TUMORIDEL FEGATO

Avvertenza per gli studenti del corso di Anatomia Patologica del corso Integrato Malattie dellapparato Gastroenterico e Infettive.

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Buon studio

Achille PICH

DIAGNOSI ANATOMO-PATOLOGICADELLE NEOPLASIE EPATICHE1) CITOLOGIA2) AGOBIOPSIA3) BIOPSIA4) ESAME ESTEMPORANEO5) IMMUNOISTOCHIMICA BIOLOGIA MOLECOLARESondaggio duodenaleStriscio dopo agobiopsiaAspirazione con ago sottile di masseo materiale biliare LaparoscopicaChirurgica

Classificazione WHOPRIMITIVI1) Tumori epiteliali benigni e lesioni pseudotumorali2) Tumori non-epiteliali benigni3) Tumori epiteliali maligni4) Tumori non-epiteliali maligniSECONDARIEpitelialiNon-epiteliali

WHO Histological classificationTumours of the liver and intrahepatic bile ductsEpithelial tumoursBenign- Hepatocellular adenoma (liver cell adenoma)- Focal nodular hyperplasia- Intrahepatic bile duct adenoma- Biliary papillomatosis- Intrahepatic bile duct cystadenoma

WHO Histological classificationTumours of the liver and intrahepatic bile ductsEpithelial tumoursMalignant- Hepatocellular carcinoma (liver cell carcinoma)- Intrahepatic cholangiocarcinoma(peripheral bile duct carcinoma)- Combined hepatocellular and cholangiocarcinoma - Bile duct cystadenocarcinoma- Hepatoblastoma- Undifferentiated carcinoma

WHO Histological classificationTumours of the liver and intrahepatic bile ductsNon-epithelial tumoursBenign- Angiomyolipoma- Lymphangioma and lymphangiomatosis- Haemangioma- Infantile haemangioendothelioma

WHO Histological classificationTumours of the liver and intrahepatic bile ductsNon-epithelial tumoursMalignant- Epithelioid haemangioendothelioma- Angiosarcoma- Others - Embryonal sarcoma (undifferentiated sarcoma)- Rabdomyosarcoma)

WHO Histological classificationTumours of the liver and intrahepatic bile ductsMiscellaneous tumours- Solitary fibrous tumour- Teratoma- Kaposi sarcoma - Yolk sac tumour (endodermal sinus tumour)- Carcinosarcoma- Rhabdoid tumour - Others

WHO Histological classificationTumours of the liver and intrahepatic bile ductsHaemopoietic and lymphoid tumours- Mesenchymal hamartoma - Nodular transformation- Inflammatory pseudotumour Secondary tumoursMiscellaneous lesions(Nodular regenerative hyperplasia)

WHO Histological classificationTumours of the liver and intrahepatic bile ductsEpithelial abnormalitiesLiver cell dysplasia (liver cell change) - Large cell type (large cell change) - Small cell type (small cell change)Dysplastic nodules (adenomatous hyperplasia) - Low grade - High grade (atypical adenomatous hyperplasia)Bile duct abnormalities - Hyperplasia (bile duct epithelium and peribiliary glands) - Dysplasia (bile duct epithelium and peribiliary glands) - Intraepithelial carcinoma (carcinoma in situ)

TUMORI EPITELIALI BENIGNI E LESIONI PSEUDOTUMORALI1) Cisti multiple congenite 2) Cisti solitarie3) Cistoadenoma dei dotti biliari4) Adenoma dei dotti biliari5) Adenoma epatocellulare6) Iperplasia nodulare focale7) Iperplasia lobare compensatrice (rigenerativa)

TUMORI NON-EPITELIALI BENIGNI E LESIONI PSEUDOTUMORALI1) Emangioma cavernoso 2) Emangioendotelioma infantile3) Peliosi epatica4) Amartoma (mesenchimale, biliare)

TUMORI PRIMITIVI EPITELIALI MALIGNI 1) Carcinoma epatocellulare (HCC) 2) Carcinoma colangiocellulare (CCC)3) Epatoblastoma4) Carcinoma misto epato-colangiocellulare5) Carcinoma indifferenziato

TUMORI PRIMITIVI EPITELIALI MALIGNI 1) Carcinoma epatocellulare (HCC)

Predisposing and associated factors. Cirrhosis. In the United States, 60% to 80% of the cases develop in livers affected by cirrhosis, clinically apparent or silent, usually macronodular. 2. Liver cell dysplasia. Large or small cell type.3. Adenomatous hyperplasia. a) Macroregenerative nodule (ordinary adenomatous hyperplasia). It has not a greater predisposition to the development of malignancy than the smaller nodules, seen in all cases of cirrhosis. b) Borderline nodule (atypical adenomatous hyperplasia). Morphologic, morphometric, DNA ploidy, cell proliferative and AgNOR studies are all consistent with its presumed preneoplastic role. Incidence: 0.2/100.000 (West C)-173/100.000 (Taiwan)

4. Hepatotropic viruses. There is strong evidence of a pathogenetic role of hepatotropic viruses in the development of liver cell carcinoma, not only through the production of cirrhosis but also in noncirrhotic livers. This is true for both hepatitis B and hepatitis C viruses and for both adult and pediatric patients.5. Thorium dioxide exposure. Average latent period: 20 years.6. Androgenic anabolic steroids. 7. Progestational agents. 8. Alpha-1-antitrypsin deficiency.

9. Tyrosinemia. In one series, 37% of forty-three patients surviving beyond 2 years of age developed this malignancy10. Ataxia-telangiectasia. 11. Aflatoxins. 12. Schistosomiasis. There is no convincing evidence that schistosomiasis per se predisposes to liver cell carcinoma.

TNM Clinical ClassificationTXPrimary tumour cannot be assessedT0Solitary tumour without vascular invasionT2Solitary tumour with vascular invasion or multiple tumours, none more than 5 cm in greatest dimensionT3Multiple tumours any more than 5 cm or tumour involving a major branch of the portal or hepatic vein(s)T3a Multiple tumours any more than 5 cmT3b Invasion of a major branch of the portal or hepatic vein(s)T4Tumor(s) with direct invasion of adjacent organsother than the gallbladder or with perforation ofvisceral peritoneum T -Primary Tumour (HCC)No evidence of primary tumourT1

TNM Clinical ClassificationN0No regional lymph node metastasisN1Regional lymph node metastasisM0No distant metastasisM1Distant metastasisN -Regional Lymph NodesNXRegional lymph nodes cannot be assessedM -Distant MetastasisMXDistant metastasis cannot be assessed

STAGE GROUPING (HCC)Stage IStage IIStage IIIAStage IIIBStage IVAStage IVBT1T2T3aT3bAny TAny TN0N0N0N0N1Any NM0M0M0M0M0M1Stage IIICT4N0M0

Prognostic Factors

1. Stage. Is the most important prognostic determinator.2. Size. Small tumors (from 2 to 5 cm in diameter) have a significantly better prognosis.3. Encapsulation. The liver cell carcinomas that are totally surrounded by a capsule are less aggressive. 4. Number of tumors. 5. Portal vein involvement. Worsened prognosis. 6. Microscopic type. The fibrolamellar variant is associated with a definitely better prognosis. No consistent correlations have been found between prognosis and the other morphologic variants of liver cell carcinoma.

7. Mitotic activity. 8. Presence of cirrhosis. Carcinomas associated with cirrhosis have a worsened prognosis.9. Serum AFP levels. High AFP levels at presentation have not only a diagnostic but also an adverse prognostic significance10. Viral antigenemia. No prognostic differences exist between hepatitis B antigenpositive and hepatitis B antigennegative cases.11. Use of progestational hormones. It has been stated that tumors in patients who have taken contraceptive pills have a better prognosis 12. Sex and age. A recent study showed a better survival for females

TUMORI PRIMITIVI EPITELIALI MALIGNI 2) Carcinoma colangiocellulare (CCC)

TNM Clinical ClassificationTXPrimary tumour cannot be assessedT0Tumour confined to the bile ductT2Tumor invades beyond the wall of the bile ductT3Tumor invades the liver, gallbladder, pancreas,and/or unilateral tributaries of the portal vein (right or left) or hepatic artery (right or left) T4Tumor invades any of the following: main portalvein or its tributaries bilaterally, common hepaticartery, or adjacent structures, e.g., colon, stomach,duodenum, abdominal wallT -Primary TumourNo evidence of primary tumourT1TisCarcinoma in situ

TNM Clinical ClassificationN0No regional lymph node metastasisN1Regional lymph node metastasisM0No distant metastasisM1Distant metastasisN -Regional Lymph NodesNXRegional lymph nodes cannot be assessedM -Distant MetastasisMXDistant metastasis cannot be assessed

STAGE GROUPINGStage IAStage IBStage IIAStage IIBStage IIIStage IVT1T2T3T1,T2,T3T4Any TN0N0N0N1Any NAny NM0M0M0M0M0M1Stage 0TisN0M0

1. Cholesterol polyps 2. Inflammatory polyps3. Adenomatous hyperplasia 4. Adenomyomatous hyperplasia5. Villous papillomas 6. AdenomasGALLBLADDERBenign tumors and tumorlike conditions

CARCINOMACarcinoma of the gallbladder is more frequent in females (3 to 4:1 ratio); over 90% of the patients are 50 years of age or older at the time of diagnosis. It is more common in some Latin American countries than in the United States. The incidence is high in American Indians, relatively low in whites of European extraction, and very rare in blacks. In Europe, the rate is very high in Germany and surrounding central countries, low in Mediterranean countries, and low and declining in Britain and Ireland.

A definite epidemiologic parallel exists between gallbladder carcinoma and cholelithiasis, but the pathogenetic relationship between them remains obscure. Other conditions associated with an increased risk of gallbladder carcinoma are cholecystoenteric fistula, porcelain gallbladder, ulcerative colitis, adenomyomatosis, polyposis coli, Gardner's syndrome, and anomalous connection between the common bile duct and the pancreatic duct. The most common clinical manifestations of gallbladder carcinoma are right upper quadrant abdominal pain and anorexia, and the most common abnormal laboratory finding is elevated alkaline phosphatase levels.

TNM Clinical ClassificationTXPrimary tumour cannot be assessedT0Tumour invades lamina propria or muscle layerT2Tumor invades perimuscular connective tissue, noextension beyond serosa or into liverT3Tumor perforates serosa and/or directly invades theliver and/or one other adjacent organ or structureT4Tumor invades main portal vein or hepatic artery, orinvades two or more extrahepatic organs or structuresT -Primary TumourNo evidence of primary tumourT1TisCarcinoma in situT1a Tumour invades lamina propriaT1b Tumour invades muscle layer

TNM Clinical ClassificationN0No regional lymph node metastasisN1Regional lymph node metastasisM0No distant metastasisM1Distant metastasisN -Regional Lymph NodesNXRegional lymph nodes cannot be assessedM -Distant MetastasisMXDistant metastasis cannot be assessed

STAGE GROUPINGStage IStage IIStage IIIAStage IIIBStage IVAStage IVBT1T2T3T1,T2,T3T4Any TN0N0N0N1Any NAny NM0M0M0M0M0M1Stage 0TisN0M0

Prognostic Factors

Stage. The 5-year survival rate is over 90% for stages I and II, 11% for stages III and IV, and zero for stage V. Even when the carcinoma becomes apparent to the surgeon at the time of exploration of the gallbladder for chronic cholecystitis and/or cholelithiasis, it is often incurable because of its tendency to spread through the wall of the gallbladder and its propensity to invade the liver, pericolic tissues, and lymph nodes and even infiltrate the duodenum. In a series of 80 cases, there was only 1 long-term survivor. The best possibility of cure is when the cancer is found incidentally by the pathologist on gross or microscopic examination. Most such cases are stage I or II disease.

2. Grading. A combination of staging and microscopic grading seems to offer the best prognostic correlation.3. DNA content. The importance of DNA content as an independent prognostic marker in gallbladder carcinoma remains to be demonstrated.Ki-ras. Ki-ras codon 12 mutations are an independent prognostic factor, contrary to c-erbB-2 oncogene amplification or overexpression.

TUMORI PRIMITIVINON-EPITELIALI MALIGNI1) Angiosarcoma2) Rabdomiosarcoma embrionale3) Altri (Sarcoma di cellule di Kpffer, Mesenchimoma maligno, Leiomiosarcoma, Fibrosarcoma)

TUMORI SECONDARIDEL FEGATO

IDONEITA DEL PARENCHIMA EPATICOALLIMPIANTO DI NEOPLASIE1. DIMENSIONI2. DOPPIA PERFUSIONE EMATICA3. DISPONIBILITA DI SOSTANZE NUTRITIZIE

METASTASI EPATICHEFrequenza globaleCasistica autopticaCarcinoma pancreaticoCarcinoma del colonCarcinoma mammarioCarcinoma gastricoCarcinoma polmonare38%70%56%53%44%41%(Edmondson HA and Peters RL, 1982)

A review of over 10,000 autopsies from Trieste, Italy, and Tokyo-Chiba, Japan, confirmed the often quoted anecdotal observation that metastases are very rare in cirrhotic livers; whatever the reason for this may be (nonreceptive soil for the metastatic growth or simply the fact that most cirrhotic patients do not live long enough to develop them), the conclusion can be drawn that the large majority of malignant tumors occurring in cirrhotic livers are primary.

A percutaneous liver biopsy will be positive in about 75% of the cases with widespread metastatic liver disease. For laparoscopically directed biopsies, the incidence of positivity is much higher. Fine-needle biopsy aspiration is being increasingly used for the diagnosis of liver metastases, with excellent results

METASTASI EPATICHE:Aspetto macroscopicoNodi pochi e voluminosiNodi medi, ombelicatiNodi grandi con satellitiNoduli miliariformiNoduli nerastriNoduli emorragiciCa. grosso intestinoCa. mammella, polmoneCa. colecistiCa. mammella, stomaco,prostataMelanomaCoriocarcinoma,CarcinoideNodi molliCa. squamosi

METASTASI EPATICHE:Aspetto microscopicoAdenoca. PAS positiviCa. solidiCa. transizionaliCa. cellule chiareTumori con melaninaSarcomi con ossoApp. gastroentericoMammella, PolmoneVescica, Pelvi renaleReneMelanomaTumori osseiCa. squamosiPolmone, Collo utero

METASTASI EPATICHE:ImmunoistochimicaTumori epitelialiLinfomiEMA, CitocheratineLCA, CD3, CD20SarcomiDesmina, Vimentina

METASTASI EPATICHE:ImmunoistochimicaCa. apparato digerenteTumori muscolariCoriocarcinomaMelanomaTeratomi, EpatomiCa. prostataCEAActina, MiosinaHCGS100, HMB45-feto-proteinaPSA, PAPTumori vascolariFatt VIII, CD31, CD34Ca. tiroideTireoglobulina