Drug-induced sarcoidosis-like reaction three months after BNT162b2 mRNA COVID-19 vaccination:A case report and review of literature

BACKGROUND A 70-year-old man with hepatitis C virus-related recurrent hepatocellular carcinoma was admitted for further diagnosis of a 1 cm iso-hyperechoic nodule in segment(S)5.CASE SUMMARY Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(EOB-MRI)revealed the nodule in S5 with a defect at the hepatobiliary phase,hyperintensity on diffusion weighted imaging(DWI)and hypointensity on apparent diffusion coefficient(ADC)map.Contrast-enhanced computed tomography revealed hypervascularity at the early phase,and delayed contrast-enhancement was observed at the late phase.Contrast-enhanced ultrasound(US)revealed incomplete defect at the late vascular phase.Inflammatory liver tumor,lymphoproliferative disease,intrahepatic cholangiocarcinoma(small duct type)and bile duct adenoma were suspected through the imaging studies.US guided biopsy,however,showed a noncaseating hepatic sarcoid-like epithelioid granuloma(HSEG),and histopathological analysis disclosed spindle shaped epithelioid cells harboring Langhans-type multinucleated giant cells.One month after admission,EOB-MRI signaled the disappearance of the defect at the hepatobiliary phase,of hyperintensity on DWI,of hypointensity on ADC map,and no stain at the early phase.CONCLUSION That the patient had received BNT162b2 messenger RNA(mRNA)coronavirus disease 2019 vaccination 3 mo before the occurrence of HSEG,and that its disappearance was confirmed 4 mo after mRNA vaccination suggested that the drug-induced sarcoidosis-like reaction(DISR)might be induced by the mRNA vaccination.Fortunately,rechallenge of drug-induced DISR with the third mRNA vaccination was not confirmed.

Long-term outcome of percutaneous ethanol injection therapy for minimum-sized hepatocellular carcinoma

AIM: To evaluate long-term follow-up of minimum-sized hepatocellular carcinoma (HCC) treated with percutaneous ethanol injection (PEI). METHODS: PEI was applied to 42 lesions in 31 patients (23 male and eight female) with HCC < 15 mm in diameter, over the past 15 years. RESULTS: Overall survival rate was 74.1% at 3 years, 49.9% at 5 years, 27.2% at 7 years and 14.5% at 10 years. These results are superior to, or at least the same as those for hepatic resection and radiofrequency ablation. Survival was affected only by liver function, but not by sex, age, etiology of Hepatitis B virus or Hepatitis C virus, α-fetoprotein levels, arterial and portal blood flow, histological characteristics, and tumor multiplicity or size. Patients in Child-Pugh class A and B had 5-, 7- and 10-years survival rates of 76.0%, 42.2% and 15.8%, and 17.1%, 8.6% and 0%, respectively (P = 0.025). CONCLUSION: Treatment with PEI is best indicated for patients with HCC < 15 mm in Child-Pugh class A.

Diagnostic sensitivity of imaging modalities for hepatocellular carcinoma smaller than 2 cm

AIM:To compare the imaging results with histology and to evaluate the diagnostic sensitivity of imaging modalities for hepatocellular carcinoma(HCC)smaller than 2 cm.METHODS:Nodules smaller than 2 cm(n=34)revealed by ultrasonography(US)in 29 patients with liver cirrhosis were analyzed.Histological diagnosis of HCC was performed by ultrasonographic guidance:moderately-differentiated HCC(n=24);well-differentiated HCC(n=10).The patterns disclosed by the four imaging modalities defined the conclusive diagnosis of HCC:(1)contrast-enhanced computed tomography(CECT),hypervascularity in the arterial phase and washout in the equilibrium phase;(2)Sonazoid contrast-enhanced US(CEUS),hypervascularity in the early vascular phase and defect in the Kupffer phase;(3)gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid(Gd-EOBDTPA)-enhanced magnetic resonance imaging(MRI),hypervascularity in the arterial phase and/or defect in the hepatobiliary phase;and(4)CT arterioportal angiography:hypervascularity by CT during arteriography and/ or perfusion defect by CT during arterial portography.RESULTS:Overall,the sensitivity of diagnosing HCC smaller than 2 cm was 52.9%(18/34)(95%CI:35.170.2)by CECT;67.6%(23/34)(95%CI:49.5-82.6)by Sonazoid CEUS;76.5%(26/34)(95%CI:58.8-89.3) by Gd-EOB-DTPA MRI;and 88.2%(30/34)(95%CI: 72.5-96.7)by CT arterioportal angiography.The diagnostic sensitivity of detecting moderately-differentiated HCC by CECT,Sonazoid CEUS,Gd-EOB-DTPA MRI and CT arterioportal angiography was 62.5%(15/24)(95%CI: 40.6-81.2),79.2%(19/24)(95%CI:57.8-92.9),75.0% (18/24)(95%CI:53.3-90.2)and 95.8%(23/24)(95% CI:78.9-99.9),respectively.A significant difference(P< 0.05)was observed between CECT and CT arterioportal angiography in all nodules.There was no difference between Sonazoid CEUS,Gd-EOB-DTPA MRI,and CT arterioportal angiography.The combined sensitivity of Sonazoid CEUS and Gd-EOB-DTPA MRI was 94.1%(32/34).CONCLUSION:Changing the main diagnostic modality for HCC smaller than 2 cm from CT arterioportal angiography to Sonazoid CEUS and Gd-EOB-DTPA MRI is recommended.

Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies

We describe a 15-mm scirrhous hepatocellular carcinoma(HCC) in a 60-year-old man with B-type cirrhosis.Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7.Contrast-enhanced US revealed heterogeneous,not diffuse,hypervascularity in the early phase and a defect in the Kupffer phase.Contrast-enhanced computed tomography(CT) revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase.Magnetic resonance imaging(MRI) revealed iso-to hypointensity at T1 and high intensity at T2-weighted sequences.Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase.Super-paramagnetic iron oxide-MRI revealed a hyperintense nodule.CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect,respectively.Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC.Histologically,the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis.Immunohistochemically,the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin,and negative for cytokeratin 19.From the above findings,the nodule was diagnosed as scirrhous HCC.Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings,as shown in our case on the basis of chronic liver disease.

Multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated hepatocellular carcinoma in a patient with alcohol-related liver cirrhosis

We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepato- cellular carcinoma (HCC) in a 56-year-old man with alcoholrelated liver cirrhosis. Ultrasound (US) disclosed a 10 mm hypoechoic nodule and contrast enhanced US revealed a hypovascular nodule, both in segment seven. US-guided biopsy revealed a high-grade dysplastic nodule characterized by enhanced cellularity with a high N/C ratio, increased cytoplasmic eosinophilia, and slight cell atypia. One year later, the US pattern of the nodule changed from hypoechoic to hyperechoic without any change in size or hypovascularity. US-guided biopsy revealed well-differentiated HCC of the same features as shown in the first biopsy, but with additional pseudoglandular formation and moderate cell atypia. Moreover, immunohistochemical staining of cyclase- associated protein 2, a new molecular marker of well- differentiated HCC, turned positive. This is the first case of multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated HCC within one year in alcohol-related liver cirrhosis.

Hepatocellular carcinoma metastasizing to the skull base involving multiple cranial nerves

We describe a rare case of HCV-related recurrent multiple hepatocellular carcinoma (HCC) metastasizing to the skull base involving multiple cranial nerves in a 50-year- old woman. The patient presented with symptoms of ptosis, fixation of the right eyeball, and left abducens palsy, indicating disturbances of the right oculomotor and trochlear nerves and bilateral abducens nerves. Brain contrast-enhanced computed tomography (CT) revealed an ill-defined mass with abnormal enhancement around the sella turcica. Brain magnetic resonance imaging (MRI) disclosed that the mass involved the clivus, cavernous sinus, and petrous apex. On contrast-enhanced MRI with gadolinium-chelated contrast medium, the mass showed inhomogeneous intermediate enhancement. The diagnosis of metastatic HCC to the skull base was made on the basis of neurological findings and imaging studies including CT and MRI, without histological examinations. Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.

Well to moderately differentiated HCC manifesting hyperattenuation on both CT during arteriography and arterial portography

We present a rare case of well-to moderately-differentiated hepatocellular carcinoma (HCC) in a 71-year-old woman with hepatitis C virus-related cirrhosis and unusual radiologic features. A 20-mm hypoechoic nodule disclosed by ultrasound in segment two showed hyperattenuation on both computed tomography hepatic arteriography and computed tomography during arterial portography. Contrast-enhanced ultrasound revealed hypervascularity in the early vascular phase and defect in the post-vascular phase, with the same pattern detected by the two imaging techniques. SPIO-MRI revealed a hyperintense nodule. These findings were compatible with those of moderately-differentiated HCC. An ultrasound-guided biopsy showed histological features of well-to moderately-differentiated HCC characterized by more than two-fold the cellularity of the non-tumorous area, fatty change, clear cell change and mild cell atypia with a thin to mid-trabecular pattern. Further studies may provide insights into the correlation between tumor neovascularity in multistep hepatocarcinogenesis and dual hemodynamics, including the artery and the portal vein.

Distant metastasis of hepatocellular carcinoma to Meckel’s cave and cranial nerves:A case report and review of literature

BACKGROUND Metastasis occurs as a late event in the natural history of hepatocellular carcinoma(HCC),and most patients die of liver failure attributed to the tumor supplanting the liver.Conversely,the brain is a less common metastatic site.CASE SUMMARY We describe a rare case of hepatitis C virus-related multiple HCC metastasizing to the cavernous sinus,Meckel’s cave,and the petrous bone involving multiple cranial nerves in an 82-year-old woman.At admission imaging studies including Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging(MRI)revealed multiple HCC nodules in both right and left lobes.Ultrasound guided biopsy of the left lobe revealed moderately differentiated HCC.Molecular targeted therapy with Lenvatinib(8 mg/d for 94 d,per os)and Ramucirumab(340 mg/d and 320 mg/d,two times by intravenous injection)were administered for 4 mo,resulting in progression of the disease.Three months after the start of molecular target therapy,the patient presented with symptoms of hyperalgesia of the right face and limited abduction of the right eye,indicating disturbances in the right trigeminal and abducens nerves.Brain MRI disclosed a mass involving the cavernous sinus,Meckel’s cave and the petrous bone.Contrast-enhanced MRI with gadolinium-chelated contrast medium revealed a well-defined mass with abnormal enhancement around the right cavernous sinus and the right Meckel’s cave.CONCLUSION The diagnosis of metastatic HCC to the cavernous sinus,Meckel’s cave,and the petrous bone was made based on neurological findings and imaging studies including MRI,but not on histological examinations.Further studies may provide insights into various methods for diagnosing HCC metastasizing to the craniospinal area.