Pathophysiology (2)

(MBS 253)
Lecture 13

Oncology Disorders
Textbook ;Pathophysiology for the
Health Professions, 4th edition, 2011
Prof.Dr. eitedal fouda
 Lung cancer
• The most common cause of cancer-related death in men and women
• Definition ;Uncontrolled growth of abnormal cells in one or both of
the lungs. This growth may lead to metastasis
• The lungs are a common site of both primary and secondary lung
cancer.
– Secondary metastatic cancer develops frequently in the lungs
because the venous return and lymphatics bring tumor cells from
many distant sites in the body to the heart and then into the
pulmonary circulation, which provides the first small blood vessels
and hospitable environment in which tumor cells can lodge
• Benign lung tumors are rare.
• Women are more develop lung cancer and die of it than are men.
• There is a higher incidence in black men than white men.
• Almost 90% of lung cancers are related to smoking.
 Lung cancer
Pathophysiology
• More than 90% of lung cancer originate from the
epithelium of bronchus.
– Bronchogenic carcinoma, arising from the bronchial
epithelium, is the most common type of malignant lung
tumor
• They slowly grow ,takes 8-10 years, for a tumor to
reach 1 cm in size
• Types of lung cancer
– Non Small Cell lung cancer(most common -80-85%)--
NSCLC
– Small cell or “oat cell” carcinomas – (15-20 % of all lung
cancers)--SCLC
 Lung cancer
Small cell or “oat cell” carcinomas (less
common ,15-20 % of all lung cancers)—SCLC
• Made of small, round cells
– a rapidly growing type of lung cancer
– often located near a major bronchus in the
central part of the lung.
– They tend to be invasive and metastasize very
early in their development.
 Lung cancer
• Non Small Cell lung cancer (most common -80-
85%)--NSCLC
– Squamous cell carcinoma ;arise from bronchial
epithelium, found in the center near the hilum and
project into the airway.
– Adenocarcinomas (majority arises from bronchial
mucus gland), often found in an outer area of the
lung. MOST COMMON
– Large cell carcinomas are usually found in the
periphery and consist of undifferentiated large cells
that have a rapid growth rate and metastasize early,
less symptomatic and more difficult to detect in the
early stages.
 Lung cancer
• The first change in the lungs is usually metaplasia, a change in the
epithelial tissue, which is reversible if the irritation ceases.
– The loss of normal protective, ciliated, pseudostratified epithelium
leaves the lung tissue more vulnerable to irritants and
inflammation
– Various chemicals in cigarette smoke are carcinogenic and act as
initiators and promoters.
• Dysplasia or carcinoma in situ then develops.
– cigarette smoking causes a change from ciliated columnar
epithelium to squamous cell epithelium.
• The alterations in the respiratory mucosa as it changes through
metaplasia to dysplasia demonstrate the cell mutations caused by
carcinogens and could perhaps lead to earlier diagnosis.
• Cancerous lung tissue cannot exchange oxygen &carbon dioxide ,it
impairs the functioning of the lung
• Etiology: risk factors ‫ﻣﮭﻢ اذﻛﺮي واﺣﺪ او اﺛﻨﯿﻦ‬
• Cigarette smoking is the major factor in its development and
“Second- hand smoke” in the environment
– The risk of developing cancer is higher in persons who begin
smoking early, persist for many years, and are considered heavy
smokers (i.e, they smoke more than a pack per day).
• A genetic factor involved that also influences the cellular changes
• Chronic obstructive pulmonary disease (COPD), also associated
with smoking
• Occupational or industrial exposure to carcinogens such as silica,
vinyl chloride, or asbestos ,especially if cigarette smoking is also
present in an occupationally exposed individual.
• Any irritant such as smoke leads to chronic inflammation and
frequent infections in the respiratory tract, which in turn cause
cellular changes.
 Lung cancer
Signs and symptoms
• The onset of lung cancer is insidious because the early signs
of cancer are often masked by signs of the predisposing
factor, such as a “smoker’s cough.”
• In many cases, the cancer has already metastasized before
diagnosis, and the signs of a metastatic tumor lead to
diagnosis.
• There are four possible categories of signs of lung cancer:
(1) those related to the direct effects of the tumor on the
respiratory structures;
(2) those representing the systemic effects of cancer;
(3) those caused by associated paraneoplastic syndromes; and
(4) Those resulting from metastatic tumors at other sites.
 Lung cancer
1. Early signs related to respiratory involvement include: ‫ﻣﺎﺷﺮﺣﺘﮭﺎ‬
• Persistent productive cough, dyspnea, and wheezing
• Detection on a chest x-ray taken when an individual develops pneumonia or
other complications
• Hemoptysis, when tumors erode tissue
• Pleural involvement, which may lead to pleural effusion, pneumothorax, or
hemothorax
• Chest pain, occurring with advanced tumors that involve the pleura or
mediastinum
• Hoarseness (laryngeal nerve compression), facial or arm edema and headache
(compression of the superior vena cava), dysphagia (compression of the
esophagus), or atelectasis, caused by large tumors or involved lymph nodes
2. Systemic signs of lung cancer include weight loss, anemia, and fatigue.
3. Paraneoplastic syndrome is indicated by the signs of an endocrine disorder
related to the specific hormone secreted, mainly with small cell lung cancer
4. Signs of metastases depend on the site. (bone and brain)
For example, metastatic bone cancer would be indicated on a bone scan and be
manifested by bone pain or pathologic fracture.
 Lung cancer
Tumors in the lungs have many effects or complications: ‫ﻣﺎﺷرﺣﺗﮭﺎ‬
• Obstruction of airflow by tumor growth into a bronchus causes abnormal
breath sounds and dyspnea.
• Inflammation surrounding the tumor stimulates a cough and predisposes
to secondary infection. Frequent infections may occur because secretions
pool distal to the tumor.
• Pleural effusion, hemothorax, pneumothorax, or combination of these is
common with tumors located on the lung periphery owing to inflammation
or erosion of the pleural membrane.
• Paraneoplastic syndrome may accompany bronchogenic carcinoma when
the tumor cell secretes hormones or hormone-like substances such as
antidiuretic hormone (ADH) or adrenocorticotropic hormone (ACTH).
ü The endocrine effects may complicate both diagnosis and treatment.
ü This syndrome may include neuromuscular disturbances or hematologic
disorders such as disseminated intravascular coagulation (DIC)
 Diagnostic tests of Lung cancer
• CT scans and MRI are more effective in early diagnosis than chest x-
rays, which demonstrate later lesions and complications such as
atelectasis or pleural effusion.
• Bronchoscopy
• Auto fluorescence bronchoscopy,
– this lights up cancer cells and it can show cells that haven't grown into a tumor
yet.
• An Endobronchial Ultrasound helps with the staging of a tumor.
– A bronchoscope is inserted into the lung with an ultrasound on the tip. There is a
slot that houses a needle to biopsy the lymph nodes.
• Mediastinoscopy is useful to check lymph nodes,
• bone scans are used to detect metastasis. These are useful in the
staging process.
• Pulmonary function tests can clarify the effects of the tumor on
airflow.
 Lung cancer
• Treatment
• Radiofrequency ablation (RFA) can be used to destroy
single small tumors .
• Surgical resection or lobectomy may be performed on
localized lesions.
• Chemotherapy and radiation may be used in conjunction
with surgery or as palliative treatment, although many
tumors are not responsive to such therapy.
• Photodynamic therapy (a chemical is injected and migrates
to tumor cells, where it is activated by laser light and
destroys the cancer cells) is sometimes effective.
• The prognosis is poor unless the tumor is in a very early
stage of development.
 Carcinoma of the Breast
• Carcinoma of the breast is a common
malignancy in women and a major cause of
death.
• Rarely breast cancer occurs in males.
• Although the disease may develop any time
after puberty,70% of cases occur in women
older than age 50.
 Carcinoma of the Breast
• Etiology:
• A strong genetic predisposition (specific genes related to breast cancer,
BRCA-1 and BRCA-2.)in 5 % of cases
• Family history of breast cancer
• Non genetic risk factors :
• hormones—specifically, exposure to high estrogen levels.
– early menarche to late menopause, nullipara (no children), nulli-
gravida (never pregnant)and the first pregnancy after age 30,
– predisposing factors:
• prior carcinoma in the uterus or in the other breast, and
• Radiation exposure(particularly in young women).
• Lack of exercise, smoking and a high-fat diet
• Obesity
• Benign breast cancer (fibrocystic disease with atypical hyperplasia ,
proliferation without invasion or metastases)
 Carcinoma of the Breast
Pathophysiology
• Malignant tumors develop in the upper outer
quadrant of the breast in approximately half the
cases;
• the central portion of the breast is the next most
common location
• Most tumors are unilateral, although bilateral
primary tumors may develop in some cases.
 Carcinoma of the Breast
• There are different types of breast carcinomas, depend on tissue of
origin and the location of the lesion.
• Ductal cancer from epithelium of the ducts, is the most common
form, develops within the ducts
– Invasive type,(90%) infiltrates the surrounding tissue and
frequently adheres to the skin, causing dimpling. The tumor
becomes fixed when it adheres to the muscle or fascia of the
chest wall.
– Noninvasive, intraductal carcinoma, remain confined to the
duct in which they originated
• Lobular cancer develops within the lobes
• Less than 1% of breast cancers originate in the nonepithelial connective tissue
• Inflammatory cancer(rare) grows rapidly and causes the overlying skin to
become edematous, inflamed and indurated
 Carcinoma of the Breast
• Lymphatic and bloodstream spread:
• The malignant cells spread at an early stage, first to the nearby
lymph nodes.
– Tumors in the upper outer quadrant and central breast area
spread to the axillary lymph nodes.
– In most cases, several nodes are affected at the time of
diagnosis.
• Then through the right side of the heart to the lungs and
eventually to the other breast and chest wall
• Common sites of metastases from the lungs include the brain,
bone, and liver.
• Signs and symptoms
• The usual initial sign is thickening of the breast tissue or
painless nodule(lump).
– It can detected on a mammogram before becomes palpable
– freely movable in the early stage but later becomes fixed.
– By palpation, a single, small, hard lump ,it may take up to 8
yrs to become palpable(1cm)
• Advanced stage
– dimpling of the skin , like orange cortex
– Nipple retraction, scaly skin around the nipple,clear,milky or
bloody discharge
– a change in breast contour.
– Edema in the arm indicates advanced nodal involvement
• Biopsy confirms the diagnosis of malignancy.
•
Carcinoma
Diagnosis ;
of the Breast
• Breast self-examination (done regularly) followed by a clinical breast examination.
– recommended for all women older than 20 years as a measure to reduce mortality and
identify cancers in an early stage.
• Mammography; the primary test for breast cancer-can be used to detect tumors that
are too small to palpate
• Fine-needle aspiration and excisional biopsy provide cells for histologic examination
to confirm diagnosis
• Hormone receptor assay can be used to pinpoint whether the tumor is estrogen or
progesterone dependent
• Ultrasound and MRI are used to identify and characterize masses( fluid –filled cyst
and a solid mass
• Chest X-rays can be used to pinpoint chest metastasis
• Scans of the bone, brain ,liver and other organs can be used to detect distant
metastasis
• Laboratory tests for detection of breast carcinoma genes ,also alkaline phosphatase
levels and liver function tests , for distant metastasis
• Ductoscopy reveals small intraductal lesions
• Ductual lavage identifies cancer cells in the milk ducts
 Carcinoma of the Breast
• Treatment ;
• May include a combination of surgery, radiation,
chemotherapy, and hormonal therapy, depending
on the disease stage and type, the woman’s age
and menopausal status.
 Carcinoma of the Breast
• The prognosis is relatively good for tumors
without nodal involvement, but as the number
of lymph nodes affected by the cancer
increases, the prognosis becomes more
negative.
• Breast cancer may recur many years later, but
generally the longer the time elapsed without
recurrence, the lower the risk of recurrence.
 THE LEUKEMIAS
• A group of neoplastic disorders characterized by increased numbers of
white cells in the blood and bone marrow.
• Pathophysiology;
• The malignant cells may be one or more of the leukocyte types
• Present as primitive (blast) ,undifferentiated, immature, nonfunctional
cells that multiply uncontrollably in the bone marrow, and large quantities
are released as such into the general circulation
• As the numbers of leukemic cells increase, they infiltrate the lymph
nodes, spleen, liver, brain, and other organs.
• Acute leukemias are characterized by a high proportion of very immature,
nonfunctional cells (blast cells) in the bone marrow and peripheral
circulation; the onset usually is abrupt, with marked signs and
complications.
• Chronic leukemias have a higher proportion of mature cells with reduced
function, with an insidious onset, mild signs, and thus a better prognosis
 THE LEUKEMIAS
• Depending on the particular stem cell affected, both acute and
chronic leukemias can be further differentiated according to the cell
type involved.
• The four major types are :
– Acute lymphocytic leukemia (ALL), Most cases of ALL involve
the precursors to B-lymphocytes
– chronic lymphocytic leukemia(CLL),
– acute myelogenous leukemia (AML),
– chronic myelogenous leukemia (CML).
– Myelogenous leukemia affects one or more of the granulocytes.
• The neoplastic stem cell may, in some cases of myelogenous
leukemia, involve all blood cells.
 THE LEUKEMIAS
• Effects of acute lymphocytic leukemia
• The proliferation of leukemic cells in the bone marrow suppresses
the production of other normal cells, leading to anemia,
thrombocytopenia, and a lack of normal functional leukocytes
• The rapid turnover of cells leads to hyperuricemia and a risk of
kidney stones and kidney failure, especially in patients who are
receiving chemotherapy.
• The crowding of the bone marrow causes severe bone pain
resulting from pressure on the nerves in the rigid bone and the
stretching of the periosteum.
• As the malignancy progresses, the increased numbers of leukemic
cells cause congestion and enlargement of lymphoid tissue,
lymphadenopathy, splenomegaly, and hepatomegaly.
• Death usually results from a complication such as overwhelming
infection or hemorrhage.
 THE LEUKEMIAS
• Etiology ‫ﺑﺲ اﻟﻠﻲ ﺑﺎﻷﺣﻤﺮ‬
• Chronic leukemias are more common in older people(peak 45),
whereas acute leukemias occur primarily in children and younger
adults.
• Acute lymphocytic leukemia (ALL), the most common childhood
cancer, usually begins between the ages of 2 and 5 years and
constitutes 80% of childhood leukemia cases.
• Acute myelogenous leukemia (AML) is common in adults.
• The cause in children has not been established.
• association of leukemia, particularly ALL, with chromosomal abnormalities,
children with Down syndrome.
• in adults, factors as exposure to radiation, chemicals such as
benzene, and certain viruses.
• many adults with chronic myeloblastic leukemia have the Philadelphia
chromosome (#22), a specific abnormal chromosomal translocation that
serves as a marker in the diagnosis of chronic myeloblastic leukemia
 THE LEUKEMIAS
Signs and symptoms
acute leukemia is usually marked by
• Infection
– that is unresponsive to treatment because of the nonfunctional WBCs.
• Excessive bleeding.
-in the brain or digestive tract occurs because of thrombocytopenia.
• Anemia develop as the erythrocyte count drops.
• Bone pain is severe and steady, continuing during rest.
• Weight loss and fatigue
ü result from the hypermetabolism associated with neoplastic growth, from
anorexia caused by infection, from pain, and from the effects of chemotherapy.
• Fever may result from hypermetabolism or infection.
• The lymph nodes, spleen, and liver are often enlarged and may cause
discomfort.
• If leukemic cells infiltrate the central nervous system, headache,
visual disturbances, drowsiness, or vomiting follows.
 THE LEUKEMIAS
• Chronic leukemia
• There is no symptoms
• may be diagnosed during a routine blood check.
• Early signs include:
– fatigue,
– weakness,
– Fever
– Weight loss
– Joint and bone pain
– frequent infections.
• Massive splenomegaly
 THE LEUKEMIAS
Diagnostic Process for Leukemia
• For most patients, the first suspicion or
presentation of a hematopoietic neoplasm will be
symptoms such as unexplained weight loss,
weakness, chronic fatigue, easy bruising, etc.
• When the physician suspects leukemia, he/she
usually orders a complete blood count (CBC) and/or
a peripheral blood smear.
– The CBC will identify abnormalities of the platelets,
hemoglobin, white blood cells or red blood cells.
• When an abnormality is identified in the blood cell
analysis, a bone marrow (BM) biopsy is usually the
next procedure.
 THE LEUKEMIAS
• Diagnostic tests
• Peripheral blood smears show:
– A high percentage of the WBCs which are immature and appear
abnormal.
– Numbers of RBCs and platelets are decreased.
– In chronic myelogenous leukemia ,may there is no
crosseponding anemia and thrombocytopenia
• Bone marrow aspiration and biopsy confirms the diagnosis
by showing a proliferation of immature WBCs and
determine the type of leukemia.
• CT scan shows which organs are affected
• Lumbar puncture to detect CNS invasion
 THE LEUKEMIAS
• Treatment
• Chemotherapy
– Some types of leukemia, such as ALL in young children, respond well
to drugs, and the prognosis is excellent, with many children enjoying a
cure.
– The best prognosis is found in children between 1 and 9 years of age
– Chemotherapy is less successful in adults with AML
• Biologic therapy, such as interferon, to stimulate the immune
system
• Proper nutrition and hydration, particularly if high uric acid levels
develop.
• Bone marrow transplantation may be tried when chemotherapy is
ineffective.
 LYMPHATIC DISORDERS
• LYMPHOMAS; malignant neoplasms involving lymphocyte
proliferation in the lymph nodes.
– 1 Malignant tumor in lymph nodes or lymphoid tissue
– The two main disorders,
• Hodgkin’s Disease/Hodgkin’s Lymphoma
• Non-Hodgkin’s Lymphomas
• are differentiated by lymph node biopsy.
• higher incidence in adults who received radiation treatments during
childhood.
• 2 MULTIPLE MYELOMA OR PLASMA CELL MYELOMA:
• Malignant tumor of bone marrow with formation of malignant
plasma cells
– An increased number of malignant plasma cells replace the bone
marrow and erode the bone.
– the plasma cells (mature B lymphocytes involved in production of
antibodies). malignant plasma cells that produce Bence Jones protein
in urine which is injurious to kidney lead to renal failure
• Unknown etiology occurring in older adults
 Lymphoma
Hodgkin’s Disease/Hodgkin’s Lymphoma
• The onset of the disease occurs primarily in
adults 20 to 40 years of age, with equal numbers
in men and women.
• A second peak occurrence is found in those over
50 years old, but primarily in men.
• The prognosis for patients in the early stages of disease,
when the malignancy is localized, is excellent; many are
considered cured with survival rates well beyond 5 years
 Hodgkin’s lymphoma‫ﺑﺲ ﺑﺎﻻﺣﻤﺮ‬
• Causes painless, progressive enlargement of the
lymph nodes, spleen, and other lymphoid tissue,
results from proliferation of lymphocytes &
macrophages.
• How it happens ;
• The cause is unknown.
• May be a virus, especially Epstein-Barr virus causing
infectious mononucleosis
• Occupational exposure to herbicides and other
chemicals
• A family history increases the incidence of it
 Hodgkin’s Disease/Hodgkin’s Lymphoma
Pathophysiology
• The malignancy initially involves a single lymph
node, frequently in the neck area.
– Later the cancer spreads to adjacent nodes in an orderly
fashion and then to organs via the lymphatics.
– The T lymphocytes appear to be defective, and the
lymphocyte count is decreased.
• The atypical cell used as a marker for diagnosis of
Hodgkin’s lymphoma is the Reed-Sternberg cell, a
giant cell present in the lymph node .
• Hodgkin’s disease can be subdivided into four
subtypes, based on the cells found at biopsy.
 Hodgkin’s Disease/Hodgkin’s Lymphoma
The Ann Arbor staging system generally defines:
• Stage I cancer as affecting a single lymph
node or region
• Stage II as affecting two or more lymph node
regions on the same side of the diaphragm or
in a relatively localized area.
• Stage III cancer involves nodes on both sides
of the diaphragm and the spleen.
• Stage IV represents diffuse extralymphatic
involvement such as bone, lung, or liver.
 Hodgkin’s Disease/Hodgkin’s Lymphoma
Signs and symptoms
• The first indicator is usually a lymph node, often cervical,
that is large, painless, and nontender
• Later splenomegaly and enlarged lymph nodes at other
locations may cause pressure effects;
– for example, enlarged mediastinal nodes may compress the
esophagus.
• General signs of cancer, such as :
– weight loss,
– anemia,
– low-grade fever and night sweats, and
– fatigue, may develop.
• Generalized pruritus is common.
• Recurrent infection is common because the abnormal
lymphocytes interfere with the immune response.
 Hodgkin’ lymphoma
• Diagnosis :
• Lymph node biopsy confirms the presence of Reed-
Sternberg cells, a giant irregular cell present in the lymph
node .
• Bone marrow,liver,mediastinal,and spleen biopsy are
used to determine the extent of lymph node involvement
• Chest X-ray,abdominal CT scan,lung and bone scans and
laproscopy are used to determine the extent and stage of
the disease
• Hematologic tests may show severe anemia,white blood
cell count, elevated serum alkaline phosphatase levels
,indicate liver or bone involvement
 Non-Hodgkin’s Lymphomas
• Multiple node involvement scattered
throughout the body and a non-organized
pattern of widespread metastases, often
present at diagnosis.
• Intestinal nodes and organs are frequently
involved in the early stage.
 MULTIPLE MYELOMA
OR
PLASMA CELL MYELOMA
• An increased number of malignant plasma
cells replace the bone marrow and erode the
bone
• Blood cell production is impaired, as well as
production of antibodies.
 MULTIPLE MYELOMA
• Multiple tumors with bone destruction
develop in the vertebrae, ribs, pelvis, and
skull.
• Pathologic or spontaneous fractures at
weakened sites in the bone are common.
• Hypercalcemia develops as bone is broken
down.
• The tumor cells can spread throughout the
body, into lymph nodes and infiltrating many
organs
 MULTIPLE MYELOMA
Signs and symptoms
The onset is usually insidious and the malignancy well advanced before
diagnosis.
• Frequent infections may be the initial sign related to impaired production
of antibodies.
• Pain, related to bone involvement, is common and is present at rest.
• Pathologic fractures may occur as bone is weakened.
• Anemia and bleeding tendencies are common because blood cell
production is affected.
• Kidney function, particularly the tubules, is affected, leading to proteinuria
and kidney failure.
Treatment
ü Chemotherapy is used to encourage remission. Median survival is 3 years.
Analgesics for bone pain and
ü treatment for kidney impairment may be needed.
ü Blood transfusions are required in the late stage.