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TUMORI

DEL FEGATO
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Achille PICH
DIAGNOSI ANATOMO-PATOLOGICA
DELLE NEOPLASIE EPATICHE
1) CITOLOGIA
2) AGOBIOPSIA
3) BIOPSIA
4) ESAME ESTEMPORANEO
5) IMMUNOISTOCHIMICA
BIOLOGIA MOLECOLARE
Sondaggio duodenale
Striscio dopo agobiopsia
Aspirazione con ago sottile di masse
o materiale biliare
Laparoscopica
Chirurgica
Classificazione WHO
PRIMITIVI
1) Tumori epiteliali benigni e lesioni
pseudotumorali
2) Tumori non-epiteliali benigni
3) Tumori epiteliali maligni
4) Tumori non-epiteliali maligni
SECONDARI
Epiteliali
Non-epiteliali
WHO Histological classification
Tumours of the liver and intrahepatic bile ducts
Epithelial tumours
Benign
- Hepatocellular adenoma (liver cell adenoma)
- Focal nodular hyperplasia
- Intrahepatic bile duct adenoma
- Biliary papillomatosis
- Intrahepatic bile duct cystadenoma
WHO Histological classification
Tumours of the liver and intrahepatic bile ducts
Epithelial tumours
Malignant
- Hepatocellular carcinoma (liver cell carcinoma)
- Intrahepatic cholangiocarcinoma
(peripheral bile duct carcinoma)
- Combined hepatocellular and cholangiocarcinoma
- Bile duct cystadenocarcinoma
- Hepatoblastoma
- Undifferentiated carcinoma
WHO Histological classification
Tumours of the liver and intrahepatic bile ducts
Non-epithelial tumours
Benign
- Angiomyolipoma
- Lymphangioma and lymphangiomatosis
- Haemangioma
- Infantile haemangioendothelioma
WHO Histological classification
Tumours of the liver and intrahepatic bile ducts
Non-epithelial tumours
Malignant
- Epithelioid haemangioendothelioma
- Angiosarcoma
- Others
- Embryonal sarcoma (undifferentiated sarcoma)
- Rabdomyosarcoma)
WHO Histological classification
Tumours of the liver and intrahepatic bile ducts
Miscellaneous tumours
- Solitary fibrous tumour
- Teratoma
- Kaposi sarcoma
- Yolk sac tumour (endodermal sinus tumour)
- Carcinosarcoma
- Rhabdoid tumour
- Others
WHO Histological classification
Tumours of the liver and intrahepatic bile ducts
Haemopoietic and lymphoid tumours
- Mesenchymal hamartoma
- Nodular transformation
- Inflammatory pseudotumour
Secondary tumours
Miscellaneous lesions
(Nodular regenerative hyperplasia)
WHO Histological classification
Tumours of the liver and intrahepatic bile ducts
Epithelial abnormalities
Liver 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
PSEUDOTUMORALI
1) Cisti multiple congenite
2) Cisti solitarie
3) Cistoadenoma dei dotti biliari
4) Adenoma dei dotti biliari
5) Adenoma epatocellulare
6) Iperplasia nodulare focale
7) Iperplasia lobare compensatrice (rigenerativa)
TUMORI NON-EPITELIALI BENIGNI E
LESIONI PSEUDOTUMORALI
1) Emangioma cavernoso
2) Emangioendotelioma infantile
3) Peliosi epatica
4) Amartoma (mesenchimale, biliare)
TUMORI PRIMITIVI
EPITELIALI MALIGNI
1) Carcinoma epatocellulare (HCC)
2) Carcinoma colangiocellulare (CCC)
3) Epatoblastoma
4) Carcinoma misto epato-colangiocellulare
5) Carcinoma indifferenziato
TUMORI PRIMITIVI
EPITELIALI MALIGNI
1) Carcinoma epatocellulare (HCC)
Predisposing and associated factors.
1. 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 malignancy
10. Ataxia-telangiectasia.
11. Aflatoxins.
12. Schistosomiasis. There is no convincing
evidence that schistosomiasis per se predisposes
to liver cell carcinoma.
TNM Clinical Classification
TX Primary tumour cannot be assessed
T0
Solitary tumour without vascular invasion
T2
Solitary tumour with vascular invasion or multiple
tumours, none more than 5 cm in greatest dimension
T3
Multiple 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 cm
T3b Invasion of a major branch of the portal or hepatic vein(s)
T4
Tumor(s) with direct invasion of adjacent organs
other than the gallbladder or with perforation of
visceral peritoneum
T - Primary Tumour (HCC)
No evidence of primary tumour
T1
TNM Clinical Classification
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M0 No distant metastasis
M1 Distant metastasis
N - Regional Lymph Nodes
NX Regional lymph nodes cannot be assessed
M - Distant Metastasis
MX Distant metastasis cannot be assessed
STAGE GROUPING (HCC)
Stage I
Stage II
Stage IIIA
Stage IIIB
Stage IVA
Stage IVB
T1
T2
T3a
T3b
Any T
Any T
N0
N0
N0
N0
N1
Any N
M0
M0
M0
M0
M0
M1
Stage IIIC T4 N0 M0
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
significance
10. 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 Classification
TX Primary tumour cannot be assessed
T0
Tumour confined to the bile duct
T2
Tumor invades beyond the wall of the bile duct
T3
Tumor invades the liver, gallbladder, pancreas,
and/or unilateral tributaries of the portal vein (right
or left) or hepatic artery (right or left)
T4
Tumor invades any of the following: main portal
vein or its tributaries bilaterally, common hepatic
artery, or adjacent structures, e.g., colon, stomach,
duodenum, abdominal wall
T - Primary Tumour
No evidence of primary tumour
T1
Tis
Carcinoma in situ
TNM Clinical Classification
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M0 No distant metastasis
M1 Distant metastasis
N - Regional Lymph Nodes
NX Regional lymph nodes cannot be assessed
M - Distant Metastasis
MX Distant metastasis cannot be assessed
STAGE GROUPING
Stage IA
Stage IB
Stage IIA
Stage IIB
Stage III
Stage IV
T1
T2
T3
T1,T2,T3
T4
Any T
N0
N0
N0
N1
Any N
Any N
M0
M0
M0
M0
M0
M1
Stage 0 Tis N0 M0
1. Cholesterol polyps
2. Inflammatory polyps
3. Adenomatous hyperplasia
4. Adenomyomatous hyperplasia
5. Villous papillomas
6. Adenomas
GALLBLADDER
Benign tumors and tumorlike conditions
CARCINOMA
Carcinoma 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 Classification
TX Primary tumour cannot be assessed
T0
Tumour invades lamina propria or muscle layer
T2
Tumor invades perimuscular connective tissue, no
extension beyond serosa or into liver
T3
Tumor perforates serosa and/or directly invades the
liver and/or one other adjacent organ or structure
T4
Tumor invades main portal vein or hepatic artery, or
invades two or more extrahepatic organs or structures
T - Primary Tumour
No evidence of primary tumour
T1
Tis
Carcinoma in situ
T1a Tumour invades lamina propria
T1b Tumour invades muscle layer
TNM Clinical Classification
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M0 No distant metastasis
M1 Distant metastasis
N - Regional Lymph Nodes
NX Regional lymph nodes cannot be assessed
M - Distant Metastasis
MX Distant metastasis cannot be assessed
STAGE GROUPING
Stage I
Stage II
Stage IIIA
Stage IIIB
Stage IVA
Stage IVB
T1
T2
T3
T1,T2,T3
T4
Any T
N0
N0
N0
N1
Any N
Any N
M0
M0
M0
M0
M0
M1
Stage 0 Tis N0 M0
Prognostic Factors
1. 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.
4. Ki-ras. Ki-ras codon 12 mutations are an
independent prognostic factor, contrary to
c-erbB-2 oncogene amplification or
overexpression.
TUMORI PRIMITIVI
NON-EPITELIALI MALIGNI
1) Angiosarcoma
2) Rabdomiosarcoma embrionale
3) Altri (Sarcoma di cellule di Kpffer,
Mesenchimoma maligno, Leiomiosarcoma,
Fibrosarcoma)
TUMORI SECONDARI
DEL FEGATO
IDONEITA DEL PARENCHIMA EPATICO
ALLIMPIANTO DI NEOPLASIE
1. DIMENSIONI
2. DOPPIA PERFUSIONE EMATICA
3. DISPONIBILITA DI SOSTANZE
NUTRITIZIE
METASTASI EPATICHE
Frequenza globale
Casistica autoptica
Carcinoma pancreatico
Carcinoma del colon
Carcinoma mammario
Carcinoma gastrico
Carcinoma polmonare
38%
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 macroscopico
Nodi pochi e voluminosi
Nodi medi, ombelicati
Nodi grandi con satelliti
Noduli miliariformi
Noduli nerastri
Noduli emorragici
Ca. grosso intestino
Ca. mammella, polmone
Ca. colecisti
Ca. mammella, stomaco,
prostata
Melanoma
Coriocarcinoma,
Carcinoide
Nodi molli Ca. squamosi
METASTASI EPATICHE:
Aspetto microscopico
Adenoca. PAS positivi
Ca. solidi
Ca. transizionali
Ca. cellule chiare
Tumori con melanina
Sarcomi con osso
App. gastroenterico
Mammella, Polmone
Vescica, Pelvi renale
Rene
Melanoma
Tumori ossei
Ca. squamosi Polmone, Collo utero
METASTASI EPATICHE:
Immunoistochimica
Tumori epiteliali
Linfomi
EMA, Citocheratine
LCA, CD3, CD20
Sarcomi Desmina, Vimentina
METASTASI EPATICHE:
Immunoistochimica
Ca. apparato digerente
Tumori muscolari
Coriocarcinoma
Melanoma
Teratomi, Epatomi
Ca. prostata
CEA
Actina, Miosina
HCG
S100, HMB45
-feto-proteina
PSA, PAP
Tumori vascolari Fatt VIII, CD31, CD34
Ca. tiroide Tireoglobulina