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germ cell neoplasia in situ

Tuesday 14 March 2006

intratubular germ cell neoplasia of testis, ITGCN, IGCNU, Intra-tubular Germ Cell Neoplasia-Unclassified ; intratubular germ cell neoplasia; GCNIS


Definition: The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies.


- Germ Cell Neoplasm in-situ (GCNIS) / Intratubular Seminoma component, Formerly called ITGCN,in a seminoma.

- GCNIS in Sertoli nodule

Initially termed ‘carcinoma in situ’ (CIS), it has also been known as ‘intratubular germ cell neoplasia, unclassified’ (IGCNU) and ‘testicular intraepithelial neoplasia’ (TIN).

Testicular germ cell cancer develops from premalignant intratubular germ cell neoplasia (ITGCN) , unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4(+)/MAGEA4(-)) into pre-spermatogonia (OCT4(-)/MAGEA4(+)).

Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described.

OCT4(+)/MAGEA4(-) cells are the most frequent and most proliferative cell population in tubules containing intratubular germ cell neoplasia, which appears to be an important factor in determining invasive potential of intratubular germ cell neoplasia to seminomas.


- Seminiferous tubules with intratubular germ cell neoplasia show large cells with clear cytoplasm, enlarged vesicular nuclei, and prominent nucleoli.
- There is no spermatogenesis.
- The tubular basement membrane is thickened.
- testicular microliths

  • Isolated testicular microliths may be seen in cryptorchid testes, prepubertal Klinefelter syndrome, male pseudohermophroditism, and rarely in normal testes.



  • Immunoreactivity for Placental-like Alkaline Phosphatase (PLAP) with cytoplasmic membrane staining and some cytoplasmic staining is a quite sensitive and specific test for ITGCN.
  • Generally less than 1% of non-neoplastic spermatocytes show staining with PLAP.
  • PLAP immunostaining in ITGCN is predominantly cytoplasmic membrane staining with some cytoplasmic staining.

- c-kit (CD17)

  • The staining pattern of C-kit is identical to that of PLAP in ITGCN.

- OCT3/4

  • OCT3/4 shows predominantly nuclear staining pattern in ITGCN.

Differential diagnosis

- spermatocytic tumor


- atrophic undescended testis (cryptorchid testis)

  • Cryptorchidism increases the risk for testicular germ cell tumors by 3.5 to 5 fold.
  • About 2% to 8% of patients with cryptorchidism have ITGCN.
  • In unilateral cryptorchidism, the non-cryptorchid testis is also at a slightly higher risk of developing germ cell tumors.



See also

- intratubular embryonal carcinoma
- non-seminomatous germ cell tumours (NSGCTs)
- intratubular germ cell neoplasia of unclassified type (IGCNU)

Open references

- Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential. Mitchell RT, E Camacho-Moll M, Macdonald J, Anderson RA, Kelnar CJ, O’Donnell M, Sharpe RM, Smith LB, Grigor KM, Wallace WH, Stoop H, Wolffenbuttel KP, Donat R, Saunders PT, Looijenga LH. Mod Pathol. 2014 Sep;27(9):1255-66. doi : 10.1038/modpathol.2013.246 PMID: 24457464


- Berney DM, Lee A, Randle SJ, Jordan S, Shamash J, Oliver RT. The frequency of intratubular embryonal carcinoma: implications for the pathogenesis of germ cell tumours. Histopathology. 2004 Aug;45(2):155-61. PMID: 15279634

- Early orchiopexy: prepubertal intratubular germ cell neoplasia and fertility outcome. Engeler DS, Hösli PO, John H, Bannwart F, Sulser T, Amin MB, Heitz PU, Hailemariam S. Urology. 2000 Jul;56(1):144-8. PMID: 10869645

- Solid tumors and germ cell tumors induce nonneoplastic germ cell proliferations in testes of infants and young children. Hawkins EP, Hicks MJ. Hum Pathol. 1998 Dec;29(12):1547-8. PMID: 9865847