Testicular carcinoma

Epidemilogy 90-95% are germ cell Incidence five times higher among white men Most common solid tumor in males ages often is in right

What is Testicular Cancer? Germ cell tumors (GCT): ~95% of TC  Seminomas: most common subtype (~50%); slow growing and radiosensitive  Nonseminomas: often occur in third decade; rapid metastasis to lymph nodes and lung Non-Germ Cell Tumors (Non-GCTs)  Stromal: ~4% of adult TC  Secondary tumors: arise in another organ

Risk factor Gonadal Dysgenesis 20-30% develop cancer (gonadoblastoma) Trauma prompts evaluation Hormones DES/OCP probably do not increase risk Atrophy (mumps orchitis)

Cryptorchidism: 7-10% of patients with testicular cancer have a history of cryptorchidism Abnormal germ cell morphology Elevated temperature Interference with normal blood supply 5-10% of patients with testicular cancer and a history of cryptorchidism develop cancer in the contralateral testis Orchidopexy does not prevent development of cancer – just allows for detection

Clinical manifestation Patients often present with a painless testicular mass  Pain, swelling, or hardness in scrotum a less frequent complaint  About 10% report recent testicular trauma  Swelling in lower extremities, back pain, cough, or dyspnea may indicate advanced disease Gynecomastia 5% germ cell 30-50% Sertoli/Leydig 1-2% have bilateral disease at diagnosis More common on the right

Diffrentiated Diagnosis Torsion Epididymitis Epididimoorchitis Hydrocele Hernia Hematoma Spermatocele Syphilitic gumma

Work-up Exam U/S CXR +/- Chest CT Abdominal CT Can identify small nodal deposits <2 cm MRI and PET scan no advantage over CT Markers Elevation after orchiectomy generally represents metastatic disease Conversely normalization does not rule out metastatic disease

Alpha-Fetoprotein Expressed by the early embryo (also liver and GI tract) Single chain Half-life: 5-7 days Produced by pure embryonal, teratocarcinoma, yolk sac, mixed tumors (NOT pure choriocarcinoma or seminoma) Falsely elevated in liver dysfunction, viral hepatitis

Human Chorionic Gonadotrophin Secretory product of the placenta Alpha unit (LH,FSH,TSH) and beta unit Half-life: hours Produced by syncytiotrophoblastic tissue All choriocarcinomas, 40-60% embryonal, 5-10% seminoma Falsely elevated in hypogonadism and marijuana use

Lactic Acid Dehydrogenase Presents normally in smooth, cardiac and skeletal muscle, liver and brain Most useful in advanced seminoma or tumors where other markers are not elevated Many false positives

Testis cancer GERM CELL Seminoma 30-60% Non-seminoma Embryonal 3-4% Yolk sac Teratoma 5-10% Choriocarcinoma 1% Mixed 40% NONGERM CELL Leydig 1-3% Sertoli <1% Gonadoblastoma 0.5%

Seminoma: Most common germ cell tumor Pure seminomas never secrete AFP 5-10% secrete HCG (usually classic) At diagnosis: 65-75% confined to the testis 10-15% with regional retroperitoneal nodes 5-10% with advanced juxtorenal or visceral disease

Seminoma

Classic 82-85% Age 30s Islands /sheets of cells with syncytiotrophoblasts (5-10%) Anaplastic 5-10% Stage for stage no different than classic Spermatocytic 2-12% Low metastatic potential Older population (>50) 6% bilateral

Emberional Peak age May secrete both AFP and B-HCG Metastatic deposits usually contain teratoma (80%)

Yolk Sac (Infantile embryonal) Peak age: infants and children Also may spread hematogenously Secretes AFB and B-HCG Embryoid bodies (Schiller-Duvall bodies) resemble 1-2 week old embryos surrounded by syncytiotrophoblasts and cytotrophoblasts

Choriocarcinoma Peak age Worst prognosis of all testis tumors Hematogenous spread (especially to lungs) Always secrete B-HCG

Teratoma Peak age Poor response to chemotherapy and XRT Pure forms should not secrete AFB or B-HCG Can arise from malignant transformation after chemotherapy for NSGCT Contains all 3 germ layers in the mature form and is undifferentiated in immature form

TNM Staging of Testicular Tumour T 0 =No evidence of Tumour T 1s =Intratubular, pre invasive T 1 =Confined to Testis T 2 =Invades beyond Tunica Albuginea or into Epididymis T 3 =Invades Spermatic Cord T 4 =Invades Scrotum N 1 =Multiple< 5 node/Single < 2 cm N 2 =Multiple < 5 node / Single 2-5 cm N 3 =Any node > 5 cm

PRINCIPLES OF TREATMENT Treatment should be aimed at one stage above the clinical stage Seminomas - Radio-Sensitive. Treat with Radiotherapy. Non-Seminomas are Radio-Resistant and best treated by Surgery Advanced Disease or Metastasis - Responds well to Chemotherapy

PRINCIPLES OF TREATMENT Radical INGUINAL ORCHIDECTOMY is Standard first line of therapy Lymphatic spread initially goes to RETRO-PERITONEAL NODES Early hematogenous spread RARE Bulky Retroperitoneal Tumours or Metastatic Tumors Initially “ DOWN-STAGED ” with CHEMOTHERAPY

Treatment of Seminomas Stage I, IIA- Radical Inguinal Orichidectomy followed by radiotherapy to Ipsilateral Retroperitonium & Ipsilateral Iliac group Lymph nodes ( rads) Bulky stage II and III Seminomas - Radical Inguinal Orchidectomy is followed by Chemotherapy

Treatment of Non-Seminoma Low Grade RADICAL ORCHIDECTOMY followed by RETROPERITONEAL LYMPH DISSECTION High Grade: Initial CHEMOTHERAPY followed by SURGERY for Residual Disease

Radical Orchiectomy

Survival at 5 years Non-seminomaSeminoma % 98% Stage I >90%92-94%Stage II A 55-80%33-75%Stage II B-III

NON_GERM CELL Leydig Cell 1-3% of all testis tumors Bimodal age distribution: ages 5-9 and Bilateral in 5-10% No association with cryptorchidism Prepubital children may present with virilization and elevated urinary 17-ketosteroid levels; adults are usually asymptomatic (25% gynecomastia) Treatment: radical orchiectomy and RPLND for malignant tumors (10% malignant)

Sertoli Cell Less than 1% of all testicular tumors Bimodal age of distribution: < 1 year and years old 10% lesions are malignant Virilization seen in children and gynecomastia in adults Treatment: Radical orchiectomy with RPLND in malignant disease

Gonadoblastoma 0.5% of testicular tumors Seen in patients with gonadal dysgenesis 4/5 patients are phenotypic females with streak gonads Treatment: Radical orchiectomy with gonadectomy of the contralateral gonad (bilateral in 50%)

Secondary testicular tumor Lymphoma Large without pain 50% bilatral ¼ with systemic symptom treatment: radical orciectomy+chemotherapy

Leukemia: in 50% bilatral Dx : biopsy Metastatic tumor: very rarely source: prostat lung GI melanoma kidney