Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature

BackgroundThe current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management.MethodsA systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015.ResultsMCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93–95%). They are usually found incidentally at the age of 40–60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0–34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%.ConclusionsCompared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.     

Accuracy of CT in predicting malignant potential of cystic pancreatic neoplasms

Background. Cystic lesions of the pancreas are being identified more frequently. Deciding which asymptomatic lesions can be safely followed with serial imaging and which require resection due to malignant potential is an increasingly common question. Current clinical practice is to rely on characteristics of the lesions on CT scan, and additional information from endoscopic ultrasound with fine-needle aspiration (EUS-FNA) and cyst fluid analysis or endoscopic retrograde pancreatography (ERCP) to assess malignant potential. Hypothesis. The malignant potential of pancreatic cystic lesions cannot be accurately predicted by CT scan. Methods. CT scans from 48 patients with cystic lesions of the pancreas were stripped of patient identifiers and retrospectively presented to two expert radiologists. The radiologists recorded specific characteristics of the lesions thought to be important in the differential diagnosis and their opinion of the likely diagnosis. Diagnostic accuracy was assessed by comparing the radiologists’ diagnoses to the final pathologic diagnosis after resection. To determine if clinical history, EUS-FNA or ERCP findings improved diagnostic accuracy, medical records were retrospectively reviewed and scored as either supporting or not supporting malignant potential of the lesion. Results. Specific diagnoses based on CT findings alone were correct in an average of 39% of the cases. Even when diagnoses were dichotomized as benign (43%) or potentially malignant (57%, papillary mucinous neoplasms, mucinous cystic neoplasms, cancer), determinations based on CT alone were accurate in an average of 61% of cases. Accuracy rates were 60.4 and 62.5% for the two radiologists, although there was only fair agreement between them (Kappa=0.28, 95% CI=(0.01–0.55), p=0.05). When all clinical information available was considered together as a single dichotomous indicator of malignant potential, the indicator was accurate in 90% of the cases (Kappa=0.73, 95% CI=(0.51–0.95, p<0.0001)). Conclusion. Specific preoperative diagnosis of pancreatic cystic neoplasms by CT alone is substantially inaccurate. Complementary tests such as EUS-FNA with fluid analysis and ERCP should be recommended to improve diagnosis especially if nonoperative treatment is planned.     

Management of mucinous cystic neoplasms of the pancreas

The purpose of this study was to investigate the actual management of mucinous cystic neoplasm (MCN) of the pancreas. A systematic review was performed in December 2009 by consulting PubMed MEDLINE for publications and matching the "pancreatic mucinous cystic neoplasm", "pancreatic mucinous cystic tumour", "pancreatic mucinous cystic mass", "pancreatic cyst", and "pancreatic cystic neoplasm" to identify English language articles describing the diagnosis and treatment of the mucinous cystic neoplasm of the pancreas. In total, 16 322 references ranging from January 1969 to December 2009 were analysed and 77 articles were identified. No articles published before 1996 were selected because MCNs were not previously considered to be a completely autonomous disease. Definition, epidemiology, anatomopathological findings, clinical presentation, preoperative evaluation, treatment and prognosis were reviewed. MCNs are pancreatic mucinproducing cysts with a distinctive ovarian-type stroma localized in the body-tail of the gland and occurring in middle-aged females. The majority of MCNs are slow growing and asymptomatic. The prevalence of invasive carcinoma varies between 6% and 55%. Preoperative diagnosis depends on a combination of clinical features, tumor markers, computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound with cyst fluid analysis, and positron emission tomography-CT. Surgery is indicated for all MCNs.     

Utility of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle aspiration for the diagnosis and management of pancreatic cystic lesions: Differences between the guidelines

Recent advances and frequent use of cross-sectional imaging studies have increased opportunities for incidental diagnoses of pancreatic cystic lesions (PCL). In the management of PCL, distinguishing between mucinous versus non-mucinous and malignant versus benign cysts is important to diagnose pancreatic cancer in its early stage. For this reason, there have been several guidelines to manage PCL. Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) play important roles in the guidelines, although there are some differences in their roles. In this review, we aimed to evaluate the current status of EUS and EUS-FNA in the management of PCL and the status of these procedures in the guidelines.     

Papillary cystic neoplasm (PCN) of the pancreas with lymph node metastasis: Case report of a 77-year-ood woman and a review of 198 reported cases

A case of papillary cystic neoplasm (PCN) of the pancreas in a 77-year-old woman, the oldest patient in the English literature, is reported. Distal pancreatectomy with regional lymphadenectomy was performed for the tumor in the pancreatic tail. Postoperative pathology examination revealed a metastatic lesion in one of the regional lymph nodes. This patient is well doing without recurrence 5 years after surgery. One hundred and ninety-eight cases of PCN, including the present case, have been reported in the English literature. The patients were aged from 2 to 77 years (mean, 25.8); there were 187 females and 11 males. Sixteen patients with metastasis, 22 with local invasion, and 3 with peritoneal dissemination were reported. Complete resection of the tumor was performed in 151 patients, including 6 with metastasis and 11 with local invasion. Only one patient died of recurrent tumor.     

Chronic immunosuppression does not potentiate the malignant progression of mucinous pancreatic cystic lesions

BackgroundPremalignant mucinous pancreatic cystic lesions (mPCLs) are increasingly identified.AimsIn this study, we aim to assess the effect of selected immunosuppressive therapies on the progression of mPCLs, including side-branch intraductal papillary mucinous neoplasms and mucinous cystic neoplasms.MethodsWe performed a retrospective cohort study of patients with mPCLs diagnosed over a 24-year period who received chronic immunosuppression. Controls were matched on age at cyst diagnosis (±11 yrs) and cyst size (±8 mm). Measured outcomes included increase in cyst size, development of “worrisome features” as defined by consensus guidelines, progression to malignancy, and rate of surgical resection.Results39 patients (mean age 60 yrs) with mPCLs were on immunosuppression. Leading indications for immunosuppression were solid organ transplant (n = 14), inflammatory bowel disease (n = 6), and rheumatoid arthritis (n = 5). 33% were on biologics, 77% on antimetabolites and 79% on multiple medications. Mean cyst size increased from 12.6 mm to 17.8 mm over a median of 16.5 months. 6 patients elected for surgical resection, and none ultimately developed malignancy. 26 cases with follow-up were matched to control subjects, with no significant differences among cases and controls in initial cyst size (12.8 mm vs 11.9 mm, P = 0.69), mean size increase (6.9 mm vs 5 mm, P = 0.47), follow-up interval (24.3 months vs 21.5 months, P = 0.44). No significant differences in the rate of worrisome features, malignancy, or surgical resection.ConclusionsPatients with mPCLs exposed to immunosuppressive medications did not have higher rates of malignancy or development worrisome features in the short term. This suggests that patients with mPCLs can be initiated or maintained on these agents without changes to surveillance practices.     

Influence of pre-operative diagnosis and frozen section on operative management of pancreatic cystic lesions

Background. Frozen section analysis of cyst wall has been advocated as standard of care prior to surgical drainage of pancreatic pseudocysts. Recent studies have indicated that frozen section may be unreliable. Our aim was to investigate the role and accuracy of frozen section analysis of the cyst wall in the operative management of pancreatic cystic lesions. Methods. A retrospective review was performed of 44 patients who underwent operation for a cystic lesion of the pancreas. Results. Of the 25 patients with a diagnosis of pseudocyst, 9 patients had frozen section intra-operatively. Eight frozen sections demonstrated pseudocyst, and correlated with final pathology. One frozen section demonstrated a true cyst. Twenty-three patients had a final diagnosis of pseudocyst. Nineteen patients had a diagnosis of cystic neoplasm, and six patients had frozen sections. Three frozen sections were consistent with cystic neoplasm and correlated with final pathology. Three frozen sections demonstrated characteristics of pseudocyst, two correlated with final pathology, and one showed cystic neoplasm on final pathology. Conclusion. Routine use of frozen section may not be necessary; however, frozen section is useful when the intra-operative appearance does not correlate with pre-operative diagnosis.     

Serous cystic neoplasms of the pancreas: a clinicopathologic and immunohistochemical analysis[This article has been retracted]

OBJECTIVE: To clarify whether the various subtypes of serous cystic neoplasms (SCNs) of the pancreas can be distinguished from each other by marker profiles. METHODS: The immunoprofiles of 13 SCNs were defined by using antibodies against cytoskeletal, neuroendocrine, hormone receptor, and mucin markers. In addition, we examined the expression of calrentinin and alpha‐inhibin. RESULTS: SCN included 7 cases of serous microcystic adenomas (SMA), 3 cases of serous oligocystic ill‐defined adenomas (SOIA), 1 case of solid serous adenoma (SSA), 1 case of von Hippel‐Lindau‐associated cystic neoplasm (VHL‐CN), and 1 case of serous cystadenocarcinoma (SCC). These neoplasms are histologically similar, but differ in their localization, gross appearance, gender distribution, and biological behavior. The various types of SCNs showed a very similar immunoprofile, characterized by positivity for cytokeratins (100%) and negativity for vimentin and synaptophysin. Other markers that were commonly expressed in the SCNs were alpha‐inhibin (85%), MUC1 (69%) and MUC6 (77%). CONCLUSION: The results suggest that, despite their biologic differences, the various types of SCNs have the same (or a very similar) cell type and may therefore have a common direction of differentiation. A centroacinar origin is supported by the finding that a number of SCNs share MUC1 and MUC6 expression with pancreatic centroacinar cells. Alpha‐inhibin, and MUC6 may be regarded as new markers for this type of pancreatic tumor.     

Papillary cystic neoplasm of the pancreas

BackgroundPapillary cystic neoplasm of the pancreas is a rare disorder that occurs most commonly in young women. It has a low potential for malignancy, and the prognosis following resection is favourable.Case outlineAn 18-year-old white girl presented with a palpable mass in the right hypochondrium on physical examination associated with epigastric pain, nausea and vomiting, but no fever. Upper gastro-intestinal endoscopy revealed extrinsic compression of the posterior wall of the antrum and duodenal bulb with no mucosal lesion. Computed tomography (CT) scan and then laparotomy revealed a large tumour adjacent to the hepatic hilum and originating from the head of pancreas. Pancreatoduodenectomy was performed, and a diagnosis of papillary cystic neoplasm of the pancreas was made.There was no evidence of recurrence after 6 years of follow-up.DiscussionA radical surgical approach is justified for papillary cystic neoplasm of the pancreas because of its biological behaviour, local aggressiveness and low incidence of metastases.     

Large mucinous cystic neoplasm of the pancreas associated with pregnancy

Mucinous cystic neoplasms （MCNs） of the pancreas occur mostly in females and are potentially sex hormone-sensitive. However, a MCN occurring during pregnancy is quite rare. A 30-year-old woman in the tenth week of pregnancy was referred to us because of a rapid increase in left hypochondrial distending pain. On ultrasound, the patient had a large intra-abdominal cystic lesion. She was thereafter diagnosed with missed abortion and a computed tomography scan showed that the lesion was a cystic tumor 18 cm in diameter originating from the pancreatic tail. The patient subsequently underwent tumor resection with distal pancreatectomy, sparing the spleen. Histopathological analysis of the specimen revealed a pancreatic MCN with moderate dysplasia. Immunohistochemically, the tumor was positive for both estrogen and progesterone receptors. To our knowledge, this is the first reported case of pancreatic MCN with moderate dysplasia in association with pregnancy. Our case strongly indicates that pancreatic MCN is female-hormone dependent.     

Molecular biomarkers have the potential to improve the diagnostic work-up of pancreatic cystic lesions

Pancreatic cysts are increasingly diagnosed due to the widespread use of cross-sectional imaging, and some of these lesions harbor malignant potential. Mucinous cystic neoplasms and intraductal papillary mucinous neoplasms are the major premalignant cystic neoplasms of the pancreas. A variety of diagnostic tools are used to predict the malignant potential of these cysts, but specificity and sensitivity are limited. Thus, many patients undergo unnecessary operations for benign cysts. Balancing the risks of watchful waiting with those of operative management is key in managing these lesions. During the last decade, genetic changes of pancreatic cysts have been examined extensively to estimate their malignant potential. In this review, we provide an overview of the latest molecular and genetic aspects of pancreatic cysts and how they may contribute to the differential diagnosis in patients with pancreatic cystic neoplasms.     

Mucinous cystic neoplasm of the pancreas: Is surgical resection recommended for all surgically fit patients?

BackgroundSurgical removal of mucinous cystic neoplasms (MCNs) is usually recommended because of the risk of malignancy. However, increased experience of MCNs suggests that the incidence of invasion is lower than had been thought. This study was designed to establish more reasonable surgical indications for MCN through re-assessment using strict pathologic diagnostic criteria.MethodsNinety-four patients who underwent surgical removal of MCNs at Seoul National University Hospital from 1991 to 2012 were retrospectively analyzed. Pathologic results were re-evaluated by an experienced pathologist. Medical records and radiologic images were reviewed to determine factors predicting malignancy.ResultsOf the 94 patients, 4 were found to have intraductal papillary mucinous neoplasms (IPMNs). Of the 90 MCNs, 60 (66.7%) were low-grade, 21 (23.3%) were intermediate-grade, and 5 (5.5%) were high-grade dysplasias; and 4 (4.4%) were invasive carcinoma. Mural nodules on CT scan (p = 0.005) and abnormal serum CA19-9 concentration (p = 0.029) were significant predictors of malignancy. All MCNs less than 3 cm in size with normal serum tumor markers were benign and all malignant MCNs had cyst fluid CA19-9 over 10,000 units/ml. The five year disease specific survival rates were 98.8% for all patients and 75.0% for those with invasive MCNs.ConclusionMCNs had a low prevalence of malignancy. Regardless of the histological grade, long-term outcome was excellent. Therefore, in the absence of specific symptoms, surgery may not be indicated for MCNs <3 cm without mural nodules or elevated serum tumor markers. Validation by a prospective study with very careful design is needed.     

Giant cell tumor of the pancreas arising in the ovarian-like stroma of a mucinous cystadenocarcinoma

Summary We describe a malignant mucinous cystic neoplasm of the pancreas with ovarian-like stroma within which an osteoclast-like giant cell rich tumor arose. This rare tumor had a unique immunohistochemical profile with the giant cells staining for vimentin, leukocyte common antigen, and the monocyte/macrophage marker CD68, whereas the mucinous epithelium stained for epithelial membrane antigen and cytokeratin. The immunohistochemical findings are consistent with two lines of differentiation, one epithelial and the other suggesting mesenchymal differentiation of the giant cell tumor with an immunophenotype similar to giant cell tumor of bone. The coexistence of these two rare tumors suggests that they are histogenetically related. The finding of a giant cell tumor arising in the ovarian stroma indicates that the stroma of mucinous tumors is not always an innocuous component of the tumor.     

国际专家组关于超声内镜引导下胰腺囊性肿瘤消融的立场声明

背景和目的最近,一些有关胰腺囊性肿瘤(pancreatic cystic neoplasms,PCNs)治疗的指南建议已经发表,但是超声内镜(endoscopic ultrasound,EUS)引导下PCNs消融的作用在这些指南中尚未明确。本文的目的是通过提出一系列临床问题并根据可获得的最佳科学证据提供答案来探讨围绕EUS引导下PCNs消融的问题。 方法我们从亚洲EUS学组和一个国际专家组中招募了一个EUS引导下PCNs消融专家小组。创建了一个临床问题列表,并将每个问题分配给一个成员以产生一个陈述。然后在2016年10月至2017年10月的三次互联网会议上讨论了这些陈述。之后相互协商对这些陈述进行修改,直到取得协商一致意见。之后,将完整的陈述总结集体发送给所有小组成员,以对陈述的强度进行投票,对陈述进行分类,对证据进行分级。 结果制定了关于EUS引导下PCNs的23个陈述。这些陈述涉及操作步骤、操作技术、操作前和操作后管理,并发症的管理以及手术中所需能力和培训。 结论在所有内镜学会中,本共识是关于EUS引导下PCNs消融的首篇共识。有兴趣进行这项技术的临床医生应参考这些共识,未来的研究应设法解决本共识中提出的重要问题。     

Gene expression analysis of pancreatic cystic neoplasm in SV40Tag transgenic mice model

AIM： To study the gene expression changes in pancreatic cystic neoplasm in SV40Tag transgenic mice model and to provide information about the prevention, clinical diagnosis and therapy of pancreatic cancer.
METHODS： Using the pBC-SV40Tag transgenic mice model of pancreatic cystic neoplasm, we studied the gene expression changes by applying high-density microarrays. Validation of part gene expression profiling data was performed using real-time PCR.
RESULTS： By using high-density oligonucleotide microarray, of 14113 genes, 453 were increased and 760 decreased in pancreatic cystic neoplasm, including oncogenes, cell-cycle-related genes, signal transduction-related genes, skeleton-related genes and metabolism-related genes. Among these, we confirmed the changes in Igf, Shh and Wnt signal pathways with real-time PCR. The results of real-time PCR showed similar expression changes in gene chip.
CONCLUSION： all the altered expression genes are associated with cell cycle, DNA damage and repair, signal pathway, and metabolism. SV40Tag may cooperate with several proteins in promoting tumorigenesis.     

Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct:A case report

Cystic hepatic neoplasms are rare tumors,and are classified into two separate entities:mucinous cystic neoplasms(MCNs)and intraductal papillary mucinous neoplasms of the bile duct(IPMN-B).We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor.Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B.This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.     

Intraductal papillary neoplasm of the bile ducts: A case report and literature review

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare bile duct neoplasm mostly found in far eastern nations where hepatolithiasis and clonorchiasis infections are endemic. In western countries, it is very rare and the etiology is unknown. In this article, we report the first IPNB patient we encountered in our clinic and a literature review. The patient is a 38-year-old female with a history of choledocholithiasis who presented with obstructive jaundice. She was found to have a papillary mass at the junction of the right hepatic duct and common hepatic duct with six masses in the liver parenchyma. The immunophenotypic and histologic features of the tumor are consistent with IPNB, gastric subtype. The patient had a partial hepatectomy and has been receiving palliative chemotherapy. In a search of PubMed database, we collected 354 IPNB patients reported in 22 articles. In these patients, 52.8% were from Japan and 27.7% were from western countries including the United States (11.0%). The age of the patients ranged from 35 to 80 years old with an average of 64.6. Male/female ratio was 1.5. Macroscopically, 57.5% of the tumors were in the left lobe and 29.5% were in the right lobe. The average size of the tumor were 4.2 cm at the time of diagnosis. Histologically, pancreato-biliary subtype accounted for 41.8%, intestinal 28.0%, gastric 13.5% and oncocytic 16%. An invasive component is most often present in the pancreato-biliary and gastric subtypes. Despite recent advanced technologies, diagnosis of IPNB is still challenging, especially in western countries due to its rarity. Defined clinico-pathologic features are in demand for the accurate diagnosis and proper treatment.