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Clinicopathological Review of Micropapillary Urothelial Carcinoma

  • Genitourinary Cancers (DP Petrylak and JW Kim, Section Editors)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review will discuss micropapillary urothelial carcinoma with respect to biology, histopathologic characteristics, genetic and molecular features, diagnosis, clinical management, and future directions of research.

Recent Findings

Recent consensus opinion study showed only moderate interobserver reproducibility in the diagnostic criteria. The most reproducible criteria with the highest consensus were multiple nests in the same lacunar spaces. There are recent reports of high rates of intratumoral heterogeneity of ERBB2 amplification within tumor containing both micropapillary and classic urothelial components.

Summary

Micropapillary urothelial carcinoma is a well-documented highly aggressive variant of urothelial carcinoma with proven worse outcomes. Accurate recognition and reporting of this pattern is critical for optimal management. Newer therapeutic strategies related to the molecular and genetic findings seen in MPUC remain to be explored further.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Teoh JY, Huang J, Ko WY, et al. Global trends of bladder cancer incidence and mortality, and their associations with tobacco use and gross domestic product per capita. Eur Urol. 2020;78(6):893–906.

    Article  PubMed  Google Scholar 

  2. Wigner P, Bijak M, Saluk-Bijak J. The green anti-cancer weapon The Role of Natural Compounds in Bladder Cancer Treatment. Int J Mol Sci. 2021;22(15):7787.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. • Lobo N, Shariat SF, Guo CC, et al. What is the significance of variant histology in urothelial carcinoma? Eur Urol Focus. 2020;6(4):653–63. This paper provides an overview of the diagnostic, therapeutic, and prognostic significance of micropapillary urothelial carcinoma.

    Article  PubMed  Google Scholar 

  4. Antoni S, Ferlay J, Soerjomataram I, et al. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol. 2017;71(1):96–108.

    Article  PubMed  Google Scholar 

  5. Moch H, Humphrey PA, Ulbright TM et al. Eds. WHO classification of tumors of the urinary system and male genital organs. Lyon, France: International Agency for Research on Cancer, 2016

  6. Amin MB, Ro JY, El-Sharkawy T, et al. Micropapillary variant of transitional cell carcinoma of the urinary bladder Histologic pattern resembling ovarian papillary serous carcinoma. Am J Surg Pathol. 1994;18(12):1224–32.

    Article  CAS  PubMed  Google Scholar 

  7. Kamat AM, Gee JR, Dinney CPN, et al. The case for early cystectomy in the treatment of nonmuscle invasive micropapillary bladder carcinoma. J Urol. 2006;175(3 Pt 1):881–5.

    Article  PubMed  Google Scholar 

  8. Nassar H. Carcinomas with micropapillary morphology: clinical significance and current concepts. Adv Anat Pathol. 2004;11(6):297–303.

    Article  PubMed  Google Scholar 

  9. Perepletchikov AM, Parwani AV. Micropapillary urothelial carcinoma: clinico-pathologic review. Pathol Res Pract. 2009;205(12):807–10.

    Article  PubMed  Google Scholar 

  10. Kamat AM, Dinney CP, Gee JR, et al. Micropapillary bladder cancer: a review of the University of Texas M D Anderson Cancer Center experience with 100 consecutive patients. Cancer. 2007;110(1):62–7.

    Article  PubMed  Google Scholar 

  11. Maranchie JK, Bouyounes BT, Zhang PL. Clinical and pathological characteristics of micropapillary transitional cell carcinoma: a highly aggressive variant. J Urol. 2000;163(3):748–51.

    Article  CAS  PubMed  Google Scholar 

  12. • Mitra AP, Fairey AS, Skinner EC, et al. Implications of micropapillary urothelial carcinoma variant on prognosis following radical cystectomy: a multi-institutional investigation. Urol Oncol. 2019;37(1):48–56. This study demonstrates that the presence of micropapillary urothelial carcinoma is associated with locally advanced disease at radical cystectomy.

    Article  PubMed  Google Scholar 

  13. Isharwal S, Huang H, Nanjangud G, et al. Intratumoral heterogeneity of ERBB2 amplification and HER2 expression in micropapillary urothelial carcinoma. Human Pathol. 2018;77:63–9.

    Article  CAS  Google Scholar 

  14. Al-Ahmadie H, Iyer G. Updates on the genetics and molecular subtypes of urothelial carcinoma and select variants. Surg Pathol Clin. 2018;11(4):713–23.

    Article  PubMed  PubMed Central  Google Scholar 

  15. • Butt SU, Malik L. Role of immunotherapy in bladder cancer: past, present and future. Cancer Chemother Pharmacol. 2018;81(4):629–45. This paper discusses advances in urothelial bladder cancer immunotherapy.

    Article  CAS  PubMed  Google Scholar 

  16. Aoun F, Rassy EE, Assi T, et al. Advances in urothelial bladder cancer immunotherapy, dawn of a new age of treatment. Immunotherapy. 2017;9(5):451–60.

    Article  CAS  PubMed  Google Scholar 

  17. •• Compérat E, Amin MB, Epstein JI, et al. The genitourinary pathology society update on classification of variant histologies, T1 substaging, molecular taxonomy, and immunotherapy and PD-L1 testing implications of urothelial cancers. Adv Anat Pathol. 2021;28(4):196–208. This paper demonstrates molecular evolution, emphasizing the aspects that impact the understanding concepts relevant to management of patients.

    Article  CAS  PubMed  Google Scholar 

  18. Johansson SL, Borghede G, Holmang S. Micropapillary bladder carcinoma: a clinicopathological study of 20 cases. J Urol. 1999;161(6):1798–802.

    Article  CAS  PubMed  Google Scholar 

  19. Alvarado-Cabrero I, Sierra-Santiesteban FI, Mantilla-Morales A, et al. Micropapillary carcinoma of the urothelial tract A clinicopathologic study of 38 cases. Ann Diagn Pathol. 2005;9(1):1–5.

    Article  PubMed  Google Scholar 

  20. Watts KE, Hansel DE. Emerging concepts in micropapillary urothelial carcinoma. Adv Anat Pathol. 2010;17(3):182–6.

    Article  PubMed  Google Scholar 

  21. Fernández MI, Williams SB, Willis DL, et al. Clinical risk stratification in patients with surgically resectable micropapillary bladder cancer. BJU Int. 2017;119(5):684–91.

    Article  PubMed  Google Scholar 

  22. Zhai QJ, Black J, Ayala AG, et al. Histologic variants of infiltrating urothelial carcinoma. Arch Pathol Lab Med. 2007;131(8):1244–56.

    Article  PubMed  Google Scholar 

  23. Guo CC, Tamboli P, Czerniak B. Micropapillary variant of urothelial carcinoma in the upper urinary tract: a clinicopathologic study of 11 cases. Arch Pathol Lab Med. 2009;133(1):62–6.

    Article  PubMed  Google Scholar 

  24. Larsen MP, Steinberg GD, Brendler CB, et al. Use of Ulex europaeus agglutinin I (UEAI) to distinguish vascular and “pseudovascular” invasion in transitional cell carcinoma of bladder with lamina propria invasion. Mod Pathol. 1990;3(1):83–8.

    CAS  PubMed  Google Scholar 

  25. Domanowska E, Jozwicki W, Domaniewski J, et al. Muscle-invasive urothelial cell carcinoma of the human bladder: multidirectional differentiation and ability to metastasize. Hum Pathol. 2007;38(5):741–6.

    Article  PubMed  Google Scholar 

  26. Epstein JI, Amin MB, Reuter VE. Histologic variants of urothelial carcinoma. Bladder Biopsy Interpretation, (Biopsy interpretation series), Lippincott Williams & Wilkins, Philadelphia, PA (2017), 148–155.

  27. Compérat E, Roupret M, Yaxley J, et al. Micropapillary urothelial carcinoma of the urinary bladder: a clinicopathological analysis of 72 cases. Pathol. 2010;42(7):650–4.

    Google Scholar 

  28. Gaya JM, Palou J, Algaba F, et al. The case for conservative management in the treatment of patients with non-muscle-invasive micropapillary bladder carcinoma without carcinoma in situ. Can J Urol. 2010;17(5):5370–6.

    PubMed  Google Scholar 

  29. Samaratunga H, Khoo K. Micropapillary variant of urothelial carcinoma of the urinary bladder; a clinicopathological and immunohistochemical study. Histopathol. 2004;45(1):55–64.

    Article  CAS  Google Scholar 

  30. Vera J, Marigil M, García MD, Abascal M, Sanz JI. Micropapillary bladder carcinoma. Virchows Arch. 2002;441(4):412–3.

    Article  PubMed  Google Scholar 

  31. Peterson JL. Breast carcinomas with an unexpected inside-out growth pattern: rotation of polarization associated with angioinvasion. Path Res Pract. 1993;189:780A.

    Google Scholar 

  32. Luna-Moré S, Gonzalez B, Acedo C, Rodrigo I, Luna C. Invasive micropapillary carcinoma of the breast A new special type of invasive mammary carcinoma. Pathol Res Pract. 1994;190(7):668–74.

    Article  PubMed  Google Scholar 

  33. Nassar H, Pansare V, Zhang H, et al. Pathogenesis of invasive micropapillary carcinoma: role of MUC1 glycoprotein. Mod Pathol. 2004;17(9):1045–50.

    Article  CAS  PubMed  Google Scholar 

  34. Sangoi AR, Beck AH, Amin MB, et al. Interobserver reproducibility in the diagnosis of invasive micropapillary carcinoma of the urinary tract among urologic pathologists. Am J Surg Pathol. 2010;34(9):1367–76.

    Article  PubMed  Google Scholar 

  35. Lopez-Beltran A, Henriques V, Montironi R, et al. Variants and new entities of bladder cancer. Histopathology. 2019;74(1):77–96.

    Article  PubMed  Google Scholar 

  36. Choi W, Porten S, Kim S, et al. Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell. 2014;25(2):152–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 2014;507(7492):315–22.

    Article  CAS  Google Scholar 

  38. Damrauer JS, Hoadley KA, Chism DD, et al. Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc Natl Acad Sci U S A. 2014;111(8):3110–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Guo CC, Dadhania V, Zhang L, et al. Gene expression profile of the clinically aggressive micropapillary variant of bladder cancer. Eur Urol. 2016;70(4):611–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Burger M, Kamat AM, McConkey D. Does variant histology change management of non-muscle-invasive bladder cancer? Eur Urol Oncol. 2021;4(3):510–4.

    Article  PubMed  Google Scholar 

  41. Schneider SA, Sukov WR, Frank I, et al. Outcome of patients with micropapillary urothelial carcinoma following radical cystectomy: ERBB2 (HER2) amplification identifies patients with poor outcome. Mod Pathol. 2014;27(5):758–64.

    Article  CAS  PubMed  Google Scholar 

  42. Tschui J, Vassella E, Bandi N, et al. Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer. Virchows Arch. 2015;466(6):703–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. •• Isharwal S, Huang H, Nanjangud G, et al. Intratumoral heterogeneity of ERBB2 amplification and HER2 expression in micropapillary urothelial carcinoma. Hum Pathol. 2018;77:63–9. This study identifies the presence of intratumoral heterogeneity of ERBB2 amplification and HER2 expression in micropapillary urothelial carcinoma.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Robertson AG, Kim J, Al-Ahmadie H, et al. Comprehensive molecular characterization of muscle-invasive bladder cancer. Cell. 2017;171(3):540-556.e25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Iyer G, Al-Ahmadie H, Schultz N, et al. Prevalence and co-occurrence of actionable genomic alterations in high-grade bladder cancer. J Clin Oncol. 2013;31(25):3133–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Fleischmann A, Rotzer D, Seiler R, et al. Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours. Eur Urol. 2011;60(2):350–7.

    Article  CAS  PubMed  Google Scholar 

  47. Lee KH, Lin FC, Hsu TI, et al. MicroRNA-296-5p (miR-296-5p) functions as a tumor suppressor in prostate cancer by directly targeting Pin1. Biochim Biophys Acta. 2014;1843(9):2055–66.

    Article  CAS  PubMed  Google Scholar 

  48. Savi F, Forno I, Faversani A, et al. miR-296/Scribble axis is deregulated in human breast cancer and miR-296 restoration reduces tumour growth in vivo. Clin Sci (Lond). 2014;127(4):233–42.

    Article  CAS  Google Scholar 

  49. Vaira V, Faversani A, Dohi T, et al. miR-296 regulation of a cell polarity-cell plasticity module controls tumor progression. Oncogene. 2012;31(1):27–38.

    Article  CAS  PubMed  Google Scholar 

  50. Nordentoft I, Birkenkamp-Demtroder K, Agerbæk M, et al. miRNAs associated with chemo-sensitivity in cell lines and in advanced bladder cancer. BMC Med Genomics. 2012;5:40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gentili C, Castor D, Kaden S, et al. Chromosome missegregation associated with RUVBL1 deficiency. PLoS One. 2015;10(7):e0133576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Taniuchi K, Furihata M, Iwasaki S, et al. RUVBL1 directly binds actin filaments and induces formation of cell protrusions to promote pancreatic cancer cell invasion. Int J Oncol. 2014;44(6):1945–54.

    Article  CAS  PubMed  Google Scholar 

  53. Lotan TL, Ye H, Melamed J, et al. Immunohistochemical panel to identify the primary site of invasive micropapillary carcinoma. Am J Surg Pathol. 2009;33(7):1037–41.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Wasco MJ, Daignault S, Zhang Y, et al. Urothelial carcinoma with divergent histologic differentiation (mixed histologic features) predicts the presence of locally advanced bladder cancer when detected at transurethral resection. Urol. 2007;70(1):69–74.

    Article  PubMed  Google Scholar 

  55. Kassouf W, Agarwal PK, Grossman HB, et al. Outcome of patients with bladder cancer with pN+ disease after preoperative chemotherapy and radical cystectomy. Urol. 2009;73(1):147–52.

    Article  PubMed  Google Scholar 

  56. Turker P, Bostrom PJ, Wroclawski ML, et al. Upstaging of urothelial cancer at the time of radical cystectomy: factors associated with upstaging and its effect on outcome. BJU Int. 2012;110(6):804–11.

    Article  PubMed  Google Scholar 

  57. Willis DL, Flaig TW, Hansel DE, et al. Micropapillary bladder cancer: current treatment patterns and review of the literature. Urol Oncol. 2014;32(6):826–32.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Ghoneim IA, Miocinovic R, Stephenson AJ, et al. Neoadjuvant systemic therapy or early cystectomy? Single-center analysis of outcomes after therapy for patients with clinically localized micropapillary urothelial carcinoma of the bladder. Urol. 2011;77(4):867–70.

    Article  PubMed  Google Scholar 

  59. Willis DL, Fernandez MI, Dickstein RJ, et al. Clinical outcomes of cT1 micropapillary bladder cancer. J Urol. 2015;193(4):1129–34.

    Article  PubMed  Google Scholar 

  60. Spaliviero M, Dalbagni G, Bochner BH, et al. Clinical outcome of patients with T1 micropapillary urothelial carcinoma of the bladder. J Urol. 2014;192(3):702–7.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Meeks JJ, Taylor JM, Matsushita K, et al. Pathological response to neoadjuvant chemotherapy for muscle-invasive micropapillary bladder cancer. BJU Int. 2013;111(8):E325–30.

    Article  PubMed  Google Scholar 

  62. Abufaraj M, Foerster B, Schernhammer E, et al. Micropapillary urothelial carcinoma of the bladder: a systematic review and meta-analysis of disease characteristics and treatment outcomes. Eur Urol. 2019;75(4):649–58.

    Article  PubMed  Google Scholar 

  63. Masson-Lecomte A, Xylinas E, Bouquot M, et al. Oncological outcomes of advanced muscle-invasive bladder cancer with a micropapillary variant after radical cystectomy and adjuvant platinum-based chemotherapy. World J Urol. 2015;33(8):1087–93.

    Article  CAS  PubMed  Google Scholar 

  64. • Sangoi AR, Cox RM, Higgins JP, et al. Non-invasive papillary urothelial carcinoma with ‘micropapillary’ architecture: clinicopathological study of 18 patients emphasizing clinical outcomes. Histopathol. 2020;77(5):728–33. This study demonstrates the clinicopathological characteristics of non-invasive papillary urothelial carcinoma with emphasis on clinical outcomes.

    Article  Google Scholar 

  65. Wang JK, Boorjian SA, Cheville JC, et al. Outcomes following radical cystectomy for micropapillary bladder cancer versus pure urothelial carcinoma: a matched cohort analysis. World J Urol. 2012;30(6):801–6.

    Article  PubMed  Google Scholar 

  66. • Casadei C, Dizman N, Schepisi G, et al. Targeted therapies for advanced bladder cancer: new strategies with FGFR inhibitors. Ther Adv Med Oncol. 2019;11:1758835919890285. This paper describes future therapeutic options of combination regimens with immune-checkpoint inhibitors for the treatment of urothelial carcinoma with FGFR2 and FGFR3 mutations.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bowden M, Nadal R, Zhou CW, et al. Transcriptomic analysis of micropapillary high grade T1 urothelial bladder cancer. Sci Rep. 2020;10(1):20135.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA

    Deepika Kumar & Adebowale J. Adeniran

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  1. Deepika Kumar
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Correspondence to Adebowale J. Adeniran.

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Kumar, D., Adeniran, A.J. Clinicopathological Review of Micropapillary Urothelial Carcinoma. Curr Oncol Rep 24, 603–610 (2022). https://doi.org/10.1007/s11912-022-01219-x

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