Comprehensive Immunophenotypic Characterization of Adult and Fetal Testes, the Excretory Duct System, and Testicular and Epididymal Appendages

Abstract

The immunophenotype of a normal testis and the excretory duct system has not been studied comprehensively in fetal and adult patients without testicular disease or hormonal manipulation so far. In addition, testicular (TA) and epididymal (EA) appendages are frequent paratesticular structures without previously reported comprehensive immunophenotypic studies. Immunohistochemistry for multiple markers, including the androgen receptor (AR), the estrogen receptor (ER), the progesterone receptor (PR), the prostate-specific antigen, the prostate-specific membrane antigen, PAX8, WT1, calretinin, CK7, CK20, OCT4, SALL4, and CD117, was performed on full sections of testicular/paratesticular tissue from a large cohort of adult and fetal autopsy patients. In contrast to adult germ cells (GC), fetal GC strongly express OCT4 and CD117, although the expression of these proteins is lost in the early postnatal period; SALL4, in contrast, is expressed in both fetal and adult GC, with only weak and focal expression in adult patients. Fetal Sertoli cells (SC) express WT1 and calretinin strongly and diffusely, in contrast to adult SC. Both fetal and adult excretory duct systems express CK7 and PAX8 with frequent AR coexpression, and all 3 main segments of the excretory duct system (ductuli efferentes, epididymis, and vas deferens) have unique immunophenotypes. The rete testis also has a unique immunohistochemical expression pattern, which includes strong expression of CK7, PAX8, WT1, calretinin, and AR. Finally, of the adult autopsy patients examined, 80% had a TA, and 60% had an EA; these paratesticular structures occurred at stereotypical locations, demonstrated reproducible morphologic features, and had a unique immunophenotype relative to other studied structures, with strong CK7, PAX8, WT1, AR, ER, and PR coexpression. The testis and the paratestis may be involved by diverse neoplastic and non-neoplastic processes, and knowledge of the immunophenotypic expression spectrum of these tissues may aid in clinical diagnosis and advance our understanding of the pathogenesis of both oncologic and nononcologic disease processes.

Epididymis-like Tubules in Adult Renal Hypodysplasia: Immunohistochemical Features Indicate a Mesonephric Origin

“…They found that the normal epididymis expressed CK7 (strong, diffuse), PAX8, and AR (variably). 28 The epididymis-like tubules in all 3 of our cases showed a similar pattern. Chen and Chang 24 demonstrated PAX2 expression (which is similar to PAX8) in the epithelium of the primitive tubules in renal dysplasia.…”

“…The epididymis-like tubules in our study showed not only a morphological similarity to the epididymis but also displayed an identical immunohistochemical profile. Magers et al 28 characterized the immunophenotype of the normal testes and the excretory system and concluded that each anatomical region had a unique and reproducible immunohistochemical profile. They found that the normal epididymis expressed CK7 (strong, diffuse), PAX8, and AR (variably).…”

“…p63 positivity of the basal cells has also been described. 31 CK7 staining of the basal cells has not been specifically mentioned, though Magers et al 28 describe the epididymis as being CK7 positive. Smooth muscle around the epididymis-like tubules was AR positive focally (nuclear), as documented by Ruizeveld de Winter et al 32 in the epididymis, vas, seminal vesicle, and prostate.…”

“…Magers et al 28 found that the rete testes (believed to be derived from mesonephric and/or sex cord elements) expressed CK7, PAX8, WT1, calretinin, and AR (and occasionally ER, CK20), while the ductuli efferentes (of mesonephric origin) stained for CK7, PAX8, AR, ER, and PR. They also studied testicular appendages, believed to be of Mullerian origin, and epididymal appendages, considered to be mesonephric derivatives.…”

CAIX and pax-8 Commonly Immunoreactive in Endolymphatic Sac Tumors: A Clinicopathologic Study of 26 Cases with Differential Considerations for Metastatic Renal Cell Carcinoma in von Hippel-Lindau Patients

“…However, this strong reactivity raises the differential diagnostic consideration with ccRCC even more so. Likewise, it is well known that pax-8 expression is found in many normal and neoplastic tissues, including epididymis, rete testis, fallopian tumor and ovary, pancreatic islets and lymph nodes, while commonly found in bladder adenocarcinoma, seminoma, endometrial adenocarcinoma, ovarian serous carcinoma, renal cell carcinoma, oncocytoma, neuroendocrine tumors, parathyroid carcinoma and papillary, follicular and medullary thyroid carcinoma [43][44][45][46][47][48][49]. During embryogenesis, pax-2 and pax-8 transcription factors play a redundant role by together regulating inner ear development, associated with otic placode induction, where they are required to maintain otic differentiation [50,51].…”