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Histology of testicular cancer

Germinal cell tumors

Due to the frequent appearance of several tumor type components in germinal tumors of the testis, the pathologist must study several microscopic sections. The correct tumor classification types and appearance in the actual tumor should be described. This is necessary in order to determine the optimal therapy.

Pure seminomas account for about 50% of all germinal cell tumors of the testis and are usually easily recognizeable by a pathologist. The other tumor types are more difficult to diagnose and more experience is necessary. These tumors are embryonal carcinoma, yolk sac tumor (endodermal sinus tumor), choriocarcinoma, or teratoma. Immunohistochemistry is often helpful in diagnosing the different types of germinal cell tumors.

The non-seminomatous tumor is are of a mixed tumor type where one part is seminoma. If non-seminomatous and seminomatous tumors coexist, the patient is treated according to the most malignant tumor type.

Since spread to abdominal lymph nodes is frequent, ultrasonography and/or radiographic examination is mandatory. When suspicious retroperitoneal  lymph nodes are detected, core biopsy or fine needle biopsy should be performed. An experienced cytopathologist can easily diagnose seminoma metastasis in fine needle aspiration smears. Primary germinal tumors of testis are diagnosed through fine needle aspiration of lymph node metastasis especially from retroperitoneum.

Testicle with seminoma. Click to enlarge. Photomicrograph of seminoma. Click to enlarge.

Intratubular germinal cell neoplasia of unclassified type (IGCNU)

IGCNU are atypical germinal cells with abundant vacuolated cytoplasm and large irregular nuclei with distinct nucleoli situated in the seminal tubules. These lesions are considered precursors to germinal cell tumors

Seminoma

Seminoma is a germinal cell tumor composed of uniform cells with glycogen-rich cytoplasm and large irregular nucleus with one or several distinct nucleoli and marked cell boundaries. Seminoma accounts for 50% of all testicular germinal cell tumors. They seldom occur in childhood, young adults, or in patients over 70 years of age. Seminoma metastasis can be diagnosed by fine needle biopsy because of its typical appearance in smears.

Non-seminomatous tumors

Non-seminomatous tumors account for 50% of all testicular germinal cell tumors. Endodermal sinus tumors and teratomas are seen in childhood and have a different clinical progress than in adults.

Embryonal carcinoma 

Embryonal carcinoma is the next most common testicular germinal cell tumor. These tumor cells are large with atypical nuclei and can grow in solid sheets,  as glands, or in a papillary fashion.

Yolk sack tumor (Endodermal sinus tumor)   

Yolk sac tumors usually present with a loose stroma and a component similar to embryonal carcinoma.  This tumor type can demonstrate different growth patterns, sometimes with differentiation towards liver and intestinal tissue. In children, this tumor appears as a single tumor type, while in adults it is part of a mixed tumor. Yolk sac tumors produce alpha fetoprotein AFP that can be detected and measured in serum, often in very high concentrations. AFP can also be detected in tumor sections by immunohistochemistry.

Teratoma

Teratoma is the next most common testicular tumor in childhood where it is considered benign. In adults, teratomatous tumors are always malignant.

Teratomas consist of different types of tissue and imitate fetal or more mature tissues. Immature components are often neuroectodermal or mesenchymal tissue, while more mature tissue is often cystic with epithelial differentiation or consists of smooth muscle, connective tissue, or cartilage. Since most teratoma consists of a mixture of tissues, the old separation into mature and immature types has been abandoned.
The different tissue components in teratoma can develop into secondary malignancies of the so-called somatic type (earlier “malignant transformation”). An example is development of squamous cell carcinoma from the skin-differentiated part of a teratoma.

Choriocarcinoma

Choriocarinoma is part of a testicular germinal cell tumor in 25% of tumors in adults. It very seldom appears as the single tumor component. Choriocarcinoma is almost never seen in childhood. This tumor produces HCG that can be detected in blood and also in histological sections by means of immunhistochemistry.

Microscopically, there are two types of cells: cyto- and syncytiotrophoblasts. The presence of syncytiotrophoblasts alone is not enough to confirm the diagnosis of choriocarcinoma. These tumors often show necrosis and vascular invasion.

Spermatocytic seminoma

This tumor was earlier believed to be a variant of seminoma, but is now considered to be a separate tumor type. Spermatocytic seminomas account for 1–2% of all germinal cells tumors of the testis and are only seen in adult men, usually older then 50 years.  Microscopically, the tumor cells are polymorphous and surrounded by a myxoid stroma. Spermatocytic seminomas very seldom metastasize, therefore, an orchiectomy is the only necessary treatment, even when the tumor is large. Development of sarcomas have been reported when spermatocytic seminomas have been left untreated for long time.

Sex cord-stromal tumors

There are several different tumor types in this group, but all of them are rare. Only a few of the most common are presented. The tumor often consists of immature tissue without tubulus, groups of leydig cells, or other gonadal stroma cells.

Leydig cell tumor    

These tumors originate from Leydig cells. They account for 1–3% of all testicular tumors and can sometimes produce hormones. Most of these tumors are benign and can be treated by local resection. Malignant transformation occurs in 10% and is related to increased size (> 5cm), increased cellular atypia, increased cell proliferation, necrosis, vessel invasion, and DNA aneuploidy

Sertoli cell tumor

< 1% of testicular tumors. Malignant variants are very rare.

Granulosa cell tumor

Granulosa cell tumors of the testis are microscopically identical to granulosa cell tumors of the ovary. This tumor is extremely rare in adult men, but a juvenile type accounts for 6% of testis tumor in childhood.

Gonadoblastoma

This tumor consists of two cell types: large germinal cell-like seminoma cells and small granulosa-like or sertoli cells. Cells looking like leydig cells or luteinized cells can also occur.

Gonadoblastoma (GB) is seen in individuals with mixed gonad dysgenesis associated with cryporchism, hypospadia, gynecomastia, or female internal genitalia. The risk of developing GB in gonad dysgenesis is about 15-25%. Gonadoblastoma has high a risk of developing germinal cell tumors. GB seldom occurs in phenotypical and genotypical males.

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