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 Previous diagnosis of cancer/cancer therapy

Environmental exposures


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

Symptoms and Signs of Cancer Mimicking Normal Childhood Illnesses: Initial Evaluation for Cancer Usually Not Warranted

Symptom / Sign
 Generalized malaise, fever,

Possible Malignancy
 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
 Thorax


Possible Malignancy

Extrathoracic
 

Soft tissue mass Bony mass Adenopathy

 

STS, PNET EWS, NBL Lymphoma, leukemia

Intrathoracic
 

 Abdomen
 

External:


soft tissue diarrhea, vomiting, hepatomegaly and/or splenomegaly

STS, PNET NBL, lymphoma, hepatic tumor, leukemia

Internal:
 

Symptom / Sign
 Genitourinary
   

Possible Malignancy

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-Hodgkins 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

Diagnosis Brain Ewings Hodgkins Leukemia NHL NBL OS RMS Wilms n 194 82 143 908 184 237 67 126 223 Mean 211 182 223 109 117 120 127 127 101 Median 93 127 136 52 62 58 98 55 31 25th % 38 79 49 20 25 15 40 25 9 75th % 237 255 270 129 141 164 191 161 120

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
Hypertension Weight loss, sudden onset Petechiae

Laboratory, imaging studies, & consultations

CXR, Abd US Abd US CBC, manual diff

Major associated tumors

Renal or abdominal tumor, NBL Any malignancy Leukemia, NBL Leukemia, Lymphoma

Adenopathy unresponsive to Surgical consultation, CXR, ABs CBC, manual diff Endocrine abnormalities
Growth failure Electrolyte disturbances Sexual abnormalities Cushings syndrome Hormonal assays CT hypothalamic area Abdominal CT Endocrine consult

Pituitary tumors Hypothalamic tumors Gonadal tumors Adrenal tumors

Brain
Headache, early AM vomiting Cranial nerve palsy, ataxia Dilated pupil, papilledema Afebrile seizures Hallucinations, aphasia Unilateral weakness, paralysis

Neurology and/or NeuroSurgery Consultation followed by Imaging Studies

Brain Tumor

Symptoms/Signs
Eyes
White Spot, proptosis,

Laboratory, imaging studies, & consultations

Ophthalmologic consultation

Major associated tumors

Retinoblastoma, metastatic neuroblastoma, rhabdomyosarcoma (RMS), or other STS LCH, RMS

blindness Wandering Eye Intraorbital hemorrhage

Ears
Bulging mass external canal Mastoid tenderness, swelling

CBC, diff, Imaging studies CBC, diff, imaging studies CBC, diff, imaging studies Dental consultation, imaging studies CBC, diff, imaging studies Mediastinal tumors RSM, lymphoma, nasopharyngeal carcinoma
LCH, Burkitts lymphoma, neuroblastoma, osteosarcoma

Puffy face & neck Pharyngeal mass Periodontal mass, loose teeth Thorax
Extrathoracic: mass Intrathoracic: coughing, SOB

Soft tissue tumors, mediastinal tumors, metastatic tumors

without fever or no history of asthma, allergies

Symptoms/Signs
Abdomen/Pelvis Intra-abdominal mass

Laboratory, imaging studies, & consultations

Abd US; CBC, diff

Major associated tumors

Wilms tumor, soft tissue sarcoma, neuroblastoma, hepatoblastoma, hepatocellular carcinoma Germ cell tumor, RMS, adrenal tumor

Genitourinary Testes, vaginal mass Masculinization / feminization Musculoskeletal Soft tissue, bone marrow, and/or pain

UA, CBC, diff US of abdomen/pelvis

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


Ewings 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 isnt)  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