Cystic Pancreatic Endocrine Tumors Research Articles

Pancreatic Cystic Tumors: A Single-Center Observational Study.

Background and Objectives: The aim of the study was to analyze the prevalence and characteristics of pancreatic cystic tumors (PCTs). Material and Methods: A retrospective analysis of the medical records of 124 patients, 102 (69%) women and 46 (31%) men, who had undergone surgery for pancreatic cystic tumors in 2014-2018. Among 148 pancreatic cysts, 24 (16%) were non-neoplasmatic and 124 (84%) were neoplasmatic. The neoplasmatic cysts (n = 124) were included in our analysis. There were five main types of PCTs: IPMN (intraductal papillary mucinous neoplasm) (n = 45), MCN (mucinous cystic neoplasm) (n = 30), SCN (serous cystic neoplasm) (n = 28), SPN (solid pseudopapillary neoplasm) (n = 8), and CPEN (cystic pancreatic endocrine neoplasm) (n = 8), as well as mixed-type tumors (n = 5). Results: A statistically significant dependency between PCT type and age was proven (p= 0.0001): IPMNs were observed in the older group of patients with an average age of 66.12 (40-79) years while SPNs were noted in the youngest group of patients with an average age of 36.22 (22-55) years. A statistically significant association between PCT type and gender (p = 0.0001) was found: IPMNs occurred among 24 (53.33%) men and 21 (46.6%) women. In the MCN and SPN groups, all patients were female (100%). Among the SCN group, the majority were women (27 (96.43%)), and there was only 1 (3.57%) man. A statistically significant dependency between PCT type and size was proven (p = 0.0007). The mean size of IPMNs was the smallest 2.95 (0.6-10 cm) and the mean size of MCNs was the largest 6.78 (1.5-19 cm). A statistically significant dependency between PCT type and tumor location was proven (p = 0.000238). The most frequent location of IPMN was the pancreatic head: 27 (60%). MCN was most frequently located in the pancreatic tail (18 (60%)). Most (10/28) SCNs were found in the pancreatic tail (10 (35.71%)). CPENs were most frequently located in the pancreatic tail (three (37.5%)) and pancreatic body and tail (three (37.5%)). SPNs were located commonly in the pancreatic head (five (62.5%)). The type of surgery depended on the tumor location. The most frequent surgery for IPMNs was pancreatoduodenectomy (44.4%), while for MCNs and SCNs, it was distal pancreatectomy (81%). The postoperative morbidity and mortality were 34.68% and 1.61%, respectively. Postoperative pancreatic fistula (POPF) was the most frequent (29%) complication. Conclusions: IPMN was the most frequent resected PCT in our material. A statistically significant association between the type of cyst and location within the pancreas, size, local lymph node involvement, and patient's age and sex was proved. POPF was the most frequent postoperative complication. In patients with PCTs, due to substantial postoperative morbidity, adequate patient selection, considering both the surgical risk as well as the long-term risk of malignant transformation, is very important during qualification for surgery.

Pancreatic cystic tumors: an update

Abstract Pancreatic cystic tumors (PCTs) comprise a heterogeneous group of entities, accounting for 2% to 10% of pancreatic lesions. The most common types are intraductal papillary mucinous neoplasms (IPMNs), mucinous cystic neoplasm (MCN), and serous cystic neoplasm (SCN), which account for approximately 90% of PCTs. This review discusses updates in pathologic features, malignant transformation, biologic behavior, and molecular evolution of PCTs. IPMN includes main duct and branch duct types. These can also be classified into 4 histologic subtypes based on cell lineages of differentiation, and may be associated with different tumorigenic pathways and clinicopathologic characteristics. The gastric type is the most common and is rarely associated with carcinomas, whereas the pancreatobiliary type is significantly more associated with invasive carcinoma. MCN is a mucinous cystic lesion with the presence of ovarian-type pericystic stroma. Prognosis of the resected non-invasive MCN is excellent, but the long-term survival of MCNs with invasive carcinoma may be poor. SCN includes microcystic adenoma, macrocystic adenoma, and solid variant serous adenoma. Serous cystadenocarcinoma is defined by the presence of distant metastases, which is rare in literature. Intraductal tubulopapillary neoplasm is characterized by uniformly high-grade dysplasia and ductal differentiation without overt production of mucin, with high risk for developing invasion. Acinar cell cystadenoma is a rare benign lesion with acinar differentiation. In addition, some pancreatic neuroendocrine tumors may assume a cystic configuration, sometimes referred to as cystic pancreatic endocrine neoplasm tumor, with a lower pathologic stage. Solid pseudopapillary tumor is composed of poorly cohesive monomorphic epithelial cells forming solid and pseudopapillary structures, with excellent prognosis.

Cystic pancreatic neuroendocrine tumors (cPNETs): a systematic review and meta-analysis of case series.

Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387) were sporadic tumors and 10.3% (n = 40) corresponded to multiple endocrine neoplasia endocrine type 1. Were diagnosed incidentally 44.6% (n = 135). Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338), and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb), and 12.2% were advanced (III-IV). Disease-free survival at 5 years in stages (I-IIIa) and (IIIb-IV) was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001) in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5%) and multifocal (28.1%) tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors.

Cystic Tumours of the Pancreas: A Challenging Pathology, Diagnosis and Management

Background: Cystic tumours of the pancreas are relatively uncommon tumours but there is an increasing awareness of their importance. Modern advances in imaging had resulted in a more prompt diagnosis of these tumours. The understanding of the pathology, clinical features, diagnosis and management of these tumours is continuously evolving. Data Sources: Systematic literature review. A PubMed database research was performed. Relevant articles published in English were identified and scrutinized. Duplications of information and persistently unsolved uncertainties were excluded. Results: Cystic tumours of the pancreas should be differentiated from pancreatic pseudocysts. Cystic tumours could be classified into: cystic serous neoplasms (SCN), mucinous cystic neoplasms (MCN), intraductal papillary neoplasms (IPMN), solid pseudopapillary neoplasms (SPPN) and the rarer tumours cystic pancreatic endocrine neoplasms (PEN). Except for SCN, all these tumours should be regarded, at least, as potentially malignant but they may be frankly malignant. The age of the patient and site of the lesion may be helpful in the diagnosis. In particular, MCN is always encountered in females in their middle age and often in the body and tail of the pancreas. Many of these tumours are diagnosed incidentally. Pancreatitis and hyperamylasaemia should be interpretted with caution as IPMN may present as pancreatitis. CT is the primary diagnostic tool although MRI, EUS, PET, abdominal ultrasound and ERCP have all been utilised. Biochemical markers are of limited value in the diagnosis. Conclusions: Management decision depends primarily on the understanding of pathology and on how confident the preoperative diagnosis is. SCN may be observed. Partial pancreatectomy is the usual operation performed for most other tumours according to the location of the lesion which means that distal pancreatectomy is usually the operation performed for MCN. Total pancreatectomy for IPMN, enucleation and central pancreatectomy have all been described in the literature. Laparoscopy is more suitable for benign or low grade malignant tumours in the context of distal pancreatectomy. Spleen should be preserved unless splenectomy is indicated and splenic vessels should be preserved wherever possible when preserving the spleen.

Pancreatic cystic neoplasms: Review of current knowledge, diagnostic challenges, and management options.

Pancreatic cystic lesions are being detected with increasing frequency, largely due to advances in cross-sectional imaging. The most common neoplasms include serous cystadenomas, mucinous cystic neoplasms, intraductal papillary mucinous neoplasms, solid pseudopapillary neoplasms, and cystic pancreatic endocrine neoplasms. Computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS) are currently used as imaging modalities. EUS-guided fine needle aspiration has proved to be a useful diagnostic tool, and enables an assessment of tumor markers, cytology, chemistries, and DNA analysis. Here, we review the current literature on pancreatic cystic neoplasms, including classification, diagnosis, treatment, and recommendations for surveillance. Data for this manuscript was acquired via searching the literature from inception to December 2014 on PubMed and Ovid MEDLINE.

Pancreatic Cystic Neoplasms: Management and Unanswered Questions

Approximately 10% of persons 70 years old or older are now diagnosed with pancreatic cysts, but it is not clear which ones require additional analysis, interventions, or follow-up. Primary care doctors rely on gastroenterologists for direction because no one wants to miss a diagnosis of pancreatic cancer, but meanwhile there is pressure to limit use of diagnostic tests and limit costs. We review the different cystic neoplasms of the pancreas and diagnostic strategies based on clinical features and imaging data. We discuss surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines. Intraductal papillary mucinous neoplasm (particularly the branch duct variant) is the lesion most frequently identified incidentally. We report what is known about its pathology, its risk of developing into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk. We also review surgical treatment and strategies for surveillance of pancreatic cysts.

The outcome of resected cystic pancreatic endocrine neoplasms: A case-matched analysis

Cystic pancreatic endocrine neoplasms (CPENs) are uncommon tumors with uncertain disease biology and ill-defined diagnostic features. A prospectively maintained pancreatic cyst registry was queried, and 31 cases of CPEN that were resected between 1995 and 2010 were identified. Patient and lesion characteristics were detailed and compared with resected non-PEN cystic lesions. Recurrence and survival outcome were compared with 31 noncystic PENs matched for functional status, differentiation, size, World Health Organization classification, grade, and presence of metastases. During the study period, CPENs accounted for 7% of resected pancreatic cysts (31/469) and 12% of resected PENs (31/255). CPENs were primarily sporadic (94%), solitary (87%), nonfunctioning (100%), and incidentally discovered (68%). The median diameter was 2.1 cm (range, 0.9-6.2 cm), and preoperative imaging identified septations in 29%, a solid component in 26%, and cyst wall enhancement or a characteristic hypervascular rim in 45% of cases. Preoperative imaging and/or cytology suggested the diagnosis of CPEN in 61%. Compared with resected nonendocrine cystic lesions, CPEN were less frequently symptomatic, less likely to contain septations, and smaller. Compared with matched noncystic PENs, CPENs had comparable demographic, radiologic, and pathologic features and statistically similar long-term outcome (5-year disease-free survival: CPEN: 100% vs PEN: 86%, P = .947). In this study, CPENs were primarily asymptomatic small lesions that could be characterized in the majority of cases by cyst wall enhancement on preoperative imaging and/or cytologic assessment. No significant difference in recurrence or survival outcome was identified between cystic and noncystic PENs.

Pancreatic Cystic Endocrine Tumors: A Different Morphological Entity Associated with a Less Aggressive Behavior

Background: Cystic pancreatic endocrine tumors (CPETs) are rare lesions and their biological features have been scarcely investigated. Aim: To compare clinical and pathological features of resected non-functioning sporadic CPETs (NF-CPETs) with solid pancreatic endocrine tumors (SPETs) in a single-institution experience. Methods: All patients with a pathologically confirmed diagnosis of sporadic non-functioning pancreatic endocrine tumors who underwent curative resection between 1990 and 2008 were included. A comparison of demographic, clinical and pathological characteristics between CPETs and SPETs was made. Univariate and multivariable analyses were performed to identify preoperative predictors of carcinoma (non-functioning pancreatic endocrine carcinoma). Results: Twenty-one (11.5%) patients with a histological diagnosis of NF-CPET were identified. The median age was 60 years (IQR 46.5–73.5 years) and a diagnosis of carcinoma (non-functioning pancreatic endocrine carcinoma) was made in 3 (14.3%) cases. In the comparison with NF-SPETs, no differences were found in terms of gender (p = 0.75), age (p = 0.81), presenting symptoms (p = 0.43), localization of the tumors (p = 0.46) and type of resection (p = 0.31). The incidence of non-functioning pancreatic endocrine carcinoma was significantly lower in the NF-CPET versus the NF-SPET group (14.3 vs. 40.4%, p = 0.04). By univariate analysis, preoperative predictors of non-functioning pancreatic endocrine carcinoma included the presence of symptoms (OR 3.96, 95% CI 2.06–7.63) and an increase in the absolute value of radiological diameter (OR 1.05, 95% CI 1.03–1.07). A cystic morphology of the lesion turned out to be a negative predictor of carcinoma (OR 0.25, 95% CI 0.70–0.87). These results were confirmed by multivariable analysis. Conclusions: NF-CPETs have a measurable propensity to be benign. In those patients affected by small and asymptomatic NF-CPET a more conservative surgical approach or a follow-up policy could be considered.

Multiple endocrine neoplasia type 1‐associated cystic pancreatic endocrine neoplasia and multifocal cholesterol granulomas

A novel combination of tumors was found in a 68 year-old female with Multiple Endocrine Neoplasia type-1 (MEN 1) that included a cystic pancreatic endocrine neoplasm (CPEN), a pituitary adenoma, and multifocal cholesterol granulomas (MCGs) in the breast, pleura, and the extremities. The pancreatic tumor displayed a single central locule surrounded by a thin rim of neoplastic parenchyma. The tumor showed heterogeneity in the architecture that included glandular, trabecular and solid patterns. The tumor cells of the pancreas were immunohistochemically positive for both endocrine and pancreatic acinar markers including chromogranin A, synaptophysin, glucagon, lipase, and reg protein. Electron microscopy revealed that there were numerous smaller dense-cored neurosecretory granules, larger zymogen-like granules and microvilli on the apical side of the tumor cells. The pancreatic tumor was diagnosed as CPEN with acinar cell features. Analysis of the DNA extracted from the tissues revealed that there is a MEN1 germline mutation in exon 10 codon 527, and somatic mutation in exon 2 codon 32 in the pancreatic tumor, and one base pair deletion in exon 2 codon 79 in the pituitary adenoma. Here, we report the case and discuss possible pathogenesis of CPEN and MCGs in a patient with MEN 1.

Cystic pancreatic endocrine tumors

Cystic pancreatic endocrine tumors (PETs) are rare neoplasms with a preoperative diagnostic challenge. The aim of this study was to evaluate the preoperative diagnostic strategy for these tumors and to assess the clinical and pathologic characteristics. Six cases of cystic PET were retrospectively enrolled. Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) was performed in 4 cases. All cytomorphologic data from conventional smears, ThinPrep preparations, and cell block preparations were reported in detail. There were 3 male and 3 female patients with a mean age of 52.3 years. Tumor size ranged from 10 mm to 60 mm (mean, 29.8 mm). EUS-FNAB contributed to an accurate diagnosis in all cases. Cytologically, loosely cohesive aggregates and single cells were predominant. Cells were small and typically plasmacytoid, with occasional cytoplasmic vacuolization. Nuclei were round or oval, uniform, with finely and evenly distributed chromatin. Immunocytochemistry confirmed the endocrine differentiation. Histologic findings were typical for endocrine proliferation. All tumors were well differentiated. Cystic PET is an unusual finding that presents diagnostic challenges for both endoscopists and cytologists. EUS-FNAB with the Thinprep preparation technique and cell block material were found to be helpful in improving diagnostic accuracy. Immunocytochemical staining with endocrine markers confirmed the diagnosis.

Cystic Pancreatic Endocrine Neoplasms: A Distinct Tumor Type?

Cystic pancreatic endocrine neoplasms (CPENs) are considered rare, and their behavior is thought to be similar to that of solid pancreatic endocrine neoplasms (PENs). This study aims to describe the characteristics of CPENs in a large patient cohort. We performed a retrospective review of 170 patients who underwent resections for PENs at Massachusetts General Hospital from 1977 to 2006. Twenty-nine patients (51% men, mean age 53) with CPENs were compared with 141 patients with solid PENs. Differences in clinical presentation, pathologic and radiographic features, and survival were described. CPENs comprised 17% of all PENs (29 of 170) and 5.4% of all resected cystic pancreatic neoplasms(29 of 535). Ten (34%) were purely cystic and 19 (66%) were partially cystic. Compared with solid PENs, CPENs were larger (49 mm versus 23.5 mm, p < 0.05), more likely symptomatic (73% versus 45%, p < 0.05), and more likely nonfunctional (80% versus 50%, p < 0.05). They expressed synaptophysin (100%), chromogranin (82%), and cytokeratin (CK)-19 (24%). Multiple endocrine neoplasia type 1 (MEN-1) was 3.5 times more common in CPENs than in solid tumors (21% versus 6%, p < 0.05). No significant difference was found in location, propensity for metastasis, invasion, or 5-year survival (87% versus 77%, p=0.38). This series, the largest report of CPENs in the literature, shows that CPENs are more common than previously thought, so they should be included in the differential of the cystic lesions of the pancreas. CPENs are larger and more likely to be symptomatic then solid PENs. They are also more likely to be associated with MEN-1 and to be nonfunctional, suggesting they may be a distinct tumor type.

Clinicopathologic analysis of 92 cases of pancreatic cystic neoplasm

To study the clinicopathologic and immunohistochemical features of cystic neoplasms of the pancreas. Ninety-two cases of cystic neoplasm of pancreas were retrieved from the Department archival file during the period from 1999 to 2005. Histologic features were studied and the tumors were typed according to WHO classification. Immunohistochemistry was also carried out using paraffin-embedded tissues. The age of patients ranged from 16 to 80 years. The patients included 33 males and 59 females. The tumors varied from 2 cm to 21 cm in diameter. They consisted of intraductal papillary mucinous neoplasm (36/92), serous cystic neoplasm (18/92), solid pseudopapillary tumor (18/92), mucinous cystic neoplasm (14/92), cystic pancreatic ductal adenocarcinoma (4/92) and cystic pancreatic endocrine neoplasm (2/92). Immunohistochemical study revealed variable staining patterns, with frequent overlaps between different tumor types. In general, serous cystic neoplasm expressed MUC1, while mucinous cystic neoplasm was positive for MUC-5AC, intraductal papillary mucinous neoplasm for MUC-2 and cystic pancreatic ductal adenocarcinoma for MUC-1. On the other hand, solid pseudopapillary tumor expressed alpha-antitrypsin, alpha-antichymotrypsin, vimentin and progesterone receptor. Accurate diagnosis of pancreatic cystic neoplasms requires correlation of clinical findings, radiologic examination, histologic features and immunostaining results. Pathologic distinction is important because of different prognostic significance. Two-thirds of pancreatic cystic neoplasms are premalignant or malignant and warrant surgical resection, whereas the remaining one-third (including pseudocyst and serous cystadenoma) are benign and can be treated conservatively.

Cystic pancreatic endocrine tumor

Most cystic pancreatic neoplasms are currently evaluated by an endoscopic ultrasound-guided fine-needle aspiration biopsy (FNAB). In the authors' experience, FNAB of cystic pancreatic endocrine tumors (PETs) frequently causes diagnostic difficulties, partly because of unexpected overlapping features with cystic ductal adenocarcinomas. The authors identified 5 histologically confirmed cystic PETs that were evaluated by FNAB and compared their cytomorphologic features to cystic ductal adenocarcinomas (n = 5) and solid PETs (n = 39) of the pancreas. Cytologically, 2 of the aspirates of cystic PETs were devoid of tumor cells whereas the other 3 were variably cellular and composed of cohesive aggregates of monomorphic cellular elements with variably coarse chromatin. Tumor necrosis and nuclear membrane irregularities were not identified in cystic PETs. Alternatively, in contrast to PETs, cystic ductal adenocarcinomas were characterized by nuclear pleomorphism, nuclear membrane irregularities, and tumor necrosis. Given the clinical implications, awareness of cystic PETs and their deceptive cytologic features would assist in distinguishing these lesions from cystic ductal adenocarcinomas.

Clinico-pathological features of cystic pancreatic endocrine neoplasms and a comparison with their solid counterparts

Aim Pancreatic endocrine neoplasms (PENs) may occasionally manifest as cystic lesions of the pancreas. The aim of this study is to report our experience with cystic PENs and to compare their clinico-pathological features with their solid counterparts. Materials and methods From 1990 to 2004, 38 patients with PENs were reviewed. Six of these tumours appeared on radiological imaging as a cystic lesion of the pancreas. Results Of the 38 patients with a PEN, 21 of the patients were female and with a median age of 54.5 (range, 33–83) years. Sixteen patients had functional endocrine tumours of which insulinoma was the most common. The six patients with cystic PEN had a median age of 55.5 (range, 41–70) years and half were female. Cystic PENs were significantly larger [48 (range, 25–170) mm vs 19 (range, 3–120) mm, P=0.013] and were less likely to be benign (0 vs 50%, P=0.017) compared to their solid counterparts. There was no difference between cystic and solid PENs in terms of age, sex, presence of symptoms, proportion of functioning tumours and location of tumours within the pancreas. Conclusion Cystic PENs share many clinico-pathological features with solid PENs. These differ only in the cystic appearance and tend to be of a larger size. Hence, these findings suggest that cystic and solid PENs are unlikely to be distinct pathological entities but are likely to be morphological variants of the same entity.

Cystic endocrine tumors of the pancreas: clinical, radiologic, and histopathologic features in 13 cases.

Cystic endocrine tumors of the pancreas are rare and raise difficult clinical problems. Our aims were to reevaluate the diagnostic and therapeutic strategy and to assess their histopathologic characteristics. Thirteen cystic endocrine tumors diagnosed in 10 patients were included. Clinical, radiologic, and pathologic data were reviewed. There were 6 male and 4 female patients (median age, 46 yrs). Six patients had evidence of multiple endocrine neoplasia type 1 (MEN1) disease. Four had a functional endocrine syndrome. Ten tumors were visible on imaging studies. The most suggestive radiologic features were the existence of a peripheral hypervascular rim (10 cases) and images of cyst into cyst (two cases). On gross and histologic examinations, two distinct types were present. Macrocystic tumors (six cases) were unilocular and limited by a thick wall containing nests of tumor cells. Microcystic tumors (seven cases) were characterized by the presence of multiple cystic spaces directly lined by tumor cells. Surgical resection was performed in all cases. Three patients had lymph node metastases at the time of diagnosis. One patient is dead with metastatic dissemination. The others are alive without recurrence or metastasis. The diagnosis of endocrine tumor must be considered for any pancreatic cyst discovered in a patient with a history of MEN1 syndrome or with clinical features suggestive of this syndrome. Cystic pancreatic endocrine tumors must be treated by surgical resection because of their possible malignant evolution.