Germ cell tumors

Germ cell tumorsGerm cell tumors are the neoplasms derived from the germ cells located in gonads and at the extragonadal sites (mediastinum and central nervous system). Germ cell cancer is a term referred to malignant tumors that originate from the germ cells.


Germ cells are the precursors of reproductive cells. When these cells fail to differentiate they develop germ cell tumors. The majority of tumors arises in the gonads, other sites include the mediastinum (commonly thymus) and central nervous system. They may be both benign and malignant. Germ cell cancer may metastasize to the lungs, lymph nodes, liver and central nervous system.



Malignant germ cell tumors are more common in males (90% of cases). These tumors comprise about 4% of all malignancies in childhood and adolescence up to 20 years.

It was estimated that seminomas account for approximately 50% of all germ cell tumors.


Causes and risk factors

The causes of germ cell cancer remain unknown, although some factors may contribute to the development of this type of cancer:

  • Family history of germ cell tumors;
  • Persons with androgen insensitivity syndrome (in this syndrome a male is resistant to male chromosomes) are at higher risk of developing germ cell tumors;
  • Cryptorchidism – the delayed descending of the testes in the scrotum, trauma of the testis/scrotum and mumps in the past increase the risk of developing testicular seminoma;
  • Somatic mutations in the C-kit gene, amplifications and deletions in the 12 chromosome,  testicular cancer susceptibility gene, TGCT1 on chromosome Xq27 are seen in testicular seminoma;
  • Turner’s syndrome (X0 mutation – a female karyotype has only one X chromosome instead of two) is associated with gonadoblastoma;
  • Klinefelter syndrome and hematologic neoplasms (acute myeloid leukemia, acute nonlymphocytic leukemia, acute lymphocytic leukemia, erythroleukemia, acute megakaryocytic leukemia, myelodysplastic syndrome, and malignant histiocytosis) are associated with extragonadal germ cell tumors (especially, mediastinal).

It is considered that abnormal migration of germ cells during the embryonal development leads to the occurrence of the tumor.



Germ cell tumors include two classes:

  • Germinomatous/seminomatous germ cell tumors (germinoma/dysgerminoma/seminoma) and nongerminomatous/nonseminomatous germ cell tumors (embryonal carcinoma, yolk sac tumor, trophoblastic tumors, teratoma and mixed forms);
  • Gonadal tumors are found in the reproductive organs, extragonadal tumors include the neoplasms located outside of the reproductive organs.



  • Testicular seminoma, the most common tumor seen in males at the age of 15-35 years, appears as a painless lump on one side of the scrotum. Usually the tumor is on one side, even if there are tumors on both sides of the scrotum, they tend to occur independently from each other. Sometimes the affected persons experience pain in the scrotum or the abdomen. Other uncommon symptoms are gynecomastia and back or flank pain. Rarely, the semen analysis shows subfertility;
  • Ovarian dysgerminoma is usually detected in girls younger than 20 years with a mean diagnosis age of 17. The symptoms of ovarian dysgerminoma are abdominal/pelvic pain, palpable abdominal mass, fever and vaginal bleeding. About 20% of ovarian dysgerminomas affect both ovaries.
    • Mediastinal tumors are the most common extragonadal germ cell tumors comprising up to 10% of all germ cell tumors. These tumors may be either seminomatous (seminoma) or non-seminomatous (choriocarcinoma, embryonal carcinoma, yolk sac carcinoma etc.). Mediastinal tumors may be asymptomatic. However, persistent cough, stridor and difficulty breathing or/and swallowing may be suggestive of the disease, especially when accompanied by weight loss, malaise and chest pain.   
    • Pineal germ cell tumor/germinoma – the tumor develops on the midline of the brain, in the majority of cases – in the pineal gland or in the suprasellar region. These tumors cause the rise of the intracranial pressure due to compression of the tectum and occlusion of the Sylvian aqueduct resulting in hydrocephalus, which manifests with headaches, nausea, vomiting and the Parinaud syndrome (the  nystagmus (rapid involuntary eye movements), upward gaze paralysis/paresis, failure of convergence and accommodation). Later ataxia, seizures and somnolence may occur.


  • Yolk sac tumor (endodermal sinus tumors) is a type of nongerminomatous germ cell tumor that may arise both in the gonads and in the extragonadal sites (for example, the mediastinum). This tumor is common for children in prepuberty. In adults, these tumors usually represent mixed with other germ cell tumor types, such as embryonal carcinoma or teratoma.
  • Embryonal carcinoma is a rare tumor, usually found in the ovaries or the testicles. The mean age of diagnosis is 20-30 years.
  • Choriocarcinoma is a malignant trophoblastic tumor that may originate in the ovaries or the testis (non-gestational choriocarcinoma when there is no link between the development of the tumor and pregnancy). This tumor may be seen in young males and females in prepuberty or postmenopausal period.


Extragonadal germ cell cancer syndrome

The syndrome was described for the first time in 1979. It was suggested that every poorly differentiated carcinoma should contain germ cell tumors. Chromosomal analysis  shows specific chromosome 12 abnormalities.

The syndrome is characterized by the following features:

  • occurs in males younger than 50 years;
  • tumors are located in the body midline (mediastinum, retroperitoneum) or multiple pulmonary nodules;
  • short symptom interval of less than 3 months and rapid tumor growth;
  • elevated levels of HCG and AFP;
  • good response to previous radiation therapy or chemotherapy.

Only in rare cases all the features of the syndrome are identified in one person.

Women can also develop these tumors. Any of these features are suggestive of a germ cell tumor.



    • Increased alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (B-hCG0) in 80% of cases of nongerminomatous germ cell cancers;
    • lactate dehydrogenase (LDH);


  • placental alkaline phosphatase (PLAP) increased in 50% of cases of seminoma;
  • CT, MRI scans;
  • X-ray imaging;
  • Ultrasound examination;
  • Bone scan;
  • Biopsy of the lesion;



Wide surgery is usually performed to remove the tumor. Orchiectomy (the removal of the testis), oophorectomy (removal of the ovary), hysterectomy (the removal of the uterus) may be required. Lymph nodes of the pelvis should also be resected.  Adjuvant radiotherapy is not routinely performed, especially for young patients, but it may be required for the treatment of recurrent or residual cancer.

Related: Leydig cell tumor

Applicable medicines

Three-four cycles of bleomycin, etoposide, and cisplatin (BEP) are usually administered. Additional chemotherapy with a combination of paclitaxel, ifosfamide, cisplatin (TIP) is recommended when the initial chemotherapy is not effective or the tumor relapses.


Prognosis and the outcomes varies widely depending on the type of tumor, the stage of the disease and the involvement of the other organs.

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