SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors

Abstract

BACKGROUND:The correct diagnosis of metastatic germ cell tumors is critical, because these tumors can be effectively treated and are even cured with modern therapy. Their histopathologic diagnosis can be challenging without immunohistochemical markers, which currently have limitations. SALL4 is a novel stem cell marker essential to maintain pluripotency and self‐renewal of embryonic stem cells. In the current study, the authors investigated the utility of SALL4 as a potential diagnostic marker for metastatic germ cell tumors.METHODS:Ninety metastatic germ cell tumors from testis, ovary, and extragonadal sites were stained with a monoclonal SALL4 antibody. In addition, 170 metastatic nongerm cell malignancies, including 158 carcinomas (6 head and neck, 8 thyroid, 12 lung, 8 breast, 7 hepatocellular, 3 cholangiocarcinomas, 2 ampullary, 10 pancreatic, 18 gastric, 15 esophageal, 10 renal cell, 10 urothelial, 12 prostatic, 18 ovarian, 6 uterine, and 13 colonic) and 12 melanomas, were also stained to test SALL4 specificity.RESULTS:All 22 seminomas, 7 dysgerminomas, 22 embryonal carcinomas, and 14 of 15 yolk sac tumors displayed strong and diffuse SALL positivity in >90% of tumor cells (80% of tumor cells were strongly positive in the remaining yolk sac tumor). Five of 7 choriocarcinomas and 9 of 18 teratomas were also variably positive for SALL4. In contrast, only 10 (esophageal, gastric, and colonic adenocarcinomas) of 170 metastatic somatic tumors demonstrated focally weak SALL4 reactivity (<25% tumor cells).CONCLUSIONS:SALL4 is a novel sensitive and highly specific marker for metastatic germ cell tumors, and is particularly useful for detecting metastatic yolk sac tumors. Cancer 2009. © 2009 American Cancer Society.

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

“…[10][11][12] In the current study we have shown 100% sensitivity of SALL4 for their counterparts in the CNS. Such high sensitivity was also observed in primary mediastinal seminomas, embryonal carcinomas, and yolk sac tumors (Cao D, unpublished results).…”

“…In previous studies, of the 461 non-germ cell tumors (273 carcinomas of almost all major types, 92 sarcomas of almost all types, 12 melanomas and 13 mesotheliomas, and 71 gonadal non-carcinomatous nongerm cell tumors), only 13 carcinomas and 1 sarcoma showed focal SALL4 staining in o30% of the tumor cells. [10][11][12] In this study none of the 99 nongerm cell tumors of all major types of the CNS showed positive SALL4 staining. Although further studies to include more non-germ cell tumors, especially those rare types, are needed to further delineate SALL4 specificity in tumor pathology, these results do indicate that besides its high sensitivity, SALL4 is also relatively specific for both gonadal and extragonadal germ cell tumors.…”

“…Recently, a novel stem cell marker, SALL4, has been identified as a novel gonadal germ cell tumor marker. [10][11][12] SALL4 was strongly positive in 490% of the tumor cells in all gonadal yolk sac tumors, seminomas/dysgerminomas, and embryonal carcinomas. The purpose of this study is to analyze the diagnostic utility of SALL4 in a large series of 77 primary germ cell tumors of the CNS (59 pure and 18 mixed 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.…”

“…Standard whole sections from each were reviewed and diagnoses for all cases were confirmed on routine hematoxylin and eosinstained sections. A tissue microarray consisting of 101 germ cell tumors (including choriocarcinoma (1), embryonal carcinoma (20), intratubular germ cell neoplasia unclassified (2), seminoma (64), spermatocytic seminoma (1), teratoma (5) and yolk sac tumor (8)) using 1.2 mm diameter tissue cores was prepared (Stanford tissue microarray 136) and evaluated as described in detailed elsewhere. 10 Similarly, a tissue microarray of 184 metastatic clear cell renal cell carcinomas from 26 unique sites using 0.7 mm diameter tissue cores was prepared (in duplicate) and evaluated as above (Stanford tissue microarray 238).…”