ovarian yolk sac tumor

Definition: Malignant germ cell tumor of the ovary developed as a result of differentiation of primitive malignant germ cell elements in the direction of yolk sac or vitelline structures (endodermal sinus tumor).

Yolk sac tumor has the pathognomonic Schiller-Duval body, consisting of a central blood vessel surrounded by germ cells. Serum AFP and alpha-1-antitrypsin are elevated. It stains by IHC for AFP, CD10 and CK. It is frequently in association with a benign teratoma.

Images

 Eosinophilic hyaline globules in a yolk sac tumor of ovary

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Clinical synopsis

 Usually children and young adults:

• median age 19 years
• ≈25% prepubertal at diagnosis
   None present with precocious puberty, amenorrhea, or hirsutism
   Vaginal bleeding in 1%
   Serum α-fetoprotein level invariably elevated
   Chorionic gonadotropin levels normal:
   resulting in consistently negative pregnancy tests

Macroscopy

 Average diameter: 15cm
 External surface: smooth, glistening
 Cut surface: variegated, partially cystic, often large foci of hemorrhage and necrosis.
 The cut surface is remarkably heterogeneous due to extensive hemorrhage, necrosis, and cystic degeneration.
 Component of benign cystic teratoma in ≈15% of cases

Miccroscopy

 Very variable:

• reticular or microcystic areas formed by loose meshwork lined by flat or cuboidal cells
• rounded or festooning pseudopapillary processes with central vessels (Schiller–Duval bodies)
• solid ‘undifferentiated’ areas

 Mesenchyme-like component has pluripotential properties:

• usually spindle cells in a well-vascularized myxoid background
• may contain heterologous elements such as skeletal muscle

 PAS-positive hyaline droplets

• hyaline globules seen in the cytoplasm of the tumor cells
• intracytoplasmic and extracellular
• nearly always present

 25% have vesicular structures with eccentric constrictions surrounded by a dense spindle cell stroma: polyvesicular vitelline pattern

 Some show:

• scattered hCG-positive syncytiotrophoblast component
• differentiation toward hepatic, intestinal, and parietal yolk sac structures
• parietal yolk sac structures recognized by thick layers of intercellular basement membrane
• hepatoid component:
  • can predominate almost to exclusion of others
  • masses, nests, and broad bands of large polyhedral cells with occasional glandular formations and numerous hyaline bodies
  • immunohistochemical profile similar to that of hepatocellular carcinoma, including reactivity for:
    • α1-antitrypsin
    • canalicular pattern with polyclonal CEA

• areas of luteinized stromal cells: sometimes responsible for virilization

Immunochemistry

 positive:

• pancreatin

 negative for:

• • keratin 7 (in contrast with endometrioid and clear cell ovarian carcinoma)
  • WT-1 (in contrast with serous ovarian carcinoma)

 Hyaline droplets:

• heterogeneous chemical composition
• usually stain for α-fetoprotein
• may also contain: α1-antitrypsin and basement membrane components (type IV collagen, laminin)

Variants

 endodermal component

• parietovisceral pattern
• glandular pattern
• tubulopapillary pattern (glandulopapillary pattern)
• mucinous carcinoid component (16096416)
   mucinous carcinoid in endodermal differentiation of ovarian yolk sac tumors (16096416)

Associations

 46XY gonadal dysgenesis (1346359)
 histiocytic sarcoma (1346359)

Pathogenesis

 Recapitulates normal yolk sac elements:

• confirmed by histochemical and ultrastructural studies,4–6 including: recent detection of GATA-4: a transcription factor that regulates differentiation and function of murine yolk sac endoderm
   Keratin immunoreactivity of mesenchyme-like component indicates early epithelial differentiation
  
  Genetics

 Invariably aneuploid

Differential diagnosis

 ovarian endometrioid carcinoma (15489654)
 ovarian clear cell carcinoma (15489654)
 tubular and microcystic pattern in ovarian dysgerminoma 15767805)
 ovarian clear cell tumors
 ovarian Sertoli-Leydig cell tumor
 ovarian dysgerminoma (seminoma )

 hepatoid yolk sac tumors and hepatoid ovarian carcinomas of probable surface epithelial origin

• Hepatoid carcinoma of ovary greatly resembles hepatocellular carcinoma, should be distinguished from yolk sac tumor with hepatoid differentiation.

 Glandular formations may simulate appearance of endometrioid carcinoma.

Therapy

 Multidrug chemotherapy has dramatically improved survival rates.
 Serial determinations of serum α-fetoprotein useful in monitoring course.

Prognosis

 Clinical stage is most important prognostic indicator.
 Polyvesicular vitelline pattern said to be associated with a good prognosis in pure form.

Links

 PathConsult

See also

 ovarian germ cell tumors
 yolk sac tumor (endodermal sinus tumor )

References

 Ramalingam P, Malpica A, Silva EG, Gershenson DM, Liu JL, Deavers MT. The use of cytokeratin 7 and EMA in differentiating ovarian yolk sac tumors from endometrioid and clear cell carcinomas. Am J Surg Pathol. 2004 Nov;28(11):1499-505. PMID: 15489654

 Nogales FF, Buritica C, Regauer S, Gonzalez T. Mucinous carcinoid as an unusual manifestation of endodermal differentiation in ovarian yolk sac tumors. Am J Surg Pathol. 2005 Sep;29(9):1247-51. PMID: 16096416

 Oh C, Kendler A, Hernandez E. Ovarian endodermal sinus tumor in a postmenopausal woman. Gynecol Oncol. 2001;82:392–394.

 Kurman RJ, Norris HJ. Endodermal sinus tumor of the ovary. A clinical and pathologic analysis of 71 cases. Cancer. 1976;38:2404–2419.

 Teilum G. Endodermal sinus tumors of the ovary and testis. Comparative morphogenesis of the so-called mesonephroma ovarii (Schiller) and extraembryonic (yolk sac-allantoic) structures of the rat’s placenta. Cancer. 1959;12:1092–1105.

 Nogales FF. Embryologic clues to human yolk sac tumors. A review. Int J Gynecol Pathol. 1993;12:101–107.

 Nogales FF, Beltran E, Pavcovich M, Bustos M. Ectopic somatic endoderm in secondary human yolk sac. Hum Pathol. 1992;23:921–924.

 Nogales-Fernandez G, Silverberg SG, Bloustein PA, Martinez-Hernandez A, Pierce GB. Yolk sac carcinoma (endodermal sinus tumor). Ultrastructure and histogenesis of gonadal and extragonadal tumors in comparison with normal human yolk sac. Cancer. 1977;39:1462–1474.

 Siltanen S, Anttonen M, Heikkila P, Narita N, Laitinen M, Ritvos O, et al. Transcription factor GATA-4 is expressed in pediatric yolk sac tumors. Am J Pathol. 1999;155:1823–1829.

 Michael H, Ulbright TM, Brodhecker CA. The pluripotential nature of the mesenchyme-like component of yolk sac tumor. Arch Pathol Lab Med. 1989;113:1115–1119.

 Gonzalez-Crussi F. The human yolk sac and yolk sac (endodermal sinus) tumors. A review. Persp Pediatr Pathol. 1979;5:179–215.

 Cohen MB, Friend DS, Molnar JJ. Gonadal endodermal sinus (yolk sac) tumor with pure intestinal differentiation. A new histologic type. Pathol Res Pract. 1987;182:609–616.

 Ulbright TM, Roth LM, Brodhecker CA. Yolk sac differentiation in germ cell tumors. A morphologic study of 50 cases with emphasis on hepatic, enteric, and parietal yolk sac features. Am J Surg Pathol. 1986;10:151–164.

 Devouassoux-Shisheboran M, Schammel DP, Tavassoli FA. Ovarian hepatoid yolk sac tumors: morphological, immunohistochemical and ultrastructural features. Histopathology. 1999;34:462–469.

 Prat J, Bhan AK, Dickersin GR, Robboy SJ, Scully RE. Hepatoid yolk sac tumor of the ovary (endodermal sinus tumor with hepatoid differentiation). A light microscopic, ultrastructural and immunohistochemical study of seven cases. Cancer. 1982;50:2355–2368.

 Ramalingam P, Malpica A, Silva EG, Liu Jl, Gershenson DM, Deavers MT. The use of cytokeratin 7 in differentiating yolk sac tumors from endometrioid and clear cell carcinomas of the ovary (Abstract). Mod Pathol. 2003;16:207a.

 Barsky SH, Hannah JB. Extracellular hyaline bodies are basement membrane accumulations. Am J Clin Pathol. 1987;87:455–460.

 Ishikura H, Scully RE. Hepatoid carcinoma of the ovary. A newly described tumor. Cancer. 1987;60:2775–2784.

 Clement PB, Young RH, Scully RE. Endometrioid-like variant of ovarian yolk sac tumor. A clinicopathological analysis of eight cases. Am J Surg Pathol. 1987;11:767–778.

 Kommoss F, Bibbo M, Talerman A. Nuclear deoxyribonucleic acid content (ploidy) of endodermal sinus (yolk sac) tumor. Lab Invest. 1990;62:223–231.

 Gershenson DM, Del Junco G, Herson J, Rutledge FN. Endodermal sinus tumor of the ovary. The M.D. Anderson experience. Obstet Gynecol. 1983;61:194–202.

 Kawai M, Furuhashi Y, Kano T, Misawa T, Nakashima N, Hattori S, et al. Alpha-fetoprotein in malignant germ cell tumors of the ovary. Gynecol Oncol. 1990;39:160–166.

 Talerman A, Haije WG, Baggerman L. Serum alphafetoprotein (AFP) in diagnosis and management of endodermal sinus (yolk sac) tumor and mixed germ cell tumor of the ovary. Cancer. 1978;41:272–278.

 Kawai M, Kano T, Furuhashi Y, Mizuno K, Nakashima N, Hattori SE, et al. Prognostic factors in yolk sac tumors of the ovary. A clinicopathologic analysis of 29 cases. Cancer. 1991;67:184–192.

 Nawa A, Obata N, Kikkawa F, Kawai M, Nagasaka T, Goto S, et al. Prognostic factors of patients with yolk sac tumors of the ovary. Am J Obstet Gynecol. 2001;184:1182–1188.

 Nogales FF, Matilla A, Nogales-Ortiz F, Galera-Davidson HL. Yolk sac tumors with pure and mixed polyvesicular vitelline patterns. Hum Pathol. 1978;9:553–566.