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PATHOLOGY
A Color Atlas
Pathology : A Color Atlas
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C.V. Mosby (November 1999)
Chronic obstructive pulmonary disease, 60
PNEUMOCONIOSES, 62
IDIOPATHIC INTERSTITIAL LUNG DISEASES, 66
PULMONARY NEOPLASMS, 68
THE HEMATOPOIETIC AND
LYMPHOID SYSTEM, 72
ANEMIAS, 74
Bone marrow changes, 74
Peripheral blood smears, 74
Tissue changes in anemia, 77
LEUKEMIAS, 78
Acute leukemias, 78
Chronic leukemias, 80
PLASMA CELL DYSCRASIAS, 82
REACTIVE LYMPHADENOPATHIES, 84
HODGKIN DISEASE, 87
Histopathologic subtypes of Hodgkin disease, 87
NON-HODGKIN LYMPHOMA, 89
OTHER HEMATOPOIETIC PROLIFERATIONS IN LYMPH
NODES, 95
NEOPLASMS INVOLVING THE SPLEEN, 96
DISEASES OF THE THYMUS, 98
THE HEART,1
CONGENITAL HEART DISEASE, 2
Cardiovascular shunts and septal defects, 2
Conotruncal anomalies, 4
Cardiovascular obstructions, 6
VALVULAR LESIONS, 9
Rheumatic heart disease, 9
Infective endocarditis, 11
Other valvular lesions, 13
MYOCARDIAL DISEASES, 14
Myocarditis, 14
Cardiomyopathy, 17
CORONARY ARTERY DISEASES, 20
Coronary atherosclerosis, 20
Myocardial infarction, 22
Complications of myocardial infarction, 22
PERICARDIAL DISEASES, 25
CARDIAC TUMORS, 27
BLOOD VESSELS, 30
ARTERIOSCLEROSIS, 32
ANEURYSMS, 35
VASCULITIS, 36
Immune-mediated vasculitis, 38
UPPER RESPIRATORY TRACT, 40 UPPER DIGESTIVE TRACT, loo
INFLAMMATORY LESIONS, 42
BENIGN TUMORS AND RELATED CONDITIONS, 44
MALIGNANT TUMORS, 45
LUNGS, 48
DEVELOPMENTAL ANOMALIES, 50
PERINATAL LUNG DISEASES, 52
PULMONARY INFECTIONS, 54
PULMONARY CIRCULATORY DISORDERS, 57
Pulmonary emboli, 57
Pulmonary hypertension, 58
IMMUNE-MEDIATED LUNG DISEASES, 58
CHRONIC INFECTIONS AND CHRONIC
OBSTRUCTIVE PULMONARY DISEASE (CORD), 60
Bronchiectasis, 60
DEVELOPMENTAL ANOMALIES, 102
INFLAMMATORY LESIONS, 103
ORGAN-SPECIFIC LESIONS, 105
Dental cysts, 105
Oral and salivary gland lesions, 108
Esophageal lesions, 110
TUMORS, 112
Oral tumors, 112
Salivary gland tumors, 112
Esophageal tumors, 118
GASTROINTESTINAL TRACT, 120
DEVELOPMENTAL DISORDERS, 122
CIRCULATORY DISTURBANCES, 124
OBSTRUCTIONS AND DILATATIONS OF INTESTINAL
LUMEN, 125
ORGAN-SPECIFIC DISEASES, 126
Gastritis and peptic ulcer, 126
Small intestinal diseases that cause malabsorption, 129
Inflammation of the appendix and the large intestine,
130
Inflammatory bowel disease (IBD), 132
TUMORS, 134
Gastric tumors, 134
Tumors of the small intestine, 136
Tumors of the appendix, 136
Intestinal polyps, 136
Carcinoma of the large intestine, 139
Anal tumors and related lesions, 140
HEPATOBILIARY TRACT, 142
HEREDITARY METABOLIC DISEASES, 144
CIRCULATORY DISORDERS, 146
INFECTIOUS HEPATITIS, 147
Viral hepatitis, 147
Hepatitis caused by pathogens other than hepatitis
viruses, 149
Biliary infections, 150
DRUG-INDUCED LIVER DISEASES, 152
ALCOHOLIC LIVER DISEASES, 153
AUTOIMMUNE LIVER DISEASES, 155
BILIARY OBSTRUCTION, 156
CIRRHOSIS, 158
TUMOR-LIKE CONDITIONS AND TUMORS, 159
Tumor-like conditions, 159
Epithelial tumors, 161
Mesenchymal tumors, 163
Metastatic tumors, 163
DISEASES OF THE GALLBLADDER, 164
PANCREAS, 166
DEVELOPMENTAL AND GENETIC DISORDERS, 168
PANCREATITIS, 169
TUMORS OF THE EXOCRINE PANCREAS, 172
Benign tumors and tumors of borderline malignancy,
172
Carcinoma of the pancreas, 174
TUMORS OFTHE ENDOCRINE PANCREAS, 176
DIABETES MELLITUS, 177
ENDOCRINE GLANDS, 180
DISEASES OF THE PITUITARY GLAND, 182
Hypopituitarism, 182
Reactive changes, 183
Tumors, 183
DISEASES OF THE THYROID GLAND, 185
Thyroid hyperplasia, 185
Thyroiditis, 186
Benign thyroid tumors, 188
Malignant thyroid tumors, 190
DISEASES OF THE PARATHYROID GLANDS, 195
DISEASES OF THE ADRENAL CORTEX, 198
Adrenocortical insufficiency, 198
Adrenocortical hyperplasia and hyperfunction, 199
Adrenocortical tumors, 201
DISEASES OFTHE ADRENAL MEDULLA, 203
KIDNEY AND URINARY TRACT, 208
DEVELOPMENTAL AND GENETIC DISORDERS, 210
Agenesis, malposition, exstrophy, and related defects,
210
Polycystic kidney disease, 212
Hereditary glomerular and tubular diseases, 213
VASCULAR DISORDERS, 216
IMMUNE-MEDIATED GLOMERULAR DISEASES, 217
Membranoproliferative glomerulonephritis, 219
Membranous glomerulonephritis, 220
IgA nephropathy and Henoch-Schonlein purpura, 222
Postinfectious glomerulonephritis, 223
Crescentic glomerulonephritis, 224
Systemic lupus erythematosus (SLE), 225
TUBULOINTERSTITIAL DISEASES, 227
LOWER URINARY TRACT INFECTIONS, 232
TUMORS, 234
Tumors of the kidney and renal pelvis, 234
Tumors of the urinary bladder, 235
MALE REPRODUCTIVE SYSTEM, 238
GENETIC AND DEVELOPMENTAL DISORDERS, 240
INFECTIONS, 241
TUMORS OF THE TESTIS, 242
Germ cell tumors, 242
Sex cord stromal tumors, 246
Mixed germ cell stromal tumors, 247
Tumors of rete testis, epididymis, and tunica vaginalis
testis, 248
TUMORS AND TUMOR-LIKE LESIONS OF THE
PROSTATE, 248
Benign prostatic hyperplasia, 248
Carcinoma of the prostate, 250
FEMALE REPRODUCTIVE SYSTEM, 256
DEVELOPMENTAL DISORDERS, 258
INFECTIONS, 260
HORMONALLY INDUCED CHANGES, 261
TUMORS OF THE VULVA, 263
TUMORS OF THE VAGINA, 265
TUMORS OF THE CERVIX, 266
TUMORS OF THE UTERUS, 268
Endometrial adenocarcinoma, 268
Endometrial stromal tumor,s 270
Tumors of the myometrium, 271
TUMORS OF THE OVARY, 273
Serous tumors, 273
Mucinous tumors, 275
Endometrioid carcinoma, 277
Clear cell carcinoma, 278
Transitional cell tumors, 278
Sex cord stromal tumors, 278
Germ cell tumors, 282
Unclassified and metastatic tumors of the ovary, 284
DISORDERS OF THE PLACENTA, 287
Abnormal implantation and separation of the placenta
and rupture of membranes, 289
Infections, 289
Gestational trophoblastic disease, 290
BREAST, 294
FIBROCYSTIC CHANGE, 296
TUMORS, 298
Fibroadenoma, 298
Adenoma, 298
Phyllodes tumor, 299
Intraductal papilloma, 300
Atypical hyperplasia, 301
Noninvasive carcinoma, 302
Invasive breast carcinoma, 303
Variants of invasive carcinoma 306
I mmunohistochemistry of breast carcinoma, 308
SKIN, 310
HEREDITARY SKIN DISEASES, 312
INFECTIONS, 312
Bacterial infections, 313
Fungal infections, 314
Viral infections, 314
INFLAMMATORY DERMATOSES, 316
I mmune-mediated dermatoses, 316
Granulomatous diseases, 319
Idiopathic skin disease, 321
NEOPLASMS AND RELATED DISORDERS, 323
Pigmentary lesions, 323
Epidermal tumors, 328
Adnexal tumors, 331
Mesenchymal tumors, 333
SOFT TISSUE, 334
FIBROBLASTIC LESIONS, 336
Benign fibroblastic tumors and tumor-like lesions, 336
Fibromatoses, 337
FIBROHISTIOCYTIC TUMORS, 338
LIPOMATOUS TUMORS, 339
VASCULAR TUMORS, 341
PERIVASCULAR TUMORS, 343
SMOOTH MUSCLE CELL TUMORS, 344
TUMORS OF STRIATED MUSCLE, 345
NEURAL TUMORS, 347
Benign neural tumors, 347
Malignant neural tumors, 348
CARTILAGE AND BONE-FORMING TUMORS, 349
MISCELLANEOUS SOFT-TISSUE TUMORS, 350
BONES AND JOINTS, 354
DEVELOPMENTAL AND GENETIC DISORDERS, 356
METABOLIC AND DEGENERATIVE DISEASES, 357
Metabolic bone diseases, 357
Hyperparathyroidism, 359
Paget disease of bone, 359
Crystal-induced arthritis, 360
Osteonecrosis, 361
Degenerative joint disease, 361
I NFLAMMATORY DISEASES, 363
Infections of bones and joints, 363
Noninfectious arthropathies, 364
NEOPLASMS, 367
Benign bone-forming tumors, 367
Malignant bone-forming tumors, 369
Fibrous lesions of bone, 377
Giant cell tumor of bone, 378
Marrowtumors, 379
Vascular tumors, 380
Miscellaneous tumors and tumor-like conditions, 380
Tumors and tumor-like lesions of joints, 383
SKELETAL MUSCLES, 384
CONGENITAL MYOPATHIES, 386
MUSCULAR DYSTROPHIES, 386
I NFLAMMATORY MYOPATHIES, 389
GENETIC-METABOLIC MYOPATHIES, 392
Carbohydrate storage diseases, 392
Lipid storage myopathies, 393
Mitochondrial myopathies, 394
DENERVATION-RELATED MUSCLE DISEASES, 395
NERVOUS SYSTEM, 398 THE EYE AND OCULAR ADNEXA, 434
DEVELOPMENTAL AND GENETIC DISORDERS, 400
PERINATAL BRAIN LESIONS, 401
TRAUMA OFTHE BRAIN AND THE SPINAL CORD, 403
CIRCULATORY DISTURBANCES, 405
Intracranial hemorrhages, 405
Cerebral ischemia, 408
INFECTIONS, 409
METABOLIC AND TOXIC DISEASES, 413
Inborn errors of metabolism, 414
DEMYELINATING DISEASES, 416
DEGENERATIVE DISEASES OF THE CENTRAL
NERVOUS SYSTEM, 417
NEOPLASMS, 420
Astrocytic tumors, 422
Oligodendroglioma, 422
Ependymoma, 422
Neuronal, mixed neuronal-glial, and neuroendocrine
neoplasms, 424
Pineal tumors, 424
Meningioma, 425
Vascular neoplasms, 425
Malformative and nonneoplastic mass lesions, 426
DISEASES OF PERIPHERAL NERVES, 426
Peripheral neuropathies, 426
Hereditary neuropathies, 428
Ischemic neuropathies, 430
Inflammatory neuropathies, 430
Neoplasms of peripheral nerves, 432
INFLAMMATION OFTHE EYE AND OCULAR
ADNEXA, 436
EYE CHANGES IN SYSTEMIC DISEASES, 437
SPECIFIC OCULAR DISORDERS, 438
Glaucoma, 438
Diseases of the cornea, 440
Retinal degenerative diseases, 441
Cataracts, 442
TUMORS, 443
Melanoma, 443
Retinoblastoma, 445
Medulloepithelioma, 446
EAR, 448
INFLAMMATORY LESIONS OF THE EXTERNAL AND
MIDDLE EAR, 450
PATHOLOGIC CHANGES OFTHE INNER EAR, 453
NEOPLASMS, 455
Tumors of the outer ear, 455
Tumors of the middle ear, 455
Tumors of the inner ear, 455
PATHOLOGY
A Color Atlas
CONGENITAL HEART DISEASE
Congenital heart disease encompasses disorders of the car-
diovascular system that result from faulty embryogenesis
and are present at birth. The most common cardiac malfor-
mations in descending order of frequency are
1.Ventricular septal defect (VSD)
2.Atrial septal defect
3. Pulmonary stenosis
4.Tetralogy of Fallot (including pulmonary atresia)
5. Patent ductal artery (ductus arteriosus)
6.Aortic stenosis
7. Coarctation of the aorta
8. Complete transposition of the great arteries
9.Atrioventricular septal defect
10.Tricuspid atresia
11.Aortic atresia (hypoplastic left ventricular syndrome)
12.Total anomalous pulmonary venous connection
13.Persistent truncal artery (truncus arteriosus)
Cardiovascular Shunts and Septa! Defects
Shunts result either from patency of normal fetal structures
that fail to close postnatally or from incomplete formation
of one or more septa during cardiac embryogenesis. Persis-
tent fetal structures include a patent oval foramen and a
patent ductal artery (Fig. 1-1). In contrast, shunts that result
from faulty embryogenesis involve defects at the level of the
atrial, atrioventricular, ventricular, ventriculoarterial, or aor-
topulmonary septa (Diagram 1-1).
Atrial septal defects occur at the oval fossa in 85% of cases
and are known as fossa or secundum atrial septal defects (Fig.
1-2). Ventricular septal defects involve the membranous part
of the septum in 75% to 80% of cases seen at operation or
autopsy (Fig. 1-3). Outlet defects located beneath the right
and left cusps of both semilunar valves account for 5% to
10% of all VSD. Inlet defects that involve the inlet septum be-
neath the septal tricuspid leaflet account for 5% of all VSD.
Defects of the muscular part of the septum account for only
10% to 20% of cases at operation or autopsy, even though
they actually represent the most common form of VSD. Most
of them are small and close spontaneously.
Diagram I-I. Cardiac and vascular shunts. Upper panel shows various levels of intracardiac
shunts. Lower panel shows various levels of shunts involving the great arteries.
3
Fig. I -I. Patent ductal artery (*), connecting the aorta with the
pulmonary artery, in adult with plexogenic pulmonary hyper-
tension.
Fig. 1-2. Atrial septal defect, fossa (secundum) type, as seen in
an adult (*).
A
C
B
D
Fig. 1-3. Ventricular septal defects (*). A, Membranous defect; B, Outlet defect; C, Muscular
defect; D, Muscular defect that has undergone spontaneous closure (arrows).
Conotruncal Anomalies
Conotruncal anomalies are related to abnormal development
of ventricular outflow tracts (Diagram 1-2). Most are asso-
ciated with an overriding great artery; in some cases one or
both arteries arise from the contralateral ventricle. Many pa-
tients have a VSD of the membranous or outlet type, as well
as valvular or subvalvular pulmonary stenosis. Clinically
these defects are associated with right-to-left shunts and pe-
ripheral cyanosis.
Tetralogy of Fallot is the most common conotruncal
anomaly, accounting for 8% to 10% of all congenital heart
defects. It comprises subpulmonary stenosis, a VSD, an over-
riding aorta, and right ventricular hypertrophy (Fig. 1-4).
Pulmonary atresia with a VSD is considered the most se-
vere form of tetralogy of Fallot (Fig. 1-5).
The persistent truncal artery (Fig. 1-6) accounts for 1% of
all congenital heart defects and complete transposition ofgreat
vessels (Fig. 1-7) accounts for 5%.
Diagram 1-2. Conotruncal anomalies.
A B
Fig. 1-4. Tetralogy of Fallot. A, Hypoplastic pulmonary trunk and enlarged ascending aorta
(anterior view); B, Displaced outlet septum (*) with pulmonary stenosis (probe), a ventricular septal
defect (arrow probe), and an overriding aorta (opened, hypertrophied right ventricle).
BA
Fig. I-S. Pulmonary atresia with ventricular septal defect. A, Atretic cordlike pulmonary trunk
(arrow) and dilated ascending aorta (anterior view). B, Ventricular septal defect, overriding aorta,
and ductal origin of the left pulmonary artery (arrow).
Cardiovascular Obstructions
Cardiovascular obstructions can occur congenitally at the
level of cardiac chambers (e.g., hypoplastic ventricle), valves
(e.g., bicuspid semilunar valves), or great vessels (e.g., coarc-
tation of aorta) (Diagram 1-3).
Aortic stenosis may be valvular, subvalvular, or supra-
valvular. Bicuspid aortic valves occur in 1% to 2% of the gen-
eral population. Such abnormal valves usually remain
asymptomatic until late in adult life. In approximately 80%
of patients bicuspid valves undergo calcification, causing
aortic stenosis (Fig. 1-8). Pure regurgitation occurs in 20%
of patients and is the result of annular dilatation, prolapse
of the conjoined cusp, or infective endocarditis. Congenital
hypoplasia or nodular thickening of a unicommissural valve,
or less commonly a bicuspid valve, may cause critical aortic
stenosis in the neonate (Fig. 1-9).
Fig. 1-6. Persistent truncal artery is located over a ventricular
septa) defect (*). The overriding truncal artery gives rise to
ascending aorta and both pulmonary arteries (opened right
ventricle).
A B
Fig. 1-7. Complete transposition of great arteries. A, Anterior view. B, Long axis view showing
ventriculoarterial discordance.
7
Diagram 1-3. Valvular and arterial stenosis. Upper panel shows aortic stenosis. Lower panel
shows pulmonary stenosis and aortic coarctation.
A B C
Fig. 1-8. Congenitally bicuspid aortic valves (surgical specimens). A, The valve is calcified and
stenotic. B, Regurgitation resulting from cuspid prolapse and annular dilatation. C, Regurgitation
resulting from healed infective endocarditis with cusp perforation.
A
B C
Fig. 1-9. Congenital aortic stenosis. A, Critical stenosis of a unicommissural valve in an infant.
B, and C, represent mild stenosis of a unicommissural valve in a young adult (opened and closed
positions).
A B C
Fig. 1-10. Pulmonary stenosis. A, Poststenotic dilatation of the pulmonarytrunk (anterior view).
B, Dome-shaped acommissural valve. C, Pronounced right ventricular hypertrophy (four-chamber
view).
9
Pulmonary stenosis, like its left-sided counterpart, may be
valvular, subvalvular, or supravalvular. It often is associated
with other cardiac anomalies. Isolated pulmonary stenosis is
associated with a dome-shaped acommissural valve in ap-
proximately 45%, a dysplastic tricuspid pulmonary valve in
25%, unicommissural valve in 15%, a bicuspid valve in 10%,
and a hypoplastic annulus in 5% of patients (Fig. 1-10).
Coarctation of the aorta is the most common form of con-
genital vascular obstruction (Fig. 1-11). It is associated with
a V-shaped invagination of the aorta, just opposite the ductal
artery. It is associated with a patent ductal artery in 50%, a
biscuspid aortic valve in 50%, a membranous VSD in 30%,
subaortic stenosis in 25%, and mitral valve anomalies in 25%
of cases.
Fig. I-I I. Coarctation of the aorta, with a typical indentation of
the aortic wall (arrow) opposite the ductal arterial ligament (*).
VALVULAR LESIONS
Cardiac valves may be congenitally deformed or they may
undergo secondary changes due to infections, hemodynamic
stress, or age-related degeneration accompanied by calcifi-
cations.
Rheumatic Heart Disease
Rheumatic fever is an immune-mediated systemic inflam-
matory disease related to sensitization of the body to beta
hemolytic group A streptococci. Even though rheumatic
heart disease may involve all parts of the heart and is thus a
pancarditis, endocarditis accounts for most important
pathologic changes and most of the morbidity. Rheumatic
carditis is less common today than it was in the preantibiotic
era.
An active rheumatic fever causes typical lesions, the most
pathognomonic of which are the Aschoff bodies (Fig 1-12).
In the granulomatous stage, which is reached three to four
weeks after the infection, these bodies consist of macro-
phages, giant cells (Aschoff cells), lymphocytes, and occa-
sional neutrophils. Aschoff bodies heal by scarring. They
most often are found in the myocardium and the subendo-
cardial connective tissue, and only rarely in the valves.
A B
Fig. I-12. Rheumatic carditis in an active phase. A, Aschoff body composed of macrophages and
lymphocytes is found in the interstitial plane of the myocardium. B, At higher magnification one
can see that the Aschoff body is composed of macrophages, which have caterpillar (arrow) or owl's
eye-shaped nuclei (curved arrow).
A
Rheumatic valvulitis presents in the form of verrucous
endocarditis characterized by the formation of tiny trans-
lucent nodules on the atrial side of atrioventricular valves
and on the ventricular surfaces of semilunar valves (Fig.
1-13). Deposits of fibrin and underlying inflammation may
extend onto the left atrial parietal endocardium and less often
onto the chordae tendineae or papillary muscles. Histologi-
cally the vegetations are composed of fibrin covering the
valve, which are focally infiltrated with lymphocytes. The
valves, which are normally avascular, become vascularized
soon after the onset of inflammation. Within 6 to 8 weeks the
valves contain relatively thick-walled blood vessels, which
may persist indefinitely. Resolution of this inflammation re-
sults in scarring, thickening of the cusps, and obliteration of
valve commisures. The chordae tendineae become short-
ened, thickened, and fused to each other. Mitral valves (Fig.
1-14) and aortic valves (Fig. 1-15) are involved more often
than the valves of the right heart. The deformed valves tend
to calcify and become infected. Clinically chronic valvular
changes present as stenosis or insufficiency.
Fig. 1-13. Acute rheumatic endocarditis. A, Acute endocarditis presents with small translucent
vegetations. B, Histologically the lesion is composed of fibrin covering a valve that is infiltrated
with mononuclear inflammatory cells. C, Higher magnification of the vegetation and the inflamed
value.
B
C
II
A
Fig. 1-14. Chronic rheumatic endocarditis of mitral valve. A, View from the opened left heart.
B, Stenotic orifice seen from the left atrium.
B
Infective Endocarditis
Inflammation may involve the valves or mural endocardium.
Accordingly, infective endocarditis is classified as either val-
vular or mural. It most often is caused by gram-positive bac-
teria such as Streptococcus pneumoniae and Staphylococcus
aureus. Valvular infection is more common and clinically
more important. The infected valves are covered with lus-
cious, friable vegetations and are composed of fibrin, bacte-
rial colonies, and inflammatory cells (Figs. 1-16 and 1-17).
Fig. I-15. Chronic rheumatic endocarditis of aortic valve. The
valves are deformed fused and the orifice is stenosed.
Fig. 1-16. Acute bacterial endocarditis. The valve is covered
with large, friable, irregular vegetations (arrow).
Fig. I-17. Acute bacterial endocarditis. The vegetation consists
of fibrin and bacteria.
Infective endocarditis affects valves of the left heart more
often than those of the right heart. Factors that predispose to
infection include congenitally deformed valves and pre-
existing valvular lesions such as those caused by rheumatic
fever (Figs. 1-18 and 1-19). Sepsis, intravenous drug abuse,
cardiovascular surgery, and insertion of prosthetic valves also
are associated with an increased risk for infective endo-
carditis.
Infective endocarditis of immunosuppressed persons
may be caused by uncommon bacteria and even fungi (Fig.
1-20), which may cause extensive local destructive lesions
(Fig. 1-21). Other complications of infective endocarditis are
listed in Table 1-1.
Direct Damage to Heart
Perforation of valve cusps and/or leaflet causing insufficiency
Valve ring or myocardial abscess and fistula formation
Suppurative and obliterative pericarditis
Dehiscence of prosthetic valves, conduits, and patch components
Late valve fibrosis causing stenosis (accompanied by insufficiency)
Septic Embolization with Abscess Formation
Cerebral abscess
Osteomyelitis
Mycotic aneurysm
Lung abscess
Sepsis
Infectious Arteritis with Thrombotic Occlusion
Infarcts—brain, myocardium, spleen, kidneys, other viscera
Ischemia in distribution of ileofemoral or other major arteries
Circulating Immune Complexes
Focal or diffuse glomerulonephritis
Fig. 1-18. Acute bacterial endocarditis superimposed on chronic
rheumatic endocarditis. Valvular deformities and thickened
chordae tendineae are evidence of the chronic process.
Potential Complications of Infective
Endocarditis
Fig. 1-19. Acute bacterial endocarditis superimposed on chronic
healing endocarditis. The arrow points to a microabscess formed
in the central part of the vegetation.
Fig. 1-20. Fungal endocarditis. Fungal hyphae can be demon-
strated in the vegetation by Gomori methenamine-silver stain.
Fig. 1-21. Infective endocarditis with extensive destruction of
the valve.
13
Other Valvular Lesions
Nonbacterial thrombotic endocarditis, which is also known as
marantic endocarditis, typically occurs in terminally ill, ema-
ciated patients who have cancer or other chronic diseases.
Small vegetations typically are found along the line of clo-
sure on otherwise normal valves (Fig. 1-22). Histologically
such vegetations resemble bland fibrin thrombi (Fig. 1-23).
Floppy mitral valves are common but they rarely cause
clinically significant changes unless they are associated with
myxomatous transformation. In floppy valve syndrome the
valve cusps expand, chordae lengthen, and one or both cusps
"billow " or prolapse into the atrium during systole (Fig.
1-24).
Carcinoid heart disease is a complication of intestinal car-
cinoids metastatic to the liver. It is characterized by fibrotic
changes in the endocardium of the right ventricle. The tri-
cuspid and pulmonary valves have focal or diffuse plaquesof
glycosaminoglycan-rich, elastin-free connective tissue (Fig.
1-25). The left ventricle also is involved in one third of pa-
tients examined at autopsy, but the changes are mild and
cause no clinically significant hemodynamic abnormalities.
Degenerative calcific aortic stenosis represents an age-
related lesion that typically is found in the elderly. The
valves are deformed by nodular calcifications within the
cusps (Fig. 1-26). Aortic insufficiency may result from the di-
latation of the aortic valve annulus caused by a variety of dis-
eases such as rheumatic fever, syphilis, or atherosclerosis,
which is the most common cause of this disease in the elderly
(Fig. 1-27).
Fig. 1-22. Nonbacterial thrombotic endocarditis. The line of
closure is covered with fine uniform vegetations.
Fig. 1-23. Nonbacterial thrombotic endocarditis. Histologically
the vegetations are composed of fibrin attached to a normal
valve.
Fig. 1-24. Floppy mitral valve. The valve appears irregularly
thickened and deformed. The greatest redundancy and gelatin-
ous change are noted in the posterior leaflet (to the right), but
there also is localized thickening along the free margin of the
anterior mitral leaflet. Chordae tendineae are variably thickened
and focally fused.
Fig. 1-25. Carcinoid heart syndrome. Greatly thickened tri-
cuspid valve and chordae show a whitish "onlay." The right
upper portion of the valve is relatively spared and appears
translucent.
A B
Fig. I -26. Degenerative calcific aortic stenosis. A, Superior view of tricuspid, fibrocalcific,
stenotic valve. The calcific nodules are most prominent inside the cusps (arrow). The commissures
are focally fused, most prominently on the posterior side. B, Similar case with more prominent
calcification.
A B
Fig. 1-27. Aortic insufficiency due to dilatation of the aortic root. The aorta has a thickened wall
and its luminal surface is covered with fibrous plaques and focal ulcerative calcific changes, most
consistent with healed aortitis. Focal endocardial thickening below the aortic valve is indicative of
regurgitation. B, Close-up view.
Causes of Myocarditis
MYOCARDIAL DISEASES
The most important myocardial diseases are myocarditis and
cardiomyopathies.
Myocarditis
Inflammations of the myocardium are classified as (1) in-
fectious, (2) immune-mediated, or (3) idiopathic (Table
1-2). Pathologically myocarditis is classified as acute or
chronic, focal or diffuse. Histologically it is classified de-
scriptively according to the predominant cell type infiltrating
the myocardium or the pattern of reaction, such as lympho-
cytic, eosinophilic, or giant cell (Fig. 1-28). Pathogens rarely
A B
15
C
E
D
F
Fig. 1-28. Microscopic appearances of myocarditis. A, Active myocarditis of the predominantly
lymphocytic type. Isolated myocytes are surrounded by the infiltrate in a background of what
appears to be edema. B, Ventricular myocardium with myocarditis and clusters of cells immuno-
reactively identified as macrophages. C, Ventricular myocardium with active myocarditis and myo-
cytolysis (arrows). The cytolysis is associated with an infiltrate of activated immune cells in a child
with suspected viral myocarditis. D, Ventricular myocardium with influenza A-related myocarditis
in a young child. The "punched-out" lesions of myocyte necrosis are best defined by lack of
positive staining (arrows) with monoclonal antibody to muscle-specific a-actin. E, Giant cell myo-
carditis with multinucleated giant cells positive for muscle-specific a-actin monoclonal antibody
staining. Some of the giant cells in the same heart were derived from muscle cells, whereas others
expressed macrophage markers. F, Giant cell myocarditis with multinucleated giant cell and neigh-
boring macrophages stained brown with an antibody CD68. Although this multinucleated cell is
immunonegative, others in this case were immunopositive with the same antibody.
if ever are identified by routine histologic examination of the
myocardium with a few exceptions such as Chagas disease,
in which the myocytes typically contain Trypanosoma cruzi
(Fig. 1-29). Myocardial abscess caused by sepsis rarely con-
tains identifiable bacteria (Fig. 1-30). Myocardial cell
necrosis with myophagocytosis in a patient with diphtherial
pharyngitis is by inference classified as diphtherial; the car-
diac lesions actually are caused by a toxin released by C. diph-
theriae, which hematogenously reaches the myocardium
(Fig. 1-31).
Transplant rejection is accompanied by an immune-
mediated myocarditis (Fig. 1-32). The type of rejection may
be classified by endocardial biopsy as: la—focal mild; lb—
diffuse mild; 2—focal moderate; 3a—multifocal moderate;
3b—diffuse moderate or severe; or 4—severe (Figs. 1-32 and
1-33).
Idiopathic myocarditis is the most common type of myo-
cardial inflammation identified at autopsy. It may present
histologically as lymphocytic, eosinophilic, giant cell, or
granulomatous inflammation (Fig. 1-34).
Fig. 1-29. Chagas disease. Myocytes contain Trypanosoma cruzi. Fig. 1-30. Myocardial abscess. Myocardium contains aggregates
of neutrophils.
Fig. 1-31. Diphtherial myocarditis. Necrosis of cardiac
myocytes is more prominent than the inflammatory infiltrate.
Fig. 1-32. Cardiac transplant rejection. Focal, moderate
(grade 2).
I7
Fig. 1-33. Cardiac transplant rejection. Multifocal, moderate
(grade 3a).
Fig. 1-34. Eosinophilic myocarditis. The interstitium contains
infiltrates of lymphocyte and eosinophils.
Cardiomyopathy
Cardiomyopathies are diseases characterized by cardiac dys-
function in which the main abnormality lies in the working
myocardium. Cardiomyopathies are divided into two
groups: primary (idiopathic, due to unknown causes) and
secondary (due to known causes). Both the primary and the
secondary categories have three possible functional states:
(1) dilated, congestive; (2) hypertrophic, hyperdynamic; and
(3) restrictive, constrictive (Diagram 1-4, p. 18).
Dilated cardiomyopathy (systolic disorder) is found in pa-
tients with hemochromatosis, chronic anemia, alcoholic car-
diomyopathy, sarcoidosis, and many other diseases. Typically
it is found in the end stages of ischemic heart disease and in
hypertensive heart disease, in which it is accompanied by
hypertrophy of all four cardiac chambers (Fig. 1-35). The di-
lated heart shows foci of scarring ("replacement fibrosis" )
(Fig. 1-36). Thrombi tend to form in the dilated ventricle and
there typically is functional mitral insufficiency.
Fig. 1-35. Dilated cardiomyopathy. Ventricles and atria are
dilated. There is a mural thrombus in the left ventricle.
Fig. 1-36. Dilated cardiomyopathy. There is replacement
fibrosis in the myocardium.
Diagram 1-4. Specific and less specific causes of dilated, hypertrophic, and restrictive
cardiomyopathy.
Hypertrophic cardiomyopathy (diastolic disorder) is found
in patients with Friedreich ataxia, glycogen storage disease,
congenital cardiomyopathies such as those related to muta-
tions of gene for beta-myosin heavy chain, and in infants of
diabetic mothers (Figs. 1-37 and 1-38). The most common
cause of left ventricular hypertrophy is arterial hypertension.
Cor pulmonale causes right ventricular hypertrophy. In all
these diseases there is marked hypertrophy of the cardiac
myocytes, often accompanied by interstitial fibrosis.
Restrictive cardiomyopathy (diastolic and systolic dis-
order) may be caused by pathologic processes involving the
endocardium (e.g., endomyocardial fibrosis), myocardium
(e.g., cardiac amyloidosis), or pericardium (e.g., constrictive
pericarditis). These diseases typically impede the diastolic
filling of the cardiac chambers and reduce systolic ejection
of blood. The pathologic changes depend on the process that
has caused the disturbance, so the ventricles can be of normal
size (as inpericarditis) or markedly thickened (as in amyloi-
dosis) (Figs. 1-39 and 1-40). Fig. 1-37. Congenital hypertrophic cardiomyopathy with asym-metric septa) hypertrophy.
I9
Fig. 1-38. Congenital hypertrophic cardiomyopathy. Histologi-
cally the cardiac myocytes are hypertrophied and show
branching and disarray. There also is considerable interstitial
fibrosis.
Fig. 1-39. Amyloidosis of the heart. The ventricular myocardium
appears thickened but pale.
A B
Fig. 1-40. Amyloidosis. A, The cardiac myocytes are surrounded by hyalinized material.
B, Electron microscopy shows pericellular amyloid fibers.
CORONARY ARTERY DISEASES
Atherosclerosis of coronary arteries is clinically the most im-
portant heart disease. Narrowing or occlusion of coronary
arteries typically causes myocardial ischemia, which clini-
cally presents as angina pectoris, myocardial infarction, or
chronic ischemic heart disease.
Coronary Atherosclerosis
Atherosclerotic plaques of coronary arteries have the same
morphologic features as plaques in other sites, that is, they
have an atheromatous, cholesterol-rich core surrounded by
a fibrous cap (Fig. 1-41). Some lesions are composed only of
fibrous tissue and are calcified. Plaques may be eccentric (Fig.
1-42) or may concentrically narrow the lumen of the coro-
naries (Fig. 1-43). Soft lipid-rich atherosclerotic plaques tend
to rupture and provoke thrombus formation in the lumen of
the coronary (Fig. 1-44). Rupture of atheroma also may cause
microemboli and fibrin thrombi in the distal small branches
of the coronary artery system (Fig. 1-45).
Coronary thrombi may be lysed through the action of fib-
rinolytic enzymes. The presence of multiple vascular chan-
nels inside a coronary artery indicates recanalization (Fig.
1-46). Consequences and potential outcomes of coronary
atherosclerotic plaque rupture are outlined in Diagram 1-5.
Fig. 1-41. Coronary artery with a fibrolipid plaque. In cross
section the plaque, which was stained by Sudan red, had a core
of lipid separated from the lumen by a white fibrous cap. The
plaque projects outward rather than inward, so the artery
appeared normal on angiography.
Fig. 1-42. Eccentric plaque causing narrowing of the coronary
artery, estimated to be over 95 percent.
Fig. 1-43. Concentric plaque causing narrowing of the coronary
artery, estimated to be over 70 percent.
21
Fig. 1-44. Coronary thrombus. In this picro-Mallory
trichome—stained slide, collagen is blue and the thrombus is red.
There is a small tissue in the plaque, which provoked the
intraluminal thrombosis.
Fig. 1-45. Microemboli in small intramyocardial vessels. This
small artery is occluded by a mass composed of platelets (blue),
red cells (yellow), and cholesterol (clefts).
Fig. 1-46. Coronary artery recanalization. The lumen of the
coronary artery has been subdivided into several channels by
fibrous strands.
Diagram 1-5. Potential outcomes of coronary plaque rupture.
Myocardial Infarction
Myocardial infarction represents the major consequence of
coronary artery occlusion; it frequently is fatal. Myocardial
infarcts can be localized or diffuse, transmural or subendo-
cardial (Figs. 1-47 to 1-49). On gross examination the in-
farcted myocardium initially is redder than the surviving ad-
jacent tissue at 12 hours after occlusion of the coronary and
then becomes paler; by day 3 it is yellow (Fig. 1-47). The pat-
tern of infarction is best appreciated at autopsy by staining
slices of cross-sectioned heart enzyme histochemically to
demonstrate dehydrogenase activity. Infarcted areas appear
pale 12 hours after the onset of necrosis due to loss of en-
zyme activity in necrotic cells (Figs. 1-48 and 1-49).
Histologic changes indicative of myocardial infarction ap-
pear approximately 6 to 12 hours after occlusion but the def-
inite signs of necrosis can be identified only after 24 hours.
The myocardial cells become hypereosinophilic, lose their
cross-striations, and show coalescence of myofibrils (Fig.
1-50). Contraction band necrosis in which the cytoplasm of
myocardial cells contains densely eosinophilic bands also
may be seen but it is more typical of reperfusion injury (Fig.
1-51). The infarcted area is invaded by neutrophils two to
three days after the coronary occlusion (Fig. 1-52).
Macrophages appear three to five days after the onset of is-
chemia and a fully established granulation tissue develops
over a few days. Granulation tissue gives rise to fibrotic scars,
which form three to six weeks thereafter.
Complications of Myocardial Infarction
The outcome of myocardial infarction depends on many
variables and includes a spectrum of clinical pictures from
sudden death to complete recovery. External cardiac rupture,
a complication of transmural infarcts, occurs during the first
10 days and typically is accompanied by hematopericardium
(Figs. 1-53 and 1-54). Rupture of the septum can cause an
acute left-to-right shunt and the rupture of papillary muscle
Fig. 1-47. Myocardial infarct. By clinical history this infarct was
six days old. The yellow necrotic area is surrounded by a
hemorrhagic red rim.
Fig. 1-48. Transmural myocardial infarct. The transverse
section of ventricles was stained to demonstrate succinic dehy-
drogenase activity. Normal myocardium is blue. The pale areas
involving the anterior and septal wall of the left ventricle repre-
sent the infarct caused by occlusion of the anterior branch of
the left coronary artery.
Fig. 1-49. Subendocardial infarct. The tissue was stained to
demonstrate succinic dehydrogenase activity. The subendo-
cardial pale areas correspond to the infarct, which extends
across the areas supplied by at least three coronary arteries.
23
Fig. 1-50. Myocardial infarct 24 hours after occlusion of the
coronary artery. The necrotic myocytes have deeply eosino-
philic amorphous cytoplasm. Adjacent surviving cells appear pale
and vacuolated.
Fig. I-5I. Contraction band necrosis. The cytoplasm of myo-
cytes contains deeply eosinophilic bands.
Fig. 1-52. Myocardial infarct. In this three-day-old infarct the
necrotic myocardial cells are surrounded by neutrophils.
Fig. 1-53. Rupture of a transmural infarct. Fig. 1-54. Hematopericardium. Pericardium is filled with blood
as a complication of cardiac rupture.
may cause acute mitral insufficiency (Figs. 1-55 and 1-56).
Mural thrombi form over the infarcted areas (Fig.1-57). Ven-
tricular aneurysms form at the site of large scars replacing
infarcted myocardium of the left ventricle (Fig. 1-58).
Fig. 1-55. Rupture of the interventricular septum. Fig. 1-56. Papillary muscle rupture. (Courtesy of Dr. Fred
Bosman, Lausanne, Switzerland.)
Fig. 1-57. Mural thrombus overlying a massive myocardial
infarct.
Fig. 1-58. Ventricular aneurysm. The bulging aneurysm has a
thin fibrotic wall.
25
PERICARDIAL DISEASES
The pericardium may be affected by a variety of infectious,
immune-mediated, and metabolic diseases, as well as by ad-
verse external influences such as -y-radiation, all of which can
causepericarditis andpericardial fibrosis or both (Table 1-3).
Hydropericardium is a common complication of congestive
heart failure and generalized edema. Hematopericardium is a
complication of heart rupture. The pericardium often is in-
volved, together with myocardium in myocarditis of viral
origin or in any form of pancarditis such as rheumatic fever.
Pericarditis also is a common complication of myocardial in-
farction.
Pericardial diseases present in several pathologic forms:
(1) serous effusion; (2) hematopericardium; (3) fibrino-
hemorrhagic or fibrinopurulent pericarditis; or (4) con-
strictive fibrosing pericarditis, which can be accompanied by
calcifications or adhesive mediastinitis (Figs. 1-59 to 1-64).
Infectious
Viral
Pyogenic
Tuberculous
Fungal
I mmune-mediated
Rheumatic fever
—Sarcoidosis
—
Systemic lupus erythematosus —
Dressler syndrome Myocardial infarction
Idiopathic
Irradiation Radiotherapy
Surgery Open heart surgery
Metabolic
Uremic Chronic renal failure
TYPE
Causes of Pericarditis
CAUSE
Coxsackievirus B
Staphylococcus aureus
Mycobacterium tuberculosis
Histoplasma capsulatum
Fig. 1-59. Fibrinous pericarditis. The surface of the heart is
covered with a layer of fibrin.
Fig. 1-60. Fibrinous pericarditis. The surface of the epicardium
is covered with fibrin. There is granulation tissue under the layer
of fibrin.
26
Fig. 1-6 I. Fibrinohemorrhagic pericarditis. The heart is covered
with blood-tinged fibrin.
Fig. 1-62. Fibrinohemorrhagic pericarditis. The layer on the
surface of the epicardium consists of fibrin and granulation
tissue.
Fig. 1-63. Tuberculous pericarditis. The inflammatory infiltrate
is composed of macrophages, lymphocytes, and multinucleated
giant cells.
Fig. 1-64. Constrictive pericarditis. The heart is encased in a
thick layer of white fibrous tissue.
27
CARDIAC TUMORS
Primary tumors of the heart are rare. The most common
tumor is myxoma (Fig. 1-65). Typically myxomas are benign
tumors, located in the left atrium. Less often they occur in
the right atrium or attached to the valves. Rhabdomyomas
are cardiac tumors of infancy and childhood (Fig. 1-66). Pri-
mary tumors of the pericardium are histologically classified
as benign or malignant mesotheliomas or hemangiosar-
comas (Fig. 1-67).
Metastases to the heart are more common than primary
tumors. They may be found on the epicardial surface, within
the cardiac chambers, or invading the myocardium (Fig.
1-68).
A
B
C D
Fig. 1-65. Cardiac myxoma in the left atrium. A, The tumor may occlude the mitral orifice as a
"ball valve." B, The external surface is smooth and the tumor appears lobulated and myxomatous.
C, The tumor is composed of elongated cells surround by myxomatous matrix that stains pink.
There also are thin-walled blood vessels. D, High-power view of stellate and elongated (lepidic)
cells and hemosiderin laden macrophages.
B
A
Fig. 1-66. Rhabdomyoma. A, The tumor presents as a myocardial mass. B, The tumor is com-
posed of glycogen-rich cells that have clear cytoplasm.
Fig. 1-67. Hemangiosarcoma of the pericardium. This hemor-
rhagic tumor was found encasing the heart.
Fig. 1-68. Metastatic melanoma of the epicardium.
29
Further Reading
Adenle AD, Edwards JE: Clinical and pathologic features of metastatic
neoplasms of the pericardium. Chest 81:166-169, 1982.
Altrichter PM, Olson LJ, Edwards WD et al: Surgical pathology of the
pulmonary valve. A study of 116 cases spanning 15 years. Mayo
Clin Prot 64:1352-1360, 1989.
Aretz HT: Myocarditis. The Dallas criteria. Hum Pathol 18:619-624,
1987.
Burke AP, Cowan D, Virmani R: Primary sarcomas of the heart. Cancer
69:387-395,1992.
Burke AP, Virmani R: Cardiac myxoma. A clinicopathologic study. Am
J Clin Pathol 100:671-680, 1993.
Burke AP, Virmani R: Cardiac rhabdomyoma. A clinicopathologic
study. Mod Pathol 4:70-74, 1991.
Davies MJ: Coronary artery remodeling and the assessment of stenosis
by pathologists. Histopathology 33:497-500, 1998.
Davies MJ: Review: the investigation of sudden cardiac death. Histo-
pathology 34:93-98, 1999.
Klacsmann PG, Bulkley BH, Hutchins GM: The changed spectrum of
purulent pericarditis. An 86 year autopsy experience in 200 pa-
tients. Am J Med 63:666-673, 1977.
Lam KY, Dickens P, Chan AC: Tumors of the heart. A 20-year experi-
ence with a review of 12,485 consecutive autopsies. Arch Pathol Lab
Med 117:1027-31, 1993.
Maron BJ: Hypertrophic cardiomyopathies. Lancet 350:127-133, 1997.
Pardo-Mindan FJ, Lazano MD, Contreras-Mejuto F, de Alava E: Path-
ology of heart transplant through endomyocardial biopsy. Semin
Diagn Pathol 9:238-48, 1992.
Silver MD: Cardiac pathology. A look at the last five years. II. The pa-
thology of cardiovascular prostheses. Hum Pathol 5:127-38, 1974.
Winters GL: The challenge of endomyocardial biopsy interpretation in
assessing allograft rejection. Curr Opin Cardiol 12:146-152, 1997.
ARTERIOSCLEROSIS
Arteriosclerosis is an inclusive generic term that is used to de-
scribe thickening and hardening of arteries. Included under
this term are four pathologic entities: (1) arteriosclerosis,
(2) hypertensive arteriosclerosis, (3) Monckeberg medial cal-
cific sclerosis, and (4) atherosclerosis.
Arteriolosclerosis, or thickening of the wall of arterioles,
occurs in two forms: hyaline arteriolosclerosis (arteriolar
hyalinosis) and hyperplastic (proliferative) arteriosclerosis.
In hyaline arteriolosclerosis the wall of arterioles appears
thickened by homogeneously glassy pink material ( "hya-
line" ) (Fig. 2-1). It may accompany hypertension or diabetes
and is a common feature of involutional atrophy (e.g., post-
menopausal ovaries) and aging. It often is prominent in the
spleen.
Hyperplastic arteriolosclerosis is characterized by nar-
rowing of the lumen of arterioles due to the concentric pro-
liferation of smooth muscle cells in the vessel wall (Fig. 2-2).
It typically is found in malignant hypertension, progressive
systemic sclerosis (scleroderma), chronic transplant rejec-
tion, and after radiotherapy (Fig. 2-3).
Hypertensive arteriosclerosis may be divided clinically and
to some extent pathologically into chronic (benign) and ac-
celerated (malignant) types.
Chronic (benign) hypertension affects all arteries and arte-
rioles. In the large elastic arteries it causes changes indistin-
guishable from those of atherosclerosis; in arterioles it causes
hyaline arteriolosclerosis; in muscular arteries it causes
thickening of the media due to increased amounts of col-
lagen, elastic tissue, smooth muscle cells, and fibroblasts (Fig.
2-4). Malignant hypertension is characterized by hyperplastic
arteriolar changes that often are accompanied by fibrinoid
necrosis of the vessel wall (Fig. 2-5).
Monckeberg medial calcific sclerosis is an age-related de-
generative process in which the media of large and medium-
sized muscular arteries undergoes calcification (Fig. 2-6). It
has little or no clinical significance.
A
B
A
B
Fig. 2-I. Hyaline arteriolosclerosis. A, Thickened arterioles in
kidney of a diabetic man appear homogeneously pink. B, Splenic
arterioles in an elderly nondiabetic man.
Fig. 2-2. Hyperplastic arteriolosclerosis. A, The lumen of the
arteriole is narrowed due to concentric proliferation of smooth
muscle cells in the vessel wall ("onionskin lesion"). B, Arterioles
have narrow lumen due to layers of fibrous tissue.
33
Fig. 2-3. Systemic sclerosis. The vessels show hyperplastic
changes and narrowing of the lumen.
Fig. 2-4. Hypertensive change in muscular arteries. The arterial
wall is thickened and contains increased amounts of collagen and
elastic tissue.
A B
Fig. 2-S. Fibrinoid necrosis. A, The wall of the arteriole is infiltrated with fibrin and
appears magenta red. B, Immunofluorescence microscopy shows deposits of fibrin in the
vessel wall.
Fig. 2-6. Monckeberg medial calcific sclerosis. Media of this
elastic artery shows a discrete area of calcification.
Fig. 2-7. Fatty streaks in the aorta of an adolescent boy.
Fig. 2-8. Fatty streak. The intima contains fat-laden foam cells
that stain with oil red O.
Fig. 2-10. Atheroma. It contains yellow, porridge-like material.Fig. 2-9. Severe atherosclerosis of aorta.
Fig. 2-I I. Atherosclerosis. Atheroma consists of amorphous
cellular debris and cholesterol crystals walled off by fibrous
tissue.
Fig. 2-12. Atherosclerotic aneurysm. Ulcerated atheromas are
seen in the aorta above the renal arteries, whereas the lower
aneurysm contains thrombi.
35
Atherosclerosis is a multifactorial disease involving pri-
marily the aorta and itsmajor branches. The earliest
changes, which are considered to be reversible, are fatty dots
and fatty streaks of the intima (Figs. 2-7 and 2-8). These
changes lead to diffuse intimal thickening followed by ec-
centric intimal thickening and ultimately to formation of fi-
brous plaques. Atheromatous plaques, the typical lesions of
atherosclerosis, consist of an irreversibly altered softened
central area filled with cholesterol crystals and cell debris
( "atheroma") surrounded by collagenous fibrous tissue
(Figs. 2-9, 2-10, and 2-11). Weakening of the arterial wall
may lead to aneurysm formation, often complicated by
thrombosis (Fig. 2-12).
ANEURYSMS
An aneurysm is a dilatation of the aorta or any other major
artery. Atherosclerotic aneurysms most often are located in the
abdominal aorta. Atherosclerosis, especially if it is combined
with hypertension, predisposes to the formation of dissecting
aneurysms of the aorta (Fig. 2-13). Hypertension combined
with cystic medial necrosis may lead to the formation of dis-
secting aneurysms even in the absence of atherosclerosis (Fig.
2-14). Atherosclerosis of the splenic artery leads to forma-
tion of cirsoid aneurysms (Fig. 2-15). Berry aneurysms are re-
lated to a defect in the muscle layer of cerebral arteries (Fig.
2-16). Syphilitic aneurysms are a consequence of infection
with Treponema pallidum. They typically occur in the tho-
racic aorta (Fig. 2-17).
Fig. 2-13. Dissecting aneurysm of the thoracic aorta. The blood
has filled the space formed by the forcible separation of intima
and media of the aorta.
Fig. 2-14. Dissecting aneurysm of the aorta. Layers of the aortic
wall are loose and have been separated by blood.
Fig. 2-I5. Cirsoid aneurysm of splenic artery. The calcified
blood vessels appear serpentine.
Fig. 2-16. Berry aneurysm of the circle of Willis (arrow).
Fig. 2-17. Syphilitic aneurysm. A, The aortic arch is dilated.
B, Intima has a "tree-bark" appearance.
B
A
VASCULITIS
Vasculitis, or inflammation of blood vessels, may be caused
by infections or may be immune mediated (Table 2-1).
Infection-induced vasculitis is an inflammation caused by
invasion of the vessel wall by pathogens. Pathogens can gain
entry into the vessel wall from outside (i.e., through exten-
sion of infection from the perivascular tissue) or from inside
(i.e., from the blood). Fungal vasculitis is a common com-
plication of pneumonia caused by Aspergillus or Rhizopus in
which these fungi invade the pulmonary arteries and veins
from outside. Fungal meningitis can spread to the cerebral
vessels (Fig. 2-18).
Hematogenous dissemination of viruses, bacteria, or
fungi during sepsis or by means of infected thromboemboli
is a common cause of infectious vasculitis. Viruses are con-
sidered to cause granulomatous vasculitis of the central ner-
vous system (Fig 2-19). Rickettsia have a predilection for the
endothelial cells of capillaries, postcapillary venules, arteri-
oles, and to a lesser extent small arteries (Figs. 2-20 and 2-21).
Aortic lesions typical of tertiary syphilis are caused by a ten-
dency of Treponema pallidum to cause inflammation of vasa
vasorum of the aorta (Fig. 2-22). Injury of these small nu-
trient vessels of the aorta results in scarring of media, weak-
ening of vessel wall, and aneurysm formation (see Fig. 2-17).
Fig. 2-18. Fungal vasculitis. Histoplasma capsulatum has invaded
the meningeal arteries.
Fig. 2-19. Granulomatous giant cell vasculitis of cerebral
arteries. This patient had a herpes zoster virus infection.
37
Types of Vasculitis Categorized on the Basis of Proposed Pathogenic Mechanisms
Direct Infection of Vessels
Bacterial vasculitis (such as neisserial)
Mycobacterial vasculitis (such as tuberculous)
Spirochetal vasculitis (such as syphilitic)
Rickettsia) vasculitis (such as Rocky Mountain spotted fever)
Fungal vasculitis (such as aspergillosis)
Viral vasculitis (such as herpes zoster)
I mmunologic Injury
Immune complex-mediated vasculitis
Henoch-Schonlein purpura
Cryoglobulinemic vasculitis
Lupus vasculitis
Rheumatoid vasculitis
Serum sickness vasculitis
Infection-induced immune-complex vasculitis
Viral (such as hepatitis B and C)
Bacterial (such as group A streptococci)
Paraneoplastic vasculitis
Behcet disease
Some drug-induced vasculitides (e.g., sulfonamide-induced vasculitis)
Direct antibody attack-mediated vasculitis
Goodpasture syndrome (anti-collagen IV)
Kawasaki disease (possibly mediated by antiendothelial antibodies)
Antineutrophil cytoplasmic autoantibody-mediated vasculitis
Wegener granulomatosis
Microscopic polyangiitis (microscopic polyarteritis)
Churg-Strauss syndrome
Some drug-induced vasculitides (such as thiouracil-induced vasculitis)
Cell-mediated vasculitis
Allograft cellular vascular rejection
Unknown
Giant cell (temporal arteritis)
Takayasu arteritis
Polyarteritis nodosa
Behcet disease
Fig. 2-20. Rocky Mountain spotted fever. Infection with
Rickettsia ricketsii causes segmental necrosis, inflammation, and
thrombosis in small blood vessels.
Fig. 2-21. Rocky Mountain spotted fever. Immunofluorescence
microscopy performed on this skin biopsy specimen demon-
strates dotlike Rickettsia ricketsii in the wall of small dermal
vessels.
A B
Fig. 2-22. Syphilitic aortitis. A, Treponema pallidum infection caused infiltrate around vasa
vasorum composed of lymphocytes and plasma cells. B, The media of the aorta shows focal loss
of elastic fibers and scarring caused by ischemia.
Immune-mediated Vasculitis
Vasculitis may be caused by antibody-mediated and cell-
mediated mechanisms elicited by a variety of antigens. The
causative antigens cannot be identified in many cases and the
exact pathogenesis of many lesions is only partially under-
stood. For practical reasons it is best to classify vasculitides
in three groups according to the type of blood vessel involved:
(1) large vessel vasculitis, (2) medium-sized vessel vasculitis,
and (3) small vessel vasculitis (Diagram 2-1).
Takayasu arteritis involves the aorta and its major
branches. Histologically it presents as a granulomatous in-
flammation, causing necrosis and disruption of the media
(Fig. 2-23). The infiltrate typically contains multinucleated
giant cells.
Diagram 2-I. Vasculitis clinical syndromes. (Modified from Jennette JC et al: Arthritis Rheum
37:187, 1994.)
Fig. 2-23. Takayasu arteritis. Destruction of the media of the
aorta is a consequence of a granulomatous inflammation. The
infiltrate contains multinucleated giant cells.
Fig. 2-24. Kawasaki disease. Right lateral view of the heart of an
infant who died of Kawasaki disease. There is pronounced
thickening and immense prominence of all coronary arteries due
to a combination of ectasia and intimal thickening, as well as
adventitial fibrosis.
39
Fig. 2-25. Polyarteritis nodosa. A small subcutaneous artery
shows focal fibrinoid necrosis and transmural inflammation
extending into the perivascular tissue.
Fig. 2-26. Polyarteritis nodosa. The pancreatic artery forms an
aneurysm that is filled with a thrombus.
Fig. 2-28. Henoch-Schinlein purpura. Small dermal vessels
are infiltrated with IgA as demonstrated by immunofluorescence
microscopy in this slide stained with antibodies to IgA.
Fig. 2-27. Small vessel vasculitis. Dermal venules show signs
of leukocytoclastic vasculitis.
Kawasaki disease often involves coronary arteries, causing
segmental mural necrosis and acute inflammation. Such le-
sions predispose to thrombosis, vascular ectasia, and aneu-
rysm formation (Fig. 2-24).
Polyarteritis nodosa is a necrotizing inflammation of
medium-sized or small arteries (Fig. 2-25). Destruction of
the vessel wall often leads to formation of microaneurysms
(Fig. 2-26).
Henoch-Schonlein purpura ( HSP) and drug-induced vas-
culitis are examples of small vessel vasculitis, typically in-
volvingpostcapillary venules, capillaries, and arterioles (Fig.
2-27). In HSP this leukocytoclastic vasculitis typically is as-
sociated with a deposition of immunoglobulin A (IgA) in the
wall of small vessels (Fig. 2-28).
Further Reading
Jennette JC, Falk RJ, Andrassy K et al: Nomenclature of systemic vas-
culitides: proposal of an international consensus conference.
Arthritis Rheum 37:187-201, 1994.
Klima T, Spjut HJ, Coelho A et al: The morphology of ascending aortic
aneurysms. Hum Pathol 14:810-817, 1983.
Ledford DK: Immunologic aspects of vasculitis and cardiovascular dis-
ease. JAMA 278:1962-1971, 1997.
Lie JT: Histopathologic specificity of systemic vasculitis. Rheum Dis
Clin NAm 21:883-909, 1995.
Parums DV: The arteritides. Histopathology 25:1-20, 1994.
Pretre R, von Segesser LK: Aortic dissection. Lancet 349:1461-1464,
1997.
Ross R: Rous-Whipple Award Lecture. Atherosclerosis. A defense
mechanism gone awry. Am J Pathol 143:987-1002, 1993.
Stary HC, Chandler AB, Dinsmore RE et al: A definition of advanced
types of atherosclerotic lesions and a histological classification
of atherosclerosis. A report of the Committee on Vascular Lesions
of the Council on Atherosclerosis, American Heart Association.
Circulation 92:1355-1374, 1995.
I NFLAMMATORY LESIONS
Inflammation of the upper respiratory tract may present as
isolated rhinitis, sinusitis, pharyngitis, or laryngitis, or as a
combined upper respiratory tract inflammation. These
pathologic processes can be caused by infectious agents, most
often by common respiratory viruses, and by bacteria or al-
lergies. The pathologic findings in such conditions are banal
and nondiagnostic. Uncommon infections such as nasal in-
fection caused byKlebsiella rhinoscleromatis (Fig. 3-1) orRhi-
nosporidium seeberi (Fig. 3-2) produce more distinct tissue
changes, which can be recognized in biopsy specimens.
Allergy is a common cause of rhinitis, which usually pre-
sents as "hay fever " or rhinorrhea ( "runny nose " ). Chronic
inflammation may result in the formation of nasal polyps.
Histologically nasal polyps represent edematous mucosa in-
filtrated with inflammatory cells, especially eosinophils and
plasma cells, and dilated vessels (Fig. 3-3). Occasionally the
stroma of nasal polyps may contain atypical stromal cells
with dysplastic or bizarre nuclei. Such changes usually are
found in polyps with ulcerated surface epithelium, and it is
important not to mistake them for malignancy.
Inflammation may be caused by chronic strain or irrita-
tion, or by foreign material. For example, chronic laryngitis
may be seen in professional speakers or singers (Fig. 3-4).
Myospherulosis is a form of inflammation related to packing
of nasal cavities with gauze that contains petroleum jelly
(Fig. 3-5).
A
B
C D
Fig. 3-1. Rhinoscleroma. A, Granulation tissue is seen in the nasal cavity. (Courtesy of Dr. M.
Fred, Houston, Texas.) B, CT scan of paranasal sinus in 43-year-old man with rhinoscleroma.
Right nasal cavity and posterior wall of left maxillary sinus are involved. C, Nasal biopsy showing
numerous foamy histiocytes (Mikulicz cells). D, Slides stained with Warthin-Starry stain show
numerous intracellular coccobacilli corresponding to Klebsiella rhinoscleromatis.
43
A B
Fig. 3-2. Rhinosporidiosis. A, The inflamed nasal mucosa contains round sporangia of Rhino-
sporidium seeberi. B, Sporangium filled with spores and surrounded by multinucleated giant cells.
Fig. 3-3. Nasal polyp. The edematous stroma contains scattered
bizarre cells between the dilated blood vessels.
Fig. 3-4. Chronic laryngitis. As seen through the laryngoscope,
the lesion appears as thickening of vocal cords. (Courtesy of Dr.
V. Kambic, Ljubljana, Slovenia.)
Fig. 3-5. Myospherulosis. The central sac, containing a
multinucleated foreign body giant cell and a cluster of sporelike
bodies representing altered erythrocytes, is surrounded by
chronic inflammatory cells and fibrous tissue.
BENIGN TUMORS AND RELATED
CONDITIONS
Benign tumors of the upper respiratory tract are mostly of
epithelial origin and present as papillomas or nodules pro-
jecting into the lumen. They also may be located inside the
wall of each organ or may cause focal thickening, which
cannot be distinguished with certainty without biopsy from
nonneoplastic nodules inflammatory lesions, cysts, and
masses such as amyloidoma. Nonepithelial tumors are less
common.
Papillomas most often originate from nasal or laryngeal
epithelium. Nasal papillomas, which are also known as
schneiderian papillomas, are of three histologic types: (1) ex-
ophytic (fungiform), (2) endophytic (inverted), and (3) on-
cocytic (cylindrical cells). Exophytic and endophytic papil-
lomas together account for 95 percent of all nasal lesions (Fig.
3-6). These papillomas are lined by basaloid cells that occa-
sionally show squamous differentiation, which may spare
isolated mucin-containing respiratory cells as "microcysts"
(Fig. 3-7). There is no reliable way to histologically predict
recurrence, which occurs in 30 percent to 60 percent of sur-
gically treated patients. Laryngeal papillomas are lined by
nonkeratinizing squamous epithelium. Multiple papillomas
are usually found in preschool children. These lesions typi-
cally contain human papilloma virus type 6 and 11.
Juvenile nasopharyngeal angiofibroma is a benign mes-
enchymal tumor restricted to adolescent boys and young
men (Fig. 3-8). Histologically these tumors are composed of
gaping, irregular vessels surrounded by fibrous stroma
(Fig. 3-9).
Vocal cord nodules and solitary laryngeal polyps of adults
are common nonneoplastic tumefactions related to strain
and abuse of voice (Fig. 3-10). These lesions represent edema
of connective tissue, which often contains hyaline material
that should not be confused with amyloid (Fig. 3-11).
Fig. 3-6. Schneiderian papilloma. The tumor involves the nasal
cavity extending onto the septum and lateral wall. (Courtesy of
Dr. R. Sirota, Oak Park, IL.)
A B
Fig. 3-7. Schneiderian papilloma. A, The tumor is exophytic but focally it shows features of an
inverted papilloma. B, Proliferation of monotonous, bland, basaloid cells with a few clear spaces
("microcysts") representing mutinous cell remnants.
45
Fig. 3-8. Juvenile nasopharyngeal angiofibroma. As viewed
through the nasal speculum, the mass filling the nasal cavity
shows prominent surface vascularity.
Fig. 3-9. Juvenile nasopharyngeal angiofibroma. The irregularly
shaped, dilated, thin-walled vessels are surrounded by
fibroblastic cells.
Fig. 3-10. Bilateral polypoid nodules of vocal cords. (Courtesy
of Dr. V. Kambic, Ljubljana, Slovenia.)
Fig. 3-I I. Vocal cord nodule ("singer's node"). The polypoid
mass consists of edematous, hyalinized stroma covered by an
intact epithelium.
MALIGNANT TUMORS
Malignant tumors of the upper respiratory tract are mostly
of epithelial origin and histologically represent squamous
cell carcinomas.
Nasal tumors, which are usually found in elderly men, typ-
ically present as mass lesions or nonbleeding ulcers, which
may require radical surgery such as nasal amputation (Fig.
3-12). Histologically these tumors show prominent kera-
tinizations and tend to invade the underlying tissues.
Olfactory neuroblastoma is a rare but important nasal
tumor. It may show typical features of neuroblastoma of
other sites such as fibrillary stroma; alternatively, it may pre-
sent as a poorly differentiated small cell tumor (Fig. 3-13).
Both variants stain with antibodies to neurofila:nents and
S-100 protein, and also paradoxically with antibodies to
keratin.
Nasopharyngeal carcinoma accounts for 85 percent of all
malignant tumors of this site. Three histologic subtypes are
A B
Fig. 3-12. Squamous cell carcinoma of the nasal vestibule. A, The friable exophytic and invasive
tumor. B,Invasive squamous cell carcinoma of the nasal vestibule encroaching on the hyaline
cartilage of the septum.
A B
Fig. 3-13. Olfactory neuroblaStoma. A, Nests of tumor cells beneath the epithelium. B, The
tumor is composed of small cells surrounded focally by fibrillar stroma.
WHO Histologic Classification of
Nasopharyngeal Carcinoma
Squamous cell carcinoma
Keratinization or intercellular bridges or both
Nonkeratinizing carcinoma
Defined cell borders, pavement like pattern
Undifferentiated carcinoma
Syncytial growth, large polygonal cells or spindle-shaped cells,
prominent nucleoli, lymphoid stroma
Fig. 3-14. Nasopharyngeal carcinoma. The tumor is composed
of polygonal cells with vesicular nuclei enclosed in a sea of
lymphocytes.
47
Fig. 3-I5. Keratinizing intraepithelial dysplasia of larynx.. Such
lesions are often aneuploid even though they show some degree
of "surface maturation" into keratinized squamous cells.
Fig. 3-16. Squamous cell carcinoma of the larynx. Laryngectomy
specimen showirig recurrent carcinoma of the right vocal cord.
A
Fig. 3-17. A, Vertical section through a carcinoma localized to
the true vocal cord. False cord and ventricle are free of tumor.
B, Vertical section through a supraglottic squamous carcinoma.
The true cord is involved.
recognized (Table 3-1). The undifferentiated carcinoma,
which occurs as a large polygonal cell tumor or as a spindle-
shaped cell tumor, accounts for 60 percent to 80 percent of
all tumors (Fig. 3-14). Tumor cells are surrounded by lym-
phocytes, which accounts for the fact that these tumors pre-
viously were called lymphoepitheliomas.
Carcinoma of the larynx is a squamous cell carcinoma in
95 percent of patients. It may begin as squamous cell dys-
plasia or carcinoma in situ (Fig. 3-15). Invasive carcinomas
show variable degrees of keratinization (Figs. 3-16 and 3-17).
Further Reading
Abbondanzo SL, Wenig BM: Non-Hodgkin's lymphoma of the sino-
nasal tract. A clinicopathologic and immunophenotypic study of
120 cases. Cancer 75:1281-1291, 1995.
Compagno J, Hyams VJ: Hemangiopericytoma-like intranasal tumors.
A clinicopathologic study of 23 cases. Am J Clin Pathol 66:672-683,
1976.
Devaney K, Wenig BM, Abbondanzo SL: Olfactory neuroblastoma and
other round cell lesions of the sinonasal region. Mod Pathol 9:658-
663, 1996.
Franquemont DW, Mills SE: Sinonasal malignant melanoma. A clini-
copathologic and immunohistochemical study of 14 cases. Am J
Clin Pathol 96:689-697, 1991.
Heffner DK, Gnepp DR: Sinonasal fibrosarcomas, malignant schwan-
nomas, and "Triton" tumors. A clinicopathologic study of 67 cases.
Cancer 70:1089-1101, 1992.
Helliwell TR: "Risky" epithelium of the larynx-a practical diagnosis?
Histopathology 34:262-265, 1999.
Helquist H, Cardesa A, Gale Net al: Criteria for grading in the Ljubljana
classification of epithelial hyperplastic laryngeal lesions. A study by
members of the Working Group on Epithelial Hyperplastic Laryn-
geal Lesions of the European Society of Pathology. Histopathology
34:226-233, 1999.
Lloreta-Trull J, Mackay B, Troncoso Petal: Neuroendocrine tumors of
the nasal cavity. An ultrastructural and morphometric study of 24
cases. Ultrastruct Pathol 16:165-175, 1992.
Michaels L: Benign mucosal tumors of the nose and paranasal sinuses.
Sem Ding Pathol 13:113-117, 1996.
Slavin RG: Nasal polyps and sinusitis. JAMA 278:1849-1854, 1997.
B
DEVELOPMENTAL ANOMALIES
The respiratory system develops as a derivative of the prim-
itive foregut. It is therefore not surprising that developmental
anomalies involving one system are accompanied by abnor-
malities in the other. The most important of these conjoined
anomalies is tracheoesophageal fistula ( Diagram 4-1), which
may be associated with abnormal or incomplete develop-
ment of trachea or tracheal agenesis. Bronchial anomalies in-
clude abnormal branching patterns, abnormalities in size,
abnormal connections with other structures, and cartilage
plate abnormalities.
Bronchogenic cyst develops from an accessory fetal lung
bud that becomes isolated from the rest of the tracheo-
bronchial tree, producing a solitary midline cyst lined by
bronchial epithelium (Figs. 4-1 and 4-2).
Pulmonary anomalies range from minor variations in the
lobar configuration to major developmental defects such as
unilateral pulmonary agenesis or hypoplasia (Fig. 4-3). Pul-
monary hypoplasia has been identified in 10 percent to 15
percent of all neonatal autopsies and in 50 percent of neo-
nates who have other significant congenital anomalies.
Anomalies limited to parts of a lung may remain asympto-
matic until adult life. The most important of these anoma-
lies are congenital cystic adenomatoid malformation and
extralobar bronchopulmonary sequestration or accessory lobe
(Figs. 4-4 and 4-5). So-called intralobar sequestration, which
is mentioned here for the sake of completeness and differ-
ential diagnosis, is considered to be an acquired abnormality
that is caused by recurrent pulmonary inflammation and
scarring (Fig. 4-6).
Fig. 4-I. Bronchogenic cyst. This posterior midline subpleural
cyst was compressing the esophagus, causing only minor
dysphagia.
Fig. 4-2. Bronchogenic cyst. This resected cyst has a rugged
internal surface.
A B C D E
Diagram 4-I. Tracheoesophageal fistulas. Type C malformations account for 85 percent of all
cases.
51
Fig. 4-4. Congenital cystic adenomatoid malformation. This
mass, which is composed of abnormal bronchiolar structures,
consists of a large cyst with several smaller cysts in the
background.
Fig. 4-3. Pulmonary hypoplasia in a neonate.
A B
Fig. 4-5. Congenital cystic adenomatoid malformation. A, The lung is composed of cystic bronchi
and air spaces. B, The wall of the cyst is lined by pseudostratified or tall columnar epithelium
resembling the lining of proximal bronchioli or small bronchi.
A B
Fig. 4-6. Intralobar sequestration. A, The mass consists of markedly dilated bronchi filled with
mucus and surrounded by fibrous tissue. B, Histologically, the mass consists of bronchi and air
spaces lined by cuboidal cells. The interstitium is fibrosed and contains inflammatory cells.
PERINATAL LUNG DISEASES
Failure of the lungs to fully expand and remain expanded is
a common complication of pulmonary immaturity encoun-
tered in neonates who are born preterm. Clinically it presents
as neonatal respiratory distress syndromeor hyaline membrane
disease. The lungs show patchy atelectasis (Fig. 4-7). Histo-
logically pulmonary alveoli are collapsed and atelectatic,
whereas the alveolar ducts are dilated and lined by fibrin-rich
hyaline membranes (Fig. 4-8). Secondary changes such as
intraalveolar hemorrhage, dilatation of bronchioles prox-
imal to atelectatic parenchyma, and dilatation of lymphatics
are common. Resorption of hyaline membranes, i.e., cleanup
by macrophages, begins 48 to 72 hours after birth and is as-
sociated with proliferation of bronchiolar reserve cells.
Oxygen therapy and mechanical ventilation cause additional
changes that cannot be separated from those caused by the
disease itself. Severe hyaline membrane disease that is treated
aggressively may result in development of chronic lung
changes known as bronchopulmonary dysplasia (Fig. 4-9).
Histologically it can be divided sequentially into three over-
lapping phases: (1) early reparative phase, (2) subacute fibro
-
proliferative phase, and (3) chronic fibroproliferative phase.
The process is dominated by organization of hyaline mem-
branes by granulation tissue, ongoing peribronchial fibrosis
and luminal obliteration (bronchiolitis obliterans), and inter-
stitial fibrosis (Fig. 4-10). Pulmonary interstitial air, or pul-
monary interstitial emphysema, which is characterized by the
presence of air in the connective tissue planes of the lungs, is
yet another complicationof treatment of hyaline membrane
disease with ventilatory support (Fig. 4-11).
Neonatal pneumonia typically is a complication of:
(1) transplacental spread of maternal infection, (2) intra-
uterine ascending amniotic fluid infection, (3) intrapartum
infection with microorganisms in the birth canal, or (4) post-
natal airborne infection.
Most neonatal pneumonias are acquired during labor and
delivery. Aspiration of infected amniotic fluid by the fetus ac-
counts for 20 percent to 40 percent of early-onset neonatal
sepsis and pneumonia. The lungs of such neonates contain
amniotic fluid with squamous and inflammatory cells (Fig.
4-12).
Fig. 4-7. Neonatal atelectasis. The atelectatic parenchyma
appears dark red in contrast to the paler areas of normally
aerated lung (right upper corner).
A B
Fig. 4-8. Neonatal respiratory distress syndrome. A, Alveoli are collapsed and the alveolar ducts
and respiratory bronchioli are dilated and lined by hyaline membranes. B, Hyaline membranes
are brown due to staining with meconium.
53
Fig. 4-9. Bronchopulmonary dysplasia. Lungs are in part
consolidated and in part cystic.
A B
Fig. 4-10. A, Bronchopulmonary dysplasia. The alveoli are partially obliterated by ingrown
granulation tissue. B, The lungs are consolidated except for a few cystic and slit-like spaces.
Fig. 4-I I. Pulmonary interstitial air. Air-filled spaces extending
the interlobular septa are seen through the pleura.
Fig. 4-I2. Amniotic fluid aspiration with early pneumonia.
The alveoli contain nucleated squamous cells and scattered
inflammatory cells.
PULMONARY INFECTIONS
Pneumonia, or pulmonary infection, can be classified (1) eti-
ologically, as viral, bacterial, fungal, and so forth; (2) topo-
logically, depending on the gross distribution, as lobar or lob-
ular, focal or diffuse, one-sided or bilateral; (3) histologically,
depending on the distribution of the inflammatory cells, as
intraalveolar or interstitial and characterized by a neutro-
philic, lymphocytic or mixed inflammatory infiltrate.
Bacterial infection presents as lobar or lobular pneumonia
(also known as bronchopneumonia). In lobar pneumonia en-
tire lobes of one or both lungs are involved (Fig. 4-13).
Bronchopneumonia presents in the form of more circum-
scribed infiltrates (Fig. 4-14). These infiltrates are initially
composed of neutrophils and are predominantly inside the
alveoli (Fig. 4-15). Without treatment, consolidation of the
lungs progresses through several phases known as: (1) red
hepatization, in which the lungs appear red due to conges-
tion; (2) gray hepatization, in which the exudate of neutro-
phils and fibrin, combined with reduced blood flow through
the compressed capillaries, imparts a gray color to the lungs;
and (3) resolution phase, in which the exudate is removed and
the air spaces become patent again. In severe cases the abun-
dant fibrin cannot be removed and it stimulates the ingrowth
of granulation tissue into the alveoli (organizing pneumonia)
(Fig. 4-16). Pneumonia caused by Staphylococcus aureus may
result in massive tissue breakdown (Fig. 4-17) and suppura-
tion resulting in abscess formation (Fig. 4-18).
Pulmonary tuberculosis presents with a spectrum of
changes. Primary tuberculosis, which is characterized by a
solitary parenchymal nodule and hilar lymph node involve-
ment, usually heals spontaneously by undergoing fibrosis
and calcification (Fig. 4-19). Secondary tuberculosis results
in widespread dissemination of mycobacteria and the for-
mation of multiple small nodules (miliary tuberculosis), con-
solidation of parenchyma (tuberculous pneumonia), or ex-
tensive destructive lung lesions (cavitary tuberculosis) (Fig.
4-20). Histologically all tuberculous lesions contain granu-
lomas (Fig. 4-21). Similar changes can be caused by fungi
such as Histoplasma capsulatum.
Fig. 4-13. Lobar pneumonia. The entire lung appears
consolidated and the parenchyma is bulging on cross section.
Fig. 4-14. Bronchopneumonia. The lungs appear only focally
consolidated. The infiltrates are peribronchial and appear
distinct from the surrounding parenchyma.
Fig. 4-15. Lobar pneumonia in the stage of gray hepatization.
The alveoli are filled with neutrophils. The alveolar walls are of
normal thickness and do not contain red blood cells.
55
Fig. 4-16. Organizing pneumonia. The alveoli contain abundant
fibrin, which is being organized by inflammatory cells and an
ingrowth of fibroblasts. Fig. 4-17. Necrotizing pneumonia. The exudate is accompanied
by necrosis of alveolar septa. The bluish material represents
bacterial colonies.
Fig. 4-18. Lung abscess. The large subpleural abscess contains
brownish-yellow pus. The surrounding parenchyma appears con-
solidated and contains scattered smaller whitish-yellow abscesses.
Fig. 4-19. Pulmonary tuberculosis. The primary lesion appears
as a sharply demarcated subpleural nodule.
Fig. 4-20. Secondary pulmonary tuberculosis. The parenchyma
and hilar lymph nodes contain numerous, often confluent
tubercles. (Courtesy of Cathy Looby, M.D., Philadelphia, PA.
From Woods CL, Gutierrez Y: Diagnostic pathology of infectious
diseases, Philadelphia, 1993, Lea & Febiger.)
Fig. 4-21. Pulmonary tuberculosis. Granulomas of tuberculosis
consist of lymphocytes, epithelioid macrophages, and
multinucleated giant cells arranged around a central area of
caseating necrosis.
Pneumocystis carinii pneumonia, an opportunistic fungal
infection that occurs in immunocompromised persons, pre-
sents histologically with an acellular intraalveolar exudate
(Fig 4-22). Fungal cysts can be seen in slides impregnated
with silver according to Gomori.
Viral infections cause alveolar cell injury, which is usually
accompanied by a predominantly interstitial mononuclear
cell infiltrate (Fig. 4-23). The alveoli contain well-developed
fibrin-rich hyaline membranes and some edema fluid. In
most instances the causative virus is not visible except in
some infections that are caused by herpes simplex virus 1
( HSV- 1) or cytomegalovirus (CMV). CMV inclusions ap-
pear as basophilic (blue) material in the nucleus and the cyto-
plasm, and are accompanied by enlargement of the infected
cells (Fig. 4-24). Alveolar cell injury caused by viruses such
as influenza or adenovirus produce histologically non-
specific changes. Such changes are indistinguishable from
other forms of diffuse alveolar damage ( DAD).
A B
Fig. 4-22. Pneumocystis carinii pneumonia. A, The alveoli contain proteinaceous acellular floccular
material. B, Pneumocystis carinii cysts are seen in silver-impregnated cytologic smear prepared
. from bronchial brushings.
Fig. 4-23. Viral pneumonia. The alveolar septa are widened.
The alveoli contain edema fluid, fibrin-rich hyaline membranes,
and a few scattered mononuclear cells.
Fig. 4-24. Viral pneumonia caused by the cytomegalovirus
(CMV). Typical intranuclear inclusions are seen in desquamated
pneumocytes, which appear enlarged.
57
PULMONARY CIRCULATORY
DISORDERS
Blood flow through the lungs depends on proper cardiac
function. Acute left heart failure results in passive pulmonary
congestion and intraalveolar hemorrhage. Chronic heart
failure results in brown induration of the lungs.
Circulatory collapse that occurs in shock and multiple
organ failure often is clinically associated with adult respira-
tory distress syndrome (ARDS). Lungs . show signs of diffuse
alveolar damage accompanied by focal atelectasis, intraalve-
olar hemorrhage, and hyaline membrane formation (Fig.
4-25).
Pulmonary Emboli
Pulmonary thromboembolism is one of the leading causes of
death, although it often is clinically unrecognized. Pul-
monary emboli may involve the main pulmonary artery, its
major branches, or small intrparenchymal vessels. Clinically
they may cause sudden death, episodes of dyspnea and
hemoptysis, or only