A primary hepatic neuroendocrine tumor disguised as hepatocellular carcinoma.

HepatoBiliary Surg Nutr 2020;9(2):263-266 | http://dx.doi. org/10.21037/hbsn.2020. 01.02 In a 72-year-old female patient, a 2 cm large lesion over liver segment 7 (S7) was incidentally diagnosed during a hepatitis C follow-up. The patient was asymptomatic and had an unremarkable physical examination. Her past medical history consists of chronic hepatitis C, diabetes mellitus type 2 and arterial hypertension. Her blood test results were normal except for highly elevated alpha-fetoprotein (AFP) (821.32 ng/mL). In the abdominal CT and MRI, the tumor lesion exhibited moderate arterial enhancement and early washout favoring the diagnosis of hepatocellular carcinoma (HCC) (Figure 1A,B,C,D). An HCC of cT1bN0M0 stage Ib was suspected and a partial S7 hepatectomy was performed. The resected tissue contained the tumor (1.5 cm × 1.4 cm × 1.3 cm) beneath the liver capsule with a 1.3 cm resection margin (Figure 1E). Surprisingly, the pathology revealed a neuroendocrine tumor with small-sized neoplastic epithelial cells with hyperchromatic, pleomorphic nuclei and salt-pepperlike nuclear chromatin. The immunohistochemical characterization of the tumor was positive for synaptophysin and CD56. The Ki-67 index was 80%, consistent with a grade 3 neuroendocrine carcinoma (NEC). The patient had an uneventful postoperative recovery and underwent further studies to rule out an extrahepatic origin of the NEC: Both panendoscopy and colonoscopy were unremarkable. PET-CT studies performed with F-18FDG and Ga-68-DOTATOC isotopes did not detect any avid lesions (Figure 1F). Also, the AFP serum level returned to normal postoperatively. Hence the final diagnosis of primary hepatic neuroendocrine tumor (HPNET) was made. The patient did not receive any adjuvant therapy because a R0 tumor resection was achieved without evidence of locoregional tumor progression. She was followed-up every 3 months with abdominal ultrasound and blood tests for the tumor markers AFP, CEA, CA19-9, which remained unremarkable. PHNETs are extremely rare, with less than 150 cases reported in the English literature (1). They represent 0.3% of all NETs (2) which originate from neuro-ectodermal cells. Patients with PHNETs present in their 40–60 s with no gender preference (1). They remain asymptomatic for a long time due to slow tumor growth and lack of endocrine functionality. Unlike liver metastasis of NETs, only 6.8% of patients with PHNETs present with carcinoid syndrome (2). Hence PHNETs are either diagnosed incidentally or at a progressed stage due to tumor mass effect. The rarity of PHNETs makes the differentiation from the more common HCCs difficult. One distinction between PHNETs and HCCs is that patients with HCCs typically have a history of alcoholic or viral hepatitis, liver cirrhosis, and elevated serum AFP levels, while patients with PHNETs have not (3). However, in congruence with Zhao’s report (4), our patient with PHNET had a history of chronic hepatitis C and highly elevated serum AFP levels. Although the specificity of elevated AFP for HCC is high (80–94%) (5), false-positive results can arise during pregnancy, active liver disease, embryonic or other gastrointestinal tumors. Since a pure AFP-producing NEC of the pancreas has been reported (6) and most PHNETs cases with elevated AFP levels were described in NECs, we hypothesize that NEC cells might re-express AFP in their dedifferentiation process. The imaging modalities CT and MRI also have low Letter to the Editor