Metasztatikus progresszió kezelése primer cutan és ocularis melanoma szinkrón előfordulását követően = Treatment of metastatic progression following the synchronous occurrence of cutaneous and ocular primary melanomas

Absztrakt: A melanoma előfordulási gyakorisága az életkorral nő, legnagyobb arányban a nem hispániai fehérekben fordul elő. Bár az ocularis melanoma gyakorisága a töredéke a cutan melanomáénak – az összes melanomás eset mintegy 4%-a, éves incidenciája 0,6 : 100 000 –, a szemtumorok között a leggyakrabban előforduló malignitás. Az ocularis és a cutan melanoma együttes előfordulása irodalmi ritkaságnak számít. Közleményünkben egy 80 éves férfi esetét prezentáljuk, akinél 2008-ban cutan nodularis melanomát excindáltak. Szemészeten 2013-ban fokozódó visuscsökkenés miatt uvealis melanomát diagnosztizáltak, amelyet brachytherapiával kezeltek. Képalkotó vizsgálatokkal és biopsziával 2015-ben melanoma hepaticus propagatiója igazolódott. A primer cutan laesio mutációanalízise BRAF V600 K típusú funkciónyerő mutációt igazolt, míg az áttétben a vad típusú gén jelenlétét mutattuk ki. Onkoteam javaslata alapján 2015 augusztusában intraarterialis májkemoterápia kezdődött, melyből 11 ciklust kapott meg, 21 napos időintervallumokkal. A beteg a kezelést jól tolerálta, mellékhatás nem jelentkezett. A 2016. februári CT a májban lévő laesio parciális regresszióját igazolta; a tizenegyedik ciklus intraarterialis májkemoterápiáját követően a beteg komplett remisszióba került, amely több mint egy évig tartott. Az ocularis és a cutan melanoma szinkrón előfordulása igen ritka, metasztatikus progresszió esetén ugyanakkor az optimális onkoterápia kiválasztása komoly kihívást jelent. A két melanomatípus molekuláris patológiai háttere eltérő, amely segítheti a metasztatikus laesiók eredetének azonosítását és az optimális, személyre szabott kezelés megválasztását. Orv Hetil. 2018; 159(16): 642–647. | Abstract: The incidence rates of cutaneous melanoma in non-Hispanic whites show an increasing tendency with age. While uveal melanoma in general is a rare disease, representing only 4% of all melanomas with an incidence rate of 0.6 per 100 000, it is still the most frequent malignancy of the eye. Synchronous occurrence of ocular and cutaneous melanoma is an exceptional rarity, due to the distinct genetic background of the diseases. We report the case of a 80-year-old man who underwent total excision of a cutaneous melanoma in 2008. In 2013, he was diagnosed with uveal melanoma as part of a routine work-up for reduced vision. The uveal melanoma was treated by brachytherapy. In 2015, liver metastases were suspected by routine ultrasonography. Core biopsy was carried out, and the histology confirmed melanoma metastases. The molecular analysis of the cutaneous lesion showed gain of function mutation of the BRAF V600 K gene, while we found a wild-type BRAF gene in the metastatic lesion. Based on the recommendation of the oncoteam, hepatic intra-arterial Epirubicin-Platidiam therapy was introduced. He received 11 doses of intra-arterial chemotherapy (IAC), in 21 cycles. IAC was well tolerated without any catheter-related complications or toxicities. Partial regression of the hepatic metastases were documented in February 2016. After completing the eleventh cycle of intrahepatic chemotherapy, the disease remained in complete remission for over a year. The parallel occurrence of cutaneous and ocular melanoma is rare, however, the metastatic progression in such cases make the selection of optimal medical therapy challenging. The distinct genetic background of two melanoma types may help the identification of the source of the metastatic lesions, in order to guide the treatment decisions. Orv Hetil. 2018; 159(16): 642–647

Enhancer of zeste homologue 2 (EZH2) is a reliable immunohistochemical marker to differentiate malignant and benign hepatic tumors

BACKGROUND: The immunohistochemical demonstration of Enhancer of zeste homologue 2 (EZH2) proved to be a useful marker in several tumor types. It has been described to distinguish reliably hepatocellular carcinomas from liver adenomas and other benign hepatocellular lesions. However, no other types of malignant liver tumors were studied so far. METHODS: To evaluate the diagnostic value of this protein in hepatic tumors we have investigated the presence of EZH2 by immunohistochemistry in hepatocellular carcinomas and other common hepatic tumors.EZH2 expression was examined in 44 hepatocellular carcinomas, 23 cholangiocarcinomas, 31 hepatoblastomas, 16 other childhood tumor types (rhabdomyosarcoma, neuroblastoma, Wilms' tumor and rhabdoid tumor), 17 metastatic liver tumors 24 hepatocellular adenomas, 15 high grade dysplastic nodules, 3 biliary cystadenomas, 3 biliary hamartomas and 3 Caroli's diseases. RESULTS: Most of the malignant liver tumors were positive for EZH2, but neither of the adenomas, cirrhotic/dysplastic nodules, reactive and hamartomatous biliary ductules stained positively. CONCLUSIONS: Our immunostainings confirm that EZH2 is a sensitive marker of hepatocellular carcinoma, but its specificity is very low, since almost all the investigated malignant liver tumors were positive regardless of their histogenesis. Based on these results EZH2 is a sensitive marker of malignancy in hepatic tumors. In routine surgical pathology EZH2 could be most helpful to diagnose cholangiocarcinomas, because as far as we know this is the first marker to distinguish transformed and reactive biliary structures. Although hepatoblastomas also express EZH2, the diagnostic significance of this observation seems to be quite limited whereas, the structurally similar, other blastic childhood tumors are also positive. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1173195902735693

High tricellulin expression is associated with better survival in human hepatoblastoma.

AIMS The more differentiated fetal component of hepatoblastoma (HB) is characterized by increased expression of tight junction (TJ) proteins claudin-1 and -2 when compared with embryonal component. Expression patterns of the recently identified TJ protein tricellulin and the epigenetic regulator enzyme EZH2 were investigated in epithelial subtypes of HB and related to survival. METHODS AND RESULTS Twenty-one cases of epithelial HBs subtyped as pure fetal (n = 12) and embryonal/fetal (n = 9), along with 16 non-tumorous samples from surrounding liver, were analysed by immunohistochemistry for tricellulin, β-catenin and EZH2 expression. No significant differences were revealed in overall survival between fetal and embryonal/fetal types of HBs. The fetal component, however, showed considerably increased tricellulin expression while the embryonal component displayed significantly increased nuclear EZH2 positivity, in comparison to other epithelial subtypes and non-tumorous surrounding hepatocytes. Strong nuclear β-catenin staining was notably more frequent in embryonal than in fetal types. High tricellulin expression was associated with significantly increased overall survival (P = 0.03), while elevated EZH2 expression was linked to the presence of distant metastases (P = 0.013). CONCLUSIONS Our data indicate that patients with treated HBs showing high expression of tricellulin have significantly better overall survival, independent of histological subtype. Increased nuclear expression of EZH2 was associated with the presence of distant metastases

microRNA expression might predict prognosis of epithelial hepatoblastoma

Hepatoblastoma (HB) is the most common primary liver cancer in childhood. The fetal and mixed embryonal/fetal epithelial subtypes of HB differ not only in grade of differentiation but probably also in prognosis. We aimed to determine microRNA (miRNA) expression patterns of the main subtypes of epithelial HBs to reveal differences and relate them to survival. We studied 20 cases of epithelial HB, subtyped as pure fetal (n = 12) or embryonal/fetal (n = 8). Tissues were sampled according to subtype to arrive at 15 purely fetal and eight purely embryonal samples (n = 8) and 15 samples of non-tumorous surrounding liver (SL). Relative expression of miR-17-5p, miR-18a, miR-21, miR-34a, miR-96, miR-122, miR-181a, miR-195, miR-210, miR-214, miR-221, miR-222, miR-223, and miR-224 was determined by TaqMan MicroRNA Assays applying miR-140 as reference. A higher level of miR-18a (p < 0.01) was found in embryonal samples than in fetal samples. Lower miR-17-5p, miR-195, miR-210, miR-214, and higher miR-221 levels were detected in fetal samples (p < 0.02) in comparison with SL samples, whereas a lower miR-122 level was observed in embryonal samples (p < 0.003). Histological subtype did not correlate with survival; however, high miR-21, low miR-222, and low miR-224 levels proved to be independently prognostic for HB with significantly increased overall survival (p < 0.03). The fetal and embryonal components of epithelial HB, as well as SL, revealed different miRNA expression patterns. Furthermore, miR-21, miR-222, and miR-224 levels predict overall survival of HB patients regardless of epithelial subtype. © 2014 Springer-Verlag Berlin Heidelberg