Goblet Cell Carcinoid Research Articles

HPB SO17 - A rare case of Goblet cell adenocarcinoma of appendix presenting as primary ampullary tumour

Abstract Background Goblet cell adenocarcinoma (GCA), formerly known as goblet cell carcinoid,is a rare appendiceal tumour with amphicrine differentiation that has distinct morphologic and clinical features compared to carcinomas seen elsewhere in the gastrointestinal tract. The tumour histologically resembles both carcinoids and adenocarcinomas. It is found in 0.3–0.9 % of appendectomy specimens; hence, ampullary GCAs are exceptionally uncommon. Method A 57-year-old Caucasian male presented with a two-month history of weight loss, pruritus, and dark urine. His blood tests revealed deranged liver enzymes. His past medical history was unremarkable. Abdominal CT identified a double duct sign, no detectable mass. Endoscopic ultrasound (EUS) revealed a dilated biliary system terminating in a slightly enlarged ampulla (15mm) without any obvious mass lesions. Endoscopic retrograde cholangiopancreatography (ERCP) was performed showing a distal common bile duct (CBD) stricture. Cytology samples were negative for malignancy, and stents were placed in the CBD and pancreatic duct (PD). Pancreaticoduodenectomy was advised given the high risk of malignancy. Results Histopathology report showed clusters of goblet-like mucinous cells in an infiltrative pattern, in addition to classic neuroendocrine tumor morphology, reminiscent of goblet cell adenocarcinoma of the appendix, staged as pT3pN1M0. This is consistent with primary ampullary GCA given the normal appendix on preoprative CT imaging. Conclusion To our knowledge, this is the fourth case of ampullary GCA report in medical literature. There is no consensus on adjunct chemotherapy regimen for systemic treatment. Chicago consensus group (2018) recommends following the colorectal cancer pathway for goblet cell adenocarcinoma. In our experience, given the anatomical location of the tumour and the normal appendix, FOLFIRINOX was offered in line with ampullary adenocarcinoma cancer pathway.

The Optimal Approach to Surgical Management of Goblet Cell Carcinoid of the Appendix: A Systematic Review.

Goblet cell carcinoid (GCC) is a rare and poorly understood appendiceal neoplasm, exhibiting mixed histological and aggressive clinical features. Current guidelines recommend right hemicolectomy in all cases, although there is conflicting evidence that appendicectomy alone may be sufficient. This review aims to identify the optimal surgical management for appendiceal GCC. A systematic review was performed by searching MEDLINE, Embase, Scopus and the Cochrane Register of Controlled Trials. Randomised controlled trials, cohort studies or large case series (>5 patients) reporting clinical outcomes for patients undergoing surgical management of GCC of the appendix were included. Outcomes extracted included participant and tumour characteristics, type of surgery and survival data. A total of 1341 studies were retrieved. After duplicate removal, 796 titles were screened for relevance prior to abstract and full text review. A total of six studies were included for analysis, comprising 3177 patients-1629 females and 1548 males. The median age ranged from 51 to 72 years. A total of 2329 patients underwent right hemicolectomy, while 824 were treated with appendicectomy only. Overall, the included studies report increased survival in patients undergoing right hemicolectomy compared to appendicectomy alone. A meta-analysis was not possible due to insufficient data reported in the published literature to date. There is no consensus regarding the optimal surgical management of appendiceal GCC, as outcomes-based data comparing surgical interventions are lacking. It is possible that some patients with favourable features are overtreated. The absence of robust evidence to support a more conservative approach means that right hemicolectomy remains the standard of care for all patients, in keeping with current international guidelines. The rarity of this condition and limited data in the published studies remain barriers to evidence-based best clinical practice.

Appendiceal goblet cell adenocarcinoma newly classified by WHO 5th edition: a case report (a secondary publication)

BackgroundAppendiceal goblet cell adenocarcinoma (AGCA) is a newly proposed cancer type in the 5th edition of the WHO Classification of Tumours in 2019. We experienced this rare form of appendiceal primary neoplasm.Case presentationAn 85-year-old male presented a positive fecal occult blood test. A series of imagings revealed a type 1 tumor, located on the appendiceal orifice. The subsequent biopsy made the diagnosis of signet-ring cell carcinoma. Consequently, he underwent the laparoscopic-assisted ileocecal resection. Initially, the tumor was suspected to be a Goblet cell carcinoid (GCC). There was a discrepancy between the histological and immunostaining findings: the tumor cells exhibited morphological similarities to GCCs, however displayed limited staining upon immunostaining. Ultimately, we concluded that the tumor should be classified as AGCA, by following WHO 5th Edition. AGCA represents a newly categorized subtype of adenocarcinomas. Because of our preoperative suspicion of malignancy, we performed tumor resection with regional lymph node dissection, despite the fact that most appendiceal malignant tumors are typically identified after an appendectomy.ConclusionWe experienced a case that provides valuable insights into the comprehension of AGCA, a recently established pathological entity in the WHO 5th Edition. This article is an acceptable secondary publication of a case report that appeared in Azuma et al. (J Jpn Surg Assoc 83:1103–1108, 2022)

Goblet cell tumors of the appendix: Clinical and molecular features.

223 Background: Goblet Cell tumors (GCTs) of the appendix are a rare, distinct, and under studied malignancy. Since 2019 the preferred World Health Organization (WHO) terminology is Goblet Cell Adenocarcinoma (GCA), but previously many terms have been used to describe these tumors including Goblet Cell Carcinoid and Adenocarcinoma ex goblet cell carcinoid as these tumors have a histological appearance that blends neuroendocrine and adenocarcinoma features. Historically goblet cell tumors have been considered one of the more aggressive subtypes of appendiceal cancer, but limited data exists and is mostly in the form of case reports. Here we present the retrospective analysis of a large single institution cohort. Methods: The internal database of the University of Texas MD Anderson Cancer Center (MDACC) was queried to identify all patients diagnosed with goblet cell appendiceal tumor. Patients were classified to two different histopathological groups, GCA (n=220) and GCA with signet ring adenocarcinoma (SRA) (n=146). Clinical, histopathological, and molecular data were extracted from the database in semi-automated fashion. Survival analysis were performed using Kaplan Meier methodology. Results: 366 patients with GCTs were identified from 1986 to 2022. 132 (36%) patients were seen during the last five years, with an average of 26 patients per year. Median follow up time was 54 months, while median age at diagnosis was 57 years. Tumor grade data was available for 294 patients. 95% of the patients had high grade tumors (moderately, moderately to poorly and poorly-differentiated) (n= 278), and 5% had low grade tumors (well and well to moderately-differentiated (n=16). The median overall survival was 85 months, and significantly different between the two groups, 118 months for the GCA group and 57 months for the GCA with SRA (p= 0.003). Lymph node (LN) status was known for 168 patients, rate of LN involvement was 53% (n=89) and significantly different between the two groups with 41% (n=39) for GCA and 68% (n=50) for GCA with SRA (p= <0.0006). The internal database of MDACC was queried for LN status of Mucinous adenocarcinoma (MA) (n=242) and SRA (n=104) for comparison purposes, rate of LN positivity was 13% in MA and 76% in SRA. Node positive patients had significantly worse overall survival with median overall survival of 51 months vs 85 months for node negative patients (p<0.004). By multivariate analysis, both LN status and SRA component were independent predictors of overall survival. 107 patients had gene mutation analysis tested, TP53, SMAD4, GNAS and KRAS were the most commonly mutated with 13%, 9%, 4%, and 3% respectively. Conclusions: This study highlights the heterogenicity of GCTs of the appendix and the importance of the histopathological classification in this distinct entity. GCT are much more likely to spread to LN and have a distinct somatic mutation profile relative to MA.

Goblet Cell Adenocarcinoma of the Appendix: Diagnosis, Prognosis and Nomenclature

Goblet cell adenocarcinoma (GCA) is a new name for goblet cell carcinoid used by the fifth edition of the World Health Organization Classification of Tumors of the Digestive System published in 2019. This name change put an end to the years’ name confusion and led to the simplification and standardization of the diagnostic criteria and grading system for this unique epithelial neoplasm almost exclusively occurring in the appendix. This is extremely important because accurate diagnosis and grading are essential to patient management and prognostication. Under this new name, GCA is recognized to have low-grade and high-grade components with variable proportions. As such, the presence of the low-grade components is required for the diagnosis, but the proportion of the high-grade components dictates the prognosis. With regard to the nomenclature, GCA does not seem to be an ideal name for this tumor because goblet cells are apparently not the cell origin nor the unique cell population of the tumor. While the histogenesis remains ambiguous, the name “crypt cell carcinoma” would appear more appropriate for this tumor, as it would at least emphasize the crypt-like architecture and cellular composition of the tumor nests.

A Case of Goblet Cell Carcinoid Coexisting with a Low-Grade Mucinous Neoplasm of the Appendix

A Case of Goblet Cell Carcinoid Coexisting with a Low-Grade Mucinous Neoplasm of the Appendix

Clinicopathological analysis and surgical strategy of primary appendiceal neoplasms

Objective: To investigate the clinicopathological features, surgical methods and prognosis of primary appendiceal neoplasms. Methods: A descriptive case series study was performed. Clinical data of patients diagnosed with primary appendiceal neoplasms in Peking University First Hospital from 2006 to 2017 were retrospectively analyzed. Patients who underwent surgery and were confirmed as appendiceal neoplasms by postoperative pathology were included. Cases of cecal tumor invading the appendix and other organ tumors implanting in the appendix and cases of recurrent appendix tumors were excluded Pathological classification was based on the 4th edition of the WHO classification of digestive tract tumors (2010 edition), and the efficacy of operation methods of low grade appendiceal mucinous neoplasm (LAMN) were analyzed. Results: A total of 115 patients were enrolled, including 52 males and 63 females with a median age of 59 (51, 71) years. Clinical symptoms usually manifested as dormant pain in the right lower quadrant, migrating right lower abdominal pain, fever and bloating. Twenty-four cases were accidentally discovered during surgery, and 21 cases were found by physical examination. The preoperative diagnosis rate of CT and ultrasound was 40.2% (43/107) and 25.5% (24/94) respectively. The postoperative pathological types contained 83 cases of LAMN, 12 cases of mucinous adenocarcinoma, 9 cases of appendiceal neuroendocrine neoplasms (aNEN), 2 cases of mucinous adenocarcinoma with signet ring cells, 3 cases of serrated adenoma, 2 cases of goblet cell carcinoid, 2 cases of lymphoma, 1 case of leiomyoma and 1 case of schwannomas. All the patients underwent surgical resection, including 41 cases of appendectomy, 21 cases of partial cecectomy, 48 cases of right hemicolectomy, and 5 cases of combined organ resection due to appendiceal tumor infiltration or dissemination. Eighteen cases were diagnosed with pseudomyxoma peritonei (PMP) during operation. A total of 98 patients were enrolled for follow-up. The median follow-up time was 58 (5-172) months. The 5-year disease-free survival (DFS) rate was 84.5% and 5-year overall survival (OS) was 88.2%. Multivariate analysis revealed that high-grade malignancy tumors (HR=25.881, 95% CI: 2.827-236.935, P=0.004) and PMP formation (HR=42.166, 95% CI: 3.470-512.439,P=0.003) were independent risk factors for prognosis. Patients undergoing right hemicolectomy presented longer operation time, more blood loss and higher morbidity of complication as compared to those undergoing appendectomy and partial cecectomy (all P<0.05), while no significant differences in 5-year DFS (P=0.627) and 5-year OS (P=0.718) were found. Conclusions: Primary appendiceal neoplasms usually have no typical features, accompanied with low preoperative diagnosis rate. The common pathological types are LAMN, mucinous adenocarcinoma and aNEN. Appendectomy or partial cecectomy for LAMN may achieve satisfactory prognosis. High-grade malignancy tumors and PMP formation are independent risk factors for prognosis.

Goblet cell adenocarcinoma of the appendix: An incidental finding of a rare tumor which was recently renamed in 2019 World Health Organization classification update

Abstract Introduction/Objective Goblet cell adenocarcinoma (formerly goblet cell carcinoid) is a rare tumor almost exclusively involving the appendix. It is an amphicrine tumor consisting of both epithelial and neuroendocrine elements containing goblet cells. In the 2019 WHO classification update, GCC was reclassified as goblet cell adenocarcinoma of the appendix as it is recognized to have predominantly mucin secreting cells and a minor neuroendocrine component. Methods/Case Report A 72 year old,morbidly obese male presented with a 2 week history of abdominal pain and bilious vomiting. Imaging revealed a peri-appendiceal abscess. Due to the chronicity of his symptoms, he was treated conservatively with drainage of the abscess and intravenous antibiotics. He responded well and underwent elective laparoscopic appendectomy; at which time, the appendix appeared grossly unremarkable, measuring 5.1 x 0.9 x 0.3 cm with a wall thickness of 0.5 cm. Microscopically small nests and clusters of goblet cells circumferentially invaded dense collagenous stroma in the appendiceal wall. The neoplastic cells had large mucin vacuoles and small basally located nuclei. The cells were positive for CK20, CDX2, CD56, synaptophysin and focally positive for chromogranin. Ki-67 was 10%. CK7 was negative. These tumors are now graded and staged similar to colonic adenocarcinomas according to the 5 th edition of the World Health Organization Classification of Tumors - Digestive System Tumors. Results (if a Case Study enter NA) NA Conclusion This case demonstrates that this rare tumor may be an incidental finding in an elderly patient presenting with appendicitis; accurate diagnosis of this rare tumor may require submission of the entire appendix for microscopic evaluation.

EP.FRI.247 Incidence and diversity of the primary appendiceal tumours in patients presenting with acute appendicitis: Our Experience

Abstract Background Primary appendiceal tumours are rare. Our experience with the incidental primary appendiceal tumours and their histological diversity. Patients and Method Operative and pathological databases of appendicectomies for presumed diagnosis of acute appendicitis between January 2015 and December 2020 were interrogated. Clinicopathological data were collected and analysed to present the incidence of primary appendiceal tumours, histopathological diversity and outcomes. Results 1908 appendicectomies were performed over the study period. 22 patients with primary appendiceal tumours (incidence rate 1.2%) had a mean age of 45.6(15-97) years and M:F ratio of 1:1.2. Only six patients (27.3%) had appendiceal tumour suspected either before or during surgery. 91% of the patients underwent laparoscopic appendicectomy. Right hemicolectomy was performed as the first intervention and further surgical procedure in 1 and 5 patients respectively. Histological tumour types included carcinoid(10), adenocarcinoma(4), low grade appendiceal mucinous neoplasm(4) mucinous adenocarcinoma &amp; carcinoid(1), goblet cell carcinoid(2) and dysplastic serrated polyp(1). Tumours were located at the tip(10), body(10) and base(2). Median tumour size was 13(2.0-55.0) mm. Median hospital stay was 1.5(0-25) days. The mean survival was 30.9(2.80-73.70) months. Disease related death was a 97-year-old lady with a T4 adenocarcinoma and peritoneal disease who stayed for 25 days and offered palliative supports post appendicectomy. Conclusion Primary appendiceal tumours are diverse in histological types and are of varying prognosis. Appendicectomy alone seemed to be adequate in most cases with early-stage disease. Further surgery such as right hemicolectomy was required for adenocarcinoma and other high-grade tumours.

TP9.2.22A six year retrospective study of appendicular neoplasms and review of literature

Abstract Aims The aim of this study was to evaluate the incidence of appendiceal neoplasm, identify possible association of pre and intra-operative factors associated with it, and to determine its clinical significance. Methods Using pathological reports from surgical specimens of appendix from January 2015 to September 2020, a single centre retrospective analysis was performed. Medical records of patients, pre-operative investigations, intra operative findings, histological reports and post operative management were evaluated. Results The incidence of appendiceal neoplasms was 2.33% (65/2791). They consisted of Neuroendocrine tumor (NET) in 35(53.85%), followed by Low grade mucinous neoplasm (LAMN) in 23(35.38%), Goblet cell carcinoid in three (4.62%), mucinous cystadenoma 2(3.08%), one (1.54%) adenocarcinoma and one (1.54%) metastasis. Appendicitis was the most common indication for surgery. 46(70.77%) patients had emergency surgery. 89.13% emergency surgeries was appendicectomy, NET being the most common tumor in 60.87%. 19(29.23%) patients had elective surgery, all had pre operative radiological investigation, LAMN being most common. Only five (7.69%) patients had intra operative suspicion of tumor. Ten patients required second procedure in the form of right hemicolectomy in nine, and cytoreducetive surgery in one. All patients were followed up as per national guidelines. Conclusions The incidence of appendiceal neoplasms though low, has been steadily rising. Its diagnosis is rarely evident on pre operative radiological investigations. Surgeons should be aware of these neoplasms and its frequent association with emergency appendicectomies done for suspected acute appendicitis.

S1737 Goblet Cell Adenocarcinoma: A Rare and Aggressive Appendiceal Neoplasm

Introduction: Goblet cell adenocarcinoma (GCA) is a rare and unique appendiceal neoplasm, containing features of both adenocarcinoma and neuroendocrine tumors (NETs). Also termed "goblet cell carcinoids" and previously considered a low-grade malignancy, these tumors are now known to be much more aggressive than traditional carcinoid tumors due to coexistence of high grade adenocarcinoma. In fact, up to 40% of cases present after development of distant metastasis, most commonly to the peritoneum. This has led to pressure for updated nomenclature removing the term "carcinoid" to prevent confusion and potential for incorrect management. Case Description/Methods: A 69-year-old Filipino male with minimal past medical history presented with a four day history of sharp, bloating-type abdominal pain and difficulty passing gas. He denied any other symptoms, specifically nausea, vomiting, constipation or diarrhea. Screening colonoscopy performed 3 years prior with intubation of the terminal ileum was normal. CT of the abdomen/pelvis demonstrated a small bowel obstruction due to a mass, appearing to arise from the terminal ileum, encompassing the cecum and appendix. Colonoscopy was requested, however after discussion with colorectal surgery service, the decision was made to proceed directly to surgical resection, given likelihood of malignancy. Pathology revealed goblet cell adenocarcinoma with peritoneal metastasis, consistent with stage 4B (T4b N2 M1b). Discussion: Goblet cell adenocarcinomas are more aggressive and have a worse prognosis than NETs. Therefore, they must be staged and treated as appendiceal carcinomas. The mixed histology of these tumors, has led to misdiagnosis and poor outcomes. Given the rapid spread of these tumors, a recent normal screening colonoscopy should not preclude prompt investigation of abdominal symptoms in at-risk patients, to include cross-sectional imaging, because surgical resection remains the primary curative treatment strategy. Furthermore, if suspected, preoperative colonoscopy for biopsy should not delay surgical resection. Current debate exists regarding extent of surgical resection required for Stage 1-2 GCAs. Additional treatment strategies for Stage 3-4 GCAs include 5-fluorouracil based adjuvant chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC). The low five-year survival, 57% for Stage 3 and 19% for Stage 4, emphasize the importance of early diagnosis and treatment.Figure 1.: A. CT abdomen/pelvis without contrast demonstrating a diffusely dilated, air-filled gastrointestinal tract extending from the stomach through the rectosigmoid colon. No transition point or obstruction noted. B. CT abdomen/pelvis with rectal contrast demonstrating an interposition of the hepatic flexure of the colon posterior and medial to the right lobe of the liver. No evidence of obstruction or strangulation noted. C. Endoscopy demonstrating a twisted, almost volvulus-like appearance at the splenic flexure, though without clear transition points.

S1783 Recurrent Metastatic Appendiceal Adenocarcinoma Presenting as Non-Specific Colitis – A Case Report

Introduction: Malignancies of the appendix are rare and there is a known association of appendicular carcinoid of the appendix and Crohn's disease. Appendicular carcinoid can be mixed with mucinous adenocarcinoma in both primary and metastatic lesions. We present an unusual case of a patient who presented with nonspecific colitis as a manifestation of recurrent metastatic appendiceal adenocarcinoma. Case Description/Methods: A 57-year-old male patient presented with 2 weeks of left lower quadrant pain, diarrhea, and hematochezia. Two years prior to this presentation, he had a perforated appendicitis due to poorly differential adenocarcinoma and goblet cell carcinoid. He was then found to have peritoneal metastasis treated with omentectomy, right hemicolectomy, multiple peritonectomy, and hyperthermic intraperitoneal chemotherapy. He also had multiple intra-abdominal abscesses requiring drainage and a Colo-cutaneous fistula requiring closure. A CT scan showed distal sigmoid colon and rectal thickening. Colonoscopy with biopsies of the terminal ileum showed mild acute inflammation, atypical submucosal glands suspicious for mucinous adenocarcinoma and acute colitis of the entire colon and rectum. After ruling out infectious etiologies, he was started on a prednisone taper with significant improvement in his symptoms. He was then referred to an outside institution for surgical considerations. However, he continued to have intermittent abdominal pain workup revealed a new peritoneal nodule consistent with his prior adenocarcinoma. He was given FOLFOX and bevacizumab for chemotherapy for metastatic disease as he was not a surgical candidate. Discussion: Appendicular carcinoid can be associated with Crohn’s colitis and this has been reported in the literature. This a unique case in which patient had a nonspecific inflammatory colitis which responded well to corticosteroid treatment and imaging identified recurrence of appendicular mucinous adenocarcinoma. If infectious etiologies for non-specific colitis have been excluded, thorough evaluation needs to be performed to rule out metastatic disease in patients with appendicular adenocarcinoma and/or carcinoid as treatment options can vary.

Incidental detection of goblet cell carcinoid in appendix‐ a case report

Incidental detection of goblet cell carcinoid in appendix‐ a case report

Appendiceal Neoplasms: Diagnosis, Management and Follow-up

Appendicectomy is one of the most performed surgical procedures. Neoplasms of the appendix are identified in approximately 1% of appendiceal specimens, and the incidence seems to be rising. The aim of this review was to summarize the current data on these neoplasms, focusing on the recent classification, clinical manifestations, management, and follow-up of such patients, which remain under debate. A literature search was performed using the database PubMed. The keywords used were related to appendiceal neoplasms, mucocele, pseudomyxoma peritonei and treatment. Records without abstracts, case reports, opinion articles and experimental studies were excluded. The appendix tumors can be classified between epithelial or nonepithelial. The epithelial variant is composed by mucinous neoplasms, nonmucinous adenocarcinoma, and signet ring cell tumors; instead, neuroendocrine tumors, lymphoma, and sarcoma are included in nonepithelial neoplasia. Goblet cell carcinoids share characteristics of both epithelial and nonepithelial tumors. The clinical presentation can be variable and the algorithm for evaluation and treatment is complex. Treatment is based on stage and histology. Our intention is to clarify some questions and help the surgeon in operative decisions, treatment strategies, and patient counseling. Doi: 10.28991/SciMedJ-2021-0303-9 Full Text: PDF

The new WHO classification of gastrointestinal neuroendocrine tumors and immunohistochemical expression of somatostatin receptor 2 and 5.

The 2019 World Health Organization (WHO) classification of gastrointestinal tumors defines well-differentiated grade 3 neuroendocrine tumors, the mixed neuroendocrine-non-neuroendocrine tumors (MiNENs) and classifies goblet cell carcinoid as goblet cell adenocarcinoma. The expression of somatostatin receptors (SSTRs) is the foundation for somatostatin analogue therapy. At present, there are only a few studies that have analyzed the immunohistochemical reactivity of SSTRs in gastrointestinal neuroendocrine neoplasms (NENs). The aim of the present study was to evaluate the immunohistochemical expression of SSTR2 and SSTR5 in gastrointestinal NENs and goblet cell adenocarcinomas and the correlation of these markers with clinical and morphological factors. The study included 67 patients with NENs and 4 patients with adenocarcinoma ex-goblet cell carcinoid diagnosed between January 2008 and December 2018. Tumors were reclassified according to the 2019 WHO classification. Immunohistochemical staining for chromogranin A, synaptophysin, Ki-67, p53, SSTR2, and SSTR5 were performed in all the cases. The results showed that, G1 and G2 neuroendocrine tumors were more common SSTR2-positive in comparison with G3 carcinomas (P<0.0001). In addition, 33.3% of neuroendocrine carcinomas and 2 cases of low-grade adenocarcinoma ex-goblet cell carcinoid were SSTR2-positive. Neuroendocrine carcinomas had significantly lower SSTR2 and SSTR5 expression compared with well-differentiated neuroendocrine tumors (P=0.0130; P=0.0437, respectively). The SSTR2 expression in the early tumor stages was 100%, more often than in advanced stages (55.6%; P=0.0011). The results demonstrated the decrease in SSTR2 expression with increasing malignancy and tumor stage. The SSTR2-positive expression in neuroendocrine carcinomas and adenocarcinoma ex-goblet cell carcinoid provides evidence for the benefits of somatostatin analog treatment associated with surgery and chemotherapy.

New insights in the pathology of peritoneal surface malignancy.

Pathology is central to the management of peritoneal surface malignancy. This article highlights some recent advances that have had an impact on patient management or could do so in the near future. Malignant peritoneal mesothelioma, particularly the epithelioid subtype, is amenable to radical therapy in selected cases, and factors such as ki67 proliferation index, expression of BAP1 and mutation in CDKN2A show promise as prognostic indicators. Our understanding of multicystic mesothelioma has improved in recent years; it is a true neoplasm for which surgery may be indicated. Serous carcinomas involving the peritoneum are now known to originate from tubal epithelium. They are of two distinct types, high grade and low grade, which are now recognized as different neoplasms with distinctive features, oncogenesis and behavior. Pseudomyxoma peritonei (PMP) is an unusual condition that usually arises from an appendiceal mucinous neoplasm. Recent consensus in the classification and nomenclature of these lesions is discussed, including the distinction between low grade and high grade appendiceal mucinous neoplasms (HAMN), and the diagnostic criteria for appendiceal adenocarcinoma. PMP is divided into four prognostic groups: acellular mucin, low grade mucinous carcinoma peritonei, high grade mucinous carcinoma peritonei, and high grade mucinous carcinoma peritonei with signet ring cells. The pseudomyxoma microbiome is a promising area for clinical intervention but has been the subject of little research activity. Goblet cell adenocarcinoma (previously known as 'goblet cell carcinoid') is a distinctive type of appendiceal adenocarcinoma. Its behavior correlates with histologic features, but no general consensus for classification has been reached.

Histologic and Racial/Ethnic Patterns of Appendiceal Cancer among Young Patients.

Appendiceal cancer incidence among individuals age < 50 years (early-onset appendiceal cancer) is rising with unknown etiologies. Distinct clinicopathologic/demographic features of early-onset appendiceal cancer remain unexplored. We compared patterns of appendiceal cancer among individuals by age of disease-onset. Using the NIH/NCI's Surveillance, Epidemiology, and End Results program data, we identified individuals age 20+ years diagnosed with appendiceal cancer from 2007 to 2016. Cochran-Armitage trend tests and multinomial logistic regression models were used to examine age-related differences in clinicopathologic/demographic features of appendiceal cancer. We identified 8,851 patients with appendiceal cancer during the 10-year study period. Histologic subtype, tumor grade, stage, sex and race/ethnicity all significantly differed by age of appendiceal cancer diagnosis. After adjustment for race/ethnicity, sex, stage, insurance status, and tumor grade, young patients were 82% more likely to be Hispanic [OR, 1.82; 95% confidence interval (CI), 1.48-2.25; P < 0.001] and 4-fold more likely to be American Indian or Alaska Native (OR, 4.02; 95% CI, 1.77-9.16; P = 0.0009) compared with late-onset cases. Patients with early-onset appendiceal cancer were also 2- to 3.5-fold more likely to be diagnosed with neuroendocrine tumors of the appendix (goblet cell carcinoid: OR, 1.96; 95% CI, 1.59-2.41; P < 0.0001; carcinoid: OR, 3.52; 95% CI, 2.80-4.42; P < 0.0001) compared with patients with late-onset appendiceal cancer. Among patients with neuroendocrine tumors, early-onset cases were also 45% to 61% less likely to present with high-grade (III-IV) tumors. Approximately one in every three patients with appendiceal cancer is diagnosed before age 50 years in the United States. Appendiceal cancer in young patients is classified by distinct histologic and demographic features. Early-onset appendiceal cancer determinants can inform discovery of risk factors and molecular biomarkers of appendiceal cancer in young patients, with implications for appendiceal cancer prevention, detection, and treatment.

Neuroendocrine neoplasms of the appendix: Characterization of 335 patients referred to the Copenhagen NET Center of Excellence

IntroductionNeuroendocrine neoplasms (NEN) of the appendix are often incidentally discovered after appendectomy. Appropriate management is debated. The purpose was to characterize a cohort of 335 appendix NEN and evaluate the risk of recurrence. MethodsRetrospective collection of data from 335 patients referred to the Neuroendocrine Tumor Center at Rigshospitalet 2000–2019. Appendix goblet cell carcinoids and mixed neuroendocrine non-neuroendocrine neoplasms were excluded.Patients were followed until December 31st, 2019. No patients were lost to follow-up. ResultsSixty-three percent of the patients were female. The median (range) age at diagnosis was 34 (9–92) years. Median follow-up was 66 (1–250) months. Median tumor size was 7 (1–45) mm with 10 (3%) tumors >20 mm. In 18 specimens (5%) resection margins were positive. Mesoappendiceal invasion was found in 113 (35%). Sixty-three (19%) patients underwent right-sided completion hemicolectomy (RHC) after appendectomy according to ENETS guidelines. Among these, 11 (17%) had lymph node metastases in the resected tissue. Further, one patient who underwent initial RHC due to colonic adenocarcinoma had lymph node metastases.All lymph node metastases were detected in patients with serotonin positive tumors. No patients with glucagon positive tumors (n = 85) had lymph node metastases. Mesoappendiceal invasion >3 mm and positive resection margins were associated with presence of lymph node metastases. No recurrences were recorded. ConclusionFollowing ENETS guidelines may lead to overtreatment of patients with respect to completion RHC. The risk of over- and undertreatment needs to be further evaluated.

Neuroendocrine neoplasms of the digestive system- current classification and terminology

The system of classification and terminology of neuroendocrine neoplasms (NENs), updated in 2017 by AJCC and in 2019 by WHO, is now recommended for general use. This article is a review of this classification with respect to NENs of the digestive tract. Within the new system, two categories of neuroendocrine neoplasms of the digestive system were introdu­ced, differing in morphology, clinical course and treatment, as based on differentiation and histological maturity grading (G). Among NENs of the digestive tract, well differentiated neuroendocrine tumours, with Ki-67 proliferation index below 20%, NET G1 and NET G2, histologically resembling normal neuroendocrine cells were distinguished. Neuroendocrine neoplasms with Ki-67 above 20% – termed neuroendocrine carcinoma NEC (poorly differentiated carcinoma G3) – were found to be heterogeneous. In every organ of the digestive tract a limited group of well differentiated tumours with Ki-67 above 20%, but typically less than 55% (well differentiated high grade NET G3) was distinguished. The remaining poorly differentiated neuroendocrine neoplasms with Ki-67 above 20%, usually over 55%, were classified as NEC (high grade neuroendocrine carcinoma). Within NEC, two groups were distinguished – large cell and small cell carcinomas. By introducing this new classification based on clinical and molecular research, any confusion between NET G3 and NEC is avoided. NEC, goblet-cell carcinoid of the appendix and MiNEN, which should be classified according to criteria applied to adenocarcinomas of their respective organs of the digestive system, are not discussed.

Extraappendiceal goblet cell carcinoid of the transverse colon

Goblet cell carcinoids (GCC) are a rare subgroup of neuroendocrine tumours which exhibit mixed endocrine and exocrine features and are almost exclusively localised to the appendix. A few cases of extraappendiceal GCC have been reported in the literature however these are exceedingly rare. They are biologically aggressive tumours that are believed to arise from pluripotent intestinal epithelial crypt base stem cells. Given their rarity, no guidelines currently exist for the management of extraappendiceal GCC, however treatment for GCC’s is generally based on their tumour stage in line with staging for typical adenocarcinomas. This case gives an account of a colonic goblet cell carcinoid within the transverse colon encountered in a 66-year-old male. A literature search did not identify any previous documented cases of a GCC at this location.