early malignant germ cells

Carcinoma in situ (CIS) of the testis is the pre-invasive stage of type II testicular germ cell tumours (TGCTs) of adolescents and adults. These tumours are the most frequently diagnosed cancer in Caucasian adolescents and young adults.

In dysgenetic gonads, the precursor of type II GCTs can be either CIS or a lesion known as gonadoblastoma (GB).

CIS/GB originates from a primordial germ cell (PGC)/gonocyte, ie an embryonic cell.

CIS can be cured by local low-dose irradiation, with limited side effects on hormonal function.

Various markers are informative to diagnose CIS in adult testis by immunohistochemistry, including c-KIT, PLAP, AP-2gamma, NANOG, and POU5F1 (OCT3/4).

OCT3/4 is the most informative and consistent in presence and expression level, resulting in intense nuclear staining.

In the case of maturational delay of germ cells, frequently present in gonads of individuals at risk for type II (T)GCTs, use of these markers can result in overdiagnosis of malignant germ cells.

This demonstrates the need for a more specific diagnostic marker to distinguish malignant germ cells from germ cells showing maturation delay.

Stem cell factor (SCF)

Immunohistochemical detection of stem cell factor (SCF), the c-KIT ligand, is informative in this context. SCF immunohistochemistry can be a valuable diagnostic tool, in addition to OCT3/4, to screen for precursor lesions of TGCTs, especially in patients with germ cell maturation delay.

References

 Stem cell factor as a novel diagnostic marker for early malignant germ cells. Stoop H, Honecker F, van de Geijn GJ, Gillis AJ, Cools MC, de Boer M, Bokemeyer C, Wolffenbuttel KP, Drop SL, de Krijger RR, Dennis N, Summersgill B, McIntyre A, Shipley J, Oosterhuis JW, Looijenga LH. J Pathol. 2008 Sep;216(1):43-54. PMID: 18566970