patoloji-ders-notlari

Title

Serdar Balcı

Cardiomyopathy, Pericardial diseases and Cardiac Tumors

Serdar BALCI, MD

CARDIOMYOPATHY

Cardiomyopathies

Cardiac diseases of intrinsic myocardial dysfunction
Primary, Secondary
**Inflammatory disorders **
- Myocarditis
Immunologic diseases
- Sarcoidosis
Systemic metabolic disorders
- Hemochromatosis
Muscular dystrophies
- Genetic disorders of myocardial fibers
Idiopathic
Dilated cardiomyopathy (DCM)
- 90%
- Includes arrhythmogenic right ventricular cardiomyopathy
Hypertrophic cardiomyopathy (HCM)
Restrictive cardiomyopathy
- Least common
Left ventricular noncompaction
- a rare congenital disorder
- Spongy appearance of the ventricles
- CHF and arrhythmias

Robbins Basic Pathology

Dilated Cardiomyopathy

Progressive cardiac dilation

Contractile (systolic) dysfunction

Concurrent hypertrophy

Regardless of cause, the clinicopathologic patterns are similar

Robbins Basic Pathology

Hereditary basis in 20-50% of cases
- Over 40 genes are known to be mutated
- Autosomal dominant inheritance is the predominant pattern
  - Cytoskeletal proteins, proteins link the sarcomere to the cytoskeleton (α-cardiac actin)
- X-linked DCM
  - Most frequently associated with dystrophin gene
  - Couples the intracellular cytoskeleton to the ECM
- Mitochondrial genome
  - Oxidative phosphorylation, fatty acid β-oxidation
- Desmin
- Nuclear lamins A and C
Infection
- Coxsackievirus B, enteroviruses
Alcohol or other toxic exposure
- Alcohol and its metabolites (acetaldehyde) have direct toxic effect on myocardium
- Chronic alcoholism associated with thiamine deficiency → beriberi heart disease
- Doxorubicin (Adriamycin), chemotherapeutic
- Cobalt
Peripartum cardiomyopathy
- Late in gestation or several weeks to months postpartum
- Multifactorial
- Pregnancy-associated hypertension, volume overload, nutritional deficiency, gestational diabetes, a cleavage product of prolactin
- Half of these patients spontaneously recover normal function
Iron overload
- Hereditary hemochromatosis
- Multiple transfusions
- Interference with metal-dependent enzyme systems
- Injury caused by iron-mediated production of reactive oxygen species

The heart is enlarged

2-3x normal weight

Dilation of all chambers

Ventricular thickness may be less than, equal to, or greater than normal

Mural thrombi often present, source of thromboemboli

**By definition, valvular and vascular lesions that can cause cardiac dilation secondarily (atherosclerotic coronary artery disease) are absent **

Autopsy Pathology: A Manual and Atlas

A: Four-chamber dilation and hypertrophy are evident. A small mural thrombus can be seen at the apex of the left ventricle (arrow)

Robbins Basic Pathology

Autopsy Pathology: A Manual and Atlas

Myocytes hypertrophy with enlarged nuclei

Many are attenuated, stretched, and irregular

Variable interstitial and endocardial fibrosis

Scattered areas of replacement fibrosis

Mark previous myocyte ischemic necrosis caused by hypoperfusion

B: The nonspecific histologic picture in typical DCM, with myocyte hypertrophy and interstitial fibrosis (collagen is blue in this Masson trichrome–stained preparation).

Robbins Basic Pathology

Arrhythmogenic Right Ventricular Cardiomyopathy

Autosomal dominant, variable penetrance
Right-sided heart failure and rhythm disturbances
Sudden cardiac death
Right ventricular wall is severely thinned
Myocyte replacement by massive fatty infiltration and lesser amounts of fibrosis
**Mutations **
- Desmosomal junctional proteins at the intercalated disk (plakoglobin)
- **Proteins that interact with the desmosome (the intermediate filament desmin). **

Arrhythmogenic right ventricular cardiomyopathy

Robbins Basic Pathology

Arrhythmogenic right ventricular cardiomyopathy

Robbins Basic Pathology

Hypertrophic Cardiomyopathy

Myocardial hypertrophy

Defective diastolic filling

Ventricular outflow obstruction

Thick-walled, heavy, and hypercontractile

Systolic function usually is preserved, myocardium does not relax, primary diastolic dysfunction

Robbins Basic Pathology

Missense mutations in contractile apparatus

Autosomal dominant

β-myosin heavy chain is most frequently affected

Myosin-binding protein C and troponin T

They all affect sarcomeric proteins and increase myofilament activation

**Massive myocardial hypertrophy without ventricular dilation **
Disproportionate thickening of the ventricular septum relative to the left ventricle free wall
- Asymmetric septal hypertrophy
- Concentric hypertrophy in 10%
Myocyte hypertrophy
Haphazard myocyte (and myofiber) disarray
Interstitial fibrosis

Autopsy Pathology: A Manual and Atlas

Robbins Basic Pathology

Restrictive Cardiomyopathy

Decrease in ventricular compliance

Impaired ventricular filling during diastole

Differential diagnosis for constrictive pericarditis or HCM

The ventricles are normal size or only slightly enlarged

Cavities are not dilated

Myocardium is firm

Variable degrees of interstitial fibrosis

Robbins Basic Pathology

Amyloidosis
- Systemic amyloidosis
- Senile cardiac amyloidosis
- Normal or mutant forms of transthyretin
- 4% of African Americans carry a specific mutation

Autopsy Pathology: A Manual and Atlas

Endomyocardial fibrosis
- Disease of children and young adults in Africa and other tropical areas
- Dense diffuse fibrosis of the ventricular endocardium and subendocardium
- Tricuspid and mitral valves
- Nutritional deficiencies, Helminthic infections (hypereosinophilia)
- Most common form of restrictive cardiomyopathy.
Loeffler endomyocarditis
- Endocardial fibrosis
- Peripheral hypereosinophilia and eosinophilic tissue infiltrates
- Release of eosinophil granule contents, major basic protein → endo- and myocardial necrosis → scarring, layering of the endocardium by thrombus → thrombus organization

Myocarditis

Viral infections
- The most common cause of myocarditis
- Coxsackieviruses A and B, other enteroviruses
- Cytomegalovirus (CMV)
- Human immunodeficiency virus (HIV)
- Influenza virus
Trypanosoma cruzi
- Chagas disease
- Half of the population in endemic areas of South America
- 10% of the patients die during an acute attack
- Chronic immune-mediated phase
- Progressive signs of CHF and arrhythmia 10 to 20 years later
- Trypanosomes accompanied by an inflammatory infiltrate of neutrophils, lymphocytes, macrophages, and occasional eosinophils

Robbins Basic Pathology

Toxoplasma gondii
- Immunocompromised persons
Trichinosis
- The most common helminthic disease with associated cardiac involvement
Borrelia burgdorferi
- Myocarditis in 5% of patients with Lyme disease
- Self-limited conduction system disease
- Require temporary pacemaker insertion

Noninfectious causes of myocarditis

Systemic lupus erythematosus

Polymyositis

Drug hypersensitivity reactions (hypersensitivity myocarditis)

Acute myocarditis

Normal or dilated
In advanced stages
- Myocardium flabby, mottled with pale and hemorrhagic areas
- Mural thrombi

mottled with pale foci or small hemorrhages signifying active inflammation

Autopsy Pathology: A Manual and Atlas

Active myocarditis

Edema, interstitial inflammatory infiltrates, and myocyte injury

Diffuse lymphocytic infiltrate is most common

Inflammatory involvement is often patchy and can be “missed” on endomyocardial biopsy

**Lesions can resolve without significant sequelae or heal by progressive fibrosis **

Robbins Basic Pathology

Hypersensitivity myocarditis

Interstitial and perivascular infiltrates

Lymphocytes, macrophages, and a high proportion of eosinophils

Robbins Basic Pathology

Giant cell myocarditis

Widespread inflammatory cellular infiltrates
Multinucleate giant cells
- Formed by macrophage fusion
Aggressive end of the spectrum of lymphocytic myocarditis
Necrosis
Poor prognosis

**Giant cell myocarditis. Areas of hemorrhage and necrosis **

Autopsy Pathology: A Manual and Atlas

Robbins Basic Pathology

PERICARDIAL DISEASE

Pericarditis

Primary pericarditis is uncommon
- Viral infection (with concurrent myocarditis)
- Bacteria, fungi, or parasites may also be involved
Secondary pericarditis
- Acute MI
- Cardiac surgery
- Radiation to the mediastinum
- Pneumonia
- Pleuritis
- Uremia
- Rheumatic fever
- Systemic lupus erythematosus
- Metastatic malignancies

Acute bacterial pericarditis

Exudate is fibrinopurulent

Suppurative

Pus

Robbins Basic Pathology

Autopsy Pathology: A Manual and Atlas

Pericarditis

Acute viral pericarditis or uremia
- Exudate is fibrinous
- Irregular, shaggy appearance to the pericardial surface
- Bread and butter pericarditis
Tuberculous pericarditis
- Areas of caseation
Malignancy
- Exuberant, shaggy fibrinous exudate
- Bloody effusion
- Metastases can be grossly evident as irregular excrescences
- Not grossly inapparent in leukemia

Pericarditis outcome

**Immediate hemodynamic complications **
- Cardiac tamponade
Resolve without significant sequelae
Progress to a chronic fibrosing process
Acute fibrinous or fibrinopurulent pericarditis resolves without any sequelae
Extensive suppuration or caseation → healing with fibrosis
- Chronic pericarditis
**Chronic pericarditis **
- Dense, fibrotic scars obliterate the pericardial space
- Heart cannot expand normally during diastole → constrictive pericarditis

Pericardial Effusions

Normally, the pericardial sac 30-50 mL of clear, serous fluid
Serous
- Congestive heart failure, hypoalbuminemia of any cause
Serosanguineous
- Blunt chest trauma, malignancy, ruptured MI or aortic dissection
Chylous
- Mediastinal lymphatic obstruction

Slowly accumulating effusions -even as large as 1000 mL-can be well-tolerated

Rapidly developing collections of as little as 250 mL (ruptured MI or ruptured aortic dissection) → Fatal cardiac tamponade

Autopsy Pathology: A Manual and Atlas

CARDIAC TUMORS

Cardiac Tumors

Metastatic Neoplasms
- Most common malignancy of the heart
- 5% of patients dying of cancer
- Lung cancer, lymphoma, breast cancer, leukemia, melanoma, hepatocellular carcinoma, and colon cancer
Primary Neoplasms
- Uncommon
Most are benign
- Myxomas, fibromas, lipomas, papillary fibroelastomas, and rhabdomyomas
Angiosarcomas
- Most common primary malignant tumor of the heart

Myxomas

Most common primary tumors of the adult heart
- 90% are atrial
- 80% of those are the left atrium
Single
Arise in fossa ovalis (atrial septum)
<1cm-10cm
Sessile or pedunculated masses
Pedunculated forms are mobile cause intermittent obstruction

Soft, translucent, villous lesions with a gelatinous appearance

Stellate, frequently multinucleated myxoma cells, with hyperchromatic nuclei

Admixed with cells showing endothelial, smooth muscle, and/or fibroblastic differentiation, undifferentiated cells

Cells are embedded in an abundant acid mucopolysaccharide ground substance

Hemorrhage, poorly organizing thrombus, and mononuclear inflammation

Atrial myxoma: Large pedunculated lesion arises from the region of the fossa ovalis and extends into the mitral valve orifice

Robbins Basic Pathology

Atrial myxoma:

Abundant amorphous extracellular matrix contains scattered multinucleate myxoma cells in various groupings, including abnormal vascular formations

Robbins Basic Pathology

Rhabdomyomas

Most frequent primary tumors of the heart in infants and children
Discovered owing to valvular or outflow obstruction
- High frequency in patients with tuberous sclerosis
- TSC1 or TSC2 tumor suppressor genes
- Loss of TSC-1 and -2 activity leads to myocyte overgrowth
Often regress spontaneously
- considered to be hamartomas rather than true neoplasms
Gray-white masses up to several centimeters in diameter
Protrude into the ventricular chambers
Mixed population of cells
- Large, rounded, or polygonal cells containing numerous glycogen-laden vacuoles separated by strands of cytoplasm running from the plasma membrane to the centrally located nucleus, so-called spider cells

Autopsy Pathology: A Manual and Atlas

Enzinger and Weiss Soft Tissue Tumors Sixth Edition

A: Acute cardiac allograft rejection, typified by a lymphocyte infiltrate associated with cardiac myocyte damage. Note the similarity of rejection and viral myocarditis

Robbins Basic Pathology

B: Allograft arteriopathy, with severe concentric intimal thickening producing critical stenosis. The internal elastic lamina (arrow) and media are intact. (Movat pentachrome stain.)

Robbins Basic Pathology