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Yolk Sac Tumor

Definition

Malignant germ cell neoplasm which recapitulates the primary embryonal yolk sac tissue.

Clinical Features

  • Unilateral
  • A yolk sac pattern is seen in testicular tumors under two circumstances:
    • as a pure form
    • as a component of a mixed germ cell tumor in adults

Pathogenesis

  • Hypermethylation of the RUNX3 gene promoter is thought to play a pathogenetic role1
  • Pediatric cases express GATA-4, a transcription factor that regulates differentiation and function of murine yolk sac endoderm2

Gross Pathology

  • Pure yolk sac tumor of infancy:
    • soft consistency
    • microcystic appearance on cross section (Fig. 1
      Gross appearance of pure yolk sac tumor in an infant.

      Fig. 1: Gross appearance of pure yolk sac tumor in an infant.

      )
  • Yolk sac element in germ cell tumor of adult:
    • difficult to discern yolk sac elements

Histopathology

  • Appearance recapitulates primary yolk sac3,4
  • Microcystic, glandular–alveolar, and papillary formations are common
  • Many of the cystic spaces are lined by a very flattened, endothelium-like layer of cells
  • Stroma:
    • can be quite cellular, spindle shaped, and reminiscent of smooth muscle
    • appears to represent a chemoresistant, pluripotential cell population
    • rarely gives rise to a sarcoma (of spindle cell type against a background of a myxoid to collagenous stroma6) after treatment7
  • Perivascular Schiller–Duval body:
    • most distinctive feature of yolk sac tumor (Fig. 2
      Schiller–Duval body in yolk sac tumor of testis.

      Fig. 2: Schiller–Duval body in yolk sac tumor of testis.

      )
    • have been compared to structures seen in rat placenta8 and represent an attempt to form yolk sacs
  • Hyaline intracytoplasmic and extracytoplasmic round inclusions (Fig. 3
    Pleomorphism and hyaline globules in yolk sac tumor of testis.

    Fig. 3: Pleomorphism and hyaline globules in yolk sac tumor of testis.

    ):

Special Stains and Immunohistochemistry

  • Most immunoreactivity for AFP:
    • diffuse or granular throughout the cytoplasm
    • not in the hyaline globules
  • Consistently positive for keratin12

Diagnosis

Variants

  • Variants of yolk sac tumor that tend to be misinterpreted exhibit:
    • an hepatoid pattern (featuring fetal-type liver cell cords)
    • a solid pattern
    • a well-differentiated glandular pattern (resembling fetal lung or intestine, the latter also referred to as primitive intestinal or enteric pattern)20–23

Genetics

  • Practically all cases have an aneuploid DNA pattern24

References

1 Kato N, Tamura G, Fukase M, Shibuya H, Motoyama T. Short communication. Hypermethylation of the RUNX3 gene promoter in testicular yolk sac tumor of infants. Am J Pathol. 2003;163:387–391.

2 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.

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

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

5 Gonzalez-Crussi F, Roth LM. The human yolk sac and yolk sac carcinoma. An ultrastructural study. Hum Pathol. 1976;7:675–691.

6 Ulbright TM, Michael H, Loehrer PJ, Donohue JP. Spindle cell tumors resected from male patients with germ cell tumors. A clinicopathologic study of 14 cases. Cancer. 1990;65:148–156.

7 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.

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

9 Grigor KM, Detre SI, Kohn J, Neville AM. Serum alphafoetoprotein levels in 153 male patients with germ cell tumours. Br J Cancer. 1977;35:52–58.

10 Jacobsen GK, Jacobsen M. Alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in testicular germ cell tumours. Acta Pathol Microbiol Immunol Scand (A). 1983;91:165–176.

11 Shirai T, Itoh T, Yoshiki T, Noro T, Tomino Y, Hayasaka T. Immunofluorescent demonstration of alpha-fetoprotein and other plasma proteins in yolk sac tumor. Cancer. 1976;38:1661–1667.

12 Eglen DE, Ulbright TM. The differential diagnosis of yolk sac tumor and seminoma. Usefulness of cytokeratin, alpha-fetoprotein, and alpha-1-antitrypsin immunoperoxidase reactions. Am J Clin Pathol. 1987;88:328–332.

13 Kramer SA, Wold LE, Gilchrist GS, Svensson J, Kelasis PP. Yolk sac carcinoma. An immunohistochemical and clinicopathologic review. J Urol. 1984;131:315–318.

14 Logothetis CJ, Samuels ML, Trindade A, Grant C, Gomez L, Ayala A. The prognostic significance of endodermal sinus tumor histology among patients treated for stage III nonseminomatous germ cell tumors of the testes. Cancer. 1984;53:122–128.

15 Talerman A. The incidence of yolk sac tumor (endodermal sinus tumor) elements in germ cell tumors of the testis in adults. Cancer. 1975;36:211–215.

16 Wurster K, Hedinger CE, Meienberg O. Orchioblastomatous foci in testicular teratoma of adults. Virchows Arch [A]. 1972;357:231–242.

17 Talerman A. Endodermal sinus (yolk sac) tumor elements in testicular germ cell tumors in adults. Comparison of prospective and retrospective studies. Cancer. 1980;46:1213–1217.

18 Parkinson C, Beilby JOW. Testicular germ cell tumours. Should current classification be revised? Invest Cell Pathol. 1980;3:135–140.

19 Talerman A. Yolk sac tumor associated with seminoma of the testis in adults. Cancer. 1974;33:1468–1473.

20 Heifetz SA, Cushing B, Giller R, Shuster JJ, Stolar CJH, Vinocur CD, et al. Immature teratomas in children: pathologic consideration: a report from the combined Pediatric Oncology Group/ Children's Cancer Group. Am J Surg Pathol. 1998;22:1115–1124.

21 Henley JD, Michael H, Young RH, Ulbright TM. Solid pattern of yolk sac tumor of the testis: A histologic and immunohistochemical study of 9 cases. Mod Pathol. 2003;16:153A.

22 Jacobsen GK, Jacobsen M. Possible liver cell differentiation in testicular germ cell tumours. Histopathology. 1983;7:537–548.

23 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.

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

Last updated: 30 Mar 2006

Yolk Sac Tumor

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