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A Family with Von Hippel-Lindau Syndrome: The Findings of Indium-111 Somatostatin Receptor Scintigraphy, Iodine-123 Metaiodobenzylguanidine Scintigraphy and Single Photon Emission Computerized Tomography

Von Hippel-Lindau syndrome (VHLS) is an autosomal dominant hereditary familial disorder characterized by development of malignant and benign neoplasms. Differential diagnosis of the adrenal and pancreatic masses are difficult in patients with VHLS. Iodine-123 metaiodobenzylguanidine (I-123 MIBG) and indium-111 somatostatin receptor scintigraphies (In-111 SRS) have important roles in the differential diagnosis of adrenal and pancreatic masses in those patients. In this case report, we present the findings of I-123 MIBG single-photon emission computerized tomography (SPECT/CT) and In-111 SRS SPECT/CT in three members of a family with VHLS. In case 1, a residual neuroendocrine tumor (NET) was detected in the head of pancreas on In-111 SRS SPECT/CT images. In case 2 and 3, I-123 MIBG SPECT/CT confirmed the adrenal masses as pheochromocytoma, and the extra-adrenal mass as NET, before surgery. We thought that In-111 SRS and I-123 MIBG scan might be helpful in the routine work up of VHLS patients for diagnostic and therapeutic purposes. Hybrid SPECT/CT system may improve diagnostic accuracy of planar images since it assesses morphologic and functional information together.


Introduction
Von Hippel-Lindau syndrome (VHLS) is an autosomal dominant hereditary familial neoplastic disorder characterized by retinal, cerebellar and spinal hemangioblastomas, liver, and kidney hemangiomas, clear cell renal carcinoma (RCC), pheochromocytoma, pancreatic tumors, pancreatic, renal, and epididymal cysts (1). The gene responsible for the disease is identified with direct gene mutation analysis (2). Clinic examination and imaging modalities are important in the diagnosis of VHLS (3). Nuclear medicine imaging modalities such as iodine-123 metaiodobenzylguanidine (I-123 MIBG) and Indium-111 somatostatin receptor scintigraphy (In-111 SRS) have important roles in the differential diagnosis of adrenal and pancreatic masses in those patients. Here in, we present the findings of I-123 MIBG single photon emission computerized tomography (SPECT/CT) and In-111 SRS SPECT/CT in three members of a family with VHLS.

Case 1
A 39-year-old man with VHLS who had had adrenalectomy for pheochromocytoma 27 years ago, partial pancreatectomy for neuroendocrine tumor (NET) 6 years ago, and partial nephrectomy for RCC 5 years ago was referred to our department for evaluation of a residual mass in his pancreas. The contrast-enhanced abdominal CT revealed a 30-mm mass at the head of the pancreas. In-111 SRS imaging was performed after injection of 185 MBq In-111 octreotide (Octreoscan, Mallinckrodt, Netherlands). Whole body and static images were obtained 4 and 24 hours later. Focal radiotracer accumulation was seen in the right upper quadrant of the abdomen on planar images. Therefore, abdominal SPECT/CT was performed following planar imaging to the abdominal region (Millennium Hawkeye 4, GE Medical Systems, Wilwaukee, WI). SPECT/ CT confined this pathologic uptake to the pancreatic region ( Figure 1). The patient had revision surgery. Histolopathologic examination revealed a recurrent NET.

Case 2
The cousin of case 1, a 20-year-old woman was diagnosed with VHLS on gene mutation analysis. Hypertension and increased metanephrine levels were detected on psychical examination and laboratory tests. Magnetic resonance imaging (MRI) detected a hemangioma in the liver and masses in bilateral adrenal glands (right side: 28x22 mm, and left side: 20x18 mm). I-123 MIBG scintigraphy was performed before surgery to confirm adrenal masses as  I-123  MIBG (I-123, Mallinckrodt, Netherlands). Planar images showed an abnormal radiotracer uptake bilaterally superior to kidneys. SPECT/CT fusion images demonstrated that those radiotracer accumulations were localized to the adrenal glands ( Figure 2). Bilateral adrenalectomy was performed. Histopathologic examination revealed that the removed adrenal tumors were pheochromocytoma. Four years later, abdominal MRI revealed a mass between the liver and right adrenal gland (33x30x36 mm) and another one in the pancreatic tail (13x15x17 mm). I-123 MIBG SPECT/CT was performed with suspicion of local recurrence. Fusion images showed an abnormal accumulation in the right adrenal gland. There was no radiotracer accumulation in the pancreas, a Ga-68 DOTATOC positron emission tomography (PET/CT) was performed. Pathologic radiotracer uptake was demonstrated in the pancreas. The patient is planned to undergo surgery.

Case 3
Case 3 was a 38-year-old woman who is the cousin of both case 1 and 2. She had no complaints, and her parameters were in normal limits. She was diagnosed with VHLS on gene mutation analysis. An abdominal MRI was performed for screening purposes. MRI revealed masses with intensive contrast enhancement between the liver and right kidney (40x36x36 mm), and inferior to the left adrenal gland (14x15x15 mm). Those findings were suspicious for bilateral pheochromocytoma. I-123 MIBG was performed to characterize those tumors. Whole body and static images were obtained 4 and 24 hours after injection of 370 MBq I-123 MIBG. Whole body-scan and static planar images showed an abnormal radiotracer uptake infero-medial to the liver, and supero-medial to the left kidney. Following planar imaging, an abdominal SPECT/CT was performed. SPECT/CT images showed radiotracer uptake in the right adrenal gland region. The activity on the left side was localized to the extraadrenal region (Figure 3). Right adrenalectomy and resection of the extra-adrenal lesion were performed following MIBG scan. Histopathologic examination confirmed the diagnosis of pheochromocytoma in the right adrenal gland, and paraganglioma in the extra-adrenal tumor. Three members of this family with VHLS are still being followed up in the endocrinology department.

Literature Review and Discussion
VHLS is an autosomal dominant disorder characterized by presence of malignant and benign neoplasms. Clinical