Pathology of Testes Flashcards
1
Q
Testicular tumors
A
- 2 major types
- Germ cell tumors: seminomas and non-seminomas
- Sex cord-stromal tumors: generally benign
- 95% arise from germ cells which are aggressive and can spread rapidly
2
Q
Germ cell tumors
A
- Occurs most commonly b/w 15-34
- Cause approx. 10% of all cancer deaths
- In the US more common in whites than in blacks
- Testicular genesis syndrome: cryptochordism, hypospadius, and poor sperm quality
- Cryptorchidism: is an important risk factor for testicular tumors
3
Q
Seminomatous tumors
A
- Germ cell tumor
- Tumors are composed of cells that resemble primordial cells or early gonocytes
4
Q
Non-seminomatous tumors
A
- Germ cell tumors
- Tumors are composed of undifferentiated cells that resemble embryonic stem cells but the malignant cells can differentiate into various lineages generating yolk sac tumors, choriocarcinomas and teratomas
- Germ cell tumors may have a single tissue component but in ~60% of cases tumors contain mixtures of seminomatous components and non-seminomatous components
5
Q
Germ cell tumors histological characteristics
A
- Lesion consists of atypical germ cells w/ large nuclei and clear cytoplasm which are about twice the size of normal germ cells
6
Q
Germ cell tumors genetic mutations
A
- Cell retain the expression of the transcription factors OCT3/4 and NANOG which are assoc. w/ pluripotentiality and are expressed in normal embryonic stem cells
- ITGCN share some of the genetic alterations found in germ cell tumors such as a gain of additional copies of the short arm of chromosome 12 which is a change found in invasive tumors regardless of histologic type
- Activating mutations of c-KIT which are present in seminomas are also present in ITGCN
7
Q
ITGCN
A
- Intratubular germ cell neoplasia; precursor to germ cell tumors
- Most germ cell tumors arise from these lesions
- Believed to occur in utero and to stay dormant until pubery when it may progress into seminomatous or non-seminomatous tumors
- ~50% of males w/ ITGCN develop invasive germ cell tumors within 5yrs after diagnosis
- It may hold true that all pts w/ ITGCN eventually develop invasive tumors
8
Q
Chromosome mutation that plays a role in a lot of testicular tumors
A
- Chromosome 12 mutations
9
Q
Seminomas
A
- Most common type of germ cell tumor making up approx. 50% of these tumors
- Peak incidence in 3rd decade
- Contain an isochromosome 12p
- Express OCT3/4 and NANOG markers
- 25% of tumors have c-KIT activating mutations
- Bulky masses may be 10x the size of the normal testis
- Homogenous, white, lobulated cut surface usually w/o hemorrhage or necrosis
- Approx. 15% contain syncytiotrophoblasts w/ elevation of serum human chorionic gonadotropin (HCG) lvls
10
Q
Seminomas histological characteristics
A
- Microscopically the tumor is composed of sheets of uniform cells divided into lobule by fibrous septae containing a moderate amt of lymphocytes
- Seminoma cells are large round to polyhedral w/ a prominent nucleus, a prominent nucleolus, clear cytoplasm and well defined cell borders
- Mitoses vary in freq.
- Cytoplasm contains glycogen
11
Q
Seminoma-nests separated by fibrous septae w/ lymphocytes histology slide
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12
Q
Seminoma-large nuclei, large nucleoli, clear cytoplasm, lymphocytes histology slide
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13
Q
Seminoma staining
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- CD 117
14
Q
Seminoma genetic mutations
A
- Diffusely pos. for c-KIT, OCT4, and placental alkaline phosphatase (PLAP) markers
-
15
Q
Anaplastic seminoma
A
- Has greater cellularity and nuclear irregularity w/ more freq. mitoses, and tumor giant cells but IS NOT assoc. w/ a worse prognosis
16
Q
Seminoma-trophoblastic giant cells histology slide
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17
Q
Spermatocytic seminoma
A
- Distinctly diff. from classic seminoma both histologically and clinically
- Uncommon, about 1-2% of testicular germ cell tumors
- Age of involvement much later in life, usually over the age of 65yrs
- Slow growing tumor that does not cause metastasis w/ an excellent prognosis
- Lakc lymphocytes, granulomas, syncytiotrophoblasts, extra-testicular sites of origin, admixture w/ other germ cell tumors, and assoc. w/ ITGCN
18
Q
Spermatocytic histological appearance
A
- Soft gray surface that sometimes has mucoid cysts
- Contain 3 cell pop., all intermixed
- Medium sized cells most of which have a round nucleus and eosinophilic cytoplasm
- Smaller cells w/ a narrow rim of eosinophilic cytoplasm
- Scattered giant cells
19
Q
Spermatocytic seminoma intratubular growth histology slide
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20
Q
Spermatocytic seminoma-medium cells and giant cells histology slide
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21
Q
Embryonal carcinoma
A
- Seen mostly in the 20-30’s
- More aggressive than seminomas
- Smaller than seminomas and does not usually replace the entire testis
- Mass is variegated and poorly demarcated at the margins
- Contains foci of hemorrhage and necrosis
- Extension to the tunica albuginea into the epididymis or cord often occurs
22
Q
Embryonal carcinoma histological characteristics
A
- Cells grow in an alveolar or tubular pattern sometimes w/ papillary convolutions
- Lack well formed glands w/ basally situated nuceli and apical cytoplasm seen in teratoms
- More undifferentiated lesions may have sheets of cells
- Neoplastic cells have an epithelial apperance are large and anaplastic w/ hyperchromatic nuclei and prominent nucleoli
- Cell borders are indistinct w/ marked variation in cell and nuclear shape
- Mitotic figures and tumor giant cells are common
- Markers: OCT3/4, PLAP, CD30 and cytokeratin
- Neg. for c-KIT
23
Q
Embryonal carcinoma gross appearance image
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- Nodular surface w/ necrosis and hemorrhage
24
Q
Embryonal carcinoma diffuse pattern of growth histology slide
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25
Embryonal carcinoma characteristic cells histology slide
26
Yolk sac tumor
- AKA **endodermal sinus tumor**
- **Most common testicular tumor in infants and children up to 3**
- In the young age grp it has a good prognosis
- In adults a pure yolk sac tumor is rare and is usually mixed w/ embryonal carcinoma
- Tumor is nonencapsulated
27
Yolk sac tumor histological characteristics
- Has a homogenous yellow white mucinous appearance
- Has a lacelike network of medium-sized cuboidal or flattened cells
- Other patterns include papillary structures and solid cords of cells
- In approx. 50% of cases structures resembling endodermal sinuses are seen these are called **Schiller-Duval bodies**
- Present within and outside of the cytoplasm are eosinophilic, hyaline-like globules containing **alpha-fetoprotein (AFP) and alpha one antitrypsin**
28
Schiller-Duval bodies
- Present in ~50% of yolk sac tumors
- Structures resembling endodermal sinuses
- Consist of a mesodermal core w/ a central capillary and a visceral and parietal layer of cells resembling primtive glomeruli
- Central blood vessel surrounded by neoplastic cells w/ a space surrounded by more neoplastic cells
29
Yolk sac tumor histology slide
30
Choriocarcinoma
- Highly malignant tumor
- Rare in its pure form
- Often cause no testicular enlargement and form a small palpable nodule
- Rarely larger than 5cm
- Hemorrhage and necrosis is very common
- Tumors contain 2 cell types: **syncytiotrophoblastic cells and cytotrophoblastic cells**
31
Syncytiotrophoblastic cells
- 1 of 2 types of cells present in choriocarcinomas
- Large w/ many irregular and lobular hyperchromatic nuclei and abundant eosinophilic vacuolated cytoplasm w/ **HCG** in the cytoplasm
32
Cytotrophoblastic cells
- 1 of 2 types of cells present in choriocarcinomas
- More regular, polygonal w/ distinct cell borders and clear cytoplasm growing in cords or masses w/ a single, uniform nucleus
33
Choriocarcinoma histology slide
34
Teratoma
- Has various cellular and organoid components similar to more than 1 germ cell layer
- Can occur at any age from infancy to adult life
- Pure forms of teratoma are common in infancy and children
- In adults pure forms are rare but may have teratomas mixed w/ other germ cell tumors
- Usually large, from 5-10cms
35
Teratoma histological characteristics
- Heterogeneous gross appearance
- Solid and cystic areas
- Composed of cartilage, neuronal tissue, squamous cells, muscle, thyroid tissue
- Elements may be mature resembling adult tissues or immature resembling fetal or embryonal tissue
36
Mature teratoma
- All tissues are well differentiated
37
Immature teratoma
- Immature tissue in the stroma, epithelium, or neural component
38
Teratoma w/ malignant transformation
- Malignancy in derivative of one or more germ cell layers such as squamous cell ca, adenocarcinoma or sarcoma
39
Mature teratoma histology slide
40
Immature teratoma histology slide
41
Teratocarcinoma
- Mixture of teratoma and embryonal carcinoma
- Gross features may include multicystic areas, solid, hemorrhagic and necrotic foci in the areas of embryonal carcinoma
- The teratoma may be mature or immature
- Term is falling into misuse
- Usually designated as a NSGCT listing the relative components
42
Clinical features of germ cell tumors
- Painless enlargement of the testis
- Treatment is orchiectomy
- **Lymphatic spread** to para-aortic nodes, may spread to mediastinum and supraclavicular nodes
- **Hematogenous spread to lungs, liver and brain**
- Histology of metastasis may be different from the original testicular lesion
- Tumors are diagnosed into broad categoreis **seminoma and nonseminomatous germ cell tumors (NSGCTs)**
- Most NSGCTs are more aggressive and have a poorer diagnosis compared to seminomas
43
Germ cell tumor markers
- May secrete biological markers such as **HCG, AFP and lactate dehydrogenase**
- These markers can aid in evaluating tumor masses, staging of tumors, assessing tumor burden, monitoring response to tumor therapy
44
Germ cell tumor treatment
- Prognosis and therapy depend on histologic type and clinical stage
- Seminomas are radiosensitive and remain localized for long periods
- NSGCTs need aggressive chemotherapy
45
Sex cord-gonadal tumors
- Leydig cell tumors
- Sertoli cell tumors
46
Leydig cell tumors
- Can arise at any age but mostly b/w **20-60**
- Most common feature is testicular swelling
- May elaborate androgens and estrogens or corticosteroids
- Initial sign may be gynecomastia or sexual precocity
- Usually \<5cm
**- Most tumors are benign**
- ~10% are invasive
47
Leydig cell tumors histological characteristics
- **Golden brown color** w/ a homogeneous cut surface
- Histologically similar to their normal counterparts, round, polygonal w/ an abundant granular eosinophilic cytoplasm and a round central nucleus
- The cytoplasm has lipid granules, vacuoles or lipofuscin pigment
- **Reinke crystals**: rod shaped crystals
48
Leydig cell tumor histology slide
49
Sertoli cell tumors
- Most present as a testicular mass
- Most are **hormonally silent**
- **Most are benign**
- Less than 10% are malignant
50
Sertoli cell tumor histological characteristics
- Firm, small nodules w/ a homegeneous gray-white cut surface
- Cells arranged in trabeculae that form cordlike structures and tubules
51
Setoli cell tumor histology slide
