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Neuroblastoma and nephroblastoma

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Neuroblastoma and nephroblastoma

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Neuroblastoma and nephroblastoma

  1. 1. Neuroblastoma and nephroblastoma Mahajna mohammed Sackler’s faculty of medicine Tel-Aviv Uni
  2. 2. definition embryonal cancers of the peripheral sympathetic nervous system heterogeneous clinical presentation and course, ranging from tumors that undergo spontaneous regression to very aggressive tumors The causes of most cases remain unknown, and although significant advances have been made in the treatment of children with these Tumors the outcomes for aggressive forms of neuroblastoma remain poor.
  3. 3.  the most common extracranial solid tumor in children and the most commonly diagnosed malignancy in infants.  8-10% of childhood malignancies and 33% of cancers in infants.  accounts for >15% of the mortality from cancer in children.  The median age of children at diagnosis of neuroblastoma is 22 months  90% diagnosed by 5 yr of age.  The incidence is slightly higher in boys and in whites. EPIDEMIOLOGY
  4. 4.  variable degrees of neural differentiation, ranging from tumors with 1. primarily undifferentiated small round cells (neuroblastoma) 2. tumors consisting of mature and maturing Schwannian stroma with ganglion cells (ganglio-neuroblastoma or ganglio-neuroma).  The tumors may resemble other small round blue cell tumors, such as rhabdomyosarcoma, Ewing sarcoma, and non Hodgkin lymphoma.  The prognosis varies with the histologic features of the tumor, and prognostic factors 1. Schwannian stroma, 2. the degree of tumor cell differentiation, 3. mitosis-karyorrhexis index. PATHOLOGY
  5. 5. • The etiology of neuroblastoma in most cases remains unknown • Familial neuroblastoma accounts for 1-2% of all cases, is associated with a younger age ,mutations in PHOX2B and ALK genes. • The BARD1 gene has also been identified as a major genetic contributor to neuroblastoma risk. • associated with other neural crest disorders, [Hirschsprung disease, central hypoventilation syndrome, and neurofibromatosis type I] and potentially congenital cardiovascular malformations (Table 498-1). • associated with parents occupation,chemical although no single environmental exposure has been shown to directly cause neuroblastoma. PATHOGENESIS
  6. 6.  Genetics include 1. amplification of the MYCN (N-myc) : strongly associated with advanced tumor stage and poor outcomes 2. ploidy :Hyperdiploidy confers better prognosis if the child is younger than 1 yr of age at diagnosis 3. Other: including loss of heterozygosity of 1p, 11q, and 14q, and gain of 17q, associated with worse outcomes.  In addition, tumor vascularity and the expression levels of nerve growth factor receptors : (TrkA, TrkB), chromogranin Aneuropeptide YLDHferritin ganglioside GD2CD44telomerase
  7. 7. CLINICAL MANIFESTATIONS Symptoms Site Staging Tumor type Tumor origin Disease extent Patient
  8. 8. Metastatic disease can cause a variety of signs and symptoms: 1. Fever 2. Irritability 3. failure to thrive 4. bone pain 5. Cytopenias 6. bluish subcutaneous nodules 7. orbital proptosis 8. periorbital ecchymoses Localized disease can manifest as an asymptomatic mass or can cause symptoms because of the mass itself: 1. spinal cord compression, 2. bowel obstruction, and superior vena cava syndrome. superior cervical ganglion can result in Horner syndrome. Paraspinal neuroblastoma tumors can invade the neural foramina, causing spinal cord and nerve root compression. paraneoplastic syndrome of autoimmune origin, termed opsoclonus– myoclonus–ataxia syndrome, in which patients experience rapid, uncontrollable jerking eye and body movements, poor coordination,
  9. 9. Some tumors produce catecholamines that can cause 1. increased sweating and hypertension some release vasoactive intestinal peptide 1. causing a profound secretory diarrhea. Children with extensive tumors can also experience tumor lysis syndrome and disseminated intravascular coagulation. Infants younger than 1 yr of age also can present in unique fashion, termed stage 4S : • widespread subcutaneous tumor nodules • massive liver involvement • limited bone marrow disease • small primary tumor without bone involvement or other metastases.
  10. 10. Staging  Neuroblastoma may develop at any site of sympathetic nervous system tissue.  50% of neuroblastoma tumors arise in the adrenal glands  Metastatic spread : 1. mainly in 1 yr of age at diagnosis, 2. occurs via local invasion 3. distant hematogenous 4. lymphatic routes. 5. The most common sites of metastasis are the regional or distant lymph nodes, long a) bones and skull, bone marrow b) liver, and skin c) Lung and brain metastases are rare, occurring in >3% of cases.
  11. 11. DIAGNOSIS RADIOLOGY : MRI / CT  mass or multiple masses may be hemorrhagic or calcified Urin samples : Tumor markers, catecholamine metabolites homovanillic acid and vanillylmandelic acid, are elevated in the urine in 95% of Evaluations for metastatic disease should include CT or MRI of the chest and abdomen, bone scans to detect cortical bone involvement, and at least 2 independent bone marrow aspirations
  12. 12. • A :CT scan of an abdominal neuroblastoma with central necrosis at diagnosis. • B :Coronal fused CT and metaiodobenzylguanidine(MIBG) image of same child with extensive retroperitoneal mass and central necrosis, probably an adrenal primary with extensive lymph node involvement. • C :MIBG avid neuroblastoma with increased uptake of radiolabeled tracer can be detected in multiple sites of disease, including bone and soft tissue.
  13. 13. These agents are almost invariably given in combination Commonly used combinations include the following: •Vincristine, cyclophosphamide, and doxorubicin •Carboplatin and etoposide •Cisplatin and etoposide •Cyclophosphamide and topotecan Consolidation regimens used in neuroblastoma include the following: •Carboplatin and etoposide with melphalan or cyclophosphamide •Thiotepa and cyclophosphamide •Melphalan and total body irradiation
  14. 14. Induction chemotherapy for children with high-risk neuroblastoma includes combinations 1. Cyclophosphamide 2. topotecan, 3. Doxorubicin 4. Vincristine 5. Cisplatin 6. etoposide.  After completion autologous stem cell rescue and focal radiation therapy to tumor sites.  significantly better survival with chemotherapy plus autologous stem cell rescue than with chemotherapy alone.  The further addition of 13-cis-retinoic acid resulted in further improvements in survival rates.
  15. 15. Now hush little baby, don't you cry Everything's gonna be alright Stiffen that upper lip up little lady, I told ya Daddy's here to hold, ya through the night
  16. 16. • Wilms tumor (WT), also known as nephroblastoma, is the most common primary malignant renal tumor of childhood; • other renal tumors are very rare. • It is the second most common malignant abdominal tumor in childhood. • The most common sites of metastases 1. lungs, 2. regional lymph nodes 3. and liver. Histologically:varying proportions 1. Blastemal 2. Stromal 3. epithelial cells
  17. 17. EPIDEMIOLOGY  6% of malignancies and more than 95% of kidney tumors.  75% occur in children younger than 5 yr with a peak incidence at 2-3 yr of age.  It can arise in 1 or both kidneys; bilateral WTs is 7%.  Most cases are sporadic, but approximately 2% of patients have a family history.  In 8-10% of patients, WT is observed in the context of hemihypertrophy, aniridia, genitourinary anomalies, and a variety of rare syndromes:  Beckwith-Wiedemann syndrome and Denys-Drash syndrome (Table 499-2). An earlier age of diagnosis and an increased incidence of bilateral disease are generally observed in syndromic and familial cases.
  18. 18. ETIOLOGY: GENETICS AND MOLECULAR BIOLOGY Wilms tumor is thought to be caused by alterations of genes responsible for normal genitourinary development. Examples of common congenital anomalies associated with Wilms tumor are 1. Cryptorchidism 2. a double collecting system 3. horseshoe kidney 4. and hypospadias. | Environmental exposures, although considered, seem relatively unlikely to play a role
  19. 19.  a gene located at 11p13 and encoding a zinc finger transcription factor  15-20% of tumors. These are homozygous and result in loss of WT1 Function.  The majority of WT1 mutations are somatic, result in loss of WT1 function, and are present homozygously.  germline WT1 mutations are also observed, primarily in patients with WT- associated syndromes, or sometimes in patients with bilateral disease.  In these instances, the wild-type allele present in the germline is mutated or lost in the tumor, resulting in loss of WT1 function. Interestingly, nephrogenic rests assessed from patients heterozygous
  20. 20. CLINICAL PRESENTATION
  21. 21.  80% asymptomatic abdominal mass:  abdominal mass occurs in 80% of children at presentation.  Abdominal pain or hematuria occurs in 25%.  Urinary tract infection  varicocele are less common findings than these.  Hypertension, gross hematuria, and fever are observed in 5-30  A few patients with hemorrhage into their tumor may present with hypotension, anemia, and fever.  Rare patients with advanced disease may present with respiratory symptoms related to lung metastases.
  22. 22. Imaging studies 1. plain abdominal radiography, 2. abdominal ultrasonography, 3. CT of the 4. Abdominal ultrasonography helps differentiate solid from cystic Masses 5. Ultrasonography with Doppler imaging of renal veins and the inferior vena cava is a useful first study that not only can look for WT but also can evaluate the collecting system and demonstrate tumor thrombi in the renal veins and inferior vena cava.
  23. 23. •Favorable - Contains well developed components mentioned above •Anaplastic - Contains diffuse anaplasia (poorly developed cells)

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