Shekhda Kalyan Mansukhbhai, Luong Tu Vinh, Krell Daniel, Navalkissoor Shaunak, Paterson Anna, Caplin Martyn
Neuroendocrine Tumor Unit, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust, London, UK.
Department of Cellular Pathology, Royal Free London NHS Foundation Trust, London, UK.
J Gastrointest Cancer. 2025 Jun 23;56(1):140. doi: 10.1007/s12029-025-01261-5.
Mixed neuroendocrine and non-neuroendocrine neoplasms (MiNENs) are rare neoplasms composed of morphologically distinguishable neuroendocrine (NE) and non-neuroendocrine components, each representing at least 30% of the tumor volume. The NE component must be substantiated by immunohistochemistry. MiNENs generally have a poor prognosis, with a more aggressive component dictating overall survival and prognosis. Owing to its rarity, there are no specific validated treatment guidelines available for these tumors, and they are generally treated with surgery if possible. However, surgically unresectable or advanced tumors are generally treated with chemotherapy.
We report a case of an elderly woman who was referred to the neuroendocrine tumor (NET) unit following incidental findings of liver lesions found on cardiac magnetic resonance imaging (MRI) performed for an asymptomatic heart murmur. Histology from the liver biopsy revealed MiNEN with up to 60% grade 2 (Ki67: 19%) well-differentiated NET and up to 30% well-differentiated to moderately differentiated adenocarcinoma of possible pancreato-biliary origin; intrahepatic ductal primary could not be excluded. Her 18-fluoro-deoxyglucose positron emission tomography (FDG-PET) revealed no FDG-avid lesions, and a Gallium 1,4,7,10-tetraazacyclododecane-tetraacetic acid Tyr3-octreotate ( Ga-DOTATATE)-PET scan revealed multiple areas of intensely DOTATATE-avid liver lesions. Due to the absence of any primary imaging findings, the patient was diagnosed with MiNEN of possible pancreato-biliary origin.
She was started on lanreotide 120 mg every 28 days for 6 months, with no response to the treatment. Subsequently, the patient was treated with four cycles of Lutetium-DOTATATE (Lutathera®) peptide receptor radionuclide therapy (PRRT). She tolerated the treatment well, with no significant side effects. MRI at the end of treatment revealed a partial response to treatment.
PRRT is currently not used in treatment protocols for the management of MiNENs; however, it could be considered a treatment option in patients with MiNENs, where there is a predominant component of well-differentiated NETs with Ga-DOTATATE avid lesions.
混合性神经内分泌和非神经内分泌肿瘤（MiNENs）是罕见肿瘤，由形态上可区分的神经内分泌（NE）和非神经内分泌成分组成，每种成分至少占肿瘤体积的30%。NE成分必须通过免疫组织化学证实。MiNENs通常预后较差，侵袭性更强的成分决定总体生存和预后。由于其罕见性，目前尚无针对这些肿瘤的经过验证的特定治疗指南，一般尽可能采用手术治疗。然而，无法手术切除或晚期肿瘤通常采用化疗。
我们报告一例老年女性病例，该患者因无症状心脏杂音行心脏磁共振成像（MRI）检查时偶然发现肝脏病变，随后转诊至神经内分泌肿瘤（NET）科室。肝脏活检组织学检查显示为MiNEN，其中高达60%为2级（Ki67：19%）高分化NET，高达30%为高分化至中分化腺癌，可能起源于胰胆管；不能排除肝内胆管原发性。她的18-氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）未发现FDG摄取阳性病变，而镓1,4,7,10-四氮杂环十二烷四乙酸酪胺酸3-奥曲肽（Ga-DOTATATE）-PET扫描显示肝脏有多个区域强烈摄取DOTATATE。由于没有任何原发性影像学表现，该患者被诊断为可能起源于胰胆管的MiNEN。
她开始接受每28天一次的120mg兰瑞肽治疗，持续6个月，但治疗无反应。随后，该患者接受了四个周期的镥-奥曲肽（Lutathera®）肽受体放射性核素治疗（PRRT）。她对治疗耐受性良好，无明显副作用。治疗结束时的MRI显示对治疗有部分反应。
PRRT目前未用于MiNENs的治疗方案；然而，对于具有Ga-DOTATATE摄取阳性病变的高分化NET占主要成分的MiNENs患者，可考虑将其作为一种治疗选择。
