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testes path
R-GU
51
Medical
Graduate
10/07/2010

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Term
what are the major types of testicular tumors?
Definition
*germ cell tumors: seminomas and non-seminomas and *sex cord-stromal tumors
Term
where do most testicular tumors arise?
Definition
from germ cells - which are aggressive and can spread rapidly
Term
what demographics are at a higher risk for testicular CA?
Definition
whites between 15-34 yrs old
Term
what % of CA deaths is testicular CA responsible for?
Definition
10%
Term
what is an important risk factor for testicular CA?
Definition
cryptorchidism (undescended testis)
Term
what characterizes the 2 types of germ cell tumors?
Definition
seminomatous: tumors composed of cells that resemble *primordial cells or early gonocytes*. non-seminomatous: tumors 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*.
Term
do most germ cell tumors have a single tissue component, or do they usually contain both seminomatous and nonseminomatous components
Definition
60% of germ cell tumors contain both seminomatous and non-seminomatous components
Term
what lesions do most germ cell tumors arise from?
Definition
*intratubular germ cell neoplasia* (ITGCN), which is believed to occur in utero and remain dormant until puberty when it may progress in to seminomatous and nonseminomatous components
Term
how does intratubular germ cell neoplasia appear?
Definition
cells w/large nuclei, clear cytoplasm that are about 2x the size of normal germ cells
Term
what are some genetic characteristics specific to intratubular germ cell neoplasia?
Definition
many ITGCNs retain the expression of the transcription factors *OCT3/4 and NANOG - which are expressed w/pluripotentiality* and are expressed normally in embryonic stem cells. ITGCNs also feature *additional copies of the short arm of chr 12* (also seen in germ cell tumors and all invasive tumors regardless of histologic type). activating mutations of c-KIT are present in ITGCNs (also seen in seminomas).
Term
what % of males with ITGCN develop invasive germ cell tumors?
Definition
50% of males with ITGCN develop invasive germ cell tumors within 5 yrs of dx. (it is hypothesized that many if not all patients with ITGCN have ability to develop invasive tumors)
Term
which is the most common type of germ cell tumor?
Definition
seminomas - which make up 50% of these germ cell tumors
Term
what characterizes germ cell tumors in terms of incidence, genetics, and morphology?
Definition
peak incidence: 3rd decade. genetics: seminomas contain isochromosome 12p, express OCT3/4 & NANOG, and 25% have c-KIT activating mutations. morphology: seminomas are *bulky masses (~10x size of normal testis) appearing homogeneous, white, w/a lobulated cut surface usually w/o hemorrhage or necrosis.
Term
can a seminoma grow to replace most of the testes?
Definition
yes, and this appears homogeneous w/fibrous septae between lobules and a yellow color indicative of glycogen
Term
how do seminomas appear histologically?
Definition
microscopically seminomas are composed of sheets of uniform cells divided into lobules by fibrous septae containing a *moderate amount 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 frequency and the cytoplasm contains glycogen. (unique appearance)
Term
[image]
Definition
Term
what are biomarkers seminomas can be stained for?
Definition
c-KIT, OCT4, and PLAP (placental alkaline phosphatase)
Term
what % of seminomas contain syncytiotrophoblasts?
Definition
15% of seminomas contain syncytiotrophoblasts which is *accompanied by elevation of serum human chorionic gonadotropin (hCG) levels
Term
can seminomas have granulomatous reactions?
Definition
yes, which are ill-defined
Term
what is an anaplastic seminoma?
Definition
a subtype of seminoma, which has greater cellularity, nuclear irregularity, more frequent mitoses, *tumor giant cells* (looks worse) - but is *not associated with w/worse prognosis.
Term
how would the morphology of a mixed/combined testicular tumor appear?
Definition
a solid area (seminomatous) and a hemorrhagic areas (non-seminomatous)
Term
what is a spermatocytic seminoma?
Definition
a slow growing tumor that does not cause metastasis (excellent prognosis) which lacks: lymphocytes, syncytiotrophoblasts, extra-testicular sites of origin, but it is associated with: admixture w/other germ cell tumors and ITGCN. spermatocytic seminomas are uncommon - about 1-2% of testicular germ cell tumors and are usually seen in pts past 65 yrs old. (distinctly different from the classic seminoma)
Term
what is the morphology of spermatocytic seminomas? what kinds of cells do they contain?
Definition
spermatocytic seminomas have a *soft gray cut surface that sometimes has *mucoid cysts and contains a mix of 3 cell types: *medium sized cells (most w/round nucleus and eosinophilic cystoplasm), *smaller cells (w/a narrow rim of eosinophilic cytoplasm), and scattered *giant cells (not trophoblastic).
Term
how do embryonal CAs compare to seminomas? what demographic are they associated with?
Definition
embryonal CAs are more aggressive than seminomas, but do not usually replace the entire testis. they are seen in 20-30 yr old males.
Term
what is the morphologic appearance of embryonal CAs grossly? what is their macro/micro growth pattern?
Definition
grossly: the cut surface of embryonal CA is variegated, poorly demarcated at the margins and contains foci of hemorrhage and necrosis (unlike homogeneous seminomas). embryonal CA *often extends to the tunica albuginea, the epididymis or cord. cells w/in embryonal CA grow in an alveolar or tubular pattern, sometimes w/papillary convolutions.
Term
how do embryonal CAs appear histologically?
Definition
embryonal CA lacks well-formed glands and cells have nuclei which are *basally situated w/apical cytoplasm (like in teratomas). the neoplastic cells have an epithelial appearance are *large and anaplastic w/hyperchromatic (*dark) and prominent nucleoli. cell borders are indistinct (w/marked variation in cell/nuclear shape) and mitotic figures, giant cells are common. *generally: diffuse pattern of growth.* more undifferentiated lesions may have sheets of cells.
Term
what biomarkers are associated with embryonal CA?
Definition
OCT 3/4, PLAP, CD30, cytokeratin (last 2 not seen in seminomas). embryonal CA is **negative for c-KIT (difference from seminoma)**
Term
who doe the yolk sac tumor usually affect?
Definition
the yolk sac tumor/endodermal sinus tumor is the most common testicular tumor found in infants/children up till 3 yrs old (good prognosis in this age group). in adults, a pure yolk sac tumor is rare and usually mixed w/embryonal CA.
Term
why are yolk sac tumors called such?
Definition
they take on the appearance of the yolk sac
Term
how do yolk sac tumors appear grossly? microscopically?
Definition
grossly: homogeneous yellow, white, mucinous appearance - resembles a small seminoma. microscopically: lace-like w/a network of medium sized cells (cuboidal or flattened). papillary structure and solid cords of cells are also observed.
Term
what are *schiller-duval bodies*? what do they contain? what do they resemble?
Definition
these entities are seen in 50% of yolk sac tumors (not pathognomonic) and consist of a mesodermal core w/a central capillary and visceral parietal layer (resemble primitive glomeruli) and contain *AFP, *alpha 1 antitrypsin, and *eosinophilic hyaline-like globules (may present inside and outside the cytoplasm). schiller-duval bodies may also resemble endodermal sinuses.
Term
how does a schiller duval body appear?
Definition
[image]
Term
what characterizes a choriocarcinoma?
Definition
a *highly malignant tumor, rare in its pure form and usually smaller than 5 cm (often causes no testicular enlargement and only forms a small palpable nodule). hemorrhage and necrosis are common.
Term
what are the 2 cell types seen in choriocarcinoma?
Definition
*synctiotrophoblastic cells: large w/many *irregular and lobular hyperchromatic (dark) nuclei and abundant eosinophilic vacuolated cytoplasm w/hCG (makes sense w/chorioCA) in the cytoplasm and *cytotrophoblastic cells: *more regular, polygonal w/distinct cell borders and clear cytoplasm growing in cords or masses w/a single, uniform nucleus.
Term
how does a choriocarcinoma appear grossly? microscopically?
Definition
grossly: reddish, hyperemic w/hemorrhage. microscopically: 2 cell populations, some are more anaplastic and blend in with one another (syncytiotrophoblastic) while others are more clear cut with well defined cell membranes and borders (cytotrophoblastic).
Term
what characterizes teratomas found in the testes?
Definition
teratomas have various cellular and organoid components similar to more than one germ cell layer. they may occur at any age, though pure forms of teratoma are more common in infancy and children and in adults teratomas are more commonly mixed w/other germ cell tumors.
Term
what characterizes teratomas morphologically?
Definition
teratomas are usually large ~5-10 cms, w/a heterogeneous gross appearance of solid and cystic areas and composed of cartilage, neuronal tissue, squamous cells, muscle, and thyroid tissue. the elements may be mature (resembling adult tissue) or immature (resembling fetal/embryonal tissue).
Term
what characterizes testicular teratomas w/mature and immature features? what characterizes teratomas w/malignant transformation?
Definition
mature teratoma: all tissues are well differentiated. immature teratoma: teratomas w/immature tissue in the stroma, epithelium, or neural component. teratoma w/malignant transformation: malignancy in derivative of one or more germ cell layers, such as SCC adenoCA or sarcoma (mostly benign tissue w/a neoplasm included).
Term
what is a teratocarcinoma? how does it appear grossly?
Definition
a mixture of a teratoma and embryonal carcinoma. gross appearance: multicystic areas, solid, hemorrhagic, and necrotic foci in the areas of the embryonic CA. the teratoma portion may be mature or immature.
Term
what is another name for teratocarcinoma?
Definition
NSGCT (non-seminomatous germ cell tumor) followed w/a list of the relative components.
Term
what are some of the clinical features of germ cell tumors? tx?
Definition
clinical features: painless enlargement of the testis. seminomas tend to be larger, more fleshy and choriocarcinomas tend to be smaller. tx: orchiectomy
Term
how might germ cell tumors spread and where?
Definition
lymphatically to para-aortic nodes - may spread to the mediastinum and supraclavicular nodes. hematogenously to brain, lungs, liver. histology of metastasis may be different from its primary tumor.
Term
how are germ cell tumors classified as a part of diagnosis?
Definition
into broad categories: seminoma and non-seminomatous germ cell tumors (NSGCTs - more aggressive, poorer prognosis)
Term
what are the stages of germ cell tumor spread?
Definition
stage 1: tumor confined to testis, epididymis or spermatic cord. stage 2: distant spread confined to retroperitoneal nodes below diaphragm. stage 3: metastases outside retroperitoneal nodes above the diaphragm (still curable)
Term
are seminomas radio-sensitive?
Definition
yes
Term
are NSGCTs sensitive to chemotherapy?
Definition
yes
Term
what are the sex cord-gonadal tumors?
Definition
leydig and sertoli cell tumors
Term
what characterizes leydig cell tumors?
Definition
leydig cells tumors can arise at any age, but most commonly 20-60 yrs old. their *most common feature is generalized testicular swelling, though a common initial sign is *gynecomastia (decreased libido) or *sexual precocity - leydig cell tumors may elaborate androgens, estrogens or corticosteroids.
Term
how do leydig cell tumors appear grossly? microscopically?
Definition
grossly: typically less than 5 cm, golden brown and a homogeneous cut surface. microscopically: similar to their normal counterparts - round, polygonal w/an *abundant granular eosinophilic cytoplasm and a round central nucleus. the cytoplasm of leydig cell tumors contains *lipid granules, vacuoles or *lipofuscin pigment. *reinke crystals, rod shaped crystals are associated with leydig cell tumors.*
Term
what is the malignant potential for leydig cell tumors?
Definition
most are benign - ~10% are invasive
Term
what characterizes sertoli tumor cells? how do they appear grossly? microscopically? what is their level of malignant conversion? do they produce hormones?
Definition
sertoli tumor cells appear grossly as firm, small nodules w/a homogenous gray-white cut surface. microscopically, cells are *arranged in trabeculae that form cord-like structures and tubules*. calcium deposits may also be visible. most are benign, less than 10% become malignant. sertoli cell tumors are typically hormonally silent.
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