Goblet Cell Carcinoid Tumor Research Articles

Treatment patterns and outcomes in goblet cell carcinoid tumors of the appendix.

Goblet cell carcinoid (GCC) tumors of the appendix are a rare malignancy. We aim to examine the overall survival per stage and the relationship between different treatment modalities and outcomes for patients with GCC tumors of the appendix. We identified patients with GCC tumors of the appendix from the National Cancer Database. The main outcome was overall patient survival and cox proportional hazard models were used to ascertain predictors of survival. There were 2552 patients identified. The median age of diagnosis was 57 (interquartile range: 49-65) and 52.3% of patients were female. The 5-year survival for Stage I disease was 91.1% (95% confidence interval [CI]: 82.2%-95.7%), for Stage II disease was 90.5% (95% CI: 85.8%-93.7%), for Stage III disease was 57.0% (95% CI: 45.0%-67.3%), and for Stage IV disease was 18.9% (95% CI: 9.3%-31.0%). In a Cox proportional hazard model, older age (hazard ratio [HR]: 1.1; 95% CI: 1.03-1.12; P < .001), lymph node metastasis (HR: 6.9; 95% CI: 2.76-17.01; P < .001), and positive surgical margins (HR: 2.9; 95% CI:1.13-7.26; P = .003) were associated with worse overall survival for Stages I to III disease while only older age (HR: 1.03; 95% CI: 1.002-1.06; P = .04) was associated with worse overall survival for Stage IV disease. Patients with GCC tumors of the appendix who have the nonmetastatic disease have a high 5-year survival. We have identified several prognostic factors for GCC.

1589 Unusual Presentation of Adenocarcinoma Ex Goblet Cell Carcinoid

INTRODUCTION: Ex Goblet cell carcinoid (eGCC) is a type of goblet cell carcinoid tumor, characterized by both endocrine and exocrine features, that has carcinomatous growth patterns. The classical presentation is compatible with symptoms of acute appendicitis. However, other signs and symptoms such as bowel obstruction, GI bleed and less commonly mesenteric adenitis or iron deficiency have been reported. CASE DESCRIPTION/METHODS: A 72 year old man with a recent hospitalization due to symptomatic anemia, presented to the ED complaining of diffuse abdominal pain for the past 3 weeks. He also reported nausea and emesis for 12 hours. At the previous admission, a CTE (Figure 1) showed thickening of the TI and an EGD was unremarkable. A colonoscopy was recommended, but it was scheduled for completion as an outpatient. At this admission, his hemoglobin was within normal limits, however his abdominal pain and nausea were persistent despite medical treatment. A repeated CT abdomen showed the same TI thickening with an associated new SBO (Figure 2). General surgery was then consulted and the patient underwent an exploratory laparotomy. Intraoperative findings showed possible carcinomatosis, and thence an ileocolectomy and ileocolostomy were performed. Pathology findings were compatible with adenocarcinoma ex goblet cell carcinoid of the appendix (Figure 3), and for this reason, he was referred to oncology for further management. DISCUSSION: GCC can be classified into 3 groups according to the presence of adenocarcinoma component and its degree of differentiation which directly correlates with its prognosis. Group A exhibits only pure goblet cell carcinoid cells; group B shows goblet cells with signet ring cells, and group C presents with goblet cell cells with a component of adenocarcinoma. eGCC corresponds with group C, which is the type presented in our case. Most patients have metastatic disease at the time of diagnosis, estimated in 60% to 91% of the cases. Due to the rarity of this type of tumor, currently there are no guidelines for treatment. However, the main approach is based on surgical resection of the appendix versus right hemicolectomy if the tumor is not confined to the submucosa. In terms of adjuvant treatment, FOLFOX/FOLFIRI are currently being used in most institutions. We present this patient due to its rarity and unusual presentation. Furthermore, we would like to incentivize future researches that can focus on implementing treatment guidelines for this tumor, due to its associated poor prognosis.

1483 Full Thickness Resection Device for the Removal of a Submucosal Sigmoid Carcinoid Tumor

INTRODUCTION: Colonic neuroendocrine tumors (NETs) are rare neoplasms, but they carry the worse prognosis. Management of these tumors is difficult and may result in repeated interventions and prolonged surveillance. Endoscopic Full Thickness Resection (FTR) is not currently included in the guidelines for management of NETs. This case describes a technically and histologically successful FTR of a sigmoid goblet cell carcinoid tumor. CASE DESCRIPTION/METHODS: A 61-year-old male presents for screening colonoscopy and was found to have an 8 mm submucosal mass in the distal sigmoid. Pathology of biopsies showed hyperplastic colonic mucosa with marked reparative stromal and epithelial changes and mixed features of prolapse. He was referred to our institution for EUS of the submucosal lesion, which revealed hypoechoic submucosal lesion in distal sigmoid measuring 7.4 × 4.7 mm. FNA was attempted but unsuccessful as the mass was small and mobile. Therefore, decision was made to perform endoscopic mucosal resection (EMR). Pathology on EMR of sigmoid lesion revealed goblet cell carcinoma. Deep and lateral margins were positive. Chromogranin A level was mildly elevated. He was referred to surgical oncology who recommended 3 month surveillance colonoscopy given low Ki index. CT Scan of Abdomen and Pelvis as well as Octreotide scan were both negative for distant metastases. At 3-month follow up colonoscopy, the decision was made to use Full Thickness Resection Device (FTRD) of the sigmoid lesion given positive margins. Pathology of FTRD was consistent with neural sheath tumor and deep and lateral margins were negative. Repeat colonoscopy revealed well healed scar at site of FTRD and cold biopsies around the scar were benign. He will follow up in 3 years for repeat colonoscopy. DISCUSSION: Primary colonic neuroendocrine tumors are rare but are generally more aggressive and carry the worst prognosis dependent on stage. Current consensus guidelines for the management of local regional NETs recommend endoscopic resection via polypectomy, EMR or endoscopic submucosal dissection. There have only been a few reported cases of the use of FTRD to treat submucosal carcinoid tumors in the colon. Success rates for endoscopic full thickness resection of gastric tumors has been described in the literature with success rates of up to 100%. High success rates of FTRD on colorectal lesions, not NETs, have also been noted. Given this, FTRD should be considered as a more definitive modality for treatment involving submucosal carcinoid tumors.

ASO Author Reflections: Outcomes of Appendiceal Goblet Cell Carcinoid Tumors.

ASO Author Reflections: Outcomes of Appendiceal Goblet Cell Carcinoid Tumors.

Histologic and Outcome Study Supports Reclassifying Appendiceal Goblet Cell Carcinoids as Goblet Cell Adenocarcinomas, and Grading and Staging Similarly to Colonic Adenocarcinomas.

Goblet cell carcinoid tumors are amphicrine tumors whose biological behavior ranges from indolent to highly aggressive, depending on tumor grade. Current grading systems for these tumors are based on identifying an adenocarcinoma arising in the setting of a goblet cell carcinoid tumor, which distinguishes this tumor from other gastrointestinal tract adenocarcinomas. Because goblet cell tumors are predominantly tumors of mucin secreting cells, we propose that they be classified as goblet cell adenocarcinomas, and graded using a methodology that has parallels in colorectal adenocarcinoma grading. We graded a large series of goblet cell adenocarcinomas by assessing the proportion of the tumor that demonstrates tubular or clustered growth. Histologic grade correlated with overall survival independent of stage, with median overall survival of 204, 86, and 29 months for low-grade, intermediate-grade, and high-grade goblet cell adenocarcinomas, respectively. Tumor stage also correlated with overall survival. We also graded the tumors according to previously proposed grading systems, and found that these systems are valid, in that they segregate patients according to prognosis.

Outcomes of Surgical and Chemotherapeutic Treatments of Goblet Cell Carcinoid Tumors of the Appendix.

Goblet cell carcinoids (GCCs) of the appendix are rare mucinous neoplasms, for which optimal therapy is poorly described. We examined prognostic clinical and treatment factors in a population-based cohort. Patients diagnosed with GCC from 1984 to 2014 were identified from the British Columbia Cancer Agency and the Vancouver Lower Mainland Pathology Archive. Of 88 cases with confirmed appendiceal GCCs, clinical data were available in 86 cases (annual population incidence: 0.66/1,000,000). Median age was 54years (range 25-91) and 42 patients (49%) were male. Metastasis at presentation was the strongest predictor of overall survival (OS), with median OS not reached for stage I-III patients, and measuring 16.2months [95% confidence interval (CI) 9.1-29] for stage IV patients. In 67 stage I-III patients, 51 (76%) underwent completion hemicolectomy and 9 (17%) received adjuvant 5-fluorouracil-based chemotherapy. No appendicitis at initial presentation and Tang B histology were the only prognostic factors, with inferior 5-year recurrence-free survival (53 vs. 83% with appendicitis, p = 0.02; 45% Tang B vs. 89% Tang A, p < 0.01). Of 19 stage IV patients, 10 (62.5%) received 5-fluorouracil-based chemotherapy and 11 (61%) underwent multiorgan resection (MOR) ± hyperthermic intraperitoneal chemotherapy (HIPEC). Low mitotic rate and MOR ± HIPEC were associated with improved 2-year OS, but only MOR ± HIPEC remained significant on multivariate analysis (hazard ratio 5.4, 95% CI 1.4-20.9; p = 0.015). In this population-based cohort, we demonstrate excellent survival outcomes in stage I-III appendiceal GCCs and clinical appendicitis. Hemicolectomy remains the standard treatment. In metastatic disease, outcomes remain poor, although MOR ± HIPEC may improve survival.

Goblet cell carcinoid of the appendix accompanied by adenomatous polyp with high-grade dysplasia at the cecum.

Goblet cell carcinoid tumor of the appendix is an uncommon neoplasia that shares the histological attributes of both adenocarcinoma and carcinoid tumors. Its prognosis has a more aggressive course than the other known carcinoid tumors. Clinical diagnosis of goblet cell carcinoid is seldom made preoperatively. The most common clinical presentation of goblet cell carcinoid tumor is acute appendicitis. In this study, we report a patient on whom right hemicolectomy was performed because of a cacal sessile polyp with high grade dysplasia; goblet cell carcinoid tumor of the appendix was revealed incidentally during microscopic evaluation of the appendectomy specimen. The patient healed uneventfully and no recurrence was observed after the 12-month follow-up period. Careful microscopic examination of the appendectomy specimen is key for the diagnosis of appendiceal tumors such as goblet cell carcinoid, especially in elderly patients.

Neuroendocrine tumors detected in appendectomy specimens: ten-year single-center experience

Background/aim: The aim of this study was to investigate neuroendocrine tumors (NETs) detected in appendectomy specimens and the incidence and clinicopathologic characteristics of these tumors in our center. Materials and methods: A total of 13,863 patients were evaluated retrospectively. All underwent appendectomy operation in the Kayseri Training and Research Hospital and had a histopathological examination at the Pathology Clinic between January 2007 and March 2017. Age, sex, preoperative clinical findings, operation procedure, and histopathological examination results of the cases reported to be NET are presented. Results: NET was detected in 29 cases (0.2%) in the histopathological examination of 13,863 appendectomy specimens. Of these, 26 were classical carcinoid tumors and 3 were goblet cell carcinoid tumors (GCCTs). For the NET cases, the mean age was 37 years and the male to female ratio was 1.07. Only 68.9% of the patients underwent an appendectomy, and 31% of the patients underwent a secondary right hemicolectomy. Recurrences were not detected in any of the cases. In the present study, coincidence was determined in all of the cases with NET in the appendix. Conclusion: Contrary to many studies, both NETs of the appendix and GCCT cases were slightly higher among males and advanced age groups in this study. The long-term life expectancy in cases of classical carcinoid tumors of the appendix is quite good.

Goblet cell carcinoid of the appendix - An interobserver variability study using two proposed classification systems.

Goblet cell carcinoid (GCC) is an uncommon tumor of the vermiform appendix. Due to a broad spectrum of morphological differentiation, subclassification and grading of GCCs remains an area of controversy. Two separate systems have proposed classifying GCC tumors into three (classical GCC; adenocarcinoma ex-GCC, signet ring cell type; adenocarcinoma ex-GCC, poorly differentiated carcinoma type) OR two subgroups (low and high grade GCC) based on morphological criteria. We independently compared the inter-observer variability associated with each classification system. Overall, both systems had moderate interobserver agreement, with the two-tiered system (κ=0.54) performing slightly better than the three-tiered system (κ=0.42). GI-specialist pathologists had substantial agreement for both two and three-tiered systems (κ=0.65 vs. 0.65). Non-GI trained pathologists had lower overall agreement than GI trained pathologists, but their agreement was better using the two-tiered system (κ=0.44) than the three-tiered system (κ=0.22). A sub-analysis of 6 cases with a high rate of discordant classification revealed several challenges that exist in applying current criteria, including differentiating "goblet" vs. "signet ring" cell morphology, applying a 1 mm2 criteria to multifocal non-contiguous glandular and single infiltrating cell architecture, differentiating fibro-inflammatory stroma from desmoplastic stroma, and solid architecture in cases with abundant extracellular mucin, and distinguishing "reactive" nuclear atypia from true "cytologic atypia". Despite these challenges, the study identified better agreement among GI pathologists than non-GI trained pathologists. While GI pathologist review may be helpful, further research on objective classification criteria remains an area of interest.

Perforated Goblet Cell Carcinoid Tumors of the Appendix: Navigating the Management Conundrum

Appendix is the most common site of occurrence for a goblet cell carcinoid tumor. A diagnosis of an appendiceal goblet cell carcinoid is made in retrospect the majority of the time. These tumors are best treated with a right hemicolectomy and adjuvant therapies tailored according to the presence or absence of residual disease. Presentation as a perforated appendix is seen in 16% of these tumors. The natural history and the ideal management strategy in such a scenario are not well described. In those with peritoneal spread cytoreductive surgery with HIPEC (hyperthermic intraperitoneal chemotherapy) offers the best disease-free and progression-free survival. Close follow-up with cross-sectional imaging helps in identifying recurrences at the earliest. Multimodality management involving patient participation in every aspect of care accomplishes high-value care in the treatment of these tumors.

Goblet Cell Carcinoid Tumors of the Appendix: A Report of Two Cases, Review of a Rare Clinical Entity, and Guidelines for Treatment

Goblet cell carcinoid tumor is a rare clinical entity which is usually diagnosed either as acute appendicitis or advanced cancer. Its main characteristic is that the histological findings are between those of adenocarcinoma and typical carcinoid tumor of the appendix. Goblet cell carcinoid tumors appear almost exclusively in the appendix, and prognosis depends mainly on the stage and the subtype of the histological classification. We report three cases of goblet cell carcinoid tumor in the appendix with different clinical presentation and evolution: a 60-year-old male admitted to the emergency room with acute abdominal pain, diagnosed with acute appendicitis and treated with laparoscopic appendectomy; a 65-year-old male undergoing right hemicolectomy to remove a cecal adenoma, with a goblet cell carcinoid tumor found incidentally in the surgical specimen; and a 77-year-old male with acute appendicitis. We discuss the main pathological and clinical findings, and propose a set of guidelines for clinical practice.

Elevated risk of subsequent malignancies in patients with appendiceal cancer: A population-based analysis.

Appendiceal cancer is extremely rare with excellent survival after curative resection. There is a concern for the development of additional cancers in survivors of appendiceal cancer. However, existing data is limited to small anecdotal reports on appendiceal carcinoid only. We aim to investigate the risk of subsequent malignancies in patients with appendiceal carcinoma and correlate the risk according to patient and clinical characteristics. We identified 3788 patients with appendiceal cancer from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database between 1992 and 2011. Standardized incidence ratios (SIRs) for the risk of additional cancers were calculated and quantified based on tumor site, gender, race, latency, primary tumor stage, and histology. Three hundred and fifty-nine subsequent malignancies were identified in 313 patients (mean age 60years, male to female ratio 1.3:1). The overall risk for a subsequent malignancy was elevated by 20% compared with the general population. Most common sites with significantly increased risk for subsequent cancers included the small intestine (n=13) and the colon/rectum (n=48). Malignant carcinoid and adenocarcinoma were the dominant histological subtypes at these sites, respectively. Significant elevated risk was observed within the first 5years of follow up in white males with either localized or regional disease. Adenocarcinomas and goblet cell carcinoid tumors of the appendix were associated with increased risk; whereas, the risk was significantly reduced in patients with malignant carcinoid tumors. There is an increased risk of subsequent cancers in patients with appendiceal carcinoma.

Appendiceal Mixed Adeno-Neuroendocrine Carcinoma: A Population-Based Study of the Surveillance, Epidemiology, and End Results Registry.

Mixed adeno-neuroendocrine carcinoma (MANEC) is a rare pathological diagnosis recently defined by the World Health Organization (WHO) in 2010. Prior to the definition by the WHO, tumors with both adenocarcinoma and neuroendocrine components were given multiple pathological designations making it difficult to characterize the disease. The aim of our study is to better characterize MANEC to better understand its natural history to influence patient care and positively impact outcomes. The surveillance, epidemiology, and end results program database was queried for all patients aged 18 years or older between 1973 and 2012 who had the diagnosis composite carcinoid (n = 249) of the appendix. Composite carcinoid tumors refer to tumors that have both adenocarcinoma and carcinoid tumor components present, consistent with that pathological diagnosis MANEC. For comparison, the database was also queried for carcinoid tumor of the appendix (n = 950), signet ring cell carcinoma of the appendix (n = 579), and goblet cell carcinoid (GCC) tumors of the appendix (n = 944). The data were retrospectively reviewed, and clinicopathological characteristics, treatment regimens, and survival data were obtained. The median age of diagnosis of MANEC tumors was 58 years of age. Eighty percent of patients were White, and 49% were female. Fifty-four percent of patients underwent hemicolectomy and 31% had partial/subtotal colectomy as their surgical management. Median overall survival for MANEC was 6.5 years (95% CI 4.5-9.7), which was statistically significantly shorter (p < 0.0001) in comparison to 13.8 years (95% CI 12.1-16.5) for GCC, 2.1 years (95% CI 1.8-2.3) for signet ring cell carcinoma, and 39.4 years (95% CI 37.1-NA) for carcinoid tumors. MANEC is a more aggressive clinical entity than both GCC of the appendix and carcinoid tumors of the appendix. Based on these findings, patients with MANEC tumors should undergo aggressive multidisciplinary cancer management.

Mixed carcinoid-mucinous adenocarcinoma arising in mature teratoma of mesentery.

Malignant transformation of mature cystic teratoma is uncommon, and occurs in approximately 2%–4% of cases [1]. The most common tumor is squamous cell carcinoma, followed by mucinous carcinoma, carcinoid tumor, thyroid carcinoma, etc.; however, any of the tissues in mature teratoma may undergo malignant transformation [1]. Goblet cell carcinoid (mucinous carcinoid) is a distinctive neoplasm with features of both carcinoid tumor and adenocarcinoma. Most cases described in the literature have occurred in the appendix and rarely, in the ovary. Although mature cystic teratomas occur in many extragonadal areas including the mesentery [2] and greater omentum, occurrence of goblet cell carcinoid arising in extragonadal teratoma has been rarely described, with only a single case in mediastinum being reported in the English literature [3]. Moreover, a combination of mucinous adenocarcinoma, goblet cell carcinoid, carcinoid tumor, and mature teratoma in an extragenital organ has not been reported. Herein, we present a rare case of combined mucinous adenocarcinoma and goblet cell and typical carcinoid tumor arising in mature cystic teratoma of the mesentery in a 48-year-old woman.

A Rare Combination of Ovarian and Uterine Leiomyomas with Goblet Cell Carcinoid of the Appendix

We present a case of the rare combination of unilateral ovarian leiomyoma, uterine leiomyoma, and goblet cell carcinoid tumor of the appendix in a premenopausal woman who presented with right iliac pain. Immunohistochemistry study for desmin (muscle marker) and chromogranin and synaptophysin (neuroendocrine markers) confirmed immunophenotyping origin. Interestingly, both tumors showed positive reaction for estrogen receptor. To our knowledge, such a combination has not been reported previously in the literature. In this paper, the pathogenesis and differential diagnosis of both types of tumors are discussed.

Abdominal Pain and Ileocolitis in a 51-Year-Old Woman

Question: A 51-year-old woman was evaluated over 2 months for abdominal pain. She had a history of appendectomy several years prior for appendicitis, abdominal hysterectomy, and multiple exploratory laparoscopies with lysis of adhesions in the remote past. At presentation, she complained of right-sided, crampy abdominal pain. An abdominal CT showed symmetrical thickening of the distal ileum and serosal inflammation around the cecum, and postoperative changes of appendectomy. Colonoscopy revealed a markedly deformed cecum and inaccessible terminal ileum. A cecal biopsy demonstrated mild chronic inflammation and edema of the lamina propria. She was treated with corticosteroids for presumed Crohn’s ileocolitis. Follow-up MRI enterography showed inflammatory changes of a long segment of distal ileum extending to the ileocecal junction evidenced by mural thickening with mucosal hyperenhancement (Figure A, arrow). Owing to persistence of symptoms and these imaging findings, medical therapy was intensified with initiation of adalimumab. There was no improvement and she developed obstructive symptoms necessitating hospitalization. Upright plain radiograph of the abdomen showed multiple dilated loops of small bowel (Figure B). She underwent a laparoscopic-assisted ileocecectomy with primary stapled anastomosis owing to the refractory nature of her symptoms and to obtain a tissue diagnosis. Histopathology is shown in Figure C. What is the diagnosis? See the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Figure C shows a poorly differentiated adenocarcinoma ex goblet cell carcinoid (GCC), which is a subtype of the rare GCC tumor that occurs almost exclusively in the appendix.1Roy P. Chetty R. Goblet cell carcinoid tumors of the appendix: An overview.World J Gastrointest Oncol. 2010; 2: 251-258Crossref PubMed Google Scholar Histologic evaluation showed malignant glands infiltrating the muscle layer (Figure C, panel 1; original magnification, ×200), residual focal areas of GCC (Figure C, panel 2; original magnification, ×400), and tumor cells positive for chromogranin (Figure C, panel 3) and cdx2 (Figure C, panel 4). Three subtypes of GCC exist and are classified as typical GCC (group A), adenocarcinoma ex GCC signet ring cell type (group B), and poorly differentiated adenocarcinoma ex GCC (group C).2Tang L.H. Shia J. Soslow R.A. et al.Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix.Am J Surg Pathol. 2008; 32: 1429-1443Crossref PubMed Scopus (221) Google Scholar Histologic examination in this case revealed a group C tumor, which is the least common, and has the highest risk of recurrence and mortality.2Tang L.H. Shia J. Soslow R.A. et al.Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix.Am J Surg Pathol. 2008; 32: 1429-1443Crossref PubMed Scopus (221) Google Scholar GCC most commonly presents as acute appendicitis, but can have a various presentations including nonspecific abdominal pain as seen in our patient.2Tang L.H. Shia J. Soslow R.A. et al.Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix.Am J Surg Pathol. 2008; 32: 1429-1443Crossref PubMed Scopus (221) Google Scholar Cross-sectional imaging findings are usually those of acute appendicitis or a prominent appendix, but are not reported to include abnormalities of long segments of bowel.3Lee K.S. Tang L.H. Shia J. et al.Goblet cell carcinoid neoplasm of the appendix: clinical and CT features.Eur J Radiol. 2013; 82: 85-89Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar There is scant literature describing GCC in general, with group C lesions representing only 7 cases in a large series of 63 patients by Tang et al2Tang L.H. Shia J. Soslow R.A. et al.Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix.Am J Surg Pathol. 2008; 32: 1429-1443Crossref PubMed Scopus (221) Google Scholar in 2008. This case of ex GCC likely arose from the appendiceal stump and to our knowledge has never been described. GCC tumors are rare, malignant lesions primarily of the appendix and may infiltrate the cecum and ileum mimicking Crohn’s ileocolitis. This case underscores the importance of considering the differential diagnosis of inflammatory thickening of the ileum and cecal regions particularly when there are atypical histologic features and lack of response to medical therapy.

Goblet cell carcinoid of the appendix: a case report

Goblet cell carcinoid of the appendix is a rare neuoroendocrine tumor that possesses histological features of both adenocarcinoma and neuoroendocrine tumor. Goblet cell carcinoid of the appendix is more aggressive than conventional neuroendocrine tumors. Here we report a case of a 54-year-old woman with goblet cell carcinoid tumor in the appendix.

High-level Microsatellite Instability in Appendiceal Carcinomas

High-level microsatellite instability (MSI-high) is found in approximately 15% of all colorectal adenocarcinomas (CRCs) and in at least 20% of right-sided cancers. It is most commonly due to somatic hypermethylation of the MLH1 gene promoter region, with familial cases (Lynch syndrome) representing only 2% to 3% of CRCs overall. In contrast to CRC, MSI-high in appendiceal adenocarcinomas is rare. Only 4 MSI-high appendiceal carcinomas and 1 MSI-high appendiceal serrated adenoma have been previously reported, and the prevalence of MSI in the appendix is unknown. We identified 108 appendiceal carcinomas from MD Anderson Cancer Center in which MSI status had been assessed by immunohistochemistry for the DNA mismatch-repair proteins MLH1, MSH2, MSH6, and PMS2 (n=83), polymerase chain reaction (n=7), or both (n=18). Three cases (2.8%) were MSI-high, and 1 was MSI-low. The 3 MSI-high cases included: (1) a poorly differentiated nonmucinous adenocarcinoma with loss of MLH1/PMS2 expression, lack of MLH1 promoter methylation, and lack of BRAF gene mutation, but no detected germline mutation in MLH1 from a 39-year-old man; (2) an undifferentiated carcinoma with loss of MSH2/MSH6, but no detected germline mutation in MSH2 or TACSTD1, from a 59-year-old woman; and (3) a moderately differentiated mucinous adenocarcinoma arising in a villous adenoma with loss of MSH2/MSH6 expression, in a 38-year-old man with a strong family history of CRC who declined germline testing. When the overall group of appendiceal carcinomas was classified according to histologic features and precursor lesions, the frequencies of MSI-high were: 3 of 108 (2.8%) invasive carcinomas, 3 of 96 (3.1%) invasive carcinomas that did not arise from a background of goblet cell carcinoid tumors, and 0 of 12 (0%) signet ring and mucinous carcinomas arising in goblet cell carcinoid tumors. These findings, in conjunction with the previously reported MSI-high appendiceal carcinomas, highlight the low prevalence of MSI in the appendix as compared with the right colon and suggest that MLH1 promoter methylation is not a mechanism for MSI in this location.

Goblet cell carcinoid tumor of the appendix

The purpose of the Journal of the Belgian Society of Radiology is the publication of articles dealing with diagnostic and interventional radiology, related imaging techniques, allied sciences, and continuing education

Goblet Cell Carcinoids of the Appendix

Goblet cell carcinoid (GCC) tumors are a rare subgroup of neuroendocrine tumors almost exclusively originating in the appendix. The tumor most often presents in the fifth or sixth decade with a clinical picture of appendicitis or in advanced cases an abdominal mass associated with abdominal pain. Histologically tumors are most often positive for chromogranin A and synaptophysin, however, less homogenous than for classic appendix carcinoids. The malignant potential is higher than that for the classic appendix carcinoids due to local spread and distant metastases at diagnosis and the proliferation markers (Ki67 index) may determine prognosis. Octreotide receptor scintigraphy is usually negative while CT/MRI scans may be useful. Chromogranin A is usually negative and other biomarkers related to the mucinous component or the tumor (CEA, CA-19-9, and CA-125) may be used. Surgery is the main treatment with appendectomy and right hemicolectomy while patients with disseminated disease should be treated with chemotherapy. Overall 5-year survival is approximately 75%. The diagnosis and treatment of GCC tumorss should be restricted to high volume NET centers in order to accumulate knowledge and improve survival in GCC NET patients. The aim of this paper is to update on epidemiology, clinical presentation, and diagnostic markers including Ki67 index, treatment, and survival.