Testicular mixed germ cell tumors: A morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas

Anuradha Gopalan, Deepti Dhall, Semra Olgac, Samson W. Fine, James Korkola, Jane Houldsworth, Raju S. Chaganti, George J. Bosl, Victor E. Reuter, Satish K. Tickoo

Research output: Contribution to journalArticle

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Abstract

Stem cell markers, OCT3/4, and more recently SOX2 and growth differentiation factor 3 (GDF3), have been reported to be expressed variably in germ cell tumors. We investigated the immunohistochemical expression of these markers in different testicular germ cell tumors, and their utility in the differential diagnosis of morphologically difficult-to-classify components of these tumors. A total of 50 mixed testicular germ cell tumors, 43 also containing difficult-to-classify areas, were studied. In these areas, multiple morphological parameters were noted, and high-grade nuclear details similar to typical embryonal carcinoma were considered embryonal carcinoma-like high-grade. Immunohistochemical staining for OCT3/4, c-kit, CD30, SOX2, and GDF3 was performed and graded in each component as 0, negative; 1, 1-25%; 2, 26-50%; and 3, 50% positive staining cells. The different components identified in these tumors were seminoma (8), embryonal carcinoma (50), yolk sac tumor (40), teratoma (40), choriocarcinoma (3) and intra-tubular germ cell neoplasia, unclassified (35). By immunohistochemistry, the staining patterns were OCT3/4 3, all seminomas, embryonal carcinomas and intra-tubular germ cell neoplasia; SOX2 3, all embryonal carcinomas and 2 to 3, 11/14 (79%) primitive neuroectodermal components in immature teratomas; GDF3 2 to 3, all yolk sac tumors, seminomas and intra-tubular germ cell neoplasia and 1 to 2, 40/50 embryonal carcinomas. A total of 34/43 (79%) of difficult-to-classify areas stained 3 for OCT3/4, CD30, and SOX2, similar to embryonal carcinoma. Among these areas, only embryonal carcinoma-like high-grade nuclear details were significantly associated with such an immunophenotype. Thus, SOX2 is expressed in embryonal carcinoma and primitive neuroectoderm of teratoma, and unlike OCT3/4, not in intra-tubular germ cell neoplasia and seminoma. Therefore, it may be useful in the distinction of seminoma from embryonal carcinoma, and potentially in diagnosing early carcinomatous differentiation in seminoma. GDF3 positivity, in the absence of OCT3/4 and CD30, combined with morphological features, is helpful in the diagnosis of yolk sac tumor. Embryonal carcinoma-like high-grade nuclear details are the most important morphological criterion for the diagnosis of embryonal carcinoma in difficult-to-classify areas.

Original languageEnglish (US)
Pages (from-to)1066-1074
Number of pages9
JournalModern Pathology
Volume22
Issue number8
DOIs
StatePublished - Aug 2009
Externally publishedYes

Fingerprint

Growth Differentiation Factor 3
Embryonal Carcinoma
Stem Cells
Seminoma
Endodermal Sinus Tumor
Germ Cells
Teratoma
Neoplasms
Staining and Labeling
Growth Differentiation Factor 2
Testicular Germ Cell Tumor
Neural Plate
Choriocarcinoma

Keywords

  • GDF3
  • Germ cell tumors
  • OCT3/4
  • SOX2
  • Stem cell
  • Testis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Testicular mixed germ cell tumors : A morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas. / Gopalan, Anuradha; Dhall, Deepti; Olgac, Semra; Fine, Samson W.; Korkola, James; Houldsworth, Jane; Chaganti, Raju S.; Bosl, George J.; Reuter, Victor E.; Tickoo, Satish K.

In: Modern Pathology, Vol. 22, No. 8, 08.2009, p. 1066-1074.

Research output: Contribution to journalArticle

Gopalan, Anuradha ; Dhall, Deepti ; Olgac, Semra ; Fine, Samson W. ; Korkola, James ; Houldsworth, Jane ; Chaganti, Raju S. ; Bosl, George J. ; Reuter, Victor E. ; Tickoo, Satish K. / Testicular mixed germ cell tumors : A morphological and immunohistochemical study using stem cell markers, OCT3/4, SOX2 and GDF3, with emphasis on morphologically difficult-to-classify areas. In: Modern Pathology. 2009 ; Vol. 22, No. 8. pp. 1066-1074.
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abstract = "Stem cell markers, OCT3/4, and more recently SOX2 and growth differentiation factor 3 (GDF3), have been reported to be expressed variably in germ cell tumors. We investigated the immunohistochemical expression of these markers in different testicular germ cell tumors, and their utility in the differential diagnosis of morphologically difficult-to-classify components of these tumors. A total of 50 mixed testicular germ cell tumors, 43 also containing difficult-to-classify areas, were studied. In these areas, multiple morphological parameters were noted, and high-grade nuclear details similar to typical embryonal carcinoma were considered embryonal carcinoma-like high-grade. Immunohistochemical staining for OCT3/4, c-kit, CD30, SOX2, and GDF3 was performed and graded in each component as 0, negative; 1, 1-25{\%}; 2, 26-50{\%}; and 3, 50{\%} positive staining cells. The different components identified in these tumors were seminoma (8), embryonal carcinoma (50), yolk sac tumor (40), teratoma (40), choriocarcinoma (3) and intra-tubular germ cell neoplasia, unclassified (35). By immunohistochemistry, the staining patterns were OCT3/4 3, all seminomas, embryonal carcinomas and intra-tubular germ cell neoplasia; SOX2 3, all embryonal carcinomas and 2 to 3, 11/14 (79{\%}) primitive neuroectodermal components in immature teratomas; GDF3 2 to 3, all yolk sac tumors, seminomas and intra-tubular germ cell neoplasia and 1 to 2, 40/50 embryonal carcinomas. A total of 34/43 (79{\%}) of difficult-to-classify areas stained 3 for OCT3/4, CD30, and SOX2, similar to embryonal carcinoma. Among these areas, only embryonal carcinoma-like high-grade nuclear details were significantly associated with such an immunophenotype. Thus, SOX2 is expressed in embryonal carcinoma and primitive neuroectoderm of teratoma, and unlike OCT3/4, not in intra-tubular germ cell neoplasia and seminoma. Therefore, it may be useful in the distinction of seminoma from embryonal carcinoma, and potentially in diagnosing early carcinomatous differentiation in seminoma. GDF3 positivity, in the absence of OCT3/4 and CD30, combined with morphological features, is helpful in the diagnosis of yolk sac tumor. Embryonal carcinoma-like high-grade nuclear details are the most important morphological criterion for the diagnosis of embryonal carcinoma in difficult-to-classify areas.",
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AU - Dhall, Deepti

AU - Olgac, Semra

AU - Fine, Samson W.

AU - Korkola, James

AU - Houldsworth, Jane

AU - Chaganti, Raju S.

AU - Bosl, George J.

AU - Reuter, Victor E.

AU - Tickoo, Satish K.

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N2 - Stem cell markers, OCT3/4, and more recently SOX2 and growth differentiation factor 3 (GDF3), have been reported to be expressed variably in germ cell tumors. We investigated the immunohistochemical expression of these markers in different testicular germ cell tumors, and their utility in the differential diagnosis of morphologically difficult-to-classify components of these tumors. A total of 50 mixed testicular germ cell tumors, 43 also containing difficult-to-classify areas, were studied. In these areas, multiple morphological parameters were noted, and high-grade nuclear details similar to typical embryonal carcinoma were considered embryonal carcinoma-like high-grade. Immunohistochemical staining for OCT3/4, c-kit, CD30, SOX2, and GDF3 was performed and graded in each component as 0, negative; 1, 1-25%; 2, 26-50%; and 3, 50% positive staining cells. The different components identified in these tumors were seminoma (8), embryonal carcinoma (50), yolk sac tumor (40), teratoma (40), choriocarcinoma (3) and intra-tubular germ cell neoplasia, unclassified (35). By immunohistochemistry, the staining patterns were OCT3/4 3, all seminomas, embryonal carcinomas and intra-tubular germ cell neoplasia; SOX2 3, all embryonal carcinomas and 2 to 3, 11/14 (79%) primitive neuroectodermal components in immature teratomas; GDF3 2 to 3, all yolk sac tumors, seminomas and intra-tubular germ cell neoplasia and 1 to 2, 40/50 embryonal carcinomas. A total of 34/43 (79%) of difficult-to-classify areas stained 3 for OCT3/4, CD30, and SOX2, similar to embryonal carcinoma. Among these areas, only embryonal carcinoma-like high-grade nuclear details were significantly associated with such an immunophenotype. Thus, SOX2 is expressed in embryonal carcinoma and primitive neuroectoderm of teratoma, and unlike OCT3/4, not in intra-tubular germ cell neoplasia and seminoma. Therefore, it may be useful in the distinction of seminoma from embryonal carcinoma, and potentially in diagnosing early carcinomatous differentiation in seminoma. GDF3 positivity, in the absence of OCT3/4 and CD30, combined with morphological features, is helpful in the diagnosis of yolk sac tumor. Embryonal carcinoma-like high-grade nuclear details are the most important morphological criterion for the diagnosis of embryonal carcinoma in difficult-to-classify areas.

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