Testis & paratestis

Germ cell tumors

Germ cell neoplasia in situ

Last author update: 1 December 2015
Last staff update: 19 April 2023 (update in progress)

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PubMed Search: Germ cell neoplasia in situ[title]

Nicholas P. Reder, M.D., M.P.H.
Maria Tretiakova, M.D., Ph.D.
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Cite this page: Reder N, Tretiakova M. Germ cell neoplasia in situ. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/testisitgcn.html. Accessed June 10th, 2023.
Definition / general
Essential features
  • In situ stage of germ cell neoplasia; the common precursor of seminomas and non-seminomas
  • Formerly known as carcinoma in-situ of the testis (CIS), intratubular germ cell neoplasia, unclassified (ITGCN, IGCNU) or testicular intraepithelial neoplasia
  • Subdivided into GCNIS (non-specific, most common), intratubular seminoma, intratubular non-seminoma, intratubular yolk sac tumor and intratubular teratoma
  • Formerly known as carcinoma in situ of the testis (CIS), intratubular germ cell neoplasia, unclassified (ITGCN, IGCNU) or testicular intraepithelial neoplasia
  • GCNIS is a better term since the lesion consists of neoplastic gonocyte-like germ cells that are NOT space filling intratubular proliferations
  • The term "unclassified" is dropped as it often caused unnecessary uncertainty
  • Noninvasive germ cell neoplasia is subdivided into GCNIS (most common type described herein) and specific forms of intratubular germ cell neoplasia (space filling proliferations) such as:
    • Intratubular seminoma: morphologically similar cells with complete filling the tubules, totally replacing normal Sertoli and germ cells (APMIS 2003;111:32)
    • Intratubular nonseminoma: embryonal carcinoma cells with crowding, overlapping, pleomorphism and necrotic foci (Arch Pathol Lab Med 2002;126:487)
    • Intratubular yolk sac tumor and intratubular teratoma (extremely rare)
Case reports
  • 23 year old man with testicular carcinoma in situ by immunocytological staining for AP-2 gamma in semen samples (Hum Reprod 2005;20:579)
  • 26 year old woman with fetus with Down syndrome and PLAP+ GCNIS/ITGCN (Mod Pathol 1992;5:547)
  • 32 year old man with testicular dysgenesis with carcinoma in situ detected via ultrasonic microlithiasis (Asian J Androl 2005;7:445)
  • Watchful waiting for unilateral GCNIS (clinical and ultrasound examination) and serum measurement of hCG, AFP, human placental lactogen (HPL)
  • Some recommend biopsy of contralateral testis and orchiectomy if bilateral, others recommend radiation therapy
Microscopic (histologic) description
  • Large atypical cells (3x normal) with clear cytoplasm, angulated nuclei with coarse chromatin, prominent nucleoli and cell borders resembling "fried egg" seminoma cells
  • Present along thickened / hyalinized basement membrane of atrophic seminiferous tubules in a pagetoid fashion or as a "string of beads" displacing Sertoli cells toward the lumen
  • Often patchy involvement throughout the testis
  • Spermatogenesis usually absent; may have calcifications (microliths)
Microscopic (histologic) images

Contributed by Maria Tretiakova, M.D., Ph.D.

GCNIS, x40

GCNIS, x100

Positive stains
Differential diagnosis
  • Normal spermatogonia or spermatogenic arrest
  • Maturation delayed gonocytes persisting after fetal / infantile period; in prepubertal boys, germ cells with abundant clear cytoplasm adjacent to GCT do NOT represent GCNIS (are negative for PLAP and c-kit), although may be p53+, PCNA+ (Hum Pathol 1997;28:404, Am J Surg Pathol 1994;18:947)
  • Intratubular malignant lymphoma, carcinoma or melanoma
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