Abstract

Introduction. Epstein — Barr virus (EBV) plays an important role in the pathogenesis of lymphoid tumors, in particular Hodgkin lymphoma. The frequency of expression of the EBV varies in different histological variants of classical Hodgkin lymphoma and is rarely observed in nodular lymphocyte predominant Hodgkin lymphoma.Aim — to study the pathomorphological features of the histological variants of Hodgkin lymphoma with lymphoid predominance associated with the EBV, as well as the frequency of their diagnosis in the structure of Hodgkin lymphoma.Materials and methods. The retrospective study included 794 patients with a verified diagnosis of Hodgkin lymphoma using histological and immunohistochemical methods on biopsy material for the period 2018–2019 (age range — 18–91 years old; median — 34 years old; men : women — 1.1 : 1). The presence of EBV in biopsies was assessed by immunohistochemical reaction with antibodies to EBV (clone LMP1), or by chromogenic in situ hybridization with probes for EBV-encoded small RNAs.Results. Classical Hodgkin lymphoma was diagnosed in 91 % (725/794) cases, nodular lymphocyte predominant Hodgkin lymphoma — in 9 % (69/794) cases. EBV-positive Hodgkin lymphoma accounted for 11 % (82/725) of all cases of classical Hodgkin lymphoma, (age range — 18–81 years old, median — 45 years old; men : women — 2.5 : 1). All cases of nodular lymphocyte predominant Hodgkin lymphoma were EBV-negative. Lymphocyte-rich classical Hodgkin lymphoma was found in 14 patients (14/725, 2 %), 4 patients showed intermediate morphoimmunohistochemical features with nodular lymphocyte predominant Hodgkin lymphoma, which were statistically significantly different from classical Hodgkin lymphoma by the presence of B-zones in the form of large nodules (p = 0.0157) and expression CD20 by tumor cells (p = 0.0404).Conclusion. Nodular lymphocyte predominant Hodgkin lymphoma is not characterized by a connection with EBV infection, unlike classical variant — lymphocyte-rich classical Hodgkin lymphoma. The obtained data support the concept of the existence of a transient form of Hodgkin lymphoma, which has the features of nodular lymphocyte predominant Hodgkin lymphoma and classical Hodgkin lymphoma, in the pathogenesis of which the Epstein — Barr virus likely plays a role.

Highlights

  • Epstein — Barr virus (EBV) plays an important role in the pathogenesis of lymphoid tumors, in particular Hodgkin lymphoma

  • Обработка результатов проведена с помощью программы Statistica 12

  • IgG and IgM antibodies to the varicella zoster virus were not detected in all cases

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Summary

Материалы и методы

Настоящее исследование представляет собой ретроспективный анализ случаев с диагнозом ЛХ, установленным в патологоанатомическом отделении ФГБУ «НМИЦ гематологии» Минздрава России на биопсийном материале больных «НМИЦ гематологии» и на консультативном материале, присланном из других лечебных учреждений России за период 2018–2019 гг. Выявление экспрессии ВЭБ выполняли с помощью ИГХ метода с целью выявления II и III типов латентности — антител к латентному мембранному протеину ВЭБ (клон LMP1, цитоплазматическая экспрессия), и методом хромогенной in situ гибридизации с зондами к малым РНК EBV (EBER — Epstein — Barr virus-encoded small RNAs) для определения всех типов латентности (ядерная реакция). С парафиновых блоков с помощью микротома выполняли срезы толщиной 3 мкм и монтировали на предметные стекла, покрытые поли-L-лизином. Стекла высушивали при температуре 37 °C в течение 12 ч и перед нанесением антител при температуре 60 °C в течение 1 ч. Перед заключением под покровное стекло проводили дегидратацию срезов с помощью этанола, для осветления среза использовали ксилол. Неуточненный вариант Unspecified variant Вариант, богатый лимфоцитами Lymphocyte‐rich subtype

Mixed cellularity subtype
Структура ЛХ на этапе диагностики
Повышены Increased
Сопоставление иммунофенотипических характеристик при нодулярном склерозе ЛХ
Findings
Параметр Parameter
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