Approach Considerations
In a patient with a suspicious testicular mass, the workup includes both laboratory tests and imaging studies. Scrotal ultrasonography may reveal features suggestive of seminoma, but the diagnosis of seminoma is established by pathologic examination of the testicle after surgical removal. Orchiectomy is thus both diagnostic and therapeutic (see Treatment). The histologic results are supported by laboratory testing, which helps differentiate seminomas from nonseminomatous germ cell tumors (NGCTs). In addition, a chest x-ray is indicated, to exclude metastases.
Once seminoma has been diagnosed, further evaluation includes the following [1] :
-
Abdominal/pelvic computed tomography (CT) scan
-
Chest CT, if abdominal CT is positive or chest x-ray shows abnormalities
-
Repeat laboratory studies, since staging is based on post-orchiectomy values
-
Brain magnetic resonance imaging (MRI) , if clinically indicated
-
Bone scan, if clinically indicated
Laboratory Studies
Laboratory studies in patients with a suspicious testicular mass include the following [1] :
-
Alpha-fetoprotein (AFP)
-
Lactate dehydrogenase (LDH)
-
Beta human chorionic gonadotropin (beta-hCG)
-
Serum chemistry profile
Yolk sac elements secrete AFP; an elevated AFP level rules out pure seminoma, despite possible contrary histopathologic orchiectomy findings. LDH is a less-specific marker for germ cell tumors (GCTs), but levels can correlate with overall tumor burden.
Beta-hCG is a glycoprotein with the same alpha unit as thyroid-stimulating hormone, follicle-stimulating hormone, and luteinizing hormone. It has a 24- to 36-hour half-life and is secreted by syncytiotrophoblast cells within GCTs. Beta-hCG levels are elevated in 5%-10% of patients with seminomas. Elevation may correlate with metastatic disease but not with overall survival.
Richie suggested that if beta-hCG levels do not normalize after orchiectomy, the treatment approach should be that for nonseminomatous GCT (NSGCT), citing a study in which one third of patients who died of metastatic seminoma were found to have nonseminomatous elements at autopsy. [11] With the 10% incidence of pure seminomas producing beta-hCG, NSGCT chemotherapy regimens may better serve these patients.
Measurement of placentalike alkaline phosphatase may be considered, as levels can be elevated in patients with seminoma, especially as the tumor burden increases. However, levels may also increase with smoking.
Imaging Studies
Consider scrotal ultrasonography in any male with a suspicious or questionable testicular mass that is palpable upon physical examination. Scrotal ultrasonography commonly shows a homogeneous hypoechoic intratesticular mass. Larger lesions may be more inhomogeneous (see the image below). [23] Calcifications and cystic areas are less common in seminomas than in nonseminomatous tumors.
Testicular seminoma. This scrotal ultrasound of a 37-year-old man with a painless mass in his right testis shows a right testis with hypoechoic solid masses compared to the homogeneous, more hyperechoic, healthy left testis. Levels of serum beta-human chorionic gonadotropin and alpha-fetoprotein were within the reference range, and the metastatic workup findings were negative. Histopathology showed a pure seminoma. Metastatic workup showed no nodal or distant spread, T1N0M0 stage I. After orchiectomy, the patient underwent adjuvant external beam radiotherapy to the para-aortic nodes. At a 3-year follow-up study, the patient is disease free and has a greater than 95% chance of remaining disease free.
Other indications for scrotal ultrasonography may include acute scrotal pain (especially when associated with a hydrocele), nonspecific scrotal pain, swelling, or the presence of a mass. If an asymptomatic hydrocele obscures physical examination of the testicle, this study may be appropriate prior to surgical intervention. It may also be appropriate for males who are at the peak age range for testicular cancer (ie, 15-35 y).
Computed tomography
Abdominal and pelvic CT scanning, with intravenous and oral contrast, can be used to identify metastatic disease to the retroperitoneal lymph nodes; however, CT scanning results in understaging in approximately 15%-20% of patients thought to be at stage I. [4]
The CT below depicts retroperitoneal involvement from testicular seminoma.
Testicular seminoma. A 57-year-old man presents with abdominal pain of slow onset. CT scanning shows a large 25-cm retroperitoneal lesion encompassing the aorta and renal vasculature and displacing the right kidney laterally. The patient had a history of cryptorchidism repaired at age 8 years. Testes were normal and descended; however, ultrasonography showed a small 5-mm lesion on the right testis, which proved to be pure seminoma at orchiectomy. The beta-human chorionic gonadotropin level was 70 mIU/mL (reference range, < 5 mIU/mL), and the alpha-fetoprotein level was within the reference range; no metastatic lesions were observed above the diaphragm, indicating stage IIb (bulky), T1N3M0. The patient was referred for 4 cycles of cisplatin-based chemotherapy.
Chest CT scanning is indicated only when abnormal findings are observed on a chest radiograph.
Positron emission tomography
Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) has been evaluated for its utility in staging and restaging of seminomatous and nonseminomatous tumors. [24, 25, 26] In primary staging, FDG-PET has been found to have no benefit over CT scanning alone. However, in restaging assessments of residual masses, FDG-PET was noted to improve the ability to detect a fibrotic residual mass compared to that of residual teratoma postchemotherapy.
Hinz et al (2008) prospectively evaluated 20 patients with a residual mass following chemotherapy for seminoma greater than stage IIa prior to surgical resection. Although all patients with viable tumor were identified, FDG-PET findings were falsely positive in 9 of the 20 patients. They concluded that FDG-PET should be as an adjunctive tool for patient counseling. [27]
Histologic Findings
Seminomas can have three histologic variants: classic, anaplastic, and spermatocytic. [5]
Classic seminoma has a uniform population of large cells that form sheets and nests separated by delicate connective tissue. Leukocytic infiltration (20%), multinucleated cells, syncytiotrophoblasts (7%-35%), and microcalcifications (60%) may be present. Upon gross examination, the tumor has a uniform yellow color and bulges from the cut surface. Classic seminoma is the most common histologic type (see images below).
Testicular seminoma. This is a classic seminoma at low power. Uniform tumor cells are observed with mild inflammatory response (lymphocytes). Other seminoma findings not seen could include a fibrovascular stroma, syncytiotrophoblastic cells, and multinucleated histiocytes.
This is a classic testicular seminoma, high-power view, from a 37-year-old man with a painless mass in his right testis. Levels of serum beta-human chorionic gonadotropin and alpha-fetoprotein were within the reference range, and the metastatic workup findings were negative. Histopathology showed a pure seminoma. Metastatic workup showed no nodal or distant spread, T1N0M0 stage I. After orchiectomy, the patient underwent adjuvant external beam radiotherapy to the para-aortic nodes. At a 3-year follow-up study, the patient is disease free and has a greater than 95% chance of remaining disease free. See related image for a scrotal sonogram of this patient. Note here that tumor cells are uniform, have abundant clear cytoplasm, a large centrally located nucleus, and a variable mitotic pattern.
Anaplastic seminoma is observed in 5%-15% of patients with seminomas. Histopathology is as described for classic seminoma but with increased mitotic figures. Patients tend to present at more advanced stages than those with classic seminoma, but stage prognosis is similar.
Spermatocytic seminoma is a rare variant that occurs in older adults. Histopathology shows tumor cells arranged in solid sheets, containing poorly developed inconspicuous septae without leukocytic infiltrate. No glycogen is present. Small, medium, and large cell types are observed. Orchiectomy alone is sufficient treatment; metastases are rare.
Staging
American Joint Committee on Cancer and the International Union Against Cancer: Testicular Cancer Staging System [28]
Table 1. Primary Tumor (T) (Open Table in a new window)
pTx |
Primary tumor cannot be assessed |
p0 |
No evidence of primary tumor |
pTis |
Germ cell neoplasia in situ |
pT1 |
Tumor limited to the testis without lymphovascular invasion |
| pT1a | Tumor smaller than 3 cm |
| pT1b | Tumor 3 cm or larger |
pT2 |
Tumor limited to the testis and epididymis with lymphovascular invasion OR |
Tumor invading hilar soft tissue or epididymis or penetrating viceral 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 |
Table 2A. Regional Lymph Nodes (N): Clinical (Open Table in a new window)
Nx |
Nodes not assessed |
N0 |
No regional lymph node metastasis |
N1 |
Lymph node mass or multiple lymph node masses ≤ 2 cm in greatest dimension |
N2 |
Lymph node mass or multiple lymph node masses >2 cm but ≤ 5 cm in greatest dimension |
N3 |
Lymph node mass >5 cm in greatest dimension |
Table 2B. Regional Lymph Nodes (N): Pathologic (Open Table in a new window)
pN0 |
No evidence of tumor in lymph nodes |
pN1 |
Lymph node mass ≤ 2 cm in greatest dimension |
≤ 5 nodes positive |
|
pN2 |
Lymph node mass >2 cm but < 5 cm in greatest dimension |
>5 nodes positive |
|
Evidence of extranodal extension of tumor |
|
pN3 |
Lymph node mass >5 cm in greatest dimension |
Table 3. Distant Metastases (M) (Open Table in a new window)
M0 |
No evidence of distant metastases |
M1a |
Nonregional nodal or pulmonary metastases |
M2b |
Nonpulmonary visceral metastases |
Table 4. 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 |
< 5,000 |
and |
< 1,000 |
S2 |
1.5-10 x N |
or |
5,000-50,000 |
or |
1,000-10,000 |
S3 |
>10 x N |
or |
>50,000 |
or |
>10,000 |
N = upper limit of normal for the LDH assay
†HCG = human chorionic gonadotropin
Table 5. 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 |
N1-3 |
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 |
Additional staging systems are well discussed by Prow. [18] See also Seminoma Testicular Cancer Staging.
-
Testicular seminoma. A 57-year-old man presents with abdominal pain of slow onset. CT scanning shows a large 25-cm retroperitoneal lesion encompassing the aorta and renal vasculature and displacing the right kidney laterally. The patient had a history of cryptorchidism repaired at age 8 years. Testes were normal and descended; however, ultrasonography showed a small 5-mm lesion on the right testis, which proved to be pure seminoma at orchiectomy. The beta-human chorionic gonadotropin level was 70 mIU/mL (reference range, < 5 mIU/mL), and the alpha-fetoprotein level was within the reference range; no metastatic lesions were observed above the diaphragm, indicating stage IIb (bulky), T1N3M0. The patient was referred for 4 cycles of cisplatin-based chemotherapy.
-
Testicular seminoma. This scrotal ultrasound of a 37-year-old man with a painless mass in his right testis shows a right testis with hypoechoic solid masses compared to the homogeneous, more hyperechoic, healthy left testis. Levels of serum beta-human chorionic gonadotropin and alpha-fetoprotein were within the reference range, and the metastatic workup findings were negative. Histopathology showed a pure seminoma. Metastatic workup showed no nodal or distant spread, T1N0M0 stage I. After orchiectomy, the patient underwent adjuvant external beam radiotherapy to the para-aortic nodes. At a 3-year follow-up study, the patient is disease free and has a greater than 95% chance of remaining disease free.
-
Testicular seminoma. This is a classic seminoma at low power. Uniform tumor cells are observed with mild inflammatory response (lymphocytes). Other seminoma findings not seen could include a fibrovascular stroma, syncytiotrophoblastic cells, and multinucleated histiocytes.
-
This is a classic testicular seminoma, high-power view, from a 37-year-old man with a painless mass in his right testis. Levels of serum beta-human chorionic gonadotropin and alpha-fetoprotein were within the reference range, and the metastatic workup findings were negative. Histopathology showed a pure seminoma. Metastatic workup showed no nodal or distant spread, T1N0M0 stage I. After orchiectomy, the patient underwent adjuvant external beam radiotherapy to the para-aortic nodes. At a 3-year follow-up study, the patient is disease free and has a greater than 95% chance of remaining disease free. See related image for a scrotal sonogram of this patient. Note here that tumor cells are uniform, have abundant clear cytoplasm, a large centrally located nucleus, and a variable mitotic pattern.
Tables
pTx |
Primary tumor cannot be assessed |
p0 |
No evidence of primary tumor |
pTis |
Germ cell neoplasia in situ |
pT1 |
Tumor limited to the testis without lymphovascular invasion |
| pT1a | Tumor smaller than 3 cm |
| pT1b | Tumor 3 cm or larger |
pT2 |
Tumor limited to the testis and epididymis with lymphovascular invasion OR |
Tumor invading hilar soft tissue or epididymis or penetrating viceral 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 |
Nx |
Nodes not assessed |
N0 |
No regional lymph node metastasis |
N1 |
Lymph node mass or multiple lymph node masses ≤ 2 cm in greatest dimension |
N2 |
Lymph node mass or multiple lymph node masses >2 cm but ≤ 5 cm in greatest dimension |
N3 |
Lymph node mass >5 cm in greatest dimension |
pN0 |
No evidence of tumor in lymph nodes |
pN1 |
Lymph node mass ≤ 2 cm in greatest dimension |
≤ 5 nodes positive |
|
pN2 |
Lymph node mass >2 cm but < 5 cm in greatest dimension |
>5 nodes positive |
|
Evidence of extranodal extension of tumor |
|
pN3 |
Lymph node mass >5 cm in greatest dimension |
M0 |
No evidence of distant metastases |
M1a |
Nonregional nodal or pulmonary metastases |
M2b |
Nonpulmonary visceral metastases |
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 |
< 5,000 |
and |
< 1,000 |
S2 |
1.5-10 x N |
or |
5,000-50,000 |
or |
1,000-10,000 |
S3 |
>10 x N |
or |
>50,000 |
or |
>10,000 |
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 |
N1-3 |
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 |
