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 Neurofibromatosis Familial polyposis Li-Fraumeni syndrome

Major categories of diseases linked with an increased cancer risk include

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

Generalized malaise, fever, adenopathy

Head & Neck Headache, nausea,

vomiting Febrile Seizure Earache Rhinitis Epistaxis Pharyngitis Adenopathy

Possible Malignancy

Lymphoma, leukemia, Ewings (EWS), neuroblastoma (NBL)

Brain tumor, leukemia

Brain tumor Soft Tissue Sarcoma (STS) STS Leukemia STS NBL, thyroid tumor, STS,

leukemia, lymphoma,

Symptom / Sign

Thorax Extrathoracic

Soft tissue mass Bony mass

Intrathoracic Adenopathy

Abdomen External:

soft tissue Internal:

diarrhea, vomiting, hepatomegaly and/or splenomegaly

Possible Malignancy

STS, PNET EWS, NBL

Lymphoma, leukemia

STS, PNET

NBL, lymphoma, hepatic tumor, leukemia

Symptom / Sign

Genitourinary Hematuria Trouble voiding Vaginitis Paratesticular mass

Musculoskeletal Soft tissue mass(es) Bony mass/pain

Possible Malignancy

Wilms’, STS Prostatic or bladder STS STS STS

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

Diagnosis 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

Distribution of Lag Time in Days by Diagnosis of Common Childhood Cancers

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 ABs

Surgical consultation, CXR, CBC, manual diff

Leukemia, Lymphoma

Endocrine abnormalitiesGrowth failureElectrolyte disturbancesSexual abnormalitiesCushing’s syndrome

Hormonal assaysCT hypothalamic areaAbdominal CTEndocrine consult

Pituitary tumorsHypothalamic tumorsGonadal tumorsAdrenal tumors

BrainHeadache, early AM vomitingCranial nerve palsy, ataxiaDilated pupil, papilledemaAfebrile seizuresHallucinations, aphasiaUnilateral weakness, paralysis

Neurology and/or Neuro-Surgery Consultation followed by Imaging Studies

Brain Tumor

Symptoms/Signs Laboratory, imaging studies, & consultations

Major associated tumors

EyesWhite Spot, proptosis, blindnessWandering EyeIntraorbital hemorrhage

Ophthalmologic consultation Retinoblastoma, metastatic neuroblastoma,rhabdomyosarcoma (RMS), or other STS

EarsBulging mass external canalMastoid tenderness, swelling

CBC, diff, Imaging studies

LCH, RMS

Puffy face & neck CBC, diff, imaging studies Mediastinal tumors

Pharyngeal mass CBC, diff, imaging studies RSM, lymphoma, naso-pharyngeal carcinoma

Periodontal mass, loose teeth

Dental consultation, imaging studies

LCH, Burkitt’s lymphoma, neuroblastoma, osteosarcoma

ThoraxExtrathoracic: massIntrathoracic: coughing, SOB without fever or no history of asthma, allergies

CBC, diff, imaging studiesSoft tissue tumors, mediastinal tumors, metastatic tumors

Symptoms/Signs Laboratory, imaging studies, & consultations

Major associated tumors

Abdomen/PelvisIntra-abdominal mass

Abd US; CBC, diff Wilms’ tumor, soft tissue sarcoma, neuroblastoma, hepatoblastoma, hepato-cellular carcinoma

GenitourinaryTestes, vaginal massMasculinization / feminization

UA, CBC, diff

US of abdomen/pelvis

Germ cell tumor, RMS, adrenal tumor

MusculoskeletalSoft tissue, bone marrow, and/or pain

CBC, diff

Imaging studies

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 MDMichael Kelly MH PhDKelly Maloney MDAnne Warwick MD MPH