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1
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Choi JH, Thung SN. Mesenchymal Tumors of the Liver: An Update Review. Biomedicines 2025; 13:479. [PMID: 40002892 PMCID: PMC11852400 DOI: 10.3390/biomedicines13020479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/11/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Hepatic mesenchymal tumors (HMTs) are non-epithelial benign and malignant tumors with or without specific mesenchymal cell differentiation. They are relatively uncommon. Except for mesenchymal hamartoma, calcified nested stromal-epithelial tumor, and embryonal sarcoma, most mesenchymal lesions are not specific to the liver. Pathologists face challenges in diagnosing HMTs due to their diverse morphologies and phenotypic variations. Accurate diagnosis is critical for directing appropriate patient care and predicting outcomes. This review focuses on mesenchymal tumors with a relative predilection for the liver, including vascular and non-vascular mesenchymal neoplasms. It provides a thorough and up-to-date overview, concentrating on clinical and pathological features, differential diagnosis, and diagnostic approaches.
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Affiliation(s)
- Joon Hyuk Choi
- Department of Pathology, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Namgu, Daegu 42415, Republic of Korea
| | - Swan N. Thung
- Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA;
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2
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Lin WY, Wu KH, Chen CY, Guo BC, Chang YJ, Lin MJ, Wu HP. Treatment of Undifferentiated Embryonal Sarcoma of the Liver in Children. Cancers (Basel) 2024; 16:897. [PMID: 38473259 DOI: 10.3390/cancers16050897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 02/15/2024] [Accepted: 02/21/2024] [Indexed: 03/14/2024] Open
Abstract
Undifferentiated embryonal sarcoma of the liver is a rare mesenchymal tumor with a highly malignant potential. It occurs almost exclusively in the pediatric population and typically has a poor outcome. Although previous studies have reported dismal prognoses, recent advances in combined treatment modalities, e.g., surgery and chemotherapy, have given cause for optimism. Even in those diseases not amenable to complete surgical resection or refractory diseases, other treatment modalities, such as liver transplant, have yielded promising results. This paper provides a review of the current treatment modalities for hepatic undifferentiated embryonal sarcoma in children.
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Affiliation(s)
- Wen-Ya Lin
- Department of Pediatrics, Taichung Veterans General Hospital, Taichung 407219, Taiwan
| | - Kang-Hsi Wu
- Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 408, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung 408, Taiwan
| | - Chun-Yu Chen
- Department of Emergency Medicine, Tungs' Taichung Metro Harbor Hospital, Taichung 43503, Taiwan
- Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli 356006, Taiwan
| | - Bei-Cyuan Guo
- Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70142, Taiwan
| | - Yu-Jun Chang
- Laboratory of Epidemiology and Biostastics, Changhua Christian Hospital, Changhua 500, Taiwan
| | - Mao-Jen Lin
- Division of Cardiology, Department of Medicine, Taichung Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, Taichung 427213, Taiwan
- Department of Medicine, College of Medicine, Tzu Chi University, Hualien 97004, Taiwan
| | - Han-Ping Wu
- College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
- Department of Pediatrics, Chiayi Chang Gung Memorial Hospital, Chiayi 613, Taiwan
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3
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Bhagat P, Vij M, Raju LP, Gowrishankar G, Menon J, Shanmugam N, Kaliamoorthy I, Rammohan A, Rela M. Update on the Pathology of Pediatric Liver Tumors: A Pictorial Review. Diagnostics (Basel) 2023; 13:3524. [PMID: 38066766 PMCID: PMC10706829 DOI: 10.3390/diagnostics13233524] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 11/18/2023] [Accepted: 11/20/2023] [Indexed: 01/04/2025] Open
Abstract
Liver tumors in children are uncommon and show remarkable morphologic heterogeneity. Pediatric tumors may arise from either the epithelial or mesenchymal component of the liver and rarely may also show both lines of differentiation. Both benign and malignant liver tumors have been reported in children. The most common pediatric liver tumors by age are benign hepatic infantile hemangiomas in neonates and infants, malignant hepatoblastoma in infants and toddlers, and malignant hepatocellular carcinoma in teenagers. Here, we provide an up-to-date review of pediatric liver tumors. We discuss the clinical presentation, imaging findings, pathology, and relevant molecular features that can help in the correct identification of these tumors, which is important in managing these children.
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Affiliation(s)
- Priyanka Bhagat
- Department of Pathology, Choithram Hospital and Research Center, Manik Bagh Road, Indore 452014, Madhya Pradesh, India;
| | - Mukul Vij
- Department of Pathology, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 600044, Tamil Nadu, India; (L.P.R.); (G.G.)
| | - Lexmi Priya Raju
- Department of Pathology, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 600044, Tamil Nadu, India; (L.P.R.); (G.G.)
| | - Gowripriya Gowrishankar
- Department of Pathology, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 600044, Tamil Nadu, India; (L.P.R.); (G.G.)
| | - Jagadeesh Menon
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 600044, Tamil Nadu, India; (J.M.); (N.S.); (I.K.); (A.R.); (M.R.)
| | - Naresh Shanmugam
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 600044, Tamil Nadu, India; (J.M.); (N.S.); (I.K.); (A.R.); (M.R.)
| | - Ilankumaran Kaliamoorthy
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 600044, Tamil Nadu, India; (J.M.); (N.S.); (I.K.); (A.R.); (M.R.)
| | - Ashwin Rammohan
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 600044, Tamil Nadu, India; (J.M.); (N.S.); (I.K.); (A.R.); (M.R.)
| | - Mohamed Rela
- The Institute of Liver Disease & Transplantation, Dr. Rela Institute & Medical Centre, No. 7 CLC Works Road Chromepet, Chennai 600044, Tamil Nadu, India; (J.M.); (N.S.); (I.K.); (A.R.); (M.R.)
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Berklite L, Malik F, Ranganathan S, Gupta A. Pediatric hepatic vascular tumors: clinicopathologic characteristics of 33 cases and proposed updates to current classification schemes. Hum Pathol 2023; 141:78-89. [PMID: 37277077 DOI: 10.1016/j.humpath.2023.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 05/30/2023] [Accepted: 05/30/2023] [Indexed: 06/07/2023]
Abstract
Pediatric hepatic vascular tumors (HVTs) are rare neoplasms with features distinct from their cutaneous counterparts. Their behavior ranges from benign to malignant, with each subtype having therapeutic differences. Histopathologic descriptions of large cohorts are scarce in the literature. Thirty-three putative HVTs diagnosed from 1970 to 2021 were retrieved. All available clinical and pathologic materials were reviewed. Lesions were reclassified according to the World Health Organization (WHO) classification of pediatric tumors [1] as hepatic congenital hemangioma (HCH; n = 13), hepatic infantile hemangioma (HIH; n = 10), hepatic angiosarcoma (HA; n = 3), and hepatic epithelioid hemangioendothelioma (HEH; n = 1). Vascular malformations (n = 5) or vascular-dominant mesenchymal hamartoma (n = 1) were excluded. HCH frequently showed involutional changes, whereas HIH often had anastomosing channels and pseudopapillae formation. HA had solid areas with epithelioid and/or spindled endothelial morphology, significant atypia, increased mitoses, high proliferation index, and occasionally necrosis. On morphology analysis, a subset of HIH showed features worrisome for progression to HA including solid glomeruloid proliferation, increased mitoses, and epithelioid morphology. The widely metastatic and fatal HEH was observed in a 5-year-old male with multiple liver lesions. Immunohistochemically, HIHs and HA were Glucose transporter isoform 1 (GLUT-1) positive. One HIH patient died from postoperative complications, whereas 3 are alive without disease. Five HCH patients are alive and well. Two of three HA patients died of disease, and 1 is alive without recurrence. To our knowledge, this is the largest series of pediatric HVTs reviewing clinicopathologic features based on current Pediatric WHO nomenclature [1]. We highlight diagnostic challenges and propose inclusion of an intermediate category between HIH and HA which warrants closer follow-up.
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Affiliation(s)
- Lara Berklite
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; University of Cincinnati, Department of Pathology, UC Health University Hospital, Laboratory Medicine Building, Cincinnati, OH 45219, USA.
| | - Faizan Malik
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
| | - Sarangarajan Ranganathan
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; University of Cincinnati, Department of Pathology, UC Health University Hospital, Laboratory Medicine Building, Cincinnati, OH 45219, USA.
| | - Anita Gupta
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
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5
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Papke DJ. Mesenchymal Neoplasms of the Liver. Surg Pathol Clin 2023; 16:609-634. [PMID: 37536892 DOI: 10.1016/j.path.2023.04.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/05/2023]
Abstract
Mesenchymal neoplasms of the liver can be diagnostically challenging, particularly on core needle biopsies. Here, I discuss recent updates in neoplasms that are specific to the liver (mesenchymal hamartoma, undifferentiated embryonal sarcoma, calcifying nested stromal-epithelial tumor), vascular tumors of the liver (anastomosing hemangioma, hepatic small vessel neoplasm, epithelioid hemangioendothelioma, angiosarcoma), and other tumor types that can occur primarily in the liver (PEComa/angiomyolipoma, inflammatory pseudotumor-like follicular dendritic cell sarcoma, EBV-associated smooth muscle tumor, inflammatory myofibroblastic tumor, malignant rhabdoid tumor). Lastly, I discuss metastatic sarcomas to the liver, as well as pitfalls presented by metastatic melanoma and sarcomatoid carcinoma.
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Affiliation(s)
- David J Papke
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA.
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6
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Jia Z, Tang CH, Zhou HS. Acute Abdomen Caused by an Impending Rupture of Cystic-Solid Liver Mass. Indian J Surg 2022. [DOI: 10.1007/s12262-022-03647-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
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7
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Chavhan GB, Schooler GR, Tang ER, Squires JH, Rees MA, Nguyen HN, Morin CE, Kolbe AB, Khanna G, Infante JC, Alazraki AL, Towbin AJ. Optimizing Imaging of Pediatric Liver Lesions: Guidelines from the Pediatric LI-RADS Working Group. Radiographics 2022; 43:e220043. [DOI: 10.1148/rg.220043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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8
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Mohamed EM, Zeidan M, Gazzaz TF, Abdullah NS, Abolyazid SM, Elaryan A. Undifferentiated embryonal sarcoma of liver arising within mesenchymal hamartoma in a child "case report". THE EGYPTIAN JOURNAL OF RADIOLOGY AND NUCLEAR MEDICINE 2022. [DOI: 10.1186/s43055-022-00871-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Primary pediatric liver tumors are scarce. Undifferentiated embryonal sarcoma of the liver (UESL) embraces nine to fifteen percent of the pediatric hepatic neoplasms. Mesenchymal hamartoma of the liver (MHL) is the second most prevalent benign pediatric hepatic neoplasm following infantile hemangioendothelioma.
Case presentation
A 6-year-old female child presented with vague diffuse abdominal pain and palpable right lumbar mass by clinical examination. The US showed a well-circumscribed large right hepatic complex multilocular cystic lesion with multiple internal septations and some turbid loculi. The constellation of CT and dynamic MRI findings raised the presence of atypical suspicious complex cystic hepatic mass lesion with hemorrhagic, calcific entities and internal soft tissue enhancement. The histopathological correlation proved UESL on the background of MHL.
Conclusions
A case of a pediatric hepatic complex cystic lesion, which had typical ultrasound features of MHL, however, CT and MRI had atypical suspicious criteria. Finally, our case is presented as UESL in the background of MHL based upon pathological diagnosis. The radiologists must be familiar with overlapped entities between MHL, UESL, and other differential diagnosis entities regarding pediatric hepatic neoplasms.
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9
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Idrees M, Chung K, Philipoff A, Jeffrey G, Garas G, Jaques B, Delriviere L, De Boer B, Bhandari M, Mou L. Liver Transplant for Adult Recurrent Hepatic Mesenchymal Hamartoma and a Feasible Treatment Modality: A Case Report and Literature Review. Transplant Proc 2022; 54:1636-1639. [PMID: 35842317 DOI: 10.1016/j.transproceed.2022.04.020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 04/12/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Adult hepatic mesenchymal hamartoma (HMH) is an extremely rare hepatic tumor. Recurrence following complete resection is uncommon. Liver transplantation (LT) is described as a possible treatment option in nonresectable HMH. We conducted a systematic review investigating LT in adult HMH followed by a case report describing evidence of extensive recurrence following complete resection of large right-sided HMH requiring LT. CASE REPORT A 46-year-old woman with symptomatic large right-hepatic HMH underwent right hemi-hepatectomy with histologic evidence of complete resection. Two and a half years postresection, she presented with abdominal pain and distension; imaging revealed large multi-septated hepatic cystic lesions within the liver suggestive of extensive recurrence of disease with concerns of malignant sarcomatous transformation. After a multidisciplinary team discussion, the lesion was deemed unresectable and the patient was referred for LT. Findings on transplantation included giant multiple hepatic cystic lesions occupying the entire abdomen and histopathological analysis confirmed recurrent HMH with no malignancy. The 6-month follow-up was unremarkable with no signs of postoperative complications or rejection. CONCLUSION We identified only 3 reported adult unresectable HMH cases in the English literature requiring LT, with good clinical outcome and no rejection on a 1-year follow-up. To our knowledge, we report the first recurrent HMH that required LT in the English literature. Current evidence suggests possible malignant sarcomatous transformation of those lesions. No guidelines exist on postresection surveillance for HMH; however, given their malignant potential, we suggest a benefit of imaging-based surveillance following HMH resection. Offering LT for nonresectable or recurrent HMH is a feasible treatment modality with a reported good outcome.
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Affiliation(s)
- Marwan Idrees
- Hepatopancreaticobiliary/General Surgery Department, Fiona Stanley Hospital, Western Australia, Australia.
| | - Kimberley Chung
- Department of Anatomical Pathology, PathWest, QE2 Medical Centre and Fiona Stanley Hospital, Hospital Avenue, Western Australia, Australia
| | - Adam Philipoff
- WA Liver and Kidney Transplant Department, Sir Charles Gairdner Hospital, Western Australia, Australia
| | - Gary Jeffrey
- WA Liver and Kidney Transplant Department, Sir Charles Gairdner Hospital, Western Australia, Australia
| | - George Garas
- WA Liver and Kidney Transplant Department, Sir Charles Gairdner Hospital, Western Australia, Australia
| | - Bryon Jaques
- WA Liver and Kidney Transplant Department, Sir Charles Gairdner Hospital, Western Australia, Australia
| | - Luc Delriviere
- WA Liver and Kidney Transplant Department, Sir Charles Gairdner Hospital, Western Australia, Australia
| | - Bastian De Boer
- Department of Anatomical Pathology, PathWest, QE2 Medical Centre and Fiona Stanley Hospital, Hospital Avenue, Western Australia, Australia
| | - Mayank Bhandari
- Hepatopancreaticobiliary/General Surgery Department, Fiona Stanley Hospital, Western Australia, Australia
| | - Lingjun Mou
- WA Liver and Kidney Transplant Department, Sir Charles Gairdner Hospital, Western Australia, Australia; Discipline of Surgery, Medical School, The University of Western Australia, Western Australia, Australia
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10
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Tsvetkova V, Magro G, Broggi G, Luchini C, Cappello F, Caporalini C, Buccoliero AM, Santoro L. New insights in gastrointestinal "pediatric" neoplasms in adult patients: pancreatoblastoma, hepatoblastoma and embryonal sarcoma of the liver. A practical approach by GIPPI-GIPAD Groups. Pathologica 2022; 114:64-78. [PMID: 35212317 PMCID: PMC9040550 DOI: 10.32074/1591-951x-559] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 11/09/2022] [Indexed: 12/11/2022] Open
Abstract
Pediatric solid neoplasms are rare and very different from those observed in adults. The majority of them are referred to as embryonal because they arise as a result of alterations in the processes of organogenesis or normal growth and are characterized by proliferation of primitive cells, reproducing the corresponding tissue at various stages of embryonic development. This review will focus on embryonal gastrointestinal pediatric neoplasms in adult patients, including pancreatoblastoma, hepatoblastoma, and embryonal sarcoma of the liver. Although they are classically considered pediatric neoplasms, they may (rarely) occur in adult patients. Hepatoblastoma represents the most frequent liver neoplasm in the pediatric population, followed by hepatocellular carcinoma and embryonal sarcoma of the liver; while pancreatoblastoma is the most common malignant pancreatic tumor in childhood. Both in children and adults, the mainstay of treatment is complete surgical resection, either up front or following neoadjuvant chemotherapy. Unresectable and/or metastatic neoplasms may be amenable to complete delayed surgery after neoadjuvant chemotherapy. However, these neoplasms display a more aggressive behavior and overall poorer prognosis in adults than in children, probably because they are diagnosed in later stages of diseases.
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Affiliation(s)
- Vassilena Tsvetkova
- Department of Diagnostics and Public Health, Section of Pathology, Verona University and Hospital Trust; Verona, Italy
| | - Gaetano Magro
- Department of Medical and Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Anatomic Pathology, University of Catania, 95123 Catania, Italy
| | - Giuseppe Broggi
- Department of Medical and Surgical Sciences and Advanced Technologies “G. F. Ingrassia”, Anatomic Pathology, University of Catania, 95123 Catania, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, Verona University and Hospital Trust; Verona, Italy
| | - Filippo Cappello
- Department of Pathology, Azienda Ospedaliera Universitaria di Padova, Padova, Italy
| | | | | | - Luisa Santoro
- Department of Pathology, Azienda Ospedaliera Universitaria di Padova, Padova, Italy
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11
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Rela M, Rammohan A, Reddy MS. Liver Tumors in Children. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:983-994. [DOI: 10.1007/978-3-030-80068-0_72] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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12
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Habibzadeh P, Ansari Asl M, Foroutan HR, Bahador A, Anbardar MH. Clinicopathological study of hepatic mesenchymal hamartoma and undifferentiated embryonal sarcoma of the liver: a single center study from Iran. Diagn Pathol 2021; 16:55. [PMID: 34162402 PMCID: PMC8223305 DOI: 10.1186/s13000-021-01117-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 06/10/2021] [Indexed: 12/04/2022] Open
Abstract
BACKGROUND Undifferentiated embryonal sarcoma of liver (UESL) and hepatic mesenchymal hamartoma (HMH) are two rare entities which mainly affect the pediatric population. The aim of this investigation was to provide a comprehensive overview of the clinicopathologic characteristics of the patients diagnosed with these two conditions in a tertiary referral center in Iran. METHODS In this retrospective study patients diagnosed with UESL or HMH between 2012 and 2020 were studied. A comprehensive histopathologic evaluation of the cases along with immunohistochemistry evaluation using a panel of antibodies was conducted. Furthermore, clinical, paraclinical, and treatment data and follow up information was collected. RESULTS A total of 16 patients (8 UESL, 8 HMH) were studied in this investigation. Patients with UESL had a significantly (p = 0.002) higher age at diagnosis compared with those with HMH. Histologically, UESL cases were characterized by anaplastic cells with eosinophilic cytoplasm and bizarre nuclei and frequent atypical mitosis and spindling in a myxoid stroma while disordered arrangement of hepatic parenchyma, bile ducts, and primitive mesenchyme was seen in HMH. Furthermore, small round cells and extramedullary hematopoiesis were seen in 2 UESL and 3 HMH cases, respectively. Concurrent HMH was also seen in two UESL cases. Immunohistochemistry panel showed positive staining for Vimentin, Glypican-3, Desmin, CD56, CD10, and BCL2 in UESL cases and immunoreactivity for Vimentin, HepPar 1, Glypican-3, SMA, CD56, BCL2, and CD34 in various components of HMH. CONCLUSIONS In this study, the clinicopathologic features of UESL and HMH cases are presented. We also evaluated the utility of an immunohistochemistry panel in the diagnosis of these two rare entities and suggested novel markers. Our study corroborated the findings of previous investigations and expanded the clinicopathologic features of these two rare entities with diagnostic and potential therapeutic implications.
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Affiliation(s)
- Parham Habibzadeh
- Persian BayanGene Research and Training Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Hamid Reza Foroutan
- Laparoscopy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Pediatric Surgery, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Bahador
- Department of Pediatric Surgery, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Hossein Anbardar
- Department of Pathology, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran.
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Abstract
The most recent advance in the care of children diagnosed with hepatoblastoma and hepatocellular carcinoma is the Pediatric Hepatic International Tumor Trial, which opened to international enrollment in 2018. It is being conducted as a collaborative effort by the pediatric multicenter trial groups in North America, Europe, and the Far East. This international effort was catalyzed by a new unified global risk stratification system for hepatoblastoma, an international histopathologic consensus classification for pediatric liver tumors, and a revised 2017 collaborative update of the PRE-Treatment EXTent of disease radiographic based staging system.
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Affiliation(s)
- Rebecka Meyers
- Division Pediatric Surgery, University of Utah, Primary Children's Hospital, 100 North Mario Capecchi Drive, Suite 3800, Salt Lake City, UT 84113, USA.
| | - Eiso Hiyama
- Department of Pediatric Surgery, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-Ku, Hiroshima 734-8551, Japan
| | - Piotr Czauderna
- Department of Surgery and Urology for Children and Adolescents, Medical University of Gdansk, Marii Skłodowskiej-Curie 3a, 80-210 Gdańsk, Poland
| | - Greg M Tiao
- Division Pediatric Surgery, Cincinnati Children's Hospital and Medical Center, 3333 Burnet Ave, Cincinnati, Ohio 45229, USA
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Zhang C, Jia CJ, Xu C, Sheng QJ, Dou XG, Ding Y. Undifferentiated embryonal sarcoma of the liver: Clinical characteristics and outcomes. World J Clin Cases 2020; 8:4763-4772. [PMID: 33195644 PMCID: PMC7642548 DOI: 10.12998/wjcc.v8.i20.4763] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 08/20/2020] [Accepted: 08/29/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Undifferentiated embryonal sarcoma of the liver (UESL) is a rare liver malignancy originating from primary mesenchymal tissue. The clinical manifestations, laboratory tests, and imaging examinations of the disease lack specificity and the preoperative misdiagnosis rate is high. The overall prognosis is poor and survival rate is low.
AIM To investigate the diagnosis, treatment, and prognosis of UESL.
METHODS We performed a retrospective, single-center cohort study in Shengjing Hospital of China Medical University, which is a central hospital in northeast China. From 2005 to 2017, we recruited 14 patients with pathologically confirmed UESL. We analyzed the clinical manifestations, laboratory tests, imaging examinations, pathological examinations, therapy, and prognosis of these patients.
RESULTS There were nine males and five females aged 2-60 years old included in the study. The major initial symptoms were abdominal pain (71.43%) and fever (57.14%). Preoperative laboratory tests revealed that seven patients had increased leukocyte levels, four showed a decrease in hemoglobin levels, seven patients had increased glutamyl transpeptidase levels, nine had increased lactate dehydrogenase levels, and three showed an increase in carbohydrate antigen 199. There was no difference in the rate of misdiagnosis in preoperative imaging examinations of UESL between adults and children (6/6 vs 5/8, P = 0.091). The survival rate after complete resection was 6/10, while that after incomplete resection was 0/4 (P = 0.040), suggesting that complete resection is important to improve survival rate. In total, five out of the eight children achieved survival. During the follow-up, the maximum survival time was shown to be 11 years and minimum survival time was 6 mo. Six adult patients relapsed late after surgery and all of them died.
CONCLUSION Preoperative imaging examination for UESL has a high misdiagnosis rate. Multidisciplinary collaboration can improve the diagnostic accuracy of UESL. Complete surgical resection is the first choice for treatment of UESL.
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Affiliation(s)
- Chong Zhang
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Chang-Jun Jia
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Can Xu
- Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Qiu-Ju Sheng
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Xiao-Guang Dou
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
| | - Yang Ding
- Department of Infectious Diseases, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
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15
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Sindhi R, Rohan V, Bukowinski A, Tadros S, de Ville de Goyet J, Rapkin L, Ranganathan S. Liver Transplantation for Pediatric Liver Cancer. Cancers (Basel) 2020; 12:cancers12030720. [PMID: 32204368 PMCID: PMC7140094 DOI: 10.3390/cancers12030720] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 03/10/2020] [Accepted: 03/12/2020] [Indexed: 02/06/2023] Open
Abstract
Unresectable hepatocellular carcinoma (HCC) was first removed successfully with total hepatectomy and liver transplantation (LT) in a child over five decades ago. Since then, children with unresectable liver cancer have benefitted greatly from LT and a confluence of several equally important endeavors. Regional and trans-continental collaborations have accelerated the development and standardization of chemotherapy regimens, which provide disease control to enable LT, and also serve as a test of unresectability. In the process, tumor histology, imaging protocols, and tumor staging have also matured to better assess response and LT candidacy. Significant trends include a steady increase in the incidence of and use of LT for hepatoblastoma, and a significant improvement in survival after LT for HCC with each decade. Although LT is curative for most unresectable primary liver sarcomas, such as embryonal sarcoma, the malignant rhabdoid tumor appears relapse-prone despite chemotherapy and LT. Pediatric liver tumors remain rare, and diagnostic uncertainty in some settings can potentially delay treatment or lead to the selection of less effective chemotherapy. We review the current knowledge relevant to diagnosis, LT candidacy, and post-transplant outcomes for these tumors, emphasizing recent observations made from large registries or larger series.
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Affiliation(s)
- Rakesh Sindhi
- Hillman Center for Pediatric Transplantation, UPMC-Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA; (A.B.); (S.T.)
- Correspondence: ; Tel.: +1-412-692-7123
| | - Vinayak Rohan
- Medical University of South Carolina, Charleston, SC 29403, USA;
| | - Andrew Bukowinski
- Hillman Center for Pediatric Transplantation, UPMC-Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA; (A.B.); (S.T.)
| | - Sameh Tadros
- Hillman Center for Pediatric Transplantation, UPMC-Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA; (A.B.); (S.T.)
| | - Jean de Ville de Goyet
- Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), 90127 Palermo, Italy;
| | - Louis Rapkin
- Department of Hematology/Oncology, UPMC-Children’s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA;
| | - Sarangarajan Ranganathan
- Department of Pathology, Children’s Hospital Medical Center of Cincinnati, Cincinnati, OH 45229, USA;
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Rare malignant liver tumors in children. Pediatr Radiol 2019; 49:1404-1421. [PMID: 31620842 DOI: 10.1007/s00247-019-04402-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 03/07/2019] [Accepted: 04/01/2019] [Indexed: 02/07/2023]
Abstract
Malignant hepatic tumors in children are rare, comprising 1.3% of all pediatric malignancies. Following hepatoblastoma, hepatocellular carcinoma is the second most common. Other malignant hepatic tumors seen in childhood include those of mesenchymal origin including undifferentiated embryonal sarcoma, angiosarcoma, rhabdomyosarcoma and epithelioid hemangioendothelioma, as well as biliary tumors such as cholangiocarcinoma. Diagnosis can be challenging because of their rarity, and the recognition of distinctive imaging features for certain tumors such as epithelioid hemangioendothelioma and biliary rhabdomyosarcoma can focus the differential diagnosis and expedite the diagnostic process. A complete MRI examination with hepatocyte-specific contrast media and diffusion-weighted imaging helps to focus the differential diagnosis, and, although findings are often nonspecific, in some cases typical features on MRI can be helpful in diagnosis. Histopathological analysis is usually required for definitive diagnosis. Hepatic tumors tend to be aggressive, and full staging is imperative to establish disease extent. Significant proportions are not amenable to upfront surgical resection and often require a multimodality approach including neoadjuvant chemotherapy within a multidisciplinary setting. Facilitating complete surgical resection is usually required for better survival. In this review, we emphasize pathology and imaging features for rare liver tumors that are useful in reaching a prompt diagnosis. We also discuss general clinical findings, prognosis and management of these tumors.
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Abstract
Cystic hepatic lesions are commonly encountered in daily practice. The diagnosis of these lesions ranges from benign lesions of no clinical significance to malignant and potentially lethal conditions. The prevalence of hepatic cyst (HC) has been reported to be as high as 15-18% in the United States. Imaging with conventional ultrasound, computed tomography, magnetic resonance imaging, or contrast-enhanced ultrasound can be used to characterize further and diagnose. The pre-test probability of a diagnosis is highly affected by the patient's comorbidities and the clinical and laboratory data; thus, imaging studies should be interpreted in the context of the other clinical information for that particular patient. Treatment modalities for hepatic cyst include fenestration, aspiration sclerotherapy, or surgical resection. In the current review, we discuss the pathophysiology, diagnosis, and treatment modalities for various cystic hepatic lesions.
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18
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Giant mesenchymal hamartoma in pediatric patients: A new indication for liver transplantation. JOURNAL OF PEDIATRIC SURGERY CASE REPORTS 2017. [DOI: 10.1016/j.epsc.2017.03.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Mathias MD, Ambati SR, Chou AJ, Slotkin EK, Wexler LH, Meyers PA, Magnan H. A single-center experience with undifferentiated embryonal sarcoma of the liver. Pediatr Blood Cancer 2016; 63:2246-2248. [PMID: 27427850 PMCID: PMC5073002 DOI: 10.1002/pbc.26154] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2016] [Revised: 06/27/2016] [Accepted: 06/28/2016] [Indexed: 12/24/2022]
Abstract
Undifferentiated embryonal sarcoma of the liver (UESL) is a rare aggressive mesenchymal pediatric tumor. Previously, reported outcomes have been very poor. Here, we report a single-center experience of five patients with UESL treated with upfront gross total resection and adjuvant chemotherapy. We have a median follow-up of 8 years with a range from 5 to 19 years with 100% event-free survival.
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Affiliation(s)
- Melissa D. Mathias
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center. New York City, New York,Correspondence to: Melissa Mathias, MD, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065.
| | - Srikanth R. Ambati
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center. New York City, New York
| | - Alexander J. Chou
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center. New York City, New York
| | - Emily K. Slotkin
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center. New York City, New York
| | - Leonard H. Wexler
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center. New York City, New York
| | - Paul A. Meyers
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center. New York City, New York
| | - Heather Magnan
- Department of Pediatrics, Memorial Sloan Kettering Cancer Center. New York City, New York
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20
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Imaging features of undifferentiated embryonal sarcoma of the liver: a series of 15 children. Pediatr Radiol 2016; 46:1694-1704. [PMID: 27562247 DOI: 10.1007/s00247-016-3670-3] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2015] [Revised: 05/21/2016] [Accepted: 07/20/2016] [Indexed: 11/27/2022]
Abstract
BACKGROUND Undifferentiated embryonal sarcoma of the liver is a rare malignant mesenchymal tumour occurring mostly in children ages 6-10 years. The discrepancy between its solid appearance on US and cystic-like appearance on CT has been described. OBJECTIVE To study the imaging particularities and similarities among our cases of undifferentiated embryonal sarcoma and to report the errors in initial diagnoses. MATERIALS AND METHODS We conducted a retrospective study of 15 children with undifferentiated embryonal sarcoma diagnosed or referred to our hospital during 1997-2015 and analysed the clinical, biological and imaging data. RESULTS We identified eight boys and seven girls ages 9 months to 14 years. Ten children presented with abdominal pain. Alpha-fetoprotein was slightly increased in one. Initial US and CT had been performed for all, while additional MRI had been done in two children. Initial CT demonstrated a hypoattenuated mass in all. Rupture was seen in five and intratumoural bleeding in seven children. Tumour volumes reduced during neoadjuvant chemotherapy in 10 children. CONCLUSION Undifferentiated embryonal sarcoma might be suggested in a non-secreting unifocal tumour with well-defined borders, fluid-filled spaces on US, hypoattenuation and serpiginous vessels on CT, and if there are signs of internal bleeding or rupture on CT or MRI.
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21
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Abstract
This article aims to give an overview of pediatric liver tumors; in particular of the two most frequently occurring groups of hepatoblastomas and hepatocellular carcinomas. Focus lays on achievements gained through worldwide collaboration. We present recent advances in insight, treatment results, and future questions to be asked. Increasing international collaboration between the four major Pediatric Liver Tumor Study Groups (SIOPEL/GPOH, COG, and JPLT) may serve as a paradigm to approach rare tumors. This international effort has been catalyzed by the Children's Hepatic tumor International Collaboration (CHIC) formation of a large collaborative database. Interrogation of this database has led to a new universal risk stratification system for hepatoblastoma using PRETEXT/POSTTEXT staging as a backbone. Pathologists in this international collaboration have established a new histopathological consensus classification for pediatric liver tumors. Concomitantly there have been advances in chemotherapy options, an increased role of liver transplantation for unresectable tumors, and a web portal system developed at www.siopel.org for international education, consultation, and collaboration. These achievements will be further tested and validated in the upcoming Paediatric Hepatic International Tumour Trial (PHITT).
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Affiliation(s)
- Daniel C Aronson
- Department of Paediatric Surgery, Noah's Ark Children's Hospital for Wales, University Hospital of Wales, Cardiff and Vale University Health Board NHS Trust, Cardiff CF14 4XW, UK.
| | - Rebecka L Meyers
- Division of Pediatric Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA
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Mesenchymal Hamartoma of the Liver in Older Children: An Adult Variant or a Different Entity? Report of a Case With Review of the Literature. Appl Immunohistochem Mol Morphol 2016; 23:667-73. [PMID: 22935827 DOI: 10.1097/pai.0b013e31826b56ae] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Mesenchymal hamartoma of the liver (MHL) is an uncommon benign hepatic tumor typically affecting children under 2 years of age. Only 5% of MHL occur after 5 years and are very rarely observed in adults. According to age, MHL may differ in their morphologic features. We report a case of an 11-year-old boy with MHL, resembling a malignant lesion from a clinical point of view, characterized by unusual histologic features: a prominent myxoid stroma, with a minimal ductular component, and absent cystic spaces. The present case and others reported in older children or adults demonstrate that these lesions may represent a potential diagnostic pitfall when occurring outside their classic clinical context especially because of their peculiar histologic findings. Moreover, it may be hypothesized that variation in morphology might be related to different evolutive stages of the cell of origin. To support this hypothesis, we therefore studied the presence of components of the Notch pathway inside and outside the lesion. Their absence inside the tumor and, in contrast, the expression of Notch2 and HES1 evident in overrepresented bile ducts present at the periphery might explain not only the lack of bile ducts, but also indicate a more adult phenotype compared with classic pediatric MHL, which show more bile ducts and liver trabeculae embedded in the mesenchymal matrix.
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Techavichit P, Masand PM, Himes RW, Abbas R, Goss JA, Vasudevan SA, Finegold MJ, Heczey A. Undifferentiated Embryonal Sarcoma of the Liver (UESL): A Single-Center Experience and Review of the Literature. J Pediatr Hematol Oncol 2016; 38:261-8. [PMID: 26925712 DOI: 10.1097/mph.0000000000000529] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive pediatric malignancy. The purpose of this study was to review the clinical, radiologic, and pathologic features and outcome of children with UESL at our institution, in the United Network of Organ Sharing database and to review the existing literature to define the state of the art for children with UESL. Six children were diagnosed with UESL at the Texas Children's Cancer Center between 1993 and 2014, 12 children underwent liver transplantation registered in the United Network of Organ Sharing database, and 198 children with UESL were described in 23 case series during 1978 to 2014. Patients were treated with multimodal treatment approaches including primary surgical resection, neoadjuvant and/or adjuvant chemotherapy, and liver transplantation resulting in overall survival reported between 20% and 100% with significant improvement over the recent years. We show that complete tumor removal remains the key element of treatment and our single-institutional experience and data in the published literature suggest that combination chemotherapy with ifosfamide and doxorubicin to facilitate complete surgical resection is an effective approach to cure children with UESL.
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Affiliation(s)
- Piti Techavichit
- *Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Departments of †Radiology ‡Pediatrics, Section Gastroenterology §Surgery ∥Pathology ¶Pediatrics, Section Hematology and Oncology, Baylor College of Medicine, Houston, TX
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Pugmire BS, Towbin AJ. Magnetic resonance imaging of primary pediatric liver tumors. Pediatr Radiol 2016; 46:764-77. [PMID: 27229495 DOI: 10.1007/s00247-016-3612-0] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Revised: 02/28/2016] [Accepted: 03/15/2016] [Indexed: 12/31/2022]
Abstract
Although primary hepatic neoplasms are less common than other intra-abdominal tumors in children, these neoplasms are a significant source of morbidity and mortality in the pediatric population. MRI is increasingly relied upon in the diagnostic evaluation of these lesions, both before and after treatment, and familiarity with the MRI findings associated with these neoplasms is a must for pediatric radiologists. Advances in MRI technology, particularly the advent of hepatocyte-specific gadolinium-based MRI contrast agents, have allowed for accurate characterization of several types of hepatic neoplasms on the basis of imaging appearance. In this review, we provide an overview of the approach to imaging hepatic neoplasms in children using MRI, including a sample imaging protocol. We also discuss the relevant clinical features and MRI findings of the most clinically relevant entities, including their appearance on post-contrast imaging using hepatocyte-specific gadolinium-based MRI contrast agents.
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Affiliation(s)
- Brian S Pugmire
- Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., MLC-5031, Cincinnati, OH, 45255, USA
| | - Alexander J Towbin
- Department of Radiology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., MLC-5031, Cincinnati, OH, 45255, USA.
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25
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Keller RB, El Demellawy D, Quaglia A, Finegold M, Kapur RP. Methylation status of the chromosome arm 19q MicroRNA cluster in sporadic and androgenetic-Biparental mosaicism-associated hepatic mesenchymal hamartoma. Pediatr Dev Pathol 2015; 18:218-27. [PMID: 25751191 DOI: 10.2350/15-01-1600-oa.1] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The C19MC gene on chromosome band 19q13.4 encodes a cluster of 46 microRNAs; those microRNAs are normally only expressed from the paternal allele and in the placenta. Placental expression correlates with selective demethylation of the paternal C19MC promoter, in contrast to methylation of both maternal and paternal alleles in nonplacental tissues. Prior investigations demonstrated "ectopic" activation of this gene in most hepatic mesenchymal hamartomas, including sporadic tumors and others with androgenetic-biparental mosaicism (subset of cells are diploid, but contain only paternally derived chromosomes). In the present investigation of C19MC promoter methylation status in a series of 14 mesenchymal hamartomas, a demethylated allele was identified in 6 tumors, including all 4 with androgenetic-biparental mosaicism. Conversely, only methylated alleles were cloned from sporadic hamartomas, including 3 tumors with chromosomal rearrangements thought likely to activate C19MC expression independent of the native promoter. In conjunction with published data, the findings suggest multiple molecular mechanisms for C19MC activation in hepatic mesenchymal hamartoma, including the existence of a normal placental imprinting pattern in mesenchymal cells in a subset of cases. Some or all of the latter hamartomas may result from placental "grafting," a hypothesis supported by endothelial expression of the placental vascular marker, glucose transporter-1, in 1 of the 6 cases with a demethylated allele.
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Affiliation(s)
- Rachel B. Keller
- Department of Pathology, University of Washington, Seattle, WA, USA
| | - Dina El Demellawy
- Pathology and Laboratory Medicine, Children's Hospital of Eastern Ontario, Ottawa, Canada
| | - Alberto Quaglia
- Institute of Liver Studies, King's College Hospital, London, UK
| | - Milton Finegold
- Department of Pathology, Baylor College of Medicine, Houston, TX, USA
| | - Raj P. Kapur
- Department of Pathology, University of Washington, Seattle, WA, USA
- Department of Laboratories, Seattle Children's Hospital, Seattle, WA, USA
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Abstract
OBJECTIVE The purpose of this article is to review the different cystic hepatic lesions, with an emphasis on the imaging features that help to differentiate them, and to propose a practical algorithm for approaching the diagnosis of these lesions. CONCLUSION The number and morphology of the lesions and determination of whether there is a solid component are key imaging features that are helpful for approaching the diagnosis of cystic hepatic lesions. Familiarity with these features and knowledge of the clinical associations will help the radiologist to establish a definitive diagnosis or provide a reasonable differential diagnosis.
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Wildhaber BE, Montaruli E, Guérin F, Branchereau S, Martelli H, Gauthier F. Mesenchymal hamartoma or embryonal sarcoma of the liver in childhood: a difficult diagnosis before complete surgical excision. J Pediatr Surg 2014; 49:1372-7. [PMID: 25148740 DOI: 10.1016/j.jpedsurg.2014.04.005] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2013] [Revised: 03/03/2014] [Accepted: 04/11/2014] [Indexed: 12/21/2022]
Abstract
BACKGROUND Clinical experience shows that the primary diagnosis of mesenchymal hamartoma (MHL) and embryonal sarcoma of the liver (ESL) recurrently is mistaken, leading to inadequate managements. We evaluated the accuracy of the primary diagnosis of those liver tumors, compared with the final histological diagnosis. METHODS Records of 25 children (0-16 years, treated 01/1989-01/2013) with final diagnosis of MHL or ESL were analyzed. RESULTS Final diagnosis was MHL in 18/25 children (10 solid-cystic, 2 cystic, 6 solid) and ESL in 7/25 (4 solid-cystic, 1 cystic, 2 solid). Only 3/7 ESL patients and 15/18 MHL patients fell into the "typical" age group. In 13/25 children primary diagnosis was based on imaging only. Overall, primary diagnosis was concordant with the final diagnosis in 17/25 patients. Of 99/25 biopsied cases, 4/9 biopsy results exposed the wrong final diagnosis; of cystic-solid masses 4/14 were mistaken, of cystic masses 1/3, of solid masses 3/8. CONCLUSION Preoperative diagnosis of MHL and ESL is challenging because of atypical clinical presentation, misleading "typical" radiological findings, and difficult interpretation of biopsies. If feasible, complete surgical resection of, in particular, solid-cystic liver masses in the pediatric age group must be aimed for, to get a definitive, final diagnosis, followed by an adequate treatment strategy.
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Affiliation(s)
- Barbara E Wildhaber
- Hôpitaux Universitaires de Genève, Department of Pediatrics, Division of Pediatric Surgery, 6 Rue Willy Donzé, 1205 Geneva, Switzerland.
| | - Ernesto Montaruli
- Hôpitaux Universitaires de Genève, Department of Pediatrics, Division of Pediatric Surgery, 6 Rue Willy Donzé, 1205 Geneva, Switzerland
| | - Florent Guérin
- Hôpitaux Universitaires Paris Sud-Bicêtre, Department of Pediatric Surgery, 78 Rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France
| | - Sophie Branchereau
- Hôpitaux Universitaires Paris Sud-Bicêtre, Department of Pediatric Surgery, 78 Rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France
| | - Hélène Martelli
- Hôpitaux Universitaires Paris Sud-Bicêtre, Department of Pediatric Surgery, 78 Rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France
| | - Frédéric Gauthier
- Hôpitaux Universitaires Paris Sud-Bicêtre, Department of Pediatric Surgery, 78 Rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France
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He B, Xu K, Huang K, Huang Y, Li P, Chen Z, Shi H, Zhang Q, Shan Y. Undifferentiated embryonal liver sarcoma in childhood: A case report. Oncol Lett 2014; 8:1127-1132. [PMID: 25120671 PMCID: PMC4114632 DOI: 10.3892/ol.2014.2262] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Accepted: 04/16/2014] [Indexed: 12/27/2022] Open
Abstract
In order to improve the diagnosis and therapy of undifferentiated embryonal liver sarcoma (UELS), the present study presents the case of a 9-year-old female with UELS and discusses UELS in childhood. The patient presented with abdominal pain and fever. The laboratory tests, radiographic examination and pathological features presented by the female were similar to those of typical cases of UELS reported in childhood. The patient initially received surgical treatment and the immunohistochemical findings suggested that the patient had UELS. The patient’s parents refused adjuvant chemotherapy and demonstrated a right prerenal mass 6 months post-surgery. Microscopic examination revealed that the tumor was evidence of undifferentiated embryonal sarcoma recurrence. However, the patient was comfortable and physical examination revealed no abnormal conditions. In addition, the laboratory results were normal. Abdominal computed tomography scan and ultrasound were performed every 3 months to monitor the tumor recurrence. At the time of writing, it has been 6 months after the second surgical procedure and there has been no appearence of abnormalities. Previous studies have shown that patients who receive combined therapy with complete tumor resection and adjuvant chemotherapy have a longer survival time than those who undergo surgical therapy alone. Complete tumor resection combined with adjuvant chemotherapy may reduce the risk of recurrence and enhance the survival time in patients with UELS.
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Affiliation(s)
- Bin He
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Keyu Xu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Kate Huang
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Yuehan Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Peng Li
- Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Zhenkun Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Hongqi Shi
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Qiyu Zhang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
| | - Yunfeng Shan
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
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Walther A, Geller J, Coots A, Towbin A, Nathan J, Alonso M, Sheridan R, Tiao G. Multimodal therapy including liver transplantation for hepatic undifferentiated embryonal sarcoma. Liver Transpl 2014; 20:191-9. [PMID: 24142883 DOI: 10.1002/lt.23773] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Accepted: 10/16/2013] [Indexed: 12/14/2022]
Abstract
The outcomes of hepatic undifferentiated embryonal sarcoma (HUES) have historically been limited by persistent, unresectable disease and the subsequent development of disease resistance and dissemination. We present our institutional experience with HUES and assess current treatment trends and outcomes in the era of liver transplantation. We conducted a retrospective chart review of cases presenting with HUES at our institution over the past 10 years. The collected data included age, sex, presenting symptoms, imaging and the associated Pretreatment Extent of Disease (PRETEXT) score, pathology, chemotherapy, surgical interventions, and outcomes. Approval was obtained from the institutional review board of the Cincinnati Children's Hospital Medical Center. HUES was identified in 6 patients (4 males and 2 females) with a median age at diagnosis of 11 years (range = 7-13 years). Initial imaging was available for all but 1 patient. The PRETEXT stage for these patients ranged from II to III. One patient was diagnosed with lung metastases. Two patients underwent upfront resection, and 1 patient received neoadjuvant therapy and then conventional resection. Three patients were treated with orthotopic liver transplantation (OLT) after neoadjuvant chemotherapy (primary OLT in 2 cases and salvage OLT for local recurrence in 1 case). Two patients received posttransplant adjuvant chemotherapy. All 6 patients remained in clinical remission with a mean follow-up of 35 months (range = 12-84 months). In conclusion, OLT has rarely been reported as a treatment option for HUES. The addition of liver transplantation as a surgical option for treating patients with HUES can result in improved survival for patients whose tumors are initially unresectable or recur.
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Affiliation(s)
- Ashley Walther
- Departments of Pediatric Surgery, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
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Finegold MJ, López-Terrada DH. Hepatic Tumors in Childhood. PATHOLOGY OF PEDIATRIC GASTROINTESTINAL AND LIVER DISEASE 2014:547-614. [DOI: 10.1007/978-3-642-54053-0_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Abstract
PURPOSE Embryonal sarcoma accounts for 6 % of liver tumors. This study reviews its features and the results of treatment in a referral center. METHODS We retrospectively reviewed liver tumors treated between 1995 and 2011. PRETEXT staging and biopsy were used to tailor chemotherapy according to SIOP protocols. Radical surgery was performed when possible. Complications and cumulative survival were the outcome endpoints. RESULTS Six out of 156 primary liver tumors (four males and two females) were sarcomas. The mean age at diagnosis was 81 ± 8.5 months. The most frequent finding was abdominal mass. Alfa-fetoprotein was normal. Imaging depicted heterogeneous tumors with septa, necrosis, and hemorrhagic areas. The diagnosis was ascertained by biopsy. Three tumors were located in the right lobe (PRETEXT II): two were bilobar (PRETEXT III) and one was in the left lobe (PRETEXT I). Two children had metastases at diagnosis and high-risk chemotherapy (vincristine, carboplatin, epirubicin) was administered with poor response. They died without operation 4 and 10 months later. Four patients with local disease underwent typical liver resections after chemotherapy (iphosphamide, vincristine, actinomycin D, and doxorrubicin). Overall actuarial survival at 70 months was 66.6 %. CONCLUSIONS Extended and metastatic embryonal sarcoma do poorly whereas localized tumors amenable to complete surgical removal after chemotherapy can cure.
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Abstract
Malignant tumors of the liver comprise a relatively small fraction of the total number of pediatric malignancies. However, these tumors can be a significant cause of morbidity and mortality, and there have been significant therapeutic gains during the past few decades through advances in systemic therapy and surgical treatment. Even in patients with advanced local disease, complete resection is now a possibility because of improvements in liver transplantation techniques. In this review, we will discuss the staging and treatment of common malignant tumors of the liver.
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Affiliation(s)
- Joshua N Honeyman
- Pediatric Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York 10065, USA
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Fang SG, Ma Q, Lin L, Li YQ, Zeng Y, Xiao HL. Analysis of clinicopathological features of bile duct adenoma of the liver. Shijie Huaren Xiaohua Zazhi 2012; 20:1791-1795. [DOI: 10.11569/wcjd.v20.i19.1791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To analyze the clinicopathological characteristics, diagnosis and differential diagnosis of bile duct adenoma (BDA) of the liver.
METHODS: Two cases of BDA of the liver were reported. Their clinical data, pathologic features, and immunophenotypes were analyzed. A review of related literature was also performed.
RESULTS: Asymptomatic nodular masses of the liver were revealed incidentally during a CT scan in both cases. Grossly, the masses were described as firm white lesions with well-defined margins, but were not encapsulated. Histologically, the tumors were composed of round ductal or irregular glandular structures and abundant fibrous stroma. Those adenoid components showed no obvious dilatation and were lined by columnar or cuboidal cells that have regular nuclei and lack dysplasia. Immunohistochemically, the tumor cells were positive for epithelial markers such as CK (pan), CK7 and E-cadherin.
CONCLUSION: BDA of the liver is a rare benigh tumor with unique clinicopathological features. It should be distinguished from some mimics such as well-differentiated intrahepatic cholangiocarcinoma (ICC) and Von Meyenburg's complex.
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Abstract
Many soft tissue tumors of childhood lack obvious differentiation toward a defined mesenchymal tissue type or have a phenotype that does not correspond to any defined normal tissue. These challenging tumors are currently regarded as neoplasms of uncertain differentiation. Nonetheless, there have been great strides in the understanding of their pathologic and genetic features and biologic underpinnings. The application of new genetic information to the pathologic diagnosis among this group of tumors is an emerging area in diagnostic pediatric pathology. This article reviews the clinicopathologic features of tumors of uncertain and/or miscellaneous origin, with an emphasis on the unique aspects of these neoplasms in children and adolescents, use of diagnostic adjuncts, and differential diagnosis.
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Affiliation(s)
- Rita Alaggio
- Department of Pathology, University of Padova, Padova, Italy.
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Levy M, Trivedi A, Zhang J, Miles L, Mattis AN, Kim GE, Lassman C, Anders RA, Misdraji J, Yerian LM, Xu H, Dhall D, Wang HL. Expression of glypican-3 in undifferentiated embryonal sarcoma and mesenchymal hamartoma of the liver. Hum Pathol 2012; 43:695-701. [PMID: 21937079 PMCID: PMC3568522 DOI: 10.1016/j.humpath.2011.06.016] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2011] [Revised: 06/06/2011] [Accepted: 06/08/2011] [Indexed: 12/25/2022]
Abstract
Glypican-3 (GPC3) is an oncofetal protein that has been demonstrated to be a useful diagnostic immunomarker for hepatocellular carcinoma and hepatoblastoma. Its expression in mesenchymal tumors of the liver, particularly undifferentiated embryonal sarcoma (UES) and mesenchymal hamartoma (MH), has not been investigated. In this study, a total of 24 UESs and 18 MHs were immunohistochemically stained for GPC3 expression. The results showed cytoplasmic staining for GPC3 in 14 (58%) UESs, of which 6 exhibited diffuse immunoreactivity and the remaining 8 showed focal positivity. The patients with GPC3-positive UES tended to be younger (mean 18 years; median 11 years) than those with GPC3-negative tumors (mean 39.4 years; median 27 years), although the difference did not reach statistical significance (P = .06). Eight MHs also exhibited GPC3 immunoreactivity (44%; 4 diffuse and 4 focal). Positive staining in all 8 cases was primarily seen in entrapped nonlesional hepatocytes with a canalicular and cytoplasmic staining pattern. In only 4 cases (22%) was GPC3 immunoreactivity also observed in the mesenchymal component. The patients with positive staining also tended to be younger (mean 2.6 years; median 1.1 years) compared with those with negative staining (mean 16.3 years; median 4.5 years), but the difference was not statistically significant (P = .15). Our data demonstrate that GPC3 is expressed in a subset of UES and MH of the liver. Caution should thus be exercised when evaluating a GPC3-expressing hepatic neoplasm, particularly on a needle biopsy when the differential diagnosis includes poorly differentiated hepatocellular carcinoma or hepatoblastoma.
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Affiliation(s)
- Mary Levy
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Anand Trivedi
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Jun Zhang
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
| | - Lili Miles
- Department of Pathology and Laboratory Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA
| | - Aras N. Mattis
- Department of Pathology, University of California San Francisco Medical Center, San Francisco, CA 94143, USA
| | - Grace E. Kim
- Department of Pathology, University of California San Francisco Medical Center, San Francisco, CA 94143, USA
| | - Charles Lassman
- Department of Pathology and Laboratory Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095, USA
| | - Robert A. Anders
- Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Joseph Misdraji
- Department of Pathology, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA
| | - Lisa M. Yerian
- Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH 44195, USA
| | - Haodong Xu
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
| | - Deepti Dhall
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Hanlin L. Wang
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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Lin J, Cole BL, Qin X, Zhang M, Kapur RP. Occult androgenetic-biparental mosaicism and sporadic hepatic mesenchymal hamartoma. Pediatr Dev Pathol 2011; 14:360-9. [PMID: 21585278 DOI: 10.2350/11-03-0999-oa.1] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The incidence of hepatic mesenchymal hamartoma (HMH) is increased in patients with placental mesenchymal dysplasia (PMD), which appears to be caused by androgenetic-biparental mosaicism (ABM). We hypothesized that occult ABM might underlie cases of HMH with no known history of PMD. Formalin-fixed, paraffin-embedded HMH specimens from 10 such patients and liver specimens from 6 non-HMH controls were identified retrospectively from the surgical pathology records of a pediatric hospital. The relative abundance of maternal and paternal alleles was assessed by quantitative polymerase chain reaction amplification of polymorphic short tandem repeats and single nucleotide polymorphisms located on 15 different chromosomes. Androgenetic-biparental mosaicism was diagnosed in one patient based on global allelic imbalances at all informative loci. In that patient, the greatest imbalances were observed in stroma-rich portions of the hamartoma, with no significant imbalance in histologically normal liver or epithelium-rich portions of the hamartoma. A retrospective, unbiased review of the histology and clinical records from all 10 patients revealed no morphologic or clinical correlates to distinguish the affected patient, except that she had multiple cutaneous hemangiomas, which like HMH, appear to be more common in patients with PMD. Our findings suggest that other patients with apparently sporadic HMH, hemangioma, or other lesions seen more frequently with PMD may harbor occult ABM. Recognition of ABM may be important because its long-term consequences are unknown but may be significant.
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Affiliation(s)
- Jingxian Lin
- Department of Obstetrics and Gynecology, Nanjing University, Nanjing, China
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