A critically ill 3-year-old boy presented with a hard mass beneath the right costal margin. Magnetic resonance tomography showed a large, inhomogeneous mass measuring 10 × 9.5 × 7.3 cm with an intra- and extra-hepatic portion (fig. ) and a partial compression of the vena cava inferior, but no metastatic disease. Laboratory tests revealed an increase of liver transaminases and a strong increase of alpha-fetoprotein (AFP) and neuron-specific enolase.
Figure 1 MRI shows a large tumor in the right upper abdomen originating from the right liver lobe. The tumor has two main parts and seems to contain different parts of tissue. The coronal view showed that the tumor is mainly situated outside the liver (a: T2 sequence). (more ...)
Pathological assessment on a bioptical specimen showed an immature teratoid tumor with no area of hepatoblastic differentiation present. After a 5-day PEI chemotherapy following the MAKEI 96 protocol of the German Society for Pediatric Oncology and Hematology (GPOH) [5
] AFP decreased, but the tumor size increased to 14 × 14 × 20 cm. An extended right hemihepatectomy was performed. The gross surgical specimen measured 23.5 × 16.8 × 11 cm (1915 g) with a lesion size of 16 × 14 × 11 cm (fig. ) and a minimal tumor-free margin of 0.3 cm. The tumor was encapsulated and macroscopically showed multiple cysts with a diameter of up to 1.5 cm, about 40% of the tumor was necrotic.
The patient recovered well and showed no signs of further tumor disease 36 months postoperatively.
Histological examination showed tumor areas of very different differentiation pattern intermixed with each other (i. e. not representing a collision tumor). Roughly, a fifth of the examined tumor displayed a hepatoblastoma-typical morphology partly resembling embryonic and fetal hepatoblastoma (fig. ). About 15% demonstrated a neuroblastoma-like morphology (fig. ) and 5-10% spindle-shaped areas with cross-striation being visible in single cells (fig. ). The remaining tumor showed necrotic tissue or grossly fibro-myxoid stroma-like areas as well as multifocally mostly cystic epithelial structures (fig. ). Rarely, squameous differentiation or osteoid formation (fig. ) was seen.
Figure 2 Conventional HE-staining demonstrated areas of embryonic (a) and fetal (b) hepatoblastic cells, which were positive for HepPar-1 (c). Of note, the tumor cells in the necrotic tumor portions were also focally still HepPar-1 positive (d). Other tumor areas (more ...)
Immunohistochemical analysis (antibodies are listed in table 1; results in table 2) revealed expression of HepPar-1 selectively in the hepatoblastic cells (fig. ) including a significant amount of the cells within the necrotic tumor areas (fig. ) suggesting that mostly the hepatoblastic tumor portions were showing regression after chemotherapy. No expression of AFP was found in any tumor portion. The spindle-shaped cells presenting focally cross-striation (fig. : insert) expressed strongly desmin (fig. ), sarcomer actin (fig. ) and partly myogenin (fig. ) in line with the rhabdomyosarcomatous phenotype of the cells. The gland-like structures expressed epithelial cytokeratins (KL-1), particularly cytokeratins 7 (fig. ) and 19 (fig. ) similar to bile duct epithelia. CK5/6 was specifically positive in the areas of squameous differentiation (fig. ). The small cell tumor component embedded in a neurofibril-like material was positive for synaptophysin (fig. ), neuron-specific enolase (NSE), S-100 protein (fig. ), and CD56, which confirmed its neuroblastic differentiation. CD-99 as well as TTF-1 (thyroid transcription factor-1) was negative. The proliferation rate was 5 to 10% except for in the spindle-cell areas, which showed an increased proliferation rate (up to 30%).
FISH analysis demonstrated no amplification of the MYCN-oncogene, which would have been an indicator of a poor prognosis.
Post-operatively, the general condition of the child improved and the first of four 10-day IPA chemotherapy cycles following the HB 99 protocol of the GPOH was started two weeks later. 36 months after initial diagnosis the patient is healthy, in good general condition, and without any sign of residual tumor disease.