eMedicine Specialties > Oncology > Carcinomas of the Genitourinary Tract
Testicular Cancer: Differential Diagnoses & Workup
Updated: Jul 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
| Abdominal Hernias | Orchitis |
| Epididymitis | Spermatocele |
| Hydrocele | Testicular Torsion |
| Lymphoma, Non-Hodgkin | Varicocele |
Other Problems to Be Considered
Epididymo-orchitis
Hematoma
Leukemia
Metastasis from other cancers such as lung cancer, melanoma, and prostate cancer
Syphilitic gumma
Trauma
Tuberculosis and other testicular infections
Workup
Laboratory Studies
The workup of patients with suspected testicular cancer includes a complete history and physical examination. Blood should be obtained for a chemistry profile including lactate dehydrogenase (LDH), complete blood count, and serum tumor markers including alpha fetoprotein (AFP), and the beta subunit of human chorionic gonadotropin (beta-hCG).
Serum levels of AFP and/or beta-hCG are elevated in approximately 80% to 85% of patients with nonseminomatous germ cell tumors (NSGCTs), even when nonmetastatic. Patients with pure seminoma may have elevated levels of beta-hCG but do not have elevated AFP levels. If AFP is elevated in patients with pure seminoma then the presence of an NSGCT component should be considered.
Elevation of serum beta-hCG and AFP levels, alone or in combination, is not sufficiently sensitive or specific to establish the diagnosis of testicular cancer in the absence of histologic confirmation, although markedly elevated levels are rarely found in normal individuals. However, AFP, beta-hCG, and LDH levels are vital in the evaluation and management of patients with testicular cancers. They are used for determining diagnosis, staging, and prognosis and for following response to therapy. Obtaining levels of AFP, beta-HCG, and LDH in patients in whom testicular cancer are suspected is mandatory prior to treatment, as is monitoring of these levels during and after treatment.
- Serum alpha-fetoprotein
- Secretion is restricted to nonseminoma.
- Reference adult concentration is <10 ng/mL.
- Serum half-life is 4-5 days.
- Concentrations above 10,000 ng/ml are seen exclusively in germ cell tumor and hepatocellular carcinoma.
- May be elevated in patients with hepatic dysfunction, hepatitis, cirrhosis, and drug or alcohol abuse.
- Beta-human chorionic gonadotropin
- Increased levels of beta-HCG can be found in either seminoma or nonseminoma.
- Serum half-life is 18-36 hours.
- Patients with high levels of beta-HCG may experience nipple tenderness or gynecomastia.
- Serum beta-hCG concentrations above 10,000 mIU/mL are seen exclusively in germ cell tumor.
- Elevated levels may also be seen in patients with trophoblastic differentiation of a lung or gastric primary cancer or with hypogonadism .
- False positive elevations may result from marijuana use.
- Lactate dehydrogenase
- LDH has independent prognostic significance. Increased levels reflect tumor burden, growth rate, and cellular proliferation.
- Levels are elevated in 30% to 80% of patients with pure seminoma and 60% of patients with nonseminomatous tumors.
- LDH is not a sensitive or specific indicator of disease recurrence and therefore is not a useful serum marker for posttreatment surveillance.
Imaging Studies
Testicular ultrasonographyUltrasound can distinguish intrinsic from extrinsic testicular lesions and can identify masses within testes. A cystic or fluid-filled mass is unlikely to represent malignancy. Seminomas appear as well-defined hypoechoic lesions without cystic areas, while nonseminomatous germ cell tumors (NSGCTs) are typically nonhomogeneous hyperechoic lesions with calcifications, cystic areas, and indistinct margins. Ultrasound is not reliable in local tumor staging.
Other radiographic imaging
Once the diagnosis of testicular cancer is made, a high-resolution computed tomography (CT) scan of the abdomen and pelvis and a chest x-ray are ordered as part of the initial staging workup. Chest CT is recommended if the chest x-ray is abnormal, or if metastatic disease in the thorax is strongly suspected clinically.
Magnetic resonance imaging (MRI) of the abdomen and pelvis or scrotum usually adds little to the information obtained by CT scan and ultrasound. MRI of the brain and a bone scan are performed if brain and bone metastases are suspected.
Because of frequent false negative results positron emission tomography (PET) scans is of limited utility in the initial staging of patients with testicular cancers. However, PET scanning is gaining a significant adjunctive role in the evaluation of posttherapy residual masses. PET scans are negative in teratoma; therefore, PET scans could be used in some cases of nonseminoma.
Lymphangiograhy is currently rarely used to evaluate microscopic nodal involvement.
Procedures
Radical inguinal orchiectomy and r etroperitoneal lymph node dissection
- Patients with a suggestive testicular mass, abnormal ultrasonographic findings, or both should undergo a radical inguinal orchiectomy. Radical inguinal orchiectomy is the definitive procedure to permit histologic evaluation of the primary tumor and to provide local tumor control. In patients with disseminated germ cell tumor, because of the incomplete penetration of the chemotherapeutic agent to the testes, orchiectomy must be performed sooner or later.
- Biopsy of a suggestive testicular lesion is not recommended.
- Transscrotal orchiectomies are contraindicated, as they have been associated with local recurrence and spread to inguinal lymph nodes.
- Retroperitoneal lymph node dissection (RPLND) is the gold standard and the only reliable method to identify nodal micrometastases and provide accurate pathologic staging of the retroperitoneal disease. Both the number and size of involved retroperitoneal lymph nodes have prognostic importance.
- In patients with early-stage nonseminoma, RPLND should be considered following radiographic evaluation of the retroperitoneum and radical inguinal orchiectomy. The transabdominal approach is technically more difficult but poses a lower risk of small bowel obstruction and requires a shorter hospital stay.
Histologic Findings
Cellular Classification
Approximately 95% of testicular tumors are germ cell tumors. These are divided into two types: pure seminoma (no nonseminomatous element present) and nonseminomatous germ cell tumors. Less than 50% of malignant testicular germ cell tumors are of a single cell type; roughly 50% of these are seminomas. Determining the cell type of these tumors is important for estimating the risk of metastasis and the response to chemotherapy.
The World Health Organization uses following histologic classification of malignant testicular germ cell tumors.
1. Intratubular germ cell neoplasia, unclassified.
2. Malignant pure germ cell tumor (showing a single cell type):
A. Seminoma
B. Embryonal carcinoma
C. Teratoma
D. Choriocarcinoma
E. Yolk sac tumor
3. Malignant mixed germ cell tumor (showing more than one histologic pattern):
A. Embryonal carcinoma and teratoma with or without seminoma.
B. Embryonal carcinoma and yolk sac tumor with or without seminoma.
C. Embryonal carcinoma and seminoma.
D. Yolk sac tumor and teratoma with or without seminoma.
E. Choriocarcinoma and any other element.
4. Polyembryoma
Seminoma
- In addition to pure seminomas, which constitute roughly 50% of pure germ cell tumors, a seminomatous component is present in 20% of mixed germ cell tumors. Serum tumor markers are usually at normal levels, but if syncytiotrophoblastic giant cells are present, beta-hCG may be elevated.
- Spermatic seminomas are a variant of seminoma that differ in their clinical characteristics.They generally occur in older men (>60 years) and rarely metastasize without sarcomatous differentiation. They do not occur as part of mixed germ cell tumor and do not contain an isochromosome 12p.
Nonseminoma
- Embryonal carcinomas constitute about 2% of all testicular germ cell tumors but are the histological type in 85% of mixed germ cell tumors. They have large pleomorphic cells with different architectural patterns.
- Teratomas are part of the mixed germ cell tumor and are generally benign but have the potential for metastasis. They have elements from all three germ layers: ectoderm, endoderm, and mesoderm. In patients with residual disease after chemotherapy, teratoma is found in approximately 45% of resected specimens.
- Choriocarcinomas are the least common type of nonseminoma but are very aggressive. Widespread hematological metastasis can occur very early in the disease course; the retroperitoneum may be spared. Choriocarcinomas are associated with increased levels of beta-hCG.
- Yolk cell tumors, also called endodermal sinus tumor, are the most common testicular tumor in infants and young children. In adults, pure yolk cell tumors are rare, but yolk cell elements are found in approximately 40% of mixed germ cell tumors. Yolk cell tumors are associated with elevated alpha fetoprotein levels but they do not produce beta-hCG.
Mixed germ cell tumors (ie, those containing two or more germ cell types) constitute approximately one third of testicular cancer. Mixed germ cell tumor behave like nonseminomas. The average age at diagnosis is older than 30 years.
Staging
Staging for testicular cancer follows the TNM (tumor, node, metastasis) system:
- Primary tumor (pT) – The extent of primary tumor is classified after radical orchiectomy
- pTX – Primary tumor cannot be assessed (if radical orchiectomy has not been performed, Tx is used)
- pT0 – No evidence of primary tumor (eg, histologic scar in testis)
- pTis – Intratubular germ cell neoplasia (carcinoma in situ)
- pT1 – Tumor limited to the testis and epididymis without vascular/lymphatic invasion, or tumor invasion into the tunica albuginea but not the tunical vaginalis
- pT2 – Tumor limited to the testis and epididymis with vascular/lymphatic invasion, or tumor extending through the tunica albuginea with involvement of the tunica vaginalis
- pT3 – Tumor invades the spermatic cord with or without vascular/lymphatic invasion
- pT4 – Tumor invades the scrotum with or without vascular/lymphatic invasion
- Regional lymph nodes – Clinical (N) or pathologic (pN) staging
- NX or pNX – Regional lymph nodes cannot be assessed
- N0 or pN0 – No regional lymph node metastasis
- N1 or pN1 – Metastases with a lymph node mass 2 cm or less in greatest dimension; or multiple lymph nodes, none more than 2 cm in greatest dimension
- N2 or pN2 – Metastases with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or multiple lymph nodes, any one mass greater than 2 cm but not more than 5 cm in greatest dimension.
- N3 or pN3 – Metastases with a lymph node mass more than 5 cm in greatest dimension
- Distant metastasis (M)
- MX – Distant metastasis cannot be assessed
- M0 – No distant metastasis
- M1 – Distant metastasis
- M1a – Nonregional nodal or pulmonary metastasis
- M1b – Distant metastasis other than to nonregional lymph nodes and lungs.
American Joint Committee on Cancer (AJCC) Stage Groupings
The AJCC stage groupings use both TNM staging and serum tumor marker levels. The designation SX indicates that markers were unavailable or not performed; S0 indicates normal levels. The table below defines other S categories.
Table. Serum Tumor Markers
Open table in new window
Table
Stage | LDH | HCG (mIU/mL) | AFP (ng/mL) |
S1 | <1.5 times normal | <5,000 | <1,000 |
S2 | 1.5-10 times normal | 5,000-50,000 | 1,000-10,000 |
S3 | >10 times normal | >50,000 | >10,000 |
Stage | LDH | HCG (mIU/mL) | AFP (ng/mL) |
S1 | <1.5 times normal | <5,000 | <1,000 |
S2 | 1.5-10 times normal | 5,000-50,000 | 1,000-10,000 |
S3 | >10 times normal | >50,000 | >10,000 |
LDH=lactate dehydrogenase; HCG=beta human chorionic gonadotropin; AFP=alpha fetoprotein.
AJCC stage groupings are as follows6 :
- Stage 0
- pTis, N0, M0, S0
- Stage I
- pT1–4, N0, M0, SX
- Stage IA
- pT1, N0, M0, S0
- Stage IB
- pT2, N0, M0, S0
- pT3, N0, M0, S0
- pT4, N0, M0, S0
- Stage IS
- Any pT/Tx, N0, M0, S1–3
- Stage II
- Any pT/Tx, N1–3, M0, SX
- Stage IIA
- Any pT/Tx, N1, M0, S0
- Any pT/Tx, N1, M0, S1
- Stage IIB
- Any pT/Tx, N2, M0, S0
- Any pT/Tx, N2, M0, S1
- Stage IIC
- Any pT/Tx, N3, M0, S0
- Any pT/Tx, N3, M0, S1
- Stage III
- Any pT/Tx, any N, M1, SX
- Stage IIIA
- Any pT/Tx, any N, M1a, S0
- Any pT/Tx, any N, M1a, 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
Used with the permission of the American Joint Committee on Cancer (AJCC), Chicago, Illinois.
Risk Classification
Good- risk nonseminoma
- Testicular or retroperitoneal primary tumor, and
- No nonpulmonary visceral metastases, and
- Good markers; all of:
- Alpha-fetoprotein (AFP) < 1,000 ng/mL, and
- Human chorionic gonadotropin (hCG) < 5,000 IU/mL (1,000 ng/mL), and
- Lactate dehydrogenase (LDH) < 1.5 times the upper limit of normal
Intermediate- risk nonseminoma
- Testicular or retroperitoneal primary tumor, and
- No nonpulmonary visceral metastases, and
- Intermediate markers; any of:
- AFP 1,000 to 10,000 ng/mL, or
- hCG 5,000 IU/L to 50,000 IU/L, or
- LDH 1.5 to 10 times the upper limit of normal
Poor-risk nonseminoma
- Mediastinal primary, or
- Nonpulmonary visceral metastases, or
- Poor markers; any of:
- AFP > 10,000 ng/mL, or
- hCG > 50,000 IU/mL (10,000 ng/mL), or
- LDH > 10 times the upper limit of normal
Intermediate-risk seminoma
Poor-risk seminoma
- No patients are classified as poor prognosis.
More on Testicular Cancer |
| Overview: Testicular Cancer |
 Differential Diagnoses & Workup: Testicular Cancer |
| Treatment & Medication: Testicular Cancer |
| Follow-up: Testicular Cancer |
| References |
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Further Reading
Keywords
testicular cancer symptoms, testicular cancer diagnosis, testicular cancer treatment, germ cell tumors, GCT, seminoma, embryonal carcinoma, teratoma, choriocarcinoma, yolk sac tumor
