neuroblastoma
TRANSCRIPT
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CASE PRESENTATION
Yassin M. Alsaleh
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بسم الله الرحمن الرحيم
)المال والبنون زينة الحياة الدنيا(
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History:
• Salem 3 3/12 years a old Saudi boy not known to have any medical illness before .
• 2 weeks prior to admission he developed URTI with on-off low grade fever followed by pallor noticed by parents, loss of appetite, headache and decrease in activity made him prefer to stay in bed .there was also history of weight loss.
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History cont.
• Patient seen two times in PHC .patient managed as URTI and discharged on antibiotic.
• Also there was history of ingestion of fava bean 1 week ago.
• History of lower limb bruising.• No history of limb pain, chest pain or abdominal pain• No change of color of the urine.• Product of NSVD.• No past admission.
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History cont.
• No knowon allergy to medication or food.• Surgical history : circumsicion.• Developmental: appropriate to his age.• Immunization: fully immunized.• Nutritoin: on family food.• Family history: 2nd degree relatives.• Father is G6PD deficient.• + ve family history of SCD and G6PD.
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Physical examination
• Vital sign:• PR: 138 bpm RR:24 bpm temp:37C• BP: 114/68. O2 sat: 100% in RA• Weight:12 Kg.• Patient looks pale, not jaundiced , not in
distress or pain.• HENT: Normal.
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Physical examination cont.
• Eye: pale conjuctiva.• RS: normal.• CVS: S1+S2+ O• Abdomin: soft. Lliver is 4 cm below costal
margin. liver span 9.5 cm.• Spleen: 1 cm below costal margin.
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Impression
• Anemia for investigation.
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Investigation:
• WBC:6.5• Lymp 59%• Mono 1%• Neut 31%• Eosin 1%• Band 6
• PLT:32• MPV:5
• Hgb:6.3• RBC:2.49• MCV:67.5• HCT:17• MCH:23.8• MCHC:35.3• RDW:15.2
• Retic: 2%
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Investigation cont.
• Hb electorphoresis:• Hgb A 64.8• Hgb A2 2.1• Hgb S 33.1
• G6PD normal• Blood film: schisocyte, target cell.• Coomb’s test: negative .• LDH: 4275• Uric acid: 433
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Impression
• Anemia and thrombocytopenia for further investigation.
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Imaging
• CXR: normal.
• Abdominal ultrasound: • showed hepatomegally with hyperechogenic
mass, heterogenous in the right lobe 12.2 X 8.4 cm with vascularity.CT is recomended
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Impression• Anaemia, thrombocytopenia,
abdominal mass under investigation.
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CT scan with contrast
• large hepatorenal pouch mass most likely arisenig from suprarenal gland with area of calicification and necrosis.
• Crossing midline shows vascular enhancement inferiorly mass extending upto lower pole of right kideny, superiorioly indenting liver with paraortic lymphadenopathy . spleen intact.
• Conclusion : mostly neuroblastoma.
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• 10 DEC 2007• Skeletal survey :• Skull: no metastatic lesion.• Chest: no metastatic lesion.• Thoracic and lumbosacral: no bony abnormalities.• Pelvis: no bony abnormalities.
• 11 DEC 2007• Bone scan : normal.
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• 11 DEC 2007• Biopsy : • initial result going with neuroblastoma.
• Bone marrow aspiration: infeltration by neuroblast cell but still waiting for final result.
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• Diagnosis:• Neuroblastoma stage 4.
• Plan:• Chemotherapy, radiotherapy, surgery to
prepare him for bone marrow transplantation.
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• Father: take this 100 riyals and buy sweets and gum.
• Son: believe me it will not be enough.
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Neuroblastoma
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Introduction
• Definition: refer to a spectrum of neuroblastic tumors that arise from primitive sympathetic ganglion cells. (including neuroblastomas, ganglioneuroblastomas, and ganglioneuromas) .
• Neuroblastomas, account for 97 percent of all neuroblastic tumors.
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Neuroblastoma Differentiation
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Epidemiology
• Neuroblastoma is almost exclusively a disease of children.
• It is the third most common childhood cancer.
• It is the most common solid extracranial tumor in children.
• most common cancer among infants .• accounts for approximately 15 percent of all
pediatric cancer fatalities.
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Epidemiology cont.
• Age distribution is as follows: - 40% of patients are younger than 1 year. - 35% are aged 1-2 years.- 25% are older than 2 years.• Males have a slightly higher incidence than
females.• Higher in white children.
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History• Generally, symptoms include :• abdominal pain.• Abdominal mass.• weight loss.• Anorexia.• Fatigue.• bone pain.• chronic diarrhea.
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History cont.
• Chronic cough.• unexplained fever.• Irritability. • periorbital ecchymosis .• pathologic fractures.
• Asymptomatic.
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Physical
• Vital sign: Blood pressure• abdominal mass.• Horner syndrome. • lower extremity weakness , paraplegia,
bladder and bowel dysfunction. • Metastatic lesions of the skin are common in
infants younger than 6 months.• Opsoclonus and myoclonus.
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Causes
• The cause of neuroblastoma is unknown.• According to SEER, factors investigated for
which evidence is limited or inconsistent include medications, hormones, birth characteristics, congenital anomalies, previous spontaneous abortion or fetal death, alcohol or tobacco use, and paternal occupational exposures.
Evidence is limited
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Differential diagnosis
• Wilm’s tumor.• Rhabdomyosarcoma.• Lymphoma.• Teratoma.• Hepatoblastoma.• Leukemia.
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• We open the Pocket it only contain 10 riyals not enough for treatment do you wanna us to bring him or keep him on the road.
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Investigation– Serum LDH– Ferritin– CBC count and differential – Urine collection for catecholamines
(VMA/HVA)– Serum creatinine– Liver function tests– Electrolytes– Uric acid
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Imaging Studies• Plain x-ray of chest and abdomin: to evaluate for the presence of a posterior mediastinal mass or
calcifications.• Abdominal ultrasound: as initial imaging for abdominal mass.
• A CT scan : essential to determine tumor extent.
• MRI :determining the presence of intraspinal tumor and cord
compression.
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Imaging Studies cont.
• 123/131-methyliodobenzylguanadine (MIBG): accumulates in catecholaminergic cells to identifying primary and metastatic disease if present.
• A technetium-99 bone scan: used to evaluate bone metastases.
• Skeletal surveys :may also be useful.
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• CT scan of abdomen in a patient with a retroperitoneal mass arising from the upper pole of the left kidne
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Procedures
• bilateral bone marrow aspirate and biopsies to exclude metastatic disease.
• Tumor biopsy or surgical resection: performed to collect tissue sample(s) for biologic studies used to assign the patient into the appropriate risk category.
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Other modalities
– immunohistochemistries can aid with tissue diagnosis.
– Molecular techniques, such as fluorescent in situ hybridization (FISH), can detect MYCN amplification, an important prognostic marker.
– Polymerase chain reaction (PCR) can identify specific translocations.
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Staging
• The International Neuroblastoma Staging System (INSS) is currently used in all group studies.
• Other staging system include:• POG.• CCG.
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International neuroblastoma staging system
STAGE 1
Localized tumor with complete gross excision, with or without microscopic residual disease; representative ipsilateral lymph nodes negative for tumor microscopically (nodes attached to and removed with the primary tumor may be positive)
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STAGE 2A
Localized tumor with incomplete gross excision; representative ipsilateral nonadherent lymph nodes negative for tumor microscopically
International neuroblastoma staging system
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STAGE 2B
Localized tumor with or without complete gross excision; with ipsilateral nonadherent lymph nodes positive for tumor. Enlarged contralateral lymph nodes must be negative microscopically
International neuroblastoma staging system
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STAGE 3
Unresectable unilateral tumor infiltrating across the midline, with or without regional lymph node involvement; or localized unilateral tumor with contralateral regional lymph node involvement; or midline tumor with bilateral extension by infiltration (unresectable) or by lymph node involvement
International neuroblastoma staging system
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STAGE 4
Any primary tumor with dissemination to distant lymph nodes, bone, bone marrow, liver, skin and/or other organs (except as defined for stage 4S)
International neuroblastoma staging system
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STAGE 4S
Localized primary tumor (as defined for stage 1, 2A or 2B), with dissemination limited to skin, liver, and/or bone marrow (limited to infants <1 year of age)
International neuroblastoma staging system
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stage Defintion
1 Localized tumor with complete gross excision, with or without microscopic residual disease; representative ipsilateral lymph nodes negative for tumor microscopically (nodes attached to and removed with the primary tumor may be positive)
2A Localized tumor with incomplete gross excision; representative ipsilateral nonadherent lymph nodes negative for tumor microscopically
2B Localized tumor with or without complete gross excision; with ipsilateral nonadherent lymph nodes positive for tumor. Enlarged contralateral lymph nodes must be negative microscopically
3 Unresectable unilateral tumor infiltrating across the midline, with or without regional lymph node involvement; or localized unilateral tumor with contralateral regional lymph node involvement; or midline tumor with bilateral extension by infiltration (unresectable) or by lymph node involvement
4 Any primary tumor with dissemination to distant lymph nodes, bone, bone marrow, liver, skin and/or other organs (except as defined for stage 4S)
4S Localized primary tumor (as defined for stage 1, 2A or 2B), with dissemination limited to skin, liver, and/or bone marrow (limited to infants <1 year of age)
International neuroblastoma staging system
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TREATMENT • The modern treatment of neuroblastoma is based
upon the risk category
risk categoryrisk category
Low-risk disease Low-risk disease Intermediate-risk Intermediate-risk High-risk disease High-risk disease
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Criteria for Risk Assignment• Histopatholgy:• Shimada histopathologic classification system .• (1) the degree of neuroblast differentiation.• (2) the presence or absence of Schwannian stromal
development .• (3) the index of cellular proliferation • (4) nodular pattern.• (5) age.
• histology groups:• Favorable VS Unfavorable .
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Criteria for Risk Assignment cont.• MYCN n-myc• The most important biologic markers is MYCN. • homologous sequence to c-myc in neuroblastoma
cells.• This gene is amplified in approximately 25% of
cases and is more common in patients with advanced-stage disease.
• Patients whose tumors have MYCN amplification tend to have rapid tumor progression and a poor prognosis, even in the setting of other coexisting favorable factors .
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Criteria for Risk Assignment cont.
• DNA index :• is another useful test that correlates with response
to therapy in infants. • have hyperdiploidy (ie, DNA index >1) have a good
therapeutic response to cyclophosphamide and doxorubicin.
• In contrast, infants whose tumors have a DNA index of 1 are less responsive to the latter combination and require more aggressive therapy.
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INSS Stage
Age (y) MYCN Status Shimada Histology
DNA Ploidy Risk Group
1 0-21 Any Any Any Low
2A/2B <1>1-21>1-21>1-21
AnyNonamplifiedAmplifiedAmplified
AnyAny
FavorableUnfavorable
Any---
LowLowLowHigh
3 <1<1
>1-21>1-21>1-21
NonamplifiedAmplified
NonamplifiedNonamplifiedAmplified
AnyAny
FavorableUnfavorable
Any
AnyAny---
IntermediateHigh
IntermediateHighHigh
4 <1<1
>1-21
NonamplifiedAmplified
Any
AnyAnyAny
AnyAny-
IntermediateHighHigh
4S <1<1<1<1
NonamplifiedNonamplifiedNonamplifiedAmplified
FavorableAny
UnfavorableAny
>1=1AnyAny
LowIntermediateIntermediate
High
Criteria for Risk Assignment
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Low-risk disease
– Patients in the low-risk category generally have low stage disease..
– Surgery — Surgery alone is the primary treatment for low-risk tumors.
– Chemotherapy — reserved for those whose tumors cannot be resected or who have threatening symptoms of spinal cord compression or respiratory or bowel compromise.
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Low-risk disease cont.
– Frequently used agents include combinations of cyclophosphamide, carboplatin or cisplatin, etoposide or teniposide, and adriamycin.
– Radiation therapy — Radiation therapy (RT) is reserved for unresectable tumors or progressive tumors unresponsive to chemotherapy.
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Intermediate-risk
• Surgery — Surgery is an important component of treatment for children with intermediate-risk neuroblastoma, but is inadequate by itself .
• Chemotherapy — Moderately intensive multiagent chemotherapy (eg, with doxorubicin, cyclophosphamide, a platinum drug, and etoposide) is recommended for children with intermediate-risk neuroblastoma, and is often applied before attempted resection.
• Radiation therapy — unclear.
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High-risk disease
• In the induction phase, intensive chemotherapy with a combination of agents (eg, platinum agents, cyclophosphamide, doxorubicin, etoposide) is used to shrink primary and metastatic tumors .
• Resection may be performed after an initial course of chemotherapy when the tumor is smaller and less invasive.
• Radiotherapy (24 to 30 Gy) dosed to the primary tumor bed and other sites of bulky disease may be beneficial in preventing local tumor
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High-risk disease cont.
• After tumor bulk has been decreased by chemotherapy and surgery, the consolidation phase includes higher-dose chemotherapy followed by autologous hematopoietic stem cell rescue
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new methods
• Immunotherapy with antibodies targeted on the surface of neuroblastoma .
• Neuroblastoma vaccines .
• Generalized targeting of tumor cells with drugs that induce apoptosis (eg, fenretinide or target angiogenesis.
• Nonmyeloablative allogeneic bone marrow transplants to induce a graft-versus-tumor effect.
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Complications
• At disease presentation– Cord compression from a paraspinal tumor.
Evaluation of the patient by a neurosurgeon and consultation with oncologist are important.
– Tumor lysis syndrome .– Patients may present with severe
hypertension or renal insufficiency.
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Complications cont.
• During therapy– Myelosuppression and immunosuppression
place the patient at risk of bleeding and infection.
– Febrile neutropenia is a medical emergency and requires immediate admission to the hospital and initiation of broad-spectrum antibiotic treatment.
– impaired renal function, hearing loss, or delayed count recovery.
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Back to our patient
• Patient started on CCG 3891.• GCSF 100 mcg/sc.
• Homovanilic acid: 11.9 normal < 4.7
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SUMMERY• Age is important prognestic factor for
staging.• MYCN amplification is the most relevant
prognostic factor.• Minimum requirement for staging is : bone
marrow biopsy, CXR, bone scan and CT or MRI.
• chemotherapy with autologous stem-cell transplantation improves the outcome for children with high-risk neuroblastoma.
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REFERENCES• EMEDICINE
• UP TO DATE
• PUBMED
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THANK YOU FOR YOUR ATTENTION