A 20-year-old man reports that he has had a nontender, heavy sensation in his scrotal area for 2 months. He jogs several miles every day but denies lifting heavy objects. He does not recall trauma to the area and has no urinary complaints. He is healthy and does not smoke. On examination, his blood pressure is 110/70 mm Hg and his heart rate is 80 beats/min; he is afebrile. The results from his heart and lung examinations are normal. There is no back tenderness. His abdomen is non-tender and without masses. The external genitalia reveal a 2-cm nontender mass in the right testis. Transillumination shows no light penetration. The findings from a rectal examination are unremarkable.
What is the most likely diagnosis?
What is the best therapy for this patient?
ANSWERS TO CASE 42: Testicular Cancer
Summary: A 20-year-old man is noted to have had a nontender heavy sensation in the scrotal area for 2 months. He jogs several miles every day but denies lifting heavy objects. He denies trauma to the area and has no urinary complaints. A 2-cm, nontransilluminating, nontender mass in the right testis is noted. The results from a rectal examination are unremarkable.
• Most likely diagnosis: Testicular cancer.
• Best therapy: Surgery (radical orchiectomy) with possible chemotherapy.
1. Know that a nontender, nontransilluminating testicular mass in a man younger than 40 years should be considered testicular cancer unless proven otherwise.
2. Understand that knowledge of the correct pathologic diagnosis or cell type(s) is crucial in directing therapy.
3. Know that a testicular carcinoma can be cured; however, patient compliance with treatment and surveillance protocols is important.
Testicular cancer is the most common malignancy in men between the age of 15 and 35, with an incidence of 3 to 5 per 100,000 men. It is more common in white males than in black males. Thus, this patient matches the most common profile. Although a painless scrotal mass is the most common presentation, references are often made to a trivial traumatic event that may have brought the scrotal mass to the patient’s attention. Further, an incorrect clinical diagnosis such as varicocele, spermatocele, hydrocele, epididymitis, or testicular torsion may further delay appropriate evaluation and treatment. Regular scrotal self-examination is advocated but rarely performed; rather, an element of embarrassment often delays presentation.
The next step for this patient is a complete examination at the time of presentation to search for evidence of metastatic disease. There are tumor markers for many cell types, most prominently β-human chorionic gonadotropin (β-hCG) and α-fetoprotein (AFP). A radical orchiectomy would be the best therapy. Tumor cell types are generally divided into seminoma and nonseminomatous germ cell tumors. Treatment protocols rely on an accurate diagnosis of the cell type(s) within the tumor. A skilled pathologist often reviews many slides from the surgical specimen, using special stainings when necessary to obtain a diagnosis.
APPROACH TO: Testicular Masses
RADICAL ORCHIECTOMY: A surgical procedure in which an inguinal incision is made over the cord leading to the testicle to be removed. The surgical specimen includes testis, epididymis, and spermatic cord taken at the internal iliac ring. Care is taken not to incise the scrotum itself during the surgical procedure.
RETROPERITONEAL LYMPHADENECTOMY: A surgical procedure performed to remove the lymph nodes draining the testicle. Testicular cancer often progresses in an orderly fashion up the lymphatic drainage of the testis. Testicular lymphatics flow from the testis through the spermatic cord following the testicular artery into the retroperitoneum where they drain into nodes around the vena cava and aorta.
GERM CELL TUMOR: Ninety percent of cancers of the testis are derived from the germinal epithelium (sperm-forming elements) of the testis. Subtypes include choriocarcinoma, embryonal carcinoma, seminoma, teratoma, and yolk sac tumor. The other 10% of testicular tumors are made up of what is known as gonadal stromal tumors, secondary tumors of the testis such as lymphoma, and metastatic tumors to the testis.
When a man presents with a chief complaint of a testicular mass, a detailed examination of the genitalia should be performed, delineating the character of the mass, painful versus painless, hard versus soft, and transilluminating versus nontransilluminating. Palpation of the lymph nodes, examination of the male breasts, and a general survey of the signs and symptoms related not only to the genitourinary system but also to the endocrine and neurologic systems are important.
Radical (inguinal) orchiectomy should be performed when it is confirmed that the lesion within the scrotum is a solid mass. An ultrasound of the scrotum is helpful in making this determination. Preoperative testing should also include tumor markers such as β-hCG and AFP, which are elevated in 80% to 85% of the patients with nonseminomatous germ cell tumors. Serum lactic acid dehydrogenase (LDH) is also routinely assessed in patients with suspected testicular cancers; even though LDH elevation does not help determine tumor type, abnormal elevations in serum LDH often correlate with tumor volume and may have prognostic implications. A chest radiograph or chest CT should be obtained preoperatively to rule out metastatic disease that may influence the anesthetic method.
Once the diagnosis of testicular cancer is confirmed, further metastatic evaluation such as a CT scan of the abdomen and chest is warranted. Therapeutic decisions depend first on an accurate pathologic diagnosis of the cell type(s) within the tumor. Often there is more than one cell type, hence the term “mixed germ cell tumor.” Other important factors determining therapeutic decisions include the extent of disease (tumor stage), risk factors (known characteristics of the tumor type or extent that are often associated with an aggressive prognosis), and compliance of the patient.
Although testicular cancer has played a part in one of the modern medical success stories, where the terms “cure” and “cancer” can be used honestly in the same sentence, it does strike men at a time when they are otherwise healthy and are not accustomed to needing medical evaluations and interventions. Compliance with the aggressive regimens of chemotherapy, radiation therapy, and/or surgery is key to avoiding tumor relapse and to detecting disease progression as early as possible.
Pure seminoma is treated differently from other nonseminomatous germ cell tumors primarily because of its exquisite sensitivity to radiation therapy and its response to chemotherapy when the disease is bulky and advanced. Residual testicular tumor following chemotherapy is treated with surgery, most often retroperitoneal lymphadenectomy. After successful treatment of a testicular tumor, patients need lifelong surveillance of their remaining testicle because the incidence of carcinoma becomes greater by a manifold factor.
42.1 A 16-year-old adolescent is being evaluated by the pediatrician for pubertal abnormalities. The physician describes a risk of malignancy of the gonads. Which of the following is most likely to be associated with testicular cancer?
A. XY gonadal dysgenesis
B. Androgen insensitivity
C. Turner syndrome
D. Noonan syndrome
E. Testicular trauma
42.2 Physical examination of a young man with testicular cancer during a routine surveillance visit reveals a hard mass just above the left clavicle. Which of the following is the most likely diagnosis?
A. Chemotherapy sclerosis of the subclavian vein
B. Metastatic testicular cancer
C. Second primary cancer of head and neck origin
D. Pathologic fracture of the clavicle
E. Thyroid goiter induced by prior cancer treatment
42.3 A 28-year-old man is found to have a mass of the right testicle, which is suspected to be a malignancy. Which of the following best describes the fertility of a patient before treatment for testicular cancer?
A. Below normal on average
B. Same as that of his peers
C. Above average
D. Far worse than average
42.4 A 22-year-old man is noted to have a painless scrotal mass. The AFP level is elevated. Which of the following statements is most accurate regarding the role of serum alpha-fetal protein in testicular cancer?
A. Marked elevation in a man with testicular mass generally indicates semi-nomatous testicular cancer.
B. Serum levels may be used to determine response to therapy.
C. The development of effective chemotherapeutic agents has eliminated the need for AFP level assessment.
D. The levels of serum AFP do not change following radical orchiectomy in a patient with a 4-cm nonseminomatous cancer of the left testicle.
E. AFP + LDH elevation indicates the presence of germ cell tumors.
42.5 Which of the following is an accurate statement regarding testicular seminomas?
A. Fertility following treatment is generally excellent.
B. Orchiectomy is never indicated for treatment.
C. Pain is the most common presentation.
D. Biopsy is best determined by core-needle biopsy under sedation.
E. Seminomas are sensitive to radiation therapy.
42.1 A. Intraabdominal male gonads with Y chromosomes tend to become malignant. In androgen insensitivity, the patient is 46 XY genotype, but defective androgen receptors do not allow the external genitalia to masculinize. Although both androgen insensitivity and XY gonadal dysgenesis have a propensity to become malignant, the nonfunctional dysgenetic gonad has the greater risk.
42.2 B. The Virchow node is palpated in this clinical question. This physical finding indicates a metastatic tumor within the lymph node. This supraclavicular lymph node is a harbinger of more extensive disease and may be the only clinical finding of more extensive retroperitoneal metastases. Palpation of this region is an essential part of the initial and follow-up examinations of men with testicular cancer because of the lymphatic predilections of the disease. Secondary malignancies are possible especially when dealing with survivors of previous cancer treatments, but this is an unusual presentation of a second malignancy.
42.3 A. For reasons not yet clear, the fertility of men at the time of diagnosis of testicular cancer is abnormal as assessed by a semen analysis. Certainly, surgery, radiation, and chemotherapy greatly further reduce the fertility of men with testicular cancer. The likelihood of reduced fertility and the side effects of treatments on fertility must be discussed with men who receive a diagnosis of testicular cancer.
42.4 B. The serum markers such as AFP levels can be useful in assessing the patient’s response to chemotherapy for nonseminomatous testicular cancers. Patients with seminomatous testicular cancers generally have normal or mildly elevated serum marker values. Serum LDH levels do not help differentiation of seminomatous tumors from nonseminomatous tumors; however, elevations generally correlate with tumor volume and can have prognostic implications.
42.5 A. Seminomas are sensitive to radiation therapy; therefore extratesticular extension of the disease such as disease involving the inguinal, iliac, and periaortic lymph nodes can be treated with radiation therapy following radical orchiectomy. Needle biopsy is contraindicated for patients with testicular masses that are suspicious for testicular cancers. Following radiation therapy, patients generally have significant reduction in fertility; therefore, the option of sperm banking should be discussed with patients prior to treatment.
Nearly all testicular cancers are of germ cell origin, and approximately half are caused by seminomas. Many cancers have multiple cell types whose delineation is crucial for the therapy.
Cryptorchidism (undescended testicle) significantly increases the risk of a germ cell tumor even if the maldescended testicle is surgically corrected.
An inguinal incision is made for a radical orchiectomy to avoid disruption of the lymphatic drainage of the testicle, which normally does not involve the scrotum itself.
A testicular mass that is solid (does not transilluminate) in a young man should be assumed to be testicular cancer until proven otherwise.
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Sim HG, Lange PH, Lin DW. Role of post-chemotherapy surgery in germ cell tumors. Urol Clin North Am. 2007;34:199-217.