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Non-Urothelial Malignancies and Other Miscellaneous Lesions

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Abstract

Non-Urothelial malignancies (NUM) are uncommon and make up less than 5% of bladder tumors. They refer to malignancies other than high-grade urothelial carcinomas (HGUC) and may present as primary or secondary disease. NUM can demonstrate epithelial or non-epithelial features and frequently pose diagnostic challenges for cytologists and pathologists, due to their morphologic overlap with HGUC.

Primary epithelial NUM, including pure squamous cell carcinoma, adenocarcinoma, and small-cell carcinoma, have been shown to carry an aggressive biological behavior and often present at an advanced stage. Non-epithelial NUM include sarcoma, melanoma, and lymphoma. Secondary involvement of the urinary bladder by NUM occurs through metastases from distant sites or by direct extension from adjacent organs, such as the cervix, colorectum, and prostate.

Urine cytology can be a helpful tool in the initial diagnosis of primary or secondary NUM, which can be critical for appropriate management and subsequent prognostication.

Keywords

  • Urinary bladder
  • Non-urothelial malignancies
  • Other malignancies
  • Metastasis
  • Epithelial tumors
  • Non-epithelial tumors
  • Tumor-like lesions of urinary bladder, Miscellaneous lesions, atypical squamous cells

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References

  1. Chalasani V, Chin JL, Izawa JI. Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer. Can Urol Assoc J. 2009;3:S193–8.

    PubMed  PubMed Central  Google Scholar 

  2. Dahm P, Gschwend JE. Malignant non-urothelial neoplasms of the urinary bladder: a review. Eur Urol. 2003;44:672–81.

    PubMed  Google Scholar 

  3. Kunze E. Histogenesis of nonurothelial carcinomas in the human and rat urinary bladder. Exp Toxicol Pathol. 1998;50:341–55.

    CAS  PubMed  Google Scholar 

  4. Barkan GA, Laucirica R, Auger M, et al. Performance characteristics of urinary tract cytology: observations from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology. Arch Pathol Lab Med. 2015;139:1009–13.

    PubMed  Google Scholar 

  5. Abol-Enein H, Kava BR, Carmack AJ. Nonurothelial cancer of the bladder. Urology. 2007;69:93–104.

    PubMed  Google Scholar 

  6. Nishiyama H, Habuchi T, Watanabe J, et al. Clinical outcome of a large-scale multi-institutional retrospective study for locally advanced bladder cancer: a survey including 1131 patients treated during 1990–2000 in Japan. Eur Urol. 2004;45:176–81.

    PubMed  Google Scholar 

  7. Deuker M, Martin T, Stolzenbach F, et al. Bladder cancer: a comparison between non-urothelial variant histology and urothelial carcinoma across all stages and treatment modalities. Clin Genitourin Cancer. 2021;19:60–8.

    PubMed  Google Scholar 

  8. Quinn DI. Non-urothelial bladder cancer. Web site: https://www.uptodate.com/contents/non-urothelial-bladder-cancer. Published 2019. Updated 02/13/2019. Last Accessed 11/01/2020.

  9. Xiao GQ, Chow J, Unger PD. Metastatic tumors to the urinary bladder: clinicopathologic study of 11 cases. Int J Surg Pathol. 2012;20:342–8.

    PubMed  Google Scholar 

  10. Hoda RS. Non-gynecologic cytology on liquid-based preparations: a morphologic review of facts and artifacts. Diagn Cytopathol. 2007;35:621–34.

    PubMed  Google Scholar 

  11. Laucirica R, Bentz JS, Souers RJ, 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. Arch Pathol Lab Med. 2010;134:19–22.

    PubMed  Google Scholar 

  12. Luo Y, She DL, Xiong H, Yang L, Fu SJ. Diagnostic value of liquid-based cytology in urothelial carcinoma diagnosis: a systematic review and meta-analysis. PLoS One. 2015;10:e0134940.

    PubMed  PubMed Central  Google Scholar 

  13. Straccia P, Bizzarro T, Fadda G, Pierconti F. Comparison between Cytospin and liquid-based cytology in urine specimens classified according to the Paris System for Reporting Urinary Cytology. Cancer Cytopathol. 2016;124:519–23.

    CAS  PubMed  Google Scholar 

  14. Elsheikh TM, Kirkpatrick JL, Wu HH. Comparison of ThinPrep and Cytospin preparations in the evaluation of exfoliative cytology specimens. Cancer. 2006;108:144–9.

    PubMed  Google Scholar 

  15. Koss LG, Hoda RS. Koss’s cytology of the urinary tract with histopathologic correlations. New York: Springer Press; 2012.

    Google Scholar 

  16. Shen SS, Al-Ahmadie HH, Mahfouz SM. Squamous cell neoplasms. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editors. WHO classification of tumors of the urinary system and male genital organs. Lyon, France: International Agency for Research on Cancer; 2016. p. 108–10.

    Google Scholar 

  17. Khaled H. Schistosomiasis and cancer in Egypt: review. J Adv Res. 2013;4:461–6.

    PubMed  PubMed Central  Google Scholar 

  18. Johansson SL, Cohen SM. Epidemiology and etiology of bladder cancer. Semin Surg Oncol. 1997;13:291–8.

    CAS  PubMed  Google Scholar 

  19. Alanee S, Alvarado-Cabrero I, Murugan P, et al. Update of the International Consultation on Urological Diseases on bladder cancer 2018: non-urothelial cancers of the urinary bladder. World J Urol. 2019;37:107–14.

    PubMed  Google Scholar 

  20. Hattori M, Nishimura Y, Toyonaga M, Kakinuma H, Matsumoto K, Ohbu M. Cytological significance of abnormal squamous cells in urinary cytology. Diagn Cytopathol. 2012;40:798–803.

    PubMed  Google Scholar 

  21. Owens CL, Ali SZ. Atypical squamous cells in exfoliative urinary cytology: clinicopathologic correlates. Diagn Cytopathol. 2005;33:394–8.

    PubMed  Google Scholar 

  22. Sojitra P, Venkataraman G, Masoom S, Kapur U, Wojcik EM. Dysplastic squamous cells are frequently present in urine cytology specimens of patients with high-grade urothelial carcinoma. Acta Cytol. 2012;56:408–12.

    PubMed  Google Scholar 

  23. Goyal A, Ray N, Chute DJ, Abdul-Karim FW. Significance of cytologic detection of low-grade squamous intraepithelial lesion in urine. J Am Soc Cytopathol. 2014;3:251–5.

    PubMed  Google Scholar 

  24. DeMay RC. The art and science of cytopathology. Chicago: ASCP Press; 2012.

    Google Scholar 

  25. Cho HW, Hong JH, Min KJ, et al. Performance and diagnostic accuracy of human papillomavirus testing on self-collected urine and vaginal samples in a referral population. Cancer Res Treat. 2021;53:829.

    CAS  PubMed  Google Scholar 

  26. Shin HY, Lee B, Hwang SH, et al. Evaluation of satisfaction with three different cervical cancer screening modalities: clinician-collected Pap test vs. HPV test by self-sampling vs. HPV test by urine sampling. J Gynecol Oncol. 2019;30:e76.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Arbyn M, Verdoodt F, Snijders PJ, et al. Accuracy of human papillomavirus testing on self-collected versus clinician-collected samples: a meta-analysis. Lancet Oncol. 2014;15:172–83.

    PubMed  Google Scholar 

  28. Rohner E, Rahangdale L, Sanusi B, et al. Test accuracy of human papillomavirus in urine for detection of cervical intraepithelial neoplasia. J Clin Microbiol. 2020;58:e01443–19.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Moch H, Humphrey PA, Ulbright TM, Reuter VE, editors. WHO classification of tumors of the urinary system and male genital organs. 4th ed. Lyon: International agency for research on cancer; 2016.

    Google Scholar 

  30. Zhong M, Gersbach E, Rohan SM, Yang XJ. Primary adenocarcinoma of the urinary bladder: differential diagnosis and clinical relevance. Arch Pathol Lab Med. 2013;137:371–81.

    CAS  PubMed  Google Scholar 

  31. Grignon DJ, Cheville J, Ro JY, Tamboli P. Glandular neoplasms. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editor. WHO classification of tumors of the urinary system and male genital organs International agency for research on cancer. Lyon; 2016:111–112.

    Google Scholar 

  32. Bardales RH, Pitman MB, Stanley MW, Korourian S, Suhrland MJ. Urine cytology of primary and secondary urinary bladder adenocarcinoma. Cancer. 1998;84:335–43.

    CAS  PubMed  Google Scholar 

  33. Guan H, Tatsas AD, Ali SZ. Signet ring cell carcinoma in urine cytology: cytomorphologic findings and differential diagnosis. Acta Cytol. 2012;56:177–82.

    PubMed  Google Scholar 

  34. Grignon DJ, Al-Ahmadie H, Algaba F, Amin MB, et al. Urothelial tumors, infiltrating urothelial carcinoma. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editors. WHO classification of tumors of the urinary system and male genital organs. Lyon: International agency for research on cancer; 2016. p. 81–98.

    Google Scholar 

  35. Young RH. Tumor-like lesions of the urinary bladder. Mod Pathol. 2009;22 Suppl 2:S37–52.

    PubMed  Google Scholar 

  36. Savant D, Bajaj J, Gimenez C, et al. Urine cytology of nonurothelial malignancies-a 10-year experience in a large multihospital healthcare system. Diagn Cytopathol. 2017;45:22–8.

    PubMed  Google Scholar 

  37. Ro JY, Shen SS, Lee HI, et al. Plasmacytoid transitional cell carcinoma of urinary bladder: a clinicopathologic study of 9 cases. Am J Surg Pathol. 2008;32:752–7.

    PubMed  Google Scholar 

  38. Ellis CL, Chang AG, Cimino-Mathews A, et al. GATA-3 immunohistochemistry in the differential diagnosis of adenocarcinoma of the urinary bladder. Am J Surg Pathol. 2013;37:1756–60.

    PubMed  Google Scholar 

  39. Fox MD, Xiao L, Zhang M, et al. Plasmacytoid urothelial carcinoma of the urinary bladder: a clinicopathologic and immunohistochemical analysis of 49 cases. Am J Clin Pathol. 2017;147:500–6.

    CAS  PubMed  Google Scholar 

  40. Al-Ahmadie H, Comperat E, Epstein JI. Neuroendocrine tumors. In: Moch HH, PA, Ulbright TM, Reuter VE, editor. WHO classification of tumors of the urinary system and male genital organs. Lyon: International agency for research on cancer; 2016. p. 117–119.

    Google Scholar 

  41. Ciesla MC, Guidos BJ, Selvaggi SM. Cytomorphology of small-cell (neuroendocrine) carcinoma on ThinPrep cytology as compared to conventional smears. Diagn Cytopathol. 2001;24:46–52.

    CAS  PubMed  Google Scholar 

  42. Alijo Serrano F, Sanchez-Mora N, Angel Arranz J, Hernandez C, Alvarez-Fernandez E. Large cell and small cell neuroendocrine bladder carcinoma: immunohistochemical and outcome study in a single institution. Am J Clin Pathol. 2007;128:733–9.

    PubMed  Google Scholar 

  43. Chen YB, Epstein JI. Primary carcinoid tumors of the urinary bladder and prostatic urethra: a clinicopathologic study of 6 cases. Am J Surg Pathol. 2011;35:442–6.

    CAS  PubMed  Google Scholar 

  44. Helpap B. Morphology and therapeutic strategies for neuroendocrine tumors of the genitourinary tract. Cancer. 2002;95:1415–20.

    PubMed  Google Scholar 

  45. van Hoeven KH, Artymyshyn RL. Cytology of small cell carcinoma of the urinary bladder. Diagn Cytopathol. 1996;14:292–7.

    PubMed  Google Scholar 

  46. Ainechi S, Pambuccian SE, Wojcik EM, Barkan GA. Cytomorphologic features and differential diagnosis of neoplasms with small cell features in liquid-based urinary tract cytologic specimens. J Am Soc Cytopathol. 2015;4:295–306.

    PubMed  Google Scholar 

  47. Acs G, Gupta PK, Baloch ZW. Cytomorphology of high-grade neuroendocrine carcinoma of the urinary tract. Diagn Cytopathol. 2000;23:92–6.

    CAS  PubMed  Google Scholar 

  48. Bates AW, Baithun SI. Secondary neoplasms of the bladder are histological mimics of nontransitional cell primary tumours: clinicopathological and histological features of 282 cases. Histopathology. 2000;36:32–40.

    CAS  PubMed  Google Scholar 

  49. Grignon DJ, Epstein J, Oliva E, Ro JY, Shen SS. Metastatic tumors In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editor. WHO classification of tumors of the urinary system and male genital organs. Lyon: International agency for research on cancer; 2016. p. 130.

    Google Scholar 

  50. Velcheti V, Govindan R. Metastatic cancer involving bladder: a review. Can J Urol. 2007;14:3443–8.

    PubMed  Google Scholar 

  51. Murphy WM, Grignon DJ, Perlman EJ. Tumors of the urinary bladder. Tumors of the kidney, bladder, and related urinary structures: American registry of pathology; 2004. p. 241–361.

    Google Scholar 

  52. Rao Q, Williamson SR, Lopez-Beltran A, et al. Distinguishing primary adenocarcinoma of the urinary bladder from secondary involvement by colorectal adenocarcinoma: extended immunohistochemical profiles emphasizing novel markers. Mod Pathol. 2013;26:725–32.

    CAS  PubMed  Google Scholar 

  53. Renshaw AA. Urine and bladder washings. In: Cibas E, Ducatman B, editors. Cytology: diagnostic principles and clinical correlates. Philadelphia: Elsevier; 2021.

    Google Scholar 

  54. Sathiyamoorthy S, Ali SZ. Urinary cytology of prostatic duct adenocarcinoma - a clinicopathologic analysis. Acta Cytol. 2013;57:184–8.

    PubMed  Google Scholar 

  55. Feldman A, Borak S, Rais-Bahrami S, Gordetsky J. Secondary malignancies of the bladder: avoiding the diagnostic pitfall. Int J Surg Pathol. 2018;26:120–5.

    PubMed  Google Scholar 

  56. Blochin EB, Park KJ, Tickoo SK, Reuter VE, Al-Ahmadie H. Urothelial carcinoma with prominent squamous differentiation in the setting of neurogenic bladder: role of human papillomavirus infection. Mod Pathol. 2012;25:1534–42.

    PubMed  Google Scholar 

  57. Gordetsky J, Spieker AJ, Pena M, et al. Squamous cell carcinoma of the bladder is not associated with high-risk HPV. Urology. 2020;144:158–63.

    PubMed  Google Scholar 

  58. Zhao P. Urine cytology of metastatic breast lobular carcinoma. Diagn Cytopathol. 2019;47:738–9.

    PubMed  Google Scholar 

  59. Liu H, Shi J, Wilkerson ML, Lin F. Immunohistochemical evaluation of GATA3 expression in tumors and normal tissues: a useful immunomarker for breast and urothelial carcinomas. Am J Clin Pathol. 2012;138:57–64.

    PubMed  Google Scholar 

  60. Vigliar E, Marino G, Matano E, Imbimbo C, de Rossella C, Insabato L. Signet-ring-cell carcinoma of stomach metastatic to the bladder: a case report with cytological and histological correlation and literature review. Int J Surg Pathol. 2013;21:72–5.

    PubMed  Google Scholar 

  61. Sanguedolce F, Loizzi D, Sollitto F, et al. Bladder metastases from lung cancer: clinical and pathological implications: a systematic review. Oncology. 2017;92:125–34.

    PubMed  Google Scholar 

  62. Karle W, Barazani Y, Tareen B. A rare case of metastatic lung cancer to the bladder. Can Urol Assoc J. 2012;6:E147–9.

    PubMed  PubMed Central  Google Scholar 

  63. Layfield LJ, Elsheikh TM, Fili A, Nayar R, Shidham V, Papanicolaou Society of C. Review of the state of the art and recommendations of the Papanicolaou Society of Cytopathology for urinary cytology procedures and reporting: the Papanicolaou Society of Cytopathology Practice Guidelines Task Force. Diagn Cytopathol. 2004;30:24–30.

    PubMed  Google Scholar 

  64. Cheville J, Folpe A. Mesenchymal tumors In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editor. WHO Classification of tumors of the urinary system and male genital organs. Lyon: International agency for research on cancer; 2016. p. 122–127.

    Google Scholar 

  65. Iwa N, Ito S, Takegaki Y, et al. Cytologic features of sarcomatoid carcinoma of the urinary bladder: a case report. Diagn Cytopathol. 2013;41:536–41.

    PubMed  Google Scholar 

  66. Hemachandran M, Nada R, Rajwanshi A. Leiomyosarcoma of the urinary bladder: a diagnostic challenge in urine cytology. Diagn Cytopathol. 2004;31:281–2.

    PubMed  Google Scholar 

  67. Mitra S, Kaur G, Kakkar N, Singh P, Dey P. Sarcoma in urine cytology; an extremely rare entity: a report of two cases. J Cytol. 2017;34:171–3.

    PubMed  PubMed Central  Google Scholar 

  68. Westfall DE, Folpe AL, Paner GP, et al. Utility of a comprehensive immunohistochemical panel in the differential diagnosis of spindle cell lesions of the urinary bladder. Am J Surg Pathol. 2009;33:99–105.

    PubMed  Google Scholar 

  69. Algaba F, Eble J. Melanocytic tumors. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editor. WHO classification of tumors of the urinary system and male genital organs. Lyon: International Agency for Research on Cancer; 2016. p. 120–21.

    Google Scholar 

  70. Khalbuss WE, Hossain M, Elhosseiny A. Primary malignant melanoma of the urinary bladder diagnosed by urine cytology: a case report. Acta Cytol. 2001;45:631–5.

    CAS  PubMed  Google Scholar 

  71. McIntire PJ, Kilic I, Wojcik EM, Barkan GA, Pambuccian SE. The color of urine: then and now-a comprehensive review of the literature with emphasis on intracytoplasmic pigments encountered in urinary cytology. J Am Soc Cytopathol. 2020;9:9–19.

    PubMed  Google Scholar 

  72. Chen N, Gong J, Chen X, et al. Cytokeratin expression in malignant melanoma: potential application of in-situ hybridization analysis of mRNA. Melanoma Res. 2009;19:87–93.

    CAS  PubMed  Google Scholar 

  73. Osunkoya AO, Humphrey PA. Hematopoietic and lymphoid tumors. In: Moch H, Humphrey PA, Ulbright TM, Reuter VE, editor. WHO classification of tumors of the urinary system and male genital organs Lyon, Lyon: International Agency for Research on Cancer; 2016. p. 128–129.

    Google Scholar 

  74. Bhutani DN, Goel DV, Kajal DP, Pawar DD, Sharma DP, Sen DR. Primary extra nodal Non-Hodgkin's lymphoma of urinary bladder presenting as a bladder tumor: a case report. Ann Med Surg (Lond). 2020;56:68–71.

    PubMed Central  Google Scholar 

  75. Quinn AM, Flanigan R, Sienko A, Wojcik EM. Cytologic features of recurrent lymphoma involving the urinary bladder. Diagn Cytopathol. 2004;31:185–8.

    PubMed  Google Scholar 

  76. Farinola MA, Lawler LP, Rosenthal D. Plasmacytoma with involvement of the urinary bladder. Report of a case diagnosed by urine cytology. Acta Cytol. 2003;47:787–91.

    PubMed  Google Scholar 

  77. Park S, Kang SY, Kwon GY, et al. Clinicopathologic characteristics and mutational status of succinate dehydrogenase genes in paraganglioma of the urinary bladder: a multi-institutional Korean study. Arch Pathol Lab Med. 2017;141:671–7.

    CAS  PubMed  Google Scholar 

  78. Lee J, Park S, Cho MS, Sung SH, Kim KH. Urine cytology findings of primary paraganglioma of the urinary bladder: case report. Diagn Cytopathol. 2017;45:350–3.

    PubMed  Google Scholar 

  79. Pina-Oviedo S, Shen SS, Truong LD, Ayala AG, Ro JY. Flat pattern of nephrogenic adenoma: previously unrecognized pattern unveiled using PAX2 and PAX8 immunohistochemistry. Mod Pathol. 2013;26:792–8.

    CAS  PubMed  Google Scholar 

  80. Rutgers JL, Young RH. Nephrogenic adenoma of the urinary bladder: a comparison of its cytologic and histopathologic features in ten cases. Diagn Cytopathol. 1988;4:210–6.

    CAS  PubMed  Google Scholar 

  81. McCroskey Z, Pambuccian SE, Wojcik EM, Barkan GA. Can we identify nephrogenic adenoma in urine cytology specimens? A study evaluating previously described cytomorphologic features in correlation with PAX8 immunohistochemical staining results. Am J Clin Pathol. 2016;145:373–8.

    CAS  PubMed  Google Scholar 

  82. Koss LG. Diagnostic cytology of the urinary tract with histopathologic and clinical correlations. Philadelphia: Lippincott-Raven; 1996.

    Google Scholar 

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Elsheikh, T.M., Hoda, R.S., Pambuccian, S.E., Ro, J.Y., Sung, S.H. (2022). Non-Urothelial Malignancies and Other Miscellaneous Lesions. In: Wojcik, E.M., Kurtycz, D.F., Rosenthal, D.L. (eds) The Paris System for Reporting Urinary Cytology. Springer, Cham. https://doi.org/10.1007/978-3-030-88686-8_8

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