Association of high-risk stigmata and worrisome features with advanced neoplasia in intraductal papillary mucinous neoplasms (IPMN): A systematic review.

BACKGROUND: This systematic review aimed to assess the diagnostic accuracy of the International Consensus Fukuoka Guidelines (ICG2017) in identifying high-risk lesions of Intraductal Papillary Mucinous Neoplasms (IPMNs). METHODS: The ICG2017 revision committee conducted a comprehensive literature review to establish evidence-based statements on IPMNs. The review focused on articles examining the diagnostic value of imaging features (e.g., cyst or main pancreatic duct diameter), clinical symptoms associated with IPMN, and serum biomarkers. Five clinical questions regarding high-risk stigmata (HRS) and worrisome features (WF) in the ICG2017 guidelines were addressed. RESULTS: A total of 210 articles were reviewed. The findings revealed a significant association between the presence of mural nodules ≥5 mm in diameter or solid components with contrast enhancement and the diagnosis of high-grade dysplasia or invasive carcinoma. Contrast-enhanced diagnostic tools, such as CT, MRI, or EUS, demonstrated the highest prediction rate and were recommended. Positive cytology was identified as an HRS, while symptoms like acute pancreatitis and cyst diameter growth ≥2.5 mm per year were considered WFs. The use of nomograms and multiple diagnostic factors was recommended for optimal IPMN management. CONCLUSIONS: This systematic review provides evidence supporting the improved diagnostic accuracy of ICG2017 in identifying high-risk lesions of IPMN. The multidisciplinary incorporation of HRS and WF based on imaging findings and clinical symptoms is crucial. These findings should inform the revision of ICG2017, enhancing the evaluation and management of IPMN patients. By implementing these recommendations, clinicians can make more informed decisions, leading to better diagnosis and treatment outcomes for high-risk IPMN cases.

Are All Cysts Created Equal?: Pancreatic Cystic Neoplasms in Patients with Familial or Genetic Risk Factors for Pancreatic Cancer.

Pancreatic cystic lesions (PCLs) have become more prevalent over time, particularly in asymptomatic individuals. Current screening guidelines for incidental PCLs offer a unified approach to surveillance and management, predicated on "worrisome features." Although PCLs are common in the general population, their prevalence may be higher in high-risk individuals (HRI, unaffected patients with specific familial and/or genetic risk factors). As more PCLs are diagnosed and more HRI identified, it is important to promote research that bridges data gaps and introduces nuance to risk assessment tools, ensuring tailoring of guidelines to the needs of HRI with varying pancreatic cancer risk factors.

Endocrine cell micronests in an ovarian mucinous borderline tumor: a potential diagnostic pitfall for microinvasion.

The occurrence of endocrine cell micronests in ovarian tumors is rarely reported. To our knowledge, there are only three prior cases reported to date: one occurring in an ovarian mucinous cystadenoma, one in an ovarian mucinous cystadenofibroma, and another in an ovarian mucinous carcinoma with a predominant borderline component. This is a 27-year-old woman that presented with a one-month history of abdominal pain and fullness. Imaging studies revealed a large multiloculated cystic and solid mass measuring 23 cm occupying the majority of the pelvis and abdomen concerning for a primary ovarian malignancy. The patient underwent a right salpingo-oophorectomy with appendectomy. Histologic sections from the ovary showed a multiloculated, cystic and focally solid mass lined by gastrointestinal-type mucinous epithelium with variable degrees of proliferation accounting for greater than 10% of the tumor. In addition to the mucinous epithelial component, there were several foci of bland, monotonous epithelioid cells arranged in solid nests with focal tubular/acinar formation within the fibrous septa and mucinous epithelium. Immunohistochemical studies showed that these cells were positive for cytokeratin, EMA, and synaptophysin, while negative for inhibin. The Ki-67 proliferation index was low (<1%). The presence of endocrine cell nests associated with an ovarian mucinous neoplasm is a rare phenomenon. Whether this represents preservation of endocrine cells in the context of epithelial degeneration or an independent neoplastic component is unclear. Progression related to this endocrine cell proliferation is unlikely and the recognition of this phenomenon holds more diagnostic value than prognostic significance, as it could be confused with microinvasion or sex cord stromal elements.

Mucinous cystic neoplasm of the liver

A 55-year-old woman was investigated for occasional epigastric pain and weight loss. T2-weighted abdominal magnetic resonance imaging and magnetic resonance cholangiography revealed a multilocular cyst with multiple septa and a solid component in the liver, measuring 6.1 × 4.8 × 6.5 cm. Given the patient's symptoms and malignant potential, a laparoscopic segmentectomy with partial resection of segments IV B and V was performed to completely remove the cystic lesion, associated with cholecystectomy. Histopathology demonstrated a cyst lined by columnar mucinous epithelium. Therefore, the diagnosis was mucinous cystic neoplasm of the liver. This article presents a case report and literature review of this entity.

Pathologic T1 and T2 encapsulated invasive carcinomas arising from mucinous cystic neoplasms of the pancreas have favorable prognosis and might be treated conservatively.

Carcinoma arising from a mucinous cystic neoplasm (MCN) of the pancreas is termed MCN with associated invasive carcinoma (MCN-AIC) in the fifth WHO classification of digestive tumors (2019). The prognosis of this malignancy varies depending on the relationship of the invasive carcinoma to the cyst capsule, but limited data are available. This study identified 165 surgically resected MCNs including 15 MCN-AICs from a single center between 2008 and 2018 and analyzed their clinicopathologic features. The results confirmed that non-invasive MCNs were completely cured by surgery. All MCN-AICs showing an encapsulated invasion pattern (defined as invasive carcinoma limited to the ovarian-type stroma, cystic septa, and capsule) had an excellent prognosis with a 5-year survival rate of 100%, even when the size of the invasive component was up to stage T2. By contrast, MCN-AICs with extracapsular involvement had unfavorable clinical outcomes. Our study demonstrates that the pattern of invasion of MCN-AIC can predict patient prognosis. Pathologic stage T1 and T2 encapsulated MCN-AICs may be completely cured with surgical resection alone or when combined with postoperative chemotherapy.

Differentiation and management of hepatobiliary mucinous cystic neoplasms: a single centre experience for 8 years.

BACKGROUND: Hepatobiliary mucinous cystic neoplasms (H-MCNs) are relatively rare cystic neoplasms in the liver. The differential diagnosis of H-MCNs remains big challenging, and the management and prognosis between the hepatic simple cyst (HSC) and H-MCNs are quite different. This study aimed to present our experience in the management of H-MCNs and provide a preoperative H-MCNs risk prediction nomogram to differentiating H-MCNs from liver cystic lesions. METHODS: 29 patients diagnosed with H-MCNs and 75 patients diagnosed with HSC between June 2011 and June 2019 at Zhejiang University School of medicine, Sir Run-Run Shaw Hospital were reviewed in this study. We analyzed the demographic and clinicopathological variables. RESULTS: US, CT, and MRI could accurately diagnose only 3.4%, 46.1%, and 57.1% of H-MCNs, respectively. After univariate analysis and multivariate logistic regression analysis, the variables significantly associated with H-MCNs were enhancement after contrast (p = 0.009), tumour located in the left lobe (p = 0.02) and biliary ductal dilation (p = 0.027). An H-MCNs risk predictive nomogram was constructed, which showed excellent discrimination (areas under the receiver operating characteristic curve were 0.940) and consistent calibration between the predicted probability and actual probability. CONCLUSION: Among patients with H-MCNs, the location of the tumour, enhancement in CT scan, and biliary duct dilation are significantly independent risk factors. The appropriate treatment of H-MCNs is radical resection. Using our Nomogram could facilitate screening and identification of patients with liver cystic lesions.

[Combination of intraductal papillary mucinous neoplasm with other cystic pancreatic tumors]. / Sochetanie vnutriprotokovoi papillyarnoi mutsinoznoi opukholi s drugimi kistoznymi opukholyami podzheludochnoi zhelezy.

Cystic tumors of the pancreas are uncommon entities. Synchronic occurrence of intraductal papillary mucinous neoplasm (IPMN) and other pancreatic tumors is extremely rare. Two patients with this diagnosis are reported in the manuscript. Cystic tumors of the pancreas can rarely occur in various combinations while malignancy potential of each neoplasm may be different. Surgery depends on localization and type of each tumor and must be determined individually.

Primary cystic and solid neuroendocrine tumor of the retroperitoneum: A case report.

RATIONALE: Primary neuroendocrine tumors (NETs) of the retroperitoneum are extremely rare. The purpose of this case report is to highlight the unusual growth pattern and radiologic features of primary retroperitoneal NETs. PATIENT CONCERNS: A 46-year-old woman was found to have a retroperitoneal cystic and solid mass during a physical checkup. DIAGNOSES: The mass was mainly multiseptated in the cystic portion and had a bead-like, lobulated appearance. The solid portion showed restricted diffusion on diffusion-weighted imaging and obvious homogeneous enhancement. The cystic portion showed ring-like and septal enhancement. The patient was diagnosed with a grade 2 (G2) NET of the retroperitoneum after surgery. INTERVENTIONS: The patient underwent resection of the large retroperitoneal tumor. OUTCOMES: The patient returned 20 months later with tumor recurrence in the retroperitoneum. She was enrolled in a clinical trial for sulfatinib, and the mass was considerably reduced in size after 4 months. During a nearly 1.5-year follow-up, the mass gradually became slightly enlarged. The expression of somatostatin receptor 2 (SSTR2) was detected, and somatuline was administered as the current treatment. LESSONS SUBSECTIONS: When a retroperitoneal mass presents as a well-defined cystic or solid hypervascular mass with a fibrous capsule, a primary retroperitoneal NET should be considered in the differential diagnosis.

Sex-dependent expression of prostatic markers and hormone receptors in cystic tumor of the atrioventricular node: A histopathological study of three cases.

We pathologically investigated three autopsy cases of cystic tumor of the atrioventricular node (CTAVN) with sudden death. Case 1 was a 36-year-old woman without any clinical history. Case 2 was a 76-year-old man with an implanted pacemaker for complete atrioventricular block. Case 3 was a 45-year-old man with a history of first-degree AV block and sinus bradycardia. Microscopically, all three cases showed the bilayered structure of tumor glands and corpora amylacea in the glandular lumens. Immunohistochemically, the inner cells of the tumor glands were positive for cytokeratin CAM5.2, CEA, EMA, olfactomedin-4 and alpha-methylacyl-coenzyme A racemase; the outer cells were positive for p63 and cytokeratin high molecular weight. In Case 1, androgen receptor and estrogen receptor were negative; progesterone receptor was focally positive in both the inner and outer cells. In Case 2, androgen receptor showed intermediate positivity in the inner cells; estrogen receptor and progesterone receptor were positive in the outer cells. Positive expression of both prostate-specific antigen and prostate-specific acid phosphate were found in the inner cells of both male cases. Because CTAVN cells exhibit different degrees of the prostatic phenotype depending on the patient's sex, we believe that CTAVN may originate from urogenital sinus tissue in some cases.

Factors Associated With the Risk of Progression of Low-Risk Branch-Duct Intraductal Papillary Mucinous Neoplasms.

Importance: Branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) are common pancreatic preneoplastic lesions, but their surveillance is not personalized. Objective: To investigate patient- and cyst-related factors associated with progression into worrisome features (WFs) or high-risk stigmata (HRS) categories of BD-IPMNs. Design, Setting, and Participants: Cyst- and patient-related factors of consecutive BD-IPMNs without WFs or HRS in 540 patients diagnosed from 2009 to 2018 with at least 12 months' surveillance until February 28, 2020, were registered in a 2-center ambispective cohort study in Italy. In a subgroup, the ABO blood group was studied for the first time in this setting. Exposure: Cyst-related and patients-related factors and ABO blood group. Main Outcomes and Measures: The study outcome was the appearance of WFs or HRS according to the 2017 International Association of Pancreatology guidelines. Survival probability was calculated using Kaplan-Meier curve and risk factors identified by Cox proportional hazards regression. ABO blood group was inferred through genotypes with DNA extraction. Results: Of 540 patients with BD-IPMNs (median age, 66 years [interquartile range, 58.5-72.0 years]; 337 women [62.4%]) undergoing surveillance for a median of 51.5 months (interquartile range, 28-84 months) for 2758 person-years, 130 patients (24.1%) experienced progression. Probability of progression was 3.7% at 1 year, 23.4% at 5 years, and 43.3% at 10 years; 15 patients (2.8%) underwent surgery, 7 patients (1.3%) had malignant histologic findings, and 3 patients (0.56%) died of pancreatic-associated disease. Initial cyst size greater than 15 mm (hazard ratio [HR], 2.05; 95% CI, 1.44-2.91), body mass index greater than 26.4 (HR, 1.72; 95% CI, 1.19-2.50), and heavy smoking (HR, 1.81; 95% CI, 1.14-2.86) were significant independent factors associated with progression risk. The AA blood genotype was also associated with progression risk (HR, 3.49; 95% CI, 1.04-11.71) compared with the OO genotype in the investigated subgroup. Conclusions and Relevance: This analysis of factors associated with progression of BD-IPMNs according to recent guidelines suggests that cyst size alone is not a reliable factor for estimation of progression risk; however, along with other readily available data, size is helpful for planning personalized surveillance of BD-IPMNs.

Nomenclature of appendiceal mucinous lesions according to the 2019 WHO Classification of Tumors of the Digestive System.

BACKGROUND/AIMS: To analysis the appendiceal mucinous lesions according to the World Health Organization (WHO) 2019 classification of tumors of the digestive system (non-neuroendocrine tumors of the appendix vermiformis) MATERIALS AND METHODS: Clinical and histopathological data of 37 patients with histopathologically proven appendiceal mucinous lesion from January 2010 to May 2019 were evaluated retrospectively. Pathology slides were re-evaluated by two pathologists according to the WHO 2019 classification of tumors of the digestive system. RESULTS: Totally 37 patients (male:19 female: 18) aged 23 to 93 years were analyzed. Majority of the patients (75.7 %) had underwent appendectomy due to preliminary diagnosis of acute appendicitis (n=22) or periappendiceal tumoral lesions (n=9), the others (n=9) underwent incidental appendectomy. Whereas acute appendicitis was histopathologically diagnosed in 16 (43.2%) patients, perforation was diagnosed in 12 (32.4%) patients (perforation without appendicitis=3, perforation with appendicitis=6). According to the initial, pathology reports were prepared as follows: mucocele (n=10), mucinous cystadenoma (n=9), low-grade mucinous neoplasm (n=6), mucinous adenocarcinoma (n=5), mucosal hyperplasia (n=5), hyperplastic polyp (n=1), adenomatous polyp (n=1). On the basis of the WHO 2019 classification, pathology reports were prepared as follows: low-grade mucinous neoplasm (n=17), simple retention cysts (n=6), hyperplastic polyp (n=6), mucinous adenocarcinoma (n=5), ruptured appendiceal diverticula (n=2), sessile serrated lesion (n=1). CONCLUSION: The term of appendiceal mucinous lesion, which is recently introduced into medical literature is suitable to distinguish between lesions with and without malignancy potential. The WHO 2019 classification system has been an important step in simplifying the classification of non- neuroendocrine tumors of the appendix vermiformis.

The utility of intracystic glucose levels in differentiating mucinous from non-mucinous pancreatic cysts.

BACKGROUND: Differentiating benign non-mucinous from potentially malignant mucinous pancreatic cysts is still a challenge. This study aims to improve this distinction with cyst fluid analysis. METHODS: A cohort study of pancreatic cyst undergoing EUS/FNA was performed from a prospectively maintained database between 2014 and 2018 was performed. RESULTS: 113 patients were analyzed (40 non-mucinous and 73 mucinous). For differentiating mucinous from non-mucinous cyst: intracyst glucose ≤41 mg/dl had a sensitivity of 92% and a specificity of 92%; positive predictive value (PPV) of 96 and negative predictive value (NPV) of 86. Glucose ≤21 mg/dl had a sensitivity of 88%, specificity of 97%, PPV of 98 and NPV of 81. CEA ≥192 ng/mL had a sensitivity of 50% and a specificity of 92%; PPV of 92 and NPV of 50. Glucose ≤21 mg/dl or CEA ≥192 ng/mL combined had a sensitivity of 93%, specificity of 92%, PPV of 96 and NPV of 87 (Fig. 1, Table 1). CONCLUSION: Intra-cyst glucose levels (≤41 mg/dl) outperforms classic CEA testing for differentiation of mucinous from non-mucinous pancreatic cysts. It was found to be an excellent diagnostic test with an AUC of 0.95 (95% CI: 0.81, 0.97).

Ovarian Seromucinous Borderline Tumors Are Histologically Different from Mucinous Borderline Tumors.

AIM: To examine the clinicopathological features of ovarian seromucinous borderline tumors (SMBTs) and compare them with those of mucinous borderline/atypical proliferative mucinous tumors (MB/APMTs). PATIENTS AND METHODS: Patients with SMBT between 2014 and 2018 and those with MB/APMT between 1988 and 2018 who underwent surgery at our Institution were identified. Pathological review was conducted using the 2014 World Health Organization criteria. Clinical features were compared retrospectively between SMBT and MB/APMT. RESULTS: In total, 11 (12.9%) patients with SMBT and 74 (87.1%) patients with MB/APMT were included in our study. The diagnosis of six patients with SMBT and 73 patients with MB/APMT was not revised on review. SMBT was diagnosed at a younger age (p=0.04), was of smaller size (p<0.01) and bilateral (p=0.03), coexisted with endometriosis (p<0.01), and more frequently recurred than MB/APMT (p=0.04). CONCLUSION: SMBT might be more aggressive than MB/APMT.

Invasive Stratified Mucin-producing Carcinoma (ISMC) of the Cervix: A Study on Morphologic Diversity.

Invasive stratified mucin-producing carcinoma (ISMC) is a recently described tumor with similar morphology to the stratified mucin-producing intraepithelial lesion. Stratified mucin-producing intraepithelial lesion and ISMC likely arise from human papillomavirus (HPV)-infected reserve cells in the cervical transformation zone that retain their pluripotential ability to differentiate into various architectural and cytologic patterns. This is important, as small studies have suggested that ISMC may be a morphologic pattern associated with more aggressive behavior than usual HPV-associated adenocarcinoma. We sought to study the morphologic spectrum of this entity and its associations with other, more conventional patterns of HPV-associated carcinomas. Full slide sets from 52 cases of ISMC were reviewed by an international panel of gynecologic pathologists and classified according to the new International Endocervical Criteria and Classification system. Tumors were categorized as ISMC if they demonstrated stromal invasion by solid nests of neoplastic cells with at least focal areas of mucin stratified throughout the entire thickness, as opposed to conventional tall columnar cells with luminal gland formation. Tumors comprising pure ISMC, and those mixed with other morphologic patterns, were included in the analysis. Twenty-nine pure ISMCs (56%) and 23 ISMCs mixed with other components (44%) were identified. Other components included 13 cases of usual-type adenocarcinoma, 6 adenosquamous carcinoma, 3 mucinous-type adenocarcinoma, 1 high-grade neuroendocrine carcinoma. ISMC displayed architectural diversity (insular, lumen-forming, solid, papillary, trabecular, micropapillary, single cells) and variable cytologic appearance (eosinophilic cytoplasm, cytoplasmic clearing, histiocytoid features, glassy cell-like features, signet ring-like features, bizarre nuclei, squamoid differentiation). Awareness of the spectrum of morphologies in ISMC is important for accurate and reproducible diagnosis so that future studies to determine the clinical significance of ISMC can be conducted.

[Clinical analysis and prognosis factors of malignancy in the patients with mucinous cystic neoplasms of the pancreas].

Objective: To examine clinic pathological features of mucinous cystic neoplasms (MCN) of the pancreas and explore the prognosis factors associated with malignant transformation of MCN of the pancreas. Methods: This multicenter retrospective study included all patients with pancreatic MCN underwent surgery at Department of Pancreatic Surgery, Zhongshan Hospital of Fudan University between January 2008 and December 2018 and patients with MCN who confirmed by postoperative pathology from Multicenter Pancreatic Cystic Tumor Database. There were 50 males (14.4%) and 297 females (85.6%) and the mean age was 48.6 years (range: 24-77 years). According to the pathological results, all patients were divided into benign lesion group (including MCN and which associated with low/medium grade dysplasia) and malignant lesion group (including MCN with high-grade dysplasia or invasive carcinoma) . The preoperative clinical pathology and imaging features of the two groups were analyzed, and the risk factors associated with malignant transformation of MCN were statistically analyzed. Results: This multicenter retrospective study included 347 patients. Twenty-four of the 347 patients were malignant, including 7 males and 17 females. Univariate analysis showed that age, gender, carcino-embryonic antigen (CEA) , CA19-9, CA125, tumor maximum diameter, and tumor location were remarkably different in the two groups (P<0.05) . Logistic regression analysis found that the preoperative tumor maximum diameter (OR=1.023, 95% CI: 1.002-1.045, P=0.035) was an independent risk factor for MCN malignant transformation. Conclusions: Age, gender, CEA, CA19-9, CA125, tumor maximum diameter, and tumor location are important features of MCN malignant lesions.The maximum diameter of the preoperative tumor is an independent risk factor for MCN malignant transformation.

Decidualized juvenile cystic adenomyoma mimicking a cornual pregnancy.

OBJECTIVE: To demonstrate the laparoscopic excision technique of a juvenile cystic adenomyoma and show how the decidualization of ectopic endometrial tissue can lead to the misdiagnosis of a focus of ectopic pregnancy. DESIGN: Description and step-by-step demonstration of the surgical procedure using a video recording (Canadian Task Force Classification 3). SETTING: Teaching and research hospital. PATIENT(S): A 27-year-old gravida 2 parity 1 patient with one previous caesarean delivery presented to the emergency department with symptoms of pelvic pain and delayed menses. Her beta-human chorionic gonadotropin level was 2,161 mIU/mL. On transvaginal ultrasonography the uterine cavity appeared empty without any signs of a gestational sac, and a 42×45 mm heterogeneous mass was observed on the right cornual area. An 18×21 mm cystic area was observed within the mass. A diagnosis of cornual pregnancy was made and two doses of systemic methotrexate treatment were administered. On the 12th day following medical treatment, the patient reported increasing abdominal pain and free fluid was observed in the pouch of Douglas on ultrasonography. The decision to perform laparoscopic cornual excision was made. MAIN OUTCOMES AND MEASURE(S): On laparoscopic exploration a tubal ectopic pregnancy was observed within the left fallopian tube. The presence of two simultaneous ectopic pregnancies, located in the left fallopian tube and the right cornual area, was suspected. However, upon careful inspection, the right fallopian tube appeared normal and the mass initially thought to be a right cornual pregnancy appeared more like a degenerated fibroid. A left salpingectomy was performed and the excision of the mass in the right cornual area was planned. An incision was made over the mass and the cystic inner area containing chocolate-brown colored fluid was drained. As there was no pseudo capsule surrounding the mass, the diagnosis of focal adenomyosis instead of degenerated fibroid was made. No endometriotic foci were observed within the pelvis. Different from the enucleation of a fibroid, the mass was dissected from the middle into two halves until healthy myometrium was reached on the floor of the mass. The two halves of the mass were resected totally by dissecting the adenomyotic tissue from the myometrium starting from the caudal end towards the cranial end. The first layer of the remaining myometrial defect was sutured extracorporeally with No.1 polyglactan sutures. The second and third layers were sutured intracorporeally with V-loc sutures. The resected left fallopian tube containing the ectopic pregnancy and the adenomyotic mass were externalized through a posterior colpotomy incision. RESULT(S): The patient was discharged 24 hours postoperatively without any complications. A diagnosis of juvenile cystic adenoma was made upon histopathological examination. The patient reported subsiding of her dysmenorrhea on the postoperative third month. CONCLUSION(S): Juvenile cystic adenomyosis (JCA), is a rare form of focal adenomyosis which is usually located in close proximity to the uterine insertion of the round ligament, contains a cystic inner area larger than 1 cm and is encountered before the age of 30 years. Some authors reported JCA to be an accessory and cavitated uterine mass (ACUM) anomaly developing as a result of gubernaculum dysfunction. The only difference between the two conditions is reported to be the presence of a denser area of adenomyosis surrounding the cystic area lined with endometrium in JCA than in ACUM. This case has shown that decidual changes observed in ectopic endometrial tissue within an adenomyotic area may be misdiagnosed as a focus of ectopic pregnancy. Atypical endometriomas demonstrating decidual changes may also be misdiagnosed as ovarian malignancies. In non-emergency situations, waiting for the decidualization effect of ectopic endometrium to subside can help in the definitive diagnosis of such cases. Our technique for JCA excision is different from enucleation of a fibroid and may aid in the total resection and dissection of the adenomyotic tissue from healthy myometrium.