We present a case of human epidermal growth factor receptor 2 (HER2)-overexpressing, alpha-fetoprotein (AFP)-producing metastatic gastric adenocarcinoma diagnosed in the USA. Both HER2 overexpression and AFP production are independently associated with poor prognosis in gastric cancer, and their co-expression is rare. This gastric cancer subtype has been reported mainly in Asian populations, with fewer cases in Western countries. Due to its rarity, optimal treatment strategies are not well-established, and clinicians typically treat with standard cytotoxic chemotherapy regimens. Our patient presented with a visceral crisis denoted by impending liver failure, prompting the urgent initiation of first-line systemic therapy with fluorouracil, leucovorin, oxaliplatin and trastuzumab. This resulted in rapid clinical improvement, normalisation of liver function tests and tumour markers, and radiographic response with approximately 50% reduction in hepatic metastatic disease burden. This case underscores the aggressive behaviour and rarity of HER2-positive, AFP-producing gastric cancer, highlighting the critical need for prompt diagnosis and initiation of systemic therapy.
Poles et al. (Sun,) studied this question.