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Figure 3: Case 2 - histochemical comparison of glycogen content and hexokinase II activity in hepatocellular carcinoma tissues (a, c, e, and g) and background
liver (b, d, f, and h) (a and b: HE, ×100; c and d: periodic acid-Schiff, ×100; e and f: diastase-periodic acid-Schiff, ×100; g and h: hexokinase II, ×400)

Guzman reported that the higher levels of HK- Decarli A, Trevisi P, Ribero ML, Martelli C, Porru S, Nardi G. Alcohol
II in HCC were associated with more aggressive and hepatocellular carcinoma: the effect of lifetime intake and hepatitis
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was not associated with DM. HK-II was expressed and hepatocellular carcinoma: a weighty connection. Hepatology
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in both the HCC tissues and background liver 4. 2010;51:1820-32.
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inversely related to PAS-positivity, being higher and prognosis: a meta-analysis of prospective cohort studies. PLoS
in cells with lower glycogen content. Histological 5. One 2011;6:e27326.
Evans RW, Littler TR, Pemberton HS. Glycogen storage in the liver in
examination showed that our HCC patients have less diabetes mellitus. J Clin Pathol 1955;8:110-3.
aggressive phenotypes. It is hypothesized that the 6. Stone BG, Van Thiel DH. Diabetes mellitus and the liver. Semin Liver
reduction of glycogen content in HCC may, therefore, 7. Dis 1985;5:8-28.
Bannasch P. The cytoplasm of hepatocytes during carcinogenesis.
be associated with the appearance of Warburg type of Electron and light microscopical investigations of the
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content of the liver might serve as a basis for 8. 100.
Dombrowski F, Bannasch P, Pfeifer U. Hepatocellular neoplasms
predicting the development of HCC. Unfortunately, induced by low-number pancreatic islet transplants in streptozotocin
such an approach is currently not available. diabetic rats. Am J Pathol 1997;150:1071-87.
9. Bannasch P, Khoshkhou NI, Hacker HJ, Radaeva S, Mrozek M,
In summary, this study described the two patients with Zillmann U, Kopp-Schneider A, Haberkorn U, Elgas M, Tolle T,
Roggendorf M, Toshkov I. Synergistic hepatocarcinogenic effect
HCC and T2DM, both of whom experienced marked of hepadnaviral infection and dietary aflatoxin B1 in woodchucks.
changes in glycogen content in HCC tissues and Cancer Res 1995;55:3318-30.
background liver parenchyma. These studies in larger 10. Altmann HW. Hepatic neoformations. Pathol Res Pract 1994;190:513-
77.
numbers of patients are needed to clarify a possible 11. Su Q, Benner A, Hofmann WJ, Otto G, Pichlmayr R, Bannasch P.
relationship between the changes in hepatocellular Human hepatic preneoplasia: phenotypes and proliferation kinetics of
glycogen content and the development of HCC in foci and nodules of altered hepatocytes and their relationship to liver
cell dysplasia. Virchows Arch 1997;431:391-406.
diabetic patients with steatohepatitis. 12. Buchanan TF, Huvos AG. Clear-cell carcinoma of the liver. A
clinicopathologic study of 13 patients. Am J Clin Pathol 1974;61:529-
Financial support and sponsorship 39.
Nil. 13. Shi Y, Wu H, Wu W, Zhang WJ, Yang J, Chen Z. Association between
occult hepatitis B infection and the risk of hepatocellular carcinoma: a
meta-analysis. Liver Int 2012;32:231-40.
Conflicts of interest 14. Bannasch P. Glycogenotic hepatocellular carcinoma with glycogen-
There are no conflicts of interest. ground-glass hepatocytes: a heuristically highly relevant phenotype.
World J Gastroenterol 2012;18:6701-8.
15. Ribback S, Calvisi DF, Cigliano A, Sailer V, Peters M, Rausch J,
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