Algorithmic Approach to Liver Masses and Cysts
Neil Theise, MDDepartments of Pathology and Medicine (Digestive Diseases)Mount Sinai Beth Israel Medical CenterNew York City
Icahn School of Medicine atMount SinaiMount Sinai
Algorithmic Approach to Liver Masses and CystsDownload at: NeilTheise on SlideShare.net
Neil Theise, MDDepartments of Pathology and Medicine (Digestive Diseases)Mount Sinai Beth Israel Medical CenterNew York City
Icahn School of Medicine atMount SinaiMount Sinai
Algorithmic Approach led by Romil Saxena Liver Masses and Cysts
Neil Theise, MDDepartments of Pathology and Medicine (Digestive Diseases)Mount Sinai Beth Israel Medical CenterNew York City
Icahn School of Medicine atMount SinaiMount Sinai
SOLID MASS
FibroticBackground
No FibroticBackground
+ + + Benign
Hepatoblastoma, except Fetal
Type
Large Renerative
Nodule
Dysplastic Nodule
HCC
FNH
HCA
HCC
Fibrolamellar HCC
Hepatoblastoma,
Fetal Type
von Meyenburg complex
Bile duct adenoma
Biliary Adenofibroma
HSA, AFP, Arg1
Any of: Bile, HSA, Arg1, CD10, pCEA
Any of: Bile, HSA, Arg1, CD10, pCEA
Hepatocytes with any of:
Bile, Arg1, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
CholangioCa
Metastasis
Combined HCC-
CholangioCa
Malignant
Immature appearing cells
Hepatocytes or other large eosinophilic cells
Ducts/glands/mucin Hepatocytes and ducts/glands/mucin
Metastasis Metastasis
Metastasis
SOLID MASS
FibroticBackground
No FibroticBackground
+ + + Benign
Hepatoblastoma, except Fetal
Type
Large Renerative
Nodule
Dysplastic Nodule
HCC
FNH
HCA
HCC
Fibrolamellar HCC
Hepatoblastoma,
Fetal Type
Bile Duct Adenoma
Peribiliary Gland Hamartoma
Biliary Adenofibroma
HSA, AFP
Arg1
Any of: Bile, HSA, Arg1, CD10, pCEA
Any of: Bile, HSA, Arg1 CD10, pCEA
Hepatocytes with any of:
Bile, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
CholangioCa
Metastasis
Combined HCC-
CholangioCa
Malignant
Immature appearing cells
Hepatocytes or other large eosinophilic cells
Ducts/glands/mucin Hepatocytes and ducts/glands/mucin
Metastasis Metastasis
Metastasis
von Meyenburg complex
Bile duct adenoma
HSA, AFP, Arg1
Any of: Bile, HSA, Arg1, CD10, pCEA
Any of: Bile, HSA, Arg1, CD10, pCEA
Hepatocytes with any of:
Bile, Arg1, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
WH
O T
um
ours
of t
he
Dig
est
ive
Tra
ct,
4W
HO
Tu
mou
rs o
f th
e D
ige
stiv
e T
ract
, 4thth
Ed.
Ed.
SOLID MASS
FibroticBackground
No FibroticBackground
+ + + Benign
Hepatoblastoma, except Fetal
Type
Large Renerative
Nodule
Dysplastic Nodule
HCC
FNH
HCA
HCC
Fibrolamellar HCC
Hepatoblastoma,
Fetal Type
Bile Duct Adenoma
Peribiliary Gland Hamartoma
Biliary Adenofibroma
HSA, AFP
Hepatocytes with any of:
Bile, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
CholangioCa
Metastasis
Combined HCC-
CholangioCa
Malignant
Immature appearing cells
Hepatocytes or other large eosinophilic cells
Ducts/glands/mucin Hepatocytes and ducts/glands/mucin
Metastasis Metastasis
Metastasis
von Meyenburg complex
Bile duct adenoma
HSA, AFP, Arg1
Any of: Bile, HSA, Arg1, CD10, pCEA
Any of: Bile, HSA, Arg1, CD10, pCEA
Hepatocytes with any of:
Bile, Arg1, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
Distinctive nodules which differ from the surrounding parenchyma in terms of:
size,color,texture, or degree of bulging from the cut surface…
Dysplastic Nodules
Distinctive nodules which differ from the surrounding parenchyma in terms of:
size,color,texture, or degree of bulging from the cut surface…
…AND contain portal tracts.
Dysplastic Nodules
Low GradeDysplasticNodules
Low GradeDysplasticNodules
Features of Low Grade DNs:
Normal cytology or
Large cell change only
No architectural atypia
High GradeDysplasticNodules
High GradeDysplasticNodules
Features of High Grade DNs:
Cytologic atypia e.g. small cell change
Clone-like domains e.g. Mallory body clustering, fatty or clear cell change, iron resistance, etc.
Architectural atypia e.g. pseudogland formation
Incidence of DNs in Cirrhotic Livers
Location Source # Cirrhotic Livers
# w/ DNs (%)
Tokushima Autopsy 315 46 (14%)
New York Explant 44 11 (25%)
San Francisco Explant 110 17 (15%)
Kanazawa Autopsy 209 45 (21%)
New York Explant 155 32 (22%)
Bordeaux Explant 41 10 (24%)
Chronic HepatitisHepatitis B and C Autoimmune hepatitis
Metabolic DiseaseGenetic hemochromatosis A-1-AT Deficiency
Chronic Biliary Tract Disease PBC, PSC
Toxic InjuryChronic alcoholic liver injury
Early HCC, vaguely nodular type
Early HCC, distinctly nodular type
Hepatology 2009; 49: 658
LGDN HGDN eHCC
Diffuse hemosiderosis X
Diffuse (or zonal) fatty change X
Angiogenesis (“unpaired arteries”) X
Scirrhous change X
Large cell change X
Features found in dysplastic nodules
LGDN HGDN eHCC
Diffuse hemosiderosis X rare rare
Diffuse (or zonal) fatty change X X X
Angiogenesis (“unpaired arteries”)
X XX XXX
Scirrhous change X X X
Large cell change X X X
Features found in dysplastic nodules
LGDN HGDN eHCC
Diffuse hemosiderosis X rare rare
Diffuse (or zonal) fatty change X
Angiogenesis (“unpaired arteries”) X XX XXX
Scirrhous change X X X
Large cell change X X X
Small cell change X X
Pseudoacinar growth X XX
Iron resistence in otherwise siderotic nodule X X
Mallory body clustering X X
Nodule-in-nodule expansile growth (with steatosis or other changes above)
X X
Features found in dysplastic nodules
LGDN HGDN eHCC
Diffuse hemosiderosis X rare rare
Diffuse (or zonal) fatty change X
Angiogenesis (“unpaired arteries”) X XX XXX
Scirrhous change X X X
Large cell change X X X
Small cell change X X
Pseudoacinar growth X XX
Iron resistence in otherwise siderotic nodule X X
Mallory body clustering X X
Nodule-in-nodule expansile growth (with steatosis or other changes above)
X X
Stromal invasion X
Features found in dysplastic nodules
Falkowski O, et al. J Hepatol 2003
SOLID MASS
FibroticBackground
No FibroticBackground
+ + + Benign
Hepatoblastoma, except Fetal
Type
Large Renerative
Nodule
Dysplastic Nodule
HCC
FNH
HCA
HCC
Fibrolamellar HCC
Hepatoblastoma,
Fetal Type
Bile Duct Adenoma
Peribiliary Gland Hamartoma
Biliary Adenofibroma
HSA, AFP
Hepatocytes with any of:
Bile, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
CholangioCa
Metastasis
Combined HCC-
CholangioCa
Malignant
Immature appearing cells
Hepatocytes or other large eosinophilic cells
Ducts/glands/mucin Hepatocytes and ducts/glands/mucin
Metastasis Metastasis
Metastasis
von Meyenburg complex
Bile duct adenoma
HSA, AFP, Arg1
Any of: Bile, HSA, Arg1, CD10, pCEA
Any of: Bile, HSA, Arg1, CD10, pCEA
Hepatocytes with any of:
Bile, Arg1, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
The Real Problem: A mass in a non-cirrhotic liver.
Focal NodularHyperplasia
Hepatocellular Adenoma
HepatocellularCarcinoma
FNH HCA HCC
Focal NodularHyperplasia
FNH
HepatocellularAdenoma
HCA
HepatocellularCarcinoma
HCC
FNH
FNH
FNH
FNH
FNH WH
O T
um
ours
of t
he
Dig
est
ive
Tra
ct,
4W
HO
Tu
mou
rs o
f th
e D
ige
stiv
e T
ract
, 4thth
Ed.
Ed.
Keratin 7 or 19:
FNH
FNH
FNH
FNH
FNH
FNH
HCA
HCA
HCA
HCA
HCA
HCAFNH
HCAFNH
NON-IMMUNO (20TH C) APPROACH
HCAFNH
NON-IMMUNO (20TH C) APPROACH
HCAFNH
DIAGNOSIS
HCAFNH
DIAGNOSIS
Dx: Benign hepatocellular lesion, favor FNHDx: Benign hepatocellular lesion, favor FNH
HCAFNH
DIAGNOSIS (or cirrhosis??)(or cirrhosis??)
HCAFNH
DIAGNOSIS (or cirrhosis??)(or cirrhosis??)
Dx: Benign hepatocellular lesion, Dx: Benign hepatocellular lesion, suggestive of FNHsuggestive of FNH
HCAFNH
DIAGNOSIS
HCAFNH
DIAGNOSIS
Dx: Benign hepatocellular lesion, favor Dx: Benign hepatocellular lesion, favor HCAHCA
HCAFNH
DIAGNOSIS
OR?OR?
HCAFNH
DIAGNOSIS
OR?OR?
Dx: Benign hepatocellular lesion, ? FNH vs LCADx: Benign hepatocellular lesion, ? FNH vs LCA
Dx: Benign hepatocellular nodule, ? FNH vs LCADx: Benign hepatocellular nodule, ? FNH vs LCA
What about HCC…?What about HCC…?Check for: thickness of plates, loss of reticulin,Check for: thickness of plates, loss of reticulin,
pleomorphism, diffuse CD34 sinusoidal staining…pleomorphism, diffuse CD34 sinusoidal staining…
Adenoma Variants: search “Bioulac-Sage P”
FromFrom “WHO Tumours of the Digestive Tract”, 4 “WHO Tumours of the Digestive Tract”, 4thth Ed. Ed.
SOLID MASS
FibroticBackground
No FibroticBackground
+ + + Benign
Hepatoblastoma, except Fetal
Type
Large Renerative
Nodule
Dysplastic Nodule
HCC
FNH
HCA
HCC
Fibrolamellar HCC
Hepatoblastoma,
Fetal Type
von Meyenburg complex
Bile duct adenoma
Biliary Adenofibroma
HSA, AFP
Hepatocytes with any of:
Bile, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
CholangioCa
Metastasis
Combined HCC-
CholangioCa
Malignant
Immature appearing cells
Hepatocytes or other large eosinophilic cells
Ducts/glands/mucin Hepatocytes and ducts/glands/mucin
Metastasis Metastasis
Metastasis
HSA, AFP, Arg1
Any of: Bile, HSA, Arg1, CD10, pCEA
Any of: Bile, HSA, Arg1, CD10, pCEA
Hepatocytes with any of:
Bile, Arg1, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
von Meyenburg complex(or bile duct hamartoma)
Bile duct adenoma(or peribiliary gland
hamartoma)
Biliary adenofibroma
SOLID MASS
FibroticBackground
No FibroticBackground
+ + + Benign
Hepatoblastoma, except Fetal
Type
Large Renerative
Nodule
Dysplastic Nodule
HCC
FNH
HCA
HCC
Fibrolamellar HCC
Hepatoblastoma,
Fetal Type
von Meyenburg complex
Bile duct adenoma
Biliary Adenofibroma
HSA, AFP
Hepatocytes with any of:
Bile, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
CholangioCa
Metastasis
Combined HCC-
CholangioCa
Malignant
Immature appearing cells
Hepatocytes or other large eosinophilic cells
Ducts/glands/mucin Hepatocytes and ducts/glands/mucin
Metastasis Metastasis
Metastasis
HSA, AFP, Arg1
Any of: Bile, HSA, Arg1, CD10, pCEA
Any of: Bile, HSA, Arg1, CD10, pCEA
Hepatocytes with any of:
Bile, Arg1, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
SOLID MASS
FibroticBackground
No FibroticBackground
+ + + Benign
Hepatoblastoma, except Fetal
Type
Large Renerative
Nodule
Dysplastic Nodule
HCC
FNH
HCA
HCC
Fibrolamellar HCC
Hepatoblastoma,
Fetal Type
Bile Duct Adenoma
Peribiliary Gland Hamartoma
Biliary Adenofibroma
HSA, AFP
Hepatocytes with any of:
Bile, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
CholangioCa
Metastasis
Combined HCC-
CholangioCa
Malignant
Immature appearing cells
Hepatocytes or other large eosinophilic cells
Ducts/glands/mucin Hepatocytes and ducts/glands/mucin
Metastasis Metastasis
Metastasis
von Meyenburg complex
Bile duct adenoma
HSA, AFP, Arg1
Any of: Bile, HSA, Arg1, CD10, pCEA
Any of: Bile, HSA, Arg1, CD10, pCEA
Hepatocytes with any of:
Bile, Arg1, HSA, CD10, pCEA
AND
Ducts/glands/mucin/K19
Combined hepatocellular/cholangiocarcinomas
1. Combined HCC-ChC2. Combined HCC-ChC with stem cell features
A. typical subtypeB. intermediate cell subtype C. cholangiolocellular subtype
Chapter 10-4, N. D. Theise, O. Nakashima, Y. N. Park, Y. Nakanuma
Solitary bile duct cyst
Fibropolycystic disease
+/- associated
renal disease
Obstructive dilatation of
bile duct
Ciliated foregut
cyst
Epithelial-linedWithout
Epithelial Lining
Cuboidal to low columnar
Ciliated Biliary / mucinous / oncocytic +/- papillary architecture
Neoplastic
Benign
Malignant
Mesench. hamartoma
Undif’d embryonal sarcoma
Cavernous heman-gioma
Cystic degener-
ation in any tumor
Cystic degener-
ation in any tumor
Hydatid cyst
Hydatid cyst
Pyogenic abscess
Amoebic abscess
Hemo-rrhagic
cyst
Necrotizing eosinophilic granuloma
Non-neoplastic
Laminated wall
Inflammation, necrosis
CYST
Ovarian-like stroma w/o Ovarian-like stroma
Cystadenomas and cystadenocarcinomas
Cystadenomas and cystadenocarcinomasSolitary bile duct cyst
Fibropolycystic disease
+/- associated
renal disease
Obstructive dilatation of
bile duct
Ciliated foregut
cyst
Epithelial-linedWithout
Epithelial Lining
Cuboidal to low columnar
Ciliated Biliary / mucinous / oncocytic +/- papillary architecture
Neoplastic
Benign
Malignant
Mesench. hamartoma
Undif’d embryonal sarcoma
Cavernous heman-gioma
Cystic degener-
ation in any tumor
Cystic degener-
ation in any tumor
Hydatid cyst
Hydatid cyst
Pyogenic abscess
Amoebic abscess
Hemo-rrhagic
cyst
Necrotizing eosinophilic granuloma
Non-neoplastic
Laminated wall
Inflammation, necrosis
CYST
Ovarian-like stroma w/o Ovarian-like stroma
Solitary bile duct cyst
Fibropolycystic disease
+/- associated
renal disease
Obstructive dilatation of
bile duct
Ciliated foregut
cyst
Mucinous cystic
neoplasm
Mucinous cystic
neoplasm with
associated invasive
carcinoma
Biliary intraductal papillary
neoplasm
Malignant biliary
intraductal papillary
neoplasm
Intrahepatic cholangio-carcinoma with cystic
change
Epithelial-linedWithout
Epithelial Lining
Cuboidal to low columnar
Ciliated Biliary / mucinous / oncocytic +/- papillary architecture
No epithelial invasion into wall
Neoplastic
Benign
Malignant
Mesench. hamartoma
Undif’d embryonal sarcoma
Cavernous heman-gioma
Cystic degener-
ation in any tumor
Cystic degener-
ation in any tumor
Hydatid cyst
Hydatid cyst
Pyogenic abscess
Amoebic abscess
Hemo-rrhagic
cyst
Necrotizing eosinophilic granuloma
Non-neoplastic
Laminated wall
Inflammation, necrosis
CYST
Ovarian-like stroma w/o Ovarian-like stroma
Epithelial invasion into wall
No epithelial invasion into wall
Epithelial invasion into wall
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