Benign Etiology for High-Risk Intraductal Papillary Mucinous Neoplasm: A Case Report and Literature Review.

Intraductal papillary mucinous neoplasms are relatively common and entail a variable risk of malignant potential. The Fukuoka guidelines present criteria for the risk of malignant transformation and are used for risk stratification and treatment decision-making. However, these guidelines entail some fallibility with limited sensitivity and specificity. In this case, we present an individual who had many of the hallmarks of malignant transformation but was found to have no evidence of malignancy or high-grade dysplasia. We discuss the suspected etiology of this individual's condition and how it might arise in others, as well as a brief review of the literature on risk factors in intraductal papillary mucinous neoplasms.

Pelvic Diagnostic Challenges of Appendiceal Neoplasm Mimicking a Hematosalpinx: A Case Report.

Appendiceal mucinous neoplasms are rare and can be easily misdiagnosed as adnexal masses. Fertility is a concern in cases requiring cytoreductive surgery involving the ovaries and if hyperthermic intraperitoneal chemotherapy is considered. We present the case of a 35-year-old patient with primary infertility who was suspected to have a hematosalpinx on ultrasonography and magnetic resonance imaging (MRI) but was found to have an appendiceal mucinous neoplasm on laparoscopy. Fertility preservation was offered to this patient. Appendiceal mucinous neoplasms should be considered in the differential diagnosis of patients in their reproductive years presenting with adnexal masses. Fertility preservation should be discussed with these patients, especially when gonadotoxic treatments are planned.

An international Multi-Institutional validation of T1 Sub-staging of intraductal papillary mucinous neoplasm-derived pancreatic cancer.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared to its biologically distinct counterpart, pancreatic intraepithelial neoplasia (PanIN)-derived PDAC. Thus, experts proposed T1 sub-staging for IPMN-derived PDAC. However, this has never been validated. METHODS: Consecutive upfront surgery patients with IPMN-derived PDAC from five international high-volume centers were classified by the proposed T1 sub-staging classification (T1a ≤ 0.5, T1b > 0.5 and ≤1.0, and T1c >1.0 and ≤2.0 cm) using the invasive component size. Kaplan-Meier and log-rank tests were utilized to compare overall survival (OS). A multivariable Cox-regression was used to determine hazard ratios (HR) with confidence intervals (95%CI). RESULTS: Among 747 patients, 69 (9.2%), 50 (6.7%), 99 (13.0%), and 531 patients (71.1%), comprised the T1a, T1b, T1c, and T2-4 subgroups, respectively. Increasing T-stage was associated with elevated CA19-9, poorer grade, nodal positivity, R1-margin, and tubular subtype. Median OS for T1a, T1b, T1c, and T2-4 were 159.0 (95%CI:126.0-NR), 128.8 (98.3-NR), 77.6 (48.3-108.2), and 31.4 (27.5-37.7) months, respectively (p < .001). OS decreased with increasing T-stage for all pairwise comparisons (all p < .05). After risk-adjustment, age > 65, elevated CA19-9, T1b [HR : 2.55 (1.22-5.32)], T1c [HR : 3.04 (1.60-5.76)], and T2-4 [HR : 3.41 (1.89-6.17)] compared to T1a, nodal positivity, R1-margin, and no adjuvant chemotherapy were associated with worse OS. Disease recurrence was more common in T2-4 tumors (56.4%) compared to T1a (18.2%), T1b (23.9%), and T1c (36.1%, p < .001). CONCLUSION: T1 sub-staging of IPMN-derived PDAC is valid and has significant prognostic value. Advancing T1 sub-stage is associated with worse histopathology, survival, and recurrence. T1 sub-staging is recommended for future guidelines.

Comprehensive Characterization of Intraductal Oncocytic Papillary Neoplasm of the Pancreas: A Systematic and Critical Review.

Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a recently recognized pancreatic tumor. Here, we aimed to determine its most essential features with the systematic review tool. PubMed, Scopus, and Embase were searched for studies reporting data on pancreatic IOPN. The clinicopathologic, immunohistochemical, and molecular data were extracted and summarized. Then, a comparative analysis of the molecular alterations of IOPN with those of pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm from reference cohorts (including The Cancer Genome Atlas) was conducted. The key findings from 414 IOPNs were as follows: 1) The male-to-female ratio was 1.5:1. Pancreatic head was the most common site (131/237; 55.3%), but a diffuse tumor extension involving more than one pancreatic segment was described in about 1 out of 5 cases (49/237; 20.6%). The mean size was 45.5 mm. An associated invasive carcinoma was present in 50% of cases (168/336). In those cases, most tumors were pT1 or pT2 and pN0 (>80%), and vascular invasion was uncommon (20.6%). Regarding survival, more than 90% of patients were alive after surgical resection. 2) Immunohistochemical and molecular features were as follows. The most commonly expressed mucins were MUC5AC (110/112; 98.2%) and MUC6 (78/84; 92.8%). Compared with pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, and GNAS were less altered in IOPN (P < .01). Moreover, fusions involving PRKACA or PRKACB gene were detected in all of the 68 cases examined, with PRKACB::ATP1B1 being the most common (27/68 cases; 39.7%). These genomic events emerged as an entity-defining molecular alteration of IOPN (P < .01). Thus, such fusions represent a promising biomarker for diagnostic purposes. Recent evidence also suggests their role in influencing the acquisition of oncocytic morphology. IOPN is a distinct pancreatic neoplasm with specific clinicopathologic and molecular features. Considering the clinical or prognostic implications, its recognition is essential for pathologists and, ultimately, patients' management.

An Incidental Finding of Low-Grade Appendiceal Mucinous Neoplasm in a Case of Borderline Brenner Tumor of the Ovary.

The concurrent presentation of a low-grade appendiceal mucinous neoplasm (LAMN) and a borderline Brenner tumor (BT) of the ovary are exceedingly rare. Brenner tumors stand out as a particularly uncommon form, making up only around 5% of all benign epithelial tumors of the ovary. Among the ovarian Brenner, the borderline subtype is even rarer. Appendiceal neoplasm (LAMN) and right ovarian BT cannot be distinguished due to their anatomical position. LAMN is often an incidental finding and at later stages when left undiagnosed may lead to pseudomyxoma peritonei (PMP). This case describes a postmenopausal woman in her 50s experiencing abdominal pain and bloating for a week. Elevated carcinoembryonic antigen (CEA) levels and imaging suggested a potential right ovarian tumor. Interestingly, it revealed a unique combination of borderline Brenner tumor of the right ovary and low-grade appendiceal mucinous neoplasm.

Appendiceal neoplasms derived from appendiceal tip remnants following appendectomy: a report of two cases.

BACKGROUND: Neoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal "stump". Here, we present two surgical cases of appendiceal neoplasms derived from appendiceal "tip" remnants. CASE PRESENTATION: The first patient was a 71-year-old man who had undergone laparoscopic appendectomy for acute appendicitis 12 years prior. During appendectomy, the appendiceal root was ligated, but the appendix was not completely removed due to severe inflammation. At the most recent presentation, computed tomography (CT) was performed to examine choledocholithiasis, which incidentally revealed a cystic lesion of approximately 90 mm adjacent to the cecum. A retrospective review revealed that the cystic lesion had increased in size over time, and laparoscopic ileocecal resection was performed. Pathology revealed no continuity from the appendiceal orifice to the cyst, and a diagnosis of low-grade appendiceal mucinous neoplasm (LAMN) was made from the appendiceal tip remnant. The patient was discharged without complications. The second patient was a 65-year-old man who had undergone surgery for peritonitis due to severe appendicitis 21 years prior. During this operation, the appendix could not be clearly identified due to severe inflammation; consequently, cecal resection was performed. He was referred to our department with a chief complaint of general fatigue and loss of appetite and a cystic lesion of approximately 85 mm close to the cecum that had increased over time. CT showed irregular wall thickening, and malignancy could not be ruled out; therefore, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological diagnosis revealed mucinous adenocarcinoma (TXN0M0) arising from the remnant appendiceal tip. The patient is undergoing follow-up without postoperative adjuvant chemotherapy, with no evidence of pseudomyxoma peritonei or cancer recurrence for 32 months postoperatively. CONCLUSIONS: If appendicitis-associated inflammation is sufficiently severe that accurate identification of the appendix is difficult, it may remain on the apical side of the appendix, even if the root of the appendix is ligated and removed. If the appendectomy is terminated incompletely, it is necessary to check for the presence of a residual appendix postoperatively and provide appropriate follow-up.

Pancreatoscopy-Guided Endotherapies for Pancreatic Diseases.

Per-oral pancreatoscopy (POP) is a pancreas-preserving modality that allows for targeted pancreatic duct interventions, particularly in cases where standard techniques fail. POP specifically has an emerging role in the diagnosis, risk stratification, and disease extent determination of main duct intraductal papillary mucinous neoplasms (IPMNs). It has also been successfully used for laser ablation of IPMNs in poor surgical candidates, lithotripsy for complex stone disease, and laser stricturoplasty. As experience with POP increases beyond select referral center practices, further studies validating POP efficacy with long-term follow-up will help clarify when POP-guided intervention is most beneficial in relation to surgical intervention.

The Incidental Pancreatic Cyst: When to Worry About Cancer.

Incidental pancreatic cystic lesions are a common challenge encountered by diagnostic radiologists. Specifically, given the prevalence of benign pancreatic cystic lesions, determining when to recommend aggressive actions such as surgical resection or endoscopic ultrasound with sampling is difficult. In this article, we review the common types of cystic pancreatic lesions including serous cystadenoma, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm with imaging examples of each. We also discuss high-risk or worrisome imaging features that warrant a referral to a surgeon or endoscopist and provid several examples of these features. These imaging features adhere to the latest guidelines from the International Consensus Guidelines, American Gastroenterological Association (2015), American College of Gastroenterology (2018), American College of Radiology (2010, 2017), and European Guidelines (2013, 2018). Our focused article addresses the imaging dilemma of managing incidental cystic pancreatic lesions, weighing the options between imaging follow-up and aggressive interventions.

SpyGlass guided PDT for advanced intraductal papillary mucinous neoplasm of the bile tract: A case report and literature review.

Intraductal papillary mucinous neoplasm of the bile tract is a rare biliary tumor characterized by mucin growth within the bile duct. In the early stages, it often presents without significant obstruction, this often leads to its discovery in the advanced stages. We report a case of a 63-year-old female with an intraductal papillary mucinous neoplasm of the bile duct (IPMN-B). The patient had a history of intrahepatic bile duct stones and biliary ascariasis. She gradually developed symptoms such as jaundice and intermittent fever before admission, and a bile duct biopsy confirmed the diagnosis of IPMN-B. Currently, endoscopic photodynamic therapy (PDT) is considered an effective treatment for bile duct cancer. In this case, we performed two sessions of PDT guided by SpyGlass. The patient experienced complete remission postoperatively, and there has been no evidence of tumor recurrence or metastasis in the three years following the procedure.

Occult appendix pathology in patients undergoing colorectal cancer resection and prophylactic appendectomy.

BACKGROUND: The risk-benefit balance of prophylactic appendectomy in patients undergoing left colorectal cancer resection is unclear. The aim of this report is to assess the proportion of histologically abnormal appendices in patients undergoing colorectal cancer resection in a unit where standard of care is appendectomy, with consent, when left-sided resection is performed. METHODS: A retrospective study on a prospectively collected database was conducted in a single tertiary-care center. Overall, 717 consecutive patients undergoing colorectal cancer resection between January 2015 and June 2021 were analyzed. The primary outcome was the proportion of histologically abnormal appendix specimens at prophylactic appendectomy. The secondary outcome was complications from prophylactic appendectomy. RESULTS: Overall, 576/717 (80%) patients had appendectomy at colorectal cancer surgery. In total, 234/576 (41%) had a right-/extended-right hemicolectomy or subtotal colectomy which incorporates appendectomy, and 342/576 (59%) had left-sided resection (left-hemicolectomy, anterior resection or abdominoperineal excision) with prophylactic appendectomy. At definitive histology, 534/576 (92.7%) had a normal appendix. The remaining 42/576 (7.3%) showed abnormal findings, including: 14/576 (2.4%) inflammatory appendix pathology, 2/576 (0.3%) endometriosis, 8/576 (1.4%) hyperplastic polyp, and 18/576 (3.1%) appendix tumors, which encompassed six low-grade appendiceal mucinous neoplasms (LAMNs), three carcinoids, and nine serrated polyps. In the 342 patients who had prophylactic appendectomy, 10 (2.9%) had a neoplasm (two LAMN, three carcinoids, and five serrated polyps). There were no complications attributable to appendectomy. CONCLUSION: Occult appendix pathology in patients undergoing colorectal cancer resection is uncommon when prophylactic appendectomy was performed. However, approximately 3% of patients had a synchronous appendix neoplasm.

The role of biomarkers in the early detection of pancreatic cancer.

Pancreatic surveillance can detect early-stage pancreatic cancer and achieve long-term survival, but currently involves annual endoscopic ultrasound and MRI/MRCP, and is recommended only for individuals who meet familial/genetic risk criteria. To improve upon current approaches to pancreatic cancer early detection and to expand access, more accurate, inexpensive, and safe biomarkers are needed, but finding them has remained elusive. Newer approaches to early detection, such as using gene tests to personalize biomarker interpretation, and the increasing application of artificial intelligence approaches to integrate complex biomarker data, offer promise that clinically useful biomarkers for early pancreatic cancer detection are on the horizon.

Total pancreatectomy in a patient with a dermadrome caused by intraductal papillary mucinous neoplasm: A case report.

INTRODUCTION: Dermadrome is a term coined by combining the words "dermatology" and "syndrome," and it refers to dermatological symptoms that reflect visceral lesions. PRESENTATION OF CASE: Herein, we present the case of an 83-year-old female patient who presented with generalized blistering and erythema during treatment for acute pancreatitis. She was referred to our dermatology department with worsening erythema, although the acute pancreatitis improved. The cause of the erythema was suspected to be drug-induced, infectious, or related to collagen disease; however, the exact cause was unknown. Computed tomography and endoscopic ultrasonography findings revealed a mixed-type intraductal papillary mucinous neoplasm (IPMN). Refractory erythema was suspected to have been caused by a dermadrome due to IPMN. Consequently, she was referred to our department. The main pancreatic duct was dilated along its entire length, and tumor extension was difficult to determine; therefore, a total pancreatectomy was performed. The postoperative course was uneventful, and erythema gradually improved. The histopathological evaluation indicated high-grade dysplasia of the IPMN. DISCUSSION: The patient's skin rash, which did not improve with treatment that included high-dose steroids, began to improve after surgery, and the disease was thought to be a dermadrome caused by IPMN. CONCLUSION: We believe that this is the first reported case of IPMN with a dermadrome that resolved after a total pancreatectomy.

Mucinous appendiceal neoplasms: Report of a case and brief literature review.

INTRODUCTION: Appendiceal tumors are rare neoplasms detected in about 2 % of appendicectomies. The clinical presentation is often unspecific, varying from unspecific abdominal pain or presenting as an acute appendicitis or being asymptomatic. CASE PRESENTATION: We present a case of a patient presenting as an acute appendicitis with a mucocele, and then classified as HAMN. The patient was treated with initial laparoscopic approach and then conversion in laparotomy with appendectomy. Histology demonstrated a high grade appendiceal mucinous neoplasm limited to submucosa (pT3), with concomitant acute phlegmonous appendicitis. The patient was subsequently sent to a referral center where a right hemicolectomy with HIPEC was performed. DISCUSSION: HAMN is a rare entity, only recently classified as a new kind of appendiceal mucinous neoplasm. Due to the supposed higher aggressivity, HAMN must be treated as an appendiceal adenocarcinoma. The treatment of this rare entity is not yet well standardized, because of the rarity of this disease. CONCLUSION: HAMN is a very rare tumor. In the emergency setting, it is mandatory to avoid rupture of the appendix, to minimize the risk of developing pseudomyxoma peritonei. Pathology is essential for further decisions in these patients and plays a very important role in treatment and prognosis.

Active surveillance for low-grade appendiceal mucinous neoplasm (LAMN).

Objectives: Due to the scarcity of low-grade appendiceal mucinous neoplasm (LAMN), there is an absence of systematized guidelines concerning its management, especially after incidental finding on an appendiceal specimen. In this study, we evaluate the active surveillance (AS) strategy adopted for a series of patients diagnosed with LAMN on resection specimens who were considered to have a low risk of pseudomyxoma progression. Methods: Thirty patients were included between April 2014 and July 2021, with a female majority and a median follow-up period of 3.1 years. The inclusion criteria were as follows: LAMN diagnosis on appendiceal specimens, confirmed in an expert center, limited extra-appendiceal mucin resected and localized around the appendix, normal biology (CEA, CA199, CA125) and normal abdominopelvic MRI. AS included physical exam (trocar scar), biology and MRI, 6 months postoperatively, then yearly for 10 years. Results: As an initial surgery, 77 % had an appendectomy as their initial intervention, 17 % had a cecectomy, and 6 % had a right colectomy. After follow-up, 87 % of patients showed no sign of disease progression by MRI, while 13 % progressed to PMP. MRI performed in the first postoperative year predicted the disease prognosis in 97 % of patients. Conclusions: The AS strategy, based on MRI, is a valid option after incidental LAMN diagnosis.

Mucinous neoplasm of the appendix: A case report and review of literature.

BACKGROUND: Appendiceal mucinous neoplasms (AMNs), although not classified as rare, are relatively uncommon tumors most often discovered incidentally during colorectal surgery. Accurate identification of AMNs is difficult due to non-specific symptoms, overlapping tumor markers with other conditions, and the potential for misdiagnosis. This underscores the urgent need for precision in diagnosis to prevent severe complications. CASE SUMMARY: This case report describes the unexpected discovery and treatment of a low-grade AMN (LAMN) in a 74-year-old man undergoing laparoscopic hemicolectomy for transverse colon adenocarcinoma (AC). Preoperatively, non-specific gastrointestinal symptoms and elevated tumor markers masked the presence of AMN. The tumor, presumed to be an AMN peritoneal cyst intraoperatively, was confirmed as LAMN through histopathological examination. The neoplasm exhibited mucin accumulation and a distinct immunohistochemical profile: Positive for Homeobox protein CDX-2, Cytokeratin 20, special AT-rich sequence-binding protein 2, and Mucin 2 but negative for cytokeratin 7 and Paired box gene 8. This profile aids in distinguishing appendiceal and ovarian mucinous tumors. Postoperative recovery was uncomplicated, and the patient initiated adjuvant chemotherapy for the colon AC. CONCLUSION: This case highlights the diagnostic complexity of AMNs, emphasizing the need for vigilant identification to avert potential complications, such as pseudomyxoma peritonei.

Low-Grade Appendiceal Mucinous Neoplasm Causing Equivocal Appendicitis: A Case Report.

Appendicitis is one of the most common diagnoses that general surgeons encounter in practice. An exceedingly rare cause of this disease is neoplasm. We report the case of a 24-year-old female who presented with non-specific right lower quadrant abdominal pain and equivocal findings of appendicitis and pelvic congestion syndrome on CT imaging. After an extensive work-up, the patient underwent a diagnostic laparoscopy with an appendectomy. The appendix appeared grossly normal; however, on a pathologic review of the specimen, a low-grade appendiceal mucinous neoplasm (LAMN) was found. This case is unique in that it demonstrates exclusive management of LAMN laparoscopically. It reinforces the need to approach non-specific abdominal pain from a multidisciplinary perspective and to utilize laparoscopy as a diagnostic/therapeutic modality when other, less invasive, modalities fail to diagnose a patient's pain.

Systematic review on surveillance for non-resected branch-duct intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND: The management of branch-duct type intraductal papillary mucinous neoplasms (BD-IPMN) varies in existing guidelines. This study investigated the optimal surveillance protocol and safe discontinuation of surveillance considering natural history in non-resected IPMN, by systematically reviewing the published literature. METHODS: This review was guided by PRISMA. Research questions were framed in PICO format "CQ1-1: Is size criteria helpful to determine surveillance period? CQ1-2: How often should surveillance be carried out? CQ1-3: When should surveillance be discontinued? CQ1-4: Is nomogram predicting malignancy useful during surveillance?". PubMed was searched from January-April 2022. RESULTS: The search generated 2373 citations. After screening, 83 articles were included. Among them, 33 studies were identified for CQ1-1, 19 for CQ1-2, 26 for CQ1-3 and 12 for CQ1-4. Cysts <1.5 or 2 cm without worrisome features (WF) were described as more indolent, and most studies advised an initial period of surveillance. The median growth rate of cysts <2 cm ranged from 0.23 to 0.6 mm/year. Patients with cysts <2 cm showing no morphological changes and no WF after 5-years of surveillance have minimal malignancy risk of 0-2%. Two nomograms created with over 1000 patients had AUCs of around 0.8 and appear to be feasible in a real-world practice. CONCLUSIONS: For patients with suspected BD-IPMN <2 cm and no other WF, less frequent surveillance is recommended. Surveillance may be discontinued for cysts that remain stable during 5-year surveillance, with consideration of patient condition and life expectancy. With this updated surveillance strategy, patients with non-worrisome BD-IPMN should expect more streamlined management and decreased healthcare utilization.

Premalignant Lesions in the Kidney Transplant Candidate.

End-stage kidney disease patients who are referred for transplant undergo an extensive evaluation process to ensure their health prior to transplant due in part to the shortage of available organs. Although management and surveillance guidelines exist for malignancies identified in the transplant and waitlist populations, less is written about the management of premalignant lesions in this population. This review covers the less common premalignant lesions (intraductal papillary mucinous neoplasm, gastrointestinal stromal tumor, thymoma, and pancreatic neuroendocrine tumor) that can be found in the transplant candidate population. High-level evidence for the management of these rarer premalignant lesions in the transplant population is lacking, and this review extrapolates evidence from the general population and should not be a substitute for a multidisciplinary discussion with medical and surgical oncologists.

Current Status of Treatment among Patients with Appendiceal Tumors-Old Challenges and New Solutions?

The 5th edition of the World Health Organization (WHO) classification of tumors of the digestive system distinguishes four categories of appendiceal tumors (ATs): serrated lesions and polyps, mucinous neoplasms, adenocarcinomas, and neuroendocrine neoplasms (NENs). The differential diagnosis of ATs can be challenging in medical practice, due to their rarity and lack of data from randomized controlled trials on a large, diverse group of patients. ATs are usually noted in specimens obtained during appendectomies due to clinical acute appendicitis. In the European population, most ATs (65%) occur over the age of 50 and among women (56.8%). According to histological type, 54.6% are neuroendocrine tumors (NETs); 26.8% cystic, mucinous, and serous neoplasms; and 18.6% adenocarcinoma not otherwise specified (NOS). On pathologic analysis, most AT findings are benign lesions or small NENs that do not require further therapeutic measures. The presence of appendiceal mucinous neoplasm (AMN) can lead to pseudomyxoma peritonei (PMP). While the multimodal treatment for abdominal malignancies has evolved over the past several decades, the clinical workup and treatment of ATs remain a challenge. Therefore, this review aims to describe the diagnostic possibilities, molecular-based diagnosis, staging, differences in the treatment process, and prognostic factors associated with ATs.