Hepatic Neoplasms in Children

Ann M. Polcari

The liver is an intraperitoneal organ located below the diaphragm in the right upper quadrant (RUQ) of the abdomen, extending from the fourth to fifth rib to just below the costal margin (Figure 50.1).
It is covered almost entirely by Glisson capsule, a tough, fibrous sheath. The posterior surface has a “bare area” where the inferior vena cava (IVC) and gallbladder lie.
The liver has dual blood supply:
- Hepatic system (25%) includes the hepatic artery, which originates from the celiac trunk.
- Portal system (75%) includes the portal vein, which carries nutrient filled blood from the gastrointestinal system to the liver, as well as venous blood from the spleen.
Venous drainage from the liver is via the IVC.
The gallbladder is located on the posteroinferior surface of the liver. It holds bile, which is removed from the liver via the hepatic duct.
The “porta hepatis,” or the hepatoduodenal ligament, contains the portal vein posteriorly, hepatic artery medially, and common bile duct laterally.

EPIDEMIOLOGY AND ETIOLOGY

Prevalence

Hepatic neoplasms in children are rare, comprising only 1% to 2% of all childhood cancers.¹
Metastatic tumors (eg, Wilms tumor, lymphoma, neuroblastoma) to the liver are more common than primary hepatic tumors.²

Etiology

Etiology varies by tumor type. Some are associated with genetic syndromes; many arise from de novo mutations.
Primary hepatic neoplasms in children can be identified as benign or malignant.
The benign tumors include (Table 50.1) the following:
- Infantile hemangioendothelioma
- Mesenchymal hamartoma
- Focal nodular hyperplasia
- Hepatocellular adenoma
The malignant lesions include (Table 50.2) the following:
- Hepatoblastoma
- Hepatocellular carcinoma
- Undifferentiated embryonal carcinoma
- Rhabdomyosarcoma of the biliary tree

Figure 50.1 Peritoneal and visceral relationships of liver. A, The liver is divided into right and left lobes by the falciform and coronary ligaments (anterior view, diaphragmatic surface). B, The posteroinferior aspect of the liver (visceral surface). (Reprinted with permission from Moore KL, Dalley AF, Agur AMR. Clinically Oriented Anatomy. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2014.)

Clinical Presentation

Classic presentation: Clinical presentation also varies by the type of tumor (Tables 50.1 and 50.2), but symptoms are most often nonspecific and one must have a high level of suspicion.

Most pediatric hepatic neoplasms are almost always found incidentally on imaging.
Some tumors grow so rapidly that they present with a palpable mass in the RUQ, with nausea or vomiting due to local compressive symptoms.
RUQ pain and jaundice are also common.

DIAGNOSIS

Laboratory Findings

Significant laboratory findings differ by tumor type (Tables 50.1 and 50.2).
Alpha-fetal protein (AFP) is elevated in many hepatic tumors and is typically followed after treatment to determine response.

Imaging Findings

The initial modality of choice is ultrasound, particularly when a patient presents with RUQ pain or palpable mass. However, additional imaging and even biopsy are typically required to make the diagnosis.
Some hepatic tumors can be diagnosed by CT with contrast alone; others are better visualized by MRI with contrast. See Tables 50.1 and 50.2 for information about key findings in particular liver neoplasms.

SURGICAL MANAGEMENT

Conservative management with serial ultrasound or CT imaging is appropriate for most benign, asymptomatic lesions.
Chemotherapy is appropriate for known-responsive lesions, which are neoadjuvant or adjuvant depending on the type of tumor.

Operative Intervention

Liver Resection

The Pretreatment Extent of Disease (PRETEXT) system was developed by the International Society of Pediatric Oncology on Childhood Liver Tumors (SIOPEL) group to identify suitable candidates for primary resection (Figure 50.2).³

TABLE 50.1 Benign Pediatric Liver Tumors

	Infantile Hepatic Hemangioma (Also Termed “Infantile Hemangioendothelioma”)	Mesenchymal Hamartoma	Focal Nodular Hyperplasia	Hepatocellular Adenoma
Epidemiology	Most common benign solid liver tumor in children Age: <6 mo; almost all <2 mo Gender: slight female predominance	Second most common benign pediatric tumor Age: <2 y Gender: male predominance	4%-10% of benign pediatric tumors Age: 2-5 y Gender: female predominance	Very rare—4% of all tumors in children Age: >10 y Gender: female predominance, especially those using oral contraceptives (OCPs)
Etiology and associations	Syndromes: Osler-Weber-Rendu, Klippel-Trenauney-Weber, Ehlers-Danlos, Beckwith-Wiedemann	Heterogeneous genetic causes	Liver trauma, hemochromatosis, Klinefelter syndrome, possibly OCP use	Infants and young children: >50% associated with glycogen storage disease, Fanconi anemia, or tyrosinemia Older children: OCP use, anabolic steroid use
Clinical presentation	May be asymptomatic Classic complex: hepatomegaly, congestive heart failure (CHF), and anemia Often with cutaneous hemangiomas	Neonates: Highoutput CHF with pulmonary hypertension Older children: abdominal distension, ascites, with or without a palpable mass (ascites) Nausea or vomiting due to compression	Typically asymptomatic If symptomatic: abdominal pain, hepatomegaly, decreased appetite with weight loss and fatigue	Typically asymptomatic May have intermittent abdominal pain 10% present with acute abdominal pain due to hemorrhage into tumor
Laboratory findings	Anemia (50%), AFP may be elevated	AFP may be elevated	LFTs may be elevated	–
Imaging	Best modality: MRI with contrast Note: Biopsies are avoided owing to vascularity	Multiseptated, multicystic (fluid-filled) mass R-sided predilection	CT with contrast will show early enhancement with central scar	CT with contrast shows multiple feeding vessels (differentiates from FNH) May show areas of calcification or hemorrhage
Pathology	Gross: May be solitary, multifocal (up to 25 lesions), or diffuse Range from 1 to 13 cm Microscopic: Layers of flat endothelial cells on a supporting fibrous stroma GLUT-1 positive	Gross: Large, well-circumscribed, solitary lesion 8-10 cm diameter Microscopic: Mixture of bile ducts, liver cells, mesenchyme with dilated bile and lymphatic ducts	Gross: Well circumscribed, lobulated, unencapsulated Single feeding artery with central stellate scar Microscopic: Disorganized hepatocyte hyperplasia in nodules Overexpression of ANGPT1 and 2	Gross: Solitary, unencapsulated Microscopic: Large sheets of cells resembling normal hepatocytes separated by dilated vessels No portal vessels or bile ducts
Treatment	Some regress spontaneously after 1 y of age Asymptomatic: Serial ultrasounds to monitor growth. Propranolol recently proposed Symptomatic: Consider surgical resection or embolization Transplant is last resort Note: Monitor for resolution, malignant transformation has been reported	Spontaneous resolution is rare Recommended therapy is excision and can be curative Risk of development into undifferentiated embryonal sarcoma	Asymptomatic: Observation with serial ultrasound Symptomatic, >5 cm, progression: biopsy followed by resection No malignant potential	Remove offending agent (OCPs, anabolic steroids). If stable, observe Resection is definitive treatment
Data from Zheng H, Finn LS, Murray KF. Neoplasms of the liver. In: Wyllie R, Hyams JS, Kay M, eds. Pediatric Gastrointestinal and Liver Disease. 5th ed. Philadelphia: Elsevier; 2016:582-589.e4; Andrews WS. Lesions of the liver. In: Holcomb GW, Murphy JP, eds. Ashcraft’s Pediatric Surgery. 5th ed. Philadelphia: Saunders Elsevier; 2010:895-914; and Sebire NJ, Ashworth M, Malone M, Jacques TS, Rogers BB, eds. Diagnostic Pediatric Surgical Pathology. 1st ed. Philadelphia: Elsevier; 2010. Images reprinted with permission from Pizzo PA, Poplack DG. Principles and Practice of Pediatric Oncology. 7th ed. Philadelphia: Wolters Kluwer Health; 2016; Sanders RC. Clinical Sonography: A Practical Guide. 5th ed. Philadelphia: Wolters Kluwer Health; 2016; Fiser S. The ABSITE Review. 5th ed. Philadelphia: Wolters Kluwer Health; 2017; Brant WE, Helms C. Fundamentals of Diagnostic Radiology. 4th ed. Philadelphia: Wolters Kluwer Health; 2013; Husain AN, Stocker JT, Dehner LP. Stocker and Dehner’s Pediatric Pathology. 6th ed. Philadelphia: Wolters Kluwer Health; 2016, Stocker JT, Dehner LP, Husain AN. Stocker and Dehner’s Pediatric Pathology. 3rd ed. Philadelphia: Wolters Kluwer Health; 2011; and Rubin R, Strayer DS, Rubin R. Rubin’s Pathology. Philadelphia: Wolters Kluwer Health; 2012.