A Patient’s Painless Testicular Lump: Is It Cancer?

A 28-year-old man with a history of chronic low back pain presented to the clinic with a testicular mass. He expressed concern about the possibility of testicular cancer.

History. Many weeks prior to presentation, he had palpated the mass while taking a shower. He reported no weight loss, night sweats, fevers, or any increase in the size of the testicular mass. In addition, he denied any urethral discharge, dysuria, or urinary frequency. He worked as a vehicle mechanic and denied a family history of testicular cancer. He lived with his girlfriend and was monogamous. He enjoyed fitness activities, including cycling for hours on the weekends.

Physical examination. The patient appeared well nourished, alert, and oriented. He had a 1-cm, nontender, mobile, palpable mass on his right testicle. The left testis was normal on palpation. He was circumcised, with no penile lesions or discharge. No inguinal or femoral hernia was appreciated. The rest of the physical examination findings were unremarkable.

Background. In 2012, an estimated 233,602 men were living with testicular cancer in the United States.¹ Approximately 0.4% of all US men will be diagnosed with this cancer in their lifetime.¹ Testicular cancer is the most common solid tumor in young men between 15 and 44 years of age.² The incidence of testicular cancer in the United States has increased steadily over the past 20 years.³ This rise in incidence is matched by significant improvements in the survival rate, with an approximate 95% cure rate in nonmetastatic disease and an 80% cure rate in metastatic disease.^2,3

Testicular cancer is most common in white patients.³ Germ cell tumors account for 95% of all testicular cancers and are categorized as seminomas or nonseminomas. The nonseminomatous germ cell tumors (NSGCTs) are subcategorized as choriocarcinomas, yolk sac carcinoma, teratomas, embryonal carcinomas, and mixed type tumors.^1,2

Cryptorchidism is the primary risk factor for testicular cancer.^3,4 Men with a history of germ cell cancer of the contralateral testis, Down syndrome, or testicular dysgenesis syndrome also are at increased risk of developing testicular germ cell cancers. In addition, a brother or father with a history of testicular cancer confers an additional risk.³

Presentation. A painless lump in the body of the testis is the presenting symptom in 95% of cases.² Patients usually are the first to notice the testicular lump, often late, given the painless and subtle nature of the lump. Rarely, patients present with testicular pain, hemorrhage, or symptoms of metastatic disease such as backache, cough, or hemoptysis. Other rarely encountered symptoms include nipple tenderness and gynecomastia, which usually are associated with increased production of human chorionic gonadotropin (hCG).²

Diagnostic tests. Testicular ultrasonography is considered the initial test of choice and has almost 100% diagnostic sensitivity. Urgent ultrasonography and urologic evaluation are recommended when testicular lumps do not transilluminate or when the body of the testis cannot be palpated due to the presence of a reactive hydrocele.^2,3

Tumor markers, which often are elevated in other types of cancers and conditions, are of limited value in the initial diagnosis of testicular cancer. Increased levels of hCG and α-fetoprotein (AFP) in the setting of a testicular lump indicate a germ cell tumor. However, the AFP level is not elevated in seminomas, and hCG is elevated in only approximately a quarter of cases. In addition, these tumor marker test results are negative in approximately one-third of patients. Health care providers are encouraged to test for tumor marker levels for prognosis, since persisting or increasing levels indicate the possibility of metastatic disease.²

Elevated tumor marker levels should decrease following orchiectomy (the half-life of hCG and AFP is less than 1 week). An orchiectomy should not cause low testosterone levels or infertility in the presence of a normal contralateral testis. Nevertheless, sperm cryopreservation and testosterone replacement may be considered in patients with an abnormal contralateral testis or for whom chemotherapy is planned.

Prostheses also should be offered prior to orchiectomy to avoid a second surgical intervention later. Patients must be educated that the shape, size, position, and weight of a testicular implant might not always be satisfactory or identical to a normal testicle.^2,3

Biopsy and staging. The diagnosis of testicular cancer does not require confirmation with a biopsy. In fact, some authors suggest that a biopsy should never be done, because the procedure could contaminate the scrotum and affect the lymphatic drainage of the primary tumor.³ Inguinal orchiectomy can be done based on imaging results and clinical findings only.

Once confirmed by histopathologic evaluation of the excised testicle, staging with thoracic, abdominal, and pelvic computed tomography (CT) and assessment of hCG, AFP, and lactate dehydrogenase (LDH) levels are recommended. LDH is not specific for testicular cancer, but elevated levels often reflect the overall disease burden.³ Positron emission tomography is not used for staging purposes but can be used in addition to a biopsy to evaluate equivocal lymph nodes.^2,4

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Nonseminomas. Most patients with NSGCTs present with clinical stage I disease. These patients are offered adjuvant chemotherapy, retroperitoneal lymph node dissection (nerve sparing), or 5-year-surveillance after orchiectomy. Each of these options are associated with a 99% long-term cure rate.³ 

The National Comprehensive Cancer Network (NCCN) surveillance guidelines⁵ recommend physical examination, monitoring of tumor markers, and chest radiographs at every visit for low-risk patients. For stage IA disease, CT (abdomen and/or pelvis) is recommended every 4 to 6 months in the first year and every 6 to 12 months thereafter. For stage IB disease, the CT recommendations are every 4 months in the first year, every 4 to 6 months in the second year, every 6 months in the third year, and annually thereafter. Although surveillance avoids unnecessary treatment in nearly 70% of patients, the length of active surveillance often can affect the adherence to the protocol.²

In high-risk patients, adjuvant chemotherapy with bleomycin, etoposide, and cisplatin (BEP) is the primary treatment. Some studies show that 2 cycles of chemotherapy are associated with an approximate 2% to 3% relapse rate of NSGCTs.^2,4 Results of a recent German study suggest that a single cycle might be equally as effective.⁶

Retroperitoneal lymph node dissection has only a 1% relapse rate within 2 years.² However, it is a major surgical procedure with potential nerve damage leading to sexual dysfunction and infertility; it usually is reserved for patients who are not willing to undergo surveillance or chemotherapy.⁴

After orchiectomy, stage II NSGCT is treated either with chemotherapy for bulky disease or retroperitoneal lymph node dissection for low-volume disease (lymph nodes < 3 cm in diameter, normal AFP and hCG levels).³

Seminomas. Most patients who present with clinical stage I seminomas are cured with orchiectomy.³ Radiotherapy had been used for treatment but currently is not recommended. Most patients at this stage are treated with active surveillance. Unlike with NSGCTs, seminomas have an indolent nature and need longer radiologic surveillance of approximately 5 years.² 

For stage I seminomas after orchiectomy, the NCCN surveillance guidelines recommend regular clinical evaluation and monitoring of markers, along with CT (abdomen and/or pelvis) at 3, 6, and 12 months in the first year, every 6 to 12 months in the second and third years, and every 12 to 24 months thereafter.⁵

The relapse rate in stage I seminomas is approximately 4% to 20% depending on the therapy (chemotherapy or surveillance).^2,3 Adjuvant chemotherapy with single-dose carboplatin has been shown to dramatically decrease the relapse rate.²

Stage II seminomas are treated with either radiation (when disease is confined to retroperitoneal lymph nodes) or chemotherapy (for bulkier disease). BEP is the preferred chemotherapy regimen, with a cure rate of approximately 98% compared with radiotherapy alone.³

Metastatic disease. Patients with metastatic germ cell cancers have an approximately 80% cure rate, given sensitivity to cisplatin-based chemotherapy.^2,4 Patients who fail first-line chemotherapy require further salvage chemotherapy with cisplatin and would benefit from specialist referral. Residual masses after chemotherapy should be managed based on tumor type. Surgical removal with lymph node dissection is recommended in nonseminomas, given the potential presence of active cancer cells or teratomas, which are often chemotherapy-resistant. Relapse rates are approximately 18% to 33%.² With seminomas, however, residual masses are fibrotic and considered benign, with no need for surgery. The relapse rate is from 11% to 59%.²

Adverse effects. Health care providers must be vigilant about the adverse effects of chemotherapy. Common effects of the standard regimen of 3 to 4 cycles of BEP, repeated every 21 days, include vomiting, alopecia, fatigue, rashes, and skin pigmentation. Nephrotoxicity is a common adverse effect of cisplatin; therefore, adequate hydration must be ensured in patients receiving this agent. Cisplatin also can cause peripheral neuropathy and ototoxicity, which may require specialist referral. Chest symptoms such as cough, hemoptysis, or pleuritic pain may represent bleomycin-induced pneumonitis, which usually is accompanied by the presence of Raynaud phenomenon.²

Long-term health consequences can include an increased risk of testicular cancer in the contralateral testis. Chemotherapy also increases the risk of leukemia, lung cancer, melanoma, and cardiac events. Survivors also may experience associated anxiety, a fear of recurrence, sexual difficulties, financial issues, and alcohol misuse.² Referrals should be considered to help with such symptoms.

Outcome of the case. We checked our patient’s levels of AFP, hCG, and LDH, all of which were within the normal range. Testicular ultrasonography showed an epididymal cyst that correlated with the palpable testicular mass. No hydroceles or varicoceles were appreciated. The patient was reassured about the benign nature of the mass, was given a patient education handout about testicular cancer, and was asked to return for a follow-up visit in 6 to 12 months.

Mustafa Kinaan, MD, is an internal medicine resident at the University of Central Florida College of Medicine in Orlando.

Sayed K. Ali, MD, serves as faculty in internal medicine and palliative care at the Orlando Veterans Affairs Medical Center in Orlando, Florida. He also is an associate professor at the University of Central Florida College of Medicine in Orlando.

References:

1. National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) Program. SEER Stat Fact Sheets: Testis Cancer. http://seer.cancer.gov/statfacts/html/testis.html. Accessed March 1, 2016.
2. Horwich A, Nicol D, Huddart R. Testicular germ cell tumours. BMJ. 2013;347:f5526. doi:http://dx.doi.org/10.1136/bmj.f5526.
3. Hanna NH, Einhorn LH. Testicular cancer — discoveries and updates. N Engl J Med. 2014; 371(21):2005-2016.
4. Winter C, Albers P. Testicular germ cell tumors: pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2011;7(1):43-53.
5. Motzer RJ, Jonasch E, Agarwal N, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Testicular Cancer, Version 1.2016. Fort Washington, PA: National Comprehensive Cancer Network; 2016. http://www.nccn.org/professionals/physician_gls/pdf/testicular.pdf. Accessed March 1, 2016.
6. Albers P, Siener R, Krege S, et al. Randomized phase III trial comparing retroperitoneal lymph node dissection with one course of bleomycin and etoposide plus cisplatin chemotherapy in the adjuvant treatment of clinical stage I nonseminomatous testicular germ cell tumors: AUO trial AH 01/94 by the German Testicular Cancer Study Group. J Clin Oncol. 2008;26(18):2966-2972.