Urosurgery 24 Testicular Tumors Hydrocele Varicocele

• A) Primary testicular tumor
• 1. Germ cell tumors - 90–95%
• - seminoma -
• - nonseminom - embryonal carcinoma (EC), yolk sac tumor, teratoma, and choriocarcinoma

2. Nongerminal neoplasms (5-6%) - Leydig cell, Sertoli cell, gonadoblastoma

B) Secondary tumors - Lymphoma, Metastatic

• During embryonal development, the totipotential germ cells can travel down normal differentiation pathways and become spermatocytes.
• However, if these totipotential germ cells travel down abnormal developmental pathways,seminoma or embryonal carcinomas (totipotential tumor cells) develop.
• If the embryonal cells undergo further differentiation along intraembryonic pathways, teratoma will result.
• If the embryonal cells undergo further differentiation along extraembryonic pathways, either choriocarcinoma or yolk sac tumors are formed. 
• This model helps to explain why specific histologic patterns of testicular tumors produce certain tumor markers. Note that yolk sac tumors produce alpha-fetoprotein (AFP) just as the yolk sac produces AFP in normal development.
• Likewise, choriocarcinoma produces human chorionic gonadotropin (hCG) just as the normal placenta produces hCG.

Cryptorchidism

Family history of testicular cancer

Personal history of testicular cancer

Intratubular germ cell neoplasia (ITGCN) - Most GCTs arise from a precursor lesion called intratubulargerm cell neoplasia (which is also referred to as carcinoma in situ

• On average, seminomas occur at an older average age than NSGCTs, with most cases diagnosed in the fourth or fifth decade of life.
• Seminoma arises from ITGCN and is considered to be the common precursor for the other NSGCT subtypes

• Teratomais resistant to chemotherapy.
• Teratomas may grow uncontrollably, invade surrounding structures,and become unresectable (known as growing teratoma syndrome). On rare occasions, teratoma may transform into a somatic malignancy such as rhabdomyosarcoma, adenocarcinoma, or primitive neuroectodermal tumor

• With the exception of choriocarcinoma, which demonstrates early hematogenous spread, germ cell tumors of the testis typically spread in a step wise lymphatic fashion.
• Lymph nodes of the testis extend from T1 to L4 but are concentrated at the level of the renal hilum because of their common embryologic origin with the kidney.

For right testicular tumors the primary drainage site is the inter-aortocaval lymph nodes inferior to the renal vessels, followed by the paracaval and para-aortic nodes.

The primary “landing zone” for left testicular tumors is the para-aortic lymph nodes, followed by the interaortocaval nodes. 

More caudal deposits of metastatic disease usually reflect retrograde spread to distal iliac and inguinal lymph nodes secondary to large volume disease and, more rarely, aberrant testicular lymphatic drainage.

• Tis: Intratubular cancer (CIS)
• T1: Limited to testis and epididymis, no vascular invasion
• T2: Invades beyond tunica albuginea and into tunica vaginalis or has vascular invasion
• T3: Invades spermatic cord
• T4: Invades scrotum

• N1: Nodal mass ≤2 cm, or multiple nodes, none >2 cm and <6 lymph nodes positive
• N2: Nodal mass >2 cm and ≤5 cm or ≥6 nodes positive
• N3: Nodal mass >5 cm

• M1a: Distant metastasis present in nonregional lymph nodes or lungs
• M1b: Nonpulmonary visceral metastases

• S - Serum tumour markers
• S1: Lactic acid dehydrogenase (LDH) <1.5 × normal and hCG<5000 mIU/mL and AFP <1000 ng/mL
• S2: LDH 1.5–10 × normal or hCG 5000–50,000 mIU/mL or AFP1000–10,000 ng/mL
• S3: LDH >10 × normal or hCG >50,000 mIU/mL or AFP>10,000 ng/mL

• The stages are:
• • Stage I: the tumour is confined to the testis;
• • Stage II: nodal disease is present but is confined to nodes below the diaphragm;
• • Stage III: nodal disease is present above the diaphragm;
• • Stage IV: nonlymphatic metastatic disease (most typically within the lungs)

• Symptoms
• - Painless unilateral enlargement of the testis.
• - Enlargement is usually gradual, and a sensation of testicular heaviness is not unusual.
• - Gynecomastia in 7% cases
• - 10% present with metastatic disease
• - Back pain (retroperitoneal metastases involving nerve roots) is the most common symptom.
• - Other symptoms include cough or dyspnea (pulmonary metastases); anorexia, nausea, or vomiting (retroduodenal metastases); bone pain (skeletal metastases); and lower extremity swelling (vena caval obstruction).

• Signs - 
• - A testicular mass or diffuse enlargement is found in mostcases. The mass is typically firm and nontender and the epididymis should be easily separable from it.
• - A hydrocele may accompany the testicular tumor and help to camouflage it.
• - Transillumination of the scrotum can help to distinguish between these entities.

• Regional or distant metastasis at diagnosis is present in approximately two thirds of NSGCTs and 15% of pure seminomas, and symptoms related to metastatic disease are the presenting complaint in 10% to 20% of patients
• A firm intratesticular mass should be considered cancer until proven otherwise and should be evaluated further with scrotal ultrasonography. In patients with a presumptive diagnosis of epididymo-orchitis, patients should be reevaluated within 2 to 4 weeks of completion of an appropriate course of oral antibiotics.
• Prior studies show that up to one third of testicular tumors are initially misdiagnosedas epididymitis or hydrocele

AFP (produced by yolk sac cells) - Although present in fetal serum in high levels, beyond the age of 1 year, it is present only in trace amounts. While present to varying degrees in many NSGCTs, it is never found in seminomas.

hCG (expression of trophoblasts) - While more commonly elevated in NSGCTs, hCG levels may be elevated in up to 7% of seminomas

LDH - LDH may also be elevated in seminoma.

Placental alkaline phosphatase (PLAP) - optional marker for pure seminoma, not recommended in smokers.

Teratomas are generally associated with normal serum tumor markers.

• USG - US sensitivity is almost 100%
• Chest x-ray and CECT - to assess the two most common sites of metastatic spread, namely, the lungs and retroperitoneum.

• Radical Inguinal Orchiectomy - removal of the tumor-bearing testis and spermatic cord to the level of the internal inguinal ring. 
• If the diagnosis is not clear, a testicular biopsy is taken for frozen section histological examination.
• A transscrotal orchiectomy or biopsy is contraindicated because it leaves the inguinal portion of the spermatic cord intact and may alter the lymphatic drainage of the testis, increasing the risk of local recurrence and pelvic or inguinal lymph node metastasis.
• Offer biopsy of the contralateral testis and discuss its consequences with patients at high risk for contralaterial Testicular Intraepithelial Neoplasia.
• Testis-sparing surgery  (or partial orchiectomy) for GCT is a consideration only in highly select patients who have a small tumor in either a solitary testis or synchronous bilateral testicular masses when preservation of the affected testis will provide the patient with sufficient testicular androgen production.
• Perform serum determination of tumour markers (AFP, hCG, and LDH), both before and 5-7 days after orchiectomy for staging and prognostic reasons. The presence of newly elevated and/or rising serum tumor marker levels after orchiectomy indicates metastatic disease, and these patients should receive induction chemotherapy as initial therapy. 
• Assess the state of the retroperitoneal, mediastinal and supraclavicular nodes and viscera in testicular cancer.

• Compared with NSGCT, seminoma is exquisitely sensitive to radiation therapy and platin-based chemotherapy. 
• Radiation therapy is a standard treatment option for CS I and IIA-B seminoma but has no role in NSGCT, with the exception of treatment for brain metastases. 
• The risk of teratoma at metastatic sites is generally not a consideration for advanced seminoma,which has important implications for the management of residual masses after chemotherapy. However, the potential for seminoma to transform into NSGCT elements is an important consideration in the management of patients who fail to respond to chemotherapy or who experience relapse after radiation therapy. Of patients with metastatic seminoma who experience relapse after treatment, 10% to 15% have NSGCT elements at the site(s) of relapse. An autopsy study has shown that 30% of patients who die of seminoma have NSGCT elements at metastatic sites. 
• Because NSGCTs are usually mixed tumors and teratoma often exists at metastatic sites with other GCT elements, “cure” often requires chemotherapy to kill the chemosensitive components and surgery to remove teratomatous components.

• Good risk - Testicular or retroperitoneal primary, No nonpulmonary visceral metastases, Postorchiectomy markers S1 level
• Intermediate risk - Testicular or retroperitoneal primary, No nonpulmonary visceral metastases, Postorchiectomy markers S2 level
• Poor risk - Mediastinal primary tumor, Nonpulmonary visceral metastases, Postorchiectomy markers S3 level

• Stage I tumours
• - Seminomas are radiosensitive, adjuvant radiotherapy to the para-aortic nodes is the mainstay of treatment for stage I disease.
• - NSGCTs are not radiosensitive, but they are highly sensitive to combination chemotherapy with bleomycin, etoposide and cis-platinum (BEP chemotherapy). Some good prognosis NSGCTs can be managed by surveillance protocols (using regular CT scanning and tumour marker measurement) with the more high risk cases receiving chemotherapy

Stage II–IV tumours - Combination BEP chemotherapy is the mainstay of treatment for stages II–IV seminoma and NSGCT. Retroperitoneal lymph node dissection is sometimes needed in some cases of NSGCT when retroperitoneal masses remain after chemotherapy. The tissue removed may contain only necrotic tissue, but some patients have foci of mature teratoma or active malignancy. The operation can be formidable (difficult) if the tumour mass is large, and retrograde ejaculation is likely unless steps are taken to preserve the sympathetic outflow to the bladder neck.

Follow up - For those who have undergone surgery (RPLND) or radiotherapy, in general, they are followed at 3-month intervals for the first 2 years, then every 6 months until 5 years, and then yearly. Follow-up visits should include careful examination of the remaining testis, the abdomen, and the lymph node areas. Laboratory investigation should include AFP, hCG, and LDH levels. A CXR and an abdominal film (if an LAG was performed) should also be included at each visit.

Leydig cell tumors - Radical orchiectomy is the initial treatment. RPLND is recommended for malignant lesions (>10times increase in 17-ketosteroids). 

Gonadoblastoma - Radical orchiectomy is the primary treatment of choice. In the presence of gonadal dysgenesis, a contralateral gonadectomy is recommended because the tumor tends to be bilateralin 50% of cases in this setting

Sertoli cell tumor - Radical orchiectomy is the initial procedure of choice. In cases of malignancy, RPLND is indicated; however, the roles of chemotherapy and radiotherapy remain unclear.

• Most common bilateral testicular tumor 
• Most common metastatic tumor of testis

A varicocele is a varicose dilatation of the veins draining the testis.

• While most varicoceles are asymptomatic, those that are symptomatic tend to present in adolescence or early adulthood when there may be an annoying dragging discomfort that is worse on standing at the end of the day.
• This presumably reflects distension of the testicular veins.
• When examined in the erect position, the scrotum on the affected side hangs lower than normal, and on palpation, with the patient standing, the varicose plexus feels like a bag of worms. There may be a cough impulse. If the patient lies down the veins empty by gravity and this provides an opportunity to ensure that the underlying testis is normal to palpation. In longstanding cases, the affected testis is smaller and softer than its fellow owing to a minor degree of atrophy.
• As left sided varicocele may be secondary to renal cell carcinoma on the left side so it is necessary to examine the abdomen to rule out any mass.

• „ Grade I: Small varicocele which is palpable only when patient performs Valsalva maneuver.
• „ Grade II: Moderate sized. Easily palpable varicocele without Valsalva’s maneuver.
• „ Grad III: Large varicocele visible through the scrotal skin.

• Grade I doesnot need treatment.
• Palomo’s operation is done for Grade II and III varicocele. Palomo's operation is high ligation of testicular vein.

• Congenital hydroceles are treated by herniotomy if they do not resolve spontaneously.
• Small acquired hydroceles do not need treatment. If they are sizeable and bothersome for the patient, then surgical treatment is indicated.
• Lord’s operation is suitable when the sac is reasonably thin-walled. There is minimal dissection and the risk of haematoma is reduced.
• Eversion of the sac with placement of the testis in a pouch prepared by dissection in the fascial planes of the scrotum is an alternative (Jaboulay’s procedure).
• Aspiration of the hydrocele fluid is simple, but the fluid always reaccumulates within a week or so. It may be suitable for men who are unfit for scrotal surgery, although hydrocele surgery can be undertaken under local anaesthetic. Aspiration can result in bleeding into the hydrocele sac and haematocele formation. Injection of sclerosants such as tetracycline is effective but painful