Testicular tumors: Pathology review

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Testicular tumors: Pathology review

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A 68-year-old man comes to his primary care provider for evaluation of “fullness in the groin,” which started 3 weeks ago. The discomfort is present in both testicles and has not improved with over-the-counter ibuprofen. On review of systems, the patient endorses a decreased appetite, 7-kg (15-lb) weight loss over the past 2 months, and occasionally wakes up at night drenched in sweat. Past medical history is notable for hypertension, peripheral vascular disease, and chronic venous insufficiency. Temperature is 37.2°C (99.0°F), pulse is 71/min and blood pressure is 147/82 mmHg. Physical examination reveals a thin man with diffuse muscle wasting. Bilateral testicular enlargement is present. The masses do not decrease in size when the patient lies flat. The testes are nontender to palpation. No erythema or rashes are noted over the scrotum. Which of the following best describes the pathophysiology of this patient’s testicular findings?

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25-year-old Kyle comes to the office after palpating a lump on his left testicle while showering this morning. On physical examination, there is a nontender, round, firm, rubbery mass in the left testicle that does not transilluminate with light. Scrotal ultrasound shows a 1.4-cm solid mass with no cystic components. Laboratory tests reveal normal serum human chorionic gonadotropin or hCG level, and normal α-fetoprotein or AFP level. Later that day, 32-year-old William comes to the physician's office complaining of heat intolerance, excessive sweating, palpitations, frequent bowel movements and recent weight loss despite increased appetite. His past medical history is insignificant. On examination, the thyroid gland is normal with no signs of goiter or nodules. However, a hard nodule is palpated in the right testicle which does not transilluminate with light and appears solid on scrotal ultrasound. Laboratory studies show increased serum T4 and T3 levels as well as extremely elevated hCG levels.

Based on the initial presentation, Kyle and William both have some form of testicular mass. In fact, testicular tumors are the most common solid malignancy in males between 20 and 35 years old.

Okay, now, for your exams, it’s important to know that the main risk factors for developing testicular cancer, especially the germ cell variety, include cryptorchidism, which is when the testicles fail to descend to the scrotum or get stuck in the inguinal canal, as well as Klinefelter syndrome, where biological male individuals inherit more than one X chromosome leading to small, undeveloped testicles.

For symptoms, a testicular tumor most often comes up as a small, firm lump that is typically painless, but can sometimes cause a sharp or dull pain in the testicles and lower abdomen. In more severe cases, symptoms may arise from a malignant tumor metastasizing to other organs. This is most commonly hematogenous to the lungs, leading to dyspnea or hemoptysis, which is the coughing of blood, or to the brain, leading to headache, nausea, vomiting or seizures. Another way for the cancer cells to metastasize is by the testicular lymphatic system that drains into retroperitoneal lymph nodes. Metastasis to these lymph nodes leads to symptoms like lower back pain.

Now, once a lump has been palpated in the testis, diagnosis can be confirmed with an ultrasound. Also remember that in a transillumination test solid tumors do not transilluminate with light, while hydrocele and cysts do. Imaging with CT or MRI scan can then be done to look for evidence of metastasis if carcinoma is suspected. Next, lab tests are used to measure levels of tumor markers like PLAP hCG, and AFP. LDH could also be measured, but it’s not very specific. Based on the type of testicular tumor, these markers rise in a different pattern. And that’s a popular way for examiners to clue you in a particular type of tumor. Another very high-yield fact that you should absolutely remember is that testicular tumors should not be biopsied. That’s because the lymph from the scrotum is drained by the superficial inguinal lymph nodes and not the retroperitoneal ones. So cutting into the scrotum would open an additional route for the cancer cells to escape and metastasize.

Treatment involves surgical removal of the whole testicle called radical orchiectomy, followed by chemotherapy and radiotherapy if the tumor has spread. After the removal a histopathological work up can be done, involving gross and microscopic examination, to determine the type of the tumor.

Alright, now, there are two types of testicular tumors: germ cell tumors, which derive from primordial germ cells which are the cells that can give rise to all other tissues and organs, and non-germ cell tumors or sex cord-stromal tumors which arise from Sertoli cells, which are supportive cells inside the seminiferous tubules, or Leydig cells which lie outside the tubules and secrete sex hormones.

Starting with germ cell tumors, a high-yield fact is that they comprise almost 95% of all testicular tumors. They can be classified into seminoma tumors, and non-seminoma tumors, which include yolk sac tumors, choriocarcinomas, teratomas and embryonal carcinomas. The reason behind this classification is that a seminoma, in general, has a slow growth, metastasizes late, responds very well to radiotherapy and has an excellent prognosis. In contrast, non-seminoma tumors are overall more aggressive, metastasize early, have a variable response to treatment and a variable prognosis. However, it’s important to know that the majority of germ cells tumors are mixed and the prognosis is based on the worst component.

Okay, so seminoma is the most common type of germ cell tumor. For your exams, remember that gross examination of this tumor typically shows a homogenous mass with no hemorrhage or necrosis. On microscopic examination, tumor cells are large with central nuclei surrounded by clear cytoplasm. A key word for that is a “fried-egg appearance”. Another high-yield thing to know is that this is the testicular analogue of ovarian dysgerminoma. Now, lab tests may show increased PLAP levels, however, remember that AFP levels are always normal. hCG is usually also normal, but in rare cases, it might be increased.

Summary

Testicular tumors are abnormal growths that can develop in one or both testicles. Most testicular tumors are germ cell tumors and can be classified into seminomas, which are the common ones and have a better prognosis; and non-seminomas, which have a worse prognosis.

Non-seminomas include yolk sac tumors, which are the most common type in children; choriocarcinomas, which are associated with hyperthyroidism and gynecomastia; teratomas, which are usually benign in children and malignant in adults; and embryonal carcinomas, which are rare as pure carcinomas but a common element of mixed germ cell tumors. Non-germ cell testicular tumors come from the Sertoli cells, which don't produce hormones, or the Leydig cells which can secrete excess male and female sex hormones. Diagnosis is made primarily with physical examination, ultrasound findings, and determination of serologic tumor markers, including PLAP, AFP, hCG, and LDH. Treatment is radical orchiectomy, chemotherapy, or radiotherapy.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Sternberg's Diagnostic Surgical Pathology" LWW (2009)
  4. "Medical Treatment of Advanced Testicular Cancer" JAMA (2008)
  5. "Testicular Cancer: A Prototypic Tumor of Young Adults" Seminars in Oncology (2009)
  6. "Testicular Choriocarcinoma Presenting as Hyperthyroidism" The American Journal of Medicine (2013)