Testicular CaAnatomy and Epidemiology Dr. S. Moses Arunsingh PG (MDRT) BIRO 14.09.2011
Anatomy The testes are located in the scrotum, a sac of skin between the upper thighs. The word Testis is derived from the a Latin word “Testiculus” meaning “to Witness” i.e witness to a male’s virility.
Coverings Some – SKIN Damned - DARTOS Muscle Englishmen – External Spermatic Fascia Called – Cremastric Muscle It – Internal Spermatic Fascia The – Tunica Vaginalis Testis – Tunica Albuginea
The epididymis is a tube about 20 feet (6 m) long that is coiled on the posterior surface of each testis The ductusdeferens extends from the epididymis in the scrotum on its own side into the abdominal cavity through the inguinal canal.
The testicular artery (the internal spermatic arteries) is a branch of the abdominal aorta that supplies blood to the testis. The testis has collateral blood supply from 1. the cremasteric artery and 2. artery to the ductus deferens
The veins emerge from the back of the testis, and receive tributaries from the epididymis; they unite and form a convoluted plexus, called the pampiniform plexus. These unite to form a single vein, which opens, on the right side, into the inferior vena cava (at an acute angle), on the left side into the left renal vein (at a right angle).
Four to eight collecting lymphatic trunks drain from the hilum of the testis. Drain into the retroperitoneal lymph glands between the levels of T11 and L4, but they are concentrated at the level of the L1 and L3 vertebrae.
Where the spermatic vessels cross ventral to the ureter, some lymphatics diverge and drain into the retroperitoneal lymph node chain Others follow the spermatic vessels to their origin.
Lymph nodes located lateral or anterior to the inferior vena cava are called paracaval or precavalnodes, respectively. Interaortocavalnodes are located between the inferior vena cava and the aorta. Nodes anterior or lateral to the aorta are preaortic or para-aortic nodes, respectively
On the left: Preaorticand para-aortic nodes and thence to the interaortocaval& left common iliac nodes. On the right: Interaortocavalregion, followed by the paracaval, preaortic, and right common iliac and para-aortic lymph nodes.
Metastatic nodal disease to the common iliac, external iliac, or inguinal lymph nodes is usually secondary to a large volume of disease with retrograde spread. If the patient has undergone a herniorrhaphy, vasectomy, or other transscrotal procedure, metastasis to the pelvic and inguinal lymph nodes is more likely.
Through the thoracic duct to lymph nodes in the posterior mediastinum and supraclavicular fossae and occasionally to the axillary nodes. Contralateral spread is mainly seen with right-sided tumors. In 15% to 20%, bilateral nodes are involved.
Nerve Supply Sympathetic nerves arising from segment T10 of the spinal cord. Both afferent for testicular sensation and efferent to the blood vessels(vasomotor).
Conventional Multi Fractionation Rams could not be sterilized with a single dose of x-rays without extensive skin damage. If the radiation were delivered in daily fractions over a period of time, sterilization was possible without skin damage.
Epidemiology – Testicular Ca The median age at diagnosis is 34 years, with 50% of incident cases between 20 and 34 years. Highest incidence in Denmark, Norway, and Switzerland and the lowest in eastern Europe and Asia.
India - Facts Testicular cancer forms about 1% of all malignancies in males in India. Incidence (ASR)– 0.6 per 100000 Mortality (ASR)– 0.3 per 100000
Risk Factors The increasing incidence has paralleled decline in semen quality over the past several decades May be caused by intrauterine exposure of the developing male embryo to factors that alter the hormonal balance.
Lower fertility and semen abnormality. The association is similar for both seminomas and non seminomas. A history of undescended testicle. The odds ratio was 5.3 for seminoma and 3 for nonseminoma
This risk is further increased if the testis is intra-abdominal. Abdominal testis is more likely to be seminoma, testis brought to scrotum by orchiopexyis more likely to be NSGCT. There is still an increased risk of developing a tumor in the contralateral normally descended testicle.
Industrial chemicals:workers in manufacturing 2-naphthylamine, benzidine, gasoline derivatives have ~fivefold increased risk
Having an inguinal hernia less than 15 years of age (odds ratio 3) A prior history of testis or groin injury Any past history of sexually transmitted disease. Late puberty seems to have a protective effect.
There is some evidence of a genetic component to the development of testis cancer. Fathers of sons with diagnosed cases have a twofold increased risk of themselves being diagnosed with a testicular cancer, while for brothers, the relative risk is over 12 .
Immunosuppressed patients. Testicular tumors represent the third most common AIDS-linked malignancy. Following Kaposi's sarcoma and non-Hodgkin's lymphoma, with a prevalence of 0.2% compared with 0.004% in the general male population.
Pathology Over 95% of testicular cancers are germ-cell tumors:Seminomas(40%) or Non seminomas(60%). Non seminomas have an age-specific incidence peak 10 years earlier than that of seminomas.
Intra tubular germ-cell neoplasia(IGCN) SeminomaClassic typeSpermatocytictype Non seminomatousgerm-cell tumors Embryonal carcinoma Yolk sac (endodermal sinus) tumor Trophoblastic tumorsChoriocarcinomaTrophoblastic neoplasms other than choriocarcinoma Monophasic choriocarcinomaPlacental site trophoblastic tumors Teratoma Dermoid cystMonodermalteratomaTeratomawith somatic type malignancies -- Mixed germ-cell tumors
Classification of Sex-Cord Stromal Tumors of the TestisLeydig cell tumorSertoli cell tumorGranulosa cell tumorFibroma-thecoma stromal tumorSex cord-stromal tumor with annular tubulesGonadoblastomaSex cord-stromal tumor unclassified type
Biology Seminoma may represent the “default” invasive histologic component. Embryonalcarcinoma arises from selective activation/inactivation of key regulators of development, accompanied by a loss of a PGC phenotype.
Further illicit initiation of lineage differentiation in embryonal carcinoma (EC) may lead to teratoma, yolk sac tumor, and choriocarcinoma development, each with a unique gene expression signature.
The precursor of all GCT is considered to be ITGCN Genetic analysis of male GCTs has shown that virtually 100% of tumors show an increased copy number of 12p.
IGCN has a 50% risk of developing into an invasive germ-cell tumor within 5 years. 100% by 8 years. Precursor lesion of all types of germ-cell tumors except spermatocytic seminoma and infantile testicular tumors. Originate from primordial germ cells early during embryogenesis, possibly due to an excess of estrogens.
Seminoma CLASSIC TYPE: Most frequent GCT, comprising over 50% . (HCG) is elevated in 15% to 30% at presentation, related to the presence of syncytiotrophoblasticcells Over 90% - Positive for a PLAP.
Spermatocyticseminoma: 2% of all GCT. Occur in an older age group - mean age of 54 years. Confined to the testes and is cured by orchidectomy. Stains negative for placental alkaline phosphatase.
Non Seminoma Embryonal Carcinoma Pure embryonalcarcinoma- 3% of all GCT 50% of mixed germ-cell tumors. Between the ages of 15 and 34 years. Embryonalcarcinomas - PLAP positive Alpha-fetoprotein -33% HCG - 21%
Yolk Sac (Endodermal Sinus Tumor) Pure yolk sac tumor<2% of testicular tumors in adults 40% of mixed germ-cell tumors. 60% of GCT in children. First 2 years of life. Elevated serum levels of alpha-fetoprotein. Microscopically, Schiller-Duval bodies are a characteristic feature.
Teratoma Pure teratoma -5% of all GCT. Seen in about 50% of mixed germ-cell tumors. HCG and AFP are normal in pure teratoma. Mature teratoma consists of mature well-differentiated somatic tissues. Despite their benign appearance, metastases can occur.
Immature teratoma contains immature elements in addition to varying amounts of well-differentiated tissue.
Both mature and immature teratomas have a similar behavior.
Teratomawith malignant transformation results from the development of a somatic carcinoma or sarcoma within the teratoma.
Choriocarcinoma Pure choriocarcinoma is the rarest type of GCT (0.05%) but present in about 4% of mixed GCT. Highly aggressive neoplasm and often presents with metastatic disease, the primary lesion being occult. The serum HCG is elevated.
Mixed Germ-Cell Tumors Mixed germ-cell tumors- 50% of germ-cell tumors. Serum markers are elevated depending on the proportion of different elements present within. Teratocarcinomais the most common form
Modified Royal Marsden Staging System for Seminoma I Tumorconfined to the testis II Infradiaphragmatic nodal involvement IIA Greatest dimension of involved nodes < 2 cm IIB Greatest dimension of involved nodes ≥2 cm but < 5cm IIC Greatest dimension of involved nodes 5 cm or more but < 10cm IID Greatest dimension of involved nodes ≥10 cm III Supraclavicular or mediastinalinvolvement IV Extranodal metastases
AJCC Staging Tis- Intratubular germ cell neoplasia (carcinoma in situ) T1- Tumorlimited to the testis and epididymis without vascular/lymphatic invasion; tumormay invade into the tunica albuginea but not the tunica vaginalis T2-Tumorlimited to the testis and epididymis with vascular/lymphatic invasion, or tumorextending through the tunica albuginea with involvement of the tunica vaginalis T3 - Tumorinvades the spermatic cord with or without vascular/lymphatic invasion T4 - Tumorinvades the scrotum with or without vascular/lymphatic invasion
N1 - Metastasis with a lymph node mass 2 cm or less in greatest dimension; or multiple lymph nodes, none more than 2 cm in greatest dimension pN1 - Metastasis with a lymph node mass 2 cm or less in greatest dimension and less than or equal to 5 nodes positive, none more than 2 cm in greatest dimension
N2 - Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, any one mass greater than 2 cm but not more than 5 cm in greatest dimension pN2 - Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or more than 5 nodes positive, none more than 5 cm; or evidence of extranodal extension of tumor
N3 - Metastasis with a lymph node mass more than 5 cm in greatest dimension pN3 - Metastasis with a lymph node mass more than 5 cm in greatest dimension
M0 - No distant metastasis M1 - Distant metastasis M1a - Non regional nodal or pulmonary metastasis M1b - Distant metastasis other than to non-regional lymph nodes and lung
0pTis N0 M0 S0 I pT1–4 N0 M0 SX IA pT1 N0 M0 S0 IB pT2 N0 M0 S0 pT3 N0 M0 S0 pT4 N0 M0 S0 IS Any pT/Tx N0 M0 S1–3 (post orchiectomy) II Any pT/Tx N1–3 M0 SX IIA Any pT/Tx N1 M0 S0 Any pT/Tx N1 M0 S1 IIB Any pT/Tx N2 M0 S0 Any pT/Tx N2 M0 S1 IIC Any pT/Tx N3 M0 S0 Any pT/Tx N3 M0 S1
III Any pT/Tx Any N M1 SX IIIA Any pT/Tx Any N M1a S0 Any pT/Tx Any N M1a S1 IIIB Any pT/Tx N1–3 M0 S2 Any pT/Tx Any N M1a S2 IIIC Any pT/Tx N1–3 M0 S3 Any pT/Tx Any N M1a S3 Any pT/Tx Any N M1b Any S
Serum TumorMarkers (S) SX Marker studies not available or not performed S0 Marker study levels within normal limits
Staging Work Up GeneralHistory (document cryptorchidism and previous inguinal or scrotal surgery)Physical examination Laboratory StudiesCBC, LFT, RFT, LDH Serum assaysAlpha fetoprotein (AFP)Beta human chorionic gonadotropin
Diagnostic Radiology Chest x-ray films, posterior/anterior and lateral views Computed tomography (CT) scan of abdomen and pelvis CT scan of chest for non seminomas and stage II seminomas Ultrasound of contralateral testis
SurgeryRadical inguinal orchiectomy Special StudiesSemen analysis
Serum tumor marker levels should be measured prior to orchiectomy for assignment of S category. The only exception is for Stage IS: Persistent elevation of serum tumor markers following orchiectomy is required.
The Serum Tumor Markers (S) category comprises the following: Alpha fetoprotein (AFP) [ <15 ng/mL]. Human chorionic gonadotropin (hCG) Lactate dehydrogenase (LDH)
Serum tumor markers can document persistent or recurrent cancer after surgery or chemotherapy and may predict the responsiveness of nonseminomas to treatment.
Serum PLAP is elevated in 50% of seminomas at presentation and has a serum half-life of 24 hours. For metastatic or recurrent disease it has a sensitivity of only 50% and a specificity of 90%, although lower in smokers.
The level of beta-HCG should decrease by 90% or more every 21 days with each successful treatment cycle of chemotherapy. The decline of AFP is less predictable.
Discuss sperm banking Followed by Radical Inguinal Orchidectomy Consider contralateral testis biospsy if Suspicious ultrasound Cryptorchid Marked atrophy
Pure Seminoma- Post Diagnostic Workup Abdominal/ pelvic CT Chest CT if : Abnormal abdominal CT or Chest X Ray Repeat serum markers Brain MRI if indicated Bone Scan if indicated
Non Seminoma- Post Diagnostic Workup Abdominal/ pelvic CT +/- Chest Imaging Repeat serum markers Brain MRI if indicated Bone Scan if indicated
Elevated Serum Markers should be followed with a repeat evaluation after orchidectomy for precise staging. (NCCN)
IHC All seminomas express PLAP, OCT3/4, and CD117 (the kit receptor). Loss of c-kit expression in seminoma may be associated with a clinically more aggressive phenotype.
Most embryonal carcinomas, but not seminoma, also express the CD30 antigen Embryonal carcinoma and yolk sac tumor display somatic differentiation and surface expression of low-molecular-weight keratins (AE-1, CAM 5.2)