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Testes and Epididymis Pathelective.Com Drs

Testes and Epididymis Pathelective.Com Drs

Katherine Saunders, DO @SaraEWobker #GUPathElective

Testes and PathElective.com Drs. Katherine Saunders and Sara E. Wobker

Anatomy: • Location • During development (around the 26th week of gestation), the testes descend from the posterior abdomen through the inguinal canal to reach the where they are then suspended from the abdomen by the • Spermatic cord contains vessels, nerves, and the (***important margin for tumor staging***) • The layers which surround the testis and epididymis from superficial to deep: skin (scrotum)→ (continuous with Colles fascia of the perineum and Scarpa’s fascia of the abdomen)→ external spermatic fascia → → internal spermatic fascia → → (only surrounds the testis, not epididymis) • The tunica vaginalis is the serous pouch that covers the testes and epididymis • It is derived from the peritoneum • The tunica albuginea is the fibrous capsule of the testis, which divides the tissue of the testis into lobules; it does not cover the epididymis

• Structure

Katherine Saunders, DO @SaraEWobker #GUPathElective

• Testes: • The testes are oval shaped and consist of a series of lobules, each containing hundreds of convoluted seminiferous which are supported by interstitial tissue • The seminiferous tubules travel to the mediastinum where they become straight seminiferous tubules and then form the • The rete testis gives rise to efferent ductules which connect with the head of the epididymis

• Epididymis: The epididymis is located on the posterolateral aspect of each and is split into the head, body, and tail • Head: Most proximal portion which connects with the efferent ductules of the testis • Body: Heavily coiled duct structure • Tail: Most distal portion; origin of the vas deferens which then travels up the spermatic cord • Function • Testes: site of production and hormone synthesis

Katherine Saunders, DO @SaraEWobker #GUPathElective

• Epididymis: sperm storage and maturation, during which time they gain their motility • Arterial supply • Testes are supplied by paired testicular arteries, which originate from the abdominal aorta and descend to the scrotum through the inguinal canal • Collateral blood supply is from branches of the cremasteric artery (from the inferior epigastric artery) and the artery of the vas deferens (from the inferior vesical artery) • The scrotum is supplied by the internal pudendal artery, which is a branch of the internal iliac artery • Venous drainage • Blood drains via the in the scrotum • The in the plexus ascend through the inguinal canal and form the paired testicular veins • The left testicular drains into the left renal vein • The right drains into the inferior vena cava • Lymphatic drainage • The testes are drained by the pre-aortic and lateral aortic lymph nodes • The scrotum is drained by the inguinal lymph nodes

Histology: • Seminiferous tubules: • Contains two cell types within a : spermatogenic (germ) cells and Sertoli cells (support cells) • The spermatogenic cells constantly multiply, go through multiple cycles of , and differentiate into mature sperm • Spermatogonia → primary → secondary spermatocytes → → spermatozoa • The Sertoli cells nourish the spermatogenic cells

Katherine Saunders, DO @SaraEWobker #GUPathElective

• Please see this diagram about spermatogenesis

Seminiferous with spermatogenesis, high power

• The tubules are surrounded by loose and secreting Leydig cells • Leydig cells: polyhedral in shape with a round nucleus, 1-2 prominent nucleoli and bright eosinophilic (pink) cytoplasm • Can also see cytoplasmic granules called crystals of Reinke

Katherine Saunders, DO @SaraEWobker #GUPathElective

• Rete testis: • Anastomosing network of delicate channels located at the testicular mediastinum which receives the contents of the seminiferous tubules and moves it to the efferent ductules • : the channels are lined by a single layer of cuboidal epithelial cells

Katherine Saunders, DO @SaraEWobker #GUPathElective

Rete testis, low power

• Efferent ductules: • Consist of multiple convoluted tubules that arise from the rete testis which then connect to the epididymis • Histology: Some cells are tall columnar and ciliated (which function to move spermatozoa to the epididymis) and some cells are short and non-ciliated • The alternating pattern of tall columnar and cuboidal cells gives the efferent ductules a “sawtooth pattern” • See this link for histologic photos

• Epididymis: • One very long, highly convoluted duct, where at the lower pole of the testis it becomes the ductus deferens • Histology: The duct is a tube of lined by pseudostratified ciliated and basal cells • In the proximal epididymis, there is one layer of smooth muscle while the distal end (tail) has three layers

Katherine Saunders, DO @SaraEWobker #GUPathElective

Common Benign Entities • Cryptorchism

Katherine Saunders, DO @SaraEWobker #GUPathElective

• Definition: Failure of the testes to descend into the scrotum, which causes atrophy • Occurs in 3% of full term newborns; more common in preterm and low birth weight infants • Presents as bilateral or unilateral mass in the inguinal or high scrotal area, although about 20% of undescended testes are not palpable due to being atrophic or present in the abdomen • Associated with increased risk of testicular tumor (seminoma is most common) • Treatment: Orchiopexy (surgical fixation of testis within scrotum) • Histology: Seminiferous tubules will appear atrophic: the basement membrane will be thickened without any evidence of spermatogenesis • Sertoli and Leydig cells are still present

• Hydrocele • Definition: Accumulation of serous fluid within the tunica vaginalis • Most common cause of scrotal enlargement • Histology: Loose connective tissue with a mesothelial lining • • Definition: Dilatation of the efferent ductules in the rete testis or head of the epididymis • Histology: Thin wall of fibromuscular soft tissue with an often ciliated flat cuboidal epithelial lining • Luminal contents = spermatozoa and proteinaceous fluid Common Malignancies Germ cell tumors (GCTs): Clinically classified as seminomas and non-seminomatous GCTs • Classic Seminoma • Definition/pearls: Most common type of GCT, derived from transformed spermatogenic cells • Presents in young men (ages 30-49) with a unilateral palpable mass

Katherine Saunders, DO @SaraEWobker #GUPathElective

• Serum LDH and PLAP may be elevated; AFP should not be increased • Macroscopic: Well-demarcated with a homogenous, solid, gray-white, lobulated cut surface without necrosis or hemorrhage • Histology: • Sheets or lobular configuration of tumor with fibrous septae • Uniform polygonal tumor cells with clear cytoplasm, distinct cell borders, and large nuclei with prominent nucleoli (fried egg appearance) • Immunohistochemistry/Special stains: • Positive: PLAP, OCT 3/4, CD117, D2-40, SALL4 • Negative: CD30, AFP, AE1/AE3

Seminoma, low power - note the fibrous septae

Katherine Saunders, DO @SaraEWobker #GUPathElective

Seminoma, high power - note the fried egg cells

• Non-seminomatous GCTs: • Embryonal carcinoma • Definition/pearls: • Second most common pure GCT, but more commonly seen as a component of a mixed GCT • Presents earlier than seminoma - men in their 30’s • Large proportion have metastases at presentation • No specific tumor marker, but can see elevated AFP and HCG • Macroscopic: Poorly circumscribed, variegated with necrosis and hemorrhage • Histology: • Characterized by large highly pleomorphic tumor cells with minimal features of differentiation • Solid, pseudoglandular, alveolar, tubular, or papillary patterns • Cells have prominent nucleoli, indistinct cell borders with nuclear overlapping • Frequent mitoses and apoptosis

Katherine Saunders, DO @SaraEWobker #GUPathElective

Embryonal carcinoma, glandular growth pattern

Katherine Saunders, DO @SaraEWobker #GUPathElective

Embryonal carcinoma, low power; note the nuclear pleomorphism and prominent nucleoli

• Immunohistochemistry/Special stains: • Positive stains: CD30, Oct 3/4, SALL4, PLAP • Negative stains: CD117, EMA, CEA, hCG • Yolk sac tumor • Definition/pearls: • Most common testicular tumor in infants and young children • Usually presents with elevated AFP • Two age peaks: • 16-18 months (prepubertal, pure yolk sac tumor) • 25-35 years old (postpubertal, yolk sac tumor in mixed GCT) • Macroscopic: • Poorly circumscribed, nonencapsulated, gray to white with a gelatinous/myxoid cut surface • If postpubertal tumor, hemorrhage and necrosis are more common • Histology: • Variable growth patterns! • Most common = microcystic, solid, and myxomatous

Katherine Saunders, DO @SaraEWobker #GUPathElective

• Microcystic: Anastomosing cords of flattened cells making a honeycomb meshwork appearance • Endodermal sinus pattern: (example below) contains Schiller-Duval bodies (central vessel surrounded by tumor cells, a space, and surrounded by another layer of flat tumor cells) • 50% of tumors contain these structures • Hyaline globules are common (PAS-D+ and alpha-1-antitrypsin+)

Yolk sac tumor; festoon pattern (resembles undulating ribbons)

Katherine Saunders, DO @SaraEWobker #GUPathElective

Schiller-Duval body

• Immunohistochemistry/Special stains: • Positive stains: AFP, Glypican 3, SALL4 • Negative stains: OCT 3/4, CD30, CD117 • Teratoma • Definition/pearls: • Tumor arising from germ cells with more than one embryonic germ layer (ectoderm, mesoderm, or endoderm) • Second most common pediatric testicular tumor (after yolk sac tumor) • Two age peaks: • < 4 years of age • 20 - 40 years old (frequently part of a mixed GCT) • Macroscopic: Well-circumscribed, heterogeneous tumors with solid and cystic features; can see with serous, mucinous, flaky material, or mature tissue with hair, cartilage, bone or teeth • Histology: • Prepubertal type: More likely to have very organized tissue arrangements mimicking organs; any tissue type may be present • No cytologic atypia or germ cell neoplasia in situ • Benign • Lacks Isochromosome 12p

Katherine Saunders, DO @SaraEWobker #GUPathElective

• Postpubertal type: Any type of tissue may be present with varying degrees of atypia, less organized arrangement of tissue types • Will have germ cell neoplasia in situ • Mature vs immature teratomas (old nomenclature but still important to know) • Mature teratoma = developed ectodermal, endodermal, or mesodermal tissue, such as epidermis, neuronal tissue, GI mucosa, respiratory mucosa, cartilage • Immature teratoma = Undifferentiated spindle cells, primitive neuroectodermal tissue, blastemal tissue

Teratoma with respiratory epithelium (mature teratoma)

• Choriocarcinoma • Definition/pearls: Malignant germ cell tumor composed of syncytiotrophoblast, cytotrophoblast and intermediate trophoblast cells • Usually is mixed with other GCT’s • Presents with marked elevation in bHCG • Macroscopic: Hemorrhagic nodule within testicular parenchyma • Histology: Mixture of: • Cytotrophoblasts: polygonal cells with clear cytoplasm, a single nucleus, and prominent nucleolus • Syncytiotrophoblast: Large, multinucleated cells with large nuclei and eosinophilic cytoplasm

Katherine Saunders, DO @SaraEWobker #GUPathElective

• Immunohistochemistry/Special stains: • Positive stains: hCG, PLAP, GATA3 • Negative stains: CD30, D2-40, inhibin

hCG stain, choriocarcinoma

Katherine Saunders, DO @SaraEWobker #GUPathElective

• Mixed germ cell tumor: • Definition/pearls: • 2nd most common GCT after seminoma • Can contain components of any of seminomatous or non- seminomatous tumor • Macroscopic: Variable and depends on components, commonly necrotic and hemorrhagic • Histology: Depends on which tumor components are involved

Embryonal carcinoma (EC) and yolk sac tumor (YST) - these two tumors are frequently identified in close association within a mixed GCT

Katherine Saunders, DO @SaraEWobker #GUPathElective

EC and YST, CD30 stain highlights the EC component

Katherine Saunders, DO @SaraEWobker #GUPathElective

EC and YST, AFP stain highlights the YST component

Katherine Saunders, DO @SaraEWobker #GUPathElective

Teratoma and yolk sac tumor

Sex cord stromal tumors (SCST): • • Definition/pearls: • Most common type of SCST • Recapitulates normal development of Leydig cells • Tumors may produce → virilization • Macroscopic: Well circumscribed, golden-brown to yellow cut surface • Histology: Large, round or polygonal cells with abundant pink cytoplasm and well-defined cell borders • Cells have round nuclei with prominent nucleoli • Can see Reinke crystals • Immunohistochemistry/Special stains: • Positive stains: SF1, Inhibin, calretinin • Negative stains: EMA, SALL4

Katherine Saunders, DO @SaraEWobker #GUPathElective

Leydig cell tumor demonstrating abundant pink cytoplasm and intracytoplasmic crystals of Reinke

• tumor • Definition/pearls: • Very rare tumor • May be seen sporadically or in patients with Peutz-Jeghers syndrome, Carney syndrome, insensitivity syndrome, and testicular feminization syndrome • Macroscopic: Well circumscribed, homogenous, lobulated, solid, yellow-brown mass • Usually unilateral • Histology: • Closely packed tubules lined by cuboidal or columnar cells with pale to lightly pink cytoplasm and bland nuclei • May demonstrate sclerosis • Immunohistochemistry/Special stains: • Positive stains: SF1, inhibin, vimentin, CD99, CD10, calretinin • EMA, chromogranin

Katherine Saunders, DO @SaraEWobker #GUPathElective

Sertoli cell tumor exhibiting the classic pattern of tubular growth

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