Tuesday, March 26, 2019

HPHS Journal Watch: January / February 2019


Journal of Hepatology


Intra-tumoral tertiary lymphoid structures are associated with a low risk of early recurrence of hepatocellular carcinoma. 
Calderaro J, Petitprez F, Becht E, et al. Journal of Hepatology 2019;70:58–65.
https://www.ncbi.nlm.nih.gov/pubmed/30213589

In most cancers explored, tertiary lymphoid structures (TLS) supply a vital microenvironment for generating anti-tumor immune responses, and are linked with enhanced clinical outcomes in most cancers, but its role in HCC is not well defined.  In this retrospective pathological study of a series of 273 patients with HCC treated with surgical resection, intratumoral TLSs were found to be associated with a low risk of early relapse after surgical resection, suggesting that they reflect the existence of in situ effective anti-tumor immunity.  The pathological results were further validated by gene expression profiling using public data set (LCI cohort).  Learn more of the details of the study in the January 2019 issue. 

American Journal of Clinical Pathology


Unexpectedly High Prevalence of Cystoisospora belli Infection in Acalculous Gallbladders of Immunocompetent Patients. 
Noor M, Katzman PJ, Huber AR, et al. American Journal of Clinical Pathology 2019; 151: 100–107. 
https://www.ncbi.nlm.nih.gov/pubmed/30285068

This study is a retrospective review of cholecystectomy specimens (n = 401) removed for various indications, and a prospective cohort of cholecystectomy specimens (n = 22) entirely submitted for histologic evaluation to determine the prevalence of C. belli.  C belli was identified in 39/401 (9.7%) of the retrospective cohort, and 6/22 (27.3%) of the entirely submitted specimens.  There was no correlations of presence of C belli with age, sex, clinical indication, and abnormalities of preoperative laboratory values.  The authors conclude that C belli resides in a latent state in the gallbladder and may be best considered a commensal organism.

Evaluation of Peritumoral Fibrosis in Metastatic Colorectal Adenocarcinoma to the Liver Using Digital Image Analysis. 
Waters KM, Cottrell TR, Besharati S, et al. American Journal of Clinical Pathology 2019, 151:226–230.
https://www.ncbi.nlm.nih.gov/pubmed/30339201

This study addresses the effect of peritumoral fibrosis to the assessment of native liver fibrosis in 25 cases of metastatic colonic adenocarcinoma to liver by digital image analysis.  The authors found that there was a 3.9 fold (range 0.9-18.6) median increase in fibrosis in the first 0.5 mm of peritumoral liver compared to distant liver. Fibrosis levels returned to baseline at median 2.5 mm (interquartile range 1.5-5.0 mm) from tumor.  The authors conclude that fibrosis is markedly increased in peritumoral liver. Fibrosis levels returned to baseline by 5 mm from tumor in approximately 75% of cases. Pathologists should be cautious of fibrosis in mass-directed liver biopsies without at least 5 mm of liver tissue distal to the mass.

American Journal of Gastroenterology


Diagnosis and Management of Primary Biliary Cholangitis.
Younossi ZM, Bernstein D, Shiffman ML, et al. Am J Gastroenterol. 2019; 114 (1):48-63.
https://www.ncbi.nlm.nih.gov/pubmed/30429590

This paper provides a good general review of PBC.  With reference to liver biopsy,  it supports the current consensus that the diagnosis  of PBC does not require liver biopsy and that the diagnosis is based on clinical and laboratory tests. It is, however, indicated when the diagnosis of PBC is uncertain or where another superimposed diagnosis (most commonly non-alcoholic fatty liver disease) is suspected. It is essential if an overlap syndrome is suspected because of clinical and laboratory features of AIH.

Hepatology


Clinical Manifestations and Outcomes of Patients with Sarcomatoid Hepatocellular Carcinoma
Liao SH, Su TH, Jeng YM, et al. Hepatology 69(1): 209-221.
https://www.ncbi.nlm.nih.gov/pubmed/30014620

This study examines 40 cases of sarcomatoid HCC and compares them to 160 cases of non-sarcomatoid HCC. The sarcomatoid group had significantly shorter median recurrence-free and overall survival. Sarcomatoid histology was an independent factor for all-cause mortality and tumor recurrence, and was associated with atypical imaging patterns.

Hepatocellular Carcinoma as a Complication of Vascular Disease of the Liver After Fontan Procedure
Mazzarelli C, Cannon MD, Hudson Mark, et al. Hepatology 69(2): 911-913.
https://www.ncbi.nlm.nih.gov/pubmed/30055116

The authors report 3 cases of HCC occurring in patients 17-18 years after Fontan procedure as children. None of the patients had features of advanced liver disease. They suggest further studies are needed on this rare, late complication of Fontan procedure.

Antiprogrammed Cell Death-1 Immunotherapy-Related Secondary Sclerosing Cholangitis
Ogawa K, Kamimura K, Terai S. Hepatology 69(2): 914-916.
https://www.ncbi.nlm.nih.gov/pubmed/30033637

The authors report a case of secondary sclerosing cholangitis due to PD-1 immunotherapy with pembrolizumab. The case adds to the list of immune-mediated adverse events that can occur in the setting of immunotherapy.

Histopathology


Histology of portal vascular changes associated with idiopathic non-cirrhotic portal hypertension: nomenclature and definition.
Guido M, Alves VAF, Balabaud C; et al, International Liver Pathology Study Group. Histopathology 2019 Jan;74(2):219-226.
https://www.ncbi.nlm.nih.gov/pubmed/30129657

Idiopathic non-cirrhotic portal hypertension (INCPH) is a vascular liver disease of unknown etiology, characterized by clinical signs of portal hypertension (PH) in the absence of cirrhosis. As much uncertainty exists about INCPH pathophysiology, and as no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis. The histological   diagnosis of INCPH is not always straightforward. The terminology and dentition are ambiguous, which adds complexity to the already complex clinicopathological scenario. An   international study group of liver pathologists and hepatologists pursued a consensus on nomenclature for the portal vascular lesions of INCPH.  The authors describe the portal and periportal changes in INCPH, characterized by portal vein narrowing, portal vascular spaces directly abutting the hepatic parenchyma at the limiting plate, increase in the number of portal vascular spaces and abnormal spaces immediately adjacent to a portal tract. The authors aim at simplification and providing a basis for standardization, proposing a nomenclature that is intended to be descriptive enough to be used without pathophysiological implications. 

Human Pathology


Somatic HNF1A mutations in the malignant transformation of hepatocellular adenomas: a retrospective analysis of data from MSK-IMPACT and TCGA.
Hechtman JF, Abou-Alfa GK, Stadler ZK, et al. Hum Pathol 2019 Jan;83:1-6.
https://www.ncbi.nlm.nih.gov/pubmed/30121369

Mutations of HNF1A gene are well documented in hepatocellular adenoma. The role of HNF1A mutations in hepatocellular carcinoma remains to be determined. In this study, all hepatocellular neoplasms evaluated by Memorial Sloan Kettering-Integrated Mutational Profiling of Actionable Clinical Targets assay or the Cancer Genome Atlas sequencing, and cases reported in the literature, were queried for HNF1A mutations. 11 of 672 (1.6%) HCCs harbored HNF1A mutations. 3 of these 11 HCCs arose in a background of adenomatosis. Information on pre-existing adenoma for the remaining cases (8) was not available. Their findings suggest that malignant transformation of HNF1A-mutated hepatocellular adenoma occurs, albeit infrequently.

Gastroenterology


Epidemiology and Management of Hepatocellular Carcinoma. 
Kulik L, El-Serag HB. Gastroenterology. 2019 Jan;156(2):477-491.

A review of the emerging data on the risk and determinants of HCC in these conditions and the implications of HCC surveillance.

Genomic Medicine and Implications for Hepatocellular Carcinoma Prevention and Therapy.
Dhanasekaran R, Nault JC, Roberts LR, et al. Gastroenterology. 2019 Jan;156(2):492-509.
https://www.ncbi.nlm.nih.gov/pubmed/30404026

A review of recent advances in genomics which have increased our understanding of the mechanisms by which hepatitis B virus, hepatitis C virus, alcohol, fatty liver disease, and other environmental factors.

Targeted and Immune-Based Therapies for Hepatocellular Carcinoma.
Greten TF, Lai CW, Li G, et al. Gastroenterology. 2019 Jan;156(2):510-524.
https://www.ncbi.nlm.nih.gov/pubmed/30287171

Provides a summary of the targeted and immune-based agents in trials of patients with advanced hepatocellular carcinoma and discusses the future of these strategies for liver cancer.

Journal of Gastroenterol and Hepatology


Biliary transporter gene mutations in severe intrahepatic cholestasis of pregnancy: Diagnostic and management implications
Yeap SP, Harley H, Thompson R, et al. Journal of Gastroenterology and Hepatology 2019, 34: 425–435

Five women with a total of 8 pregnancies with Intrahepatic cholestasis were included in the study.
Two cases showed biallelic heterozygosity for several ABCB11 mutations, one was homozygous for an ABCB4mutation and a fourth case was heterozygous for another ABCB4 mutation.

Archives of Pathology and Laboratory Medicine


Colorectal Liver Metastases. A Pathologist’s Guide to Creating an Informative Report and Improving Patient Care.
Moreno Prats M, Sasatomi E1, Stevenson HL. Arch Pathol Lab Med. 2019 Feb;143(2):251-257.
https://www.ncbi.nlm.nih.gov/pubmed/29790787

The authors review the important pathologic elements for reporting colorectal cancer (CRC) liver metastases as well as background changes that can be seen in the liver, including those following chemotherapy for CRC.

Calcifying Nested Stromal-Epithelial Tumor of the Liver: An Update and Literature Review
Benedict M, Zhang X. Arch Pathol Lab Med. 2019 Feb;143(2):264-268.

This is a resident short review that covers the clinical, radiologic, behavioral, and pathologic findings as well as the differential diagnosis and treatment of calcifying nested stromal-epithelial tumor of the liver.


Prepared by (in alphabetical order):
Daniela Allende MD (Editor), Cleveland Clinic
Vishal Chandan, MBBS; University of California Irvine
Robert Goldin MD; Imperial College, London
Bella Goyal, MD; California Pacific Pathology Medical Group
Grace Guzman MD; University of Illinois
Mojgan Hosseini MD; University of California San Diego
Nafis Shafizadeh MD; Southern California Permanente Medical Group
Maria Westerhoff MD; University of Michigan
Eric Yee MD; University of Arkansas for Medical Sciences

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