Resected Mucinous Cystic Neoplasms Research Articles

Intralobular distribution of ovarian-like stroma in pancreatic mucinous cystic neoplasms: a discussion on its tumorigenesis

Pancreatic mucinous cystic neoplasm (MCN) has two histological components: tumor epithelia and ovarian-like stroma (OLS). To examine the progression and changes in pancreatic MCNs, we analyzed the distribution, amount, immunohistochemical phenotype, presence of theca cells of OLS, and tumor epithelium in 45 surgically resected MCN cases, comparing them with tumor sizes. The OLS data of female MCN cases were also compared between those who were ≤ 51 years old and those > 51 years old to see the effect of menopause on MCN histology. Non-mucinous type epithelium was present in all low-grade MCNs, but its ratio decreased with tumor size (p < 0.001), suggesting that epithelial mucinous changes are a progression phenomenon. The intralobular distribution of OLS was observed in 28.8% of MCN cases and was related to smaller tumor size (p < 0.0001), suggesting intralobular involvement of early MCNs. The nuclear expression of β-catenin and the cytoplasmic expression of α-smooth muscle actin (SMA) was observed in almost all OLS. OLS tended to be lesser among female cases aged > 51 years than those ≤ 51 years old, however it did not reach statistical significance. This is the first study to show the intralobular distribution of OLS.

MRI is useful to suggest and exclude malignancy in mucinous cystic neoplasms of the pancreas.

To evaluate the value of MRI in differentiating benign (b-MCN) and malignant (m-MCN) MCN. European guidelines suggest that certain mucinous cystic neoplasms (MCN) of the pancreas can be conservatively managed. A retrospective single-center study of consecutive patients with resected MCN. MRIs were independently reviewed by two readers blinded to the pathological results. The authors compared b-MCN (i.e., mucinous-cystadenoma comprising high-grade dysplasia (HGD)) and m-MCN (i.e., cystadenocarcinoma). Sixty-three patients (62 women [98%]) with 63 MCN (6 m-MCN, 2 HGD) were included. m-MCN tumors had a tendency to be larger than b-MCN (median 86 [25-103] vs. 45 [17-130] mm, p = .055). The combination of signal heterogeneity on T2-weighted imaging, wall thickness ≥ 5 mm, the presence of mural nodules ≥ 9 mm, and enhancing septa had an area under the ROC curve of 0.97 (95% CI 0.91-1.00) for the diagnosis of m-MCN. A total of 24 (37%), 20 (32%), 10 (16%), 5 (8%), and 4 (6%) out of 63 MCNs showed 0, 1, 2, 3, and 4 of these features, respectively. The corresponding rate of m-MCN was 0%, 0%, 10%, 20%, and 100%, respectively, with a good-to-excellent inter-reader agreement. Patterns with a high NPV for m-MCN included an absence of enhancing septa or walls (NPV 97% and 100%, respectively), wall thickness < 3 mm (NPV 100%), and no mural nodules (NPV 100%). A combination of 4 imaging features suggests malignant MCN on MRI. On the other hand, visualization of a thin non-enhancing wall with no mural nodules suggests benign MCN. • A heterogenous signal on T2-weighted MRI, a ≥ 5-mm-thick wall, mural nodules ≥ 9 mm, and/or enhancing septa suggest malignant MCNs. • A thin non-enhancing wall with no mural nodules suggests benign MCNs. • MRI should be performed in the pre-therapeutic evaluation of MCN to help determine the therapeutic strategy in these patients.

It's not all about the size-characteristics and risk factors for malignancy of mucinous cystic neoplasms of the pancreas.

BackgroundMucinous cystic neoplasms (MCN) of the pancreas are rare mucin-producing cystic tumors. As they harbor malignant potential, surgical resection is frequently performed. Current guidelines recommend surgery in asymptomatic patients only for MCN exceeding 4 cm. The aim of this study was to identify radiological and clinical risk factors for malignancy in a single-center cohort of MCN.MethodsAll resected MCN from a single high-volume center between 2004 and 2019 were retrospectively analyzed. Patient characteristics, preoperative findings, histopathological results, and data on the postoperative course were recorded. Variables associated with malignancy were evaluated using χ2 and Mann-Whitney U test. Receiver operating characteristic (ROC) curves were used to model predictive capabilities of preoperative tumor marker levels. Furthermore uni- and multivariate logistic regression analysis were performed for binary variables. Survival time was plotted as Kaplan-Meier curves and evaluated by log-rank test.ResultsA total of 63 patients were included. Median age was 62 years; 51 (81.0%) of them were women; median tumor size was 3.5 cm (range, 0.5–18.5); 16 (25.4%) of tumors harbored invasive carcinoma and 13 presented intraepithelial dysplasia (20.6%); 7 (43.8%) invasive carcinomas were smaller than 4 cm. All malignant MCN were radiologically suspected of malignancy (calcifications, mural nodules, or wall thickness) preoperatively. Elevated levels of carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) were strongly associated with malignancy (odd’s ratio 33.600; 7.000–161.270); P<0.001 and odd’s ratio 19.250; 3.370–109.970; P<0.001). Other factors associated with malignancy were preoperative weight loss (P=0.015) and higher age (P=0.048). Tumor size, abdominal or back pain or jaundice showed no significant correlation to malignancy in our cohort.ConclusionsMalignant potential of MCN should not be underestimated and a close clinical and radiological follow-up is mandatory in all suspected cases. This is especially important for small lesions. Risk assessment should not rely only on tumor size but consider all clinical, radiological and laboratory findings of each case. Follow-up should be performed by experienced surgeons and radiologists in high volume centers for pancreatic surgery. Surgery should be performed in all cases in which malignancy is suspected.

Mucinous cystic neoplasms of the pancreas: high-resolution cross-sectional imaging features with clinico-pathologic correlation.

To describe the high-resolution cross-sectional (MDCT/MRI) features of mucinous cystic neoplasms (MCN) of the pancreas with clinico-pathologic correlation; to identify imaging predictors of high-grade dysplasia/carcinoma; and to estimate MCN growth rate. Thirty-two women (mean age: 46; range, 25-79years) with resected MCN who underwent preoperative MDCT (n=20) or MRI (n=12) examinations over a 14-year period were included. Two radiologists examined retrospectively in consensus the following MDCT/MRI features: MCN location, size/volume, presence of capsule and thickness of the capsule, and presence of mural nodules, enhancing septations, calcifications, chronic pancreatitis, and main pancreatic duct dilation. Imaging features were correlated with clinical symptoms, biochemistry results, and histopathologic features. A univariate model was analyzed for the prediction of high-grade dysplasia/carcinoma. Preoperative MCN growth rate was assessed using a subset of patients with more than one imaging study available (n=6). Twenty-five (78%) patients presented with symptoms and 8 (25%) patients had abnormal serum biochemical values. Mean MCN maximum dimensions were 48×45×45mm with a mean volume of 169mL. MCN were located in the tail (n=18), body (n=10), neck (n=2), and (head=2); 30 (93.5%) MCN were encapsulated, 3 (9%) had calcifications, 4 (12%) showed enhancing nodules, 9 (28%) had enhancing septations, and 5 (15%) had main pancreatic duct dilation. Associated chronic pancreatitis was observed in 4 (12%) patients. The only predictors for high-grade dysplasia/carcinoma were MCN size and volume. Using a cut-off size greater than 8.5cm, the specificity and sensitivity for high-grade dysplasia/carcinoma were 97 and 60%, respectively (p=0.003; OR 81, 95% CI 3.9-1655.8). Mean MCN growth rate was estimated at 4.2mm/year with a doubling time of 8.23years. MCN size (>8.5cm) and volume are the only features on MDCT/MR imaging that correlate with high-grade dysplasia/carcinoma. The average growth rate for MCNs is slow at approximately 4mm per year.

Association of Preoperative Risk Factors With Malignancy in Pancreatic Mucinous Cystic Neoplasms

Pancreatic mucinous cystic neoplasms (MCNs) harbor malignant potential, and current guidelines recommend resection. However, data are limited on preoperative risk factors for malignancy (adenocarcinoma or high-grade dysplasia) occurring in the setting of an MCN. To examine the preoperative risk factors for malignancy in resected MCNs and to assess outcomes of MCN-associated adenocarcinoma. Patients who underwent pancreatic resection of MCNs at the 8 academic centers of the Central Pancreas Consortium from January 1, 2000, through December 31, 2014, were retrospectively identified. Preoperative factors of patients with and without malignant tumors were compared. Survival analyses were conducted for patients with adenocarcinoma. Binary logistic regression models were used to determine the association of preoperative factors with the presence of MCN-associated malignancy. A total of 1667 patients underwent resection of pancreatic cystic lesions, and 349 (20.9%) had an MCN (310 women [88.8%]; mean (SD) age, 53.3 [14.7] years). Male sex (odds ratio [OR], 3.72; 95% CI, 1.21-11.44; P = .02), pancreatic head and neck location (OR, 3.93; 95% CI, 1.43-10.81; P = .01), increased radiographic size of the MCN (OR, 1.17; 95% CI, 1.08-1.27; P < .001), presence of a solid component or mural nodule (OR, 4.54; 95% CI, 1.95-10.57; P < .001), and duct dilation (OR, 4.17; 95% CI, 1.63-10.64; P = .003) were independently associated with malignancy. Malignancy was not associated with presence of radiographic septations or preoperative cyst fluid analysis (carcinoembryonic antigen, amylase, or mucin presence). The median serum CA19-9 level for patients with malignant neoplasms was 210 vs 15 U/mL for those without (P = .001). In the 44 patients with adenocarcinoma, 41 (93.2%) had lymph nodes harvested, with nodal metastases in only 14 (34.1%). Median follow-up for patients with adenocarcinoma was 27 months. Adenocarcinoma recurred in 11 patients (25%), with a 64% recurrence-free survival and 59% overall survival at 3 years. Adenocarcinoma or high-grade dysplasia is present in 14.9% of resected pancreatic MCNs for which risks include male sex, pancreatic head and neck location, larger MCN, solid component or mural nodule, and duct dilation. Mucinous cystic neoplasm-associated adenocarcinoma appears to have decreased nodal involvement at the time of resection and increased survival compared with typical pancreatic ductal adenocarcinoma. Indications for resection of MCNs should be revisited.

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.

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.