Biology of cancer Prepared by: Sir Flas Julius Floresta

1. 5. CELLULAR ABERRATION
The Biology of Cancer Part 4

2. LUNG CARCINOMA
 Currently the most frequently diagnosed major
cancer in the world and the most common cause of
cancer mortality worldwide
 Largely due to carcinogenic effects of cigarette
smoke
 Adenocarcinoma (males 37%, females 47%)
 Squamous cell carcinoma (males 32%, females
25%)
 Small cell carcinoma (males 14%, females 18%)
 Large cell carcinoma (males 18%, females 10%)

3. LUNG CARCINOMA
 In the usual case it is discovered in patients in their
50s whose symptoms are several months duration
 Major presenting complaints:
a. Cough (75%)
b. Weight loss (40%)
c. Chest pain (40%)
d. Dyspnea (20%)

4. LUNG CARCINOMA
 In general, the adenocarcinoma and squamous cell
patterns tend to remain localized longer and have a
slightly better prognosis than do the others
 Paraneoplastic syndromes – clinical manifestations
produced by lung tumors that secrete hormones
like ADH, ACTH, PTH, calcitonin, gonadotropins,
serotonin
 Lambert-Eaton syndrome – probably due to
antibodies produced by certain lung carcinomas

9. LUNG CARCINOMA
 Diagnosis
1. Chest x-ray
2. CT or combined PET–CT
3. Cytopathology examination of pleural fluid or
sputum
4. Usually, bronchoscopy-guided biopsy and fine-
needle aspiration
5. Sometimes open lung biopsy

10. LUNG CARCINOMA
 Management
1. Surgery (depending on cell type and stage)
2. Chemotherapy
3. Radiation therapy
4. Nursing care is based on supportive treatment

11. LUNG CARCINOMA
 NURSING INTERVENTIONS
(http://nursingcrib.com/nursing-notes-reviewer/lung-cancer/)
1. Elevate the head of the bed to ease the work of
breathing and to prevent fluid collection in upper body
(from superior vena cava syndrome).
2. Teach breathing retraining exercises to increase
diaphragmatic excursion and reduce work of
breathing.
3. Augment the patient’s ability to cough effectively by
splinting the patient’s chest manually.
4. Instruct the patient to inspire fully and cough two to
three times in one breath.

12. LUNG CARCINOMA
 NURSING INTERVENTIONS
(http://nursingcrib.com/nursing-notes-reviewer/lung-
cancer/)
5. Provide humidifier or vaporizer to provide moisture to
loosen secretions.
6. Teach relaxation techniques to reduce anxiety
associated with dyspnea.
7. Allow the severely dyspneic patient to sleep in
reclining chair. Encourage the patient to conserve
energy by decreasing activities.
8. Ensure adequate protein intake such as milk, eggs,
oral nutritional supplements; and chicken, fowl, and
fish if other treatments are not tolerated – to promote
healing and prevent edema.

13. LUNG CARCINOMA
 NURSING INTERVENTIONS
(http://nursingcrib.com/nursing-notes-reviewer/lung-
cancer/)
9. Advise the patient to eat small amounts of high-calorie
and high-protein foods frequently, rather than three
daily meals.
10. Suggest eating the major meal in the morning if rapid
satiety is the problem.
11. Change the diet consistency to soft or liquid if patient
has esophagitis from radiation therapy.
12. Consider alternative pain control methods, such as
biofeedback and relaxation methods, to increase the
patient’s sense of control.
13. Teach the patient to use prescribed medications as
needed for pain without being overly concerned about
addiction.

14. THYROID CARCINOMA
 1.5% of all cases in the US
 Female > Male in incidence in those that develop
during the early and middle adult years
 F = M if it develops during childhood and late adult
life
 Papillary carcinoma (>85%)
 Follicular carcinoma (5% to 15%)
 Anaplastic (undifferentiated) carcinoma (<5%0
 Medullary carcinoma (5%)

15. THYROID CARCINOMA
Papillary carcinoma Follicular carcinoma
Most common form 5% to 15% of thyroid malignancies
Occur throughout life, but most often More common in women
between the ages of 25 and 50 Present at an older age with a peak
incidence between 40 and 60 years
of age
Account for the majority of thyroid More frequent in areas with dietary
carcinomas associated with previous deficiency of iodine
exposure to ionizing radiation
Excellent prognosis Prognosis is largely dependent on
the site of invasion and stage
Spread is though the lymphatics Spread is both through the
lymphatics and vascular route

16. THYROID CARCINOMA
 Neck lump - in the front of the neck near the Adam's apple
 Neck nodule
 Painless neck lump
 Neck swelling
 Hoarseness
 Difficulty speaking
 Voice changes
 Swollen neck lymph nodes
 Swollen lymph nodes
 Difficulty swallowing
 Difficulty breathing
 Throat pain
 Neck pain
http://www.wrongdiagnosis.com/t/thyroid_cancer/symptoms.htm

17. THYROID CARCINOMA
 Physical exam - especially a neck exam.
 Thyroid blood tests
 TSH blood test
 Thyroglobulin blood test
 Calcium blood test
 Ultrasonography
 Radionuclide scanning
http://www.wrongdiagnosis.com/t/thyroid_cancer/symptoms.htm

18. THYROID CARCINOMA
 Biopsy Fine-needle aspiration
 Surgical biopsy
 Pathology analysis
 Neck ultrasound
 Neck MRI
 Neck CT
 Diagnostic I-131 whole body scan - looks for thyroid
cancer cells throughout the body.
http://www.wrongdiagnosis.com/t/thyroid_cancer/symptoms.htm

21. THYROID CARCINOMA
 Thyroid cancer is most treatable and curable if caught in
the earliest stage of the disease.
 Treatment is individualized to the type and stage of
advancement of the disease, a person's age, medical
history, coexisting diseases and other factors.
 Treatment of thyroid cancer may include a combination
of surgery, radioactive iodine treatment, chemotherapy,
and radiation therapy.
 Surgery generally includes removing most of the thyroid.
 Thyroid hormone replacement therapy is prescribed to
replace the hormones that were produced by the
thyroid.
http://www.wrongdiagnosis.com/t/thyroid_cancer/symptoms.htm

23. PANCREATIC CARCINOMA
 4th leading cause of cancer in the US
 5-year survival rate is dismal, less than 5%
 Primarily a disease of the elderly
 80% of cases occur between the ages of 60 and 80
 Strongest influence is cigarette smoking
 Other risk factors: fatty diet, chronic pancreatitis,
DM, heredity (?)

25. CLINICAL FEATURES
 Remain silent until they invade adjacent structures
 Obstructive jaundice – specially if carcinoma of the
pancreatic head
 Migratory thrombophlebitis (Trousseau sign) –
attributable to the elaboration of platelet-aggregating
products and procoagulants from the carcinoma or its
necrotic products (10% of cases)
 Course is typically brief and progressive
 Serum levels of CEA and CA19-9 are often elevated
 CT-guided biopsy
 Treatment is surgical (Whipple procedure),
chemotherapy and radiotherapy, supportive

27. WHIPPLE PROCEDURE
 The Whipple procedure (pancreatoduodenectomy)
is the most common operation performed for
pancreatic cancer and may be used to treat other
cancers such as small bowel cancer.
 Surgeons remove the head of the pancreas, most
of the duodenum (a part of the small intestine), a
portion of the bile duct and sometimes a portion of
the stomach.
 After the pancreatoduodenectomy, the surgeon
reconstructs the digestive tract.

28. WHIPPLE PROCEDURE
 At Mayo Clinic, surgeons perform more than 100
Whipple procedures annually.
 Patients leave the hospital in an average of 14
days.
 http://www.mayoclinic.org/pancreatic-
cancer/whippleprocedure.html

30. LEUKEMIA
 The uncontrolled replication of the hematologic
progenitor cells involved in the development of
white blood cells, red blood cells, and platelets
 May originate in any of the blood-forming organs,
including the bone marrow, lymphatic system, and
spleen
 A heterogenous disease with various biologic and
clinical presentations that influence a person’s
response to therapy

31. LEUKEMIA
 Classification depends on which progenitor cell it
originated (lymphoid or myeloid) and is further classified
as being acute or chronic on the basis of clinical
presentation and cell maturity
 In the acute phase, the malignancy occurs during early
cell differentiation, resulting in rapid replication with
blasts
 In the chronic phase, unregulated replication of
differentiated cells occurs
 The four major classifications of leukemia:
1. Acute lymphocytic leukemia (ALL)
2. Chronic lymphocytic leukemia (CLL)
3. Acute myelogenous leukemia (AML)
4. Chronic myelogenous leukemia (CML)

32. INCIDENCE
 2004 – estimated 33,440 new cases diagnosed
 10x likelier to occur on adulthood than in childhood
 Overall incidence: M>F
 More often in the older adult, with more than half the
cases occurring in the 6th decade
 Most common leukemias among adults: AML and CML
 CML: seen more frequently in adults and accounting for
a small proportion of the overall leukemias
 ALL: makes up the smallest proportion of leukemias,
and is most frequently seen among pediatric patients

33. RISK FACTORS
 Genetics
 Environmental exposures
 Viral infections
 Immunodeficiency
 Children with Trisomy 21 are approximately 20x
likelier to develop leukemia than the general
population
 Children younger than 3 years of age likeliest to
develop megakaryoblastic subset of AML
 Older children are likeliest to develop ALL
 Siblings are to- to fourfold greater risk of AML
 High risk among identical twins

38. RISK FACTORS
 Diagnostic and ionizing radiation
 Cigarette smoke
 Electromagnetic fields or high power lines
 Alkylating agents is associated with secondary AML
 Viruses – T and B cell lymphoma
 Immunodeficiency – high risk for lymphoma

40. DETECTION – ACUTE LEUKEMIA
 The patient experiences symptoms within weeks to months of
the beginning of the acute malignant process
 The most common symptoms and physical findings at
diagnosis
a. Anemia
b. Fever
c. Thrombocytopenia
d. Neutropenia
e. Pallor
f. Fatigue
g. Anorexia
h. Petechiae
i. Bleeding
j. Infection

41. DETECTION - ACUTE LEUKEMIA
 In addition, the patient may have extramedullary
disease and present with generalized or local
lymphadenopathy , bone pain, bone fracture
 Extramedullary disease:
a. CNS involvement – vertigo, nausea, vomiting,
papilledema, and blurred vision
b. Parotid gland infiltration
c. Testicular infiltration
d. Hepatomegaly
e. Splenomegaly

42. DETECTION – CHRONIC LEUKEMIA
 Clinical manifestations similar to acute leukemia but
have an insidious onset
 Fatigue
 Exercise
 Intolerance
 Night sweats
 Abnormal fullness secondary to splenomegaly
 Infection secondary to hypogammaglobulinemia

43. DIAGNOSIS
 Complete PE and history
 CBC with platelets and differential count –
peripheral smear
 Chemistry panel
 Bone marrow aspirate
 Morphology/cytochemistry
 Flow cytometry
 Immunophenotype
 Cytogenetic/molecular features
 LAP (leukocyte alkaline phosphatase) score

44. Peripheral Smear
Normal
granulocytes
AML

45. Normal lymphocyte
and monocyte
CLL

46. Normal bone
marrow aspirate
Leukemia - bone
marrow aspirate

47. Flow
cytometry

48. Immunophenotyping

49. LAP Score

50. LEUKEMIA
Classification of myeloid malignancies
FAB
Chronic myeloproliferative diseases
 Myelodysplastic syndromes
 Acute myeloid leukamia
WHO
 Chronic myeloproliferative diseases
 Myelodysplastic/myeloproliferative diseases
 Myelodysplastic syndromes
 Acute myeloid leukemias
Note: The WHO classification system puts a few diseases that show
characteristics of both myeloproliferative and myelodysplastic
conditions into a new, separate group
(myeloproliferative/myelodysplastic diseases).
(http://xenia.sote.hu/depts/pathophysiology/hematology/e/who-
classification.html#myeloid)

51. CLASSIFICATION OF CHRONIC
MYELOPROLIFERATIVE DISEASES
FAB
 Chronic myelogenous leukemia (CML)
 Agnogenic myeloid metaplasia with myelofibrosis (MF)
 (Idiopathic myelofibrosis)
 Polycythemia vera (PV)
 Essential thrombocythemia (ET)

52. CLASSIFICATION OF CHRONIC
MYELOPROLIFERATIVE DISEASES
WHO
 CML Ph+: t(9;22)(qq34;q11), BCR/ABL
 Chronic neutrophilic leukemia
 Chronic eosinophilic leukemia/hypereosinophilic
syndrome
 Chronic idiopathic myelofibrosis
 Polycythemia vera
 Essential thrombocythemia

53. ACUTE MYELOID LEUKEMIAS (AML)
FAB
 M0: minimally differentiated
 M1: myeloblastic leukemia without maturation
 M2: myeloblastic leukemia with maturation
 M3: hypergranular promyelocytic leukemia
 M4: myelomonocytic leukemia
 M4Eo: variant, increase in marrow eosinophils
 M5: monocytic leukemia
 M6: erythroleukemia (DiGuglielmo's disease)
 M7: megakaryoblastic leukemia

54. ACUTE MYELOID LEUKEMIAS (AML)
WHO
 AML with recurrent cytogenetic translocations
 AML with multilineage dysplasia
 AML with myelodysplastic syndrome, therapy related
 AML not otherwise categorized
AML minimally differentiated
AML without maturation
AML with maturation
Acute myelomonocytic leukemia
Acute monocytic leukemia
Acute erythroid leukemia
Acute megakaryocytic leukemia
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis

56. LYMPHOMAS
 WHO classification
1. Non-Hodgkin lymphoma
 B-cell lymphoma
 T-cell lymphoma
2. Hodgkin lymphoma
 Nodular lymphocyte-predominant
 Hodgkin's disease
 Classical Hodgkin's disease
 Nodular sclerosis Hodgkin's disease
 Lymphocyte-rich classical Hodgkin's disease
 Mixed-cellularity Hodgkin's disease
 Lymphocyte-depletion Hodgkin's disease

57. TREATMENT
 Goal
1. Eradicate the malignant clone
2. Allowing growth of normal hematopoietic cells
 ALL – treatment is divided into stages
1. Induction
2. Consolidation
3. Maintenance
 Based on the patient’s prognostic factors, the
remission induction chemotherapy program
generally includes some if not all of the following
drugs:

58. TREATMENT
ALL
 Based on the patient’s prognostic factors, the
remission induction chemotherapy program
generally includes some if not all of the following
drugs:
1. Cyclophosphamide
2. Vincristine
3. Dexamethasone or prednisone
4. L-asparaginase
5. Doxorubicin

59. TREATMENT
ALL
 Some programs include high doses of methotrexate
and cytosine arabinose as part of the induction
scheme
 Others use a drug called etoposide
 The patient is monitored closely for the disappearance
of peripheral blasts and treatment-related side effects
 At the end of the induction, the marrow is examined for
morphologic and molecular presence of disease
 Many treatment regimens have a month of reintensive
induction within the first year of therapy

60. TREATMENT
ALL
 Consolidation is several weeks long and includes
courses of methotrexate or cytarabine
 At the consolidation of treatment, maintenance
therapy begins with drugs used in a combination,
rotational schedule

61. TREATMENT
ALL
 Maintenance therapy may include:
1. Cytarabine
2. Thioguanine
3. Methotrexate
4. Cyclophosphamide
5. Vincristine
6. Prednisone/dexamethasone
7. Doxorubicin
8. L-aspariginase
9. Mitoxantrone
10. 6-mercaptopurine

62. TREATMENT
ALL
 The rotational therapy is administered over a 2- to
3-year course
 Patients also receive intrathecal chemotherapy
with methotrexate or cytarabine for prophylaxis or
treatment of CNS involvement
 If leukemia cells are positive in the spinal fluid,
radiation therapy may also be given to the brain
 Bone marrow/stem cell transplantation may be a
treatment option for patients who have an early
relapse, have disease that is unresponsive to
therapy, or have unfavorable cytogenetics

63. TREATMENT
AML
 Two phases:
1. Induction – cytarabine and daunorubicin or
idarubicin; intensive therapy that lasts for 1 week
2. Postremission or consolidation to maintain
remission – options:
a. Several courses of high-dose cytarabine
chemotherapy
b. Allogenic (donor) stem cell transplantation
c. Autologous stem cell transplantation

64. TREATMENT
CML
 Allogenic bone marrow or stem cell
transplantation – the only curative therapy
 Interferon alfa and imatinib mesylate (Gleevec) –
treatment options for ineligible, unwilling, or
waiting to undergo transplantation
 Avoid grapefruit juice when giving Gleevec,
because this juice is known to increase the drug’s
level

65. TREATMENT
CLL
 Observation
 Chemotherapy
 Monoclonal antibiotics, which target the surface
antigen
 Bone marrow transplantation

66. REHABILITATION
 The patient and family must balance the treatment
regimen and uncertainty of the future, while
attempting to maintain a sense of control and
normalcy
 Fatigue is a common complaint of patients –
feelings of sadness, sleepiness, dizziness, nausea,
feeling heavy, mentally tired, not one’s self, and
feeling sorry for one’s self
 Patient may not resume their life as it was before
leukemia

67. THE ROLE OF THE NURSE
 Patient and family education
 A supportive presence
 Active monitoring and anticipates events
 Technically competent
 Advocacy

68. LYMPHOMA
 One of the group of malignancies that originate
from the lymphatic system
 Two groups:
1. Hodgkin lymphoma
2. Non-Hodgkin lymphoma

69. HODGKIN LYMPHOMA
 Age-related bimodal incidence distribution
 Peaks in mid 20s
 Declines until mid 40s
 Increases after age 60
 Rare before the age of 10
 More common in males
 One of the most curable malignancies

70. HODGKIN LYMPHOMA
 Risk factors
1. Etiology is not known
2. EBV – has been suggested
3. Defects in the immune system function
4. Increased incidence among siblings – genetic risk
(?)

71. HODGKIN LYMPHOMA
 Clinical manifestations
1. Often asymptomatic
2. Painless lymphadenopathy most commonly found
in the supraclavicular, cervical, and mediastinal
3. Spleen, liver, and retroperitoneal lymph nodes
may be involved
4. Unexplained weight loss of more than 10% of
body weight in 6 months before diagnosis
5. Frequent, drenching night sweats; fever with
temperatures above 38C
6. Pruritus may be present

72. HODGKIN LYMPHOMA
 Diagnosis and Staging
1. Thorough history and physical examination
2. Hematology
3. Chemistry profile
4. Histology: Reed-Sternberg cells
5. Chest X-ray to demonstrate mediastinal
involvement

73. Ann Arbor Costwold Staging Classification Indicated for Hodgkin and Non-
Hodgkin Lymphoma
Clinical Staging
Stage I Involvement of a single lymph node region. Extension into an
extralymphatic organ or site (IE)
Stage II Involvement of two or more lymph node regions on the same
side of the diaphragm. Extension into an extralymphatic site
(IIE)
Stage III Involvement of lymph node regions or structures on both sides
of the diaphragm. May be divided into disease of the upper (III1)
or lower (III2) abdomen, if spleen is involved (IIIS); if
extralymphatic extension (IIIE)
Stage IV Diffuse involvement of liver, bone marrow, lung, or diffuse
extralymphatic disease
For all stages A. No symptoms
B. Presence of symptoms (fever, sweats, weigh loss of >10%
of BW)

79. HODGKIN LYMPHOMA
 Treatment
1. Radiation therapy – curative in most patients with
stage I or II disease
2. Chemotherapy – used in most patients with stage
III and stage IV disease and in some patients with
earlier stage of the disease
3. Hematopoietic stem cell transplantation

80. NON-HODGKIN LYMPHOMA (NHL)
 Seven times more common than HL
 Overall 5 years survival rate with optimum
treatment for all patients – approximately 50%-60%
 Males more affected than females
 Risk factors:
a. Congenital or acquired immune deficiencies
b. Those undergoing organ transplantation
c. Autoimmune disease

81. ETIOLOGY
 Malignancy of the B or T lymphocytes
 Clones of the malignant cells may infiltrate the
lymph nodes, bone marrow, peripheral blood, or
other organs
 Pattern of spread is less predictable than in HL
 Frequently disseminated at the time of diagnosis

82. CLINICAL MANIFESTATIONS
 Localized or generalized lymphadenopathy that
waxes or wanes over a period of several months
 Early involvement of the oropharyngeal lymphoid
tissue or infiltration of the bone marrow is common
 Abdominal mass may be detected with GIT
involvement
 Night sweats
 Fever
 Weight loss
 Splenomegaly or hepatomegaly – 1/3 of patients

83. DIAGNOSIS AND STAGING
 Careful examination of the all lymph nodes
 CBC
 Chemistry
 Bone marrow and lymph node biopsy
 Ann Arbor-Costwold Staging Classification – useful
but has less value for NHL (does not account for
the histology or type of tumor)

89. TREATMENT
 Surgery – primary role is to establish diagnosis and to
assist with staging, and is rarely needed to prevent
bowel obstruction or for splenectomy in patients with
hypersplenism
 Radiation and chemotherapy – NHL is spread via the
vascular system (HL is spread contiguously via node
extension), so radiotherapy is used as an adjuvant to
chemotherapy as opposed to being the primary
treatment
 Immunotherapy/Biotherapy – rituximab (monoclonal
antibody) is used for the treatment of relapsed or
refractory low-grade or follicular CD20-positive B-cell
lymphoma
 Rituximab is also indicated as a first line treatment with
combination chemotherapy for aggressive lymphomas

91. SYMPTOM MANAGEMENT, LONG-TERM
SEQUELAE
 Education
 Protection of patients because patients remain
neutropenic for a long time
 Proper referral to the Oncologist
 Cyclophosphamide is used in chemotherapy – risk
of developing secondary malignancies