Clinical Assessment and
Differential Diagnosis of a
Child with Suspected Cancer
Pediatric Resident Education Series
General Points
 Signs and symptoms of cancer are relatively
non-specific and mimic a variety of more
common childhood problems
 For an oncologist the index of suspicion for
cancer is high
 For a primary care physician the opposite is
true
 You have to think about the possibility of
cancer before you can make the diagnosis
General Points
 Nothing replaces a thorough medical history, family history and
physical exam
 Familial/genetic diseases associated with increased cancer
risk




Major categories of diseases linked with an increased cancer
risk include




Neurofibromatosis
Familial polyposis
Li-Fraumeni syndrome
Immune deficiencies
Metabolic disorders
Disorders of chromosome stability
Environmental exposures

Previous diagnosis of cancer/cancer therapy
Common things are not always common…
 Symptoms and Signs of cancer mimicking normal
childhood illnesses for which an initial evaluation for
cancer is usually Not warranted include:






Generalized malaise, fever, adenopathy
Headache, rhinorrhea, epistaxis, febrile seizure,
rhinitis, pharyngitis, earache
Nausea, vomiting, diarrhea,
Hepatomegaly, splenomegaly
Hematuria, trouble voiding, vaginitis
Masses (bony or soft tissue), pain/swelling
Symptom / Sign
Possible Malignancy
 Generalized malaise, fever,
 Lymphoma, leukemia, Ewings
adenopathy
 Head & Neck
 Headache, nausea,
vomiting
 Febrile Seizure
 Earache
 Rhinitis
 Epistaxis
 Pharyngitis
 Adenopathy
(EWS), neuroblastoma (NBL)

Brain tumor, leukemia

Brain tumor
Soft Tissue Sarcoma (STS)
STS
Leukemia
STS
NBL, thyroid tumor, STS,
leukemia, lymphoma,





Symptom / Sign
Possible Malignancy
 Thorax

Extrathoracic



Soft tissue mass
Bony mass

STS, PNET
EWS, NBL

Lymphoma, leukemia

STS, PNET

NBL, lymphoma,
hepatic tumor,
leukemia

Intrathoracic

Adenopathy
 Abdomen

External:


soft tissue
Internal:

diarrhea, vomiting,
hepatomegaly and/or
splenomegaly
Symptom / Sign
Possible Malignancy
 Genitourinary




Hematuria
Trouble voiding
Vaginitis
Paratesticular mass




Wilms’, STS
Prostatic or bladder STS
STS
STS
 Musculoskeletal


Soft tissue mass(es)
Bony mass/pain


RMS, other STS, PNET
Osteosarcoma, EWS,
Non-Hodgkin’s lymphoma
(NHL), NBL, Leukemia
Signs and Symptoms in the
Child with Cancer
 If the signs and symptoms listed in previous
table do not subside within a reasonable
period, a consult with an oncologist is
warranted
 Exception to this rule – soft tissue mass in a
child without a explanatory traumatic event
warrants an early evaluation
Distribution of Lag Time in Days by
Diagnosis of Common Childhood Cancers
n
Mean
Median
25th %
75th %
Brain
194
211
93
38
237
Ewing’s
82
182
127
79
255
Hodgkin’s
143
223
136
49
270
Leukemia
908
109
52
20
129
NHL
184
117
62
25
141
NBL
237
120
58
15
164
OS
67
127
98
40
191
RMS
126
127
55
25
161
Wilms’
223
101
31
9
120
Diagnosis
Table 7-1. Pizzo & Poplack, 4th ed.
Common things are not always common… (part 2)
 Unusual Symptoms and Signs that warrant an
immediate laboratory and/or imaging studies and
consultation include:







Hypertension, unexplained weight loss
Focal neurologic abnormalities
Masses
Petechiae, pallor
Adenopathy not responding to antibiotics
Early morning vomiting
Pain waking from sleep, not responsive to
acetaminophen or NSAIDs
Symptoms/Signs
Laboratory, imaging
studies, & consultations
Major associated tumors
Hypertension
CXR, Abd US
Renal or abdominal tumor,
NBL
Weight loss, sudden onset
Abd US
Any malignancy
Petechiae
CBC, manual diff
Leukemia, NBL
Adenopathy unresponsive to Surgical consultation, CXR,
ABs
CBC, manual diff
Leukemia, Lymphoma
Endocrine abnormalities
Growth failure
Hormonal assays
Pituitary tumors
Electrolyte disturbances
CT hypothalamic area
Hypothalamic tumors
Sexual abnormalities
Abdominal CT
Gonadal tumors
Cushing’s syndrome
Endocrine consult
Adrenal tumors
Brain
Neurology and/or NeuroSurgery Consultation
followed by Imaging Studies
Brain Tumor
Headache, early AM vomiting
Cranial nerve palsy, ataxia
Dilated pupil, papilledema
Afebrile seizures
Hallucinations, aphasia
Unilateral weakness, paralysis
Symptoms/Signs
Eyes
Laboratory, imaging
studies, & consultations
Major associated tumors
Ophthalmologic consultation
Retinoblastoma,
metastatic neuroblastoma,
rhabdomyosarcoma (RMS),
or other STS
White Spot, proptosis,
blindness
Wandering Eye
Intraorbital hemorrhage
Ears
Bulging mass external canal
LCH, RMS
CBC, diff, Imaging studies
Mastoid tenderness, swelling
Puffy face & neck
CBC, diff, imaging studies
Mediastinal tumors
Pharyngeal mass
CBC, diff, imaging studies
RSM, lymphoma, nasopharyngeal carcinoma
Periodontal mass, loose
teeth
Dental consultation, imaging
studies
LCH, Burkitt’s lymphoma,
neuroblastoma, osteosarcoma
CBC, diff, imaging studies
Soft tissue tumors,
mediastinal tumors,
metastatic tumors
Thorax
Extrathoracic: mass
Intrathoracic: coughing, SOB
without fever or no history of
asthma, allergies
Symptoms/Signs
Abdomen/Pelvis
Intra-abdominal mass
Genitourinary
Testes, vaginal mass
Masculinization /
feminization
Musculoskeletal
Soft tissue, bone marrow,
and/or pain
Laboratory, imaging
studies, & consultations
Abd US; CBC, diff
UA, CBC, diff
US of abdomen/pelvis
CBC, diff
Imaging studies
Major associated tumors
Wilms’ tumor, soft tissue
sarcoma, neuroblastoma,
hepatoblastoma, hepatocellular carcinoma
Germ cell tumor, RMS,
adrenal tumor
Osteosarcoma, Ewings
sarcoma, leukemia,
neuroblastoma, soft tissue
sarcoma
CNS Symptoms Concerning for Brain
Tumors
 Masses can be suspected on the basis of a
symptom complex that reflects the site of the
tumor (seizures, weakness, difficulties with
coordination)
 Pediatric tumors are often situated such that
they interfere with CSF circulation resulting in
increased intracranial pressure

Headaches and vomiting are common
presenting signs in these cases
Symptoms and/or Signs concerning for
Leukemia
 Unexplained fever > 101oF for more than a
week
 Petechiae
 Unexplained anemia / pallor
 Generalized lymphadenopathy
 Hepatosplenomegaly
 Bone or joint pain (30%) not relieved with
pain medications or that wakes from sleep
Conditions Suggesting the Need for Radiographic
Evaluation in Children with Headaches
 Presence of neurologic abnormality
 Ocular findings, papilledema
 Vomiting that is persistent, increasing or preceded by





recurrent headaches
Changing character of the headache
Recurrent morning headaches or headaches that
awaken or incapacitate the child
Short stature or deceleration of linear growth
Diagnosis of Neurofibromatosis
Previous history of leukemia or CNS radiation
Lymphadenopathy
 Diagnosis
 Lymph Node is considered large if > 10 mm;
exceptions:
 Epitrochlear nodes > 5 mm
 Inguinal node > 15 mm
 Most enlarged lymph nodes in children are related to
infections




Bacterial – Staph and Strep
Atypical mycobacterium
Cat scratch disease
Viral – EBV and other herpes viruses
Lymphadenopathy
 Regional or generalized?
 Generalized more likely malignant (except EBV)
 Regional adenopathy not involving the head and neck
more likely malignant
 Characteristics of the enlarged node(s)
 Hard/rubbery, non-tender, matted (fixed, non-mobile)
node is more likely malignant
 Location of the adenopathy
 Adenopathy in the posterior auricular, epitrochlear or
supraclavicular areas is abnormal
 Mediastinal adenopathy is frequently malignant
Need for Lymph Node Biopsy is Suggested by
the Following Signs and Symptoms
 Enlarging nodes after 2-3 weeks of antibiotic therapy
 Nodes that are not enlarging but have not diminished
in 6-8 weeks
 Nodes associated with any abnormal chest X-ray
 Adenopathy with associated weight loss,
hepatosplenomegaly, unexplained fevers, and/or
drenching night sweats
 Adenopathy in the posterior auricular, epitrochlear or
supraclavicular areas
Masses
 Abdominal, Thoracic and Soft Tissue Masses
(without a traumatic explanation)

All require evaluation
Bone and Joint Pain
 Most pain associated with cancer is caused by bone,
nerve or visceral involvement or encroachment
 Bone pain is usually not an early symptom of cancer
except for malignancies involving bone

Ewing’s sarcoma, osteosarcoma
 Come and go early on disappearing for weeks or
months
 Bone or joint pain is a presenting symptom in about
30% of patients with ALL

Can be confused with rheumatic diseases
Bone and Joint Pain
 Evaluation should be performed when





Bone/joint pain is persistent
associated with swelling or mass
Limited mobility or joint motion
Consistently wakes from sleep at night
Not relieved by NSAIDs
Another way to think of things…..
 What is it?
 Where is it?
 Where can it go?
 The answer to any one of the above can help
answer the other two
Work-up: Two Components
 Staging – find out where the tumor is (and isn’t)
 X-ray of 1o site
 CT body; CXR baseline, bone scan
 Specialty tests
 Gallium, MIBG
 Tumor markers (HCG, HVA/VMA, ….
 Bone marrow
 Evaluate for Complications of the tumor
 CBC w/manual differential, TPN panel
 Other studies
 DIC screen, UA, …
Approach to the diagnosis….
 Tissue diagnosis
 Incisional biopsy
 Excisional biopsy
 Special cases…
 Calicified suprarenal mass + bone scan – in the
absence of any desire for biologic studies, might
consider getting diagnosis from bone marrow
 FNA vs. excisional biopsy
 Bias towards excisional -> sufficient sample to be
representative and to send for special research
studies (histology, chromosomes, special studies,
research studies)
Summary
 Presenting signs and symptoms of childhood cancer
are common to many childhood illnesses
 Early diagnosis of cancer may improve outcome
 If the possibility of cancer is not considered, delayed
diagnosis is the result
 Although the incidence of childhood cancer is low, the
impact of cancer makes it imperative that all
professionals have a high index of suspicion of
cancer
Credits
 Tables from:
 Principles and Practice of Pediatric Oncology, 4th
edition, Pizzo PA & Poplack DG eds., Lippicott Williams
& Wilkins, Philadelphia, 2002
 Bruce Camitta MD
Michael Kelly MH PhD
Kelly Maloney MD
Anne Warwick MD MPH