Testis Cancer – Core curric, Weider’s NCCN – Flashcards
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Germ cell tumors make about about what percent of testis neoplasms? What are the two subtypes of germ cell tumors?
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95% - are semionoma or non-seminoma. OF this, 65% are seminoma and rest are nonseminoma.
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Sex cord/stromal tumors (nongerm cell tumors) make up what percent of tumors? What kind are they?
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5% - are mainly leydig cell and sertoli cells.
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Incidence of testis cancer in US?
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5 in 100,000 men
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Most common presentation of testis cancer (in terms of what kind of cancer?
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Localized seminoma - 50% of all cases.
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Risk factors for testis cancer?
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Cryptorchidism, family history, intratubular germ cell neoplasia (ITGCN). HIV as well, along with gonadal dysgensis.
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What percent of men with intratubular germ cell neoplasia (ITGCN) will have GCT within 5 years?
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50%
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Seminoma is classified into what types?
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Classic and spermatocytic. Clasic most common type, most common testis tumor in adults, most common in UDT
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What is most common testis tumor in UDT?
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Classic seminoma.
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In spermatocytic seminoma, what age presentation? More or less aggressive than classic?
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Older folks in 50's-60's, and less aggressive.
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What is the most common testis tumor in bilateral testois tumor?
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Lymphoma
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what is most common testis tumor in older men above 50?
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Lymphoma
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What is most common metastatic tumor of the testis?
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Lymphoma
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What i sthe msot common testis cancer in infants/children?
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Yolk sac tumor
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What is the most common NON germ cell tumor?
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Leydig cell
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WHat is the most common intersex tumor?
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Gonadoblastoma
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Which side is cryptorchidism more common on whcih side?
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On the R side - so testis tumors in kids more common on R
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What is risk of cancer in contralateral testis if had cancer on one side?
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15%.
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What is risk of gonadoblastoma?
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Intersex - gonadal dysgenesis.
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Types of testis cancer nonseminoma?
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Yolk sac, choriocarcinoma, embryonal, and teratoma, along with lymphoma.
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What is a symptom 30-50% of time with certain sertoli or leydig tumors?
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Gynecomastia
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How do testis cancers spread? (Lymphatically, hematogenously, or both?)
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Mostly lymphatics, BUT chorio and yolk sacs can spread hematogenously.
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Where is the most common site of testis cancer mets? And how does cancer spread depending on which side?
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Retroperitoneal nodes. Spread from right to left - R sided cancer spreads to R to left side, L sided cnacer stays on left.
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Metastasis to inguinal nodes happens? If it does, when does it happen?
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Yes it happens invades through tunica vaginalis or into scrotum. OR if previous scrotal or inguinal surgery or trans scrotal abiopsy/orchiectomy. Mets to pelvic nodes can happen if tumor goes into epididymis or cord.
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What is the work up for testis cancer pre surgery?
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Imaging of scrotum, tumor markers (AFP, B HCG, LDH), chest x ray, and furhter work up after radical inguinal orchiectomy.
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What is T1 stage of testis cancer?
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T1 is tumor limited to testis and with no LVI and can go into tunica albuginea
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What is stage T2 testis cancer?
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Tumor in testis WITH LVI OR INTO TUNICA VAGINALIS through albuginea
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What is stage T3 testis cancer?
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Tumor INTO SPERMATIC CORD with or without LVI
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What is stage T4 cancer?
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Tumor invades into the scrotum/scrotal wall
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What is N1 disessase testis cancer?
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5 or less lymph nodes with less than 2cm in size (regional lymph nodes - retroperitoneal)
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What is N2 disease testis cancer?
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N2 is any number of nodes between 2-5 cm in size.
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What is N3 diseases testis cancer?
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Mets of any nodes over 5 cm in size.
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What is M1 disease?
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M1a - pulmonary metastasis or nonregional nodal mets M2a - Distant mets at sites other than nonregional LN on lung
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What is S1 disease testis cancer?
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LDH of less than 1.5, AFP of less than 1,000, B HCG of less than 5,000.
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What is S2 disease testis cancer?
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LDH less between 1.5 and 10, AFP between 1,000 and 10,000, and B HCG between 5,000 and 50,000.
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What is S3 disease cancer?
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LDH of over 10, AFP of over 10,000, and B HCG of over 50,000
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What is considered stage 1 disease testis cancer?
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Stage 1a is T1 disease Stage 1b is T2-4 disease. Stage 1S is Any T disease with S1-3 Any N or M is stage 2 or 3.
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What is stage 2 disease testis cancer?
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Stage IIa disease is any T, with N1 disease and up to S1 Stage IIb is any T, with N2 disease and up to S1 Stage IIc is any T, with N3 disease and up to S1 ANY M, and S2 or above = stage 3
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Stage 3 disease of testis cancer is?
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Stage IIIa - Any T or N, with M1a and S0 or 1 disease Stage IIIb - Any T , and EITHER any N and S2 with M1a dieease, OR N1-3 with no M and S2 disease Stage IIIc - Any T, and EITHER any N and S3 disease OR N1-3 disease withno M and S3 disease
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What is the risk category for Good risk nonSeminoma and Seminoma?
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Seminoma - Any primary site with M0 or M1a and normal AFP Non seminoma - Testicular or retroperitoneal primary tumor, with M0 or M1a, and S0 or S1
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What is the risk category for intermiediate risk non semioma and seminoma?
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Nonsemionma - testicular or retroperitoneal primary tumor, M0 or M1a, and S2 disease Seminoma - Any primary site, M1b, normal AFP
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What is the risk category for poor risk non seminoma and seminoma?
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Nonseminoma - Non testicular or retroprertineal primary tumor, with M1b and S3 disease. Seminoma - no such thing as poor risk seminoma.
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PET scans can be used in nonseminoma after treatment for mets - true or false?
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False - PET scans are used after seminoma, NOT nonseminoma. The options are fibrosis/necrosis (40% of time), residual tumor (20% of time) and teratoma (20%) for nonseminoma//mixed tumors. PET helps tease out the 40% of time you don't do anything (fibrosis/necrosis). However, teratoma is not often PET avid. Therefore, if a PET is negative doesn't mean there is not teratoma potentially there (20% of time). However, with seminoma the options are residual tumor vs fibrosis/necrosis - so if its PET avid, it needs to be treated.
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Median time to tumor in contralateral testis after cancer is how long?
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6 years - which is why surveillance for long time is important.
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AFP - when is it elevated? When is it never elevated? What is the half life?
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Elevated in yolk sac tumorand embryonal, NEVER in chorio or pure seminoma. Half life is 7 days Mnemonic - AFP is shortest spelling, longest half life.
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b HCG - when is it elevated? When is it not elevated? What is half life? What secretes it?
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Elevated in embryonal tumor, sometimes in seminoma. Always elevated with choriocarcioma Half life is 1-3 days (Mnemonic - longest b/c 4 letters - B HCG, so longest half life)
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LDH - when is it elevated? WHen is it not elevated? What is half life?
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Elevated with seminoma and nonseminoma both. Half life is 3-5 days (middle of the other two).
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Gonadal stromal cell tumors - what are they?
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Leydig cell and sertoli cell, and granulosa cell tumors.
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Leydig cell tumors - describe them. What percent is malignant? What do they produce? What is their histology. What is the treatment?
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10% of leydig cells are malignant. Histology has REINKE'S CRYSTALS (cigar shaped red crystals). Produce testosterone adn 17 ketosteroid. So CAN PRESENT with precocious puberty (like pubic hair, masculine voice, prominent genitals. Also adults can presents with impotence, low lebido, gunecomastia). Treatment is orchiectomy with surveillance after. Metastatict tumros often resistance to chemo.
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What kind of histology found with leydig cell tumors?
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Reinke's crystals (icgar shaped cystals).
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SSertoli cell tumors - how many percentage wise are malignant? What do they secrete? Treatment?
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10% are malignant. Secrete testosteone or estrogen. Treamtnet if nonmetastaic are with orchiectomy.
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Granulosa cellstumors - characteristics?
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Usually a neonatal - 75% diagnosed wihin one mont of birth. Usu benign - orchiectomy is curative. ds
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IGCN risk factors are?
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Hx of germ cell tumor in contralateral kidney, family history of kidney cancer, cryptorchidism, atrophic testicle, intersex. IGCN is a risk of 50% of testis cancer in 5 eyars if untreated.
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IGCN is diagnosed how? When is this indicate?
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Diagnosed with testis biopsy. Indicated to biopsy if tumro on one side and is high risk extranodal germ cell tumor or if or multiple risk factors. HOWVER, do not need to biopsy in prepubertals b/c natural hx of IGCN in chilrean not well recognized.
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What is the treatment for IGCN?
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Controversial - can surveillance, inginal orchiectomy, testis radiation, or chemo. Orchiectomy and radiation cures almost all, chemo only cures 66%.
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If solitary testicle and patient would like to undergo surveillance but wants fertility. Biopsy shows IGCN. WHat is best next step?
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Surveillance of testis, especially if IGCN of stolitary testicle, is appropriate.
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Classic seminoma - describe it. Histology? Types of cells? What does it produce?
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95% of seminomas .Histology is a large uniform cells with clear cytoplasm. Have synccytiotrophoblases (make b HCG in 10% of classic seminoma cases.
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Spermatocytic semionma - what is pathology? What is age of onset? Does it usually metastsize? What is treatmnet?
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Pathologic looks is cells of varying size looking like maturing spermatogonia. Age of presentation is over 50 years of age, unlike lassic semionoma. Mets occurs in retro perit lymph nodse. Shouldnl't have BHCG. Low metastatic potential - so treatment is just radial inginal ochiectomy and surveillance.
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What are other characterisistics of seminoma overalL? (What does it secrete? What cells secretes it? What should NOT be elevated?
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Seminoma is in young people (30's). Requires normal AFP. Occasionally does secrete b HCG - from syncitiotrophoblasts. It is chemosensitive and and radiosensitive.
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If seminoma seen on path but AFP is elevated, what does this mean?
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That is is a mixed germ cell tumor, and even no other signs it MUST be treated as mixed germ cell tumor.
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How do you treat mixed germ cell tumors? Like seminoma or nonseminom?
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Treat them like nonseminoma
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Describe embryonal carcinoma. Histologic findings? Tumor marker elevation? Other descriptions?
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Embryonal is a high risk of mets but very chemo sensitive. If found in mixed, is higher risk. See PAPILLARY PROJECTIONS. AFP and b HCG both can be elevated. Oftne necrosis and hemorrhage on gross path.
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Describe yolk sac tumor. Histologic findings? Tumor marker elevations? Other descriptions?
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Usually under 2 year sof age. Histologically SCHILLER DUVAL BODIES (central vessel with tumor cells around it). Can have AFP, usually not BHCG (mostly AFP). Often mets HEMATOGENOUSLY (along with chorio).
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Describe choriocarcinoma. Histologic findingss/ Tumor marker elevations? Other descriptons?
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Present usually at 20-30 years old. Syncitiotrophoblasts (mltiple nuclei, eosinophilic cytopaslm) secrete B HCG. DO NOT have AFP. Mets early HEMATOGENOUS SPREAD to lungs. Worst prognosis of all testis cancers.
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Describe teratoma. Histologic findings? Tumor marker elevations? Other descriptions?
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Present around 25-35 yeaars of age. Have MULTIPLE GERM CELL LAYERS IN DIFF STAGES OF MATURATION (endo with GI/resp, meso with bone/muscle, ecto with neural/squamous NO TUMOR MARKER ELEVATION RESISTANT to chemo/radiation - so treatment is take it out.
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Prepubertal teratoma - what is the prognosis?
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Its usually BENIGN
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Seminoma - is it sensitive or resistant to chemo? What about radiation?
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Sensitive to both!
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Nonseminoma - is it sensitive or resistant to chemo? What about radiation?
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Sensitive to chemo, resistant to to radiation. (other than teratoma- resistant to all)
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Gonadoblastoma - what kind of patients get it? Benign or malig? Treatment?
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Intersex disorder patients (after puberty in virilized females or in males with cryptorchidism/hypospadias). Usually benign, but 60% undergo malignant germ cell transformation. So treatment is orchiectomy.
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Papillary projections are histologic finding in what testis cancer?
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Embryonal carcinoma. AFP and B HCG
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SChiller duval bodies are what? and in what testis cancer?
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Central vessel with tumor cells around it. Found in yolk sac tumor. AFP and b HCG
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Multiple nuclei eosiophilic cytoplasm - describing what kind of cell in testis cancer?
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Syncytiotrophoblasts. In choriocarcinoma. Make b HCG.
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What is the work up for solid intratesticular mass?
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Radical INGUINAL orchiectomy (clamp spermatic cord proximally and excize testis. Labs (including tumor markers), chest xray. OFFER SPERM BANKING.
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Initial treatment for testis mass?
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Radical inguinal orchiectomy - calmp spermatic cord proximally and remove testis and cord. If solitary or in children,, can try testis sparing but must send for frozen for margins.
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If high risk for IGCN -- first of all, what are high risk factors? -- then what is the treatment consideration?
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Risk factors for IGCN are hx of germ cell cancer, atrophic testicle, crytorchidism, infertility, intersex. Consider biopsy of contralateral testicle during tumor excision. HOWEVER< in prepubescent boys, rarely have IGCN so don't have to.
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After orchiectomy, what do you need to do?
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Stage patient - so get tumor markers again and imaging (CT c/a/p). Takes 5 half lives to eliminate circulating markers, so must wait 5 weeks before checking. (so bHCG is 1 day, AFP is 1 week, and LDH is 3-5 days - meaning the longst 5 half life is 5 weeks for bHCG)
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How long must you wait to get post orchiectomy tumro markers? WHy?
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Wait 5 half lives, b/c thats how long it takes for it to eliminate circulating markers. (so bHCG is 1 day, AFP is 1 week, and LDH is 3-5 days - meaning the longst 5 half life is 5 weeks for bHCG)
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What is the treatment for testis lymphoma?
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Orchiectomy and then systemic treatment.
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When can scrotal violation happen? What is the treatment?
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Scrotal violation can occur in T4 disease or with transscrotal biopsy or transscrotal orchiectomy. Treatment is to excise ipsilateral spermatic cord and scar, and if it was a biopsy then complete the orchiectomy. Consider excising ipsilateral hemiscrotum. In seminoma, chemo and XRT for seminoma are options if up to Stage III with M1a disease (good prognosis). For seminoma radiation, SHOULD include bilateral pelvic and inguinal lymph nodes, and radiate ipsilateral hemiscrotum if not completely excised or spillage. In nonseminoma up to IIB, chemo or RPLND - and chemo if not completely excised. If M1a in nonseminoma, chemo.
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For radiation therapy, what type of testis cancer can you do it for (seminoma or non seminoma?) And what is the field you need to radiate?
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Radiation used in seminoma, NOT nonseminoma. Do radiation for stage I, stage IIA and B, or stage IS - should include the RPLN under diaphagm, shield contalateral testis. If local tumor not totally removed, include ipsilateral himiscrotum. (dog leg)
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In children, is testis cancer usuallly seminoma or nonseminoma?
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Usually nonsemionoma - MC type is yolk sac.
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In children, testis cancer usu presents with mets. True or false?
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True.
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Teratoma is benign in children. True or false?
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True, usually.
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Treatment for nonsemionma (seminoma rare) in children?
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If up to stage IB, radical orchiectomy and surveillance. If Stage IS, II, or III then orchiectomy and chemo (BEP)
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Tratment for teratoma in kids?
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Usu benign - so orchiectomy and potentially testis sparing.
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Treatment for granulosa cell tumor?
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Usu benign - usually within one month of birth. So orchiectomy is curative.
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SEMINOMA - treatment for stage IA or IB?
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If T1-3, then observe vs chemo (carboplatin 1-2 cycles) vs radiation (20 gy in 10 fractions) If T4, then chemo (carboplatin 1-2 cycles) vs radiation (20 gy in 10 fractions) to RPLN plus or minus ipsilateral iliac nodes)
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SEMINOMA - treatment for stage IIA or IIB?
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If Stage IIA or B, then chemo (carboplatin 1-2 cycles) vs radiation (30-36 GY) to RPLN PLUS ipsilateral iliac nodes
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SEMINOMA - treatment for stage IIC or III?
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If good risk seminoma (so and T and up to M1a, and up to S1), then chemo with either EP x 4 or BEP x3 cycles. If intermediate risk seminoma (so any T and M1b and S2 or S3) then BEP x 4. After this, wait
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SEMINOMA - after treatment with chemo for stage IIC or III, what three things can occur? and what are treatments for each?
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Tumor shrinks with residual mass less than or equal to 3cm and markers neg - observe (if relapse, salvage chemo or XRT) ' Tumor shrinks but residual mass ovefr 3 cm and markers neg - then PET SCAN. If positive, then resect or biopsy masses (desmoplastic reaction with semioma after chemo, so tough to do RPLND). Two options - residual tumor (20% of time) - do salvage chemo or XRT. Or fibrosis/necrosis - then observe (80% of the time) If relapse, salvage therapy. Page 102 of weider's.
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In nonseminoma, what are the three things that a residual mass in RPLN could be? How often?
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Could be necrosis/fibrosis 40% of the time, could be residual tumor 20% of the time, could be teratoma 20% of the time.
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What is most important factor for predicting occult mets in retroperitoneal LN?
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LVI
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What are the salvage therapy regimens possible?
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VIP - etoposide, ifosfamide (with mesna), cisplatin VeIP - vinblastine, ifosfamide (with mesna), cisplatin TIP - Paclitaxel, ifosfamide with mesna, cisplatin
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NONSEMINOMA - treatment for stage IA and IB?
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If T1, then observe. RPLND is an option. If T2-4, then chemo with BEP x2 vs RPLND with unilateral modified template
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NONSEMINOMA - treatment for stage IIA or IIB?
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Chemo with BEP x 3 doses or EP x 4 doses vs RPLND with modified bilateral template and chemo after if positive (N1-2 with EP 2 or BEP 2, and if N3 then EP 4 or BEP 3. BUT if S1, then chemo and CT scan and treat like stage IIC or III
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NONSEMINOMA - treatment for stage IS?
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BEP x3 or EP x4 then treat like IIC or III.
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NONSEMINOMA - treatment for stage IIC or III?
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If good risk (up to M1a, up to S1, RPLN) then EP x4 or BEP x 3. If intermediate or poor risk (up to S2 for intermed, and M1b for poor), then BEP x 4. THEN after, CT scan and markers. Three options - -Tumor shrinks less than 1 cm, and normal markers = observe. -Tumor shrinks but over/equal to 1cm - then resect lesions and/or bilateral full template RPLND -- three options = teratoma (20%) = resect and observe, residual tumor (20%) - resect and two cycles of chemo, or fibrosis/necrosis = observe. - Tumor grows, unresectable mass, or markers elevated - then salvage treatment.
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IF cancer on one side, what chance there is cancer on the other side in future?
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15%
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Chemotherapy results in higher or lower incidence of contralateral germ cell testis tumors compared to XRT?
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LOWER incidence with chemo of GCT.
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With RPLND, what are the risks with it?
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Risk of ED (due to injury of post ganglionic symp nerves at T2 - L4) and hypogastric plexus, symp nerv near IMA), bowel obstruction, symphathetic system causing tachycardia, chylous ascites.
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Toxicity from XRT in seminoma - what are the risks?
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Acute toxicity - usu nausea, sometime bone marrow suppression. Chronic toxicity - peptic ulcer, gastritis, secondary germ cell cancers like leukemia - risk of secondary cancer.
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Which chemo agent has risk of secondary cancer?
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Etoposide.
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If patient with prior abdominal radiation, IBD, or kidney in radiation field (like horshe or ectopic - is radiation ok?
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NO- - consider surv vs chemo as appropriate.
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WIth RPLND, what is sexual side effect? WHy?
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Risk of ED (due to injury of post ganglionic symp nerves at T2 - L4) and hypogastric plexus, symp nerv near IMA)
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When are we doing RPLND templates?
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Nonseminomas. Stage 1B - unilateral modified template. Stage IIA and B - bilateral modified template. Stage IIC and III - bilateral full template
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Explain the RPLND template limits?
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Unilateral modified - superior renal vein, medially is the IVC if on L, aorta if on R and following down to bifurcation to the ureter hitting iliacs, laterally is ureter down to the iliacs. Bilateral modified is same as unilateral except the contralateral limit is to the contralateral ureter superior to IMA , and inferior to IMA contralateral limit is the aorta. Bilateral full template is renal vein superiorly, laterally ureters laterally until hit the iliacs, and inferior is the iliacs up to bifurcation. IF PALPABLE NODE FOUND AT ANY MODIFIED< MUST SWITCH TO FULL BILATERAL TEMPLATE.
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What to watch out for postop with RPLND? WHY?
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Post op tachycardia due to sympathetic discharge - so don't give tons of fluids.
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What is most efffective chemo agent for GCT? Side effect of this?
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Platins - side effect is myelosuppression and nephrotoxic!
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Bleomycin works how? Side effect?
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Antitumor antibiotic that binds and breaks DNA. Side effects are pulmonary. Avoid over hydration, judicious use of crystalloids and using more colloids.
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Etoposide - how does it work? Side effects? What to worry about?
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Alkylating agent - binds covalently to DNA. AKA VP 16 (is the V in VIP) Side effect - big one is dose related leukemia risk, latent 204 years. Also with myelosuppression, mucositis.
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Where does testis cancer drain from left? from Right?
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Left - paraaortic lymph nodes for most part. Right - mostly interaortocaval and paracaval and then para aortic. GO RIGHT TO LEFT.
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What are risk factors for predicting relapse in seminoma?
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Rete testis invation, and tumors over 4 cm in semionma.
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Overall survival in seminoma stage 1? Surveillance?
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98%. CT at every 3 months for 1st year, then 6 months until 3 years, then 1 year until 5 years.
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What are the two most important factors to predict occult mets in NSGCT?
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LVI and embyronal predominance
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Secondary lymphatic spread can occur in retrograde fashion to common and external iliac or cephalad with cysterna chyli and thoracic ducts - true or flase?
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True
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Sympathetic trunks - describe the anatomy?
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Bilateral, paravertebral chains giving rise to postganglionic fibers - course POSTERIO TO VENA CAVA AND ANTERIOR TO AORTA, COALESSGE AT INFEIOR HYPOGASTRIC PLEXUS (Caudal to IMA)
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WHat is the surgical technique for the RPLND?
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Split and roll technique - control lumbar vessels to allow circumferencial dissection of great vessesl. Lymph tissue split on anterior surface of great vessela nd roled off, ligating lumbar vessels and removing lymph en bloc.
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Relpase after NSGCT - early or late - define this?
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before or after 2 years of initial therapy - if withing 2 years - should receive 2nd line or salvage therapy - UNLES TERATOMA (with no tumor markers and growing rtroperitoneal mass - then RPLND with resection of gross disease. Late relapse rare - usu chemo resistant and managed surically.
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If early relapse (recurrence before 2 years) and normalized/declining tumor markers and retroperitoneal masses still growing, what coudl it be?
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Growing teratoma syndrome - RPLND with resection of gross disease.
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Late relapse, after 2 years - what is this usually?
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Usually retroperitoneam and usually chemo resistant - often managed surgically.
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What is other salvage therapy after VIP, VeIP, and TIP?
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High dose chemo with autologous sten cell support - kills bone marrow and transplant given to reconstitue marrow. Is poor prognosis or poor response to standard chemo. Treatment mortality can be 5-10% Can also do salvage surgical resection.
