Testicular Tumors

SERTOLI CELL TUMOR

This hormonally silent benign tumor of the testicle displays a calcification and growth of cells arranged in trabeculae that form cordlike structures and tubules.

TERATOMA

This testicular pathology has various cellular and organoid components to it. It can occur at any age from infancy to adult life; tumors tend to be large and heterogenous.

1. Mature teratomas 2. Choriocarcinomas 3. Yolk sac tumors or endodermal sinus tumors 4. Embryonal Carcinoma

While Germ cells can divide into seminomas, they can further divide into other types of germ cell tumors. Name them.

Leydig tumors are hormonally ACTIVE SERTOLI tumors are hormonally SILENT

While Leydig and Sertoli cell tumors are both benign sex cord tumors in the testicle, what is the key difference between them?

These TFs are associated with pluripotentiality and are expressed in normal embryonic stem cells As these cells should be maturing and start to differentiate they can maintain the pluripotentiality and that is why you can have them dividing along a bunch of otherwise somewhat primitive cell lines

Why is the ability to retain transcription factors OCT3 and 4 and NANOG important for germ cell tumors?

EMBRYONAL CARCINOMA

This mass is mainly seen in the 20-30yo age group and is more aggressive than seminomas, but smaller. Small and lethal tumor that has a "Variegated" cut surface with areas of hemorrhage and necrosis so some areas may be hemorrhagic and necrotic while others may be cystic.

intratubular germ cell neoplasia (ITGCN)

Activating mutations of c-KIT is present in seminomas as well as _________.

EMBRYONAL CARCINOMA

Cells growing in an alveolar or tubular pattern sometimes with papillary convolutions with foci of hemorrhage and necrosis is characteristic of what testicular tumor?

1) lymphatically -> para-aortic nodes, mediastinum, clavicular nodes 2) hematogenously -> LUNGS, LIVER, BRAIN *Histology of mets may be different from the original testicular lesion*

Clinically, germ cell tumors result in painLESS enlargment of the testis and can spread through lymphatics or hematogenously. To what sites of does a germ cell tumor spread via those two mechanisms? What is important to regarding histology of metastasis?

*Stage I*- Tumor confined to testis, epididymis or spermatic cord *Stage II*- Distant spread confined to retroperitoneal nodes below the diaphragm *Stage III*-Metastases outside the retroperitoneal nodes or above the diaphragm

Describe the 3 stages of germ cell tumor progression.

SEMINOMATOUS

Due to the *tan, white, large, bulky* lobulated appearance of this testicular tumor without areas of hemorrhage or necrosis, it is safe to say this is a ______________ tumor.

LD is elevated because this is a sign that we need oxygen. Cancer cells in general will perform more anaerobic respiration and LD gets released during tissue damage, it is a marker of common injuries and disease. Lactate dehydrogenase catalyzes the interconversion of pyruvate and lactate with concomitant interconversion of NADH and NAD+. It converts pyruvate, the final product of glycolysis, to lactate when oxygen is absent or in short supply

Germ cell tumors may secrete biomarkers like hCG and AFP, why do we also see lactate dehydrogenase being secreted?

Anaplastic is more cellular with nuclear irregularity, more frequent mitoses and tumor giant cells. *Does not mean anaplastic has worse prognosis!*

How does an anaplastic seminoma differ from regular one?

Distinctly different histologically and clinically: *clinically:* appears later in life >65yo; slow growing tumor with no metastasis and excellent prognosis *Histologically:* lacks lymphocytes, granulomas, syncitiotrophoblasts, extra-testicular sites of origin or admixture with other germ cell tumors and association with ITGCN --> Consists of 3 cell types: small, medium, giant cells. *Grossly:* soft gray cut surface sometimes having MUCOID cysts

How is a spermatocytic seminoma different from a regular seminoma?

Choriocarcinoma

If a patient tests positive for hCG and the tumor has hemorrhage and necrosis, the tumor is a ____________.

SPERMATOCYTIC SEMINOMA

In this picture it is clear to see a mucoid cysts. This tumor classically present later in life >65yo, is not associated with ITGCN, has an excellent prognosis and contains 3 cell types with expression of eosinophilic cytoplasm and scattered giant cells.

Teratomas and Yolk sac tumors

In what two tumors are pure forms rare in adulthood, common in infancy, with the adult forms being mixed with other germ cell tumors?

C) MIXED

Majority of testicular tumors are: a) seminomatous b) nonseminomatous c) mixed d) sex cord

15-34

Most testicular tumors arise in what age group of men?

LEYDIG cell tumor

REINKE crystals are rod shaped crystals present in what tumor of the testicle?

LEYDIG CELL TUMOR

This golden brown tumor with homogenously cut surface often will lead to testicular swelling with the initial sign often gynecomastia or sexual precocity.

*Embryonal Carcinoma*

This tumor has a very diffuse pattern of growth. It lacks well formed glands. Cell borders are indistinct with marked variation in cell and nuclear shape. This tumor can be identified via the following biomarkers: (+) OCT3/4, PLAP, CD30 and Cytokeratin (-) c-KIT

*TeratoCarcinoma* - mix of teratoma and embryonal carcinoma

This tumor is a mixture of two non-seminomatous tumors. Grossly, we see features of multicystic areas, solid, hemorrhagic and necrotic foci.

ANAPLASTIC SEMINOMA

This tumor is very cellular with nuclear irregularity, frequent mitoses and tumor giant cells.

YOLK SAC tumor

This tumor will have *eosinophilic, hyaline-like globules* present within and outside of the cytoplasm that contain *alpha-fetoprotein (AFP) and alpha 1 antitrypsin.*

1) Cryporchidism 2) hypospadius 3) poor sperm quality

What 3 things comprise the testicular genesis syndrome and contribute to the formation of testicular cancer?

1) *Smaller cells* - narrow rim of eosinophilic cytoplasm 2)*Medium sized cells* - round nucleus with *eosinophilic cytoplasm* 3) *Scattered giant cells*

What are the 3 cell populations seen in a spermatocytic seminoma?

c-KIT, PLAP (placental alkaline phosphatase), OCT 4, hCG

What are the 4 key markers for seminoma?

Sheets/nests of uniform cells dividied into lovule by fibrous septate with a moderate amount of lymphocytes. *Cells are large with clear cytoplasm due to the build up of glycogen.*

What are the key microscopic findings for a seminoma?

Lesions called *intratubular germ cell neoplasia (ITGCN)*

What do most germ cell tumors arise from ?

It is believed that germ cell tumors arise from ITGCNs because these lesions consists of *atypical GERM cells* with large nuclei and clear cytoplasm - the same morphology as a seminomatous germ cell tumor. It is also noted that ITGCN shares some of the same genetic alterations, such as isochromosome 12 and activating mutations in c-KIT

What evidence is there that germ cell tumors likely arise from intratubular germ cell neoplasia (ITGCN)?

Gain of additional copies of the *short arm of chromosome 12*

What genetic alterations found in germ cell tumors are also found in ITGCN that is also found in invasive tumors?

CRYPTORCHIDISM - failure of testes to descend

What is an important risk factor for testicular tumors that is surgically correctable and should be readily identified in young boys?

BIOPSY b/c basically all testicular tumors are malignant, so if you biopsy there's a chance you may seed that tumor and allow it the opportunity to spread

What is one thing you will never do if you suspect a testicular tumor? Why?

Orchiectomy = removal of the testicles Tx for testicular tumors 1. First you do the orchiectomy or chemotherapy and hopefully see these tumor markers decrease a. Tumor markers should drop pretty significantly after treatment 2. If you see the numbers creeping up again it may be indicative of a metastasis somewhere

What is orchiectomy and what is it used for?

Seminomas are large and tan with NO areas of necrosis and hemorrhage NON-seminomas have hemorrhage and necrosis

What is the key gross difference between seminomas and non-seminamatous tumors?

ATYPICAL Germ cells with large nuclei and clear cytoplasm, twice the size of normal germ cells

What is the key histologic feature of a germ cell tumor?

LYMPHOMA - usually diffuse large B cell type

What is the most common cause of a testicular tumor in a man after age 60?

YOLK SAC/endodermal sinus tumor

What is the most common testicular cancer in infants and children, but has a good prognosis in this population?

Tumor cells in general use anaerobic respiration to survive. Because we will be going through lactic respiration, will see higher levels of lactate dehydrogenase.

What is the reason that we can use lactate dehydrogenase as a biomarker for germ cell tumors?

CD117

What special stain could you use to confirm diagnosis of a seminoma?

1) Syncitiotrophoblasts - large irregular cells with abundant eosinophilic vacuolated cytoplasm with *hCG* 2) Cytotrophoblasts- more regular, polygonal shaped cells with distinct borders and clear cytoplasm growing in cords

What two cell types comprise choriocarcinoma? What are the differences between the two? Which one expresses hCG?

Occurs in UTERO and stays dormant until puberty when it may progress into seminomatous or non-seminomatous

When does an intratubular germ cell neoplasia (ITGCN) typically develop?

SEMINOMA

large nuclei, clear cytoplasm, and lymphocytes are the key micro findings in what testicular tumor?

Seminoma

If a patient tests positive for hCG but the tumor does not have hemorrhage and necrosis, the tumor is a ____________.