Hepatoid Adenocarcinoma Research Articles

“Pure” hepatoid tumors of the pancreas harboring CTNNB1 somatic mutations: a new entity among solid pseudopapillary neoplasms

Hepatoid tumors (HTs) represent a rare group of neoplasms that are histologically similar to hepatocellular carcinoma but arise outside the liver. The current World Health Organization classification recognizes the hepatoid morphology of pancreatic tumors only as a possible variant of pancreatic ductal adenocarcinoma (PDAC). Here, we describe two cases of “pure” HT of the pancreas showing common features and characterized by indolent biological behavior. These tumors were roundish nodules with pushing borders, hyaline globules, and pure hepatoid histology; they were diffusely positive for β-catenin and LEF1 on immunohistochemistry. At next-generation sequencing, both neoplasms harbored only one pathogenic somatic mutation that affected the CTNNB1 gene at exon 3 and showed a loss of heterozygosity on chromosomes 18 and 21. By integrating macroscopic and microscopic features, along with their molecular profiles, we advocate that such tumors represent a distinct entity from PDAC and should be considered a new variant of solid pseudopapillary neoplasms. The recognition of this new neoplastic category may have immediate implications not only for tumor taxonomy but also for clinical practice.

Distinct molecular phenotype and the potential prognostic value of immune prognostic index and tumor infiltrating lymphocytes in hepatoid adenocarcinoma of stomach

Hepatoid adenocarcinoma of the stomach (HAS) is a particular subtype of Gastric cancer (GC) with distinct pathological characteristics and genetic profile, but most HAS patients were received identical regimens as common GC. To date, only a few studies has been conducted to investigate the molecular characteristics of HAS, which may prevent the rational application of new anticancer strategies. To further obtain the genetic features and potential predictive and prognostic biomarkers of HAS, our current study evaluated the clinical implications of spectrum molecular markers in 36 surgical resection specimens. None Epstein-Barr virus (EBV) positive and/or micro-satellite instable high (MSI-h) tumors occurred in our study implies that the molecular classification of HAS should be mainly categorized into genomic stable (GS) and chromosomal instability (CIN) phenotypes, and wild type P53 status predicts better prognosis. More importantly, although the prognosis and clinical characteristics were independent of programmed cell death-ligand 1 (PD-L1), the presence of tumor infiltrating lymphocytes (TILs) still suggested that a portion of the enrolled HAS patients are potentially appropriate candidates for immune checkpoint blockade therapy. Additionally, the immune prognostic index (IPI) and derived neutrophil to lymphocyte ratio (dNLR) demonstrated their potential as reliable and economic indicators for predicting prognosis of HAS. We hope this first systematic evaluation will help in deciphering the molecular characterization and potential individualized regimens for this particular subtype of GC.

Dedifferentiation-like tubular and solid carcinoma of the stomach shows phenotypic divergence and association with deficient SWI/SNF complex.

Gastric carcinoma showing an abrupt transition from a tubular to solid pattern is an unusual phenomenon reminiscent of dedifferentiation. The phenotypic and molecular characteristics of this transition are still unclear. We retrospectively collected 41 gastric carcinomas exhibiting dedifferentiation-like tubular to solid transition and applied an array of immunohistochemical stains, including neuroendocrine and hepatocytic markers, to delineate their lineage. The status of Epstein-Barr virus (EBV) infections, mismatch repair proteins, SWI/SNF complex proteins and p53 expression levels were examined. The clinicopathologic differences were assessed by statistical analysis. Except for 10 cases with neuroendocrine differentiation and 2 EBV-associated carcinomas, we identified 8 hepatoid carcinomas and 21 solid adenocarcinomas with loss of CDX2 and/or hep-par1 expression in solid part (12/29). A subset of solid adenocarcinoma was associated with MSI (8) and mutant p53 expression was frequent in non-MSI cases (10/13). We found hepatoid carcinomas usually harbored SMARCA2 loss (5/8), MSI-associated cases commonly had ARID1A loss (6/8), and non-MSI solid adenocarcinomas frequently showed SMARCA2/A4 loss (7/13) with a high rate of concurrent ARID1A loss (4/7). Spatial correlation between solid transition and loss of SWI/SNF complex subunits were seen in 63% of tumors (12/19). Dedifferentiation-like tubular and solid carcinoma was associated with a propensity to inferior survival outcomes (p = 0.034), especially hepatoid carcinoma and in the non-MSI/EBV intestinal subgroup. In conclusion, gastric cancer exhibiting dedifferentiation-like tubular to solid transition is a phenotypically divergent group that shares common alterations in the SWI/SNF complex.

The Value of Perioperative Chemotherapy for Patients With Hepatoid Adenocarcinoma of the Stomach Undergoing Radical Gastrectomy.

BackgroundHepatoid adenocarcinoma of the stomach (HAS) is a rare type of gastric cancer, but the role of perioperative chemotherapy is still poorly understood. The aim of this retrospective study was to investigate the associations between perioperative chemotherapy and prognosis of HAS.MethodWe retrospectively analyzed patients with locally advanced HAS who received radical surgery in Peking University Cancer Hospital between November 2009 and October 2020. Patients were divided into neoadjuvant chemotherapy-first (NAC-first) group and surgery-first group. The relationships between perioperative chemotherapy and prognosis of HAS were analyzed using univariate, multivariate survival analyses and propensity score matching analysis (PSM).ResultsA total of 100 patients were included for analysis, including 29 in the NAC-first group and 71 in the surgery-first group. The Her-2 amplification in HAS patients was 22.89% (19/83). For NAC-first group, 4 patients were diagnosed as tumor recession grade 1 (TRG1), 4 patients as TRG 2, and 19 patients as TRG 3. No significant difference in prognosis between the surgery-first group and the NAC-first group (P=0.108) was found using PSM analysis. In the surgery-first group, we found that the survival rate was better in group of ≥6 cycles of adjuvant chemotherapy than that of <6 cycles (P=0.013).ConclusionNAC based on platinum and fluorouracil may not improve the Overall survival (OS) and Disease-free survival time (DFS) of patients with locally advanced HAS. Patients who received ≥6 cycles of adjuvant chemotherapy had better survival. Therefore, the combination treatment of radical gastrectomy and sufficient adjuvant chemotherapy is recommended for patients with locally advanced HAS.

Hepatic Metastasis from Hepatoid Adenocarcinoma of the Stomach Mimicking Hepatocellular Carcinoma: Diagnostic Challenge

Hepatoid adenocarcinoma (HAC) is a unique type of extrahepatic adenocarcinoma that histologically mimics the appearance of hepatocellular carcinoma (HCC). Hepatoid adenocarcinoma of the stomach has a poor prognosis with increased potential for liver metastasis. HCC and HAC share clinicopathological and immunohistochemical features. The diagnosis of metastatic hepatoid adenocarcinoma to the liver is challenging. It is often misdiagnosed as hepatocellular carcinoma. The diagnostic dilemma is more

Integrative analysis reveals a clinicogenomic landscape associated with liver metastasis and poor prognosis in hepatoid adenocarcinoma of the stomach.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) that histologically resembles hepatocellular carcinoma (HCC). Despite its low incidence, HAS had a poor 5-year survival rate. Currently, the linkages between clinicopathological and genomic features of HAS and its therapeutic targets remain largely unknown. Herein, we enrolled 90 HAS patients and 270 stage-matched non-HAS patients from our institution for comparing clinicopathological features. We found that HAS had worse overall survival and were more prone to develop liver metastasis than non-HAS in our cohort, which was validated via meta-analysis. By comparing whole-exome sequencing data of HAS (n=30), non-HAS (n=63), and HCC (n=355, The Cancer Genome Atlas), we identified a genomic landscape associated with unfavorable clinical features in HAS, which contained frequent somatic mutations and widespread copy number variations. Notably, signaling pathways regulating pluripotency of stem cells affected by frequent genomic alterations might contribute to liver metastasis and poor prognosis in HAS patients. Furthermore, HAS developed abundant multiclonal architecture associated with liver metastasis. Encouragingly, target analysis suggested that HAS patients might potentially benefit from anti-ERBB2 or anti-PD-1 therapy. Taken together, this study systematically demonstrated a high risk of liver metastasis and poor prognosis in HAS, provided a clinicogenomic landscape underlying these unfavorable clinical features, and identified potential therapeutic targets, laying the foundations for developing precise diagnosis and therapy in this rare but lethal disease.

Clinicopathological and molecular characteristics of the alpha-fetoprotein-producing gastric cancer: emphasis on two major subtypes.

Alpha-fetoprotein-producing gastric cancer (AFPGC) is associated with high invasion and poor prognosis, but has not been well-documented due to its rarity. To develop the understanding of AFPGC, and further facilitate its clinical decision-making and treatment, we performed clinicopathological and molecular characterization of AFPGC and its two major subtypes, namely, gastric adenocarcinoma with enteroblastic differentiation (GAED) and hepatoid adenocarcinoma (HAC). The clinicopathological and molecular characteristics of AFPGC patients (n = 54) were mainly investigated by immunohistochemistry and next-generation sequencing (NGS) approaches. AFPGC exhibited a higher incidence of lymphatic and vascular invasion than conventional gastric adenocarcinoma (CGA). Despite various morphological patterns, there was mostly no evident difference in clinicopathological characteristics between the GAED and HAC subtypes. Target-enriched NGS profiling of disease mutation landscapes discovered 17 differentially mutated genes between AFPGC and CGA. The AFPGC patients carrying ZNF217 mutations had poorer overall survival than the ZNF217 wildtype. Furthermore, ATR showed a significantly higher mutation rate in GAED than in HAC. Overall, our study of clinicopathological characteristics shed light on the differences between CGA and AFPGC, as well as the relationships between the GAED and HAC subtypes of AFPGC. Furthermore, mutation landscape profiling revealed potential diagnostic and prognostic markers for AFPGC and its two subtypes.

Computed Tomography Features and Clinical Prognostic Characteristics of Hepatoid Adenocarcinoma of the Stomach.

PurposeHepatoid adenocarcinoma of the stomach (HAS) is a highly malignant and aggressive tumor. The purpose of this study was to describe the clinical, computed tomography (CT), and prognostic features of HAS to increase the awareness of this entity and determine its distinguishing features from non-HAS tumors.MethodsThe CT features and clinical data of 47 patients in our hospital with pathologically documented HAS were retrospectively analyzed, and the relevant differences between pure HAS (pHAS) and mixed HAS (mHAS) were determined. In addition, 141 patients with non-HAS tumors in the same T stage in the same period were selected as the control group. The data were compared between the two groups, and factors affecting the prognosis of HAS were analyzed. In addition, we included 9 patients with HAS and 27 patients with non-HAS tumors from another center for external validation.ResultsThe patients in the HAS group were predominantly men (n = 33), and the tumor location was mostly the cardia or fundus (n = 27). Between the HAS and non-HAS groups, there were observed differences in terms of: sex, serum alpha-fetoprotein (AFP), carbohydrate antigen (CA)-125, and CA-724 levels; longest tumor diameter; degree of differentiation; vascular invasion; N stage, M stage, and tumor-node-metastasis (TNM) stage; thickest tumor diameter; plain CT attenuation; arterial-phase CT attenuation; CT attenuation between the venous and arterial phases; enhancement modes; and degrees of enhancement (all P < 0.05). In the data from another center for external validation, there were observed differences in terms of: age, degree of differentiation, vascular invasion, thickest tumor diameter, the ratio of arterial CT attenuation to CT attenuation of the abdominal aorta at the same level (RA), CT attenuation difference between the venous phase and arterial phase (HUv-a) (all P < 0.05). The results of the multivariate analysis revealed that the independent factors for differentiation were serum AFP level (P = 0.001), M stage (P = 0.038), and tumor enhancement on CT (P = 0.014). Among patients in the HAS group, 72.34% had pHAS and 27.66% had mHAS. The thickest tumor diameter and the longest short diameter of the metastatic lymph nodes of the mHAS group were on average 6.39 cm and 1.45 cm, respectively, which were larger than those in the pHAS group. The median progression-free survival time was 18.25 months in the HAS group, which was shorter than that in the non-HAS group (72.96 months; P = 0.001). The median overall survival time in the HAS group was 24.80 months, which was shorter than that in the non-HAS group (67.96 months; P = 0.001). The factors affecting the prognosis of HAS were M stage (P = 0.001), overall TNM stage (P = 0.048), presence of vascular cancer emboli (P = 0.040), and pHAS type (P = 0.046). Multifactorial analysis revealed that M stage (P = 0.027) and pHAS type (P = 0.009) were independent risk factors affecting the prognosis of HAS.ConclusionAlthough HAS is a rare clinical entity, it should be considered in the differential diagnosis of gastric tumors. Patients with HAS often have advanced-stage disease at presentation and a worse prognosis than patients with non-HAS tumors. CT findings, combined with laboratory results, can support the diagnosis of HAS. However, the final diagnosis needs to be confirmed with a histopathologic examination. If the postoperative pathologic findings reveal the mHAS type, a rapid clinical intervention and a detailed follow-up with CT are essential.

Clinicopathological features and genomic profiles of hepatoid adenocarcinoma of the lung: Report of four cases

ObjectivePathological features of hepatoid adenocarcinoma of the lung (HAL) are similar to those of hepatocellular carcinoma (HCC) and HAL has a poor prognosis. In this study, we aimed to elucidate clinicopathologic and molecular features of HAL. MethodsFour cases of HAL patients with one lobe of the lung resected were enrolled into the study. Next generation sequencing (NGS) of a 425-gene panel was performed on tumor tissue samples. ResultsThe most frequently mutated gene was TP53 in three cases of primary HAL and one case of metastatic HAL, with a mutation rate of 100%. Also, CDK8, CDKN2A, EPHA5, SMARCA4, and STK11 were detected as high-frequency mutations, with a mutation rate of 50%. The types of TP53 mutation included two missense variants and two frameshift ones. The TP53 mutation was related to the occurrence of HAL. ConclusionHAL could be caused by genetic mutations and is closely related to TP53 mutation.

Both the serum AFP test and AFP/GPC3/SALL4 immunohistochemistry are beneficial for predicting the prognosis of gastric adenocarcinoma

BackgroundBoth gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) (including hepatoid adenocarcinoma) and alpha-fetoprotein (AFP)-producing gastric adenocarcinoma have poor prognoses. However, the value of the serum AFP test and AFP/glypican-3 (GPC3)/spalt-like transcription factor 4 (SALL4) immunohistochemistry is still not clear, and these two methods have not yet been thoroughly compared.MethodsWe collected 421 consecutive non-neoadjuvant surgically or endoscopically resected gastric adenocarcinoma patients with serum AFP results before surgery (group A). We divided these cases into serum AFP-high (sAFP-H) and serum AFP-normal (sAFP-N) by serum AFP levels, and into GAPEP (expressing AFP, GPC3, or SALL4) and non-GAPEP (nGAPEP) by AFP/GPC3/SALL4 immunohistochemistry results. We also collected 12 non-resected gastric adenocarcinoma patients with serum AFP ≥ 7 ng/mL before treatment (group B). We analyzed these patients’ clinicopathological characteristics and prognoses.ResultsSeventeen (4.04%) patients in group A were sAFP-H. These patients were younger and mainly had tubular adenocarcinoma with later pT (P = 0.014) and pN (P = 0.047) categories and more lymphovascular invasion (P < 0.001), perineural spread (P = 0.008), and metastases or recurrence (P < 0.001). For immunohistochemistry, 34 (8.08%) cases were GAPEP, and GAPEP cases also had later pT categories than nGAPEP cases (P = 0.001). Most group B patients with elevated serum AFP (especially > 1000 ng/mL) had simultaneous metastases, mainly liver metastases. Both the serological method and immunohistochemical method were useful for predicting prognosis (AUC sAFP = 0.625, AUC A/G/S-IHC = 0.723, z statistic = 1.726, P = 0.084). The serum AFP level (especially > 1000 ng/mL) is more specific (100%), and immunohistochemistry is more sensitive (50%).ConclusionBoth the serum AFP level and immunohistochemical expression of AFP/GPC3/SALL4 can be used to indicate a poor prognosis for gastric adenocarcinoma.

Assessment of Clinicopathological Characteristics and Development of an Individualized Prognostic Model for Patients With Hepatoid Adenocarcinoma of the Stomach

Few studies have examined the clinicopathological characteristics and prognoses of patients with hepatoid adenocarcinoma of the stomach (HAS). To explore the clinicopathological characteristics and prognoses of patients with HAS and develop a nomogram to predict overall survival (OS). This prognostic study involved a retrospective analysis of data from 315 patients who received a diagnosis of primary HAS between April 1, 2004, and December 31, 2019, at 14 centers in China. OS and prognostic factors. Patients were randomly assigned to a derivation cohort (n = 220) and a validation cohort (n = 95). A nomogram was developed based on independent prognostic factors identified through a multivariable Cox mixed-effects model. Among 315 patients with HAS (mean [SD] age, 61.9 [10.2] years; 240 men [76.2%]), 137 patients had simple HAS (defined as the presence of histologically contained hepatoid differentiation areas only), and 178 patients had mixed HAS (defined as the presence of hepatoid differentiation areas plus common adenocarcinoma areas). Patients with simple HAS had a higher median preoperative α-fetoprotein level than those with mixed HAS (195.9 ng/mL vs 48.9 ng/mL, respectively; P < .001) and a higher rate of preoperative liver metastasis (23 of 137 patients [16.8%] vs 11 of 178 patients [6.2%]; P = .003). The 3-year OS rates of patients with simple vs mixed HAS were comparable (56.0% vs 60.0%; log-rank P = .98). A multivariable Cox analysis of the derivation cohort found that the presence of perineural invasion (hazard ratio [HR], 2.13; 95% CI, 1.27-3.55; P = .009), preoperative carcinoembryonic antigen levels of 5 ng/mL or greater (HR, 1.72; 95% CI, 1.08-2.74; P = .03), and pathological node category 3b (HR, 3.72; 95% CI, 1.34-10.32; P = .01) were independent risk factors for worse OS. Based on these factors, a nomogram to predict postoperative OS was developed. The concordance indices of the nomogram (derivation cohort: 0.72 [95% CI, 0.66-0.78]; validation cohort: 0.72 [95% CI, 0.63-0.81]; whole cohort: 0.71 [95% CI, 0.66-0.76]) were higher than those derived using the American Joint Committee on Cancer's AJCC Cancer Staging Manual (8th edition) pathological tumor-node-metastasis (pTNM) staging system (derivation cohort: 0.63 [95% CI, 0.57-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]) and those derived using a clinical model that included pTNM stage and receipt of adjuvant chemotherapy (derivation cohort: 0.64 [95% CI, 0.58-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]). Based on the nomogram cutoff of 10 points, the whole cohort was divided into high-risk and low-risk groups. The 3-year OS rate of patients in the high-risk group was significantly lower than that of patients in the low-risk group (29.7% vs 75.9%, respectively; log-rank P < .001), and the 3-year prognosis of high-risk and low-risk groups could be further distinguished into pTNM stage I to II (33.3% vs 80.2%; exact log-rank P = .15), stage III (34.3% vs 71.3%; log-rank P < .001), and stage IV (15.5% vs 70.3%; log-rank P = .009). This study found that perineural invasion, preoperative carcinoembryonic antigen levels of 5 ng/mL or greater, and pathological node category 3b were independent risk factors associated with worse OS. An individualized nomogram was developed to predict OS among patients with HAS. This nomogram had good prognostic value and may be useful as a supplement to the current American Joint Committee on Cancer TNM staging system.

Genomic characterization of hepatoid tumors: context matters

Hepatoid tumors (HT) are rare neoplasmsmorphologically resembling hepatocellular carcinoma, which arise in several organs other than the liver. A comprehensive molecular profile of this group of neoplasms is still lacking. Genomic characterization of 19 HTs from different organs (three colon HTs, four esophagogastric HTs, four biliary HTs, six genitourinary HTs, two lung HTs) was performed using a multigene next-generation sequencing panel. NGS unraveled a composite molecular profile of HT. Their genetic alterations were clearly clustered by tumor site: (i) colorectal HT displayed microsatellite instability, high tumor mutational burden, mutations in ARID1A/B genes and NCOA4-RET gene fusion (2/3 cases); (ii) gastric HT had TP53 mutations (2/4); (iii) biliary HT displayed loss of CDKN2A (3/4) and loss of chromosome 18 (2/4); (iv) genital HT showed gain of chromosome 12 (3/6); (v) lung HT had STK11 somatic mutations (2/2). The only commonly mutated gene occurring in HT of different sites was TP53 (8/19 cases: colon 2, esophagogastric 2, biliary 2, genital 1, lungs 1). This study shows that most genetic alterations of HT were clustered by site, indicating that context matters. The novel potential targets for HT precision oncology are also clustered based on the anatomic origin. This study shed light on the biology of these rare cancersand may have important consequences for treatment decisions and clinical trial selection for HT patients.

Surgical outcomes are hampered after endoscopic ultrasonography-guided ethanol lavage and/or Taxol injection in cystic lesions of the pancreas.

Backgrounds/AimsEndoscopic ultrasonography-guided ethanol lavage and Taxol injection (EUS-ELTI) for pancreatic cystic lesions have been recently performed in some medical centers. The aim of this study was to optimize patient selection and analyze outcomes of patients who underwent surgeries after EUS-ELTI for pancreatic cystic lesions.MethodsAmong 310 patients who underwent EUS-ELTI between January 2007 and December 2014, 23 underwent surgeries after EUS-ELTI owing to incomplete treatment and/or adverse events. Surgical outcomes of patients who underwent surgeries after EUSELTI were evaluated. Clinical outcomes of patients who underwent surgeries after EUS-ELTI were then retrospectively compared with those of patients who underwent upfront surgery for left-sided pancreatic lesions without an EUS-ELTI procedure.ResultsThe pathology revealed degenerated cysts in 12 patients, mucinous cyst neoplasms in five, neuroendocrine tumors in two, intraductal papillary mucinous neoplasm (IPMN) in one, solid pseudopapillary tumor in one, pancreatic ductal adenocarcinoma arising from an IPMN in one, and hepatoid carcinoma in one. Twelve patients underwent laparoscopic distal pancreatectomy and five patients underwent open distal pancreatectomy. When clinical outcomes were retrospectively compared between patients who underwent laparoscopic distal pancreatectomy after EUS-ELTI and those who did not receive an EUS-ELTI procedure, the spleen-preserving rate was 0% in the EUS-ELTI group and 61.7% (365/592) in the control group (p < 0.001).ConclusionsSurgical outcomes are compromised after EUS-ELTI for cystic tumor of the pancreas. Further studies are needed to investigate the efficacy and safety of the EUS-ELTI procedure.

‘Away from home’ extra hepatic hepatocellular adenocarcinoma in gastric fundal submucosa

Patient presented with upper gastrointestinal bleeding which was scoped and diagnosed as bleeding gastrointestinal tumour intra procedure, subjected to laparotomy and wedge resection with unchanged postoperative diagnosis. Only later to find out the tissue was interpreted as metastases hepatoid adenocarcinoma without primary liver pathology. Thus likely point towards malignancy changes of undiagnosed ectopic liver tissue on gastric wall.

Prognostic Analysis of Gastric Signet Ring Cell Carcinoma and Hepatoid Adenocarcinoma of the Stomach: A Propensity Score-Matched Study.

BackgroundHepatoid adenocarcinoma of the stomach (HAS) is a rare type of primary gastric cancer, and most previous studies have reported that HAS has a poor prognosis due to its aggressive biological behavior. The aim of this study was to compare the prognosis of HAS to that of gastric signet ring cell carcinoma (SRC).MethodsThis was a single-center, retrospective, observational cohort study (January 2010 to January 2016) of gastric cancer patients with pathological HAS and SRC. Overall survival was compared between HAS and SRC patients. We used univariate Cox regression, multivariate Cox regression, propensity score matching (PSM), inverse probability of treatment weighting, standardized mortality ratio weighting, standardized mortality ratio weighting, and overlap weighting to perform a prognostic analysis.ResultsA total of 725 (672 SRC and 53 HAS) patients were included. After nearest-neighbor 1:4 PSM, 200 SRC patients and 50 HAS patients were matched. Only in univariate Cox regression analysis with the cohort before PSM did HAS show a significantly worse prognosis than SRC [hazard ratio (HR), 1.66; 95% confidence interval (CI), 1.02–2.69, p = 0.040]. However, in the analysis of multivariate Cox regression with the cohort before PSM and series analysis based on the propensity score, all of the results indicated that there was no statistically significant difference in overall survival between HAS and SRC (all p > 0.05). Furthermore, in the subgroup of proximal location (p = 0.027), T stage 4a & 4b (p = 0.001), N stage 3a & 3b (p = 0.022), with cancer nodules (p = 0.026), serum CEA higher than the normal value (p = 0.038), and serum CA199 higher than the normal value (p = 0.023), the prognosis of HAS was significantly worse than that of SRC.ConclusionBased on our study, there was no statistically significant difference in overall survival between HAS and gastric SRC patients. However, in patients with an advanced tumor stage, HAS may have a worse overall survival than SRC.

Pancreatic hepatoid carcinoma: A case report and literature review

Hepatoid carcinomas (HCs) are a group of heterogeneous tumors that are similar to hepatocellular carcinoma (HCC). Pancreatic hepatoid carcinoma (PHC) is a very rare disease. The present study presents the case of a 63‑year‑old male patient with PHC with synchronous liver, spleen and stomach metastasis, in an aim to enhance our understanding of this disease. A 63‑year‑old male presented with abdominal distension for 3 months and slightly developed asthenia and anorexia. Laboratory tests of serum tumor markers revealed the alpha fetoprotein level was markedly elevated (&gt;10,00.0 ng/ml). The radiological findings of computed tomography, magnetic resonance imaging, diffusion‑weighted imaging and magnetic resonance cholangiopancreatography revealed a malignant tumor in the tail of the pancreas with synchronous liver, spleen, stomach and retroperitoneal lymph node metastasis. A post‑operative immunohistochemical analysis revealed that the tumor cells in the tail of the pancreas exhibited positivity for glypican‑3; right liver positivity was also observed for CK‑18 and weak positivity for glypican‑3, suggestive of primary PHC. On the whole, PHC is very rare, and exhibits morphological features similar to those of HCC. Its diagnosis is mainly achieved via morphological analysis and immunohistochemical staining of the tissue specimens, since the clinical manifestation and laboratory test results are often unspecific.

Hepatoid Adenocarcinoma of the Lung: A Systematic Review of the Literature From 1981 to 2020

ObjectivesWe report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study its main treatment methods, prognosis, and the relationship between prognosis and the serum alpha-fetoprotein (AFP) level before treatment.MethodsWe report a 66-year-old male case who was diagnosed with locally advanced HAL with PIK3CA mutation and carried out a systematic literature search for HAL cases documented between 1981 and 2020. General patient information including case characteristics was extracted and summarized. The median OS (mOS) of HAL patients was determined using the KM survival curve. The Cox proportional hazards regression model was used to evaluate the effect of tumor size, location, and serum AFP value before treatment and radical surgery (RS) on the prognosis of patients.ResultsA total of 46 studies including 51 HAL patients was included in our review. Our study revealed that 52.9% of tumors were located in the upper lobe of the right lung. The proportion of serum AFP-positive patients before treatment, early-stage patients (TNM stage I and II), and patients who had received surgery were 69.2%, 34.1%, and 40%, respectively. The mOS of HAL patients was 16.0 months. The 2-year and 5-year survival rates of the patients were 35.3% and 8.0%, respectively. In the subgroup analysis, the 2-year survival rate for patients who received RS was 62.5%, while for patients who were unable to undergo RS, it was only 12.5% (p = 0.009). The Cox proportional hazards regression model indicated that RS can significantly improve the prognosis of HAL patients (p = 0.011), although the location and size of tumor as well as the serum AFP value before treatment had no significant effect on their prognosis (p = 0.82, p = 0.96, p = 0.25).ConclusionsHAL patients have a poor prognosis, and the survival benefits for patients receiving chemoradiotherapy or chemotherapy alone appear to be limited. We demonstrate statistically for the first time that pretreatment serum AFP values are not related to the prognosis of HAL patients and RS can significantly improve patient prognosis.

Pancreatic Origin Hepatoid Adenocarcinoma with Liver Metastasis

Hepatoid Adenocarcinoma (HAC) is a rare form of aggressive extrahepatic neoplasm with similar morphologic features to Hepatocellular Carcinoma (HCC). HAC with pancreatic origin is rare and the exact incidence is unknown. Given shared morphological and Immunohistochemical (IHC) characteristics, it may be difficult to distinguish metastatic HAC with liver involvement from primary HCC. We present a rare case of ductal type pancreatic hepatoid adenocarcinoma involving the pancreatic head, ampulla of Vater, and liver, and illustrate strategies for diagnosis and treatment. A 65-year-old woman presented with epigastric pain, vomiting, melena, and weight loss. There was direct hyperbilirubinemia with elevated hepatic markers. Imaging displayed a pancreatic head mass with moderate biliary obstruction and a hepatic lobe lesion. Fine needle biopsy of the liver mass initially was consistent with HCC, and biopsies of the pancreatic mass and ampulla walls showed pancreatic adenocarcinoma. Due to the unusual finding of co-existing HCC and pancreatic adenocarcinoma, the hepatic mass biopsy was sent for external evaluation, which revealed poorly differentiated adenocarcinoma, consistent with HAC of pancreatic origin. The tumor was positive for mucicarmine stain, HepPar1, CEA, and CK7. It was negative for MOC-31, Arginase, ALBISH, MGB, ER, TTF-1, GCDFP15, CK-20 and CDX2, thus confirming HAC. The patient was referred to outpatient chemotherapy with gemcitabine and paclitaxel however demonstrated progression and expired following recurrent bilateral pulmonary emboli. HAC may present with non-specific symptoms, is highly aggressive, and may be difficult to distinguish from primary HCC from histopathologic characteristics alone. Accurate diagnosis requires clinicohistopathologic and IHC analysis.

Genomic and transcriptomic profiling of hepatoid adenocarcinoma of the stomach.

Hepatoid adenocarcinoma of the stomach (HAS), a rare subtype of gastric cancer (GC), has a low incidence but a high mortality rate. Little is known about the molecular features of HAS. Here we applied whole-exome sequencing (WES) on 58 tumours and the matched normal controls from 54 HAS patients, transcriptome sequencing on 30 HAS tumours, and single-cell RNA sequencing (scRNA-seq) on one HAS tumour. Our results reveal that the adenocarcinomatous component and hepatocellular-like component of the same HAS tumour originate monoclonally, and HAS is likely to initiate from pluripotent precursor cells. HAS has high stemness and high methionine cycle activity compared to classical GC. Two genes in the methionine cycle, MAT2A, and AHCY are potential targets for HAS treatments. We provide the first integrative genomic profiles of HAS, which may facilitate its diagnosis, prognosis, and treatment.

Benign vs malignant pancreatic lesions: Molecular insights to an ongoing debate.

Several benign conditions such as chronic pancreatitis, autoimmune pancreatitis, and paraduodenal pancreatitis can present as mass lesions and may mimic pancreatic ductal adenocarcinoma (PDAC) clinically and radiologically. Thorough histologic examination with attention to certain morphologic features can assist in deciphering neoplastic from reactive, however small biopsies often remain a challenge. Variable histologic patterns in conventional PDAC may also confound the diagnosis of PDAC. Uncommon subtypes of pancreatic carcinoma such as adenosquamous and squamous cell carcinoma, colloid carcinoma, medullary carcinoma, hepatoid carcinoma and signet ring cell carcinoma necessitate excluding metastasis from other sites prior to rendering the diagnosis of pancreatic carcinoma. The use of immunohistochemical staining and molecular markers can aid in separating benign from malignant and PDAC from metastasis. PDAC expresses a few non-specific epithelial and mucin immunomarkers such as CK7, CK19, MUC1, MUC4 and MUC5AC. However, the only immunohistochemical marker that is specific for PDAC in the right clinical context is SMAD4. Loss of SMAD4 within atypical glands and ducts supports the diagnosis of PDAC in a limited sample. Unfortunately, this finding is seen only in 50% of PDAC cases. The identification of certain mutations can help support a diagnosis of PDAC when benign conditions are in the differential. At the molecular level, KRAS oncogene mutations are seen in approximately 93% of PDACs. Subsequent neoplastic progression is driven by additional mutations of tumor suppressor genes, such as CDKN2A, TP53, and SMAD4. Molecular markers can also provide an insight to the prognosis. For instance, the loss of SMAD4 is associated with a poor outcome whereas mutations in MLL, MLL2, MLL3, and ARID1A are associated with improved survival.