Person:

Thayer, Sarah P.

Objective: To determine whether intraductal papillary mucinous neoplasms of the pancreas (IPMNs) have a different genetic background compared with ductal adenocarcinoma (PDAC). Summary Background Data: The biologic and clinical behavior of IPMNs and IPMN-associated adenocarcinomas is different from PDAC in having a less aggressive tumor growth and significantly improved survival. Up to date, the molecular mechanisms underlying the clinical behavior of IPMNs are incompletely understood. Methods: 128 cystic pancreatic lesions were prospectively identified during the course of 2 years. From the corresponding surgical specimens, 57 IPMNs were separated and subdivided by histologic criteria into those with low-grade dysplasia, moderate dysplasia, high-grade dysplasia, and invasive cancer. Twenty specimens were suitable for DNA isolation and subsequent performance of array CGH. Results: While none of the IPMNs with low-grade dysplasia displayed detectable chromosomal aberrations, IPMNs with moderate and high-grade dysplasia showed frequent copy number alterations. Commonly lost regions were located on chromosome 5q, 6q, 10q, 11q, 13q, 18q, and 22q. The incidence of loss of chromosome 5q, 6q, and 11q was significantly higher in IPMNs with high-grade dysplasia or invasion compared with PDAC. Ten of 13 IPMNs with moderate dysplasia or malignancy had loss of part or all of chromosome 6q, with a minimal deleted region between linear positions 78.0 and 130.0. Conclusions: This study is the first to use array CGH to characterize IPMNs. Recurrent cytogenetic alterations were identified and were different than those described in PDAC. Array CGH may help distinguish between these 2 entities and give insight into the differences in their biology and prognosis.

Objective: To assess changing patterns in the detection and outcomes of pancreatic neuroendocrine neoplasms (PNENs). Design: Retrospective review from May 21, 1977, through September 16, 2005. Setting: Massachusetts General Hospital, a tertiary care center. Patients: We evaluated 168 patients (51% male; mean age, 56 years) who underwent surgery for histologically confirmed PNENs. Main Outcome Measures: Surgical outcomes, survival, and changes in presentation of PNENs in 2 time groups: 1977-1999 (77 patients) and 2000-2005 (91 patients). Results: Ninety-eight patients (58.3%) had nonfunctioning PNENs, 86 of which were incidental. Insulinomas were the most common type of functional neoplasm (33.3%), followed by gastrinomas and glucagonomas; 12 patients (7.1%) had multiple endocrine neoplasia type 1. Of the neoplasms, 107 (63.7%) were located in the pancreatic body or tail. A pancreaticoduodenectomy was performed in 37 patients (22.0%), distal pancreatectomy was done in 88 (52.4%), and the rest had either middle segment pancreatectomy or enucleation. There were no operative deaths. We classified 76.8% of neoplasms as benign; of those classified as malignant, 25.6% had liver metastases. Of the patients, 10.1% received adjuvant therapy. Complete follow up was available in 90.5% of patients (mean, 63.3 months). Five- and 10-year actuarial survival rates were 77% and 62%, respectively. Incidentally discovered nonfunctioning neoplasms were significantly more frequent in the last 5 years (60.4% vs 40.3%; = .007), with a trend toward smaller neoplasms (mean, 4.2 cm vs 5.6 cm; = .19) and lesser likelihood of malignancy (21.8% vs 40.0%; = .08). Conclusions: We report a large single-center experience with PNENs. Increasing numbers of PNENs are being resected, largely owing to the incidental detection of nonfunctioning neoplasms. This may lead to the treatment of smaller and less malignant neoplasms. Pancreatic neuroendocrine neoplasms (PNENs) are rare entities with a wide spectrum of clinical presentation. The secretion of hormonal products into the blood results in functional neoplasms that cause clinical symptoms, and thus they are classified according to their hormonal product. In contrast, nonfunctional neoplasms do not secrete a hormonal product with a known clinical effect, and usually disease does not become apparent until they are large enough to cause impingement of adjacent structures with symptoms of jaundice, abdominal pain, or weight loss. Pancreatic neuroendocrine neoplasms differ both biologically and clinically from pancreatic adenocarcinoma. In comparison to pancreatic adenocarcinoma, in which the 5-year and 10-year actual survival rates in patients who have undergone resection remain very low (15% and 4%, respectively), most PNENs are reported to display an indolent course and are associated with longer survival. The natural history of PNENs is largely unknown. Although they are found in 0.5% to 1.5% of autopsies, they occur with an annual incidence of only about 5 to 10 cases per million persons, which is thought to reflect the asymptomatic nature of most of these neoplasms. Currently, complete surgical resection is thought to be the only curative treatment for PNENs. Our study aims to describe a large single-center experience with the operative management of PNENs, including analysis of clinical presentation, operative course, surgical morbidity, and long-term survival.

Objective: Mucinous cystic neoplasms (MCNs) of the pancreas have often been confused with intraductal papillary mucinous neoplasms. We evaluated the clinicopathologic characteristics, prevalence of cancer, and prognosis of a large series of well-characterized MCNs in 2 tertiary centers. Methods: Analysis of 163 patients with resected MCNs, defined by the presence of ovarian stroma and lack of communication with the main pancreatic duct. Results: MCNs were seen mostly in women (95%) and in the distal pancreas (97%); 25% were incidentally discovered. Symptomatic patients typically had mild abdominal pain, but 9% presented with acute pancreatitis. One hundred eighteen patients (72%) had adenoma, 17 (10.5%) borderline tumors, 9 (5.5%) in situ carcinoma, and 19 (12%) invasive carcinoma. Patients with invasive carcinoma were significantly older than those with noninvasive neoplasms (55 vs. 44 years, P = 0.01). Findings associated with malignancy were presence of nodules (P = 0.0001) and diameter ≥60 mm (P = 0.0001). All neoplasms with cancer were either ≥40 mm in size or had nodules. There was no operative mortality and postoperative morbidity was 49%. Median follow-up was 57 months (range, 4 –233); only patients with invasive carcinoma had recurrence. The 5-year disease-specific survival for noninvasive MCNs was 100%, and for those with invasive cancer, 57%. Conclusions: This series, the largest with MCNs defined by ovarian stroma, shows a prevalence of cancer of only 17.5%. Patients with invasive carcinoma are older, suggesting progression from adenoma to carcinoma. Although resection should be considered for all cases, in low-risk MCNs (≤4 cm/no nodules), nonradical resections are appropriate.