Preliminary Study Of CT Features Of Hepatoid Adenocarcinoma Of Stomach

BackgroundHepatoid adenocarcinoma(HAC)of stomach is very rare tumor with frequently seen in older age,with mostly high Alpha fetal protein(AFP)production.HAC is identified as tumor with hepatoid differentiation resembling hepatocellular carcinoma morphologically.HAC as defined histologically as hematoxylin and eosin staining tumor with eosinophilic polygonal cells arranged in sheet like pattern like hepatocytes.Its incidence has been reported to be between 0.17% and 0.36%.It has worse prognosis because of very aggressive behavior,which is evident by its early involvement of lymphnode and liver metastasis.HAC is mostly reported in stomach,but there are cases reported in other organs like pancreas,lungs,urinary bladder,oesophagus,ovary,gallbladder,colon,duodenum,ureter,extra hepatic bile duct and mediastinum too.Clinically,patients present with vague gastrointestinal complains like abdominal pain,abdominal discomfort,increasing nausea vomiting to hematemesis and melena.HAC is found to produce high AFP,but HAC without AFP production has also been reported.Another tumor marker CEA(Carcinoembryonic antigen)has also been associated with HAC.Immunohistochemically,mostly HAC,Glypican-3(GPC3)and Hepatocyte Paraffin 1 antibody(Hep Par-1)has also associated with hepatoid differentiation of HAC tumor and is being used in clinical practice.HAC can be divided into several subtypes based on tumor cell types present in it.Most common histological type seen in clinical practice is hepatoid carcinoma cells mixed with adenocarcinoma cells,i.e mixed hepatoid carcinoma.There are fewer case with predominantly only hepatoid differentiation,i.e pure hepatoid carcinoma.Hepatoid adenocarcinoma is more aggressive than the most commonly reported Gastric Adenocarcinoma.This can be evident by most of the HAC cases that have presented with early lymphnode and liver metastasis.Despite proper clinical and surgical management asdone in gastic adenocarcinoma patients,there is very short survival and poor prognosis due to repeated tumor recurrence leading to treatment failure leading to early death.ObjectiveStudy histopathological and CT features of two forms of HAC(one with only hepatoid carcinoma cells and another with combination of adenocarcinoma+hepatoid carcinoma cells).Compare these two subtypes in terms of their clinical,pathological and radiological characteristics.MethodsThis retrospective study was approved by independent ethics committee.Histopathologically confirmed 39 HAC cases(16 pure hepatoid and 23 mixed hepatoid carcinoma),with 30 males and 9 females,of mean age 60 years(36 to 78 year)were included in this study.Clinical(patient age,sex,clinical features,serum AFP and CEA level)and pathological findings(largest tumor size,T stage of tumor,N stage of tumor,AFP staining,GPC3 staining and Hep Par-1 status)were extracted from the system.Single blinded two radiologists reviewed the image and assessed tumor location,growth pattern,T stage,N stage,tumor enhancement pattern,Liver metastasis,Lymph node metastasis,and tumor thrombosis).We compared available data of two subtypes of HAC using Fisher's exact test,Independent student's t-test and Mann-Whitney test and considered any data with p-value ? 0.05 as statistically significant.ResultThere were total 39 HAC cases of mean age 60 years(36 to 78 years),with 30 males and 9 females.In Pure hepatoid carcinoma group M:F ratio was 7:1 but in Mixed hepatoid carcinoma it was 2:1(combining two types 3:1).The serum AFP was statistically significantly higher in Pure type compared to Mixed type(U= 86.5,p=0.008).Pure hepatoid carcinoma group was statistically significantly larger than Mixed hepatoid carcinoma group,with average largest tumor size of 5.75± 2.13 cm Vs 4.27± 1.48 at t(25)=2.42,p=0.02.Largest tumor size of Pure group was 9.5cm.In immunohistochemistry also,Pure hepatoid carcinoma group had statistically significant association with positive AFP staining of 57.10% Vs 9.10 % in Mixed hepatoid carcinoma(P=0.005,two sided Fisher's exact test).This association was substantially positive.Whereas,GPC3 and Hep Par 1 were not significantly associated.There was no statistically significant difference in pathological T and N staging between these groups.But,Pure hepatoid carcinoma showed more aggression with 81.3% of cases in T3 stage Vs 47.8% of Mixed hepatoid carcinoma cases in that stage.Similarly,31.3% of Pure hepatoid carcinoma cases were in N2 and N3 a stage each Vs 30.4 % of Mixed hepatoid carcinoma in N1 stage.On CT image analysis,HAC showed predominantly eccentric growth pattern with eccentric : circumferential growth pattern ratio of 3:1 in Pure group Vs 4:1 in Mixed group.Liver metastasis and tumor thrombosis were significantly negatively associated with HAC but,there was no significant difference in between these two groups in terms of liver metastasis,lymph node metastasis and tumor thrombosis.Most of the Pure group cases(12out of 16)had lymphnode metastasis Vs(12 out of 23)Mixed group patients.Single case of tumor thrombus was seen in Pure group at junction of superior mesenteric vein and portal vein.The Hepatoid adenocarcinoma of both groups enhanced heterogenously.There was no statistically significant difference in terms of enhancement phase in CT scan(unenhanced,arterial and portal-venous phase).HAC tumors are predominantly located in pyloric area,with majority of Mixed and Pure hepatoid carcinoma in pyloric area of stomach(78.3% and75% of cases respectively).While considering pyloric part of stomach,Mixed tumor was more common at 60% Vs 40% of pure type.There was no significant difference while comparing T and N stage of both groups of tumor,but 87.5% of Pure hepatoid carcinoma had T4 stage compared to 69.50% of Mixed hepatoid carcinoma.Similarly,56.30 % of Pure type had N stage more than N1 compared to47.80% of Mixed type.Only case of T4 b stage with pancreatic spread was of Mixed hepatoid carcinoma.100% of N3 a,N3b nodal status that was reported was present only in Mixed type.Mixed hepatoid carcinoma appears to be more aggressive in terms of T4 b and N3 b stage involvement.Major percentage of these two subtypes of HAC occupied extreme spectrum of T and N phase.ConclusionHAC of stomach is a rare tumor,mainly affecting older males.On CT,it enhances heterogeneously with significant eccentric wall thickening in pylorus of the stomach.Pure hepatoid carcinoma differs significantly from Mixed hepatoid carcinoma only pathologically in terms of its large tumor size,high serum AFP level and positive tissue AFP staining.