• Dmytro Zerbino Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
  • Solomiya Fedevych Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
  • Yuliia Kuzyk Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
Keywords: clear cell renal cell carcinoma, peritumoral tissue, renal intratubular neoplasia, ultrastructure


The aim was to investigate in a comparative plan the ultrastructural peculiarities of cells, cellular and noncellular elements of renal intratubular neoplasia of peritumoral tissue with highly, average and low grades of differentiation at clear cell renal cell carcinoma (CCRCC).

Material and methods. Material for conducting transmission electron microscopic researches was postoperative biopsies of the peritumoral tissue at highly differentiated CCRCC (G1) – five cases; at an average grade of differentiation (G2) – five cases; at low grade of differentiation (G3) – six cases.

The renal tubules (RT) and tangential stroma elements with different differentiation (G1, G2, G3) in peritumoral tissue at the ultrastructural level were investigated.

Results. It was revealed that in RT of peritumoral tissue at highly differentiated CCRCC (G1) and the average degree of differentiation (G2) cells of renal intratubular neoplasia zones are represented mainly in the average electronic density by little-differentiated epithelial cells with a large nuclear-cytoplasmic ration. Epithelial cells with small nuclear-cytoplasmic ratio, the cytoplasm of which is filled with disorganized small mitochondria, Mallory bodies, glycogen granules and autophagosomes, are present in separate cells zones of the renal intratubular neoplasia with the CCRCC of the indicated degrees of differentiation. Peritumoral tissue at highly differentiated CCRCC (G1) and the average degree of differentiation (G2) contains hemocapillaries, small venules, clusters of fibroblasts, macrophages, plasmocytes.

A characteristic ultrastructural feature of peritumoral tissue with a low degree of differentiation (G3) at CCRCC is the presence of a small diameter RT coated with very thick and simultaneously flaky basal membranes. Typical for separate small differentiated epithelial cells of renal intratubular neoplasia zones RT of peritumoral tissue at CCRCC of low degree of differentiation (G3) is the presence in their cytoplasm of a very large size, spherical form of Mallory body with the electron-density, connected with the outer membrane of the nuclear shell. It was also revealed that in the conditions of renal intratubular neoplasia, a number of zones of renal intratubular neoplasia RT of peritumoral tissue are filled with epithelial cells, the cytoplasm of which contains a giant size of the autophagosome and electron-density cluster of glycogen granules. The autophagosome contains small lipid drops of insignificant electron density and approximately the same size of a very high electron density spherical formation of unspecified nature.

Conclusions. Epithelial cells of the renal intratubular neoplasia zones of peritumoral tissue at CCRCC of low degree of differentiation (G3), in the comparative plan with similar epithelial cells of the renal intratubular neoplasia zones of peritumoral tissue with high (G1) and the average (G2) degrees of differentiation, have cytoplasm, which is the most saturated Mallory bodies, autophagosomes, electron-density clusters of granules of glycogen.


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Altshuler-Keylin S, Shinoda K, Haseqawa Y, Ikeda K, Yonq H, Kanq Q, et al. Beige Adipocyte Maintenance is Regulated by Authophagy – Induced Mitochondrial Clearance. Cell Metab. 2016;24(3):402-19. doi: 10.16/j.cmet.2016.08.002 Epub 2016 Aug 25.

Chekhun VF. Berezhnaya NM. Fiziologicheskaya sistema soyedinitelnoy tkani i onkogenez. III. Formirovaniye rezistentnosti k khimiopreparatam [Physiological system of connective tissue and oncogenesis. III. Formation of resistance to chemotherapy]. Onkologiya. 2017;19(3):156-170. (in Ukrainian)

Cherdantseva TM, Bobrov IP, Klimachev VV, Bryukhanov VM, Lazarev AF, Avdalyan AM, i dr. Peritumoroznaya zona raka pochki: vse li problemy resheny? [The peritumourous zone of a renal carcinoma: whether all problems are solved?]. Fundamentalnyye issledovaniya. 2012;(4):141-145. (in Russian)

Cherdantseva TM, Bobrov IP, Klimachev VV, Bryukhanov VM, Lazarev AF, Avdalyan AM, i dr. Razmer opukholevogo uzla i gistologicheskoye stroyeniye peritumoroznoy zony raka pochki [The size of a tumour and histologic structure peritumourous zones of a cancer of a renal cell carcinoma]. Fundamentalnyye issledovaniya. 2013;(7):188-193. (in Russian)

Czyzyk-Kreska MF, Meller J, Plas DR. All autophagy is equal. Autophagy. 2012;8 (7):1155-6. doi:10.416/auto.20650.

Eble JN, Sauter G, Epstein IJ, Sesterhenn IA. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARCPress; 2004. 353 p.

Fedevych SV. Ultrastrukturna orhanizatsiia hemomikrotsyrkuliatornoho rusla svitloklitynnoho raku nyrky riznykh stupeniv dyferentsiatsii [Ultrastructural Organization of Microcirculatory Bed in Clear Cell Renal Cell Carcinoma of Different Grades of Differentiation]. Lvivskyi klinichnyi visnyk. 2016;(4):27-35. (in Ukrainian)

Folkman J. What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst. 1990;82(1):4-6.

Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 1982;6(7):655-63.

Gao Ch, D’Angelis ChA, Qin J, Xu B. Hyaline Globules in Epithelial Neoplasm of Kidney. NASD Med Sci. 2013;6(1):41-3.

Glauert AM. Fixation, dehydration and embedding of biological specimens. In: Practical methods in electron microscopy/ Ed. by. Glauert AM. Amsterdam: North-Hollond; New York : American Elsevier; 1975. 207 p.

Janji B, Viry E, Moussay E, Arakelian T, Mgrditchian T, Messai Y, et al. The Multifaceted role of autophagy in tumor evasion from immune surveillance. Oncotarget. 2016;7(14):17591-607.

Kirkali Z, Yorukoglu K. Premalignant Lesions in the Kidney. Scientific World. 2001;1:855-67.

Minervini A, di Cristofano C, Lapini A, Marchi M, Lanzi F, Giubilei G, et al. Histologic analysis of peritumoral pseudocapsule and surgical margin status after tumor enucleation for renal cell carcinoma. Eur Urol. 2009 Jun;55(6):1410-8.

Mourad WA, Nestor BR, Saleh GY, Solez K, Power RF, Jewell LD. Dysplastic tubular epithelium in “normal” kidney associated with renal cell carcinoma. Am J Surg Pathol. 1994;18(11):1117-24.

Obokata H, Wakayaama T, Sasai Y, Kojima K, Vacanti MP, Niwa H, et al. Stimulus triggerd fate conversion of somatic cells into pluripotency. Nature. 2014;505(7485): 641-7. doi: 10.1038/nature12968.

Padera TP, Stoll BR, Tooredman JB, Capen D, di Tomaso E, Jain RK. Pathology: cancer cells compress intratumour vessels. Nature. 2004;427(6976):695.

Pavelka M, Poth J. Functional Ultrastructure: Atlas of Tissue of Biology and Pathology. Trid Edition. Vienna: Springer-Verlag; 2015. 397 p. DOI:10.1007/978-3-7091-1830-6_23.

Pennock R, Bray E, James S, McKeegan P, Sturmey R, Genever P. Human cell dediferentiation in mesenchymal condensates through controlled autophagy. Scientific Reports. 2015;5:13113. doi: 10.1038/srep13113.

Van Poppel H, Nilsson S, Algaba F, Bergerheim U, Dal Cin P, Fleming S, et al. Precancerous Lesions in the Kidney. Scand J Urol Nephron. 2000;(205):136-65.

Reynolds ES. The use of lead citrate at high pH as an electronopague stain in electron microscopy. J Cell Biology. 1963;(17):208-12.

Rilley NE, Li J, McPhaul LW, Bardag-Gorce F, Lue YH, French SW. Heat shock proteins are present in Mallory bodies (cytokeratin agresomes) in human liver biopsi specimens. Exp Mol Pathol. 2003;74(2):168-72.

Romanenko AM, Nepomniashchyi VM, Zbarko LB. Epitelialni pukhlyny nyrky: suchasna mizhnarodna histolohichna klasyfikatsiia [Epithelial tumors of kidneys: modern international histological classification]. Urolohiia. 2002;(4):48-54. (in Ukrainian)

Romanenko AM, Vozianov SO, Nepomniashchyi VM, Zbarko LB, Zubko VI, Danylets RO, ta in. Renalna intratubuliarna neoplaziia yak peredrak nyrky [Renal intratubular neoplasm as renal precancer]. Urolohiia. 2003;(4):4-9. (in Ukrainian)

De la Rosette JMCH, Stemberg CN, Van Poppel HA. Renal cell cancer: diagnosis and therapy. London: Springer Verlag; 2008. xvii + 584 p.

Schlafli A.M., Berezowska S. Adams O., Langer R., Tschan M.P. Reliable LC3 and p62 autophagy marker detektion in fixed paraffin embedded human tissue by immunochemistry. European Journal of Histochemistry. 2015;59(2):2481.[page 137-144].doi:10.408/ejh.2015.2481.

Shuliak OV, Vozianov SO, Banyra OB, Stroi OO. Operatyvni vtruchannia v onkourolohii [Operative participation in oncourology]. Lviv; 2012. 299 s. (in Ukrainian)

Stempac JG, Ward RT. An improved staining method for electron microscopy. J Cell Biology. 1964;22:697-701.

Yörükoġlu K, Aktas S, Mungan MU, Kirkali Z. Tubular dysplasia and carcinoma in situ: precursors of renal cell carcinoma. Urology. 1999;53(4):684-9.

Zerbyno DD, Fedevych SV, Kovalyshyn VI. Svitloklitynnyi rak nyrky riznykh stupeniv dyferentsiatsii: osoblyvosti ultrastruktury pukhlynnykh klityn [Clear cell renal carcinoma of different grades of differentiation: peculiarity of tumor cells ultrastructure]. Onkolohyia. 2017;19(3):192-201. (in Ukrainian)

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Zerbino D, Fedevych S, Kuzyk Y. SUMMARY PECULIARITIES OF ULTRASTRUCTURE OF RENAL INTRATUBULAR NEOPLASIA ZONES AT CLEAR CELL RENAL CELL CARCINOMA. Proc Shevchenko Sci Soc Med Sci [Internet]. 2018Dec.28 [cited 2023Mar.25];54(2):67-. Available from: