Gastric neuroendocrine neoplasm with late liver metastasis

Gastric neuroendocrine neoplasms (GNENs) are classified into three types according to their aetiology. We present a clinical case of a female patient of 66 years and a well-differentiated (grade 2), type 3 GNEN with late liver metastasis (LM). The patient underwent surgical excision of a gastric lesion at 50 years of age, without any type of follow-up. Sixteen years later, she was found to have a neuroendocrine tumour (NET) metastatic to the liver. The histological review of the gastric lesion previously removed confirmed that it was a NET measuring 8 mm, pT1NxMx (Ki67 = 4%). 68Ga-DOTANOC PET/CT reported two LM and a possible pancreatic tumour/gastric adenopathy. Biopsies of the lesion were repeatedly inconclusive. She had a high chromogranin A, normal gastrin levels and negative anti-parietal cell and intrinsic factor antibodies, which is suggestive of type 3 GNEN. She underwent total gastrectomy and liver segmentectomies (segment IV and VII) with proven metastasis in two perigastric lymph nodes and both with hepatic lesions (Ki67 = 5%), yet no evidence of local recurrence. A 68Ga-DOTANOC PET/CT was performed 3 months after surgery, showing no tumour lesions and normalisation of CgA. Two years after surgery, the patient had no evidence of disease. This case illustrates a rare situation, being a type 3, well-differentiated (grade 2) GNEN, with late LM. Despite this, it was possible to perform surgery with curative intent, which is crucial in these cases, as systemic therapies have limited efficacy. We emphasise the need for extended follow-up in these patients. Learning points: GNENs have a very heterogeneous biological behaviour. Clinical distinction between the three types of GNEN is essential to plan the correct management strategy. LMs are rare and more common in type 3 and grade 3 GNEN. Adequate follow-up is crucial for detection of disease recurrence. Curative intent surgery is the optimal therapy for patients with limited and resectable LM, especially in well-differentiated tumours (grade 1 and 2). Background Gastric neuroendocrine neoplasms (GNENs) represent about 7% of all digestive NET, with a prevalence rate of 35/100 000 (1, 2). According to the 2010 World Health Organization classification, they may present as neuroendocrine tumours (NETs) with Ki67 ≤2% (Grade 1 – G1), 3–20% (Grade 2 – G2) or neuroendocrine carcinoma (NEC) with Ki67 >20% (Grade G3) (1). GNENs may be classified into three types, according to their aetiology: type 1 is associated with autoimmune atrophic gastritis, and it has the lowest metastatic potential from all three types; type 2 is histologically similar to type 1 but is associated with gastrinomas (Zollinger–Ellison syndrome), usually as part of MEN1 syndrome; type 3 is sporadic, without hypergastrinaemia or a gastric condition as predisponent factors. Type 3 lesions are larger and often accompanied by lymph node and distant metastases, resulting in a poor prognosis (1, 2, 3, 4, 5). Serum gastrin levels are crucial on determining the GNEN subgroup, i.e. type 3 GNEN is non-gastrin dependent, unlike type 1 and 2 GNEN. It is essential to obtain an adequate clinical, biochemical and pathological assessment of the tumour in order to plan the correct management strategy, as each of the 3 GNEN types have distinct biological behaviour and prognosis (2, 3). The most common NEN with LM are pancreatic and small bowel NET. There is sparse data on the prevalence of LM in GNEN, although it is estimated that it rarely occurs in these patients and they are mostly synchronous (Table 1). At the time of the LM diagnosis, only 20–30% may still have the chance for curative intent surgery (5). Table 1 Classification of GNEN (1).