A 34-year-old man presented with right upper quadrant pain in 2006. Ultrasound, magnetic resonance imaging and computed tomography showed a 15 cm × 12 cm × 9 cm low density heterogeneous mass in the right liver lobe. Blood tests showed slightly elevated aspartate aminotransferase, γ-glutamyl transferase, alkaline phosphatase and a very high α-fetoprotein (AFP: 56 500 μg/L, normal level < 20 μg/L). Other biochemical parameters (renal and liver function) and tumor markers such as carbohydrate antigen 19-9, and carcinoembryonic antigen (CEA) were within normal limits. Results of serology testing showed that serum hepatitis B virus surface antigen and anti-hepatitis C virus antibody were negative. The patient had not received any treatment before operation. No other tumor site was detected by extensive preoperative staging. After the liver tumor was resected, the serum AFP level went down to 512 μg/L.
Macroscopically, the partial liver resection specimen from the right lobe contained a single, firm mass with partially necrotic areas. It measured 16 cm × 12 cm × 8 cm. The cut surface was reddish-purple, whitish, gray to tan, slightly lobular with fibrous septa, and showed cystic spaces and areas of hemorrhage.
Histologically, the resected tumor was composed of two GCTs components: yolk sac tumor and immature teratoma. The morphological appearance of yolk sac tumor included endodermal sinus-like (with Schiller-Duval bodies), papillary and glandular components (Figure ). The predominant components of immature teratoma were composed of several types of tissue that represented different germinal layers (endoderm, mesoderm and ectoderm) and showed varying degrees of differentiation. The endoderm components were primitive mesenchyme and various mesenchyme-derived tissues, which were composed predominantly of primitive to spindle cells with rhabdomyoblastic (Figure ), chondroid and osteoblastic differentiation. The mesoderm components were composed of respiratory, intestinal-type epithelium (Figure ), and glandular, ductal or acinar structures that resembled pancreatic acinar tissue (Figure ). The ectoderm components were composed of keratinizing or non-keratinizing epithelium (Figure ), which resembled neuroblastoma tissue that exhibited rosettes formation (Figure ), ganglion differentiation or embryonic neural tube. Mitotic figures were found frequently in various tumorous components. Areas of necrosis were also present. Hepatocellular differentiation was not found in the tumor. Uninvolved liver demonstrated no obvious cirrhosis but slight steatosis. The surgical resection margins were clear.
Figure 1 Histological features of mixed GCT of the liver with sarcomatous components. A: Papillary structures resemble yolk sac tumor with Schiller-Duval bodies; B: Rhabdomyoblastic cells in primitive mesenchymal cell components; C: Intestinal-type epithelium (more ...)
Immunohistochemically, the yolk sac tumor stained positively for AFP (Figure ) and cytokeratin (AE1/AE3). The cells of immature glandular or ductal structures were positive for pCEA, mCEA, AE1/AE3, CK7, CK18 and CK19. Focal hepatocyte marker (HepPar1) protein reaction was seen in the glandular epithelium. The acinar structures that resembled pancreatic acinar cells were positive for AFP (Figure ), α-1-antitrypsin, α-chymotrypsin (Figure ) and AE1/AE3. The primitive mesenchymal spindle cells were stained prominently with vimentin, and focally stained with smooth muscle actin, CD56 (Figure ), CD117 and CD34. Desmin and myoglobin were positive in the immature skeletal muscle tissue (Figure ). The cells of immature chondroid and osteoblastic components were positive for both vimentin and S-100 protein. The neuroblastoma-like areas and ganglion cells were positive for vimentin, synaptophysin (Figure ), neuron-specific enolase (NSE), glial fibrillary acid protein (GFAP), and focally stained with HMB45, CD99 and CD117. The immature glandular structures and neuroblastoma-like areas showed a high proliferative activity of Ki-67 positivity, whereas proliferative activity in the spindle cell areas was lower. P53 showed strong nuclear expression in all epithelial and rhabdomyoblastic cells. All tumor cells stained negatively for CD30, human chorionic gonadotropin or placental alkaline phosphatase (PLAP). The immunohistochemical profile of tumor in the differential diagnosis of GCT of the liver is shown in Table .
Figure 2 Immunohistochemical features of mixed GCT of the liver with sarcomatous components. A: Strong staining for AFP in the yolk sac tumor component; B: Strong staining for AFP in acinar structures resembling pancreatic acinar tissue; C: Strong staining for (more ...)
Immunohistochemical and FISH profiles of tumor that is considered in the differential diagnosis of GCT of the liver
Interphase cytogenetic analysis using fluorescence in situ hybridization (FISH) revealed that the yolk sac tumor and immature teratoma components were positive for i(12p) and 12p overrepresentation (Figure ). In particular, the rhabdomyoblastic cell components also showed typical i(12p) and 12p overrepresentation (Figure ). The FISH ratios ranged from 1.21 to 3.30 in various tumor components (mean: 2.1 ± 0.8).
Figure 3 Tumor cells possess isochromosome 12p and 12p overrepresentation, which are characteristic of tumors of germ cell origin. FISH showing cells with 2-7 (green) 12p signals and 1-4 (orange) 12 centromere signals in yolk sac tumor (A), and rhabdomyoblastic (more ...)
Based on the clinical features, histological findings, immunohistochemical stains and cytogenetic studies, the pathological diagnosis of hepatic mixed tumor with significant sarcomatous components was made. Gonads and retroperitoneal lymph nodes were examined, and did not reveal any abnormality. This patient was cured with a standard protocol of cisplatin, etoposide and bleomycin. Five months after surgery, the patient died of hepatic failure with tumor recurrence and thrombosis of the intrahepatic veins, which indicates that this tumor had the low chemosensitivity. Permission for an autopsy was not granted.