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Vascular architectural patterns in clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma

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Abstract

Renal cell carcinomas (RCC) are well-vascularized tumors. Although clear cell RCC (CCRCC) show a characteristic vascular network, some cases show overlapping features with other RCC. We aimed to evaluate vascular architectural patterns, microvessel density (MVD), and endothelial cell density (ECD) in CCRCC compared to clear cell papillary RCC (ccpRCC). Thirty-four RCC (17 CCRCC and 17 ccpRCC) were included in the study. CD34 was used to evaluate vascular architectural patterns by microscopic estimation in all cases. CD34, ERG, and Bioquant Osteo 2019 Imaging Analysis Software were used to evaluate MVD and ECD in 17 CCRCC and 15 ccpRCC. Mean MVD was 526.63 in CCRCC vs. 426.18 in ccpRCC (p = 0.16); mean ECD was 937.50 in CCRCC vs. 1060.21 in ccpRCC (p = 0.25). CD34 highlighted four distinct vascular architectural patterns: pseudoacinar, Golgi-like, lacunae, and scattered. Lacunae and pseudoacinar was the most frequent combination in CCRCC; lacunae and Golgi-like was the predominant combination among ccpRCC. Pseudoacinar was most extensive in CCRCC and least in ccpRCC; Golgi-like was predominant in ccpRCC and uncommon in CCRCC. The extent of pseudoacinar and Golgi-like vascular architectural patterns was significantly different between CCRCC and ccpRCC (p < 0.05). Pathologists acquainted with these different vascular architectural patterns may utilize them as an additional tool in the distinction of CCRCC from ccpRCC.

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  • 17 October 2021

    The citation of the author name Maria del Carmen Rodriguez Pena has been updated.

References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer statistics, 2021. CA Cancer J Clin 71:7–33. https://doi.org/10.3322/caac.21654

    Article  Google Scholar 

  2. Moch H, Bonsib SM, Delahunt B, Eble JN, Egevad L, Grignon DJ, Linehan WM, Reuter VE, Srigley JR, Sulser T, PH T (2016) Clear cell renal cell carcinoma. In: Moch H, Humphrey PA, Ulbright TM, VE R (eds) WHO classification of tumours of the urinary system and male genital organs. International Agency for Research on Cancer, Lyon, pp. 18–21

  3. Wang G, Rao P (2018) Succinate dehydrogenase-deficient renal cell carcinoma: a short review. Arch Pathol Lab Med 142:1284–1288. https://doi.org/10.5858/arpa.2017-0199-RS

    Article  PubMed  CAS  Google Scholar 

  4. Perrino CM, Grignon DJ, Williamson SR, Idrees MT, Eble JN, Cheng L (2018) Morphological spectrum of renal cell carcinoma, unclassified: an analysis of 136 cases. Histopathology 72:305–319. https://doi.org/10.1111/his.13362

    Article  PubMed  Google Scholar 

  5. Williamson SR, Taneja K, Cheng L (2019) Renal cell carcinoma staging: pitfalls, challenges, and updates. Histopathology 74:18–30. https://doi.org/10.1111/his.13743

    Article  PubMed  Google Scholar 

  6. Warren AY, Harrison D (2018) WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies. World J Urol 36:1913–1926. https://doi.org/10.1007/s00345-018-2447-8

    Article  PubMed  PubMed Central  Google Scholar 

  7. Michal M, Hes O, Havlicek F (2000) Benign renal angiomyoadenomatous tumor: a previously unreported renal tumor. Ann Diagn Pathol 4:311–315. https://doi.org/10.1053/adpa.2000.17890

    Article  PubMed  CAS  Google Scholar 

  8. Tickoo SK, dePeralta-Venturina MN, Harik LR, Worcester HD, Salama ME, Young AN, Moch H, Amin MB (2006) Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia. Am J Surg Pathol 30:141–153. https://doi.org/10.1097/01.pas.0000185382.80844.b1

    Article  PubMed  Google Scholar 

  9. Williamson SR, Gupta NS, Eble JN, Rogers CG, Michalowski S, Zhang S, Wang M, Grignon DJ, Cheng L (2015) Clear cell renal cell carcinoma with borderline features of clear cell papillary renal cell carcinoma: combined morphologic, immunohistochemical, and cytogenetic analysis. Am J Surg Pathol 39:1502–1510. https://doi.org/10.1097/PAS.0000000000000514

    Article  PubMed  Google Scholar 

  10. Zhao J, Eyzaguirre E (2019) Clear cell papillary renal cell carcinoma. Arch Pathol Lab Med 143:1154–1158. https://doi.org/10.5858/arpa.2018-0121-RS

    Article  PubMed  CAS  Google Scholar 

  11. Srigley JR, Cheng L, Grignon DJ, Tickoo S (2016) Clear cell papillary renal cell carcinoma. In: Moch H, Humphrey PA, Ulbright TM, VE R (eds) WHO classification of tumours of the urinary system and male genital organs. International Agency for Research on Cancer, Lyon, pp. 40–41

  12. Chen WJ, Pan CC, Shen SH, Chung HJ, Lin CC, Lin ATL, Chang YH (2018) Clear cell papillary renal cell carcinoma - an indolent subtype of renal tumor. J Chin Med Assoc 81:878–883. https://doi.org/10.1016/j.jcma.2018.04.005

    Article  PubMed  Google Scholar 

  13. Leroy X, Camparo P, Gnemmi V, Aubert S, Flamand V, Roupret M, Fantoni JC, Comperat E (2014) Clear cell papillary renal cell carcinoma is an indolent and low-grade neoplasm with overexpression of cyclin-D1. Histopathology 64:1032–1036. https://doi.org/10.1111/his.12359

    Article  PubMed  Google Scholar 

  14. Trpkov K, Hes O, Williamson SR, Adeniran AJ, Agaimy A, Alaghehbandan R, Amin MB, Argani P, Chen YB, Cheng L, Epstein JI, Cheville JC, Comperat E, da Cunha IW, Gordetsky JB, Gupta S, He H, Hirsch MS, Humphrey PA, Kapur P, Kojima F, Lopez JI, Maclean F, Magi-Galluzzi C, McKenney JK, Mehra R, Menon S, Netto GJ, Przybycin CG, Rao P, Rao Q, Reuter VE, Saleeb RM, Shah RB, Smith SC, Tickoo S, Tretiakova MS, True L, Verkarre V, Wobker SE, Zhou M, Gill AJ (2021) New developments in existing WHO entities and evolving molecular concepts: the Genitourinary Pathology Society (GUPS) update on renal neoplasia Mod Pathol. https://doi.org/10.1038/s41379-021-00779-w

  15. Williamson SR (2021) Clear cell papillary renal cell carcinoma: an update after 15 years. Pathology 53:109–119. https://doi.org/10.1016/j.pathol.2020.10.002

    Article  PubMed  CAS  Google Scholar 

  16. Williamson SR, Eble JN, Cheng L, Grignon DJ (2013) Clear cell papillary renal cell carcinoma: differential diagnosis and extended immunohistochemical profile. Mod Pathol 26:697–708. https://doi.org/10.1038/modpathol.2012.204

    Article  PubMed  CAS  Google Scholar 

  17. Gobbo S, Eble JN, Maclennan GT, Grignon DJ, Shah RB, Zhang S, Martignoni G, Brunelli M, Cheng L (2008) Renal cell carcinomas with papillary architecture and clear cell components: the utility of immunohistochemical and cytogenetical analyses in differential diagnosis. Am J Surg Pathol 32:1780–1786. https://doi.org/10.1097/PAS.0b013e31818649ed

    Article  PubMed  Google Scholar 

  18. Dhakal HP, McKenney JK, Khor LY, Reynolds JP, Magi-Galluzzi C, Przybycin CG (2016) Renal neoplasms with overlapping features of clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma: a clinicopathologic study of 37 cases from a single institution. Am J Surg Pathol 40:141–154. https://doi.org/10.1097/PAS.0000000000000583

    Article  PubMed  Google Scholar 

  19. Lopez JI, Erramuzpe A, Guarch R, Cortes JM, Pulido R, Llarena R, Angulo JC (2017) CD34 immunostaining enhances a distinct pattern of intratumor angiogenesis with prognostic implications in clear cell renal cell carcinoma. APMIS 125:128–133. https://doi.org/10.1111/apm.12649

    Article  PubMed  CAS  Google Scholar 

  20. MacLennan GT, Bostwick DG (1995) Microvessel density in renal cell carcinoma: lack of prognostic significance. Urology 46:27–30. https://doi.org/10.1016/S0090-4295(99)80153-8

    Article  PubMed  CAS  Google Scholar 

  21. Jilaveanu LB, Puligandla M, Weiss SA, Wang XV, Zito C, Flaherty KT, Boeke M, Neumeister V, Camp RL, Adeniran A, Pins M, Manola J, DiPaola RS, Haas NB, Kluger HM (2018) Tumor microvessel density as a prognostic marker in high-risk renal cell carcinoma patients treated on ECOG-ACRIN E2805. Clin Cancer Res 24:217–223. https://doi.org/10.1158/1078-0432.CCR-17-1555

    Article  PubMed  CAS  Google Scholar 

  22. Cheng SH, Liu JM, Liu QY, Luo DY, Liao BH, Li H, Wang KJ (2014) Prognostic role of microvessel density in patients with renal cell carcinoma: a meta-analysis. Int J Clin Exp Pathol 7:5855–5863

    PubMed  PubMed Central  Google Scholar 

  23. Sato M, Nakai Y, Nakata W, Yoshida T, Hatano K, Kawashima A, Fujita K, Uemura M, Takayama H, Nonomura N (2014) Microvessel area of immature vessels is a prognostic factor in renal cell carcinoma. Int J Urol 21:130–134. https://doi.org/10.1111/iju.12231

    Article  PubMed  Google Scholar 

  24. Weidner N (1995) Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat 36:169–180. https://doi.org/10.1007/BF00666038

    Article  PubMed  CAS  Google Scholar 

  25. Wang D, Stockard CR, Harkins L, Lott P, Salih C, Yuan K, Buchsbaum D, Hashim A, Zayzafoon M, Hardy RW, Hameed O, Grizzle W, Siegal GP (2008) Immunohistochemistry in the evaluation of neovascularization in tumor xenografts. Biotech Histochem 83:179–189. https://doi.org/10.1080/10520290802451085

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Wang ZB, An XJ, Deng JF, Liu JH, Shi HY (2017) Characteristics of ERG, Fli-1, CD34, CD31 and FRAg expression in hepatic malignant vascular tumors. Zhonghua Bing Li Xue Za Zhi 46:760–763. https://doi.org/10.3760/cma.j.issn.0529-5807.2017.11.005

    Article  PubMed  CAS  Google Scholar 

  27. Mezei T, Horvath E, Turcu M, Gurzu S, Raica M, Jung I (2012) Microvascular density in non-Hodgkin B-cell lymphomas measured using digital morphometry. Rom J Morphol Embryol 53:67–71

    PubMed  CAS  Google Scholar 

  28. Gaumann AK, Schermutzki G, Mentzel T, Kirkpatrick CJ, Kriegsmann JB, Konerding MA (2008) Microvessel density and VEGF/VEGF receptor status and their role in sarcomas of the pulmonary artery. Oncol Rep 19:309–318

    PubMed  Google Scholar 

  29. Meert AP, Paesmans M, Martin B, Delmotte P, Berghmans T, Verdebout JM, Lafitte JJ, Mascaux C, Sculier JP (2002) The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer 87:694–701. https://doi.org/10.1038/sj.bjc.6600551

    Article  PubMed  PubMed Central  Google Scholar 

  30. de Vilhena AF, das Neves Pereira JC, Parra ER, Balancin ML, Ab Saber A, Martins V, Farhat C, Abrantes MM, de Campos JRM, Tedde ML, Takagaki T, Capelozzi VL (2018) Histomorphometric evaluation of the Ki-67 proliferation rate and CD34 microvascular and D2-40 lymphovascular densities drives the pulmonary typical carcinoid outcome Hum Pathol 81:201-210. doi: https://doi.org/10.1016/j.humpath.2018.07.007

  31. Marcon J, Graser A, Horst D, Casuscelli J, Spek A, Stief CG, Reiser MF, Rubenthaler J, Buchner A, Staehler M (2020) Papillary vs clear cell renal cell carcinoma. Differentiation and grading by iodine concentration using DECT-correlation with microvascular density. Eur Radiol 30:1–10. https://doi.org/10.1007/s00330-019-06298-2

    Article  PubMed  CAS  Google Scholar 

  32. Cioca A, Muntean D, Bungardean C (2019) CD105 as a tool for assessing microvessel density in renal cell carcinoma. Indian J Pathol Microbiol 62:239–243. https://doi.org/10.4103/IJPM.IJPM_773_17

    Article  PubMed  Google Scholar 

  33. Ruiz-Sauri A, Garcia-Bustos V, Granero E, Cuesta S, Sales MA, Marcos V, Llombart-Bosch A (2018) Distribution of vascular patterns in different subtypes of renal cell carcinoma. a morphometric study in two distinct types of blood vessels. Pathol Oncol Res 24:515–524. https://doi.org/10.1007/s12253-017-0262-y

    Article  PubMed  Google Scholar 

  34. Sandlund J, Hedberg Y, Bergh A, Grankvist K, Ljungberg B, Rasmuson T (2007) Evaluation of CD31 (PECAM-1) expression using tissue microarray in patients with renal cell carcinoma. Tumour Biol 28:158–164. https://doi.org/10.1159/000102980

    Article  PubMed  CAS  Google Scholar 

  35. Ferician O, Cimpean AM, Ceausu AR, Dema A, Raica M, Cumpanas A (2016) Heterogeneous vascular patterns in renal cell carcinomas. Pol J Pathol 67:46–53. https://doi.org/10.5114/pjp.2016.59477

    Article  PubMed  CAS  Google Scholar 

  36. Nikolova-Krstevski V, Yuan L, Le Bras A, Vijayaraj P, Kondo M, Gebauer I, Bhasin M, Carman CV, Oettgen P (2009) ERG is required for the differentiation of embryonic stem cells along the endothelial lineage. BMC Dev Biol 9:72. https://doi.org/10.1186/1471-213X-9-72

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Han E, Kim J, Jung MJ, Chin S, Lee JH, Won KY, Moon A (2021) ERG and nestin: useful markers of immature vessels and novel prognostic markers in renal cell carcinoma Int J. Clin Exp Pathol 14:116–125

    CAS  Google Scholar 

  38. Iakovlev VV, Gabril M, Dubinski W, Scorilas A, Youssef YM, Faragalla H, Kovacs K, Rotondo F, Metias S, Arsanious A, Plotkin A, Girgis AH, Streutker CJ, Yousef GM (2012) Microvascular density as an independent predictor of clinical outcome in renal cell carcinoma: an automated image analysis study. Lab Invest 92:46–56. https://doi.org/10.1038/labinvest.2011.153

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, University of Alabama at Birmingham, NP 3545A, 1802 6th Avenue South, Birmingham, AL, 35249-7331, USA

    Sofia Canete-Portillo, Maria del Carmen Rodriguez Pena, Dezhi Wang, George J. Netto & Cristina Magi-Galluzzi

  2. Instituto de Patología E Investigación, Asunción, Paraguay

    Diego F. Sanchez

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  1. Sofia Canete-Portillo
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Contributions

S. C.-P. conceived of the study, formulated its design, coordinated the conduct of the study including data collection, performed the statistical analysis and interpreted the data, and drafted the manuscript; C. M.-G. participated in the design of the study, assisted in interpreting the data, and helped to draft the manuscript; M. C. R. P. participated in the design of the study, assisted in interpreting the data, and helped to draft the manuscript; D. W. coordinated the conduct of the study including data collection; D. F. S. performed the statistical analysis and interpreted the data; G. J. N. reviewed and edited the manuscript. All authors read and approved the final manuscript.

This study was approved by the university human research ethics committee, and all procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Correspondence to Cristina Magi-Galluzzi.

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Canete-Portillo, S., Rodriguez Pena, M.d.C., Wang, D. et al. Vascular architectural patterns in clear cell renal cell carcinoma and clear cell papillary renal cell carcinoma. Virchows Arch 479, 1187–1196 (2021). https://doi.org/10.1007/s00428-021-03214-2

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