Case Author(s): David Hillier, M.D., Ph.D. and Keith Fischer, M.D. , 6/15/99 . Rating: #D2, #Q3

Diagnosis: Neuroblastoma

Brief history:

8 month old female with failure to thrive and episodes of stiffening and eye rolling.

Images:

Bone scintigraphy

View main image(bs) in a separate image viewer

View second image(mr). MRI of abdomen

Full history/Diagnosis is available below

Diagnosis: Neuroblastoma

Full history:

8 month old female with developmental delay, dysmorphic features, infantile spasms (with episodes of stiffening and eye rolling) and failure to thrive. She was found to have an abdominal mass. Further work-up revealed a 1p36 chromosome deletion.

Radiopharmaceutical:

2.7 mCi methylene diphosphonate, IV

Findings:

1. Bone scintigraphy:

Extraosseous abdominal activity. No evidence of bone metastases.

2. MRI of abdomen (same day):

Large mid-abdominal mass, originating from the right adrenal gland.

The mass encases vessels (including the aorta, inferior vena cava, portal vein, celiac axis, SMA and renals).

Discussion:

The neuroblastic tumors (neuroblastoma, ganglioneuroblastoma and ganglioneuroma) derive from primitive pluripotential sympathetic cells that are derived from the neural crest and that normally differentiate to form the tissues of the sympathetic nervous system, including spinal sympathetic ganglia and adrenal chromaffin cells. The three classic histopathological patterns of neuroblastic tumors (neuroblastoma, ganglioblastoma, and ganglioneuroma) reflect a spectrum of maturation, differentiation, and clinical behavior. In contrast to the malignant varieties of these tumors, the fully differentiated, and benign, counterpart is the ganglioneuroma, which grows slowly and has no metastatic potential."(2) Neuroblastoma is one of the several small blue round cell neoplasms of childhood and must be distinguished from other tumors such as Ewings sarcoma, non-Hodgkin s lymphoma, primitive neuroendocrinee tumors, and undifferentiated soft-tissue sarcomas including rhabdomyosarcoma. . . . Electron microscopy often demonstrates the typical subcellular features of neuroblastoma, including dense core, membrane-bound neurosecretory granules, microfilaments, and parallel arrays of microtubules. Immunohistochemistry has also become an important adjunct to light microscopy . . . ."(2)

Neuroblastoma accounts for 8 to 10% of all childhood tumors and has an incidence of approximately 8 per million per year in children under 15. Over 95% occur before age 10. The tumors have differentiation patterns similar to that of normal neuronal differentiation. Furthermore, neuroblastic nodules, or in situ neuroblastoma are found in autopsies of infants that died of other causes. It is unclear if these cell rests represent the origin of neuroblastic tumors, but it has been suggested that the tumors may result from error in cell differentiation. Neuroblastic tumors reveal the highest rate of spontaneous regression of all human tumors. They generally also have a very poor prognosis when presenting as disseminated disease. Two hypotheses exist regarding the pathologic differentiation of neuroblastic tumors. In one, the tumor is thought to progress from a relatively benign form to a more malignant form with time. In the other hypothesis, the tumor is thought to have a fixed character from the start and to not change with time. If the former is true, then screening programs designed to catch neuroblastic tumors while they are still in a relatively benign form should result in a reduced mortality rate. Several studies in such countries as Japan and Canada have not shown such a mortality benefit, lending credence to the latter hypothesis.

The international staging system for neuroblastoma is as follows:

Stage 1: Confined to area of origin. Complete gross resection, with or without microscopic residual disease. Lymph nodes negative.

Stage 2A: Unilateral with incomplete gross resection. Lymph nodes negative.

Stage 2B: Unilateral with complete or incomplete gross resection. Ipsilateral lymph nodes positive (contralateral negative).

Stage 3: Crosses midline with or without lymph nodes; or unilateral tumor with contralateral lymph nodes.

Stage 4: Distant metastases to lymph nodes, bone marrow, liver or other organs (except as defined in 4S).

Stage 4S: Localised primary (as defined in stage 1 or 2) with dissemination limited to liver, skin or bone marrow.

Three-year event free survival for patients of all ages with stage 1, 2 and 4S disease is 75 - 90%. For infants less than 1-year-old, it is 90% for stage 3 and 60 - 75% for stage 4. For children, it is 50% for stage 3 and 15% for stage 4. A variety of serum tests (e.g., ferritin, neuron-specific enolase, lactate dehydrogenase) have been hypothesized to have prognostic value, but are non-specific. Tumor genetic factors, such as N-myc copy number (N-myc is a proto-oncogene which is amplified in approximately 25% of neuroblastomas and is associated with poor prognosis), ploidy (tumor hyperdiploidy in infants is associated with a good prognosis), and deletions (especially 1p chromosome deletion, associated with a poor prognosis) provide important prognostic information.

Most patients with neuroblastoma undergo surgical resection and chemotherapy. Some patients also receive radiation therapy. Aggressiveness of therapy is dictated by the prognostic factors. Treatment with large doses of I-131-labelled metaiodobenzylguanidine (mIBG) is under investigation.

References:

1. Acharya, Suchitra et. al. Prenatally Diagnosed Neuroblastoma. American Cancer Society. 80: 2; 304-310, 1997.

2. Castleberry, Robert P. Biology and Treatment of Neuroblastoma. Pediatric Clinics of North America. 44: 4; 919-937, 1997.

3. Castleberry, R.P. Neuroblastoma. European J of Cancer. 33: 9; 1430-1438, 1997.

4. Favrot, M.C. Comparison of the Diagnostic and Prognostic Value of Biological Markers in Neuroblastoma. 7: 607-611, 1996.

5. Flower, Maggie A. and Fielding, Sue L. Radiation Dosimetry for I-131 mIBG Therapy of Neuroblastoma. Phys Med Biol. 41: 1933-1940, 1996.

6. Gaze, M.N. and Wheldon, T.E. Radiolabelled mIBG in the Treatment of Neuroblastoma. 32A: 1; 93-96, 1996.

Followup:

The patient underwent laparascopic biopsy of the mass, revealing neuroblastoma (grade III). Further work-up revealed a 1p36 chromosome deletion (a deletion from the short arm of chromosome 1 is associated with neuroblastoma). The patient underwent chemotherapy (cytoxan).

Follow-up computed tomography three months later did not reveal a significant change in the size of the tumor. Calcification is apparent within the tumor.

Differential Diagnosis List

Bone scintigraphy reveals mid-abdominal soft tissue uptake in an 8-month-old. In cases of apparent soft-tissue uptake, one should first rule out artifact (e.g., free pertechnetate uptake by stomach, thyroid and salivary glands; radiopharmaceutical colloid formation uptake by liver, spleen and lungs; aluminum breakthrough; contamination; gamma camera malfunction). Gamma camera malfunction and some cases of contamination will show activity in a constant location with respect to the camera, but not the patient. There are many possible causes of soft tissue uptake in and around the abdomen in adults, including calcified liver metastases (usually from colon, lung, esophagus, breast or prostate), malignant ascites, peritoneal carcinomatosis, amyloid deposition in the liver, metastatic calcification (due to a high calcium - phosphate product with uptake seen in the kidneys, lungs and stomach), muscle trauma and dermatomyositis. However, in an infant with an abdominal mass with this pattern of ill-defined abdominal uptake, there is little in the differential diagnosis other than neuroblastoma.

ACR Codes and Keywords:

References and General Discussion of Bone Scintigraphy (Anatomic field:Gasterointestinal System, Category:Neoplasm, Neoplastic-like condition)

Search for similar cases.

Edit this case

Add comments about this case

Return to the Teaching File home page.

Case number: bs101

Copyright by Wash U MO