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Testis carcinoma- etiopathogenesis
- 1. Etiopathogenesis And Classification of Testicular Tumors Dept of Urology Govt Royapettah Hospital and Kilpauk Medical College Chennai 1
- 2. Moderators: Professors: • Prof. Dr. G. Sivasankar, M.S., M.Ch., • Prof. Dr. A. Senthilvel, M.S., M.Ch., Asst Professors: • Dr. J. Sivabalan, M.S., M.Ch., • Dr. R. Bhargavi, M.S., M.Ch., • Dr. S. Raju, M.S., M.Ch., • Dr. K. Muthurathinam, M.S., M.Ch., • Dr. D. Tamilselvan, M.S., M.Ch., • Dr. K. Senthilkumar, M.S., M.Ch. Dept of Urology, GRH and KMC, Chennai. 2
- 3. INTRODUCTION • 1% of male neoplasms • 5% of urological tumours • three to ten new cases occurring per 100,000 males/per year in Western societies • Tumors with very good prognosis, one of the most curable solid tumors! • Affects mainly young productive population 3 Dept of Urology, GRH and KMC, Chennai.
- 4. • Most common malignancy in men in the age group 15-35 yrs • Incidence- 0.2 -1% • Age group -late adolescence-early adulthood(20-40 yrs) -late adulthood (>60 yrs) -infancy(0-10 yrs) • Higher incidence -upper and middle socio economic class -professional men • Race – more in whites, rare in blacks • Laterality– common in right testis Bilateral – 2 – 3% 4 Dept of Urology, GRH and KMC, Chennai.
- 5. Etiology : •Familial clustering noted; not well proved beyond doubt •An isochromosome of the short arm of chromosome 12, i(12p) is found in virtually all germ cell tumors, regardless of their histologic type. •association between genetic polymorphism in the PTEN tumour suppressor gene and testicular germ cell tumours (TGCT) has been recently described . 5 Dept of Urology, GRH and KMC, Chennai.
- 6. • Alterations in the p53 locus have been identified in 66% of cases of GCNIS • A deregulation in the pluripotent programme of foetal germ cells (identified by specific markers, M2A, C-KIT and OCT4/NANOG) is likely responsible for the development of GCNIS and germ cell neoplasia. • single nucleotide polymorphisms (SNPs) associated with an increased risk of developing TGCT, in particular at 15q21.3 6 Dept of Urology, GRH and KMC, Chennai.
- 7. Epidemiological risk factors • testicular dysgenesis syndrome (i.e. cryptorchidism, hypospadias, decreased spermatogenesis evidenced by sub- or infertility) • familial history of testicular tumors among first-grade relatives • contralateral tumour or GCNIS • body height (TGCT risk with an odds ratio of 1.13 per 5 cm increase in body height) ( four well-established risk factors for testis cancer:cryptorchidism,family history of testis cancer,a personalhistoryof testis cancer,and intratubulargerm cell neoplasia(ITGCN).) 7 Dept of Urology, GRH and KMC, Chennai.
- 8. Cryptorchidism • four to six times more likely to have testis cancer • the relative risk decreases to two to three times more likely if orchidopexyis performed before puberty • 7 – 10% of pts with testicular tumors have h/o cryptorchidism / maldescent • 5 – 10% of pts with cryptochidism will developtesticular tumor in later life Factors- abnormal germ cell morphology elevated temperature interferencewith blood supply endocrine dysfunction gonadal dysgenisis 8 Dept of Urology, GRH and KMC, Chennai.
- 9. NO CONVINCING ASSOCIATION BETWEEN • Trauma • DES exposure • Viral infection • Vasectomy 9 Dept of Urology, GRH and KMC, Chennai.
- 10. Pathogenesis 10 Dept of Urology, GRH and KMC, Chennai.
- 11. Intra tubular germ cell neoplasia, unclassified (IGCNU) • Incidence- 0.8% • Precedes invasive GCT in all adult cases • Absent in prepubertal presentations, EGGCT and Spermatocytic seminoma • Median time for progression – 5 yr- 50% 11 Dept of Urology, GRH and KMC, Chennai.
- 12. Patients at risk of CIS •History of testicular carcinoma (5% to 6%), • Extra gonadal GCT(40%), • Cryptorchidism (3%), •Contralateral testis with unilateral testis cancer (5% to 6%), •Somatosexual ambiguity (25% to 100%) •Atrophic testis 30 % •Infertility (0.4% to 1.1%) TESTICULAR BIOPSY Gold standard for diagnoses of CIS 12 Dept of Urology, GRH and KMC, Chennai.
- 13. • Testicular CIS develops from fetal gonocytes & is characterized histologically by seminiferous tubules containing only Sertoli cells and malignant germ cells. 13 Dept of Urology, GRH and KMC, Chennai.
- 14. Embryologic origin of testis tumors Primitive gonad Germ cells Seminoma Embryonalcarcinoma Yolk sac Teratoma Choriocarcinoma Mixed cell types Stromal cells Specialized Leydig cell Sertoli cell Granulosa cell Mixed types undifferentiated Generalized Mesenchmal Mesothelial Mullerian 14 Dept of Urology, GRH and KMC, Chennai.
- 15. 15 Dept of Urology, GRH and KMC, Chennai.
- 16. Type Incidence • GCT 90-95% • Sex cord or gonadal stromal tumors 2-4% • Mixed 0.5% • Miscellaneous 0.5-1% • Secondary tumors 5% Lymphoid hematopoietictumors metastatic 16 Dept of Urology, GRH and KMC, Chennai.
- 17. Germcelltumors-GCT Incidence Age Group • Seminoma 40-50% 35-39 yrs • Non seminomatous GCT Embryonal carcinoma 15-20% 25-35 Yolk sac tumors 1-2% infants ,children Trophoblastic tumors 1% 20-30 yrs Teratoma 20-25% infants ,children 17 Dept of Urology, GRH and KMC, Chennai.
- 18. Seminoma •40% of GCTs •Fourth decade of life •Classic seminoma •Anaplastic seminoma •Atypical seminoma •Spermatocytic seminoma 18 Dept of Urology, GRH and KMC, Chennai.
- 19. Classical Seminoma: • Large cell sheets with abundant cytoplasm • round hyperchromatic nuclei with abundant nucleoli • Lymphocytic infiltrate • Trophoblastic giant cells that produce hCG – 10% • Atypical Seminoma: More necrosis and higher nuclear - cytoplasmic ratio and Keratin positivity 19 Dept of Urology, GRH and KMC, Chennai.
- 20. Anaplastic Seminoma • 5-10%of seminomas • 30-40yrs • Moreaggressive • Morelethal: localinvasion metastasis hCGproduction Microscopy: • Increased mitotic activity ( 3 or more mitotic figures ) • Nuclear pleomorphism • Cellular anaplasia 20 Dept of Urology, GRH and KMC, Chennai.
- 21. Spermatocytic seminoma • 2-12% of seminomas • >50 yrs • No cases of metastatic disease reported • Good prognosis (Older men not ass. with IGCNU or Bilaterality no special IHC marker expression ) •Microscopy Cells vary in size-different stages of maturing spermatogonia Deeply pigmented cytoplasm Rounded nuclei Characteristic filamentous chromatin 21 Dept of Urology, GRH and KMC, Chennai.
- 22. NSGCT • 55% of GCTs • Third decade of life • Most tumor types are mixed including seminoma • All have equal prognosis 22 Dept of Urology, GRH and KMC, Chennai.
- 23. Embryonal carcinoma Gross Small rounded irregular mass Invading tunica vaginalis , cord structures Cut surface Variegated grayish white fleshy tumor Areas of necrosis and hemorrhage Poorly defined capsule 23 Dept of Urology, GRH and KMC, Chennai.
- 24. microscopy • Malignant epithelioid cells as tubules • In distinct cell borders • Cytoplasm – pale or vacuolated • Round nuclei with coarse chromatin Highly malignant tumors Pleomorphism Mitotic figures Giant cells 24 Dept of Urology, GRH and KMC, Chennai.
- 25. Choriocarcinoma • 1-2% of GCTs • 20-30yrs • Produces Beta-hCG • Pure form - rare • Wide spread hematogenous mets which are hemorrhagic (Brain) • Palpablenodule • Distantmetastasis withsmallintra testicularlesion Cut surface Central h`ge Viable grayish white tumor at periphery 25 Dept of Urology, GRH and KMC, Chennai.
- 26. Microscopy Syncytiotrophoblast- • Large multinucleated cells • Abundant vacuolated eosinophilic cytoplasm • Large heperchromatic irregular nuclei Cytotrophoblast- • Closely packed uniform cells • Distinct cell borders , clear cytoplasm 26 Dept of Urology, GRH and KMC, Chennai.
- 27. Teratoma • 20-25% • Derived from a pluripotent malignant precursor • Teratoma with malignant transformation • Non-ALL • Rhabdomyosarcoma • Carcinoma (enteric) • PNET • children • More than one germcelllayer • Gross Large lobulated nonhomogenous • In various stages of maturation mature immature 27 Dept of Urology, GRH and KMC, Chennai.
- 28. Mature •Consists of adult type differentiated cells from all three elements- ectoderm, mesoderm and endoderm •Cartilage ,glandular epithelium and nerve tissue 28 Dept of Urology, GRH and KMC, Chennai.
- 29. Immature •Partial somatic differentiation • similar to that seen in fetus 29 Dept of Urology, GRH and KMC, Chennai.
- 30. Contd… Cut surface • Cysts- gelatinous,mucinous,hyalinised • Islands of solid tissue- cartilage or bone Intestinal ,liver ,pancreatic tissue Smooth or skeletal muscle Neural or connective tissue Microscopy • Cysts are lined by Squamous, cuboidal ,columnar ,transitional epithelium cartilage mature immature 30 Dept of Urology, GRH and KMC, Chennai.
- 31. Yolk sac tumors Edodermalsinstumors Adenocarcinomaof infantiletestis Juvenileembryonalcarcinoma orchioblastoma •Infantsand children •Pure form – uncommon in adult •AFP •Gross: Papillary, glandular, microcystic or solid appearance 31 Dept of Urology, GRH and KMC, Chennai.
- 32. Microscopy • Epitheloidcells in colums • Embryoid bodies – resembling1-2 week old embryos • perivascular arrangements of epithelialcells with an intervening extra-cellular space (Schiller-Duval Bodies) Yolk sac tumor o Ebryoid body f embryo 32 Dept of Urology, GRH and KMC, Chennai.
- 33. Mixedtumors •Combinationofembryonalcarcinoma, yolksactumors, teratoma&syncytiotrophoblast •Metastaticdeposits- embryonalcarcinoma Eg. teratoma + embryonal carcinoma > teratocarcinoma 33 Dept of Urology, GRH and KMC, Chennai.
- 34. Sex cord tumors LeYdig’s tumor Sertoli’s cell tumors 34 Dept of Urology, GRH and KMC, Chennai.
- 35. Leydig’s cell tumors •1-3% of testicular tumors •Focal or diffuse interstitial cell hyperplasia Gross •Small yellow to brown , well circumscribed Microscopy • Uniform closely packed cells with eccentric nuclei and eosinophilic granular cytoplasm • Reinke’s crystals • 10% are malignant • Benign-goodprognosis 35 Dept of Urology, GRH and KMC, Chennai.
- 36. Sertoli’s cell tumors •< 1% •Any age group •10% malignant Gross •1-20 cm Cut surface •Gray white to yellow with cystic changes Microscopy • Nodules of immature seminiferous tubules • Lumen is lined by undifferentiatedcells 36 Dept of Urology, GRH and KMC, Chennai.
- 37. Mixed tumors-gonadoblastoma • 0.5% •All age groups Gross Round smoothsurface Soft and fleshy-firm and hard Cut surface Grayish white to yellow with calcification Microscopy Sertolicells, germcells, interstitialcells 37 Dept of Urology, GRH and KMC, Chennai.
- 38. Secondary tumors 38 Dept of Urology, GRH and KMC, Chennai.
- 39. Lymphoma •Most common secondary neoplasm •Later manifestation of disseminated disease •Initial manifestation of occult disease •Gross 4-5 cm, gray to pink Foci of necrosis & h’ge Extention to epididymis •microscopy Diffusereplacementof normalpatternby reticuloendothelialcells focalSparingof seminiferoustubules 39 Dept of Urology, GRH and KMC, Chennai.
- 40. Leukemic infiltartion • Initialsiteof relapsein ALL • Deathin 5m-2yrs • Infitration at intertsitialspaceswithdestructionof tubules • Biopsy 40 Dept of Urology, GRH and KMC, Chennai.
- 41. Metastastic tumors Primary Lung prostate GIT melanoma kidney • Microscopy Neoplastic cellsin interstitiumwithsparing of tubules •Route- hematogenous ,lymphatic ,direct invation •Renal adenocarcinoma- spermatic vessels •Intra-abdominal malignancy- patent processus vaginalis 41 Dept of Urology, GRH and KMC, Chennai.
- 42. Immunohistochemical markers • Seminoma : • OCT3/4 • CD117 • Embryonal cell carcinoma: • OCT3/4 • SOX2 • CD30 • LMW Keratins • Yolk sac tumor : LMW Keratins • Mature teratoma : vimentin (mesenchymal component) • Useful in tumors of Uncertain histiogenesis 42 Dept of Urology, GRH and KMC, Chennai.
- 43. EXTRA GONADAL GERM CELL TUMORS • Primary tumors of extragonadal origin are rare • 3-5% of all GCTs are extragonaldal • Most common sites: 1. Mediastinum 2. Retroperitoneum 3. Sacrococcygeal region 4. Pineal gland 43 Dept of Urology, GRH and KMC, Chennai.
- 44. EXTRA GONADAL GERM CELL TUMORS • Histologically all germ cell types are represented • Pure seminoma accounting for nearly half • May reach large size with relatively few symptoms • High potential for local invasion and distant metastasis • Primary retroperitoneal GCTs are indistinguishable biologically from testicular GCTs and carry the same prognosis 44 Dept of Urology, GRH and KMC, Chennai.
- 45. Primary mediastinal NSGCTs • less sensitive to chemotherapy • have a poor prognosis with a 5-year overall survival of about 45% • more likely to have yolk sac tumor components (elevations in serum AFP) • associated with Kleinfelter syndrome and with hematologic malignancies that carry extra copies of the short arm of chromosome 12, • In contrast, mediastinal seminomas have a prognosis similar to testicular seminomas, • mature teratomas of the mediastinum have low metastatic potential and can generally be cured surgically 45 Dept of Urology, GRH and KMC, Chennai.
- 46. Thank you... 46 Dept of Urology, GRH and KMC, Chennai.