Diagnostic utility of SALL4 in primary germ cell tumors of the central nervous system: A study of 77 cases

Primary germ cell tumors of the central nervous system (CNS) sometimes pose diagnostic difficulty. In this study we analyzed the diagnostic utility of a novel marker, SALL4, in 77 such tumors (59 pure and 18 mixed) consisting of the following tumors/tumor components: 49 germinomas, 7 embryonal carcinomas, 27 yolk sac tumors, 3 choriocarcinomas, and 14 teratomas. We also stained SALL4 in 99 primary non-germ cell tumors to test SALL4 specificity. We compared SALL4 with OCT4 in all germ cell tumors and compared SALL4 with α-fetoprotein and glypican-3 in all yolk sac tumors. The staining was semiquantitatively scored as 0 (no staining), 1 (30%), 2(31-60%), 3 (61-90%), and 4 (90%). Strong SALL4 staining was observed in all 49 germinomas (4 in 48, 3 in 1), 7 embryonal carcinomas (all 4), and 27 yolk sac tumors (1 in 1, 2 in 2, 3 in 7, 4 in 17). SALL4 staining, 1 weak to focally strong, was observed in 2 of 3 choriocarcinomas (in mononucleated trophoblasts) and in 9 of 14 teratomas (in primitive neuroepithelium and teratomatous glands). All germinomas and embryonal carcinomas showed strong OCT4 staining (4 in all except 1 germinoma with 3), whereas other germ cell tumors were negative. Out of 27 yolk sac tumors, 26 showed positive α-fetoprotein staining (1 in 9, 2 in 7, 3 in 5, and 4 in 5). All yolk sac tumors showed positive glypican-3 staining (1 in 6, 2 in 6, 3 in 7, and 4 in 8). The mean percentage of yolk sac tumor cells stained was 84% with SALL4, 45% with α-fetoprotein, and 63% with glypican-3 (P0.01). No non-germ cell tumors showed SALL4 staining. Our results indicate that SALL4 is a novel sensitive diagnostic marker for primary germ cell tumors of the CNS with high specificity. SALL4 is a more sensitive marker than α-fetoprotein and glypican-3 for yolk sac tumors.