Testicular tumors are common and potentially annihilating to the male population. With a brief prologue to testicular tumors; this article focuses on the significant, relevant types of testicular tumors such as Germ Cell Tumors (GCTs) and Non-Germ Cell Tumors (NGCT).Various clinical, patho-physiological and prognostic aspects of the same have been expatiated.

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Testicular Tumor

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 % in 15-35 years aged males.

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:

Precursor lesions

 

Pure form tumors(of single histology)

 

 

 

 

 

 

 

Trophoblastic tumors

 

Teratoma

 

 

Mixed tumors

 
Intratubular malignant germ cell tumor(carcinoma in situ)
Seminoma

(variant: seminoma with syncytiotrophoblastic cells)

Spermatocytic seminoma

(variant: spermatocytic seminoma with sarcoma)

Embryonal carcinoma

Yolk sac tumor

Polyembryoma

Choriocarcinoma
Immature teratoma

Mature teratoma

Dermoid cyst

Teratoma with malignant areas.

 
Sex cord/Gonadal Stromal Tumors:

Pure forms

 

 

 

Incompletely differentiated sex cord/gonadal stromal tumors

Tumors of the thecoma/fibroma group

Mixed forms

Miscellaneous tumors:

Unclassified forms

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

Carcinoid tumors

Adult type of granulosa cell tumor

Juvenile type of granulose cell tumor

Gonadoblastoma

Mixed germ cell-sex cord/gonadal stromal tumors

Unclassified

Lymphoid and hematopoietic tumors: Lymphoma

Plasmacytoma

Leukemia

Tumors of collecting duct and rete testis Adenoma

Carcinoma

Tumors of tunica, epididymis, spermatic cord, supporting structures, and appendices Adenomatoid tumor

Mesothelioma

Adenoma

Carcinoma

Melanotic neuroectodermal tumor

Soft tissue tumors

Unclassified tumors

Secondary tumors

 

Simply put, Testicular tumors are either Germ cell tumors (GCTs) or Non-germ cell tumors (NGCTs). A succinct description of each follows:

Germ Cell Tumors (GCTs)

Introduction

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.

Epidemiology

GCTs are 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 Caucasian population.

With equivocal evidence for genetic factors; there is about 2-3% incidence of bilateral tumors.

The incidence of various histologic types of GCTs is as follows:

Type Incidence
Seminoma 30-60%
Embryonal carcinoma 40%(mixed form); 2-4% pure form
Teratoma 5-10%
Mixed GCT 60%
Pure Choriocarcinoma 1%

Classification

There are 5 basic types of GCTs which can be tabulated as follows:

Seminoma
Teratoma
Choriocarcinoma
Embryonal cell carcinoma
Yolk sac tumor

Pathogenesis

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:

Tumor Origin
Seminoma

Teratoma

Yolk sac tumors

Totipotent germ cell
 
Choriocarcinoma

Yolk sac tumor

Extraembryonic differentiation of totipotent germ cells
 
Teratoma Intraembryonic differentiation

 

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:

Predisposing condition Evidence
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.

Presentation

The most frequent presentation of testicular malignancy is painless unilateral scrotal swelling. Other infrequent symptoms can be summarized as follows:

Infertility
Dull aching pain
Difficulty in walking
Heaviness in scrotum, lower abdomen and perianal region
Acute pain

About 10% patients present with 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. They can be summarized as follows:

Symptom Interpretation
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

Diagnosis

Clinical examination offers 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:

Test Explanation
Transillumination Negative
Fluctuation Negative
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 almost 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:

Diagnostic Test Explanation
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.

Treatment

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.

The AJCC staging for GCTs is universally followed. Based on four parameters: T (Tumor size), 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:

Parameter Subset
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):

 

 

S0:

 

S1:

 

S2:

 

S3:

AFP LDH HCG
 

≤ N

 

≤ N

 

≤ N

 

<1000

 

< 1.5 times N

 

<5000

1000-10,000

 

1.5-10 times N 5000-50,000
>10,000 >10times N >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
Surveillance

The individual tumor types of GCTs can be summarized as follows:

Tumor Characteristics Serum marker Prognosis
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. AFP 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.

Summary

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 as 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.

Review Questions

The correct answers can be found below the references.

1. Which of the following testicular tumor is most common in pre-pubertal males?

  1. Embryonal tumors
  2. Yolk sac tumors
  3. Seminomas
  4. Leydig cell tumors.

2. Which of the following statement is false?

  1. Most common testicular cancer in older men is lymphoma.
  2. Yolk sac tumors are positive for ALP.
  3. Choriocarcinoma stain positive for HCG.
  4. Teratomas are most sensitive to carboplatin based chemotherapy.

3. Mark the false statement:

  1. Clinical examination and history suffice to decide about orchiectomy.
  2. AJCC staging for GCTs determine further management of these tumors.
  3. Fried egg appearance is seen in seminomas.
  4. Testicular malignancy can present with bone pains.
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