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ovarian yolk sac tumor

Wednesday 10 March 2004

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).

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.