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Neuroblastoma

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Neuroblastoma.. a uncommon Malignancy

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Neuroblastoma

  1. 1. NEUROBLASTOMA
  2. 2. CASE HISTORY • 8 year boy from Jumla • Presented with – Sudden onset of increased frequency of urine in Asar 26, 2068 – Relieved by foley’s catheterisation • Referal – Jumla- Nepaljung- KMC- TUTH- Bir Hospital
  3. 3. EXAMINATION • GPE- unremarkable • Per Abdomen: – Midline suprapubic mass, 4cmx4cm, illdifined firm,fixed, nontender – Bulge in the perineum • Investigation – Blood count – Urine – PSA – Imaging (USG,IVU,MRI,Cx-R) – cystoscopy – Biopsy
  4. 4. INVESTIGATION 12x6.5x7 cm
  5. 5. BIOPSY Small round cell tumor STAGE III DISEASE
  6. 6. CX-RAY Stage IV
  7. 7. NEUROBLASTOMA MODERATOR Prof. Dr. RV/ Dr. PMS/ Dr. AS Presenter: Bikash Bk Thapa
  8. 8. INTRODUCTION • Spectrum of neuroblastic tumors that arise from primitive sympathetic ganglion cells. »neuroblastoma, »ganglioneuroblastoma and » ganglioneuromas
  9. 9. EPIDEMIOLOGY • 97 % of neuroblastic tumor • Heterogeneous • Broad spectrum of clinical behavior • Third most common childhood tumor • Most common below 1 year • Most common extracranial solid malignancy
  10. 10. 1 in 10,000 17.3 months 15 % overall mortality
  11. 11. Risk factors • Maternal – Opiate consumption – Folate deficiency • Toxic exposure – Alcohol, sex hormones, diuretics, hair color, electromagnetic • Congenital abnormalites – Down syndrome, leukaemia, pyloric stenosis, GTDM – Urogenital and cardiac anamolies • Genetic factors – Girls with turners syndrome, hirschsprungs’s, NF-I • Familial neuroblastoma – 2 % , autosomal dominant
  12. 12. Pathogenesis • Embryogenesis – Develop from residual microscopic neuroblastic nodules, – Origin of extraadrenal neuroblastomas is unknown • Molecular – Chromosomal deletion (1p, 11q, 14p)- 50% – Over expression of the oncogene MYCN ( n-myc)- 25% – Gain of chromosome 17q material (trisomy 17q) – Alterations in total DNA content – Expression of neurotrophic factors: • NGF and BDNF and receptors
  13. 13. Genetic model of neuroblastoma development
  14. 14. PATHOLOGY • Tumors of neuroblastic origin are classified according to the balance between neural-type cells and Schwann-type cells • Neuroblastomas are the most aggressive – undifferentiated, poorly differentiated, or differentiating • Neuroblastomas distinguished by – -neuron-specific enolase , synaptophysin, chromogranin, and S100
  15. 15. SPREAD • LYMPHATC-35% – Regional – disseminated • HAEMATOGENOUS – bone, bone marrow, liver,brain, lung
  16. 16. CLINCAL PRESENTATION – Adrenal gland-40% – Abdominal-25% – Thoracic-15% – Cervical-5% – Pelvic sympathetic-5%
  17. 17. Clincal features • Abdominal mass • Abdominal pain or constipation • Horner syndrome • Localized back pain, weakness • Scoliosis • Bladder dysfunction • Heterochromia iridis • Opsoclonus myoclonus ataxia syndrome • Unexplained secretory diarrhea • Hypertension • Systemic symptoms (fever, weight loss) • Bone pain • Anemia • Proptosis • Periorbital ecchymoses ("raccoon eyes", • Palpable nontender subcutaneous nodules • Unilateral nasal obstruction
  18. 18. Abdominal tumors “organs of Zuckerkandl” • Abdominal pain, fullness, mass • Intestinal obstruction • Compression of bowel or bladder • Constipation, reduced bladder capacity, enuresis • Vascular compression • Scortal edema, LL edema • Incidental mass- nontender, fixed and firm
  19. 19. Differential diagnosis • Wilm’s tumor • Hepatoblastoma • Lymphoma, germ cell tumour, infection • Lymphoma, small round cell osteosarcoma, Ewings sarcoma • Rhabdomyosarcoma • Infantile myofibromatosis • Dermoid cyst
  20. 20. DIAGNOSTIC EVALUATION • CLINICAL • LAB • IMAGING • BIOPSY
  21. 21. LAB – Routine blood count – RFT n Electrolytes – LFT – Serum / urine cathchecholamines metabolites: vanillylmandelic acid, homovanillic acid – Serum ferritin (>142ng/ml) – Serum LDH(>1500 IU/ml) – Neuron specific enolase (>100ng/ml)
  22. 22. IMAGING • USG • CT-SCAN • MRI • RADIONUCLEIDE BONE SCAN – technetium radionuclide scan or I123-MIBG scan BIOPSY • BIOPSY (HPE, IMMUNOHISTOCHEMISTRY) • BONE MARROW BIOPSY/ASPIRATE
  23. 23. DIAGNOSTIC CRITERIA • An unequivocal histologic diagnosis from tumor tissue by light microscopy, with or without immunohistochemistry, electron microscopy, or increased urine (or serum) catecholamines or their metabolites. • Evidence of metastases to bone marrow on an aspirate or trephine biopsy with concomitant elevation of urinary or serum catecholamines or their metabolites.
  24. 24. STAGING WORKUP • Bone marrow biopsy • Radionuclide scan or I123- MIBG scan • CT/MRI abdomen • CxR • CT /MRI chest • CT-head
  25. 25. SCREENING • Urinary cantchecholamines • Not recommended • Positive family history
  26. 26. STAGING • International neuroblastoma staging system (INSS) – Resectability – Lymph nodes – Distant mets – Age at diagnosis • International Neuroblastoma Risk Group Staging system (INRGSS) – Multiple pretreatment imaging paratmeters
  27. 27. INTERNATIONAL NEUROBLASTOMA STAGING SYSTEM 1986/1993
  28. 28. The International Neuroblastoma Pathology Classification (INPC) system,, favorable tumors include those that are: • Poorly differentiated or differentiating neuroblastoma, with low or intermediate mitosis-karyorrhexis index (MKI),patient age ≤1.5 years • Differentiating neuroblastoma and low MKI tumors in patients 1.5 to 5.0 years • Ganglioneuroblastoma, intermixed, regardless of age • Ganglioneuroma, regardless of age Unfavorable tumors include those that are: • Undifferentiated or high MKI tumors in patients of any age • Poorly differentiated / intermediate MKI tumors in patients 1.5 to 5.0 years o • Any grade of differentiation and any MKI class in patients ≥5 years of age • Nodular ganglioneuroblastoma, regardless of age
  29. 29. TREATMENT • Patients are classified into low-, intermediate-, and high-risk » Stage of the disease » Patient age » Histologic appearance of the tumor » Quantitative DNA content of the tumor (DNA index or ploidy) » Presence or absence of amplification of the MYCN oncogene
  30. 30. TREATMENT MODALITES • SURGERY • CHEMOTHERPAY – cyclophosphamide, carboplatin or cisplatin, etoposide or teniposide, and doxorubicin. • RADIOTHERAPY • OBSERVATION • Autologous hematopoietic stem cell rescue
  31. 31. COG risk strata for TREATMENT
  32. 32. NEWER MODALITIES »Immunotherapy »Neuroblastoma Vaccine »Angiogenesis Inhibitor • fenretinide »Iodine-131-metaiodobenzylguanidine (MIBG), in conjunction with hematopoietic cell transplantation
  33. 33. PROGNOSTIC FACTORS »TUMOR STAGE »AGE AT DIAGNOSIS »CYTOGENETICS AND MOLECULAR GENETICS »PATHOLOGICAL RISK CLASSIFICATION
  34. 34. References • Sabiston textbook of surgery 18th edn • Schwartz’s principle of surgery 9th edn • Uptodate 2011
  35. 35. THANK YOU

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