Journal of Pediatric Gastroenterology & Nutrition:
Wildhaber, Barbara E.
Department of Pediatrics, Division of Pediatric Surgery, University of Geneva Children's Hospital, Geneva, Switzerland.
Address correspondence and reprint requests to Prof Barbara E. Wildhaber, MD, Médecin-Cheffe de Service, Chirurgie Pédiatrique, Hôpital des Enfants, Hôpitaux Universitaires de Genève, Rue Willy-Donzé 6, 1211 Genève 14, Switzerland (e-mail: Barbara.Wildhaber@hcuge.ch).
Received 17 July, 2011
Accepted 25 July, 2011
The author reports no conflicts of interest.
See “Widening Spectrum of Liver Angiosarcoma in Children” by Ackermann et al on page 615.
Pediatric vascular liver tumors are divided into infantile hemangioendothelioma (HE), cavernous hemangioma, and arteriovenous malformations. HE and cavernous hemangioma are mostly benign, asymptomatic, and found incidentally, and treatment is not necessary (1). They can be solitary or multifocal, they can be present in early infancy or appear later in childhood, they can recur even after having disappeared, and they can be of different histological types. Nevertheless, there is more than just the harmless incidental pediatric vascular liver tumor. Before we start a clinical discussion, we need to recognize that there are 2 types of histological patterns of liver HE in infants and children: HE type 1 is an orderly tumor having a pattern identical to that of the cutaneous hemangiomas, is usually benign, and regresses spontaneously with time; type 2 HE has, histologically, a more aggressive, irregular appearance, also can be called angiosarcoma, and is clearly a malignant tumor that needs aggressive treatment (2).
Unfortunately, imaging studies do not easily help to definitely differentiate between HE types 1 and 2. They show different contrast enhancements in computed tomography scans (centripetal vs irregular central) (3), but this may only raise suspicion and must lead to the decision to perform a biopsy. Because HE can present as multifocal disease, definite histological diagnosis is difficult to obtain in such cases because histology may be different from nodule to nodule. Serum parameters help neither; α-fetoprotein has no diagnostic value, because most often it is normal.
What can help us to distinguish between children with HE type 1 or type 2? There are different clinical pictures that must raise suspicion. First, HE of the neonate or infant may present with complications (eg, congestive heart failure) needing treatment (eg, steroids, chemotherapy, interferon, embolization), but it usually resolves with time and will not bother anymore. But beware! It seems that multifocal disease can show different behavior: As we learn from more than just sporadic case reports (as described in the article by Ackermann et al in this issue of JPGN(4)), this benign classified tumor if multifocal, may reappear later in childhood, and will have a devastating outcome; the relapse often is malignant and presents as HE type 2—as an angiosarcoma. This later presentation of HE type 2 probably indicates sarcomatous change in benign hemangiomatous tissue rather than an initial misdiagnosis (5). We may compare this observation to the possible evolution of mesenchymal hamartoma of the liver, in which an initially benign tumor can degenerate into a sarcoma (6). Another situation may be that imaging studies and clinical experience may clearly diagnose a type 1 HE in an infant, yet it may not respond to medical treatment. Cases have been described in which liver transplantation (LT) was needed to cure a baby; HE type 2 was discovered in the explants (4). A vascular liver tumor in a toddler also may lead us to the quick and easy diagnosis of “hemangioma.” Beware! it well may be an angiosarcoma, especially when the lesion is multifocal. Accordingly, and well outlined by Ackermann et al (4), there are 3 different situations that should alert us in the context of vascular tumors in the pediatric patient: a nonresponding HE in an infant; a recurrent HE in a toddler after recovery of infantile disease; and a newly appearing vascular tumor, solitary or mulfifocal, in a toddler (4). Beware of vascular tumors of the liver in children.
How will we treat these children? Angiosarcoma, that is, HE type 2, in children still is considered an uncontrollable oncological problem (7). Nonetheless, if localized in the pediatric liver and not associated with metastasis, LT may be a way out, with a good prognosis (4). In contrast, in adults, the results of LT for angiosarcoma are disastrous and angiosarcoma remains an absolute contraindication to LT (8). So, how can we dare to think of LT in children for the “same” indication? Certain features of the biology of malignant vascular tumors of the liver in childhood, with their counterpart in adults, have been reported (9) and may explain why LT in children for the same indication is much more successful than in adults. LT may indeed be superior to surgical tumor resection, because HE type 2 has a most aggressive behavior, and the risk of relapse in the remaining liver is high (4). If we compare, who would have thought that panhepatic and even metastatic pediatric hepatoblastoma would ever be accepted indications for LT, with a good prognosis (10)? HE type 2 may fit into the same category of pediatric liver tumors. The treatment outlined by Ackermann et al and others (4), that is LT, must indeed earn its place in the treatment of HE type 2.
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