Rene Y. McNall-Knapp, MD, FAAP Pedatric Hematology/Oncology, OUHSC Pediatric Zebras Rene Y. McNall-Knapp, MD, FAAP Pedatric Hematology/Oncology, OUHSC

Telling the Difference Keep worst possible diagnosis (UGLY ZEBRA) in mind Family, patient, caregivers partner in care Expected course of disease May take more than one visit Bad things don’t get better on their own Stay humble Telling the Difference

Day 1 4 y.o. boy presents with back and leg pain for 2-3 days History – no fever, hurting mostly at night, usually very active Physical – unremarkable, scattered bruises of various ages Labs/Imaging - ? Case study #1

Case Study #1 Visit 2 WBC 4.4K (80% lymphs) Hemoglobin 5.2 g/dL History – pain worsening, not walking, lethargy, bruising, fever PE – bruising, pallor, lymphadenopathy Labs/Imaging WBC 4.4K (80% lymphs) Hemoglobin 5.2 g/dL Platelets 10K Case Study #1

Diagnosis Leukemia – in this case ALL ALL/AML – most common cancer in childhood Presenting symptoms, findings Anemia – pallor, fatigue Thrombocytopenia – bruising, bleeding Leukocytopenia – infections, thrush, fever Adenopathy – mediastinal, peripheral Splenomegaly Bone pain Leukemia cutis Diagnosis

Started on induction therapy for standard risk ALL On day 29 was in remission Continues on chemotherapy Treatment and Results

Importance of identifying zebras Cancer is #1 disease killer in children Cancer is diagnosed in 1:300 boys and 1:330 girls before 21 Stage at diagnosis has dramatic effect on prognosis (morbidity and mortality) 75% cure for all children walking in door Importance of identifying zebras

Challenges of delay in diagnosis Imagine if you didn’t catch it on visit 2 Patient worsened and worsened over next 2 weeks Presents to local ER Codes due to severe anemia and infection Revived but multisystem organ dysfunction and disseminated Aspergillus Must treat leukemia in face of all of this Challenges of delay in diagnosis

1st visit Almost 2 y.o. girl with complaint of vomiting for last month No rhyme or reason to the vomiting PE – small, fluid behind TM, otherwise unremarkable Labs/imaging Assessment and plan – otitis, amoxicillin, RTC 2 weeks for ear recheck Case #2

2nd Visit History – continues to have daily vomiting, also acting as if hurting inactive, losing milestones PE – weight loss, sleepy Labs/Imaging – Assessment/Plans - Case #2

Presents to ER 2 weeks later because parents worried she might have a parasite History – vomiting everything, lost 1/3 of her weight Physical – emaciated, lethargic Labs/Imaging – normal labs, US abdomen and Xray normal Admitted to hospital for observation That night stopped breathing – Code Blue Revived and imaging done Case #2 – Imagine If

Diagnosis Brain Tumor (Specifically Medulloblastoma) 2nd most common cancer in childhood Prognosis depends on type and stage of diagnosis, surgical resection Presenting symptoms – common for posterior fossa Nausea/vomiting Headache Head tilt Ataxia Lethargy Double vision Diagnosis

Other Symptoms of Brain Tumors Infants – macrocephaly, sunset eyes, loss of milestones, wasting Seizures – not febrile seizures Abnormal eye movements or looking through peripheral vision Delayed or precocious puberty Abnormal growth Other cranial nerve palsies – drooling, aspirating, facial droop Other Symptoms of Brain Tumors

Approaches to zebra symptoms First – do no harm Least invasive/radioactive test you can do to reassure yourself Let the kid keep some of his own blood Second – build rapport with family for close follow-up Third – act deliberately using history and physical as your guide Hint – there are algorithms out there to help! Approaches to zebra symptoms

Red light zebra symptoms Hypertension – should test at least annually and at every sick visit Varies by age and height Renal tumors disease, adrenal tumors and disease, coarctation of the aorta (arm > leg), others W/U – H&P, UA, CMP, renal US Horses – essential hypertension Fever > 5 days 101 F Leukemia, Kawasaki, unusual infections W/U – H&P, CBC, appropriate cultures Horses – I don’t know what but Zithromax will make it better Red light zebra symptoms

Red light zebra symptoms Eye – abnormal eye movements, proptosis, white reflex Brain tumor, retinoblastoma, metastatic disease, rhabdomyosarcoma, orbital cellulitis W/U – urgent ophthalmology referral, MRI brain/orbit Horses – normal for baby, conjunctivitis Adenopathy >1 cm all except inguinal (>1.5 cm) and supraclavicular (any) Leukemia, lymphoma, EBV, other infections, abdominal malignancy (Virchow’s node) W/U – CBC, CMP, uric acid, LDH, CXR, response to antibiotics (if appropriate case), biopsy Horses – common infections Warning – do not give steroids Red light zebra symptoms

Red light zebra symptoms Wheezing, shortness of breath Foreign body, mediastinal mass, vascular ring W/U – H&P, CXR Warning – again steroids! Abdominal mass Renal disease, tumors, benign lesions, severe constipation W/U – H&P, Xray or abdominal US Red light zebra symptoms

Red light zebra symptoms Bone or joint pain Infection, leukemia, sarcomas, metastatic lesions W/U – H&P, CBC, Xray entire bone, consider bone scan Horses – growing pains, injury Soft tissue mass Sarcoma W/U – image (MRI) then excisional biopsy Horses – lipoma, ganglion cyst Red light zebra symptoms

Signs to collect yourself Poor growth – growth charts essential Brain tumor, Turner’s syndrome, other syndromes W/U – H&P, ?endocrinology referral, ?imaging Horses – normal for patient Delayed or precocious puberty Testicular mass Testicular cancer W/U – H&P, testicular ultrasound Signs to collect yourself