Clinicopathologic analysis of upper urinary tract carcinoma with variant histology

  • Inês Rolim
  • Vanessa Henriques
  • Nídia Rolim
  • Ana Blanca
  • Rita Canas Marques
  • Metka Volavšek
  • Inês Carvalho
  • Rodolfo Montironi
  • Alessia Cimadamore
  • Maria R. Raspollini
  • Liang Cheng
  • Antonio Lopez-BeltranEmail author
Original Article


We report on the clinicopathologic features of 115 cases of high-grade urothelial carcinoma of the upper urinary tract with variant histology present in 39 (34%). Variant histology was typically seen in high pathological stage (pT2-pT4) (82%, 32 cases) patients with lower survival rate (70%, 27 cases, median survival 31 months) and consisted in urothelial with one (23%), two (3%), and three or more variants (3%); 4% of cases presented with pure variant histology. Squamous divergent differentiation was the most common variant (7%) followed by sarcomatoid (6%) and glandular (4%), followed by 3% each of micropapillary, diffuse-plasmacytoid, inverted growth, clear cell glycogenic, or lipid-rich. The pseudo-angiosarcomatous variant is seen in 2%, and 1% each of nested, giant-cell, lymphoepithelioma-like, small-cell, trophoblastic, rhabdoid, microcystic, lymphoid-rich stroma, or myxoid stroma/chordoid completed the study series. Loss of mismatch repair protein expression was identified in one case of upper urinary tract carcinoma with inverted growth variant (3.6%). Variant histology was associated to pathological stage (p = 0.007) and survival status (p = 0.039). The univariate survival analysis identified variant histology as a feature of lower recurrence-free survival (p = 0.046). Our findings suggest that variant histology is a feature of aggressiveness in urothelial carcinoma of the upper urinary tract worth it to be reported.


Renal pelvis Ureter Urothelial carcinoma Variant histology Micropapillary Nested Plasmacytoid Sarcomatoid Squamous Glandular Divergent MMR 


Authors’ Contribution

IR, VH, and ALB drafted the article. ALB, IR, NR, RM, MV, RCM, MRR, and LC formulated and designed the study. IC and IR conducted the immunohistochemical analysis of MMR proteins. RCM, MRR, AC, and VH made the literature search. AB completed the statistical analysis. All the authors critically read, edited, and approved the final manuscript.

Funding information

This study was supported in part by the Grant PI17/01981 [FIS (Ministry of Health), Madrid, Spain].

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Siegel R, Miller KD, Jemal A (2018) Cáncer statistics. CA Cancer J Clin 68:7–30. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bianconi M, Cimadamore A, Faloppi L, Scartozzi M, Santoni M, Lopez-Beltran A, Cheng L, Scarpelli M, Montironi R (2019) Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter. Ther Adv Urol 8:1756287218815372. CrossRefGoogle Scholar
  3. 3.
    Mbeutcha A, Rouprêt M, Kamat AM, Karakiewicz PI, Lawrentschuk N, Novara G, Raman JD, Seitz C, Xylinas E, Shariat SF (2017) Prognostic factors and predictive tools for upper tract urothelial carcinoma: a systematic review. World J Urol 35:337–353. CrossRefPubMedGoogle Scholar
  4. 4.
    Lopez-Beltran A, Cheng L, Raspollini MR et al (2017) Variants of bladder cancer: the pathologist’s point of view. Eur Urol Suppl 16:210–222. CrossRefGoogle Scholar
  5. 5.
    Moch H, Humphrey PA, Ulbright TM, Reuter VE (2016) WHO classification of tumours of the urinary system and male genital organs, 4th edn. IARC, LyonGoogle Scholar
  6. 6.
    Amin MB (2009) Histological variants of urothelial carcinoma: diagnostic, therapeutic and prognostic implications. Mod Pathol. CrossRefGoogle Scholar
  7. 7.
    Kim SP, Frank I, Cheville JC, Thompson RH, Weight CJ, Thapa P, Boorjian SA (2012) The impact of squamous and glandular differentiation on survival after radical cystectomy for urothelial carcinoma. J Urol 188:405–409. CrossRefPubMedGoogle Scholar
  8. 8.
    Phelan A, Lopez-Beltran A, Montironi R, Zhang S, Raspollini MR, Cheng M, Kaimakliotis HZ, Koch MO, Cheng L (2018) Inherited forms of bladder cancer: a review of lynch syndrome and other inherited conditions. Future Oncol 14:277–290. CrossRefPubMedGoogle Scholar
  9. 9.
    Rink M, Robinson BD, Green DA, Cha EK, Hansen J, Comploj E, Margulis V, Raman JD, Ng CK, Remzi M, Bensalah K, Kabbani W, Haitel A, Rioux-Leclercq N, Guo CC, Chun FK, Kikuchi E, Kassouf W, Sircar K, Sun M, Sonpavde G, Lotan Y, Pycha A, Karakiewicz PI, Scherr DS, Shariat SF (2012) Impact of histological variants on clinical outcomes of patients with upper urinary tract urothelial carcinoma. J Urol 188:398–404. CrossRefPubMedGoogle Scholar
  10. 10.
    Lopez-Beltran A, Cheng L (2006) Histologic variants of urothelial carcinoma: differential diagnosis and clinical implications. Hum Pathol 37:1371–1388. CrossRefPubMedGoogle Scholar
  11. 11.
    Chalasani V, Chin JL, Izawa JI (2009) Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer. J Can Urol Assoc 3:193–198CrossRefGoogle Scholar
  12. 12.
    Hayashi H, Mann S, Kao CS, Grignon D, Idrees MT (2017) Variant morphology in upper urinary tract urothelial carcinoma: a 14-year case series of biopsy and resection specimens. Hum Pathol 65:209–216. CrossRefPubMedGoogle Scholar
  13. 13.
    Sakano S, Matsuyama H, Kamiryo Y, Hayashida S, Yamamoto N, Kaneda Y, Nasu T, Baba Y, Shimabukuro T, Suga A, Yamamoto M, Aoki A, Takai K, Yoshihiro S, Oba K, Yamaguchi Uro-Oncology Group (2015) Impact of variant histology on disease aggressiveness and outcome after nephroureterectomy in Japanese patients with upper tract urothelial carcinoma. Int J Clin Oncol 20:362–368. CrossRefPubMedGoogle Scholar
  14. 14.
    Perez-Montiel D, Wakely PE, Hes O, Michal M, Suster S (2006) High-grade urothelial carcinoma of the renal pelvis: clinicopathologic study of 108 cases with emphasis on unusual morphologic variants. Mod Pathol 19:494–503. CrossRefPubMedGoogle Scholar
  15. 15.
    Olgac S, Mazumdar M, Dalbagni G, Reuter VE (2004) Urothelial carcinoma of the renal pelvis: a clinicopathologic study of 130 cases. Am J Surg Pathol 28:1545–1552CrossRefGoogle Scholar
  16. 16.
    Tang Q, Xiong G, Li X, Fang D, Xi C, Zhang L, Yang K, Yao L, Zhang C, Yu W, He Q, Gong K, He Z, Zhou L (2016) The prognostic impact of squamous and glandular differentiation for upper tract urothelial carcinoma patients after radical nephroureterectomy. World J Urol 34:871–877. CrossRefPubMedGoogle Scholar
  17. 17.
    Shibing Y, Turun S, Qiang W et al (2015) Effect of concomitant variant histology on the prognosis of patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy. Urol Oncol 33:204e9–204e16. CrossRefGoogle Scholar
  18. 18.
    Kim JK, Moon KC, Jeong CW, Kwak C, Kim HH, Ku JJ (2017) Variant histology as a significant predictor of survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma. Urol Oncol 35:458.e9–458.e15CrossRefGoogle Scholar
  19. 19.
    Masson-Lecomte A, Colin P, Bozzini G et al (2014) Impact of micropapillary histological variant on survival after radical nephroureterectomy for upper tract urothelial carcinoma. World J Urol 32:531–537CrossRefGoogle Scholar
  20. 20.
    Lopez-Beltran A, Paner G, Blanca A, Montironi R, Tsuzuki T, Nagashima Y, Chuang SS, Win KT, Madruga L, Raspollini MR, Cheng L (2017) Lymphoepithelioma-like carcinoma of the upper urinary tract. Virchows Arch 470:703–709. CrossRefPubMedGoogle Scholar
  21. 21.
    Lopez-Beltran A, Henriques V, Montironi R, Cimadamore A, Raspollini MR, Cheng L (2019) Variants and new entities of bladder cancer. Histopathology 74:77–96. CrossRefPubMedGoogle Scholar
  22. 22.
    Cimadamore A, Scarpelli M, Santoni M, Cheng L, Lopez-Beltran A, Montironi R (2018) Upper urinary tract urothelial carcinoma and its variants: transition from morphology to personalized molecular characterization in diagnosis, prognosis, and therapy. Exp Rev Mol Diagn 18:1021–1028. CrossRefGoogle Scholar
  23. 23.
    Soria F, Shariat SF, Lerner SP, Fritsche HM, Rink M, Kassouf W, Spiess PE, Lotan Y, Ye D, Fernández MI, Kikuchi E, Chade DC, Babjuk M, Grollman AP, Thalmann GN (2017) Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC). World J Urol 35:379–387. CrossRefPubMedGoogle Scholar
  24. 24.
    Elawdy M, Taha DE, Elbaset MA, Abouelkheir RT, Osman Y (2016) Histopathologic characteristics of upper tract urothelial carcinoma with emphasis on their impact in cancer survival: a single institute experience in 305 patients with long-term follow-up. Clin Genitourin Cancer. CrossRefGoogle Scholar
  25. 25.
    Langner C, Hutterer G, Chromecki T, Rehak P, Zigeuner R (2006) Patterns of invasion and histological growth as prognostic indicators in urothelial carcinoma of the upper urinary tract. Virchows Arch 448:604–611CrossRefGoogle Scholar
  26. 26.
    Harper HL, McKenney JK, Heald B et al (2017) Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and lynch syndrome. Mod Pathol 30:146–156CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  1. 1.Serviço de Anatomia PatológicaInstituto Português de Oncologia de Lisboa Francisco Gentil E.P.ELisbonPortugal
  2. 2.Anatomic Pathology ServiceChampalimaud Clinical CenterLisbonPortugal
  3. 3.Serviço de UrologiaHospital de Egas MonizLisbonPortugal
  4. 4.Maimonides Biomedical Research Institute of CordobaCordobaSpain
  5. 5.Institute of Pathology, Faculty of MedicineUniversity of LjubljanaLjubljanaSlovenia
  6. 6.Institute of Pathological Anatomy and HistopathologyAnconaItaly
  7. 7.Histopathology and Molecular DiagnosticsCareggi University HospitalFlorenceItaly
  8. 8.Departments of Pathology and Laboratory Medicine and UrologyIndiana UniversityIndianapolisUSA
  9. 9.Department of Surgery and Pathology, Faculty of MedicineCordoba UniversityCordobaSpain
  10. 10.Champalimaud Clinical CenterLisbonPortugal

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