Journal
of Pathology
Genomic landscape of lymphoepithelioma-like
hepatocellular carcinoma.
Chan AW, Zhang Z,
Chong CC, et al. J Pathol. 2019 Oct;249(2):166-172.
Lymphoepithelioma-like
hepatocellular carcinoma (LEL-HCC) is a distinct variant of HCC, characterized
by dense tumor-infiltrating lymphocytes (TILs) and better clinical outcomes. The
authors studied the genomic landscape of 12 LEL-HCC using whole-exome
sequencing, and further underpinned those genetic alterations related to an
immune active microenvironment by comparing findings to 15 classic HCC (c-HCC)
that were sequenced in parallel. They found similar mutational burden between
LEL-HCC and c-HCC. Interestingly, somatic nucleotide variation incidences of
specific genes (CTNNB1, AXIN1, NOTCH1, and NOTCH2) were significantly higher in
c-HCC than LEL-HCC, suggesting a plausible link between activated Wnt/β-catenin
and Notch signaling pathways and immune avoidance. LEL-HCC had a higher
frequency of positive PDL-1 protein expression than c-HCC (66.7% vs 6.6%). Marked
focal amplification of chromosome 11q13.3 was prevalent in LEL-HCC. Using The
Cancer Genome Atlas dataset, they further established oncogenes expressed from
chromosome 11q13.3 (CCND1, FGF19, and FGF4) to be strongly associated with the
immune checkpoint signature (CD274, PDCD1, BTLA, CTLA4, HAVCR2, IDO1, and
LAG3). Their results illustrate the somatic landscape of LEL-HCC, and highlight
molecular alterations that could be exploited in combinatory therapy with
checkpoint inhibitors in targeting HCC.
Histopathology
Keratin
19-expressing hepatocellular carcinoma and small-duct type intrahepatic
cholangiocarcinoma show a similar postoperative clinical course but have
distinct genetic features.
Akita
M, Ajiki T, Fukumoto T, Itoh T, Zen Y. 2019 Sep;75(3):385-393.
The
authors compared
clinicopathological and genetic features between keratin 19 (K19)-expressing
hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Consecutive cases of HCC (n = 430) were classified into K19+
and K19- using immunohistochemistry. ICCA cases were also separated into
small-(S-iCCA; n = 36) and large-duct types (n = 22) based on recently proposed
criteria, with the former being used in the present study. Mutational hot-spots
in TERT, CTNNB1, KRAS and IDH1 were sequenced. Twenty-six cases (6%) of HCC
expressed K19. K19+ HCC was more strongly associated with chronic hepatitis B
than K19- HCC and S-iCCA (46% versus 17% and 6%; both P < 0.001). Lymph node
metastasis was observed in K19+ HCC (8%) and S-iCCA (22%), but was exceptional
in K19- HCC (1%). K19+ HCC had TERT promoter mutations less frequently than
K19- HCC (31% versus 59%; P = 0.022), and lacked alterations in KRAS and IDH1.
CTNNB1 mutations were similarly observed in K19+ and K19- HCC (23% and 19%,
respectively), but rare in S-iCCA (3%). The postoperative survival curve of
K19+ HCC was almost identical to that of S-iCCA in the first 5 years
(approximately 50% at 5 years), and significantly worse than that of K19- HCC
(P = 0.040). Extrahepatic recurrence was more common in K19+ HCC (50%) and
S-iCCA (35%) than in K19- HCC (15%) (P = 0.001). The authors conclude that
although K19+ HCC and S-iCCA showed similar biological behaviors, they did not
share any driver gene mutations, suggesting the possible involvement of
epigenetic alterations in the iCCA-like features of K19+ HCC.
American Journal of Surgical Pathology
Prognostic Value
of Poorly Differentiated Clusters in Liver Metastatic Lesions of Colorectal
Carcinoma.
Yonemura K,
Kajiwara Y, Ao T, Mochizuki S, Shinto E, Okamoto K, Hase K, Ueno H. Am J Surg
Pathol. 2019 Oct;43(10):1341-1348.
Poorly
differentiated clusters (PDC) have been shown in multiple studies to be a
prognostic marker in colorectal carcinoma (CRC). Most previous studies,
however, have been based on the primary tumor and not metastases. This
retrospective study aimed to determine the prognostic impact of PDC in
colorectal liver metastases (CRLM) and compare them to their respective primary
tumor in 204 patients. PDC was graded as G1 (<5 clusters), G2 (5-9
clusters), and G3 (³10 clusters). PDC grade G2/G3 in CRLM was
found to be an independent prognostic factor of overall and recurrence free
survival on multivariate analysis. PDC grade in CRLM also correlated to PDC
grade in their respective primary sites. In summary, PDC may be an important
prognostic marker in CRLM.
The Pathologic
and Genetic Characteristics of the Intestinal Subtype of Intraductal Papillary
Neoplasms of the Bile Duct.
Nakanuma Y,
Kakuda Y, Fukumura Y, Sugino T, Uesaka K, Serizawa M, Terada T, Ohnishi Y. Am J
Surg Pathol. 2019 Sep;43(9):1212-1220.
This study
characterized histologic findings in 34, and genetic mutations in 21, cases of
intestinal subtype intraductal papillary neoplasm of the bile duct (iIPNB).
Intrahepatic iIPNBs tended to show a villous-papillary pattern, MUC5AC
expression, and mutations in KRAS and GNAS. Meanwhile,
extrahepatic iIPNBs more often showed a papillary pattern, CD10 expression, and
mutations in TP53 and PIK3CA. Predominant high-grade dysplasia
and/or presence of architectural complexity were more common in extrahepatic
iIPNBs. Awareness of these differences may aid in diagnosis and are suggestive
of differences in tumor biology between intrahepatic and extra hepatic iIPNBs.
Tumor Budding in
Intrahepatic Cholangiocarcinoma: A Predictor of Postsurgery Outcomes.
Tanaka M,
Yamauchi N, Ushiku T, Shibahara J, Hayashi A, Misumi K, Yasunaga Y, Morikawa T,
Kokudo T, Arita J, Sakamoto Y, Hasegawa K, Fukayama M. Am J Surg Pathol. 2019
Sep;43(9):1180-1190.
This
retrospective study evaluated 107 intrahepatic cholangiocarcinomas (ICC) and
compared them to 54 perihilar cholangiocarcinomas (PCC) and 40 extrahepatic
cholangiocarcinomas (ECC) to determine the prognostic significance of tumor
budding (TB). TB was performed in whole tumor areas and graded as low (0-4
buds), intermediate (5-9 buds), and high (³10
buds). ICC was also subtyped as type 1 (hilar) and type 2 (peripheral).
Univariate and multivariate analysis showed intermediate and high TB to be a
negative prognostic factor for recurrence-free and overall survival in ICC and
PCC, but not ECC. With regards to ICC subtypes, TB was a statistically
significant prognostic factor in type 2 but not in type 1. In summary, TB may
be an important prognostic marker in ICC and PCC.
Modern pathology
Immunohistochemical
and molecular features of cholangiolocellular carcinoma are similar to
well-differentiated intrahepatic cholangiocarcinoma.
Balitzer D, Joseph NM, Ferrell L, Shafizadeh N, Jain D, Zhang X,
Yeh M, di Tommaso L, Kakar S. Mod Pathol. 2019 Oct; 32(10): 1486-1494.
Cholangiolocellular
carcinoma is characterized by low grade cytologic atypia, and anastomosing
cords and glands resembling cholangioles or canals of Hering. Capture-based
next generation sequencing targeting the coding regions of 479 cancer genes and
select introns was performed on 17 cases (5 cholangiolocellular carcinomas, 7
intrahepatic cholangiocarcinomas, 5 mixed cholangiolocellular-intrahepatic
cholangiocarcinomas) along with immunohistochemistry for CK19, SALL4, CD56,
CD117, and EMA. CK19 and EMA were positive in all cases; both luminal and
cytoplasmic EMA was seen in 3/5 cholangiolocellular carcinoma and 3/6
intrahepatic cholangiocarcinomas. CD117 and SALL4 were negative in all cases.
CD56 was positive in 2/5 cholangiolocellular carcinoma, 4/6 intrahepatic
cholangiocarcinoma and 2/5 mixed cases. Mutations typical of intrahepatic
cholangiocarcinoma (IDH1/2, PBRM1, FGFR2) were present in 90% of cases
with cholangiolocellular carcinoma component. The genomic profile (IDH1/2 mutations, FGFR2 fusions,
chromatin-remodeling gene mutations such as ARID1A, PBRM1)
and copy number alterations were similar in cholangiolocellular carcinoma,
intrahepatic cholangiocarcinoma and mixed cholangiolocellular-intrahepatic
cholangiocarcinoma. In all mixed cases, the immunohistochemistry results,
mutational profile and copy number alterations in both components were similar.
The authors conclude that cholangiolocellular carcinoma should be categorized
as a histologic subtype of well-differentiated intrahepatic cholangiocarcinoma,
and should not be considered a distinct entity, or a variant of combined
hepatocellular-cholangiocarcinoma unless a distinct hepatocellular component is
also present.
Journal of Gastroenterology and Hepatology
Non‐invasive structure–function assessment of
the liver by 2D time‐harmonic elastography and the dynamic Liver MAximum
capacity (LiMAx) test.
Heucke N, Wuensch T, Mohr J, et al. J Gastroenterol Hepatol. 2019 Sep; 34(9): 1611-1619.
The aim
of this study was the combined measurement of liver function by the 13C‐methacetin
Liver MAximum capacity (LiMAx) test and tissue‐structure related stiffness by
2D time‐harmonic elastography for the assessment of liver disease progression.
LiMAx test and time‐harmonic elastography, serological scores fibrosis 4 index
and aspartate aminotransferase to platelet ratio index were used in patients
with chronic liver diseases (n = 75) and healthy control subjects
(n = 22). LiMAx values correlated negatively with liver
stiffness (r = −0.747), aminotransferase to platelet ratio
index (r = −0.604), and fibrosis 4 (r = −0.573).
Median (interquartile range) LiMAx values decreased with fibrosis progression
from 395 μg/kg/h (371–460 μg/kg/h) in participants with no fibrosis
to 173 μg/kg/h (126–309 μg/kg/h) in patients with severe fibrosis.
Median liver stiffness increased progressively with the stage of fibrosis from
no fibrosis (1.56 m/s [1.52–1.63 m/s]) to moderate fibrosis
(1.60 m/s [1.54–1.67 m/s]) to severe fibrosis 1.85 m/s
[1.76–1.92 m/s]). The authors
conclude that structural changes in the liver correlate with a functional
decline of the organ.
Clinical
Gastroenterology and Hepatology
Health-related Quality of Life in
Nonalcoholic Fatty Liver Disease Associates With Hepatic Inflammation.
Huber Y,
Boyle M, Hallsworth K, Tiniakos D, Straub BK, Labenz C, Ruckes C, Galle PR,
Romero-Gómez M, Anstee QM, Schattenberg JM; EPoS Consortium Investigators. Clin
Gastroenterol Hepatol. 2019 Sep; 17(10):2085-2092.
Chronic liver disease has negative
effects on health-related quality of life (HRQL). The authors collected data
from 304 patients with histologically defined NAFLD that were enrolled
prospectively into the European NAFLD Registry that included subjects from
Germany, the United Kingdom, and Spain. They observed a substantial burden of
symptoms in patients. In addition to increased age, female sex, and the
presence of diabetes, detection of lobular inflammation in biopsies correlated
with lower health-related quality of life (HRQL).
Human Pathology
Fine-needle aspiration of the liver: a 10-year single institution retrospective review.
McHugh KE, Policarpio-Nicolas MLC,
Reynolds JP. Hum Pathol. 2019 Oct; 92:25-31.
Fine-needle aspiration (FNA) of liver
masses is a minimally invasive means of evaluation, with diagnostic accuracy of
over 85%. The authors conducted a 10-year retrospective review of a single
institution's cytopathology experience with the diagnosis of liver lesions.
Associated concurrent and subsequent surgical pathology and cytopathology cases
were identified. All FNA
cases were organized into four diagnostic categories: positive for malignancy,
atypical, negative for malignancy, and non-diagnostic. 713 hepatic FNAs were
categorized as follows: positive for malignancy 467 (65.5%), atypical 49
(6.9%), negative 171 (24.0%) and non-diagnostic 26 (3.6%). Based on the review,
diagnostic performance of hepatic FNA shows a sensitivity of 93.4% and
specificity of 96.7%. Read more to learn the specifics of both diagnostic
performance and the frequency with which various diagnostic entities present as
hepatic lesions.
Distinct histomorphological features are associated with IDH1 mutation
in intrahepatic cholangiocarcinoma.
Wang T, Drill E, Vakiani E, Pak LM,
Boerner T, Askan G, Schvartzman JM, Simpson AL, Jarnagin WR, Sigel CS. Hum
Pathol. 2019 Sep; 91:19-25.
Mutations
in IDH1 (mIDH1) define a molecular
subclass of intrahepatic cholangiocarcinoma (ICC) and IDH-targeted therapies
are in development. Characterizing mIDH1 ICC histomorphology is of clinical
interest for efficient identification. Resected ICCs with targeted
next-generation sequencing were selected. By slide review, blinded to IDH
status, data were collected for histology type, mucin production, necrosis,
fibrosis, cytoplasm cell shape, and architectural pattern. Parameters were
compared between mIDH1and IDH wild-type controls. In the examined cohort (113
ICC: 29 mIDH1 and 84 IDH wild-type), all IDH1-mutant
tumors were of small duct-type histology, thus analysis was limited to 101
small duct-type tumors. The authors conclude that mIDH1 ICCs are more likely to
have plump cuboidal/polygonal shape (P = .014) and geographic-type fibrosis
(P = .005); however, IDH1 mutation is not associated with
a distinct architectural pattern.
The expression of gastrointestinal
differentiation markers in extrahepatic cholangiocarcinoma: clinicopathological
significance based on tumor location.
Ishida K,
Osakabe M, Eizuka M, Tai S, Sugimoto R, Fujita Y, Katagiri H, Takahara T,
Uesugi N, Nitta H, Sasaki A, Sugai T. Hum Pathol. 2019 Oct;
92:91-100.
The authors aimed to clarify the role
of gastrointestinal differentiation marker expression in extrahepatic CCA based
on tumor location. MUC2, MUC5AC, MUC6, CD10, CDX-2, and CK 20
immunohistochemical expression was examined in perihilar (n=30) and distal
(n=54) CCAs. Through semi-quantitative scoring and hierarchical clustering,
perihilar and distal CCAs were stratified into two subgroups.
Gastroenterology
Liver
Fibrosis and Metabolic Alterations in Adults With alpha-1-antitrypsin
Deficiency Caused by the Pi*ZZ Mutation.
Hamesch
K, et al. Gastroenterology. 2019 Sep; 157(3):705-719.
The authors assessed the liver disease
burden and associated features in adults with the severe alpha-1 antitrypsin
deficiency (AATD). A variety of demographic parameters, comorbidities, lung-
and liver-related health, and blood samples were collected. Liver fibrosis was
assessed non-invasively via AST/platelet ratio index, HepaScore, and via
transient elastography. Liver steatosis was determined via transient
elastography. The authors found evidence of liver steatosis, impaired lipid
secretion, and factors associated with significant liver fibrosis in adults
carriers versus controls.
Journal of
Hepatology
Molecular and histological
correlations in liver cancer.
Calderaro
J, Ziol M, Paradis V, Zucman-Rossi, J.
Journal of Hepatology 2019. Sep 71(3); 616–630.
This article reviews the most recent data
regarding hepatocellular carcinoma (HCC), a highly diverse cancer, focusing on
its molecular and histological characteristics. Employing high-throughput
sequencing and gene expression profiling, novel distinct transcriptomic
subclasses and several recurrent genetic alterations are characterized.
Numerous HCC subtypes with distinct histological features are discussed.
HCC phenotype seems parallel to certain gene mutations, tumor subgroups and/or
oncogenic pathways. For instance, well-differentiated, CTNNB1-mutated HCCs
exhibit a homogeneous subtype characterized by cholestasis, microtrabecular and
pseudoglandular architectural patterns; another non-proliferative subtype shows
a gene expression pattern similar to that of mature hepatocytes and displays a
steatohepatitic phenotype. In contrast, proliferative HCCs are most often
poorly differentiated and possess progenitor features. A new morphological
variant of proliferative HCC referred to as ‘‘macrotrabecular-massive”, is linked
with angiogenesis activation and poor prognosis. This article discusses a
compilation of novel information that will potentially lead to improved
precision medicine for this highly aggressive malignancy.
American Journal of Clinical Pathology
Recurrent Idiopathic Liver
Allograft Failure.
Schiano TD, Florman S, Fiel MI. Am
J Clin Pathol. 2019 Aug 1; 152(3): 369-376.
This article better characterizes clinical and
histopathological features of antibody-mediated rejection (AMR) as a major
contributing factor of recurrent idiopathic liver allograft failure,
highlighting the need for pathologists and transplant physicians to recognize
the varied histopathological features of AMR necessary for allograft-saving
timely medical interventions.
American Journal of
Gastroenterology
Histologic Findings of Advanced Fibrosis and Cirrhosis
in Patients With Nonalcoholic Fatty Liver Disease Who Have Normal
Aminotransferase Levels.
Gawrieh S, Wilson LA, Cummings OW, Clark JM, Loomba R,
Hameed B, Abdelmalek MF, Dasarathy S, Neuschwander-Tetri BA, Kowdley K, Kleiner
D. Am J Gastroenterol. 2019 Oct 1; 114(10):1626-35.
This paper studied 534 adults with biopsy-proven NAFLD
and alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
<40U/L within 3 months of their liver biopsy. The authors found that the
prevalence of NASH F2-F3 and cirrhosis was 19% and 7%, respectively. The main
risk factors for NASH F2-3 were type 2 diabetes, white race, lower low-density
lipoprotein, lower platelet count, higher AST/ALT ratio, higher serum
triglycerides, and hypertension. The conclusion was that patients with these
risk factors are more likely to have significant fibrosis in their liver biopsy.
Combined Hepatocellular Cholangiocarcinoma: A Population-Based
Retrospective Study.
Ramai D, Ofosu A, Lai JK, Reddy M, Adler DG. Am
Journal Gastroenterol. 2019 Sep 1; 114(9):1496-501.
In this study the overall incidence of combined
hepatocellular cholangiocarcinoma (CHC) between 2004 and 2014 was 0.05 per
100,000 per year. Incidence increased with age, with the highest incidence in
men occurring between 60 and 64 years and 75–79 years for women. Women had a
higher incidence of CHC. Most tumors were poorly differentiated while the most
common stage at presentation was stage 4.
This paper adds to our knowledge, but in the absence of histological
review the conclusions must be considered provisional.
Prepared by:
Nafis
Shafizadeh MD (Editor); Southern California Permanente Medical Group
Daniela Allende MD; 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
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
Heather Stevenson-Lerner MD PhD; University of Texas
Eric Yee MD; University of Arkansas
Eric Yee MD; University of Arkansas
No comments:
Post a Comment