Ovary

Germ cell tumors

Yolk sac tumor


Editorial Board Member: Ricardo R. Lastra, M.D.
Deputy Editor-in-Chief: Jennifer A. Bennett, M.D.
Gulisa Turashvili, M.D., Ph.D.

Topic Completed: 11 May 2021

Minor changes: 17 May 2021

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PubMed Search: Ovarian yolk sac tumor[TIAB]

Gulisa Turashvili, M.D., Ph.D.
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Cite this page: Turashvili G. Yolk sac tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarytumoryolksac.html. Accessed September 21st, 2021.
Definition / general
  • Primitive germ cell tumor with a variety of morphologic patterns, ranging from endodermal extraembryonic structures (secondary yolk sac, allantois) to, less commonly, endodermal somatic tissues (intestine, liver, mesenchyme)
Essential features
  • Most common before the age of 30
  • Usually occurs as a pure form or rarely as a component of a mixed germ cell tumor
  • Numerous morphologic patterns, with the hallmark Schiller-Duval bodies in some cases and immunohistochemical expression of SALL4, glypican 3 and AFP
  • Often associated with elevated serum alpha fetoprotein (AFP)
  • Usually favorable clinical outcomes due to chemosensitivity
Terminology
  • Primitive endodermal tumor (not recommended)
  • Endodermal sinus tumor (not recommended)
ICD coding
  • ICD-O: 9071/3 - yolk sac tumor
  • ICD-10: C56 - malignant neoplasm of ovary
  • ICD-11:
    • 2C73.5 - endodermal sinus tumor, unspecified site, female
    • 2C73.Y & XH09W7 - other specified malignant neoplasms of the ovary, yolk sac tumor
Epidemiology
Sites
Pathophysiology
Clinical features
Diagnosis
  • Microscopic examination
Laboratory
  • Elevated serum levels of AFP (may be used diagnostically and in monitoring therapy)
Radiology description
  • Ultrasonography:
  • Computed tomography:
    • Usually appears as a unilateral large complex mass with solid and cystic components, heterogeneous enhancement and enlarged intratumoral vessels with hemorrhage and capsular tear (Acta Radiol 2016;57:197)
    • Helpful features for differentiating yolk sac tumor from other ovarian tumors include a mixed solid / cystic nature, intratumoral hemorrhage, marked enhancement and dilated intratumoral vessels (Sci Rep 2015;5:11000)
    • Intratumoral calcification and fatty tissue if associated with teratoma
  • Magnetic resonance imaging:
Radiology images

Images hosted on other servers:

Large mass with ascites

Bilateral ovarian mass

Prognostic factors
  • Usually favorable prognosis due to chemosensitivity, with complete cure in > 80% of cases
  • Stage dependent, with 5 year survival rates of > 95% for stage I - II, 70% for stage III and 50% for stage IV (Gynecol Oncol 2017;147:296, Int J Gynecol Cancer 2018;28:77)
  • Prominent polyvesicular vitelline pattern associated with more indolent behavior (Am J Surg Pathol 2013;37:393)
  • Pure hepatoid and glandular intestinal type yolk sac tumors associated with poorer prognosis
Case reports
Treatment
Clinical images

Images hosted on other servers:

Large ovarian tumor

Gross description
  • Usually unilateral ovarian mass with predilection for right ovary
  • Encapsulated with smooth and glistening surface, round, oval or globular, may be firm or somewhat lobulated
  • Rupture in 25% of cases (Int J Surg Pathol 2014;22:677)
  • Mean size 15 cm (range 3 - 30)
  • Fleshy, gray-yellow to gray-tan, solid and cystic friable cut surface, often with gelatinous changes and areas of hemorrhage and necrosis (Cancer 1976;38:2404)
  • May form adhesions to surrounding structures
  • When part of a mixed germ cell tumor, other components, such as a mature cystic teratoma or dysgerminoma, may be grossly recognizable
  • Honeycomb appearance (multiple small cysts) on cut surface if polyvesicular vitelline component is present (Am J Surg Pathol 2013;37:393)
Gross images

Contributed by Debra L. Zynger, M.D. and AFIP images
Smooth, nodular exterior

Smooth, nodular exterior

Gelatinous cut surface

Gelatinous cut surface

Gelatinous cystic surface

Honeycomb surface (polyvesicular vitelline pattern)

Frozen section description
  • Admixure of characteristic growth patterns and tumor cells with clear to eosinophilic cytoplasm, variable cytologic atypia and mitotic activity, with or without Schiller-Duval bodies
Frozen section images

Contributed by Gulisa Turashvili, M.D., Ph.D.

High grade neoplasm

Cytologic atypia

Microscopic (histologic) description
  • Multiple histologic patterns with predominance of 1 or 2 patterns
  • Reticular / microcystic pattern:
    • Most common pattern
    • Loose meshwork of anastomosing channels and variably sized cysts (macro or microcysts) lined by primitive tumor cells with varying amounts of clear to eosinophilic cytoplasm (Cancer 1976;38:2404, Histopathology 2012;60:1023, Int J Surg Pathol 2014;22:677)
    • Lining cells may be flattened and deceptively bland
    • Tumor cells occasionally contain lipid and have a signet ring-like morphology
    • Cysts may contain eosinophilic hyaline globules and amorphous, eosinophilic acellular basement membrane-like material
    • Loose, hypocellular or myxoid stroma
  • Endodermal sinus pattern:
    • Anastomosing network of labyrinthine-like spaces lined by tumor cells
    • Formation of vaguely glomeruloid perivascular structures (Schiller-Duval bodies)
      • Hallmark of yolk sac tumor but their absence does not rule out the diagnosis
      • Variably present, ranging from 20 - 75% of cases (Surg Pathol Clin 2019;12:621)
      • Rounded to elongated papillary structures containing a central fibrovascular core with a single central vessel, surrounded by tumor cells projecting into a cystic / sinusoidal space (resembling immature glomeruli) (Histopathology 2012;60:1023)
  • Papillary pattern:
    • Papillae containing fibrovascular cores lined by pleomorphic tumor cells with brisk mitoses
    • Fibrovascular cores may be hyalinized
    • May contain tumor giant cells (mono or multinucleated)
  • Solid pattern:
    • Sheets of polygonal tumor cells with large vesicular or pyknotic nuclei with prominent nucleoli, brisk mitoses, clear to eosinophilic cytoplasm and well defined borders, sometimes with prominent hyaline globules
    • Cells may be smaller and more blastema-like with scant cytoplasm
    • May contain tumor giant cells (mono or multinucleated)
  • Festoon pattern:
    • Complex ribbons and undulating cords
    • Occasionally with a drape-like arrangement
  • Glandular pattern (forming endodermal somatic derivatives):
    • Endometrioid type areas with glandular or villoglandular structures lined by single or multiple layers of tall columnar cells containing subnuclear or supranuclear vacuoles resembling secretory endometrium
    • Intestinal type areas with glandular structures lined by mucinous columnar or low columnar glands, ranging from primitive cribriform structures to well differentiated glands with goblet cells and rarely Paneth cells
    • Both types may occur in pure form and may contain tumor giant cells (mono or multinucleated)
  • Polyvesicular vitelline pattern (Am J Surg Pathol 2013;37:393):
    • May occur in pure form
    • Variably sized cysts or vesicles lined by flat to cuboidal to columnar cells, sometimes with basal or paraluminal vacuolation
    • Variably cellular stroma, occasionally with eccentric constriction (resembling subdivision of primary yolk sac vesicle)
  • Parietal pattern:
    • Tumor cells embedded in extracellular linear bands of PAS positive basement membrane-like material
  • Hepatoid pattern:
    • Tends to occur in pure form
    • Aggregates, clusters or cords of large polygonal cells with abundant uniform or granular eosinophilic cytoplasm, round nuclei and prominent nucleoli, separated by thin fibrous bands (Cancer 1982;50:2355)
  • Mesenchyme-like pattern:
    • Cords, tubules and gland-like structures of tumor cells scattered in edematous to myxoid stroma
    • May be markedly myxoid (magma reticulare)
  • General features:
    • Variable cytologic atypia and mitotic activity
    • Pale eosinophilic to clear cytoplasm
    • Prominent nucleoli
    • Intracellular hyaline globules
    • Tumor cells lining cystic structures can be deceptively bland
    • Rarely stromal luteinization
    • May show areas of extramedullary hematopoiesis
    • May be admixed with other malignant germ cell tumor, usually with dysgerminoma or gonadoblastoma in patients with gonadal dysgenesis
    • May be associated with synchronous or metachronous ipsilateral or contralateral mature cystic teratoma
Microscopic (histologic) images

Contributed by Gulisa Turashvili, M.D., Ph.D., Sharon Song, M.D. and AFIP images

Reticular / microcystic pattern

Glandular pattern

Endometrioid-like glandular variant

Solid pattern


Papillary pattern

Polyvesicular vitelline pattern

Schiller-Duval body

Hepatoid variant


AFP

SALL4

GATA3

Pancytokeratin

CK7

Virtual slides

Images hosted on other servers:

Yolk sac tumor

Yolk sac tumor

Yolk sac tumor

AFP

Glypican 3

Positive stains
Negative stains
Electron microscopy description
  • Glandular intestinal type yolk sac tumor shows large nuclei with prominent nucleolonema, numerous intracytoplasmic ribosomes, rough endoplasmic reticulum, mitochondria and dense amorphous intracellular material (Pathol Res Pract 1987;182:609)
Molecular / cytogenetics description
Sample pathology report
  • Right fallopian tube and ovary, salpingo-oophorectomy:
    • Ovary: yolk sac tumor (see synoptic report)
    • Fallopian tube: benign
Differential diagnosis
Board review style question #1

Which immunohistochemical markers are useful for differentiating this ovarian tumor from a dysgerminoma?

  1. CD10, FOXL2, glypican 3 and SALL4
  2. FOXL2, CD30, SALL4 and OCT 3/4
  3. OCT 3/4, glypican 3, inhibin and SF1
  4. OCT 3/4, glypican 3, CD30 and AFP
  5. SALL4, CD10, glypican 3 and CD30
Board review style answer #1
D. OCT 3/4, glypican 3, CD30 and AFP

Comment Here

Reference: Yolk sac tumor
Board review style question #2
Which of the following is true about yolk sac tumors?

  1. Call-Exner bodies
  2. Expression of SALL4, AFP and glypican 3 by immunohistochemistry
  3. Homer Wright rosettes
  4. Low serum AFP levels
  5. Most common in postmenopausal women
Board review style answer #2
B. Expression of SALL4, AFP and glypican 3 by immunohistochemistry

Comment Here

Reference: Yolk sac tumor
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