K. Myra Lalas, MD

PGY 3

difficulty walking and difficulty breathing

Clumsiness when walking that evolved over a month

(+) cough x 2wksTactile fever at home x 1wkDifficulty breathing x 2 daysDecreased PO x 2 wksWeight loss x 1 mo

VS Temp 38.2F HR 110 RR 44 O2sat 93%Gen awake, alert, mod resp distressHEENT PERRLA, EOMI, OP clearm no LADLungs no Rx, dec AE on R mid-lower lung field,

no w/r/rHeart N S1/S2, no murmursAbd soft, NT/NDExt FEP, CRT < 2sNeuro CN intact, no sensory deficits, normotonic,

no dysmetria, (+) ataxia, ++ reflexes

13 mo male with difficulty walking and clumsiness when walking. (+) history of cough, difficulty breathing, and decreased PO. Symptoms worsened over a month.

Went to PMD- referred to ER. In the ER was noted to have respiratory distress.

7/6/08- CT of the abdomen and thorax revealed a large calcified posterior mediastinal mass.

neurogenic tumors esophageal tumorsesophageal duplication cystshiatal hernia, neurenteric cystsAortic aneurysm

CT of the abdomen and thorax- large calcified posterior mediastinal mass with expansion of the neural foramina as well as mediastinal LAD. Most likely neuroblastoma; (+) multifocal pneumonia with right pleural effusion

MRI of the thoracic spine- large posterior mediastinal mass invading the epidural space of the central spinal canal. (+) cord compression with anterior and left lateral displacement of the cord at the T7-T9 level

Bone Marrow Aspiration/ biopsy (2 sites) were negative.

He was transferred to the ICU for chest tube placement and drainage of right pleural effusion.

Most common extracranial malignancy of infancy

Embryonal malignancy of the the SNS arising from neuroblasts

In the developing embryo, these cells invaginate, migrate along the neuraxis, and populate the sympathetic ganglia, adrenal medulla, and other sites.

Pathophysiology: 1. MYCN gene (oncogene) amplification-

overexpressed in approximately one quarter of cases of neuroblastoma via the amplification of the distal arm of chromosome 2.

amplified in about 25% of de novo cases and is more common in patients with advanced-stage disease.

2. H-ras oncogene amplification- seen in lower disease stages

3. Disruption of normal apoptotic pathways

Location of tumors varies with age.: infants- thoracic and cervical tumors; older children- abdominal tumors.

Tumors can develop in the abdominal cavity (40% adrenal, 25% paraspinal ganglia) or other sites (15% thoracic, 5% pelvic, 3% cervical tumors, 12% miscellaneous).

Whites > blacksM: F ration of 1.2:140% of patients are < 1 year when diagnosed,35% are aged 1-2 years25% are older than 2 years when diagnosed. Incidence decreases every consecutive year up

to age 10 years, after which the disease is rare.

Abdominal pain, emesis, weight loss, anorexia, fatigue, and bone pain

Hypertension (renal artery compression)Unexplained feverPeriorbital ecchymosis (mets to orbits)

weakness, limping, paralysis, and even bladder and bowel dysfunction (tumors from parasympathetic ganglia can impinge on the SC)

Horner SyndromeIntractable diarrhea(due to VIP secretion/

paraneoplastic)

RhabdomyosarcomaWilms TumorOsteomyelitisRheumatoid arthritisDisseminated bone diseasePrimary neurologic diseaseInflammatory bowel disease

CBC with differential count (to test for BM involvement)

CMPUrine collection for VMA/HVA and UAUric acidLDHFerritinTFT’s

CXR, AXRCT ScanMRIMIBG accumulates in catecholaminergic

cells and provides a specific way of identifying primary and metastatic disease if present.

Tc 99 bone scan

Arrows point to pseudorosetttes (circles of tumor cells surrounding nerve fibers); small round blue cells with scant cytoplasm

STAGE TUMOR EXTENT

LYMPH NODE INVOLVEMENT

Stage 1 Localized tumor with complete gross excision, microscopic residual disease, or both

Ipsilateral lymph nodes negative for tumor

Stage 2A Localized tumor with incomplete gross resection

Representative ipsilateral nonadherent lymph nodes microscopically negative for tumor

Stage 2B Stage 2B

Localized tumor, complete gross excision, or both with ipsilateral nonadherent lymph nodes positive for tumor

Enlarged contralateral lymph nodes, which are negative for tumor microscopically

Stage 3 Unresectable unilateral tumor infiltrating across the midline, regional lymph node involvement, or both

Alternatively, localized unilateral tumor with contralateral regional lymph node involvement

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)

Stage 4S Localized primary tumor (as defined for stages 1, 2A, or 2B) with dissemination limited to skin, liver, and/or bone marrow (<10% involvement) Limited to infants

Chest CT Scan- Neuroblastoma on the left and over the spine

Obtain the following as baseline studies before therapy with anthracyclines:

ECG Echocardiogram

Baseline hearing tests are recommended before cisplatin therapy.

Prognosis dependent upon patient’s age and disease staging.

Early disease treatment may only involve tumor resection.

Surgery, radiation therapy, chemotherapy for advanced disease.

Cyclophosphamide (activates production of alkylating agents)

Doxorubicin (DNA strand breakage though topisomerase II)

Etoposide (DNA strand break) Cisplatin, (binds and x-links DNA strands)Vincristine (mitotic inhibitor by binding

tubulin)

MIBG- selectively absorbed by neuroblastoma cells; used to deliver targeted radiation to neuroblastoma cells by binding it to I-131 ( iodine radioisotope)

Isotretinoin- Vitamin A derivative. Interacts with retinoic acid responsive elements on DNA, which results in gene activation and differentiation of target cells.

I-3F8- experimental; attached to GD 2 marker on NB cells, which activates the immune system (renders NB cells foreign and immune system attacks them)

7/7/08- laminectomy and partial resection of the mass; started on ANBL0531 protocol x 4 cycles

10/16/08- tumor resection; pathology consistent with bone mets

5/26/09 – retrieval tx per N8 protocol for relapse

6/11/09- extensive resection of the disease8/27/09- underwent neurosurgical resection

for residual disease in the epidural space9/10/09- started a cycle of high dose

cyclophosphamide, topotecan, and Vincristine10/09- no evidence of neuroblastoma11/16/09- 3 F8 tx11/17/09- started on isotretinoin

www.emedicine.comwww.mskcc.orgNelson’s Textbook of Pediatrics