medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2020-20-134-142medsovet-5948Research ArticleОБЗОРЫREVIEWSФиброламеллярный рак печени: современный взгляд на проблемуFibrolamellar liver cancer: the modern concepthttps://orcid.org/0000-0002-9740-3839АнтоноваЕ. Ю.AntonovaE. Yu.

Антонова Елена Юрьевна, аспирант отделения лекарственных методов лечения (химиотерапевтическое) №17 Научно-исследовательского института клинической онкологии имени Н.Н. Трапезникова

SPIN-код: 6335-7053

115478, Россия, Москва, Каширское шоссе, д. 23

Elena Yu. Antonova, graduate student of the Department of Medicinal Treatment (Chemotherapy №17 Department)

24, Kashirskoye Shosse, Moscow, 115478, Russia

elenaantonova5@mail.ruhttps://orcid.org/0000-0002-6244-4294БредерВ. В.BrederV. V.

Бредер Валерий Владимирович, доктор медицинских наук, ведущий научный сотрудник онкологического отделения лекарственных методов лечения (химиотерапевтическое) №17 Научно-исследовательского института клинической онкологии имени Н.Н. Трапезникова

SPIN-код: 9846-4360; Author ID: 280121

115478, Россия, Москва, Каширское шоссе, д. 24

Valery V. Breder, Dr. of Sci. (Med.), Leading Researcher, Department of Medicinal Treatment (Chemotherapy №17 Department)

24, Kashirskoye Shosse, Moscow, 115478, Russia

vbreder@yandex.ruhttps://orcid.org/0000-0002-6775-3678МорозЕ. А.MorozE. A.

Мороз Екатерина Александровна, кандидат медицинских наук, врач-патологоанатом патологоанатомического отделения Научно-исследовательского института клинической онкологии имени Н.Н. Трапезникова

115478, Россия, Москва, Каширское шоссе, д. 24

Ekaterina A. Moroz, Cand. of Sci. (Med.), pathologist of the pathology Department

24, Kashirskoye Shosse, Moscow, 115478, Russia

moroz-kate@yandex.ruhttps://orcid.org/0000-0003-4469-502XЛактионовК. К.LaktionovK. K.

Лактионов Константин Константинович, доктор медицинских наук, профессор, профессор кафедры онкологии и лучевой терапии лечебного факультета

SPIN-код: 7404-5133, Author ID: 160970

117997, Россия, Москва, ул. Островитянова, д. 1

Konstantin K. Laktionov, Dr. of Sci. (Med.), Professor of the Department of Oncology and Radiation Therapy, Faculty of Medicine

1, Ostrovityanov St., Moscow, 117997, Russia

lkoskos@mail.ruhttps://orcid.org/0000-0002-6323-511XДжанянН. А.DzhanyanI. A.

Джанян Ирина Анатольевна, врач-хирург онкологического отделения лекарственных методов лечения (химиотерапевтическое) №17 Научно-исследовательского института клинической онкологии имени Н.Н. Трапезникова

115478, Россия, Москва, Каширское шоссе, д. 24

Irina A. Dzhanyan, Surgeon, Department of Medicinal Treatment (Chemotherapy №17 Department)

24, Kashirskoye Shosse, Moscow, 115478, Russia

i-dzhanyan@mail.ruhttps://orcid.org/0000-0003-4412-2256ВолковА. Ю.VolkovA. Yu.

Волков Александр Юрьевич, аспирант хирургического отделения №6 (абдоминальной онкологии) торакоабдоминального отдела Научно-исследовательского института клинической онкологии имени Н.Н. Трапезникова

115478, Россия, Москва, Каширское шоссе, д. 24

Alexander Yu. Volkov, graduate student of the Surgical Department №6 (abdominal oncology) of Thoracoabdominal Department

24, Kashirskoye Shosse, Moscow, 115478, Russia

79164577128@yandex.ruНациональный медицинский исследовательский центр онкологии им. Н.Н. БлохинаРоссияBlokhin National Medical Research Center of OncologyRussian FederationРоссийский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияPirogov Russian National Research Medical UniversityRussian Federation202020122020020134142Copyright © Антонова Е.Ю., Бредер В.В., Мороз Е.А., Лактионов К.К., Джанян Н.А., Волков А.Ю., 20202020Антонова Е.Ю., Бредер В.В., Мороз Е.А., Лактионов К.К., Джанян Н.А., Волков А.Ю.Antonova E.Y., Breder V.V., Moroz E.A., Laktionov K.K., Dzhanyan I.A., Volkov A.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/5948

Фиброламеллярная гепатоцеллюлярная карцинома (ФлК) является относительно редкой первичной опухолью печени без известных факторов риска (хронические инфекции вирусами гепатитов В или С, хронические алкогольные отравления, цирроз печени), которая встречается в основном у молодого населения. ФлК чаще диагностируется уже на распространенных стадиях ввиду отсутствия у пациентов выраженных клинических проявлений в течение длительного времени. При патоморфологической диагностике ФлК представляет собой скопление больших полигональных эозинофильных клеток с четко выраженным везикулярным ядром, окруженным обильными разрастаниями ламеллярного фиброза. Коллагеновые волокна в большинстве случаев располагаются параллельными тяжами, в метастазирующих опухолях коллагеновые волокна могут быть расположены бессистемно (т. н. спутанные волокна). В течение многих лет предпринимались попытки идентифицировать надежные маркеры для выявления дифференциальной диагностики ФлК и определить причину возникновения опухолей у молодых пациентов, изучались молекулярные механизмы канцерогенеза ФлК. В 2014 г. при проведении полнотранскриптомного анализа образцов ФлК был открыт химерный транскрипт DNAJB1PRKACA, образующийся в результате делеции участка 19-й хромосомы размером 400 тыс. пар нуклеотидов (т.п.н.), приводящий к слиянию двух генов, который встречается в большинстве образцов ФлК. Основным методом лечения ФлК является хирургический – радикальный метод лечения заболевания. Учитывая, что поражение лимфатических узлов является важным прогностическим фактором, полная перипортальная лимфаденэктомия должна выполняться как часть радикальной операции пациентов с ФлК. Роль и возможности локорегионального и лекарственного методов лечения не до конца ясны, а поиск эффективных схем терапии и потенциальных мишеней, специфических для этой формы ГЦР, является актуальной. Исследования показывают противоречивые результаты для различных схем химиотерапии и применения таргетной терапии. В литературе описаны единичные клинические случаи успешного применения иммунотерапии у пациентов с экспрессирующей PD-L1-опухолью. Важнейшим условием для успешного лечения является глубокое изучение молекулярных механизмов канцерогенеза ФлК.

В обзоре представлены современные данные об эпидемиологии, классификациях, клинико-морфологических и молекулярногенетических аспектах, особенностях диагностики и лечения ФлК.

Fibrolamellar hepatocellular carcinoma (FLC) is a relatively rare primary liver tumor of unknown etiology (chronic infections with hepatitis B or C viruses, chronic alcohol poisoning, cirrhosis of the liver), which occurs mainly in the young population. FLK is more often diagnosed already at common stages due to the absence of pronounced clinical manifestations in patients for a long time. In pathomorphological diagnostics, FLC is a cluster of large polygonal eosinophilic cells with a clearly defined vesicular nucleus, surrounded by abundant growths of lamellar fibrosis. In most cases, collagen fibers are arranged in parallel strands; in metastatic tumors, collagen fibers can be arranged haphazardly (the so-called “tangled fibers”).For many years, attempts have been made to identify reliable markers for the detection and differential diagnosis of FLC and to determine the cause of tumors in young patients, and the molecular mechanisms of FLC carcinogenesis have been studied. In 2014 during the full transcriptome analysis of FLC samples, the chimeric transcript DNAJB1PRKACA was discovered, which is formed as a result of deletion of a section of chromosome 19 with a size of 400 thousand nucleotide pairs and leads to the fusion of two genes, which Is found in most FLC samples. Surgery is the only curative treatment of this tumor type and radical method of treating the disease. Given that lymph node involvement is an important prognostic factor, complete periportal lymphadenectomy should be performed as part of radical surgery for patients with FLK. The role and possibilities of locoregional and drug-based treatment methods are not fully clear, and the search for effective treatment regimens and potential targets specific to this form of HCR is urgent. Studies show conflicting results for different chemotherapy regimens and the use of targeted therapy. The literature describes isolated clinical cases of successful use of immunotherapy in patients with PD-L1-expressing tumors. The most important condition for successful treatment is an in-depth study of the molecular mechanisms of FLC carcinogenesis. This review presents current data on epidemiology, classification, clinico-morphological, molecular and genetic aspects, as well as some diagnostic features and FLC treatment modalities.

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