Malignant rhabdoid tumor of liver.

Malignant rhabdoid tumor (MRT) is a rare, but aggressive tumor commonly arising from the kidney in young children. Extrarenal MRT has been reported in the literature in various other sites including the liver, pelvis, CNS, abdomen, heart and other soft-tissues. Reported herein are the presentation, radiology, histopathology, immunohistochemistry, treatment and outcome of a 6 month infant with primary MRT of liver.

INTRODUCTION

Malignant liver tumor accounts for approximately 1% of all childhood tumor and two-third of all liver masses in children. Hepatoblastoma and Hepatocellular carcinoma together account for the majority of malignant liver tumors in children. Other rare liver malignancies include sarcoma, germ cell tumor and rhabdomyosarcoma. Malignant rhabdoid tumor (MRT) is a very rare malignant liver tumor with very dismal prognosis.[1]

CASE REPORT

A 6-month-old boy presented with a 15 days history of abdominal distension, irritability and reluctance to feed. There was no vomiting, constipation or jaundice. On physical examination, the child was febrile with normal vitals; abdomen was distended with hepatomegaly, no lump was felt. Ultrasound of the abdomen revealed the presence of hyperechoic lesions in the liver. Contrast enhanced computed tomography (CT) scan of the abdomen revealed multiple lesions in the liver (both lobes), which were homogeneously hypodense; had no evidence of calcification [Figure 1a and b]. There was no change in the caliber of the infraceliac abdominal aorta or enlargement of the hepatic artery. Magnetic resonance imaging (MRI) showed that the lesions were hypointense on T1-Weighted (W) and hyperintense on T2-W images [Figure 1c and d]. MIBG (meta-iodobenzylguanadine) scan did not reveal any uptake. A 24 h urinary vanillylmandelic acid was with in normal limits (0.46 mg/g of creatinine); serum homovanillic acid was mildly raised (28.18 mg/g of creatinine); and serum alpha-fetoprotein (αFP) was within normal limits. Fine needle aspiration cytology of the lesion was inconclusive; hence, a wedge biopsy was performed through a minilaparotomy. Macroscopic examination of the wedge showed a stretched out capsule on the exterior aspect with a tan colored tumor within showing areas of necrosis. On microscopic examination of H and E stained sections [Figure 2] a tumor was seen adjacent to normal liver tissue. The tumor was arranged in nodules with the absence of trabeculae and sinusoids. The tumor cells had large nucleus having prominent nucleoli and moderate to abundant cytoplasm with pink inclusion bodies. The immunohistochemistry revealed positivity for cytokeratin and vimentin while it was negative for glycogen, desmin and chromogranin. Immunocytochemistry for INI-1 was not available. The histology was consistent with MRT of the liver. Patient was started on chemotherapy (carboplatin, etoposide and cyclophosphamide), but died soon after of progressive tumor and massive unrelenting ascites.

Figure 1

(a and b) Axial contrast enhanced computed tomography images of the liver reveals multiple hypodense well-defined mass lesions in both lobes. Axial magnetic image of the liver (c) reveals the lesions to be homogeneously hypointense spin-echo (SE) T1-Weighted (W) (d) and SE T2-W with fat suppression shows multiple hyperintense masses in both lobes

Figure 2

Histology showing tumor cells with cytoplasmic eosinophilic inclusions and prominent nucleoli (a); immunopositive for cytokeratin (b); immunopositive for vimentin (c); absence of cytoplasmic glycogen on diastase Periodic acid-Schiff stain (d) (all images at ×400)

DISCUSSION

MRT was first described in 1978 by Beckwith and Palmer[2] as a rhabdomyosarcomatoid variant of Wilms tumor with unfavorable prognosis. It was later recognized to be a distinct renal neoplasm of children with very dismal prognosis. It was labeled as rhabdoid tumor[3] as the tumor contains sheets, cords and nest of cells resembling rhabdomyoblast with eosinophilic cytoplasm and eccentric nuclei. However, there is no evidence of muscle differentiation in these tumors. MRT mainly affects the kidney, but it has also been described in various other sites including liver, pelvis, central nervous system, abdomen, heart and other soft-tissues.

Percutaneous or open biopsy has been used for diagnosis, but sometimes it may be confused with undifferentiated hepatoblastoma. MRT are best characterized[4] by the presence of round or polygonal cells with abundant eosinophilic cytoplasm, typical eosinophilic perinuclear inclusions, vesicular nuclei and prominent nucleoli. Immunohistochemical expression of vimentin and epithelial markers and lack of staining for S-100, myoglobin and desmin are commonly found, but are non-specific. In rhabdoid tumors SMARCB1 appears to function as classic tumor suppressor gene and inactivation of both copies of the gene leads to loss of protein expression in the nucleus, which can be detected by immunohistochemistry. It has been demonstrated that MRT lacks immunostaining for BAF 47 protein (SMARCB1 protein) in the tumor cells due to a clonal mutation in INI1 gene. This abnormality is the hallmark of all rhabdoid tumors.[5] Further, recurrent deletion of region 11.2 of the long arm of chromosome 22 (22q11.2) has been reported in the majority of MRT's. There is a lot of controversy regarding the histogenesis[4] of MRT and no definite agreement has been reached. Various cellular origins have been described such as neuroectodermal, myogenic, histiocytic, epithelial and mesodermal. In the present case, a diagnosis of MRT of the liver was possible due to its characteristic histopathological finding of prominent nucleoli and typical cytoplasmic inclusions in the absence of elevated alpha fetoprotein levels. Ini-1 immunostaining was not available.

MRT of the Liver was first described in 1982 by Gonzalez-Crussi et al.[6] Until date, there are fewer than 50 case reports of MRT of the Liver in the English literature. MRT of the liver occurs mostly in infancy (median age 8 months) and affects male gender more commonly.[7] These tumors typically present as right upper abdominal mass or abdominal distension or rarely with spontaneous rupture of the liver tumor and have systemic symptoms including fever, anorexia/vomiting and lethargy/malaise.[7] Of potential significance, 17% of patients present with spontaneous rupture of tumor, which is much more frequent than rupture in any other hepatic malignancy.[7] The αFP is usually within normal range. They have been associated with secretion of parathoromone like substances causing hypercalcemia and with vasointestinal peptide induced watery diarrhea.[8] Presenting features that might be distinctive are systemic signs or symptoms like fever, a very elevated lactate dehydrogenase, a normal or near normal AFP (Alphafeto Protein) level at diagnosis and perhaps the occurrence of spontaneous tumor rupture.[7] The tumor has no specific clinical or radiological diagnostic features. Some studies have reported that these tumors have a tendency to be large and hypodense on CT and show a heterogeneous hyperintensity on T2-W MRI.[9] Unlike other malignant hepatic tumors in children, the MRT is notorious for its resistance to treatment and invariably fatal outcome.[1] The recommended chemotherapy[10] for MRT consists of carboplatin and etoposide alternating with cyclophosphamide. However, this strategy has not improved outcomes. Recent case reports have documented successful outcomes in patients with metastatic MRT treated with ifosfamide-carboplatin and etoposide or ifosfamide-etoposide alternating with vincristine-doxorubicin-cyclophosphamide and ifosfamide, vincristine and actinomycin.[7811] The average survival rates of these children ranged from 5 days to 5 months.[8] There are only a few reports of children achieving long-term survival with different therapeutic regimens.[7811] It has been observed that cyclin D1 is expressed at high levels in rhabdoid tumor. SMARCB1 binds to the cyclin D1 promoter and regulates its expression. Ablation of cyclin D1 has been shown to prevent rhabdoid tumor growth in the mouse model. This may hold promise for future targeted therapy in patients with MRT.[12]