Patología Hepática. Enfermedades no neoplásicas MalformacionesMalformaciones Inflamatorias:...

Patología Hepática

Enfermedades no neoplásicasEnfermedades no neoplásicas

• MalformacionesMalformaciones• Inflamatorias: hepatitisInflamatorias: hepatitis• Alteraciones de la vía biliar intrahepática Alteraciones de la vía biliar intrahepática • Hepatopatías por fármacos y tóxicosHepatopatías por fármacos y tóxicos• Cirrosis (vía final común)Cirrosis (vía final común)• Errores innatos del metabolismoErrores innatos del metabolismo• Trastornos circulatoriosTrastornos circulatorios• Alteraciones vinculadas al transplanteAlteraciones vinculadas al transplante

Hepatitis aguda• El grado de afectación varía de caso a caso• Todos presentan:

• Desorganización de los acinos• Infiltrado inflamatorio portal• Balonamiento de los hepatocitos• Cuerpos apoptóticos dispersos• Necrosis periportal• Hiperplasia de células de Kupffer

Hepatitis crónica

• Causas– Virus hepatotropos

– Otros agentes infecciosos

– Autoinmune

– Fármacos

– Metabólicas

Hepatitis crónica

• ELEMENTOS DE ACTIVIDAD NECROINFLAMATORIA

• Exudado linfocitario portal• Hepatitis de interfase• Inflamación y Necrosis en puente• Inflamación y necrosis lobulillar

Cambios arquitecturales (fibrosis) evolutivos 0 Ausencia de fibrosis 1 Expansión fibrosa de algunos tractos portales (con o sin

septos fibrosos) 2 Expansión fibrosa de la mayoría de los tractos portales

(con o sin septos fibrosos) 3 Expansión fibrosa de la mayoría de los tractos portales

con ocasionales puentes fibrosos porto portales 4 Expansión fibrosa de la mayoría de los tractos portales

con abundantes puentes fibrosos porto portales y ocasionales puentes porto centrales

5 Abundantes puentes (P-P y/o P-C) con ocasionales nódulos (cirrosis incompleta)

6 Cirrosis, probable o definitiva

Disease

Característica Hepatitis B Hepatitis C Hepatitis AI Esteatohepatitis

Cambios portales

Difusos En parches

++

-++

++-

-+

Tipo de infiltrado portal

LinfocitosPlasmocitosEosinófilos

+++-

++--

+++++

+++-

Actividad necroinflamatoria

Hepatitis de interfase

+ + ++ -

Necrosis lobulillar - - + +

Infiltrado lobulillar

GradoTipoLocalización

-

+LinfocitosSinusoidal

+PlasmocitosCon necrosis

+Linfoplasmocit.

En parches

Ductos biliares Daño ductalPérdida ductalProliferación

+--

+--

+--

--+

Hialina de Mallory

- - - +

Cobre - - - -

Granulomas - - - -

Vidrio esmerilado + - - -

Tipos de virus y cambios histológicos

---+-Fibrosis

-+ ----Degeneración de los ductos biliares

+ -+ -+ -+ -+ -Proliferación ductular

NLLPLPLPPLENTipos de células inflamatorias

+++++Inflamación portal

+---+ - Hipertrofia de c.de Kupffer y acumulación de bilis

-++++Hipertrofia de c.de Kupffer y/o hierro y/o lipofucsina

+---+ -Colestasis

+ --+++ - Esteatosis

?++++Necrosis masiva

---+-Balonamiento panacinar

----+Balonamiento en zona 1

-+ -++ --Balonamiento en zona 3

+++-+Necrosis focal

EDCBA

Hepatitis fulminante

• Produce insuficiencia hepatocítica con encefalopatía en 2 a 3 semanas

• Puede producirse como coinfección, siendo uno de los virus el B

• Puede producirse por fármacos (paracetamol, alfa metil dopa, isoniazida, antidepresivos) o tóxicos

Hepatitis fulminante

• Puede afectar áreas o todo el hígado• Macroscópicamente el hígado se ve

gelatinoso • Microscopicamente: gran necrosis con

destrucción de la trama• Escaso exudado inflamatorio• Si el paciente sobrevive, se ve regeneración

de los hepatocitos

Sistemas actuales de clasificación de las hepatitis crónicas

• Los sistemas posteriores incorporaron la visión respecto de la inflamación y la necrosis como parámetro de la actividad evolutiva de la enfermedad, siendo el parámetro potencialmente respondedor a la terapia. Esto fue referido como “GRADO”

• Las lesiones de fibrosis y remodelación parenquimatosa o vascular indicó la progresión de la enfermedad a largo plazo (pronóstico) y fue referido como el “ESTADIO”

• El grado puede fluctuar con la actividad necroinflamatoria o la intervención terapéutica. En cambio el estadio se considera relativamente constante.

Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol 1991;13:372-374.

Patología Hepática

Colestasis

Características histológicas de los cuadros de colestasis

• Colestasis activa– Hepatocelular primaria y/o secundaria

• Colestasis crónica– Enfermedades colestásicas crónicas

• Colestasis ductal– Obstrucción de grandes ductos y variantes

• Colestasis ductular– Sepsis

COLESTASIS ACTIVA

COLESTASIS CRÓNICA

COLESTASIS DUCTAL

COLESTASIS DUCTULAR

Característica histológica

Trombos biliares canaliculares

Cambios en los hepatocitos Periportales

Pigmento en ductos biliares interlobulares

Pigmento en ductulos biliares proliferados

Se ve pigmento

biliar?

SI Ocasional SI SI

Localización de los

cambios

Centrolobular Periportal/Periseptal

Portal Portal

Característica auxiliar

Daño hepatocelular; inflamación lobular

Acumulación de cobre;

Cuerpos de Mallory

Colestasis Canalicular;

Cambios portales obstructivos

Colestasis Canalicular;

Neutrófilos portales

Cuadro clínico Condiciones colestáticas activas

Condiciones colestáticas crónicas

Obstrucción biliar

Sepsis

Colestasis activa

• Trombos biliares hepatocanaliculares

• Bilirrubinostasis

• Daño hepatocelular asociado

• Inflamación lobular

• Condiciones asociadas– Drogas, hepatitis viral, etc

Colestasis Crónica

• Cambios en ductos biliares portales– Proliferación ductular atípica

• Cambios periportales / periseptales:– Degeneración plumosa– Acumulación de cobre– Cuerpos de Mallory

• Condiciones asociadas– Cirrosis biliar primaria– Colangitis esclerosante primaria

Enfermedades colestásicas

• Cirrosis biliar primaria – Granulomas periductales– Daño epitelial ductal– Evolución a la cirrosis

• Colangitis esclerosante primaria– Colangitis fibroobliterativa– Evolución a la cirrosis

Disease

Característica CBP CEP Wilson Medicamentos

Cambios portales

Difusos En parches

-++

++-

++-

++

Tipo de infiltrado portal

LinfocitosPlasmocitosEosinófilos

+++++

++++

++--

++++

Actividad necroinflamatoria

Hepatitis de interfase

+ - - +

Necrosis lobulillar - - - +

Infiltrado lobulillar

GradoTipoLocalización

+LinfocitosSinusoidal

-

-

+

Ductos biliares Daño ductalPérdida ductalProliferación

++++++

++

++

---

+++

Hialina de Mallory

+Tardía

+Tardía

+Tardía

+

Cobre + + + -

Granulomas + - - +

Vidrio esmerilado - - - +

Table 22. Staging of primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC)

Stage Scheuer system for PBC (56) Ludwig (Mayo) system for PBC/PSC (54)

1 Florid duct lesion: portal inflammation with damage to septal or interlobular bile ducts

Portal stage: inflammation without expansion of portal tracts or piecemeal necrosis

2 Ductular proliferation: expansion of portal tracts with piecemeal necrosis and ductular proliferation

Periportal stage: piecemeal necrosis or fibrosis without bridging

3 Scarring: decreased inflammation with fibrous septum formation

Septal stage: bridging necrosis or fibrosis

4 Cirrosis Cirrhosis

Colestasis Ductal

• Cambios en ductos biliares interlobulares

• Cambios portales:– Edema– Trombos biliares ductales– Proliferación ductular típica

• Condiciones asociadas– Obstrucción de grandes ductos

Evolución

• El estadio final de:– Obstrucción biliar crónica– Enfermedades colestásicas crónicas

• Cirrosis biliar primaria

• Colangitis esclerosante primaria

Es la cirrosis de tipo biliar

Colestasis Ductular

• Cambios en ductos biliares proliferados• Cambios portales:

– Edema– Colangitis y / o pericolangitis– Proliferación ductular con pigmento biliar

intraluminal

• Condiciones asociadas– Sepsis

CLASIFICACIÓN DE ENFERMEDADES COLESTÁSICAS

GRANDES DUCTOS

PEQUEÑOS DUCTOS

HEPATOCELULAR

AGUDA

Obstrucción biliar aguda

Colangitis aguda

Injuria por drogas

Colestasis pura

Injuria por drogas

Colestasis compuesta

CRÓNICA

Obstrucción biliar crónica

Colangitis esclerosante Primaria

Cirrosis biliar Primaria

Colangitis esclerosante Primaria

Injuria por drogas

Colestasis familiar progresiva

Hepatopatía crónica con esteatosis

• 3 cuadros:

• Esteatosis

• Esteatohepatitis (alcoholica o No alcoholica)

• Cirrosis

• Los dos primeros son reversibles

Esteatosis: micro y macrovacuolar

Se inicia en el centro del lobulillo, puede llegar hasta el EP

Hepatomegalia amarilla y frágil

Esteatohepatitis: tumefacción y necrosis hepatocítica

cuerpos de Mallory

infiltración por PMN en el lobulillo

infiltración por linfocitos y macrófagos portales

fibrosis perisinusoidal y perivenular

Cirrosis

Esteatohepatitis no alcoholica

Evolución de la graduación y estadio

Table 1. Necroinflammatory Grading System for Steatohepatitis Mild, grade 1Steatosis (predominantly macrovesicular) involving up to 66% of biopsy; may see occasional ballooned zone 3 hepatocytes; scattered rate intra-acinar pmn's ± intra-acinar lymphocytes; no or mild portal chronic inflammation. Moderate, grade 2Steatosis of any degree; ballooning of hepatocytes (predominantly zone 3) obvious; intra-acinar pmn's noted, may be associated with zone 3 pericellular fibrosis; portal and intra-acinar chronic inflammation noted, mild to moderate.Severe, grade 3Panacinar steatosis; ballooning and disarray obvious, predominantly in zone 3; intra-acinar inflammation noted as scattered pmn's, pms's associated with ballooned hepatocytes ± mild chronic inflammation; portal chronic inflammation mild or moderate, not marked. Grade (n) Steatosis* Ballooning Inflammation1—Mild 22 1-2 Minimal 1-2 acinar; 0-1 portal2—Moderate 23 2-3 Present-zone 3 2 acinar; 1-2 portal3—Severe 6 3 Marked-zone 3 3 acinar; 1-2 portal

Staging

Stage 1.: Zone 3 perisinusoidal/pericellular fibrosis; focally or extensively present.Stage 2.: Zone 3 perisinusoidal/pericellular fibrosis with focal or extensive periportal fibrosis.Stage 3.: Zone 3 perisinusoidal/pericellular fibrosis and portal fibrosis with focal or extensive bridging fibrosis.Stage 4.: Cirrhosis.

NAS scores of 0-2 are not diagnostic of NASH, scores of 3-4 not diagnostic, borderline, or positive for NASH. Scores of 5-8 are diagnostic of NASH

Item Score Extent Definition and Comment

Steatosis 0 <5% Refers to amount of surface area involved 1 5-33% by steatosis as evaluated on low to medium

2 >33-66% power examination; minimal steatosis 3 >66% (<5%) receives a score of 0 to avoid giving

excess weight to biopsies with very little fatty change

Lobular Inflammation0 No foci Acidophil bodies are not included in this 1 2 foci/200x assessment, nor is portal inflammation2 2-4 foci/200x 3 >4 foci/200x Hepatocyte Ballooning0 None The term "few" means rare but definite 1 Few balloon cells ballooned hepatocytes as well as cases that 2 Many cells/prominent ballooning are diagnostically borderline

Most cases with prominent ballooning also had Mallory's hyalin, but Mallory's hyaline is not scored separately for the NAS

Fibrosis Stage (Evaluated separately from NAS)Fibrosis

0 None 1 Perisinusoidal or periportal 1A Mild, zone 3, perisinusoidal "delicate" fibrosis

1B Moderate, zone 3, perisinusoidal "dense" fibrosis

1C Portal/periportal This category is included to accommodate cases with portal

and/or peri portal fibrosis without accompanying pericellular/perisinusoidal

fibrosis

2 Perisinusoidal and portal/periportal 3 Bridging fibrosis 4 Cirrhosis

• Total NAS score represents the sum of scores for steatosis, lobular inflammation, and ballooning, and ranges from 0-8.

• Diagnosis of NASH (or, alternatively, fatty liver not diagnostic of NASH) should be made first, then NAS is used to grade activity.

• In the reference study, NAS scores of 0-2 occurred in cases largely considered not diagnostic of NASH,

• scores of 3-4 were evenly divided among those considered not diagnostic, borderline, or positive for NASH.

• Scores of 5-8 occurred in cases that were largely considered diagnostic of NASH

Table 1. Classification of primary hepatic neoplasms and nonneoplastic masses

BenignBenign MalignantMalignant

Epithelial Epithelial

Hepatocellular Hepatocellular

Hepatocellular adenoma Hepatocellular carcinoma (HCC)a

Focal nodular hyperplasia HCC, fibrolamellar variant

Nodular regenerative hyperplasia Combined HCC-cholangiocacarcinoma

Macroregenerative nodule Hepatoblastoma, epithelial type

Borderline (dysplastic) nodule

Compensatory lobar hyperplasia

Accessory lobe




Cholangiocellular Cholangiocellular

Bile duct hamartoma (von Meyenburg complex)

Cholangiocarcinoma (CC)a

Bile duct adenoma Intraductal variant (“biliary papillomatosis”)

Biliary cysts (nonneoplastic) Cholangiocellular carcinoma

Solitary Adenosquamous carcinoma

Polycystic disease (noncommunicating) Mucoepidermoid carcinoma

Caroli’s disease Squamous cell carcinoma

Multiple hilar cysts Combined CC-neuroendocrine tumor

Biliary cystadenoma Biliary cystadenocarcinoma

Mucinous (+/-mesenchymal stroma)

Serous



Mesenchymal Mesenchymal

Vascular Vascular

Hemangioma Angiosarcoma

Infantile hemangioendothelioma Epithelioid hemangioendothelioma

Hemangiomatosis Kaposi’s sarcoma

Lymphangioma (-tosis)

Hereditary hemorrhagic telangiectasia

Peliosis hepatis




Fatty tumors Fatty tumors

Angiomyolipoma (and related tumors) Liposarcoma

Pseudolipoma

Focal (hepatocellular) fatty change




Other Other

Solitary (localized) fibrous tumor Undifferentiated (embryonal) sarcoma

Inflammatory myofibroblastic tumor pseudotumor)

Rhabdomyosarcoma

Leiomyoma Fibrosarcoma, malignant fibrous histiocytoma

Leiomyosarcoma

Osteosarcoma

Mixed epithelial and mesenchymal Mixed epithelial and mesenchymal

Mesenchymal hamartoma Mixed hepatoblastoma

Sarcomatoid carcinoma (carcinosarcoma)

Table 2. The relative prevalence rates of primary hepatic tumors in the general and pediatric populations in the United States

General population Pediatric population

(%) (%)

Malignant (total) (94) (55–68)

Hepatocellular carcinoma 82 19–20

Hepatoblastoma 1 26–36

Cholangiocarcinoma 10 —

Angiosarcoma <1 < 2

Undifferentiated sarcoma <1 7–9

Other malignant tumors <1 < 1

Table 2. The relative prevalence rates of primary hepatic tumors in the general and pediatric populations in the United States

General population Pediatric population

(%) (%)

Benign (total) (6) (32–45)

Infantile hemangioendotelioma

— 18

Hepatocellular adenoma 1 2–4

Focal nodular hyperplasia 3 3–10

Nodular regenerative hyperplasia

— 0–5

Mesenchymal hamartoma — 8

Other benign tumors 2 —

Table 3. Cystic masses of the liver

Classification Diagnostic findings

Abcesses

Amebic Cavities filled with oderless necrotic hepatic tissue(“anchovy sauce”);

neutrophils rare or absent; trophozoites at periphery, don’t mistake

for histiocytes; reactive hepatocytes may be present; PAS and iron

hematoxylin stains may be helpful

Pyogenic Cavities filled with foul-smelling necrotic hepatic tissue containing many

neutrophils; often polymicrobial; E. coli most common; anaerobes

frequently isolated

Parasitic (echinococcal) cysts Echinococcus granulosus-unilocular cysts (three layers) often with

daughter cysts; brood capsules; protoscolices with attached or

detached acid-fast, birefringent hooklets

Nonparasitic (nonneoplastic) cysts Typically, cuboidal flattened, biliary type epithelial lining; rarely

Solitary (unilocular) squamous; thin fibrous wall; found in<1% of routinely performed autopsies

Polycystic liver disease

Adult polycystic disease; (ADPKD; Typically multiple cysts with autosomal dominant inheritance; prevalence

non communicating ductal cysts) of 0.15% at autopsy; associated with adult polycystic kidney disease

in 71% to 93% of cases; rarely, liver is massively enlarged; histologically

similar to solitary type

Communicating ductal cysts Typically autosomal recessive inheritance

Caroli's disease Ectatic intrahepatic bile ducts, inspisatted bile ± hepatolithiasis, cholangitis

Caroli's syndrome Caroli's disease plus congenital hepatic fibrosis

Congenital hepatic fibrosis/ARPKD Angulated bile ducts often with inspissated bile in fibrotic portal tracts with

portal-portal bridging fibrosis; only rarely macroscopic hepatic cysts

Multiple hilar cysts Noncommunicating cysts arising from dilatation of peribiliary glands

typically in hilum; often associated with cirrhosis, portal vein

thrombosis. Common in patients with ADPKD

Mesenchymal hamartoma Solid and cystic mass, 75% 1 yr of age; admixture of nonneoplastic tissue types

(myxoid stroma, hepatocytes, bile ducts, blood vessels); association with translocation involving

chromosome 19q; rare association with undifferentiated sarcoma

Alimentary tract-related cysts Intrahepatic ileal and duodenal duplications and ciliated

foregut cyst described

Pseudocysts (trauma, ischemia, pancreatic origin) Fibrous lining; may contain blood (hematoma), bile (biloma)

Neoplastic cysts

Biliary cystadenoma/cystadenocarcinoma

Mucinous type Most common type of multilocular cyst, but only 5% of all solitary cysts; 95% occur in women; lined columnar-cuboidal mucin containing epithelium; spindle-cell stroma (85%) only in women; search carefully for dysplasia (borderline lesion),

cystadenocarcinoma; rule out metastasis from other primary site(pancreas, ovary, appendix)

Serous (microcystic, glycogen rich) type Very rare; multilocular; bland, flattened to cuboidal cell lining; clear,

glycogen-rich, mucin-negative cytoplasm; no spindle-cell stroma;

rule out metastasis from pancreas

Teratoma Derivatives from three germ layers; problem of “teratoid hepatoblastoma”

Other Cystic degeneration of various neoplasms

ADPKD, autosomal dominant polycystic kidney disease; ARPKD, autosomal recessive polycystic kidney disease; PAS, periodic acid-Schiff.




Hepatocellular Hepatocellular

Hepatocellular adenoma Hepatocellular carcinoma (HCC)a

Focal nodular hyperplasia HCC, fibrolamellar variant

Nodular regenerative hyperplasia Combined HCC-cholangiocacarcinoma

Macroregenerative nodule Hepatoblastoma, epithelial type

Borderline (dysplastic) nodule

Compensatory lobar hyperplasia

Accessory lobe

Features HCA

Clinical

Peak age(decade) 3rd–4th

M/F 1:15

Usual presentation Acute abdominal pain

Associated conditions OCS use (85–90%),

androgens,

metabolic disorders

Serum AFP Normal Range

Macroscopic

Number of nodules 70–80% single

Nodule diameter 75% 10cm

Cut surface often Tan-white, often hemorrhagic

Fibrous septa/scar Rare

Microscopic

Portal tracts Absent

Hepatocyte plate thickness 1–2 cells (sheet like)

Nuclear atypia, macronucleoli Rare

Mitoses Absent or rare

Septa (arteries, bile ductules Absent

inflammation; few portal

veins bile ducts)

Nontriadal (intranodular) arteries Common

Hepatocytes inside and outside Absent

nodule very in size, plate

arrangement

Table 5. Nodular regenerative hyperplasia: associated conditions

Immunologic disorders Connective tissue diseases Glomerulonephritis

Systemic lupus erythematosis

Progressive systemic sclerosis

Raynaud’s phenomenon

Rheumatoid arthritis ± Felty’s syndrome

Common variable immunodeficiency

Hepatic venous outflow obstruction

Cryoglobulinemia Myasthenia gravis Hyper-/hypothyroidism

Idiopathic thrombocytopenic purpura

Primary and secondary hepatic carcinomas

Extrahepatic portal vein thrombosis

Neoplastic disorders Myeloproliferative disorders Lymphoproliferative disorders

Drugs and toxins Chemotherapeutic agents Azathioprine

Toxic oil syndrome Arsenic Vinyl chloride

Obliterative portal venopathy

Corticosteroids Anabolic steroids

Vascular disorders Contraceptive steroids Arteritis

Table 7. Histologic features useful in differential diagnosis of benign, borderline (dysplastic), and malignant hepatocellular nodules typically arising in the cirrhotic livera

Borderline nodule

Histologic feature MRN LGD HGD WD-HCC MD-HCC

Primary diagnostic utility

Mitoses, at least moderate (>5/10 HPF) – – – – +

Hepatocellular plates >3 cells thick – – – – +

Reticulin uniformly < normal – – – – +

Positive endothelial markers (endothelium) – – ? +/– +

Uniformly prominent nucleoli – – – – +

Nuclear density >2 normal – – – + +

Irregular nuclear contour, ³ moderate – – – + +

Nuclear hyperchromasia – – + + +

Intranodular (nontriadal) arteries – + + + +

Subpopulations (“clonelike”) – + + + +

Table 8. Factors implicated in the pathogenesis of hepatocellular carcinoma (HCC)

Chronic hepatic injury (60–90%) Hereditary hemochromatosis

Cirrhosis (most common) Hereditary tyrosinemia

High rate of associated HCC (>15%)Chronic hepatitis only (far less common)

Membranous obstruction of the inferior vena cava

Porphyria cutanea tarda Hypercitrullinemia

Intermediate rate associated HCC (~5–15%) Alcohol

Alpha1-antitrypsin deficiency Glycogen storage disease (types 1 and 3)

Autoimmune hepatitis

Low rate presence of associated HCC (<5%) Primary biliary cirrhosis

Primary sclerosing cholangitis Hereditary fructose intolerance

Paucity of intrahepatic bile ducts Progressive intrahepatic cholestasis

Congenital hepatic fibrosis Biliary atresia

Wilson’s disease Oral contraceptive steroids

Anabolic-androgenic steroids Exposure to various chemicals/toxins

Table 9. pTMN staging of primary hepatic epithelial malignanciesa

T—Primary tumor

T1—Solitary mass, 2cm, without vascular invasion

T2—Solitary mass, 2cm, with vascular invasion, or multiple

masses, one lobe, all 2cm, without vascular invasion, or

solitary mass, >2 cm, without vascular invasion

T3—Solitary mass, >2 cm with vascular invasion, or multiple

masses, one lobe, 2 cm, with vascular invasion, or multiple

masses, one lobe, >2 cm, with or without vascular invasion

T4—Multiple masses in more than one lobe, or invasion of

major branch of portal or hepatic vein, or invasion of adjacent

organs other than gallbladder

N—Regional lymph nodes

N0—Negative regional lymph nodes

N1—Positive regional lymph nodes

M—Distant metastases

MX—Cannot be assessed

M0—No distant metastases

M1—Distant metastases present

Stage groupings

Stage I—T1N0M0

Stage II—T2N0M0

Stage IIIA—T3N0M0

Stage IIIB—T1N1M0, T2N1M0, T3N1M0

Stage IVA—T4 any N M0

Stage IVB—any T any N M1

Modified from ref. 176. Vascular invasion includes either macroscopic or microscopic involvement of vessels.

Table 10. Histologic grading of hepatocellular carcinomaa

Well differentiated (Grades I/II of Edmondson and Steiner)

Thin plates, three or fewer hepatocytes thick, that are typically smaller than

normal, demonstrate minimal nuclear atypia, and have a nuclear density greater

than twice that of the nonneoplastic liver. Fatty change and pseudoglandular

architecture are common. Clear-cut histologic distinction from hepatocellular more

poorly adenoma may not be possible in some cases without finding other,

differentiated foci and knowing the status of the nonneoplastic liver. This pattern is

typical of small (<2 cm) HCC.

Moderately differentiated (Grades II/III of Edmondson and Steiner)

Typically characterized by a trabecular pattern in which tumor cells are arranged

in plates more than three cells thick. Tumor cells are larger and have more

abundant eosinophilic cytoplasm and distinct nucleoli, compared with

well-differentiated tumors. Pseudoglandular structures and bile are usually seen,

and tumor giant cells may be present This is the most common type of

differentiation seen in advanced (>2 cm) HCC.

Poorly differentiated (Grades III/IV of Edmondson and Steiner)

Tumor cells have larger and more hyperchromatic nuclei and are typically

arranged in a compact (solid) growth pattern with rare or no trabeculae or bile.

Pleomorphism may be prominent and spindle-cell or small-cell areas may be seen.

May be difficult to recognize as hepatocellular in origin.

aModified from refs. 2, 4, 120, 172. More than one pattern is frequently seen in tumors larger than 1.5 cm diameter.

Table 15. Fibrolamellar hepatocellular carcinoma (FL-HCC): distinguishing clinicopathologic features from the usual HCC

FL-HCC Usual HCC

Clinical features

% HCC 1–5% 95–99%

Epidemiologic factors

Age Peak, 3rd 6th–7th

decade decade

Sex (male/female) 1:1 3–6:1

Serum markers

(% elevated)

AFP 10–15% 60–80%

DCP 100% 60–90%

NT, B12 UB12BC Often increased Rarely increased

Imaging studies

Calcification 40–80% 5% (no RX)

Central scar 50–70% Rare

Resectability 48–75% 10–20%

Macroscopic features

% Solitary 75%; left > Uncommon

right lobe

Fibrous septa, scar 10–63% Absent

Necrosis, hemorrhage Occasional Common

(larger

tumors)

Associated cirrhosis <10% 60–90%

Microscopic features

Cell size, shape Larger Smaller

Cytoplasm

Abundance More Less

Granularity More Less

Pale bodies 50% 10%

Hyaline globules 50% 10–15%

Stroma Prominent lamellar bands Scant

EM (mitochondria) Numerous Less common

Survival (5 yr)

Overall 25–30% 0–7%

Resected 56–75% 20–30%

AFP, alpha-fetoprotein; DCP, des-Y-carboxy prothrombin; NT, neurotensin; UB12BC, unsaturated B12 binding capacity; RX, treatment.

Table 18. Staging of hepatoblastoma according to the children’s cancer study group

Stage I—Complete resection

Stage II—Microscopic residual disease only

Stage III—Gross residual disease or positive lymph nodes or

spilled tumor

Stage IV—Metastases

aModified from ref.236.




Cholangiocellular Cholangiocellular

Bile duct hamartoma (von Meyenburg complex)

Cholangiocarcinoma (CC)a

Bile duct adenoma Intraductal variant (“biliary papillomatosis”)

Biliary cysts (nonneoplastic) Cholangiocellular carcinoma

Solitary Adenosquamous carcinoma

Polycystic disease (noncommunicating) Mucoepidermoid carcinoma

Caroli’s disease Squamous cell carcinoma

Multiple hilar cysts Combined CC-neuroendocrine tumor

Biliary cystadenoma Biliary cystadenocarcinoma

Mucinous (+/-mesenchymal stroma)

Serous

Table 20. Intrahepatic cholangiocarcinoma: predisposing and premalignant conditions

No predisposing conditions (80–90%)

Predisposing conditions (10–20%)

Chronic cholangitis (by far most common)

Clonorchis sinensis (Hong Kong, Canton)

Hepatolithiasis (Far East, including Japan)

Hepatic cysts Ductal plate malformation PSC/CUC (Western countries)

Opisthorchis viverrini (Thailand)

Congenital dilatation of the intrahepatic bile ducts

Congenital hepatic fibrosis

Bile duct hamartomas Caroli’s disease Anabolic steroids

Toxins/drugs Hereditary hemochromatosis Thorotrast

Nonbiliary cirrhosis (<5%) Premalignant conditions: Dysplasia




Vascular Vascular

Hemangioma Angiosarcoma

Infantile hemangioendothelioma Epithelioid hemangioendothelioma

Hemangiomatosis Kaposi’s sarcoma

Lymphangioma (-tosis)

Hereditary hemorrhagic telangiectasia

Peliosis hepatis

Table 22. Hepatic angiosarcoma: associated etiologic agents/conditionsa

Idiopathic (58–75%)

Associated agents/conditions (25–42%)

Thorotrastb

Vinyl chlorideb

Inorganic arsenicb

Androgenic steroidsb

Copper sulfate

Estrogenic steroids

Phenelzine

Radiotherapy

Chemotherapeutic agents

Hereditary hemochromatosis (cirrhotic stage)

aData from references 282, 302, 303. Cases potentially arising from preexisting benign vascular tumors, such as infantile hemangioendothelioma and a unique case of cavemous hemangioma, are excluded.

bBy far the most commonly associated agents.

Table 23. Clinicopathologic features of angiosarcoma and epithelioid hemangioendothelioma

Feature Epithelioid hemangioendothelioma Angiosarcoma

Clinical features

Sex (male/female) 1:1.6 3–4:1

Mean age (range), yrs 47 (3–86) 53 (<1, > 80)

Etiologic factors None well documented 25–42%; Thorotrast, VC, arsenic,

androgens, etc.

Symptoms and signs

Abdominal pain, mass Most common Most common

Intraabdominal bleeding Rare 30%

Asymptomatic 50% Virtually never

Thrombocytopenia No 50%

Radiographic features

Abdominal films, calcification 20% Virtually never; Thorotrast causes

radiodensity

Angiography Typically avascular Typically vascular

Pathologic features

Macroscopic

Multiple nodules 80% 70%

Nodule size (cm) <1–12 cm; rarely cirrhotomimetic <1–5

Nodule appearance White-gray, tan, firm, infiltrative borders Blood cysts, spongy, occasionally white,

firm

Microscopic

Zonation Present Absent

Tumor cellularity Scanty in fibrotic areas Abundant

Spindle and epithelioid cells Present Present

Intracytoplasmic lumina Prominent Inconspicuous

Marked nuclear pleomorphism Absent Present

Sinusoidal/venous invasion Extensive Extensive

Stroma Myxoid/dense sclerosis, Scant, focally fibrotic, no calcification

Extramedullary hematopoiesis Absent Often present

Tumor cell immunohistochemistry

Endothelial markers Positive Positive

Cytokeratin Occasionally positive Occasionally positive

Adjacent liver Usually normal, Fibrosis, cirrhosis common with known

etiologic factors

Outcome Unpredictable, 19% 5 yrs Dismal, 3% alive at 2 yrs

NRH, nodular regenerative hyperplasia; VC, vinyl chloride.

Patología Hepática. Enfermedades no neoplásicas MalformacionesMalformaciones Inflamatorias:...

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