descent normally begins around 8 to 15 weeks of gestation and is normally completed by the 35th week of gestation. This is a common condition affecting approximately 2% to 8% of male children. Risk factors for cryptorchidism include low birth weight, being small for gestational age, and prematurity.2
Figure 4.1. Low power image of multiple normal spermatic tubules demonstrating intact spermatogenesis. Leydig cell clusters are present in the interstitium along with small blood vessels.
Figure 4.2. The interstitium of the testis contains blood vessels, lymphatic vessels, nerves, and Leydig cells within loose fibrous stroma.
Figure 4.3. Leydig cells are found within the interstitium of the testis and produce androgens to support germ cell development.
Figure 4.4. The rete testis is located in the hilum or mediastinum of the testis and comprises slitlike, complex glands that act as a conduit between the spermatic tubules and the epididymis.
Tubular atrophy with decreased tubular diameter
Sertoli-only pattern or Sertoli cell nodules “Pick adenoma” (Figure 4.18)
Microlithiasis within tubules (Figure 4.19)
Peritubular fibrosis, fibrotic interstitium with prominent Leydig cells
Hemosiderin deposition (Figure 4.20)
In adults with cryptorchid testis that has undergone orchidopexy, may see a mixed pattern of maturation arrest, Sertoli-only pattern, and hypospermatogenesis, along with Leydig cell hyperplasia
TABLE 4.1: Normal Testicular Cellular Components
Figure 4.6. In Table 4.1: Spermatogonium. Arrows point to the basally oriented spermatogonia. These are the most primitive germ cell within the spermatic tubule.
Figure 4.7. In Table 4.1: Primary spermatocyte. Arrows point to primary spermatocytes, which are present just above the basal aspect of the tubule, but not yet to the luminal surface.
Figure 4.8. In Table 4.1: Secondary spermatocyte. Arrows point to secondary spermatocytes. These cells are located more towards the luminal aspect when compared to primary spermatocytes. In reality, they are incredibly difficult to differentiate from primary spermatocytes on H&E alone.
Figure 4.9. In Table 4.1: Spermatid. Arrows point to spermatids, which still show attachment to the Sertoli cells within the tubule.
Figure 4.10. In Table 4.1: Spermatozoa. Arrows point to spermatozoa, which have been released into the lumen and will be carried out of the testis via the vas deferens.
Figure 4.11. In Table 4.1: Sertoli cell. Arrows point to Sertoli cells, which are pyramidal shaped cells with prominent nucleoli. They have indistinct cell borders as they interdigitate between the germ cells of the tubule.
Figure 4.12. In Table 4.1: Leydig cell. Arrows point to Leydig cells present in the interstitium surrounding the tubule.
Figure 4.13. The fetal testis comprises immature seminiferous tubules without lumens. The tubules are lined by immature, cuboidal Sertoli cells. Immature Leydig cells are present in the interstitium.
Figure 4.14. Prepubertal seminiferous tubules showing incomplete maturation lacking spermatozoa. Sertoli cells are prominent.
of the ovarian parenchyma with the fallopian tube is present in close association with immature spermatic tubules (Figure 4.22). The seminiferous tubules are lined by immature Sertoli cells, lack open lumens, and germ cells are absent (Figure 4.23). Ovarian fibrous stroma is indicative of the ovarian component, along with the serous-epithelium-lined fallopian tube (Figure 4.24).
TABLE 4.2: Testicular Development and Histology by Developmental Age Group
Figure 4.16. In cryptorchid testes, the testicle is often identified in the inguinal canal or even in the abdomen. The testicle is small and fibrotic.
Figure 4.17. At medium power, numerous vessels, hemosiderin deposition, and calcifications are present and well-formed spermatic tubules are absent.
Gonadoblastoma usually arises in the setting of disordered sexual development
Most commonly identified in gonadal dysgenesis involving the Y chromosome
Tumors comprise of a mixture of GCT and sex cord stromal tumor
Areas that resemble seminoma/dysgerminoma with annular tubules surrounded by ovarian stroma (Figure 4.25)
Calcifications are common (Figure 4.26)
Figure 4.18. The finding of Sertoli cell-only pattern, discussed below, is common in cryptorchid testis. A discrete nodule of Sertoli cells, the so-called Pick adenoma, is also associated with cryptorchidism.
Figure 4.19. Microlithiasis within the remnant of spermatic tubules is another feature of cryptorchid testis.
Figure 4.20. Hemosiderin deposition is a common feature of cryptorchid testis, along with prominent vessels.
Figure 4.21. Gross photograph of an ovotestis demonstrates the intact fallopian tube on the left, leading to a combined ovary and testis. The fimbriated end of the fallopian tube is present at the right side of the image.
Figure 4.22. Low-power image of an ovotestis with the fallopian tube coursing along the right and top of the image and immature spermatic tubules on the left.
Figure 4.23. At higher power, the spermatic tubules in the ovotestis show fetal-type immature Sertoli cells, without any germ cells present.
Figure 4.24. Ovarian fibrous stroma is present in ovotestis, surrounding the fallopian tube with serous-type epithelium.
Figure 4.28. A higher power image of testicular tumor of the adrenogenital syndrome (TTAGS) shows their granular eosinophilic cytoplasm, round nuclei with random atypia—consistent with their endocrine origin.
Nodules of benign adrenal cortical tissue found in the paratesticular soft tissue, as well as along the spermatic cord and epididymis
Exceedingly rare instances of adrenal tissue within testicular tissue reported
May be more common in cryptorchid males
Occurs when adrenal tissue follows testis from abdomen into the inguinal region during development
Rests are well circumscribed, contain only adrenal cortical tissue, and lack a medullary component (Figure 4.30)
Spleen: Splenogonadal fusion occurs when the embryonic gonad fuses with ectopic spleen and migrates to the scrotum. The left testicle is exclusively involved, consistent with the usual anatomic location of the spleen.6
Liver: Hepatotesticular fusion has been reported in hernia specimens and in undescended testis.7
Kidney: Ectopic renal tissue associated with undescended testis.8
Various metaplastic tissues may be seen in testes including fat, cartilage, and bone.9
Figure 4.29. Histologic examination of androgen insensitivity syndrome showing small, packed seminiferous tubules lined by immature Sertoli cells. Germ cells are largely absent.
Figure 4.30. Adrenocortical rests are benign nodules of adrenal cortical cells most commonly identified in the paratesticular soft tissue.
TABLE 4.3: Common Patterns for Testicular Biopsy for Infertility
Klinefelter syndrome occurs in males with an extra X chromosome (47,XXY)
Findings include infertility and small testicular volume with decreased testosterone production
Testicular biopsy demonstrates numerous sclerotic tubules and Leydig cell hyperplasia, with overall reduction in the number of germ cells
When sperms are present, microtesticular sperm extraction (TESE) may be successful for assisted reproduction
□ Look for intact spermatogenesis in all tubules; if absent in any tubules, consider diagnostic entities in Table 4.3
□ Determine if the process involves all tubules versus heterogeneous, mixed pattern
□ If heterogeneous, give approximate percentage of tubules involved by each pattern
□ Comment on presence or absence of germ cell neoplasia in situ (GCNIS)
□ Assess interstitium for presence of Leydig cells and other findings such as fibrosis, inflammation, or granulomas
□ Report the number of tubular cross sections present as a biopsy-quality indicator
Figure 4.34. Higher power image of tubular lumen showing mature spermatozoa with tapered nuclei and no appreciable cytoplasm. The presence of spermatozoa is consistent with intact spermatogenesis.
Figure 4.36. In maturation arrest, germ cells are present and show maturation to the secondary spermatocyte stage in this tubule. The tubular lumen is obscured and no spermatids or spermatozoa are identified.
a prominent neutrophilic infiltrate is expected, with a dominant abscess or microabscesses commonly identified. Chronic epididymo-orchitis may result from a long-standing bacterial infection, with a transition to more lymphoplasmacytic inflammatory cells and associated fibrosis and tubular destruction. This fibrotic stage is more likely to be confused for a possible malignancy as the tissues become fixed to surrounding soft tissue.
Figure 4.38. Sertoli cell-only pattern at low power, the tubules show a single cell type and lack mature spermatozoa in the lumens.
Figure 4.39. At high power, the classic cytologic features of Sertoli cells are present—pyramidal cells with wispy eosinophilic cytoplasm and ill-defined cell borders. Nuclei are round with prominent nucleoli.
Figure 4.40. Atrophic testis showing hyalinized tubules with small diameters. The interstitium appears fibrotic with loss of Leydig cells.
Figure 4.41. At high power, atrophic testis showing obliteration of tubular lumens and loose collagen occupying the majority of the surface area. No germ cells or Sertoli cells are present within the tubule.
Orchitis and epididymitis usually co-occur, and isolated epididymitis is rare
In a patient with isolated epididymitis, mumps should be the primary clinical consideration as epididymitis often occurs prior to orchitis
Mumps epididymo-orchitis is an important diagnosis to make as it can often lead to infertility
□ Fungal infection
□ Sperm granuloma
□ Sclerosing lipogranuloma
□ Seminoma with brisk granulomatous response
Figure 4.42. Granulomatous inflammation within the testis presents a broad differential diagnosis. In this image, the giant cells are of Langhans type, raising the possibility of tuberculous epididymo-orchitis.
Figure 4.43. At low power, malakoplakia appears as sheets of eosinophilic histiocytes with scattered chronic inflammation.
granulomatosis with polyangiitis is responsible for testicular vasculitis.15 The full differential diagnosis of the specific type of vasculitis depends on the size of vessels involved and is beyond the scope of this chapter. Regardless, recognition of a vasculitic process in the testis should prompt additional clinical workup.
Figure 4.47. A segmental infarct of the testis resulting in focal necrosis of tubules, surrounded by viable tubules. This finding should prompt close examination of the vessels both adjacent and remote from the infarct.
Figure 4.48. Another low-power image demonstrating the focal necrosis of a segmental infarct, with necrotic tubules immediately adjacent to viable tubules.
Figure 4.49. Area of remote infarction showing outlines of necrotic tubules with surrounding inflammation.
Figure 4.50. Close examination of the vessels of the testis should be undertaken for signs of vasculitis. At high power, leukocytoclasis—neutrophils transgressing the vessel wall—is identified in this specimen.
seminoma would be considered “nonseminomatous,” despite the presence of a seminoma component. This can be confusing as “nonseminomatous” does not exclude the presence of some amount of seminoma in a mixed GCT.
TABLE 4.4: Malignant Testicular Tumors, Organized by Cell of Origin
Figure 4.52. Gross photograph of a testis with seminoma. The gross appearance shows a white-tan, lobulated mass that bulges on cut section.
Figure 4.53. At low power, fibrous septa are evident as pink bands intersecting lobules of tumor. These bands correspond to the gross lobulated appearance.
Figure 4.54. Lymphocytes are often closely associated with seminoma and often congregate along the fibrous septa.
Figure 4.56. Nuclear features of seminoma are demonstrated in this image with the polygonal, squared-off nuclei and prominent macronucleoli.
Figure 4.58. A brisk histiocytic response and numerous admixed lymphocytes in this image should raise suspicion for a possible seminoma.
Figure 4.59. The presence of germ cell neoplasia in situ (GCNIS) (arrow) within the tubules also suggests a germ cell tumor is present.
While classically solid, less common patterns of seminoma have been described and may cause confusion with other GCTs
Unusual morphologic variants and their nonseminomatous mimickers include:
Microcystic → yolk sac tumor (YST)18
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