| Abstract | Hodgkinov limfom (HL) rijetka je vrsta maligne bolesti kod koje dolazi do zloćudnog bujanja stanica limforetikularnog sustava. Incidencija HL-a povećana je kod osoba starijih od 55 godina, ali i kod mlađih odraslih osoba, u čijoj je populaciji jedan od najčešće dijagnosticiranih malignih tumora. Na temelju razlika u histološkoj slici i fenotipu tumorskih stanica HL je podijeljen na nodularni limfocitno predominantni HL i klasični HL koji se sastoji od četiri podtipa (HL mješovitih stanica, nodularna skleroza HL, HL s limfocitnom deplecijom i HL bogat limfocitima). Karakteristične maligne stanice klasičnog HL-a su Hodgkinove i Reed Sternbergove (HRS), a stanice nodularno limfocitno-predominantnog HL-a nazivaju se limfocitno predominantne (LP) te su u oba slučaja vrlo rijetke u tumorskom tkivu. Glavni simptom bolesti je bezbolna limfadenopatija, katkad praćena vrućicom, noćnim znojenjem, gubitkom tjelesne mase, svrbežom, splenomegalijom i hepatomegalijom. Patofiziologija bolesti temelji se na genetskim lezijama koje uzrokuju poremećaje u signalnim putevima (NFkB, JAK–STAT, PI3K/Akt, MAPK/ERK i PD-1/PD-L1) i transkripcijskim faktorima malignih stanica, ali i iznimno bitnim interakcijama unutartumorskog mikrookruženja. Epstein-Barr virus, također, ima ulogu u etiologiji bolesti te su njime latentno inficirane HRS stanice u otprilike 40% pacijenata s cHL-om, izražavajući EBV nuklearni antigen 1 i latentne membranske proteine 1 i 2a. HL se dijagnosticira ekscizijskom biopsijom limfnog čvora, a potvrda dijagnoze ovisi o pronalasku HRS stanica ili njihovih varijanti u odgovarajućem histološkom mikrookruženju. Za potvrdu dijagnoze, ali i razlikovanje podtipova HL-a također se koristi protočna citometrija, jer HRS i LP stanice imaju specifičan imunofenotip. Trenutačno su kombinirani kemoterapijski režimi i radioterapija standardna terapija HL-a, čime se postiže šansa od preko 80% za desetogodišnje preživljavanje svih novodijagnosticiranih pacijenata mlađih od 60 godina. Cilj daljnjeg unaprjeđenja terapije je smanjenje doživotne zaostale toksičnosti povezane s liječenjem uz održavanje visoke razine učinkovitosti. |
| Abstract (english) | Hodgkin's lymphoma (HL) is a rare type of malignant disease, which belongs to B cell lymphomas. The incidence of HL is increased in people older than 55 years, but also in young adults, in whose population it is one of the most frequently diagnosed malignant tumors. Based on differences in the histological picture and tumor cell phenotype, HL is divided into nodular lymphocyte-predominant HL and classic HL, which consists of four subtypes (mixed cellularity HL, nodular sclerosis HL, lymphocyte-depleted HL, and lymphocyte-rich HL). Characteristic malignant cells of classic HL are Hodgkin and Reed-Sternberg (HRS), and the cells of nodular lymphocyte-predominant HL are called lymphocyte-predominant (LP) and in both cases are very rare in the tumor tissue. The main symptom of the disease is painless lymphadenopathy, sometimes accompanied by fever, night sweats, weight loss, itching, splenomegaly and hepatomegaly. Pathophysiology of the disease is based on genetic lesions, which cause disturbances in signaling pathways (NF-kB, JAK-STAT, PI3K/Akt, MAPK/ERK and PD-1/PD-L1) and transcription factors of malignant cells, but also extremely important interactions within the tumor microenvironment. Epstein-Barr virus also plays a role in the etiology of the disease, and HRS cells are latently infected with it in approximately 40% of cHL patients, expressing EBV nuclear antigen 1 and latent membrane proteins 1 and 2a. HL is diagnosed by excisional lymph node biopsy, and confirmation of the diagnosis depends on the finding of HRS cells or their variant in the appropriate histological microenvironment. Flow cytometry is also used to confirm the diagnosis, but also to distinguish the subtype of HL, because HRS and LP cells have a specific immunophenotype. Currently, combined chemotherapy regimens and radiotherapy are used as standard therapy for HL, which achieves a chance of over 80% for ten-year survival of all newly diagnosed patients under the age of 60. The goal of further therapy improvement is to reduce lifelong residual toxicity associated with treatment while maintaining a high level of efficacy. For this purpose, various immunotherapies are being investigated as independent drugs or in combination with already existing therapies. |
