Focal Nodular Hyperplasia-Like Lesion Mimicking a Neuroendocrine Tumour Liver Metastasis on Ga-68 DOTATATE PET/CT

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A 51-year-old woman with resected midgut neuroendocrine tumour (NET) and cryptogenic cirrhosis underwent a [⁶⁸Ga] Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) for post-surgical surveillance. A focus of intense uptake was seen in segment VI of the liver, suggestive of a NET liver metastasis [Fig 1]. A subsequent liver magnetic resonance imaging (MRI) demonstrated an 8mm arterialised lesion in segment VI with restricted diffusion and no washout [Fig 2]. This lesion was not visible on a triple-phase CT seven months earlier. It was felt likely to represent a new NET liver metastasis, and not hepatocellular carcinoma. The liver is the most common site of NET distant metastasis, affecting 82% of patients with a poor prognosis.^[1] [⁶⁸Ga]Ga-DOTATATE PET/CT has a high sensitivity and specificity for detecting well-differentiated NETs,^[2] which overexpress somatostatin receptors (SSRs), particularly subtype 2.^[3] It has higher accuracy as a staging modality when compared to conventional contrast-enhanced cross-sectional imaging.^[2] False negatives can occur due to physiological peptide metabolism in the liver and the inherent spatial resolution of PET,^[4] Making MRI preferred for the assessment of NET liver metastasis. The NET multidisciplinary team advised ultrasound-guided biopsy and radiofrequency ablation of the segment VI liver lesion.

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Fig 1: (A) There is focal intense increased uptake of [⁶⁸Ga]GaDOTATATE within the segment VI of the liver (red arrow) in the maximum intensity projection (MIP); (B) PET (red arrow); (C) CT; and (D) PET/CT (red arrow), (SUVmax is 12.3 for the liver lesion, and 7.5 for the liver background). The diminished spleen reflects a previous splenectomy for immune thrombocytopenia. PET: Positron emission tomography; CT: Computed tomography; SUVmax: maximum standardised uptake value

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Fig 2: (A) Magnetic resonance imaging (MRI) demonstrated a liver lesion in segment VI which is arterially enhancing, and (B) Demonstrates restricted diffusion (yellow arrows in A and B)

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Histological analysis of the liver lesion biopsy demonstrated a benign hepatocellular lesion with fibrous septa, bile ductular reaction and mild chronic inflammation with no evidence of malignancy. Immunostaining of the sample with glutamine synthase displayed a broad, anastomosing map-like pattern [Fig 3]. The histological architecture and immunophenotypic profile were consistent with focal nodular hyperplasia (FNH). In this case of cirrhotic liver, the findings were interpreted as an FNH-like lesion. FNH is classically characterised by nodular hepatocyte proliferation surrounding a central fibrous scar containing malformed vessels and ductular reactions.^[5] Its pathogenesis has been hypothesised to be due to abnormal circulatory supply.^[6] In cirrhosis, FNH-like nodules may develop due to the altered blood flow and vascular architecture characteristic of the diseased liver.^[7] Although FNH may present with non-specific abdominal pain, it is often detected incidentally,^[8] like in this case.

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Fig 3: Histology (H&E X3) in panel (A) showing nodules of bland appearing hepatocytes, arranged in plates 1-2 cells thick, separated by fibrous septa. Proliferating ductules and mild chronic inflammatory cell infiltrate are seen at the junction of the fibrous bands and hepatocellular nodules. Immunostaining (glutamine-synthetase X6) in panel (B) demonstrates strong, patchy, map-like staining. The histological architecture and immunophenotypic profile are consistent with focal nodular hyperplasia (FNH). H&E: Haematoxylin and eosin and magnification used is 100x.

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To our knowledge, this is the first report of an FNH-like lesion demonstrating uptake on [⁶⁸Ga]Ga-DOTATATE PET/ CT and masquerading as a liver metastasis. Reports of uptake in non-NET hepatic lesions on [⁶⁸Ga]Ga-DOTATATE PET/ CT include focal fatty sparing,^[9] and lymphomas expressing SSR subtype 2,^[10] potentially leading to false-positive interpretations for metastatic disease. FNH are typically solitary lesions which appear hypo- or iso-attenuating compared to normal liver parenchyma,^[11] with notable increased enhancement following contrast injection.^[12] Additionally, unlike malignant masses, FNH lesions appear hyper- or iso-intense on the hepatobiliary phase when performing hepatobiliary contrast agent-enhanced MRI.^[13] There is no documentation in the literature of SSR expression in FNH-like lesions. However, preclinical reports exist of SSR expression in hepatic stellate cells^[14], which have been shown to be activated in FNH.^[15] The patient’s background of cryptogenic cirrhosis may have contributed to the [⁶⁸Ga] Ga-DOTATATE avidity seen on PET/CT, as inflammatory pathways in animal studies have demonstrated hepatic SSR upregulation in cirrhotic liver.^[16] This rare case underscores that hepatic SSR expression is not pathognomonic of metastatic disease, necessitating careful correlation with MRI findings. If there remains uncertainty, definitive histopathological analysis should be performed. On annual surveillance imaging, the patient remains disease-free five years after surgical resection.