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Published on: September 17, 2019
Germ cells positive for PLAP and c-Kit in 11-16 year old normal boys with ongoing spermatogenesis
Kolja Kvist1, Simone Hildorf2, Erik Clasen-Linde3
1The Department of Pediatric Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. koljakvist@gmail.com.
Insights
Positive staining for PLAP and c-Kit in testicular germ cells is common in pubertal boys, indicating normal germ cell maturation rather than pre-malignancy. This finding is crucial for understanding male reproductive development.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Oncology
Background:
- Germ Cell Neoplasia In Situ (GCNIS) is a pre-malignant condition associated with positive staining for PLAP and c-Kit in testicular germ cells beyond infancy.
- Previous research indicated positive staining for PLAP and c-Kit in normal infantile germ cells up to 2 years of age.
- The current study investigates the expression of PLAP, c-Kit, Oct3/4, and D2-40 in the testes of boys undergoing puberty.
Purpose of the Study:
- To determine if normal testes in boys undergoing puberty express PLAP, c-Kit, Oct3/4, or D2-40.
- To differentiate between normal maturational changes and potential pre-malignant conditions in pubertal male germ cells.
Main Methods:
- Biopsies were obtained from 31 boys aged 11.5-16.5 years undergoing surgery for testicular torsion.
- Immunohistochemical staining was performed for PLAP, c-Kit, Oct3/4, and D2-40 on testicular biopsy samples.
- Histological examination included H&E staining to assess for GCNIS and spermatogenesis.
Main Results:
- 87% of boys showed positive staining for both PLAP and c-Kit.
- No expression of D2-40 or Oct3/4 was observed in any of the samples.
- No histological features characteristic of GCNIS were identified, suggesting the staining is not indicative of pre-malignancy.
Conclusions:
- Positive staining for PLAP and c-Kit in testicular germ cells is a normal finding in boys who have not completed puberty.
- This positivity reflects an ongoing maturational process of germ cells, not a pre-malignant transformation.
- The findings challenge previous assumptions and provide a clearer understanding of germ cell development during male puberty.
Introduction:
Positive staining of testicular germ cells for PLAP and c-Kit beyond infancy may be associated with the presence of GCNIS (Germ Cell Neoplasia In Situ). We recently reported our findings of positive staining of normal, infantile germ cells for PLAP, and c-Kit up to 2 years of age, contrary to previous studies. The present study aims to elucidate whether otherwise normal testes of boys undergoing puberty express PLAP, c-Kit, Oct3/4, or D2-40.
Materials And Methods:
Biopsies were taken from 31 boys (11.5-16.5 years of age, mean and median of 13.5 years), who underwent surgery either for torsion of the testis (15) or a history suspicious of intermittent torsion of the testis (16). 21 were biopsied on both sides, making a total of 52 biopsies. Four testes were necrotic. The biopsies were fixed in Stieve's medium, cut into 2 μm sections, and mounted on coated slides. One slide was processed for H-E, and the others incubated with primary antibody for PLAP, c-Kit, D2-40, and Oct3/4.
Results:
87% of the boys stained positive for both PLAP and c-Kit. None were positive for either D2-40 or Oct3/4. None had any histological features characteristic of GCNIS. Only two boys showed no signs of having initiated spermatogenesis. Those positive for PLAP were likewise for c-Kit, and vice versa, except 2; one boy, 13 years, was positive for PLAP, but negative for c-KIT, another, 16 years, was negative for PLAP and positive for c-Kit. Three boys stained positive for PLAP and c-Kit on the right side, and negative on the left. One boy was negative for c-Kit on the right side, positive on the left, and positive for PLAP bilaterally.
Conclusion:
Positive staining of testicular germ cells for PLAP and c-Kit seems to be a normal finding in boys not having completed puberty. Rather than indicating pre-malignant transformation, the positivity is indicative of an ongoing maturational process of the germ cells.
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