1

Introduction to Pathology

OUTLINE
Disease Hemorrhage Disorders of Immunity
Inflammation Alterations of Cell Growth Infectious Disease Exposure
Edema Neoplasia Acquired Immunodeficiency
Ischemia and Infarction Hereditary Diseases Syndrome

KEY TERMS
abscess epidemiology mutations
acquired immunodeficiency etiology neoplasia
syndrome (AIDS) grading nosocomial
active immunity granulation tissue oncology
anaphylactic hematogenous spread permeable
anaplastic hematoma personal protective equipment
antibodies hemorrhage prognosis
antigens hereditary diseases pyogenic
asymptomatic hyperplasia recessive
atrophy iatrogenic sarcomas
autosomes idiopathic signs
bacteremia immune staging
benign infarct Standard Precautions
cancers inflammation symptoms
carcinomas ischemia syndrome
community acquired lymphatic spread toxoid
diagnosis malignant Transmission-Based Precautions
dominant metastasize undifferentiated
dysplasia morbidity vaccine
edema mortality

OBJECTIVES
After reading this chapter, the reader will be able to: • Differentiate inflammation, edema, infarction,
• Classify the more common diseases in terms of their hemorrhage, and neoplasia
attenuation of x-rays • Characterize the various alterations of cell growth
• Explain the changes in technical factors required for • Describe the various immune reactions of the body
obtaining optimal quality radiographic images in patients • Describe AIDS and the precautions necessary when
with various underlying pathologic conditions taking a radiograph of patients with AIDS or any patient
• Define and describe all boldface terms in this chapter with whom contact with any body fluid is possible
(Standard Precautions)

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2 CHAPTER 1 Introduction to Pathology

DISEASE RADIOGRAPHER NOTES

Pathology is the study of diseases that can cause abnormali- Radiography of patients with underlying pathologic condi-
tions can present problems for even the most experienced
ties in the structure or function of various organ systems. In
radiographers. Adjustments in patient position may be
essence, a disease is the pattern of the body’s response to some
necessary to prevent excessive pain caused by the body’s
form of injury that causes a deviation from or variation of nor- response to trauma or certain disease processes. A change
mal conditions. Diseases may be hereditary or may result from in routine projections may be indicated to visualize subtle
a broad spectrum of traumatic, infectious, vascular, or meta- alterations in the normal imaging appearance. Many disease
bolic processes manifesting as a set of characteristics known as processes also alter the density of the structures being
signs and symptoms. Signs represent the measurable or objec- radiographed and therefore require changes in technique.
tive manifestations of the disease process. The experiences the For example, extensive edema may require an increased
patient feels and describes are the symptoms, those (subjective) technique, whereas severe atrophy may require a decreased
manifestations that are not measurable or observable. A patient technique. Unless the radiographer has access to previous
showing no evidence of diseases is considered asymptomatic. images with recorded exposure factors, a standard tech-
nique chart should be used to determine the initial expo-
Symptoms may reflect alterations of cell growth, as in neopla-
sures. Any necessary adjustments can then be made on
sia (tumors), or may even be caused by physicians and their
subsequent images.
treatment (iatrogenic). Imaging modalities are used to assist Box 1-1 lists the relative attenuation of x-rays that can be
in making a diagnosis, the precise disease process affecting the expected in advanced stages of various disease processes.
patient. To best treat a disease process, it is important to dis- In chest radiography, 110 to 125 kilovolts peak (kVp) is opti-
cover its underlying cause, known as the etiology. If the under- mal; therefore, milliampere-second (mAs) factors should be
lying cause is unknown, the disease is termed idiopathic. Once adjusted to control density. In skeletal radiography, when
the specific diagnosis and etiology are confirmed, the physician bone quality changes are expected, the best exposure
offers a prognosis, which describes the expected patient out- factor to change is the kilovolt peak (beam quality change
come. A condition characterized by a group of signs, symp- for structural change). When bone quantity changes, the
toms, and disease processes may be categorized as a syndrome. milliampere-second (mAs) value is the exposure factor
to change to control density (beam quantity increases to
Incidences of the development of infections at the acute
ensure that enough radiation reaches the image receptor
care facility are called nosocomial, whereas infections that
without changing the contrast). For example, in osteoporo-
develop outside the healthcare facility are known as commu- sis there is a decrease in bone quantity and quality; however,
nity acquired. a decrease in kilovolts produces a higher-quality image. The
This chapter discusses several basic reactions of the body normal kilovolt peak easily penetrates the diseased bone,
that characterize the underlying mechanisms for the radio- producing a low-contrast image with loss of visibility of
graphic manifestations of most pathologic conditions. These detail. As imaging progresses into the digital imaging arena,
processes are inflammation, edema, ischemia and infarction, the same theories apply; however, the processing algorithm
hemorrhage, and alterations of cell growth leading to the will control brightness (density) and contrast. The exposure
development of neoplasms (tumors). In addition, this chap- index (number) will represent the over- or underexposure
ter deals with hereditary diseases and immune reactions, such of the image.
Certain diseases suppress the normal immune response.
as acquired immunodeficiency syndrome (AIDS).
Immunocompromised patients (e.g., those with advanced
leukemia) may require special care to prevent their acquiring
Summary of Terms for Disease a disease from the radiographer. Personal protective equip-
Term Definition ment (PPE) aids in preventing the spread of microorganisms
to the patient and to the healthcare worker. The patient may
Signs Measurable or objective manifestations have to be placed in protective isolation (or “reverse” isola-
Symptoms Feelings that the patient describes— tion), and the radiographer may be required to put on a mask,
subjective manifestations gown, and gloves before approaching the patient. Diseases
Asymptomatic Without subjective or objective such as AIDS and hepatitis require that the radiographer wear
manifestations rubber or latex gloves to be protected against exposure to
Diagnosis Identification of disease process blood and body fluids, which could contaminate any area near
Etiology Study of the cause of the disease process the patient. When examining a patient with AIDS who has a
Idiopathic Underlying cause is unknown productive cough, the radiographer must wear a mask and
Prognosis Probable patient outcome possibly protective eye goggles if there is a need to be very
Syndrome Linked combination of signs and close to the patient’s face. It is important to remember that
symptoms many patients undergoing radiographic procedures have not
Iatrogenic Disease caused by physician or treatment been diagnosed, and thus all patients should be treated as
Nosocomial Infections contracted in the acute care though they may have a communicable disease. Therefore,
infections facility whenever exposure to any type of body secretion or blood
Community- Infections contracted in a public setting may occur, the healthcare worker should wear appropriate
acquired outside of the acute care facility PPE.
infections
 CHAPTER 1 Introduction to Pathology 3

BOX 1-1 Relative Attenuation of X-Rays in Advanced Stages of Diseases

Skeletal System Respiratory System
Additive (Increased Attenuation) Additive (Increased Attenuation)
Acromegaly Actinomycosis
Acute kyphosis Arrested tuberculosis (calcification)
Callus Atelectasis
Charcot’s joint Bronchiectasis
Chronic osteomyelitis (healed) Edema
Exostosis Empyema
Hydrocephalus Encapsulated abscess
Marble bone Hydropneumothorax
Metastasis (osteosclerotic) Malignancy
Osteochondroma Miliary tuberculosis
Osteoma Pleural effusion
Paget’s disease Pneumoconiosis
Proliferative arthritis Anthracosis
Sclerosis Asbestosis
Calcinosis
Destructive (Decreased Attenuation) Siderosis
Active osteomyelitis Silicosis
Active tuberculosis Pneumonia
Aseptic necrosis Syphilis
Atrophy (disease or disuse) Thoracoplasty
Blastomycosis
Carcinoma Destructive (Decreased Attenuation)
Coccidioidomycosis Early lung abscess
Degenerative arthritis Emphysema
Ewing’s tumor (in children) Pneumothorax
Fibrosarcoma
Giant cell tumor Circulatory System
Gout Additive (Increased Attenuation)
Hemangioma Aortic aneurysm
Hodgkin’s disease Ascites
Hyperparathyroidism Cirrhosis of the liver
Leprosy Enlarged heart
Metastasis (osteolytic)
Multiple myeloma Soft Tissue
Neuroblastoma Additive (Increased Attenuation)
New bone (fibrosis) Edema
Osteitis fibrosa cystica
Destructive (Decreased Attenuation)
Osteoporosis/osteomalacia
Emaciation
Radiation necrosis
Solitary myeloma

Even though disease processes increase or decrease the attenuation of the x-rays, it is important to produce a quality image to demonstrate
the change in attenuation. Excessive variation of the technical exposure factors may obscure the pathophysiologic changes due to the disease
process.
From Thompson TT: Cahoon’s formulating x-ray techniques, ed 9, Durham, NC, 1979, Duke University Press.

Inflammation inflammation. As hyperemia develops, the venules and cap-

Acute inflammation is the initial response of body tissues to illaries become abnormally permeable, allowing passage of
local injury. The various types of injury include those caused protein-rich plasma across vessel walls into the interstitium.
by blunt or penetrating trauma, infectious organisms, and This inflammatory exudate in the tissues results in the swell-
irritating chemical substances. Regardless of the underlying ing associated with inflammation, which produces pressure
cause, the inflammatory response consists of four overlap- on sensitive nerve endings and causes pain. The protein-rich
ping events that occur sequentially (Box 1-2). exudate of inflammation must be differentiated from a tran-
The earliest bodily response to local injury is dilation sudate, a low-protein fluid such as that seen in the pulmonary
of arterioles, capillaries, and venules, leading to a dramatic edema that develops in congestive heart failure.
increase in blood flow in and around the injury site. This Very early in the inflammatory response, leukocytes (white
hyperemia produces the heat and redness associated with blood cells, especially neutrophils and macrophages) of the
4 CHAPTER 1 Introduction to Pathology

BOX 1-2 Events That Occur in leads to the production of a thick, yellow fluid called pus,
Inflammatory Response which contains dead white blood cells, inflammatory exu-
date, and bacteria. A suppurative inflammation is one that
1. Alterations in blood flow and vascular permeability is associated with pus formation. When a pyogenic infec-
2. Migration of circulating white blood cells to the interstitium
tion occurs beneath the skin or in a solid organ, it produces
of the injured tissue
an abscess, a localized, usually encapsulated, collection of
3. Phagocytosis and enzymatic digestion of dead cells and
tissue elements
pus. All pyogens, wherever they become implanted, have
4. Repair of injury by regeneration of normal parenchymal the ability to invade blood vessels to produce bacteremia,
cells or proliferation of granulation tissue and eventual scar with the potential involvement of other organs and tissues
formation in the body.
A granulomatous inflammation manifests as a distinct
pattern seen in relatively few diseases, including tuberculo-
circulating blood migrate to the area of injury. These white sis, syphilis, and sarcoidosis. A granuloma is a localized area
blood cells cross the capillary walls into the injured tissues, of chronic inflammation, often with central necrosis. It is
where they engulf and enzymatically digest infecting organ- characterized by the accumulation of macrophages, some of
isms and cellular debris, a process called phagocytosis. which fuse to form multinucleated giant cells.
The removal of necrotic debris and any injurious agents,
such as bacteria, makes possible the repair of the injury that
triggered the inflammatory response. In many tissues, such Summary of Terms for Inflammatory Process
as the lung after pneumococcal pneumonia, regeneration of
Term Definition
parenchymal cells permits reconstitution of normal anatomic
structure and function. However, some tissues, such as the Inflammation Initial response of the tissue to
heart after myocardial infarction, cannot heal by regeneration. local injury
A fibrous scar replaces the area of destroyed tissue with gran- Permeable Allows fluids/cells to pass from
ulation tissue. Granulation tissue refers to a combination of membrane one tissue to another tissue or
location
young developing capillaries and actively proliferating fibro-
Granulation tissue Fibrous scar replaces
blasts, which produce connective tissue fibers (collagen) that
destroyed tissue
replace the dead tissue. Eventually, the strong connective tis- Pyogenic bacteria Thick, yellow fluid called pus
sue contracts to produce a fibrous scar. In the abdomen, such (dead white cells)
fibrous adhesions can narrow loops of intestine and result in Abscess Localized, usually encapsulated,
an obstruction. The accumulation of excessive amounts of col- collection of fluid
lagen (more common in African Americans) may produce a Bacteremia Potential involvement of other
protruding, tumor-like scar known as a keloid. Unfortunately, organs and tissues in the body
surgery to remove a keloid is usually ineffective because the by organisms invading the
subsequent incision tends to heal in the same way. blood vessels
Many injuries heal by a combination of regeneration and
scar tissue formation. An example is the response of the liver
to repeated and persistent alcoholic injury; the result is cir- Edema
rhosis, in which irregular lobules of regenerated liver cells Edema is the accumulation of abnormal amounts of fluid
are crisscrossed and surrounded by bands of scar tissue. Scar in the intercellular tissue spaces or body cavities. Localized
tissue formation consists of fibrous connective tissue, which edema results from an inflammatory reaction, whereas
can be divided into primary union (surgical incision) and generalized edema occurs with pronounced swelling of
secondary union (nonsurgical; gunshot wound). subcutaneous tissues throughout the body (anasarca).
The five clinical signs of acute inflammation are rubor Localized edema may result from inflammation, with the
(redness), calor (heat), tumor (swelling), dolor (pain), and escape of protein-rich intravascular fluid into the extra-
loss of function. The localized heat and redness result from vascular tissue. It may also result from a local obstruction
increased blood flow in the microcirculation at the site of to lymphatic drainage; for example, in filariasis, a para-
injury. The swelling occurs because the exudate increases the sitic worm causes lymphatic obstruction, and the result-
amount of interstitial fluid, resulting in pressure on nerve ing localized edema is termed elephantiasis. Generalized
endings and thus pain, which results in a loss of function. edema occurs most frequently in patients with congestive
Acute inflammation can also lead to systemic manifes- heart failure, cirrhosis of the liver, and certain forms of
tations. Fever is especially common in inflammatory con- renal disease. Because of the effect of gravity, generalized
ditions associated with the spread of organisms into the edema is usually most prominent in dependent portions of
bloodstream. The number of circulating white blood cells the body. Thus, ambulatory patients tend to accumulate
also increases (leukocytosis). fluid in tissues around the ankles and lower legs, whereas
Some bacterial organisms (e.g., staphylococci and strep- in hospitalized patients who are nonambulatory or sed-
tococci) produce toxins that damage the tissues and incite an entary, the edema fluid collects most prominently in the
inflammatory response. The presence of pyogenic bacteria lower back, sacral areas, and lungs.
 CHAPTER 1 Introduction to Pathology 5

Extravascular fluid can also accumulate in serous cavities

to produce pleural and pericardial effusions and peritoneal
ascites. Edema may produce minimal clinical symptoms or be
potentially fatal. If localized to the subcutaneous tissues, large
amounts of edema may cause minimal functional impair-
ment. In contrast, pulmonary edema, pericardial e­ ffusion, or
edematous swelling of the brain may have dire consequences.

Summary of Terms for Edema A

Term Definition
Edema Accumulation of abnormal amounts of
fluid in the intercellular tissue spaces or
body cavities
Anasarca Generalized edema that occurs with
pronounced swelling of subcutaneous
tissues throughout the body
Elephantiasis Localized lymphatic obstruction resulting
in localized edema

Ischemia and Infarction

Ischemia refers to an interference with the blood supply to
an organ or part of an organ, depriving the organ’s cells and
tissues of oxygen and nutrients. Ischemia may be caused by
a narrowing of arterial structures, as in atherosclerosis, or by
thrombotic or embolic occlusion (Figure 1-1). Depending on
several factors, occlusion of an artery or vein may have little or
no effect on the involved tissue, or it may cause death of the B
tissue and even of the individual. A major determinant is the
availability of an alternative or newly acquired route of blood
supply (collateral vessels). Other factors include the rate of
development of the occlusion, the vulnerability of the tissue to
hypoxia, and the oxygen-carrying capacity of the blood. Slowly
developing occlusions are less likely to cause tissue death
(necrosis) because they provide an opportunity for the devel-
opment of alternative pathways of flow. Ganglion cells of the
nervous system and myocardial muscle cells undergo irrevers-
ible damage if deprived of their blood supply for 3 to 5 min- FIGURE 1-1 Computed tomography (CT) scan of pulmo-
utes. Anemic or cyanotic patients tolerate arterial insufficiency nary embolism. (A) Filling defect in both the right and the
less well than normal individuals do, and thus occlusion of left pulmonary arteries (saddle type), and (B) a blockage (fill-
even a small vessel in such a patient may lead to death of tissue. ing defect) nearly complete on the right.
An infarct is a localized area of ischemic necrosis within a tis-
sue or organ produced by occlusion of either its a­ rterial supply Infarctions tend to be especially severe because they occur
or its venous drainage. The two most common clinical forms more often in the patients least able to withstand them. Thus,
of infarction are myocardial and pulmonary. Almost all infarcts infarcts tend to occur in elderly individuals with advanced
result from thrombotic or embolic occlusion. Infrequent causes atherosclerosis or impaired cardiac function and are more
include twisting of an organ (volvulus), compression of the blood likely to occur after surgery or delivery.
supply of a loop of bowel in a hernia sac, or trapping of a viscus
under a peritoneal adhesion. Hemorrhage
In cases in which ischemia continues to progress, result- The term hemorrhage implies rupture of a blood vessel. Rupture
ing in an infarction, necrosis may occur as a result of lack of of a large artery or vein is almost always caused by some form of
blood flow. This progressive situation can lead to a condition injury, such as trauma, atherosclerosis, or inflammatory or neo-
called gangrene. Severe arterial disease of the lower extremi- plastic erosion of the vessel wall. Hemorrhage may be external,
ties may result in necrosis of several toes or a large segment of or the blood may be trapped within body tissues, resulting in an
the foot, causing gangrene. A frequent presenting symptom accumulation termed a hematoma (Figure 1-2). The accumula-
in diabetic patients is ischemia of the foot, which may pro­ tion of blood in a body cavity results in hemothorax, hemoperi-
gress to infarction and result in gangrene. cardium, hemoperitoneum, or hemarthrosis (blood in a joint).
6 CHAPTER 1 Introduction to Pathology

Alterations of Cell Growth

Changes in the number and size of cells, their differentiation,
and their arrangement may develop in response to physi-
ologic stimuli. Atrophy refers to a reduction in the size or
number of cells in an organ or tissue, with a corresponding
decrease in function. It must be distinguished from hypo-
plasia and aplasia, in which failure of normal development
accounts for small size.
An example is the disuse atrophy that occurs with immo-
bilization of a limb by a plaster cast. The muscle mass of
the encased limb reduces dramatically. Because the cast
also removes the stress and strain from the enclosed bone

Summary of Terms for Alterations of

Cell Growth
Term Definition
Atrophy Reduction in the size or number of
cells in an organ or tissue, with a
corresponding decrease in function
Hypertrophy Increase in the size of the cells of a
tissue or organ in response to a
FIGURE 1-2 Subdural hematoma. Concave appearance of demand for increased function
increased attenuation on the left causing midline shift of the Hyperplasia Increase in the number of cells in a
ventricles. tissue or organ
Dysplasia Loss of uniformity of individual cells and
Minimal hemorrhages into the skin, mucous membranes, or their architectural orientation
serosal surfaces are called petechiae; slightly larger hemorrhages Neoplasia Ungoverned abnormal proliferation of
are termed purpura. A large (>1 to 2 cm) subcutaneous hema- cells
toma, or bruise, is called an ecchymosis. Oncology Study of neoplasms (tumors)
The significance of hemorrhage depends on the volume Benign Growth that closely resembles the cells of
of blood loss, the rate of loss, and the site of the hemorrhage. origin in structure and function
Malignant Neoplastic growth that invades and
Sudden losses of up to 20% of the blood volume or slow
destroys adjacent structures
losses of even larger amounts may have little clinical signif- Metastasize Malignant neoplasms that travel to
icance. The site of the hemorrhage is critical. For example, distant sites
an amount of bleeding that would have little clinical signif- Carcinoma Malignant neoplasm of epithelial cell
icance in the subcutaneous tissues may cause death when origin
located in a vital portion of the brain. Large amounts of Anaplastic Undifferentiated cell growth—without
external bleeding lead to the chronic loss of iron from the form (bizarre)
body and anemia. In contrast, internal hemorrhages into Sarcoma Highly malignant tumor originating from
body cavities, joints, or tissues permit the iron to be recap- connective tissue
tured for the synthesis of hemoglobin and the development Lymphatic Major route by which carcinoma
of normal red blood cells. spread metastasizes
Hematogenous Malignant tumors that have invaded
spread the circulatory system and travel as
neoplastic emboli
Summary of Terms for Blood Vessels Grading Assessment of aggressiveness or
degree of malignancy
Term Definition Staging (1) Extensiveness of tumor at the
Ischemia Interference of blood supply to an organ; primary site
deprives cells and tissues of oxygen (2) Presence or absence of metastases to
and nutrients lymph nodes and distant organs
Infarct Localized area of ischemic necrosis; Epidemiology Study of determinants of disease events
produced by occlusion of either arterial in given populations
supply or venous drainage Morbidity Rate that an illness or abnormality
Hemorrhage Implies rupture of a blood vessel occurs
Hematoma Accumulation of blood trapped within Mortality Reflects the number of deaths by
body tissues disease per population
 CHAPTER 1 Introduction to Pathology 7

that normally stimulates new bone formation, normal bone

resorption continues unchecked and the loss of calcified
bone can be detected on radiographs. In this situation, there
is rapid recovery from the atrophic appearance when the cast
is removed and normal function is resumed.
Pathologic, irreversible atrophy may be caused by loss of
innervation, by hormonal stimulation, or by decreased blood
supply. For example, stenosis of a renal artery may cause
atrophy of the kidney with shrinkage of individual nephrons A
and loss of interstitial tissue.
Hypertrophy refers to an increase in the size of the cells
of a tissue or organ in response to a demand for increased
function. This must be distinguished from hyperplasia, an
increase in the number of cells in a tissue or organ (Figure
1-3). Hypertrophy occurs most often in cells that cannot mul-
tiply, especially those in myocardial and peripheral striated
muscle. Myocardial hypertrophy is necessary to maintain car-
diac output despite increased peripheral resistance in patients
with arterial hypertension or aortic valve disease. After the
loss of a normal kidney, hypertrophy of the other kidney
occurs in an attempt to continue adequate renal function.
Examples of hyperplasia include: (1) proliferation of gran-
ulation tissue in the repair of injury and (2) the increased B
cellularity of bone marrow in patients with hemolytic ane-
mia or after hemorrhage. Hyperplasia of the adrenal cortex
is a response to increased adrenocorticotropic hormone
(ACTH) secretion; hyperplasia of the thyroid gland occurs
with increased thyrotropic hormone secretion by the pitu-
itary gland. FIGURE 1-3 Infantile cortical hyperostosis (Caffey’s dis-
Dysplasia is a loss in the uniformity of individual cells and ease). Affected bones demonstrate cortical thickening with
their architectural orientation; it is typically associated with new periosteal bone formation bilaterally on the femurs (A)
prolonged chronic irritation or inflammation. Removal of and tibias (B) (arrows).
the irritant may result in a return to normal, but often the
tissue change persists, and it may evolve into a totally abnor-
mal growth pattern. Thus, dysplasia is generally considered at Nevertheless, some benign tumors can have severe con-
least potentially premalignant—a borderline lesion that may sequences because of their position or hormonal secretion.
heal or progress to cancer. For example, a benign pituitary tumor can cause pressure
atrophy and destruction of the surrounding gland, and a
Neoplasia benign tumor of the islets of Langerhans in the pancreas
Neoplasia, from the Latin word for “new growth,” refers to can produce excessive amounts of insulin, resulting in
an abnormal proliferation of cells that are no longer con- possibly fatal low levels of blood glucose. Other poten-
trolled by the factors that govern the growth of normal cells. tially dangerous benign tumors include those arising in
Neoplastic cells act as parasites, competing with normal cells the brain or spinal cord, which may influence central ner-
and tissues for their metabolic needs. Thus, tumor cells may vous system function. Tumors of the trachea or esopha-
flourish and the patient becomes weak and emaciated, a con- gus may occlude the air supply or make it impossible to
dition termed cachexia. swallow.
Neoplasms are commonly referred to as tumors; indeed, Malignant neoplasms invade and destroy adjacent struc-
the study of neoplasms is called oncology, derived from the tures and spread to distant sites (metastasize), causing death.
Greek word oncos, meaning “tumor.” Although the word Malignancies tend to be poorly differentiated so that it may
tumor originally referred to any swelling, which could also be be impossible to determine the organ from which they origi-
produced by edema or hemorrhage in tissue, the word now nate. Malignant tumors are collectively referred to as cancers.
refers almost exclusively to a neoplasm. This term is derived from the Latin word for “crab,” possibly
Neoplasms are divided into benign and malignant catego- because the finger-like projections that extend into underly-
ries on the basis of their potential clinical behavior. Benign ing tissue resemble crablike claws.
tumors closely resemble their cells of origin in structure and All tumors, both benign and malignant, have two basic
function. They remain localized, without spreading to other components: (1) the parenchyma (organ tissue), made up
sites, and thus can usually be surgically removed with resul- of proliferating neoplastic cells, and (2) the supporting
tant survival of the patient. stroma (supporting tissue), made up of connective tissue,
8 CHAPTER 1 Introduction to Pathology

to grow slowly, whereas bizarre, undifferentiated neoplasms

have a rapid growth rate.
Although the cause of cancer is still unknown, many pos-
sible causative factors (carcinogens) have been implicated.
Chemical carcinogens may cause structural alteration of the
deoxyribonucleic acid (DNA) molecule (mutation), which
may lead to the development of a neoplasm. Examples of
chemical carcinogens include air and water pollution, ciga-
rette smoke, asbestos, and a variety of other substances used
in industry, food, cosmetics, and plastics. The development
of specific types of cancer in certain families suggests a pos-
sible genetic predisposition. Excessive exposure to ultravio-
let radiation (sunshine) may lead to the development of skin
cancer. Survivors of the atom bomb who received huge doses
FIGURE 1-4 Enchondroma. A lobulated area with increased
of radiation have demonstrated a high incidence of leukemia.
bone density in the supra-acetabular region on the right side A greater-than-expected rate of leukemia was also seen in
(arrow). persons working with x-radiation before the need for proper
protection was appreciated.
The study of experimental animal tumors has offered
convincing evidence that DNA and ribonucleic acid (RNA)
blood vessels, and possibly lymphatic vessels. The paren- viruses can induce neoplastic transformation. Viruses that
chyma of the neoplasm largely determines its biologic invade normal cells may alter their genetic material, leading
behavior and is the component that determines how the to the abnormal cell divisions and rapid growth observed in
tumor is named. malignant tumors.
Most benign tumors consist of parenchymal cells that The clinical symptoms of cancer vary with the site of
closely resemble the tissue of origin. Their names come malignancy. A blood-tinged stool, a change in bowel
from adding the suffix -oma to the cell type from which the activity (e.g., intermittent constipation and diarrhea),
tumor arose. For example, benign tumors of fibrous tissue or intestinal obstruction is suggestive of gastrointestinal
are termed fibromas, whereas benign cartilaginous tumors malignancy. Difficulty in swallowing (dysphagia) or loss
are chondromas (Figure 1-4). The term adenoma is applied of appetite (anorexia), especially if accompanied by rapid
to benign epithelial neoplasms that grow in glandlike pat- weight loss, suggests a neoplasm in the esophagus or stom-
terns. Benign tumors that form large cystic masses are ach. Hematuria may indicate kidney or bladder cancer,
called cystadenomas. Lipomas consist of soft fatty tissue, whereas difficulties in urination (e.g., urgency, a burning
myomas are tumors of muscle, and angiomas are tumors sensation, or an inability to start the stream of urine) in an
composed of blood vessels. An epithelial tumor that grows elderly man may be a sign of prostate tumor. Hemopty-
as a projecting mass on the skin or from an inner mucous sis (coughing up blood), a persistent cough, or hoarseness
membrane (e.g., the gastrointestinal tract) is termed a pap- may suggest a neoplasm in the respiratory tract. Severe
illoma or a polyp. anemia may develop from internal bleeding or from mal-
Malignant neoplasms of epithelial cell origin are called function of the bone marrow caused by growth of a malig-
carcinomas, from the Greek word karkinos, meaning “crab.” nant lesion in the skeleton.
Carcinomas affect epithelial tissues, skin, and mucous mem- It should be stressed that these clinical symptoms may also
branes lining body cavities. Adenocarcinoma refers to malig- be caused by benign disease. Nevertheless, because they may
nancies of glandular tissues, such as the breast, liver, and signal an underlying malignancy, they should be carefully
pancreas, and of the cells lining the gastrointestinal tract. investigated to exclude the presence of cancer.
Squamous cell carcinoma denotes a cancer in which the tumor Pain is frequently not an early sign of cancer. Unfortu-
cells resemble stratified squamous epithelium, as in the lung nately, pain may be appreciated only when the malignancy
and head and neck regions. At times, the tumor grows in such has spread too extensively to be curable. Secondary infections
a bizarre pattern that it is termed undifferentiated or ana- are common and an increasing cause of death. Most cancer
plastic (without form). patients are immunologically compromised, either because
Sarcomas are highly malignant tumors arising from con- of their original disease or as a result of irradiation or che-
nective tissues, such as bone, muscle, and cartilage. Although motherapy. In addition to having typical bacterial and viral
they are less common than carcinomas, sarcomas tend to infections, immunocompromised patients with malignancy
spread more rapidly. are especially susceptible to unusual opportunistic infections,
Substantial evidence exists indicating that most tumors such as Pneumocystis jirovecii (formerly Pneumocystis carinii)
arise from a single cell (monoclonal origin). The rate of pneumonia and cytomegalovirus.
growth generally correlates inversely with the level of paren- Some cancers that are still at a curable stage can be
chymal differentiation. Thus, well-differentiated tumors tend detected by screening procedures. Routine mammography
 CHAPTER 1 Introduction to Pathology 9

may identify nonpalpable breast cancer; a Papanicolaou the presence or absence of metastases to lymph nodes and
(Pap) smear may show otherwise unsuspected cancer of the distant organs, such as the liver, lungs, and skeleton. The
cervix. Surgical removal of these small tumors without meta- staging of a tumor aids in determining the most appro-
static spread offers an excellent prognosis. priate therapy. Well-localized tumors without evidence
Malignant neoplasms disseminate to distant sites by one of metastases may be surgically removed. Fast-growing,
of three pathways: (1) seeding within body cavities, (2) lym- undifferentiated tumors, such as those found in patients
phatic spread, and (3) hematogenous spread. with Hodgkin’s disease, may respond best to radiation
Seeding (diffuse spread) of cancers occurs when neo- therapy. Cancer of the prostate responds to hormonal ther-
plasms invade a natural body cavity. For example, a tumor apy, which consists of either the removal of the sources of
of the gastrointestinal tract may penetrate the wall of the male gonadal hormones that stimulate tumor growth or
gut (visceral peritoneum), permitting metastases to enter the administration of the female gonadal hormone (estro-
the peritoneal cavity and implant at distant sites. A sim- gen) that inhibits it. Chemotherapy uses one or a combi-
ilar sequence may occur with lung cancers in the pleural nation of cytotoxic substances that kill neoplastic cells, but
cavity. Neoplasms of the central nervous system (medullo- these drugs may injure many normal cells and result in sig-
blastoma and ependymoma) may spread from the cerebral nificant complications.
ventricles by means of the cerebrospinal fluid to reimplant Upon determination of the type of neoplastic involve-
on the meningeal surfaces within the brain or in the spinal ment, a study of determinants is compiled for the specific
cord. disease in a given population, which is called epidemiology.
Lymphatic spread is the major metastatic route of carci- Using epidemiology and the grading of the neoplasms then
nomas, especially those of the lung and breast. The pattern of becomes part of establishing morbidity. Morbidity is the rate
lymph node involvement depends on the site of the primary that an illness or abnormality occurs. Depending on the stage
neoplasm and the natural lymphatic pathways of drainage of of the tumor, mortality is calculated by reviewing the pop-
that region. Carcinomas of the lung metastasize first to the ulation involved to statistically calculate the expected death
regional bronchial lymph nodes and then to the tracheobron- rate. These factors will be taken into consideration when the
chial and hilar nodes. Carcinoma of the breast usually arises best course of treatment for the patient is being determined.
in the upper outer quadrant and first spreads to the axillary
nodes. Medial breast lesions may drain through the chest wall
to nodes along the internal mammary artery.
HEREDITARY DISEASES
The hematogenous spread of cancer is a complex pro- Hereditary diseases pass from one generation to the next
cess involving several steps. Tumor cells invade and pen- through the genetic information contained in the nucleus of
etrate blood vessels, traveling as neoplastic emboli in the each cell. They reflect an abnormality in the DNA, which pro-
circulation. These emboli of tumor cells are trapped in small vides the blueprint for protein synthesis in the cell. In many
vascular channels of distant organs, where they invade the hereditary diseases, an error in a single protein molecule leads
wall of the arresting vessel and infiltrate and multiply in the to enzyme defects; membrane receptor and transport system
adjacent tissue. The localization of hematogenous metasta- defects; alterations in the structure, function, or quantity of
ses tends to be determined by the vascular connections and nonenzyme proteins; and unusual drug reactions.
anatomic relationships between the primary neoplasm and The most common hereditary abnormality is an enzyme
the metastatic sites. For example, carcinomas arising in deficiency. This leads to a metabolic block that results either
abdominal organs, such as the gastrointestinal tract, tend in a decreased amount of a substance needed for normal
to metastasize to the liver because of the flow of portal vein function or in an accumulation of a metabolic intermediate
blood to that organ. Cancers arising in midline organs close that may cause injury. An example of the first mechanism
to the vertebral column (e.g., prostate and thyroid) tend to is albinism, the absence of pigmentation resulting from
embolize through the paravertebral venous plexus to seed an enzymatic deficiency that prevents the synthesis of the
the vertebral column. Neoplasms in organs drained by the pigment melanin. An example of the second mechanism
inferior and superior vena cava, such as the kidney, tend is phenylketonuria, in which the absence of an enzyme
to metastasize to the lung. However, several well-defined leads to the accumulation of toxic levels of the amino acid
patterns of metastatic spread cannot be easily explained by phenylalanine.
vascular–anatomic relationships. Some examples are the A defect in the structure of the globin molecule leads to
tendency for carcinoma of the lung to involve the adrenal the development of the hemoglobinopathies, such as sickle
glands, simultaneous metastatic deposits in the brain and cell disease and thalassemia. An example of a genetically
adrenal glands, and pituitary metastases occurring from determined adverse reaction to drugs is glucose 6-phosphate
breast carcinomas. dehydrogenase deficiency, in which an insufficient amount
The grading of a malignant tumor assesses aggressive- of the enzyme results in a severe hemolytic anemia in patients
ness, or degree of malignancy. The grade of a tumor usually receiving a common antimalarial drug.
indicates its biologic behavior and may allow prediction of Despite our extensive knowledge of the biochemical
its responsiveness to certain therapeutic agents. Staging basis of many genetic disorders, there are a large number
refers to the extensiveness of a tumor at its primary site and of conditions for which the underlying mechanism is still
10 CHAPTER 1 Introduction to Pathology

unknown. This list includes neurofibromatosis, retinoblas-

toma, and familial colonic polyposis (see Chapter 5). Each
human cell contains 46 chromosomes divided into 23 pairs.
The chromosomes in turn contain thousands of genes, each
of which is responsible for the synthesis of a single protein.
Forty-four of the chromosomes are called autosomes; the
other two are the X and Y chromosomes, which determine
the sex of the person. A combination of XY chromosomes
results in a male, whereas an XX configuration results in a
female.
Each person inherits half of his or her chromosomes
from each parent. If the genes inherited from each parent
are the same for a particular trait, the person is homozy-
gous for that trait. If the genes differ (e.g., one for brown
eyes and one for blue eyes), the person is heterozygous for
that trait. Dominant genes always produce an effect regard-
less of whether the person is homozygous or heterozygous;
recessive genes manifest themselves only when the person is
homozygous for the trait. In determining eye color, brown
is dominant, whereas blue is recessive. It must be remem-
bered that although a recessive trait must have been con-
tributed by both parents, the possibility exists that neither
parent demonstrates that trait. For example, two parents,
each with one gene for brown eyes and one gene for blue
eyes, would show the dominant brown coloration, although
they could each contribute a blue-eye gene to their offspring,
who would manifest the recessive blue-eye trait.
For some traits, the genes are codominant so that both FIGURE 1-5 Polydactyly. Right foot image with seven meta-
are expressed. An example is the AB blood type, in which the tarsals and eight digits.
gene for factor A is inherited from one parent and that for
factor B is inherited from the other. average, siblings have a one-in-four chance of being affected;
Mutations are alterations in the DNA structure that two out of four will be carriers of the gene, and one will be
may become permanent hereditary changes if they affect normal. Recessive genes appear more frequently in a family,
the gonadal cells. Mutations may result from radiation, and close intermarriage (as between first cousins) increases
chemicals, or viruses. They may have minimal effect and the risk of the particular disease. Unlike in autosomal domi-
be virtually undetectable or may be so serious that they nant diseases, the expression of the defect tends to be uniform
are incompatible with life, causing the death of a fetus and in autosomal recessive diseases and the age of onset is fre-
spontaneous abortion. quently early in life. Examples of autosomal recessive disor-
Autosomal dominant disorders are transmitted from ders are phenylketonuria (see Chapter 12), cystic fibrosis (see
one generation to the next. These disorders affect females Chapter 3), galactosemia, glycogen and lipid storage diseases
and males, and both can transmit the condition. When (see Chapter 12), Tay–Sachs disease, and sickle cell anemia
an affected person marries an unaffected person, half the (see Chapter 9).
children (on average) will have the disease. The clinical Sex-linked disorders generally result from defective genes
manifestations of autosomal dominant disorders can be on the X chromosome because the Y chromosome is small
modified by reduced penetrance and variable expressivity. and carries very few genes. Most of these conditions are trans-
Reduced penetrance means that not everyone who has the mitted by heterozygous female carriers virtually only to sons,
gene will demonstrate the trait; variable expressivity refers who have only the single, affected X chromosome. Sons of a
to the fact that a dominant gene may manifest somewhat heterozygous woman have a one-in-two chance of receiving
differently in different individuals (Figure 1-5) (e.g., poly- the mutant gene. An affected man does not transmit the dis-
dactyly may be expressed in the toes or in the fingers as one order to his sons, but all his daughters carry the genetic trait.
or more extra digits). Examples of autosomal dominant dis- In rare cases, a female may have the sex-linked disease if she
orders include achondroplasia (see Chapter 4), neurofibro- is homozygous for the recessive gene. Virtually all sex-linked
matosis, Marfan’s syndrome (see Chapter 12), and familial disorders are recessive. The most common example of a sex-
hypercholesterolemia. linked disorder is color blindness. Other conditions are glu-
Autosomal recessive disorders result only when a person is cose 6-phosphate dehydrogenase deficiency and some types
homozygous for the defective gene. The trait does not usually of hemophilia (see Chapter 9) and muscular dystrophy (see
affect the parents, although siblings may show the disease. On Chapter 12).
 CHAPTER 1 Introduction to Pathology 11

Summary of Terms for Hereditary Diseases mast cells release histamine, which causes a local increase
in vascular permeability and smooth muscle contraction.
Term Definition Disorders resulting from localized reactions of this type
Hereditary Genetic information contained in the (which probably have a genetically determined predis-
process nucleus of each cell passed to the position) include hay fever, asthma, and gastrointestinal
next generation allergies. Generalized, or systemic, anaphylactic reac-
Autosomes 44 chromosomes other than X and Y tions are characterized by hypotension and vascular col-
Dominant gene Always produces an effect lapse (shock) with urticaria (hives), bronchiolar spasm,
Recessive gene Manifests when a person is homozy-
and laryngeal edema. This reaction causes sudden death
gous for the trait
Mutation Alteration in the DNA structures that
in patients who are hypersensitive (“allergic”) to the sting
may become permanent hereditary of bees, wasps, and other insects and to medications, such
change as penicillin and the iodinated contrast materials used in
radiology.
In the second type of immune reaction, called a cytotoxic
reaction, either the antigen is a component of a cell or it attaches
DISORDERS OF IMMUNITY to the wall of red blood cells, white blood cells, platelets, or
The immune reaction of the body provides a powerful vascular endothelial cells. The reaction with an antibody leads
defense against invading organisms by allowing it to rec- to cell destruction by lysis or phagocytosis. Examples of a
ognize foreign substances (antigens), such as bacteria, cytotoxic immune reaction include the transfusion reaction
viruses, fungi, and toxins, and to produce antibodies to occurring after the administration of ABO-incompatible
counteract them. The antibody binds together with the blood, and erythroblastosis fetalis, the hemolytic anemia of
antigen to make the antigen harmless. Once antibodies the Rh-positive newborn whose Rh-negative mother has pro-
have been produced, a person becomes immune to the duced anti-Rh antibodies.
antigen. The third type of immune reaction, a delayed reaction,
Antibodies, or immunoglobulins, form in lymphoid occurs in an individual previously sensitized to an antigen.
tissue, primarily in the lymph nodes, thymus gland, and As an example, the first time a person touches poison ivy,
spleen. Although an infant has some immunity at birth, no reaction occurs. However, on the next exposure to poi-
most immunity is acquired either naturally by exposure son ivy, antibodies are present to attack the antigen, and
to a disease or artificially by immunization. There are two the patient develops the typical rash and irritation. A sim-
types of artificial immunity: active and passive. In active ilar process produces a reaction to tuberculosis, leprosy,
immunity, a person forms antibodies to counteract an many fungal diseases, and other infections. This process
antigen in the form of a vaccine or a toxoid. A vaccine also represents the principal component of rejection in
consists of a low dose of dead or deactivated bacteria or organ transplants.
viruses. Although these organisms cannot cause disease,
they are foreign proteins containing antigens that stimu-
late the body to produce antibodies against them. A toxoid
INFECTIOUS DISEASE EXPOSURE
is a chemically altered toxin, the poisonous material pro- Working in the healthcare environment means that expo-
duced by a pathogenic organism. As with a vaccine, the sure to infectious microorganisms will occur. To minimize
toxin cannot cause disease but does trigger the develop- exposure, all healthcare workers should follow the Centers
ment of antibodies. Examples of active immunity are the for Disease Control and Prevention’s (CDC) Standard
vaccines given to prevent smallpox, polio, measles, teta- Precautions. Exposure to blood-borne pathogens such
nus, and diphtheria. Active immunity persists for a long as human immunodeficiency virus (HIV) and hepatitis
time, although a relatively long time is required to build up B virus (HBV) can be minimized for all persons involved
immunity, and a booster shot frequently gives a stronger with the use of the appropriate personal protective equip-
effect. ment (PPE). The CDC recommends that all such persons
Passive immunity refers to the administration of a dose be considered potentially infected and that Standard Pre-
of preformed antibodies from the immune serum of an ani- cautions be applied when they are delivering health services
mal, usually a horse. This type of immunity acts immediately to every patient. In cases of highly transmissible pathogens,
but lasts for a relatively short time. It is used in situations additional precautions are necessary; Transmission-Based
in which a person is exposed to a serious disease (hepatitis, Precautions should be used for persons with pathogens
rabies, and tetanus) but has no immunity against it and thus transmissible by contact, droplet, or through air (airborne).
requires an immediate supply of antibodies to prevent a pos- Each healthcare facility is responsible for administering
sibly fatal infection. the precautions; educating, training, and monitoring its
Several fundamental mechanisms of immunologic employees; and providing a protective environment. Every
responses to antigens exist. The first type is a rapidly healthcare worker must take personal responsibility to help
occurring reaction in which antigens are attacked by anti- contain the infectious process in the work environment by
bodies previously bound to the surface of mast cells. The following CDC standards.
12 CHAPTER 1 Introduction to Pathology

Summary of Terms for Immunity Disorders

Term Definition
Antigens Foreign substance that evokes an
immune response
Antibodies Immunoglobulins responding to the
antigens to make them harmless
Immune Protected against antigens;
antibodies binding with antigens
to make them harmless
Active immunity Forming antibodies to counteract
an antigen by way of vaccine or
toxoid
Vaccine Contact with dead or
deactivated microorganisms to
form antibodies
Toxoid Treated toxin with antigenic power
to produce immunity by creating
antibodies
Anaphylactic Hypersensitive reaction resulting in
reaction a histamine release FIGURE 1-6 Kaposi’s sarcoma. Small bowel study shows
Standard Protection used when multiple intramural nodules (predominantly involving the jeju-
Precautions delivering healthcare services to num) that distort the mucosal pattern and produce contour
any person defects and intraluminal lucencies.
Personal protective PPE—gowns, gloves, masks, shoe
equipment covers, and eye protection used to
prevent transmission of potential Gastrointestinal manifestations of AIDS include a variety
infectious agents of sexually transmitted diseases involving the rectum and
Transmission- Additional protective equipment to colon, infectious processes (e.g., shigellosis, amebiasis, can-
Based prevent the spread of highly infec- didiasis, and giardiasis), and alimentary tract dissemination
Precautions tious pathogens through contact, (spread) of Kaposi’s sarcoma. Kaposi’s sarcoma, a systemic
droplet, or airborne transmission
disease, characteristically affects the skin and causes an ulcer-
ated hemorrhagic dermatitis. Metastases to the small bowel,
which are relatively common, consist of multiple reddish or
ACQUIRED IMMUNODEFICIENCY SYNDROME bluish red nodules that intrude into the lumen of the bowel
Acquired immunodeficiency syndrome (AIDS), which most (Figure 1-6). Similar lesions can develop throughout the gas-
commonly affects young homosexual men and intravenous trointestinal tract. Central ulceration of the metastases causes
drug abusers, is characterized by a profound and sustained gastrointestinal bleeding and a characteristic radiographic
impairment of cellular immunity that results in recurrent or appearance of multiple “bull’s-eye” lesions simulating met-
sequential opportunistic infections and a particularly aggres- astatic melanoma.
sive form of Kaposi’s sarcoma. AIDS has also been reported Approximately 40% of all AIDS victims have neurologic
in a substantial number of hemophiliac patients, in recipients symptoms, most commonly progressive dementia. Patients
of transfusions, and increasingly in heterosexual partners of with mass lesions of the brain commonly have focal neuro-
affected individuals. AIDS is attributable to infection with logic symptoms and signs.
retroviruses (RNA viruses) known as human immunodefi- Imaging appearance. The typical early radiographic find-
ciency viruses (HIV). This immune deficiency predominantly ing of P. jirovecii pneumonia is a hazy, perihilar, granular
involves the lungs, gastrointestinal tract, and central nervous infiltrate that spreads to the periphery and appears predom-
system. Pulmonary infections are extremely common in inantly interstitial. In later stages, the pattern progresses to
patients with AIDS and are frequently caused by organisms patchy areas of air-space consolidation with air broncho-
that only rarely produce disease in individuals with normal grams, indicating the alveolar nature of the process (Figure
immune systems. Approximately 60% of AIDS victims expe- 1-7). The radiographic appearance may closely resemble that
rience one or more attacks of P. jirovecii pneumonia, which of pulmonary edema or bacterial pneumonia.
is characterized by a sudden onset, a rapid progression to dif- Magnetic resonance imaging (MRI) best demonstrates
fuse lung involvement, and a considerable delay in resolution. the multiple manifestations of AIDS in the central nervous
The fungus cannot be cultured, and the disease is usually fatal system, where areas of increased signal intensity can be seen
if untreated. An open-lung biopsy is often necessary to make on T2-weighted images. Atypical brain abscesses and menin-
the diagnosis if a sputum examination reveals no organisms geal infection often occur, most commonly related to toxo-
in a patient in whom this disease is suspected. plasmosis, cryptococcosis, cytomegalovirus, and herpesvirus
 CHAPTER 1 Introduction to Pathology 13

(Figure 1-8). Increasing evidence indicates that cerebral

infections may manifest from the HIV itself. Patients with
AIDS also have a high incidence of lymphoma involving the
central nervous system.
Treatment. Although much research has been initiated, no
cure for AIDS has been found. Currently, treatment assists in
maintaining quality of life and managing symptoms as they
manifest. Antiviral drugs help suppress the HIV infection.
A healthy lifestyle free of stress, alcohol, and illegal drugs
is recommended. An HIV carrier should avoid infections if
possible because they may accelerate the HIV process.

FIGURE 1-7 Pneumocystis jirovecii pneumonia. Diffuse

bilateral air-space consolidation is suggestive of severe bac-
terial pneumonia or pulmonary edema.

A B

FIGURE 1-8 Neurologic manifestations of AIDS. (A) Computed tomography (CT) scan shows
multiple ring-enhancing lesions caused by cryptococcal brain abscesses. (B) MRI, after intrave-
nous administration of contrast medium, demonstrates multiple enhancing abscesses caused by
toxoplasmosis.