endofocusFOCUS ЭндокринологияFOCUS. Endocrinology2713-01772713-0185ООО "Издательство "Перо"10.62751/2713-0177-2024-5-1-07endofocus-70Research ArticleОБЗОР ЛИТЕРАТУРЫLITERATURE REVIEWАдренокортикальный рак: принципы морфологической диагностики для эндокринологаAdrenocortical cancer: principles of morphological diagnostics for the endocrinologisthttps://orcid.org/0000-0002-2611-9320ПорубаеваЭ. Э.PorubayevaE. E.

Порубаева Эрика Эдуардовна  –  младший научный сотрудник, ординатор

117036, г.  Москва, улица Дм. Ульянова, д. 11

Erica E.  Porubaeva –  Junior Researcher, resident

Moscow

porubaeva.erika@bk.ruhttps://orcid.org/0000-0002-8136-0117ПачуашвилиН. В.PachuashviliN. V.

Пачуашвили Нано Владимеровна –  младший научный сотрудник, ординатор

117036, г.  Москва, улица Дм. Ульянова, д. 11

Nano V.  Pachuashvili –  Junior Researcher, resident

Moscow

npachuashvili@bk.ruhttps://orcid.org/0000-0001-6891-0009УрусоваЛ. С.UrusovaL. S.

Урусова Лилия Сергеевна  –  к.  м.  н., заведующая Отделом фундаментальной патоморфологии, ведущий научный сотрудник

117036, г.  Москва, улица Дм. Ульянова, д. 11

Lilia  S.  Urusova, Can. Sci. (Med.), Head of the Department of Fundamental Pathomorphology, Leading Researcher

Moscow

liselivanova89@yandex.ruГосударственный научный центр Российской Федерации федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр эндокринологии» Министерства здравоохранения Российской ФедерацииEndocrinology research center202407052024515258Copyright © Порубаева Э.Э., Пачуашвили Н.В., Урусова Л.С., 20242024Порубаева Э.Э., Пачуашвили Н.В., Урусова Л.С.Porubayeva E.E., Pachuashvili N.V., Urusova L.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://endofocus.elpub.ru/jour/article/view/70

Адренокортикальный рак (АКР) – редкое злокачественное эндокринное новообразование из клеток коры надпочечника. Несмотря на орфанный характер заболевания, увеличение случаев инциденталом в современной клинической практике требует осведомленности эндокринолога о принципах диагностики и тактики ведения пациента с этим заболеванием, отличающимся крайне вариабельным биологическим поведением. Эта особенность АКР обуславливает необходимость персонализированного подхода для каждого клинического случая, который должен обеспечиваться не только междисциплинарным взаимодействием специалистов онкологов, хирургов, эндокринологов, но и анализом патоморфологических особенностей каждой опухоли. Настоящая статья освещает современные представления о морфологической диагностике АКР, полученные в результате исследований последнего десятилетия, которые необходимо учитывать эндокринологу.

Adrenocortical cancer (ACС) is a rare malignant endocrine neoplasm from adrenocortical cells. Despite the orphan character of the disease, the increase of incidentalomas in modern clinical practice requires endocrinologist's awareness of the principles of diagnostics and tactics of patient management. This disease is characterized by highly variable biological behavior. This peculiarity of ACC necessitates a personalized approach for each clinical case, which should be ensured not only by interdisciplinary interaction between oncologists, surgeons and endocrinologists, but also by analysis of the pathomorphological features of each tumor. The present article highlights the current views on the morphological diagnosis of ACC, obtained as a result of research in the last decade, which should be taken into account by the endocrinologist.

адренокортикальный ракАКРморфологическая диагностикаперсонализированный подходadrenocortical cancerACCmorphologic diagnosticspersonalized approachReferencesWHO Classification of Tumours Editorial Board. Endocrine and neuroendocrine tumours. Lyon (France): International Agency for Research on Cancer; 2022. (WHO classification of tumours series, 5th ed.; vol. 10).WHO Classification of Tumours Editorial Board. Endocrine and neuroendocrine tumours. Lyon (France): International Agency for Research on Cancer; 2022. (WHO classification of tumours series, 5th ed.; vol. 10).Adrenal Cortical Carcinoma. In: Brierley JD, Gospodarowicz MK, Wittekind C, eds. TNM Classification of Malignant Tumours (8th edition). Oxford, UK: Wiley-Blackwell, 2017.Adrenal Cortical Carcinoma. In: Brierley JD, Gospodarowicz MK, Wittekind C, eds. TNM Classification of Malignant Tumours (8th edition). Oxford, UK: Wiley-Blackwell, 2017.Fassnacht M, Dekkers O, Else T, Baudin E, Berruti A, de Krijger RR, Haak HR, Mihai R, Assie G, Terzolo M. European Society of Endocrinology Clinical Practice Guidelines on the Management of Adrenocortical Carcinoma in Adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2018;179(4): G1-G46. https://doi.org/10.1530/EJE-18–0608.Fassnacht M, Dekkers O, Else T, Baudin E, Berruti A, de Krijger RR, Haak HR, Mihai R, Assie G, Terzolo M. European Society of Endocrinology Clinical Practice Guidelines on the Management of Adrenocortical Carcinoma in Adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2018;179(4): G1-G46. https://doi.org/10.1530/EJE-18–0608.Giordano TJ, Berney D, de Krijger RR, Erickson L, Fassnacht M, Mete O, Papathomas T, Papotti M, Sasano H, Thompson LDR, Volante M, Gill AJ. Data set for reporting of carcinoma of the adrenal cortex: explanations and recommendations of the guidelines from the International Collaboration on Cancer Reporting. Hum Pathol. 2021;110:50–61. https://doi.org/10.1016/j.humpath.2020.10.001.Giordano TJ, Berney D, de Krijger RR, Erickson L, Fassnacht M, Mete O, Papathomas T, Papotti M, Sasano H, Thompson LDR, Volante M, Gill AJ. Data set for reporting of carcinoma of the adrenal cortex: explanations and recommendations of the guidelines from the International Collaboration on Cancer Reporting. Hum Pathol. 2021;110:50–61. https://doi.org/10.1016/j.humpath.2020.10.001.Weiss L. M. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumor. American Journal of Surgical Pathology. 1984;8(3):163–169.Weiss L. M. Comparative histologic study of 43 metastasizing and nonmetastasizing adrenocortical tumor. American Journal of Surgical Pathology. 1984;8(3):163–169.Bisceglia M, Ludovico O, Di Mattia A, Ben-Dor D, Sandbank J, Pasquinelli G, Lau SK, Weiss LM. Adrenocortical oncocytic tumors: report of 10 cases and review of the literature. Int J Surg Pathol. 2004;12(3):231–43. https://doi.org/10.1177/106689690401200304.Bisceglia M, Ludovico O, Di Mattia A, Ben-Dor D, Sandbank J, Pasquinelli G, Lau SK, Weiss LM. Adrenocortical oncocytic tumors: report of 10 cases and review of the literature. Int J Surg Pathol. 2004;12(3):231–43. https://doi.org/10.1177/106689690401200304.Duregon E, Fassina A, Volante M, Nesi G, Santi R, Gatti G, Cappellesso R, Dalino Ciaramella P, Ventura L, Gambacorta M, Dei Tos AP, Loli P, Mannelli M, Mantero F, Berruti A, Terzolo M, Papotti M. The reticulin algorithm for adrenocortical tumor diagnosis: a multicentric validation study on 245 unpublished cases. Am J Surg Pathol. 2013;37(9):1433–40. https://doi.org/10.1097/PAS.0b013e31828d387b.Duregon E, Fassina A, Volante M, Nesi G, Santi R, Gatti G, Cappellesso R, Dalino Ciaramella P, Ventura L, Gambacorta M, Dei Tos AP, Loli P, Mannelli M, Mantero F, Berruti A, Terzolo M, Papotti M. The reticulin algorithm for adrenocortical tumor diagnosis: a multicentric validation study on 245 unpublished cases. Am J Surg Pathol. 2013;37(9):1433–40. https://doi.org/10.1097/PAS.0b013e31828d387b.Pennanen M, Heiskanen I, Sane T, Remes S, Mustonen H, Haglund C, Arola J. Helsinki scorea novel model for prediction of metastases in adrenocortical carcinomas. Hum Pathol. 2015;46(3):404–10. https://doi.org/10.1016/j.humpath.2014.11.015.Pennanen M, Heiskanen I, Sane T, Remes S, Mustonen H, Haglund C, Arola J. Helsinki scorea novel model for prediction of metastases in adrenocortical carcinomas. Hum Pathol. 2015;46(3):404–10. https://doi.org/10.1016/j.humpath.2014.11.015.Urusova L, Porubayeva E, Pachuashvili N, Elfimova A, Beltsevich D, Mokrysheva N. The new histological system for the diagnosis of adrenocortical cancer. Front Endocrinol (Lausanne). 2023;14:1218686. https://doi.org/10.3389/fendo.2023.1218686.Urusova L, Porubayeva E, Pachuashvili N, Elfimova A, Beltsevich D, Mokrysheva N. The new histological system for the diagnosis of adrenocortical cancer. Front Endocrinol (Lausanne). 2023;14:1218686. https://doi.org/10.3389/fendo.2023.1218686.Aubert S, Wacrenier A, Leroy X, Devos P, Carnaille B, Proye C, Wemeau JL, Lecomte-Houcke M, Leteurtre E. Weiss system revisited: a clinicopathologic and immunohistochemical study of 49 adrenocortical tumors. Am J Surg Pathol. 2002;26(12):1612–9. https://doi.org/10.1097/00000478–200212000–00009.Aubert S, Wacrenier A, Leroy X, Devos P, Carnaille B, Proye C, Wemeau JL, Lecomte-Houcke M, Leteurtre E. Weiss system revisited: a clinicopathologic and immunohistochemical study of 49 adrenocortical tumors. Am J Surg Pathol. 2002;26(12):1612–9. https://doi.org/10.1097/00000478–200212000–00009.Dehner LP, Hill DA. Adrenal cortical neoplasms in children: why so many carcinomas and yet so many survivors? Pediatr Dev Pathol. 2009;12(4):284–91. https://doi.org/10.2350/08–06–0489.1.Dehner LP, Hill DA. Adrenal cortical neoplasms in children: why so many carcinomas and yet so many survivors? Pediatr Dev Pathol. 2009;12(4):284–91. https://doi.org/10.2350/08–06–0489.1.Wieneke JA, Thompson LD, Heffess CS. Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients. Am J Surg Pathol. 2003;27(7):867–81. https://doi.org/10.1097/00000478–200307000–00001.Wieneke JA, Thompson LD, Heffess CS. Adrenal cortical neoplasms in the pediatric population: a clinicopathologic and immunophenotypic analysis of 83 patients. Am J Surg Pathol. 2003;27(7):867–81. https://doi.org/10.1097/00000478–200307000–00001.Mete O, Asa SL, Giordano TJ, Papotti M, Sasano H, Volante M. Immunohistochemical Biomarkers of Adrenal Cortical Neoplasms. Endocr Pathol. 2018;29(2):137– 149. https://doi.org/10.1007/s12022–018–9525–8.Mete O, Asa SL, Giordano TJ, Papotti M, Sasano H, Volante M. Immunohistochemical Biomarkers of Adrenal Cortical Neoplasms. Endocr Pathol. 2018;29(2):137– 149. https://doi.org/10.1007/s12022–018–9525–8.Ткачук А. В., Тертычный А. С., Бельцевич Д. Г., Рослякова А. А., Белоусов П. В., Селиванова Л. С. Адренокортикальный рак: морфологические варианты, иммуногистохимическая характеристика. Архив патологии. 2021; 83(3):10–18.Tkachuk AV, Tertychnyi AS, Beltsevich DG, Roslyakova AA, Belousov PV, Selivanova LS. Adrenocortical cancer: morphological variants, immunohistochemical characteristics. Arkh Patol. 2021;83(3):10–18. (in Russ.)]. https://doi.org/10.17116/patol20218302110.Mete O, Gucer H, Kefeli M, Asa SL. Diagnostic and Prognostic Biomarkers of Adrenal Cortical Carcinoma. Am J Surg Pathol. 2018;42(2):201–213. https://doi.org/10.1097/PAS.0000000000000943.Mete O, Gucer H, Kefeli M, Asa SL. Diagnostic and Prognostic Biomarkers of Adrenal Cortical Carcinoma. Am J Surg Pathol. 2018;42(2):201–213. https://doi.org/10.1097/PAS.0000000000000943.Martins-Filho SN, Almeida MQ, Soares I, Wakamatsu A, Alves VAF, Fragoso MCBV, Zerbini MCN. Clinical Impact of Pathological Features Including the Ki-67 Labeling Index on Diagnosis and Prognosis of Adult and Pediatric Adrenocortical Tumors. Endocr Pathol. 2021;32(2):288–300. https://doi.org/10.1007/s12022–020–09654-x.Martins-Filho SN, Almeida MQ, Soares I, Wakamatsu A, Alves VAF, Fragoso MCBV, Zerbini MCN. Clinical Impact of Pathological Features Including the Ki-67 Labeling Index on Diagnosis and Prognosis of Adult and Pediatric Adrenocortical Tumors. Endocr Pathol. 2021;32(2):288–300. https://doi.org/10.1007/s12022–020–09654-x.Duregon E, Molinaro L, Volante M, Ventura L, Righi L, Bolla S, Terzolo M, Sapino A, Papotti MG. Comparative diagnostic and prognostic performances of the hematoxylineosin and phosphohistone H3 mitotic count and Ki-67 index in adrenocortical carcinoma. Mod Pathol. 2014;27(9):1246–54. https://doi.org/10.1038/modpathol.2013.230.Duregon E, Molinaro L, Volante M, Ventura L, Righi L, Bolla S, Terzolo M, Sapino A, Papotti MG. Comparative diagnostic and prognostic performances of the hematoxylineosin and phosphohistone H3 mitotic count and Ki-67 index in adrenocortical carcinoma. Mod Pathol. 2014;27(9):1246–54. https://doi.org/10.1038/modpathol.2013.230.Beuschlein F, Weigel J, Saeger W, Kroiss M, Wild V, Daffara F, Libé R, Ardito A, Al Ghuzlan A, Quinkler M, Oßwald A, Ronchi CL, de Krijger R, Feelders RA, Waldmann J, Willenberg HS, Deutschbein T, Stell A, Reincke M, Papotti M, Baudin E, Tissier F, Haak HR, Loli P, Terzolo M, Allolio B, Müller HH, Fassnacht M. Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection. J Clin Endocrinol Metab. 2015;100(3):841–9. https://doi.org/10.1210/jc.2014–3182.Beuschlein F, Weigel J, Saeger W, Kroiss M, Wild V, Daffara F, Libé R, Ardito A, Al Ghuzlan A, Quinkler M, Oßwald A, Ronchi CL, de Krijger R, Feelders RA, Waldmann J, Willenberg HS, Deutschbein T, Stell A, Reincke M, Papotti M, Baudin E, Tissier F, Haak HR, Loli P, Terzolo M, Allolio B, Müller HH, Fassnacht M. Major prognostic role of Ki67 in localized adrenocortical carcinoma after complete resection. J Clin Endocrinol Metab. 2015;100(3):841–9. https://doi.org/10.1210/jc.2014–3182.Селиванова Л. С., Рослякова А. А., Боголюбова А. В., Тертычный А. С., Бельцевич Д. Г., Абросимов А. Ю., Мельниченко Г. А. Молекулярно-генетические маркеры и критерии прогноза адренокортикального рака. Архив патологии. 2019;81(5):92–96.Selivanova LS, Roslyakova AA, Bogolyubova AV, Tertychny AS, Bel'tsevich DG, Abrosimov AIu, Melnichenko GA. Molecular genetic markers and criteria for the prediction of adrenocortical carcinoma. Arkhiv Patologii. 2019;81(5):92–96. (In Russ.)]. https://doi.org/10.17116/patol20198105192.Picard C, Orbach D, Carton M, Brugieres L, Renaudin K, Aubert S, Berrebi D, Galmiche L, Dujardin F, Leblond P, Thomas-Teinturier C, Dijoud F. Revisiting the role of the pathological grading in pediatric adrenal cortical tumors: results from a national cohort study with pathological review. Mod Pathol. 2019;32(4):546–559. https://doi.org/10.1038/s41379–018–0174–8.Picard C, Orbach D, Carton M, Brugieres L, Renaudin K, Aubert S, Berrebi D, Galmiche L, Dujardin F, Leblond P, Thomas-Teinturier C, Dijoud F. Revisiting the role of the pathological grading in pediatric adrenal cortical tumors: results from a national cohort study with pathological review. Mod Pathol. 2019;32(4):546–559. https://doi.org/10.1038/s41379–018–0174–8.Juhlin CC, Bertherat J, Giordano TJ, Hammer GD, Sasano H, Mete O. What Did We Learn from the Molecular Biology of Adrenal Cortical Neoplasia? From Histopathology to Translational Genomics. Endocr Pathol. 2021;32(1):102–133. https://doi.org/10.1007/s12022–021–09667–0.Juhlin CC, Bertherat J, Giordano TJ, Hammer GD, Sasano H, Mete O. What Did We Learn from the Molecular Biology of Adrenal Cortical Neoplasia? From Histopathology to Translational Genomics. Endocr Pathol. 2021;32(1):102–133. https://doi.org/10.1007/s12022–021–09667–0.Domènech M, Grau E, Solanes A, Izquierdo A, Del Valle J, Carrato C, Pineda M, Dueñas N, Pujol M, Lázaro C, Capellà G, Brunet J, Navarro M. Characteristics of Adrenocortical Carcinoma Associated With Lynch Syndrome. J Clin Endocrinol Metab. 2021;106(2):318–325. https://doi.org/10.1210/clinem/dgaa833.Domènech M, Grau E, Solanes A, Izquierdo A, Del Valle J, Carrato C, Pineda M, Dueñas N, Pujol M, Lázaro C, Capellà G, Brunet J, Navarro M. Characteristics of Adrenocortical Carcinoma Associated With Lynch Syndrome. J Clin Endocrinol Metab. 2021;106(2):318–325. https://doi.org/10.1210/clinem/dgaa833.Araujo-Castro M, Pascual-Corrales E, Molina-Cerrillo J, Alonso-Gordoa T. Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance. Biomedicines. 2021;9(3):304. https://doi.org/10.3390/biomedicines9030304.Araujo-Castro M, Pascual-Corrales E, Molina-Cerrillo J, Alonso-Gordoa T. Immunotherapy in Adrenocortical Carcinoma: Predictors of Response, Efficacy, Safety, and Mechanisms of Resistance. Biomedicines. 2021;9(3):304. https://doi.org/10.3390/biomedicines9030304.Georgantzoglou N, Kokkali S, Tsourouflis G, Theocharis S. Tumor Microenvironment in Adrenocortical Carcinoma: Barrier to Immunotherapy Success? Cancers (Basel). 2021;13(8):1798. https://doi.org/10.3390/cancers13081798.Georgantzoglou N, Kokkali S, Tsourouflis G, Theocharis S. Tumor Microenvironment in Adrenocortical Carcinoma: Barrier to Immunotherapy Success? Cancers (Basel). 2021;13(8):1798. https://doi.org/10.3390/cancers13081798.Volante M, Terzolo M, Fassnacht M, Rapa I, Germano A, Sbiera S, Daffara F, Sperone P, Scagliotti G, Allolio B, Papotti M, Berruti A. Ribonucleotide reductase large subunit (RRM1) gene expression may predict efficacy of adjuvant mitotane in adrenocortical cancer. Clin Cancer Res. 2012;18(12):3452–61. https://doi.org/10.1158/1078–0432.CCR-11–2692.Volante M, Terzolo M, Fassnacht M, Rapa I, Germano A, Sbiera S, Daffara F, Sperone P, Scagliotti G, Allolio B, Papotti M, Berruti A. Ribonucleotide reductase large subunit (RRM1) gene expression may predict efficacy of adjuvant mitotane in adrenocortical cancer. Clin Cancer Res. 2012;18(12):3452–61. https://doi.org/10.1158/1078–0432.CCR-11–2692.Ronchi CL, Sbiera S, Volante M, Steinhauer S, Scott-Wild V, Altieri B, Kroiss M, Bala M, Papotti M, Deutschbein T, Terzolo M, Fassnacht M, Allolio B. CYP2W1 is highly expressed in adrenal glands and is positively associated with the response to mitotane in adrenocortical carcinoma. PLoS One. 2014;9(8): e105855. https://doi.org/10.1371/journal.pone.0105855.Ronchi CL, Sbiera S, Volante M, Steinhauer S, Scott-Wild V, Altieri B, Kroiss M, Bala M, Papotti M, Deutschbein T, Terzolo M, Fassnacht M, Allolio B. CYP2W1 is highly expressed in adrenal glands and is positively associated with the response to mitotane in adrenocortical carcinoma. PLoS One. 2014;9(8): e105855. https://doi.org/10.1371/journal.pone.0105855.

The authors declare that there are no conflicts of interest present.