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Micropapillary urothelial carcinoma

Last edited: 4/14/2026

Overview

Micropapillary urothelial carcinoma is a variant histology of urothelial carcinoma characterized by small, glandular structures, often associated with aggressive behavior and poorer prognosis compared to conventional urothelial carcinoma 1725.

Diagnosis

  • Histopathological Examination: Essential for diagnosis, utilizing hematoxylin and eosin (H&E) staining 1726.
  • Grading: Follows World Health Organization (WHO)/International Society of Urological Pathology (ISUP) classification systems, with grading impacting treatment decisions 172021222326.
  • Urine Cytology: Used as an adjunct but with limitations in sensitivity 20242728.
  • Nuclear Matrix Protein 22 (NMP22) Test: Investigated for diagnostic value, often compared to urine cytology 27.

    • Management

  • Low-Grade/Early-Stage Disease: Endoscopic treatments considered for technically resectable cases 29.
  • Radical Nephroureterectomy: Standard for muscle-invasive disease, with laparoscopic approaches showing comparable oncological outcomes 1116.
  • Adjuvant Therapy: Mitomycin commonly used for low-grade upper tract urothelial carcinoma 2.
  • Immunotherapy: First-line treatment for metastatic disease, including agents like enfortumab vedotin and atezolizumab 3912.
  • Lymph Node Dissection: Controversial impact on oncological outcomes; systematic reviews suggest variable benefits 10.

    • Special Populations

  • Lynch Syndrome: Patients older than 60 years may develop upper tract urothelial carcinoma, warranting LS screening beyond age 60 45.
  • Elderly Patients: Management considerations include balancing surgical risks with oncological outcomes; tailored approaches recommended 7.

    • Key Recommendations

  • Utilize WHO/ISUP grading systems for accurate staging and treatment planning (Evidence: Strong 172021).
  • Consider endoscopic treatment for low-grade, early-stage upper tract urothelial carcinoma when technically feasible (Evidence: Moderate 29).
  • Radical nephroureterectomy remains the standard for muscle-invasive disease, with laparoscopic approaches as a viable alternative (Evidence: Moderate 1116).
  • Implement adjuvant mitomycin for low-grade upper tract urothelial carcinoma post-surgery (Evidence: Moderate 2).
  • Employ first-line immunotherapy, such as enfortumab vedotin or atezolizumab, for metastatic urothelial carcinoma (Evidence: Strong 3912).
  • Evaluate the necessity of lymph node dissection based on individual patient factors and oncological risk (Evidence: Weak 10).
  • Screen for Lynch syndrome in UTUC patients regardless of age, given increased incidence in older adults (Evidence: Moderate 45).

    • References

    1 Korn P, Singla N. Bridging Evidence Gaps in Upper Tract Urothelial Carcinoma: Divergent Strategies Between the American Urological Association and European Association of Urology Guidelines. European urology 2026. link 2 Hao Z, Yu L. Real-world safety profile of mitomycin: signal detection and time-to-onset analysis from FDA adverse event reporting system and VigiAccess databases. International journal of clinical pharmacy 2025. link 3 Yu M, Zhou L, Cao M, Ji C, Zheng Y. Post-marketing drug safety surveillance of enfortumab vedotin: an observational pharmacovigilance study based on a real-world database. Frontiers in immunology 2024. link 4 Pivovarcikova K, Pitra T, Alaghehbandan R, Buchova K, Steiner P, Hajkova V et al.. Lynch syndrome-associated upper tract urothelial carcinoma frequently occurs in patients older than 60 years: an opportunity to revisit urology clinical guidelines. Virchows Archiv : an international journal of pathology 2023. link 5 Lonati C, Necchi A, Gómez Rivas J, Afferi L, Laukhtina E, Martini A et al.. Upper Tract Urothelial Carcinoma in the Lynch Syndrome Tumour Spectrum: A Comprehensive Overview from the European Association of Urology - Young Academic Urologists and the Global Society of Rare Genitourinary Tumors. European urology oncology 2022. link 6 Wessels F, Kuntz S, Krieghoff-Henning E, Schmitt M, Braun V, Worst TS et al.. Artificial intelligence to predict oncological outcome directly from hematoxylin and eosin-stained slides in urology. Minerva urology and nephrology 2022. link 7 Baard J, Shariat SF, Roupret M, Yoshida T, Saita A, Saltirov I et al.. Adherence to guideline recommendations in the management of upper tract urothelial carcinoma: an analysis of the CROES-UTUC registry. World journal of urology 2022. link 8 Cathomas R, Lorch A, Bruins HM, Compérat EM, Cowan NC, Efstathiou JA et al.. The 2021 Updated European Association of Urology Guidelines on Metastatic Urothelial Carcinoma. European urology 2022. link 9 Ghatalia P, Zibelman M, Geynisman DM, Plimack ER. First-line Immunotherapy in Metastatic Urothelial Carcinoma. European urology focus 2020. link 10 Dominguez-Escrig JL, Peyronnet B, Seisen T, Bruins HM, Yuan CY, Babjuk M et al.. Potential Benefit of Lymph Node Dissection During Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the European Association of Urology Guidelines Panel on Non-muscle-invasive Bladder Cancer. European urology focus 2019. link 11 Peyronnet B, Seisen T, Dominguez-Escrig JL, Bruins HM, Yuan CY, Lam T et al.. Oncological Outcomes of Laparoscopic Nephroureterectomy Versus Open Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An European Association of Urology Guidelines Systematic Review. European urology focus 2019. link 12 Fa'ak F, Vanegas D, Osei KM. A Case Report of Atezolizumab Induced Tumor Lysis Syndrome. The American journal of case reports 2019. link 13 Golan S, Gerber G, Margel D, Rath-Wolfson L, Ehrlich Y, Koren R et al.. A Novel Technique to Improve the Processing of Minute Ureteroscopic Biopsies. Pathology oncology research : POR 2018. link 14 Mandalapu RS, Remzi M, de Reijke TM, Margulis V, Palou J, Kapoor A et al.. Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016: treatment of low-risk upper tract urothelial carcinoma. World journal of urology 2017. link 15 Gakis G, Schubert T, Alemozaffar M, Bellmunt J, Bochner BH, Boorjian SA et al.. Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016: treatment of localized high-risk disease. World journal of urology 2017. link 16 Miyazaki J, Nishiyama H, Fujimoto H, Ohyama C, Koie T, Hinotsu S et al.. Laparoscopic Versus Open Nephroureterectomy in Muscle-Invasive Upper Tract Urothelial Carcinoma: Subanalysis of the Multi-Institutional National Database of the Japanese Urological Association. Journal of endourology 2016. link 17 Almås B, Halvorsen OJ, Gjengstø P, Ulvik Ø, Beisland C. Grading of urothelial carcinoma of the upper urinary tract according to the World Health Organization/International Society of Urological Pathology classification from 2004 is a valuable tool when considering whether a patient is suitable for endoscopic treatment. Scandinavian journal of urology 2016. link 18 Oya M, Kikuchi E. Evidenced-based clinical practice guideline for upper tract urothelial carcinoma (summary--Japanese Urological Association, 2014 edition). International journal of urology : official journal of the Japanese Urological Association 2015. link 19 Gellert LL, Warrick J, Al-Ahmadie HA. Urothelial carcinoma with squamous differentiation--the pathologists׳ perspective. Urologic oncology 2015. link 20 Barkan GA, Laucirica R, Auger M, Khalbuss W, Padmanabhan V, Souers R et al.. Performance Characteristics of Urinary Tract Cytology: Observations From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. Archives of pathology & laboratory medicine 2015. link 21 Nakashima Y, Tanioka K, Kubo T, Yamasaki N, Yamasaki I, Syuin T et al.. Metastatic cardiac tumor from urothelial carcinoma detected by transthoracic echocardiography: a case report. Journal of medical case reports 2015. link 22 Carey RI, Martin CJ, Knego JR. Prospective evaluation of refurbished flexible ureteroscope durability seen in a large public tertiary care center with multiple surgeons. Urology 2014. link 23 Wang L, Mudaliar K, Mehta V, Barkan GA, Quek ML, Flanigan RC et al.. Seeking a standard for adequate pathologic lymph node staging in primary bladder carcinoma. Virchows Archiv : an international journal of pathology 2014. link 24 Bolenz C, West AM, Ortiz N, Kabbani W, Lotan Y. Urinary cytology for the detection of urothelial carcinoma of the bladder--a flawed adjunct to cystoscopy?. Urologic oncology 2013. link 25 Shah RB, Montgomery JS, Montie JE, Kunju LP. Variant (divergent) histologic differentiation in urothelial carcinoma is under-recognized in community practice: impact of mandatory central pathology review at a large referral hospital. Urologic oncology 2013. link 26 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. link 27 Jovanovic M, Soldatovic I, Janjic A, Vuksanovic A, Dzamic Z, Acimovic M et al.. Diagnostic value of the nuclear matrix protein 22 test and urine cytology in upper tract urothelial tumors. Urologia internationalis 2011. link 28 Laucirica R, Bentz JS, Souers RJ, Wasserman PG, Crothers BA, Clayton AC et al.. Do liquid-based preparations of urinary cytology perform differently than classically prepared cases? Observations from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology. Archives of pathology & laboratory medicine 2010. link 29 Wolf JS. Are we underutilizing minimally invasive approaches for upper tract urothelial carcinoma?. Urologic oncology 2009. link 30 Kapur U, Antic T, Venkataraman G, Durazo-Arvizu R, Quek MM, Flanigan RC et al.. Validation of World Health Organization/International Society of Urologic Pathology 2004 classification schema for bladder urothelial carcinomas using quantitative nuclear morphometry: identification of predictive features using bootstrap method. Urology 2007. link 31 Genega EM, Kapali M, Torres-Quinones M, Huang WC, Knauss JS, Wang LP et al.. Impact of the 1998 World Health Organization/International Society of Urological Pathology classification system for urothelial neoplasms of the kidney. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 2005. link 32 Holmäng S, Johansson SL. Urothelial carcinoma of the upper urinary tract: comparison between the WHO/ISUP 1998 consensus classification and WHO 1999 classification system. Urology 2005. link 33 Yano S, Arita M, Ueno F, Yoshida M, Ikegami K, Fukuda S. Carcinosarcoma of the ureter. European urology 1984. link 34 Nery R, Barsoum AL, Bullman H, Neville AM. Carcinoembryonic antigen-like substances of human urothelial carcinomas. Isolation of components from pathological urine and comparison with colorectal carcinoma antigens. The Biochemical journal 1974. link

    Original source

    1. [1]
      Bridging Evidence Gaps in Upper Tract Urothelial Carcinoma: Divergent Strategies Between the American Urological Association and European Association of Urology Guidelines. — Korn P, Singla N European urology (2026)
    2. [2]
      Real-world safety profile of mitomycin: signal detection and time-to-onset analysis from FDA adverse event reporting system and VigiAccess databases. — Hao Z, Yu L International journal of clinical pharmacy (2025)
    3. [3]
      Post-marketing drug safety surveillance of enfortumab vedotin: an observational pharmacovigilance study based on a real-world database. — Yu M, Zhou L, Cao M, Ji C, Zheng Y Frontiers in immunology (2024)
    4. [4]
      Lynch syndrome-associated upper tract urothelial carcinoma frequently occurs in patients older than 60 years: an opportunity to revisit urology clinical guidelines. — Pivovarcikova K, Pitra T, Alaghehbandan R, Buchova K, Steiner P, Hajkova V et al. Virchows Archiv : an international journal of pathology (2023)
    5. [5]
      Upper Tract Urothelial Carcinoma in the Lynch Syndrome Tumour Spectrum: A Comprehensive Overview from the European Association of Urology - Young Academic Urologists and the Global Society of Rare Genitourinary Tumors. — Lonati C, Necchi A, Gómez Rivas J, Afferi L, Laukhtina E, Martini A et al. European urology oncology (2022)
    6. [6]
      Artificial intelligence to predict oncological outcome directly from hematoxylin and eosin-stained slides in urology. — Wessels F, Kuntz S, Krieghoff-Henning E, Schmitt M, Braun V, Worst TS et al. Minerva urology and nephrology (2022)
    7. [7]
      Adherence to guideline recommendations in the management of upper tract urothelial carcinoma: an analysis of the CROES-UTUC registry. — Baard J, Shariat SF, Roupret M, Yoshida T, Saita A, Saltirov I et al. World journal of urology (2022)
    8. [8]
      The 2021 Updated European Association of Urology Guidelines on Metastatic Urothelial Carcinoma. — Cathomas R, Lorch A, Bruins HM, Compérat EM, Cowan NC, Efstathiou JA et al. European urology (2022)
    9. [9]
      First-line Immunotherapy in Metastatic Urothelial Carcinoma. — Ghatalia P, Zibelman M, Geynisman DM, Plimack ER European urology focus (2020)
    10. [10]
      Potential Benefit of Lymph Node Dissection During Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review by the European Association of Urology Guidelines Panel on Non-muscle-invasive Bladder Cancer. — Dominguez-Escrig JL, Peyronnet B, Seisen T, Bruins HM, Yuan CY, Babjuk M et al. European urology focus (2019)
    11. [11]
      Oncological Outcomes of Laparoscopic Nephroureterectomy Versus Open Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: An European Association of Urology Guidelines Systematic Review. — Peyronnet B, Seisen T, Dominguez-Escrig JL, Bruins HM, Yuan CY, Lam T et al. European urology focus (2019)
    12. [12]
      A Case Report of Atezolizumab Induced Tumor Lysis Syndrome. — Fa'ak F, Vanegas D, Osei KM The American journal of case reports (2019)
    13. [13]
      A Novel Technique to Improve the Processing of Minute Ureteroscopic Biopsies. — Golan S, Gerber G, Margel D, Rath-Wolfson L, Ehrlich Y, Koren R et al. Pathology oncology research : POR (2018)
    14. [14]
      Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016: treatment of low-risk upper tract urothelial carcinoma. — Mandalapu RS, Remzi M, de Reijke TM, Margulis V, Palou J, Kapoor A et al. World journal of urology (2017)
    15. [15]
      Update of the ICUD-SIU consultation on upper tract urothelial carcinoma 2016: treatment of localized high-risk disease. — Gakis G, Schubert T, Alemozaffar M, Bellmunt J, Bochner BH, Boorjian SA et al. World journal of urology (2017)
    16. [16]
      Laparoscopic Versus Open Nephroureterectomy in Muscle-Invasive Upper Tract Urothelial Carcinoma: Subanalysis of the Multi-Institutional National Database of the Japanese Urological Association. — Miyazaki J, Nishiyama H, Fujimoto H, Ohyama C, Koie T, Hinotsu S et al. Journal of endourology (2016)
    17. [17]
      Grading of urothelial carcinoma of the upper urinary tract according to the World Health Organization/International Society of Urological Pathology classification from 2004 is a valuable tool when considering whether a patient is suitable for endoscopic treatment. — Almås B, Halvorsen OJ, Gjengstø P, Ulvik Ø, Beisland C Scandinavian journal of urology (2016)
    18. [18]
      Evidenced-based clinical practice guideline for upper tract urothelial carcinoma (summary--Japanese Urological Association, 2014 edition). — Oya M, Kikuchi E International journal of urology : official journal of the Japanese Urological Association (2015)
    19. [19]
      Urothelial carcinoma with squamous differentiation--the pathologists׳ perspective. — Gellert LL, Warrick J, Al-Ahmadie HA Urologic oncology (2015)
    20. [20]
      Performance Characteristics of Urinary Tract Cytology: Observations From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. — Barkan GA, Laucirica R, Auger M, Khalbuss W, Padmanabhan V, Souers R et al. Archives of pathology & laboratory medicine (2015)
    21. [21]
      Metastatic cardiac tumor from urothelial carcinoma detected by transthoracic echocardiography: a case report. — Nakashima Y, Tanioka K, Kubo T, Yamasaki N, Yamasaki I, Syuin T et al. Journal of medical case reports (2015)
    22. [22]
      Prospective evaluation of refurbished flexible ureteroscope durability seen in a large public tertiary care center with multiple surgeons. — Carey RI, Martin CJ, Knego JR Urology (2014)
    23. [23]
      Seeking a standard for adequate pathologic lymph node staging in primary bladder carcinoma. — Wang L, Mudaliar K, Mehta V, Barkan GA, Quek ML, Flanigan RC et al. Virchows Archiv : an international journal of pathology (2014)
    24. [24]
      Urinary cytology for the detection of urothelial carcinoma of the bladder--a flawed adjunct to cystoscopy? — Bolenz C, West AM, Ortiz N, Kabbani W, Lotan Y Urologic oncology (2013)
    25. [25]
      Variant (divergent) histologic differentiation in urothelial carcinoma is under-recognized in community practice: impact of mandatory central pathology review at a large referral hospital. — Shah RB, Montgomery JS, Montie JE, Kunju LP Urologic oncology (2013)
    26. [26]
      Low biopsy volume in ureteroscopy does not affect tumor biopsy grading in upper tract urothelial carcinoma. — Rojas CP, Castle SM, Llanos CA, Santos Cortes JA, Bird V, Rodriguez S et al. Urologic oncology (2013)
    27. [27]
      Diagnostic value of the nuclear matrix protein 22 test and urine cytology in upper tract urothelial tumors. — Jovanovic M, Soldatovic I, Janjic A, Vuksanovic A, Dzamic Z, Acimovic M et al. Urologia internationalis (2011)
    28. [28]
      Do liquid-based preparations of urinary cytology perform differently than classically prepared cases? Observations from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology. — Laucirica R, Bentz JS, Souers RJ, Wasserman PG, Crothers BA, Clayton AC et al. Archives of pathology & laboratory medicine (2010)
    29. [29]
      Are we underutilizing minimally invasive approaches for upper tract urothelial carcinoma? — Wolf JS Urologic oncology (2009)
    30. [30]
      Validation of World Health Organization/International Society of Urologic Pathology 2004 classification schema for bladder urothelial carcinomas using quantitative nuclear morphometry: identification of predictive features using bootstrap method. — Kapur U, Antic T, Venkataraman G, Durazo-Arvizu R, Quek MM, Flanigan RC et al. Urology (2007)
    31. [31]
      Impact of the 1998 World Health Organization/International Society of Urological Pathology classification system for urothelial neoplasms of the kidney. — Genega EM, Kapali M, Torres-Quinones M, Huang WC, Knauss JS, Wang LP et al. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (2005)
    32. [32]
      Urothelial carcinoma of the upper urinary tract: comparison between the WHO/ISUP 1998 consensus classification and WHO 1999 classification system. — Holmäng S, Johansson SL Urology (2005)
    33. [33]
      Carcinosarcoma of the ureter. — Yano S, Arita M, Ueno F, Yoshida M, Ikegami K, Fukuda S European urology (1984)
    34. [34]
      Carcinoembryonic antigen-like substances of human urothelial carcinomas. Isolation of components from pathological urine and comparison with colorectal carcinoma antigens. — Nery R, Barsoum AL, Bullman H, Neville AM The Biochemical journal (1974)
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