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MBBS 3: Pediatrics > Common Childhood Malignancies > Flashcards

Common Childhood Malignancies Flashcards

1
Q

Cell growth vs cell proliferation?

A

Cell growthan increase in cell mass and size
Cell proliferationan increase in cell number

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2
Q

What is the cell cycle?

A

Provides biochemical pathways that enable a cell to double its DNA content and divide into two daughter cells
- Ability to produce exact replica: essential component of life

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3
Q

What are the checkpoints in a cell cycle?

A
  1. defective DNA repair or aberrant chromosomal segregation
  2. genomic instability
  3. somatic mutation
  4. potentially cellular transformation
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4
Q

What are the 2 phases of the cell cycle?

A
  1. interphase
  2. mitosis
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5
Q

What is interphase?

A

interval between cell divisions in which the cell prepares for the next division

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6
Q

What are the sub-phases of interphase?

A
  1. G1 phase
    - synthesis of RNA, proteins, cell organelles
    - cell growth
  2. S phase
    - DNA replication results in 2 sister chromatids per chromosome
    - synthesis of proteins required for DNA packaging
  3. G2 phase
    - further synthesis of proteins required for mitosis
    - repair of DNA replication errors
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7
Q

What is G0 phase?

A
  • cell enters after exiting the cell cycle from the G1 phase
  • cells are differentiated, have specific functions and are no longer undergoing cell division
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8
Q

What is M phase?

A
  • process of cell division from the distribution of DNA to the budding of a cellular body
  • the final phase of the cell cycle, following the replication of DNA
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9
Q

Purpose of the strict controls of the cell cycle?

A
  1. Prevent cells with damaged or faulty DNA from further dividing and passing on defects to daughter cells.
  2. Controlled cell death (apoptosis) is initiated if the DNA damage is irreparable.
    Note: Disorders of these regulatory mechanisms play an important role in carcinogenesis
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10
Q

What is cell cycle regulation?

A

Balance between division and death (apoptosis)

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11
Q

What limits proliferation of cells?

A
  1. Physical boundaries (e.g basement membranes)
  2. Tissue pressure (contact inhibition)
  3. Growth factors
  4. Regulatory proteins
  5. Tumour suppressor genes
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12
Q

What are oncogenes?

A

Genetic sequence (gene) that causes cancer
- Normal function is to promote cell proliferation.
- Gain of function mutations.
e.g. Proto-oncogene - RAS, WNT, MYC, Ph

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13
Q

What are tumour suppressor genes?

A

Normal function is to prevent cell proliferation.
- So-called “cancer protection” genes
- Loss of function mutations.
e.g. BRCA1/BRCA2, p53, RB

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14
Q

What is cancer?

A

A disease caused by an uncontrolled division of abnormal cells in a part of the body
- In normal tissues, the rates of new cell growth and old cell death are kept in balance.
- Loss of balance between oncogenic stimulus and tumour suppressor activity
- Arises from a loss of normal growth control

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15
Q

What is a benign growth?

A

called a tumour
- Well circumscribed, slow growing, non invasive, non metastatic

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16
Q

What is a malignant growth?

A

called a cancer
- Not well organized, irregularly shaped, fast growing, infiltrative growth, metastatic.
Note: Initial stages of malignant cancer may typically show benign growth - Further accumulation of mutations may make it malignant.

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17
Q

What are the hallmarks of cancer?

A

Autocrine stimulation; grow in the absence of growth factors
Lack of gap junctions
Lack of contact inhibition
Resistance to cell death- persistent telomerase activity
Rapid growth- overtake population, invade other tissues.
Angiogenesis
Clonal nature of cancer
Genomic Instability- accumulation of successive mutations
Presence of a permissive microenvironment

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18
Q

Describe childhood cancer?

A

Cannot be prevented or identified through screening
No known cause
Few caused by environmental or lifestyle factors.
Chronic infections can increase the risk of childhood cancer.
Genetic factors account for 10% of children with cancer.

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19
Q

Name childhood cancer in Lilongwe?

A
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20
Q

Why are rates of leukemia diagnoses increasing?

A

increased awareness and improved pathology support

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21
Q

What is responsible for the low survival rates?

A
  1. diagnostic delay
  2. inaccessible therapy
  3. treatment related mortality
  4. available relapse
  5. inability to obtain an accurate diagnosis
  6. treatment abandonment
22
Q

Why treat childhood cancers in LMICs?

A
  1. epidemiologic transition
  2. ineffectiveness of prevention and screening
  3. achievability of cure
  4. spillover effect from paediatric to adult oncology
23
Q

Overview of presenting features?

A

Difficult to detect in its early stages
Associated signs and symptoms are nonspecific, insidious in onset, and mimic other more common disorders.
Early detection and treatment may reduce disease-related morbidity and complications.
10 to 15 percent of tumours are associated with unusual signs and symptoms and are more difficult to diagnose in the early stages

24
Q

Delays in cancer diagnosis is related to?

A

Child’s age (older children are at a higher risk for delay)
Type of cancer
Presenting symptoms
Tumour site
Cancer stage
First medical specialty consulted

25
Q

Important considerations about early warning signs?

A

Many signs and symptoms are NOT specific to childhood cancer

26
Q

Important aspects of the paediatric physical exam?

A
  1. Ophthalmologic exam (red reflex) in all children <5
    check conjunctivae for pallor / sclerae for icterus
  2. Feel for lymph nodes (cervical, supraclavicular, axillary, inguinal)
  3. Abdominal exam (liver, spleen, ? masses)
  4. Inspection and palpation of extremities
27
Q

Childhood cancer warning signs?

A

Pallor, bruising, bleeding
Lumps or swelling (enlarged lymph nodes or jaw mass)
Weight loss, persistent fevers, night sweats
Eye changes
Abdominal swelling
Persistent or severe headaches
Limb or bone pain, lumps or swelling in the limbs
Fatigue, weakness
Dizziness, loss of balance

28
Q

What is Burkitts lymphoma?

A
29
Q

Types of Burkitt lymphoma?

A
  1. endemic
  2. sporadic
30
Q

Endemic burkitt?

A

Occurs in SSA
Endemic in regions with high rates of malaria
Always EBV positive
Often occurs in jaw but also commonly presents with abdominal tumor
Most common pediatric cancer in the region

31
Q

Sporadic burkitt?

A

Occurs throughout the entire world
Most common non hodgkin lymphoma in children throughout the world (40%)
EBV+ in ~ 30%
Often presents in abdomen
Almost never presents in the jaw

32
Q

Most common diagnosis of an abdominal mass?

A

Burkitt lymphoma
Wilms tumor
Neuroblastoma
Germ cell tumor
Hodgkin lymphoma
Other NHL
N.B. TB rarely presents as massive abdominal mass

33
Q

Early warning signs with eye changes?

A

1) the red reflex may look more or less RED depending on the race/ethnicity of the patient – what you are mainly looking for is SYMMETRY; 2) esotropia or exotropia can be a sign of RB (though usually is eye muscle imbalance, but be sure people are aware).

34
Q

Early warning signs for pallor, bleeding and bone pain?

A

ACUTE LEUKEMIA can present with severe anemia, low platelet count, bone pains, fevers
Clinical presentation can overlap with severe malaria
Difficult to recognize without FBC
Advisable to obtain FBC for patients with clinical picture of severe anemia and fevers, especially when the malaria test is negative
Lymphadenopathy, enlarged liver or spleen, persistent symptoms despite malaria treatment are warning signs

35
Q

Ddx for jaw mass?

A

Burkitt lymphoma
Rhabdomyosarcoma

36
Q

DDX for abdominal mass?

A

Burkitt lymphoma
Wilms tumor
Neuroblastoma
Germ cell tumors
Hodgkin lymphoma

37
Q

Ddx for severe anemia?

A

acute leukemia

38
Q

Ddx for neck masses?

A

Hodgkin lymphoma
Other NHL
Kaposi sarcoma
Burkitt lymphoma

39
Q

Ddx of extremity mass?

A

Bone or rhabdoymyosarcoma

40
Q

Ddx of periorbital mass?

A

Retinoblastoma
Burkitt lymphoma
Rhabdomyosarcoma

41
Q

Oncologic mergencies?

A

Mediastinal masses causing airway or major blood vessel compression.
Elevated intracranial pressure from brain tumours
Hyperleukocytosis due to acute leukaemia, which can cause neurologic morbidity, including intracranial haemorrhage or ischemic stroke. Also respiratory distress
Hyperuricemia, electrolyte derangements (hyperkalaemia, hyperphosphatemia, hypocalcaemia), and acute kidney injury due to tumour lysis syndrome (TLS).
Usually occurs after the initiation of cytotoxic therapy.
Can occur spontaneously with malignancies that have a high proliferative rate (eg, some forms of lymphoma and acute leukaemia).

42
Q

General principles of evaluation?

A

Treatment for malignancy can begin only after the tumour has been accurately diagnosed and the extent of disease defined precisely.

Establish the correct diagnosis and accurately determine the extent of disease before therapy begins

43
Q

Investigations?

A

Computed tomography (CT), diagnostic ultrasonography, magnetic resonance imaging (MRI), positron emission tomographic (PET) scans, and nuclear medicine scans have improved the assessment and staging for cancer.
Tissue biopsy remains the primary way of establishing a definitive diagnosis.

44
Q

Diagnostic and staging biopsies?

A

Fine-needle aspiration
Bone marrow aspirate and biopsy
Excisional biopsy of affected lymph node(s)
Core needle biopsies
Surgical resection- pre/post chemotherapy
Image-guided core needle biopsy

45
Q

Modalities of treatment for cancer?

A
  1. surgical interventions
  2. radiation therapy
  3. chemotherapy
  4. gene therapy
  5. stem cell and bone marrow transplants
  6. immunotherapy
46
Q

What is chemotherapy?

A

Use of antineoplastic drugs to promote tumour cell destruction by interfering with cellular function and reproduction

47
Q

What is radiotherapy?

A

DNA damage of cancer cell and destroy ability to reproduce
Usually combined with other treatment modalities
Use high-energy ionising radiation
To cure cancer and reduce symptoms
External beam radiation and brachytherapy

48
Q

Supportive care for complications of chemotherapy?

A

Antibiotics
Blood/platelet transfusions
IV fluids
Prevention of nausea/vomiting
Prevention of tumor lysis syndrome
Palliative care

49
Q

Describe survivorship?

A

Lifespan after a cure from cancer is expected to be long,

Potential for long-term toxicities

Risk of second malignancies, cardiovascular health, mental health and fertility preservation

50
Q
A

MBBS 3: Pediatrics (43 decks)

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