Management of Rare Liver Tumours

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1 Gian Luca Grazi Hepato-Biliary-Pancreatic Surgery National Cancer Institute Regina Elena Rome

2 Fibrolamellar Carcinoma Mixed Hepato Cholangiocellular Carcinoma Hepatoblastoma Carcinosarcoma Primary Hepatic Carcinoid Cystoadenoma and Cystoadenocarcinoma Sarcomas Limphoma

3 Surveillance, Epidemiology and End Results Program of the National Cancer Institute USA 6391 Cases Type Subtype % Carcinoma 95.3 Hepatocellular 67.5 Cholangio 19.1 Mixed 2.2 Other adenocarcinomas 1.2 Carcinomas 5.1 Other specified 0.2 Sarcoma 2 Angiosarcomas 1 Other sarcomas 1 Hepatoblastoma 1.5 Others and not specified 1.3

4

5 Klein WM, Am J Clin Pathol 2005; 124:

6 Fibrolamellar Hepatocellular Carcinoma FLHCC

7 Fibrolamellar HCC

8 Fibrolamellar HCC Diagnosis is made on the basis of clinical presentations and imaging studies, such as ultrasound, computed tomography (CT) scan, and magnetic resonance imaging. Negative serum tumor markers such as α fetoprotein may support the diagnosis. If a diagnostic uncertainty occurs, fine needle biopsy guided by CT or ultrasound would be highly beneficial. Pathological diagnosis is always the gold standard. It must be stressed that sometimes the diagnosis can be difficult to establish, even with a needle biopsied specimen, and several passes or an open wedge biopsy may be necessary to obtain adequate tissues for correct diagnosis. Liu S, Am J Gastroenterol 2009; 104:

9 Fibrolamellar HCC The cornerstone for treatment is surgical resection with adequate lymph node dissection. FLHCC is a better candidate for resection than conventional HCC The presence of advanced stage disease, invasion of tumor to adjacent organs or local lymph node spread, or limited distant metastasis should not be considered as contraindications for curative resection In case partial hepatectomy is not technically feasible because of the size of the tumor or because of its deep extension and adhesion with adjacent organs, OLT should be considered Liu S, Am J Gastroenterol 2009; 104:

10 Fibrolamellar HCC

11 Fibrolamellar HCC Maniaci V, EJSO 2009; 35:

12 Fibrolamellar HCC Adjuvant chemotherapy was given to 5 of the 10 resected patients and clearly did not prevent relapse which is consistent with the findings of other investigators Active management of disease relapse requires early detection. (combination of CT or MRI and B12 binding proteins and, in selected cases FDG PET). There is no published evidence regarding the use of locoregional treatments such as TACE or RFA in FLHCC. Chemotherapy has not been systematically assessed (two confirmed responses to platinum based therapy). Maniaci V, EJSO 2009; 35:

13 Fibrolamellar HCC

14 Fibrolamellar HCC Kakar S, Modern Pathology 2005; 18:

15 Fibrolamellar HCC Kakar S, Modern Pathology 2005; 18:

16 Hepatoblastoma

17 Hepatoblastoma Almost exclusively in children between 6 months and 3 years, with a male predominance 50% of liver malignancies in children Derived from undifferentiated embryonal tissue and thought to develop from pluripotent hepatic stem cells. More commonly in families with familial adenomatous polyposis. Lesions are often a solitary mass in the right lobe of the liver.

18 Hepatoblastoma αfp is a reliable marker (higher in 90% of cases) Treatment of choice: Hepatic resection ± CHT CHT led to downstage 75% 85% of unresectable patients, with a postoperative survival ranging from 25 to 70%. Liver transplantation for unresectable patients: Al Qabandi et al, J Ped Surg, patients mean age: 24 months pre op CHT (SIOPEL: cddp + adr ± cbdca) complete response in 3 cases Survival: 88% after 1 year 65% after 5 years

19 Hepatoblastoma

20 Hepatoblastoma D Antiga L, Cancer 2007; 110:

21 Hepatoblastoma Cillo U, Transpl Proc 2003; 35:

22 Cystoadenocarcinoma

23 Cystoadenocarcinoma Nearly 200 cystadenomas and 100 cystadenocarcinomas have been reported. Cystadenomas are usually found in middle aged women. The cause is unknown. The typical appearance is of a lobulated, multiloculated mass. Histologically, most contain an ovarian like stroma. CA 19 9 may be elevated. J Gastrointestin Liver Dis. 2008: 17:203-6.

24 Cystoadenocarcinoma Better prognosis than HCC and CCC Insurgence from intra or extra hepatic biliary tree Diagnosis is based on imaging. Differential diagnosis with cystoadenoma, choledochal cysts, Carolì disease, polycystic liver disease, cholangiocarcinoma with marked biliary dilatation or cystic degeneration, cystic metastases (pancreas, ovary) Two types: non invasive (limited to the cysts) and invasive (parenchyma infiltrating), with different prognosis (Nakajima et al, Cancer, 1982).

25 Cystoadenocarcinoma

26 Cystoadenocarcinoma Kim JY, AJR 2010; 195:

27 Cystoadenocarcinoma Kim JY, AJR 2010; 195:

28 Cystoadenocarcinoma

29 Cystoadenocarcinoma Koffron A, Surgery 2004; 136:

30 Hemangioendothelioma

31 Hemangioendothelioma More than 200 cases reported, with a link to oral contraceptives. Mean age 47 years, but occurs at any age Female predominance (60%) Non specific symptoms; in over 40% the tumor is found incidentally. Histologically: dendritic and epithelioid cells with immunohistochemistry positivity for at least one endothelial cell marker (FVIII RAg,CD34,CD31) Indolent and slow growing; 5 year survival 43% Am Surg 2008; 74 :64 8 Cancer 1999; 85 :

32 Hemangioendothelioma In the first series published by Ishak (1984, 32 cases), 20% of patients died within 2 years from diagnosis and 20% survived more then 5 years. Surgical resection has been the first proposed therapy with a curative scope. Penn and coll. (1991) described 21 patients undergoing liver transplantation. 5 year survival 43% with a recurrence rate of 33%.

33 Hemangioendothelioma

34 Hemangioendothelioma 9 patients single center Retrospective study ( ) Monolobar 2 patients Bilobar 7 patients Hepatic resection: 3 patients OLT 6 patients Mean Follow Up: 117 months 7/9 (2 resections, 5 transplants) alive and disease free Mosoia L, J Surg Oncol 2008; 98:

35 Hemangioendothelioma Surgical treatment offers good results in terms of survival in the medium period Liver transplantation should be considered for patients with bilobar involvement Hepatic resection should be performed in patients with limited and monolobar disease Mosoia L, J Surg Oncol 2008; 98:

36 Hemangioendothelioma

37 Hemangioendothelioma 59 patients transplanted in Europe (ELTR) Questionnaire with 216 questions 32 centers 10 (16.9%) patients with extrahepatic disease Bilobar 47 (86%) Portal vein/hepatic vein thrombosis10/20 (50%) 7 previous partial hepatectomy Lerut JP, Ann Surg 2007; 246

38 Hemangioendothelioma Lerut JP, Ann Surg 2007; 246

39 Hemangioendothelioma Lerut JP, Ann Surg 2007; 246

40 Hemangioendothelioma Lerut JP, Ann Surg 2007; 246

41 Hemangioendothelioma Results of OLT are excellent Extrahepatic or lymph node involvement are not contraindications to OLT Micro vascular infiltration or the combination of micro and macro vascular infiltrations significantly influences survival Disease recurrence must be aggressively treated Antiangiogenetic therapies (anti V EGF antibodies or rapamicine/everolimus) should be evaluated Lerut JP, Ann Surg 2007; 246

42 Angiosarcoma

43 Angiosarcoma Vascular tumors, associated with the exposures to vinyl chloride, arsenic, thorotrast and irradiation (etiologic cofactors) (25 42%). Mainly in the adults (50 60 yrs). M/F 4:1. Often multiple. Late symptoms. Immunohistochemical staining for CD31, CD34, MIB 1 confirm the diagnosis Mean survival: 6 months after diagnosis (Falk et al, Environ Health Perspect, 1981). Surgery as main therapy Differential diagnosis: Hemangioendothelioma World J Surg Oncol ;6:104 World J Gastroenterol ; 12(5):

44 Angiosarcoma R.S., female, 21 years Symptoms: abdominal pain, fever, leucocytosis. Diagnosis: Hemangioendothelioma 23/11/92: Liver transplantation No postoperative CHT Today: alive and disease free

45 Gian Luca Grazi Hepato Biliary Pancreatic Surgery National Cancer Institute Regina Elena, Rome, Italy

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