Seminoma

Summarize

1. General remarks

● Overview: Spermatocytoma is a type of germ cell tumor, belonging to germ cell tumors, occurring in the testis.

● Manifestation: As a kind of testicular tumor, spermatocytoma often presents as nodules or painless swelling in one testicle. Some patients have dull pain or heaviness in the lower abdomen, perianal area or scrotum, and a few patients may have acute pain.

● Treatment: The treatment of spermatocytic tumors includes surgery, radiotherapy and chemotherapy. For stage I spermatocytic tumors, orchiectomy is usually curative; for stage II spermatocytic tumors, chemotherapy or radiotherapy should be combined.

● Prognosis: The prognosis of spermatocytoma is very good, the overall five-year survival rate is more than 90%, and the survival rate of stage I tumors is almost 100%.

2. Disease definition

Seminoma is a type of germ cell tumor (GCT) that originates from the primitive germ cells in the embryonic germinal epithelium and seminiferous tubules. It is a common form of testicular cancer, occurring exclusively in the testes.

3. Disease staging and grouping

1) Disease staging

Pediatric seminoma can be classified into four stages according to the staging system of testicular germ cell tumors of the American Collaborative Group on Childhood Oncology (GOG):

● Stage I: The tumor is confined to the testis. A high inguinal incision is made, and the spermatic cord is ligated at the internal ring of the inguinal canal without rupture. The testis is then resected in a direction toward the scrotum. Clinical, radiological, or histological examinations show no lesions outside the testis. Postoperative tumor markers decline rapidly to normal levels due to their half-life. If the patient's tumor markers are normal or undetermined at diagnosis, the lymph nodes in the same side must be negative (if imaging suggests that the lymph node diameter is greater than 2 cm).

● Stage II: Transferred to orifices of the scrotum and testis resection with gross tumor ulceration via a high inguinal incision, followed by peritoneal tumor puncture; microscopic lesions in the scrotum or high spermatic cord (≤5 cm from the proximal end); postoperative serum tumor markers not decreasing or abnormal.

● Stage III: gross tumor residue; retroperitoneal lymph node metastasis (CT suggests lymph nodes> 4 cm or positive biopsy of lymph nodes> 2cm and <4 cm); visceral or extraperitoneal metastasis.

● Stage IV: distant metastasis, including liver, brain, bone, and lung.

Adult seminoma is staged using the comprehensive TNM staging system of the American Joint Commission on Cancer (AJCC):

• Phase 0

Testicular intraepithelial neoplasia or germ cell tumor of the seminiferous tubules, abnormal cells are found in the seminiferous tubules of the testis, which may develop into cancer and invade surrounding areas. Tumor marker levels are normal.

•I designated time

●IA stage: cancer is confined to the testis and epididymis, tumor marker levels are normal.

● Stage IB: The cancer is located in the testis and epididymis, has spread to the blood vessels and lymphatic vessels of the testis, or has spread to the outer layer of the testicular capsule. It may also be present in the spermatic cord or scrotum, potentially affecting the blood vessels and lymphatic vessels of the testis. In all these cases, tumor marker levels are normal.

● Stage IS: Cancer is located in the testis, spermatic cord or scrotum, and tumor markers are elevated.

• Ⅱ Period: The specific period should be determined after inguinal orchiectomy.

● Stage II A: Cancer is located in the testis, spermatic cord or scrotum and involves up to 5 abdominal lymph nodes, all of which are less than 2cm.

● Stage II B: Cancer is located in the testis, spermatic cord or scrotum and has one of the following conditions: Involvement of up to 5 abdominal lymph nodes, at least one of which is greater than 2cm and less than 5cm; involvement of more than 5 abdominal lymph nodes, all of which are no larger than 5cm.

● Stage II C: Cancer is located in the testis, spermatic cord or scrotum and involves abdominal lymph nodes with a diameter greater than 5cm.

• Ⅲ Period: The specific period should be determined after inguinal orchiectomy.

● Stage III A: Cancer is located in the testis, spermatic cord or scrotum, involves abdominal lymph nodes, and spreads to distant lymph nodes or lungs. Tumor marker levels are normal or slightly elevated.

● Stage III B: Cancer is located in the testis, spermatic cord or scrotum, involves abdominal lymph nodes, and spreads to distant lymph nodes or lungs. One or more tumor markers are significantly higher than normal.

● Stage III C: The cancer is located in the testes, spermatic cord, or scrotum, has spread to abdominal lymph nodes, and has reached distant lymph nodes or the lungs. One or more tumor markers are elevated. Alternatively, the cancer is located in the testes, spermatic cord, or scrotum, has spread to abdominal lymph nodes, but has not reached distant lymph nodes or the lungs, and has spread to other parts of the body. Tumor marker levels can range from normal to high.

2) Disease grouping

Seminoma can be classified as low risk or intermediate risk according to the degree of danger:

● Low risk: confined to the testis without metastasis, that is, stage I (stage 0 or stage I in adults) spermatocytic tumor.

● Intermediate risk: the tumor is not confined to the testis and has metastasis, that is, stage II-IV spermatocytic carcinoma.

Epidemiological

Seminoma is a type of testicular cancer. Testicular cancer can occur in children and adults, most commonly between the ages of 15 and 44. In childhood tumors, testicular tumors account for 1 to 2 percent of all solid tumors in children.

Etiology & Risk Factors

1. General remarks

The cause of spermatocytoma is not clear, but it is hypothesized that it may be related to the mutation of primitive germ cells during development. The specific mechanism is not clear.

2. Basic etiology

Spermatogonial cell tumors are a type of germ cell tumor that originate from the germinal epithelium and primordial germ cells in the seminiferous tubules during the embryonic period. These normal germ cells gradually migrate to the gonads (testes or ovaries) during embryonic development and mature into mature germ cells, such as sperm or eggs, after puberty. The prevailing hypothesis suggests that some of these germ cells undergo mutations during embryonic development, reach the testes, but fail to differentiate further. Instead, they retain their primitive characteristics, proliferate uncontrollably, and form spermatogonial cell tumors. However, this hypothesis requires experimental evidence to support it.

3. Triggering factors

Spermatocytoma is a type of testicular cancer. Factors associated with the development of testicular cancer include:

● Cryptorchidism: Cryptorchidism is the most common congenital malformation of the urogenital system. It increases the risk of testicular cancer and is the most important factor affecting the incidence of testicular cancer in children. Testicular fixation can reduce the risk of malignant tumors.

● Hypospadias: Hypospadias is a congenital malformation of abnormal opening of the urethra, and patients with hypospadias have a higher incidence of testicular cancer than children in general.

● Testicular cancer on the opposite side: Having testicular cancer on one side increases the likelihood of cancer on the opposite side.

● Family history and genetic susceptibility: Brothers or sons of testicular cancer patients are at higher risk of developing testicular cancer than others.

● Chromosomal abnormalities: Patients with testicular cancer over the age of 11 often have anisomic chromosome i12P with a broken arm of chromosome 12.

● Androgen insensitivity syndrome and mixed gonadal dysgenesis: Patients with chromosomal abnormalities of sex development disorders (e.g., Swyer syndrome with 45, X/46, XY) have a higher risk of testicular cancer.

● Down syndrome: This is a relatively common chromosomal abnormality that increases the risk of multiple cancers, including testicular cancer.

Classification & Staging

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Clinical Manifestations

1. General remarks

Spermatocytomas typically present with symptoms of the testis and nearby areas, such as nodules, painless swelling or pain. If there is metastasis, symptoms vary depending on where the metastasis occurs.

2. Typical symptoms

The most common symptom of spermatocytoma is a nodule or painless swelling in one testicle. Some patients may experience dull pain or heaviness in the lower abdomen, perianal area, or scrotum. 10% of patients may present with acute pain as the main symptom.

If a seminoma metastasizes, it will present symptoms specific to the site of metastasis: if it metastasizes to the supraclavicular lymph nodes, the primary symptom is a neck mass; if it metastasizes to the lungs, the main symptoms are coughing or difficulty breathing; if it metastasizes to the posterior duodenum, the primary symptoms include loss of appetite, nausea, vomiting, or gastrointestinal bleeding; if the tumor affects the lumbar muscles or causes a large retroperitoneal space-occupying lesion involving nerve roots, back pain may occur; if it metastasizes to the bone, bone pain may occur; if it affects the brain, spinal cord, or peripheral nerve roots, neurological symptoms may occur; if the tumor causes obstruction of the iliac vein or vena cava, or thrombosis, swelling in one or both legs may occur.

In addition, the tumor markers of spermatocytoma are generally normal or slightly higher. Some patients may have elevated lactate dehydrogenase (LDH) levels; a few patients may have elevated human chorionic gonadotropin β-subunit (β-hCG) levels; and alpha-fetoprotein (AFP) is usually normal.

Clinical Department

1. General remarks

Patients should seek medical attention if they develop a lump or discomfort in the testicles, or other abnormalities that may be caused by metastasis.

The diagnosis of spermatocytoma includes physical examination, imaging, tumor marker tests, and histopathological examination.

2. Department of treatment

Pediatric oncology, pediatric oncology surgery, oncology, oncology surgery, surgery

Examination & Diagnosis

1. Diagnostic basis

The definitive diagnosis of spermatocytoma is based on postoperative pathological examination. Other tests can be used for staging, guiding treatment and postoperative monitoring.

2. Related inspection

1) Physical examination

For children suspected of having testicular cancer, in addition to routine tests, a primary focus should be on testicular examination: first, examine the normal testicle to assess its size, shape, and texture, and compare it with the abnormal side. A healthy testicle is smooth, mobile, and can be easily separated from the epididymis. If any areas feel hard, tough, or fixed upon touch, these should raise suspicion. Seminomas often expand within the testicle, presenting as painless, rubber-like masses.

The physical examination should also include abdominal palpation to see if there are nodular lesions or visceral involvement.

2) Imaging examination

I) Scrotal ultrasound

Bilateral scrotal ultrasound is highly accurate in distinguishing between internal and external testicular lesions and can detect intratesticular lesions as small as 1-2mm. Seminoma appears as a non-cystic area with clearly defined hypoechoic lesions. This method can help rule out conditions such as hydrocele or epididymitis, making it a quick, safe, and reliable diagnostic tool. Any male suspected of having a testicular tumor should undergo scrotal ultrasound examination.

ii)CT

Patients with spermatocytoma usually require high-resolution CT of the abdomen and pelvis to check for regional metastasis in retroperitoneal lymph nodes. If metastatic lesions are suspected in the chest, a chest CT should be added.

iii) Magnetic Resonance Imaging (MRI)

If a brain metastasis is suspected, a brain magnetic resonance imaging is required.

IV) PET-CT (positron emission computed CT tomography)

PET-CT has a high false negative rate and is not suitable for initial diagnosis, but can be used to evaluate residual lesions after treatment.

3) Serum tumor marker examination

i) Human chorionic gonadotropin β subunit (β-hCG)

In patients with seminoma, about 15-20% show elevated levels of the human chorionic gonadotropin β-subunit in their serum, indicating a higher tumor burden, but this does not necessarily mean a high likelihood of metastasis. If the levels of the human chorionic gonadotropin β-subunit return to normal after a testicular resection, it does not indicate disease progression. However, if the levels remain persistently elevated after the resection, it suggests the presence of a hidden disease, which requires further investigation.

ii) alpha-fetoprotein (AFP)

A single spermatocytoma does not cause an increase in serum alpha-fetoprotein levels. If a higher level of serum alpha-fetoprotein is present, other components of the tumor with non-spermatocytoma can be diagnosed and it should no longer be diagnosed as a spermatocytoma but treated as another cancer.

iii) Lactate dehydrogenase (LDH)

Some patients with testicular cancer have elevated levels of lactate dehydrogenase. For some patients with seminoma, lactate dehydrogenase may be the only tumor marker that is elevated.

4) Histopathological examination

Testicular tumors can be sampled for histopathological examination by surgery (radical orchiectomy). The results of histopathological examination are the final diagnostic basis for confirming seminoma.

5. Differential diagnosis

The differential diagnosis of testicular mass includes testicular torsion, epididymitis or orchitis, and less commonly hydrocele, varicocele, hernia, hematoma or sperm cyst. These diseases can be differentiated by imaging examination and tumor marker examination.

Clinical Management

1. General remarks

Most spermatocytomas are focal lesions, with 80% being stage I (limited to the testis) and 15% being stage II (limited to retroperitoneal lymph nodes), and less than 5% of patients may spread beyond the retroperitoneal lymph nodes.

Stage I is usually cured by orchiectomy. Stage II is followed by radiotherapy or chemotherapy depending on the degree and stage of lymph node involvement after orchiectomy.

2. Surgical treatment

In seminoma, radical inguinal orchiectomy is used both as a means of pathological diagnosis and as an initial treatment.

For patients in stage I, surgery can cure spermatocellular tumor, and later observation and monitoring can be combined.

For patients with stage II or above, chemotherapy or radiotherapy should be combined with surgery according to the specific situation.

3. Chemotherapy

1) Chemotherapy regimen

Spermatocytic tumors are highly sensitive to chemotherapy. For patients aged 11 and under with stage II or higher spermatocytic tumors, chemotherapy is typically required after surgery, to avoid radiation therapy. A second surgery can be performed to remove any remaining tumors after chemotherapy. The chemotherapy regimen involves a 4-cycle PEB regimen (Paclitaxel + Etoposide + Bortezomib). For infants and young children, to prevent potential pulmonary fibrosis from bortezomib, the EP regimen (Paclitaxel + Etoposide) can be used.

For patients with stage II or higher seminoma over 11 years old, treatment may involve a combination of radiotherapy and chemotherapy, depending on the specific stage. Typically, for tumors located in the testis, spermatic cord, or scrotum, involving no more than 5 abdominal lymph nodes, and with all affected lymph nodes measuring less than 2 centimeters in diameter, postoperative radiotherapy is usually sufficient. If the affected lymph nodes are larger than 2 centimeters but less than 3 centimeters in diameter, or if there are more than 5 affected lymph nodes, each measuring less than 3 centimeters in diameter, radiotherapy alone may also be considered. All other stage II or higher patients will require chemotherapy.

For patients aged 11 years and older with stage II or higher seminoma, chemotherapy typically involves a 3-cycle PEB regimen (cisplatin + etoposide + bleomycin) or a 4-cycle EP regimen (etoposide + cisplatin). The choice of regimen should be based on the medical institution's experience and the patient's expected tolerance to bleomycin.

2) Adverse reactions

The adverse reactions of chemotherapy mainly include bone marrow suppression (manifested as neutropenia, thrombocytopenia, anemia, etc.), nausea and vomiting, etc. Renal toxicity (carboplatin), hair loss, hearing damage caused by ototoxicity (carboplatin), fatigue, etc.

4. Radiotherapy

1) Radiotherapy regimen

Spermatocytic tumors are highly sensitive to radiotherapy. For patients over 11 years old with stage II or higher spermatocytic tumors, if the tumor is located in the testis, spermatic cord, or scrotum and involves no more than 5 abdominal lymph nodes, all of which are less than 2 cm in diameter, radiotherapy alone is usually recommended after surgery. If the affected abdominal lymph nodes are between 2 and 3 cm in diameter, or if there are more than 5 lymph nodes involved, but each is less than 3 cm in diameter, radiotherapy alone may also be considered after surgery.

The radiotherapy regimen for seminoma involves low-dose irradiation of the para-aortic lymph nodes and the upper pelvic region on the same side, followed by a small additional dose to the affected lymph node area. The total radiation dose to the enlarged lymph node area is 30-36 Gy. Radiotherapy is not routinely administered to the inguinal and lower pelvic lymph nodes, scrotum, or mediastinum.

2) Adverse reactions

Acute side effects of radiotherapy include fatigue, gastrointestinal effects, mild bone marrow transplantation and darkening of the skin in the irradiated area. Protection of the opposite testicle should be paid attention to during radiotherapy to avoid damage to fertility.

Prognosis

1. General remarks

Seminoma is a type of testicular cancer. Testicular cancer is one of the solid tumors with the highest survival rate, with a five-year survival rate of more than 95% for patients and nearly 100% for stage I patients. The histological type, extent and stage of the tumor will affect the prognosis.

2. Aftereffects

Because patients with seminoma need to undergo radical orchiectomy, for children who develop the disease before puberty, attention should be paid to testicular hormone secretion and body development when they reach puberty. If necessary, exogenous sex hormones can be supplemented.

Follow-up & Review

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Daily Care

1. General remarks

After the completion of spermatocytoma treatment, it is important to carry out timely review and follow-up, on the one hand to monitor the side effects caused by treatment, on the other hand to pay attention to whether the disease is recurrent.

2. Reexamination

Patients with seminoma should adhere to regular follow-up examinations after surgery. Within 1-2 years after treatment, they should have a check-up every 3 months. In the third year after treatment, they should have a check-up every six months. From the fourth to the fifth year after treatment, they should have a check-up every six months to one year. Each follow-up visit should include a physical examination and imaging tests (usually an ultrasound; if an ultrasound is not available, a CT scan can be used as an alternative).

3. Daily life management

1) Diet

It is important to provide patients with a nutritious and balanced diet, ensuring the intake of high-quality proteins such as meat, eggs, dairy, poultry, fish, shrimp, soybeans, and soy products. Additionally, patients should consume more whole grains, vegetables, and fruits, and moderately eat dairy products and nuts to ensure the intake of other essential nutrients. Patients can consult a clinical nutritionist from the hospital's nutrition department for a suitable nutritional plan. If there is a significant weight loss, consider using tube feeding or parenteral nutrition to support the patient's nutrition.

2) Movement

It is important to ensure that patients get enough sleep. Regular and quality sleep is very helpful for physical recovery and immunity. A suitable sleep environment (usually dark, quiet and at a comfortable temperature) may help improve the quality of sleep.

If the patient's physical condition allows, encourage and assist the patient to do some simple activities. Moderate exercise is helpful in preventing muscle atrophy, enhancing physical strength and endurance, and promoting appetite.

3) Lifestyle

If the patient is caused by treatment of neutropenia, attention should be paid to prevent infection. Pay attention to personal and living environment hygiene, do not approach patients with infectious diseases, and do not go to crowded places.

If the treatment causes thrombocytopenia, you should avoid bleeding. You should stay away from sharp, spiky toys and objects, and avoid strenuous sports (such as jumping, soccer, basketball, etc.).

4. Daily disease monitoring

Patients should pay attention to monitor the normal testicles in daily life, and seek medical treatment in time if there is pain. If testicular torsion occurs, timely treatment can save it. After puberty, patients should monitor testosterone levels to ensure normal sexual development.

If serum human chorionic gonadotropin β-subunit (β-hCG) or lactate dehydrogenase (LDH) levels are elevated before surgery, these markers should be rechecked after surgery. If elevated, it may be evidence of tumor recurrence.

5. Special Precautions

Patients with spermatocytic tumors who have undergone radiotherapy and chemotherapy are at risk of long-term side effects and secondary cancer, which may occur many years after the end of treatment, and this risk is related to the regimen and dose of treatment. Therefore, all medical records of patients should be kept for future review and reference.

6. Prevention

Because the exact cause of spermatocytoma is not clear, there is no good way to prevent the occurrence of spermatocytoma. However, regular follow-up and maintaining a good healthy lifestyle can help prevent and detect the recurrence or long-term effects of the disease as early as possible.

Cutting-edge therapeutic and clinical Trials

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References

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2. Key points of expert consensus on multidisciplinary diagnosis and treatment of extracranial germ cell tumors in children, CCCC-GCTs-2018

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6. PDQ® Adult Treatment Editorial Board. PDQ Testicular Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <05/21/2020>. Available at: https://www.cancer.gov/types/testicular/hp/testicular-treatment-pdq. Accessed <07/01/2020>. [PMID: 26389220]

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