Germ cell neoplasia in situ

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Germ cell neoplasia in situ
Diagnosis in short

GCNIS (left of image). H&E stain.

Synonyms intratubular germ cell neoplasia (old term)

LM "large" round or polygonal nuclei, prominent nucleoli, clear cytoplasm, +/-cells (completely) fill the tubule
Subtypes undifferentiated, differentiated (intratubular seminoma, intratubular non-seminoma)
LM DDx seminoma, embryonal carcinoma, Sertoli cell-only syndrome, mixed germ cell tumour
IHC OCT4, PLAP +ve, D2-40 +ve
Site testis

Prognosis premalignant
Treatment radiotherapy (?)

Germ cell neoplasia in situ, abbreviated GCNIS, is a premalignant lesion of the testis.

It was previously known previously known as intratubular germ cell neoplasia (abbreviated ITGCN) and testicular intraepithelial neoplasia.[1][2]


  • 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 GCNIS:


  • Undifferentiated GCNIS.
  • Differentiated GCNIS.[6]
    • Intratubular seminoma.
    • Intratubular non-seminoma.


  • Radiotherapy.[1]



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


  • Sertoli cells may have a nucleolus... but they have eosinophilic ctyoplasm.[citation needed]



Case 1

Case 2

Case 3



ISUP consensus

GCNIS (ITGCN) versus atypical intratubular germ cells:[10]

  • OCT4 +ve.



  • CD117 +ve.
    • Disputed: doesn't differentiate neoplastic from non-neoplastic according to Biermann et al.[12]
  • OCT3/4 +ve.

See also


  1. 1.0 1.1 Dieckmann, KP.; Wilken, S.; Loy, V.; Matthies, C.; Kleinschmidt, K.; Bedke, J.; Martinschek, A.; Souchon, R. et al. (May 2013). "Treatment of testicular intraepithelial neoplasia (intratubular germ cell neoplasia unspecified) with local radiotherapy or with platinum-based chemotherapy: a survey of the German Testicular Cancer Study Group.". Ann Oncol 24 (5): 1332-7. doi:10.1093/annonc/mds628. PMID 23293116.
  2. Berney, DM.; Looijenga, L.; Idrees, M.; Oosterhuis, JW.; Rajpert-De Meyts, E.; Ulbright, TM.; Skakkebaek, NE. (Feb 2016). "Germ Cell Neoplasia In Situ (GCNIS). Evolution of the Current Nomenclature for Testicular Pre-invasive Germ Cell Malignancy.". Histopathology. doi:10.1111/his.12958. PMID 26918959.
  3. Müller J, Skakkebaek NE, Parkinson MC (February 1987). "The spermatocytic seminoma: views on pathogenesis". Int. J. Androl. 10 (1): 147–56. PMID 3583416.
  4. 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.
  5. 5.0 5.1 5.2 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.;2.
  6. 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.
  7. URL: Accessed on: 18 May 2010.
  8. Gondos, B.; Migliozzi, JA. (Nov 1987). "Intratubular germ cell neoplasia.". Semin Diagn Pathol 4 (4): 292-303. PMID 3328244.
  9. URL: Accessed on: 25 March 2013.
  10. Amin, MB.; Epstein, JI.; Ulbright, TM.; Humphrey, PA.; Egevad, L.; Montironi, R.; Grignon, D.; Trpkov, K. et al. (Aug 2014). "Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference.". Am J Surg Pathol 38 (8): 1017-22. doi:10.1097/PAS.0000000000000254. PMID 25025364.
  11. 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.
  12. 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.