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Extragonadal Germ Cell Tumors Workup

  • Author: Kush Sachdeva, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
Updated: Apr 16, 2015

Laboratory Studies

Tumor markers serum alpha fetoprotein (AFP) and/or the beta subunit of human chorionic gonadotropin (beta-hCG) are elevated in extragonadal nonseminomatous germ cell tumors. These tumor markers provide diagnostic, staging, and prognostic information. Check these levels before and then at regular intervals after therapy.

Choriocarcinoma, embryonal carcinoma, and a minority of seminomas (< 10%) produce bhCG. Neoplasms with which bhCG elevation can be seen are prostate, bladder, ureteral, and renal cancers. The levels of bhCG in the cerebrospinal fluid of patients with primary intracranial germ cell tumors (ICGCT) were elevated more frequently than in the plasma before treatment and became detectable prior to any increase of the serum values in case of relapse.

Serum AFP elevations are seen in yolk-sac tumors and embryonal carcinoma. Pure seminomas and pure choriocarcinomas do not produce AFP. Pregnancy, hepatocellular carcinoma, cirrhosis, and hepatitis also may be associated with increased levels of serum AFP.

The half-life of beta-hCG is 24 hours, and that of AFP is 4-6 days.

AFP, bhCG, or both are elevated in approximately 85% of extragonadal nonseminomatous germ cell tumors. Small increases in serum beta-hCG can be seen in up to 50% of patients with disseminated seminoma.

Lactate dehydrogenase (LDH) is a nonspecific marker. Its level correlates well with the tumor burden and with the number of i(12p) copies.

Placental alkaline phosphatase is used in some centers as a marker and is useful in the immunohistochemical characterization of midline tumors.

Cytogenetic analysis of patients with mediastinal germ cell tumors (MGCTs) reveals trisomy 8 in 16% of cases and Klinefelter syndrome (XXY) in 14-20% of cases. However, the most common karyotype abnormality is i(12p), present in 38% of patients. The presence of this abnormality helps identify midline germ cell tumors presenting as poorly differentiated carcinomas with atypical features.

Obtain baseline evaluation of pituitary function (ie, thyroid-stimulating hormone, cortisol, GH, follicle-stimulating hormone, luteinizing hormone, prolactin) before treatment and then at regular intervals in patients with intracranial germ cell tumors.

Evaluation of blood counts, liver function, and kidney function before therapy and after recovery is necessary.


Imaging Studies

See the list below:

  • Testicular ultrasound: This should be ordered whenever a malignant germ cell tumor is diagnosed to rule out a gonadal primary site.
  • CT scan of the chest, abdomen, and pelvis
    • Mature teratomas appear as heterogeneous cystic, well-defined, anterior mediastinal masses with walls of different thicknesses. Calcifications are present in approximately one quarter, with a bone or a tooth rarely identifiable. The combination of fluid, soft tissue, calcium, and/or fat attenuation in an anterior mediastinal mass is highly specific for mature teratoma.
    • Seminomas present as bulky, lobulated, homogeneous, anterior mediastinal masses. Although invasion of adjacent organs is uncommon, metastases to regional lymph nodes and bone can be seen. Calcifications are rare.
    • Nonseminomatous mediastinal germ cell tumors (NS-MGCTs) appear as irregular, anterior mediastinal masses, often with extensive, central heterogeneous areas of low attenuation caused by necrosis, hemorrhage, and/or cyst formation. Adjacent organ involvement and metastases to regional lymph nodes as well as to distant sites may occur.
  • Chest x-ray films show enlargement of the mediastinum on the anteroposterior view. The lateral view reveals the anterior location of the mass.
  • CT scan or MRI of the brain shows pineal seminoma as a discrete mass that usually reaches 3-4 cm in diameter. It compresses the superior colliculi and sometimes the superior surface of the cerebellum and narrows the sylvian aqueduct. Obstructive hydrocephalus may be evinced by the presence of dilated ventricles and interstitial edema.
  • Early published studies have compared positron emission tomography (PET) to CT for the evaluation of patients with newly diagnosed disease or residual germ cell neoplasms after chemotherapy and have suggested that PET may be more sensitive than CT, disease smaller than 0.5 cm was not detected. [11, 12, 13] In patients with nonseminomatous germ cell tumors (NSGCT), PET has not been consistently able to identify residual viable malignant germ cell tumors (GCTs) and also does not detect teratoma. One study has shown that PET is useful in the detection of residual viable seminoma in patients with masses larger than 3 cm in diameter after chemotherapy. [14]

Other Tests

See the list below:

  • Assess neuropsychologic status in children before they undergo cranial radiation and at regular intervals thereafter.
  • Perform formal visual examination in patients with suprasellar/hypothalamic tumors.
  • Biopsy of the tumor mass
    • Histologic confirmation of germ cell tumors (GCTs) may be obtained by open biopsy of an abdominal mass, anterior median sternotomy of a mediastinal mass, and neuroendoscopy of a pineal tumor. Fine-needle aspiration frequently establishes the diagnosis, obviating the need for open biopsy.[15] Pathologic studies help determine the histologic subtype, the presence of non–germ cell elements, or the rare cases of marker-positive non–small cell lung cancer.
    • Tumor marker elevation in the appropriate clinical setting makes the diagnosis of germ cell tumors highly likely.[16] Chemotherapy can be initiated in these cases without tissue diagnosis if a need for immediate treatment is present.

Histologic Findings

Extra-gonadal germ cell tumor (EGGCTs) show the same histologic features as gonadal germ cell tumors (GCTs).



See the list below:

  • Clinical staging of mediastinal germ cell tumors (MGCT)
    • Stage I - Well-circumscribed tumor with or without focal adhesions to the pleura or pericardium but without microscopic evidence of invasion into adjacent organ
    • Stage II - Tumor confined to the mediastinum with macroscopic and/or microscopic evidence of infiltration into adjacent structures
    • Stage III - Tumor with metastases
      • Stage IIIA - With metastases to intrathoracic organs
      • Stage IIIB - With extrathoracic metastases
  • Pediatric Oncology Group/Children's Cancer Group Staging for Malignant Extragonadal Germ Cell Tumors
    • Stage I - Complete resection at any site; coccygectomy for sacrococcygeal site; negative tumor margins; tumor markers positive or negative
    • Stage II - Microscopic residual; lymph nodes negative; tumor markers positive or negative
    • Stage III - Gross residual or biopsy only; retroperitoneal nodes negative or positive; tumor markers positive or negative
    • Stage IV - Distant metastases, including liver
Contributor Information and Disclosures

Kush Sachdeva, MD Southern Oncology and Hematology Associates, South Jersey Healthcare, Fox Chase Cancer Center Partner

Disclosure: Nothing to disclose.


Brendan Curti, MD Director, Genitourinary Oncology Research, Robert W Franz Cancer Research Center, Earle A Chiles Research Institute, Providence Cancer Center

Brendan Curti, MD is a member of the following medical societies: American College of Physicians, American Society of Clinical Oncology, Oregon Medical Association, Society for Immunotherapy of Cancer

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Prometheus Pharmaceuticals<br/>Received research grant from: Prometheus Pharmaceuticals.

Issam Makhoul, MD Associate Professor, Department of Medicine, Division of Hematology/Oncology, University of Arkansas for Medical Sciences

Issam Makhoul, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology

Disclosure: Nothing to disclose.

Bagi RP Jana, MD Associate Professor of Medicine (Genitourinary Oncology), Division of Hematology and Oncology, University of Texas Medical Branch

Bagi RP Jana, MD is a member of the following medical societies: American Cancer Society, American Medical Association, SWOG, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Additional Contributors

Robert C Shepard, MD, FACP Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International

Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American Association for Physician Leadership, European Society for Medical Oncology, Association of Clinical Research Professionals, American Federation for Clinical Research, Eastern Cooperative Oncology Group, Society for Immunotherapy of Cancer, American Medical Informatics Association, American College of Physicians, American Federation for Medical Research, American Medical Association, American Society of Hematology, Massachusetts Medical Society

Disclosure: Nothing to disclose.

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