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Leukemija vlasastih stanica ili triholeukemija je rijetka, limfoproliferativna bolest s malobrojnim cirkulirajućim tumorskim stanicama u perifernoj krvi. Trihociti su stanice čiji su citoplazmatski izdanci nalik vlasima te karakteriziraju ovu bolest. TL je kronična tijeka i sporo progresivna, te dobro reagira na terapiju purinskim analozima koji su standard u liječenju. Bolest uglavnom zahvaća slezenu, a limfni čvorovi su pošteđeni. TL je povezana s mutacijom BRAF gena i to s najčešćom mutacijom gena, BRAF V600E. Ta mutacija dovodi do konstitutivne aktivnosti RAS-RAF-MEK-ERK signalnog puta i do proliferacije stanica. BRAF mutacije do sad su povezane s brojnim malignomima, a najčešće s melanomom. Otkriće povezanosti triholeukemije s BRAF mutacijom donosi mogućnosti za novu terapiju BRAF inhibitorima, vemurafenibom i dabrafenibom, te praćenje bolesti uz pomoć RT-PCR metode. U ovom istraživanju analizirano je 15 ispitanika dijagnosticiranih s TL-om u KB Dubrava, u Zagrebu. Korišteni su uzorci periferne krvi i koštane srţi uklopljene u parafin. U istraživanju se utvrđivalo postojanje BRAF V600E mutacije u oboljelih te ocjenjivala uloga alel specifičnog RT-PCR-a u praćenju bolesti i otkrivanju minimalne ostatne bolesti. Zaključeno je da je RT-PCR metoda dovoljno osjetljiva za otkriće mutacije u aktivnoj bolesti te relapsu, a slabije osjetljiva u remisiji bolesti te kod minimalno aktivne bolesti. Povećan postotak limfocita u perifernoj krvi u ispitanika se pokazao kao dobar prediktor utvrđivanja BRAF V600E mutacije., Hairy cell leukemia, also called trycholeukemia, is a rare lymphoproliferative disorder with few circulating tumor cells in the peripheral blood. Hairy cells, characteristic of this disorder, are cells that have hair-like cytoplasmic projections. HCL has a chronic course. It is slowly progressive and has a good response to the standard treatment with purine analogues. Usually it affects the spleen, and lymph nodes are spared. HCL is associated with the BRAF gene mutation, more precisely with the most common, BRAF V600E mutation. That mutation leads to the constitutive activity of the RAS-RAF-MEK-ERK signal pathway and cell proliferation. BRAF mutations are related to many malignomas, but most commonly to melanoma. The discovery of the association between the HCL and the BRAF mutation lead to new possibilites in the treatment of the disorder, such as BRAF inhibitors, vemurafenib, and dabrafenib, as well as the possibility to follow up the disease with the RT-PCR method. In our study, 15 patients diagnosed with HCL were analyzed in the Clinical Hospital Dubrava in Zagreb. We used peripheral blood samples and samples of bone marrow embedded in paraffin. In this study we tried to detect the BRAF V600E mutation in patients diagnosed with HCL, and we also evaluated the allele-specific RT-PCR in the follow up of the disease and in the detection of the minimal residual disease. We concluded that the RT-PCR method is sensitive enough to detect the mutation in the active disease and in the relapse, but is less sensitive in the remission and in the minimal residual disease. A high percentage of lymphocytes in the peripheral blood has proved to be a good predictor of the BRAF V600E mutation.

Cilj: Cilj rada je prikazati slučaj pacijenta s metakronom pojavom liposarkoma, leukemije vlasastih stanica (engl. Hairy cell leukemia, HCL) i karcinomom bubrega te se osvrnuti na dosadašnje literaturne podatke o pojavi višestrukih malignih bolesti u pacijenata s HCL. Prikaz slučaja: Prikazan je slučaj 38-godišnjeg pacijenta kojemu je nakon operacije i radioterapije liposarkoma utvrđena patološka metabolička aktivnost koštane srži na PET/CT-u (engl. Positron emission tomography/Computed tomography) što je pobudilo sumnju na postojanje limfoproliferativne bolesti te je upućen na hematološku obradu kojom je utvrđena HCL. Bolesnik je neko vrijeme samo praćen te se nakon pogoršanja parametara bolesti sprovelo liječenje HCL kladribinom čime se postigla remisija hematološke bolesti. U daljnjem tijeku se rutinski učinila ultrasonografija abdomena kojom se ustanovi fokalna lezija lijevog bubrega. Nakon učinjene urološke obrade, učinjena je parcijalna nefrektomija, a patohistološkom analizom utvrđeno je da se radi o svijetlostaničnom tipu karcinoma podrijetla bubrežnih tubula. Zaključak: Bolesnici oboljeli od HCL imaju povećan rizik od razvoja drugih zloćudnih bolesti, kako različitih solidnih tumora, tako i drugih hematoloških novotvorina. Tijekom praćenja pacijenta s HCL potrebno je misliti na moguću pojavu drugih tumora budući da su sekundarne maligne bolesti čest uzrok morbiditeta i mortaliteta u ovoj grupi pacijenata. Važno je bolesnike s ovom vrstom limfoproliferativne bolesti pažljivo pratiti i vršiti sve uobičajene mjere primarne i sekundarne prevencije drugih vrsta raka. Potrebna su daljnja istraživanja mogućeg učinka kemoterapije na pojavu sekundarnih tumora u ovoj grupi bolesnika, ali isto tako imunoloških i eventualnih drugih patofizioloških mehanizama same HCL koji mogu dovesti do češće pojave drugih zloćudnih novotvorina., Aim: To present a patient with metachronous occurrence of liposarcoma, HCL (hairy cell leukemia) and renal cell carcinoma and analyze previous literature data about occurrence of multiple malignancies in HCL patients. Case report: We report a case of a 38-year-old patient who operated and treated liposarcoma with radiotherapy and in whom was found pathological metabolic activity of bone marrow on PET/CT (Positron emission tomography/Computed tomography). This finding raised a suspicion about the existence of lymphoproliferative disease and the patient was sent to hematological examination in which was revealed that patient has HCL. The patient was monitored and treatment with cladribine was started after there was deterioration in the blood count. Subsequently remission occured. Abdominal ultrasound was done and focal lesion of left kidney was found. Partial nefrectomy of the left kidney was done. Histopathological analysis revealed clarocellular kidney carcinoma. Conclusion: The patients with HCL have a higher risk of developing other malignant diseases, both solid tumors, and other hematologic neoplasms. It is important to think of secondary malignancies during the patient's monitoring, since secondary malignances are a frequent cause of morbidity and mortality in HCL patients. The patient with this type of limphoproliferative disease needs to be closely monitored and also needs to keep up with primary and secondary measures to prevent cancer development. Further research about the correlation of chemotherapy and incidence of secondary malignancies is needed, but also it is important to research immunological and other pathophysiological mechanisms which can increase the occurence of secondary malignancies.