Testicular Choriocarcinoma Workup

Updated: Sep 07, 2019
  • Author: Michael B Williams, MD, MS; Chief Editor: Bradley Fields Schwartz, DO, FACS  more...
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Workup

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 nonseminomatous germ cell tumors (NSGCTs). 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. [22] 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.

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. [23, 24]

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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. [25]

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. [12] 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. [26]

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. [27]  

Primary tumor (T)

Pathologic

  • pTx - Primary tumor cannot be assessed

  • p0 - No evidence of primary tumor

  • pTis - Germ cell neoplasia in situ

  • pT1 - Tumor limited to the testis (including rete testis invasion) without lymphovascular invasion

  • pT2 - Tumor limited to the testis (including rete testis invasion) with lymphovascular invasion or tumor invading hilar soft tissue or epididymis or pentrating visceral mesothelial layer covering the external surface of tunica albuginea with or without lymphovascular invasion

  • pT3 - Tumor invades the spermatic cord with or without lymphovascular invasion

  • pT4 - Tumor invades the scrotum with or without lymphovascular invasion

Regional lymph nodes (N)

Clinical

  • cNx - Nodes not assessed

  • cN0 - No regional lymph node metastasis

  • cN1 - Metastasis with a lymph node mass ≤2 cm in greatest dimension or multiple lymph nodes, none > 2 cm in greatest dimension

  • cN2 - Metastasis with a lymph node mass >2 cm and ≤5 cm in greatest dimension or multiple lymph nodes, any one mass > 2 cm but ≤5 cm in greatest dimension

  • cN3 - Metastasis with a lymph node mass > 5 cm in greatest dimension

Pathologic

  • pNX - Regional lymph nodes cannot be assessed

  • pN0 - No regional lymph node metastasis

  • pN1 - Metastasis with a lymph node mass  ≤2 cm in greatest dimension, 5 or fewer nodes positive

  • pN2 - Metastasis with a lymph node mass  > 2 cm but ≤5 cm in greatest dimension; or 5 or fewer nodes positive, none > 5 cm; or evidence of extranodal extension of tumor

  • pN3 - Metastasis with a lymph node mass > 5 cm in greatest dimension

Distant metastases (M)

Distant metastases

  • M0 - No evidence of distant metastases

  • M1a - Nonretroperitoneal 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

Normal

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

pT1-T4

N0

M0

Sx

Stage IA

pT1

N0

M0

S0

Stage IB

pT2-4

N0

M0

S0

Stage IS

Any pT/TX

N0

M0

S1-S3

Stage II

Any pT/TX

N1-3

M0

Sx

Stage IIA

Any pT/TX

N1

M0

S0-S1

Stage IIB

Any pT/TX

N2

M0

S0-S1

Stage IIC

Any pT/TX

N3

M0

S0-S1

Stage III

Any pT/TX

Any N

M1

Sx

Stage IIIA

Any pT/TX

Any N

M1a

S0-S1

Stage IIIB

Any pT/TX

N1-3

M0

S2

Any pT/TX Any N M1a S2

Stage IIIC

Any pT/TX

N1-3

M0

S3

Any pT/TX Any N M1a S3

Any pT/TX

Any N

M1b

Any S

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