Hemangioendothelioma

* Hepatic infantile hemangioendothelioma (IHE) is a rare benign vascular tumor of the liver found mostly in infancy and early childhood. We describe herein a tumor of the liver, morphologically indistinguishable from IHE, that presented in an adult. The patient is a 56-year-old woman with a history of ductal carcinoma in situ of the left breast and a mass in the liver. The patient underwent resection of the tumor, and after 23 months of follow-up she is alive with no evidence of expansion of the liver tumor.

(Arch Pathol Lab Med. 2001;125:931-932)

Infantile hemangioendothelioma (IHE) is a rare benign vascular tumor of the liver. It is the most common mesenchymal tumor of liver in infancy.' Infantile hemangioendothelioma has been reported in children up to 3 years old, but most cases are diagnosed in children younger than 6 months? It has also been reported in an 18-yearold patient,2 but it has never been described in older patients.

Herein, we describe a liver tumor, morphologically indistinguishable from IHE, in an adult with no apparent risk factors.

REPORT OF A CASE

A 56-year-old woman with a history of lumpectomy and radiation therapy for ductal carcinoma in situ of the left breast underwent routine evaluation for metastatic disease. An abdominal computed tomography (CT) revealed 2 lesions in the right lobe of the liver: a hypodense enhancing lesion in the posterior segment of the right lobe 5 cm in diameter and a smaller (1 cm in diameter), similar-looking lesion in the medial segment. Laboratory results, including liver function tests and a--fetoprotein levels, were within normal limits. There were no serologic markers for hepatitis A, B, or C viruses. The patient had no known history of drug or toxin exposure, including vinyl chloride, thorotrast, oral contraceptive, or anabolic steroids.

The patient underwent right hepatic lobectomy with total resection of the lesions based on surgical exploration and intraoperative ultrasound examination. A follow-up CT 17 months later revealed a lesion 1.5 cm in diameter in the left hepatic lobe and a second lesion 0.7 cm in diameter in the lower aspect of the liver. These lesions remained unchanged on a subsequent CT 4 months later. No further investigation was performed.

PATHOLOGIC FINDINGS

The right hepatic lobe measured 15 x 21 x 7 cm. On cut section 3 discrete tumors were found, measuring 5, 1, and 0.5 cm in greatest dimension. They all looked alike. The 3 tumors were identical-spongy, red-brown, with illdefined margins. Microscopically, they consisted of thinwalled vascular channels lined by a single layer of plump endothelial cells. The vascular channels typically had small lumina and contained red blood cells and foci of extramedullary hematopoiesis. Toward the center of the neoplasms, the vascular spaces were enlarged and dilated, resembling a cavernous hemangioma. In the central region, an organized thrombus was noted. The tumor grew in an expansile fashion into the adjacent liver, spreading along portal veins. Tumor cells were relatively monomorphic, with small to medium regular nuclei and conspicuous eosinophilic nucleoli (Figure 1). They displayed mild pleomorphism and minimal mitotic activity. Small bile ducts were scattered throughout the mass. The neoplastic cells stained with vimentin and factor VIII-related antigen (Figure 2) and did not stain with cytokeratin and S100 protein. Ki-67/MIB-1 stained only occasional nuclei. The surrounding hepatic parenchyma showed normal architecture and mild centrilobular steatosis.

COMMENT

We describe herein a multifocal vascular neoplasm with features of IHE type I found incidentally in a 56-year-old woman.

Infantile hemangioendotheliomas of the liver, as the name implies, are tumors of infancy and childhood.-3 The age distribution is from prematurity to 3 years, with most cases diagnosed within the first 6 months of life. One patient aged 18 years was mentioned in a review of 91 cases of IHE .2 There have been no detailed case reports of IHE of the liver in adults. These tumors may be solitary or multiple, 2,4 and 30% of the reported cases are associated with hemangioendothelioma of skin, lymph nodes, spleen, lung, and bone. Infantile hemangioendotheliomas are ill defined and locally invasive.2 Histologically, the most common form (type 1) is composed. of small vessels with plump endothelium; in places they may appear solid due to inconspicuous vascular lumina. Mitoses are rare and there is no significant cellular pleomorphism. Residual hepatic parenchyma, including portal tracts, can be incorporated into the lesion. In the rarer second form (type 2), there is nuclear pleomorphism, multilayering of cells, and budding of endothelium into the vessels.4 5 The biological behavior of IHE is benign, but the patient may have a poor outcome because of complications. These include arteriovenous shunts, giving rise to congestive heart failure, bleeding diathesis due to platelet consumption, and massive hemoperitoneum resulting in rupture. In a series of 91 patients, Selby et alz found the presence of multiple tumor nodules and the absence of cavernous differentiation to be the only poor prognostic indicators. However, cases of angiosarcoma of the liver developing in IHE of the liver have been recorded.6

The tumor described in this report does not have the appearance of capillary or cavernous hemangioma or angiosarcoma, which are the most commonly encountered vascular hepatic neoplasm in adults. Hemangiomas are usually well demarcated and composed of vessels supported by a collagenous stroma that do not contain portal tracts or hepatocytes, whereas in our case the tumor grew in an expansile fashion into the adjacent liver tissue. In angiosarcoma, the cells are spindled, hyperchromatic, and arranged in solid sheets in the center, whereas atypical cells are seen lining sinusoids at the periphery of the lesion. The lack of cellular atypia and anastomosing vascular channels in our case do not support a diagnosis of angiosarcoma. Mesenchymal hamartoma can also be ruled out, since it is made up of a mixture of edematous myxoid tissue, with blood and lymph vessels, bile ducts, and cords of hepatocytes. This combination of elements is lacking in our case. The tumor, although cytologically benign, seemed to spread along portal veins in an infiltrating fashion. The fact that the tumor was multifocal is somewhat disturbing, raising the possibility of metastases from an extrahepatic neoplasm. However, at present, 23 months after resection, there is no evidence of a primary malignant tumor outside the liver, no clinical symptoms related to the liver, and no evidence of metastatic foci outside the liver. The findings in the follow-up CTs were interpreted by the radiologist as consistent with metastasis of a vascular tumor. In view of the multifocality present in the pathological specimen and the slow-growing course of the present lesions, we believe that the findings represent slow-growing residual disease, although recurrent disease in the remaining liver tissue cannot be ruled out.

Surgical resection is usually required for hepatic IHE both due to the difficulty of diagnosing the lesion on needle biopsy because of its histological diversity and since the tumor is of undetermined malignant potential. The slow-growing residual tumor in our case stresses the difficulty in achieving clean surgical margins in this infiltrative tumor. Therefore, postoperative adjuvant therapy should be considered.

We thank Dr Demetris from University of Pittsburgh Medical Center for reviewing the case and helping confirm the diagnosis.

References

1. Dachman AH, Lichtenstein JE, Friedman AC, Hartman D. Infantile hemangioenclothelioma of the liver: a radiologic-pathologic-clinical correlation. A]RAm Roentgenol. 1983; 140:1093-1096,

2. Selby DM, Stocker JT, Waclawiw MA, Hitchcock CL, Ishak KG. Infantile hemangioendothelioma of the liver. Hepatology. 1994;20:39-45.

3. Luks Fl, Yazbeck S, Brandt ML, Bensoussan AL, Brochu P, Blanchard H. Benign liver tumors in children: a 25-year experience. j Pediatr Surg. 1991;26: 1326-1330.

4. Dehner LF, Ishak KG. Vascular tumors of the liver in infants and children. Arch Pathol. 1971;92:101 -111.

5. Yasunaga CH, Sueishi K, Ohgami H, Suita S, Kawanami T Heterogenous expression of endothelial cell markers in infantile hemangioendothelioma. Am Clin Pathol. 1989;91:673-681.

6. Weinberg AG, Finegold MI. Primary hepatic tumors of childhood. Hum Pathol. 1983;14:512-537.

Judith Diment, MD; Oded Yurim, MD; Orit Pappo, MD

Accepted for publication January 11, 2001.

From the Departments of Pathology (Drs Diment and Pappo) and Surgery (Dr Yurim), Hadassah University Hospital, Jerusalem, Israel.

Reprints: Orit Pappo, MD, Department of Pathology, Hadassah University Hospital, P.O. Box 12000, Jerusalem 91120, Israel (e-mail: Pappo@cc.huji.ac.il).

Copyright College of American Pathologists Jul 2001
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