Can neuroblastoma (neuroblastic tumor) present with facial asymmetry?

Can Neuroblastoma Present with Facial Asymmetry?

Yes, neuroblastoma can present with facial asymmetry, though this is an uncommon presentation that typically indicates either primary head and neck disease or metastatic involvement of facial bones.

Mechanisms of Facial Asymmetry in Neuroblastoma

Primary Head and Neck Neuroblastoma

• Primary neuroblastoma of the head and neck region is rare but well-documented, and these tumors can cause facial asymmetry through direct mass effect and local tissue invasion 1
• When neuroblastoma arises primarily in the head and neck, the prognosis is poor with rapid and widespread metastasis being typical 1

Metastatic Disease to Facial Structures

• Metastatic neuroblastoma to the mandible can present with facial swelling as the first sign of disseminated disease 2
• Mandibular involvement manifests as painful swelling in the mandibular region with destructive bone lesions visible on imaging 2
• Beyond the mandible, neuroblastoma can metastasize to multiple sites of the axial and appendicular skeleton, including facial bones 2, 3

Clinical Presentation Patterns

Typical Presenting Features

• Patients with neuroblastoma most commonly present with abdominal mass or distension, but symptoms vary depending on tumor location 4
• When facial asymmetry occurs, it may be accompanied by bone pain, swelling, and radiographic evidence of destructive bone lesions 2
• The median age for aggressive neuroblastoma is just under 2 years, though it can occur throughout childhood 5

Associated Symptoms to Assess

• Loss of appetite, weight loss, irritability, fever, hypertension, anemia, and pancytopenia may accompany facial asymmetry in neuroblastoma 4
• Bruising or swelling around the eyes (periorbital ecchymosis/"raccoon eyes") is a classic sign of metastatic disease 4
• Bone pain and body soreness may precede or accompany facial swelling 2

Diagnostic Approach When Neuroblastoma is Suspected

Imaging Priorities

• Obtain cross-sectional imaging (MRI with/without contrast or CT with contrast) to evaluate soft tissue disease and bone involvement 4
• MRI of the brain with/without contrast or CT skull/orbits with contrast should be performed if neurologic symptoms are present or facial asymmetry is noted 4
• Panoramic radiography and CT can demonstrate destructive bone lesions in the mandible or maxilla when facial asymmetry is present 2

Metastatic Disease Evaluation

• 123I-MIBG imaging is essential to assess for metastatic disease, as it demonstrates uptake in up to 90% of neuroblastoma tumors 4
• 18F-FDG-PET imaging should be obtained in patients with 123I-MIBG nonavid disease or suspected mixed-avidity disease 4
• Bilateral bone marrow aspirates and trephine biopsies are required for complete staging 4

Tissue Diagnosis

• Microscopic analysis of facial lesions reveals diffuse proliferation of small, round, blue cells with hyperchromatic nuclei and scant cytoplasm 2
• Immunohistochemistry shows expression of neural markers including CD56, neuron-specific enolase, chromogranin, and synaptophysin 2
• High proliferation index (Ki67 >70%) is typical of aggressive neuroblastoma 2

Critical Differential Diagnosis Considerations

Other Causes of Facial Asymmetry in Children

• Facial asymmetry in children requires exclusion of intracranial pathology, facial nerve disorders, and strabismus with compensatory head posture before attributing it to structural causes 6
• Brain MRI with contrast is the first-line imaging study to evaluate for intracranial mass or tumor affecting the facial nerve 6
• Complete cranial nerve assessment and House-Brackmann scale evaluation are essential to rule out Bell's palsy or other facial nerve pathology 6

Distinguishing Neuroblastoma from Other Tumors

• In the internal auditory canal and cerebellopontine angle, neuroblastoma is a rare differential diagnosis alongside more common vestibular schwannomas and meningiomas 4
• Metastases to facial bones from neuroblastoma must be distinguished from other pediatric tumors including Ewing sarcoma, Langerhans cell histiocytosis, and retinoblastoma metastases 3

Important Clinical Pitfalls

Do Not Delay Evaluation

• New-onset progressive facial asymmetry in a child should be considered potentially serious requiring prompt evaluation 6
• Facial asymmetry may be the first sign of disseminated neuroblastoma requiring urgent attention 6, 2
• Do not assume benign structural asymmetry without appropriate imaging and workup 6

Recognition of High-Risk Features

• Destructive bone lesions on imaging indicate aggressive disease requiring immediate oncologic evaluation 2
• Multiple bone metastatic lesions are common when facial involvement is present, necessitating comprehensive staging 2
• Primary adrenal lesions are typically identified on PET-CT when facial metastases are the presenting feature 2

Treatment Implications

• Treatment of neuroblastoma with facial involvement consists of induction chemotherapy, surgical resection of primary tumor (adrenalectomy if adrenal primary), consolidation chemoradiotherapy, and post-consolidation therapy 2
• Early and massive therapy involving surgery, chemotherapy, and radiation therapy is required for invasive neuroblastoma of the head and neck 1
• Despite multimodal therapy, high-risk neuroblastoma with metastatic disease has poor outcomes 1, 5