Neuroblastoma Cheat Sheet

Neuroblastoma Neuroblastoma is a malignant tumor arising from immature nerve cells called neuroblasts, typically found in the adrenal glands but can also develop in other areas of the sympathetic nervous system, such as the abdomen, chest, pelvis, or neck. It is the most common extracranial solid tumor in children, predominantly affecting infants and young children. Understanding the etiology, clinical features, diagnosis, and management of neuroblastoma is essential for accurate diagnosis and effective treatment. Etiology The exact cause of neuroblastoma is unknown, but it is believed to arise from abnormal development and differentiation of neural crest cells during embryogenesis. Genetic mutations and chromosomal abnormalities play a significant role in the pathogenesis of neuroblastoma, with alterations in genes such as MYCN, ALK, PHOX2B, and others implicated in tumor initiation and progression. Approximately 1-2% of cases are associated with hereditary syndromes such as familial neuroblastoma, multiple endocrine neoplasia type 2 (MEN 2), or neurofibromatosis type 1 (NF1). Clinical Features 1. Abdominal Mass: The most common presenting symptom of neuroblastoma is an abdominal mass, which may be palpable on physical examination. The mass may cause abdominal distension, pain, or discomfort and can be associated with other symptoms such as constipation, urinary retention, or respiratory symptoms if it compresses adjacent organs. 2. Sympathetic Nervous System Symptoms: Neuroblastoma arises from sympathetic nervous system tissues and can produce symptoms related to excess catecholamine secretion, such as hypertension, tachycardia, diaphoresis, flushing, and irritability. These symptoms may occur episodically or persistently, depending on the degree of catecholamine production by the tumor. 3. Metastatic Spread: Neuroblastoma has a propensity for metastasis, most commonly to regional lymph nodes, liver, bone marrow, bones, and skin. Metastatic spread may manifest with symptoms such as bone pain, lymphadenopathy, hepatomegaly, splenomegaly, or purpura. 4. Opsoclonus-Myoclonus Syndrome: A subset of children with neuroblastoma may develop opsoclonus-myoclonus syndrome (OMS), a paraneoplastic neurological disorder characterized by rapid, chaotic eye movements (opsoclonus), myoclonus, ataxia, irritability, and developmental regression. OMS is thought to result from an autoimmune response to neural antigens expressed by the tumor. Diagnosis 1. Imaging Studies: Diagnosis of neuroblastoma typically begins with imaging studies such as ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) of the abdomen and pelvis to evaluate the extent of the tumor, assess for local invasion or metastasis, and guide biopsy or surgical planning. 2. Biopsy and Histopathology: Definitive diagnosis of neuroblastoma requires tissue biopsy with histopathological examination, which typically demonstrates characteristic features such as small round blue cells with scant cytoplasm, HomerWright rosettes, and high mitotic activity. Immunohistochemical staining may be performed to confirm neural crest origin and assess tumor markers such as synaptophysin, chromogranin, and neuron-specific enolase (NSE). 3. Tumor Markers: Serum and urine levels of tumor markers such as catecholamines (norepinephrine, epinephrine), vanillylmandelic acid (VMA), and homovanillic acid (HVA) may be elevated in patients with neuroblastoma and can be used for diagnostic evaluation, monitoring response to treatment, and detecting residual or recurrent disease. 4. Genetic Testing: Genetic testing may be performed to identify chromosomal abnormalities, gene mutations, or other genetic alterations associated with neuroblastoma, such as MYCN amplification or ALK mutations. Molecular profiling of the tumor can help stratify patients into risk groups and guide treatment decisions. Management 1. Risk Stratification: Treatment planning for neuroblastoma is based on risk stratification, which takes into account factors such as age at diagnosis, tumor stage, histopathological features, extent of metastasis, and genetic markers such as MYCN amplification and ALK mutations. Risk groups include low-risk, intermediate-risk, high-risk, and ultra-high-risk categories, each requiring tailored treatment approaches. 2. Multimodal Therapy: Treatment for neuroblastoma typically involves a multimodal approach combining surgery, chemotherapy, radiation therapy, and immunotherapy, depending on the risk group and extent of disease. Surgical resection of the primary tumor is performed whenever feasible, followed by systemic chemotherapy to eradicate residual disease and prevent metastatic spread. 3. Stem Cell Transplantation: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) may be considered for patients with high-risk or relapsed neuroblastoma to achieve deeper remission and improve survival outcomes. Allogeneic HSCT may be considered in selected cases, particularly for patients with refractory disease or relapse after autologous HSCT. 4. Immunotherapy: Targeted immunotherapy with monoclonal antibodies such as dinutuximab or immune checkpoint inhibitors such as nivolumab or ipilimumab may be used as adjuvant therapy for high-risk neuroblastoma to enhance antitumor immune responses and improve outcomes. Prognosis The prognosis for neuroblastoma varies widely depending on risk group, stage of disease, age at diagnosis, histopathological features, and genetic markers. Overall survival rates range from more than 95% for low-risk disease to less than 50% for high-risk or ultra-high-risk disease. Advances in risk stratification, multimodal therapy, targeted therapy, and immunotherapy have led to significant improvements in survival outcomes for children with neuroblastoma in recent years. However, challenges such as treatment-related toxicities, relapse, and long-term sequelae remain significant concerns, highlighting the need for ongoing research and innovative treatment approaches to further improve outcomes and quality of life for patients with neuroblastoma.