Surgical Pathology Diagnostic Pitfalls of Hepatoblastoma

Abstract

Hepatoblastoma (HB) is the most common malignancy within the rare cohort of pediatric primary liver tumors. It may arise sporadically or in association with germline mutations in specific genetic syndromes. Histogenesis recapitulates fetal hepatic development, however, this tumor can exhibit a markedly heterogeneous appearance both macroscopically and under the microscope. Histologic subtypes are classified based on morphologic appearance, with additional discrimination based on emerging molecular and immunohistochemical features. Numerous diagnostic pitfalls exist from clinical presentation through to ancillary testing; at all stages, the surgical pathologist must be discerning and open to collaboration with colleagues of different specialties. Problematic areas include the adequacy of tissue sampling, correlation of histology with radiologic appearance and alpha feto-protein (AFP) serology, forming a diagnostic consensus within the pediatric pathology community and choosing a shrewd immunohistochemical panel. This review discusses the sequence of events leading up to histologic assessment, and the nuances of microscopic evaluation. Along the way, pitfalls are highlighted, providing a tool for the surgical pathologists to support their individual approach.

Keywords: Hepatoblastoma; beta-catenin; hepatoblastoma diagnostic pitfalls; hepatocellular neoplasm; pediatric liver histology; pediatric liver tumor.

Figure 1.

a) Gross picture of a hepatoblastoma extensively invading the liver and perforating the glisson's capsule. The tumor appears solid, grey but also displays some hemorrhage. b) Microphotograph of an intraoperative frozen section performed during a liver biopsy to identify the viability of tissue for COG studies and differentiation from hepatocellular carcinoma or embryonal sarcoma. The presence of a trabecular arrangement of the tumor cells displaying hepatocytic morphology is quite typical. There is a resemblance to the fetal liver (Hematoxylin-eosin staining, X100, original magnification). c) Microphotograph of a fetal hepatoblastoma with numerous hematopoietic cells between the trabecular arrangement of the hepatoblasts (Hematoxylin-eosin staining, X50, original magnification). d) Microphotograph of an embryonal hepatoblastoma with an increase of the nucleus to cytoplasm ratio and focal megakaryoblasts (arrow). Megakaryoblasts need to be confirmed using anti-platelet immunohistochemical markers (eg, CD61). Megakaryoblasts may be mis-interpreted as marked atypia or anaplasia in a setting of a small round blue cell tumor. (Hematoxylin-eosin staining, X200, original magnification). e) Microphotograph of an embryonal hepatoblastoma showing trabecular arrangement in cords and scattered islands of extramedullary hematopoiesis (Hematoxylin-eosin staining, X200, original magnification). f) Microphotograph of a fetal hepatoblastoma showing glypican 3 staining. The arrow shows a periluminal accentuation of the staining. (Anti-Glypican 3 immunostaining, Avidin-Biotin Complex, X200, original magnification).

Figure 2.

a) Microphotograph of a hepatoblastoma following chemotherapy with degenerations including fibrosis and hemorrhage (arrow) and some residual hepatoblasts showing some signs of maturation with clear cytoplasm (hematoxylin-eosin staining, X100, original magnification). b) Microphotograph of a hepatoblastoma following chemotherapy and clear cell change (arrow), which needs to be taken into the differential diagnosis with other tumors potentially showing clear cell morphology. Some islands of hematopoiesis could be recognized (Hematoxylin-eosin staining, X40, original magnification). c-d) Microphotograph showing lung tissue of a partial pneumectomy including a metastasis of a hepatoblastoma of embryonal type. The high magnification in d) shows a packed arrangement of the cells (c: hematoxylin-eosin staining, X20, original magnification; d: hematoxylin-eosin staining, X200, original magnification).