University of Zagreb. School of Medicine. Chair of Internal Medicine.
Abstract
Hodgkinov limfom zloćudna je novotvorina porijekla iz limnog tkiva. Hodgkinov limfom i Hodgkinova bolest su istoznačnice. Porijeklom iz B-limfocita bolest je karakterizirana atipičnim oblikom stanica. Reed - Sternberg te Hodgkinove stanice koje se nalaze u limfnom čvoru patognomonične su za Hodgkinovu bolest. Navedene stanice okružene su upalnim infiltratom koji varira zavisno od oblika bolesti. Tako Hodgkinov limfom možemo podijeliti na nodularnu limfocitnu predominaciju koja čini 5% bolesti i klasičan Hodgkinov limfom koji čini preostalih 95%, te se može podijeliti na četiri podvrste: nodularna skleroza, miješana celularnost, Hodgkinov limfom bogat stanicama, limfocitna deplecija. Sve navedene podvrste imaju svoja karakteristična histološka obilježja. Hodgkinov limfom rijetka je bolest koja ima bimodalnu dobnu distribuciju s najvećom učestalošću javljanja u pacijenata 15-35 te 55+ godina. Češća je u pripadnika bijele nego drugih rasa. Iako jedinstveni uzrok Hodgkinove bolesti nije poznat, u etiopatogenezi veliku ulogu igraju genetske promjene i infekcije virusima od kojih je predominantan utjecaj Epstein – Barr virusa. Mutagene promjene uzrokuju konstitutivnu aktivnost NF-κB puta. HD se dijagnosticira biopsijom te korištenjem imunohistokemijskih metoda. Pacijent se prezentira bezbolnim uvećanjem jednog ili više limfnih čvorova jednostrano. Najčešće zahvaćena regije su vrat i supraklavikularna regija. U četvrtine bolesnika prisutni su B simptomi u koje ubrajamo: gubitak tjelesne težine (>10% u 6 mj), pojačano noćno znojenje i povišenu tjelesnu temperaturu (>38°C) bez infekcije. Kemoterapija zajedno sa radioterapijom indicirana je u ranom obliku bolesti. U razvijenom obliku bolesti preporuča se samo kemoterapija premda postoje i iznimke kada se u modalitet liječenja uključuje i radioterapija. Odnedavno su u upotrebu uključena i monoklonalna protutijela. U liječenju se najčešće koristi kombinirana kemoterapija ABVD koja se sastoji od doksorubicina, bleomicina, vinblastina, dakarbazina. Danas postoje različite kombinacije kemoterapeutika poput BEACOPP, međutim zbog najmanje toksičnosti ABVD je terapija izbora u većine bolesnika. Liječenje radioterapijom se kretalo od zračenja širokog polja (Extensive field radiotherapy - EFRT) prema suženom zračenju površine tijela (Involved field radiotherapy - IFRT). Desetogodišnje preživljenje bolesnika s Hodgkinovom bolešću danas iznosi preko 80%. Od otkrića kemoterapije i njihoveprimjene u liječenju bolesti Hodgkinov limfom je primjer uspjeha medicine u liječenju nekoć neizlječive bolesti. Stoga se današnja istraživanja baziraju na smanjenju toksičnosti kemoradioterapije za pacijente kako bi se sekundarni malignomi i druge komplikacije smanjili na minimum.Hodgkin's lymphoma is a malignant neoplasm originating from germinative center B cells. Hodgkin's lymphoma and Hodgkin's dissease are synonims. Disease is characterized by an atypical form of cells, Reed – Sternberg and Hodgkin cells, which are patognomonic for dissease. These cells, found in lymph nodes are surrounded by an inflammatory infiltrate, which varies depending on the form of the disease. Hodgkin's lymphoma can be divided two main types. Nodular lymhocite predominance which makes 5% of the disease and classical Hodgkin's lymphoma, making the remaining 95%, and can be divided into four subtypes: nodular sclerosis, mixed cellularity subtype, lymphocyte rich Hodgkin lymphoma, lymphocyte depletion. All these subtypes have their characteristic histological features. Hodgkin's lymphoma is a rare disease that has bimodal age distribution with the highest frequency of occurence in patients form 15 to 35 and 55+ years old. Although a single cause of Hodgkin's disease is not known, genetic mutations and infection, predominantly by Epstein – Barr virus play important role in pathogenesis of the disease. Mutagenic changes cause constitutive activity of NF-κB pathway. HD is diagnosed by biopsy and using immunohistochemical methods. The patient presents with painless enlargement of one or more lymph nodes unilaterally.The most commonly affected regions are neck and supraclavicular region. One fourth of patients presents with B symptoms consisting of: body weight loss ( more than 10% in 6 months), increased night sweating and high temperature (> 38°C ) without temperature. Chemotherapy along with radiotherapy is indicated in early form of disease. In the developed form only chemotherapy is recommended although there are exceptions when the modality of treatment also includes radiation therapy. Recently, monoclonal antibodies were discovered and used in treating the disease. The treatment most often used is ABVD chemotherapy consisting of doxirubicin, bleomycin, vinblastine, dacarbazine. Today, there are different combinations of chemotherapeutic agents such as BEACOPP and MOPP, however, because ABVD has least side effects, it is the treatment of choice. Treatment with radiotherapy ranged from wide extended- field radiation treatment (EFRT) towards narrowinvolved- field radiotherapy (IFRT). Ten-year survival of patientstoday is over 80 %. Since the discovery of chemotherapy and its application, Hodgkin's disease is an example of the sucess of medicine in treatment of once incurable disease. Thus, the present studies are based on the reduction od the toxicity of chemoradiotherapy in purpose of preventing secondary malignancies and other complications to a minimum
