NEUROBLASTOMA

Dr. B B ThapaMS –General Surgery

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

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

INVESTIGATION

12x6.5x7 cm

BIOPSY

Small round cell tumor

STAGE III DISEASE

CX-RAY

Stage IV

NEUROBLASTOMA

MODERATORProf. Dr. RV/ Dr. PMS/ Dr. AS Presenter:

Bikash Bk Thapa

INTRODUCTION

• Spectrum of neuroblastic tumors that arise from primitive sympathetic ganglion cells.

»neuroblastoma, »ganglioneuroblastoma and» ganglioneuromas

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

1 in 10,00017.3 months15 % overall mortality

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

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

Genetic model of neuroblastoma development

• 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

PATHOLOGY

SPREAD

• LYMPHATC-35%– Regional– disseminated

• HAEMATOGENOUS– bone, bone marrow, liver,brain, lung

CLINCAL PRESENTATION

– Adrenal gland-40%– Abdominal-25%– Thoracic-15%– Cervical-5%– Pelvic sympathetic-5%

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

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

Differential diagnosis

• Wilm’s tumor• Hepatoblastoma• Lymphoma, germ cell tumour, infection• Lymphoma, small round cell osteosarcoma,

Ewings sarcoma• Rhabdomyosarcoma• Infantile myofibromatosis• Dermoid cyst

DIAGNOSTIC EVALUATION

• CLINICAL• LAB• IMAGING• BIOPSY

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)

IMAGING• USG• CT-SCAN• MRI• RADIONUCLEIDE BONE SCAN

– technetium radionuclide scan or I123-MIBG scan

BIOPSY• BIOPSY (HPE, IMMUNOHISTOCHEMISTRY)• BONE MARROW BIOPSY/ASPIRATE

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.

STAGING WORKUP

• Bone marrow biopsy• Radionuclide scan or I123- MIBG scan• CT/MRI abdomen• CxR• CT /MRI chest• CT-head

SCREENING

• Urinary cantchecholamines• Not recommended• Positive family history

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

INTERNATIONAL NEUROBLASTOMA STAGING SYSTEM 1986/1993

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

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

TREATMENT MODALITES

• SURGERY

• CHEMOTHERPAY– cyclophosphamide, carboplatin or cisplatin, etoposide or

teniposide, and doxorubicin.

• RADIOTHERAPY

• OBSERVATION

• Autologous hematopoietic stem cell rescue

COG risk strata for TREATMENT

NEWER MODALITIES

» Immunotherapy»Neuroblastoma Vaccine»Angiogenesis Inhibitor• fenretinide

» Iodine-131-metaiodobenzylguanidine (MIBG), in conjunction with hematopoietic cell transplantation

PROGNOSTIC FACTORS

»TUMOR STAGE»AGE AT DIAGNOSIS»CYTOGENETICS AND MOLECULAR GENETICS»PATHOLOGICAL RISK CLASSIFICATION

References

• Sabiston textbook of surgery 18th edn• Schwartz’s principle of surgery 9th edn• Uptodate 2011

THANK YOU