Gastroenterol Res

Gastroenterology Research, ISSN 1918-2805 print, 1918-2813 online, Open Access

Article copyright, the authors; Journal compilation copyright, Gastroenterol Res and Elmer Press Inc

Journal website http://www.gastrores.org

Review

Volume 11, Number 6, December 2018, pages 391-396

Steatohepatitic Variant of Hepatocellular Carcinoma: A Focused Review

Figure 1. Histological features of steatohepatitic hepatocellular carcinoma (SH-HCC). (a) Core biopsy of hepatic parenchyma with extensive steatosis (H&E, × 40); (b) trichrome stain highlights thick bands of fibrosis with bridging (× 40); (c) absence of bile ducts/portal tracts as demonstrated by immunostain for cytokeratin 7 (× 40); (d) capillarization of tumor sinusoids highlighted by immunostain for CD34 (× 40).

Figure 2. Histological features of steatohepatitic hepatocellular carcinoma (SH-HCC). (a) High magnification (H&E, × 400) reveals steatosis, ballooning and Mallory-Denk bodies within tumor cells; (b) isolated arterioles (arrows) without associated portal tracts (H&E, × 200).

Figure 3. Potential tumorigenic pathways in the development of steatohepatitic hepatocellular carcinoma.

**Table 1.** Comparison of SH-HCC, Steatohepatitis, Conventional HCC and Steatohepatitic FNH on Resection
	SH-HCC	Steatohepatitis	Conventional HCC	Steatohepatitic FNH
SH-HCC: steatohepatitic hepatocellular carcinoma; HCC: hepatocellular carcinoma; FNH: focal nodular hyperplasia. *It usually shows a map-like staining pattern.
Clinical setting	Mass, ill-defined lesion or abnormal imaging finding	Random biopsy from patients with or without metabolic risk factors, with or without liver function abnormalities	Mass or ill-defined lesion	Mass, ill-defined lesion or abnormal imaging finding, with or without a central scar
Macroscopic findings	Mass, ill-defined lesion or vague abnormalities with gold-yellow appearance	Non-specific	Mass or ill-defined lesion with cut surface different from adjacent liver	Mass or ill-defined lesion with or without a central scar
Histology
Relationship to adjacent liver parenchyma	Variable (well demarcated to focally invasive into adjacent portal tracts)	Non-invasive	Variable (well demarcated or invasive into adjacent portal tracts)	Non-invasive
Central scar	Variable	Absent	Absent	Present in large lesions but variable in small lesions
Portal tracts	Absent	Present	Absent	Absent
Ductular reaction	Absent	Variable but present in most cases	Absent	Present in fibrous septa
Thick-walled vessels within fibrous bands	Absent	Absent	Absent	Present
Fibrous bands	Variable	Variable	Variable	Present
Isolated arteries immediately in contact with hepatocytes	Present	May be present (small)	Present	Absent
Small cell change	Variable	Absent	Present in many cases	Absent
Increased nuclear/cytoplasmic ratio	Variable	Absent	Present	Absent
Pleomorphism	Variable (minimal to marked)	Minimal to mild	Variable (mild to marked)	Minimal to mild
Acinar/rosette formation	Absent to minimal	Absent	Variable (absent to marked)	Variable (small rosettes, focal)
Mitotic figures	Variable (can be rare)	Absence	Variable (usually identifiable)	Absence
Capillarization of endothelium	Variable	Absence	Presence	Absence
Steatosis	Presence	Presence	Absence	Presence
Hepatocyte ballooning	Presence	Presence	Absence	Presence
Mallory-Denk Bodies	Presence	Presence	Absence	Presence
Inflammation	Presence (mild to severe)	Presence (mild to severe)	Variable	Variable
Thick plates > 3 hepatocytes	Variable presence	Absence	Variable presence	Variable presence (limited in extent, focal)
Reticulin fiber	May be lost	May be slightly attenuated	Lost in most cases	May be slightly attenuated
Immunostain
Diffuse sinusoidal CD34 staining	Presence in most cases	Absence	Presence	Absence
Glypican-3	Variable presence (cytoplasmic and canalicular)	Absence	Presence in many cases	Absence
Diffuse glutamine synthetase	Variable presence (cytoplasmic staining with perinuclear accentuation)	Absence	Presence in many case	Absence*
Nuclear β-catenin	Presence in 6% cases	Absence	Presence in some cases	Absence

Table 1. Comparison of SH-HCC, Steatohepatitis, Conventional HCC and Steatohepatitic FNH on Resection

SH-HCC

Steatohepatitis

Conventional HCC

Steatohepatitic FNH

SH-HCC: steatohepatitic hepatocellular carcinoma; HCC: hepatocellular carcinoma; FNH: focal nodular hyperplasia. *It usually shows a map-like staining pattern.

Clinical setting

Mass, ill-defined lesion or abnormal imaging finding

Random biopsy from patients with or without metabolic risk factors, with or without liver function abnormalities

Mass or ill-defined lesion

Mass, ill-defined lesion or abnormal imaging finding, with or without a central scar

Macroscopic findings

Mass, ill-defined lesion or vague abnormalities with gold-yellow appearance

Non-specific

Mass or ill-defined lesion with cut surface different from adjacent liver

Mass or ill-defined lesion with or without a central scar

Histology

Relationship to adjacent liver parenchyma

Variable (well demarcated to focally invasive into adjacent portal tracts)

Non-invasive

Variable (well demarcated or invasive into adjacent portal tracts)

Non-invasive

Central scar

Variable

Absent

Present in large lesions but variable in small lesions

Portal tracts

Absent

Present

Absent

Ductular reaction

Absent

Variable but present in most cases

Absent

Present in fibrous septa

Thick-walled vessels within fibrous bands

Absent

Present

Fibrous bands

Variable

Present

Isolated arteries immediately in contact with hepatocytes

Present

May be present (small)

Present

Absent

Small cell change

Variable

Absent

Present in many cases

Absent

Increased nuclear/cytoplasmic ratio

Variable

Absent

Present

Absent

Pleomorphism

Variable (minimal to marked)

Minimal to mild

Variable (mild to marked)

Minimal to mild

Acinar/rosette formation

Absent to minimal

Absent

Variable (absent to marked)

Variable (small rosettes, focal)

Mitotic figures

Variable (can be rare)

Absence

Variable (usually identifiable)

Absence

Capillarization of endothelium

Variable

Absence

Presence

Absence

Steatosis

Presence

Absence

Presence

Hepatocyte ballooning

Presence

Absence

Presence

Mallory-Denk Bodies

Presence

Absence

Presence

Inflammation

Presence (mild to severe)

Variable

Thick plates > 3 hepatocytes

Variable presence

Absence

Variable presence

Variable presence (limited in extent, focal)

Reticulin fiber

May be lost

May be slightly attenuated

Lost in most cases

May be slightly attenuated

Immunostain

Diffuse sinusoidal CD34 staining

Presence in most cases

Absence

Presence

Absence

Glypican-3

Variable presence (cytoplasmic and canalicular)

Absence

Presence in many cases

Absence

Diffuse glutamine synthetase

Variable presence (cytoplasmic staining with perinuclear accentuation)

Absence

Presence in many case

Absence*

Nuclear β-catenin

Presence in 6% cases

Absence

Presence in some cases

Absence