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Mesenchymal hamartoma of the liver
Hepatology Research 28 (2004) 216–219
Mesenchymal hamartoma of the liver Clinicopathological, immunohistochemical and flow cytometric study of two cases Ihab Abdulkader a,∗ , Máximo Fraga a , Eugenio Pérez-Becerra a , Rosa M. Reyes-Sant´ıas a , Adolfo Bautista b , Elizabeth Chaves a , Jerónimo Forteza a a
Department of Pathology, Hospital Cl´ınico Universitario, C/Choupana s/n, Santiago de Compostela, Spain b Department of Pediatric Surgery, Hospital Cl´ınico Universitario, Santiago de Compostela, Spain Received 19 June 2003; received in revised form 16 November 2003; accepted 20 November 2003
Abstract Mesenchymal hamartoma (MH) is a rare liver lesion of infancy. Due to its rapid increase in size, it is often misdiagnosed clinically as a malignant tumour or as a hepatic cyst because of its cystic appearance. We present the clinicopathological, immunohistochemical and flow cytometric features of two cases, involving an 11-month-old boy and a 13-month-old girl. In both cases, the histological appearance and the immunohistochemical findings were identical. Bile ducts and blood vessels showed the expected immunohistochemical profile, whereas the mesenchymal component showed immunoreactivity not only for vimentin but also for muscular markers. Flow cytometry disclosed an aneuploid population in one case, thus favouring the interpretation of MH as a neoplastic lesion. Unlike the characteristically continuous and rapid growth of MH before or shortly after birth, these two cases showed low proliferative and apoptotic indexes and a high immunohistochemical expression of bcl-2 protein. This prompted us to hypothesize that MH might undergo a brief initial proliferative phase, but the cells would later become ‘immortalized’ by bcl-2 overexpression. © 2003 Elsevier B.V. All rights reserved. Keywords: Mesenchymal hamartoma; Liver; Immunohistochemistry; Flow cytometry
1. Introduction
2. Case report
Hepatic neoplasms account for only 1–4% of solid tumours in children, and are generally consist of hepatoblastomas, hepatocellular carcinomas and infantile hemangioendothelioma [17]. Mesenchymal hamartoma (HM) of the liver is a rare disease that makes up about 5–8% of primitive hepatic tumours in children [2,7,17]. It is a benign lesion that presents mostly before the age of 2 years [17]. We report the clinicopathological, immunohistochemical and flow cytometric features of two cases and review the literature on this unusual entity.
2.1. Case 1
∗
Corresponding author. Tel.: +34-981-950854; fax:+34-981-950889. E-mail address: [email protected] (I. Abdulkader).
1386-6346/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.hepres.2003.11.007
Involves an 11-month-old boy who was admitted because of enlargement of the abdominal perimeter. Abdominal ultrasonography showed a large multicystic mass in the right lobe. The intravenous contrast-enhanced computed tomography scan (CT) demonstrated a well defined, multicystic and hypodense lesion with peripheral enhancement. The alfa-fetoprotein (AFP) level was 49.3 ng/ml, alfa-1-antitrypsin 256 mg/dl. The serological test results for echinococcus, cytomegalovirus, HIV, and hepatitis were negative. The lesion was completely resected by right hemihepatectomy. The surgical specimen measured 21 cm × 14 cm × 7 cm, and weighed 640 g. The cut surface showed a predominantly unilocular cyst with a few small locules that were filled with yellow gelatinous material and surrounded by a fibrous capsule and brown to yellow solid
I. Abdulkader et al. / Hepatology Research 28 (2004) 216–219
217
Fig. 1. (A) CT scan with the large cystic mass in the hepatic lobe. (B) A section of the mesenchymal hamartoma showing multiple cysts of varied size.
parts. Ten years later, this boy still remains in complete remission. 2.2. Case 2 Involves a 13-month-old girl presenting a large mass in the left liver lobe containing multiple cysts. The CT showed a 13-cm × 12-cm multicystic lesion arising from the left lateral segment of the liver (Fig. 1A). The kidneys appeared normal. Tumour markers were negative. The patient underwent a partial resection of the left lateral segment. The tumour measured 11 cm×8 cm×4 cm, weighed 240 g. The cut surface showed multiple, variable-sized cysts with a smooth lining, as well as solid tan-brown tissue (Fig. 1B). The cysts were filled with clear amber to yellow fluid/gelatinous material. Four months after resection, physical examination, chest radiography, and CT of the abdomen reveal no evidence of disease.
In both cases, the histological appearance and immunohistochemical profile were identical. The tumours consisted of a mixture of mesenchyma, bile ducts, hepatocyte strands, and variable-sized cysts (Fig. 2A). Their overall appearance was very similar to mammary fibroadenoma (Fig. 2B) [16]. Immunohistochemical studies were performed on formalinfixed, paraffin-embedded tissue sections. The Envision Plus method (Dako Glostrup, Denmark) for immunostaining was employed in a capillary gap-based automatic immunostainer (Tech-Mate). Non-immune mouse and rabbit serum samples were substituted for the primary antibodies as negative controls. The mesenchymal component was positive for vimentin (V9, Concepta Biosystems, Barcelona, Spain) and the following muscular markers: smooth-muscle actin (1A4, BioGenex, San Ramon, CA), actin (HHF35, Enzo, Farmingdale, NY) and desmin (DE-R-11, Dako). The bile ducts were positive for broad-spectrum cytokeratins (AE1AE3, Concepta Biosystem), CAM5.2 (cytokeratins 8 and
Fig. 2. (A) Low-power view shows the admixture of ducts, cysts, vessels, irregular liver cell plates and mesenchymal stroma (H&E, X50). (B) Combination of collapsed ducts and abundant fibromatous stroma (H&E, X100). (C) Positive nuclear staining for the Ki-67 in scattered cells (MIB-1, X200). (D) Bcl-2 immunostaining in mesenchymal and epithelial cells (Bcl-2, X200).
218
I. Abdulkader et al. / Hepatology Research 28 (2004) 216–219
18, Becton Dickinson, Mountainview, CA) and cytokeratin 7 (OV-TL 12/30, Dako). The vascular component of the lesion was stained by Factor VIII-related marker (F8/86, Dako) and CD34 (QBEnd/10, BioGenex). Proliferation index Ki67 (MIB1, Immunotech, Marseille, France) was low in both the mesenchymal and the epithelial component of the lesion (Fig. 2C). On the other hand, bcl-2 (124, Dako) immunoreactivity was widespread in both populations (Fig. 2D). There was no immunoreactivity for p53 protein (DO-7, Dako). TUNEL based methodology (ApopTag Peroxidase In Situ Apoptosis Detection Kit, Intergen, Oxford, UK) was employed for the detection of apoptosis. The apoptotic index was very low in the two cases. Flow cytometric analysis was performed, using a Facs Calibur flow cytometer (BectonDickinson, San Jose, CA), on paraffin embedded material in case 1 and frozen tissue in case 2. An aneuploid population (index: 1.35) was disclosed in the first case and a diploid population in the second. S-phase fractions were low in both cases (2.86 and 3.65%, respectively).
This could lead to the speculation that the initial growth of the lesions is not as dependent on cell proliferation as it is on the enlargement of cystic spaces due to secretion-fluid accumulation. In line with this, MH might undergo a brief initial proliferative phase, but, more importantly, the cells would later become ‘immortalized’ by bcl-2 overexpression. In fact, TUNEL technique showed a very low apoptotic index. The prolonged survival of the cells could increase the possibility of additional genetic mutations, and might explain the reported malignant transformation of MH. The treatment of choice remains surgical resection, although the large size of the lesion and the involvement of vital structures may sometimes make complete excision difficult or impossible [17]. A few authors even indicate that these lesions may undergo spontaneous regression [2,20] and, consequently, they propose nonoperative management of the asymptomatic mass. Nevertheless, the possibility of malignant transformation of MH suggests that complete resection should be performed whenever possible [9,15]
3. Discussion
Acknowledgements
Mesenchymal hamartoma of the liver is an uncommon benign lesion that is usually diagnosed during the first 2 years of life, although some cases have also been reported in adults [6,14]. Patients present with enlarged abdomen and are usually asymptomatic. On rare occassions there may be symptoms related to compression of other organs [1,4,5,18]. Abdominal ultrasound, computed tomography and magnetic resonance play a key role in preoperative diagnosis since they reveal the well-defined circumscription of the tumour and its characteristic multicystic nature [5,8,19]. The definitive diagnosis by histopathological examination is usually straightforward because of the typical microscopical features of the tumour [1]. The pathophysiology of the development of this hamartoma is, as yet, unknown. The question of whether this is a true neoplasm or is, instead, the result of a developmental anomaly, a reaction to biliary obstruction, or even the result of a regional ischemic process is still the subject of debate [10,12,18]. A neoplastic process, however, is suggested by recent reports of the balanced translocation between chromosomes 11 and 19 with a breakpoint at 19q13.4 [3,11]. Like some other authors, we have detected DNA aneuploidy in one case [7,13]; this finding also supports the suggestion that MH is a true neoplasm rather than a developmental anomaly. With respect to histogenesis, the immunoreactivity in our cases for myogenic markers suggests that Ito cells could be involved in the development of MH, as previously reported by von Schweinitz [20]. Unlike the characteristically continuous and rapid growth of these lesions before or shortly after birth, we found a low proliferative index (MIB-1, low S-phase fraction) in both epithelial and mesenchymal components. In contrast there was a high expression of the anti-apoptotic protein bcl-2.
We thank Ms. I. Fernandez Campos and Mr. A. VázquezBoquete for excellent technical assistance.
References [1] Balmer B, Coultre CL, Feldges A, Hanimann B. Mesenchymal liver hamartoma in a newbron; case report. Eur J Pediatr Surg 1996;6:303– 5. [2] Barnhart DC, Hirschl RB, Garver KA, Geiger JD, Harmon CM, Coran AG. Conservative management of mesenchymal Hamartoma of the liver. J Pediatr Surg 1997;32:1495–8. [3] Bove KE, Blough RI, Soukup S. Third report of t(19q)(13.4) in mesenchymal hamartoma of the liver with comments on link to embryonal sarcoma. Pediatr Dev Pathol 1998;1:438–42. [4] De Maioribus CA, Lally KP, Sim K, Isaacs H, Mahour G. Mesenchymal hamartoma of the liver. A 35-year review. Arch Surg 1990;125:598–600. [5] Donovan AT, Wolverson MK, De Mello D, Craddock T, Silberstein M. Multicystic hepatic mesenchymal hamartoma of childhood. Computerized tomography and ultrasound characteristics. Pediatr Radiol 1981;11:163–5. [6] Drachenberg CB, Papadimitriou JC, Rivero MA, Wood C. Distinctive case. Adult mesenchymal hamartoma of the liver: report of a case with light microscopic, FNA cytology, immunohistochemistry and ultrastructural studies and review of the literature. Modern Pathol 1991;4:392–5. [7] Justrabo E, Martin L, Yaziji N, Couillault JP, Gounot E, Olsson NO. Hepatic mesenchymal hamartoma in children. Immunohistochemical, ultrastructural and flow cytometric case study. Gastroentol Clin Biol 1998;22:964–8. [8] Koumanidou C, Vakaki M, Papadaki M, Pitsoulakis G, Savvidou D, Kakavakis K. New sonographic appearance of hepatic mesenchymal hamartoma in chilhood. J Clin Ultrasound 1999;27:164– 7. [9] Lauwers GY, Grant LD, Donelly WH, Meloni AM, Foss RM, Sanberg AA. Hepatic undifferentiated (embryonal) sarcoma arising in a mesenchymal hamartoma. Am J Surg Pathol 1997;21:1248– 54.
I. Abdulkader et al. / Hepatology Research 28 (2004) 216–219 [10] Lennington WJ, Gary GF, Page DL. Mesenchymal hamartoma of the liver: a regional ischemic lesion of a sequestred lobe. Am J Dis Child 1993;147:193–6. [11] Mascarello JT, Krous HF. Second report of a translocation involving 19q13.4 in a mesenchymal hamartoma of the liver. Cancer Genet Cytogenet 1992;58:141–2. [12] Okeda R. Mesenchymal hamartoma of the liver: an autopsy case with serial section and some comments on its pathogenesis. Acta Pathol Jpn 1976;26:229–36. [13] Otal TM, Hendricks JB, Pharis B, Donnelly WH. Mesenchymal hamartoma of the liver. Cancer 1994;74:1237–42. [14] Papastratis G, Margaris H, Zografos GN, Korkolis D, Mannika Z. Mesenchymal hamartoma of the liver in an adult: a review of the literature. Int J Clin Pract 2000;54:552–4. [15] Ramanujam TM, Ramesh JC, Goh DW, Wong KT, Ariffin WA, Kumar G. Malignant transformation of mesenchymal hamartoma of
[16]
[17] [18]
[19]
[20]
219
the liver: case report an review of the literature. J Pediatr Surg 1999;34:1684–6. Rosai J, Mesenchymal tumors and tumorlike conditions. In: Rosai J, editor. Ackerman’s surgical pathology. 8th ed. St. Louis: Mosby; 1996. p. 915–21. Stocker JT. Hepatic tumor in children. Clin Liver Dis 2001;5:259–81. Stocker JT, Ishak KG. Mesenchymal hamartoma of the liver: report of 30 cases and review of the literature. Pediatr Pathol 1983;1:245– 67. Vandendriessche L, Bonhomme A, Breysem L, Smet MH, Uyttebroeck A, Brock P. Mesenchymal hamartoma: radiological differentiation from other possible liver tumors in childhood. J Belge Radiol 1996;79:74–5. von Schweinitz D, Dammeier BG, Glüer S. Mesenchymal hamartoma of the liver—new insight into histogenesis. J Pediatr Surg 1999;34:1269–71.
Mesenchymal hamartoma of the liver Clinicopathological, immunohistochemical and flow cytometric study of two cases Ihab Abdulkader a,∗ , Máximo Fraga a , Eugenio Pérez-Becerra a , Rosa M. Reyes-Sant´ıas a , Adolfo Bautista b , Elizabeth Chaves a , Jerónimo Forteza a a
Department of Pathology, Hospital Cl´ınico Universitario, C/Choupana s/n, Santiago de Compostela, Spain b Department of Pediatric Surgery, Hospital Cl´ınico Universitario, Santiago de Compostela, Spain Received 19 June 2003; received in revised form 16 November 2003; accepted 20 November 2003
Abstract Mesenchymal hamartoma (MH) is a rare liver lesion of infancy. Due to its rapid increase in size, it is often misdiagnosed clinically as a malignant tumour or as a hepatic cyst because of its cystic appearance. We present the clinicopathological, immunohistochemical and flow cytometric features of two cases, involving an 11-month-old boy and a 13-month-old girl. In both cases, the histological appearance and the immunohistochemical findings were identical. Bile ducts and blood vessels showed the expected immunohistochemical profile, whereas the mesenchymal component showed immunoreactivity not only for vimentin but also for muscular markers. Flow cytometry disclosed an aneuploid population in one case, thus favouring the interpretation of MH as a neoplastic lesion. Unlike the characteristically continuous and rapid growth of MH before or shortly after birth, these two cases showed low proliferative and apoptotic indexes and a high immunohistochemical expression of bcl-2 protein. This prompted us to hypothesize that MH might undergo a brief initial proliferative phase, but the cells would later become ‘immortalized’ by bcl-2 overexpression. © 2003 Elsevier B.V. All rights reserved. Keywords: Mesenchymal hamartoma; Liver; Immunohistochemistry; Flow cytometry
1. Introduction
2. Case report
Hepatic neoplasms account for only 1–4% of solid tumours in children, and are generally consist of hepatoblastomas, hepatocellular carcinomas and infantile hemangioendothelioma [17]. Mesenchymal hamartoma (HM) of the liver is a rare disease that makes up about 5–8% of primitive hepatic tumours in children [2,7,17]. It is a benign lesion that presents mostly before the age of 2 years [17]. We report the clinicopathological, immunohistochemical and flow cytometric features of two cases and review the literature on this unusual entity.
2.1. Case 1
∗
Corresponding author. Tel.: +34-981-950854; fax:+34-981-950889. E-mail address: [email protected] (I. Abdulkader).
1386-6346/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.hepres.2003.11.007
Involves an 11-month-old boy who was admitted because of enlargement of the abdominal perimeter. Abdominal ultrasonography showed a large multicystic mass in the right lobe. The intravenous contrast-enhanced computed tomography scan (CT) demonstrated a well defined, multicystic and hypodense lesion with peripheral enhancement. The alfa-fetoprotein (AFP) level was 49.3 ng/ml, alfa-1-antitrypsin 256 mg/dl. The serological test results for echinococcus, cytomegalovirus, HIV, and hepatitis were negative. The lesion was completely resected by right hemihepatectomy. The surgical specimen measured 21 cm × 14 cm × 7 cm, and weighed 640 g. The cut surface showed a predominantly unilocular cyst with a few small locules that were filled with yellow gelatinous material and surrounded by a fibrous capsule and brown to yellow solid
I. Abdulkader et al. / Hepatology Research 28 (2004) 216–219
217
Fig. 1. (A) CT scan with the large cystic mass in the hepatic lobe. (B) A section of the mesenchymal hamartoma showing multiple cysts of varied size.
parts. Ten years later, this boy still remains in complete remission. 2.2. Case 2 Involves a 13-month-old girl presenting a large mass in the left liver lobe containing multiple cysts. The CT showed a 13-cm × 12-cm multicystic lesion arising from the left lateral segment of the liver (Fig. 1A). The kidneys appeared normal. Tumour markers were negative. The patient underwent a partial resection of the left lateral segment. The tumour measured 11 cm×8 cm×4 cm, weighed 240 g. The cut surface showed multiple, variable-sized cysts with a smooth lining, as well as solid tan-brown tissue (Fig. 1B). The cysts were filled with clear amber to yellow fluid/gelatinous material. Four months after resection, physical examination, chest radiography, and CT of the abdomen reveal no evidence of disease.
In both cases, the histological appearance and immunohistochemical profile were identical. The tumours consisted of a mixture of mesenchyma, bile ducts, hepatocyte strands, and variable-sized cysts (Fig. 2A). Their overall appearance was very similar to mammary fibroadenoma (Fig. 2B) [16]. Immunohistochemical studies were performed on formalinfixed, paraffin-embedded tissue sections. The Envision Plus method (Dako Glostrup, Denmark) for immunostaining was employed in a capillary gap-based automatic immunostainer (Tech-Mate). Non-immune mouse and rabbit serum samples were substituted for the primary antibodies as negative controls. The mesenchymal component was positive for vimentin (V9, Concepta Biosystems, Barcelona, Spain) and the following muscular markers: smooth-muscle actin (1A4, BioGenex, San Ramon, CA), actin (HHF35, Enzo, Farmingdale, NY) and desmin (DE-R-11, Dako). The bile ducts were positive for broad-spectrum cytokeratins (AE1AE3, Concepta Biosystem), CAM5.2 (cytokeratins 8 and
Fig. 2. (A) Low-power view shows the admixture of ducts, cysts, vessels, irregular liver cell plates and mesenchymal stroma (H&E, X50). (B) Combination of collapsed ducts and abundant fibromatous stroma (H&E, X100). (C) Positive nuclear staining for the Ki-67 in scattered cells (MIB-1, X200). (D) Bcl-2 immunostaining in mesenchymal and epithelial cells (Bcl-2, X200).
218
I. Abdulkader et al. / Hepatology Research 28 (2004) 216–219
18, Becton Dickinson, Mountainview, CA) and cytokeratin 7 (OV-TL 12/30, Dako). The vascular component of the lesion was stained by Factor VIII-related marker (F8/86, Dako) and CD34 (QBEnd/10, BioGenex). Proliferation index Ki67 (MIB1, Immunotech, Marseille, France) was low in both the mesenchymal and the epithelial component of the lesion (Fig. 2C). On the other hand, bcl-2 (124, Dako) immunoreactivity was widespread in both populations (Fig. 2D). There was no immunoreactivity for p53 protein (DO-7, Dako). TUNEL based methodology (ApopTag Peroxidase In Situ Apoptosis Detection Kit, Intergen, Oxford, UK) was employed for the detection of apoptosis. The apoptotic index was very low in the two cases. Flow cytometric analysis was performed, using a Facs Calibur flow cytometer (BectonDickinson, San Jose, CA), on paraffin embedded material in case 1 and frozen tissue in case 2. An aneuploid population (index: 1.35) was disclosed in the first case and a diploid population in the second. S-phase fractions were low in both cases (2.86 and 3.65%, respectively).
This could lead to the speculation that the initial growth of the lesions is not as dependent on cell proliferation as it is on the enlargement of cystic spaces due to secretion-fluid accumulation. In line with this, MH might undergo a brief initial proliferative phase, but, more importantly, the cells would later become ‘immortalized’ by bcl-2 overexpression. In fact, TUNEL technique showed a very low apoptotic index. The prolonged survival of the cells could increase the possibility of additional genetic mutations, and might explain the reported malignant transformation of MH. The treatment of choice remains surgical resection, although the large size of the lesion and the involvement of vital structures may sometimes make complete excision difficult or impossible [17]. A few authors even indicate that these lesions may undergo spontaneous regression [2,20] and, consequently, they propose nonoperative management of the asymptomatic mass. Nevertheless, the possibility of malignant transformation of MH suggests that complete resection should be performed whenever possible [9,15]
3. Discussion
Acknowledgements
Mesenchymal hamartoma of the liver is an uncommon benign lesion that is usually diagnosed during the first 2 years of life, although some cases have also been reported in adults [6,14]. Patients present with enlarged abdomen and are usually asymptomatic. On rare occassions there may be symptoms related to compression of other organs [1,4,5,18]. Abdominal ultrasound, computed tomography and magnetic resonance play a key role in preoperative diagnosis since they reveal the well-defined circumscription of the tumour and its characteristic multicystic nature [5,8,19]. The definitive diagnosis by histopathological examination is usually straightforward because of the typical microscopical features of the tumour [1]. The pathophysiology of the development of this hamartoma is, as yet, unknown. The question of whether this is a true neoplasm or is, instead, the result of a developmental anomaly, a reaction to biliary obstruction, or even the result of a regional ischemic process is still the subject of debate [10,12,18]. A neoplastic process, however, is suggested by recent reports of the balanced translocation between chromosomes 11 and 19 with a breakpoint at 19q13.4 [3,11]. Like some other authors, we have detected DNA aneuploidy in one case [7,13]; this finding also supports the suggestion that MH is a true neoplasm rather than a developmental anomaly. With respect to histogenesis, the immunoreactivity in our cases for myogenic markers suggests that Ito cells could be involved in the development of MH, as previously reported by von Schweinitz [20]. Unlike the characteristically continuous and rapid growth of these lesions before or shortly after birth, we found a low proliferative index (MIB-1, low S-phase fraction) in both epithelial and mesenchymal components. In contrast there was a high expression of the anti-apoptotic protein bcl-2.
We thank Ms. I. Fernandez Campos and Mr. A. VázquezBoquete for excellent technical assistance.
References [1] Balmer B, Coultre CL, Feldges A, Hanimann B. Mesenchymal liver hamartoma in a newbron; case report. Eur J Pediatr Surg 1996;6:303– 5. [2] Barnhart DC, Hirschl RB, Garver KA, Geiger JD, Harmon CM, Coran AG. Conservative management of mesenchymal Hamartoma of the liver. J Pediatr Surg 1997;32:1495–8. [3] Bove KE, Blough RI, Soukup S. Third report of t(19q)(13.4) in mesenchymal hamartoma of the liver with comments on link to embryonal sarcoma. Pediatr Dev Pathol 1998;1:438–42. [4] De Maioribus CA, Lally KP, Sim K, Isaacs H, Mahour G. Mesenchymal hamartoma of the liver. A 35-year review. Arch Surg 1990;125:598–600. [5] Donovan AT, Wolverson MK, De Mello D, Craddock T, Silberstein M. Multicystic hepatic mesenchymal hamartoma of childhood. Computerized tomography and ultrasound characteristics. Pediatr Radiol 1981;11:163–5. [6] Drachenberg CB, Papadimitriou JC, Rivero MA, Wood C. Distinctive case. Adult mesenchymal hamartoma of the liver: report of a case with light microscopic, FNA cytology, immunohistochemistry and ultrastructural studies and review of the literature. Modern Pathol 1991;4:392–5. [7] Justrabo E, Martin L, Yaziji N, Couillault JP, Gounot E, Olsson NO. Hepatic mesenchymal hamartoma in children. Immunohistochemical, ultrastructural and flow cytometric case study. Gastroentol Clin Biol 1998;22:964–8. [8] Koumanidou C, Vakaki M, Papadaki M, Pitsoulakis G, Savvidou D, Kakavakis K. New sonographic appearance of hepatic mesenchymal hamartoma in chilhood. J Clin Ultrasound 1999;27:164– 7. [9] Lauwers GY, Grant LD, Donelly WH, Meloni AM, Foss RM, Sanberg AA. Hepatic undifferentiated (embryonal) sarcoma arising in a mesenchymal hamartoma. Am J Surg Pathol 1997;21:1248– 54.
I. Abdulkader et al. / Hepatology Research 28 (2004) 216–219 [10] Lennington WJ, Gary GF, Page DL. Mesenchymal hamartoma of the liver: a regional ischemic lesion of a sequestred lobe. Am J Dis Child 1993;147:193–6. [11] Mascarello JT, Krous HF. Second report of a translocation involving 19q13.4 in a mesenchymal hamartoma of the liver. Cancer Genet Cytogenet 1992;58:141–2. [12] Okeda R. Mesenchymal hamartoma of the liver: an autopsy case with serial section and some comments on its pathogenesis. Acta Pathol Jpn 1976;26:229–36. [13] Otal TM, Hendricks JB, Pharis B, Donnelly WH. Mesenchymal hamartoma of the liver. Cancer 1994;74:1237–42. [14] Papastratis G, Margaris H, Zografos GN, Korkolis D, Mannika Z. Mesenchymal hamartoma of the liver in an adult: a review of the literature. Int J Clin Pract 2000;54:552–4. [15] Ramanujam TM, Ramesh JC, Goh DW, Wong KT, Ariffin WA, Kumar G. Malignant transformation of mesenchymal hamartoma of
[16]
[17] [18]
[19]
[20]
219
the liver: case report an review of the literature. J Pediatr Surg 1999;34:1684–6. Rosai J, Mesenchymal tumors and tumorlike conditions. In: Rosai J, editor. Ackerman’s surgical pathology. 8th ed. St. Louis: Mosby; 1996. p. 915–21. Stocker JT. Hepatic tumor in children. Clin Liver Dis 2001;5:259–81. Stocker JT, Ishak KG. Mesenchymal hamartoma of the liver: report of 30 cases and review of the literature. Pediatr Pathol 1983;1:245– 67. Vandendriessche L, Bonhomme A, Breysem L, Smet MH, Uyttebroeck A, Brock P. Mesenchymal hamartoma: radiological differentiation from other possible liver tumors in childhood. J Belge Radiol 1996;79:74–5. von Schweinitz D, Dammeier BG, Glüer S. Mesenchymal hamartoma of the liver—new insight into histogenesis. J Pediatr Surg 1999;34:1269–71.