Determination of the volume of surgical intervention for high-grade gliomas, taking into account the characteristics of the peritumorous zone

   Summary. The processes occurring at the molecular, cellular and organismal level in the carcinogenesis and progression of tumors are far from understanding and require in-depth morphological studies. Currently, great
importance is attached to the study of not only the tumor itself, but also what occurs in tissues in close proximity to pathological focus.

   Aim of the study: determination of the volume of surgical intervention based on the pathomorphological features of the peritumorous zone of high-grade gliomas, considering the contamination of the herpes simplex virus.

   Materials and methods: archived biopsies of 748 high-grade glial tumors (glioblastomas) contaminated with the herpes simplex virus (HSV) in patients from 18 to 80 years old, operated on at the Republican Scientific and Practical
Center of Neurology and Neurosurgery (Minsk). To detect the herpes simplex virus (HSV) in tumors, an immunohistochemical (IHC) study was performed with antibodies to the HSV type I and II antigen. Antibodies to Ki‑67 were used to determine proliferative activity. Monoclonal antibodies to CD 34 were used to count the number of vessels (as an important factor in tumor progression). To identify inflammatory infiltration, an IHC study was performed with a set of monoclonal antibodies CD 45 (total leukocyte factor), CD 8 (T-lymphocytes), CD 20 (B-lymphocytes), and Plasmosel. To study apoptosis, IHC study with p53 and bcl‑2 was used. We also used unique data obtained from 6 deceased with glioblastoma aged 18 to 63 years by employees of the Russian Research Institute. prof. A. L. Polenov, a unique comprehensive study of GM macropreparations using postmortem MRI was carried out.

   Results. For glioblastoma, which proceeded against the background of exacerbation of chronic inflammation, the index of proliferative activity of the vascular endothelium is significantly higher than the index of proliferative activity of the tumor cell, as well as the ratio of growth factors such as bcl‑2 and p53 convincingly indicate the prevalence of the rate of division of the endothelial cell lining the vessels over the tumor, which manifested itself by an increase in the number of vessels in the tumor proceeding against the background of exacerbation of productive inflammation. At the same time, studies carried out with MRI of tumors during autopsy showed that around tumors of various histostructures, both intravital and postmortem, there is a zone of hyperintense MR signal on T2 WI and FLAIR PI, with fuzzy contours. On anatomical sections, the area of the hyperintense MR signal macroscopically represents an unchanged white matter of the brain or there was a slight flabbiness and paleness of the tissue.

    Conclusion. A targeted microscopic examination revealed structural changes in the brain substance in these zones, with histological signs of inflammation. Changes in the white matter detected in the peritumorous zone corresponding to the hyperintense MR signal in the T2 VI mode were expressed in the manifestation of alteration in the form of dystrophic changes and cell necrosis, demyelination and damage to nerve fibers. Morphologically, edema was manifested by the rarification (discharge) of the white matter with the development of spongiform structures and the formation of microcysts. Hyperplasia and reactive changes in glial elements were also found. The reaction from the local phagocytic system was manifested by an increase in the number of microgliocytes, their transformation into granular balls and an accumulation around the vessels. One of the most important components of the peritumorous zone of glioblastoma is the presence of proliferating vessels.

1. Murayi R., Chittiboina P. G lucocorticoids in the management of peritumoral brain edema : a review of molecular mechanisms. Childs Nerv Syst. 2016;32(12):2293–2302. doi: 10.1007/s00381–016–3240-x

2. Yakovenko I. V ., Zabrodskaya Yu.M., Medvedev Yu.A., Nezdorovina V . G . V vedenie v patologiu operirovannogo mozga. SPb.: FGBU «RNHI im. prof. A. L. Polenova» Minzdrava Rossii; 2013. (In Russ.)

3. Akovbyana V . A ., Prokhorenkova V . I., Sokolovsky E . V . Infekcii, peredaushiesya polovyim putem. М.: MediaSfera; 2007 (In Russ.)

4. Trofimova T. N., Medvedev Yu .A., Anan'yeva N.I., Sukhatskaya A. V., Zabrodskaya Yu. M., Kaznacheyeva A. O. Ispol'zovaniye posmertnoy magnitno-rezonansnoy tomografii golovnogo mozga pri patologo-anatomicheskom issledovanii. Arkhiv patologii. 2008;70 (3): 23–28. (In Russ.)

5. Zabrodskaya, Yu .M., Gaykova O. N., Gan O. V ., Trofimova A. V., Gadzhiyev K. V. Patomorfology and water erectrolytic content in peritumoral brain white matter of malignant neuroectodermal tumors. Vestnik VolgGMU. 2011;3 (39):42–45 (In Russ.)

6. Engelhorn, T., Savaskan N. E., Schwarz M. A ., Kreutzer J., Meyer E. P., Hahnen E., Ganslandt, A. Dorfler O, Nimsky C., Buchfelder M., Eyupoglu I. Y. Cellular characterization of the peritumoral edema zone in malignant brain tumors. Cancer Science. 2009;100:1856–1862. doi: 10.1111/j.1349-7006.2009.01259.x

7. Ghukova T., Smeynjvic A., Pashkevich L., Bezubik C., L. Parkhach, Ahremchuk A ., Chirinsky A, Khmara М. Clinic-morphologic features of the growth and recurrence of neuroepithelial tumors contaminated with herpes simplex virus. Izvestiya natsional’noy akademii nauk Belarusi. Seriya meditsinskikh nauk. 2013; 4: 21–24. (In Russ.)

8. Nedz’ved’ M.K., Khmara M. Y e., Protas I. I., Guzov A . S. M orfologicheskiye osobennosti ostrykh i khronicheskikh gerpeticheskikh entsefalitov. Materialy I kongressa morfologov Belarusi. Minsk; 1996; 2: 65–66. (In Russ.)

9. Preiser W., Weber B., Klos G. Unusual course of herpes simplex virus encephalitis after acyclovir therapy. Infection. 1996; 24: 384–389. doi: 10.1007/BF01716086

10. Xinping F., Lihua T., Jin A. E xpression of a Fusogenic Membrane Glycoprotein by an Oncolytic Herpes Simplex Virus Potentiates the Viral Antitumor Effect. Molecular therepi. 2003;7 (6): 611–623. doi: 10.1016/s1525-0016(03)00092-3

11. Gawdi R, Gawdi R., Emmady P. D. Blood Brain Barrier Physiology, In: StatPearls. Treasure Island (FL) StatPearls Publishing. 2020;13: 1123–1131.

12. Murayi R., Chittiboina P. G lucocorticoids in the management of peritumoral brain edema : a review of molecular mechanisms. Childs NervSyst. 2016;32(12):2293–2302. doi: 10.1007/s00381–016–3240-x

13. Zubritskiy M. G ., Nedz’ved’ M. K. Morfologicheskaya diagnostika zabolevaniy, vyzvannykh virusom prostogo gerpesa. Zhurnal Grodnenskogo gosudarstvennogo meditsinskogo universiteta. 2008;4(24):1–4. (In Russ.)

14. Heimberger A.B., Abou-Ghazal M., Reina-Ortiz C., Yang D. S.,.Sun, W. Qiao W, Hiraoka N., Fuller G . N. Incidence and prognostic impact of FoxP³⁺ regulatory T cells in human gliomas. Clin. Cancer Res. 2008;14 (16):5166–5172. doi: 10.1158/1078-0432.CCR-08-0320

15. Borisov K. E ., Sakaeva D. D. Tumor microenvironment as a target of malignant gliomas treatment. Malignant Tumours 2015; 4:14–23. (In Russ.) doi: 10.18027/2224–5057–2015–4-14-23

16. Albesiano E., Han J. E, Lim M. Mechanisms of local immunoresistance in glioma. Neurosurgery Clinics of North America. 2010; 21(1):17–29. doi: 10.1016/j.nec.2009.08.008

17. A rto I., Vapalahti M., Tyyne K., Hurskainen H. A dvHSV-tk Gene Therapy with Intravenous Ganciclovir. Improves Survival in Human Malignant Glioma. Molecular therapy. 2004; 5:181–191. doi: 10.1016/j.ymthe.2004.08.002