Diagnostic utility of SALL4 in extragonadal yolk sac tumors: An immunohistochemical study of 59 cases with comparison to placental-like alkaline phosphatase, alpha-fetoprotein, and glypican-3

Fenghua Wang, Aijun Liu, Yan Peng, Dinesh Rakheja, Lixin Wei, Debing Xue, Robert W. Allan, Kyle H Molberg, Jianping Li, Dengfeng Cao

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Abstract

Extragonadal yolk sac tumors (YSTs; primary and metastatic) are rare but are malignant germ cell tumors. Pathologic diagnosis of extragonadal YSTs can be challenging without immunohistochemical markers but markers used for diagnosing these tumors such as placental-like alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), and glypican-3 lack adequate sensitivity and/or specificity. In earlier studies with gonadal germ cell tumors, SALL4 has been identified as a novel diagnostic marker for YSTs and other types of primitive germ cell tumors. Here, we investigated the diagnostic utility of SALL4 in 59 extragonadal YSTs (27 primary sacrococcygeal, 15 primary nonsacrococcygeal, and 17 metastatic) by immunohistochemical staining. We also compared SALL4 with PLAP, AFP, and glypican-3. In addition, we performed immunostains for pancytokeratin, epithelial membrane antigen, and OCT4 in these tumors. Our results showed that all 59 YSTs showed strong pancytokeratin staining (70% tumor cells in 1 case, >90% tumor cells in 58) and 10 (17%) of them also showed focal epithelial membrane antigen staining (<3% tumor cells). All 59 YSTs were negative for OCT4. Strong SALL4 staining was seen in all 59 YSTs (in more than 90% tumor cells in 54 and 70% to 85% tumor cells in 5 YSTs). Only 39 of 59 (66%) YSTs showed positive PLAP staining and the staining was often focal (in less than 30% tumor cells) (28 of 39 cases). Positive AFP staining was seen in the vast majority of YSTs (56 of 59 or 95%); however, 32 (54%) YSTs showed staining in less than 30% tumor cells. Although all 59 YSTs showed positive glypican-3 staining, 18 (30%) showed staining in less than 30% tumor cells, and additional 10 (17%) showed staining in between 30% and 60% tumor cells. In these 59 YSTs, the mean percentage of tumor cells stained with PLAP was 14% (range: 0% to 90%), with AFP 35% (range 0% to 95%), and with glypican-3 57% (range: 1% to 100%), whereas the mean percentage of tumor cells stained for SALL4 was 94% (range: 70% to 100%) (P<0.001). Our results indicate that SALL4 is a novel sensitive (100% sensitivity) diagnostic marker for extragonadal YSTs. SALL4 is a more sensitive marker than PLAP, AFP, or glypican-3 for extragonadal YSTs.

Original languageEnglish (US)
Pages (from-to)1529-1539
Number of pages11
JournalAmerican Journal of Surgical Pathology
Volume33
Issue number10
DOIs
StatePublished - Oct 2009

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Glypicans
Endodermal Sinus Tumor
alpha-Fetoproteins
Staining and Labeling
Neoplasms
Germ Cell and Embryonal Neoplasms
Mucin-1
germ-cell AP isoenzyme

Keywords

  • Alpha-fetoprotein
  • Extragonadal
  • Glypican-3
  • Sacrococcygeal
  • SALL4
  • Yolk sac tumor

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery

Cite this

Diagnostic utility of SALL4 in extragonadal yolk sac tumors : An immunohistochemical study of 59 cases with comparison to placental-like alkaline phosphatase, alpha-fetoprotein, and glypican-3. / Wang, Fenghua; Liu, Aijun; Peng, Yan; Rakheja, Dinesh; Wei, Lixin; Xue, Debing; Allan, Robert W.; Molberg, Kyle H; Li, Jianping; Cao, Dengfeng.

In: American Journal of Surgical Pathology, Vol. 33, No. 10, 10.2009, p. 1529-1539.

Research output: Contribution to journalArticle

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title = "Diagnostic utility of SALL4 in extragonadal yolk sac tumors: An immunohistochemical study of 59 cases with comparison to placental-like alkaline phosphatase, alpha-fetoprotein, and glypican-3",
abstract = "Extragonadal yolk sac tumors (YSTs; primary and metastatic) are rare but are malignant germ cell tumors. Pathologic diagnosis of extragonadal YSTs can be challenging without immunohistochemical markers but markers used for diagnosing these tumors such as placental-like alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), and glypican-3 lack adequate sensitivity and/or specificity. In earlier studies with gonadal germ cell tumors, SALL4 has been identified as a novel diagnostic marker for YSTs and other types of primitive germ cell tumors. Here, we investigated the diagnostic utility of SALL4 in 59 extragonadal YSTs (27 primary sacrococcygeal, 15 primary nonsacrococcygeal, and 17 metastatic) by immunohistochemical staining. We also compared SALL4 with PLAP, AFP, and glypican-3. In addition, we performed immunostains for pancytokeratin, epithelial membrane antigen, and OCT4 in these tumors. Our results showed that all 59 YSTs showed strong pancytokeratin staining (70{\%} tumor cells in 1 case, >90{\%} tumor cells in 58) and 10 (17{\%}) of them also showed focal epithelial membrane antigen staining (<3{\%} tumor cells). All 59 YSTs were negative for OCT4. Strong SALL4 staining was seen in all 59 YSTs (in more than 90{\%} tumor cells in 54 and 70{\%} to 85{\%} tumor cells in 5 YSTs). Only 39 of 59 (66{\%}) YSTs showed positive PLAP staining and the staining was often focal (in less than 30{\%} tumor cells) (28 of 39 cases). Positive AFP staining was seen in the vast majority of YSTs (56 of 59 or 95{\%}); however, 32 (54{\%}) YSTs showed staining in less than 30{\%} tumor cells. Although all 59 YSTs showed positive glypican-3 staining, 18 (30{\%}) showed staining in less than 30{\%} tumor cells, and additional 10 (17{\%}) showed staining in between 30{\%} and 60{\%} tumor cells. In these 59 YSTs, the mean percentage of tumor cells stained with PLAP was 14{\%} (range: 0{\%} to 90{\%}), with AFP 35{\%} (range 0{\%} to 95{\%}), and with glypican-3 57{\%} (range: 1{\%} to 100{\%}), whereas the mean percentage of tumor cells stained for SALL4 was 94{\%} (range: 70{\%} to 100{\%}) (P<0.001). Our results indicate that SALL4 is a novel sensitive (100{\%} sensitivity) diagnostic marker for extragonadal YSTs. SALL4 is a more sensitive marker than PLAP, AFP, or glypican-3 for extragonadal YSTs.",
keywords = "Alpha-fetoprotein, Extragonadal, Glypican-3, Sacrococcygeal, SALL4, Yolk sac tumor",
author = "Fenghua Wang and Aijun Liu and Yan Peng and Dinesh Rakheja and Lixin Wei and Debing Xue and Allan, {Robert W.} and Molberg, {Kyle H} and Jianping Li and Dengfeng Cao",
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T1 - Diagnostic utility of SALL4 in extragonadal yolk sac tumors

T2 - An immunohistochemical study of 59 cases with comparison to placental-like alkaline phosphatase, alpha-fetoprotein, and glypican-3

AU - Wang, Fenghua

AU - Liu, Aijun

AU - Peng, Yan

AU - Rakheja, Dinesh

AU - Wei, Lixin

AU - Xue, Debing

AU - Allan, Robert W.

AU - Molberg, Kyle H

AU - Li, Jianping

AU - Cao, Dengfeng

PY - 2009/10

Y1 - 2009/10

N2 - Extragonadal yolk sac tumors (YSTs; primary and metastatic) are rare but are malignant germ cell tumors. Pathologic diagnosis of extragonadal YSTs can be challenging without immunohistochemical markers but markers used for diagnosing these tumors such as placental-like alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), and glypican-3 lack adequate sensitivity and/or specificity. In earlier studies with gonadal germ cell tumors, SALL4 has been identified as a novel diagnostic marker for YSTs and other types of primitive germ cell tumors. Here, we investigated the diagnostic utility of SALL4 in 59 extragonadal YSTs (27 primary sacrococcygeal, 15 primary nonsacrococcygeal, and 17 metastatic) by immunohistochemical staining. We also compared SALL4 with PLAP, AFP, and glypican-3. In addition, we performed immunostains for pancytokeratin, epithelial membrane antigen, and OCT4 in these tumors. Our results showed that all 59 YSTs showed strong pancytokeratin staining (70% tumor cells in 1 case, >90% tumor cells in 58) and 10 (17%) of them also showed focal epithelial membrane antigen staining (<3% tumor cells). All 59 YSTs were negative for OCT4. Strong SALL4 staining was seen in all 59 YSTs (in more than 90% tumor cells in 54 and 70% to 85% tumor cells in 5 YSTs). Only 39 of 59 (66%) YSTs showed positive PLAP staining and the staining was often focal (in less than 30% tumor cells) (28 of 39 cases). Positive AFP staining was seen in the vast majority of YSTs (56 of 59 or 95%); however, 32 (54%) YSTs showed staining in less than 30% tumor cells. Although all 59 YSTs showed positive glypican-3 staining, 18 (30%) showed staining in less than 30% tumor cells, and additional 10 (17%) showed staining in between 30% and 60% tumor cells. In these 59 YSTs, the mean percentage of tumor cells stained with PLAP was 14% (range: 0% to 90%), with AFP 35% (range 0% to 95%), and with glypican-3 57% (range: 1% to 100%), whereas the mean percentage of tumor cells stained for SALL4 was 94% (range: 70% to 100%) (P<0.001). Our results indicate that SALL4 is a novel sensitive (100% sensitivity) diagnostic marker for extragonadal YSTs. SALL4 is a more sensitive marker than PLAP, AFP, or glypican-3 for extragonadal YSTs.

AB - Extragonadal yolk sac tumors (YSTs; primary and metastatic) are rare but are malignant germ cell tumors. Pathologic diagnosis of extragonadal YSTs can be challenging without immunohistochemical markers but markers used for diagnosing these tumors such as placental-like alkaline phosphatase (PLAP), alpha-fetoprotein (AFP), and glypican-3 lack adequate sensitivity and/or specificity. In earlier studies with gonadal germ cell tumors, SALL4 has been identified as a novel diagnostic marker for YSTs and other types of primitive germ cell tumors. Here, we investigated the diagnostic utility of SALL4 in 59 extragonadal YSTs (27 primary sacrococcygeal, 15 primary nonsacrococcygeal, and 17 metastatic) by immunohistochemical staining. We also compared SALL4 with PLAP, AFP, and glypican-3. In addition, we performed immunostains for pancytokeratin, epithelial membrane antigen, and OCT4 in these tumors. Our results showed that all 59 YSTs showed strong pancytokeratin staining (70% tumor cells in 1 case, >90% tumor cells in 58) and 10 (17%) of them also showed focal epithelial membrane antigen staining (<3% tumor cells). All 59 YSTs were negative for OCT4. Strong SALL4 staining was seen in all 59 YSTs (in more than 90% tumor cells in 54 and 70% to 85% tumor cells in 5 YSTs). Only 39 of 59 (66%) YSTs showed positive PLAP staining and the staining was often focal (in less than 30% tumor cells) (28 of 39 cases). Positive AFP staining was seen in the vast majority of YSTs (56 of 59 or 95%); however, 32 (54%) YSTs showed staining in less than 30% tumor cells. Although all 59 YSTs showed positive glypican-3 staining, 18 (30%) showed staining in less than 30% tumor cells, and additional 10 (17%) showed staining in between 30% and 60% tumor cells. In these 59 YSTs, the mean percentage of tumor cells stained with PLAP was 14% (range: 0% to 90%), with AFP 35% (range 0% to 95%), and with glypican-3 57% (range: 1% to 100%), whereas the mean percentage of tumor cells stained for SALL4 was 94% (range: 70% to 100%) (P<0.001). Our results indicate that SALL4 is a novel sensitive (100% sensitivity) diagnostic marker for extragonadal YSTs. SALL4 is a more sensitive marker than PLAP, AFP, or glypican-3 for extragonadal YSTs.

KW - Alpha-fetoprotein

KW - Extragonadal

KW - Glypican-3

KW - Sacrococcygeal

KW - SALL4

KW - Yolk sac tumor

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