Do we have cancer? Gavivann Veerakul, MD.

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1 Do we have cancer? Gavivann Veerakul, MD.

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5 Type of pediatric malignancies at Siriraj Hospital Leukemias Lymphomas other hem.malig Neuroblastoma Retinoblastoma Rhabdo Wilms' tumor GCT CNS osteosarcoma Hepatoblastoma others

6 Improved outcome in Pediatric Cancers 100 % surviv Siriraj Hodgkin's ALL NHL ANLL Wilms' GCT Rhabdo osteosarc brain tumors

7 Common Presenting Symptoms BM failure Anemia, prolonged fever, thrombocytopenia Masses Abdomen, mediastinal, orbital, extremities & trunk, hepatosplenomegaly lymphadenopathy etc. Pain Headache, bone pain, back pain, Unexplained abnormal bleeding vaginal bleeding, hematuria, hematochezia Neurological symptoms CN, paraplegia, limping gait, Horner s syndrome Cord compression Endocrine abnormalities: DI, precocious puberty, growth failure

8 Headaches Obstruction of CSF circulation Increased intracranial pressure

9 Distribution of common brain tumors in children

10 Headaches Infratentorium Supratentorium Vomit 76% Headache 56% Vomit 46% Headache 43% Coordination 59% difficulty

11 Clinical manifestations Increased intracranial pressure Impaired vision Diplopia (6 th nerve palsy) Frequent blinking or intermittent strabismus in small child Parinaud syndrome (impaired upward gaze, sun set eye) Cranial enlargement Focal seizures Mental disturbances Somnolence Irritability Personality changes Disturbance of gait and balance Endocrine abnormalities (midline, supratentorial tumor) Diencephalic syndrome Failure to thrive, emaciation Caused by hypothalamic tumor

12 Headaches: the need for CT/MRI Presence of neurological abnormality 95% Vomit: persistent, increasing frequency, preceded by recurrent headache Headache: increase severity and frequency or recurrent morning headaches or repeatedly awaken child from sleep Ocular findings: papilledema, loss of visual acuity, visual field defect Endocrine abnormal: Growth failure, Diabetes inspidus, Age < 3 years Neurofibromatosis, Li Fraumeni syndrome, tuberous sclerosis, von Hipple-Lindau Hx of cranial irradiation for leukemia/lymphoma

13 Lymphadenopathy Waldeyer's ring localized vs. generalized Size Site Tenderness Matted Consistency

14 Etiology: generalized lymphadenopathy Infectious Systemic viral infection: EBV, CMV, HIV, roseola Systemic bacterial infection: TB, Salmonella Malignancy Leukemia, lymphoma, metastatic tumors Firm, non-tender, matted, non mobile Present of systemic symptoms Storage disease Gaucher disease, lipid storage disease: Niemann-Pick Drug reaction : phenytoin Lymphadenopathy, maculopapular rash and fever Others: autoimmune, SLE, sarcoidosis, histiocytoses

15 Investigations CBC / hemoculture Serology EBV (fever, pharyngitis, splenomegaly) Toxoplasmosis Imaging study CXR (hilar node, TB) CT scan (abdominal masses, mediastinal mass) Others : PPD, BM aspiration

16 Treatment of lymphadenopathy Wait and see Treat cause Antibiotics Anti-staphylococcal/Streptococcal agent Cover Anaerobe for cervical lymphadenopathy Empirical Cephalexin 50 mg/kg/day (4 divided doses) Cloxacillin + clindamycin Cefoxitine mg/kg/day IV/IM (3-4 divided dose) Penicillin allergic patient : erythromycin 50 mg/kg/day)

17 Lymph node biopsy : R/O malignancy No obvious infection & rapidly enlarging Nodes enlarged after 2-3 wk of antibiotics or not diminish in size after 5-6 wk or not normal after wk Associated symptoms: weight loss, prolonged fever, sweats, Horner syndrome, hepatosplenomegaly Persistent supraclavicular, epitroclear, lower neck

18 A 3-year old boy Generalized lymphadenopathy Hepatosplenomegaly Anemia

19 CBC II Hct 25%, Hb 8.1 g/dl WBC 2.3 x10 9 /L I Hct 19%, Hb 7.1 g/dl WBC 56.5 x10 9 /L N5, L15, blast70% Platelet 25.0 x10 9 /L N20, L75, Mo5 % Platelet 75.0 x10 9 /L III Hct 31%, Hb 10.5 g/dl WBC 32.0 x10 9 /L N40, L45, Mo15 % Platelet x10 9 /L

20 Peripheral blood smear 1 Hct 19%, Hb 7.1 g/dl WBC 56.5 x10 9 /L N5, L15, blast70% Platelet 25.0 x10 9 /L

21 Peripheral blood smear 2 Hct 25%, Hb 8.1 g/dl WBC 2.3 x10 9 /L N20, L75, Mo5 % Platelet 75.0 x10 9 /L

22 Peripheral blood smear 3 III Hct 31%, Hb 10.5 g/dl WBC 32.0 x10 9 /L N40, L45, Mo15 % Platelet x10 9 /L

23 BM aspiration

24 lymphadenopathy

25 Hodgkin s disease

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28 Thoracic masses non-malignant malignant anterior middle thymus angioma,lipoma thyroid mass infections: TB hernia, cardiac or bronchogenic cysts lymphoma thymoma teratoma lymphoma, metastatic tumor posterior thoracic meningocele, enterogenous cyst, neurogenic tumors: neuroblastoma, ganglioneuroma, neurilemmoma, EWS, Rhabdo, pheochromocytoma,

29 SVC obstruction Signs & Symptoms Swelling at face, neck, arms and upper chest superficial dilated veins orthopnea headache, dizziness, fainting pulsus paradoxus >> cardiac failure cough, dyspnea, air way obstruction >> respiratory failure

30 Mediastinal mass LBL

31 hepatosplenomegaly Differential Dx Non malignancy thalassemia chronic hemolytic anemia storage disease infection: TB, viral, typhoid, malaria malignancies leukemia lymphoma histiocytosis (LCH) MDS/MPD

32 bone and joint pain Differential Dx Non malignancy polyarthritis septic arthritis JRA SLE infection malignancies leukemia neuroblastoma bone tumor: EWS, osteosarcoma,

33 bone and joint pain Persistent pain Abrupt onset Occur at night Significant pain Swelling, mass, limitation of motion Associate with neutropenia Promptly obtain radiography with experienced interpretation

34 Abdominal mass

35 Abdominal masses in Children newborn Benign: Kidney: polycystic, multicystic, hydronephrosis bowel mass: duplication, intussusception, volvulus Malignancies Hepatoblastoma, neuroblastoma children Kidney : Wilms tumor Adrenal : neuroblastoma Hepatic : hepatoblastoma, sarcomas Lymph node : lymphoma (Burkitt s) Ovary, gonad: germ cell tumors Others : rhadomyosarcoma, leiomyosarcoma

36 Abdominal masses in Children Abdominal examination Relaxed Liver edge, spleen, kidney, aorta, sigmoid colon, feces, may be palpable in normal child Enema Bladder catheterized CBC Rectal examinations in infant and young girls Bimanual palpation Pelvic examination should be avoid Ultrasound abdomen/ CT scan with contrast CXR, IVP Tumor markers : AFP, βhcg, CEA, LDH Bone marrow aspiration / biopsy

37 Abdominal mass Neuroblastoma Wilms tumor Symptoms abdominal pain, bone pain, metastasis, pale Firm to hard consistency, irregular surface Intra-abdominal palpable and may cross midline Calcification is common CT scan shows multiple intraabdominal lymphadenopathy with extensive organ involvement Symptomless accidental palpable by caretaker Tense cystic or firm consistency, smooth surface Bimanual palpable, usually unilateral Calcification is rare CT scan usually show well circumscribed renal mass, may extend into IVC and intracardiac

38 At diagnosis

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40 3 5 months later

41 18 months later

42 Pancytopenia 936 untreated ALL Hb < 7.5 g/dl 51% Plt < /mm 3 73% WBC < 5,000 30% 171 untreated AML Plt < /mm 3 82% WBC < 5,000 39%

43 Acute Lymphoblastic Leukemia Kaplan Meyer Survival Analysis Acute Lymphoblastic Leukemia in Children Cumulative Proportion Surviving Survival Time (months) 5 year overall survival = 76% (71-88%)

44 Acute non-lymphoblastic Leukemia 1.0 Kaplan-Meier Survival Analysis of Pediatric Patients with ANLL Department of Pediatrics, Siriraj Hospital Cumulative Proportion Surviving Survival Time (months) 5-yr survival = 38%

45 Childhood Lymphoma Gavivann Veerakul, M.D. Div of Hematology/Oncology, Dept of Pediatrics, Siriraj Hospital

46 Classifications Lymphoma Hodgkin's Lymphoma Non-Hodgkin's Lymphoma Lymphoblastic Small non-cleaved Large cell Immature T 90% Pre-B 10% Burkitt's non-burkitt's Immunoblastic: B>T Anaplastic Ki-1 +:T> B Peripheral T cell Large B cell

47 Childhood NHL Study at Siriraj Hospital ( total of 8 years) n=100 SNC 29 % LBL 35 % LCL 36 %

48 Abdominal mass & ascites

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50 Non-Hodgkin s lymphoma treated at Siriraj Hospital Cumulative Proportion Surviving (Kaplan-Meier) Non-Hodgkin's Lymphoma in Siriraj Hospital n = Cumulative Proportion Surviving SNC n = 29 LCL n = 36 LBL n = 35 Time (months after diagnosis)

51 Outcome of pediatric solid tumors Type of disease Stage at diagnosis Histology : favorable and unfavorable Age of the patients Treatment protocol

52 orbital mass unilateral retinoblastoma rhabdomyosarcoma lymphoma benign lesion : infection, trauma, hemangioma bilateral leukemia lymphoma retinoblastoma neuroblastoma histiocytosis

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56 Exolpthalmos

57 Exolpthalmos

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59 Rhabdomyosarcoma Retinoblastoma

60 AML

61 AML

62 Acute Non-Lymphoblastic Leukemia

63 Burkitt s lymphoma

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65 Neuroblastoma Periorbital ecchymosis

66 Neuroblastoma

67 What are their diagnoses?

68 scrotal mass Non malignancies hernia hydrocele Malignancies leukemia lymphoma germ cell tumor rhabdomyosarcoma

69 SPINAL CORD COMPRESSION

70 PNET Peripheral Neuroepithelioma Tumor

71 Ewings Sarcoma Cord compression and lung metastasis

72 Rhabdomyosarcoma with spinal cord compression

73 Rhabdomyosarcoma with BM metastasis

74 Rhabdomyosarcoma Pre-Chemotherapy 5 days post chemotherapy 10 days post chemotherapy

75 Rhabdomyosarcoma

76 Rhabdomyosarcoma

77 Horner's syndrome ptosis anhydrosis miosis NB stage III

78 Classification of histiocytosis disorders Class I Langerhans cell histiocytosis Class II FEL: Familial hemophagocytic lymphohistiocytosis IAHS: Infectious-associated hemophagocytic syndrome MAHS: Malignant-associated hemophagocytic syndrome Class III AMoL (M5) True histiocytic lymphoma malignant histiocytosis

79 Class I : Langerhans cell histiocytosis Letterer Siwe Cutaneous, nodal, visceral, BM Hand-Schuller-Christian disease Skull defect, DI, exopthalmos Eosinophilic Granuloma Bone, lungs, nodes

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81 LCH : seborrheic dermatitis

82 LCH : osteolytic lesion

83 DISORDERS OF VARIED BIOLOGICAL BEHAVIOR Dendritic cell related disorders LCH Juenile xanthogranuloma Macrophage related disorders Hemophagocytic syndrome Primary : Familial Hemophagocytic Lymphohistiocytosis (FEL) Secondary : IAHS, MAHS Rosai-Dofman disease (SHML or Sinus histiocytosis with massive lymphadenopathy) MALIGNANT DISORDERS Monocyte related Leukemia M5 Extramedullary monocytic sarcoma Macrophage related histiocytic sarcoma Dendritic cell related histiocytic sarcoma

84 Treatment of childhood cancer Multidisciplinary approach

85 Outcome of treatment

86 Cumulative Proportion Surviving (Kaplan-Meier) Different types of Solid Tumor Outcome for Pediatric Patients Treated at Siriraj Hospital during Cumulative Proportion Surviving NB RB WT GCT HP BR OS RD Time (month)

87 Pediatric oncologist hardly give up!

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89 Not only 5-year-survival, but long term outcome and best quality of life is the concern and goal of our treatment

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91 Quiz

92 A 3-month-old baby with abdominal mass

93 A child with abdominal mass

94 A child with mediastinal mass

95 A child with proptosis

96 A 3-yr-old child with cervical lymphadenopathy

97 A child with bone pain, refuse to walk