low- and high-grade papillary UC, urothelial carcinoma in situ and noninvasive urothelial carcinoma with glandular differentiation; upper urinary tract urothelial carcinoma with intratubular spread; invasive urothelial carcinoma: different differentiation components and different variants; other non-urothelial malignancy: inflammatory myofibroblastic tumor, lymphoma, and rhabdoid tumor; Non-neoplastic tumor-like conditions: ureteropelvic junction (UPJ) obstruction and immunoglobulin G4-related kidney disease


Upper urinary tract Urothelial carcinoma Invasion Differentiation Variants Tumor mimicker 


  1. 1.
    Melzer M, Braf Z, Beyar H, Rakowszczyk M. Primary tumors of the renal pelvis and ureter. Int Surg. 1972;57(9):699–702 Epub 1972/09/01.PubMedGoogle Scholar
  2. 2.
    Patel N, Arya M, Muneer A, Powles T, Sullivan M, Hines J, et al. Molecular aspects of upper tract urothelial carcinoma. Urologic oncology. 2014;32(1):28 e11-20 Epub 2013/02/23. doi: 10.1016/j.urolonc.2012.10.002. PubMed PMID: 23428541.CrossRefGoogle Scholar
  3. 3.
    Green DA, Rink M, Xylinas E, Matin SF, Stenzl A, Roupret M, et al. Urothelial carcinoma of the bladder and the upper tract: disparate twins. J Urology. 2013;189(4):1214–21. Epub 2012/10/02. doi: 10.1016/j.juro.2012.05.079. PubMed PMID: 23023150.CrossRefPubMedGoogle Scholar
  4. 4.
    Azemar MD, Comperat E, Richard F, Cussenot O, Roupret M. Bladder recurrence after surgery for upper urinary tract urothelial cell carcinoma: frequency, risk factors, and surveillance. Urologic Oncology. 2011;29(2):130–6. Epub 2009/09/19. doi: 10.1016/j.urolonc.2009.06.003. PubMed PMID: 19762256.CrossRefPubMedGoogle Scholar
  5. 5.
    Leow JJ, Orsola A, Chang SL, Bellmunt J. A contemporary review of management and prognostic factors of upper tract urothelial carcinoma. Cancer Treatment Rev. 2015;41(4):310–9. Epub 2015/03/05. doi: 10.1016/j.ctrv.2015.02.006. PubMed PMID: 25736461.CrossRefPubMedGoogle Scholar
  6. 6.
    Cosentino M, Palou J, Gaya JM, Breda A, Rodriguez-Faba O, Villavicencio-Mavrich H. Upper urinary tract urothelial cell carcinoma: location as a predictive factor for concomitant bladder carcinoma. World J Urology. 2013;31(1):141–5. Epub 2012/05/04. doi: 10.1007/s00345-012-0877-2. PubMed PMID: 22552732.CrossRefPubMedGoogle Scholar
  7. 7.
    Hofstadter F, Delgado R, Jakse G, Judmaier W. Urothelial dysplasia and carcinoma in situ of the bladder. Cancer. 1986;57(2):356–61 Epub 1986/01/15.CrossRefPubMedGoogle Scholar
  8. 8.
    Humphrey PA. Urothelial carcinoma in situ of the bladder. J Urology. 2012;187(3):1057–8. Epub 2012/01/24. doi: 10.1016/j.juro.2011.12.020. PubMed PMID: 22265997.CrossRefPubMedGoogle Scholar
  9. 9.
    Rojas CP, Castle SM, Llanos CA, Santos Cortes JA, Bird V, Rodriguez S, et al. Low biopsy volume in ureteroscopy does not affect tumor biopsy grading in upper tract urothelial carcinoma. Urologic Oncology. 2013;31(8):1696–700. Epub 2012/07/24. doi: 10.1016/j.urolonc.2012.05.010. PubMed PMID: 22819696.CrossRefPubMedGoogle Scholar
  10. 10.
    Mazzucchelli R, Scarpelli M, Galosi AB, Di Primio R, Lopez-Beltran A, Cheng L, et al. Pathology of upper tract urothelial carcinoma with emphasis on staging. Int J Immunopath Pharmacol. 2014;27(4):509–16 Epub 2015/01/13.CrossRefGoogle Scholar
  11. 11.
    Gillan A, El-Mokadem I, Rai B, Lang S, Alcorn J, Shams Ud Din A, et al. Carcinoma in situ is significantly underdetected by prenephroureterectomy ureteroscopy in the management of upper tract urothelial cancers. BioMed Res Int. 2015;2015:547586. Epub 2015/02/06. doi: 10.1155/2015/547586. PubMed PMID: 25654112; PubMed Central PMCID: PMC4310489.CrossRefGoogle Scholar
  12. 12.
    Otto W, Shariat SF, Fritsche HM, Gupta A, Matsumoto K, Kassouf W, et al. Concomitant carcinoma in situ as an independent prognostic parameter for recurrence and survival in upper tract urothelial carcinoma: a multicenter analysis of 772 patients. World J Urology. 2011;29(4):487–94. Epub 2011/01/21. doi: 10.1007/s00345-011-0645-8. PubMed PMID: 21249372.CrossRefPubMedGoogle Scholar
  13. 13.
    Sarungbam J, Kurtis B, Phillips J, Cai D, Zhang D, Humayun I, et al. Upper urinary tract urothelial carcinoma with intratubular spread. Am J Clini Experimental urology. 2014;2(2):102–10. Epub 2014/11/07. PubMed PMID: 25374911; PubMed Central PMCID: PMC4219305.Google Scholar
  14. 14.
    Gupta R, Paner GP, Amin MB. Neoplasms of the upper urinary tract: a review with focus on urothelial carcinoma of the pelvicalyceal system and aspects related to its diagnosis and reporting. Advances in Anatomic Pathology. 2008;15(3):127–39. Epub 2008/04/25. doi: 10.1097/PAP.0b013e31817145a9. PubMed PMID: 18434765.CrossRefPubMedGoogle Scholar
  15. 15.
    Raman JD, Ng CK, Scherr DS, Margulis V, Lotan Y, Bensalah K, et al. Impact of tumor location on prognosis for patients with upper tract urothelial carcinoma managed by radical nephroureterectomy. European Urology. 2010;57(6):1072–9. Epub 2009/07/22. doi: 10.1016/j.eururo.2009.07.002. PubMed PMID: 19619934.CrossRefPubMedGoogle Scholar
  16. 16.
    Yates DR, Catto JW. Distinct patterns and behaviour of urothelial carcinoma with respect to anatomical location: how molecular biomarkers can augment clinico-pathological predictors in upper urinary tract tumours. W J Urology. 2013;31(1):21–9. Epub 2012/09/19. doi: 10.1007/s00345-012-0946-6. PubMed PMID: 22986906.CrossRefPubMedGoogle Scholar
  17. 17.
    Sakano S, Matsuyama H, Kamiryo Y, Hayashida S, Yamamoto N, Kaneda Y, et al. Impact of variant histology on disease aggressiveness and outcome after nephroureterectomy in Japanese patients with upper tract urothelial carcinoma. Int J Clini Oncology. 2015;20(2):362–8. Epub 2014/06/27. doi: 10.1007/s10147-014-0721-3. PubMed PMID: 24964974.CrossRefPubMedGoogle Scholar
  18. 18.
    Hsieh MC, Sung MT, Chiang PH, Huang CH, Tang Y, Su YL. The Prognostic Impact of Histopathological Variants in Patients with Advanced Urothelial Carcinoma. PloS one. 2015;10(6):e0129268. Epub 2015/06/27. doi: 10.1371/journal.pone.0129268. PubMed PMID: 26114748; PubMed Central PMCID: PMC4482548.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Rink M, Robinson BD, Green DA, Cha EK, Hansen J, Comploj E, et al. Impact of histological variants on clinical outcomes of patients with upper urinary tract urothelial carcinoma. J urology. 2012;188(2):398–404. Epub 2012/06/16. doi: 10.1016/j.juro.2012.04.009. PubMed PMID: 22698626.CrossRefPubMedGoogle Scholar
  20. 20.
    Makise N, Morikawa T, Kawai T, Nakagawa T, Kume H, Homma Y, et al. Squamous differentiation and prognosis in upper urinary tract urothelial carcinoma. International journal of clinical and experimental pathology. 2015;8(6):7203–9. Epub 2015/08/12. PubMed PMID: 26261615; PubMed Central PMCID: PMC4525949.Google Scholar
  21. 21.
    Lee YJ, Moon KC, Jeong CW, Kwak C, Kim HH, Ku JH. Impact of squamous and glandular differentiation on oncologic outcomes in upper and lower tract urothelial carcinoma. PloS one. 2014;9(9):e107027. Epub 2014/09/06. doi: 10.1371/journal.pone.0107027. PubMed PMID: 25191845; PubMed Central PMCID: PMC4156382.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Shanks JH, Iczkowski KA. Divergent differentiation in urothelial carcinoma and other bladder cancer subtypes with selected mimics. Histopathology. 2009;54(7):885–900. Epub 2009/01/31. doi: 10.1111/j.1365-2559.2008.03167.x. PubMed PMID: 19178589.CrossRefPubMedGoogle Scholar
  23. 23.
    Ouzzane A, Ghoneim TP, Udo K, Verhasselt-Crinquette M, Puech P, Betrouni N, et al. Small cell carcinoma of the upper urinary tract (UUT-SCC): report of a rare entity and systematic review of the literature. Cancer Treatment Rev. 2011;37(5):366–72. Epub 2011/01/25. doi: 10.1016/j.ctrv.2010.12.005. PubMed PMID: 21257269.CrossRefPubMedGoogle Scholar
  24. 24.
    Koga F, Yokoyama M, Fukushima H. Small cell carcinoma of the urinary bladder: a contemporary review with a special focus on bladder-sparing treatments. Expert Rev anticancer therapy. 2013;13(11):1269–79. Epub 2013/10/31. doi: 10.1586/14737140.2013.851605. PubMed PMID: 24168010.CrossRefPubMedGoogle Scholar
  25. 25.
    Loghin A, Chibelean C, Orsolya M, Nechifor-Boila A, Borda A. Micropapillary urothelial carcinoma: an aggressive variant of urothelial carcinoma. Romanian journal of morphology and embryology =. Revue roumaine de morphologie et embryologie. 2014;55(3):939–45 Epub 2014/10/21.PubMedGoogle Scholar
  26. 26.
    Porten SP, Willis D, Kamat AM. Variant histology: role in management and prognosis of nonmuscle invasive bladder cancer. Current Opinion Urology. 2014;24(5):517–23. Epub 2014/06/13. doi: 10.1097/MOU.0000000000000089. PubMed PMID: 24921905.CrossRefPubMedGoogle Scholar
  27. 27.
    Venyo AK. Nested variant of urothelial carcinoma. Advances in urology. 2014;2014:192720. Epub 2014/03/04. doi: 10.1155/2014/192720. PubMed PMID: 24587796; PubMed Central PMCID: PMC3920611.CrossRefGoogle Scholar
  28. 28.
    Montgomery EA, Shuster DD, Burkart AL, Esteban JM, Sgrignoli A, Elwood L, et al. Inflammatory myofibroblastic tumors of the urinary tract: a clinicopathologic study of 46 cases, including a malignant example inflammatory fibrosarcoma and a subset associated with high-grade urothelial carcinoma. Am J Sur Pathology. 2006;30(12):1502–12. Epub 2006/11/24. doi: 10.1097/01.pas.0000213280.35413.1b. PubMed PMID: 17122505.CrossRefPubMedGoogle Scholar
  29. 29.
    Bozas G, Tassidou A, Moulopoulos LA, Constandinidis C, Bamias A, Dimopoulos MA. Non-Hodgkin’s lymphoma of the renal pelvis. Clini Lymphoma Myeloma. 2006;6(5):404–6. Epub 2006/04/28. doi: 10.3816/CLM.2006.n.018. PubMed PMID: 16640818.CrossRefPubMedGoogle Scholar
  30. 30.
    Vujanic GM, Sandstedt B, Harms D, Boccon-Gibod L, Delemarre JF. Rhabdoid tumour of the kidney: a clinicopathological study of 22 patients from the International Society of Paediatric Oncology (SIOP) nephroblastoma file. Histopathology. 1996;28(4):333–40 Epub 1996/04/01.CrossRefPubMedGoogle Scholar
  31. 31.
    Hu G, Luo M, Xu Y. Giant hydronephrosis secondary to ureteropelvic junction obstruction in adults: report of a case and review of literatures. Int J clini Experimental Med. 2015;8(3):4715–7. Epub 2015/06/13. PubMed PMID: 26064410; PubMed Central PMCID: PMC4443244.Google Scholar
  32. 32.
    Khan F, Ahmed K, Lee N, Challacombe B, Khan MS, Dasgupta P. Management of ureteropelvic junction obstruction in adults. Nature Rev Urology. 2014;11(11):629–38. Epub 2014/10/08. doi: 10.1038/nrurol.2014.240. PubMed PMID: 25287785.CrossRefPubMedGoogle Scholar
  33. 33.
    Lei WH, Xin J, Shao CX, Mao MF, Zhu CY, Wu CF, et al. IgG4-related Kidney disease mimicking malignant ureter tumor: case report and literature review. Medicine. 2016;95(3):e2550. Epub 2016/01/29. doi: 10.1097/MD.0000000000002550. PubMed PMID: 26817905; PubMed Central PMCID: PMC4998279.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Divatia M, Kim SA, Ro JY. IgG4-related sclerosing disease, an emerging entity: a review of a multi-system disease. Yonsei medical journal. 2012;53(1):15–34. Epub 2011/12/22. doi: 10.3349/ymj.2012.53.1.15. PubMed PMID: 22187229; PubMed Central PMCID: PMC3250325.CrossRefPubMedGoogle Scholar
  35. 35.
    Nishi S, Imai N, Yoshida K, Ito Y, Saeki T. Clinicopathological findings of immunoglobulin G4-related kidney disease. Clini Experimental nephrology. 2011;15(6):810–9. Epub 2011/08/27. doi: 10.1007/s10157-011-0526-x. PubMed PMID: 21870078.CrossRefPubMedGoogle Scholar

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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PathologyWestchester Medical Health Network/New York Medical CollegeValhallaUSA

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