Testis & paratestis
Germ cell tumors
Germ cell neoplasia in situ
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Last staff update: 19 April 2023 (update in progress)
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PubMed Search: Germ cell neoplasia in situ[title]
Table of Contents
Definition / general | Essential features | Terminology | Classification | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Differential diagnosisCite 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
- In situ stage of germ cell neoplasia; the common precursor of seminomas and nonseminomas
- GCNIS is seen in 80% - 95% of testes adjacent to germ cell tumor (GCT) (Arch Pathol Lab Med 1985;109:555, Hum Pathol 1990;21:941), in ~5% contralateral testis (Eur Urol 2007;51:175) and nearly 50% of patients with extragonadal GCT (Lancet 1987;2:528)
- 50% progress to GCT in 5 years (all types except spermatocytic tumor) (Br Med J (Clin Res Ed) 1986;293:1398)
- Commonly extends to rete testis in pagetoid fashion or resembling invasive seminoma (Hum Pathol 1994;25:235)
- Also associated with gonadal dysgenesis, androgen insensitivity syndrome, infertility (0.4% - 1%), cryptorchidism (2% - 8% of patients)
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
Terminology
- 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
Classification
- 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)
Treatment
- 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
- PLAP (membrane accentuated, 97% of cases, Mod Pathol 1988;1:475), but note that PLAP is positive in infantile germ cells until age one (Histopathology 1993;22:373)
- OCT3 / 4 (Am J Surg Pathol 2005;29:368)
- SALL4 (Am J Surg Pathol 2009;33:1065)
- D2-40 (podoplanin) (Ann Diagn Pathol 2010;14:331)
- PAS without diastase (contains glycogen)
- NANOG (Cancer 2005;104:2092), SOX17
- CD117 (Hum Pathol 1988;19:663), but note that spermatogonia exhibit patchy membranous or cytoplasmic c-kit staining (Histopathology 2012;60:1017)
Negative stains
- Pan cytokeratin (AE1 / AE3), EMA, CD30, AFP, Glypican 3, SOX2, RNA binding motif (Hum Pathol 2000;31:1116)
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
