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Testicular Choriocarcinoma Workup

  • Author: Michael B Williams, MD, MS; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
 
Updated: Apr 16, 2015
 

Laboratory Studies

The workup for testicular choriocarcinoma should include assays of the following:

  • Alpha-fetoprotein (AFP)
  • Human chorionic gonadotropin, beta subunit (beta-hCG)
  • Liver function

AFP is secreted by yolk sac elements; elevated levels of AFP are consistent with NSGCT. Choriocarcinoma could be a component of such a tumor, but AFP is within the reference range in pure choriocarcinoma. AFP has a serum half-life of between 5 and 7 days.

Human chorionic gonadotropin is a glycoprotein with the same alpha unit as thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Therefore, the beta subunit must be assayed. Beta-hCG has a 24- to 36-hour half-life and is secreted by syncytiotrophoblast cells within the tumor. Beta-hCG levels are usually markedly elevated in pure choriocarcinoma. Persistently elevation of beta-hCG levels is defined as continued elevation of the tumor marker above the predicted levels based on serum half-life of 24-36 hours.[7] This can also be applied to AFP, in which levels above that expected for the zero order kinetics of a 5- to 7-day expected half-life represent persistent elevation. From a clinical perspective, persistent tumor marker elevation represents residual disease. As such, more advanced treatment modalities (eg, chemotherapeutic) may be required.

The liver enzyme profile should include lactate dehydrogenase (LDH). Elevated levels of LDH may indicate bulky or advanced disease; however, the sensitivity and specificity are limited compared with beta-hCG and AFP. Rising levels after treatment may indicate relapse. Elevation of the remaining liver function tests may correlate with metastatic liver disease.

Placental alkaline phosphatase (PLAP) levels are elevated in some patients with seminoma and advanced disease; however, smoking and several other tumors also cause elevations. Therefore, this marker not commonly used.

Recent research has identified a number of molecular biomarkers for testicular germ cell tumors, including microRNAs. In addition to diagnosis, these hold the potential for use in treatment selection and establishing prognosis.[8, 9]

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Imaging Studies

Scrotal ultrasonography

Any male with a palpable testicular mass should undergo scrotal ultrasonography. Other indications for ultrasonography may include acute scrotal pain, hydrocele, or other nonspecific scrotal pain, swelling, or mass.

Choriocarcinoma is associated with hemorrhage and necrosis and may appear more cystic, inhomogeneous, and calcified than a seminoma.[10]

Abdominal CT scanning of the abdomen and pelvis with intravenous and oral contrast

In all other forms of testis GCT, CT scanning can be used to most commonly identify metastatic disease to the retroperitoneal lymph nodes, and it understages approximately 15%-20% of patients thought to have stage I.

In patients with pure choriocarcinoma, metastatic disease via hematogenous routes may skip the retroperitoneal lymphatics.

CT scanning of the brain

Choriocarcinoma is associated with brain metastases. In a review of 242 patients with metastatic germ cell testis cancer undergoing treatment with a multi-agent chemotherapy protocol, Vugrin et al (1979) found 38 cases of brain metastases.[11] Among patients with pure embryonal carcinomas, 13% had brain metastases, compared to 83% of patients with pure choriocarcinomas. Furthermore, choriocarcinomas tended to have multiple brain metastatic sites with cerebellar involvement.

In almost all cases, pulmonary metastases preceded or coincided with brain metastases.

Chest radiography/chest CT scanning

Chest CT scan is indicated only for an abnormal finding on chest radiography; however, choriocarcinoma has a high metastatic rate, and CT scanning of the chest is usually indicated.

Bone scan

In an autopsy study by Bredael et al (1982), GCTs had bony metastases at autopsy, including seminoma (56%), mixed choriocarcinoma (35%), teratocarcinoma (30%), and embryonal carcinoma (24%); however, 0 of 6 cases of pure choriocarcinoma metastasized to the bone.[12]

In pure choriocarcinoma, a bone scan can probably be omitted in the absence of bone pain.

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Histologic Findings

Gross findings include a small hemorrhagic nodule with some grayish-white viable tumor at the periphery. Histology shows that choriocarcinoma contains both syncytiotrophoblastic cells and cytotrophoblastic cells in intimate association (see image below).

Testicular choriocarcinoma has multinucleated sync Testicular choriocarcinoma has multinucleated syncytiotrophoblastic cells that drape over smaller cytotrophoblastic cells, which together appear to form a border along a blood-filled villouslike space (upper right). Used with permission from Ernstoff MS, Heaney JA, and Peschel RE, eds. Testicular and Penile Cancer. Malden, Mass: Blackwell Science, Inc; 1998:20.

Syncytiotrophoblastic cells are responsible for beta-HCG production.

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Staging

American Joint Committee on Cancer and the International Union Against Cancer staging systems are described below.[13] Additional staging systems are well discussed by Prow (1998).[14]

Primary tumor (T)

See the list below:

  • pTx - Primary tumor cannot be assessed
  • p0 - No evidence of primary tumor
  • pTis - Intratubular germ cell neoplasia
  • pT1 - Tumor limited to the testis and epididymis, no vascular/lymphatic invasion, may invade the tunica albuginea, no invasion of the tunica vaginalis
  • pT2 - Tumor limited to the testis and epididymis, vascular/lymphatic invasion or tumor extending through the tunica albuginea with involvement of the tunica vaginalis, invades beyond the tunica albuginea or into the epididymis
  • pT3 - Tumor invades the spermatic cord with or without vascular/lymphatic invasion.
  • pT4 - Tumor invades the scrotum with or without vascular/lymphatic invasion, invades the scrotum

Regional lymph nodes (N)

Clinical

  • Nx - Nodes not assessed
  • N0 - No regional lymph node metastasis
  • N1 - Lymph node mass or multiple lymph node masses less than or equal to 2 cm in greatest dimension
  • N2 - Lymph node mass or multiple lymph node masses greater than 2 cm but less than or equal to 5 cm in greatest dimension
  • N3 - Lymph node mass greater than 5 cm in greatest dimension

Pathologic

  • pN0 - No evidence of tumor in lymph nodes
  • pN1 - Lymph node mass less than or equal to 2 cm in greatest dimension, 5 or fewer nodes positive
  • pN2 - Lymph node mass greater than 2 cm but less than 5 cm in greatest dimension, more than 5 nodes positive, evidence of extranodal extension of tumor
  • pN3 - Lymph node mass greater than 5 cm in greatest dimension

Distant metastases (M)

See the list below:

  • M0 - No evidence of distant metastases
  • M1a - Nonregional nodal or pulmonary metastases
  • M2b - Nonpulmonary visceral metastases

Table 1. Serum Tumor Markers (S) (Open Table in a new window)

S LDH HCG (mIU/mL) AFP (ng/mL)
Sx Not assessed Not assessed Not assessed
S0 ≤N* and Normal and Normal
S1 < 1.5 x N and < 5000 and < 1000
S2 1.5-10 x N or 5000-50,000 or 1000-10,000
S3 >10 x N or >50,000 or >10,000
*N=upper limit of reference range for the LDH assay

Table 2. Stage Grouping (Open Table in a new window)

Stage grouping T N M S
Stage 0 pTis N0 M0 S0
Stage I T1-T4 N0 M0 Sx
Stage IA T1 N0 M0 S0
Stage IB T2-4 N0 M0 S0
Stage IS Any T N0 M0 S1-S3
Stage II Any T Any N M0 Sx
Stage IIA Any T N1 M0 S0-S1
Stage IIB Any T N2 M0 S0-S1
Stage IIC Any T N3 M0 S0-S1
Stage III Any T Any N M1 Sx
Stage IIIA Any T Any N M1a S0-S1
Stage IIIB Any T Any N M0-M1a S2
Stage IIIC Any T Any N M0-M1a S3
Any T Any N M1b Any S
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Contributor Information and Disclosures
Author

Michael B Williams, MD, MS Assistant Professor, Department of Urology, Leroy T Canoles, Jr, Cancer Research Center, Eastern Virginia Medical School

Michael B Williams, MD, MS is a member of the following medical societies: American Association for Cancer Research, American Urological Association, Society of Urologic Oncology, Texas Medical Association, American Society of Clinical Oncology, American Association of Clinical Urologists

Disclosure: Nothing to disclose.

Coauthor(s)

Paul F Schellhammer, MD Professor of Urology, Eastern Virginia Medical School; Urologist, Urology of Virginia, PC

Paul F Schellhammer, MD is a member of the following medical societies: American Medical Association, American Urological Association, Society of Surgical Oncology, Society of Urologic 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

Bradley Fields Schwartz, DO, FACS Professor of Urology, Director, Center for Laparoscopy and Endourology, Department of Surgery, Southern Illinois University School of Medicine

Bradley Fields Schwartz, DO, FACS is a member of the following medical societies: American College of Surgeons, Society of Laparoendoscopic Surgeons, Society of University Urologists, Association of Military Osteopathic Physicians and Surgeons, American Urological Association, Endourological Society

Disclosure: Nothing to disclose.

Additional Contributors

Leonard Gabriel Gomella, MD, FACS The Bernard W Godwin Professor of Prostate Cancer Chairman, Department of Urology, Associate Director of Clinical Affairs, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Leonard Gabriel Gomella, MD, FACS is a member of the following medical societies: American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Laser Medicine and Surgery, American Urological Association, Sigma Xi, Society for Basic Urologic Research, Society of University Urologists, Society of Urologic Oncology

Disclosure: Received consulting fee from GSK for consulting; Received honoraria from Astra Zeneca for speaking and teaching; Received consulting fee from Watson Pharmaceuticals for consulting.

Acknowledgements

John W Davis, MD Assistant Professor, Department of Urology, University of Texas MD Anderson Cancer Center

John W Davis, MD is a member of the following medical societies: American College of Surgeons and American Urological Association

Disclosure: Nothing to disclose.

Dan Theodorescu, MD, PhD Paul A Bunn Professor of Cancer Research, Professor of Surgery and Pharmacology, Director, University of Colorado Comprehensive Cancer Center

Dan Theodorescu, MD, PhD is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Urological Association, Medical Society of Virginia, Society for Basic Urologic Research, and Society of Urologic Oncology

Disclosure: Key Genomics Ownership interest Co-Founder-50% Stock Ownership; KromaTiD, Inc Stock Options Board membership

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Testicular choriocarcinoma has multinucleated syncytiotrophoblastic cells that drape over smaller cytotrophoblastic cells, which together appear to form a border along a blood-filled villouslike space (upper right). Used with permission from Ernstoff MS, Heaney JA, and Peschel RE, eds. Testicular and Penile Cancer. Malden, Mass: Blackwell Science, Inc; 1998:20.
Table 1. Serum Tumor Markers (S)
S LDH HCG (mIU/mL) AFP (ng/mL)
Sx Not assessed Not assessed Not assessed
S0 ≤N* and Normal and Normal
S1 < 1.5 x N and < 5000 and < 1000
S2 1.5-10 x N or 5000-50,000 or 1000-10,000
S3 >10 x N or >50,000 or >10,000
*N=upper limit of reference range for the LDH assay
Table 2. Stage Grouping
Stage grouping T N M S
Stage 0 pTis N0 M0 S0
Stage I T1-T4 N0 M0 Sx
Stage IA T1 N0 M0 S0
Stage IB T2-4 N0 M0 S0
Stage IS Any T N0 M0 S1-S3
Stage II Any T Any N M0 Sx
Stage IIA Any T N1 M0 S0-S1
Stage IIB Any T N2 M0 S0-S1
Stage IIC Any T N3 M0 S0-S1
Stage III Any T Any N M1 Sx
Stage IIIA Any T Any N M1a S0-S1
Stage IIIB Any T Any N M0-M1a S2
Stage IIIC Any T Any N M0-M1a S3
Any T Any N M1b Any S
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