Pediatric and Developmental Pathology 18, 353–361, 2015 DOI: 10.2350/14-04-1467-PB.1 ª 2015 Society for Pediatric Pathology
Perspectives in Pediatric Pathology, Chapter 8. Persistence of Embryonal Remnants in the Testis and Epididymis MANUEL NISTAL,1 RICARDO PANIAGUA,2 PILAR GONZA´LEZ-PERAMATO,1
AND
MIGUEL REYES-MU´GICA3*
1
Pathology, Hospital La Paz, Universidad Auto´noma de Madrid, Calle Arzobispo Morcillo #2, Madrid 28029, Spain Department of Cell Biology, Universidad de Alcala, Madrid, Spain 3 Department of Pathology, Children’s Hospital of Pittsburgh of University of Pennsylvania Medical Center, One Children’s Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA 2
Received April 19, 2014; accepted May 20, 2014; published online August 8, 2014.
INTRODUCTION Histological analysis of surgical specimens from testes, epididymis, spermatic cords, and hernia sacs frequently shows glandular and tubular structures that may lead to erroneous diagnoses if one does not take into account their embryonal origin (Fig. 8.1). The Wolffian duct is the precursor of the ductus epididymis, the ductus or vas deferens, seminal vesicles, and ejaculatory duct. The mesonephric ducts, located near the gonad, form the efferent ductuli, while the Mu¨llerian ducts degenerate early, due to the action of anti-Mu¨llerian hormone [1]. Nevertheless, remnants of these three embryonic ducts can remain even in adult age and be found during microscopic examination of autopsy or surgical specimens [2]. One of every two adult men has cysts derived from these embryonal remnants. The most useful technique for exploration of these structures is ultrasonography [3].
APPENDIX TESTIS (SESSILE HYDATID OF MORGAGNI) The embryonal remnants we know today as appendix testis and appendix epididymis were first described by Giovanni Battista Morgagni in 1761. Morgagni is considered the founding father of anatomic pathology, and in his long tenure as professor of anatomy in Padua, he described many morbid findings observed during his accurate anatomic studies [4]. It is, therefore, humbling that his name gained posterity associated with this small and seemingly insignificant structure, described by him as a “hydatid” (from a term meaning water-filled vesicle). It was Griffiths in 1893 who individualized both structures based on their gross and microscopic differences. Luschka in 1954 observed that the appendix of the testis was preferably sessile, whereas the appendix of the epididymis was pediculate. The terms *Corresponding author, e-mail: [email protected]
sessile hydatid of Morgagni and pediculate hydatid of Morgagni, as these structures are also described, refer to these observations. The appendix testis derives from the Mu¨llerian (or paramesonephric) duct, which undergoes regression in the male embryo at the eighth week of gestation. Only the cephalic and caudal portions of the duct remain in the adult, forming the appendix testis and prostatic utricle, respectively. The Mu¨llerian duct segment that originates the appendix testis is similar to the one from which the fimbriae develop in the female uterine tubes. The appendix testis is located in the anterosuperior testicular pole or in the epididymotesticular fold in 76% of adult men and 83.3% of newborns and infants [5]. They are bilateral in two-thirds of cases. Consensus regarding their incidence in patients with cryptorchid testes has reached only 24% according to Jozsa and colleagues [6], whereas other investigators find no statistical differences in incidence and distribution of the appendix testis between normal or undescended testis [7]. The appendix testis is often a sessile structure of variable size, ranging from several millimeters to a few centimeters (Fig. 8.2). It is formed by a central core of loose connective tissue with variable vascularization, including lymphatic vessels (Fig. 8.3). Its outer surface appears scalloped and is lined with columnar or pseudostratified epithelium with hyperchromatic basal nuclei and ciliated cells [5,8]. The epithelium expresses both androgen and estrogen receptors [9], whereas the stroma is positive for anti-Mu¨llerian hormone receptor type II (AMHR2) [10] and CD10 (Fig. 8.4). Within the core of connective tissue, glandular or tubular structures are found. They are lined with an epithelium similar to that of the hydatid surface. Most of the time, this represents deep invaginations of the superficial epithelium. The glandular lumen often contains mucus or calcified material. In some cases, a real tube in the stroma has been interpreted as a Mu¨llerian duct remnant (Fig. 8.5–8.7). In others, only a focus of fibrosis or
Figures 8.1–8.12. Figure 8.1. A. Schematic representation of possible Mu¨llerian and Wolffian embryonic rests. Figure 8.2. Appendix testis. (Left) Macroscopic image of appendix testis at the upper testicular pole, close to epididymis. (Right) Appendix testis with superficial epithelium showing a festoon-like arrangement and calcifications at the tip. Figure 8.3. Appendix testis. Immunohistochemical staining with D2-40 showing abundant lymphatic vessels. Figure 8.4. Appendix testis. CD10 showing a positive band of stroma underlying the superficial epithelium. Figure 8.5. Testicular hydatid showing a small ductal structure within the core of connective tissue, possibly corresponding to a Mu¨llerian structure. Figure 8.6. Longitudinal
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thickened albuginea is observed at the anatomical location where the hydatid would be expected (Fig. 8.8). The physiological role of the appendix testis, if any, could be the control of fluid volume within the tunica vaginalis cavity [2]. The superficial epithelium, subepithelial capillaries, and lymphatic vessels of the appendix testis could be a functional unit [11]. Pathologies related to the appendix testis include cystic transformation, torsion (see vascular pathology [12]), and less frequently in adults, tumors such as cystadenomas and cystadenocarcinomas (Fig. 8.9) [13,14].
APPENDIX EPIDIDYMIS (PEDICULATE HYDATID OF MORGAGNI) The appendix epididymis or pediculate hydatid of Morgagni corresponds to the blind cephalic end of the Wolffian duct. This embryonal remnant is a small cyst attached to the caput epididymis by a pedicle. It is found in 21.9% to 28% of adult epididymes [15] (Fig. 8.10). The cyst wall is lined with a slightly basophilic, ciliated, columnar or pseudostratified epithelium with vacuolated cells containing periodic acid–Schiff- and Alcian-blue– positive material. The stroma around the cyst may show a few smooth muscle cells, and the outer surface of the hydatid is lined with mesothelium. Like the appendix testis, the hydatid may undergo torsion [16] and marked cystic transformation [17,18] and, rarely in the adult, can give rise to a tumor [19,20].
ABERRANT DUCTS Aberrant ducts, also termed Haller’s organs, are mesonephric duct remnants located in the fissure between testis and epididymis. There are two aberrant ducts: superior and inferior. The superior aberrant duct is located in the corpus epididymis. This is an inconstant and blind sacended duct (Figs. 8.11 and 8.12). The inferior aberrant duct is located along the corpus and cauda of the epididymis, following a sinuous course parallel to the main epididymal axis. The inferior aberrant duct measures 3.5 to 35 mm in length [21]. The cranial extreme is blind, whereas the caudal end opens to the ductus epididymis in the cauda. Both of the aberrant ducts are tubular structures lined with a columnar or cuboidal epithelium, surrounded by a few smooth muscle rings. Cystic transformation and torsion of the inferior aberrant duct have been reported [22,23].
PARADIDYMIS The paradidymis (organ of Giralde´s, Henle’s paraepididymis or innominate body) consists of a few small ductuli derived from caudal mesonephric ducts and located in the anterior face of the inferior spermatic cord end, near the caput of the epididymis (Figs. 8.14 and 8.15). The paradidymis ductuli do not communicate with the ductus deferens lumen, and their structure is similar to that of the aberrant ducts. Torsion [24,25] and cystic transformation [26] of the paradidymis have been reported. Most cysts are asymptomatic, usually diagnosed by ultrasonography, and only clinical, noninvasive explorations are advisable [27].
CYSTS OF THE TUNICA ALBUGINEA Cysts of the tunica albuginea are malformations located either within the tunica albuginea or inside the testicular parenchyma. These lesions were first reported nearly a century ago [28], and their recognition can prevent unnecessary amputations and orchidectomies. For many years, these cysts were considered unusual malformations [29,30]. With the systematic use of high-resolution ultrasonography for testicular exploration, the recorded incidence is higher than previously expected, not only for cysts located in the tunica albuginea but also for intratesticular cysts [31]. The spectrum of their sonographic features has been recently reviewed [32]. Presently, it is estimated that these non-neoplastic cysts occur in 2.1% [33] to 9.8% [34] of testes examined. Most cysts of the tunica albuginea occur in men in the fifth and sixth decades of life [35] and are usually an incidental finding with no associated pain or testicular enlargement. The most common location is the anterolateral aspect of the testis. Their sizes range from 2 to 7 mm, and they may be big enough to occupy the entire testis (Figs. 8.16 and 8.17) [36]. They can be single or multiple, uni- or multilocular, and in some cases bilateral [37]. Their lumina show a clear fluid, devoid of spermatozoa. These cysts may be found deep within the tunica albuginea and may protrude from its inner aspect into the testicular parenchyma or outwardly from the external surface. Scrotal ultrasonography not only facilitates preoperative diagnosis but also helps to plan treatment and to avoid unnecessary orchidectomies [36,38-40]. The cysts’ epithelial lining may be simple columnar or cuboidal stratified. Cysts with columnar epithelium
r section from a testicular hydatid showing a duct with irregular architecture parallel to the testicular tunica. Figure 8.7. Small testicular hydatid composed of a central axis with a straight duct of possible Mu¨llerian origin. Figure 8.8. Testicular hydatid with papillomatous superficial architecture and underlying ovarian-like stroma. Figure 8.9. Testicular hydatid with cystic transformation and inward papillary projections. Figure 8.10. Appendix epididymis. (Left) Macroscopic image showing a large appendix of the epididymis associated with a small appendix testis. (Right) Cystic transformation of a hydatid of the epididymis. Figure 8.11. Aberrant duct: the larger lumen corresponds to an aberrant duct adjacent to an efferent duct (upper left) showing a smaller diameter and irregular smooth muscle coat. Figure 8.12. Higher magnification from Figure 8.11, showing the cribriform architecture of the epithelium in an aberrant duct with abundant intraluminal spermatozoa.
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Figures 8.13–8.20. Figure 8.13. Cross-section of an inferior aberrant duct located in the epididymis body. Note the thick muscle coat and associated concentric connective tissue. Figure 8.14. Paradidymis showing groups of tubules located on the anterior aspect of the spermatic cord, above the caput epididymis. Figure 8.15. Cross-section though the lower third of the spermatic cord in a child, showing the group of tubules conforming the paradidymis, adjacent to the vas deferens. Figure 8.16. Large
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usually show ciliated cells [41], whereas those with cuboidal epithelium usually feature two layers of nonciliated cells. Both of the epithelial types rest on well-collagenized connective tissue. Some cysts may show psammoma bodies [42], calcifications, and fluid with small crystals of carbonate-apatite, hydroxyapatite or calcium carbonate (“milk of calcium”) [43]. Focal endometriosis has been observed in a mesothelial inclusion cyst of the tunica vaginalis in a 46-year-old man who underwent a radical right-sided orchidectomy for seminoma [44]. The histogenesis of cysts of the tunica albuginea was the subject of discussions in the past, and post-traumatic [28] or post-inflammatory [45] origins were proposed. Currently, most investigators agree that these cysts are derived from mesonephric duct remnants [41,46], ductuli efferentes [47], or mesothelial cells that remained embedded in the tunica albuginea during embryonal development [35,48,49], which may undergo Mu¨llerian metaplasia (Fig. 8.18).
CYSTS OF THE RETE TESTIS Because these cysts may be located at a distance from the rete testis, their identification rests upon their epithelial lining (Fig. 8.19). This lining is similar to the postpubertal epithelium of the rete testis, with two types of cells, flat and columnar. The size of the cysts ranges from 8 to 12 mm. In the adult, these cysts frequently contain spermatozoa and for this reason are also known as intratesticular spermatoceles [50–52]. In some patients, cysts of the rete are associated with multiple epididymal cysts.
SIMPLE TESTICULAR CYST Simple testicular cysts are intraparenchymal and usually lined with a cuboidal or flat epithelium. They lack spermatozoa because they occur in infantile testes or due to the discontinuity between the cysts and the seminiferous tubules in adults [53–55]. Their sizes range from 0.2 to 8 cm. The first case was reported in a child by Schmidt in 1966 [53], although testicular cysts had been observed many years before in dog [56]. Years ago these cysts were usually incidental findings in autopsy or orchidectomy specimens from patients with prostatic carcinoma. Currently, the frequent use of ultrasonography has revealed many infantile cases [40,57]. Simple cysts were observed in 8% of 40 normal male volunteers [31] and in 9.8% of 307 normal men undergoing high-resolution scrotal ultrasonographic scanning [34]. Approximately 35% of these cysts are incidental findings (Fig. 8.20).
Testicular cysts have been reported in patients from 5 months to 80 years of age, with 2 peaks: 1 at 8 months of age and the other at 60 years of age. Approximately 50 cases have been reported in children, but only a few have been reported in children younger than 2 years of age [40,57,58]. Bilateral examples [59] and two cysts in the same testis [60] have been reported. In one case, cysts were found in a man with von Hippel-Lindau disease [61]. Testicular cysts range in size from 2 mm to 2 cm. The most frequent clinical symptom is enlargement of the testis or scrotum (50%) and then testicular pain (10%). Simple testicular cysts are thought to originate from Mu¨llerian or Wolffian remnants, but they can also have a mesothelial origin. This mesothelial origin has been demonstrated by immunohistochemical studies (epithelial cells are positive for AE1/AE3, calretinin, D240, mesothelin, and thrombomodulin) [62]. Some of these cysts, such as those of the rete testis, may derive from tubular formations of ectopic rete testis (Fig. 8.21). Differential diagnosis includes epidermoid cyst, cystic dysplasia, and teratoma [63]. Simple testicular cysts differ from epidermoid cysts on ultrasonographic imaging [64–66] and histology. Epidermoid cysts show squamous stratified epithelium and contain keratin. Cystic dysplasia is located in the testicular mediastinum, and the cysts represent transformation of multiple rete testis cavities. Diagnosis of cystic teratoma requires histological demonstration of derivatives of the three blastodermal layers [63]. Cyst growth seems to be limited, based on ultrasonographic follow-up of individual cases [65,67]. Presently, the testis is not removed, and the cysts are not excised unless their growth hinders normal testicular development in infancy [68,69] or produces symptoms in adults [62,71]. In these cases, cyst elimination is carried out by testis-sparing surgery [71,72].
OTHER EMBRYONAL REMNANTS Embryonal duct remnants are frequent in patients with ambiguous genitalia (Figs. 8.22 and 8.23). These remnants are usually ductal or glandular structures with a ciliated epithelium and may or may not communicate with the urethra. Similar embryonal remnants have been reported in otherwise normal males in three locations of special interest: hernia sac wall (Fig. 8.24), tunica vaginalis testis (Fig. 8.25), and spermatic cord wall (Figs. 8.26 and 8.27). The incidence of glandular inclusions in the walls of hernia sacs [73] in infants varies according to the series studied, for example, 1.5% [74], 2.6% [75], 2.9% [76],
r albugineal cyst, protruding into the testicular parenchyma. Figure 8.17. D2-40 immunostaining in a large cyst of the tunica albuginea showing septa lined with positive mesothelium. Figure 8.18. Cysts of the tunica albuginea lined with ciliated pseudostratified epithelium with focal apocrine features. Figure 8.19. Cyst of the rete testis. Macroscopic image of cysts with smooth surface within the rete testis compressing the surrounding testicular parenchyma. Figure 8.20. Simple testicular cyst on ultrasound imaging.
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Figures 8.21–8.28. Figure 8.21. Intraparenchymal empty cyst with low, flat epithelial lining. Figure 8.22. Tubular structure surrounded by mesenchyme in the vaginal wall of a patient with disorders of sex development (DSD). Figure 8.23. Vaginal wall in a DSD patient showing ductular structures lined with cuboidal pseudostratified epithelium. Figure 8.24. Embryonal remnants embedded within the wall of a hernia sac. Figure 8.25. Parietal layer of the tunica vaginalis with four small cysts. The upper portion of the image shows the caput epididymis. Figure 8.26. Cross-section of the spermatic cord showing
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and 6.0% [77]. The highest peak occurs at 4 months of age. The incidence reported in adults is remarkably lower, probably because the number of adult samples is much smaller. Embryonal remnants are frequent in the spermatic cord, occurring in 28% of pediatric and adult autopsies. Most remnants are found in the proximal third of the spermatic cord. Although it is possible that some of them correspond to the paradidymis, embryonal remnants have also been found in the middle and distal third of the spermatic cord [78]. Histological examination of embryonal remnants reveals glandular or tubular structures reminiscent of ductuli efferentes, ductus epididymis, or vas deferens. However, these remnants feature luminal diameters (0.17 mm) that are smaller than those in the above-mentioned normal ducts; they do not enlarge with age, and lack a true smooth muscle wall. The epithelial lining is columnar or pseudostratified, sometimes ciliated, and may be surrounded by condensed mesenchymal tissue [75,79]. Like aberrant ducts, these embryonal remnants undergo changes with age. Their lumens show a granular, proteinaceous, eosinophilic material with cholesterol clefts and multinucleate giant cells. Their walls can reach a remarkable thickness due to an irregular proliferation of vascularized connective tissue without concentric layer formation. Recognition of these embryonal remnants is important from the viewpoint of histogenesis and pathological diagnosis. For the pathologist, their recognition may prevent confusing them with ductuli efferentes, ductus epididymis, or ductus deferens, with subsequent legal implications; and misdiagnosing them as malignant tumors. Some authors have hypothesized that the remnants are Mu¨llerian derivatives [77]. This has been supported by descriptions of cysts behind the bladder discovered incidentally in patients with recurrent urinary tract infections and dysuria [80], recurrent epididymoorchitis [81], or paratesticular tumors such as serous cystadenomas [82] and mucinous cystadenomas [83]. However, most investigators concur that theses cysts derive from mesonephric ducts [84]. This latter hypothesis is based on the similarities in topographic and architectural patterns with the paradidymis, which has a well-known mesonephric origin [85]. In addition, the columnar and often ciliated epithelium is similar to that of ductuli efferentes, appendix epididymis, and Haller’s aberrant ducts. The presence of renal glomeruli in remnants of the middle and inferior portions of the spermatic cord and spermatozoa in the lumen of some remnants provide further such evidence. Finally, the linear expression of CD10 in the luminal pole of epithelial cells suggests mesonephric origin [86].
Embryonal remnants located in the spermatic cord can evolve into cysts. As a matter of fact, more than onethird of the spermatic cord cysts have this origin [78]. They can also originate tumors. A Wolffian origin has been documented in an intrahepatic paratesticular cyst in a patient with bilateral undescended testes [87] and in some papillary cystadenomas, urothelial papilloma, and Wolffian hamartomas described in the spermatic cord, epididymis, and tunica vaginalis of the testis [14]. Other embryonal remnants that can give rise to cysts in the spermatic cord include the persistence of a segment of the peritoneovaginal duct (Fig. 8.28). These mesothelial cysts are more frequent in young adults and they present clinically as an irreducible inguinal mass [88] or may be the cause of an acquired cryptorchidism [89]. These cysts may be uni- or multilocular. Their mesothelial nature is confirmed by strong immunostaining with calretinin, WT1 or D2-40. REFERENCES 1. Moore KL. The Developing Human: Clinically Oriented Embryology. Philadelphia: W. B. Saunders, 1973. 2. Jacob M, Barteczko K. Contribution to the origin and development of the appendices of the testis and epididymis in humans. Anat Embryol (Berl) 2005;209:287–302. 3. Hamm B. Sonography of the testis and epididymis. Andrologia 1994;26:193–210. 4. Pe´rez-Tamayo R. Historia de Diez Gigantes. Me´xico: El Colegio Nacional; Me´xico, D. F. 1991. 5. Sahni D, Jit I, Joshi K, Sanjeev. Incidence and structure of the appendices of the testis and epididymis. J Anat 1996;189(Pt 2): 341–348. 6. Jozsa T, Csizy I, Kutasy B, Cserni T, Flasko T. Decreased incidence of appendix testis in cryptorchidism with intraoperative survey. Urol Int 2008;80:317–320. 7. Favorito LA, Cavalcante AG, Babinski MA. Study on the incidence of testicular and epididymal appendages in patients with cryptorchidism. Int Braz J Urol 2004;30:49–52. 8. Sundarasivarao D. The Mullerian vestiges and benign epithelial tumours of the epididymis. J Pathol Bacteriol 1953;66:417–432. 9. Samnakay N, Cohen RJ, Orford J, King PA, Davies RJ. Androgen and oestrogen receptor status of the human appendix testis. Pediatr Surg Int 2003;19:520–524. 10. Kistamas K, Ruzsnavszky O, Telek A, Kosztka L, Kovacs I, Dienes B, et al. Expression of anti-Mullerian hormone receptor on the appendix testis in connection with urological disorders. Asian J Androl 2013;15: 400–403. 11. Posinovec J. [Is the unstalked hydatid a functioning organ?]. Verh Anat Ges 1969;63:751–759. 12. Nicolay L, Gitlin J, Palmer LS. Torsion of the appendix testis in an undescended testis: a case report. Can J Urol 2013;20:6805–6807. 13. Kernohan NM, Coutts AG, Best PV. Cystadenocarcinoma of the appendix testis. Histopathology 1990;17:147–154. 14. Nistal M, Gonzalez-Peramato P, Serrano A, Vega-Perez M, De Miguel MP, Regadera J. Paratesticular cysts with benign epithelial proliferations of Wolffian origin. Am J Clin Pathol 2005;124: 245–251.
r embryonal rests with thick-walled ductular structures. Figure 8.27. Embryonal rests in the spermatic cord of an adult, with a cyst adjacent to a small cluster of Leydig cells. Figure 8.28. Cross-section of the spermatic cord (lower left) in a 3-year-old boy showing rests of the peritoneovaginal duct.
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46. Mennemeyer RP, Mason JT. Non-neoplastic cystic lesions of the tunica albuginea: an electron microscopic and clinical study of 2 cases. J Urol 1979;121:373–375. 47. Tanaka K, Kamidono S, Yoshimura K, Umezu K. Benign cystic lesion of the tunica albuginea: a case report. Hinyokika Kiyo 2004; 50:45–48. 48. Mancilla-Jimenez R, Matsuda GT. Cysts of the tunica albuginea. Report of 4 cases and review of the literature. J Urol 1975;114:730–733. 49. Warner KE, Noyes DT, Ross JS. Cysts of the tunica albuginea testis: a report of 3 cases with a review of the literature. J Urol 1984;132: 131–132. 50. Davis RS. Intratesticular spermatocele. Urology 1998;51(suppl 5A]: 167–169. 51. Tejada E, Eble JN. Simple cyst of the rete testis. J Urol 1988;139: 376–377. 52. Yalowitz BR, Eble JN, Wilks DC. Spermatozoa-containing simple cysts of the rete testis. J Urol 1989;142:1572–1573. 53. Schmidt SS. Congenital simple cyst of the testis: a hitherto undescribed lesion. J Urol 1966;96:236–238. 54. Takihara H, Valvo JR, Tokuhara M, Cockett AT. Intratesticular cysts. Urology 1982;20:80–82. 55. Tosi SE, Richardson JR Jr. Simple cyst of the testis: case report and review of the literature. J Urol 1975;114:473–475. 56. Barach AL. Report of a case of cysts of the testicle in a dog. Proceedings of the New York Pathological Society 1919;19:38. 57. Ceylan H, Karaca I, Sari I, Ortac R, Ozokutan BH, Kervancioglu S. Simple testicular cyst: a rare cause of scrotal swelling in infancy. Int J Urol 2004;11:352–354. 58. Gucer S, Tanyel C, Caglar M. Simple cyst of the testis: a rare and benign cause of testicular swelling in infancy. Turk J Pediatr 2007; 49:448–450. 59. Lam KY. Bilateral intratesticular cysts—a specific entity. Scand J Urol Nephrol 1996;30:329–331. 60. Sahin A, Ozen H, Gedikoglu G, Ozyavuz R, Remzi D. Two simple cysts of the same testis. Br J Urol 1994;73:107–108. 61. Brown JA, Segura JW. A symptomatic testicular cyst in a patient with von Hippel-Lindau disease. Urology 1996;48:494–495. 62. Kuwamoto S, Okuno K, Kato M, Hayashi K. Simple cysts of testis with immunohistochemical evidence of mesothelial origin. Pathol Int 2009;59:656–659. 63. Hatsiopoulou O, Dawson C. Simple intratesticular cysts in adults: a diagnostic dilemma. BJU Int 2001;88:248–250. 64. Garcia CJ, Zuniga S, Rosenberg H, Arce JD, Zuniga F. Simple intratesticular cysts in children: preoperative sonographic diagnosis and histological correlation. Pediatr Radiol 1999;29:851–855. 65. Hobarth K, Kratzik C. High resolution ultrasonography in the diagnosis of simple intratesticular cysts. Br J Urol 1992;70:546–549. 66. Rifkin MD, Jacobs JA. Simple testicular cyst diagnosed preoperatively by ultrasound. J Urol 1983;129:982–983. 67. Kratzik C, Hainz A, Kuber W, Donner G, Lunglmayr G, Frick J, et al. Surveillance strategy for intratesticular cysts: preliminary report. J Urol 1990;143:313–315. 68. Altadonna V, Snyder HM, 3rd, Rosenberg HK, Duckett JW. Simple cysts of the testis in children: preoperative diagnosis by ultrasound and excision with testicular preservation. J Urol 1988;140:1505–1507. 69. Shergill IS, Thwaini A, Kapasi F, Potluri BS, Barber C. Management of simple intratesticular cysts: a single-institution 11-year experience. Urology 2006;67:1266–1268. 70. Al-Jabri T, Misra S, Maan ZN, Khan K, Coker C, Thompson P. Ultrasonography of simple intratesticular cysts: a 13 year experience in a single centre. Diagn Pathol 2011;6:24. 71. Honjo O, Uemura S, Murakami I. Simple testicular cyst in infants: a case report and review of the literature. Eur J Pediatr Surg 2001; 11:425–427. 72. Pumberger W, Hallwirth U, Horcher E. [Intratesticular epithelial cyst in an infant]. Klin Padiatr 1998;210:370–372. 73. Taylor GP. Pathology of the pediatric regio inguinalis: mysteries of the hernia sac exposed. Pediatr Dev Pathol 2000;3:513–524.
74. Popek EJ. Embryonal remnants in inguinal hernia sacs. Hum Pathol 1990;21:339–349. 75. Gomez-Roman JJ, Mayorga M, Mira C, Buelta L, Fernandez F, ValBernal JF. Glandular inclusions in inguinal hernia sacs: a clinicopathological study of six cases. Pediatr Pathol. 1994;14:1043–1049. 76. Steigman CK, Sotelo-Avila C, Weber TR. The incidence of spermatic cord structures in inguinal hernia sacs from male children. Am J Surg Pathol 1999;23:880–885. 77. Walker AN, Mills SE. Glandular inclusions in inguinal hernial sacs and spermatic cords. Mullerian-like remnants confused with functional reproductive structures. Am J Clin Pathol 1984;82:85–89. 78. Nistal M, Iniguez L, Paniagua R, Redondo E, Regadera J. Tubular embryonal remnants in the human spermatic cord. Urol Int 1987;42: 260–264. 79. Gill B, Favale D, Kogan SJ, Bennett B, Reda E, Levitt SB. Significance of accessory ductal structures in hernia sacs. J Urol 1992;148(pt 2):697–698. 80. Kuo HJ, Karmazyn B, Cain MP. Duplicated Mu¨llerian remnant in a 6-year-old boy. Pediatr Radiol. 2009;39:854–856. 81. Gupta AD, Loeb S, Stec A, Wang MH. Unusual presentation of a Mullerian remnant in an infant with recurrent epididymo-orchitis. Urology 2011;78:1414–1416. 82. McCluggage WG, Shah V, Nott C, Clements B, Wilson B, Hill CM. Cystadenoma of spermatic cord resembling ovarian serous epithelial
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tumour of low malignant potential: immunohistochemical study suggesting Mullerian differentiation. Histopathology 1996;28:77–80. Uschuplich V, Hilsenbeck JR, Velasco CR. Paratesticular mucinous cystadenoma arising from an oviduct-like Mu¨llerian remnant: a case report and review of the literature. Arch Pathol Lab Med 2006;130: 1715–1717. Nistal M, Iniguez L, Paniagua R. Histological classification of spermatic cord cysts in relation to their histogenesis. Eur Urol 1987; 13:327–330. Arey LB. Developmental Anatomy. A Textbook and Laboratory Manual of Embryology, 7th ed. Philadelphia: W. B. Saunders, 1974. Cerilli LA, Sotelo-Avila C, Mills SE. Glandular inclusions in inguinal hernia sacs: morphologic and immunohistochemical distinction from epididymis and vas deferens. Am J Surg Pathol 2003;27:469–476. Ceccanti S, Mele E, Masselli G, Bosco S, Cozzi DA. Intrahepatic paratesticular cyst: unique presentation of vestigial remnants of Wolffian duct. Urology 2012;79:212–214. Aarabi S, Drugas G, Avansino JR. Mesothelial cyst presenting as an irreducible inguinal mass. J Pediatr Surg 2010;45:e19–21. Vaos G, Zavras N, Velaoras K, Ereikat K. Muesothelial cyst of the spermatic cord as a cause of acquired cryptorchidism. Hernia 2009; 13:439–441.
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Perspectives in Pediatric Pathology, Chapter 8. Persistence of Embryonal Remnants in the Testis and Epididymis MANUEL NISTAL,1 RICARDO PANIAGUA,2 PILAR GONZA´LEZ-PERAMATO,1
AND
MIGUEL REYES-MU´GICA3*
1
Pathology, Hospital La Paz, Universidad Auto´noma de Madrid, Calle Arzobispo Morcillo #2, Madrid 28029, Spain Department of Cell Biology, Universidad de Alcala, Madrid, Spain 3 Department of Pathology, Children’s Hospital of Pittsburgh of University of Pennsylvania Medical Center, One Children’s Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA 2
Received April 19, 2014; accepted May 20, 2014; published online August 8, 2014.
INTRODUCTION Histological analysis of surgical specimens from testes, epididymis, spermatic cords, and hernia sacs frequently shows glandular and tubular structures that may lead to erroneous diagnoses if one does not take into account their embryonal origin (Fig. 8.1). The Wolffian duct is the precursor of the ductus epididymis, the ductus or vas deferens, seminal vesicles, and ejaculatory duct. The mesonephric ducts, located near the gonad, form the efferent ductuli, while the Mu¨llerian ducts degenerate early, due to the action of anti-Mu¨llerian hormone [1]. Nevertheless, remnants of these three embryonic ducts can remain even in adult age and be found during microscopic examination of autopsy or surgical specimens [2]. One of every two adult men has cysts derived from these embryonal remnants. The most useful technique for exploration of these structures is ultrasonography [3].
APPENDIX TESTIS (SESSILE HYDATID OF MORGAGNI) The embryonal remnants we know today as appendix testis and appendix epididymis were first described by Giovanni Battista Morgagni in 1761. Morgagni is considered the founding father of anatomic pathology, and in his long tenure as professor of anatomy in Padua, he described many morbid findings observed during his accurate anatomic studies [4]. It is, therefore, humbling that his name gained posterity associated with this small and seemingly insignificant structure, described by him as a “hydatid” (from a term meaning water-filled vesicle). It was Griffiths in 1893 who individualized both structures based on their gross and microscopic differences. Luschka in 1954 observed that the appendix of the testis was preferably sessile, whereas the appendix of the epididymis was pediculate. The terms *Corresponding author, e-mail: [email protected]
sessile hydatid of Morgagni and pediculate hydatid of Morgagni, as these structures are also described, refer to these observations. The appendix testis derives from the Mu¨llerian (or paramesonephric) duct, which undergoes regression in the male embryo at the eighth week of gestation. Only the cephalic and caudal portions of the duct remain in the adult, forming the appendix testis and prostatic utricle, respectively. The Mu¨llerian duct segment that originates the appendix testis is similar to the one from which the fimbriae develop in the female uterine tubes. The appendix testis is located in the anterosuperior testicular pole or in the epididymotesticular fold in 76% of adult men and 83.3% of newborns and infants [5]. They are bilateral in two-thirds of cases. Consensus regarding their incidence in patients with cryptorchid testes has reached only 24% according to Jozsa and colleagues [6], whereas other investigators find no statistical differences in incidence and distribution of the appendix testis between normal or undescended testis [7]. The appendix testis is often a sessile structure of variable size, ranging from several millimeters to a few centimeters (Fig. 8.2). It is formed by a central core of loose connective tissue with variable vascularization, including lymphatic vessels (Fig. 8.3). Its outer surface appears scalloped and is lined with columnar or pseudostratified epithelium with hyperchromatic basal nuclei and ciliated cells [5,8]. The epithelium expresses both androgen and estrogen receptors [9], whereas the stroma is positive for anti-Mu¨llerian hormone receptor type II (AMHR2) [10] and CD10 (Fig. 8.4). Within the core of connective tissue, glandular or tubular structures are found. They are lined with an epithelium similar to that of the hydatid surface. Most of the time, this represents deep invaginations of the superficial epithelium. The glandular lumen often contains mucus or calcified material. In some cases, a real tube in the stroma has been interpreted as a Mu¨llerian duct remnant (Fig. 8.5–8.7). In others, only a focus of fibrosis or
Figures 8.1–8.12. Figure 8.1. A. Schematic representation of possible Mu¨llerian and Wolffian embryonic rests. Figure 8.2. Appendix testis. (Left) Macroscopic image of appendix testis at the upper testicular pole, close to epididymis. (Right) Appendix testis with superficial epithelium showing a festoon-like arrangement and calcifications at the tip. Figure 8.3. Appendix testis. Immunohistochemical staining with D2-40 showing abundant lymphatic vessels. Figure 8.4. Appendix testis. CD10 showing a positive band of stroma underlying the superficial epithelium. Figure 8.5. Testicular hydatid showing a small ductal structure within the core of connective tissue, possibly corresponding to a Mu¨llerian structure. Figure 8.6. Longitudinal
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thickened albuginea is observed at the anatomical location where the hydatid would be expected (Fig. 8.8). The physiological role of the appendix testis, if any, could be the control of fluid volume within the tunica vaginalis cavity [2]. The superficial epithelium, subepithelial capillaries, and lymphatic vessels of the appendix testis could be a functional unit [11]. Pathologies related to the appendix testis include cystic transformation, torsion (see vascular pathology [12]), and less frequently in adults, tumors such as cystadenomas and cystadenocarcinomas (Fig. 8.9) [13,14].
APPENDIX EPIDIDYMIS (PEDICULATE HYDATID OF MORGAGNI) The appendix epididymis or pediculate hydatid of Morgagni corresponds to the blind cephalic end of the Wolffian duct. This embryonal remnant is a small cyst attached to the caput epididymis by a pedicle. It is found in 21.9% to 28% of adult epididymes [15] (Fig. 8.10). The cyst wall is lined with a slightly basophilic, ciliated, columnar or pseudostratified epithelium with vacuolated cells containing periodic acid–Schiff- and Alcian-blue– positive material. The stroma around the cyst may show a few smooth muscle cells, and the outer surface of the hydatid is lined with mesothelium. Like the appendix testis, the hydatid may undergo torsion [16] and marked cystic transformation [17,18] and, rarely in the adult, can give rise to a tumor [19,20].
ABERRANT DUCTS Aberrant ducts, also termed Haller’s organs, are mesonephric duct remnants located in the fissure between testis and epididymis. There are two aberrant ducts: superior and inferior. The superior aberrant duct is located in the corpus epididymis. This is an inconstant and blind sacended duct (Figs. 8.11 and 8.12). The inferior aberrant duct is located along the corpus and cauda of the epididymis, following a sinuous course parallel to the main epididymal axis. The inferior aberrant duct measures 3.5 to 35 mm in length [21]. The cranial extreme is blind, whereas the caudal end opens to the ductus epididymis in the cauda. Both of the aberrant ducts are tubular structures lined with a columnar or cuboidal epithelium, surrounded by a few smooth muscle rings. Cystic transformation and torsion of the inferior aberrant duct have been reported [22,23].
PARADIDYMIS The paradidymis (organ of Giralde´s, Henle’s paraepididymis or innominate body) consists of a few small ductuli derived from caudal mesonephric ducts and located in the anterior face of the inferior spermatic cord end, near the caput of the epididymis (Figs. 8.14 and 8.15). The paradidymis ductuli do not communicate with the ductus deferens lumen, and their structure is similar to that of the aberrant ducts. Torsion [24,25] and cystic transformation [26] of the paradidymis have been reported. Most cysts are asymptomatic, usually diagnosed by ultrasonography, and only clinical, noninvasive explorations are advisable [27].
CYSTS OF THE TUNICA ALBUGINEA Cysts of the tunica albuginea are malformations located either within the tunica albuginea or inside the testicular parenchyma. These lesions were first reported nearly a century ago [28], and their recognition can prevent unnecessary amputations and orchidectomies. For many years, these cysts were considered unusual malformations [29,30]. With the systematic use of high-resolution ultrasonography for testicular exploration, the recorded incidence is higher than previously expected, not only for cysts located in the tunica albuginea but also for intratesticular cysts [31]. The spectrum of their sonographic features has been recently reviewed [32]. Presently, it is estimated that these non-neoplastic cysts occur in 2.1% [33] to 9.8% [34] of testes examined. Most cysts of the tunica albuginea occur in men in the fifth and sixth decades of life [35] and are usually an incidental finding with no associated pain or testicular enlargement. The most common location is the anterolateral aspect of the testis. Their sizes range from 2 to 7 mm, and they may be big enough to occupy the entire testis (Figs. 8.16 and 8.17) [36]. They can be single or multiple, uni- or multilocular, and in some cases bilateral [37]. Their lumina show a clear fluid, devoid of spermatozoa. These cysts may be found deep within the tunica albuginea and may protrude from its inner aspect into the testicular parenchyma or outwardly from the external surface. Scrotal ultrasonography not only facilitates preoperative diagnosis but also helps to plan treatment and to avoid unnecessary orchidectomies [36,38-40]. The cysts’ epithelial lining may be simple columnar or cuboidal stratified. Cysts with columnar epithelium
r section from a testicular hydatid showing a duct with irregular architecture parallel to the testicular tunica. Figure 8.7. Small testicular hydatid composed of a central axis with a straight duct of possible Mu¨llerian origin. Figure 8.8. Testicular hydatid with papillomatous superficial architecture and underlying ovarian-like stroma. Figure 8.9. Testicular hydatid with cystic transformation and inward papillary projections. Figure 8.10. Appendix epididymis. (Left) Macroscopic image showing a large appendix of the epididymis associated with a small appendix testis. (Right) Cystic transformation of a hydatid of the epididymis. Figure 8.11. Aberrant duct: the larger lumen corresponds to an aberrant duct adjacent to an efferent duct (upper left) showing a smaller diameter and irregular smooth muscle coat. Figure 8.12. Higher magnification from Figure 8.11, showing the cribriform architecture of the epithelium in an aberrant duct with abundant intraluminal spermatozoa.
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Figures 8.13–8.20. Figure 8.13. Cross-section of an inferior aberrant duct located in the epididymis body. Note the thick muscle coat and associated concentric connective tissue. Figure 8.14. Paradidymis showing groups of tubules located on the anterior aspect of the spermatic cord, above the caput epididymis. Figure 8.15. Cross-section though the lower third of the spermatic cord in a child, showing the group of tubules conforming the paradidymis, adjacent to the vas deferens. Figure 8.16. Large
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usually show ciliated cells [41], whereas those with cuboidal epithelium usually feature two layers of nonciliated cells. Both of the epithelial types rest on well-collagenized connective tissue. Some cysts may show psammoma bodies [42], calcifications, and fluid with small crystals of carbonate-apatite, hydroxyapatite or calcium carbonate (“milk of calcium”) [43]. Focal endometriosis has been observed in a mesothelial inclusion cyst of the tunica vaginalis in a 46-year-old man who underwent a radical right-sided orchidectomy for seminoma [44]. The histogenesis of cysts of the tunica albuginea was the subject of discussions in the past, and post-traumatic [28] or post-inflammatory [45] origins were proposed. Currently, most investigators agree that these cysts are derived from mesonephric duct remnants [41,46], ductuli efferentes [47], or mesothelial cells that remained embedded in the tunica albuginea during embryonal development [35,48,49], which may undergo Mu¨llerian metaplasia (Fig. 8.18).
CYSTS OF THE RETE TESTIS Because these cysts may be located at a distance from the rete testis, their identification rests upon their epithelial lining (Fig. 8.19). This lining is similar to the postpubertal epithelium of the rete testis, with two types of cells, flat and columnar. The size of the cysts ranges from 8 to 12 mm. In the adult, these cysts frequently contain spermatozoa and for this reason are also known as intratesticular spermatoceles [50–52]. In some patients, cysts of the rete are associated with multiple epididymal cysts.
SIMPLE TESTICULAR CYST Simple testicular cysts are intraparenchymal and usually lined with a cuboidal or flat epithelium. They lack spermatozoa because they occur in infantile testes or due to the discontinuity between the cysts and the seminiferous tubules in adults [53–55]. Their sizes range from 0.2 to 8 cm. The first case was reported in a child by Schmidt in 1966 [53], although testicular cysts had been observed many years before in dog [56]. Years ago these cysts were usually incidental findings in autopsy or orchidectomy specimens from patients with prostatic carcinoma. Currently, the frequent use of ultrasonography has revealed many infantile cases [40,57]. Simple cysts were observed in 8% of 40 normal male volunteers [31] and in 9.8% of 307 normal men undergoing high-resolution scrotal ultrasonographic scanning [34]. Approximately 35% of these cysts are incidental findings (Fig. 8.20).
Testicular cysts have been reported in patients from 5 months to 80 years of age, with 2 peaks: 1 at 8 months of age and the other at 60 years of age. Approximately 50 cases have been reported in children, but only a few have been reported in children younger than 2 years of age [40,57,58]. Bilateral examples [59] and two cysts in the same testis [60] have been reported. In one case, cysts were found in a man with von Hippel-Lindau disease [61]. Testicular cysts range in size from 2 mm to 2 cm. The most frequent clinical symptom is enlargement of the testis or scrotum (50%) and then testicular pain (10%). Simple testicular cysts are thought to originate from Mu¨llerian or Wolffian remnants, but they can also have a mesothelial origin. This mesothelial origin has been demonstrated by immunohistochemical studies (epithelial cells are positive for AE1/AE3, calretinin, D240, mesothelin, and thrombomodulin) [62]. Some of these cysts, such as those of the rete testis, may derive from tubular formations of ectopic rete testis (Fig. 8.21). Differential diagnosis includes epidermoid cyst, cystic dysplasia, and teratoma [63]. Simple testicular cysts differ from epidermoid cysts on ultrasonographic imaging [64–66] and histology. Epidermoid cysts show squamous stratified epithelium and contain keratin. Cystic dysplasia is located in the testicular mediastinum, and the cysts represent transformation of multiple rete testis cavities. Diagnosis of cystic teratoma requires histological demonstration of derivatives of the three blastodermal layers [63]. Cyst growth seems to be limited, based on ultrasonographic follow-up of individual cases [65,67]. Presently, the testis is not removed, and the cysts are not excised unless their growth hinders normal testicular development in infancy [68,69] or produces symptoms in adults [62,71]. In these cases, cyst elimination is carried out by testis-sparing surgery [71,72].
OTHER EMBRYONAL REMNANTS Embryonal duct remnants are frequent in patients with ambiguous genitalia (Figs. 8.22 and 8.23). These remnants are usually ductal or glandular structures with a ciliated epithelium and may or may not communicate with the urethra. Similar embryonal remnants have been reported in otherwise normal males in three locations of special interest: hernia sac wall (Fig. 8.24), tunica vaginalis testis (Fig. 8.25), and spermatic cord wall (Figs. 8.26 and 8.27). The incidence of glandular inclusions in the walls of hernia sacs [73] in infants varies according to the series studied, for example, 1.5% [74], 2.6% [75], 2.9% [76],
r albugineal cyst, protruding into the testicular parenchyma. Figure 8.17. D2-40 immunostaining in a large cyst of the tunica albuginea showing septa lined with positive mesothelium. Figure 8.18. Cysts of the tunica albuginea lined with ciliated pseudostratified epithelium with focal apocrine features. Figure 8.19. Cyst of the rete testis. Macroscopic image of cysts with smooth surface within the rete testis compressing the surrounding testicular parenchyma. Figure 8.20. Simple testicular cyst on ultrasound imaging.
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Figures 8.21–8.28. Figure 8.21. Intraparenchymal empty cyst with low, flat epithelial lining. Figure 8.22. Tubular structure surrounded by mesenchyme in the vaginal wall of a patient with disorders of sex development (DSD). Figure 8.23. Vaginal wall in a DSD patient showing ductular structures lined with cuboidal pseudostratified epithelium. Figure 8.24. Embryonal remnants embedded within the wall of a hernia sac. Figure 8.25. Parietal layer of the tunica vaginalis with four small cysts. The upper portion of the image shows the caput epididymis. Figure 8.26. Cross-section of the spermatic cord showing
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and 6.0% [77]. The highest peak occurs at 4 months of age. The incidence reported in adults is remarkably lower, probably because the number of adult samples is much smaller. Embryonal remnants are frequent in the spermatic cord, occurring in 28% of pediatric and adult autopsies. Most remnants are found in the proximal third of the spermatic cord. Although it is possible that some of them correspond to the paradidymis, embryonal remnants have also been found in the middle and distal third of the spermatic cord [78]. Histological examination of embryonal remnants reveals glandular or tubular structures reminiscent of ductuli efferentes, ductus epididymis, or vas deferens. However, these remnants feature luminal diameters (0.17 mm) that are smaller than those in the above-mentioned normal ducts; they do not enlarge with age, and lack a true smooth muscle wall. The epithelial lining is columnar or pseudostratified, sometimes ciliated, and may be surrounded by condensed mesenchymal tissue [75,79]. Like aberrant ducts, these embryonal remnants undergo changes with age. Their lumens show a granular, proteinaceous, eosinophilic material with cholesterol clefts and multinucleate giant cells. Their walls can reach a remarkable thickness due to an irregular proliferation of vascularized connective tissue without concentric layer formation. Recognition of these embryonal remnants is important from the viewpoint of histogenesis and pathological diagnosis. For the pathologist, their recognition may prevent confusing them with ductuli efferentes, ductus epididymis, or ductus deferens, with subsequent legal implications; and misdiagnosing them as malignant tumors. Some authors have hypothesized that the remnants are Mu¨llerian derivatives [77]. This has been supported by descriptions of cysts behind the bladder discovered incidentally in patients with recurrent urinary tract infections and dysuria [80], recurrent epididymoorchitis [81], or paratesticular tumors such as serous cystadenomas [82] and mucinous cystadenomas [83]. However, most investigators concur that theses cysts derive from mesonephric ducts [84]. This latter hypothesis is based on the similarities in topographic and architectural patterns with the paradidymis, which has a well-known mesonephric origin [85]. In addition, the columnar and often ciliated epithelium is similar to that of ductuli efferentes, appendix epididymis, and Haller’s aberrant ducts. The presence of renal glomeruli in remnants of the middle and inferior portions of the spermatic cord and spermatozoa in the lumen of some remnants provide further such evidence. Finally, the linear expression of CD10 in the luminal pole of epithelial cells suggests mesonephric origin [86].
Embryonal remnants located in the spermatic cord can evolve into cysts. As a matter of fact, more than onethird of the spermatic cord cysts have this origin [78]. They can also originate tumors. A Wolffian origin has been documented in an intrahepatic paratesticular cyst in a patient with bilateral undescended testes [87] and in some papillary cystadenomas, urothelial papilloma, and Wolffian hamartomas described in the spermatic cord, epididymis, and tunica vaginalis of the testis [14]. Other embryonal remnants that can give rise to cysts in the spermatic cord include the persistence of a segment of the peritoneovaginal duct (Fig. 8.28). These mesothelial cysts are more frequent in young adults and they present clinically as an irreducible inguinal mass [88] or may be the cause of an acquired cryptorchidism [89]. These cysts may be uni- or multilocular. Their mesothelial nature is confirmed by strong immunostaining with calretinin, WT1 or D2-40. REFERENCES 1. Moore KL. The Developing Human: Clinically Oriented Embryology. Philadelphia: W. B. Saunders, 1973. 2. Jacob M, Barteczko K. Contribution to the origin and development of the appendices of the testis and epididymis in humans. Anat Embryol (Berl) 2005;209:287–302. 3. Hamm B. Sonography of the testis and epididymis. Andrologia 1994;26:193–210. 4. Pe´rez-Tamayo R. Historia de Diez Gigantes. Me´xico: El Colegio Nacional; Me´xico, D. F. 1991. 5. Sahni D, Jit I, Joshi K, Sanjeev. Incidence and structure of the appendices of the testis and epididymis. J Anat 1996;189(Pt 2): 341–348. 6. Jozsa T, Csizy I, Kutasy B, Cserni T, Flasko T. Decreased incidence of appendix testis in cryptorchidism with intraoperative survey. Urol Int 2008;80:317–320. 7. Favorito LA, Cavalcante AG, Babinski MA. Study on the incidence of testicular and epididymal appendages in patients with cryptorchidism. Int Braz J Urol 2004;30:49–52. 8. Sundarasivarao D. The Mullerian vestiges and benign epithelial tumours of the epididymis. J Pathol Bacteriol 1953;66:417–432. 9. Samnakay N, Cohen RJ, Orford J, King PA, Davies RJ. Androgen and oestrogen receptor status of the human appendix testis. Pediatr Surg Int 2003;19:520–524. 10. Kistamas K, Ruzsnavszky O, Telek A, Kosztka L, Kovacs I, Dienes B, et al. Expression of anti-Mullerian hormone receptor on the appendix testis in connection with urological disorders. Asian J Androl 2013;15: 400–403. 11. Posinovec J. [Is the unstalked hydatid a functioning organ?]. Verh Anat Ges 1969;63:751–759. 12. Nicolay L, Gitlin J, Palmer LS. Torsion of the appendix testis in an undescended testis: a case report. Can J Urol 2013;20:6805–6807. 13. Kernohan NM, Coutts AG, Best PV. Cystadenocarcinoma of the appendix testis. Histopathology 1990;17:147–154. 14. Nistal M, Gonzalez-Peramato P, Serrano A, Vega-Perez M, De Miguel MP, Regadera J. Paratesticular cysts with benign epithelial proliferations of Wolffian origin. Am J Clin Pathol 2005;124: 245–251.
r embryonal rests with thick-walled ductular structures. Figure 8.27. Embryonal rests in the spermatic cord of an adult, with a cyst adjacent to a small cluster of Leydig cells. Figure 8.28. Cross-section of the spermatic cord (lower left) in a 3-year-old boy showing rests of the peritoneovaginal duct.
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