Hepatoid adenocarcinoma of the stomach: an unusual case of elevated alpha-fetoprotein with prior treatment for hepatocellular carcinoma
A 68-year-old man was evaluated for elevated serum AFP level. He had been diagnosed with chronic HBV infection and cirrhosis twenty years ago. He was receiving antiviral treatment with oral antiviral agents (lamivudine and adefovir dipivoxil) from 2003 to 2008 due to HBV reactivation with elevated liver enzyme, positive for HBeAg and HBV DNA of 199.1 pg/mL. Tests for HCV and human immunodeficiency virus (HIV) were negative. After the administration of antiviral agents, liver enzyme was normalized and HBeAg seroconversion occurred. In December 2001, ten years prior to this evaluation, an arterial enhancing lesion approximately 3 cm in size with delayed washout at the segment 6/7 area of the liver (), along with elevated serum AFP level (7,463 ng/mL), was found. The patient was diagnosed with HCC and treated with a right lobectomy, which revealed Edmondson grade II HCC (). Six months after the liver resection, a 1.5 cm sized enhancing nodule with delayed washout was found in the caudate lobe. In August and October 2002, two times of transarterial chemoembolization were performed at the lesion and follow-up computed tomography (CT) showed complete lipiodol uptake at the lesion. Serum AFP had returned to normal level (4.8 ng/mL) and since then, he had been regularly followed up for nine years without evidence of tumor recurrence.\nIn July 2010, elevation of serum AFP level was noticed (from 6.5 ng/mL to 625.4 ng/mL during a period of six months). At this point, he had no specific symptoms or physical findings. A white blood cell count was 3,990/mm3, a hemoglobin level was 14.6 g/dL, a platelet count was 73,000/mm3, a serum protein level was 7.7 g/dL, a serum albumin level was 3.8 g/dL, a serum bilirubin level was 1.5 mg/dL, a serum aspartate aminotrasferase level and a serum alanine aminotransferase level were 56 IU/L and 57 IU/L, a serum creatinine level was 0.84 mg/dL, and a prothrombin time (%) was 81%. Other tumor markers were within normal range (serum proteins induced by vitamin K absence or antagonist-II (PIVKA-II): 23 mAU/mL, carcinoembryonic antigen (CEA): 1.8 ng/mL and carbohydrate antigen 19-9 (CA 19-9): 9.2 IU/mL). Liver CT revealed a 2.5 cm low-attenuated nodular lesion around the common hepatic artery, suggesting metastatic lymphadenopathy without intrahepatic lesion. Positive emission tomography (PET)-CT found a hypermetabolic lymph node (p-SUV=4.1) at the common hepatic artery area, but no other fluorodeoxyglucose (FDG) uptake that suggested the presence of a malignant tumor was found. Based on elevated AFP level and prior history of HCC, metastatic lymphadenopathy from HCC was the differential diagnosis. Radiation therapy for regional lymph node was planned, and he underwent upper endoscopy for screening purposes before receiving radiation therapy. Incidentally, a 4.0 cm ulcerative lesion at the lesser curvature side of the antrum was found during an upper endoscopy (). Gastric biopsy showed poorly differentiated tubular adenocarcinoma. The patient underwent Billroth type II subtotal gastrectomy with D2 lymph node dissection. Microscopic examination revealed HAC with lymph node metastasis as immunohistochemical (IHC) study showed that tumor cells were positive for AFP and polyclonal CEA ().\nAfter the operation, serum AFP level decreased, and he received titanium silicate (TS)-1 for adjuvant chemotherapy. However, 6 months after the gastrectomy, multiple small hepatic nodules were found in the liver during adjuvant chemotherapy (). A liver biopsy was taken and HAC was diagnosed as IHC positive for AFP and CK19, focally positive for CEA, whereas negative for CK7 and CK20 (Fig. 3B, C, D, E). He was then switched to palliative chemotherapy with carpecitabine and cisplatin (XP regimen). After 4 months (four cycles) of chemotherapy, a CT scan revealed a progression of liver metastasis and newly developed pulmonary metastasis. He was put under the second-line palliative chemotherapy with fluorouracil, leucovorin and irinotecan (FOLFIRI regimen). He is currently being followed up for 21 months.