Testicular cancer

From Wikipedia, the free encyclopedia - View original article

Testicular Cancer
Classification and external resources

7.4 × 5.5-cm seminoma in a radical orchiectomy specimen.
ICD-10C62
ICD-9186.9
OMIM273300
DiseasesDB12966
MedlinePlus001288
eMedicinemed/2250 med/863
MeSHD013736
 
Jump to: navigation, search
Testicular Cancer
Classification and external resources

7.4 × 5.5-cm seminoma in a radical orchiectomy specimen.
ICD-10C62
ICD-9186.9
OMIM273300
DiseasesDB12966
MedlinePlus001288
eMedicinemed/2250 med/863
MeSHD013736

Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system.

In the United States, between 7,500 and 8,000 diagnoses of testicular cancer are made each year.[1][2] In the UK, approximately 2,000 men are diagnosed each year.[3] Over his lifetime, a man's risk of testicular cancer is roughly 1 in 250 (0.4%). It is the most common cancer in males aged 20–39 years, the period of peak incidence, and is rarely seen before the age of 15 years.[4]

Testicular cancer has one of the highest cure rates of all cancers: in excess of 90 percent overall; almost 100 percent if it has not spread (metastasized).[5] Even for the relatively few cases in which malignant cancer has spread widely, modern chemotherapy offers a cure rate of at least 80%.[6]

Not all lumps on the testicles are tumors, and not all tumors are malignant (cancerous). There are many other conditions, such as testicular microlithiasis, epididymal cysts, and appendix testis (hydatid of Morgagni), which may be painful but are non-cancerous.

Contents

Classification

Although testicular cancer can be derived from any cell type found in the testicles, more than 95% of testicular cancers are germ cell tumors. Most of the remaining 5% are sex cord-gonadal stromal tumours derived from Leydig cells or Sertoli cells. Correct diagnosis is necessary to ensure the most effective and appropriate treatment. To some extent, this can be done via blood tests for tumor markers, but definitive diagnosis requires examination of the histology of a specimen by a pathologist.

Most pathologists use the World Health Organization Classification system for testicular tumours:[7][8]

Signs and symptoms

One of the first signs of testicular cancer is often a lump or swelling in the testes. The U.S. Preventive Services Task Force (USPSTF) recommends against routine screening for testicular cancer in asymptomatic adolescent and adults, which means that men should not perform routine testicular self-exams.[9] This practice was encouraged in the past, but current scientific evidence suggests that screening for testicular cancer does not lead to decreased morbidity and mortality.[10] However, the American Cancer Society suggests that some men should examine their testicles monthly, especially if they have a family history of cancer.[11]

Symptoms may also include one or more of the following:

It is not very common for testicular cancer to spread to other organs, apart from the lungs. However, if it has, the following symptoms may be present:

Genetic defects

Most testicular germ cell tumors have too many chromosomes, and most often they are triploid to tetraploid. An isochromosome 12p (the short arm of chromosome 12 on both sides of the same centromere) is present in about 80% of the testicular cancers, and also the other cancers usually have extra material from this chromosome arm through other mechanisms of genomic amplification.[14]

Diagnosis

Micrograph (high magnification) of a seminoma. H&E stain.

The main way testicular cancer is diagnosed is via a lump or mass inside the testis. More generally, if a young adult or adolescent has a single enlarged testicle, which may or may not be painful, this should give doctors reason to suspect testicular cancer.

Other conditions may also have symptoms similar to testicular cancer:

Incorrect or mistaken diagnosis can delay access to appropriate treatment; this is thought to occur in up to 25% of cases[citation needed]

The nature of any palpated lump in the scrotum is often evaluated by scrotal ultrasound, which can determine exact location, size, and some characteristics of the lump, such as cystic vs solid, uniform vs heterogeneous, sharply circumscribed or poorly defined. The extent of the disease is evaluated by CT scans, which are used to locate metastases.

The differential diagnosis of testicular cancer requires examining the histology of tissue obtained from an inguinal orchiectomy - that is, surgical excision of the entire testis along with attached structures (epididymis and spermatic cord). A biopsy should not be performed, as it raises the risk of spreading cancer cells into the scrotum.

Inguinal orchiectomy is the preferred method because it lowers the risk of cancer cells escaping. This is because the lymphatic system of the scrotum, through which white blood cells (and, potentially, cancer cells) flow in and out, links to the lower extremities, while that of the testicle links to the back of the abdominal cavity (the retroperitoneum). A transscrotal biopsy or orchiectomy will potentially leave cancer cells in the scrotum and create two routes for cancer cells to spread, while in an inguinal orchiectomy only the retroperitoneal route exists.

Blood tests are also used to identify and measure tumor markers (usually proteins present in the bloodstream) that are specific to testicular cancer. AFP alpha1 feto protein, Beta-HCG, and LDH are the typical markers used to identify testicular cancer.

A pregnancy test may be used to identify high levels of Beta-HCG, however the first sign of testicular cancer is normally a lump[15].

Staging

After removal, the testicle is fixed with Bouin's solution[16][17] because it better conserves some morphological details such as nuclear conformation. Then the testicular tumor is staged by a pathologist according to the TNM Classification of Malignant Tumors as published in the AJCC Cancer Staging Manual. Testicular cancer is categorized as being in one of three stages (which have subclassifications). The size of the tumor in the testis is irrelevant to staging.[18] In broad terms, testicular cancer is staged as follows:

Further information on the detailed staging system is available on the website of the American Cancer Society.[20]

Treatment

The three basic types of treatment are surgery, radiation therapy, and chemotherapy.[21]

Surgery is performed by urologists; radiation therapy is administered by radiation oncologists; and chemotherapy is the work of medical oncologists. In most patients with testicular cancer, the disease is cured readily with minimal long-term morbidity. While treatment success depends on the stage, the average survival rate after five years is around 95%, and stage 1 cancers cases (if monitored properly) have essentially a 100% survival rate (which is why prompt action, when testicular cancer is a possibility, is extremely important).

Initial treatment (orchiectomy)

The initial treatment for testicular cancer is surgery to remove the affected testicle (orchiectomy). While it may be possible, in some cases, to remove testicular cancer tumors from a testis while leaving the testis functional, this is almost never done, as the affected testicle usually contains pre-cancerous cells spread throughout the entire testicle. Thus removing the tumor alone without additional treatment greatly increases the risk that another cancer will form in that testicle.

Since only one testis is typically required to maintain fertility, hormone production, and other male functions, the afflicted testis is almost always removed completely in a procedure called inguinal orchiectomy. (The testicle is almost never removed through the scrotum; an incision is made beneath the belt line in the inguinal area.) In the UK, the procedure is known as a radical orchidectomy.

Retroperitoneal Lymph Node Dissection (RPLND)

In the case of nonseminomas that appear to be stage I, surgery may be done on the retroperitoneal/Paraaortic lymph nodes (in a separate operation) to accurately determine whether the cancer is in stage I or stage II and to reduce the risk that malignant testicular cancer cells that may have metastasized to lymph nodes in the lower abdomen. This surgery is called retroperitoneal lymph node dissection (RPLND). However, this approach, while standard in many places, especially the United States, is out of favor due to costs and the high level of expertise required to perform successful surgery. The urologist may take extra care in the case of males who have not fathered children, to preserve the nerves involved in ejaculation.

Many patients are instead choosing surveillance, where no further surgery is performed unless tests indicate that the cancer has returned. This approach maintains a high cure rate because of the growing accuracy of surveillance techniques.

Adjuvant treatment

Since testicular cancers can spread, patients are usually offered adjuvant treatment - in the form of chemotherapy or radiotherapy - to kill any cancerous cells that may exist outside of the affected testicle. The type of adjuvant therapy depends largely on the histology of the tumor (i.e. the size and shape of its cells under the microscope) and the stage of progression at the time of surgery (i.e. how far cells has 'escaped' from the testicle, invaded the surrounding tissue, or spread to the rest of the body). If the cancer is not particularly advanced, patients may be offered careful surveillance by periodic CT scans and blood tests, in place of adjuvant treatment.

Before 1970, survival rates from testicular cancer were low. Since the introduction of adjuvant chemotherapy, chiefly platinum-based drugs like cisplatin and carboplatin, the outlook has improved substantially. Although 7000 to 8000 new cases of testicular cancer occur in the United States yearly, only 400 men are expected to die of the disease.

In the UK, a similar trend has emerged: since improvements in treatment, survival rates have risen rapidly to cure rates of over 95%.[22]

Radiation therapy

Radiation may be used to treat stage 2 seminoma cancers, or as adjuvant (preventative) therapy in the case of stage 1 seminomas, to minimize the likelihood that tiny, non-detectable tumors exist and will spread (in the inguinal and para-aortic lymph nodes). Radiation is ineffective against and is therefore never used as a primary therapy for nonseminoma.

Chemotherapy

Non-seminoma

Chemotherapy is the standard treatment for non-seminoma when the cancer has spread to other parts of the body (that is, stage 2B or 3). The standard chemotherapy protocol is three, or sometimes four, rounds of Bleomycin-Etoposide-Cisplatin (BEP). BEP as a first-line treatment was first reported by Professor Michael Peckham in 1983.[23] The landmark trial published in 1987 which established BEP as the optimum treatment was conducted by Dr. Lawrence Einhorn at Indiana University.[24] An alternative, equally effective treatment involves the use of four cycles of Etoposide-Cisplatin (EP).

Lymph node surgery may also be performed after chemotherapy to remove masses left behind (stage 2B or more advanced), particularly in the cases of large nonseminomas.

Seminoma

As an adjuvant treatment, use of chemotherapy as an alternative to radiation therapy in the treatment of seminoma is increasing, because radiation therapy appears to have more significant long-term side effects (for example, internal scarring, increased risks of secondary malignancies, etc.). Two doses, or occasionally a single dose of carboplatin, typically delivered three weeks apart, is proving to be a successful adjuvant treatment, with recurrence rates in the same ranges as those of radiotherapy. The concept of carboplatin as a single-dose therapy was developed by Tim Oliver, Professor of Medical Oncology at Barts and The London School of Medicine and Dentistry.[25] However, very long term data on the efficacy of adjuvant carboplatin in this setting does not exist.

Since seminoma can recur decades after the primary tumor is removed, patients receiving adjuvant chemotherapy should remain vigilant and not assume they are cured 5 years after treatment.

Prognosis

In the New England Journal of Medicine, treatment of testicular cancer has been called one of the success stories of modern medicine, with sustained response to treatment in more than 90% of cases, regardless of stage.[26] Because of advances in chemotherapy, cure rates now approach 85% overall, with better than 95% for localized disease and 80% for metastatic disease—the best response by any solid tumor.[6]

Surveillance

For many patients with stage I cancer, adjuvant (preventative) therapy following surgery may not be appropriate and patients will undergo surveillance instead.[27] The form this surveillance takes, e.g. the type and frequency of investigations and the length time it should continue, will depend on the type of cancer (non-seminoma or seminoma), but the aim is to avoid unnecessary treatments in the many patients who are cured by their surgery, and ensure that any relapses with metastases (secondary cancers) are detected early and cured. This approach ensures that chemotherapy and or radiotherapy is only given to the patients that need it. The number of patients ultimately cured is the same using surveillance as post-operative “adjuvant” treatments, but the patients have to be prepared to follow a prolonged series of visits and tests.

For both non-seminomas and seminomas, surveillance tests generally include physical examination, blood tests for tumour markers, chest x-rays and CT scanning. However, the requirements of a surveillance programme differ according to the type of disease since, for seminoma patients, relapses can occur later and blood tests are not as good at indicating relapse.

CT scans are performed on the abdomen (and sometimes the pelvis) and also the chest in some hospitals. Chest x-rays are increasingly preferred for the lungs as they give sufficient detail combined with a lower false-positive rate and significantly smaller radiation dose than CT.

The frequency of CT scans during surveillance should ensure that relapses are detected at an early stage while minimising the radiation exposure.

For patients treated for stage I non-seminoma, a randomised trial (Medical Research Council TE08[28]) showed that, when combined with the standard surveillance tests described above, 2 CT scans at 3 and 12 months were as good as 5 over 2 years in detecting relapse at an early stage.

For patients treated for stage I seminoma who choose surveillance rather than undergoing adjuvant therapy, there have been no randomised trials to determine the optimum frequency of scans and visits, and the schedules vary very widely across the world, and within individual countries. In the UK there is an ongoing clinical trial called TRISST.[29][30] This is assessing how often scans should take place and whether magnetic resonance imaging (MRI) can be used instead of CT scans. MRI is being investigated because it does not expose the patient to radiation and so, if it is shown to be as good at detecting relapses, it may be preferable to CT. It is possible that one or more centres in Canada may join the trial in the next year or so.

For more advanced stages of testicular cancer, and for those cases in which radiation therapy or chemotherapy was administered, the extent of monitoring (tests) after treatment will vary on the basis of the circumstances, but normally should be done for five years in uncomplicated cases and for longer in those with higher risks of relapse.

Fertility

A man with one remaining testis can lead a normal life, because the remaining testis takes up the burden of testosterone production and will generally have adequate fertility.[31] However, it is worth the (minor) expense of measuring hormone levels before removal of a testicle, and sperm banking may be appropriate for younger men who still plan to have children, since fertility may be lessened by removal of one testicle[citation needed], and can be severely affected if extensive chemotherapy and/or radiotherapy is done.

Less than five percent of those who have testicular cancer will have it again in the remaining testis. A man who loses both testicles will normally have to take hormone supplements (in particular, testosterone, which is created in the testicles), and will be infertile, but can lead an otherwise normal life.

Epidemiology

Testicular cancer is most common among Caucasian men and rare among men of African descent.[32] Testicular cancer is uncommon in Asia and Africa. Worldwide incidence has doubled since the 1960s, with the highest rates of prevalence in Scandinavia, Germany, and New Zealand.

Incidence among African Americans doubled from 1988 to 2001 with a bias towards seminoma. The lack of significant increase in the incidence of early-stage testicular cancer during this timeframe suggests that the overall increase was not due to heightened awareness of the disease.

Although testicular cancer is most common among men aged 15–40 years, it has three peaks: infancy through the age of four as teratomas and yolk sac tumors, ages 25–40 years as post-pubertal seminomas and nonseminomas, and from age 60 as spermatocytic seminomas.[33]

Germ cell tumors of the testis are the most common cancer in young men between the ages of 15 and 35 years.[34]

A major risk factor for the development of testis cancer is cryptorchidism (undescended testicles). It is generally believed that the presence of a tumor contributes to cryptorchidism; when cryptorchidism occurs in conjunction with a tumor then the tumor tends to be large. Other risk factors include inguinal hernias, Klinefelter syndrome, and [35] mumps orchitis. [36] Physical activity is associated with decreased risk and sedentary lifestyle is associated with increased risk. Early onset of male characteristics is associated with increased risk. These may reflect endogenous or environmental hormones.

In other animals

Testicular tumors occur also in animals. In horses, these include interstitial cell tumors and teratomas. Typically, the former are found in older stallions (affected stallions may become extremely vicious, suggesting excessive production of androgen), and the latter are found in young horses and are large.[37]

References

  1. ^ Cancer Facts and Figures 2003. Atlanta, GA: American Cancer Society. 2003. http://www.cancer.org/downloads/STT/CAFF2003PWSecured.pdf. Retrieved 2008-04-24.
  2. ^ Cancer Facts and Figures 2007. Atlanta, GA: American Cancer Society. 2007. http://www.cancer.org/downloads/STT/CAFF2007PWSecured.pdf. Retrieved 2008-04-24.
  3. ^ CancerStats, 2007 UK incidence data, Cancer Research UK.
  4. ^ Hayes-Lattin, Brandon; Nichols, Craig R. (October 2009). "Testicular Cancer: A Prototypic Tumor of Young Adults". Seminars in oncology 36 (5): 432–438. doi:10.1053/j.seminoncol.2009.07.006. PMC 2796329. PMID 19835738. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2796329/.
  5. ^ "Testicular Cancer Overview". American Cancer Society. http://www.cancer.org/cancer/testicularcancer/overviewguide/testicular-cancer-overview-survival-rates. Retrieved 2012-11-10.
  6. ^ a b Feldman DR; Bosl GJ, Sheinfeld J, Motzer RJ (February 13, 2008). "Medical treatment of advanced testicular cancer". JAMA 299 (6): 672–684. doi:10.1001/jama.299.6.672. PMID 18270356. http://jama.ama-assn.org/cgi/content/full/299/6/672. Retrieved June 24, 2011.
  7. ^ Eble J.N., Sauter G., Epstein J.I., Sesterhenn I.A. (Eds.): World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARC Press: Lyon 2004. ISBN 92-832-2412-4
  8. ^ Mills, S (ed.) 2009.Sternberg's Diagnostic Pathology. 5th Edition. ISBN 978-0-7817-7942-5
  9. ^ "Screening for Testicular Cancer". uspreventiveservicestaskforce.org. U.S. Preventive Services Task Force. April 2011. http://www.uspreventiveservicestaskforce.org/uspstf/uspstest.htm. Retrieved 4 December 2011.
  10. ^ Screening for testicular cancer: a brief evidence update for the U.S. Preventive Services Task Force. Rockville, MD: Agency for Healthcare Research and Quality; February 2004. http://www.ahrq.gov/clinic/3rduspstf/testicular/testiculup.htm
  11. ^ "Can testicular cancer be found early?". Testicular Cancer: Early Detection, Diagnosis, and Staging. American Cancer Society. 19 January 2011. http://www.cancer.org/Cancer/TesticularCancer/DetailedGuide/testicular-cancer-detection. Retrieved 4 December 2011.
  12. ^ a b c d e Motzer, Robert J.; Bosl, George J. (2005). "82. Testicular Cancer". In Kasper, Dennis L.; Jameson, J. Larry. Harrison's Principles of Internal Medicine (16th ed.). McGraw-Hill. pp. 550–553. ISBN 0-07-139140-1.
  13. ^ a b c d e f g Shaw, Joel (February 15, 2008). "Diagnosis and Treatment of Testicular Cancer". American Family Physician (American Academy of Family Physicians) 77 (4): 469–474. ISSN 1532-0650. PMID 18326165. http://www.aafp.org/afp/2008/0215/p469.html. Retrieved August 5, 2010.
  14. ^ Atkin NB, Baker MC (December 1982). "Specific chromosome change, i(12p), in testicular tumours?". Lancet 2 (8311): 1349. PMID 6128640.
  15. ^ http://abcnews.go.com/Health/CancerPreventionAndTreatment/pregnancy-test-man-joke-reveals-testicular-cancer/story?id=17653036#.UJqDuG80UR8
  16. ^ Bonin, S; Petrera, F; Rosai, J; Stanta, G (2011-09-29). "DNA and RNA obtained from Bouin's fixed tissues". cancer.org (Journal of Clinical Pathology) 58 (3): 313–6. doi:10.1136/jcp.2004.016477. PMC 1770606. PMID 15735167. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1770606/.
  17. ^ "Lectin-binding sites in normal human testis?". cancer.org. Journal of Clinical Pathology. 2011-09-29. http://www.ncbi.nlm.nih.gov/pubmed/2469362/. Retrieved 29 September 2011.
  18. ^ http://www.cancerstaging.org/cstage/CSPart1Manual.pdf
  19. ^ "Testicular Cancer Resource Center's Staging Page". http://tcrc.acor.org/staging.html. Retrieved 2007-12-13.
  20. ^ "How is testicular cancer staged?". cancer.org. American Cancer Society. 2011-01-19. http://www.cancer.org/Cancer/TesticularCancer/DetailedGuide/testicular-cancer-staging. Retrieved 12 July 2011.
  21. ^ "Testicular Cancer Treatment (PDQ)". National Cancer Institute. 2009-01-15. http://www.cancer.gov/cancertopics/pdq/treatment/testicular/HealthProfessional/page8. Retrieved 2009-02-13.
  22. ^ "Testicular Cancer survival statistics". cancerresearchuk.org. Cancer Research UK. 9 October 2009. http://info.cancerresearchuk.org/cancerstats/types/testis/survival/. Retrieved 4 December 2011.
  23. ^ Peckham, MJ; Barrett, A; Liew, KH; Horwich, A; Robinson, B; Dobbs, HJ; McElwain, TJ; Hendry, WF (1983). "The treatment of metastatic germ-cell testicular tumours with bleomycin, etoposide and cisplatin (BEP).". British Journal of Cancer 47 (5): 613–619. doi:10.1038/bjc.1983.99. PMC 2011384. PMID 6189504. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2011384/.
  24. ^ "Chemotherapy - BEP and EP". http://www.tc-library.com/chemotherapy-bep-and-ep/. Retrieved 2009-02-16.
  25. ^ "MRC trial shows single dose of drug is as effective as two weeks' radiotherapy for testicular cancer". News and Publications. Medical Research Council. 22 July 2005. http://www.mrc.ac.uk/Newspublications/News/MRC001863. Retrieved 4 December 2011.
  26. ^ Huang, William C. (June 5, 2008). "Book Review: Urological Oncology". The New England Journal of Medicine (Massachusetts Medical Society) 358 (23): 2527. doi:10.1056/NEJMbkrev59744. ISSN 1533-4406. http://www.nejm.org/doi/full/10.1056/NEJMbkrev59744. Retrieved August 9, 2010.
  27. ^ Krege, S.; Beyer, J.; Souchon, R.; Albers, P.; Albrecht, W.; Algaba, F.; et al., Michael; Bodrogi, István et al. (2008). "European consensus conference on diagnosis and treatment of germ cell cancer: a report of the second meeting of the European Germ Cell Cancer Consensus group (EGCCCG): part I". European Urology 53 (3): 478–496. doi:10.1016/j.eururo.2007.12.024. PMID 18191324.
  28. ^ Rustin, G. J.; Mead, G. M.; Stenning, S. P.; Vasey, P. A.; Aass, N.; Huddart, R. A.; et al., M. P.; Joffe, J. K. et al. (2007). "Randomized trial of two or five computed tomography scans in the surveillance of patients with stage I nonseminomatous germ cell tumors of the testis: Medical Research Council Trial TE08; ISRCTN56475197—the National Cancer Research Institute Testis Cancer Clinical Studies Group". JCO 25 (11): 1310–1315. doi:10.1200/JCO.2006.08.4889.
  29. ^ "A trial to find the best way of using scans to monitor men after treatment for seminoma testicular cancer (TRISST MRC TE24)". CancerHelp UK. Cancer Research UK. http://www.cancerhelp.org.uk/trials/a-trial-to-find-the-best-way-of-using-scans-to-monitor-men-after-treatment-for-seminoma-testicular-cancer. Retrieved 4 December 2011.
  30. ^ "Would it be better to use MRI scans instead of CT scans to monitor men with early stage testicular cancer? And is it safe to use less CT scans than we do now?". Medical Research Council. http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=40. Retrieved 4 December 2011.
  31. ^ http://www.fda.gov/fdac/features/196_test.html[dead link]
  32. ^ "Cancer of the testicle Causes - Health encyclopaedia - NHS Direct". Archived from the original on 2007-12-10. http://web.archive.org/web/20071210081436/http://www.nhsdirect.nhs.uk/articles/article.aspx?articleId=85&sectionId=5. Retrieved 2007-12-13.
  33. ^ Leendert H. J. Looijenga; J. Wolter Oosterhuis (May 1999). "Pathogenesis of testicular germ cell tumours" (PDF). Rev. Reprod. 4 (2): 90–100. doi:10.1530/ror.0.0040090. ISSN 1359-6004. PMID 10357096. http://ror.reproduction-online.org/cgi/reprint/4/2/90.
  34. ^ Holmes L; Escalante C, Garrison O, Foldi BX, Ogungbade GO, Essien EJ, Ward D (September 2008). "Testicular cancer incidence trends in the United States (1975−2004): Plateau or shifting racial paradigm?". Public Health 122 (9): 862–872. doi:10.1016/j.puhe.2007.10.010. PMC 2551560. PMID 18555499. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2551560/.
  35. ^ Forman, D; M C Pike, G Davey, S Dawson, K Baker, C E D Chilvers, R T D Oliver, C A C Coupland (28 May 1994). "Aetiology of testicular cancer: association with congenital abnormalities, age at puberty, infertility, and exercise. United Kingdom Testicular Cancer Study Group". BMJ 308 (6941): 1393–9. PMC 2540340. PMID 7912596. http://www.bmj.com/cgi/content/full/308/6941/1393.
  36. ^ Swerdlow, AJ; Huttly SR, Smith PG. (January 1987). "Testicular cancer and antecedent diseases". Br. J. Cancer 55 (1): 97–103. doi:10.1038/bjc.1987.20. PMC 2001571. PMID 2880604. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2001571/.
  37. ^ Jones, T. C., R. D. Hunt, and N. W. King (1997). Veterinary pathology (6th ed.). Wiley-Blackwell. p. 1210. ISBN 0-683-04481-8, 9780683044812. http://books.google.com/?id=8fXzJrDfFgUC.

External links