BRIEF REPORTInfantile Hemangioendothelioma of the Liver

Prashant Amonkar, Sangeeta Desai, MD,* Rahul Deb, Shubhada Kane, MD,Purna Kurkure, MD, R.K. Deshpande, MS, and Roshni Chinoy, MD

Key words: infantile hemangioendothelioma; liver tumor; vascular tumors

Infantile hemangioendothelioma (IHE) of the liver isan uncommon tumor. Two subtypes have been described.Type 1 has recognizable but irregularly dilated vascularspaces in a fibromyxomatous stroma. Type 2 is describedas having a more aggressive histology. It is marked bypoorly formed and anastamosing channels with papillaelined by atypical endothelial cells and is potentially ma-lignant [1].

Our experience with the disease in a male child high-lights the pathologic aspects of this rare tumor with spe-cial reference to the immunohistochemistry and electronmicroscopy as well as the subsequent clinical course. Theinitial part of the disease course of this patient, especiallypertaining to raised alpha-feto protein levels, has alreadybeen reported [2].

Our patient was the first born of a nonconsanguineousmarriage. He presented with increasing hepatomegalyand anemia in 1992 at the age of 3 months. Computedtomography (CT) revealed massive hepatomegaly withmultiple hypoechoic areas in the liver. The alpha fetoprotein (AFP) level was 700 ng/ml (normal4 0 ng/ml at2 months), which was elevated but equivocal for the ageof 3 months (upper limit of normal4 10–350 ng/ml at 3months). CT-guided fine-needle aspiration cytology(FNAC) revealed a hemorrhagic aspirate showing someround cells admixed with normal hepatocytes. The work-ing diagnosis was neuroblastoma stage 4 S (primary siteunknown) and chemotherapy was started. About 2 weekslater, the child developed a reddish lesion at the angle ofmouth. This was biopsied and showed a hemangioma. Aliver biopsy was then done and the diagnosis waschanged to IHE.

There was a good response to the chemotherapy thatincluded cyclophosphamide and doxorubicin. There wasradiologically documented regression in the size of thetumor nodules. The child was apparently well controlledfor about 4 years with no evidence of relapse, but hepa-titis B surface antigen (HBsAg) was constantly positive.

The size of the hepatic lesions, one of which wasexophytic, then increased at the age of 4 years in 1996. A

malignant change in the preexisting IHE was suspected,and the exophytic mass was excised. The clinical coursecontinued downhill with congestive cardiac failure(CCF), ascites, loss of weight, and enlargement of theintrahepatic lesions. He was not expected to live, but waslost to follow-up.

The excised tumor weighed 580 g and measured 15 ×10 × 8 cm. It was bosselated and the cut surface was soft,reddish with few whitish, fibrous areas. On light micros-copy, it was composed of multiple vascular channelslined by one or more layers of plump endothelial cells(Fig. 1). Lying in the stroma between these cells wereprominent perithelial cells. The vascular lumina weresmall or collapsed in most of the spaces. Cavernousspaces were absent. A vague lobular configuration waspresent. The tumor was not well circumscribed and wasinfiltrating the surrounding parenchyma as multiple nod-ules. Large areas of necrosis and hemorrhage were seen.Mitotic activity was in the range of 0–2/hpf. Adjacentliver parenchyma showed chronic portal triaditis; how-ever, no liver cell injury was seen. A diagnosis of infan-tile hemangioendothelioma type 2 was made on lightmicroscopy.

The endothelial cells were strongly immunoreactive tofactor VIII, Ulex europaeus, and vimentin. The perithe-lial cells were immunoreactive to smooth muscle actinand vimentin, confirming their pericytic nature. Ultra-structurally, the tumor cells showed the presence of basallamina on the antiluminal border (Fig. 2). The cells alsoshowed the presence of cell junctions (Fig. 3). Thesefindings confirmed the endothelial nature of the cells.

Departments of Pathology, Medical Oncology and Surgery, Tata Me-morial Hospital, Parel, Mumbai, India

*Correspondence to: Dr. Sangeeta Desai, Tata Memorial Hospital, Dr.Ernest Borges Road, Parel, Mumbai, 400 012, India. E-mail:medimail@tmc.ernet.in

Received 7 April 1998; Accepted 25 September 1998

Medical and Pediatric Oncology 32:392–394 (1999)

© 1999 Wiley-Liss, Inc.

DISCUSSION

Infantile hemangioendothelioma is a rare tumor foundalmost exclusively in children before 6 months of age. Itis a highly cellular hemangioma that may appear as soli-tary or multiple nodules that may be associated withhemangiomas in other sites, particularly the skin. Fiftypercent of patients have one or more cutaneous heman-giomas [1,3]. A female preponderance has been noted.Our child was a boy with only multiple hepatic nodulesat presentation.

Dehner and Ishak have subdivided IHE into two his-tologic types: type 1 and type 2. The latter is character-ized by aggressive behavior and needs to be distin-guished from angiosarcoma or epithelioid hemangioen-dothelioma [1,4,5]. Although type 2 IHE is supposed tobe associated with a poorer prognosis, some large serieshave not substantiated this observation [6,7].

In our case, light microscopy, immunohistochemistry,and ultrastructural examination confirmed the diagnosisof IHE, corroborating previously reported cases [7–10].Conventionally, IHE is associated with asymptomatic he-patomegaly, congestive cardiac failure, thrombocytope-nia, hepatic dysfunction, and massive hemoperitoneum.Spontaneous involution in the first year has been de-scribed [1]. There may be slight elevation of AFP inthese tumors [11].

In our patient, the initial differential was betweenhepatoblastoma and neuroblastoma based on a fine-needle aspiration cytology report of round cells, and theage. The AFP levels of 700 ng/ml were equivocal as theupper limit of normal level at 3 months is 10–350 ng/ml.Thus, though increased, the levels were not as high aswould be expected in a case of hepatoblastoma. Also,considering the multifocality of the lesions and the factthat the child was thriving well in spite of the disease, adiagnosis of neuroblastoma stage 4 S (primary site un-known) was favored. Subsequent development of a hem-angioma at the angle of the mouth proved to be a clue to

the true diagnosis. With the known association of hepa-tomegaly, CCF, and integumentary hemangiomata, avascular tumor was suspected, which was later proved tobe an IHE. Thus, somewhat elevated AFP levels do noteliminate vascular tumors from the differential diagnosisof liver tumors in a child.

The presence of multiple nodules, infiltrative borders,and lack of cavernous spaces, as in our case, are poorprognostic features [7]. A high mortality rate is associ-ated with such tumors largely as a result of progressivehepatic failure, CCF, or hyperconsumptive coagulopathy(Kasabach Merritt syndrome) [11]. In our child, evenafter resection of the exophytic lesion, the patient’s gen-eral condition worsened.

ACKNOWLEDGMENTS

We thank Dr. Shubhada Bharde for the invaluablehelp rendered.

Fig. 1. Intraluminal buds in the vascular lumina. H&E, ×200.Fig. 2. Cell invested by a continuous layer of basal lamina (arrow).EM, ×12,000.

Fig. 3. A row of cell junctions is seen (arrow). EM, ×15,000.

Infantile Hemangioendothelioma of Liver 393

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