Testicular tumors

Testicular tumors most commonly occur in men between 20 and 35 years of age, and are the most common solid malignancy in this group. Most often, patients present with a painless nodule or swelling of the testis. Diagnosis is made primarily based on palpation and findings on testicular ultrasound. Diagnostic staging further includes an abdominopelvic and chest CT, determination of serologic tumor markers (AFP, HCG, LDH), and radical inguinal orchiectomy of the affected side to confirm the diagnosis and to evaluate the histopathology (seminoma vs. nonseminoma). The necessity and choice of adjuvant treatment depends on tumor pathology, staging, and prognosis. Treatment options include active surveillance, retroperitoneal radiotherapy, retroperitoneal lymph node dissection, and platinum-based chemotherapy. The overall prognosis of testicular tumors is excellent; patients can often be cured even in advanced, metastatic stages.

• Most common solid malignant tumor in young men in the US
• Peak incidence: 20–35 years; (nonseminomas peak in the third decade, seminomas in the fourth decade of life)

References:^[1]

Epidemiological data refers to the US, unless otherwise specified.

• Risk factors
  • Cryptorchidism (increased risk for germ cell tumors) ^[2]
  • Contralateral testicular cancer
  • Germ cell neoplasia in situ (GCNIS)
  • Family history of testicular cancer
  • Klinefelter syndrome; , trisomy 21 (increased risk for germ cell tumors)
  • Subfertility/infertility, hypospadia

References:^[2][3][4]

Testicular tumors are classified according to pathology.

HCG is always elevated in choriocarcinoma and sometimes elevated in seminoma. AFP is always elevated in yolk sac tumors. Both AFP and HCG may be elevated in mixed germ cell tumors.

Testicular tumors metastasize early into the retroperitoneum via the lymphatic system (drain to the para-aortic lymph nodes first), with the exception of early hematogenous metastasizing choriocarcinomas.

References:^{[8][9][10][10][11]}

• Painless testicular nodule or swelling
• Negative transillumination test
• Dull lower abdominal or scrotal discomfort is more common than acute scrotal pain.
• In metastatic disease
  • Cough, shortness of breath, chest pain
  • Lower back or bone pain
• Gynecomastia
• In Leydig cell tumors
  • Androgen excess features
    • Prominent external genitalia, pubic hair growth, accelerated skeletal and muscle development, and mature masculine voice
    • May cause precocious puberty in boys
  • Occassionally, estrogen excess features: gynecomastia, breast tenderness, and gonadogenital underdevelopment.
• Paraneoplastic hyperthyroidism: alpha subunits of HCG and TSH are identical, enabling weak stimulation of the TSH receptor in tumors with HCG overproduction. ^[12]

Until proven otherwise, a firm nodule on the testis should be considered cancer!

References:^[1][12]

Extragonadal germ cell tumors

• Definition: primary germ cell tumors that arise outside of the gonads, anywhere along the body's midline from the pineal gland to the coccyx.
• Epidemiology: 5–10% of all germ cell tumors; mostly affects young males
• Location
  • Midline organs
  • Mediastinal > retroperitoneal > intracranial (pineal gland and suprasellar region)
  • Sacrococcygeal teratomas (most common in infancy or early childhood) ^[13]
• Symptoms :
  • Chest pain, dyspnea (on exertion), cough
  • Palpable abdominal mass, back pain, weight loss
  • Headache, nausea, vomiting, ataxia, change in vision
• Diagnosis
  • Testicular ultrasound: to rule out gonadal primary tumor
  • Tumor markers: alpha fetoprotein (AFP) and human chorionic gonadotropin (HCG)
  • Tumor biopsy (confirmatory) :Nonseminomas are more common than seminomas
• Therapy
  • Determined by the location, size, and histology of the tumor
  • Chemotherapy , radiation therapy , and/or surgical resection
• Prognosis: The 5-year survival is ∼ 95% for seminomas and 45–60% for nonseminomas.

References:^[14][15][16]

Staging of testicular tumors is based on the American Joint Committee on Cancer (AJCC) groups, which combines TNM stage and serum tumor marker levels.

Suspicion of a testicular tumor is usually established based on the clinical findings and ultrasound (to localize the tumor).

• Laboratory tests
  • Tumor markers : alpha fetoprotein (AFP), human chorionic gonadotropin (HCG) (see overview of testicular tumors) and lactate dehydrogenase (LDH)
• Imaging
  • Ultrasound
    • Seminoma: hypoechoic, homogenous, sharp margins
    • Nonseminomas: variable echogenicity; , inhomogenous; , may be calcified or cystic
    • Microlithiasis: disseminated calcification as a possible precursor of carcinoma (starry sky appearance)
  • CT: Because of the descended testis, the regional lymph nodes are located retroperitoneally (e.g., para-aortocaval) beneath the diaphragm.
    • High-resolution abdominopelvic and chest CT
    • Cranial CT or MRI if distant metastasis to the brain is suspected
• Histopathological confirmation: following radical inguinal orchiectomy

If a testicular tumor is suspected, the testis should be removed and sent to pathology. Transscrotal biopsy should not be conducted because of the risk of tumor seeding!

References:^[1][17]

References:^[18]

The differential diagnoses listed here are not exhaustive.

Surgery

• Prior to surgery: sperm cryopreservation
• Radical inguinal orchiectomy

Adjuvant radiotherapy and chemotherapy

• Adjuvant therapy is based on the clinical staging group, histology (seminoma vs. nonseminoma), and the prognosis.

References:^{[9][19][20][21]}

• The overall prognosis of testicular tumors is excellent, with a high cure rate and 5-year survival rates of > 95%.
• Even in advanced, metastatic stages, testicular tumors are often curable.

Testicular tumors, particularly seminomas, are one of the few cancers that can be cured even in very advanced stages with adequate treatment. Patients with nonseminomas have a significantly poorer prognosis but still an excellent overall survival rate!
References:^[22]

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2. Michaelson MD, Oh WK. Epidemiology of and risk factors for testicular germ cell tumors. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/epidemiology-of-and-risk-factors-for-testicular-germ-cell-tumors.Last updated: January 10, 2017. Accessed: March 5, 2017.
3. Berney DM, Looijenga LH, Idrees M, et al. Germ cell neoplasia in situ (GCNIS): evolution of the current nomenclature for testicular pre-invasive germ cell malignancy. Histopathology. 2016; 69 (1): p.7-10. doi: 10.1111/his.12958 . | Open in Read by QxMD
4. Testicular Cancer. https://old.cancer.org/acs/groups/cid/documents/webcontent/003142-pdf.pdf. Updated: February 12, 2016. Accessed: March 5, 2017.
5. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs.
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7. Trabert B, Stang A, Cook MB, Rusner C, McGlynn KA. Impact of classification of mixed germ-cell tumours on incidence trends of non-seminoma. Int J Androl. 2011; 34 (4pt2): p.e274-e277. doi: 10.1111/j.1365-2605.2011.01187.x . | Open in Read by QxMD
8. Cheah CY, Wirth A, Seymour JF. Primary testicular lymphoma. Blood. 2014; 123 (4): p.486-493. doi: 10.1182/blood-2013-10-530659 . | Open in Read by QxMD
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10. Testicular cancer.
11. Hirsch MS. Anatomy and pathology of testicular tumors. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/anatomy-and-pathology-of-testicular-tumors.Last updated: January 9, 2017. Accessed: March 5, 2017.
12. Oosting SF, De haas EC, Links TP, et al. Prevalence of paraneoplastic hyperthyroidism in patients with metastatic non-seminomatous germ-cell tumors. Ann Oncol. 2009; 21 (1): p.104-108. doi: 10.1093/annonc/mdp265 . | Open in Read by QxMD
13. Marth D, Scheidegger J, Studer UE. Ultrasonography of Testicular Tumors. Urol Int. 1990; 45 (4): p.237-240. doi: 10.1159/000281715 . | Open in Read by QxMD
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15. Steele GS, Richie JP, Oh WK, Michaelson MD. Clinical manifestations, diagnosis, and staging of testicular germ cell tumors. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. http://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-staging-of-testicular-germ-cell-tumors?source=search_result&search=Testicular+Cancer&selectedTitle=1~127#H11.Last updated: February 8, 2016. Accessed: February 15, 2017.
16. Testicular Cancer Treatment (PDQ®): Health Professional Version. https://www.cancer.gov/types/testicular/hp/testicular-treatment-pdq#section/all. Updated: January 26, 2017. Accessed: February 15, 2017.
17. Oh WK. Overview of the treatment of testicular germ cell tumors. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/overview-of-the-treatment-of-testicular-germ-cell-tumors.Last updated: January 18, 2017. Accessed: February 15, 2017.
18. Cancer Stat Facts: Testis Cancer. https://seer.cancer.gov/statfacts/html/testis.html. Updated: March 5, 2017. Accessed: March 5, 2017.
19. Goel P, Yadav D, Acharya S, Bagga D, Jain V, Dhua A. Sacrococcygeal teratoma: Clinical characteristics, management, and long-term outcomes in a prospective study from a Tertiary Care Center. Journal of Indian Association of Pediatric Surgeons. 2020; 25 (1): p.15. doi: 10.4103/jiaps.jiaps_219_18 . | Open in Read by QxMD
20. Schmoll HJ. Extragonadal germ cell tumors. Ann Oncol. 2002; 13 (Suppl 4): p.265-272. doi: 10.1093/annonc/mdf669 . | Open in Read by QxMD
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