Imaging Analysis

Metastatic neuroendocrine tumor to the interatrial septum: Differentiating lipomatous hypertrophy from metastatic disease

This case focuses on a 69-year-old man found to have an enlarged liver by his primary care physician in May 2016.

Imaging workup showed a solitary lesion in the liver, for which the patient underwent partial hepatectomy at an outside institution.

Pathology was consistent with high-grade neuroendocrine tumor. The patient did not receive adjuvant chemotherapy or radiation therapy at that time.

Munir Ghesani, MD, FACNM
Munir Ghesani

The patient did well until late summer 2016, when he developed a syncopal episode while on vacation.

Subsequent head CT revealed two lesions in the brain — one in the left occipital lobe and another in the cerebellum — for which he underwent surgical resection.

Pathology was consistent with neuroendocrine tumor metastases, with the tumor cells positive for synaptophysin and chromogranin, and negative for CK7, CK20 and Hep-par 1. The Ki-67 proliferation index was focally up to 40% to 60%. The patient then received partial brain fractionated radiotherapy, completed in January.

The patient then presented for follow-up brain MRI and re-staging PET/CT examination.

Imaging findings

Brain MRI in August showed the patient to be status after left suboccipital craniotomy for resection of left occipital and cerebellar metastatic lesions.

There were expected postoperative changes in the left cerebellum and left occipital lobe, with gliosis as well as heterogeneous and slightly nodular enhancement along the left tentorium leaflet, which was less conspicuous than on prior MRI.

No new enhancing lesions were seen to suggest metastatic disease in the brain.

The 18F-FDG PET/CT examination demonstrated the patient to be status after prior left partial hepatectomy, with no evidence of new liver masses or abnormal FDG uptake in the liver.

Figure 1. PET/CT fusion images in axial, sagittal and coronal planes show a hypermetabolic mass in the interatrial septum (maximum standard uptake value, 5.7), highly concerning for intracardiac metastatic disease.
Figure 1. PET/CT fusion images in axial, sagittal and coronal planes show a hypermetabolic mass in the interatrial septum (maximum standard uptake value, 5.7), highly concerning for intracardiac metastatic disease.

Source: Munir Ghesani, MD. Reprinted with permission.

Figure 2. Follow-up dedicated cardiac MRI shows a 2.3 cm by 2 cm mass in the interatrial septum (four-chamber view), which is intermediate signal intensity on T1-weighted sequences.
Figure 2. Follow-up dedicated cardiac MRI shows a 2.3 cm by 2 cm mass in the interatrial septum (four-chamber view), which is intermediate signal intensity on T1-weighted sequences.
Figure 3. The mass measures 2.1 cm in craniocaudal dimension (short-axis view) and is hyperintense on T2-weighted sequences.
Figure 3. The mass measures 2.1 cm in craniocaudal dimension (short-axis view) and is hyperintense on T2-weighted sequences.
Figure 4. There is prompt enhancement of the interatrial septum mass on perfusion imaging. The findings are consistent with intracardiac metastasis to the interatrial septum.
Figure 4. There is prompt enhancement of the interatrial septum mass on perfusion imaging. The findings are consistent with intracardiac metastasis to the interatrial septum.

However, there was a new FDG-avid soft tissue nodule posterior to the upper pole of the right kidney, as well as an enlarging non-FDG-avid soft tissue nodule posterior to the dome of the liver, possibly a retroperitoneal lymph node. The findings were concerning for metastatic disease.

There also was a focal area of increased FDG uptake in the cardiac tissue at the interatrial septum (maximum standard uptake value, 5.7), with associated subtle soft tissue nodularity at this location on CT, highly concerning for cardiac metastasis. In addition, there were two newly enlarged, FDG-avid paratracheal and subcarinal lymph nodes, also highly concerning for metastatic disease.

Subsequent cardiac MRI continued to show the interatrial septum mass, which measured 2.3 cm by 2 cm (four-chamber view) by 2.1 cm in craniocaudal dimension (short-axis view). The lesion demonstrated intermediate signal intensity on T1 and high signal intensity on T2-weighted sequences, as well as prompt enhancement on perfusion imaging.

The findings were consistent with intracardiac metastasis to the interatrial septum. No additional intracardiac lesions were identified.

Transbronchial biopsy of the FDG-avid level 4R and level 7 lymph nodes was consistent with metastatic neuroendocrine carcinoma. The tumor cells stained immune-positive for chromogranin and CAM5.2, supporting the diagnosis.

In both samples, fragments of tumor consisting of cells with round nuclei growing in nests and cords were intermixed with lymphoid tissue, with a Ki67 proliferation index of up to 40%. Of note, the tumor was histologically similar to the prior brain specimen.

Discussion

Cardiac metastases are a relatively infrequent finding, even in patients with known malignancy. Initial estimates of incidence of intracardiac metastatic disease were about 1% in vivo, and approaching 2% to 18% on autopsy specimens.

However, with advances in cardiac imaging — including dedicated cardiac MRI and hybrid imaging modalities, such as PET/MRI — there has been increasing detection of cardiac lesions in the oncologic setting, with a prevalence of 9% among patients with widespread metastatic disease.

Additionally, when interpreting a suspicious intracardiac finding, it is important to consider that the incidence of metastatic disease to the heart is far more common that primary cardiac malignancy, with a ratio of approximately 30:1.

The most common primary malignancies to harbor intracardiac metastases are lung cancer, breast cancer and hematologic malignancies, such as non-Hodgkin lymphoma. This is primarily due to their overall frequency, as well as the relative proximity to the heart, especially in the setting of lung neoplasm.

However, if we consider the incidence of intracardiac metastatic disease for a specific primary tumor, the highest rate is in metastatic melanoma — a setting in which 28% to 56% of patients have cardiac metastases — followed by malignant pleural mesothelioma and mediastinal malignancies, such as thymoma.

Other malignancies that tend to spread to the heart include renal cell, pancreatic, ovarian and gastric carcinomas. It is important to keep in mind that the risk for intracardiac metastatic disease is proportional to the patient’s overall metastatic burden.

As intracardiac masses are rarely amendable to biopsy, knowledge of characteristic imaging features is crucial for differentiating malignancy from other lesions that occur in the heart in order to provide a clinically meaningful differential diagnosis.

One potentially confusing finding is lipomatous hypertrophy of the interatrial septum (LHIS), characterized by benign fatty infiltration of the interatrial septum. This occurs in approximately 1% to 8% of the population.

LHIS — typically detected in older obese patients as an incidental finding on imaging — has been associated with diffuse mediastinal lipomatosis, chronic steroid use and increased epicardial fat.

Histologically, LHIS is characterized by fatty infiltration between the myocardial fibers of the atrial septum. This can create a mass-like soft tissue bulge, typically anterior to — and sparing — the fossa ovalis.

Important CT imaging characteristics include a nonenhancing, well-marginated fat-containing lesion in the interatrial septum that has a dumbbell shape, with relative sparing of the fossa ovalis. This is best seen on short-axis views.

Dedicated cardiac MRI will classically demonstrate interatrial septal thickening with homogeneous high signal intensity similar to that of subcutaneous fat tissue, which is hyperintense on both T1- and T2-weighted sequences and does not enhance following the administration of gadolinium.

The exclusively fatty nature of LHIS can be confirmed on fat-suppressed imaging. Misclassification of LHIS is a common pitfall on F18-FDG PET/CT imaging, as these lesions typically are associated with a moderate degree of FDG uptake, likely caused by metabolic activity of brown adipose tissue.

Therefore, it is important to utilize additional imaging modalities and hybrid scanning techniques when analyzing a hypermetabolic mass in the interatrial septum to avoid unnecessary confusion and further work-up of this overall benign entity.

In contrast to LHIS, intracardiac metastatic disease typically presents as multiple masses or soft tissue nodules with a heterogeneous enhancement pattern on contrast-enhanced CT imaging.

Further, diffuse infiltration of the myocardium with associated changes in the contour of the cardiac chambers or interatrial septum is another typical imaging appearance, whereas epicardial and pericardial metastatic deposits typically are associated with a complex malignant pericardial effusion.

Electrocardiographic-gated, dedicated cardiac MRI is the imaging modality of choice to assess for metastatic disease burden in the heart due to its superior soft tissue contrast and high temporal resolution of 30 milliseconds to 50 milliseconds.

As expected, cardiac metastatic lesions typically are hypointense to intermediate signal intensity on T1-weighted sequences and hyperintense on T2-weighted sequences, with significant enhancement on post gadolinium T1-weighted images.

A characteristic finding of melanoma metastases is their intrinsically high T1 signal due to the paramagnetic properties of melanin in these lesions. Hybrid imaging techniques — including F18-FDG PET/CT and PET/MRI — help confirm the diagnosis of intracardiac malignancy, demonstrating increased FDG uptake. They also allow for assessment of the widespread nature of the causative primary tumor.

In our case, the patient was referred for restaging 18F-FDG PET/CT for his known metastatic neuroendocrine tumor. In addition to the cardiac metastatic lesion, additional metastatic deposits were detected in the mediastinal lymph node stations, as well as in the retroperitoneum. Therefore, the patient was started on palliative systemic chemotherapy with carboplatin and etoposide.

References:

Fan CM, et al. AJR Am J Roentgenol. 2005;184:339-342.

Hoey ET, et al. Clin Radiol. 2009;doi:10.1016/j.crad.2009.09.002.

Lichtenberger JP 3rd, et al. AJR AM J Roentgenol. 2016;Aug. 4:1-9.

Nadra I, et al. Heart. 2004;doi:10.1136/hrt.2004.045930.

O’Donnell DH, et al. AJR Am J Roentgenol. 2009;doi:10.2214/AJR.08.1895.

Rahbar K, et al. J Nucl Med. 2012;doi:10.2967/jnumed.111.095364.

For more information:

Munir Ghesani, MD, FACNM, is assistant professor of radiology and director of PET/CT fellowship at NYU Langone Medical Center in New York. He also is a HemOnc Today Editorial Board Member. He can be reached at munir.ghesani@nyumc.org.

Ana M. Franceschi, MD, is a neuroradiology fellow at NYU Langone Medical Center.

Disclosures: Ghesani and Franceschi report no relevant financial disclosures.

This case focuses on a 69-year-old man found to have an enlarged liver by his primary care physician in May 2016.

Imaging workup showed a solitary lesion in the liver, for which the patient underwent partial hepatectomy at an outside institution.

Pathology was consistent with high-grade neuroendocrine tumor. The patient did not receive adjuvant chemotherapy or radiation therapy at that time.

Munir Ghesani, MD, FACNM
Munir Ghesani

The patient did well until late summer 2016, when he developed a syncopal episode while on vacation.

Subsequent head CT revealed two lesions in the brain — one in the left occipital lobe and another in the cerebellum — for which he underwent surgical resection.

Pathology was consistent with neuroendocrine tumor metastases, with the tumor cells positive for synaptophysin and chromogranin, and negative for CK7, CK20 and Hep-par 1. The Ki-67 proliferation index was focally up to 40% to 60%. The patient then received partial brain fractionated radiotherapy, completed in January.

The patient then presented for follow-up brain MRI and re-staging PET/CT examination.

Imaging findings

Brain MRI in August showed the patient to be status after left suboccipital craniotomy for resection of left occipital and cerebellar metastatic lesions.

There were expected postoperative changes in the left cerebellum and left occipital lobe, with gliosis as well as heterogeneous and slightly nodular enhancement along the left tentorium leaflet, which was less conspicuous than on prior MRI.

No new enhancing lesions were seen to suggest metastatic disease in the brain.

The 18F-FDG PET/CT examination demonstrated the patient to be status after prior left partial hepatectomy, with no evidence of new liver masses or abnormal FDG uptake in the liver.

Figure 1. PET/CT fusion images in axial, sagittal and coronal planes show a hypermetabolic mass in the interatrial septum (maximum standard uptake value, 5.7), highly concerning for intracardiac metastatic disease.
Figure 1. PET/CT fusion images in axial, sagittal and coronal planes show a hypermetabolic mass in the interatrial septum (maximum standard uptake value, 5.7), highly concerning for intracardiac metastatic disease.

Source: Munir Ghesani, MD. Reprinted with permission.

Figure 2. Follow-up dedicated cardiac MRI shows a 2.3 cm by 2 cm mass in the interatrial septum (four-chamber view), which is intermediate signal intensity on T1-weighted sequences.
Figure 2. Follow-up dedicated cardiac MRI shows a 2.3 cm by 2 cm mass in the interatrial septum (four-chamber view), which is intermediate signal intensity on T1-weighted sequences.
Figure 3. The mass measures 2.1 cm in craniocaudal dimension (short-axis view) and is hyperintense on T2-weighted sequences.
Figure 3. The mass measures 2.1 cm in craniocaudal dimension (short-axis view) and is hyperintense on T2-weighted sequences.
Figure 4. There is prompt enhancement of the interatrial septum mass on perfusion imaging. The findings are consistent with intracardiac metastasis to the interatrial septum.
Figure 4. There is prompt enhancement of the interatrial septum mass on perfusion imaging. The findings are consistent with intracardiac metastasis to the interatrial septum.

However, there was a new FDG-avid soft tissue nodule posterior to the upper pole of the right kidney, as well as an enlarging non-FDG-avid soft tissue nodule posterior to the dome of the liver, possibly a retroperitoneal lymph node. The findings were concerning for metastatic disease.

PAGE BREAK

There also was a focal area of increased FDG uptake in the cardiac tissue at the interatrial septum (maximum standard uptake value, 5.7), with associated subtle soft tissue nodularity at this location on CT, highly concerning for cardiac metastasis. In addition, there were two newly enlarged, FDG-avid paratracheal and subcarinal lymph nodes, also highly concerning for metastatic disease.

Subsequent cardiac MRI continued to show the interatrial septum mass, which measured 2.3 cm by 2 cm (four-chamber view) by 2.1 cm in craniocaudal dimension (short-axis view). The lesion demonstrated intermediate signal intensity on T1 and high signal intensity on T2-weighted sequences, as well as prompt enhancement on perfusion imaging.

The findings were consistent with intracardiac metastasis to the interatrial septum. No additional intracardiac lesions were identified.

Transbronchial biopsy of the FDG-avid level 4R and level 7 lymph nodes was consistent with metastatic neuroendocrine carcinoma. The tumor cells stained immune-positive for chromogranin and CAM5.2, supporting the diagnosis.

In both samples, fragments of tumor consisting of cells with round nuclei growing in nests and cords were intermixed with lymphoid tissue, with a Ki67 proliferation index of up to 40%. Of note, the tumor was histologically similar to the prior brain specimen.

Discussion

Cardiac metastases are a relatively infrequent finding, even in patients with known malignancy. Initial estimates of incidence of intracardiac metastatic disease were about 1% in vivo, and approaching 2% to 18% on autopsy specimens.

However, with advances in cardiac imaging — including dedicated cardiac MRI and hybrid imaging modalities, such as PET/MRI — there has been increasing detection of cardiac lesions in the oncologic setting, with a prevalence of 9% among patients with widespread metastatic disease.

Additionally, when interpreting a suspicious intracardiac finding, it is important to consider that the incidence of metastatic disease to the heart is far more common that primary cardiac malignancy, with a ratio of approximately 30:1.

The most common primary malignancies to harbor intracardiac metastases are lung cancer, breast cancer and hematologic malignancies, such as non-Hodgkin lymphoma. This is primarily due to their overall frequency, as well as the relative proximity to the heart, especially in the setting of lung neoplasm.

However, if we consider the incidence of intracardiac metastatic disease for a specific primary tumor, the highest rate is in metastatic melanoma — a setting in which 28% to 56% of patients have cardiac metastases — followed by malignant pleural mesothelioma and mediastinal malignancies, such as thymoma.

Other malignancies that tend to spread to the heart include renal cell, pancreatic, ovarian and gastric carcinomas. It is important to keep in mind that the risk for intracardiac metastatic disease is proportional to the patient’s overall metastatic burden.

PAGE BREAK

As intracardiac masses are rarely amendable to biopsy, knowledge of characteristic imaging features is crucial for differentiating malignancy from other lesions that occur in the heart in order to provide a clinically meaningful differential diagnosis.

One potentially confusing finding is lipomatous hypertrophy of the interatrial septum (LHIS), characterized by benign fatty infiltration of the interatrial septum. This occurs in approximately 1% to 8% of the population.

LHIS — typically detected in older obese patients as an incidental finding on imaging — has been associated with diffuse mediastinal lipomatosis, chronic steroid use and increased epicardial fat.

Histologically, LHIS is characterized by fatty infiltration between the myocardial fibers of the atrial septum. This can create a mass-like soft tissue bulge, typically anterior to — and sparing — the fossa ovalis.

Important CT imaging characteristics include a nonenhancing, well-marginated fat-containing lesion in the interatrial septum that has a dumbbell shape, with relative sparing of the fossa ovalis. This is best seen on short-axis views.

Dedicated cardiac MRI will classically demonstrate interatrial septal thickening with homogeneous high signal intensity similar to that of subcutaneous fat tissue, which is hyperintense on both T1- and T2-weighted sequences and does not enhance following the administration of gadolinium.

The exclusively fatty nature of LHIS can be confirmed on fat-suppressed imaging. Misclassification of LHIS is a common pitfall on F18-FDG PET/CT imaging, as these lesions typically are associated with a moderate degree of FDG uptake, likely caused by metabolic activity of brown adipose tissue.

Therefore, it is important to utilize additional imaging modalities and hybrid scanning techniques when analyzing a hypermetabolic mass in the interatrial septum to avoid unnecessary confusion and further work-up of this overall benign entity.

In contrast to LHIS, intracardiac metastatic disease typically presents as multiple masses or soft tissue nodules with a heterogeneous enhancement pattern on contrast-enhanced CT imaging.

Further, diffuse infiltration of the myocardium with associated changes in the contour of the cardiac chambers or interatrial septum is another typical imaging appearance, whereas epicardial and pericardial metastatic deposits typically are associated with a complex malignant pericardial effusion.

Electrocardiographic-gated, dedicated cardiac MRI is the imaging modality of choice to assess for metastatic disease burden in the heart due to its superior soft tissue contrast and high temporal resolution of 30 milliseconds to 50 milliseconds.

As expected, cardiac metastatic lesions typically are hypointense to intermediate signal intensity on T1-weighted sequences and hyperintense on T2-weighted sequences, with significant enhancement on post gadolinium T1-weighted images.

A characteristic finding of melanoma metastases is their intrinsically high T1 signal due to the paramagnetic properties of melanin in these lesions. Hybrid imaging techniques — including F18-FDG PET/CT and PET/MRI — help confirm the diagnosis of intracardiac malignancy, demonstrating increased FDG uptake. They also allow for assessment of the widespread nature of the causative primary tumor.

PAGE BREAK

In our case, the patient was referred for restaging 18F-FDG PET/CT for his known metastatic neuroendocrine tumor. In addition to the cardiac metastatic lesion, additional metastatic deposits were detected in the mediastinal lymph node stations, as well as in the retroperitoneum. Therefore, the patient was started on palliative systemic chemotherapy with carboplatin and etoposide.

References:

Fan CM, et al. AJR Am J Roentgenol. 2005;184:339-342.

Hoey ET, et al. Clin Radiol. 2009;doi:10.1016/j.crad.2009.09.002.

Lichtenberger JP 3rd, et al. AJR AM J Roentgenol. 2016;Aug. 4:1-9.

Nadra I, et al. Heart. 2004;doi:10.1136/hrt.2004.045930.

O’Donnell DH, et al. AJR Am J Roentgenol. 2009;doi:10.2214/AJR.08.1895.

Rahbar K, et al. J Nucl Med. 2012;doi:10.2967/jnumed.111.095364.

For more information:

Munir Ghesani, MD, FACNM, is assistant professor of radiology and director of PET/CT fellowship at NYU Langone Medical Center in New York. He also is a HemOnc Today Editorial Board Member. He can be reached at munir.ghesani@nyumc.org.

Ana M. Franceschi, MD, is a neuroradiology fellow at NYU Langone Medical Center.

Disclosures: Ghesani and Franceschi report no relevant financial disclosures.