Wolffian Duct Origin Research Articles

PAX8 and PAX2 Immunostaining Facilitates the Diagnosis of Primary Epithelial Neoplasms of the Male Genital Tract

PAX8 and PAX2 are cell-lineage-specific transcription factors that are essential for the development of Wolffian and Müllerian ducts and have recently emerged as specific diagnostic markers for tumors of renal or Müllerian origin. Little is known about their expression in the Wolffian duct-derived human male genital tract. We report our findings of PAX8 and PAX2 expression in the epithelium of the normal male genital tract and in epithelial tumors derived therefrom using immunohistochemistry (IHC). We found that PAX8 and PAX2 were expressed in the epithelium of the male genital tract from the rete testis to the ejaculatory duct. Rare glands in the prostatic central zone, a tissue of purported Wolffian duct origin, were focally positive for PAX2, but no PAX8 was detected in this area, a finding that may warrant further study. We found diffuse expression of PAX8 and PAX2 in 1 case each of serous cystadenoma of the epididymis, carcinoma of the rete testis, Wolffian adnexal tumor of the seminal vesicle, and endometrioid carcinoma of the seminal vesicle. Neither PAX8 nor PAX2 was detected in the seminiferous tubules and interstitium of the normal testis, nor in Leydig cell tumors (n=6), Sertoli cell tumors (n=2), or 48 of 49 germ cell tumors. One pediatric yolk sac tumor showed focal and weak staining for PAX8. Tumors of mesothelial origin, that is, adenomatoid tumors (n=3) and peritoneal malignant mesotheliomas (n=37) in men, were negative for PAX2 and PAX8. Neither PAX2 nor PAX8 was present in other areas of the prostate. Expression of PAX8 and PAX2 in these primary epithelial neoplasms of the male genital tract is due to their histogenetic relationship with Wolffian or Müllerian ducts. PAX8 and PAX2 IHC may facilitate the diagnosis of these tumors and should be included in the differential diagnostic IHC panel.

PKA Regulates Vacuolar H+-ATPase Localization and Activity via Direct Phosphorylation of the A Subunit in Kidney Cells

The vacuolar H(+)-ATPase (V-ATPase) is a major contributor to luminal acidification in epithelia of Wolffian duct origin. In both kidney-intercalated cells and epididymal clear cells, cAMP induces V-ATPase apical membrane accumulation, which is linked to proton secretion. We have shown previously that the A subunit in the cytoplasmic V(1) sector of the V-ATPase is phosphorylated by protein kinase A (PKA). Here we have identified by mass spectrometry and mutagenesis that Ser-175 is the major PKA phosphorylation site in the A subunit. Overexpression in HEK-293T cells of either a wild-type (WT) or phosphomimic Ser-175 to Asp (S175D) A subunit mutant caused increased acidification of HCO(3)(-)-containing culture medium compared with cells expressing vector alone or a PKA phosphorylation-deficient Ser-175 to Ala (S175A) mutant. Moreover, localization of the S175A A subunit mutant expressed in HEK-293T cells was more diffusely cytosolic than that of WT or S175D A subunit. Acute V-ATPase-mediated, bafilomycin-sensitive H(+) secretion was up-regulated by a specific PKA activator in HEK-293T cells expressing WT A subunit in HCO(3)(-)-free buffer. In cells expressing the S175D mutant, V-ATPase activity at the membrane was constitutively up-regulated and unresponsive to PKA activators, whereas cells expressing the S175A mutant had decreased V-ATPase activity that was unresponsive to PKA activation. Finally, Ser-175 was necessary for PKA-stimulated apical accumulation of the V-ATPase in a polarized rabbit cell line of collecting duct A-type intercalated cell characteristics (Clone C). In summary, these results indicate a novel mechanism for the regulation of V-ATPase localization and activity in kidney cells via direct PKA-dependent phosphorylation of the A subunit at Ser-175.

Male adnexal tumour of wolffian origin: The first report of metastatic disease

The first case of a male adnexal tumour of probable wolffian duct origin to develop metastatic disease is reported. The characteristic histological appearance and immunohistochemical profiles of the primary and metastatic male tumours are discussed. The scanty experience relating to metastatic disease makes decisions about the most appropriate treatment challenging.

A Gartner duct cyst of the vagina causing dysuria and dyschezia in a Yorkshire Terrier

A 5 year-old, intact female Yorkshire terrier was referred for dysuria and dyschezia. The radiographic and ultrasound examination showed a round shaped mass caudal to the urinary bladder that contained anechoic fluid within the thin walls. During surgery, the cyst was noted to be attached to the outer wall of the vagina, not connected to the vaginal lumen. Cystic fluid was removed and the cystic wall was resected. Then the remaining cystic wall was omentalized to prevent a recurrence.Histological examination confirmed that the cyst was of Wolffian duct origin. In this case, a large Gartner duct cyst causing urological problems was diagnosed and removed by surgical resection.

Male adnexal tumour of probable Wolffian duct origin

Male adnexal tumours of Wolffian duct origin are very rare. They have variable malignant potential and surgical excision is recommended. We report the case of a 56-year-old male who presented with a swelling in the perineum thought to be a haematoma as the result of a complication of a laparoscopic inguinal hernia repair. It recurred after incision and two attempts at drainage and was then completely excised. Histology revealed the lesion to be an adnexal tumour of probable Wolffian duct origin. To our knowledge there have only been two previous cases of male adnexal tumour of Wolffian duct origin reported in the literature.

Uroplakin and androgen receptor expression in the human fetal genital tract: insights into the development of the vagina.

Although a dual origin of the vagina has been popularized, other theories support a müllerian or wolffian duct origin or various combinations of these structures and the urogenital sinus. Uroplakins are specialized membrane proteins of the urothelial plaque, constituting the asymmetrical unit membrane of the bladder, and represent specific molecular markers of urothelial differentiation. We hypothesize that the epithelium of the dorsal wall of the urogenital sinus is involved in the formation of the sinovaginal bulbs and will express uroplakins. In addition, localization of the androgen receptor and its temporal expression during development may in part explain the varied effects of androgens on the lower female genital tract in congenital adrenal hyperplasia. Lower genitourinary tracts from 4 human female fetuses (9 to 18 weeks) were serially sagittally sectioned. Representative sections were stained with hematoxylin and eosin, rabbit antibodies against panuroplakin and antibodies to the androgen receptor. At 9 weeks of gestation the urogenital sinus showed evidence of evagination and the formation of the sinovaginal bulbs. The urothelium of the entire urogenital sinus expressed uroplakins including the region of the dorsal wall involved in evagination and formation of the sinovaginal bulbs. The müllerian ducts were in direct contact with the area of urogenital sinus evagination but were not in continuity with the sinus. Androgen receptors were expressed in the epithelium and the stroma of the urogenital sinus, sinovaginal bulbs, and müllerian and wolffian ducts. By 14 weeks androgen receptor expression was almost absent in the urothelium of the urogenital sinus, and the epithelium and surrounding stroma of the lower vagina and müllerian ducts. The area of evagination of the urogenital sinus expresses uroplakins, is involved in the formation of the sinovaginal bulbs and further substantiates the urogenital sinus origin of the lower vagina. Since testosterone inhibits formation of the lower vagina, the timing of exposure to systemic testosterone in congenital adrenal hyperplasia will determine the phenotypic appearance of the external genitalia and effect of testosterone on the development of the lower genital tract. If exposure to testosterone occurs after 12 weeks only clitoromegaly occurs. Androgen receptor is absent in the urogenital sinus urothelium, vaginal epithelium and müllerian ducts by 14 weeks, suggesting that these tissues become androgen insensitive and vaginal development will proceed normally after that critical time.

UROPLAKIN AND ANDROGEN RECEPTOR EXPRESSION IN THE HUMAN FETAL GENITAL TRACT: INSIGHTS INTO THE DEVELOPMENT OF THE VAGINA

Purpose: Although a dual origin of the vagina has been popularized, other theories support a mullerian or wolffian duct origin or various combinations of these structures and the urogenital sinus. Uroplakins are specialized membrane proteins of the urothelial plaque, constituting the asymmetrical unit membrane of the bladder, and represent specific molecular markers of urothelial differentiation. We hypothesize that the epithelium of the dorsal wall of the urogenital sinus is involved in the formation of the sinovaginal bulbs and will express uroplakins. In addition, localization of the androgen receptor and its temporal expression during development may in part explain the varied effects of androgens on the lower female genital tract in congenital adrenal hyperplasia.Materials and Methods: Lower genitourinary tracts from 4 human female fetuses (9 to 18 weeks) were serially sagittally sectioned. Representative sections were stained with hematoxylin and eosin, rabbit antibodies against panuroplakin and ant...

Parovarian Fibroma with Heterotopic Bone Formation of Probable Wolffian Origin

Parovarian neoplasms of wolffian duct origin are very unusual. This article presents the first report of a case of parovarian fibroma with heterotopic bone formation of probable wolffian duct origin. The tumor cells present among mature collagen bundles were fibroblast-like cells, while those at the sites of cellular proliferation were either undifferentiated mesenchymal cells or had differentiated into osteoblasts. In the bone matrix, the tumor cells had differentiated into osteoblasts and connective tissue had ossified.

Papillary cystadenoma of the broad ligament in von Hippel-Lindau disease

We present radiologic-pathologic correlation in a case of von Hippel-Lindau disease diagnosed on the basis of the discovery of papillary cystadenoma of wolffian duct origin, a rare calcified tumor of the broad ligament that was visible on the abdominal radiograph.