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 (left of image). 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 OCT4, PLAP +ve, D2-40 +ve
Site testis
Prognosis premalignant
Treatment radiotherapy (?)

It is also known as testicular intraepithelial neoplasia.[1]

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:[4]

  • Undifferentiated ITGCN.
  • Differentiated ITGCN.[5]
    • Intratubular embryonal carcinoma.
    • Intratubular seminoma.

Treatment:

  • Radiotherapy.[1]

Microscopic

Features:[6][7]

  • "Large" round or polygonal nuclei.
    • Size in relation to normal often not defined.
      • Rakheja et al. say >= 5x a lymphocyte for intratubular embryonal carcinoma.[4]
    • Polygonal nuclei = squared-off nuclear membrane.
  • Prominent nucleoli - key feature.
  • Clear cytoplasm - important.
  • +/-Cells fill the tubule.

Note:

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

DDx:

  • Sertoli cell-only syndrome - Sertoli cells also have nucleoli, wind swept appearance.[8]
  • Seminoma - especially intratubular predominant growth pattern.
  • Embryonal carcinoma.

Images

Case 1

  • ITGCN - intermed. mag.

  • ITGCN - high mag.

  • ITGCN - very high mag.

  • ITGCN - very high mag.

Case 2

  • ITGCN - cropped. (WC/Nephron)

  • ITGCN. (WC/Nephron)

Case 3

  • ITGCN & SCO - intermed. mag.

  • ITGCN & SCO - high mag.

  • ITGCN & SCO - intermed. mag.

  • ITGCN & SCO - high mag.

  • ITGCN & SCO - very high mag.

www

IHC

ISUP consensus

ITGCN versus atypical intratubular germ cells:[9]

  • OCT4 +ve.

Alternates:

Others

  • CD117 +ve.
    • Disputed: doesn't differentiate neoplastic from non-neoplastic according to Biermann et al.[11]
  • OCT3/4 +ve.

See also

References

  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. ↑ Müller J, Skakkebaek NE, Parkinson MC (February 1987). "The spermatocytic seminoma: views on pathogenesis". Int. J. Androl. 10 (1): 147–56. PMID 3583416.
  3. ↑ 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.
  4. ↑ 4.0 4.1 4.2 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.
  5. ↑ 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.
  6. ↑ URL: http://www.webpathology.com/image.asp?case=30&n=1. Accessed on: 18 May 2010.
  7. ↑ Gondos, B.; Migliozzi, JA. (Nov 1987). "Intratubular germ cell neoplasia.". Semin Diagn Pathol 4 (4): 292-303. PMID 3328244.
  8. ↑ URL: http://www.webpathology.com/image.asp?n=3&Case=28. Accessed on: 25 March 2013.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
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