Progress and current perspectives of diagnosis and treatment of hepatoid adenocarcinoma of the stomach

Hepatoid adenocarcinoma of the stomach(HAS)is a rare malignant gastric tumor exhibiting both hepatocellular and adenocarcinomatous differentiation.Patients are often diagnosed at an advanced stage,and their clinical symptoms closely resemble those of gastric adenocarcinoma.Because of its rarity,misdiagnosis and missed diagnoses are prevalent.Compared with gastric adenocarcinoma,HAS typically exhibits higher invasiveness and amore unfavorable prognosis.This review aimed to elaborate on the pathological features,potential mechanisms,clinical characteristics,diagnosis,and prognosis of HAS.The insights provided aimed to contribute robust guidance for the clinical management of patients with HAS.

Hepatoid adenocarcinoma of the stomach with neuroendocrine differentiation:A case report and review of literature

BACKGROUND Both hepatoid adenocarcinoma of the stomach(HAS)and neuroendocrine differentiation(NED)are rare histological subtypes of gastric cancer with unique clinicopathological features and unfavorable outcomes.HAS with NED is even rarer.CASE SUMMARY Here,we report a 61-year-old man with HAS with NED,as detected by gastric wall thickening by positron emission tomography/computed tomography for a pulmonary nodule.Distal gastrectomy was performed,and pathological examination led to the diagnosis of HAS with NED.However,liver metastases occurred 6 mo later despite adjuvant chemotherapy,and the patient died 27 mo postoperatively.CONCLUSION We treated a patient with HAS with NED who underwent adjuvant chemotherapy after radical surgery and still developed liver metastases.We first report the detailed processes of the treatment and development of HAS with NED,providing an important reference for the clinical diagnosis and treatment of this condition.

Alpha-fetoprotein-producing hepatoid adenocarcinoma of the lung responsive to sorafenib after multiline treatment:A case report

BACKGROUND Hepatoid adenocarcinoma of the lung(HAL) is an extremely rare malignant tumor,and many patients with HAL exhibit high levels of alpha-fetoprotein(AFP) expression.Currently,there is no standardized treatment strategy for advanced HAL and its prognosis is poor.CASE SUMMARY We report a 55-year-old man with unresectable AFP-related HAL.The largest cross-sectional area of the mass in the upper lobe of the left lung at the beginning of treatment was 8.46 cm × 6.53 cm.The patient’s serum AFP level was 9283 ng/m L.The mass increased in size to 8.86 cm × 8.21 cm after two courses of platinum-based combination chemotherapy and immunotherapy,and serum AFP reached its highest level(71232.2 ng/m L).The patient was treated with sorafenib(400 mg twice daily,per os).Forty days later,the mass was reduced to 5.63 cm × 5.29 cm and serum AFP level dropped to 786.8 ng/m L.The patient achieved partial remission for > 9 mo with sorafenib and an excellent biomarker response,as well as survival > 13 mo,which is among the longest reported for unresectable stage IV HAL.CONCLUSION This is the first report to document successful treatment of unresectable AFPrelated HAL with single-agent sorafenib after multiline therapy.

Treatment of gastric hepatoid adenocarcinoma with pembrolizumab and bevacizumab combination chemotherapy:A case report

BACKGROUND Gastric hepatoid adenocarcinoma(GHA)is a rare and aggressive cancer that is characterized by foci with features of both hepatocellular differentiation and adenomatous differentiation.However,there is currently no standard treatment for this disease,which has a poor prognosis.CASE SUMMARY A 72-year-old male with a body mass index of 20.9 was diagnosed with GHA with perigastric lymph node and liver metastasis.He underwent first-line chemotherapy but that failed.Pembrolizumab and bevacizumab with chemotherapy were used in the second-line treatment.The progression-free survival and overall survival were 14 mo and 16 mo,respectively,after treatment.In addition,the main adverse reaction was tolerable.The patient did not die of tumor progression.CONCLUSION The combination of pembrolizumab and bevacizumab with chemotherapy is an effective and safe regimen for GHA and may be recommended as a new choice for GHA treatment.Further studies should evaluate this treatment in a larger cohort or a randomized controlled trial.

Multi-Metastatic Hepatoid Adenocarcinoma of the Lung: Report of Case

Hepatoid adenocarcinoma of the lung is a rare tumor with a poor prognosis. There are no specific treatment-recommendations for this cancer. We report a 59-year-old man, a former smoker, with this condition. He presented with a cough and computed tomography revealed a pulmonary nodule (50 × 47 × 48 mm) with a right pleural effusion, together with a cerebral right temporal-lobe lesion and a right adrenal lesion. The serum alpha-fetoprotein value was normal. Histological examination via bronchoscopic biopsy revealed an adenocarcinoma. Positive CK7, AE1/AE2, and TTF1 with granular cytoplasmic staining on immunohistochemical study confirmed the diagnosis of hepatoid adenocarcinoma of the lung, stage IV-B. The patient had received chemotherapies (carboplatin-pemetrexed, gemcitabine) and cerebral radiotherapy, but he died at eight months of the treatment as a result of tumor progression.

Liver metastasis from hepatoid adenocarcinoma of the stomach mimicking hepatocellular carcinoma: Dynamic computed tomography findings

AIM: To evaluate the dynamic computed tomography(CT) findings of liver metastasis from hepatoid adenocarcinoma of the stomach(HAS) and compared them with hepatocellular carcinoma(HCC).METHODS: Between January 2000 and January 2015, 8 patients with pathologically proven HAS and liver metastases were enrolled. Basic tumor status was evaluated for the primary tumor location and metastatic sites. The CT findings of the liver metastases were analyzed for tumor number and size, presence of tumor necrosis, hemorrhage, venous tumor thrombosis, and dynamic enhancing pattern.RESULTS: The body and antrum were the most common site for primary HAS(n = 7), and observed metastatic sites included the liver(n = 8), lymph nodes(n = 7), peritoneum(n = 4), and lung(n = 2). Most of the liver metastases exhibited tumor necrosis regardless of tumor size. By contrast, tumor hemorrhage was observed only in liver lesions larger than 5 cm(n = 4). Three patterns of venous tumor thrombosis were identified: direct venous invasion by the primary HAS(n = 1), direct venous invasion by the liver metastases(n = 7), and isolated portal vein tumor thrombosis(n = 2). Dynamic CT revealed arterial hyperattenuation and late phase washout in all the liver metastases.CONCLUSION: On dynamic CT, liver metastasis from HAS shared many imaging similarities with HCC. For liver nodules, the presence of isolated portal vein tumor thrombosis and a tendency for tumor necrosis are imaging clues that suggest the diagnosis of HAS.

Gastric hepatoid adenocarcinoma: A computed tomography report of six cases

We describe the computed tomography(CT)imaging findings in six cases(five males and one female;age range 61-78 years;mean age 67.3 years)with histologically proven hepatoid adenocarcinoma of the stomach(HAS).Five of the six patients had elevated serum alpha-fetoprotein levels.The most common type of gross appearance HAS on CT is a polypoid mass(83%,5/6).The most common contrast enhancement pattern was heterogeneous.All six patients had a regional lymphadenopathy larger than 6 mm in its short axis.Liver metastases(n=3)were noted.Venous tumor thrombosis was identified in the portal vein(n=2)of the regions near primary gastric tumors or metastatic masses.Our findings suggest in an elderly,male patients with a large heterogeneous enhancement tumor,the presence of distant metastases,regional lymphadenopathy and characteristically increased serum alphafetoprotein levels indicates a high likelihood of HAS.

Hepatoid adenocarcinoma of the colon in a patient with inflammatory bowel disease

A case is presented of a 36-year-old male with primary sclerosing cholangitis-associated inflammatory bowel disease(PSC-IBD) and two synchronous stage 1 adenocarcinomata of the colon,who was initially treated with a subtotal colectomy with ileostomy.One year later,the patient presented with extensive intra-abdominal lymphadenopathy and peritoneal carcinomatosis,as well as a markedly elevated serum level of alpha-fetoprotein(AFP).Fine needle aspiration biopsy of a porta hepatis lymph node revealed a metastatic hepatoid adenocarcinoma.Subsequent review of the previous colectomy specimen showed that one of the previously identified adenocarcinomata had features suggestive of a hepatoid colonic adenocarcinoma.The patient was subsequently treated with a cytotoxic regimen of FOLFOX(oxaliplatin,leucovorin,5-fluorouracil) and bevacizumab,with stable results being achieved after six months.This case presents the first known report of PSC-IBD associated with synchronous typical and hepatoid adenocarcinomata of the colon and highlights the importance of considering hepatoid adenocarcinoma as a differential diagnosis in patients with an increasing serum AFP level.

Hepatoid adenocarcinoma of the stomach:Thirteen case reports and review of literature

BACKGROUND The aim of the present study was to examine the clinical characteristics of hepatoid adenocarcinoma of the stomach (HAS) and its diagnosis,treatment,and prognosis.CASE SUMMARY A retrospective analysis of 13 HAS cases was performed.The mean age of the 13patients was 66.08 years,and 10 of the 13 patients were male.Prior to treatment,the alpha-fetoprotein levels in the serum were elevated in 7 patients,the tumour was located in the distal or gastric body in 11 patients,and the gastroscopy pathological results showed that 3 patients had poorly differentiated tumours and that 8 patients had moderately/poorly differentiated tumours.Abdominal CT scans showed local stomach wall thickening,and enlarged lymph nodes were visible around the stomach in 8 patients.Of the 13 patients,11 underwent radical surgery.The clinical pathological staging was as follows:Stage Ⅱ in 2 cases;stage Ⅲ in 8 cases;and stage Ⅳ in 1 case.A total of 3 patients were lost to follow-up.Otherwise,as of the last follow-up,3 patients had survived for 56 mo,and the other 7 patients failed to achieve long-term survival (survival period of 1-56 mo).CONCLUSION HAS is a special type of gastric cancer,and the prognosis of HAS has improved compared with past prognoses.Measurement of alpha-fetoprotein,early diagnosis,active surgical treatment,and application of new diagnostic and treatment techniques are conducive to improving the prognosis of HAS.

Gastric adenocarcinoma with hepatoid adenocarcinoma:A case report and literature review

Objective Hepatoid adenocarcinoma of the stomach is exceedingly rare. Only a few cases have been reported worldwide. In this report, we describe our pathological findings along with a review of the literature to improve our understanding of the disease and prevent misdiagnosis, as well as to provide evidence for its treatment and prognosis.Methods A 68-year-old male patient was admitted to our hospital(Dalian Municipal Central Hospital, Dalian, China) complaining of upper abdominal pain. Physical examination and regular laboratory blood tests showed no obvious abnormalities. A contrast-enhanced computed tomography scan displayed a 3.0 cm × 3.0 cm mass in the gastric antrum, but no metastasis was found in the adjacent organs.Results A radical gastrectomy was performed and postoperative histopathology showed a moderately differentiated adenocarcinoma with partial hepatoid adenocarcinoma.Conclusion Hepatoid adenocarcinoma of the stomach is a rare malignant neoplasm. The diagnostic criteria for hepatoid adenocarcinoma of the stomach depends mainly on the clinical, radiographic, and histopathological findings. Pathomorphology and immunohistochemical staining can be utilized to confirm the diagnosis.

Hepatoid adenocarcinoma of the lung:A case report

BACKGROUND Hepatoid adenocarcinoma of the lung(HAL)is a rare type of non-small cell lung cancer(NSCLC),histologically similar to hepatocellular carcinoma.HAL has high malignancy and poor prognosis,and a better treatment plan needs further study.CASE SUMMARY In order to deeply understand the occurrence and development of HAL,here we report a case of HAL with extensive metastasis of alpha fetoprotein negative KRAS A146T mutation.The patient refused chemotherapy and received one course of treatment(immune checkpoint inhibitors),and died three months later due to progressive disease.CONCLUSION HAL is a special type of NSCLC.The surgical treatment of HAL in the limited stage can achieve long-term survival,but most of them were in the advanced stage when they were found,and the prognosis was poor,which requires multidisciplinary comprehensive treatment.

Clinicopathological and prognostic features of hepatoid adenocarcinoma of the stomach

Background Hepatoid adenocarcinoma of the stomach （HAS） is a rare type of gastric carcinoma, which has its unique clinicopathological features and poorer prognosis than that of the ordinary gastric adenocarcinoma. At present, there is still a lack of understanding about this disease. The current study aimed to summarize and discuss the clinical,pathological, immunohistochemical, and prognostic features of this disease.Methods A total of 20 patients of HAS were retrospectively studied. All the patients were treated in Cancer Hospital of Chinese Academy of Medical Sciences between March 1998 and October 2009. Statistical analysis, including the Kaplan-Meier method, log-rank test and Cox model, were performed by the SPSS 15.0 software.Results Seventeen patients （85%） had at least 1 lymph node metastases; 17 patients （85%） received postoperative immunohistochemical examinations, with an alpha-fetoprotein （AFP） positive rate of 94.1% （16/17）; 14 patients had distant metastases （including 12 liver metastases, 1 lung metastasis, and 1 celiac widespread metastases）, and one simultaneously had anastomotic recurrence and liver metastases. The overall survival time was 2-99 months （median：12.0 months）. The 3-year survival rate of the 20 patients was 17.2%. The 3-year survival rate of patients with complete hepatocyte-like regions and those with both hepatocellular carcinoma and adenocarcinoma regions was 20.0% and 17.5%, respectively （P=0.361）. The survival difference among the radical surgery group, palliative surgery group and no surgery group was statistically significant （P=0.022）. The Kaplan-Meier method and log-rank test showed that surgery,pTNM stages, and adjuvant chemotherapy were associated with prognosis （P 〈0.05）. The Cox model only confirmed that the pTNM stages and adjuvant chemotherapy had statistical significance for the prognosis of HAS （P〈0.05） due to the limited cases.Conclusions HAS is a special type of gastric carcinoma and has a poor prognosis. The pTNM stage is an independent risk factor for HAS. Multidisciplinary therapy, including surgery and chemotherapy, may improve the prognosis of HAS.

弥漫性腹膜肝样腺癌一例

肝样腺癌是一种罕见的特殊类型腺癌,在组织病理学上类似肝细胞癌,大多数病例发生于胃,临床和影像学表现缺乏特异性,容易造成漏诊和误诊,而腹膜肝样腺癌更为罕见。本文报道1例原发于腹膜、临床表现为腹膜弥漫性增厚的肝样腺癌病例,旨在为临床诊断及治疗提供参考。

胆囊原发性肝样腺癌影像学特征分析及文献复习

肝样腺癌(hepatoid adenocarcinoma,HAC)是发生于肝脏以外组织器官的特殊类型腺癌,可发生于胃肠道、胆囊、肺、子宫等部位,发生于胆囊者罕见,临床上仅数例报道[1-8]。现就我院诊治的一例胆囊肝样腺癌并结合相关文献,报道如下。1病例资料患者,男,70岁。无明显诱因出现上腹痛4个小时,并放射至腰背部,无反跳痛及肌紧张,既往无特殊病史。

^(18)F-FDG PET/CT在胃肝样腺癌诊断中的价值

目的分析胃肝样腺癌的^(18)F-FDG PET/CT显像特征,结合血清AFP水平,两者联合提高对该病认识及诊断准确率。方法选取5例经病理学证实胃肝样腺癌患者的^(18)F-FDG PET/CT检查资料,分析患者的临床表现、原发病灶位置及形态、最大标准摄取值(SUVmax)、肿瘤标志物水平、预后情况。结果原发病灶位于胃窦3例,位于贲门-胃体处2例。5例病灶的SUVmax范围为7.58~23.6,平均值13.8±6.4。5例中位生存期为8个月。结论胃肝样腺癌是一种特殊类型癌,侵袭性强,临床表现无特异性,明确诊断有赖于影像学与病理结合,无肝脏病变时患者血清AFP升高具有重要的诊断提示意义。

甲胎蛋白阳性胃癌和胃肝样腺癌预后危险因素对比分析

目的 研究甲胎蛋白阳性胃癌(AFPGC)和胃肝样腺癌(HAS)临床病理特征异同及预后危险因素分析。方法 回顾性分析西京医院2015年1月至2020年12月胃癌手术患者信息,共筛选出AFPGC手术患者60例,HAS手术患者39例。从患者病历中检索临床数据并通过电话和短信获得随访数据。采用χ^(2)检验和Fisher精确检验进行统计分析。基于Kaplan-Meier检验方法进行生存分析并使用GraphPad Prism 9绘制变量的生存曲线。所有检验均以α=0.05作为检验标准。结果 HE染色显示HAS具有独特的组织结构,正常胃上皮、肝细胞样分化胃腺癌区和普通胃腺癌区常共存于同一肿瘤组织中。相关性分析显示AFPGC患者肿瘤组织尾型同源盒基因转录因子2免疫组化染色阳性率高于HAS患者(85.0%vs 66.7%,P=0.032),HAS患者肿瘤组织肝细胞样分化标志物甲胎蛋白(AFP)、谷氨酰胺合成酶和人类婆罗双树样基因-4的阳性率均为41.0%,肝细胞石蜡抗原、磷脂酰肌醇蛋白聚糖3的阳性率均为64.1%。AFPGC和HAS的术后3年生存分析无显著性差异,但HAS的术后5年预后差于AFPGC(P=0.062)。血清AFP≥60.4μg/L的AFPGC组3年(P=0.030)及5年(P=0.022)预后均明显差于血清AFP<60.4μg/L组。血清AFP<20μg/L的HAS组3年(P=0.050)和5年(P=0.084)预后均明显差于血清AFP升高的HAS组。结论 HAS目前诊断依赖病理学检查,极易漏诊。HAS术后长期预后差于AFPGC,血清AFP≥60.4μg/L是AFPGC的预后危险因素,血清AFP低表达是HAS的预后危险因素。

12例胃肝样腺癌临床病理特征及预后分析

目的总结12例胃肝样腺癌(HAS)患者临床资料,探讨胃肝样腺癌的临床病理特征及预后。方法回顾性分析2016年1月至2022年12月宁夏医科大学总医院收治的12例HAS患者的临床病理学资料,病理及免疫组化结果由两位病理科医师复阅肿瘤组织切片判定。通过描述性统计方法总结患者的人口统计学和肿瘤特征。运用COX单因素和多因素回归分析胃肝样腺癌患者预后。结果12例患者中男性9例、女性3例,男女比例为3∶1;疾病中位诊断年龄为60岁;最常见发病部位为胃窦(41.7%),病变类型以BorrmannⅢ型(溃疡型)为主(45.5%),Lauren分型以弥漫型为主(58.3%),肿瘤分化程度多呈低分化(83.3%);8例患者血清癌胚抗原(CEA)≥5 ng·mL^(-1),6例患者进行血清甲胎蛋白(AFP)检测,其中4例(66.7%)升高,1例(16.7%)AFP≥300 ng·mL^(-1)。11例患者进行了手术治疗,术前远处转移5例,其中4例同时发生肝脏、腹膜后淋巴结转移;1例仅发生腹膜后淋巴结转移。10例患者(83.3%)发生脉管浸润,7例患者(58.3%)发生神经侵犯。根据肝样分化区所占比例不同,4例患者(33.3%)为单纯型HAS、8例患者(66.7%)为混合型HAS。临床分期:Ⅰ期1例、Ⅱ期1例、Ⅲ期5例、Ⅳ期5例。12例患者中位生存期为16个月,1、3、5年存活率分别为83.0%、41.0%、20.0%。根据单因素分析结果,不排除CEA水平、临床分期、肝样腺癌类型、是否行根治性手术、是否存在远处转移、远处转移是否为肝转移HepPar-1是否表达与患者预后可能有关。结论HAS是一种罕见的异质性肿瘤,常伴血清AFP升高及部分肝细胞癌标记物表达,易发生脉管浸润、淋巴结及远处转移,预后极差。

首诊时伴血清甲胎蛋白升高胃癌的临床病理特点和预后分析

目的:探讨首诊时伴血清AFP升高的胃癌的临床病理特点及预后。方法:收集中国人民解放军联勤保障部队第904医院安徽医科大学无锡临床医学院2008年1月至2020年12月经胃镜活检首诊为胃腺癌的931例患者,以血清AFP≥20 ng/mL为标准筛选病例。H&E染色、免疫组织化学法和特殊染色明确病理学特点和免疫表型,并分析患者的临床特点和生存期。结果:931例胃腺癌中有36例(3.9%)首诊时出现血清AFP升高(20.7~6558.0 ng/mL)。患者无特异临床表现,影像学检查发现,36例患者中17例有远处转移,以肝转移最多见(13例),其余19例患者无远处转移。远处转移的病例其血清AFP水平明显高于无转移者(P=0.003)。病理分析显示,36例患者中16例为肝样腺癌,11例为伴有肠母细胞分化的腺癌,9例为普通腺癌。上述胃癌亚型均表达原始分化的标志物SALL4、GPC3、AFP。随访显示,无远处转移的19例患者的总生存期明显高于有远处转移的17例患者(P=0.002)。无远处转移的19例患者有16例进行了胃癌根治手术,其与经手术根治的AFP正常的314例普通胃癌相比,无病生存期更短(P=0.044),但总生存期差异无统计学意义(P=0.093)。结论:首诊时伴血清AFP升高的胃癌较罕见,其病理类型主要为肝样腺癌和伴有肠母细胞分化的腺癌。此类患者近一半在首诊时可见以肝脏为主的远处转移,有远处转移者预后极差,而无远处转移者手术治疗后预后较好,但相对于无AFP升高的胃癌预后仍可能较差。

Clinical Significance of a Rise in AFP in Lung Adenocarcinoma Patients with Liver Metastasis:One Case Report and Literatures Review

Introduction Usually the alpha fetoprotein (AFP) concentration of patients with metastatic liver cancer is slightly raised.

分泌超高血清甲胎蛋白的胃肝样腺癌1例

目的提高对胃肝样腺癌(HAS)的临床特点、病理特点、诊断及治疗的认识。方法回顾性分析2021年10月22日江苏省肿瘤医院收治的1例HAS病人的临床资料。结果男,70岁,以“发现胃小弯部腺癌1周”收入院。胃镜提示胃小弯侧巨大溃疡,肝区未见明显占位,甲胎蛋白(AFP)>1000μg/L,经胃病理切片免疫组化诊断为肝样腺癌,后经免疫联合化疗病人AFP降至157μg/L。结论HAS无特异的临床表现,胃镜及影像学出现胃部肿物、溃疡、淋巴结转移,同时出现无法解释的AFP异常升高,应该考虑HAS,做到早发现早治疗。