Pediatric Mesenchymal Hamartomas of the Liver can Show Both Foregut and Hindgut Phenotype

Abstract

Cystic epithelium in mesenchymal hamartoma (MH) is typically biliary type. Mucinous differentiation of the epithelium and increased hepatocellular component may pose a diagnostic challenge. We studied MH in 7 children (6 M, 1 F; age 4 months to 8 years, median 1 year). Resected tumors varied from 3.0 to 17.0 cm. All tumors showed biliary epithelium in the cystic component with strong and diffuse reactivity for CK7 and CK19. Expression of CK20 and CDX2 was additionally seen in 2 tumors, rare/focal in 1, and diffuse with mucinous differentiation in the other. Strong and continuous nuclear reactivity for Sox9 was seen in the cyst epithelium in all 7 tumors including focal staining in mucinous areas. It was also positive in the hepatocellular component. CD56 and vimentin were variably positive in the cystic epithelium of all cases. Alpha-fetoprotein showed patchy weak staining in the hepatocellular component and was negative in the cystic epithelium. Hepar-1 showed focal staining in the cystic epithelium in 4/7 cases and diffuse in the hepatocellular component. Both patients showing CK20 and CDX2 expression had abnormal chromosomal analysis: one with balanced translocation between chromosomes 2 and 19 and other with loss of chromosome Y. Among others, one showed 46,XY,inv(9)(p11q12), one did not grow cells, and the remaining 3 had normal karyotype. Six patients underwent resection and one had liver transplantation. All were alive and well with a median follow-up of 1.5 years. In conclusion, mucinous epithelium can be seen in MH. Expression of Sox9 in the cyst epithelium and hepatocytes suggests a common origin for these components. Expression of vimentin indicates an overlapping epithelial-mesenchymal phenotype. Hepatic MH can show divergent epithelial differentiation including both foregut and hindgut phenotype, which may provide insights into the pathogenesis of this rare neoplasm but does not seem to affect the outcome in this limited series.

Keywords

mesenchymal hamartoma liver children foregut hindgut mucinous

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References

Motiwale

Karmarkar

Oak

Kalgutkar

Deshmukh

. Cystic mesenchymal hamartoma of the liver—a rare condition. Indian J Cancer 1996; 33(3): 157–160.

Edmondson

. Differential diagnosis of tumors and tumor-like lesions of liver in infancy and childhood. AMA J Dis Child 1956; 91(2): 168–186.

Stringer

Alizai

. Mesenchymal hamartoma of the liver: a systematic review. J Pediatr Surg 2005; 40(11): 1681–1690.

Dehner

Ewing

Sumner

. Infantile mesenchymal hamartoma of the liver. Histologic and ultrastructural observations. Arch Pathol 1975; 99(7): 379–382.

von Schweinitz

Dammeier

Gluer

. Mesenchymal hamartoma of the liver—new insight into histogenesis. J Pediatr Surg 1999; 34(8): 1269–1271.

Yesim

Gupse

Zafer

Ahmet

. Mesenchymal hamartoma of the liver in adulthood: immunohistochemical profiles, clinical and histopathological features in two patients. J Hepatobiliary Pancreat Surg 2005; 12(6): 502–507.

Boman

Bossard

Fabre

Diab

Bonnevalle

Boccon-Gibod

. Mesenchymal hamartomas of the liver may be associated with increased serum alpha foetoprotein concentrations and mimic hepatoblastomas. Eur J Pediatr Surg 2004; 14(1): 63–66.

Barnhart

Hirschl

Garver

Geiger

Harmon

Coran

. Conservative management of mesenchymal hamartoma of the liver. J Pediatr Surg 1997; 32(10): 1495–1498.

Mathews

Duncavage

Pfeifer

. Characterization of translocations in mesenchymal hamartoma and undifferentiated embryonal sarcoma of the liver. Exp Mol Pathol 2013; 95(3): 319–324.

10.

Stocker

Ishak

. Mesenchymal hamartoma of the liver: report of 30 cases and review of the literature. Pediatr Pathol 1983; 1(3): 245–267.

11.

Cook

Pfeifer

Dehner

. Mesenchymal hamartoma of the liver in the adult: association with distinct clinical features and histological changes. Hum Pathol 2002; 33(9): 893–898.

12.

Dooley

Scheuer

Hobbs

Sherlock

. A giant cystic mesenchymal hamartoma of the liver: diagnosis, management, and study of cyst fluid. Gastroenterology 1983; 85(4): 958–961.

13.

Yamamoto

Hagihara

Mogaki

et al.

Adult mesenchymal hamartoma of the liver mimicking bile duct cystadenoma. J Gastroenterol 1994; 29(4): 518–524.

14.

Torbenson

Wang

Abraham

Maitra

Boitnott

. Bile ducts and ductules are positive for CD56 (N-CAM) in most cases of extrahepatic biliary atresia. Am J Surg Pathol 2003; 27(11): 1454–1457.

15.

Van Den Heuvel

Slooff

Visser

et al.

Expression of anti-OV6 antibody and anti-N-CAM antibody along the biliary line of normal and diseased human livers. Hepatology 2001; 33(6): 1387–1393.

16.

Fabris

Strazzabosco

Crosby

et al.

Characterization and isolation of ductular cells coexpressing neural cell adhesion molecule and Bcl-2 from primary cholangiopathies and ductal plate malformations. Am J Pathol 2000; 156(5): 1599–1612.

17.

Aishima

Tanaka

Kubo

Shirabe

Maehara

Oda

. Bile duct adenoma and von Meyenburg complex-like duct arising in hepatitis and cirrhosis: pathogenesis and histological characteristics. Pathol Int 2014; 64(11): 551–559.

18.

Delous

Yin

Shin

et al.

Sox9b is a key regulator of pancreaticobiliary ductal system development. PLoS Genet 2012; 8(6): e1002754.

19.

Alison

Lin

. Hepatocyte turnover and regeneration: virtually a virtuoso performance. Hepatology 2011; 53(4): 1393–1396.

20.

Furuyama

Kawaguchi

Akiyama

et al.

Continuous cell supply from a Sox9-expressing progenitor zone in adult liver, exocrine pancreas and intestine. Nat Genet 2011; 43(1): 34–41.

21.

Chang

Jin

Park

et al.

Mesenchymal hamartomas of the liver: comparison of clinicopathologic features between cystic and solid forms. J Korean Med Sci 2006; 21(1): 63–68.

22.

Leong

Sormunen

Tsui

Liew

. Hep Par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma. Histopathology 1998; 33(4): 318–324.

23.

Shintaku

Watanabe

. Mesenchymal hamartoma of the liver: A proliferative lesion of possible hepatic stellate cell (Ito cell) origin. Pathol Res Pract 2010; 206(7): 532–536.

24.

Chang

Kim

Han

Kim

Lee

. Choledochal cyst rupture with an intrahepatic pseudocyst mimicking hepatic mesenchymal hamartoma in an infant. Clin Imaging 2015; 39(5): 914–916.

25.

Qian

Zhu

Zhuang

Xia

Liu

. Spectrum of multilocular cystic hepatic lesions: CT and MR imaging findings with pathologic correlation. Radiographics 2013; 33(5): 1419–1433.

26.

Jakowski

Lucas

Seth

Frankel

. Ciliated hepatic foregut cyst: a rare but increasingly reported liver cyst. Ann Diagn Pathol 2004; 8(6): 342–346.

27.

Bahador

Geramizadeh

Rezazadehkermani

Moslemi

. Mesenchymal hamartoma mimicking hepatoblastoma. Int J Organ Transplant Med 2014; 5(2): 78–80.

28.

Cajaiba

Sarita-Reyes

Zambrano

Reyes-Múgica

. Mesenchymal hamartoma of the liver associated with features of Beckwith-Wiedemann syndrome and high serum alpha-fetoprotein levels. Pediatr Dev Pathol 2007; 10(3): 233–238.

29.

Unal

Koksal

Akcoren

Tavl

Gunel

Kerimoglu

. Mesenchymal hamartoma of the liver mimicking hepatoblastoma. J Pediatr Hematol Oncol 2008; 30(6): 458–460.

30.

Hadzic

Finegold

. Liver neoplasia in children. Clin Liver Dis 2011; 15(2): 443–462, vii–x.

31.

Rao

Haricharan

Ramanujacharyulu

Reddy

. Tail gut cyst. Indian J Gastroenterol 2002; 21(6): 228–229.

32.

Williams

Rojiani

Quisling

Mickle

. Retrorectal cyst-hamartomas and sacral dysplasia: MR appearance. AJNR Am J Neuroradiol 1998; 19(6): 1043–1045.

33.

Aguirre

Nieto

Lazos

et al.

Extragonadal germ cell tumors are often associated with Klinefelter syndrome. Hum Pathol 2006; 37(4): 477–480.