Gonadoblastoma and hepatoid and endometrioid-like yolk sac tumor: An update

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Abstract

Dr Robert E. Scully greatly advanced our understanding of germ cell neoplasia to the extent that it is difficult to narrow the discussion of his contributions to this topic so that it can be covered in a brief article. This article accordingly focuses on some of the recent developments concerning 2 of his major contributions in this area-the gonadoblastoma (GB) and variant morphologies of yolk sac tumor. GB was defined by Dr Scully in 1953 and its features elaborated in detail by him in 1970. This neoplasm occurred in young patients who often displayed phenotypic sex ambiguities and frequently presented with primary amenorrhea. It was bilateral in 40%, and consisted of circumscribed nests of small sex cord cells and germinoma-like cells admixed with round deposits of eosinophilic, hyaline, often calcified material. These nests were set in a spindle cell gonadal stroma with Leydig-like or lutein-like cells. Because of his work we now understand that this precursor to invasive germ cell tumors occurs in patients with a specific form of disorder of sex development, namely gonadal dysgenesis, and only in those who have a particular portion of the Y chromosome, the GB locus/TSPY gene, within the gonadal tissue. An essential element to the development of GB appears to be a defect in the genetic pathway that leads to the development of Sertoli cells. Improperly formed Sertoli cells predispose to "delayed maturation" of the gonocytes of the gonad and predispose them to undergo malignant transformation. "Undifferentiated gonadal tissue" has been proposed as the precursor to the development of GB and consists of an unorganized mixture of apparently non-neoplastic germ cells, germ cells with delayed maturation, and neoplastic germ cells with sex cord cells and gonadal stroma. Two variant morphologies of yolk sac tumor were also recognized by Dr Scully. In the hepatoid variant features similar to hepatocellular carcinoma occurred, although primitive glandular foci and lack of liver involvement permitted its distinction in most cases. More recently this variant has been found to occasionally produce bile in canalicular-like structures and to stain strongly for both SALL4 and glypican 3, 2 recently described markers of yolk sac tumor. Recognition of hepatoid yolk sac tumor was followed by the description of a potential mimic, primary ovarian hepatoid carcinoma, which, however, occurred in a significantly older patient population and was occasionally associated with surface epithelial neoplasia. The endometrioid-like variant of yolk sac tumor simulated primary endometrioid adenocarcinoma. It can be suspected on routine stains because of primitive appearing nuclei, frequent subnuclear vacuoles, and in some cases association with more usual yolk sac tumor. Its recognition is now facilitated by a panel of immunohistochemical stains that are often expressed differentially in these 2 neoplasms-endometrioid-like yolk sac tumor: positive for SALL4, glypican 3, and α-fetoprotein; endometrioid adenocarcinoma: positive for cytokeratin 7 and epithelial membrane antigen. Finally, Dr Scully contributed one of the first cases in the literature of yet another nuance in the complicated world of yolk sac neoplasia, namely the development of some tumors on the background of a surface epithelial neoplasm. This is analogous to the more common development of choriocarcinoma from carcinoma and, in the case of yolk sac tumor, diagnosis is aided clinically by the usual older age of the patient and nature of the associated neoplasia.

Original languageEnglish (US)
Pages (from-to)365-373
Number of pages9
JournalInternational Journal of Gynecological Pathology
Volume33
Issue number4
DOIs
StatePublished - Jul 2014

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Gonadoblastoma
Endodermal Sinus Tumor
Glypicans
Germ Cells
Neoplasms
Endometrioid Carcinoma
Coloring Agents
Sertoli Cells
Germinoma
Fetal Proteins
Gonadal Dysgenesis
Keratin-7
Carcinoma
Luteal Cells
Disorders of Sex Development
Mucin-1
Yolk Sac
Choriocarcinoma
Hyalin
Glandular and Epithelial Neoplasms

Keywords

  • Disorder of sex development
  • Endometrioid-like carcinoma
  • Germ cell tumors
  • Gonadal dysgenesis
  • Gonadoblastoma
  • Hepatoid carcinoma
  • Ovarian neoplasms
  • Yolk sac tumor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Obstetrics and Gynecology
  • Medicine(all)

Cite this

Gonadoblastoma and hepatoid and endometrioid-like yolk sac tumor : An update. / Ulbright, Thomas M.

In: International Journal of Gynecological Pathology, Vol. 33, No. 4, 07.2014, p. 365-373.

Research output: Contribution to journalReview article

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KW - Gonadal dysgenesis

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KW - Hepatoid carcinoma

KW - Ovarian neoplasms

KW - Yolk sac tumor

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