GERM CELL NEOPLASIA INSITU PF TESTIS .pptx

Regarding testis ca insitu

1. GERM CELL NEOPLASIA INSITU DR DHILSHA

2. RISK FACTORS OF GCT White race Cryptorchidism Family history of testis cancer Personal history of testis cancer, G Germ cell neoplasia in situ (GCNIS), also referred to as intratubular germ cell neoplasia (ITGCN) (Stevenson and Lowrance, 2015). Infertile and subfertile males also have a higher incidence of testis cancer

3. RISK FACTORS OF GCT Cryptorchidism F our to six times more likely to be diagnosed with testis cancer in the affected gonad. Relative risk falls to 2- 3 times if orchidopexy is performed before puberty contralateral descended testis is also at slightly increased risk (relative risk [RR] 1.74 [95% confidence interval) CI 1.01–2.98])

4. RISK FACTORS OF GCT First-degree relative with testis cancer Substantially increased risk of testis cancer. The median age at diagnosis in these patients is 2 to 3 years younger than in the general population (Mai et al., 2009). RR - 8 to 12 with an affected brother RR - 2 to 4 in those with an affected father

5. RISK FACTORS OF GCT Personal history of testis Twelvefold increased risk of developing GCT in the contralateral testis. Incidence is only 2% (Fossa et al., 2005).

6. GERM CELL NEOPLASIA INSITU Most GCTs arise from a precursor lesion called GCNIS Varying terms used are intratubular germ cell neoplasia and testicular intraepithelial neoplasia. Exceptions to this are -Prepubertal GCT -Ovarian cystic teratomas - Dermoid cysts, -Spermatocytic tumors (previously referred to as spermatocytic seminoma .

7. GCNIS is present in adjacent testicular parenchyma in 80-90% of cases of invasive GCT 50% risk of GCT in 5 years and 70% in 7 years 5% and 9% of patients with GCT have GCNIS within the unaffected contralateral testis, incidence of contralateral GCNIS increases to about 36% in males with testicular atrophy or cryptorchidism Gene expression profile analysis indicates that GCNIS develops before birth from an arrested gonocyte In males with a history of GCT, the finding of testicular microlithiasis on ultrasound of the contralateral testis have increase risk of GCNIS.

8. CIS cells stay quiescent during infancy followed by proliferation in puberty, probably due to hormonal stimulation, with subsequent progression into overt tumours

9. Genes relate d to the pathogenesis KIT , protooncogene - migration and differentiation of primordial germ cells , expression in developmentally delayed germ cells could contribute to the neoplastic development by prolonging their survival. OCT3/4 has been reported to maintain stem cells in the pluripotent stage and prevent differentiati o n AP-2g - self-renewal and survival of immature germ cells. Stem-cell-like phenotype of CIS cells, as CIS and embryonic stem cells share expression of many genes that are of importance for fetal development

10. RISK FACTORS OF GCNIS Infertile men , CIS (0.5–1% ) highest risk - atrophic testes and extremely low sperm counts (<3 × 10⁶/cm) One sided testicular tum our - prevalence of contralateral CIS seems to be around 5–8%. C ryptorchidism , CIS prevalence is 2–4% , There is an increased risk of CIS in patients with cryptorchidism irrespective of the age of surgical orchidopexy. Children with ambiguous genitalia and testicular tissue harbour CIS in >6% of cases

11. Histopathology and biological aspects Normal germcells are replaced by CIS - large cells with clear cytoplasm Enlarged vesicular nuclei Distinct nucleoli Located in a single row ,usually thickened basement membrane of seminiferous tubules, Such seminiferous tubules have decreased diameters.

12. Section of a testicularbiopsy containing seminiferous tubules withabundant CIS(CISarrows)andSertolicells(Sarrows),haematoxylin–eosinstainin

13. Histopathology and biological aspects The most commonly used marker in clinical practice to identify GCNIS - Placental-like alkaline phosphatase - Tissue-specific alkaline phosphatase with unknown biological function in CIS cells Testicular parenchyma with CIS is frequently atrophic and may contain signs of dysgenesis with incompletely differentiated tubules, poor spermatogenesis and microliths (microcalcification)

14. A tubulewithCIS(left)and atubulewithpreserved spermatogenesis(right)areshownsidebyside.OnlymalignantCIScellsarestainedred/brownwiththeplacentalalkalinephosphataseantibody[7]. (D)NuclearstainingofCIScellswithanAP-2g antibody

15. Section of a testicularbiopsy with a large intratubular microlith.(F)Ultrasound image of a testis containing CIS.Ultrasonic pattern is irregular with microlithiasis(arrows).Scalebar

16. Clinical diagnosis No imaging technique and no serological method for the diagnosis of CIS , usually asymptomatic The diagnosis of CIS is established by a surgical biopsy , which should be ~ 3× 3mm in diameter, Should contain a minimum of 30–40 tubules upon histological cross-section to be representative of the whole testis . If a biopsy is performed in this way, the diagnostic sensitivity is close to 100%

17. Patients who have had a negative contralateral biopsy performed, the follow-up period may be limited to 5 years. Patients in whom a contralateral biopsy has not been performed, the follow-up period should be extended to 25 years

18. Auxiliary method to select patients at-risk for CIS is ultrasonography, as testes harbouring CIS : - Irregular echo pattern with so-called microliths detected by ultrasound. -Especially in patients with smaller testes, indicates an increased risk of CIS

19. General recommendations on screening and treatment of carcinoma in situ (CIS) testis

20. Radiation therapy in GCNIS Radiation therapy typically involves a dose of 18-20 Gy, delivered in fractions (e.g.1.8- 2 Gy per fraction Per day over a two week period). The rationale for this procedure is to destroy the dividing CIS cells and germ cells, and to preserve the non-dividing and more radioresistant Leydig cells and the external shape of the testis Treatment modality depends mainly on the age of the patient and whether the neoplasia is unilateral or bilateral

21. Points to remember Testicular CIS may accompany up to one-third of cases with an extragonadal GCT, especially those with a retroperitoneal tumour - staging procedure need to be done. -X-ray of the che st -C omputed tomography - abdomen - Measurement of serum tumour markers (alpha-fetoprotein and b-human chorionic gonadotrophin) should be performed in, even without an overt tumour. This maps the extent of the pathology.

22. Pretreatment fertility is usually poor , cryopreservation of semen should always be considered prior to initiation of treatment, and testicular cancer . Follow-up after the treatment of CIS should include determination of serum testosterone levels, and replacement therapy be offered in patients with subnormal levels.

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