虫垂杯細胞カルチノイドの１例

稀な虫垂goblet cell carcinoidの1例を経験した。症例は39歳, 女性で, 主訴は右下腹部痛。急性虫垂炎の診断で虫垂切除術を施行した。虫垂の先端部は硬結を呈し, 蜂窩織炎性虫垂炎と診断した。病理組織所見で虫垂先端部に憩室を認め, 近接して粘液産生性の腺上皮が全層性にみられた。核の不整, クロマチン増量が目立ち, 胞体は印環細胞癌様で核を周辺に圧排していた。神経浸潤が著明でリンパ管浸潤も認めた。免疫染色でクロモグラニンAで少量の腫瘍細胞が陽性, CEAでほぼ100%が陽性, Ki-67で50%以上が陽性であった。以上より, 虫垂憩室炎を伴ったgoblet cell carcinoidと診断し, 再手術でD2りンパ節郭清を伴う回盲部切除兼回腸上行結腸吻合術を施行した。回盲部に残存病変はなく, リンパ節転移も認めなかった。虫垂goblet cell carcinoidは悪性度が高く癌として取り扱うべきとの報告が多く, 経過観察が重要である。

Goblet cell carcinoid (GCC) is a rare type of mixed endocrine–exocrine tumor of the appendix often showing a clinically aggressive behavior. On a molecular basis, this tumor is only poorly understood. To analyze possible molecular similarities between GCC and colorectal cancer, we examined 14 cases of GCC for mutations in exons 18, 19 and 21 of the EGFR-gene, exon 2 in the KRAS gene and for V600E mutations of the BRAF gene. Although the sensitive pyrosequencing method was used, no EGFR, KRAS or BRAF mutations could be found. Furthermore, using immunohistochemistry, no evidence for microsatellite instabillity (MSI) could be found. Despite the partial intestinal differentiation of GCC, our study indicates that the molecular pathogenesis of GCC significantly differs from conventional colorectal adenocarcinoma. This finding might also have implications in adjuvant chemotherapeutic treatment of advanced GCC.

Appendiceal carcinoids with glandular differentiation pose difficulties in classification and prediction of clinical behavior. Sixty-four such cases were divided into three histologic groups on the basis of routine and immunohistochemical stains: (1) Tubular carcinoids were small and confined to the appendix, had small amounts of intraluminal mucin with few or no goblet cells, were nonargentaffin, lacked serotonin, and were diffusely positive for glucagon. All ten with follow-up (mean, 17 months) were without metastasis. (2) Goblet cell carcinoids were confined to the appendix and mesoappendix, circumferentially surrounded the appendiceal lumen, and were often not suspected grossly. Histologically, they were often mixed with small crypt-like glands and were serotonin positive. All 22 with follow-up (mean, 19 months) were without metastasis whether or not right hemicolectomy was performed. (3) Mixed carcinoid-adenocarcinomas showed spread into the cecum or adjacent viscera at the time of diagnosis and had a large carcinomatous pattern with areas of mucinous, signet-ring, or single-file structure, in addition to goblet cell or insular carcinoid. All patients had right hemicolectomies, and all but two with follow-up died of the disease (mean, 16 months). Although a histologic spectrum exists among carcinoid tumors and certain adenocarcinomas of the appendix, it is possible to delineate three biologically distinct groups. Surgical margins should be taken of all appendices because these tumors often do not form discrete masses.

e14170 Background: Goblet cell carcinoid (GCC) of the appendix is a rare tumor comprising 5% of primary appendiceal tumors. GCC shares histological features of both neuroendocrine tumor (NET) and adenocarcinoma. Clinically, GCC also has an intermediate behavior between them. The management of GCC is mostly based on small retrospective series. We report the clinicopathological features, treatments, and outcomes of patients with appendiceal GCCs and NETs from a merged database between Emory University and the Ohio State University. Methods: We identified patients with appendiceal GCCs and NETs treated at these institutions over the period of 12 years from 1999 to 2011. Chart reviews for age, gender, date of diagnosis, TNM stage, chemotherapy, intraperitoneal hyperthermic perfusion (IPHP), surgery, and survival were performed. Results: See table. In the GCC patients with stage I, II, and III, 30 received surgery alone and 1 received surgery plus IPHP. 29 out of 31 (94%) patients are alive without disease recurrence. Out of 6 GCC patients with stage IV, 5 received chemotherapy, 1 received chemotherapy plus IPHP, and 2 (33%) are alive. In the NET patients with stage I,II, and III, all 29 were treated with surgery alone. 29 out of 31 patients are alive and there was no disease-related mortality. Out of 2 NET patients with stage IV, one received chemotherapy and both are alive. Conclusions: Our data confirms the excellent prognosis of appendiceal NET regardless of stage. The outcomes of surgery for patients with stage I, II, and III in both GCCs and NETs were excellent. Patients with stage IV GCCs have higher possibility of aggressive clinical courses. Chemotherapy or IPHP should be considered in the management of stage IV GCCs. [Table: see text]

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.

Goblet cell carcinoid is a poorly understood tumour of the appendix. The aim of this study was to determine whether it should be regarded as a separate entity or as a variant of classical carcinoid. The immunohistochemical expression pattern of 21 markers and the mutation status of KRas codon 12 were determined in 16 goblet cell carcinoids and compared with 14 classical carcinoids, 19 colonic adenocarcinomas and 10 appendiceal mucinous cystadeno (carcino)mas. The results were subjected to a stepwise linear discriminant analysis. Goblet cell carcinoids were significantly different from the control groups. The most important markers for discriminating between the groups were CEA (classical carcinoid versus all others), KRas mutation (present in all mucinous cystadeno (carcino)mas), beta-catenin (goblet cell carcinoid versus left sided colonic adenocarcinoma) and chromogranin (goblet cell carcinoid versus right sided colonic adenocarcinoma). Expression of Math1 and HD5 was similar in goblet cell carcinoid and colonic adenocarcinoma but absent in classical carcinoid. The results suggest that goblet cell carcinoids should be regarded as a separate entity. The formerly used term 'crypt cell carcinoma' may be more appropriate because it reflects the more aggressive clinical behaviour of these tumours as well as their greater similarity to adenocarcinomas rather than to carcinoids.

Goblet cell carcinoids are uncommon tumours with histological features of both adenocarcinoma and carcinoid tumour. They occur predominantly in the appendix and although the malignant potential remains unclear, adenocarcinoids appear to be more aggressive than conventional carcinoids. In this case report, we present a goblet cell carcinoid with laparoscopic operative treatment in two stages. A 43-year-old female patient with constant dullness in the right lower quadrant was diagnosed with acute appendicitis and underwent laparoscopic appendectomy. Macroscopically, a diffusely inflamed appendix was found with no sign of perforation. Histopathological examination revealed a goblet cell carcinoid with characteristics of aggressive behaviour, indicating the need for laparoscopic right hemicolectomy in which, however, neither residual tumour nor metastatic lymph nodes could be found. The postoperative course was uneventful. As they may present the same clinical presentation, pathological diagnosis is required to distinguish goblet cell carcinoid from acute appendicitis. Two-stage surgery for goblet cell carcinoid is advocated in the literature, but the debate still continues as to whether the goblet cell carci-noid should be treated by appendectomy alone, as for most carcinoids, or by right hemicolectomy, as for the appendiceal adenocarcinoma.

Goblet cell carcinoids (GCC) and other atypical neuroendocrine tumors (NET) of the appendix as well as appendiceal adenocarcinoma are usually managed with the same algorithm as colon cancers. This study investigates clinicopathological features that are predictive of survival outcomes for appendiceal NET and adenocarcinoma. Survival profiles for the histologic subtypes of appendiceal NET and adenocarcinoma were compared. A retrospective review of appendiceal NET and adenocarcinoma for patients who are 18 years and above in the SEER database from 2010 to 2014. Females outnumbered males in a 1.3 to 1 ratio in the NET subgroup and 1.1 to 1 ratio in the adenocarcinoma group. The mean age at diagnosis for all NET was 50.3±17 years while that of adenocarcinomas was 60.8±14.1 years. Within the NET subgroups, the mean ages for typical carcinoids (TC), GCC, NEC and MANEC were 42.9±17.3, 56.7±13.7, 45.6±17.4 and 59.7±12.8 years, respectively. Overall survival for adenocarcinoma was 86.3%, 73.5%, 65.7%, and 57.6% for 1-, 2-, 3- and 4-year OS, respectively. For NET, TC showed better survival profile with 1- and 4-year overall survival of 97.4% and 95.7%, respectively while MANEC had the worst survival outcome with 1- and 4-year OS of 88.6% and 62.2%, respectively. GCC had a better 1-year OS compared to NEC (95.5% versus 92.9%) but showed slightly worse 4-year OS (82% versus 84.8%). Age at diagnosis (HR 1.03), African-American race (HR 1.47) and stage IV disease (HR 9.58) were independent predictors of survival for appendiceal adenocarcinoma. For NET, advanced age at diagnosis, advanced disease stage and the African-American race were identified as negative independent predictors of survival. While prior studies have suggested that atypical NET (GCC, NEC and MANEC) are more likely to present at more advanced stages, this study showed that most cases of GCC, MANEC and NEC were diagnosed at stages I and II. Appendiceal adenocarcinoma, on the other hand, presented mostly at stage IV. With respect to OS, atypical histologic subtypes of NET have worse outcome compared to TC. Although better OS was noted for GCC, NEC and MANEC when compared to adenocarcinoma, this benefit was lost in stage IV disease where adenocarcinoma recorded better 1- and 4-year OS. Prospective and randomized studies which provide granular details of treatment are needed to better define treatment algorithm for appendiceal NET.

The 2019 World Health Organization Classification of appendiceal, colorectal and anal canal tumours: an update and critical assessment

Introduction/BackgroundOvarian carcinoids are uncommon tumors. Mucinous carcinoids, particularly if associated with atypical features, may have an aggressive behavior.MethodologyA 34-year old woman underwent removal of a left ovarian mass which was...

Goblet cell carcinoid, a rare tumor of intermediate malignant potential, is known to account for a significant minority of appendiceal neoplasms. Sixteen new cases of gastrointestinal goblet cell carcinoid were reviewed to describe their presentation, treatment, and outcome. A review of 16 cases from a single institution. Sixteen patients were diagnosed with goblet cell carcinoid between 1995 and 2005. Presenting diagnoses included appendicitis (n=8), abdominal or liver mass (n=5), uterine fibroids (n=1), ovarian mass (n=1), and Crohn's Disease exacerbation (n=1). Mean follow-up was 12 months with a mortality of 19% (n=3). Patients were divided into two groups: those where the diagnosis was an incidental finding at operation (Group 1) and those where the presentation was of an abdominal mass or metastatic disease (Group 2). Nine of ten patients in Group 1 initially received appendectomies. Group 2 included patients presenting with Krukenberg type lesions (n=2) and abdominal masses (n=4). Goblet cell carcinoid is a rare malignant tumor largely affecting the appendix. In patients presenting with appendicitis, our series does not support the recommendation of right hemicolectomy based on pathologic diagnosis alone and surgical intervention must be customized to the individual patient.

Goblet cell carcinoid (GCC) is a clinicopathologically distinctive tumor that typically arises in appendix and metastasizes frequently. Although rare cases of ostensibly primary extraappendiceal GCC (EGCC) have been reported, the distinction from extraappendiceal metastasis of occult appendiceal primary may be problematic and has not been dealt with systematically in literature. We reviewed our combined experience with EGCC at four North American hospitals and reevaluated all EGCC cases published in literature. We encountered 16 cases that were initially reported as EGCC. Five cases presented with disseminated abdominopelvic spread, nine cases with mass lesions in stomach, ileum, cecum, ascending colon, hepatic flexure, sigmoid, and rectum. One case was found incidentally in an ascending colon adenomatous polyp. A negative appendix was confirmed in 2 (12.5%) cases, whereas a primary appendiceal GCC was discovered in 4 (25%) cases at a later date, and appendix was not available for review in 10 cases (62.5%). Of 10 cases of EGCC found in literature, the tumor sites included stomach, duodenum, jejunum, ileum, cecum, splenic flexure, and rectum. Primary appendiceal tumor was excluded histologically in one (10%), grossly in three (30%), and not at all in six (60%). Nine of our cases were initially misdiagnosed as signet-ring cell adenocarcinomas. True EGCC is extremely rare. GCC found at locations other than appendix are most likely extraappendiceal presentations of appendiceal primary. A thorough review of the pathologic status of appendix should be a mandatory diagnostic criterion and should always be documented in the pathology reports.

Four cases of mixed carcinoid and adenocarcinoma of the appendix were reported. All cases presented with a dominant cecal-appendiceal tumor mass and local metastasis. Two patients had multiple peritoneal implants mimicking primary peritoneal serous adenocarcinoma or carcinomatosis. Histopathologic features of the tumors are similar, with infiltrating microglandular and cribriform patterns of tumor nests, and variable numbers of goblet cells. A literature review of "goblet cell carcinoid" that included nonlocalized cases revealed a significant percentage (>14%) of tumor-associated death, in contrast to the classic carcinoid tumor. Immunohistochemical stains were helpful to separate these tumors from carcinoid tumors and primary peritoneal serous adenocarcinoma. Mixed carcinoid and adenocarcinomas were cytokeratin (CK)-20 positive, and negative or weakly positive for chromogranin A and synaptophysin. Carcinoid tumors were CK20 negative and diffusely positive for chromogranin A and synaptophysin. Peritoneal serous adenocarcinomas were CK20 negative. These cases were clinically aggressive, and 1 patient had multiple recurrences and responded partially to chemotherapy.

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)

Twenty-two appendiceal carcinoid tumours, comprising 10 classical carcinoids, six tubular carcinoids and six goblet cell carcinoids were examined by histochemistry and immunohistochemistry. All of the tumours showed evidence of neuroendocrine differentiation. Classical carcinoids were invariably intimately associated with S-100 protein positive cells, supporting an origin from sub-epithelial neuroendocrine cells. Both tubular and goblet cell carcinoids expressed cytoplasmic mucin and immunoglobulin A, and neither were associated with S-100 protein positive cells. These observations suggest that tubular and goblet cell carcinoids are derived from epithelial crypt stem cells.