Michael O’Neill, MD, Samantha Block, BS, Gaurav Saigal, MD,...
1
1. Park, J., Et. Al. Neuroblastoma: Biology, Prognosis, and Treatment. Hematol Oncol Clin North Am. 2010 Feb;24(1):65-86. 2. Papaioannou, G., Mchough, K. Neuroblastoma in childhood: review and radiologicalfindings Cancer Imaging (2005) 5, 116–127 3. Franks, L. Et. Al. Neuroblastoma In Adults and Adolescents: An Indolent Course with Poor Survival. Cancer 1997;79:2028–35. 4. Cotterill, S.J., Et. Al. Clinical prognostic factors in 1277 patients with neuroblastoma: Results of The European Neuroblastoma Study Group Survey 1982 1992. European Journal of Cancer 36 (2000) 901 908 5. Lonergan, G., Et. Al., Neuroblastoma, Ganglioneuroblastoma,and Ganglioneuroma: Radiologic- Pathologic Correlation. Radiographics 2002; 22 (4): 911-934. 6. Rosado-de-Christenson, M.,Et. Al. Mediastinal Germ Cell Tumors: Radiologic and Pathologic Correlation Radiographics 1992;12:1013-1030. 22 Year Old Female with Mediastinal Neuroblastoma Michael O’Neill, MD, Samantha Block, BS, Gaurav Saigal, MD, Andre Pinto, M.D. University of Miami Miller School of Medicine Jackson Memorial Hospital, Miami, FL • Neuroblastoma remains the third most common childhood malignancy, after leukemia and CNS tumors, representing 8-10% of childhood cancers, causing 15% of all childhood cancer deaths. 1,2 • Median age of presentation overall is 23 months, with only 5% of all cases presenting after 10 years of age. However, it can uncommonly present in adolescence, and rarely even well into adulthood, with cases reported even up to 75 years of age. 3 • Tumors are of ganglion cell origin and are derived from primordial neural crest cells; tumors are found along the typical distribution of sympathetic ganglia, most commonly in the adrenal medulla (35%), but can also be found in the extra-adrenal paraspinal ganglia (30%–35%), followed by the posterior mediastinum in 20%. • Interestingly, the disease distribution in younger patients (<1 year) compared to older (>1yr) patients in a previous investigation, found that the mediastinum was an even less common site of presentation in older patients. 1 Other more uncommon sites include the pelvis (2%–3%) and the neck (1%–5%). 2 • Prognosis is determined by age, Evans stage, and especially histopathologic as well as cytogenetic characteristics. Older ages of presentation, advanced stages (3-4), and presence of cytogenetic abnormalities such as MYCN amplification (25-35%), DNA ploidy, and loss of chromosome 1 p (30–40%) are associated with a poorer prognosis. History and Physical Examination • A 22-year-old woman with a 6 month history of dyspnea; intolerable over the previous 2 months. • Symptoms: right chest pain and back pain. • Signs: Hypoxemia, hypotension, and tachycardia, with swelling in the right supraclavicular region, right arm, and right face with signs of venous collaterals on the right chest wall. • Absent right lung sounds on auscultation Diagnostic Evaluation • Pertinent laboratory findings: AST level of 91 U/L and an ALP level of 177 U/ ml. LDH was greater than 2150 U/L, homovanillic acid was 7.7 mg/ g, and vanillylmandelic acid was 4.9 mg/ g. • Portable AP Chest radiograph, Contrast-Enhanced Computerized Tomography (CT) of the Chest, Abdomen, and Pelvis, and Contrast-Enhanced Magnetic Resonance Imaging (MR) of the Thoracic Spine were ordered Discussion •The imaging findings of Neuroblastoma are often well characterized on CT and MRI. 5 •CT is the most commonly used imaging modality for initial assessment and preliminary diagnosis of Neuroblastomas, often showing stippled calcifications, necrosis, and prominent adenopathy as well as possible metastatic lesions. •On MRI, the tumors are heterogenously enhancing masses, with low T1 and high T2 signals, possibly also demonstrating foci of hemorrhage on T1 as well. •Bone marrow disease appears bright on T2 and dark on T1 weighted imaging. •Our 22 year old female’s differential diagnosis would be led by lymphoma given the age, anatomic location of the lesion, as well as statistical likelihood. •The mass in this case was centered in the posterior mediastinum. •In addition, our patient had no constitutional or “B” symptoms. •There was an elevated urinary HVA and VMA. •Osteosarcoma, Metastases, Ewings Sarcoma, and Germ cell tumors must also be considered and excluded. •Mediastinal germ cell tumors are rare and less likely to be symptomatic. •On Imaging, they are usually cystic lesions that demonstrate a combination of fat, calcification, fluid and soft tissue attenuation values. •The absence of these benign features, along with the presence of elevated urinary catecholamines in the setting of a highly aggressive tumor is suggestive of Adult Neuroblastoma. Conclusion References Diagnostic Imaging •Neuroblastoma is a rare but often highly aggressive tumor when presenting in an Adult. •To avoid diagnostic delays, Neuroblastoma should also be remembered for the differential diagnosis of mediastinal masses in an adult as well as a child. Figure 1- Initial AP Chest Radiograph shows a large right hemithorax opacity with associated leftward deviation of the cardiomediastinal silhouette. Figure 5- Sagittal T2-weighted MRI image through the right upper thoracic spine demonstrates infiltration of several upper thoracic vertebral foramina and encroachment of the exiting nerves, most notably at the T2-T4 levels. In addition, there is associated abnormal marrow signal suggesting marrow invasion. Figure 2- CT Chest with IV contrast demonstrates a large, exophytic and Heterogenous enhancing mass with scattered calcifications, which is centered in the posterior mediastinum. There is associated leftward shift of the great vessels and cardiomediastinum. Note the prominence of the ipsilateral posterior extrathoracic muscles, suggesting tumor infiltration. Figure 6- Axial T2 weighted image shows tumor infiltration of the right T2-T3 neural foramen and encroachment of the exiting nerve. Other Axial images showed similar involvement of adjacent levels. Figure 7 – MIBG Scan showing diffuse uptake of the radiotracer in the right hemithorax, left base, and upper abdomen, consistent with diffuse tumor involvement. Figure 3- Coronal MIP reconstruction demonstrates the bulky, heterogeneously enhancing upper mediastinal mass occupying the right superior and mid hemithorax, large effusion and collapse of the right lung. Figure 4- Coronal MIP Reconstruction of the abdomen shows scattered focal enhancing hepatic lesions consistent with metastases Figure 8- Medium power view (20X) of immunohistochemistry for Neuroblastoma antigen (NB), a highly specific marker for neuroblastoma. Note the intense cytoplasmic staining.
Transcript of Michael O’Neill, MD, Samantha Block, BS, Gaurav Saigal, MD,...
1. Park, J., Et. Al. Neuroblastoma: Biology, Prognosis, and Treatment. Hematol Oncol Clin North Am. 2010 Feb;24(1):65-86.
2. Papaioannou, G., Mchough, K. Neuroblastoma in childhood: review and radiologicalfindings Cancer Imaging (2005) 5, 116–127
3. Franks, L. Et. Al. Neuroblastoma In Adults and Adolescents: An Indolent Course with Poor Survival. Cancer 1997;79:2028–35.
4. Cotterill, S.J., Et. Al. Clinical prognostic factors in 1277 patients with neuroblastoma: Results of The European Neuroblastoma Study Group Survey 1982 1992. European Journal of Cancer 36 (2000) 901 908
5. Lonergan, G., Et. Al., Neuroblastoma, Ganglioneuroblastoma,and Ganglioneuroma: Radiologic-Pathologic Correlation. Radiographics 2002; 22 (4): 911-934.
6. Rosado-de-Christenson, M.,Et. Al. Mediastinal Germ Cell Tumors: Radiologic and Pathologic Correlation Radiographics 1992;12:1013-1030.
22 Year Old Female with Mediastinal Neuroblastoma Michael O’Neill, MD, Samantha Block, BS, Gaurav Saigal, MD, Andre Pinto, M.D.
University of Miami Miller School of Medicine Jackson Memorial Hospital, Miami, FL
Background
• Neuroblastoma remains the third most common childhood malignancy, after leukemia and CNS tumors, representing 8-10% of childhood cancers, causing 15% of all childhood cancer deaths.1,2
• Median age of presentation overall is 23 months, with only 5% of all cases presenting after 10 years of age. However, it can uncommonly present in adolescence, and rarely even well into adulthood, with cases reported even up to 75 years of age.3
• Tumors are of ganglion cell origin and are derived from primordial neural crest cells; tumors are found along the typical distribution of sympathetic ganglia, most commonly in the adrenal medulla (35%), but can also be found in the extra-adrenal paraspinal ganglia (30%–35%), followed by the posterior mediastinum in 20%.
• Interestingly, the disease distribution in younger patients (<1 year) compared to older (>1yr) patients in a previous investigation, found that the mediastinum was an even less common site of presentation in older patients. 1 Other more uncommon sites include the pelvis (2%–3%) and the neck (1%–5%).2
• Prognosis is determined by age, Evans stage, and especially histopathologic as well as cytogenetic characteristics. Older ages of presentation, advanced stages (3-4), and presence of cytogenetic abnormalities such as MYCN amplification (25-35%), DNA ploidy, and loss of chromosome 1 p (30–40%) are associated with a poorer prognosis.
History and Physical Examination
• A 22-year-old woman with a 6 month history of dyspnea; intolerable over the previous 2 months.
• Symptoms: right chest pain and back pain.
• Signs: Hypoxemia, hypotension, and tachycardia, with swelling in the right supraclavicular region, right arm, and right face with signs of venous collaterals on the right chest wall.
• Absent right lung sounds on auscultation
Diagnostic Evaluation • Pertinent laboratory findings: AST level of 91 U/L and an ALP level of 177 U/ ml. LDH was greater than 2150 U/L, homovanillic acid was 7.7 mg/ g, and vanillylmandelic acid was 4.9 mg/ g.
• Portable AP Chest radiograph, Contrast-Enhanced Computerized Tomography (CT) of the Chest, Abdomen, and Pelvis, and Contrast-Enhanced Magnetic Resonance Imaging (MR) of the Thoracic Spine were ordered
Discussion •The imaging findings of Neuroblastoma are often well characterized on CT and MRI. 5 •CT is the most commonly used imaging modality for initial assessment and preliminary diagnosis of Neuroblastomas, often showing stippled calcifications, necrosis, and prominent adenopathy as well as possible metastatic lesions. •On MRI, the tumors are heterogenously enhancing masses, with low T1 and high T2 signals, possibly also demonstrating foci of hemorrhage on T1 as well. •Bone marrow disease appears bright on T2 and dark on T1 weighted imaging. •Our 22 year old female’s differential diagnosis would be led by lymphoma given the age, anatomic location of the lesion, as well as statistical likelihood. •The mass in this case was centered in the posterior mediastinum. •In addition, our patient had no constitutional or “B” symptoms. •There was an elevated urinary HVA and VMA. •Osteosarcoma, Metastases, Ewings Sarcoma, and Germ cell tumors must also be considered and excluded. •Mediastinal germ cell tumors are rare and less likely to be symptomatic. •On Imaging, they are usually cystic lesions that demonstrate a combination of fat, calcification, fluid and soft tissue attenuation values. •The absence of these benign features, along with the presence of elevated urinary catecholamines in the setting of a highly aggressive tumor is suggestive of Adult Neuroblastoma.
Conclusion
References
Diagnostic Imaging
•Neuroblastoma is a rare but often highly aggressive tumor when presenting in an Adult.
•To avoid diagnostic delays, Neuroblastoma should also be remembered for the differential diagnosis of mediastinal masses in an adult as well as a child.
Figure 1- Initial AP Chest Radiograph shows a large right hemithorax opacity with associated leftward deviation of the cardiomediastinal silhouette.
Figure 5- Sagittal T2-weighted MRI image through the right upper thoracic spine demonstrates infiltration of several upper thoracic vertebral foramina and encroachment of the exiting nerves, most notably at the T2-T4 levels. In addition, there is associated abnormal marrow signal suggesting marrow invasion.
Figure 2- CT Chest with IV contrast demonstrates a large, exophytic and Heterogenous enhancing mass with scattered calcifications, which is centered in the posterior mediastinum. There is associated leftward shift of the great vessels and cardiomediastinum. Note the prominence of the ipsilateral posterior extrathoracic muscles, suggesting tumor infiltration.
Figure 6- Axial T2 weighted image shows tumor infiltration of the right T2-T3 neural foramen and encroachment of the exiting nerve. Other Axial images showed similar involvement of adjacent levels.
Figure 7 – MIBG Scan showing diffuse uptake of the radiotracer in the right hemithorax, left base, and upper abdomen, consistent with diffuse tumor involvement.
Figure 3- Coronal MIP reconstruction demonstrates the bulky, heterogeneously enhancing upper mediastinal mass occupying the right superior and mid hemithorax, large effusion and collapse of the right lung.
Figure 4- Coronal MIP Reconstruction of the abdomen shows scattered focal enhancing hepatic lesions consistent with metastases
Figure 8- Medium power view (20X) of immunohistochemistry for Neuroblastoma antigen (NB), a highly specific marker for neuroblastoma. Note the intense cytoplasmic staining.
