Mesenchymal Hamartoma With Elevated Alpha-Fetoprotein: A Diagnostic Pitfall

Abstract

Mesenchymal hamartoma (MH) is a benign liver tumor accounting for 3% to 8% of all liver tumors in children, commonly manifesting before 3 years of life. Distinguishing MH from hepatoblastoma and other liver tumors relies on imaging and alpha-fetoprotein (which is usually within normal range in MH), before histologic examination. We report a case of a hepatic MH associated with elevated alpha-fetoprotein, leading to a misdiagnosis of hepatoblastoma and the administration of chemotherapy. We draw the attention to the diagnostic difficulty and pitfalls related to alpha-fetoprotein elevation in the setting of a liver tumor, and we highlight the importance of imaging and histology in establishing the diagnosis.

Introduction

Mesenchymal hamartoma (MH) of the liver is a benign neoplasm, composed of abnormal elements of blood vessels, small groups of hepatocytes, and bile ducts. ¹

It accounts for 3% to 8% of all liver tumors in children, and is the second most common benign liver neoplasm after infantile hemangioendothelioma in children below the age of 3 years. ² Hepatoblastoma is the most frequent primary malignant liver neoplasm, and is, hence, an important differential diagnosis that should be evoked in the case of a pediatric hepatic tumor. ³

Our case draws attention to the diagnostic difficulty and pitfalls related to alpha-fetoprotein elevation in the setting of a liver tumor in a child, and highlights the importance of imaging characteristics on ultrasound and computed tomography, and the importance histology in the diagnosis.

Case Report

An 11-month-old female infant with unremarkable personal and family history and no anomalies during pregnancy, presented for abdominal distension for more than a month.

The biological work-up showed an elevated and fluctuating alfa-fetoprotein (AFP) measured at 653 ng/ml initially, 1000 ng/ml 2 days later, and 783 ng/ml the next week. ASAT and ALAT were slightly elevated at 111 and 55 u/l respectively, with no elevation of biological infectious markers.

An abdominal ultrasound was performed, showing a voluminous multiseptated cystic mass in the liver, with no detected flow on color doppler mode (Figure 1). A chest-abdomen-pelvis computed tomography (CT) was performed subsequently, showing a multicystic well-defined hepatic mass with regular contours, a thick wall, containing fluid and thick enhanced septas with a hyper-enhanced nodule within, occupying segments VIII, V and IV of the liver (Figure 2). No other hepatic lesions, lymphadenopathies nor distal lesions were found.

Figure 1.

Ultrasound image on the transverse view, using a convex probe, showing the mesenchymal hamartoma manifesting as a predominantly cystic mass of the liver.

Figure 2.

Axial post-contrast CT image of the abdomen, showing the mesenchymal hamartoma (Orange arrows) of the liver. A hyper-enhancing nodule was seen within (Blue arrow). Spared segments II and VI of the liver can be seen (Asterisk).

The 2 main suggested differential diagnoses were mesenchymal hamartoma and hepatoblastoma, due to the age of the patient. The diagnosis of hepatoblastoma was favored, because of the elevated serum AFP levels. Subsequently, the patient received 4 cures of Cisplatin-based chemotherapy.

Next, a control CT was performed 2 months after the initial one, showing a 33% increase in the size of the hepatic mass. This finding was worrying, and made the diagnosis of hepatoblastoma not likely, as it’s a tumor that is usually sensitive to chemotherapy. And AFP levels were still fluctuating around 700 ng/ml.

The decision to perform surgery was made for both diagnostic and therapeutic purposes. It involved a complete resection of the encapsulated mass, as well as a retrograde cholecystectomy due to the gallbladder’s adherence to the mass (Figure 3).

Figure 3.

Images of liver mass: intraoperative (A), and after resection (B).

The histological examination showed a mixture of bile ducts, hepatocyte trabeculae, and congestive vessels on a hemorrhagic fibrous background (Figure 4).

Figure 4.

Histopathologic examination images (A and B) (Routine stain, 40X magnification), showing a mixture of bile ducts, hepatocyte trabeculae, and congestive vessels on a hemorrhagic fibrous background.

No post-operative complications were observed, and control AFP serum levels were back to normal range, 1 month after surgery,

Discussion

Hepatoblastomas are the main liver tumors associated with elevated AFP serum levels, usually excessively high, up to or even above 10 000 ng/ml. Nevertheless, a mild to moderate AFP elevation can also be seen in hepatoblastomas, along with other liver tumors; hepatocellular carcinomas, yolk sac tumors, and other benign tumors (mesenchymal hamartoma, focal nodular hyperplasia and infantile hepatic hemangioendotheliomas), nevertheless, hepatoblastomas are usually associated with excessively high levels of AFP up to or even above 10 000 ng/ml.^4,5

In case of MH, serum AFP can sometimes be elevated, mildly to moderately, ⁴ especially in predominantly slid masses, up to 920 ng/ml in Chang et al series, ⁶ however, it can, more rarely, reach thousands of ng/ml,^7-9 up to 9240 ng/ml in a 7-month-old reported case. ¹⁰

The amount of hepatocytes in the MH is positively correlated with the serum level of AFP. This correlation may also support that the hepatocytes within the tumor mass are a true component of MH. ⁶

To note that a physiologic elevation of serum AFP levels can be found in healthy term infants in the first 6 months of life; As high as 200 000 ng/ml during the first days of life, rapidly decreasing to 30 to 5800 ng/ml at the end of the first month of life, 88 to 418 ng/ml at the end of the second month, 16 to 127 ng/ml at the end of the fourth month, and further decreases to 1 to 67 ng/ml at 6 months of age, which is very close to normal adult levels, then a further gradual decrease is observed. Premature infants tend to have higher levels of AFP than term infants. Hence, age and prematurity should be taken into account in the interpretation of AFP levels should take into account. ¹¹

In our 11-month-old patient, the serum AFP elevation was mild to moderate, and a predominantly cystic component, with thick septas and a thick wall on imaging, with presence of hepatocytes on histology.

Increased serum Alpha-Fetoprotein concentration due to MH or due to young patient’s age are 2 pitfalls that may lead to misdiagnosis of hepatoblastoma and the administration of chemotherapy. ¹

MH is most often cystic (85%); these cysts strongly favor a diagnosis of MH on imaging, but may be absent, especially in very young patients. ⁸ On ultrasound, MH typically manifests as a poorly vascularized multiseptated (thin or thick septas) cystic mass with possible hyperechoic nodules in the septas. On computed tomography it generally presents as a multiloculated mass with septas enhanced after contrast. The presence and the proportion of solid components is variable, and calcifications are exceptional. ¹ In our case no nodules were seen on ultrasound, however, on CT, a single hyper-enhancing nodule was visualized. To note that hepatoblastomas can also rarely manifest as a multiloculated mass.^12,13

Imaging also helps in planning the MH liver resection, the tumor position relative to the liver segments, bile ducts and vessels. ¹

When the imaging appearance is not suggestive, a biopsy can be proposed. ¹⁴

Complete surgical resection for both therapeutic purposes (due to the risk of recurrence and malignant transformation), and diagnostic purposes by histologic examination of the resected specimen. Liver transplantation can be considered for unresectable tumors. ¹⁴

Conclusion

Differentiating mesenchymal hamartoma from hepatoblastoma can be a diagnostic challenge; a mild to moderate elevation of AFP in the context of infantile hepatic mass is not an enough argument to establish the diagnosis of hepatoblastoma nor to initiate chemotherapy, as such elevation can be associated with MH along with other liver tumors. And an excessive elevation of AFP is, however, very suggestive of hepatoblastoma. The interpretation of this biological marker should also consider age and prematurity. Imaging can be suggestive of MH when it manifests as a multicystic liver mass, and histology confirms diagnosis.