Figure 1A Frontal radiograph of both hips and the pelvis- A minimally displaced linear fracture is seen in the neck of the left femur. Few well defined sclerotic lesions are seen involving the right iliac blade and shaft of the left femur.

Lateral radiograph of cervical spine [Figure 1b] shows a well defined lytic lesion measuring approximately 1.5 x 1 cm in the spinous process of the C2 vertebra with degenerative changes in the cervical spine.

Figure 1b: Lateral radiograph of the cervical spine shows a lytic lesion involving the spinous process of the C2 vertebra

Trans-abdominal ultrasonography showed multiple, well-defined, heterogeneously iso to hyperechoic lesions in both lobes of the liver. They had minimal vascularity [Figure 2A-C]. 

Figure 2A,B,C : Trans-abdominal ultrasonography shows multiple well-defined heterogeneously iso to hyperechoic lesions in the both lobes of the liver showing minimal vascularity.

Contrast enhanced CT scan of the abdomen and pelvis shows multiple, well defined, peripherally enhancing lesions with central non enhancing areas in the liver parenchyma - the largest measuring 7.7x5.7x6.5 cm. The lesions show washout in the delayed phase [figure 3 A-D]. 

Figure 3A, 3B,: Contrast enhanced CT scan of the abdomen and pelvis shows multiple fairly well defined, peripherally enhancing lesions with central non enhancing areas in the liver parenchyma. 

Figure 3C, 3D: The lesion shows washout in the delayed phase. 

MRI study of the abdomen shows multiple, variable sized, T2 hyper- to isointense lesions scattered in both lobes of the liver indicating hypervascular lesions [Figure 4A and 4B]. There is a small hyperintense lesion in segment VII of the liver suggestive of calcification.

Figure 4A , 4B: MRI of the abdomen shows: Multiple variable sized T2 hyperintense to isointense lesions scattered in both lobes of the liver suggestive of hyper vascular lesions. 

PET CT shows a hypermetabolic, heterogeneously enhancing soft tissue mass involving segment VII/VIII of the liver. Hypermetabolic lymph nodes are noted in the periportal, portocaval, aortocaval and in left para-aortic regions [Figure 5A, 5B].

Figure 5A and 5B: PET CT shows hypermetabolic heterogeneously enhancing soft tissue mass involving segment VII/VIII of the liver. 

Radiological diagnosis:

1. Metastatic lesions from unknown primary NET.

2. Primary hepatic neuro endocrine tumour.

3. Hepatocellular carcinoma. 

Pathological diagnosis:

A liver biopsy was performed . On immunohistochemistry there was strong chromogranin A positivity, consistent with neuroendocrine differentiation. 

Final diagnosis:

Multicentric primary hepatic NET with bone metastases.

Management: 

The femoral fracture was surgically stabilized, and the patient was referred to for systemic oncological management which includes somatostatin analogues, or targeted agents. The patient had an uneventful postoperative period. He was started on a soft oral diet, which he tolerated well, and was discharged stable after one week of hospital stay. 

Discussion:

Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms arising from neuroendocrine cells capable of secreting peptide hormones. They most frequently occur in the gastrointestinal (GI) tract (55%) and lungs (30%), but may also originate in the pancreas (2%), reproductive organs (1%), biliary tract (1%), and head and neck region (0.4%) [1]. Among GI tract NETs, the small bowel is the most common site (45%). Hepatic involvement is usually metastatic from a gastrointestinal or pancreatic primary; however, primary hepatic neuroendocrine tumours (PHNETs) are exceedingly rare, accounting for only 0.3–0.4% of all NETs [1, 2].

The global incidence of NETs is estimated at 5–7 per 100,000 population, with a prevalence of approximately 35 per 100,000 [1]. The pathogenesis of PHNETs remains unclear, but three major hypotheses have been proposed: [1] 

1. Origin from neuroendocrine cells within the intrahepatic biliary epithelium

2. Development from heterotopic pancreatic or adrenal tissue within the liver, or 

3. Neuroendocrine differentiation of malignant hepatic stem cells [1, 2].

PHNETs are typically non-hormone-secreting, slow-growing, and often clinically silent, discovered incidentally or in advanced stages [3]. Functional symptoms such as flushing or diarrhoea are uncommon, unlike gastrointestinal carcinoids. According to the WHO 2022 classification, neuroendocrine neoplasms are divided into: (a) well-differentiated NETs (G1–G3), (b) poorly differentiated NECs (small- or large-cell, always G3), and (c) mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) [3].

Radiologically, PHNETs are difficult to differentiate from hepatocellular carcinoma (HCC) or cholangiocarcinoma, since their blood supply is predominantly from the hepatic artery [2, 4]. Based on histological grading, imaging appearances vary: Grade 1 tumours are usually single, solid nodules showing arterial enhancement and rapid wash-in; Grade 2 lesions may be multiple, with necrosis and ring enhancement; while Grade 3 tumours exhibit internal necrosis, haemorrhage, and capsular disruption [2].

Imaging modalities such as CT, MRI, and nuclear medicine techniques—especially PET/CT using 18F-FDG or 68Ga-DOTATATE—play a crucial role in localization, staging, and detection of metastases [5, 6]. PHNETs are typically hypervascular, highlighting the importance of arterial phase imaging. On MRI, these tumours show T2 hyperintensity and restricted diffusion on DWI, with hepatobiliary-specific contrast agents improving detection of smaller lesions [5].

PHNETs are often mistaken for other hepatic tumours due to overlapping radiologic features, including solid or cystic morphology with necrosis and arterial hyperenhancement [7–9]. Conventional tumour markers such as AFP, CEA, and CA19-9 are generally normal [8]. Histopathology and immunohistochemistry are pivotal for definitive diagnosis—chromogranin A and synaptophysin positivity confirm neuroendocrine differentiation [5, 10, 11].

In the present case, strong chromogranin A positivity on IHC confirmed the diagnosis of multicentric primary hepatic NET with skeletal metastases.

Learning points:

• PHNETs are extremely rare and may be misdiagnosed as metastatic disease.

• Imaging shows arterial hyperenhancement with delayed washout.

• Non-functional tumours remain asymptomatic until late or metastatic stages.

• Diagnosis requires histopathological confirmation with chromogranin A and synaptophysin positivity.

• Multimodality imaging, including PET-CT, is essential for accurate staging and differentiation from other hepatic tumours.

References:

1. Qu C, Wang M, Chen Y, et al. Clinical characteristics and treatment of primary hepatic neuroendocrine tumours after comprehensive therapy. World J Clin Oncol. 2020;12(9):1031–45.

2. Lin CW, Lai CH, Hsu CC, Hsu CT, Hsieh PM, Hung KC, et al. Primary hepatic carcinoid tumour: a case report and review of the literature. Cases J. 2009;2:90.

3. Wang LX, Liu K, Lin GW, Jiang T. Primary hepatic neuroendocrine tumours: comparing CT and MRI features with pathology. Cancer Imaging. 2015;15(1):13.

4. Shetty PK, Baliga SV, Balaiah K, Gnana PS. Primary hepatic neuroendocrine tumor: an unusual cystic presentation. Indian J Pathol Microbiol. 2010;53:760–2.

5. Kellock T, Tuong B, Harris AC, Yoshida E. Diagnostic Imaging of Primary Hepatic Neuroendocrine Tumours: A Case and Discussion of the Literature. Case Rep Radiol. 2014;2014:156491.

6. Chotai TJ, Sindhu RS, J N. A case report of primary hepatic neuroendocrine tumour (VIPoma) of liver. Int Surg J. 2025;12(7):1172–1175.

7. Houat AP, von Atzingen AC, Velloni FG, de Oliveira RAS, Torres UDS, D'Ippolito G. Hepatic neuroendocrine neoplasm: imaging patterns. Radiol Bras. 2020;53(3):195–200.

8. Morgan M, Knipe H, Campos A, et al. Hepatic neuroendocrine tumour. Radiopaedia.org (Accessed on 24 Aug 2025).

9. Scarsbrook AF, Ganeshan A, Statham J, Thakker RV, Weaver A, Talbot D, et al. Anatomic and functional imaging of metastatic carcinoid carcinomas. Radiographics. 2007;27:455–76.

10. Yang K, Cheng YS, Yang JJ, et al. Primary hepatic neuroendocrine tumours: multimodal imaging features with pathological correlations. Cancer Imaging. 2017;17:20.

11. Quartey B. Primary Hepatic Neuroendocrine Tumour: What Do We Know Now? World J Oncol. 2011;2:209–16.