Seminoma overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2] Alberto Castro Molina, M.D.
Overview
Seminoma is the most common testicular tumor and accounts for approximately 45% of all primary testicular tumors. However, seminoma can arise outside of the testicle, most often within the anterior mediastinum, e.g. anterior mediastinal germ cell tumor.[1] Seminoma is the most common germ cell tumor of the testis. It is the male counterpart of the dysgerminoma, which arise in the ovary. It should not be confused with the unrelated tumor called spermatocytic seminoma.[2] Based on the histology, testicular seminoma may be classified into three subtypes: classic, anaplastic, and spermatocytic.[3] On gross pathology, seminoma is characterized by pale gray to yellow nodules that are uniform or slightly lobulated and often bulge from the cut surface.[3] On microscopic pathology, seminoma is characterized by the cells with fried egg appearance with clear cytoplasm and central nucleus with prominent nucleolus, with interspersed lymphocytes and syncytiotrophoblasts.[4] Approximately 24% of Stage I seminomas have lymphovascular invasion for stage I (Tx, N0, M0). Intertubular seminoma may not form a discrete mass and mimic a benign testis.[4] Seminoma is demonstrated by positivity to tumor markers, such as OCT4, CD117, D2-40, and CD117.[5] There are no known direct causes for seminoma.[6] To view a comprehensive list of risk factors that increase the risk of seminoma, click here.[7][8] Testicular germ cell tumor accounts for around 1-2% of all malignancies in males up to the age of 65, but they are the most common nonhematologic malignancy in males 15-49 years old. Approximately 50% of germ cell tumours are seminomas.[9] The mean age at diagnosis of testicular seminoma is between 15 and 35 years. This is about 5 to 10 years older than men with other germ cell tumors of the testis.[10] Testicular seminoma usually affects individuals of the Caucasian race. African american individuals are less likely to develop testicular seminoma.[9] Seminoma grows slower than non-seminomatous germ cell tumors.[11] Common complications of seminoma include recurrence, lymph node metastasis, distant metastasis, and secondary malignancies.[12] Prognosis of seminoma is good for all stages with greater than 90% cure rate.[13] The International Germ Cell Cancer Consensus Group divides seminoma into two prognosis groups: good and intermediate.[14] Symptoms of seminoma include painless testicular mass with discomfort, back pain, abdominal discomfort, or abdominal mass.[15] Laboratory findings consistent with the diagnosis of seminoma include abnormal serum tumor marker levels (LDH, HCG).[16][17] Abdominal and pelvic CT scans may be diagnostic of seminoma.[18] CT scan may detect metastases of seminoma to the para-aortic, inguinal, or iliac lymph nodes. Visceral metastasis may also be seen.[18] Pelvic MRI may be diagnostic of testicular seminoma. On MRI, seminoma is characterized by multinodular tumors of uniform signal intensity. Findings on MRI suggestive of seminoma include hypo- to isointense on T2-weighted images and inhomogenous enhancement on contrast enhanced T1-weighted images.[19] Other diagnostic studies for seminoma include biopsy, FDG-PET scan, and bone scan.[4] Radical inguinal orchiectomy is the first treatment for any stage of testicular seminoma and it is usually done as part of diagnosis.[20] Adjunctive radiotherapy and chemotherapy may be given.[20]
Recent reviews emphasize that seminoma should be considered within the broader framework of testicular germ cell tumors, in which management is guided by histology, stage, serum tumor markers, and the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification for metastatic disease.[21] Patients with testicular germ cell tumors have excellent outcomes overall, with reported 5 year survival rates of approximately 99% for stage I disease, 92% for stage II disease, and 85% for stage III disease.[21]
Classification
Based on the histology, testicular seminoma may be classified into three subtypes: classic, anaplastic, and spermatocytic.[3]
- Contemporary classification of testicular germ cell tumors broadly separates tumors into:
- Pure seminoma belongs to the seminomatous tumor pathway and is composed entirely of seminomatous elements without nonseminomatous components.[21]
- Seminoma should be distinguished from mixed germ cell tumors and from spermatocytic tumor, which is biologically distinct from classic seminoma.[21]
Pathophysiology
On gross pathology, seminoma is characterized by pale gray to yellow nodules that are uniform or slightly lobulated and often bulge from the cut surface.[3] On microscopic pathology, seminoma is characterized by the cells with fried egg appearance with clear cytoplasm and central nucleus with prominent nucleolus, with interspersed lymphocytes and syncytiotrophoblasts.[4] Approximately 24% of Stage I seminomas have lymphovascular invasion for stage I (Tx, N0, M0). Intertubular seminoma may not form a discrete mass and mimic a benign testis.[4] Seminoma is demonstrated by positivity to tumor markers, such as OCT4, CD117, D2-40, and CD117.[5]
- Seminoma typically has a relatively homogeneous gross and imaging appearance compared with many NSGCTs, which are often more heterogeneous and may contain both solid and cystic components.[21]
- Pure seminoma commonly shows abundant clear glycogen rich cytoplasm, prominent nucleoli, and admixed lymphocytes, with occasional syncytiotrophoblasts and granulomatous inflammation.[21]
Causes
There are no known direct causes for seminoma.[6] To view a comprehensive list of risk factors that increase the risk of seminoma, click here.[7][8]
Differentiating Primary Central Nervous System Lymphoma from other Diseases
Seminoma must be differentiated from other diseases that cause testicular mass, such as non seminomatous germ cell tumor, sex cord tumors, focal orchitis, focal intratesticular hemorrhage, testicular torsion, tuberculosis, and polyorchidism.[15][22]
Epidemiology and Demographics
Testicular germ cell tumor accounts for around 1-2% of all malignancies in males up to the age of 65, but they are the most common nonhematologic malignancy in males 15-49 years old. Approximately 50% of germ cell tumours are seminomas.[9] The mean age at diagnosis of testicular seminoma is between 15 and 35 years. This is about 5 to 10 years older than men with other germ cell tumors of the testis.[10] Testicular seminoma usually affects individuals of the Caucasian race. African american individuals are less likely to develop testicular seminoma.[9]
- Global incidence of testicular cancer has increased in many regions, and testicular germ cell tumors remain the dominant solid malignancy in young adult men.[23]
- Seminoma generally presents at an older age than nonseminomatous germ cell tumors.[21]
Risk Factors
Common risk factors for testicular seminoma include undescended testis, caucasian race, previous tumor in the contralateral testis, and family history of testicular germ cell tumor.[7][8][6]
- Additional risk factors reported in contemporary reviews of testicular germ cell tumors include cryptorchidism, family history of testicular cancer, infertility, and cannabis use.[21]
- Klinefelter syndrome is particularly associated with mediastinal germ cell tumors rather than typical primary testicular seminoma.[21]
Screening
There is insufficient evidence to recommend routine screening for seminoma.[24]
Natural History, Complications and Prognosis
Seminoma grows slower than non-seminomatous germ cell tumors.[11] Common complications of seminoma include recurrence, lymph node metastasis, distant metastasis, and secondary malignancies.[12] Prognosis of seminoma is good for all stages with greater than 90% cure rate.[13] The International Germ Cell Cancer Consensus Group divides seminoma into two prognosis groups: good and intermediate.[14]
- In metastatic seminoma, the IGCCCG classifies patients into:
- Good prognosis
- Intermediate prognosis
- Contemporary reviews also note that recent refinements in prognostic stratification incorporate additional factors such as markedly elevated LDH as adverse features in metastatic germ cell tumors.[25][21]
Diagnosis
Staging
Seminoma grows slower than non-seminomatous germ cell tumors.[11] Common complications of seminoma include recurrence, lymph node metastasis, distant metastasis, and secondary malignancies.[12] Prognosis of seminoma is good for all stages with greater than 90% cure rate.[13] The International Germ Cell Cancer Consensus Group divides seminoma into two prognosis groups: good and intermediate.[14]
- Initial staging of suspected seminoma is based on:
- Radical inguinal orchiectomy pathology
- CT of the chest, abdomen, and pelvis
- Serum tumor markers including AFP, beta-hCG, and LDH[21]
- An additional stage IS may be assigned when serum tumor markers remain elevated after orchiectomy in the absence of radiographically evident nodal or distant metastases.[21]
Symptoms
Symptoms of seminoma include painless testicular mass with discomfort, back pain, abdominal discomfort, or abdominal mass.[15]
- In approximately 90% of patients with testicular cancer, the presenting symptom is a testicular abnormality, most often a painless testicular mass.[21]
- About 10% of patients may present with acute testicular pain due to rapid tumor growth, intratesticular hemorrhage, infarction, or, rarely, testicular torsion.[21]
- Less common symptoms include scrotal swelling, heaviness, discomfort, testicular shrinkage, gynecomastia, neck mass, lower extremity swelling, or symptoms related to retroperitoneal disease.[21]
Physical Examination
Common physical examination findings of seminoma include unilateral, nontender mass with or without retroperitoneal or inguinal lymphadenopathy.[26]
Laboratory Findings
Common laboratory tests performed in seminoma include complete blood count and blood chemistry tests.[16] Laboratory findings consistent with the diagnosis of seminoma include abnormal serum tumor marker levels (LDH, HCG).[16][17]
- Serum tumor markers routinely obtained in suspected testicular germ cell tumors include:
- Pure seminoma may have elevated beta-hCG and/or LDH, but a true elevation of AFP suggests a nonseminomatous component and should prompt management as NSGCT.[21][27]
Ultrasound
- Scrotal ultrasound is the preferred initial imaging study in patients with suspected seminoma or other testicular germ cell tumors.[21]
- High resolution scrotal ultrasound can detect nearly 100% of testicular lesions and is useful for distinguishing malignant from benign intratesticular masses.[28]
- Pure seminomas typically have a relatively homogeneous sonographic appearance, whereas mixed NSGCTs are more often heterogeneous and may contain both solid and cystic components.[21][29]
CT
Abdominal and pelvic CT scans may be diagnostic of seminoma.[18] CT scan may detect metastases of seminoma to the para-aortic, inguinal, or iliac lymph nodes. Visceral metastasis may also be seen.[18]
- Staging CT typically includes the chest, abdomen, and pelvis, with particular attention to retroperitoneal lymph nodes.[21]
MRI
Pelvic MRI may be diagnostic of testicular seminoma. On MRI, seminoma is characterized by multinodular tumors of uniform signal intensity. Findings on MRI suggestive of seminoma include hypo- to isointense on T2-weighted images and inhomogenous enhancement on contrast enhanced T1-weighted images.[19]
Other Imaging Findings
There are no other imaging findings associated with seminoma.
Other Diagnostic Studies
Other diagnostic studies for seminoma include biopsy, FDG-PET scan, and bone scan.[4]
- Radical inguinal orchiectomy is both diagnostic and therapeutic and is the standard initial procedure for a suspicious testicular mass with malignant features on imaging, even in the absence of elevated serum tumor markers.[21]
- FDG-PET scan is not routinely required for initial diagnosis but may have a selective role in the evaluation of residual masses after treatment of seminoma.[30]
Treatment
Medical Therapy
The optimal therapy for seminoma depends on the stage at diagnosis.[31]
- Guideline based management of seminoma is stage specific and aims to balance oncologic control with minimization of long term treatment related toxicity.[21]
Stage I seminoma
- After radical inguinal orchiectomy, active surveillance is the preferred management option for many patients with clinical stage I seminoma.[21][32]
- Acceptable alternatives in selected patients include:
- Adjuvant carboplatin for 1 cycle
- Adjuvant radiation therapy
- Surveillance avoids overtreatment but requires adherence to follow up because relapse remains possible.[33]
Stage II seminoma
- For stage IIA or IIB seminoma, management options may include:
- Radiation therapy
- Cisplatin based chemotherapy
- Primary retroperitoneal lymph node dissection (RPLND) in selected patients at experienced centers
- For stage IIA, IIB, or IIC seminoma requiring systemic treatment, commonly used regimens include:
- Primary RPLND is being investigated and used in selected patients with limited retroperitoneal seminoma, especially stage IIA or limited IIB disease, but should be considered in specialized centers only.[34][35]
Metastatic seminoma
- Metastatic seminoma is treated according to IGCCCG risk based criteria.
- Cisplatin based chemotherapy is the mainstay of treatment in metastatic seminoma.
- Prognostic grouping for seminoma includes:
- Good prognosis
- Intermediate prognosis[25]
Surgery
Radical inguinal orchiectomy is the first treatment for any stage of testicular seminoma and it is usually done as part of diagnosis.[20]
- Retroperitoneal lymph node dissection is not routine for all seminoma patients but may be considered for carefully selected stage IIA or IIB disease in experienced centers.[34][35]
Primary Prevention
There are no primary preventive measures available for seminoma.[36]
Secondary Prevention
Secondary prevention strategies following seminoma include regular follow-ups for every 2–6 months for the first 3 years and every 6–12 months after 3 years.[37] Tests are often part of follow-up care include blood tests to check serum tumor marker levels, chest x-rays, and CT scans of the abdomen and pelvis.[37]
- Surveillance protocols generally include serial:
- History and physical examination
- Serum tumor markers
- Cross sectional imaging as clinically indicated
- Long term follow up is important not only to detect relapse but also to monitor for late effects of treatment, including secondary malignancy, cardiovascular disease, metabolic complications, neuropathy, nephrotoxicity, and thromboembolic events after chemotherapy or radiotherapy.[21]
References
- ↑ Testicular seminoma. Dr Marcin Czarniecki and Dr Andrew Dixon et al. Radiopaedia 2016. http://radiopaedia.org/articles/testicular-seminoma-1. Accessed on February 25, 2016
- ↑ Overview of seminoma. Libre pathology 2016. http://librepathology.org/wiki/Seminoma. Accessed on March 3, 2016
- ↑ 3.0 3.1 3.2 3.3 Pathology of testicular seminoma. Dr Marcin Czarniecki and Dr Andrew Dixon et al. Radiopaedia 2016. http://radiopaedia.org/articles/testicular-seminoma-1. Accessed on February 25, 2016
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Microscopic pathology of seminoma. Libre pathology 2016. http://librepathology.org/wiki/Seminoma. Accessed on March 3, 2016
- ↑ 5.0 5.1 IHC for seminoma. Libre pathology 2016. http://librepathology.org/wiki/Seminoma. Accessed on March 3, 2016
- ↑ 6.0 6.1 6.2 Causes of seminoma. US National Library of Medicine 2016. https://www.nlm.nih.gov/medlineplus/ency/article/001288.htm. Accessed on February 29, 2016
- ↑ 7.0 7.1 7.2 Risk factors for testicular seminoma. Dr Marcin Czarniecki and Dr Andrew Dixon et al. Radiopaedia 2016. http://radiopaedia.org/articles/testicular-seminoma-1. Accessed on February 25, 2016>
- ↑ 8.0 8.1 8.2 Risk factors for testicular germ cell tumors. Dr Matt A. Morgan and Dr Andrew Dixon et al. Radiopaedia 2016. Accessed on February 25, 2016
- ↑ 9.0 9.1 9.2 9.3 Epidemiology of testicular seminoma. Dr Marcin Czarniecki and Dr Andrew Dixon et al. Radiopaedia 2016. http://radiopaedia.org/articles/testicular-seminoma-1. Accessed on February 25, 2016
- ↑ 10.0 10.1 Presentation of seminoma. Wikipedia 2016. https://en.wikipedia.org/wiki/Seminoma. Accessed on February 25, 2016
- ↑ 11.0 11.1 11.2 Cancerous tumours of the testicle. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/testicular/testicular-cancer/cancerous-tumours/?region=on. Accessed on February 26, 2016
- ↑ 12.0 12.1 12.2 Testicular seminoma. Dr Marcin Czarniecki and Dr Andrew Dixon et al. Radiopaedia 2016. http://radiopaedia.org/articles/testicular-seminoma-1. Accessed on March 3, 2016
- ↑ 13.0 13.1 13.2 Treatment and prognosis of testicular seminoma. Dr Marcin Czarniecki and Dr Andrew Dixon et al. Radiopaedia 2016. http://radiopaedia.org/articles/testicular-seminoma-1. Accessed on March 2, 2016
- ↑ 14.0 14.1 14.2 Prognosis and survival for testicular cancer. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/testicular/prognosis-and-survival/?region=on. Accessed on February 29, 2016
- ↑ 15.0 15.1 15.2 Clinical presentation of testicular seminoma. Dr Marcin Czarniecki and Dr Andrew Dixon et al. Radiopaedia 2016. http://radiopaedia.org/articles/testicular-seminoma-1. Accessed on February 25, 2016
- ↑ 16.0 16.1 16.2 Diagnosis of testicular cancer. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/testicular/diagnosis/?region=on. Accessed on March 2, 2016
- ↑ 17.0 17.1 Diagnosis of seminoma. Wikipedia 2016. https://en.wikipedia.org/wiki/Seminoma. Accessed on March 3, 2016
- ↑ 18.0 18.1 18.2 18.3 Radiographic features of testicular seminoma. Dr Marcin Czarniecki and Dr Andrew Dixon et al. Radiopaedia 2016. http://radiopaedia.org/articles/testicular-seminoma-1. Accessed on February 29, 2016
- ↑ 19.0 19.1 Radiographic features of testicular seminoma. Dr Marcin Czarniecki and Dr Andrew Dixon et al. Radiopaedia 2016. http://radiopaedia.org/articles/testicular-seminoma-1. Accessed on March 7, 2016
- ↑ 20.0 20.1 20.2 Surgery for testicular cancer. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/testicular/treatment/surgery/?region=on. Accessed on March 2, 2016
- ↑ 21.00 21.01 21.02 21.03 21.04 21.05 21.06 21.07 21.08 21.09 21.10 21.11 21.12 21.13 21.14 21.15 21.16 21.17 21.18 21.19 21.20 21.21 21.22 21.23 Singla N, Bagrodia A, Baraban E, Fankhauser CD, Ged Y (2025). "Testicular Germ Cell Tumors". JAMA. 333 (9): 793–804. doi:10.1001/jama.2024.27122.
- ↑ Differential diagnosis of testicular seminoma. Dr Marcin Czarniecki and Dr Andrew Dixon et al. Radiopaedia 2016. http://radiopaedia.org/articles/testicular-seminoma-1. Accessed on February 25, 2016
- ↑ Znaor A, Skakkebaek NE, Rajpert-De Meyts E; et al. (2022). "Global patterns in testicular cancer incidence and mortality in 2020". Int J Cancer. 151 (5): 692–698. doi:10.1002/ijc.33999.
- ↑ Screening of seminoma. U.S. preventive services task force 2016. http://www.uspreventiveservicestaskforce.org/BrowseRec/Search?s=seminoma. Accessed on March 3, 2016
- ↑ 25.0 25.1 International Germ Cell Cancer Collaborative Group (1997). "International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers". J Clin Oncol. 15 (2): 594–603. doi:10.1200/JCO.1997.15.2.594.
- ↑ Boujelbene, Noureddine; Cosinschi, Adrien; Boujelbene, Nadia; Khanfir, Kaouthar; Bhagwati, Shushila; Herrmann, Eveleyn; Mirimanoff, Rene-Olivier; Ozsahin, Mahmut; Zouhair, Abderrahim (2011). "Pure seminoma: A review and update". Radiation Oncology. 6 (1): 90. doi:10.1186/1748-717X-6-90. ISSN 1748-717X.
- ↑ Stenman UH, Alfthan H, Hotakainen K (2004). "Human chorionic gonadotropin in cancer". Clin Biochem. 37 (7): 549–561. doi:10.1016/j.clinbiochem.2004.05.008.
- ↑ Rifkin MD, Kurtz AB, Pasto ME, Goldberg BB (1985). "Diagnostic capabilities of high-resolution scrotal ultrasonography: prospective evaluation". J Ultrasound Med. 4 (1): 13–19. doi:10.7863/jum.1985.4.1.13.
- ↑ Marko J, Wolfman DJ, Aubin AL, Sesterhenn IA (2017). "Testicular seminoma and its mimics: from the radiologic pathology archives". Radiographics. 37 (4): 1085–1098. doi:10.1148/rg.2017160164.
- ↑ Patrikidou A, Cazzaniga W, Berney D; et al. (2023). "European Association of Urology Guidelines on Testicular Cancer: 2023 update". Eur Urol. 84 (3): 289–301. doi:10.1016/j.eururo.2023.04.010.
- ↑ Treatments for testicular cancer. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/testicular/treatment/?region=on. Accessed on March 1, 2016
- ↑ Stephenson A, Bass EB, Bixler BR; et al. (2024). "Diagnosis and treatment of early-stage testicular cancer: AUA guideline amendment 2023". J Urol. 211 (1): 20–25. doi:10.1097/JU.0000000000003694.
- ↑ Boormans JL, Sylvester R, Anson-Cartwright L; et al. (2024). "Prognostic factor risk groups for clinical stage I seminoma: an individual patient data analysis by the European Association of Urology Testicular Cancer Guidelines Panel and Guidelines Office". Eur Urol Oncol. 7 (3): 537–543. doi:10.1016/j.euo.2023.10.014.
- ↑ 34.0 34.1 Hiester A, Che Y, Lusch A; et al. (2023). "Phase 2 single-arm trial of primary retroperitoneal lymph node dissection in patients with seminomatous testicular germ cell tumors with clinical stage IIA/B (PRIMETEST)". Eur Urol. 84 (1): 25–31. doi:10.1016/j.eururo.2022.10.021.
- ↑ 35.0 35.1 Daneshmand S, Cary C, Masterson T; et al. (2023). "Surgery in early metastatic seminoma: a phase II trial of retroperitoneal lymph node dissection for testicular seminoma with limited retroperitoneal lymphadenopathy". J Clin Oncol. 41 (16): 3009–3018. doi:10.1200/JCO.22.00624.
- ↑ Prevention of seminoma. Embrace 2016. http://www.embracepetinsurance.com/health/seminoma. Accessed on March 3, 2016
- ↑ 37.0 37.1 Follow-up after treatment for testicular cancer. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/testicular/treatment/follow-up/?region=on. Accessed on March 2, 2016