A 32-year-old Chinese woman presented with upper abdominal distension for two weeks. Physical examination: The abdomen was slightly protuberant and a hard mass was palpable, with smooth surface and clear boundary, no tenderness in the liver region, hepato-jugular reflux(+). The patient had no history of hepatitis and lack of icteric skin or sclera. Serum levels of AFP, bilirubin, transaminase and tumor markers including carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125) were all within normal limits. Ultrasound showed a huge hyperechoic mass with heterogeneous echo-texture in the left lobe of liver, approximately 11.4*7.9*15.3cm, No duct dilatation either in the liver or in the extrahepatic bile ducts was found. The pancreas was normal in size and shape, no pancreatic duct dilatation was seen. Computed tomography (CT) scans showed a large solid mass of low density in the left lobe of liver with complete envelop and clear boundary. Magnetic resonance imaging (MRI) showed a giant mass with slightly long T1 and long T2 signal in the left hepatic lobe. T1WI showed a soft tissue mass about 11.8*7.4cm in diameter, with a slightly weak signal and a well-demarcated border (). T2WI showed a strong signal image, with an asteriform stronger signal in and a clear capsule of low signal around the tumor (). The lesion was irregular enhancement in T1 contrast-enhanced arterial phase scanning, mostly with borderline enhancement (). The lesion was persistent enhancement in T1 contrast-enhanced venous phase scanning, which was a little lower than the obviously enhanced liver parenchyma. The enhanced signal was gradually present from surrounding to interior of the mass, with a significant envelope enhancement (). Signal intensities of the capsular of delayed phase was strengthen.
Figure 1 A: T1WI showed a soft tissue mass about 11.8*7.4cm in diameter, with a slightly weak signal and a welldemarcated border. B: T2WI showed a strong signal image, with an asteriform stronger signal in and a clear capsule of low signal around the tumor. C: (more ...)
The resected tumor was fixed in 10% formalin and embedded in paraffin, sectioned at 4 μm, and stained with hematoxylin and eosin. Immunohistochemical staining was performed using the streptavidin-peroxidase system (Ultrasensitive, MaiXin Inc, Fuzhou, China) according to the manufacturer’s instruction. The following antibodies (MaiXin Inc, China, prediluted) were used: Cytokeratin(pan), Vimentin, synaptophysin, chromogranin, a-fetoprotein (AFP), Polyclonal carcinoembryonic antigen (CEA), Placental Alkaline Phosphatase (PLAP), CD99, CD21, CD34, CD10, β-catenin and the Ki-67. Positive and negative controls were evaluated appropriately for each procedure.
The patient was diagnosed with malignant liver tumor and carried out left hepatectomy. No ascites and enlarged retroperitoneal lymph nodes were found during the operation. The tumor appeared heterogeneous, off-white and solid, which was surrounded by a slim envelope. No tumor necrosis was found and cirrhosis was absence in adjacent non-tumor liver tissues.
Hematoxylin and eosin sections showed that the tumor was clear bordered and characterized by cells with hyperchromatic nuclei and without prominent nucleoli and scant cytoplasm, growing in a solid pattern (). Occasional rosettes were seen (), the mitotic activity was about 5 mitoses/10HPF, mucoid degeneration () and vascular invasion () were seen in the tumor, but necrosis was absent. Immunohistochemical stainings showed that the tumor cells were positive for Cytokeratin(pan) (), and neuroendocrine markers [Including Syn () and CgA ()], but negative for AFP (), Polyclonal CEA, PLAP, CD99, CD21, Vimentin, CD34, and the Ki-67 labeling index was about 35%-40%. The tumor showed high proliferative activity and presented some similar characteristics of neuroendocrine tumor, such as formed the rosettes and diffused expression of neuroendocrine markers. Therefore, the patient was diagnosed as neuroendocrine tumor (G3) and was referred to the Department of Oncology to evaluate the possibility of chemotherapy or reirradiation. Because larger neuroendocrine tumors (G3) were prone to hemorrhage and necrosis, and usually presented with high mitotic activity, the oncologist advised a revision of the pathological diagnosis.
Figure 2 A: The tumor was clear boundary (hematoxylin-eosin, original magnification ×100). B: The tumor cells presented some similar characteristics of neuroendocrine tumor, formed focal rosette and a large number of Squamous corpuscles. (hematoxylin-eosin, (more ...)
Figure 3 The tumor cells were positive for Cytokeratin(pan) A, Syn B and CgA C (Original magnification ×200). D: The tumor cells were negative for AFP, but Scattered cells in the squamous corpuscles showed a nuclear staining (Original magnification ×200). (more ...)
Revision was performed in the Department of Pathology in the First Affiliated Hospital of China Medical University. The hematoxylin and eosin-stained sections showed that the tumor was made up of two epithelial cell types. One epithelial component comprised small uniform embryonal cells with increased nuclear/cytoplasmic ratio, grouped in nodules and formed focal rosette. Some solid areas were found in the center of the nodules, which were composed of large, spindled squamoid cells that formed small morular arrangements, occasionally with keratinization, known as squamous corpuscles (). Scattered cells in the squamous corpuscles showed a nuclear staining with all the immunohistochemical markers. However, all the morular cells showed cytoplasmic positivity for CD10 (), which further highlighted the squamous corpuscles. β-catenin staining exhibited a mixed nuclear and cytoplasmic pattern of the tumor cells (), and was only present in the membrane of normal liver cells (, the lower right corner). Based on the histological findings and immunohistochemical stainings, we concluded that this is a rare case of adult hepatoblastoma with neuroendocrine differentiation, which has been only described twice in infants in the literature [3