Though representing only about 1% of all human neoplasms; testicular tumor is the most common cancer in males of reproductive age group. Evidence suggests an approximate incidence of about 23 % of 15-35 years aged males. The tumors are more common in males aged 15-35 years and the incidence increases with age for unknown reasons.
Testicular tumors have been variously classified based on histology and prognostic outcome. The World Health Organization (WHO) has standardized the pathologic segregation of testicular malignancies.
The WHO taxonomy for testicular tumors is as follows:
|Tumor type||Subsets(if applicable)|
|Germ cell tumor:
Pure form tumors(of single histology)
|Intratubular malignant germ cell tumor(carcinoma in situ)|
(variant: seminoma with syncytiotrophoblastic cells)
(variant: spermatocytic seminoma with sarcoma)
Yolk sac tumor
Teratoma with malignant areas.
|Sex cord/Gonadal Stromal Tumors:
Incompletely differentiated sex cord/gonadal stromal tumors
Tumors of the thecoma/fibroma group
Granulosa cell tumor:
Tumors containing both germ cell and sex cord/gonadal stromal elements:
|Leydig’s cell tumor|
|Sertoli’s cell tumor:
Lipid rich cell
Large cell calcifying
|Ovarian epithelial tumors
|Adult type of granulosa cell tumor
Juvenile type of granulose cell tumor
Mixed germ cell-sex cord/gonadal stromal tumors
|Lymphoid and hematopoietic tumors:||Lymphoma
|Tumors of collecting duct and rete testis||Adenoma
|Tumors of tunica, epididymis, spermatic cord, supporting structures, and appendices||Adenomatoid tumor
Melanotic neuroectodermal tumor
|Soft tissue tumors
Simply put, Testicular tumors are either Germ cell tumors (GCTs) or Non-germ cell tumors (NGCTs). A succinct description of each is as follows:
Germ Cell Tumors (GCTs)
GCTs are the most common of all testicular tumors. The nomenclature follows origin from totipotent germ cells. They account for about 95% of all testicular malignancies and are classified into seminomatous and non-seminomatous types with about 60% being of mixed type. Literature suggests that the only known risk factor for the germ cell tumors (GCTs) is Klinefelter syndrome (47XXY), which is associated with mediastinal nonseminomatous germ cell tumors. This is commonly characterized by their location on the midline plane of the human body and thus may appear anywhere from the pineal gland to the coccyx.
GCTs are the most prevalent solid tumors of males of reproductive age group from 20-34 years and second most common in men age 35-40 years. There is predisposition to GCTs in the Caucasian population.
With equivocal evidence for genetic factors; there is about 2-3% incidence of bilateral tumors.
Study in Norway incidence of GCT is at 0.5 per 1000.000 population per year. This is around 2% of the number of testicular cancers reported.
The incidence of various histologic types of GCTs is as follows:
|Embryonal carcinoma||40%(mixed form); 2-4% pure form|
There are 5 basic types of GCTs which can be tabulated as follows:
|Seminoma: This type of tumor generally occurs in men between the ages of 25 and 55.|
|Embryonal cell carcinoma|
|Yolk sac tumor|
Note that: Seminoma may resemble a yolk sac tumor by forming tubular and microcystic growth patterns.
GCTs arise from totipotent germ cells which undergo further differentiation into extraembryonic and intraembryonic cell types. The origin of the basic types of GCTs can be summarized as follows:
Yolk sac tumors
|Totipotent germ cell|
Yolk sac tumor
|Extraembryonic differentiation of totipotent germ cells|
Various conditions predispose an individual to developing a GCT. These conditions with potential hypotheses and evidence rationalizing this probable relationship can be summarized as follows:
|Testicular atrophy||While the exact role is not yet defined; there are speculations that nonspecific or mumps associated atrophy have probable causal effect in testicular cancer.|
|Trauma||While some call it an incidental finding; or something that brings the scrotal mass to the patient’s notice; there is little evidence to suggest otherwise.|
|Cryptorchidism||About 6-10% of testicular malignancy patients have undescended testes. Evidence attests to about 13 times increased risk of developing cancer in maldescended testis compared to normal. Almost one fourth patients with bilateral cryptorchidism and history of testicular tumor progress to develop a second GCT.|
|Hormonal||Male children of mothers exposed to Diethylstilbestrol and oral contraceptives are prone to develop testicular cancer.|
The most frequent presentation of testicular malignancy is painless unilateral scrotal swelling. Other infrequent symptoms can be summarized as follows:
|Dull aching pain|
|Difficulty in walking|
|Heaviness in scrotum, lower abdomen and perianal region|
About 10% patients present symptoms of metastasis with chronic long standing; often ignored scrotal swelling. These signs must caution the medical personnel to look for the primary etiology whenever relevant. Despite the name, germ cell tumors occur both within and outside the testis. They can be summarized as follows:
|Painless neck swelling||Supraclavicular lymph node metastasis|
|Abdominal discomfort||Retroduodenal metastasis|
|Lumbar back pain||Psoas muscle involvement|
|Back pain, bony pains||Skeletal metastasis|
|Lower extremity edema||Venous obstruction|
Clinical examinations offer few salient features traditionally used to differentiate benign scrotal massed from testicular tumors. Bimanual palpation is the key and the findings can be summarized as follows:
|Palpate the testes||Firm, hard or fixed mass can occasionally be felt.|
|Getting above the swelling||Possible.|
Ultrasonography is the most basic preliminary radiological imaging investigation always performed. Hypoechoic region within the tunica albuginea is of crucial relevance. Other advanced radioimaging tests are of ancillary nature. Their findings can be summarized as follows:
|Abdominal CT||It is most effective in identifying retroperitoneal lymph node involvement. Clear visualization of kidney, ureters, retro-crural space and the para-aortic region is feasible.|
|MR Imaging||Testicular tumors enhance early on MRI and are T2 hypointense.|
|PET scan||It is used to detect radiographic aberrations after chemotherapy. It fails to identify microscopic nodal metastatis.|
|Chest Skiagram||Used to screen the chest in patients with negative abdominal CT findings.|
|Chest CT||Performed in patients with abnormal abdominal CT findings.|
The treatment of GCT is heavily dependent on the stage of the disease. The first step towards staging is to perform orchiectomy to determine the histologic features. Histology and Radiology with Tumor markers assessment whenever relevant; help in ascertaining the correct stage of the disease and developing the most definite management protocol. Most patients with germ cell cancer will need to be treated with combination chemotherapy for at least 3 cycles. The chemotherapy regimen most commonly used in germ cell tumors is called PEB (or BEP), and consists of bleomycin, etoposide, a platinum-based antineoplastic (cisplatin)
The AJCC staging for GCTs is universally followed. Based on four parameters: T for Primary Tumor, N for lymph node status, M for metastasis and S for serum markers status; there are 4 stages defined from stage I for locally contained disease to a progressively increasingly complex grading where stage IV implies distant metastatic illness. AJCC staging details are as follows:
|Primary tumor (T)||pTx: primary tumor cannot be assessed
pT0: no evidence of primary tumor
pTis: intratubular germ cell neoplasia
pT1: tumor limited to the testis and epididymis and no vascular or lymphatic invasion
pT2: tumor limited to the testis and epididymis with vascular or lymphatic invasion or tumor extending through the tunica albuginea with involvement of tunica vaginalis.
pT3: Invasion of the spermatic cord with or without vascular/lymphatic invasion
pT4: Invasion of the scrotum.
|Regional lymph nodes (N)||Nx: Cannot be assessed.
No: No regional lymph node metastasis.
N1: Lymph node mass 2 cm or less in greatest dimension.
N2: Lymph node mass more than 2, less than 5 cm.
N3: Lymph node mass more than 5 cm.
|Distant metastasis(M)||M0: no evidence of distant metastasis.
M1: non regional nodal or pulmonary metastasis.
M2: nonpulmonary visceral metastasis.
|Serum tumor markers(S):
< 1.5 times N
|1.5-10 times N||5000-50,000|
Seminomas tend to spread lymphatically to the para-aortic lymph nodes (versus penile drainage through the inguinal LNs) and nonseminomatous metastasize hematogenously, for example: to the lungs.
Once staged, patient is treated using the following modalities:
|Surgical resection with retroperitoneal lymph node dissection(RPLND)|
|Chemotherapy: Cisplatin based chemotherapy.|
|Radiation: abdominal and pelvic|
The individual tumor types of GCTs can be summarized as follows:
|Seminoma||Seminoma constitutes 35-70% of GCTs. Only 5-10% of tumors are anaplastic with lethal potential; the rest have a very good outcome. Typical morphological appearance resembles “Fried-egg”||Placental ALP(PLAP) is present in about 90% of seminomas.
About 10% patients stain positive for HCG(HCG is from syncytiotrophoblastic cells and does not behave as choriocarcinoma.
|Late metastasis, lymphatics, radiosensitive.
Excellent outcome with good response to radiation and carboplatin based chemotherapy.
The female ovarian tumor “dysgerminoma” is its counterpart.
|Embryonal||Contributing to about 3-6% of GCTs; Embryonal carcinoma is seen in males of age 25-35 years.||Embryonal carcinomas stain positive for CD30, keratin and infrequently to PLAP. HCG positivity is attributed to syncytiotrophoblasts adjacent to EC cells.||Prognosis is not as favorable as seminoma.|
|Yolk sac(EST)||Most prevalent testicular malignancy in pre-pubertal males, especially boys < 3 yrs of age. Schuller-Duval bodies are characteristically seen.||ALP positive in about 90% of these tumors.||Aggressive|
|Choriocarcinoma||Represent about 1-2% of all GCTs.
Trophoblastic cells are appreciated on histology.
|HCG positivity in more than 90% of patients; some also stain for PLAP.||Aggressive associated with hemorrhagic tendency and hyperthyroidism.|
|Teratoma||Teratomas comprise of 2 or more embryonic germ cell layers. They are incriminated in almost one third of childhood GCTs. Childhood teratomas are benign; while adult teratomas are malignant.||Immature form is aggressive||Prognosis is heterogenous depending on the cell lines involved; less favorable compared to Embryonal.|
Other NGCTs are relatively very rare and their clinical characteristics can be summarized as follows:
|Non-germ cell tumors(NGCTs)||Clinical presentation|
|Leydig cell tumor||Golden brown color, contains Reinke crystals (eosinophilic cytoplasmic inclusions) produces androgens or estrogens: leads to gynaecomastia in males, precocious puberty in boys.|
|Sertoli cell tumor||Androblastoma from sex cord stroma|
|Testicular lymphoma||Most common testicular cancer in older men; not a primary cancer; arises from metastatic lymphoma to testes.|
Testicular tumors can be segregated into Germ cell tumors and Non-germ cell tumors based on cell of origin.
Germ cell tumors are divided into seminomatous and non-seminomatous types, whereby seminomatous have very good prognosis and are chemo-radiosensitive.
It is of crucial importance to differentiate between testicular neoplasm and benign scrotal masses.
History, clinical examination and ultrasonography findings often corroborate to form a preliminary diagnosis of testicular neoplasm. Further management depends exclusively on the stage of malignancy; determination of which begins with orchiectomy.
Adjuvant treatment options include Radiation, chemotherapy, surgical resection with RPLND and surveillance.
The correct answers can be found below the references.
1. Which of the following testicular tumor is most common in pre-pubertal males?
- Embryonal tumors
- Yolk sac tumors
- Leydig cell tumors.
2. Which of the following statement is false?
- Most common testicular cancer in older men is lymphoma.
- Yolk sac tumors are positive for ALP.
- Choriocarcinoma stain positive for HCG.
- Teratomas are most sensitive to carboplatin based chemotherapy.
3. Mark the false statement:
- Clinical examination and history suffice to decide about orchiectomy.
- AJCC staging for GCTs determine further management of these tumors.
- Fried egg appearance is seen in seminomas.
- Testicular malignancy can present with bone pains.