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

Abstract

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 a-fetoprotein and glypican-3 in all yolk sac tumors. The staining was semiquantitatively scored as 0 (no staining), 1 þ (o ¼ 30%), 2 þ (31-60%), 3 þ (61-90%), and 4 þ (490%). Strong SALL4 staining was observed in all 49 germinomas (4 þ in 48, 3 þ in 1), 7 embryonal carcinomas (all 4 þ ), and 27 yolk sac tumors (1 þ in 1, 2 þ in 2, 3 þ in 7, 4 þ in 17). SALL4 staining, 1 þ 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 þ in all except 1 germinoma with 3 þ ), whereas other germ cell tumors were negative. Out of 27 yolk sac tumors, 26 showed positive a-fetoprotein staining (1 þ in 9, 2 þ in 7, 3 þ in 5, and 4 þ in 5). All yolk sac tumors showed positive glypican-3 staining (1 þ in 6, 2 þ in 6, 3 þ in 7, and 4 þ in 8). The mean percentage of yolk sac tumor cells stained was 84% with SALL4, 45% with a-fetoprotein, and 63% with glypican-3 (Po0.01). 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 a-fetoprotein and glypican-3 for yolk sac tumors.

Specificity of brachyury in the distinction of chordoma from clear cell renal cell carcinoma and germ cell tumors: a study of 305 cases

“…Other immunohistochemical stains would obviously be useful adjuncts in this differential diagnostic setting. The widely available renal cell carcinoma marker PAX-8 18,19 and the novel germ cell marker SALL-4 [20][21][22] would be useful in an immunohistochemical panel when renal cell carcinoma or a germ cell tumor are considered, respectively. Although no chordomas expressed SALL-4 in this study, 1 of 12 cases had patchy weak nuclear immunoreactivity for PAX-8.…”

RNA-binding protein LIN28 is a marker for primary extragonadal germ cell tumors: an immunohistochemical study of 131 cases

“…Primary extragonadal germ cell tumors are uncommon tumors that most often occur in the midline structures and mediastinum, but they can also occur in many other organs, not only in children but also in adults. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Morphologically, primary extragonadal germ cell tumors can mimic many types of non-germ cell tumors. For example, mediastinal seminomas may mimic type B thymomas and embryonal carcinoma may mimic other types of carcinomas.…”

“…The yolk sac tumor is the extragonadal germ cell tumor that poses the greatest diagnostic challenges because of its multiple histological patterns and wide organ distribution. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] Previous markers for diagnosing extragonadal yolk sac tumors included placental-like alkaline phosphatase, a-fetoprotein, and glypican-3, but they lack adequate sensitivity and specificity. Recent studies have shown that SALL4 is a more sensitive marker for primary extragonadal yolk sac tumors.…”

“…[10][11][12] We compared LIN28 with SALL4 for its diagnostic utility in all primary extragonadal germ cell tumors. Both LIN28 and SALL4 showed 100% sensitivity for seminomas/ germinomas and embryonal carcinomas with staining in 490% tumor cells in nearly all or all cases (95 and 98% for seminomas/germinomas, 100 and 100% for embryonal carcinomas, respectively), indicating that LIN28 had a similar level of diagnostic sensitivity as did SALL4 for primary extragonadal seminomas/germinomas and embryonal carcinomas.…”

“…The result of SALL4 in these germ cell tumors was previously reported. [10][11][12] To determine its specificity, we also examined LIN28 in 82 primary non-germ cell tumors of the CNS and in 17 primary mediastinal epithelial tumors (thymomas and thymic carcinomas). The immunohistochemical status of LIN28 in other extragonadal non-germ cell tumors (103 carcinomas, 91 sarcomas, 83 lymphomas, 9 plasmacytomas, 12 mesotheliomas, and 9 melanomas) was previously reported.…”