Focal Nodular Hyperplasia

Slide 1 · Focal nodular hyperplasia

A benign, nonneoplastic hepatic mass

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning outcomes

Explain why altered hepatic blood flow is implicated in FNH.

Recognize the gross and microscopic findings that define FNH.

Interpret the diagnostic map-like glutamine synthetase pattern.

Distinguish FNH from hepatocellular adenoma and other hepatic masses.

Slide 3 · The hepatic-mass framework

Hepatic mass lesions

Nonneoplastic

Focal nodular hyperplasia

Regenerative nodules

Abscess / infectious processes

Neoplastic

Benign hepatocellular adenoma

Primary malignancies

Metastatic tumors

Slide 4 · FNH belongs among nonneoplastic lesions

FNH in the nonneoplastic mass-lesion category.

A localized, nodular collection of hepatocytes can form a discrete hepatic mass without being a true neoplasm.

This classification has direct implications for prognosis and the need for intervention.

Slide 5 · Defining the entity

FNH is a benign, nonneoplastic hepatocellular lesion.

It is a well-circumscribed hepatic mass.

Its architecture reflects a localized hyperplastic response.

Absence of cytologic and architectural atypia supports its benign nature.

Slide 6 · Who most commonly develops FNH?

FNH is most common in adult females.

The demographic association is descriptive: It does not by itself establish the diagnosis.

Morphology and characteristic imaging findings remain central to recognizing the lesion.

Slide 7 · FNH often comes to attention incidentally

Most lesions are asymptomatic.

Detection commonly occurs during imaging undertaken for another reason.

Some lesions are recognized during surgery or in resection specimens.

An incidental liver mass requires correct classification before treatment decisions.

Slide 8 · The pathogenesis is hemodynamic

Altered local blood flow

Hyperplastic hepatocyte response

Focal nodular liver mass

This is the proposed mechanism.

The model is an association-based pathogenesis, not proof of one initiating event.

Slide 9 · Why the vascular hypothesis matters

FNH-like nodules can arise in conditions with disturbed hepatic circulation.

Vascular alterations and hyperplasia occur together in its characteristic structure.

This helps interpret the thick-walled arteries and nodular parenchyma as linked findings.

Slide 10 · Vascular settings associated with FNH-like nodules

Altered-flow settings

Hemangiomas

Budd–Chiari syndrome

Vascular malformations

Adjacent tumors

Slide 11 · FNH-like nodules can occur beside other tumors

FNH-like nodules adjacent to other tumors.

The accompanying lesion and altered local circulation are useful diagnostic context.

The term “FNH-like” should not be mistaken for a claim that the neighboring tumor is FNH.

Slide 12 · Budd–Chiari syndrome provides a vascular context

Hepatic venous outflow obstruction

Abnormal hepatic vascular environment

FNH-like or regenerative nodules

Budd–Chiari syndrome to both FNH-like and large regenerative nodules.

This is a clinicopathologic association, not a universal sequence.

Slide 13 · Multifocal FNH has characteristic associations

Multifocal FNH

Hepatic hemangiomas

Extrahepatic hemangiomas

Vascular malformations

Some brain tumors

Slide 14 · Brain tumors mentioned in the multifocal setting

Meningioma and astrocytoma are among the associated brain tumors named.

The source describes an association; It does not establish causality.

Clinical history should be interpreted with the hepatic findings rather than replacing them.

Slide 15 · Single versus multifocal disease

Solitary FNH

Multifocal FNH

One identifiable hepatic mass

Several FNH-type nodules

Characteristic architecture still matters

Consider associated vascular disorders

No neoplastic implication from the label

Multiplicity alone does not establish malignancy

Slide 16 · Gross recognition begins with circumscription

FNH is well circumscribed within surrounding liver.

Its interface is usually visible despite lacking a true capsule.

A well-defined border and absence of a capsule are compatible observations.

Slide 17 · A capsule is typically absent

Central stellate scar

No complete capsule

Schematic cut surface: Not a gross specimen

The lesion typically lacks a capsule.

The liver–lesion boundary is distinct without a continuous fibrous shell.

Do not equate circumscription with encapsulation.

Slide 18 · Most FNH lesions are relatively small

Most lesions measure 5 cm or less in diameter.

This is a descriptive distribution, not a stand-alone diagnostic cutoff.

Robbins reserves resection mainly for large symptomatic lesions.

Slide 19 · The central stellate scar is a key gross finding

Central stellate scar

Nodular parenchyma

Schematic cut surface: Not a gross specimen

A central fibrous scar has a stellate configuration.

It provides a core from which septa radiate.

This configuration is highly characteristic, but not universal.

Slide 20 · The central scar is not present in every case

A central stellate scar is present in up to 80% of FNH cases.

Its presence is a strong diagnostic clue.

Its absence does not by itself exclude FNH.

Architecture and immunohistochemistry provide additional evidence.

Slide 21 · Lobulated architecture at the cut surface

Central stellate scar

Nodular parenchyma

Schematic cut surface: Not a gross specimen

Radiating septa partition the lesion into nodules.

The resection specimen may show a lobulated contour.

The lobular pattern reflects architectural organization, not infiltrative growth.

Slide 22 · Gross morphology: Integrated pattern

Central stellate scar

Nodular parenchyma

Schematic cut surface: Not a gross specimen

Well-circumscribed, usually unencapsulated mass

Often a central stellate fibrous scar

Radiating septa subdividing nodules

Slide 23 · Fibrous septa radiate from the central scar

Hepatocyte nodules

Fibrous septa

Schematic low-power architecture: Not histology

Septa extend from central fibrous tissue into the lesion.

They partition hepatic parenchyma into discrete nodules.

The pattern can be appreciated at low magnification.

Slide 24 · Hepatocyte nodules occupy the intervening spaces

Hepatocyte nodules

Fibrous septa

Schematic low-power architecture: Not histology

The nodules consist of hepatocytes rather than atypical tumor cells.

Fibrous bands, rather than invasive tumor borders, separate the nodules.

Architecture must be interpreted at low and higher magnification.

Slide 25 · Central scar and septa contain abnormal arteries

Thick-walled septal artery

Schematic comparator

Hyperplastic arterial wall

Thick-walled arteries are a characteristic finding.

The changes are particularly prominent in the central scar and septa.

Vascular morphology supports the proposed altered-flow mechanism.

Slide 26 · Characteristic arterial wall abnormalities

Wall abnormality

Key Pathologic Findings

Intimal changes

Intimal hyperplasia

Muscular changes

Fibromuscular hyperplasia

Elastic architecture

Poorly formed elastic lamina

Slide 27 · Vessel wall versus lumen: Schematic anatomy

Thick-walled septal artery

Schematic comparator

Hyperplastic arterial wall

An enlarged muscular wall should not be mistaken for a typical portal tract artery.

The altered arteries occur in scar and septa.

Diagram is conceptual; Not a measurement or specimen image.

Slide 28 · Ductular reaction is often prominent

Small ductular profiles in a fibrous band

Schematic ductular reaction; No mature portal tract shown

Ductular structures are often abundant along fibrous bands.

Their prominence is part of the FNH morphologic pattern.

A ductular reaction does not imply intact normal portal-tract architecture.

Slide 29 · Interlobular bile ducts are absent

Small ductular profiles in a fibrous band

Schematic ductular reaction; No mature portal tract shown

Interlobular bile ducts are absent within the lesion.

Ductular reaction and mature interlobular bile ducts are distinct findings.

This distinction is important when assessing FNH histology.

Slide 30 · Ductular reaction is not a normal portal tract

Ductular reaction

Interlobular bile duct

Proliferating ductular profiles in fibrous tissue

A mature component of a normal portal tract

Often conspicuous in FNH septa

Absent in FNH lesional architecture

Supports the characteristic reaction pattern

Would imply preserved portal-tract organization

Slide 31 · Hepatocyte plates retain normal thickness

1–2-cell-thick plates

Spaces between cords represent sinusoids

Schematic hepatocyte plates; Not microscopy

Hepatocytes form one- to two-cell-thick plates.

This arrangement resembles nonneoplastic liver organization.

Plate thickness should be assessed alongside cellular and architectural features.

Slide 32 · Cytologic atypia is not a feature of typical FNH

No cytologic atypia in the lesional hepatocytes.

Absence of conspicuous nuclear abnormalities supports benign hyperplasia.

This finding should be integrated with architecture rather than used in isolation.

Slide 33 · Architectural atypia is also absent

FNH lacks the architectural atypia expected in an aggressive hepatocellular lesion.

Preserved thin hepatocyte plates are one expression of orderly architecture.

Fibrous nodules and abnormal arteries are organized alterations, not malignant invasion.

Slide 34 · A low-power–to–high-power review sequence

Scar and septal layout

Vessels and ductular reaction

Hepatocyte plates and atypia

GS immunostaining

An organized examination avoids overinterpreting a single microscopic detail.

Slide 35 · The morphologic constellation is more informative

FNH morphologic diagnosis

Gross / low power

Well circumscribed

Stellate scar ± radiating septa

Hepatocyte nodules

Microscopic

Thick-walled arteries

Ductular reaction; No interlobular ducts

Thin plates; No atypia

Slide 36 · Glutamine synthetase normally has zonal expression

Centrizonal hepatocytes

Schematic GS distribution; Not an immunohistochemical image

GS is an enzyme normally expressed in centrizonal hepatocytes.

Normal zonation provides the comparator for lesional expression.

A staining pattern is evaluated spatially, not only as positive or negative.

Slide 37 · FNH has a characteristic map-like GS pattern

Irregular interconnected GS-positive zones

Schematic GS distribution; Not an immunohistochemical image

Strong cytoplasmic GS expression involves anastomosing hepatocyte groups.

The network-like distribution is described as map-like.

This pattern is particularly useful diagnostically.

Slide 38 · “Map-like” refers to spatial distribution

Irregular interconnected GS-positive zones

Schematic GS distribution; Not an immunohistochemical image

Broad, irregularly interconnected zones stain strongly.

The pattern is not simply uniform positivity across all hepatocytes.

Interpret the topology of positive groups rather than the color intensity alone.

Slide 39 · GS staining must be read with morphology

Typical scar / septa / arteries

No cellular or architectural atypia

Map-like cytoplasmic GS

Integrated support for FNH

GS is very useful; It does not replace histologic correlation.

Slide 40 · An integrated FNH recognition checklist

Well-circumscribed, usually nonencapsulated mass

Central stellate scar when present

Radiating septa and thick-walled arteries

Ductular reaction without interlobular bile ducts

One- to two-cell-thick bland hepatocyte plates

Map-like glutamine synthetase staining

Slide 41 · Clinical presentation is usually silent

Most FNH cases are asymptomatic.

The diagnosis often follows imaging or an unrelated operation.

An asymptomatic lesion with convincing FNH features generally does not require treatment.

Slide 42 · The central scar helps establish an imaging diagnosis

The central scar as a highly characteristic imaging finding.

The scar is supportive, not compulsory, because some FNH lesions lack one.

Imaging findings and clinical context should be concordant.

Slide 43 · Imaging and pathology answer different questions

Imaging assessment

Tissue assessment

Mass, contours, central scar

Scar, septa, vessel and hepatocyte morphology

Can suggest a characteristic FNH pattern

Can evaluate GS spatial distribution

May establish the diagnosis in context

Useful when diagnostic uncertainty warrants tissue review

Slide 44 · Benign natural history drives management

FNH is benign and generally needs no treatment.

Classification as nonneoplastic is central to risk assessment.

Correct recognition avoids management based solely on the presence of a mass.

Treatment decisions depend on clinical circumstances, not FNH morphology alone.

Slide 45 · Resection is reserved for selected cases

Establish FNH diagnosis

Asymptomatic / typical lesion

No treatment ordinarily needed

Resection for large symptomatic lesions.

This is a pathology-oriented summary, not a substitute for an individual multidisciplinary decision.

Slide 46 · A symptomatic large lesion changes the decision

Large FNH lesions may become symptomatic.

Large symptomatic lesions as the principal resection setting.

The reason for surgery is symptoms and lesion-specific context—not malignant transformation of typical FNH.

Slide 47 · The major differential is hepatocellular adenoma

Focal nodular hyperplasia

Hepatocellular adenoma

Benign, nonneoplastic hyperplasia

Benign hepatocellular neoplasm

Linked to altered blood flow

Distinct molecular subtypes described

No treatment for typical lesions

Hemorrhage and transformation risks affect management

Slide 48 · FNH and adenoma overlap demographically

FNH is most common in adult females.

Hepatocellular adenoma also commonly occurs in young females.

Female sex is not sufficient to discriminate these two lesions.

Exposure history, morphology, immunohistochemistry and clinical course become more useful.

Slide 49 · Hormonal associations distinguish adenoma

FNH

Hepatocellular adenoma

Altered blood flow

Strong association with oral contraceptive use

No hormonal cause specified in FNH section

Association with anabolic steroids

A distinct nonneoplastic mechanism

Obesity / metabolic syndrome noted for rising adenoma incidence

Slide 50 · FNH versus adenoma: Gross anatomy

FNH

Hepatocellular adenoma

Often central stellate scar

Discrete mass; Sometimes hemorrhage

Radiating fibrous septa

No characteristic FNH-type scar required

Typically lacks a capsule

Gross appearance assessed with clinical context

Slide 51 · Both lesions may form thin hepatocyte plates

FNH

Hepatocellular adenoma

One- to two-cell-thick plates

One- to two-cell-thick plates

Thick-walled arteries in scar / septa

Arteries in scant fibrous stroma

Ductular reaction; No interlobular ducts

Normal portal tracts and interlobular ducts absent

Slide 52 · Inflammatory adenoma may mimic FNH

Inflammatory HCA may show fibrous septa and a ductular reaction.

These features overlap with FNH and cannot be considered in isolation.

Sinusoidal dilation and acute-phase protein expression in inflammatory HCA.

Slide 53 · Histologic overlap demands pattern integration

Fibrous septa / ductular proliferation

Evaluate central scar and arteries

Review GS pattern and adenoma features

Classify lesion using the full constellation

Do not assume septa alone establish FNH.

Slide 54 · Adenoma has molecularly distinct subtypes

Hepatocellular adenoma

Molecular classes

HNF1A-inactivated

Inflammatory (JAK–STAT)

β-catenin–activated

Sonic hedgehog–activated

Why these matter

Diagnostic phenotype differs

Hemorrhage risk varies

Malignant potential varies

Slide 55 · IHC findings may favor adenoma instead

Pattern / biomarker

Adenoma context

Loss of liver fatty acid–binding protein

HNF1A-inactivated adenoma

Nuclear β-catenin staining

β-catenin pathway activation

C-reactive protein / serum amyloid A

Inflammatory adenoma

Map-like GS distribution

Characteristic support for FNH

Slide 56 · Management contrast emphasizes the diagnosis

Established FNH

Hepatocellular adenoma

No treatment in most cases

Some tumors require resection or follow-up

Large symptomatic FNH may be resected

Hemorrhage and malignancy risk inform decisions

No source-described malignant progression

Risk differs by subtype and lesion features

Slide 57 · Cavernous hemangioma is a vascular tumor

FNH

Cavernous hemangioma

Hepatocyte nodules separated by fibrous septa

Dilated, thin-walled vascular channels

Stellate scar and thick-walled arteries

Red-blue soft vascular nodule

Nonneoplastic hyperplasia

Most common benign liver tumor

Slide 58 · Regenerative nodules belong in the nonneoplastic differential

Large regenerative nodules can arise in noncirrhotic liver.

Budd–Chiari syndrome, hemangioma and vascular malformations as settings.

The shared vascular background requires careful interpretation of nodule type.

Slide 59 · Nodular regenerative hyperplasia is diffuse

Focal nodular hyperplasia

Nodular regenerative hyperplasia

Localized hepatic mass lesion

The entire liver may become nodular

Central scar and septa often present

Can occur without significant fibrosis

Usually incidental / benign

Can cause portal hypertension and mimic cirrhosis on imaging

Slide 60 · Inflammatory mass lesions can mimic tumors

Other nonneoplastic mass lesions

Inflammatory / infectious

Abscesses

Granulomas

Inflammatory pseudotumors

Regenerative / biliary

Large regenerative nodules

Nodular regenerative hyperplasia

Benign biliary proliferations

Slide 61 · Case 1: Incidentally detected scarred liver lesion

An adult woman undergoes imaging for an unrelated indication. A circumscribed hepatic mass has a central scar and no symptoms.

Which diagnosis is strongly suggested, and why?

FNH is strongly suggested.

The incidental presentation and central scar match the characteristic pattern.

The scar alone is supportive, not definitive.

Slide 62 · Case 2: Scar, septa, and bland hepatocytes

Resection reveals a central stellate scar, thick-walled septal arteries, ductular reaction and one- to two-cell-thick hepatocyte plates without atypia.

Which combined findings establish the morphologic pattern?

Fibrous/nodular architecture plus abnormal vessels

Prominent ductular reaction without interlobular bile ducts

Bland hepatocytes with preserved thin plates

Slide 63 · Case 3: Interpret the GS stain

A hepatocellular lesion demonstrates strongly positive cytoplasmic GS staining in irregular anastomosing groups of hepatocytes.

What is the diagnostic significance of this pattern?

It is the characteristic map-like GS distribution of FNH.

Use it alongside the scar, arterial and ductular features.

It is not a reason to ignore contradictory histology.

Slide 64 · Case 4: A misleading ductular reaction

A hepatocellular mass shows fibrous septa and a prominent ductular reaction. Sinusoidal dilation and inflammatory phenotype are also described.

Which competing entity must remain in the differential?

Inflammatory hepatocellular adenoma.

It can mimic FNH through fibrous septa and ductular proliferation.

Evaluate the broader morphology and IHC profile.

Slide 65 · Case 5: Multiple nodules and vascular abnormalities

Multiple FNH-like nodules occur in a patient with a vascular malformation and hepatic vascular disturbance.

How does this context inform the pathogenesis?

It supports the association with altered blood flow.

Multiplicity alone does not establish a neoplastic process.

Correlate the lesion architecture with the vascular disease.

Slide 66 · A practical recognition pathway

Hepatic mass detected

Characteristic scar / septa / altered arteries

Bland thin plates + ductular reaction

Map-like GS pattern

FNH supported

Consider hepatocellular adenoma and regenerative lesions when features are discordant.

Slide 67 · Core pathologic discriminators

Benign, nonneoplastic hepatocellular lesion

Altered-flow hypothesis and vascular associations

Well-circumscribed; Generally unencapsulated

Central scar and septa; Abnormal thick-walled arteries

Ductular reaction without mature interlobular ducts

Bland thin hepatocyte plates; Map-like GS staining

Slide 68 · Clinicopathologic synthesis

Recognizing FNH links hemodynamics, architecture, and benign clinical behavior.

Altered blood flow is associated with hepatocyte hyperplasia.

Scar–septum–artery organization and map-like GS are distinctive.

Most patients need no treatment once the diagnosis is established.

Slide 69 · Selected source and image provenance

Robbins, Cotran & Kumar. Pathologic Basis of Disease. 11th ed. 2026. Chapter 18, pp. 787–790.

FNH definition, pathogenesis, morphology and clinical features: pp. 787–788.

Comparison context: hepatic nodules, hepatocellular adenoma, hemangioma and regenerative nodules: pp. 787–790.

All architectural illustrations in this lecture are original editable schematics—not clinical specimens or reproduced textbook figures.