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Testicular Neoplasm

Testicular Cancer

Testicular tumors comprise around 1% of all male tumors, but it is the most common malignancy encountered in men between 15-35 years. The cause remains unknown, but cryptorchidism and gonadal dysgenesis are shown to be significant risk factors. Males present with a painless scrotal mass and the diagnosis can be made by ultrasound and laboratory studies. Treatment depends on staging and includes surgery, chemotherapy, and radiation.


Presentation

The hallmark of testicular neoplasia is the appearance of a painless mass in the testicle that can be palpated during a physical examination, but patients often notice themselves and recognize the presence of a mass. In rare cases, pain and tenderness may be observed. Constitutional and other symptoms are very rare, as very few patients reach advanced metastatic disease.

Abdominal Obesity
  • The metabolic syndrome, a constellation of 3 or more characteristics (abdominal obesity, hypertriglyceridemia, low high-density lipoprotein, hypertension, or insulin resistance) has recently received attention as a risk factor for cardiovascular morbidity[doi.org]
Cyanosis
  • Raynaud phenomenon is characterized by transient vasoconstriction of the digital arteries causing pallor or cyanosis from ischemia followed by redness and pain upon reperfusion (hyperemia).[doi.org]
Meningism
  • […] of testicular cancer was found to be raised for men with a history of cryptorchidism (RR based on comparison with all controls 6.3; P less than 0.001), inguinal hernia (RR 1.6; P 0.14), mumps orchitis (RR 12.7; P 0.006), atopy (RR 1.8; P 0.03), and meningitis[ncbi.nlm.nih.gov]
Painless Testicular Mass
  • Patients presenting with a painless testicular mass, scrotal heaviness, a dull ache, or acute pain should receive a thorough examination. Testicular masses should be examined with scrotal ultrasonography.[ncbi.nlm.nih.gov]
  • Dr Ahluwalia says that testicular cancer may develop painless testicular mass. Acute pain is less common or is either the result of bleeding within the tumour or due to rapid tumour growth.[timesofindia.indiatimes.com]
  • At a Glance When a patient discovers a usually painless testicular mass, either unintentionally or by self-examination, or when a testicular mass is discovered by routine physical examination, testicular cancer should be suspected.[cancertherapyadvisor.com]
  • A painless testicular mass is the classic presentation for testicular cancer, although a number of patients present with diffuse pain or swelling. Ultrasonography may be helpful in confirming the presence of a scrotal mass within the testicle.[aafp.org]
Swelling of the Scrotum
  • Consult a doctor if you have any of these symptoms: Swelling in the scrotum A lump or swelling in either testicle Build-up of fluid on the scrotum Dull ache in the groin or lower abdomen Pain or discomfort in the scrotum or a testicle Cleveland Clinic[my.clevelandclinic.org]
  • Look for swelling in the scrotum or any changes in appearance. Gently feel the scrotal sac to find a testicle. Examine the testicles one at a time.[urologyhealth.org]
  • Patients presenting with a swelling in the scrotum should be examined carefully and an attempt made to distinguish between lumps arising from the testis and other intrascrotal swellings.[patient.info]
  • Check for any swelling on the scrotum skin. Examine each testicle with both hands. Place the index and middle fingers under the testicle with the thumbs placed on top. Roll the testicle gently between the thumbs and fingers.[washington.edu]
Testicular Swelling
  • A 19 year old man presented with unilateral testicular swelling and pain. An initial diagnosis of epididymo-orchitis was modified to a presumed testicular neoplasm following ultrasonography.[ncbi.nlm.nih.gov]
  • When symptoms do appear, they can include: testicular pain or discomfort testicular swelling lower abdominal or back pain enlargement of breast tissue Make an appointment with your doctor if you have any of these symptoms.[healthline.com]
  • Patients present with unilateral testicular swelling or recurrent hydrocele. Only rarely is the presentation incidental in a hernia sac or is there a palpable mass clinically suggestive of a neoplasm.[nature.com]
Epididymal Mass
  • In addition to testicular cancer, potential causes of a scrotal mass include epididymal mass, epididymitis, hydrocele, swelling of the testicular appendix, and varicocele. Abnormal testicular findings include a firm, hard, or fixed mass.[aafp.org]
  • Adenocarcinoma of the pancreas presenting as an epididymal mass. A case report and literature review. J Urol Pathol 1997; 6 :159–170. 43 Ordonez NG.[nature.com]
Delayed Menarche
  • menarche and induce amenorrhoea. 59 There is also evidence that circulating concentrations of one specific gonadotrophin, follicle stimulating hormone, are higher in men with stage I testicular cancer, 42 especially in those who later develop second[doi.org]

Workup

The initial diagnosis can be made upon palpation of a painless mass, but to support this finding, both laboratory and imaging studies need to be conducted. Serum levels of β-hCG are elevated in 100% of patients with choriocarcinoma, while 90% mixed tumors have both β-hCG and AFP elevations [2]. On the other hand, embryonal carcinomas never give increased values of these markers, which may further help in making the diagnosis prior to microscopic confirmation [2]. Although nonspecific, lactate dehydrogenase (LDH) is also a valuable parameter, as it is often elevated in the presence of virtually all forms of testicular neoplasia. In terms of imaging studies, testicular ultrasonography may be performed to differentiate between testicular and benign testicular masses, as the latter may not require immediate intervention [4]. If a suspicion of metastatic disease is made, X-ray or computed tomography (CT) may be performed. Because biopsy may cause tumor dissemination, a radical orchiectomy is indicated for all patient in whom a painless mass is observed [10]. Once orchiectomy is performed, the mass is sampled for histopathological analysis and confirms the tumor subtype depending on morphological characteristics.

Hypertriglyceridemia
  • The metabolic syndrome, a constellation of 3 or more characteristics (abdominal obesity, hypertriglyceridemia, low high-density lipoprotein, hypertension, or insulin resistance) has recently received attention as a risk factor for cardiovascular morbidity[doi.org]

Treatment

Treatment encompasses surgery, radiation, and chemotherapy, as well as surveillance and long-term follow-up [11]. Radical orchiectomy, with or without retroperitoneal lymph node dissection, is indicated in early clinical stages, while adjunctive therapy is recommended in patients with evidence of advanced and metastatic disease [4]. Cisplatin, etoposide, and bleomycin are chemotherapeutic agents that are used in stages II, III, and IV and show very high rates of success [5]. Regardless of the subtype, a combination of surgery and adjuvant therapy provides very high success rates, especially in early stages of the disease.

Prognosis

The overall prognosis of testicular tumors is very good, as they are quite sensitive to current therapeutic principles. According to TNM classification, tumors are divided into four stages [4]:

  • Stage I - The tumor is confined to the testis and epididymis without dissemination through vascular and lymphatic pathways, as well as a possible invasion into the tunica albuginea.
  • Stage II - Vascular or lymphatic dissemination of the tumor, although still confined to the testis, with the invasion of both tunica albuginea and tunica vaginalis.
  • Stage III - Invasion of the spermatic cord is observed that may or may not be accompanied by either lymphatic or vascular dissemination.
  • Stage IV - The tumor invades the scrotum, while distant metastases are not necessary.

For nonseminomas, cure rates for stages I and II extend over 95%, while 80-85% of patients with the advanced metastatic disease are effectively treated, implying that therapy is quite successful against this type of tumor. Similar cure rates have been observed in seminomas and fortunately, the majority of patients are diagnosed in the initial stages of the disease (stage I), which significantly improves chances of complete cure [5]. Relapses may occur but are adequately managed with chemotherapy [4].

Etiology

The cause of testicular neoplasia remains unknown, although several findings regarding its etiology have been established. In almost all germ cell tumors, an isochromosome of the short arm of chromosome 12 is found, while alterations in chromosomes 7 and 8 have also been identified in numerous cases [6]. The role of genetic factors further includes a much frequent appearance of testicular tumors in individuals with a positive family history, indicating that some inherited defects may play a role as well [2]. However, exact mutations and gene alterations are yet to be determined. 95% of testicular tumors arise from germ cells and are divided into two main categories: seminoma and nonseminoma, with approximately equal distributions. Nonseminomas are further classified into embryonal carcinomas, choriocarcinomas, and teratomas, while yolk sac and mixed tumors are also mentioned in literature [2].

Epidemiology

Testicular neoplasia comprises only 1% of all tumors in males, but it is the most common tumor between 15-35 years of age in men, with marked increases in its appearance over the last 40 years [3]. In the United States, the incidence rates have risen between 40-60% [7], depending on the subtype of tumor, and today, approximately 8000 males are diagnosed every year [2]. Incidence rates significantly vary depending on the geographical region, with lowest rates seen in Africa, Asia and South America (0.5 cases per 100 000 males in Egypt and 1.6 per 100 000 in China, Hong Kong) compared to Europe (5.3 cases per 100 000 in Sweden, 7.6 per 100 000 in the United Kingdom, 9.2 cases per 100 000 in Denmark and 9.6 per 100 000 in Norway) [3] [8]. Additionally, a significant predilection toward Caucasians compared to African Americans and Asians has been observed, with potential reasons being hormonal variations, mainly in testosterone and other androgens [3]. In terms of risk factors, cryptorchidism is shown to substantially increase the risk of testicular neoplasia. It is seen in approximately 10% of patients and causes a two-fold to even five-fold increased risk for testicular neoplasia according to various studies [1]. Other risk factors include both personal and family history of a previous testicular tumor and male infertility, while numerous other environmental, genetic and hormonal factors have been mentioned sporadically as potential contributors [3] [9].

Sex distribution
Age distribution

Pathophysiology

The pathogenesis model of testicular neoplasia is currently not known and only limited information exist regarding its development. Aside from documented alterations in short arm of chromosome 12, evidence that cryptorchidism open link and previous testicular neoplasia substantially increase the risk for this tumor, little is known in this field. In situ carcinomas (or intratubular germ cell neoplasia) are considered to be prerequisite lesions for this tumor and are thought to occur as a result of varying levels of testicular dysgenesis [2] [3]. Moreover, it is thought that virtually all patients who develop this lesion will eventually result in testicular neoplasia, especially during the younger age.

Prevention

In terms of preventing the development of this tumor, little can be done having in mind the fact that the cause remains to be discovered. However, studies have established a significantly reduced risk of testicular neoplasia if prior management of cryptorchidism and undescended testes was performed [12]. Additionally, self-examination may be a helpful preventive measure, particularly during the adolescent period when these tumors most commonly appear.

Summary

Testicular neoplasm comprises only 1-2% of all tumors seen in men, but it is the most common malignancy seen in males between 15-35 years of age. Almost 95% of tumors arise from germ cells, but a very small proportion of tumors arise from either Leydig or Sertoli cells and are usually benign in nature [1]. Based on histological differentiation, testicular neoplasms derived from germ cells are divided into seminomas and nonseminomas, but there are four malignant subtypes: seminomas, choriocarcinomas, embryonic cell carcinomas and teratomas [2]. The pathogenesis of testicular tumors remain unknown, but various risk factors have been identified. Cryptorchidism is shown to increase the risk by several-fold and is present in around 10% of all patients, while gonadal dysgenesis and hormonal factors are also considered to be associated factors [2]. Current data show that the incidence ranges from 1-9 per 100,000 males, depending on the geographical region [1], but more importantly, rates of this tumor have doubled in the past few decades [3]. In the United States, approximately 8000 new cases occur every year [2]. The main clinical presentation is the appearance of a painless mass in the scrotum, while pain and tenderness in the testes are rarely seen. Findings during the physical examination may be sufficient to make a presumptive diagnosis, but both laboratory and imaging studies may be used to support these findings. β-Human chorionic gonadotropin (β-hCG), α-fetoprotein (AFP) and lactate dehydrogenase (LDH) are serum markers that are often elevated in testicular neoplasms, while ultrasonography of the palpated mass, as well as plain chest radiography may be useful. A biopsy is rarely indicated for this type of cancer, as it may cause dissemination of the tumor, which is why radical inguinal orchiectomy is performed with subsequent histopathological analysis. Testicular cancers respond very well to all forms of therapy and strategies somewhat vary depending on tumor staging. According to the tumor, node, metastasis, or TNM classification, tumors are stages from 1 to 4, 1 being testicular involvement only and 4 invasions of the scrotum with or without distant metastases [4]. Surgery, chemotherapy, radiation therapy and close monitoring are modalities used in managing testicular cancer. Cure rates are very high, exceeding 95% for almost all types of cancers in milder stages, whereas 75-80% of patients with evidence of disseminated disease are effectively treated [5].

Patient Information

Testicular neoplasia is not commonly encountered, as it comprises of about 1% of all tumors seen in males, but it is established to be the most common tumor in males between 15-35 years of age. There are various subtypes, and more than 95% of tumors are malignant in nature. The cause remains unknown, but several risk factors have been established. Undescended testicles (cryptorchidism), male infertility and family history of testicular cancer are all shown to be important risks. Additionally, an ethnic predilection toward Caucasians has been observed throughout various studies. This tumor appears in approximately 8000 males every year in the United States, whereas epidemiological data from Europe suggest that the number of new cases ranges from about 3-9 per 100,000 males. The main symptoms of testicular neoplasia are the appearance of a painless mass in the testicle that is either palpated by the patient himself or during the physical examination. In rare cases, the mass may be tender and painful, while other symptoms are very rare. To confirm the diagnosis of a testicular neoplasia, laboratory studies that evaluate levels of β-Human chorionic gonadotropin (β-hCG), α-fetoprotein (AFP) and lactate dehydrogenase (LDH) may be of significant value, as these parameters are almost always elevated in these patients. Because biopsy is contraindicated due to the risk of disseminating the tumor, an ultrasound of the mass may be performed to potentially differentiate between a testicular and extratesticular mass, that is most often benign. If a testicular mass is confirmed, radical testicular removal is indicated and the mass is further analyzed to confirm the subtype of the tumor. Fortunately, the vast majority of patients present in early stages of the tumor and current treatment modalities result in almost 100% cure for some subtypes of testicular neoplasia. In patients with advanced disease, such as the presence of metastases, cure rates are between 80-85%, but the overall prognosis is very good. In addition to surgical treatment, chemotherapy and radiation are often used, especially in advanced stages of the disease and show a marked success. Relapses may occur, but the little risk exists with the proper use of chemotherapy.

References

Article

  1. Manecksha RP, Fitzpatrick JM. Epidemiology of testicular cancer. BJU Int. 2009;104(9 Pt B):1329-1333
  2. Aster, JC, Abbas, AK, Robbins, SL, Kumar, V. Robbins basic pathology. Ninth edition. Philadelphia, PA: Elsevier Saunders; 2013.
  3. Garner MJ, Turner MC, Ghadirian P, Krewski D. Epidemiology of testicular cancer: an overview. Int J Cancer. 2005;116(3):331-339.
  4. Porter RS, Kaplan JL. Merck Manual of Diagnosis and Therapy. 19th Edition. Merck Sharp & Dohme Corp. Whitehouse Station, N.J; 2011.
  5. Kollmannsberger C, Tyldesley S, Moore C, et al. Evolution in management of testicular seminoma: population-based outcomes with selective utilization of active therapies. Ann Oncol. 2011;22(4):808-814.
  6. Summersgill B, Goker H, Weber-Hall S, Huddart R, Horwich A, Shipley J. Molecular cytogenetic analysis of adult testicular germ cell tumours and identification of regions of consensus copy number change. Br J Cancer. 1998;77(2):305-313.
  7. McGlynn KA, Devesa SS, Sigurdson AJ, Brown LM, Tsao L, Tarone RE. Trends in the incidence of testicular germ cell tumors in the United States. Cancer. 2003;97(1):63-70.
  8. Huyghe E, Matsuda T, Thonneau P. Increasing incidence of testicular cancer worldwide: a review. J Urol. 2003;170:5–11.
  9. Walsh TJ, Croughan MS, Schembri M, Chan JM, Turek PJ. Increased risk of testicular germ cell cancer among infertile men. Arch Intern Med. 2009;169(4):351-356.
  10. Hayes-Lattin B, Nichols CR. Testicular Cancer: A Prototypic Tumor of Young Adults. Semin Oncol. 2009;36(5):432-438.
  11. Motzer RJ, Agarwal N, Beard C, Bolger GB, Boston B, Carducci MA, et al. NCCN clinical practice guidelines in oncology: testicular cancer. J Natl Compr Canc Netw. 2009;7(6):672-693.
  12. Pettersson A, Richiardi L, Nordenskjold A, Kaijser M, Akre O. Age at surgery for undescended testis and risk of testicular cancer. N Engl J Med. 2007;356(18):1835-1841.

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Last updated: 2019-07-11 21:16