Red Flags in the Diagnosis of Pediatric Cancer - PowerPoint Presentation

Slide1

Red Flags in the Diagnosis of Pediatric Cancer

Geoff Cuvelier MD FRCPCPediatric OncologistCancerCare ManitobaAssociate Professor, Dept of Pediatrics and Child Health. University of Manitoba

Canadian Association of Physician Assistants Conference

Winnipeg, MB. October 29, 2016

Slide2

DisclosuresNone

I will not be discussing any off-label indications for any drugs or medical devices.I’m really sympathetic towards front-line health care workers and their role in diagnosing children with cancer. It can be difficult!

Slide3

Objectives

To increase understanding among front-line healthcare workers (including physician assistants) that cancer in children does occur and to help you identify common and less-common cancer presentations.To discuss how acute leukemia, lymphoma and brain tumors in children present to primary care health workers and what you can do to help make the diagnosis.

Provide you with the knowledge to initiate diagnostic and therapeutic interventions where there is an

oncologic emergency

.

Slide4

How Often Will Primary Care Physicians See A Case of

Childhood Cancer?Infrequently:Children (<15 yrs

): 14.7 cases / 100,000 children / year.

Adults:

467.7

cases / 100,000 adults / year

Manitoba:

About 60

new cases childhood cancer / year

In primary care …. Perhaps one child every 10-15 years

.

Problem

: The parent expects

you

will know what to do and they are not happy when the diagnosis has been missed! (may have multiple health care visits)

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Types of Childhood Cancer

* 1. Leukemia (ALL>AML>Chronic Leukemia) ……….31.0%*

2. CNS tumors………………………………………

…

18.3

%

*

3. Lymphomas (Hodgkin

’

s, NHL) …………………

…13.8

%

4. Neuroblastoma ……………………………………….. 6.8%

5. Soft tissue sarcomas …………………………………..6.2%

6.

Wilms

’

tumors ………………………………………

.

5.7%

7. Bone tumors ………………………………………….. 4.7%

8. Retinoblastoma ………………………………………. 2.5%

9. Germ cell tumors …………………………………….. 2.4%

10. Liver tumors …………………………………………… 1.3%

11. Other …………………………………………………… 7.4%

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So…Isn

’t Pediatric Oncology Sad?Well sometimes … but not usually. In very “general” terms - Long-Term Survival

:

1962

2016

Acute Lymphoblastic Leukemia

4

%

93%

Acute Myelogenous Leukemia

4

%

60% (variable on genetics)

CNS tumors

35

% 74% (

variable on type)

Hodgkin

’

s Disease

50

% 95%

NHL

6

% 84%

Neuroblastoma

10% 69% (variable on stage)

Wilms

’

tumor

50

% 92%

Osteosarcoma

20

% 63%

Ewing

’

s sarcoma

5% 65

% (variable on stage)

Rhabdomyosarcoma

30% 64

% (variable on stage)

Slide7

Why Cancer Diagnosis

Is Missed in ChildrenNot expecting the diagnosis “Cancer Doesn’t Happen in Children”The parents are telling the story – quick assumptions

Mimics

other conditions

“

Mono

”

– Acute Leukemia, Lymphoma

“

Asthma

”

– Acute Leukemia with

Mediastinal

Mass

“

Tension Headache

”

/ Migraine – Brain Tumor

“

Trauma

”

–

Osteogenic

sarcoma

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Case One

3 year old girl brought to walk-in-clinicPale and tired for 1 week, feversDx:

“

Viral Infection

”

1 week later:

Still tired, pale, fevers

Limping,

“

Legs hurt

”

Dx

:

“

Growing Pains

”

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Case One

1 week later:Getting worseNow getting a red rash

Petechiae

– Sign of Thrombocytopenia

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Case One

Physical Exam:HR: 120 BP: 100/70 RR: 34 Temp: 38.8oCUnwell, Tired AppearingSubconjunctival

hemorrhages

Cervical Lymphadenopathy

Hyperdynamic

precordium

Systolic flow murmur

Hepatosplenomegaly

to just

above umbilicus

.

** What is the most important test?

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Complete Blood Count

WBC: 35 x 109/L (N: 5-15)Hemoglobin: 45 g/L

(

N: 120-160)

Platelets: 2 x 10

9

/L (N: 150-450)

Neutrophils:

0.2

x 10

9

/L (N: 2.5-7.0)

Lymphocytes: 1.0 x 10

9

/L (N: 2.0-7.0)

Other Cells:

33.5

x 10

9

/L (N: none)

What is the most likely diagnosis?

Acute Leukemia

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Blood Smear Under Microscope

Normal

“

Other Cells

”

=

Blasts

–

when there is a preponderance of blasts on the CBC you are very likely dealing with acute leukemia.

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Acute Leukemia

Clonal malignancy of early blood cells that presents “acutely”:Uncontrolled proliferation of immature malignant blood cells starting in bone marrow.

Destruction of normal hematopoiesis.

Systemic infiltration of organs (e.g. liver, spleen, lymph nodes, CNS, testes)

2 Subtypes:

Acute Lymphoblastic Leukemia (ALL) – most common childhood cancer

Acute

Myelogenous

Leukemia (AML)

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AML

ALL

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Acute Leukemia Presentation

Often over short time – days to weeks.Constitutional symptoms:Fevers

Malaise (often not going to school)

Anorexia / weight loss (sometimes

)

Consequence of bone marrow being packed with blasts

:

Limping

Bone Pain (legs, pelvis especially)

Hematologic (anemia / thrombocytopenia)

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Acute Leukemia Presentation

Consequence of anemia:PallorTired / HeadachesTachycardia / Tachypnea

Consequence of thrombocytopenia:

Petechiae

/

Purpura

Subconjunctival

Hemorrhages

Consequence of organ infiltration:

Hepatosplenomegaly

Lymphadenopathy

Mediastinal

mass

Testiculomegaly

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Classification of Acute Leukemias

by Cell of OriginFor perspective only .. Don’t need to memorize these. Acute leukemias have been classified according to the predominant cell type.

ALL

(still used)

pre-B cell (

“

precursor

”

B)

T-cell ALL

AML

(older

“

FAB

”

– used still by convention but replaced by WHO classification)

M0 – Undifferentiated AML

M1 – AML without maturation

M2 – AML with maturation

M3 –

“

APL

”

Acute promyelocytic leukemia

M4 – Acute myelomonocytic leukemia

M5 – Acute monoblastic leukemia

M6 – Acute erythroid leukemia

M7 – Acute megakaryoblastic leukemia

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Classification of Leukemia By Prognosis and Genetics

Classification systems are constantly changing – but in general increasing knowledge of molecular genetics and how this impacts prognosis is identifying different

subclassifications

.

Aiding to guide therapy – Very High Risk – Intensified therapies, stem cell transplant. Standard Risk – De-escalating traditional therapy.

ALL:

Standard Risk Low

(

double

trisomies

of chromosomes 4,

10)

Standard Risk Average

Standard Risk High (MLL gene translocation but rapid response to chemotherapy)

High Risk (MLL gene translocation but slow response to chemotherapy)

Very High Risk (e.g. genetic translocations with known high risk features such as t 9:22

“

Philadelphia

”

chromosome, <44 chromosomes in the blasts

“

hypodiploid

”

)

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Case Two - Variation on the Leukemia Theme

– Leukemia as an Oncologic Emergency14 year old boy presents with one week fevers, bone pain, headaches, tired and pale. Now trouble breathing.

O/E:

Subconjunctival

hemorrhages, multiple

petechiae

, lymphadenopathy,

hepatosplenomegaly

and facial plethora and fullness.

CBC: WBC: 252 x 10

9

/L 98% Blasts

(

=

Hyperleukocytosis

)

Hg

: 75 g/L

Plts

: 2 x 10

9

/

L

Hyperleukocytosis

–

WBC >100 x 10

9

/L. Blood becomes viscous and

sludges

. Increases the risk of:

cerebrovascular accident (ischemic and hemorrhagic).

pulmonary “

sludging

” and hypoxemia.

tumor

lysis

syndrome.

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To Remind You – A Normal Chest X-Ray

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Mediastinal Mass and SVC Syndrome with

Hyperleukocytosis = Emergency

Mediastinal Mass:

Compromised airway

Anesthesia concerns

SVC Obstruction

Facial, Neck, and Arm Edema

Poor venous return from CNS – potential for stroke and cerebral edema.

Adolescent with hyperleukocytosis and anterior mediastinal mass likely T-cell ALL.

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The Anterior Mediastinal

MassWide differential diagnosis – some malignant some not.“

Terrible T

’

s

”

:

T-cell ALL

T-lymphoblastic lymphoma (cousin disorder to T-ALL)

Thymoma

(or normal thymus in infant)

Thyroid Cancer

Teratoma

(germ cell tumor)

Tuberculosis

Hodgkin

’

s Lymphoma

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Normal Thymus of Infancy

Wavy Sign

Looks like a mediastinal mass – don

’

t be confused. Most infants <1 years old you will see this and it is normal. Involutes between 1-3 years. Only 2% will still be visible on CXR by 4 years.

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Case 2 – Adolescent with Hyperleukocytosis

, Blasts, Large Mediastinal Mass, SVC syndromeWhat is the responsibility of the physician assistant working in the ER or primary care clinic?Recognize this is an oncologic emergencyGet the child out of your ER and to the tertiary children’s hospital.Call the pediatric oncologist on call.

Start two peripheral intravenous lines.

Do extended

bloodwork

–

lytes

, urea,

creatinine

,

Ca

, PO4, Mg, LDH, uric acid.

Start IV fluids WITHOUT ADDED POTASSIUM at 2-4 x maintenance fluid (assuming kidney function OK).

Do not start corticosteroids! (in some urgent situation may need to

–

but speak to pediatric oncologist first).

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Case Three

– CNS Tumors4 year old, bit more cranky and irritable over last few weeks. Decreased play.Complaining of headaches more often past week.

Mom has migraine history and thought it was this. Doctor agrees.

Dx

: Migraines. Tylenol, rest, fluids.

Comes back – vomiting, walking

abnormally (ataxia).

Sees the

physician assistant who came

to this talk and remembered…….

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The Headache RED FLAGS

A headache is a brain tumor until proven otherwise when:Child 7 or less years.Particularly bad in the early morning.Awakening at night from headache.

Progressively getting worse over time.

Associated with increased ICP or other neurologic symptoms and signs – vomiting, ataxia,

nystagmus

, deteriorating developmental milestones or school

performance.

In an infant (<1 year) the head circumference is getting larger due to non-closure of the

fontanelles

and sutures.

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Why Pediatric Brain

Tumors are MissedNot listening to the patient / parent – history, history , historyNot remembering the headache red flags

.

Not doing a head circumference on an infant with open

fontanelles

and appreciating it is getting bigger too fast

.

Not appreciating declining school performance or behavioral disturbance with headaches could be a brain tumor

.

You need a

CT scan

of the head to rule in/out a brain tumor.

Slide28

Slide29

CT Scan of Head

This is a Normal CT Scan showing normal ventricle size and basal cisterns.

Slide30

This is Not Normal - Hydrocephalus

Something is blocking the flow of CSF

Slide31

Normal Flow of CSF

Brain Tumor Blocking Here (Posterior Fossa)

Produces Hydrocephalus Here = Increased Intracranial Pressure

Slide32

Brain Tumors in Children

Classification – In part by location, cell of origin, and aggressiveness but in general profoundly confusing nomenclature and classification.Some aren’t really even cancer (e.g. low grade

gliomas

)

Cause symptoms by compression

Removed by surgery only and are

“

cured

”

or at least no longer a problem for many years.

Others are highly aggressive malignancies with very poor survival (e.g.

gliobastoma

multiforme

).

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Posterior Fossa Tumor

2 year old. Vomiting. Irritable. Walking “funny

”

(ataxia). Not hitting mouth with spoon / fork. Hydrocephalus on CT scan.

Dx

:

Medulloblastoma

. Mets to CSF. Surgery, Intensive chemotherapy, stem cell transplant, radiation therapy. High-risk disease. Survival ≈ 50%.

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Posterior Fossa Tumor

12 year oldEarly morning headaches, awakening at night with headaches.Low grade gliomaSurgery – complete removal = cure

Excellent outcome

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Posterior Fossa Tumor

5-year old. 1 week history of going cross-eyed, double vision, trouble swallowing food.Note cranial nerve symptoms.Dx: Diffuse Intrinsic Pontine GliomaNot curable (will try radiation and chemo)

6-12 month survival

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Brain Tumors Can Mimic Other Things

8 year-old. Disruptive in class for last 2-years. Dx ADHD. Trials of behavior management and Ritalin.

Getting worse. Declining school performance. Slowed speech. Very disinhibited.

MRI – Diffusely infiltrating CNS

germinoma

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Brain Tumors are Often First Seen by the Neurosurgeon

Medical Emergencies - rare (Increased ICP with herniation):Altered Level of ConsciousnessFixed and Dilated PupilEye “Down and Out

”

due to CNIII palsy

Abnormal posturing

Paralysis due to spinal cord

lesion

Medical Urgencies

– more common (some suggest ICP):

Headache and vomiting

Papilledema

Ataxia

Visual changes (loss of vision)

Nystagmus

Slide38

Case Four

– Hodgkin Lymphoma14-year old boy. Increasing “

swelling

”

of neck. 3 Large matted palpable masses (lymphadenopathy) in R anterior triangle and a supraclavicular node.

Fevers, tired, night-sweats, 20 pound weight loss in last 4 weeks

Confused with infectious mononucleosis (EBV).

Normal CBC and Differential.

LDH: 1400 (N: 150-350)

Mediastinal Mass

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Clinical Pearl

Small (1x1cm) lymphadenopathy in anterior/posterior cervical triangle or occipital area is common in children and

often

(but not always) related to infection…. BUT

A supraclavicular node is cancer until proven otherwise.

Clavicle

Node

Slide40

Lymphoma

“Cancer of the lymphatic system

”

Lymph nodes

Tonsils and adenoids (

Waldeyer

’

s Ring)

Spleen

About 14% of childhood malignancies

Lymph nodes are all over – know where they are

Slide41

Lymphoma

2 “

broad

”

types:

Hodgkin lymphoma (HL)

Non-Hodgkin lymphoma (NHL

)

Although named

“

lymphoma

”

the cancer is very different in children than adults:

Children: 50% HL 50% NHL

Adults: 10% HL 90% NHL

Adult NHL – most tend to be indolent,

“

slow growing

”

, non-aggressive

.

Child NHL – very aggressive, widely spread to non-lymphatic tissues such as bone marrow and CNS.

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How is Lymphoma Different Than Leukemia?

Leukemia

– clone arises from a immature blood cell (e.g. lymphoblast) in the bone marrow and

“

spreads out

”

systemically to the lymph nodes, spleen, liver, etc…

Lymphoma

– clone arises from a mature blood cells (e.g. T-lymphocyte) in lymphatic tissue and metastasizes to other lymphatic tissue, bone marrow, and other tissues.

Slide43

Clinical

Presentation of Lymphoma

Lymphadenopathy – often painless

Splenomegaly

Hepatomegaly

“

B-symptoms

”

– weight loss, fevers, night sweats.

Itching

Pain in lymph nodes after alcohol consumption!

Anemia

Rapidly expanding abdominal mass =

Burkitt

’

s lymphoma (a type of NHL)

Slide44

Questions?