Pathology Journals

Segmental atrophy of the liver: a distinctive pseudotumor of the liver with variable histologic appearances.
Singhi AD, Maklouf HR, Mehrotra AK, Goodman ZD, Drebber U, Dienes HP, Torbenson M.  Am J Surg Pathol. 2011 Mar;35(3):364-71. (CUMC Full Text PDF)

Singhi et al describe the clinical and pathologic features of a group of 18 patients presenting with a pseudotumor secondary to segmental atrophy of the liver. The authors conclude that these pseudotumors occur in the setting of of an intralesional abnormal and/or thrombosed vessel and, histologically, may progress through several "stages": from areas of parenchymal collapse with brisk ductular proliferation (early lesions), nodular elastosis (more advanced lesions), and finally nodular fibrosis (end-stage lesion).

 Prevalence and clinical significance of Küpffer cell hyperplasia with hemophagocytosis in liver biopsies.
Prendki V, Stirnemann J, Lemoine M, Lohez M, Aras N, Ganne-Carrié N, Larroche C, Roulot D, Tengher-Barna I, Fain O, Ziol M. Am J Surg Pathol. 2011 Mar;35(3):337-45. (CUMC Full Text PDF)

Prendki and colleagues discuss the prevalence and clinical significance of Kupffer cell hyperplasia with accompanying hemophagocytosis in liver biopsy samples. The authors identified hemophagocytosis in 69 of 5194 liver biopsies (1.3%) obtained over a 6-year period. Complete hemophagocytic syndrome (fever, splenomegaly, bicytopenia, hypertriglyceridemia, hyperferritinemia, and/or hypofibrinogenemia) was seen in 36% of patients in which hemophagocytosis was identified. Almost all patients had at least one of the following conditions: HIV infection, hematologic malignancy, autoimmune diseases, or an ongoing infectious process, including tuberculosis, CMV, or EBV. A decreased perforin to CD3+ lymphocyte ratio was associated with hemophagocytosis in this study.

This is a case we had in our service a couple of weeks ago. This young female presented with complete hemophagocytic syndrome and underwent liver biopsy for severe hepatic dysfunction. Decreased perforin to CD3 lymphocytes is seen in this case, as described in the study above.

The concept of hepatic artery-bile duct parallelism in the diagnosis of ductopenia in liver biopsy samples.
Moreira RK, Chopp W, Washington MK. Am J Surg Pathol. 2011 Mar;35(3):392-403. (CUMC Full Text PDF)

In this paper, my colleagues and I essentially apply the concept of hepatic artery-bile duct parallelism (i.e. parallel arrangement of these two structures within portal tracts) to propose specific diagnostic criteria for the diagnosis of bile duct loss (ductopenia) in liver biopsy samples. The final set of proposed criteria is relatively simple: two or more portal tracts containing an unpaired hepatic artery (representing at least 10% of all portal tracts in a given sample) is indicative of bile duct loss. The article is definitely information-heavy and may best be appreciated with a couple of glasses of fine wine.

 This liver biopsy from a patient with stage 1 PBC illustrates the application of the "unpaired hepatic artery" method for evaluation of ductopenia (click on image to enlarge). A total of seven portal tracts are present in the sample below, five of which contain an interlobular bile duct (BD+). Therefore, the speciment is not diagnostic for bile duct loss. However, two of seven portal tracts contain an unpaired hepatic artery (UHA+), which is indicative of bile duct loss according to the data presented in this study.

Fibrolamellar carcinomas are positive for CD68.
Ross HM, Daniel HD, Vivekanandan P, Kannangai R, Yeh MM, Wu TT, Makhlouf HR, Torbenson M. Mod Pathol. 2011 Mar;24(3):390-5. (CUMC Full Text PDF)

This is one of a series of articles by Michael Torbenson's group on the subject of fibrolamellar HCC (see other links below). In this study, the authors demonstrate a generally strong CD68 expression in a granular or dot-like pattern in 31/32 FL-HCCs. CD68 was also expressed by a minority of conventional HCCs, especially those arising in non-cirrhotic livers (overall sensitivity of 96% and specificity of 80%).
(see also: Mod Pathol 2010;23(6):790-8; Mod Pathol 2008;21(6):670-5; Adv Anat Pathol 2007;14(3):217-23; Hum Pathol 2007;38(4):639-44).

Comparing morphometric, biochemical, and visual measurements of macrovesicular steatosis of liver.
Li M, Song J, Mirkov S, Xiao SY, Hart J, Liu W. Hum Pathol. 2011 Mar;42(3):356-60. (CUMC Full Text PDF)

The authors measure the degree of steatosis in liver samples by biochemical measure of fat content (weight percentage of fat) and digital morphometric analysis (percentage of areas occupied by fat) and compare these with traditional ("visual") pathologic evaluation. Biochemical and digital analyses generated similar results, while "visual" estimates systematically yielded values approximately four times higher than the other two methods (but with highly reproducible values among 3 pathologists).  The fact that different methods yield different absolute values and percentages for "fat content" should come at no surprise. In this study, for instance, the visual assessment evaluated the "proportion of hepatocytes involved by macrovesicular steatosis". This is in sharp contrast with what is being measured biochemically (i.e. total fat content, regardless of cellular location or droplet size, using the entire tissue fragment - portal tracts and fibrous septa included - as denominator). As for digital analysis, it is generally just as accurate as the individual selecting the fields and operating the software. The excellent intra- and interobserver agreement among the three study pathologist is noteworthy as it contradicts previous studies (see Ann Surg 2009;250(5):691-7).

Gastroenterology and Hepatology Journals

"Pardon the interruption": Comments on the International Liver Cancer Association Fourth Annual Conference, 2010. Is there really no role for liver biopsy interpretation in liver cancer?
Brunt EM, Gores G. Hepatology. 2011 Mar;53(3):721-2. (CUMC Full Text PDF)

The authors question the widespread belief among clinicians and surgeons that liver biopsies have a very limited role in the era of -omics, gene array, micro-RNA, and other molecular markers. Also, are liver pathologists a dying breed?

Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. 
Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA; for the NASH Clinical Research Network (CRN). Hepatology. 2011 Mar;53(3):810-820. (CUMC Full Text PDF)

In this issue of Hepatology, Elizabeth Brunt and colleagues from the NASH Clinical Research Network (CRN) reiterate the fact that the NAFLD activity score (NAS) - a scoring system originally designed to serve a similar purpose as the various chronic hepatitis grading systems, or the Banff scoring system for rejection - is not an efficient substitute to traditional diagnostic criteria for NASH. As the authors point out, the composite NAS above a certain value (usually >5) has been adopted by some investigators as the basis for a diagnosis of NASH, although the validity of this approach is unproven. In this regard, the authors show that only 75% of biopsies with definite SH had an NAS >5 and that among biopsies with NAS >5, 86% had SH. They conclude that the diagnosis of NASH does not always correlate with specific threshold values of the semiquantitative NAS.

Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stem/progenitor cells in humans. Yoon SM, Gerasimidou D, Kuwahara R, Hytiroglou P, Yoo JE, Park YN, Theise ND. Hepatology. 2011 Mar;53(3):964-73. (CUMC Full Text PDF)

The expression of EpCAM as a marker of hepatic stem/progenitor cells is studied in the setting of hepatitis B and C in various stages. EpCAM expression in hepatocytes is reported to become more prominent in later stages of chronic hepatitis, accompanied by development of ductular reaction (CK19+, w/ high proliferation) and, on a molecular level, presence of telomeres of longer length. The data support the concept that EpCAM+ hepatocytes represent a population of newly-formed hepatocytes from hepatobiliary stem/progenitor cells.

Management of hepatocellular carcinoma: An update.
Bruix J, Sherman M. Hepatology. 2011 Mar;53(3):1020-2. (CUMC Full Text PDF)

Human hepatic stem cell and maturational liver lineage biology.
Turner R, Lozoya O, Wang Y, Cardinale V, Gaudio E, Alpini G, Mendel G, Wauthier E, Barbier C, Alvaro D, Reid LM. Hepatology. 2011 Mar;53(3):1035-45. (CUMC Full Text PDF)
A detailed review of the histogenesis and development of the liver with excellent illustrations.

Obliterative portal venopathy: Portal hypertension is not always present at diagnosis.
Cazals-Hatem D, Hillaire S, Rudler M, Plessier A, Paradis V, Condat B, Francoz C, Denninger MH, Durand F, Bedossa P, Valla DC. J Hepatol. 2011 Mar;54(3):455-61. (CUMC Full Text PDF)

Intratumoral neutrophils: A poor prognostic factor for hepatocellular carcinoma following resection.
Li YW, Qiu SJ, Fan J, Zhou J, Gao Q, Xiao YS, Xu YF. J Hepatol. 2011 Mar;54(3):497-505. (CUMC Full Text PDF)

Anabolic-androgenic steroids: a possible new risk factor of toxicant-associated fatty liver disease.
PA, Cotrim HP, Salles BR, Almeida CE, dos Santos CR Jr, Nachef B, Andrade AR, Zoppi CC.

Liver Int. 2011 Mar;31(3):348-53. (CUMC Full Text PDF)
It's all about looking good for Canaval. Forget about your liver! This group from Salvador, Brazil studied the prevalence of fatty liver disease in asymptomatic non-competitive male bodybuilders with a history of anabolic-androgenic steroid use. In this case-control study, 12.6% of these athletes met criteria for fatty liver disease, as defined in this study, compared to 2.4% of controls (bodybuilders with no history of anabolic steroid use) (OR=6.0, 95% CI: 1.3-27.6). The authors include anabolic steroid-induced liver disease as a cause of what has been referred to as TAFLD (toxicant-associated fatty liver disease) and TASH (toxicant-associated steatohepatitis).

Surgery and transplantation journals

The Significance of Donor-Specific HLA Antibodies in Rejection and Ductopenia Development in ABO Compatible Liver Transplantation.
Musat AI, Agni RM, Wai PY, Pirsch JD, Lorentzen DF, Powell A, Leverson GE, Bellingham JM, Fernandez LA, Foley DP, Mezrich JD, D'Alessandro AM, Lucey MR. Am J Transplant. 2011 Mar;11(3):500-10. (CUMC Full Text PDF)
This is the latest addition to a rapidly increasing number of articles showing a possible important role for humoral rejection in cases of liver allograft rejection. Applying the currently used strategy for detection of antibody-mediated rejection in other solid organs (using C4d staining and presence of donor-specific HLA antibodies), the authors conclude that humoral alloreactivity is frequently present in cases of "cellular" rejection in ABO-compatible liver allografts.

Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma.
Shibuya M, Kondo F, Sano K, Takada T, Asano T. J Hepatobiliary Pancreat Sci. 2011 Jan 14. (CUMC Full Text PDF)
The authors identify expression of cholangiocyte markers in the majority of HCC cases included in this study, while hepatic stem/progenitor cell marker (C-kit) was present in a small minorit y of cases.

The clinicopathological significance of heat shock protein 70 and glutamine synthetase expression in hepatocellular carcinoma.
Shin E, Ryu HS, Kim SH, Jung H, Jang JJ, Lee K. J Hepatobiliary Pancreat Sci. 2011 Jan 14. [Epub ahead of print] (CUMC Full Text PDF)
HSP-70 was expressed by the majority of HCCs in this study (71.9%) and correlated with microscopic vascular invasion, larger tumor size, higher Edmondson-Steiner grade, and lower disease-free survival.