Pediatric hepatic rhabdoid tumor: A rare cause of abdominal mass in children.

Pediatric hepatic rhabdoid tumors are rare tumors of the liver, with few cases reported in the literature. These aggressive tumors can be difficult to differentiate from hepatoblastomas on imaging alone, and surgical biopsy combined with special immunohistochemical stains can assist in differentiating these 2 tumor types. We present a case of hepatic rhabdoid tumor in a 7-month-old female infant, which was originally thought to be a hepatoblastoma; however, using BAF47 staining for INI-1 we were able to diagnose a rhabdoid tumor and affect the patient's medical oncologic therapy. Earlier detection and a better understanding of the imaging features of hepatic rhabdoid tumor may aid in improved patient management and treatment planning.

Introduction

Primary, malignant hepatic neoplasms in pediatric patients are rare, accounting for only 1%-2% of pediatric cancers. Hepatoblastoma is the most common primary malignant hepatic neoplasm, followed by hepatocellular carcinoma, undifferentiated sarcoma, angiosarcoma, and embryonal rhabdomyosarcoma [1]. Malignant rhabdoid tumors (MRTs) are rare, aggressive lesions most commonly found in the kidney but also arising in other soft tissues and the central nervous system. Rhabdoid tumors may be seen in the liver commonly presenting with abdominal distension and hepatomegaly. It may be difficult to distinguish rhabdoid tumors from hepatoblastoma, although the poorer prognosis and differing treatment approaches make early differentiation important. As opposed to hepatic MRT, hepatoblastoma typically has an older age at diagnosis (16 months vs 8 months), less frequently undergoes spontaneous rupture with systemic symptoms, and often has an elevated alpha fetal protein (AFP) (90% of cases) [2]. There is also strong evidence suggesting that the prevalence of hepatoblastoma is inversely proportional to birth weight [1]. We present a case of pediatric hepatic rhabdoid tumor, which resembled hepatoblastoma on imaging and required surgical biopsy and immunohistochemical staining for final diagnosis.

Case report

A 7-month-old female infant was transferred from an outside hospital for management of fever in the setting of suspected leukemia. She had a 1-week history of fever with nonbilious, nonbloody emesis, 0.5 lb weight loss, and progressive abdominal distension. At the outside hospital, she was initially diagnosed with a viral infection and prescribed alternating doses of acetaminophen and ibuprofen. The fever appeared to resolve; however, her family noticed cessation of solid food intake, increased irritability, and a slight regression in motor milestones. She was taken back to the emergency department where laboratory results were significant for the following: white blood cells count 29.89 (4-10 × 109/L), hemoglobin 5.8 (12-15 g/dL), platelet count 578 (150-400 × 109/L), and absolute neutrophil 15,540 (1500-8000/mm3). The physicians at the outside hospital were concerned about possible leukemia, and she was transferred to our institution for further evaluation.

Additional laboratory results on admission demonstrated reticulocytes 12.88% (0.5%-1.5%), gamma-glutamyl transferase 99 (6-50 U/L), aspartate/alanine aminotransferase 348 and 296 respectively (5-30 U/L), lactatde dehydrogenase 872 (5-150 U/L), and mildly elevated AFP. An abdominal radiograph demonstrated marked hepatomegaly without visible calcification, and abdominal ultrasound revealed a heterogeneous solid and cystic mass in the right hepatic lobe with some demonstrable internal blood flow (Fig. 1, Fig. 2, Fig. 3). The differential diagnosis included hepatoblastoma, mesenchymal hamartoma, and less likely hemangioendothelioma or neuroblastoma. Elevated reticulocytes in combination with anemia made a primary marrow process less likely. Magnetic resonance imaging (MRI) of the abdomen showed a solid and cystic mass with peripheral enhancement in the superior cystic component, including a few enhancing septations, and heterogeneously enhancing solid components. There were multiple fluid-fluid levels noted within the mass on T2-weighted images, which were concerning for hemorrhage. Computed tomography failed to demonstrate calcifications or macroscopic fat within the mass, which favored hepatoblastoma. No metastases were noted on any of the imaging obtained. A surgical biopsy of the mass was performed and pathology showed an undifferentiated small round cell tumor or extrarenal malignant rhabdoid tumor. On immunohistochemical staining it was cytokeratin positive, INI-1 deficient, weakly CD99 positive, and negative for desmin (confirms myogenic tissue origin), CD45 (immune cells), HepPar-1 (sensitive for hepatocellular carcinoma), beta-catenin (fibroblasts), and myogenin. Following biopsy, the patient had a declining hematocrit with concern for hemorrhage into the mass, which resulted in a hepatic arteriogram and polyvinyl alcohol embolization performed by interventional radiology.

Fig. 1

Sagittal grayscale image through the right hepatic lobe showing a heterogeneous solid and cystic mass. The contents of the cyst are not completely anechoic due to the presence of hemorrhage into the cyst at the time of diagnosis. Mass effect is noted on the adjacent right kidney

Fig. 2

Coronal T2-weighted magnetic resonance sequence through the right hepatic lobe. Compared to the normal left lobe, the lesion is relatively T2 hyperintense. A large cystic component superior demonstrates intermediate T2 signal, compatible with the presence of hemorrhage into the cyst. The interior portion of the lesion demonstrates heterogeneous T2 signal with both cystic and solid components

Fig. 3

Left: T1 volumetric interpolated breath-hold examination, volumetric interpolated brain examination (VIBE) precontrast; Right: T1 VIBE postcontrast. Images through the right hepatic lobe showing a large lesion that primarily replaces the right hepatic lobe. The solid component of the mass is hypointense to the normal hepatic parenchyma in the left hepatic lobe. On postcontrast images, there is a rim enhancing cystic component superiorly with a more solid heterogeneously enhancing portion inferiorly

Following embolization the patient continued to have fever and electrolyte imbalance likely due to tumor necrosis. Chemotherapy composed of vincristine, doxorubicin, and cyclophosphamide was initiated with the intention to decrease tumor size before possible resection or transplant. The patient developed a pseudomonas bacteremia and continued to hemorrhage, which eventually resulted in multiorgan failure requiring intubation, vasopressors, and an extended course of broad-spectrum antibiotics. Following numerous multidisciplinary meetings the care team and family agreed to withdraw care and pursue comfort measures, and less than 1 month after admission, the patient passed away quickly and peacefully.

Discussion

MRTs were first described in 1978 by Beckwith and Palmer as a variant of Wilms' Tumor [3] and subsequently discovered in the liver in 1982 [4]. The term “rhabdoid” was originally employed to describe rhabdomyosarcoma-like features, most notably the cytoplasmic aggregates of intermediate filaments (eg, keratin and vimentin) [5].

The incidence of MRT is low, 0.6 per 1 million people, with a median age of 11-18 months for the extrarenal subtypes [6]. The most frequent presenting symptoms include fever, anorexia or emesis, and lethargy or malaise. Clinical signs include abdominal distension, hepatomegaly, and systemic signs of tumor rupture. Laboratory abnormalities include anemia, thrombocytosis, elevated liver function tests, and elevated lactate dehydrogenase [2]. Overall prognosis is extremely poor, with 5-year survival rates of 17%-36%. Age may be a significant prognostic indicator, with younger patients having lower survival rates, although this could be secondary to use of less aggressive chemotherapy and avoidance of radiation in the younger population [6].

The current literature on extrarenal rhabdoid tumors in pediatric patients includes only a few isolated case reports. Among the reported cases, the most common radiographic findings associated with rhabdoid tumors include solid, lobulated, heterogeneously enhancing masses on computed tomography and MRI. On MRI the tumors are generally hypointense on T1-weighted images and hyperintense on T2-weighted images, as demonstrated in our patient. There are occasional cystic components or fluid-fluid levels appreciable on T2-weighted sequences and these lesions rarely have internal calcifications [7]. Hepatoblastomas, which may confound the diagnosis of MRT, are often well circumscribed with possible lobulation and septation. They may appear heterogenous or homogenous depending on whether it is the epithelial or mixed type tumor. A useful distinguishing radiographic feature is the presence of calcifications found in more than 50% of hepatoblastomas as compared to MRT in which they are less frequently encountered [1].

Histologically, these tumors are composed of noncohesive, single-cell clusters or sheets with eosinophilic cytoplasm, eccentric nuclei, and prominent nucleoli [5]. One of the most distinguishing features is the deficiency of INI-1 demonstrated with BAF47 immunohistochemical staining. This gene encodes an ATP-dependent chromatin-remodeling complex expressed in all normal cells throughout development. INI-1 has a role in tumor suppression via the Rb-Cyclin D1 pathway, although the specific pathogenesis in rhabdoid tumors is still unclear [8]. Potential future targets of treatment may focus on these allelic mutations with attempts to restore function of the downstream products and oncogene repressors. Current treatment regimens utilize chemotherapies, mainly a combination of vincristine, doxorubicin, and high-dose cyclophosphamide. Current literature supports consolidation with carboplatin, etoposide and melphalan followed by an autologous bone marrow transplant once the patient is in radiographic remission [6].

While MRTs have low prevalence, they are highly aggressive with poor outcomes and should thus be included in the differential diagnosis to assist with early diagnosis and treatment. As a hepatic lesion they may resemble hepatoblastoma, underscoring the importance of combined radiologic, pathologic, and laboratory correlation. Special attention should be paid to the risk of spontaneous rupture associated with MRT, and early chemotherapy should be initiated once a diagnosis is made with the goal of prolonged survival.