Hepatoid yolk sac tumor (HYST), hepatocellular carcinoma (HCC) and hepatocytic teratoma (HT): A morphologic and immunohistochemical (IHC) study of 31 cases

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Conference Proceeding

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Modern Pathology


Background: YST is known for its multiple patterns, which assist in its diagnosis. Purely hepatoid differentiation is rare, consisting of nests and cords of cells with abundant, eosinophilic to clear cytoplasm, well-defined cell borders, and round nuclei with prominent nucleoli. It is usually seen in metastases of patients with late recurrence, often years after orchiectomy, which complicates its recognition. Additionally, hepatocytic differentiation is a rare aspect of teratoma; it requires separation from HYST, and both should be distinguished from de novo HCC. We therefore investigated the morphologic and IHC features of these entities. Design: We retrieved 12 metastatic HYSTs (representing >90% of the tumor), 17 HCCs and 2 HTs (Figures 1-3, respectively) from tissue archives. Hematoxylin and eosin stained slides were reviewed to confirm each diagnosis. 4 μm-thick sections were stained with antibodies against SALL4, CK7, CK19, CDX2, glypican-3, arginase, HepPar-1, and villin in a Dako automated instrument. Results: The median and mean age of patients with HYST was 36 years (range, 20-63). 3 presented with metastatic disease and 9 recurred at a median of 10 years (range, 2-24) after initial diagnosis. The tumors formed trabeculae and cords, occasional gland-like structures, and had frequent basement membrane deposits. SALL4 (100%), glypican-3 (100%), CK19 (85%), CDX2 (85%) and villin (75%) were prominently positive; HepPar-1 stained rare single tumor cells (70%) and arginase was infrequently reactive (26%) (patchy in 1 and rare cells in 4). In HCC, HepPar-1 (94%) and arginase (82%) were diffusely positive, whereas glypican-3 (35%) and villin (12%) were less common. SALL4, CK19 and CDX2 were negative. HTs formed sheets of hepatocytes with abortive ducts and portal triads (Figure 1). The hepatocytes stained positively for glypican-3, arginase, and HepPar-1 (2/2). Villin was positive in 1. CK7 (1/2) and CK19 (2/2) highlighted ductular formation. SALL4 and CDX-2 were negative (0/2). (Figure presented) Conclusions: In summary, SALL4, glypican-3, CDX2, and CK19 are sensitive markers for HYST, as is widely scattered single cell reactivity with HepPar-1. SALL4, CK19 and CDX2 positivity are specific in the differential with HCC, as are prominent intercellular basement membrane deposits. HTs show more consistent staining for arginase and HepPar-1 than HYST; they lack SALL4, contrasting with HYST.





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