This is a Chinese case of a 69-year-old female who noticed distention of the hypogastrium accompanied by constipation 20 days ago. No pain, nausea, vomiting, fever, oppression in the chest, jaundice, and bloody stool were found during the period, and she went to the local hospital and received enema treatment. However, distention of the hypogastrium still existed. There were no liver palms, spider-burst, superficial lymph node enlargement, tenderness, rebound tenderness, masses, fluid thrill, shifting dullness, hepatojugular reflux, and pathological reflex on relevant physical examination. The patient denied familial genetic, alcohol abuse, hepatitis, hepatic cirrhosis, psychosocial and exposure to radiation, and toxin history. Furthermore, she was examined in line with the care checklist, as shown in  Supplementary Figure 1 .
Laboratory tests of the tumor biomarkers (alpha-fetoprotein (AFP), CEA, CA125, CA199, CA153), liver function (ALT, AST, TP, ALB, GLB, TBIL, DBIL, IBIL), and lipid index (TG, TC, HDL-C, LDL-C) of serum were normal.
She was admitted and underwent abdominal computed tomography (CT), which demonstrated a 3.3-4-cm soft tissue mass shadow in the neck of the gallbladder which was significantly enhanced on enhanced scan with an unclear boundary to the duodenum and head of pancreas ( Figures 1A, B  ). Unclear cystic duct, dilation of the common bile duct, and bile ducts inside and outside the liver were shown. No dilation of the pancreatic duct or definite abnormality of the liver was detected. Porta hepatis lymph node enlargement was also observed ( Figure 1C ). Magnetic resonance imaging (MRI) also showed gallbladder neck mass ( Figure 1D ). Therefore, a gallbladder carcinoma was suspected and laparoscope cholecystectomy was performed.
The mass was about 3.8 x 3.5 x 1 cm3 in size on the gallbladder wall ( Figure 2A ). The primary lesions consisted of two components: high-grade intraepithelial neoplasia of glands ( Figure 2B ) and hepatoid glands ( Figure 2C ). The tumor cells were cuboidal or polygonal with abundant eosinophilic granular hepatocyte-like neoplastic cells, and the nucleus was large and ovoid; moreover, one to two nucleoli were also shown in the area of the hepatoid component. The lymph node around the gallbladder had been invaded by the hepatoid tumor cells ( Figure 2D ).
Immunohistochemical staining shows positiveness of glypican-3 and MUC-1 of high-grade intraepithelial neoplasia of glands, but negativeness or weak positiveness in the hepatoid glands ( Figures 3A, B  ). Hepatocyte paraffin 1 (Hep par-1) showed contrasting results ( Figure 3C ). AFP, arginase-1, and Sall-4 were all negative ( Figures 3D-F ), and P53 was strongly positive ( Figure 3G ). The Ki-67 index in hepatoid glands was much stronger than that of other areas ( Figure 3H ). Besides, positiveness of CK-pan, CK7, CK8, CK18, and CK19 and negativeness of CK20 were also detected.
TMB of 688 genes detected by MGISEQ-2000 of Beijing Genomics Institute (BGI, Shenzhen, China) was used in the case. The MB21D2 gene showed Exon 2E p.Q311E (c.931C > G) mutation, and abundance of mutation was 10.5%. The GALNT12 gene revealed Exon 1 p.L133Q (c.338T > A) mutation, and abundance of mutation was 13.56%. The ARID2 gene indicated Exon 10 p.L381V (c.1141C > G) mutation, and abundance of mutation was 11.47% ( Table 1 ). No microsatellite instability (MSI) and germline mutation were detected. Finally, we made the diagnosis of primary hepatoid adenocarcinoma of the gallbladder with MB21D2, GALNT12, and ARID2 mutations.
The patient remained under careful observation by radiological and ultrasonic examination, and there was no visceral metastasis in the 5-month follow-up. The patient got an appropriate perspective including the assessment and the episode of care in every month, such as ultrasound examination, rehabilitation training, dietary guidance, regular physical examination, and mental status assessment. The patient healed well, and the distention of hypogastrium disappeared. No adverse or unanticipated events and symptoms in physical examination happened during the period.