Mixed Adenoneuroendocrine Carcinoma of the Caecum Presenting As Extensive Ileocolonic Intussusception

An 84-year-old Caucasian female presented with a 2-month history of vague abdominal pain and clinically significant involuntary weight loss (10 kg over the past 6 months). She reported acute onset of cramping pain followed by haematochezia 24 h prior to hospital admission. Her past medical history included ischaemic heart disease, hypertension, appendectomy and cholecystectomy. Laboratory work-up revealed microcytic normochromic anaemia (haemoglobin 105 g/L) and slight increase in liver enzymes (alanine aminotransferase 54 U/L, gamma-glutamyl transpeptidase 106 U/L). The serum tumour markers were in normal range except cancer antigen 19.9 (65.5 U/mL; normal values 0.0–34.0) and carcinoembryonic antigen (7.8 ng/mL; normal values 0.0–4.7). Oesophagogastroduodenoscopy was unremarkable. A computed tomography scan showed multiple large confluent liver nodules suspected of metastases and invagination of the distal ileum and ascending colon into the distal transverse colon (Fig. 1). An explorative laparotomy confirmed the radiological findings, that is, extensive ileocolic intussusception sustained by a circumferential caecal mass (Fig. 2). A right hemicolectomy was performed allied to excisional biopsy of a liver nodule in segment 3. Post-operative course was uneventful and the patient was discharged on post-operative day 7. Histopathology showed high-grade large-cell neuroendocrine carcinoma associated with moderately differentiated adenocarcinoma, metastasis in two out of 13 lymph nodes and neuroendocrine liver metastasis (pT3N1bM1, G3). The immunohistochemical evaluation revealed a spotty positivity for chromogranin A. CD56 and synaptophysin were positive, with Ki67 proliferative index above 80%. Given the poor performance status due to comorbidities, the patient was deemed unfit for chemotherapy and died of disease progression 4 months after surgery. The first description of a gastrointestinal tumour with a neuroendocrine and an exocrine component was published by Cordier in 1924.1 In 2010, the World Health Organization introduced the term MANEC (mixed adenoneuroendocrine carcinoma) to define mixed neoplasms containing a double component, each involving at least 30% of the tumour mass and presenting malignant features.2 In a recent systematic review of 752 MANEC of the lower gastrointestinal tract,3 only 28 cases affected the caecal region (Table 1). Mean age was 67 years with similar gender distribution. Survival outcome was substantially poor, reaching a mean of 11 months overall, with stage IV disease at diagnosis observed in more than one-third of patients. Despite a previous report of early bowel invagination sustained by the primary tumour,4 extensive ileocolonic intussusception represents a unique clinical example of MANEC presentation. The participant has consented to the submission of the case report to the journal. Alessandro Iacomino: Conceptualization; data curation; writing-original draft; writing-review and editing. Ugo Grossi: Conceptualization; data curation; supervision; writing-original draft; writing-review and editing. Stefano Doratiotto: Investigation. Alberto Brun Peressut: Data curation; writing-review and editing. Patrizia Pelizzo: Data curation; writing-review and editing. Giacomo Zanus: Conceptualization; writing-review and editing. Data S1. Complete reference list of studies described in Table 1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.