Germ cell neoplasia in situ

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Intratubular germ cell neoplasia, abbreviated ITGCN, is a premalignant lesion of the testis.

Germ cell neoplasia in situ
Diagnosis in short

ITGCN. H&E stain.

LM "large" round or polygonal nuclei, prominent nucleoli, clear cytoplasm, +/-cells (completely) fill the tubule
Subtypes undifferentiated, differentiated (intratubular seminoma, intratubular embyronal carcinoma)
LM DDx seminoma, embryonal carcinoma, Sertoli cell-only syndrome
IHC PLAP +ve, OCT3/4 +ve, CD117 +ve
Site testis

Prognosis premalignant

General

  • Considered the precursor lesion for germ cell tumours.
  • Not all germ cell tumours (GCTs) arise from intratubular germ cell neoplasia.

The following testicular GCTs do not arise from ITGCN:

Classification:[3]

  • Undifferentiated ITGCN.
  • Differentiated ITGCN.[4]
    • Intratubular embryonal carcinoma.
    • Intratubular seminoma.

Microscopic

Features:[5][6]

  • "Large" round or polygonal nuclei.
    • Size in relation to normal often not defined.
      • Rakheja et al. say >= 5x a lymphocyte for intratubular embryonal carcinoma.[3]
    • Polygonal nuclei = squared-off nuclear membrane.
  • Prominent nucleoli - key feature.
  • Clear cytoplasm.
  • +/-Cells fill the tubule.

DDx:

Images

www:

IHC

Features:[8]

  • PLAP +ve.[9]
  • CD117 +ve.
    • Disputed: doesn't differentiate neoplastic from non-neoplastic according to Biermann et al.[10]
  • OCT3/4 +ve.

Note:

  • Normal testis PLAP -ve, CD117 -ve.[11]

See also

References

  1. Müller J, Skakkebaek NE, Parkinson MC (February 1987). "The spermatocytic seminoma: views on pathogenesis". Int. J. Androl. 10 (1): 147–56. PMID 3583416.
  2. Manivel JC, Simonton S, Wold LE, Dehner LP (June 1988). "Absence of intratubular germ cell neoplasia in testicular yolk sac tumors in children. A histochemical and immunohistochemical study". Arch. Pathol. Lab. Med. 112 (6): 641–5. PMID 2837162.
  3. 3.0 3.1 3.2 Rakheja, D.; Hoang, MP.; Sharma, S.; Albores-Saavedra, J. (Apr 2002). "Intratubular embryonal carcinoma.". Arch Pathol Lab Med 126 (4): 487-90. doi:10.1043/0003-9985(2002)1260487:IEC2.0.CO;2. PMID 11900581. http://www.archivesofpathology.org/doi/full/10.1043/0003-9985(2002)126%3C0487:IEC%3E2.0.CO;2.
  4. Lau, SK.; Weiss, LM.; Chu, PG. (Jul 2007). "Association of intratubular seminoma and intratubular embryonal carcinoma with invasive testicular germ cell tumors.". Am J Surg Pathol 31 (7): 1045-9. doi:10.1097/PAS.0b013e31802b8712. PMID 17592271.
  5. URL: http://www.webpathology.com/image.asp?case=30&n=1. Accessed on: 18 May 2010.
  6. Gondos, B.; Migliozzi, JA. (Nov 1987). "Intratubular germ cell neoplasia.". Semin Diagn Pathol 4 (4): 292-303. PMID 3328244.
  7. URL: http://www.webpathology.com/image.asp?n=3&Case=28. Accessed on: 25 March 2013.
  8. Honecker, F.; Stoop, H.; de Krijger, RR.; Chris Lau, YF.; Bokemeyer, C.; Looijenga, LH. (Jul 2004). "Pathobiological implications of the expression of markers of testicular carcinoma in situ by fetal germ cells.". J Pathol 203 (3): 849-57. doi:10.1002/path.1587. PMID 15221945.
  9. Schreiber, L.; Lifschitz-Mercer, B.; Paz, G.; Yavetz, H.; Elliott, DJ.; Kula, K.; Slowikowska-Hilczer, J.; Maymon, BB. (Jan 2003). "Double immunolabeling by the RBM and the PLAP markers for identifying intratubular (in situ) germ cell neoplasia of the testis.". Int J Surg Pathol 11 (1): 17-20. PMID 12598912.
  10. Biermann, K.; Stoop, H.; Looijenga, L. (May 2012). "c-KIT protein expression does not discriminate neoplastic from non-neoplastic intratubular germ cells.". Histopathology 60 (6): 1017-9. doi:10.1111/j.1365-2559.2011.04157.x. PMID 22340755.
  11. Hawkins, E.; Heifetz, SA.; Giller, R.; Cushing, B. (Apr 1997). "The prepubertal testis (prenatal and postnatal): its relationship to intratubular germ cell neoplasia: a combined Pediatric Oncology Group and Children's Cancer Study Group.". Hum Pathol 28 (4): 404-10. PMID 9104938.