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

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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

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Dig

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Tra

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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