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Adrenal neuroblastoma

Published:September 07, 2021DOI:https://doi.org/10.1016/j.ajog.2021.06.037

      Introduction

      The fetal adrenal glands can be seen by ultrasonography by the end of the first trimester of pregnancy.
      • Norton M.E.
      Callen's Ultrasonography in Obstetrics and Gynecology E-Book.
      They appear as pyramidal hypoechoic structures superior to the hyperechoic kidney. During the second trimester of pregnancy, corticomedullary differentiation can be observed with a hypoechoic cortex and hyperechoic medulla. The size of the gland increases throughout gestation but remains smaller than the kidney. During the third trimester of pregnancy, the appearance of the fetal adrenal glands is similar to that of the neonatal adrenal glands.
      • Norton M.E.
      Callen's Ultrasonography in Obstetrics and Gynecology E-Book.
      Neuroblastomas account for 50% of fetal adrenal masses.
      • Goodman M.T.
      • Gurney J.
      • Smith M.
      • Olshan A.
      Sympathetic nervous system tumors
      Cancer incidence and survival among children and adolescents: United States SEER Program.
      ,
      • Sauvat F.
      • Sarnacki S.
      • Brisse H.
      • et al.
      Outcome of suprarenal localized masses diagnosed during the perinatal period: a retrospective multicenter study.
      They are more common in White infants and slightly more common in males than in females.
      • Goodman M.T.
      • Gurney J.
      • Smith M.
      • Olshan A.
      Sympathetic nervous system tumors
      Cancer incidence and survival among children and adolescents: United States SEER Program.
      Neuroblastomas originate in the neural crest cells of the sympathetic nervous system. Although most cases arise from the adrenal gland, they can also occur in the posterior mediastinum.
      • Goodman M.T.
      • Gurney J.
      • Smith M.
      • Olshan A.
      Sympathetic nervous system tumors
      Cancer incidence and survival among children and adolescents: United States SEER Program.

      Definition

      The term neuroblastoma refers to a spectrum of neuroblastic tumors (eg, neuroblastomas, ganglioneuroblastomas, and ganglioneuromas) that arise from sympathetic ganglion cells.
      • Goodman M.T.
      • Gurney J.
      • Smith M.
      • Olshan A.
      Sympathetic nervous system tumors
      Cancer incidence and survival among children and adolescents: United States SEER Program.
      Although neuroblastomas are malignant tumors, and some can metastasize, the prognosis is excellent, and many cases regress spontaneously.
      • Fisher J.P.H.
      • Tweddle D.A.
      Neonatal neuroblastoma.

      Ultrasound Findings

      Adrenal neuroblastoma generally appears as a well-encapsulated cystic or solid mass adjacent to but separate from the kidney and other retroperitoneal structures (Figure).
      • Sauvat F.
      • Sarnacki S.
      • Brisse H.
      • et al.
      Outcome of suprarenal localized masses diagnosed during the perinatal period: a retrospective multicenter study.
      Assessment of the contralateral adrenal gland to rule out normal but prominent adrenal glands is recommended. Findings on color Doppler interrogation are variably reported and include peripheral flow, no flow, or internal vascularization of the hyperechogenic aspects of the mass.
      • Sauvat F.
      • Sarnacki S.
      • Brisse H.
      • et al.
      Outcome of suprarenal localized masses diagnosed during the perinatal period: a retrospective multicenter study.
      ,
      • Schwärzler P.
      • Bernard J.P.
      • Senat M.V.
      • Ville Y.
      Prenatal diagnosis of fetal adrenal masses: differentiation between hemorrhage and solid tumor by color Doppler sonography.
      A single feeding artery is not typically present and would suggest the more common subdiaphragmatic bronchopulmonary sequestration (BPS).
      • Curtis M.R.
      • Mooney D.P.
      • Vaccaro T.J.
      • et al.
      Prenatal ultrasound characterization of the suprarenal mass: distinction between neuroblastoma and subdiaphragmatic extralobar pulmonary sequestration.
      Figure thumbnail gr1
      FigureFetal neuroblastoma
      A, Solid suprarenal well-encapsulated mass. B, Doppler ultrasound showing limited vascular flow.
      RT, right.
      Society for Maternal-Fetal Medicine. SMFM Fetal Anomalies Consult Series #4. Am J Obstet Gynecol 2021.

      Associated Abnormalities

      Postnatally, neuroblastoma has been associated with Li-Fraumeni syndrome, Hirschsprung disease, and neurofibromatosis type 1, but these associations have not been reported in prenatal cases. If a neuroblastoma markedly enlarges and compresses the gastrointestinal tract, polyhydramnios may develop.
      • Cho J.Y.
      • Lee Y.H.
      Fetal tumors: prenatal ultrasonographic findings and clinical characteristics.
      Elevated catecholamines have been reported and may cause maternal symptoms, such as tachycardia, hypertension, nausea, and vomiting.
      • Jennings R.W.
      • LaQuaglia M.P.
      • Leong K.
      • Hendren W.H.
      • Adzick N.S.
      Fetal neuroblastoma: prenatal diagnosis and natural history.
      In addition, catecholamine release has been associated with fetal cardiomyopathy, tachycardia, and hydrops.
      • Inoue T.
      • Ito Y.
      • Nakamura T.
      • Matsuoka K.
      • Sago H.
      A catecholamine-secreting neuroblastoma leading to hydrops fetalis.
      Rarely, fetal neuroblastomas may metastasize to the liver.
      • Desai G.
      • Filly R.A.
      • Rand L.
      Prenatal detection of an extra adrenal neuroblastoma with hepatic metastases.

      Differential Diagnosis

      The differential diagnosis of a mass in this region includes adrenal cysts
      • Patti G.
      • Fiocca G.
      • Latini T.
      • Celli E.
      • Bellussi A.
      • Nazzicone P.
      Prenatal diagnosis of bilateral adrenal cysts.
      (isolated or associated with multicystic dysplastic kidneys or Beckwith-Wiedemann syndrome), adrenal hemorrhage,
      • Strouse P.
      • Bowerman R.A.
      • Schlesinger A.E.
      Antenatal sonographic findings of fetal adrenal hemorrhage.
      subdiaphragmatic BPS,
      • Rubenstein S.
      • Benacerraf B.
      • Retik A.
      • Mandell J.
      Fetal suprarenal masses: sonographic appearance and differential diagnosis.
      hepatic tumor, and adrenogenital syndrome (secondary to congenital adrenal hyperplasia).
      • Maki E.
      • Oh K.
      • Rogers S.
      • Sohaey R.
      Imaging and differential diagnosis of suprarenal masses in the fetus.
      Hemorrhage in adrenal cysts associated with Beckwith-Wiedemann syndrome has been reported, in which case the appearance is that of a complex mass.
      • Gocmen R.
      • Basaran C.
      • Karcaaltincaba M.
      • et al.
      Bilateral hemorrhagic adrenal cysts in an incomplete form of Beckwith-Wiedemann syndrome: MRI and prenatal US findings.
      • Birkemeier K.L.
      Imaging of solid congenital abdominal masses: a review of the literature and practical approach to image interpretation.

      Genetic Evaluation

      Fetal neuroblastoma is typically a sporadic finding. If no further abnormalities are noted on ultrasound and the family history is unremarkable, no genetic evaluation beyond standard aneuploidy screening is typically recommended.

      Pregnancy and Delivery Management

      Hydrops fetalis, polyhydramnios, or both may develop in rare circumstances, typically with large lesions or in the setting of metastatic disease; therefore, serial ultrasound examinations should be performed. Serial ultrasound assessment can help rule out adrenal hemorrhage, which can evolve over time.
      • Fisher J.P.H.
      • Tweddle D.A.
      Neonatal neuroblastoma.
      ,
      • Birkemeier K.L.
      Imaging of solid congenital abdominal masses: a review of the literature and practical approach to image interpretation.
      A consultation with pediatric oncology, neonatology, and surgery should be obtained to plan and coordinate prenatal and postnatal management. In general, pregnancy termination is an option that should be offered to patients when a major fetal anomaly is detected. However, in most cases of neuroblastoma, the prognosis is favorable, and the outcome is good. Shared patient decision-making requires a thorough evaluation and multidisciplinary counseling regarding prognosis. If pregnancy termination is pursued, histologic evaluation can confirm the diagnosis.
      In most cases, vaginal delivery is appropriate, and cesarean delivery should be reserved for the usual obstetrical indications. Cesarean delivery has been suggested as potentially preferable for very large cystic adrenal masses to prevent rupture or soft tissue dystocia. Adrenal cyst aspiration before delivery is controversial because this may cause bleeding, malignancy seeding, preterm labor, or infection. Delivery in a tertiary care center is recommended with consideration of early delivery if there is evidence of fetal compromise. Postnatal investigation, including ultrasound, magnetic resonance imaging, or other imaging modalities, is recommended. Expectant management, needle biopsy, or surgical exploration may be needed on the basis of the results of the above imaging, final diagnosis, and neonatal condition.

      Prognosis

      In general, the prognosis is good, and neuroblastomas may even resolve in utero or shortly after birth.
      • Sauvat F.
      • Sarnacki S.
      • Brisse H.
      • et al.
      Outcome of suprarenal localized masses diagnosed during the perinatal period: a retrospective multicenter study.
      ,
      • Rubenstein S.
      • Benacerraf B.
      • Retik A.
      • Mandell J.
      Fetal suprarenal masses: sonographic appearance and differential diagnosis.
      Survival rates of infants with low-stage disease are excellent, even for those with metastatic disease.
      • London W.
      • Castleberry R.
      • Matthay K.
      • et al.
      Evidence for an age cutoff greater than 365 days for neuroblastoma risk group stratification in the Children's Oncology Group.
      Cases of spontaneous involution have been reported.
      • Holgersen L.O.
      • Subramanian S.
      • Kirpekar M.
      • Mootabar H.
      • Marcus J.R.
      Spontaneous resolution of antenatally diagnosed adrenal masses.
      The recurrence risk of this lesion is unknown but likely low.

      Summary

      Fetal adrenal neuroblastomas, derived from neural crest cells, are the most frequently diagnosed extracranial solid tumor of childhood. These rare tumors are associated with an excellent postnatal prognosis. Close surveillance with serial ultrasound examinations evaluating for signs of hydrops fetalis and polyhydramnios is recommended. Antenatal consultation with pediatric oncology, neonatology, and surgery is advised.

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