Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Marie Elaine Stevens, IV Gillian Lieberman, MD October 20, 2008 Imaging and Management of Pancreatic Endocrine Tumors in MEN 1 Marie Elaine Stevens Georgetown University School of Medicine, Year IV Dr. Gillian Lieberman, MD Marie Elaine Stevens, IV Gillian Lieberman, MD Agenda • • • • Discuss Our Patient’s Presentation Review MEN Syndromes Present Our Patient’s Imaging Studies Discuss Pancreatic Endocrine Tumors – Pathophysiology – Imaging – Treatment • Present Conclusions 2 Marie Elaine Stevens, IV Gillian Lieberman, MD Our Patient: History • Mr. T is a 32 yo male with a strong family history of MEN 1 presenting with severe abdominal pain • He has a known history of Zollinger-Ellison syndrome from presumed gastrinoma (although prior imaging studies were negative) • His disease is currently fairly well controlled with Omeprazole 40mg BID 3 Marie Elaine Stevens, IV Gillian Lieberman, MD Our Patient: Laboratory Findings • In addition to elevated serum gastrin, laboratory work-up revealed hyperprolactinemia and hypercalcemia – These findings are suggestive of a prolactinoma and parathyroid adenoma, compatible with Mr. T’s presumed diagnosis of MEN 1 • At this time, Mr. T elected to undergo a full imaging work-up 4 Marie Elaine Stevens, IV Gillian Lieberman, MD Agenda • • • • Discuss Our Patient’s Presentation Review MEN Syndromes Present Our Patient’s Imaging Studies Discuss Pancreatic Endocrine Tumors – Pathophysiology – Imaging – Treatment • Present Conclusions 5 Marie Elaine Stevens, IV Gillian Lieberman, MD Multiple Endocrine Neoplasia: Epidemiology • MEN syndromes are part of a group of autosomal dominant endocrine disorders first recognized in the early part of the 20th century • The population prevalence of MEN 1 is about 1 in 30,000 • MEN 2 affects about 1 in 40,000 individuals – MEN 2-A accounts for most cases of MEN 2 – MEN 2-B represents about 5% of all cases of MEN 2 6 Marie Elaine Stevens, IV Gillian Lieberman, MD Spectrum of Disease: MEN 1 (Wermer Syndrome) • Parathyroid Adenoma - 95% • Pituitary Adenoma - 50% – Prolactinoma 25% – Nonfunctioning 10% – Growth Hormone 5%, ACTH 2%, Thyrotropin 5% • Pancreatic Endocrine Tumors - 80% – – – – Gastrinoma 40% Insulinoma 10% Nonfunctioning 20% Glucagonoma 2%, VIPoma 2%, Somatostatinoma 2% • Other Features – Forgut Carcinoid 15%, Adrenal Neoplasms 30% – Facial Angiofibroma 85%, Collagenoma 70%, Lipoma 30%, Leiomyoma 5%, Meningioma 5% 7 Marie Elaine Stevens, IV Gillian Lieberman, MD Spectrum of Disease: MEN 2 MEN 2-A (Sipple Syndrome) • Medullary Thyroid Carcinoma - 100% • Pheochromocytoma 50% • Parathyroid Adenoma 10-35% MEN 2-B • Medullary Thyroid Carcinoma - 100% • Pheochromocytoma 50% • Marfanoid Habitus - >95% • Intestinal Ganglioneuromatosis and Mucosal Neuromas >98% 8 Marie Elaine Stevens, IV Gillian Lieberman, MD Multiple Endocrine Neoplasia: Pathophysiology • Patients with MEN 1 possess a germline mutation in the MENIN gene – The MENIN gene is located on chromosome 11 and produces a tumor suppressor protein called menin • The gene responsible for MEN 2 is protooncogene RET – RET is expressed in neural crest-derived cells and encodes for RET protein (the tyrosine kinase subunit of a cell surface receptor) – Activation of RET leads to hyperplasia of target cells in vivo 9 Marie Elaine Stevens, IV Gillian Lieberman, MD MEN Syndromes: Comparison MEN 1 MEN 2-A MEN 2-B Pituitary Adenoma >50% Pancreatic Endocrine >80% Tumor Parathyroid Adenoma 95% 10-35% Pheochromocytoma 50% 50% Medullary Thyroid 100% 100% Carcinoma Intestinal Neuromas >98% Marfanoid Habitus >95% 10 Marie Elaine Stevens, IV Gillian Lieberman, MD Agenda • • • • Discuss Our Patient’s Presentation Review MEN Syndromes Present Our Patient’s Imaging Studies Discuss Pancreatic Endocrine Tumors – Pathophysiology – Imaging – Treatment • Present Conclusions 11 Marie Elaine Stevens, IV Gillian Lieberman, MD Our Patient: Imaging WorkUp for Hyperprolactinemia 12 Marie Elaine Stevens, IV Gillian Lieberman, MD MRI of the Brain Axial post-gadolinium T1WI Sagittal post-gadolinium T1WI * * PACS, BIDMC • PACS, BIDMC Findings: a 1.4 x 1.4 x 1.5 cm enhancing lesion likely representing a macroadenoma invading the left sphenoid sinus 13 Marie Elaine Stevens, IV Gillian Lieberman, MD CT of the Sella and Sinuses Axial C- CT PACS, BIDMC • Findings: expansion, scalloping and erosion of the floor of the sella, with scalloping of the anterior and posterior aspects of the sella 14 Marie Elaine Stevens, IV Gillian Lieberman, MD Mr. T: Follow-up of Hyperprolactinemia Our Patient Underwent Transsphenoidal Resection of the Prolactinoma 15 Marie Elaine Stevens, IV Gillian Lieberman, MD Our Patient: Imaging Work-Up for Hypercalcemia 16 Marie Elaine Stevens, IV Gillian Lieberman, MD Nuclear Medicine Scan Technetium-99m Sestamibi Scan * * * Technetium-99m Sestamibi Scan * Parotid Glands * * Submandibular Glands Thyroid PACS, BIDMC PACS, BIDMC • Findings: no focal tracer uptake to indicate a parathyroid adenoma 17 Marie Elaine Stevens, IV Gillian Lieberman, MD Thyroid Ultrasound Thyroid Ultrasound Technetium-99m Sestamibi Scan Submandibular Glands * PACS, BIDMC • • * * Thyroid Probable Parathyroid Adenoma PACS, BIDMC Findings: a probable enlarged left parathyroid gland, which could represent adenoma Can this be visualized retrospectively seen on the patient’s Sestamibi scan? 18 Marie Elaine Stevens, IV Gillian Lieberman, MD Mr. T: Follow-up of Hypercalcemia Our Patient Underwent Resection of a Left Inferior Parathyroid Adenoma 19 Marie Elaine Stevens, IV Gillian Lieberman, MD Our Patient: Follow-Up Imaging for Known History of Zollinger-Ellison Syndrome 20 Marie Elaine Stevens, IV Gillian Lieberman, MD CT of the Abdomen Axial C+ CT PACS, BIDMC • Axial C+ CT PACS, BIDMC Findings: new nodular hyperenhancing area within the pancreatic head, relative to the remainder of the pancreas and several smaller foci of relative hyperattenuation seen within the pancreatic tail, suggestive of multiple gastrinomas 21 Marie Elaine Stevens, IV Gillian Lieberman, MD Follow-Up of Zollinger-Ellison Syndrome: Newly Discovered Multiple Pancreatic Gastrinomas Mr. T Elected to Undergo Further Imaging Work-Up for Staging and Surgical Planning to Resect the Gastrinomas 22 Marie Elaine Stevens, IV Gillian Lieberman, MD Agenda • • • • Discuss Our Patient’s Presentation Review MEN Syndromes Present Our Patient’s Imaging Studies Discuss Pancreatic Endocrine Tumors – Pathophysiology – Imaging – Treatment • Present Conclusions 23 Marie Elaine Stevens, IV Gillian Lieberman, MD Pancreatic Endocrine Tumors: Pathophysiology • Pancreatic endocrine tumors occur in 80% of patients with MEN 1 – Tumors are often multicentric and may undergo malignant transformation • Patients with MEN 1 have a decreased life expectancy, with a 50% probability of death by age 50 years – Half of the deaths result from a malignant process or a sequela of the endocrine disease – ZES is the major cause of morbidity and mortality in patients with MEN 1 24 Marie Elaine Stevens, IV Gillian Lieberman, MD Types of Pancreatic Endocrine Tumors: Nonfunctioning Tumors • Nonfunctioning pancreatic endocrine tumors are the most common pancreatic tumors, occurring in 80100% of cases • The name is a misnomer because most of them produce pancreatic polypeptide 25 Marie Elaine Stevens, IV Gillian Lieberman, MD Types of Pancreatic Endocrine Tumors: Gastrinomas • Gastrinomas are the most common cause of symptomatic disease and are found in approximately 60% of patients with MEN 1 • Compared to the sporadic form in Zollinger-Ellison syndrome, gastrinomas in MEN 1 are more often duodenal, small, and multicentric 26 Marie Elaine Stevens, IV Gillian Lieberman, MD Types of Pancreatic Endocrine Tumors: Insulinomas and Glucagonomas • Insulinomas account for approximately 2035% of pancreatic endocrine tumors – Similar to gastrinomas, they can be multicentric (10-20%), where 25% metastasize either to regional lymph nodes or to the liver • Glucagonomas occur in 3% of patients with MEN 1 and are silent or present with hyperglycemia – Typical skin lesions (necrolytic migratory erythema) are rare in patients with MEN 1 27 Marie Elaine Stevens, IV Gillian Lieberman, MD Agenda • • • • Discuss Our Patient’s Presentation Review MEN Syndromes Present Our Patient’s Imaging Studies Discuss Pancreatic Endocrine Tumors – Pathophysiology – Imaging – Treatment • Present Conclusions 28 Marie Elaine Stevens, IV Gillian Lieberman, MD Pancreatic Endocrine Tumors: Imaging Modalities • • • • • Contrast- Enhanced CT MRI Somatostatin Receptor Scintigraphy Endoscopic Ultrasound Intraoperative Ultrasound 29 Marie Elaine Stevens, IV Gillian Lieberman, MD Our Patient: CT of the Pancreas Axial C+ CT of the Abdomen • High-resolution contrastenhanced CT is the initial imaging technique used to localize and stage most pancreatic endocrine tumors • However, it fails to help identify as many as 70% of lesions • • Nodular hyperenhancing lesion in the pancreatic head Several smaller hyperattenuating lesions in the pancreatic tail PACS, BIDMC Axial C+ CT of the Abdomen PACS, BIDMC 30 Marie Elaine Stevens, IV Gillian Lieberman, MD Our Patient: Reconstructed Images C+ CTA Reconstruction of the Abdominal Aorta C+ CTA Reconstruction of the Portal Vein Celiac Trunk * * PACS, BIDMC SMA Portosplenic Confluence * PACS, BIDMC • High-resolution contrast-enhanced CT can also be used to generate reconstructed images used in operative planning 31 Marie Elaine Stevens, IV Gillian Lieberman, MD Pancreatic Endocrine Tumors: Imaging Modalities • • • • • Contrast- Enhanced CT MRI Somatostatin Receptor Scintigraphy Endoscopic Ultrasound Intraoperative Ultrasound 32 Marie Elaine Stevens, IV Gillian Lieberman, MD Companion Patient #1: MRI of the Pancreas Axial Fat-Saturated T1WI Owen NJ. British J Rad 2001; 74: 968-973. • • Axial Fat-Saturated T2WI Owen NJ. British J Rad 2001; 74: 968-973. Pancreatic endocrine tumors have high relaxation times result in greater enhancement on T1- and T2-weighted images of pancreatic endocrine tumors, compared to adenocarcinomas The images above show lesions of the pancreas with solid and cystic components 33 Marie Elaine Stevens, IV Gillian Lieberman, MD Pancreatic Endocrine Tumors: Imaging Modalities • • • • • Contrast- Enhanced CT MRI Somatostatin Receptor Scintigraphy Endoscopic Ultrasound Intraoperative Ultrasound 34 Marie Elaine Stevens, IV Gillian Lieberman, MD Companion Patient #2: Somatostatin Receptor Scintigraphy (SRS) • • • • Pancreatic endocrine tumors express large numbers of SST receptors on their cell surfaces (except SSTomas) Radiolabeled octreotide used in SRS preferentially binds to SST receptors SRS is helpful in diagnosing small extrapancreatic metastases The octreotide scan to the right shows a large pancreatic-tail neoplasm, several tracerenhancing hepatic metastases, and excretion of tracer in the bladder Octreotide Scan * http://www.emedicine.com/med/images/276262-276943-4313.JPG 35 Marie Elaine Stevens, IV Gillian Lieberman, MD Companion Patient #3: Somatostatin Receptor Scintigraphy Octreotide Scan Endoscopic Ultrasound * * Norton JA. Annals of Surgery 2004; 240: 757-773. Norton JA. Annals of Surgery 2004; 240: 757-773. • • Another example of SRS localization of a gastrinoma in the area of the duodenum/pancreatic head The same patient undersent endoscopic ultrasound (EUS), which revealed a lesion situated between the pancreatic duct and CBD 36 Marie Elaine Stevens, IV Gillian Lieberman, MD Pancreatic Endocrine Tumors: Imaging Modalities • • • • • Contrast- Enhanced CT MRI Somatostatin Receptor Scintigraphy Endoscopic Ultrasound Intraoperative Ultrasound 37 Marie Elaine Stevens, IV Gillian Lieberman, MD Companion Patient #4: Endoscopic Ultrasound Endoscopic Ultrasound Endoscopic Ultrasound * * Gauger PG. British Journal of Surgery 2003; 90: 748-754. • • • Gauger PG. British Journal of Surgery 2003; 90: 748-754. EUS can help localize pancreatic endocrine tumors assess lymph node metastases It cannot, however, be used to evaluate hepatic and distant spread The images above show of pancreatic endocrine tumors in the pancreatic tail and uncinate process 38 Marie Elaine Stevens, IV Gillian Lieberman, MD Distribution of Tumors by Endoscopic Ultrasound • In this study, 43 pancreatic endocrine tumors were demonstrated on initial EUS in 15 asymptomatic patients with MEN 1 • 60% of tumors were found in tail of pancreas – 16% body – 24% head/uncinate process Distribution of Pancreatic Endocrine Tumors by EUS Gauger PG. British Journal of Surgery 2003; 90: 748-754. 39 Marie Elaine Stevens, IV Gillian Lieberman, MD Pancreatic Endocrine Tumors: Imaging Modalities • • • • • Contrast- Enhanced CT MRI Somatostatin Receptor Scintigraphy Endoscopic Ultrasound Intraoperative Ultrasound 40 Marie Elaine Stevens, IV Gillian Lieberman, MD Our Patient: Intraoperative Ultrasound Intraoperative Ultrasound Intraoperative Ultrasound * * PACS, BIDMC • • PACS, BIDMC The advantage of intraoperative ultrasound is that it provides realtime images and information about the location and number of pancreatic endocrine tumors (sensitivity 90%) The images above show multiple solid hypoechoic nodules in the tail of our patient’s pancreas 41 Marie Elaine Stevens, IV Gillian Lieberman, MD Agenda • • • • Discuss Our Patient’s Presentation Review MEN Syndromes Present Our Patient’s Imaging Studies Discuss Pancreatic Endocrine Tumors – Pathophysiology – Imaging – Treatment • Present Conclusions 42 Marie Elaine Stevens, IV Gillian Lieberman, MD Pancreatic Endocrine Tumors: Surgical Treatment Options • Role of surgery in MEN 1 is controversial – Most tumors are multicentric and cure is achieved only occasionally • Surgery may be indicated in patients with no distant metastases – Removal of tumors > 2 cm in reduces the frequency of liver metastasis – Local tumor excision is preferred, with larger tumors of the pancreatic body or tail removed by distal pancreatectomy 43 Marie Elaine Stevens, IV Gillian Lieberman, MD Goals of Surgical Therapy • The goals of surgical therapy for pancreatic endocrine neoplasms include: – Controlling the symptoms of hormone excess – Safely resecting the maximal amount of tumor mass possible – Preserving the maximal amount of pancreatic parenchyma possible 44 Marie Elaine Stevens, IV Gillian Lieberman, MD Surgical Treatment Options: Total Pancreatectomy Total Pancreatectomy http://www.aafp.org/afp/20071201/afp20071201p1679-f3.jpg • Long-term benefit of total pancreatectomy is unproven in pancreatic endocrine tumors and the associated surgical morbidity seems unacceptable 45 Marie Elaine Stevens, IV Gillian Lieberman, MD Surgical Treatment Options: Classic Whipple Procedure Axial C+ CT Classic Whipple Procedure In our patient, the lesion in the head of the pancreas was excised with a classic Whipple Procedure Unfortunately, multiple lesions in the pancreatic tail were left behind PACS, BIDMC Intraoperative Ultrasound Axial C+ CT * http://www.aafp.org/afp/20071201/afp20071201p1679-f3.jpg PACS, BIDMC PACS, BIDMC • Lesions in the head or uncinate process of the pancreas can be resected with pancreaticoduodenectomy (Whipple Procedure) 46 Marie Elaine Stevens, IV Gillian Lieberman, MD Surgical Treatment Options: Distal Pancreatectomy Endoscopic Ultrasound Distal Pancreatectomy * Gauger PG. British Journal of Surgery 2003; 90: 748-754. Gauger PG. British Journal of Surgery 2003; 90: 748-754. • • The EUS above of companion patient #4 shows a tumor in the tail of the pancreas This patient underwent distal pancreatectomy and splenectomy, enucleation of a pancreatic head endocrine tumor, and duodenotomy with excision of duodenal gastrinoma 47 Marie Elaine Stevens, IV Gillian Lieberman, MD Agenda • • • • Discuss Our Patient’s Presentation Review MEN Syndromes Present Our Patient’s Imaging Studies Discuss Pancreatic Endocrine Tumors – Pathophysiology – Imaging – Treatment • Present Conclusions 48 Marie Elaine Stevens, IV Gillian Lieberman, MD Pancreatic Endocrine Tumors: Conclusions • The major cause of morbidity and mortality in patients with MEN 1 is the sequela of endocrine disease (eg Zollinger-Ellison Syndrome) • Contrast-enhanced CT, MRI, somatostatin receptor scintigraphy, EUS and intraoperative ultrasound all have important, complimentary roles in the diagnosis and treatment of pancreatic endocrine tumors • The role of surgery in MEN 1 is controversial and efforts should be made to preserve the maximal amount of pancreatic parenchyma possible while resecting the tumor mass 49 Marie Elaine Stevens, IV Gillian Lieberman, MD References • • • • • • • • • • Kroneberg: Williams Textbook of Endocrinology, 11th Edition. Chapter 40 - Multiple Endocrine Neoplasia. Robert F. Gagel, Stephen J. Marx. Saunders, 2008. Squire’s Fundamentals of Radiology: 6th Edition. Robert A. Novelline, MD. Harvard University Press, 2004. eMedicine: Multiple Endocrine Neoplasia. Robert J Ferry Jr, MD. Article Last Updated: Jun 12, 2008 eMedicine: Wermer Syndrome (MEN Type 1). Irina Lendel, MD. Article Last Updated: Jan 8, 2007 eMedicine: Neoplasms of the Endocrine Pancreas. Eric J Hanly, MD. Article Last Updated: Jun 29, 2006. Hellman P, Hennings J, Akerstrom G, Skogseid B. Endoscopic ultrasonography for evaluation of pancreatic tumours in multiple endocrine neoplasia type 1. British Journal of Surgery 2005; 92: 1508-1512. Owen NJ, Sohaib SAA, Peppercorn PD, Monson JP, Grossman AB, Besser GM, Reznek RH. MRI of pancreatic neuroendocrine tumours: Pictoral Review. The British Journal of Radiology 2001; 74: 968-973. Doherty GM. Multiple Endocrine Neoplasia Type 1. Journal of Surgical Oncology 2005; 89: 143-150. Norton JA, Jensen RT. Resolved and Unresolved Controversies in the Surgical Management of Patients With Zollinger-Ellison Syndrome. Annals of Surgery 2004; 240: 757-773. Gauger PG, Scheiman JM, Wamsteker EG, Richards MI, Doherty GM, Thompson NW. Role of endoscopic ultrasonography in screening and treatment of pancreatic endocrine tumours in asymptomatic patients with multiple endocrine neoplasia type 1. British Journal of Surgery 2003; 90: 748-754. 50 Marie Elaine Stevens, IV Gillian Lieberman, MD Acknowledgements • • • • • • Dr. Robert Kane Dr. Katie Krajewski Dr. Andrew Hines-Peralta Dr. Gillian Lieberman Maria Levantakis Larry Barbaras 51