A single hepatic mass with two tales: hepatic tuberculosis and hepatocellular carcinoma

Hepatic tuberculosis (HTB) is an uncommon manifestation of tuberculous infections, and there has been no proven causal link between HTB and hepatocellular carcinoma (HCC). We herein present a rare case of a synchronous presentation of HTB and HCC within a single hepatic mass. A 57-year-old Chinese gentleman with recently diagnosed sigmoid adenocarcinoma was found to have a left lower lobe pulmonary nodule and solitary hepatic mass on staging computed tomography. Biopsies showed the hepatic mass to have both HTB and HCC components. This serves as a reminder that HTB is an important differential to consider for space-occupying lesions in the liver. Histological evaluation of suspected hepatic malignancies is recommended to exclude the presence of HTB in appropriate clinical settings.

Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis

Background/Aims@#Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. @*Methods@#We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. @*Results@#We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). @*Conclusions@#IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Non-alcoholic fatty liver disease: the pathologist’s perspective

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases characterized by fatty accumulation in hepatocytes, ranging from steatosis, non-alcoholic steatohepatitis, to cirrhosis. While histopathological evaluation of liver biopsies plays a central role in the diagnosis of NAFLD, limitations such as the problem of interobserver variability still exist and active research is underway to improve the diagnostic utility of liver biopsies. In this article, we provide a comprehensive overview of the histopathological features of NAFLD, the current grading and staging systems, and discuss the present and future roles of liver biopsies in the diagnosis and prognostication of NAFLD.

Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis.

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing globally, but its molecular features are not well defined. We aimed to identify unique molecular traits characterising NASH-HCC compared to other HCC aetiologies. METHODS: We collected 80 NASH-HCC and 125 NASH samples from 5 institutions. Expression array (n = 53 NASH-HCC; n = 74 NASH) and whole exome sequencing (n = 52 NASH-HCC) data were compared to HCCs of other aetiologies (n = 184). Three NASH-HCC mouse models were analysed by RNA-seq/expression-array (n = 20). Activin A receptor type 2A (ACVR2A) was silenced in HCC cells and proliferation assessed by colorimetric and colony formation assays. RESULTS: Mutational profiling of NASH-HCC tumours revealed TERT promoter (56%), CTNNB1 (28%), TP53 (18%) and ACVR2A (10%) as the most frequently mutated genes. ACVR2A mutation rates were higher in NASH-HCC than in other HCC aetiologies (10% vs. 3%, p <0.05). In vitro, ACVR2A silencing prompted a significant increase in cell proliferation in HCC cells. We identified a novel mutational signature (MutSig-NASH-HCC) significantly associated with NASH-HCC (16% vs. 2% in viral/alcohol-HCC, p = 0.03). Tumour mutational burden was higher in non-cirrhotic than in cirrhotic NASH-HCCs (1.45 vs. 0.94 mutations/megabase; p <0.0017). Compared to other aetiologies of HCC, NASH-HCCs were enriched in bile and fatty acid signalling, oxidative stress and inflammation, and presented a higher fraction of Wnt/TGF-ß proliferation subclass tumours (42% vs. 26%, p = 0.01) and a lower prevalence of the CTNNB1 subclass. Compared to other aetiologies, NASH-HCC showed a significantly higher prevalence of an immunosuppressive cancer field. In 3 murine models of NASH-HCC, key features of human NASH-HCC were preserved. CONCLUSIONS: NASH-HCCs display unique molecular features including higher rates of ACVR2A mutations and the presence of a newly identified mutational signature. LAY SUMMARY: The prevalence of hepatocellular carcinoma (HCC) associated with non-alcoholic steatohepatitis (NASH) is increasing globally, but its molecular traits are not well characterised. In this study, we uncovered higher rates of ACVR2A mutations (10%) - a potential tumour suppressor - and the presence of a novel mutational signature that characterises NASH-related HCC.

Disseminated peritoneal leiomyomatosis: a devastating sequelae of unconfined laparoscopic morcellation

There has been growing concern surrounding the use of unconfined power morcellation in laparoscopic surgeries for uterine leiomyoma due to its associated risks and long-term clinical sequelae, including parasitic leiomyomas and disseminated peritoneal leiomyomatosis (DPL). We present a case of DPL resulting from previous laparoscopic morcellation and a review of the existing literature. DPL is a potentially devastating consequence of unconfined laparoscopic morcellation in the surgical management of uterine fibroids. A multidisciplinary approach is recommended in the management of DPL, especially in cases of multivisceral involvement. Clinical caution ought to be exercised when using power morcellators; when unavoidable, confined laparoscopic morcellation offers a promising mitigation and should be adopted if practicable.

Sinonasal haemangiopericytoma: histomorphology and differential diagnoses

A 39-year-old female presented with a fleshy nasal polyp occluding the left nasal cavity, associated with haemopurulent discharge. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) scans of the paranasal cavities revealed a large polypoid tumour arising from the left middle turbinate and obstructing the left maxillary sinus ostium. However, no bony or intracranial involvement was identified. A biopsy revealed a tumour with small blue round cell morphology. The tumour cells showed diffuse strong membranous CD99 positivity and patchy CD34 positivity. Ancillary cytogenetic tests for the EWSR1 and SS18/SYT gene translocations were negative. In view of the non-invasive nature of the tumour and the low cell proliferative index (Ki-67) of 5%, a medial maxillectomy resection was performed. The resection revealed additional areas with spindle-cell morphology and focal haemangiopericytic vasculature. The tumour continued to show immunoreactivity to CD99 and CD34, as well as Smooth Muscle Actin (SMA) and Muscle Specific Actin (MSA). The overall findings are in keeping with a sinonasal haemangiopericytoma. With clear surgical resection margins, the patient is on routine follow-up and is currently disease-free.