Noninvasive Mucinous Cystic Neoplasms Research Articles

Risk Factors of Invasive Mucinous Cystic Neoplasm of Pancreas and Its Prognosis

Introduction: Mucinous cystic neoplasm (MCN) of pancreas is a rare pancreatic disease which has potential to become malignant. While early surgical resection of MCN is a mainstay of treatment, radical pancreatic surgery involves high morbidity. The aim of this study was to investigate risk factors of invasive MCN with its prognosis and to establish an appropriate treatment modality for MCN. Methods: From January 2004 to December 2018, a total of 129 patients underwent surgical resection for MCN in Samsung Medical Center, and their clinicopathological data were retrospectively reviewed. Risk factor analyses for recurrence and survival were performed. Results: There were 108 patients in non-invasive group and 21 patients in invasive group. There were more patients with preoperative elevated CA19-9 and mural nodules on preoperative images in invasive group than in non-invasive group (p=0.003 and p=0.003, respectively). In comparison of surgical outcomes, patients who underwent laparoscopic surgery had fewer major complications than those with open surgery (p=0.022). Elevated CA19-9 and mural nodules were independent risk factors for invasive MCNs (p=0.016 and p=0.011, respectively). Patients with invasive MCN showed poorer recurrence-free survival comparing to those with non-invasive MCN (p<0.001), and elevated CA19-9 was an associated factor (p=0.007). Invasive group had worse overall survival (p<0.001), and American Society of Anesthesiologists score and elevated CA19-9 were associated factors (p=0.005 and p=0.005, respectively). Conclusion: Preoperative elevated CA19-9 and mural nodules on image were associated with invasive MCN, which showed poor recurrence-free and overall survival. Surgery should actively be considered in patients with these features.

The value of cytology in the management of patients with pancreatic cysts.

The value of cytology in the management of patients with pancreatic cysts.

A Case of laparoscopic distal pancreatectomy for giant MCN

Summary: MCN (Mucinous cystic neoplasm )is a tumor that consists of mucus-producing epithelial cells with ovarian-like stroma, which is commonly found in the pancreas body or tail of middle-aged women. In regards to surgery, MCN less than 4 cm and without mural nodules is less likely indicated as malignant cases, and therefore laparoscopic distal pancreatectomy is applied. It is recommended that all noninvasive MCN be removed if there is no surgical risk, as they are unlikely to recur if completely removed. We report a Case of laparoscopic distal pancreatectomy for giant non-invasive MCN. The Case is 45 years old, female. She visited our hospital with chief complaint of discomfort in the upper left abdomen. Computed tomography showed a 116 * 94 mm cystic mass in the tail of the pancreas. There was a septum inside, and the cyst wall was thickened. There was no dilation of the main pancreatic duct. MRI also showed polycystic lesions. There was no dilation of the main pancreatic duct and no traffic was suggested. Therefore, we suspected a giant MCN in the pancreatic tail and performed laparoscopic distal pancreatectomy. She was in a supine position under general anesthesia. 5 mm ports were placed in the epigastrium, right abdomen, and left abdomen, and 12 mm ports were placed in the umbilicus and left abdomen. The tumor was large and the operation view was insufficient, but there was no adhesion with the surrounding area and the tumor could be resected laparoscopically while changing the position. Here, we report this Case with the procedual video.

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.

Clinicopathologic characteristics of 29 invasive carcinomas arising in 178 pancreatic mucinous cystic neoplasms with ovarian-type stroma: implications for management and prognosis.

Information on the clinicopathologic characteristics of invasive carcinomas arising from mucinous cystic neoplasms (MCNs) is limited, because in many early studies they were lumped and analyzed together with noninvasive MCNs. Even more importantly, many of the largest prior studies did not require ovarian-type stroma (OTS) for diagnosis. We analyzed 178 MCNs, all strictly defined by the presence of OTS, 98% of which occurred in perimenopausal women (mean age, 47 y) and arose in the distal pancreas. Twenty-nine (16%) patients had associated invasive carcinoma, and all were female with a mean age of 53. Invasion was far more common in tumors with grossly visible intracystic papillary nodule formation ≥1.0 cm (79.3% vs. 8.7%, P=0.000) as well as in larger tumors (mean cyst size: 9.4 vs. 5.4 cm, P=0.006); only 4/29 (14%) invasive carcinomas occurred in tumors that were <5 cm; however, none were <3 cm. Increased serum CA19-9 level (>37 U/L) was also more common in the invasive tumors (64% vs. 23%, P=0.011). Most invasive carcinomas (79%) were of tubular type, and the remainder (5 cases) were mostly undifferentiated carcinoma (2, with osteoclast-like giant cells), except for 1 with papillary features. Interestingly, there were no colloid carcinomas; 2 patients had nodal metastasis at the time of diagnosis, and both died of disease at 10 and 35 months, respectively. While noninvasive MCNs had an excellent prognosis (100% at 5 y), tumors with invasion often had an aggressive clinical course with 3- and 5-year survival rates of 44% and 26%, respectively (P=0.000). The pT2 (>2 cm) invasive tumors had a worse prognosis than pT1 (≤2 cm) tumors (P=0.000), albeit 3 patients with T1a (<0.5 cm) disease also died of disease. In conclusion, invasive carcinomas are seen in 16% of MCNs and are mostly of tubular (pancreatobiliary) type; colloid carcinoma is not seen in MCNs. Serum CA19-9 is often higher in invasive carcinomas, and invasion is typically seen in OTS-depleted areas with lower progesterone receptor expression. Invasion is not seen in small tumors (<3 cm) and those lacking intracystic papillary (mural) nodules of ≥1 cm, thus making the current branch-duct intraductal papillary mucinous neoplasm management protocols also applicable to MCNs.

Noninvasive intraductal papillary mucinous neoplasms and mucinous cystic neoplasms: Recurrence rates and postoperative imaging follow-up

Although surveillance guidelines for resected invasive mucinous neoplastic cysts are well-established, those for noninvasive cysts are not defined. We used our experience with resected noninvasive mucinous neoplastic cysts to define recurrence rates and the optimal frequency of postoperative imaging follow-up. We reviewed the medical records of 134 patients with resected, pathologically confirmed noninvasive mucinous neoplasms between 2002 and 2012. Demographics, comorbidities, cyst characteristics, and recurrence were evaluated. Survival analysis was used to estimate the distribution of time to recurrence and regression models were used to investigate factors associated with recurrence. Eighty-seven patients with intraductal papillary mucinous neoplasms (IPMNs) were compared with 47 patients with mucinous cystic neoplasms (MCNs). Those with MCNs were more often females (P=.001), significantly younger (P=.001), more symptomatic (P=.009), and had cysts more often located in the tail (P<.001). Median follow-up was 42months. Recurrence rates for IPMNs were 0%, 5%, and 10% versus 0% for MCNs respectively at postoperative years 1, 2, and 3 (P=.014). On multivariable analysis, size >3cm (P=.027), higher grade dysplasia (P=.043), and positive resection margins (P<.001) were significantly associated with recurrence. Resected noninvasive IPMNs with moderate- or high-grade dysplasia and negative resection margins require imaging follow-up every 2years, given the 16% overall recurrence rate. Although the follow-up interval for noninvasive, low-grade, dysplastic IPMNs with negative margins could be lengthened, all noninvasive IPMNs having positive margins require yearly follow-up at the minimum. Resected noninvasive MCNs--irrespective of grade and margin status--do not require surveillance, although the development of branch duct-IPMNs in the remnant pancreas can be investigated in the long term at the discretion of the provider.

Prognosis of Minimally Invasive Carcinoma Arising in Mucinous Cystic Neoplasms of the Pancreas

Although patients with surgically resected noninvasive mucinous cystic neoplasms (MCNs) of the pancreas are cured, the behavior of surgically resected minimally invasive adenocarcinomas arising in MCN has not been well established. We report 16 surgically resected MCNs with minimal invasion defined as unifocal or multifocal microscopic invasive adenocarcinoma confined to the ovarian stroma of the MCN without capsular or pancreatic parenchymal invasion. Pathologic findings were correlated with patient demographics, type of surgery, and long-term follow-up. Our study included 15 women and 1 man ranging in age from 25 to 66 years. The patients were followed up for a mean of 48.6 months (range, 12 to 148 mo). The MCNs ranged in size from 3.5 to 25 cm and were all located in the body/tail of the gland. Lymphovascular invasion was not identified in any of the cases, and all lymph nodes were negative for tumor. Ten neoplasms had unifocal invasion, whereas 6 had multifocal invasion. Twelve of the neoplasms were partially submitted for microscopic examination, whereas 4 were submitted entirely. Only 1 of the 16 minimally invasive MCNs recurred, and that tumor had been lighlty sampled pathologically. Our study demonstrates that the majority of patients with minimally invasive adenocarcinoma arising in MCNs are cured by surgery, particularly if the neoplasms are completely examined histologically.

Mucinous cystic neoplasms of the pancreas with ovarian stroma

Mucinous cystic neoplasms (MCNs) of the pancreas are rare, but have recently been increasing in incidence. The aim of this retrospective clinical study was to elucidate the clinicopathological features and prognosis of MCNs with ovarian stroma at a single centre. Using the presence of ovarian stroma as a requisite criterion for diagnosis of MCNs, the medical records of 47 surgically treated patients with MCNs from January 2004 to April 2011 were reviewed and classified according to the new 2010 World Health Organization classification. Included were 37 cases of low-grade (78.7%), 4 intermediate-grade (8.5%) and 1 high-grade dysplasia (8.5%), and 5 cases of invasive carcinomas (10.6%). Patients were exclusively women (91.5%) with a mean age of 48.5 years. Most tumours were in the pancreatic body/tail (89.4%) with a mean size of 5.24 cm. More than half were asymptomatic. Findings associated with malignancy were presence of mural nodules (P < 0.001) and cyst wall calcifications (P = 0.017). All invasive MCNs were ≥5.0 cm or had mural nodules. No lymph node metastasis was seen in 20 cases of lymph nodes dissected. None of the 42 patients with non-invasive MCNs recurred after a mean follow-up of 25 months. However, two of five patients with invasive MCNs recurred, and one died within 2 years. The prognosis of the resected non-invasive MCNs was excellent. Although resection should be considered for all cases, in low-risk MCNs (<5 cm and without nodules), nonradical resections (i.e. enucleations) are appropriate.

A noninvasive mucinous cystic neoplasm with intermediate-grade dysplasia of the pancreas and extensive squamous metaplasia: a case report with clinicopathological correlation

Squamous metaplasia presenting in noninvasive mucinous cystic neoplasm (MCN) of the pancreas is extremely rare. We described a case of 39-year-old Chinese female with a 5-year history of a slow growing mass in the left upper abdomen and an 18-month history of surgical incision exudation. The patient underwent cystojejunostomy, laparotomy and distal pancreatectomy consecutively because of the initial diagnosis of “pancreatic cyst”. The histological section showed columnar mucin-producing epithelium formed small papillary projections and extensively visible squamous metaplasia. Therefore the diagnosis of “noninvasive MCN with intermediate-grade dysplasia of the pancreas and extensive squamous metaplasia” was made finally. The squamous component of the pancreas may be derived from pluripotent stem cells, and may be in association with cystojejunostomy.Virtual slidesThe virtual slide(s) for this article can be found here http://www.diagnosticpathology.diagnomx.eu/vs/1322364365718540

Mucinous Cystic Neoplasm of the Pancreas is Not an Aggressive Entity

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. Analysis of 163 patients with resected MCNs, defined by the presence of ovarian stroma and lack of communication with the main pancreatic duct. 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 > or =60 mm (P = 0.0001). All neoplasms with cancer were either > or =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%. 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 (< or =4 cm/no nodules), nonradical resections are appropriate.

Current understanding of precursors to pancreatic cancer

Precursors to pancreatic cancer have been investigated for a century. Previous studies have revealed three distinct precursors, i.e. mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and pancreatic intraepithelial neoplasia (PanIN), harboring identical or similar genetic alterations as does invasive pancreatic carcinoma. The current understanding of precursors to pancreatic cancer can be illustrated by progressive pathways from noninvasive MCN, IPMN, and PanIN toward invasive carcinoma. MCNs consist of ovarian-type stroma and epithelial lining with varying grades of atypia, and are occasionally associated with invasive adenocarcinoma. The epithelium of noninvasive IPMNs shows a variety of different directions of differentiation, including gastric, intestinal, pancreatobiliary (PB), and oncocytic types. IPMNs can also harbor varying grades of architectural and cytologic atypia. IPMNs confined to branch ducts are mostly the gastric type, and IPMNs involving the main ducts are often intestinal type, while PB and oncocytic types are rare. Small (<1 cm) IPMNs of the gastric type are not always morphologically distinguishable from low-grade PanINs. Mucin expression profiles suggest intestinal-type IPMNs progress to mucinous noncystic (colloid) carcinoma, while PB-type IPMNs progress toward ductal adenocarcinoma. It is a well-described paradigm that PanIN lesions progress toward ductal adenocarcinoma through step-wise genetic alterations. The activation of Hedgehog and Notch signaling pathways in PanIN lesions as well as in pancreatic adenocarcinoma suggest that developmental pathways may be disregulated during carcinogenesis of the pancreas. Further study is needed to elucidate the pathways from precursors toward invasive carcinoma of the pancreas.

Mucins in the diagnosis and differential diagnosis of pancreatic cystic neoplasms

胰的膀胱的瘤说明 10% ～ 15% 所有膀胱的胰腺的损害。胰的膀胱的损害的多数(85% ～ 90%) 是胰的膀胱的瘤是的 pseudocysts.Although 稀罕，他们从对恶意的瘤良性。临床的挑战是膀胱的瘤的微分诊断和管理，它代表 10% ～ 25% 主要的胰腺的瘤。象有膀胱的特征的损害一样的胰腺的瘤和瘤最近被考察了。报导的胰腺的膀胱的瘤的发生是可变的。因为从把胰的膀胱的瘤的发生和生物学比作西方的系列的中国的 tne 案例上没有大、系统的学习，我们在 6 年从中山医院考察了膀胱的瘤的所有案例。大多数在我们的系列的瘤根据最近的世界健康组织被分类() 分类。粘蛋白是广泛地在上皮的房间被表示的一组高相对的分子的集体 glycoproteins。上皮的房间的恶意的转变通常与粘蛋白的反常 glycosylation 被联系。在现在的学习，我们在胰的膀胱的瘤检验了很好描绘的粘蛋白(MUC1， MUC2， MUC4， MUC5AC，和 MUC6 ) 的表示。目标是识别粘蛋白侧面，它是在胰腺的膀胱的瘤的微分诊断的一个特定的标记。

Diagnosis and differential diagnosis of intraductal papillary mucinous neoplasm of pancreas

To study the clinicopathologic features of intraductal papillary mucinous neoplasm (IPMN) and its distinction from mucinous cystic neoplasm of pancreas. The clinical, radiologic and histologic features of 17 cases of IPMN and 13 cases of mucinous cystic neoplasm (MCN) were reviewed. Mucin profiles (MUC1, MUC2 and MUC5AC) were studied by histology (HE) and immunohistochemistry (EnVision). 10 of the 17 cases of IPMN were males. 13 cases of the IPMN were located in head of pancreas. Communication with the main pancreatic duct was demonstrated in 15 cases. Histologically, there were mild to severe papillary ingrowths of dysplastic epithelial cells, associated with intervening normal or atrophic pancreatic parenchyma. Ovarian-like stroma was not seen. Ancillary investigations showed that MUC2 and MUC5AC were detected in tumor cells of 9 and 4 cases respectively. The 4 cases with invasive component showed MUC1 positivity. On the other hand, 11 of the 13 cases of MCN occurred in middle-aged to elderly females and were located in the body and tail of pancreas. Ovarian-like stroma was commonly seen and there was no connection with the main pancreatic duct. All non-invasive MCN, regardless of the degree of cytologic atypia, were positive for MUC5AC (but not MUC2). In the 2 cases with invasive component, MUC1 expression was observed, as in IPMN. The age and sex of patients, tumor location, absence of ovarian-like stroma, communication with main pancreatic duct and characteristic mucin profiles represent useful parameters in distinguishing IPMN from MCN of pancreas. The tumor cells of IPMN express mainly MUC2, while those of MCN express MUC5AC. MUC1 may also be a useful marker in demonstration of stromal invasion in these tumors.

The Mucin Profile of Noninvasive and Invasive Mucinous Cystic Neoplasms of the Pancreas

Recently, it was shown that ductal adenocarcinomas and intraductal papillary-mucinous neoplasms of the pancreas differ in their expression of the mucin markers MUC1 and MUC2 while both tumors express MUC5AC. It is not known whether mucinous cystic neoplasms of the pancreas have their own mucin profile. To clarify this issue, 22 mucinous cystic neoplasms were examined immunohistologically for their expression of MUC1, MUC2, MUC5AC, and MUC6 and also for the protein products of the tumor suppressor genes p53 and DPC4 and the mismatch repair genes. Noninvasive mucinous cystic neoplasms, regardless of the degree of cellular atypia, were all positive for MUC5AC and negative for MUC1, with the exception of the cyst-lining epithelium of a single case with eosinophilic cytology (case no. 16). Only in cases with an invasive component was MUC1 expression observed. MUC2 expression was restricted to goblet cells scattered within the epithelium of the mucinous cystic neoplasms and was often accompanied by endocrine cells, a further indication of intestinal differentiation. DPC4 expression was maintained in all tumors, except for three invasive carcinomas. p53 nuclear reactivity was found in one borderline tumor and four invasive mucinous cystic carcinomas. The results suggest that the epithelium of noninvasive mucinous cystic neoplasms does not differ in its expression of MUC5AC from ductal adenocarcinomas, intraductal papillary-mucinous neoplasms, and metaplastic pancreatic duct epithelium. The fact that noninvasive mucinous cystic neoplasms lack MUC1 expression (except for an eosinophilic variant) but express it when they become invasive might be used as a marker indicating the step of progression from noninvasiveness to invasiveness.

Dpc4 protein in mucinous cystic neoplasms of the pancreas: frequent loss of expression in invasive carcinomas suggests a role in genetic progression.

DPC4 (MADH4, SMAD4) is a nuclear transcription factor shown to be genetically inactivated in over half of infiltrating ductal adenocarcinomas of the pancreas. Immunohistochemical labeling for the DPC4 gene product using a monoclonal antibody has recently been shown to be an extremely sensitive and specific marker for DPC4 gene alterations in pancreatic adenocarcinomas. Mucinous cystic neoplasms (MCNs) are a biologically less aggressive subtype of pancreatic neoplasm that may show benign, borderline, or overtly malignant features. However, the role of DPC4 inactivation in the development of MCNs has not been examined. The immunohistochemical expression of Dpc4 protein was therefore examined in 36 mucinous cystic neoplasms using this previously characterized monoclonal antibody. The 36 mucinous cystic neoplasms studied included 23 adenomas, 1 tumor with borderline potential, 5 tumors with carcinoma in situ, and 7 invasive carcinomas. Twenty-nine (100%) of the 29 noninvasive mucinous cystic neoplasms strongly expressed Dpc4 in the neoplastic epithelium. In striking contrast, only one (14%) of seven infiltrating carcinomas expressed Dpc4 in the neoplastic epithelium (p = 0.0001). The adjacent stroma retained expression of this protein in all 36 cases. In invasive MCNs with loss of Dpc4 expression, areas of carcinoma in situ were identified in the same paraffin sections, and these areas of carcinoma in situ retained expression of Dpc4. The frequent loss of Dpc4 expression in invasive MCNs indicates that genetic inactivation of Dpc4 occurs late in the neoplastic progression of these tumors and suggests a relationship to the development of invasion.