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Extragonadal Germ Cell Tumors

Definition

Extragonadal germ cell tumors (EGCT) originate from germ cells outside the testis, which may be found near the midline in the abdomen, pelvis, mediastinum, or brain. By definition, no malignancy is present in the testis.

Epidemiology

3–5% of all germ cell tumors are extragonadal, occurring slightly more often in men than women.

Age of onset and location:

Sacrococcygeal tumors in neonates or infants, cranial location in children and young adults, in other locations, age of onset is 20–30 years.

Etiology and Pathology

Misplaced germ cells:

Primordial germ cells actually migrate amoeboid from the yolk sac into the gonad, and misplaced germ cells may cause EGCT near the midline. Another theory postulates the origin of germ cell tumors from other pluripotent embryonic cells (DeFelici et al., 2021).

Localization:

Near the midline (in decreasing frequency): mediastinum, retroperitoneum, sacrococcygeal, and skull base.

Growth pattern:

EGCT are not encapsulated and infiltrate the neighboring structures.

Histology:

Signs and Symptoms

Abdominal pain or back pain, weight loss, cough, shortness of breath, palpable abdominal tumor. Cranial location causes headaches, neurological symptoms (vision, hearing), hormonal symptoms. Over 50% of EGCT become symptomatic when already metastatic.

Diagnosis

See also section germ cell tumor:

• tumor markers (AFP, HCG, LDH)
• testicular ultrasound imaging to search for a testicular tumor
• CT scan of abdomen, chest and possibly head
• fertility counseling
• CT-guided tumor biopsy is unnecessary if specific tumor markers (AFP oder HCG) are clearly elevated.

Differential diagnosis:

It is important to distinguish extragonadal germ cell tumors from retroperitoneal metastatic testicular germ cell tumors with "burned out" primary tumors.

Treatment and Prognosis of Extragonadal Germ Cell Tumors

Prognostic Risk Groups of Metastatic Testicular Cancer

The prognostic risk groups of metastatic or extragonadal germ cell tumors are classified according to the guidelines of the International Germ Cell Cancer Collaborative Group (IGCCCG). The grouping determines the prognosis and the number of recommended chemotherapy cycles for treatment. The lowest value (nadir) of the tumor markers after orchiectomy is used for grouping (Kier et ak., 2017).

Good prognosis

• 90% of seminomas have a good prognosis with a five-year progression-free survival (PFS) of 82–87% and a five-year survival rate (5-YSR) of 86–93%: any tumor marker and no non-pulmonary visceral metastases and any tumor location.
• 56% of nonseminomas have a good prognosis with a five-year progression-free survival (PFS) of 89–90% and a five-year survival rate (5-YSR) of 92–95%: Tumor marker stage S0–S1 and No non-pulmonary visceral metastases primary tumor in testicular or retroperitoneal location.

Intermediate prognosis

• 10% of seminomas have an intermediate prognosis with a five-year progression-free survival (PFS) of 67% and a five-year survival rate (5-YSR) of 72%: any tumor marker and non-pulmonary visceral metastases and any tumor location.
• 28% of nonseminomas have an intermediate prognosis with a five-year progression-free survival (PFS) of 75% and a five-year survival rate (5-YSR) of 80–85%: Tumor marker stage S2 and No non-pulmonary visceral metastases primary tumor in testicular or retroperitoneal location.

Poor prognosis

• The poor prognosis does not apply to seminomas.
• 16% of nonseminomas have a poor prognosis with a five-year progression-free survival (PFS) of 41–55% and a five-year survival rate (5-YSR) of 48–64%: Tumor marker stage S3 or non-pulmonary visceral metastases or primary tumor in mediastinal location.

Retroperitoneal nonseminomatous EGCT:

Retroperitoneal nonseminomatous EGCT are treated like metastatic testicular GCT: 3–4 cycles of chemotherapy depending on prognosis, and resection of residual tumor (RLA).

Mediastinal nonseminomatous EGCT:

Mediastinal nonseminomatous EGCT are classified as poor prognosis regardless of size and tumor markers and are treated analogously: high-dose chemotherapy and resection of residual tumors. The 5-years survival rate is below 50%.

Mediastinal seminomatous EGCT:

3–4 cycles of PEB depending on prognosis, resection of residual tumor is often unnecessary (only for masses larger than 3 cm). Radiotherapy is an additional option. 5-years survival rate is 70–100%.

Cranial EGCT:

Multimodal therapy: chemotherapy, residual tumor resection, and, if necessary, radiation therapy.

References

Albers, P.; Albrecht, W.; Algaba, F.; Bokemeyer, C.; Cohn-Cedermark, G.; Fizazi, K.; Horwich, A.; Laguna, M.; Nicolai, N. & Oldenburg, J. EAU Guidelines: Testicular Cancer
. https://uroweb.org/guidelines/testicular-cancer/

DGU, DKG, AWMF, and L. Onkologie, “S3-Leitlinie Diagnostik, Therapie und Nachsorge der Keimzelltumoren des Hodens. Langversion 1.1.” [Online]. Available: https://www.leitlinienprogramm-onkologie.de/leitlinien/hodentumoren/

A. Stephenson, E. B. Bass, and B. R. Bixler, “Diagnosis and Treatment of Early-Stage Testicular Cancer: AUA Guideline.” [Online]. Available: https://www.auanet.org/guidelines-and-quality/guidelines/testicular-cancer-guideline

M. De Felici, F. G. Klinger, F. Campolo, C. R. Balistreri, M. Barchi, and S. Dolci, “To Be or Not to Be a Germ Cell: The Extragonadal Germ Cell Tumor Paradigm.,” Int J Mol Sci, vol. 22, no. 11, 2021, doi: 10.3390/ijms22115982.

  Deutsche Version: extragonadale Keimzelltumoren