Liver metastasis from hepatoid adenocarcinoma of the stomach: a case report and literature review.

Hepatoid adenocarcinoma of the stomach (HAS) represents a rare malignant neoplasm sharing morphological and immunophenotypic similarities with hepatocellular carcinoma (HCC). Pathological morphology serves as the cornerstone for diagnosis, often accompanied by elevated alpha-fetoprotein (AFP) levels, nonspecific clinical symptoms, and imaging features reminiscent of gastric adenocarcinoma (GA). Liver metastases from HAS can mimic the enhancement patterns of HCC, posing challenges in differentiation from high-risk HCC cases. Conversely, HAS typically exhibits poorer prognostic outcomes compared to HCC and GA. This report presents a case of HAS with liver metastasis alongside a comprehensive literature review covering its pathology, molecular mechanisms, clinical presentations, and treatment modalities. Special focus is given to imaging characteristics and the utilization of radiomics for early-stage detection. The integration of imaging findings with laboratory results aids in HAS diagnosis, while radiomics provides novel insights for precise discrimination. In conclusion, the identification of distinct imaging markers distinguishing HAS from HCC and GA shows promise in facilitating optimal treatment strategies and improving patient outcomes.

Clinicopathological features of hepatoid adenocarcinoma of the stomach: A multicenter retrospective study.

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare and aggressive subtype of gastric cancer (GC), accounting for less than 1% of all cases. It is characterized by frequent liver metastasis recurrence and a poorer prognosis than conventional GC. However, established treatment guidelines for HAS are currently not available.In this report, we present the results of a clinicopathological study of 19 patients diagnosed with HAS, including seven patients with liver metastasis, conducted by the Hiroshima Surgical Study Group of Clinical Oncology (HiSCO) between 2016 and 2018. AIMS: The aim of the study was to retrospectively observe the outcomes of HAS with gastrectomy and hepatectomy for liver metastasis and determine relevant prognostic factor. We also examined the criteria and outcomes of hepatectomy for liver metastasis and aimed to suggest the optimal treatment for HAS, including chemotherapy. METHODS AND RESULTS: A total of 2147 patients underwent gastrectomy for GC at HiSCO-affiliated institutions during the study period; 19 patients, all male with a mean age of 70.9 years, were diagnosed with HAS by hematoxylin-eosin and immunohistochemical staining. Patients underwent gastrectomy at varying pathological stages: six at Stage I, three at Stage II, seven at Stage III, and three at Stage IV. Ten patients received postoperative chemotherapy and the 5-year survival rate was 67.7% after gastrectomy. Among the seven patients with pre or postoperative liver metastasis, five patients underwent hepatectomy. Although one patient had recurrence, the 3-year survival rate was 100% after hepatectomy. CONCLUSION: Contrary to previous reports suggesting a 3-year survival rate of approximmately 30% for HAS, our findings indicate that the prognosis for HAS may not be as poor as reported previously. This study contributes valuable insights into the management and potential treatment strategies for HAS.

Assessing clinical pathological characteristics and gene expression patterns associated with hepatoid adenocarcinoma of the stomach.

OBJECTIVE: The objective of this study is to assess the clinical pathological attributes of Hepatoid Adenocarcinoma of the Stomach (HAS) and to delineate the differential diagnostic considerations about it. METHOD: The investigation involved analyzing 31 HAS cases using histomorphological assessment, immunohistochemical profiling, and relevant gene detection methodologies. RESULTS: Among the 31 HAS cases, 9 (29.0%) were of trabecular hepatoid adenocarcinoma of the stomach, 7 (22.6%) were of glandular hepatoid adenocarcinoma of the stomach, 4 (12.9%) were of nesting hepatoid adenocarcinoma of the stomach, 3 (9.7%) were of clear cell hepatoid adenocarcinoma of the stomach, and 8 (25.8%) were of diverse hepatoid adenocarcinoma of the stomach. Of these 31 cases, 24 were male, accounting for 77.4% of the cases. Serum alpha-fetoprotein (AFP) levels were notably elevated, with radioimmunoassay results reaching 1240 ng/ml; 28 out of 31 cases had AFP levels below 25 µg/l, accounting for 90.3%. Related genes: HER2 protein indicated positive expression on the cell membrane in 35.5% (11/31) of the cases; HER2 gene amplification detected by the FISH technique was 12.9% (4/31). Tumoral stromal lymphocytes exhibited a PD-1 positive expression rate of 58.1% (18/31). In gastric cancer tissues, the PD-L1 positive rate was 45.1% (14/31). CONCLUSION: HAS represents a distinctive subtype of gastric cancer with a propensity for mimicking other forms of tumors, underscoring the significance of discerning its unique histopathological attributes for accurate differential diagnosis and tailored therapeutic interventions.

An unusual cause of significantly elevated blood alpha-fetoprotein levels: a case report and literature review.

Alpha-fetoprotein (AFP) serves as a crucial diagnostic marker for primary hepatocellular carcinoma (HCC) and germ cell tumors (GCTs), with rare instances of significantly elevated levels in other diseases. In this study, we present a case of an elderly patient who was diagnosed with AFP-producing gastric cancer (AFPGC) following an elevated AFP result during physical examination. In investigating liver cancer at an early stage, the diagnosis was missed because of failure in detecting the lesion, resulting in delayed treatment initiation. AFPGC is a rare aggressive tumor that demands heightened awareness among clinicians to foster early detection, diagnosis, and treatment for improved prognosis.

Hepatoid Adenocarcinoma of the Esophagus with Thyroid Metastasis: A Case Report.

Rare hepatoid adenocarcinomas are highly heterogeneous. In this case, hepatoid adenocarcinoma occurred in both the esophagus and thyroid, and the combination of chemotherapy and immunotherapy may be a promising therapeutic tool for rare tumors. Laryngoscope, 134:3673-3676, 2024.

Exceptional Long-Term Survival of a Patient With Hepatoid Adenocarcinoma of the Colon and the Treatment Strategy: A Case Report.

Hepatoid adenocarcinoma (HAC) of the colon is a rare type of tumor with hepatocellular differentiation. HAC often produces alpha-fetoprotein (AFP) and metastasizes to lymph nodes and the liver. HAC is usually aggressive with a poor prognosis and has a propensity for intravascular growth and frequent distant metastasis. Because the biology of HAC is not fully understood, there are very limited therapeutic options known to reduce recurrence and improve survival. In addition, because HAC is so rare, it is difficult to acquire data from large randomized clinical trials to guide practice; therefore, case reports can provide valuable information for the treatment of HAC. In this report, we present a case of a 30-year-old male patient with HAC with high AFP levels and liver metastases. The patient underwent hepatic arterial infusion chemotherapy (HAIC) with doxorubicin/oxaliplatin to treat the liver metastasis, and three weeks later, he received radical sigmoid and rectal resection, left liver resection, and ileostomy. Then, the patient received eight cycles of chemotherapy with epirubicin plus folinic acid, fluorouracil, and oxaliplatin (FOLFOX) every three weeks, followed by maintained therapy with capecitabine for 2.5 years without relapse. This case report indicates that, although HAC is usually an aggressive disease with frequent distant metastasis, patients with HAC may still have a good prognosis if treated with appropriate strategy.

CT Findings of Hepatic Metastasis from Hepatoid Adenocarcinoma of the Rectum Mimicking Hepatocellular Carcinoma: A Case Report.

Hepatoid adenocarcinoma (HAC) is a rare form of adenocarcinoma that is diagnosed based on immuno-histochemical findings reminiscent of hepatocellular carcinoma (HCC). The clinical characteristics of HAC include increased levels of serum alpha-fetoprotein and a poor prognosis due to early liver metastasis. In particular, diagnosing liver metastasis of HAC can be challenging owing to radiological findings similar to those of HCC. Although HAC can occur in various organs, the stomach is the most common site. We present the case of a 64-year-old femalewho presented with multiple tumors in the liver. During subsequent examination, rectal cancer was identified and diagnosed as HAC through a biopsy. Herein, we report this case along with a literature review.

Long survival after neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery in a patient with hepatoid adenocarcinoma of the lung: A case report.

Hepatoid adenocarcinoma of the lung (HAL) is a rare and aggressive subtype of lung cancer. The prognosis for patients with HAL is generally poor and currently, there are only limited treatment options. Here, we present a case of a 47-year-old male diagnosed with locally advanced-stage HAL who achieved a remarkably long disease-free survival after receiving neoadjuvant and adjuvant camrelizumab plus chemotherapy and surgery. This case highlights the potential of immunochemotherapy plus surgery in improving outcomes for patients with HAL.

[Diffuse Hepatoid Adenocarcinoma in the Peritoneal Cavity:Report of One Case].

Hepatoid adenocarcinoma is a rare and unique type of adenocarcinoma,resembling hepatocellular carcinoma in histopathology.Most cases occur in the stomach,lacking specific clinical and imaging manifestations,which leads to high rates of missed diagnosis and misdiagnosis.Hepatoid adenocarcinoma in the peritoneal cavity is even rarer.This article reports a case of hepatoid adenocarcinoma with the manifestation of diffuse peritoneal thickening,aiming to provide reference for clinical diagnosis and treatment.

Hepatoid adenocarcinoma in ureter with next-generation sequencing: A case report and literature review.

BACKGROUND: Hepatoid adenocarcinoma (HAC) is rare in the urinary system, with only 7 reported cases in upper urinary tract. This report aimed to explore the genetic characteristics of ureteral HAC for first time, and to describe the treatment prognosis of ureteral HAC. CASE PRESENTATION: We present a rare case of ureteral HAC in a 53-year-old female, showing elevated serum levels of AFP and CEA, prolonged chronic irritation may be an important cause of her ureteral HAC. Radical nephroureterectomy was performed, the serum levels of AFP and CEA decreased significantly, and metastasis in lymph nodes was found at 9 months after surgery, she had no related symptoms after 18 months postoperatively without adjuvant chemotherapy. Three driver somatic mutations in cancer were identified by NGS testing, including: TP53D281H, KMT2DL1211Ifs*2, KMT2DT1843Nfs*5, demonstrating that ureteral HAC has the similar mutational features to upper tract urothelial carcinoma. Homologous-recombination deficiency (HRD) was positive in this tumor with no mutations in HRD-related genes, which was possibly induced by the copy number deletion of SETD2 gene. CONCLUSIONS: We report a rare case of ureteral HAC with elevated serum levels of AFP and CEA. NGS testing demonstrated that ureteral HAC has the similar mutational features to upper tract urothelial carcinoma, which is an important guide for the diagnosis and treatment of ureteral HAC.

A case report of challenges in distinguishing gastroesophageal junction hepatoid adenocarcinoma from testicular germ cell tumor: Insights for improved diagnosis with gene expression profiling.

Gastroesophageal junction hepatoid adenocarcinoma is a rare form of gastroesophageal cancer. We present a case of a 38-year-old man with no significant medical history who was diagnosed with gastroesophageal junction hepatoid adenocarcinoma but initially misdiagnosed with a testicular germ cell tumor, given the elevated alpha-feto protein and poorly differentiated pathology. We will elaborate on the importance of gene expression profiling in modern oncology to better define the tumor of origin in patients with cancer of unknown primary origin, how it helped us to diagnose gastroesophageal junction hepatoid adenocarcinoma and how it can help identify potential additional therapeutic targets in some cases. Due to the rarity of this subtype of gastroesophageal junction cancer there is a lack of standard therapeutic options, and we will discuss the most commonly used treatment regimens. The patient underwent three lines of antineoplastic therapy and unfortunately passed after 51 weeks of follow-up.

Immunohistochemical characteristics and potential therapeutic regimens of hepatoid adenocarcinoma of the stomach: a study of 139 cases.

Hepatoid adenocarcinoma of stomach (HAS) is a special subtype of gastric cancer with poor prognosis. Immunohistochemical analysis could provide important clues for the treatment of HAS. A total of 159 patients were diagnosed as HAS and 139 were enrolled in this study. Statistical differences were determined using relative test methods and survival analyses were performed by the Kaplan-Meier method to find survival differences. All tumors in this study were negative for Epstein-Barr virus-encoded small RNAs (EBERs) and almost all showed no loss of mismatch repair (MMR) proteins and were positive for alpha fetoprotein (AFP or spalt like transcription factor 4 (SALL4). About half of the tumors had a positive programmed death-ligand 1 combined positive score (CPS) and 17.3% were positive for human epidermal growth factor receptor 2 (HER2). In addition, there was a relatively high proportion of cmet expression. We also found that HAS patients with recurrent disease treated by emerging therapy had a better survival than those treated with traditional chemotherapy (p = 0.002, median recurrence-to-death survival: 23 months versus 6 months); HAS patients who received anti-HER2 therapy or harbored MMR deficiency had favorable prognosis. Overall, high proportions of MMR protein proficiency, positivity for AFP or SALL4, overexpression of HER2, CPS and cmet, as well as negative EBER findings, are distinctive characteristics of HAS patients. While negative EBER and MMR proficiency indicate molecular features of HAS, positivity for AFP or SALL4 could aid in the diagnosis of HAS. In addition, HAS patients could benefit from anti-HER2 therapy, immunotherapy, and anti-angiogenesis therapy.

α-Conotoxin recombinant protein ImI-AFP3 efficiently inhibits the growth and migration of lung cancer cells.

α-Conotoxin ImI is a selective antagonist of alpha7 nicotinic acetylcholine receptor (α7 nAChR) that is involved in cancer development. Human alpha fetoprotein domain 3 (AFP3) is a prototype of anticancer agents. In an effort to design drugs for anticancer treatments, we fused the ImI peptide to AFP3 as a fusion protein for testing. The fusion protein (ImI-AFP3) was highly expressed in the insect Bac-to-Bac system. The purified fusion protein was found to have improved anticancer activity and synergized with the drug gefitinib to inhibit the growth and migration of A549 and NCI-H1299 lung cancer cells. Our data have demonstrated that the recombinant protein ImI-AFP3 is a promising candidate for drug development to suppress lung cancer cell growth, especially to suppress hepatoid adenocarcinoma of the lung (HAL) cell growth.

Colostomy-site carcinoma with primitive phenotype in a rectal cancer patient after achieving pathological complete response with neoadjuvant chemoradiotherapy.

Herein, we report a rare case of a carcinoma with primitive phenotype (enteroblastic and/or hepatoid differentiation) occurring at a colostomy site. The patient was an elderly male who underwent neoadjuvant chemoradiotherapy for rectal cancer, followed by abdominoperineal resection. A biopsy specimen for the rectal carcinoma before neoadjuvant chemoradiotherapy was conventional tubular adenocarcinoma. Moreover, a pathological complete response was confirmed in the proctectomy specimen. However, a colostomy-site tumor appeared 6 months after the proctectomy, and it was resected 1 year after the initial proctectomy. The colostomy-site tumor comprised solid to focal glandular growth of atypical polygonal cells with clear to pale eosinophilic cytoplasm and was immunohistochemically positive for cytokeratin, spalt-like transcription factor 4, glypican-3, caudal type homeobox 2, and special AT-rich sequence-binding protein 2. Thus, the tumor was diagnosed as poorly differentiated adenocarcinoma with primitive phenotype, with suggested origin from the colorectal epithelium. Additionally, a multilocular cystic lesion comprising various types of epithelia was found adjacent to the tumor, suggestive of metaplasia or heterotopia. Changes in the histology and immunophenotype, and the findings of an adjacent cystic lesion suggest a metachronous tumor rather than a recurrence of the primary tumor.

Hepatoid adenocarcinoma of the lung with PD-L1 expression and the response to anti-PD-1 therapy: a case report.

Hepatoid adenocarcinoma of the lung (HAL) is extremely rare; a standardized treatment strategy for HAL has not been established. The prognosis of patients with unresectable HAL is extremely poor. Here, we reported a 64-year-old male patient with unresectable alpha-fetoprotein-producing HAL who showed moderate harboring programmed death ligand 1 (PD-L1) expression and no targetable driver mutations. The patient was treated with brain radiotherapy, multiple lines of chemotherapies, and PD-1 inhibitor and achieved a survival rate of 9 months. The patient finally died because of the progression of brain metastasis. The case report provides valuable information for the treatment strategy development of advanced HAL patients and reminds us of the therapeutic particularity of brain metastasis.

A rare case of hepatoid adenocarcinoma of the lung.

Hepatoid adenocarcinoma of the lung is a special type of primary origin in the lung with obvious pathological features and short survival time. However, standard treatment guidelines have not yet been established. Herein, we report a case of hepatoid adenocarcinoma with the primary lesion located in the left upper lung. The tumour size was reduced after four cycles of combined therapy. Subsequent postoperative pathology confirmed complete remission.

Primary hepatoid adenocarcinoma of lung: A rare malignancy mimicking tuberculosis.

Hepatoid adenocarcinoma of lung (HAL) is a rare aggressive malignant tumour which histologically resembles hepatocellular carcinoma (HCC). Hepatoid adenocarcinoma (HAC) mostly produces high levels of alphafetoprotein (AFP) and is frequently found in extrahepatic organs including stomach, testes, ovaries, lungs and pancreas. Our patient was a male in his 40s with a chronic smoking history, presented with complaints of fever, weight loss, cough and anorexia for one month. On the basis of history, examination and initial investigation patient were started on empirical antitubercular therapy. However, within a span of 10 days, patient's condition worsened, and he developed a pulmonary embolism, which despite adequate treatment did not improve and the patient succumbed to his illness. Postmortem biopsy revealed a rare primary lung tumour, HAL.

Exploration of molecular markers related to chemotherapy efficacy of hepatoid adenocarcinoma of the stomach.

PURPOSE: Preoperative neoadjuvant chemotherapy may not improve the prognosis of patients with hepatoid adenocarcinoma of the stomach (HAS), a rare pathological type of gastric cancer. Thus, the study aimed at the genomic and transcriptomic impacts of preoperative chemotherapy on HAS. METHODS: Patients with HAS who underwent surgical resection at Peking University Cancer Hospital were retrospectively included in this study. Whole exome sequencing and transcriptome sequencing were performed on pre-chemotherapy, non-chemotherapy and post-chemotherapy samples. We then compared the alterations in molecular markers between the post-chemotherapy and non-chemotherapy groups, and between the chemotherapy-effective and chemotherapy-ineffective groups, respectively. RESULTS: A total of 79 tumor samples from 72 patients were collected. Compared to the non-chemotherapy group, the mutation frequencies of several genes were changed after chemotherapy, including TP53. In addition, there was a significant increase in the frequency of frameshift mutations and cytosine transversion to adenine (C > A), appearance of COSMIC signature 6 and 14, and a reduced gene copy number amplification. Interestingly, the same phenomenon was observed in chemotherapy-ineffective patients. In addition, many HAS patients had ERBB2, FGFR2, MET and HGF gene amplification. Moreover, the expression of immune-related genes, especially those related to lymphocyte activation, was down-regulated after chemotherapy. CONCLUSION: Chemotherapy is closely associated with changes in the molecular characteristics of HAS. After chemotherapy, at genomic and transcriptome level, many features were altered. These changes may be molecular markers of poor chemotherapeutic efficacy and play an important role in chemoresistance in HAS. In addition, ERBB2, FGFR2, MET and HGF gene amplification may be potential therapeutic targets for HAS.