Goblet cell adenocarcinoma (GCA) is a rare, aggressive type of appendix cancer (AC) often presenting with peritoneal disease (PD). While cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is standard for other AC subtypes, its role in GCA, particularly with high peritoneal cancer index (PCI), remains controversial. We conducted a retrospective analysis of two prospective databases, including patients with GCA undergoing first CRS/HIPEC. We described clinical characteristics and compared outcomes between PD patients with high (≥20) and low PCI. Progression-free (PFS) and overall survival (OS) were analyzed using the Kaplan Meier method. Prognostic factors were evaluated via multivariable Cox regression. Of 183 patients, 30 (16.4%) were non-metastatic (NM) and 153 (83.6%) had PD. In PD, median PCI was 20 (interquartile range [IQR]: 13-28). Complete cytoreduction (CC-0) was achieved in 61.4% of PD patients. Major complications (Clavien Dindo III-IV) occurred in 10% of NM and 33% of PD, with higher rates in PCI≥20 (p = 0.011). After median follow-up of 59 months, no NM recurred or died and 62.7% of PD patients recurred (77.1% intraperitoneal). Five-year PFS and OS for PD were 11.2% and 29.5%, respectively. Incomplete cytoreduction independently predicted worse PFS (hazard ratio [HR] 1.7, p = 0.009) and OS (HR 2.3, p < 0.001), while PCI≥20 did not. Five-year OS was similar in patients with high and low PCI (28.3% vs 32.0%, p = 0.551). Complete CRS/HIPEC offers promising survival in GCA with PD. NM patients at risk of PD show excellent survival. Further studies are warranted to optimize selection criteria.

Appendiceal neoplasms (AN) are an uncommon condition that are typically diagnosed incidentally following an appendicectomy for appendicitis. However, there has been an increased incidence of AN, thought to be secondary to the increased use of computer tomography scans. Therefore, understanding of a broad range of differentials and management of potential AN is necessary for general surgeons. This case report describes an exceptionally rare occurrence of three distinct neoplastic processes-mixed neuroendocrine tumor, goblet cell adenocarcinoma, and low-grade appendiceal mucinous neoplasm-coexisting within a single appendix. We believe this case provides valuable clinical and pathological insights into the broad range of AN, highlighting the diagnostic challenges and the role of the multidisciplinary team.

Goblet cell carcinoma (GCC) of the appendix is an exceptionally rare and distinct appendiceal neoplasm characterized by mixed features of both neuroendocrine tumors and adenocarcinomas. Its insidious presentation, frequently mimicking more common conditions like acute appendicitis, contributes to diagnostic challenges and highlights its rarity. We present the case of a 70-year-old female who presented to clinic with right-sided abdominal aching and intermittent nausea. Workup revealed colon nodule and she was taken to the operating room for colon resection. An incidental appendectomy was performed given the abnormal appearance of her appendix intraoperatively. Pathology revealed high grade GCC of the appendix, and she was taken back for a laparoscopic right hemicolectomy during the same admission. This case underscores the profound rarity of appendiceal GCC, with an estimated incidence of 0.01 to 0.05 per 100 000 individuals. The diagnostic ambiguity necessitates a high index of suspicion and meticulous pathological review.

Appendiceal goblet cell carcinoma (GCA) is a rare tumor type that has no known precursor. In our diagnostic practice, we observed co-occurrence of GCA with sessile serrated lesions (SSLs) and low-grade appendiceal mucinous neoplasms (LAMNs). Reviewing clinical archives, we identified 35 in-house resections of GCA, in which six (17%) harbored coincident SSLs or LAMNs. Here, we performed paired next-generation sequencing of adenocarcinomas and the coincident lesions to investigate the possibility of shared clonal relationships. For comparison, we also performed paired sequencing on three conventional appendiceal adenocarcinomas with goblet cell differentiation and coincident SSLs or LAMNs. All nine sequenced SSLs or LAMNs harbored activating KRAS mutations, two with concurrent GNAS mutations. There were no apparent shared somatic alterations between the coincident lesions and the six GCAs, the latter of which harbored alterations in other genes including ARID1A, ERBB2, RHOA, and ARHGAP35. In the three conventional adenocarcinomas, there were shared somatic alterations between the adenocarcinomas and the coincident SSLs or LAMNs, including in KRAS, SMAD4, and TP53. In contrast to conventional adenocarcinoma, GCAs do not evidently arise from KRAS-mutated precursor lesions. Based on our paired sequencing study, GCAs were clonally unrelated to coincident KRAS-mutant SSLs and LAMNs, and the reason for the relatively high prevalence of co-occurring lesions among appendectomies containing GCA remains uncertain.

Dual tumors, comprising two different types of tumor, are uncommon pathologic findings. Appendiceal goblet cell carcinoid is an unusual and unique subtype of primary appendiceal neuroendocrine tumor defined by the World Health Organization, showing hybrid epithelial-neuroendocrine features. Low-grade mucinous neoplasms are also rare appendiceal neoplasms. However, the relationship between these two types of tumors is not well known. We present the case of a 46-year-old woman with a 5 cm appendiceal cystic tumor that was incidentally detected on abdominal computed tomography. She showed no abdominal symptoms, enlarged lymph nodes, or obvious distant metastases. Laparoscopic ileocecal resection was performed without complications or tumor injury. No disseminated lesions or mucus accumulation was found in the abdominal cavity during the operation. Pathologic examination revealed low-grade mucinous tumor cells lining the cystic mucosal cavity and a chromogranin A-positive goblet cell carcinoid near the mucinous cell components. As there was no mixture of the two cell types, the tumor was suspected of a collision tumor. Although reports on appendiceal collision tumors are limited, these two tumor types might arise from different types of progenitor cells. Furthermore, the laparoscopic approach, which allows for a more detailed and safer observation of the entire abdominal cavity, could be useful for accurate staging and treatment decisions in mucinous appendiceal tumors at risk of intraperitoneal mucinous dissemination and peritoneal pseudomyxoma. Accumulation of case reports of such dual tumors and analysis at the molecular and cellular level are necessary to elucidate their pathogenesis and development.