Primary Cardiac Tumors

Slide 1 · Primary Cardiac Tumors

Morphology · mechanisms · clinicopathologic correlation

Benign neoplasms, clinically consequential masses, and rare sarcomas

Dr Abu Suraih Sakhri

MBBS, MD (Pathology)

www.abusuraihsakhri.com

Slide 2 · Learning objectives

Classify the principal benign and rare malignant primary cardiac tumors.

Recognize the defining gross and microscopic patterns of myxoma, papillary fibroelastoma, and rhabdomyoma.

Link tumor location and architecture to obstruction, embolization, and other clinical effects.

Explain the syndromic signaling abnormalities described for myxoma and rhabdomyoma.

Slide 3 · Primary cardiac tumors are uncommon

Frequency

Primary cardiac tumors are uncommon in routine clinical practice.

Biology

The majority are benign rather than malignant.

Why they matter

A benign mass may still impair intracardiac blood flow or embolize.

Slide 4 · Five common benign entities

Order

Primary cardiac tumor

Teaching discriminator

1

Myxoma

Most frequent in the combined population

2

Fibroma

Benign; Resembles extracardiac counterpart

3

Lipoma

Benign; Resembles extracardiac counterpart

4

Papillary fibroelastoma

Endocardial, often valvular

5

Rhabdomyoma

Leading pediatric primary tumor

Slide 5 · Almost 90% belong to these five types

Five frequent benign entities

No malignant potential

≈90% of primary cardiac tumors

Slide 6 · Adult and pediatric leading entities differ

Adults: Myxoma

Myxoma predominates in adult hearts.

Commonly attached to the atrial septum.

Atrial obstruction, embolization, and constitutional effects.

Children: Rhabdomyoma

Rhabdomyoma is the leading pediatric type.

Often multiple in ventricular myocardium.

Associated with tuberous sclerosis in about half.

Slide 7 · The compartment predicts the mechanism

Atrial cavity

A mobile intracavitary myxoma may obstruct an atrioventricular orifice.

Valve surface

Papillary fibroelastoma is often silent but can embolize.

Ventricular myocardium

Rhabdomyoma may project into the lumen and obstruct flow.

Slide 8 · Benign histology does not ensure benign physiology

Benign intracardiac mass

Mechanical or embolic complication

Clinically significant disease

Slide 9 · Primary malignant cardiac tumors are exceptionally rare

Angiosarcoma among the usual malignant histologic types.

It also identifies undifferentiated sarcomas with MDM2 oncogene amplification.

Cardiac sarcomas are not described as clinically or morphologically unique relative to sarcomas elsewhere.

Slide 10 · Myxoma is the most common adult primary tumor

Benign neoplasm arising from primitive multipotent mesenchymal cells.

Most often an atrial rather than ventricular lesion.

Clinical significance reflects obstruction, embolization, or cytokine-associated effects.

RA

LA

RV

LV

Schematic · cardiac chambers

Septal attachment

Slide 11 · Myxoma arises from multipotent mesenchymal cells

Primitive multipotent mesenchymal cell

Benign myxoma

Myxoid tumor within atrial cavity

Slide 12 · Sporadic myxoma lacks a consistent genetic signature

Sporadic myxomas have no consistent genetic alteration in the supplied Robbins section.

This statement differs from the defined gene defects of recognized syndromic associations.

Do not assume that every myxoma is syndromic from its histology alone.

Slide 13 · Two recognized syndromic associations

McCune–Albright

McCune–Albright syndrome

Activating GNAS1 mutation

Enhanced G-protein signaling

Carney complex

Carney complex

Loss-of-function PRKAR1A mutation

Increased cAMP-dependent signaling

Slide 14 · GNAS1: Gain of function enhances signaling

GNAS1 gain of function

Gsα signaling ↑

Enhanced G-protein signaling

Slide 15 · PRKAR1A: Loss of regulatory restraint

PRKAR1A loss of function

PKA regulatory subunit affected

CAMP-dependent signaling ↑

Slide 16 · Syndromic myxoma: Contrast the direction

Syndrome

Gene

Alteration

Signaling consequence

McCune–Albright

GNAS1

Gain of function

Enhanced G-protein signaling

Carney complex

PRKAR1A

Loss of function

Increased cAMP-dependent signaling

Slide 17 · Approximately 90% of myxomas are atrial

Atria are overwhelmingly favored over ventricles.

The location helps explain why an intracavitary lesion can involve a valve opening.

The fossa ovalis region of the atrial septum is the favored origin.

RA

LA

RV

LV

Schematic · cardiac chambers

Septal attachment

Slide 18 · Left atrial myxoma is more frequent

Left atrial site

Left atrium is the predominant atrial site.

Often near the interatrial septum.

May interfere with the mitral orifice.

Right atrial site

Right atrium is less frequently involved.

The approximate left:right atrial ratio is 4:1.

Both sites fit the atrial predominance.

Slide 19 · Fossa ovalis: The preferred attachment site

Myxomas usually arise from the region of the fossa ovalis.

This site lies in the interatrial septum.

A lesion can remain septally attached while projecting into the atrial cavity.

RA

LA

RV

LV

Schematic · cardiac chambers

Septal attachment

Slide 20 · Myxomas are usually single

Usual pattern

Most myxomas are solitary.

A single endocardial attachment may anchor a relatively large mass.

Less common pattern

Multiple tumors can occur, but are rare.

The provided source does not assign a numerical multiplicity rate.

Slide 21 · Myxoma size spans a very broad range

Small lesions

Some are under 1 cm in diameter.

Large lesions

Some reach 10 cm or more.

Clinical implication

Size and mobility together determine how a mass encounters an orifice.

Slide 22 · Sessile versus pedunculated myxoma

Sessile

Broad attachment at the origin.

May form a large intracavitary mass.

Robbins figure depicts a large sessile myxoma.

Pedunculated

Attached by a stalk.

Can move appreciably with the cardiac cycle.

May intermittently enter an atrioventricular opening.

Slide 23 · Gross myxomas have variable texture

Firm or globular

Some masses are relatively hard and mottled by hemorrhage.

Soft or gelatinous

Other masses are translucent with a gelatinous quality.

Papillary or villous

Some lesions show surface projections rather than a smooth mass.

Slide 24 · A gelatinous mass reflects abundant matrix

The microscopic tumor contains abundant acid mucopolysaccharide-rich extracellular ground substance.

The large matrix compartment accounts for much of the myxoid or gelatinous appearance.

Cellular elements are relatively dispersed within this matrix.

Vessel-like space

Schematic · not an H&E specimen

Slide 25 · Mobile myxoma can create “ball-valve” obstruction

A pedunculated mass may move into an atrioventricular valve opening.

The orifice is transiently occupied by tumor tissue.

Obstruction can vary from moment to moment rather than remaining fixed.

RA

LA

RV

LV

Schematic · cardiac chambers

Septal attachment

Slide 26 · Position can change the severity of obstruction

Change in body position or cardiac phase

Mobile mass meets valve orifice

Intermittent flow obstruction

Slide 27 · The obstruction is anatomical, not malignant

A benign myxoma can restrict valve-orifice flow without invading the valve.

Physical mobility and the attachment site explain episodic symptoms.

Histologic benignity and hemodynamic significance should be assessed separately.

Slide 28 · Myxoma histology: Abundant myxoid matrix

Extracellular ground substance is rich in acid mucopolysaccharides.

The matrix separates scattered tumor cells.

The dominant microscopic pattern is myxoid rather than densely cellular.

Vessel-like space

Schematic · not an H&E specimen

Slide 29 · Myxoma cells may be stellate or globular

Stellate cells extend delicate cytoplasmic processes.

Other tumor cells appear globular within the myxoid ground substance.

Cell shape alone is not the entire diagnosis; Architectural context matters.

Vessel-like space

Schematic · not an H&E specimen

Slide 30 · Vessel-like and gland-like formations

Unusual vessel-like or gland-like structures are characteristic morphologic features.

These patterns sit within the abundant extracellular matrix.

The schematic represents architecture, not a patient photomicrograph.

Vessel-like space

Schematic · not an H&E specimen

Slide 31 · Hemorrhage and inflammation are usually present

Hemorrhage frequently accompanies the tumor matrix and cells.

Mononuclear inflammatory infiltrates are usually encountered.

A hemorrhagic gross surface and inflammatory microscopic background may coexist.

Slide 32 · Morphology integrates matrix, cells, and structures

Component

Histologic description

Extracellular compartment

Abundant acid mucopolysaccharide ground substance

Tumor-cell appearance

Stellate or globular myxoma cells

Distinctive arrangements

Unusual vessel-like or gland-like structures

Associated findings

Hemorrhage and mononuclear inflammation

Slide 33 · Three pathways produce myxoma symptoms

Obstruction

Intermittent ball-valve interference with intracardiac flow.

Embolization

Fragments may enter the systemic circulation.

Constitutional

Fever and malaise may reflect tumor-derived cytokines.

Slide 34 · Fragmentation produces systemic embolization

Tumor fragmentation

Detached material reaches circulation

Systemic embolic event

Slide 35 · Fever and malaise can be tumor related

A constitutional syndrome including fever and malaise.

These manifestations may accompany an otherwise benign neoplasm.

They should be interpreted alongside obstruction and embolization.

Slide 36 · Interleukin-6 links tumor and acute-phase response

IL-6 elaborated by some myxomas

Acute-phase response

Constitutional symptoms

Slide 37 · Echocardiography identifies the intracardiac mass

Echocardiography provides a noninvasive way to identify the myxoma.

Its structural utility follows from the lesion projecting into a cardiac chamber.

The source does not specify modality-specific performance metrics or universal imaging protocols.

Slide 38 · Resection is usually curative

Usual outcome

Surgical removal is typically curative.

The physical mass and its associated complications are addressed.

Rare recurrence

Rare recurrence occurs months to years later.

Incomplete excision is suggested as a likely explanation in the source.

Slide 39 · Apply the pattern: Obstructing atrial mass

An adult has intermittent symptoms that vary with position; Imaging shows a mobile atrial mass attached to the septum.

Discriminating clues

Adult age group

Atrial septal attachment

Position-dependent obstruction

Most compatible tumor?

Atrial myxoma — the attachment, mobility, and clinical physiology match the textbook pattern.

Slide 40 · Papillary fibroelastoma: Endocardial tumor

A distinctive, sea-anemone-shaped endocardial lesion.

Commonly found incidentally rather than through symptoms.

Its ability to embolize makes an apparently small benign tumor clinically significant.

Slide 41 · More than 80% occur on valves

Common location

Valvular surfaces account for more than 80% of lesions.

Gross identity

Delicate hair-like projections arise from a small endocardial base.

Clinical meaning

Valvular attachment does not guarantee functional insignificance.

Slide 42 · Valve surface orientation is characteristic

Semilunar valves

Semilunar valves: Ventricular surfaces are especially favored.

These include the aortic and pulmonary valve family.

Atrioventricular valves

Atrioventricular valves: Atrial surfaces are especially favored.

These include the mitral and tricuspid valve family.

Slide 43 · Typical fibroelastoma diameter: 0.5–2 cm

The principal mass is typically 0.5–2 cm in diameter.

The projecting filaments may reach 1 cm in length.

A limited mass diameter does not eliminate embolic significance.

Slide 44 · Papillary fibroelastoma has hair-like fronds

Numerous delicate projections create a sea-anemone-like outline.

Hair-like fronds arise from a compact valvular or endocardial attachment.

This gross architecture is distinct from the gelatinous mass of a myxoma.

Schematic · endothelial-covered fronds

Slide 45 · Each papillary projection has an endothelial cover

An endothelial layer lines the outside of each projection.

The central portion is connective tissue rather than densely packed neoplastic cells.

The overall growth pattern is a branching papillary structure.

Schematic · endothelial-covered fronds

Slide 46 · The fibroelastoma core contains elastic fibers

Layer / component

Textbook description

Surface

Endothelium

Central stroma

Myxoid connective tissue

Matrix

Abundant mucopolysaccharide ground substance

Other core component

Elastic fibers

Slide 47 · Clonal abnormalities support neoplastic status

Clonal cytogenetic abnormalities have been reported in papillary fibroelastomas.

These findings support their interpretation as benign neoplasms.

The source does not provide a specific recurrent chromosomal change or diagnostic molecular test.

Slide 48 · Lambl excrescences are the main named look-alike

Papillary fibroelastoma

Small, papillary, endothelial-covered fibroelastic tumor.

Often on valves; Can cause embolic consequences.

Clonal cytogenetic abnormalities have been observed.

Lambl excrescence

Much smaller projections from sites of valve apposition.

Usually regarded as trivial comparison.

Morphologic resemblance does not make them identical lesions.

Slide 49 · Fibroelastoma may first matter through embolization

Incidental endocardial lesion

Potential embolization

Clinically important event

Slide 50 · Apply the pattern: Valvular fronded lesion

A small incidental valvular tumor has many hair-like projections, and its stalk is attached to the valve surface.

Discriminating clues

Often valvular location

Sea-anemone-like contour

Fibroelastic papillary core

Most compatible tumor?

Papillary fibroelastoma; Distinguish it from the much smaller Lambl excrescence.

Slide 51 · Rhabdomyoma predominates in pediatric hearts

The most frequent primary tumor of the pediatric heart.

Often detected during the first years of life.

Evaluation may be prompted by valve dysfunction or flow obstruction.

RA

LA

RV

LV

Schematic · cardiac chambers

Slide 52 · About half are associated with tuberous sclerosis

Syndromic group

Approximately 50% of cardiac rhabdomyomas are associated with tuberous sclerosis.

The syndrome involves TSC1 or TSC2 tumor suppressor gene mutations.

Sporadic group

Approximately half are attributed to sporadic mutations.

Do not label every cardiac rhabdomyoma as tuberous-sclerosis-associated.

Slide 53 · TSC1 and TSC2 encode hamartin and tuberin

Gene / complex

Product

Role in source

TSC1

Hamartin

Tumor suppressor protein

TSC2

Tuberin

Tumor suppressor protein

TSC1/TSC2 complex

Functional pair

Inhibits mTOR activity

Slide 54 · TSC1–TSC2 complex inhibits mTOR

Hamartin + tuberin

MTOR activity restrained

Cell growth and size controlled

Slide 55 · Loss of inhibitory control permits overgrowth

Loss of TSC1 or TSC2 expression

Reduced restraint of mTOR

Myocyte overgrowth

Slide 56 · Spontaneous regression challenges strict tumor labels

Observed biological behavior

Rhabdomyomas often regress spontaneously.

The natural history does not resemble relentless malignant growth.

Interpretive consequence

Some authors consider them hamartomas rather than true neoplasms.

This is a classification interpretation, not a universal requirement.

Slide 57 · Rhabdomyoma prefers ventricular myocardium

Myocardial masses preferentially involve the ventricles.

Lesions can bulge into the ventricular cavity.

The intraluminal projection can account for flow obstruction.

RA

LA

RV

LV

Schematic · cardiac chambers

Slide 58 · Rhabdomyoma: Multiple gray-white masses

Gross color

Typically gray-white myocardial masses.

Multiplicity

Usually multiple rather than solitary.

Size and site

From small lesions to masses several centimeters in ventricular myocardium.

Slide 59 · Enlarged cardiac myocytes contain glycogen

Microscopy shows bizarre, markedly enlarged myocytes.

Large intracellular glycogen collections are a central feature.

Routine tissue processing removes much of the glycogen.

Slide 60 · “Spider cells” reflect processing of glycogen

Glycogen extraction leaves the cytoplasm appearing empty.

Residual cytoplasm remains as thin strands from nucleus to cell membrane.

This produces the classic spider-cell appearance.

Central nucleus

Thin residual cytoplasmic strands

Schematic · glycogen extraction artifact

Slide 61 · Rhabdomyoma effects depend on position

Ventricular myocardial mass

Protrusion into lumen

Valve dysfunction or flow obstruction

Slide 62 · Apply the pattern: Infant ventricular masses

An infant is evaluated for cardiac flow obstruction; Imaging shows multiple ventricular myocardial masses.

Discriminating clues

Age in first years of life

Ventricular and multiple lesions

Possible tuberous sclerosis association

What further mechanism fits?

Cardiac rhabdomyoma; Consider TSC1/TSC2-mediated loss of mTOR restraint.

Slide 63 · Fibroma and lipoma: Limited textbook detail

Fibroma

Among the five most common primary benign cardiac tumors.

Morphologically resemble fibromas arising elsewhere.

No site-specific mechanism is detailed here.

Lipoma

Also among the five most common benign primary tumors.

Resemble lipomas at extracardiac sites.

No additional cardiac-specific morphology is supplied.

Slide 64 · Primary cardiac sarcoma: The rare exception

Angiosarcoma

Angiosarcoma is one of the typical malignant types.

The section provides no special cardiac-specific diagnostic morphology.

MDM2-amplified sarcoma

Undifferentiated sarcoma with MDM2 amplification is another named type.

MDM2 is a molecular finding mentioned in this source.

Slide 65 · Primary tumor versus cardiac metastatic deposit

Primary cardiac tumor

Originates within the heart.

Most examples are benign.

Myxoma, fibroelastoma, and rhabdomyoma are the detailed prototypes.

Metastatic involvement

Reaches heart or pericardium from a noncardiac cancer.

The adjacent section identifies several metastatic routes.

Cardiac secondary involvement is a separate diagnostic category.

Slide 66 · Compare the three diagnostic prototypes

Entity

Predilection

Morphology

Clinical link

Myxoma

Adult; Atrial

Gelatinous mass; Myxoid matrix

Obstruction / emboli / IL-6

Fibroelastoma

Valvular endocardium

Hair-like endothelial papillae

Potential emboli

Rhabdomyoma

Child; Ventricle

Glycogen-rich spider cells

Flow obstruction; Regression

Slide 67 · A pattern-based approach to a cardiac mass

Patient age + anatomical site

Gross / microscopic pattern

Most compatible tumor identity

Slide 68 · Three patterns worth retaining

Atrial myxoma

Myxoid matrix + septal attachment + variable obstruction.

Papillary fibroelastoma

Valvular hair-like fronds + endothelial covering + embolic risk.

Cardiac rhabdomyoma

Ventricular pediatric masses + glycogen-laden spider cells + TSC association.

Slide 69 · Reference

Robbins, Cotran & Kumar: Pathologic Basis of Disease. 11th edition. Elsevier; 2026.

The Heart — Primary Cardiac Tumors.