Clinical Assessment and Differential Diagnosis of a Child with Suspected Cancer

1. Clinical Assessment and Differential Diagnosis of a Child with Suspected Cancer Pediatric Resident Education Series

2. 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

3. 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

4. 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

5. 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,

6. 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

7. 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

8. 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

9. Distribution of Lag Time in Days by Diagnosis of Common Childhood Cancers Table 7-1. Pizzo & Poplack, 4th ed.

10. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. Masses • Abdominal, Thoracic and Soft Tissue Masses (without a traumatic explanation) • All require evaluation

21. 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

22. 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

24. 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

25. 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, …

26. 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)

27. 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

29. 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