Volume 2, Issue 4 | July 2015
Case Report | Pediatrics

Mesenchymal Hamartoma of the Liver in an Infant With Beckwith-Wiedemann Syndrome: A Rare Condition Mimicking Hepatoblastoma

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Lucas F. Abrahao-Machado, MD1,2, Fabiane C. de Macedo, MD2,3, Carlos Dalence, MD4, Glenn Stambo, MD5, Eduarda F. Abrahao-Machado, MD6, Elaine C.F. Abrahao-Machado, MD7, Armita Bahrami, MD2, and Antonio G. Nascimento, MD2

1Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
2Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
3Department of Pathology, Hospital Federal de Ipanema, Rio de Janeiro, Brazil
4Department of Pathology, St. Joseph’s Hospital, Tampa, FL
5Department of Radiology, St. Joseph’s Hospital, Tampa, FL
6Jundiai Medical College, Jundiai, São Paulo, Brazil
7Catholic University of Campinas, Campinas, São Paulo, Brazil

ACG Case Rep J 2015;2(4):258-260. http://dx.doi.org/10.14309/crj.2015.78. Published: July 9, 2015.

Abstract

Patients with Beckwith-Wiedemann syndrome (BWS) are known to be at an increased risk for childhood malignancies, particularly Wilms tumor and hepatoblastoma. We report a case of genetically confirmed BWS in a 5-month-old girl who presented with a 9.5-cm abdominal mass associated with elevated α-fetoprotein levels. The clinical impression was strongly suggestive of hepatoblastoma. Histologic examination of the surgically excised mass revealed mesenchymal hamartoma of the liver (MHL), a benign hepatic neoplasm.


Introduction

Beckwith-Wiedemann syndrome (BWS) is a heterogeneous condition classified as an overgrowth syndrome and is characterized by macrosomia, macroglossia, abdominal wall defects, hemihypertrophy, and ear anomalies.1-5 Children with BWS have an increased risk for embryonic tumors, mainly Wilms tumor and hepatoblastoma.1,6,7


Case Report

A 5-month-old female infant with known Beckwith-Wiedemann syndrome (BWS) was admitted following episodes of diarrhea and the discovery of an abdominal mass. The patient was born through an uneventful spontaneous vaginal delivery at 34 weeks of gestation, with a birth weight of 3,275 g (>97th percentile). Early in the postnatal period, the patient manifested hemihypertrophy, omphalocele, a “dimple” on the right ear lobe, capillary hemangioma, and persistent hypoglycemia; methylation analysis confirmed BWS.4,5 Serum α-fetoprotein (AFP) level was elevated at 814.3 ng/mL. Abdominal ultrasound (US) confirmed a large heterogeneous mass in the upper abdomen, displacing regional structures. Computed tomography (CT) and magnetic resonance imaging (MRI) suggested that the mass originated from the liver, measuring 8.8 x 8.4 x 7.7 cm (Figure 1). These clinical and laboratory findings suggested the mass was a hepatoblastoma.

Abrahao-Figure-1

Figure 1. Abdominal magnetic resonance imaging (T2) demonstrates a large mass in the anterior upper abdomen.

Exploratory laparotomy and excision of the abdominal mass found a 268-g, 9.5 x 7.0 x 5.0-cm well-circumscribed cystic mass with a smooth, pink-tan and glistening external surface (Figure 2). On sectioning, the mass was predominantly cystic with a variegated red to white-tan gelatinous cut surface containing multiloculated cystic and lobulated solid areas (Figure 2).

Abrahao-Figure-2-comp

Figure 2. The mass shows (A) a smooth and glistening external surface, and (B) a multiloculated cystic and solid appearance on cut section.

The tumor was predominantly composed of a mesenchymal component with a vaguely lobulated and myxoid appearance, containing stellate fibroblasts and thin-walled blood vessels. Within the loose mesenchymal tissue, particularly at the periphery of the lesion, there were entrapped cords of hepatocytes (Figure 3). Atypical epithelial elements were not present, and no heterologous differentiation was seen in the mesenchymal component. Small foci of extramedullary hematopoiesis were present within the tumor (Figure 4).

Abrahao-Figure-3-comp

Figure 3. (A) Entrapped cords of immature hepatocytes in a myxoid stroma (100x). (B) A group of small hepatocytes in detail within the loose myxomatous stroma.

Abrahao-Figure-4-comp

Figure 4. (A) The mesenchymal component composed of bland spindled to stellate cells at high magnification. (B) Foci of extramedullary hematopoiesis.


Discussion

Children with BWS are at a 7.5–10% risk of developing several types of tumors, mainly embryonic malignancies that vary based on the genetic alterations involved.1,6,7 The most common tumors seen in these patients are Wilms tumor and hepatoblastoma, and less frequently, rhabdomyosarcoma, adrenal cortical carcinoma, and neuroblastoma.6-8 The majority of the tumors occurs before age 4 years and only rarely develop after the first decade of life.1 With positive findings, focused investigation for an underlying tumor should be undertaken in consultation with a pediatric oncologist.1 AFP can be measured periodically to age 4 years for early detection of hepatoblastoma.7,9

The association between BWS and benign hamartomatous tumors is rare,3,10 and there are only 2 other cases of MHL in patients with BWS previously described in the literature, neither of which had a confirmed diagnosis of BWS by molecular analysis.11,12 Of note, one of the reported cases did not meet all the clinical diagnostic criteria for the syndrome.

MHL is an uncommon tumor, accounting for just 6% of pediatric liver tumors.13 It presents with an upper abdominal mass or abdominal swelling that varies in size from a few centimeters to up to 30 cm.14 There is no specific laboratory marker for MHL. Serum AFP levels can be elevated, but other liver function tests usually remain normal.13,15,16 Although the serum AFP in patients with BWS may be higher than in normal children, the serum level in our patient was beyond the expected baseline range in these patients, causing concern for hepatoblastoma.1,3 On imaging studies, MHL often appears as a nonspecific heterogeneous solid-cystic tumor that may be mistaken for hepatoblastoma, particularly when cysts are absent.16-18 The characteristic histopathological features consist of mesenchymal and epithelial (hepatocytes) components without atypia.14 However, if the groups of hepatocytes are abundant and large in size, MHL may resemble other tumors (such as hepatoblastoma), particularly in small biopsies.18 Hence, a generous sample of the tumoral tissue is essential for the correct diagnosis. MHL is a benign tumor with excellent outcome following surgery, and malignant transformation in MHL is rare.13,19

It is not clear whether patients with BWS are more likely to develop MHL compared to healthy children. The molecular characteristics of BWS, mainly alterations involving 11p15 chromosomal region, do not seem to be related to cytogenetic abnormalities of MHL.20,21 Although the presence of a liver mass in children with BWS with a high serum AFP should be concerning for hepatoblastoma, other tumors of the liver including MHL should be considered in the differential diagnosis in such patients. Tissue diagnosis, therefore, is mandatory for proper management plan, even in the presence of high clinical suspicion for a malignant process.


Disclosures

Author contributions: LF Abrahao-Machado participated in the histopathological analysis, developed and led the overall manuscript, and is the article guarantor. FC de Macedo assisted with the histopathological analysis and manuscript preparation. C. Dalence assisted with clinical diagnosis and pathological analysis and provided clinical data. G. Stambo provided the radiological images. EF Abrahao-Machado, ECF Abrahao-Machado, and A. Bahrami revised the manuscript. A. Nascimento is the senior author and participated in the histopathological diagnosis.

Financial disclosure: None to report.

Informed consent was obtained for this case report.

Correspondence: Lucas F. Abrahao-Machado, Rua Antenor Duarte Villela, 1331, Barretos, 14784-400, São Paulo, Brazil (lucasfariamachado@yahoo.com).

Received: February 11, 2015; Accepted: April 30, 2015


References

  1. Weksberg R, Shuman C, Beckwith JB. Beckwith-Wiedemann syndrome. Eur J Hum Genet. 2010;18(1):8–14. Article | PubMed
  2. Elliott M, Bayly R, Cole T, et al. Clinical features and natural history of Beckwith-Wiedemann syndrome: Presentation of 74 new cases. Clin Genet. 1994;46(2):168–74. Article | PubMed
  3. Cohen MM, Jr. Beckwith-Wiedemann syndrome: Historical, clinicopathological, and etiopathogenetic perspectives. Pediatr Dev Pathol. 2005;8(3):287–304. ArticlePubMed
  4. Milani D, Pezzani L, Tabano S, Miozzo M. Beckwith-Wiedemann and IMAGe syndromes: Two very different diseases caused by mutations on the same gene. Appl Clin Genet. 2014;7:169–75. ArticlePubMed
  5. Soejima H, Higashimoto K. Epigenetic and genetic alterations of the imprinting disorder Beckwith-Wiedemann syndrome and related disorders. J Hum Genet. 2013;58(7):402–9. Article | PubMed
  6. Rump P, Zeegers MP, van Essen AJ. Tumor risk in Beckwith-Wiedemann syndrome: A review and meta-analysis. Am J Med. 2005;136(1):95–104. Article | PubMed
  7. Santiago J, Muszlak M, Samson C, et al. Malignancy risk and Wiedemann-Beckwith syndrome: What follow-up to provide? [Article in French]. Arch Pediatr. 2008;15(9):1498–502. Article | PubMed
  8. Trobaugh-Lotrario AD, Venkatramani R, Feusner JH. Hepatoblastoma in children with Beckwith-Wiedemann syndrome: Does it warrant different treatment? J Pediatr Hematol Oncol. 2014;36(5):369–73. Article | PubMed
  9. Tan TY, Amor DJ. Tumour surveillance in Beckwith-Wiedemann syndrome and hemihyperplasia: A critical review of the evidence and suggested guidelines for local practice. J Paediatr Child Health. 2006;42(9):486–90. Article | PubMed
  10. Cardinalli IA, de Oliveira-Filho AG, Mastellaro MJ, et al. A unique case of synchronous functional adrenocortical adenoma and myelolipoma within the ectopic adrenal cortex in a child with Beckwith-Wiedemann syndrome. Pathol Res Pract. 2012;208(3):189–94. Article | PubMed
  11. Cajaiba MM, Sarita-Reyes C, Zambrano E, Reyes-Mugica M. Mesenchymal hamartoma of the liver associated with features of Beckwith-Wiedemann syndrome and high serum alpha-fetoprotein levels. Pediatr Dev Pathol. 2007;10(3):233–8. ArticlePubMed
  12. Garcia de la Torre J, Sotelo-Rodriguez M, Santos-Briz A, et al. Mesenchymal hamartoma of the liver in Beckwith-Wiedemann syndrome: The first reported case. Pediatr Pathol Molec Med. 2000;19(6):455–60. Article
  13. Stringer MD, Alizai NK. Mesenchymal hamartoma of the liver: A systematic review. J Pediatr Surg. 2005;40(11):1681–90. Article | PubMed
  14. Ishak KG, Goodman ZD, Stocker JT. Tumors of the Liver and Intrahepatic Bile Ducts. Washington, DC: Armed Forces Institute of Pathology; 2001:356.
  15. Bertino G, Ardiri A, Demma S, et al. Rare benign tumors of the liver: Still rare? J Gastrointest Cancer. 2014;45(2):202–17. Article | PubMed
  16. Harman M, Nart D, Acar T, Elmas N. Primary mesenchymal liver tumors: radiological spectrum, differential diagnosis, and pathologic correlation. Abdom Imaging. Published online ahead of print October 14, 2014. Article | PubMed
  17. Qian LJ, Zhu J, Zhuang ZG, et al. Spectrum of multilocular cystic hepatic lesions: CT and MR imaging findings with pathologic correlation. Radiographics. 2013;33(5):1419–33. Article | PubMed
  18. Wildhaber BE, Montaruli E, Guérin F, et al. Mesenchymal hamartoma or embryonal sarcoma of the liver in childhood: A difficult diagnosis before complete surgical excision. J Pediatr Surg. 2014;49(9):1372–7. Article | PubMed
  19. O’Sullivan MJ, Swanson PE, Knoll J, et al. Undifferentiated embryonal sarcoma with unusual features arising within mesenchymal hamartoma of the liver: Report of a case and review of the literature. Pediatr Dev Pathol. 2001;4(5):482–9. PubMed
  20. Rakheja D, Margraf LR, Tomlinson GE, et al. Hepatic mesenchymal hamartoma with translocation involving chromosome band 19q13.4: A recurrent abnormality. Cancer Genet Cytogenet. 2004;153(1):60–3. Article | PubMed
  21. Mathews J, Duncavage EJ, Pfeifer JD. Characterization of translocations in mesenchymal hamartoma and undifferentiated embryonal sarcoma of the liver. Exp Mol Pathol. 2013;95(3):319–24. Article | PubMed

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© 2015 Abrahao-Machado et al. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0.