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E-JCRT CORRESPONDENCE
Year : 2015  |  Volume : 11  |  Issue : 4  |  Page : 1022

Hepatic angiosarcoma developing in an infantile hemangioendothelioma: A rare case report


1 Department of Pathology, M.S. Ramaiah Medical College and Hospital, Bengaluru, Karnataka, India
2 Department of Pediatric Surgery, M.S. Ramaiah Medical College and Hospital, Bengaluru, Karnataka, India

Date of Web Publication15-Feb-2016

Correspondence Address:
Sulata M Kamath
38, 18th Cross Road, Malleswaram West, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.146132

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 > Abstract 


Angiosarcomas are rare tumors that predominantly affect adults. Hepatic angiosarcoma in a child is extremely rare and associated with a poor prognosis. Herein, we report the pathologic features of a hepatic angiosarcoma developing in a 31/2-year-old child who had been earlier diagnosed and was being treated for hepatic hemangioendothelioma.

Keywords: Angiosarcoma, infantile hemangioendothelioma, liver tumors


How to cite this article:
Kamath SM, Mysorekar VV, Kadamba P. Hepatic angiosarcoma developing in an infantile hemangioendothelioma: A rare case report. J Can Res Ther 2015;11:1022

How to cite this URL:
Kamath SM, Mysorekar VV, Kadamba P. Hepatic angiosarcoma developing in an infantile hemangioendothelioma: A rare case report. J Can Res Ther [serial online] 2015 [cited 2021 Jan 24];11:1022. Available from: https://www.cancerjournal.net/text.asp?2015/11/4/1022/146132




 > Introduction Top


Angiosarcoma is a rare primary malignant tumor constituting 2% of all primary hepatic neoplasms. It has been noted rarely in children, occasionally in the setting of infantile hemangioendothelioma (IHE). IHE is usually detected within the first 6 months of life with fetal ultrasonography (USG). Proliferation of hepatic masses after the first year is less characteristic of hepatic hemangioendothelioma and should raise the suspicion of a malignant tumor. The mortality rate for pediatric hepatic angiosarcoma is high and death usually occurs in the first 6 months.


 > Case Report Top


A 2-year-old male child presented to the pediatric outpatient department about 18 months ago with the mother who noticed distension of abdomen since 5 months. It was insidious in onset and gradually progressive. The child also experienced dyspnea on playing and had difficulty in moving about. There was no history of fever, jaundice, pain in the abdomen, vomiting or constipation. No history of delayed milestones or neurological symptoms was noted. The clinical differential diagnoses were malaria, hepatoma or viral hepatitis. USG and computed tomography (CT) scan revealed a highly vascular lesion measuring 16 cm × 10 cm involving most of the liver with a cap of compressed normal liver surrounding it. With the clinical diagnosis of hemangioendothelioma, he was treated with high dose steroids for 2 months initially and later with propranolol, with no response to either drug. Since it was unresectable, an open liver biopsy was done which showed liver parenchyma with a lesion composed of plenty of variably sized proliferated vascular channels of varying caliber, predominantly small-sized vessels lined by a single layer of endothelial cells [Figure 1]a and [Figure 1]b. Vague lobules of tumor tissue separated by hyalinized fibrous tissue bands were seen [Figure 1]b. Entrapped bile ducts and hepatocytes were evident. At places, papillary tufts lined by endothelium were apparent [Figure 2]a. There was no nuclear pleomorphism of the endothelial lining cells or mitotic activity noted. There were no foci of necrosis or solid areas. Immunohistochemical staining done for Ki-67 revealed nuclear positivity in only 2% of the cells, indicating a low proliferative index [Figure 2]b. A diagnosis of IHE of the liver was made. The child then received eight cycles of chemotherapy composed of vinblastine and methotrexate along with propranolol. There was a dramatic response to this therapy, and the child was planned for resection of the residual mass measuring about 8 cm × 5 cm. Subsequently, unfortunately, the tumor significantly grew in size, within a matter of 1 month, measuring about 16 cm × 10 cm on contrast-enhanced computed tomography abdomen [Figure 3], with the consistency being firm with a bosselated surface. In addition, there was a significant increase in the vascularity of the tumor and CT scan of the chest showed multiple lung nodules suggestive of metastases with a bilateral basal consolidation. An open liver biopsy done at this time showed features of a vascular tumor as described above. Also seen were cavernous spaces at the edge of the tumor [Figure 4]a. In addition, an infiltrating solid tumor arranged in lobules with foci of hemorrhage and necrosis was seen [Figure 4]b. A few spindle cell areas were also seen in the tumor [Figure 5]a. Lining the vascular spaces were atypical endothelial cells which were large, oval with vesicular nuclei and prominent nucleoli. The mitotic count was 10 per 10 high power fields [Figure 5]b. Immunohistochemistry revealed strong positivity for CD34 throughout the tumor, including the solid area, and 65% of the cells in the solid area showed nuclear positivity for Ki-67 indicating high proliferative activity [Figure 6]a and [Figure 6]b. Based on the radiological, histopathological and immunohistochemical features, a final diagnosis of hepatic angiosarcoma arising in an IHE was arrived at. After the diagnosis of angiosarcoma, the child was treated with chemotherapy but could not withstand the treatment as he developed progressive neutropenia and thrombocytopenia. The patient refused further treatment and the family was told about the prognosis. The patient was lost to further follow-up.
Figure 1: (a) Anastomosing vascular channels adjacent to a portal tract; (b) vascular tumor with fibrocollagenous stroma (H and E, ×100)

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Figure 2: (a) Papillary tufts lined by endothelial cells (H and E, ×100); (b) tumor cells show 2% nuclear staining for Ki-67 (IHC, ×200)

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Figure 3: Contrast-enhanced computed tomography abdomen showing a large, heterogeneous, hypoattenuated vascular lesion involving the liver

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Figure 4: (a) Cavernous vascular spaces at the edge of the tumor (H and E, ×100); (b) solid area of tumor with foci of hemorrhage and necrosis (H and E, ×100)

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Figure 5: (a) Entrapped bile ductule in a spindle cell-rich area of tumor arranged in fascicles (H and E, ×200); (b) solid area in the tumor with mitoses in the center (H and E, ×200)

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Figure 6: (a) Tumor cells show strong membrane positivity for CD34 (IHC, ×200); (b) tumor cells show 65% nuclear staining for Ki-67 (IHC, ×200)

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 > Discussion Top


Malignant liver tumors account for approximately 1% of all pediatric malignancies.[1] Pediatric hepatic angiosarcoma is not only extremely rare but has been regarded by some authors to be a distinct entity from the hepatic angiosarcomas seen in adults.[2] Histologically, the tumors often consist of hypercellular whorls of spindled cells arranged in fascicles or bundles with slit-like vascular spaces or in a whorl-like arrangement, and mitotic figures range from few to many.[2],[3] Epithelioid features may predominate, but the presence of pleomorphic cells with endothelial differentiation is a feature common for all variants. The tumor shows mixed histology with sinusoidal, solid, papillary and cavernous growth patterns. In our case, the tumor showed solid, papillary and cavernous growth patterns.[4] Invasion of hepatic venules and portal vein branches is common and may account for hemorrhage and necrosis. Proliferation of hepatic masses after the first year is less characteristic of IHE and should raise suspicion of a malignant tumor. The etiology of hepatic vascular neoplasms in children is unknown, although the regression of most such tumors within months of the child's birth suggests that the maternal milieu plays some role. There is convincing evidence that the adult form of hepatic angiosarcoma follows exposure to thorotrast, arsenic, vinyl chloride, cyclophosphamide and anabolic steroids, but more than 75% of the cases have no apparent risk factor. Falk et al. have described 4 cases of pediatric HAS, in which one case had exposure to elevated levels of arsenic that led to its progression.[5] Our case highlights the development of angiosarcoma in an IHE. Most often the IHE progresses to a benign cavernous hemangioma or becomes obliterated by diffuse fibrosis. In our case, the presence of the IHE component as well as the angiosarcoma component adjacent to each other suggests development of the latter from the former. The clinical presentations can include hepatomegaly, ascites, jaundice, thrombocytopenia, hemoperitoneum and liver failure.[6] These lesions can lead to high mortality early on due to severe hypothyroidism from expression of type 3 iodothyronine deiodinase in these lesions.[2] In children, these tumors present with a rapidly enlarging liver and by the time they are diagnosed, the lesion is often unresectable.[2] Nord et al. have reported a case of a 3-year-old boy whose initial percutaneous biopsy showed benign hemangioendothelioma, later autopsy revealed HAS with pulmonary metastasis.[2] Metastasis is common, frequently to the lung as in our case. Nord et al. have reported a case of multiple cutaneous infantile hemangiomas associated with a vascular lesion of the liver in an infant that was proven to be hepatic angiosarcoma after surgical excision.[2] Even in the best of hands, imaging alone cannot definitively distinguish a benign from a malignant vascular tumor, therefore, histopathology remains the “gold standard.”[2] HAS has a limited response to chemotherapy, radiation and resection with universal tumor recurrence with liver transplant.[7] In our case the liver biopsy specimen provided the answer for the progressive hepatomegaly and resistance to chemotherapy and steroids.

This case report highlights the rarity of pediatric hepatic angiosarcomas developing in the background of hepatic IHE. The diagnosis is crucial as it alerts the clinician about treatment failure strategies. Risk of hemorrhage on biopsy and sampling error are the main limitations for the clinician. At the same time, histopathology gives the accurate diagnosis. The prognosis is essentially poor especially when the child has metastatic deposits in the lungs, as in our case. There is a need to evaluate a wide range of pediatric hepatic vascular tumors in terms of environmental, hormonal or other exposures to the child before and after birth besides multidisciplinary treatment protocol for a favorable outcome.


 > Acknowledgments Top


The authors are grateful to Dr. A. C. Ashok, Principal and Dean, M. S. Ramaiah Medical College, for his kind support in publishing this paper. They also thank Dr. Usha RaviKumar for helping out for immunohistochemistry.

 
 > References Top

1.
Litten JB, Tomlinson GE. Liver tumors in children. Oncologist 2008;13:812-20.  Back to cited text no. 1
    
2.
Nord KM, Kandel J, Lefkowitch JH, Lobritto SJ, Morel KD, North PE, et al. Multiple cutaneous infantile hemangiomas associated with hepatic angiosarcoma: Case report and review of the literature. Pediatrics 2006;118:e907-13.  Back to cited text no. 2
    
3.
Dimashkieh HH, Mo JQ, Wyatt-Ashmead J, Collins MH. Pediatric hepatic angiosarcoma: Case report and review of the literature. Pediatr Dev Pathol 2004;7:527-32.  Back to cited text no. 3
    
4.
Fletcher CD. Diagnostic Histopathology of Tumors. 3rd ed., Vol. 1. Philadelphia, USA: Churchill Livingstone Elsevier Publication; 2007. p. 439-40.  Back to cited text no. 4
    
5.
Falk H, Herbert JT, Edmonds L, Heath CW Jr, Thomas LB, Popper H. Review of four cases of childhood hepatic angiosarcoma – elevated environmental arsenic exposure in one case. Cancer 1981;47:382-91.  Back to cited text no. 5
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6.
Premalata CS, Kumar RV, Appaji L, Prabhakaran PS. Childhood hepatic angiosarcoma – a case report. Indian J Pathol Microbiol 2005;48:487-9.  Back to cited text no. 6
    
7.
Xue M, Masand P, Thompson P, Finegold M, Leung DH. Angiosarcoma successfully treated with liver transplantation and sirolimus. Pediatr Transplant 2014;18:E114-9.  Back to cited text no. 7
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

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