16. PAEDIATRIC ONCOLOGICAL CONDITIONS (Neuroblastoma, Burkit’s Lymphoma, Nephroblastoma).pptx

Paediatric oncology

1. PAEDIATRIC ONCOLOGICAL CONDITIONS DR.SHABAN

2. . Throughout our lives, healthy cells in our bodies divide and replace themselves in a controlled .fashion.   Cancer  starts when a cell is somehow altered so that it multiplies out of control. A tumor is a mass composed of a cluster of such abnormal cells. Nb. Most cancers form tumors, but not all tumors are cancerous. Benign, or noncancerous, tumors do not spread to other parts of the body, BUT Malignant, or cancerous, tumors crowd out healthy cells, interfere with body functions, and draw nutrients from body tissues. Cancers continue to grow and AND do metastasis, through the lymphatic or blood vessels -- eventually forming new tumors in other parts of the body.

3. FORMS OF CANCER The major types of cancer are carcinoma,  sarcoma melanoma   lymphoma Leukemia Blastoma

4. OBJECTIVES Explain aetiology/risk factors of common oncological conditions Outline epidemiology of common paediatric oncological conditions Explain clinical features of common paediatric oncological conditions Establish diagnosis/ provisional and differential diagnosis of common paediatric oncological conditions Provide pre-referral treatment of common paediatric oncological conditions Provide appropriate supportive care for oncological conditions Provide counselling and follow-up services of common paediatric oncological conditions

5. LYMPHOMA Study case BURKIT LYMPHOMA

6. Burkitt lymphoma; - introduction- Burkitt lymphoma  is the malignancy  of the  B lymphocytes. It is named after Denis Burkitt, the surgeon  who first described the disease in 1958 while working in  Mulago Hospital in Uganda. Burkitt's lymphoma is commonly associated with the infection of B cell lymphocytes with the  Epstein-Barr virus  (EBV ) Almost by definition, Burkitt lymphoma are associated with c- myc gene translocation on chromosome 8 .

7. Lymphoma; classification The classification depends on how the lymphoma cells look under a microscope Into HODKINS and NON-HODKINS LYMPHOMA . B-cell neoplasms e.g Burkitt lymphoma T-cell & NK-cell neoplasms Hodgkin Lymphomas Non-Hodgkin lymphoma Pathologically , the disease is characterized by the presence of Reed-Sternberg cells Thomas Hodgkin  (17 August 1798 – 5 April 1866) was a British  doctor and   pathologists known for the first account of Hodgkin's lymphoma   in 1832

8. EPIDEMIOLOGY Frequent in tropics where malaria is holoendemic (Tropical Africa, Cuba, South America, Papua New Guinea) Endemic BL, Geographically called the Burkitt’s Lymphoma belt Distribution corresponds to: High rainfall (with high intense or low intermittent malaria transmission). Morphologically identical tumor occur sporadically throughout the world - sporadic BL . Age Distribution: In endemic areas mostly children less than 10 years are affected while in sporadic regions the tumor occurs in adults

9. Map - Distribution of BL

10. CAUSES The etiology of BL is not known clearly. But there is association with Epstein-Barr virus (EBV). RISK FACTORS Age/sex . M ost likely to affect children. It’s rare in adults. More common in males  Weak immune system NHL is more common among people with inherited immune deficiencies, autoimmune diseases or HIV/AIDS, and among people taking immunosuppressant drugs following organ transplants Viruses . Epstein-Barr virus is infectious agents that increase the chance of developing BL Environmental And radiation Exposure to certain chemicals, such as pesticides, solvents, or fertilizers, Hair dyes.

11. Burkitt lymphoma CLINICAL FEATURES Patients with BL present with rapidly growing tumor. The tumor doubling time is very short hour. The feature depends on the site affected eg . On jaw, orbit, lungs, liver etc.

12. J A W : most affected maxilla more affected than the mandible. Often painless. Mainly the 4-5 years age-group Associated disfigurement, loosening and loss of teeth, halitosis( A foul odor from the mouth) , difficulty feeding and speech

13. ORBIT : T h e m axi l l a ry tu m or oft e n spre a ds to in v o l ve the or b i t , and pres e nts as P roptosis May lead to poor vision, and disf i g u re m ent . 14

14. ABDOMINAL Involves the spleen, liver, ovaries, kidneys, lymphnodes Presents with m asses, distention, pain, constipation, diarrhea, difficulty breathing. Median age of 7 years. 16

15. CNS presents as paraplegia, sphincter abnormalities, CSF pleocytosis and Cranial nerve palsies CHEST - Pleural effusion CLINICAL PRESENTATION; OTHER SITES

16. Burkitt lymphoma Classification Burkitt lymphoma can be divided into three main clinical variants: The Endemic, ……………………………………… . The Sporadic, ……………………………………  Immunodeficiency-associated Variants. 1. The  endemic variant (also called "African variant") most commonly occurs in children living in malaria endemic regions of the world (e.g., equatorial Africa, Brazil, and Papua New Guinea ).  Epstein-Barr virus (EBV) infection is found in nearly all patients. Chronic  malaria is believed to reduce resistance to EBV, allowing it to take hold. The disease characteristically involves the jaw or other facial bone, distal  ileum , ovaries, kidney, or breast .

17. Classification………. 2. The  sporadic type of Burkitt lymphoma ( "non-African") is the most common variant found in places where malaria is not  holoendemic . The tumor cells have a similar appearance to the cancer cells of classical endemic Burkitt lymphoma . Sporadic lymphomas are rarely associated with the Epstein–Barr virus. The jaw is less commonly involved, compared to the endemic variant. The   Abdominal tumor is the common site of involvement . 3. Immunodeficiency-associated  Burkitt lymphoma This is usually associated with HIV  infection [ or occurs in the setting of post-transplant patients who are taking immunosuppressive drugs. Burkitt lymphoma can be one of the diseases associated with the initial manifestation of AIDS.

18. Burkitt lymphoma STAGING St. Jude /Ann- Arbor staging; Stage I - disease in single lymph node or lymph node region . Stage II - disease in two or more lymph node regions on same side of diaphragm. Stage III - disease in lymph node regions on both sides of the diaphragm are affected. Stage IV - disease is wide spread, including multiple involvement at one or more extra nodal sites, . such as the bones, liver, pleura

19. Burkitt lymphoma Diagnosis Proper history taking Physical examination Diagnostic formulation- DDx Investigations-specific. -general.

20. Investigations; FBP Serum electorlytes ; ca , phosphorus, LFT RFT LP for CSF analysis Bone Marrow aspiration and biopsy CXR, neck x ray, serum lactate dehydrogenase and uric acid levels CT chest, neck, abdomen HISTOLOGY: described as having the ‘STARRY SKY’ appearance- this is the specific investigatons

21. The “Starry-sky ” appearance ,

22. Differential Diagnoses Tb adenitis (head and neck lymphadenopathy) Germ cell tumor . ( mediastinal mass) Willimstumor , neuroblastoma , rhabdomyosarcoma (abdominal malignant masses) Leukaemia (BM involvement) Dental cysts Jaw abscess Osteomyelitis of jaw

23. Burkitt lymphoma Treatment Supportive care Nutrition Transfusion Broad spectrum antibiotics Treatment of the tumour cutaneous excision chemotherapy; stem cell transplantation.

24. Treatment Results 32 Complete Re m is sion

25. Burkitt lymphoma Prognosis and follow up Tumour burden (size) BM/CNS involvement/stage of disease Age > 13 years High serum lactate dehydrogenase and uric acid levels . Patients generally followed up for 5 years post chemotherapy

26. BLASTOMA A  blastoma  is a type of cancer caused by malignancies in precursor cells, which are commonly referred to as blasts Study case- NEPHROBLASTOMA, NEUROBLASTOMA

27. Nephroblastoma Wilm’s Tumor . .

28. INTRODUCTION: Wilms Tumor Is A Cancerous Tumor Of The Kidney That Usually Occurs In Young Childern Wilms Tumor , Or Nephro blastoma Is The Most Frequent IntraAbdominal Tumor Of Childhood And The Most Common Type Of Renal Cancer It Is Named For Max Wilms,a German Surgeon (1867-1981)and Also Known As Nepheroblastoma

29. EPIDEMIOLOGY Its Frequencey Is Estimated To 1 In 50,000 Live Birth It Is The Most Common Cancer Of The Kidneys In Children, And The Fourth Most Common Type Of Cancer In Children.   Wilms ’ Tumors Are Most Often Unilateral, Affecting Only One Kidney.  5-10% Of Children With Wilms ’ Tumors Have More Than One Tumor In The Same Kidney, Approximately 5% Of Children With The Cancer Have Bilateral Wilms ’ Tumors, Affecting Both Kidneys.

30. CAUSES :- The Exact Cause of Wilms Tumour Is Not Known Probably Arises From Amalignant , Undifferentiated Cluster Of Primitive Cells Capable Of Initiating The Regeneration Of An Abnormal Structutleridity

31. PATHOPHYSIOLOGY:- When An Unborn Baby Is Developing, The Kidneys Are Formed From Primitive Cells The Cells Mature &Organize Into The Normal Kidney Structure Sometimes Clumps Of These Cells Remain In Their original, Primitive Form If These Cells Begin To Muitiply After Birth They May Uitimately Form A Large Mass Of Abnormal Cells. This Is Known As A Wilms Tumor.

32. CLINICAL MANIFISTATION Abdominal Mass Abdominal pain Hematuria As Tumor Extension In The Renal Pelvis Hypertension Occurs Occacionally Of Excess Amt Of Renin By Tumour Fever Anaemia Weight Loss Anorexia Vomiting

33. On Examination, Mass Within The Abdomen The Mass Is Firm , Non-tender If M e t a s t asis Ha s Occur r e d usually to lungs There Symptoms Of Lung Involvement Such As Dyspnea , Cough, Shortness Of Breath & Pain In The Chest CLINICAL FEATURES

34. DIAGNOSIS:- History and Physical Examination:- Children With Wilms Tumor Generally First Present To Physicians With A Swollen Abdomen Or With An Obvious Abdominal Mass . INVESTIGATIONS FBP, URINALYSIS, Abdominal ultrasound C T Scan { Computed Tomography Scan} Biop s y F inal D i a gnosis This Biopsy Is Usually Done During Surgery To Remove Or Decrease The Size Of The Tumor O the r S tud i e s Ch e s t – Xr a y , CT- S can O f Th e L ungs,bone M a r ro w Biop s y May Also Be Done In Metastatic conditions MRI

35. S T A GING S t a ge 1 : - t u mor c o n fine d t o the kidney & completely excised S t a ge 2 : - t u mor e x t e n d s be y o n d kidney b u t completely excised S t a ge 3 : - t um o r infi l t r a t e s renal f a t r e sid u al tumor after surgery lymphnode involvement of hilum , para -aortic or beyond Stage 4 :- metastasis in lung or liver rarely in bone and brain Stage 5 :- bilateral renal involvement

36. Staging… .

37. . TREATMENT Surgery Chemotherapy Radiotherapy

38. 1. Surgery:- An Operation To Remove The Cancer Apartial Nephrectomy : - Is When The Cancer And Part Of The Kidney Are Removed .Its Usuaiil Done If The Oher Kidney Is Damaged Or Has Already Been Removed A Radical Nephrectomy :- Removes The Entire Kidney And Tissue Around It. Some Time Some Lymph Nodes May Also Be Removed.

39. 2.CHEMOTHERAPY:- Medication Used To Kill Cancer Cells . It Is a Systemic Treatment Because The Drugs Enter The Blood And Kill Cancer Cell Throughout The Body. Chem o the r a p y can also be Given A ft e r An O p e r a t i o n

40. (3) Radiation Therapy:- X-rays Or Other High Enregy Rays Are Used To Kill Cancer Cells And Shrink Tumors. It May Be Used Before And After Surgery And /Or Chemotherapy. Radiation Therapy Is Not Given In Children Below Age Of 1yrs.

41. P R OGNO S I S :- Is The Prediction Of The Course And Out Come Of The Disease. For Wilms , The Prognosis Is Generally Very Good.More Than 85%cure Rate. Quite A Bit Depends, Though On The Staging Of The Tumour And The Histology Of The Tumore

42. Neuroblastoma .

43. Neuroblastoma introduction Neuroblastoma is a form of cancer that originates in the nerve cells, specifically within the sympathetic nervous system.  The cancer is found in the primitive cells of a fetus or an embryo, and then the cancer cells proliferate in the young child.  The cancer typically arises from the following areas of the body: retroperitoneal area, posterior mediastinum , pelvis, and neck

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45. The most common cancer in infants “<1 year old” T h e m o st co m m o n ex t r a -c r an i a l s oli d c a n c e r i n childhood Accounts for about 7% of all cancers in children. The average age diagnosis “ 18 months” . 90% of cases are diagnosed by age 5. Very rare in people over the age of 10 years. EPIDEMIOLOGY

46. Non- specific and mimic many childhood illnesses Site of primary tumor Local infiltration Sites of metastatic disease Metabolic disturbances

47. Abdominal pain Palpable mass fixed, hard abdominal mass Bone or joint pain Periorbital ecchymosis Cough Dyspnea Neurologic deficits Urinary retention Constipation Paraneoplastic syndromes Paroxysmal hypertension Palpitations Flushing Headache Severe watery diarrhea Hypokalemia Acute myoclonic encephalopathy

48. Abdominal pain, discomfort, fullness or rarely obstruction. Cough, dysphagia, breathlessness, thoracic inlet obstruction leading to superior vena caval syndrome . Horner ’ s syndrome Some tumors have intra - spinal and extra - spinal components (dumb - bell tumors) and it can l e a d to causing c o r d compre s si o n fla c ci d pa r al y si s a n d urinary and bowel disturbances. bladder or bowel obstruction. Site of primary tumor

49. Laboratory tests CBC, LDH N SE fer r i t in LFT, KFT, e l e c trol y tes Urine HV A -VMA

50. Investigations Laboratory investigations Complete blood count Basic metabolic panel Urinary catecholamines; Urinary homovanillic acid (HVA), metabolite of DOPA and dopamine, and vanillylmandelic acid (VMA), Metabolite of norepinephrine and epinephrine are measures in 24- hour.

51. Investigations Imaging; >ultrasound. Bone: Skeletal survey and bone scan (technetium 99) Bone marrow: Bilateral bone marrow aspiration and biopsy from posterior superior iliac spine. Abdominal imaging with CT or MRI Chest x-ray.

52. S t aging International Neuroblastoma Staging System (INSS) was developed to make the staging of neuroblastomas around the world; Stage 1: Localized tumor confined to the area of origin. Stage 2A: Unilateral tumor with incomplete gross resection; identifiable ipsilateral and contralateral lymph node negative for tumor. Stage 2B: Unilateral tumor with complete or incomplete gross resection; with ipsilateral lymph node positive for tumor; identifiable contralateral lymph node negative for tumor.

53. S t aging Stage 3: Tumor infiltrating across midline with or without regional lymph node involvement; or unilateral tumor with contralateral lymph node involvement; or midline tumor with bilateral lymph node involvement. Stage 4: Dissemination of tumor to distant lymph nodes, bone marrow, bone, liver, or other organs except as defined by Stage 4S. Stage 4s; Localized primary tumour, as defined for stage 1, 2A or 2B, with dissemination limited to skin, liver and/or bone marrow (limited to infants younger than 1 year). Marrow involvement should be minimal, i.e. less than 10% of total nucleated cells identified as malignant by bone biopsy or by bone marrow aspirate. More extensive bone marrow involvement would be considered to be stage 4 disease

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55. S t aging

56. Treatment Surgery Chemotherapy Radiation therapy

57. Surgery Goals Establish the diagnosis Stage the tumor Excise the tumor(if localized) Provide tissue for biologic studies Liver biopsy indicated if Stage 4S Patients with incomplete resection initially-delayed attempt at resection of residual tumor is undertaken at the end of induction chemotherapy Surgery is not indicated for those patients who have progressive disease at this time

58. Radiotherapy Local control stage IV or bulky stage III tumors* Intraoperative radiation therapy-unresectable disease

59. Differential diagnoses The ddx are; >Wilms tumor >Lymphoma >Leukemia.

60. Prognostic factors Age: Infants have better prognosis than older children Early stage of disease (I and II) is better Tumour site: Cervical neuroblastomas have better prognosis, may be due to their early detection. Pelvic and thoracic tumours carry a better prognosis than abdominal tumours Cortical bone involvement is associated with poor Prognosis. Tumour pathology: Favorable or unfavorable.