Address correspondence to Judy A. Estroff, MD, from Diagnostic Ultrasound Associates, 333 Longwood Avenue, Boston Massachusetts, 02115 Ph: 617-739-0245; Fax: 617-738-6703. Dept. of Radiology and Surgery at Children"s Hospital, and Radiology and Obstetrics & Gynecology at Brigham & Women"s Hospital, Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston Massachusetts.

Synonyms: Ganglioneuroblastoma, neuroblastoma in situ. BDE: Cancer, neuroblastoma.

Definition: Malignant neoplasm of poorly differentiated nerve cells of embryonic type.

Prevalence: 0.3-1:10,000. M1:F1

Pathogenesis: Defect in neuroblast maturation with embryonal sympathetic ganglion cells undergo malignant transformation. Associated with n-myc onogene and tumor cell ploidy: if n-myc gene is positive and cells are diploid, then the prognosis is worse^10,11.

Diagnosis: Suprarenal or posteromediastinal mass. Over 95% of children have elevated catecholamine metabolites. Values in fetuses are not known. Occasionally the mother may exhibit signs due to the increased catecholamine.

Primary sites: See figure 3.

Evans staging system: Stage I: Tumor confined to the organ or structure of origin. Stage II: Tumor extending in continuity beyond the organ or structure of origin but not crossing the midline. Regional lymph nodes on homolateral side may be involved. Stage III: Tumor extending in continuity beyond the midline with or without positive regional nodes. Stage IV: Distant metastases. Stage lV-S: Stage I-II primaries with metastases to liver, skin and/or bone marrow (not bone). Almost all stage IV-S are infants.

Metastatic sites: Frequent: Bone, lymph nodes,bone marrow, liver, skin; occasional: extradural extension into spinal canal, rare: lung.

Associated anomalies: Hydrops, neurofibromatosis, Hirschprung"s disease, some chromosomal abnormalities. May be part of the fetal hydantoin and fetal alcohol syndromes.

Differential diagnosis: Adrenal site: renal duplex anomaly or tumor, adrenal cyst or hemorrhage are less likely. Extra-adrenal site: solid mass of lung, pelvis, head or neck.

Prognosis: Better with younger age and lower stage at diagnosis. Better with primary thoracic site of tumor. Some may mature into ganglioneuroma.

Survival: See figure 4.

Recurrence risk: unknown.

Management: Stage I: Surgical resection; no other treatment. Stage II: Surgical resection in infants. Older children: chemotherapy with or without added radiation. Stage III & IV. Surgical debulking, then chemotherapy and radiation. Bone marrow transplant in high risk patients (older patients and those with n-myc amplification).

MESH Neuroblastoma BDE 2736 MIM 256700 ICD9 194.0 CDC 194.000

Introduction

The prenatal diagnosis of neuroblastoma has occasionally been reported^2,3,5-7. The reported cases of prenatally diagnosed neuroblastomas do not display a specific sonographic pattern. Both prenatal and postnatally diagnosed neuroblastomas have been described as cystic, mixed cystic and solid, and solid with areas of calcification^2,3.

We describe two cases of prenatally diagnosed neuroblastoma, which differ in sites of origin and in sonographic appearance.

Case reports

Case #1

A 31-year-old woman who presented at 41 weeks" gestation for a post-dates biophysical profile. Incidental note was made of a 28 mm, cystic mass above the right kidney. The prior scan at 16 weeks had been normal. A postnatal ultrasound confirmed the presence of a cystic mass, which, at surgery, was a low-grade neuroblastoma. The mass was resected at two weeks of life. The metastatic workup was negative and the infant has done well, with no evidence of recurrence or of metastatic disease, after 15 months.

Case #2

A 28-year-old woman seen for a second opinion regarding a fetal thoracic mass noted at 38 weeks" gestation. A 27 x 20 mm echogenic solid posterior left mediastinal mass with areas of calcification was noted in the fetus. The differential diagnosis offered at prenatal evaluation was a ganglioneuroma, neuroblastoma or teratoma. The infant was delivered at a tertiary care hospital and showed no signs of respiratory distress during the first few hours after birth. However, at approximately 24 hours of life, respiratory compromise became evident.

The patient underwent diagnostic imaging showing a large posterior mediastinal mass which invaded the spinal canal and encroached upon the tracheo- bronchial tree. Surgical resection was followed by chemotherapy. The child showed no evidence of disease at 22 months of age.

Discussion

Neuroblastoma is the most common malignant tumor in infancy and early childhood, originating anywhere along the sympathetic nervous system, and in the adrenal gland (fig. 3). More than half of neuroblastomas are in the abdomen, and two-thirds of these originate in an adrenal gland. Fifteen percent of neuroblastomas are thoracic, arising posteriorly along the sympathetic chain. Other sites include the cervical region, sympathetic chain in the abdomen, nasopharynx and brain^2,4,8,9.

More than half of patients are less than two years of age at diagnosis. Seventy-five percent of tumors are discovered prior to four years of age. The prognosis ranges from over 90% survival if discovered in patients under one year of age, to less than 10% survival when discovered in older children^2,8,9 (fig 4). Accurate early diagnosis is crucial, as the best prognosis is in the youngest patients.

Differential diagnosis

Although the correct diagnosis was suggested in our two cases, other diagnostic possibilities were recognized as well. For the first case, a cystic lesion in the suprarenal region may suggest renal abnormalities such as duplex anomalies of the kidney with upper pole hydronephrosis or cystic dysplasia of an upper pole moiety. Other rare cystic neoplasms of the kidney, such as cystic Wilms" tumor, must be considered.

Other adrenal lesions are possible, including adrenal cysts or hemorrhage. Unfortunately, both of these benign entities are less common in the fetus and newborn than adrenal neuroblastoma.

Although approximately 70% of neuroblastomas are located in the adrenal gland, other sites of origin are well described. The appearance of the lesion in our second case could be confused with that of a lung mass such as pulmonary sequestration or cystic adenomatoid malformation. The paraspinal location of the mass in case #2 suggested a tumor of neurogenic origin, but this could not be confirmed prenatally. Lesions previously described in the literature had variable appearances (Table 1).

Table 1: Review of the literature.

Conclusion

Prenatal recognition of fetal masses allows the opportunity for delivery at a specialized center with access to urgent care by neonatologists and surgical subspecialists. Although the first infant was asymptomatic at birth from the adrenal neuroblastoma, the second infant deteriorated under observation and required immediate intervention, which may not have been available had the infant been delivered outside of a specialized center. Neuroblastoma can mimic other lesions in utero; however, it is important to recognize neuroblastoma in the differential diagnosis since aggressive follow-up results in the best outcome.

References

1. Atkinson GO, Jr, Zaatari GS, Lorenzo RL, et al: Cystic neuroblastoma in infants: Radiographic and pathologic features. AJR 146:113-117, 1986.

2. Ferraro EM, Fakhry J, Aruny JE, et al: Prenatal adrenal neuroblastoma: case report with review of the literature. J Ultrasound Med 7:275-278, 1988.

3. Giulian BB, Chang CCN, Yoss BS: Prenatal ultrasonographic diagnosis offetal adrenal neuroblastoma. JCU 14:225-227, 1986.

4. Silverman FN (ed): Coffey"s Pediatric X-Ray Diagnosis, 8th ed. Chicago, Year Book Medical 1733-1737, 1985.

5. Janetschek G, Weitzel D, Stein W, et al: Prenatal diagnosis of neuroblastoma by sonography. Urology 24:397, 1984.

6. defilippi G, Canestri G, Bosio V, et al: Thoracic neuroblastoma: antenatal demonstration in a case with unusual postnatal radiographic findings. Br J Radiol 59:704, 1986.

7. Fowlie F, Giacomantonio M, McKenzie E, et al: Antenatal sonographic diagnosis of adrenal neuroblastoma. J Can Assoc Radiol 37:50, 1986.

8. Hayes FA, Smith El: Neuroblastoma.In: Principles and Practice of Pediatric Oncology, Pizzo PA, Poplack DG, (eds.) Lippincott, Philadelphia, 1989, p.61 1.

9. Rosen EM, et al. Neuroblastoma: Joint center for radiation therapy: Dana Farber Cancer Institute / The Children"s Hospital experience. J Clin Oncol 2:719,1984.

10. Look T et al: Clinical relevance of tumor cell ploidy and n-myc gene amplification in neuroblatoma. J Clin Oncol 9:581-91, 1991

11. Look T et al: Association of n-myc oncogene with neuroblastoma. NEJM 313:1111-6, 1985.