Spermatic Cord and Testicular Adnexa

14

Spermatic Cord and Testicular Adnexa DA V ID G . B O ST WI C K A N D J UN M A

C HA P T E R OU T LI N E Introduction 834 Embryology and Normal Anatomy 834 Embryology 834 Anatomy 834 Congenital Anomalies 836 Splenogonadal Fusion 836 Adrenal Heterotopia and Renal Ectopia 836 Wolffian and M€ ullerian Remnants 837 Hernia Sac Specimens: Glandular Inclusions Versus Vas Deferens or Epididymis 837 Cystic Fibrosis 837 Nonneoplastic Diseases of the Spermatic Cord and Testicular Adnexa 838 “Celes” and Cysts 838 Inflammatory and Reactive Diseases 840 Other Nonneoplastic Diseases 843 Neoplasms 844 Benign Neoplasms and Pseudotumors 844 Malignant Neoplasms 848

Introduction The paratesticular region includes the testicular tunics, efferent ductules, epididymis, spermatic cord, and vas deferens. Most studies of paratesticular region pathology include the rete testis despite its intratesticular location.1 Numerous rare and interesting lesions arise in this region, including cysts, “celes,” inflammatory diseases, embryonic remnants, neoplasms, and neoplasm-like proliferations (Table 14.1). In children, one of the common neoplasms is paratesticular rhabdomyosarcoma. In adults the most common pathologic conditions, in order of frequency and excluding “celes,” are epididymitis, lipoma of the spermatic cord, adenomatoid tumor of the epididymis, and sarcoma of the spermatic cord.2 It is often difficult to diagnose paratesticular masses before or during surgery due to their varied morphologic appearance and rarity. An inguinal surgical approach is usually indicated when there is a suspicion of malignancy. The pathologist should document the anatomic site of origin, histologic classification, and extent of spread of the lesion. 834

Embryology and Normal Anatomy The paratesticular region contains numerous anatomically complex epithelial and mesenchymal structures, often within embryonic remnants (Fig. 14.1). The rete testis of the mediastinum of the testis, the first element of the wolffian collecting system, connects the seminiferous tubules and efferent ductules. The most common abnormalities of the paratesticular region are benign, including hydrocele, lipoma, and inflammatory conditions such as epididymitis, but a variety of cystic and proliferative lesions also occur and are diagnostically challenging.

Embryology The embryology of the testis and its adnexa is described in Chapter 12; herein is a brief summary of significant events in the development of paratesticular tissues. The testis and head of the epididymis arise from the genital ridge. The wolffian ducts, the male genital ducts, are paired tubes that are associated with the developing gonads and degenerating mesonephric tubules.3 The body and tail of the epididymis, the vas deferens, and the ejaculatory duct arise from the mesonephric tubules; other degenerating tubules often persist as embryonic remnants including the appendix epididymis, paradidymis, and cranial and caudal aberrant ductules (Fig. 14.1). The paired vasa deferentia connect to the ejaculatory ducts within the prostate that, in turn, have their outlets in the prostatic urethra adjacent to the m€ullerian tubercle. Blind diverticula of the distal vas deferens form the seminal vesicles. The m€ ullerian duct, or paramesonephros, regresses in men but may persist as embryonic remnants such as the appendix testis and prostatic utricle.

Anatomy Scrotum and Testicular Tunics The sac of the scrotum is divided by a partial median septum into two compartments, each of which contains a testis and epididymis and the lower portion of the spermatic cord. The scrotal wall consists of six layers, from the inside outward: the tunica vaginalis, the internal spermatic fascia, the cremasteric muscle, the external spermatic fascia, the dartos muscle, and the skin. The tunica vaginalis is a thin mesothelium-covered layer of the parietal peritoneum that

C H A P T E R 14

TABLE 14.1

Spermatic Cord and Testicular Adnexa

835

Paratesticular Tumors and Cysts in the Ccanadian Reference Center for Cancer Pathology, 1949 to 1986

Diagnosis

No. of Cases

Cysts Mesothelial cyst Epididymal cyst

4 1

Benign Neoplasms and Pseudotumors Adenomatoid tumor Nodular and diffuse fibrous proliferation Leiomyoma Cystadenoma of epididymis Hamartoma of rete testis Adenomatous hyperplasia of epididymis Adenomatous hyperplasia of rete testis Mixed gonadal stromal tumor Adrenal cortical heterotopia Rhabdomyoma Miscellaneous soft tissue tumors

23 6 6 3 1 1 1 1 1 1 8

Malignant Neoplasms Primary Rhabdomyosarcoma Liposarcoma Leiomyosarcoma Malignant mesothelioma Malignant fibrous histiocytoma Malignant mesenchymoma Plasmacytoma Papillary serous cystadenocarcinoma of low malignant potential Sarcoma, not otherwise specified

14 9 7 7 3 1 1 1 3

Secondary Metastatic carcinoma Metastatic carcinoid tumor Metastatic non-Hodgkin lymphoma

4 2 2

From Srigley JR, Hartwick RWH. Tumors and cysts of the paratesticular region. Pathol Annu 1990:25(Pt 2):51–108 (review), with permission.

also covers the white fibrous tunica albuginea of the testis and epididymis; it is initially in contact with the peritoneal cavity from which it arises but becomes isolated with regression of the processus vaginalis. A common stimulus such as androgens is likely required for obliteration of the processus vaginalis and epididymal development, a hypothesis supported by the common coexistence of epididymal anomalies and patency of the processus vaginalis.4 The internal spermatic fascia is a continuation of the transversalis fascia, and the external fascia is a continuation of the external oblique aponeurosis. The cremasteric muscle consists of incomplete slips of muscle, usually in the upper part of the scrotal wall. The dartos muscle consists of smooth muscle embedded in loose areolar tissue. The scrotum is supplied by the external and internal pudendal, cremasteric, and testicular arteries. Lymphatics drain to the superficial inguinal lymph nodes.

Rete Testis The rete testis is formed by the convergence of the seminiferous tubules (see Chapter 12). The tubules follow a cranial and dorsal course through the fibrous connective tissue of the mediastinum

Fig. 14.1 Anatomy of the testis and paratesticular adnexa, including embryonic remnants.

testis, eventually merging into 12 to 20 ducts (the efferent ductules, or ductuli efferentes that perforate the tunica vaginalis and form the head of the epididymis at the upper pole of the testis). After puberty, elastic fibers are present in the muscular coat of the ductules, epididymis, and vas deferens.

Epididymis The epididymis is a highly convoluted tubule that is attached to the dorsomedial portion of the testis, connecting the efferent ductules of the rete testis with the vas deferens. It is about 6 m long. The head consists of a series of conical masses, the lobules, each of which contain a single duct measuring 15 to 20 cm long; it is lined by tall columnar epithelium and invested with a thick layer of smooth muscle. The body of the epididymis is a single highly convoluted tube that increases in diameter distally to form the tail. The tail distally merges with the vas deferens. Development of the efferent ducts and ductus epididymis follows a biphasic pattern. Progressive development occurs from the fetal period to infancy between 2 and 4 months of age, but this development is transient and regresses during later infancy. At childhood, definitive development is initiated and finishes at puberty. These changes are probably related to the androgen dependence of the epididymis, the different stages of testicular maturation, and the steroidogenic activity of the Leydig cells.5 The epididymis plays a critical role in maturation and viability of spermatozoa; SED1 facilitates epididymal cell adhesion, and its loss leads to breakdown of the epididymal epithelium and consequent development of spermatic granulomas.6 A variety of morphologic variations occur in the epididymal columnar cells and vas deferens including cribriform hyperplasia (42% of patients), patchy or diffuse eosinophilic granular cell change (Paneth cell–like metaplasia) (8.3%), intranuclear eosinophilic inclusions, nuclear atypia with “monstrous” cells (14%), adenomatous hyperplasia, prostatic-type glands, epithelial luminal pitting, multiple diverticula in the cauda epididymis in the elderly, and accumulation of lipofuscin pigment.7-18

836 CHA P T E R 14

Spermatic Cord and Testicular Adnexa

Vas Deferens (Ductus Deferens) and Spermatic Cord The vas deferens is about 46 cm long, traversing the spermatic cord and inguinal canal to connect the tail of the epididymis with the ejaculatory ducts. In the spermatic cord, it is invested with a thick, muscular coat that includes the internal spermatic, cremasteric, and external spermatic fasciae; other structures of the spermatic cord include the pampiniform plexus, the testicular artery, lymphatics, and nerves. Upon exiting the spermatic cord, the vas deferens passes extraperitoneally upward, and laterally in the pelvis, then medial to the distal ureter and the posterior wall of the bladder, and terminates at an acute angle in a dilated ampulla that, with the duct of the seminal vesicle, forms the ejaculatory duct. The vas deferens is supplied by its own artery, the artery of the vas deferens, which is usually a branch of the internal iliac or umbilical artery. The vas deferens is lined by columnar epithelium in low folds, with morphologic variations like those in the epididymis (see earlier). The wall of the vas deferens consists of three layers of smooth muscle: the inner longitudinal, middle circular, and outer longitudinal layers. Elastic fibers appear in the muscular wall after puberty.

Congenital Anomalies Abnormal development of the paratesticular region may result in a variety of anomalies, including embryonic remnants, agenesis, atresia, ectopia, and cysts. There is an increased frequency of anomalies in boys with cryptorchidism and congenital rubella. Bilateral anomalies result in sterility. Agenesis and atresia of the testis, epididymis, and vas deferens result from failure of development of the genital ridge, often with anomalies of other wolffian derivatives and renal ectopia, agenesis, or dysplasia. Congenital absence of the vas deferens may be autosomal recessive, partial or complete, unilateral or bilateral, and is often associated with cystic fibrosis (see later). Testicular biopsies in patients with congenital absence of the vas deferens reveal normal spermatogenesis or hypospermatogenesis in up to 45% of cases, and clinical investigation should include semen analysis, renal ultrasound, and genetic cystic fibrosis screening.19,20 Congenital unilateral absence of the vas deferens is more commonly associated with renal agenesis than bilateral absence (74% versus 12%, respectively).19 Duplications may involve any structure of the adnexa, but they are rare. Ectopic insertion of the ureteric bud in the epididymis, vas deferens, or seminal vesicles also may occur. Congenital or developmental cysts of the epididymis are rare and may be associated with intrauterine exposure to diethylstilbestrol.21 The cysts are usually solitary but may be multiple and bilateral. Ectopic epididymis may be found anterior to the testis, in the retroperitoneum, and within the kidney. Epididymal abnormalities are commonly associated with ectopic or cryptorchid testes (72% of cases), ranging from simple elongation of the epididymis (33%) to more complex changes such as complete disruption (39%).22

or surgery for cryptorchidism or inguinal hernia. About 57% are associated with other congenital anomalies, including peromelia, micrognathia, and cardiac anomalies. Hepatogonadal fusion has also been reported.24 There are two types of splenogonadal fusion. The continuous type is characterized by connection of the spleen and the splenogonad by a fibrous cord. The cord usually arises in the upper pole of the spleen and may be retroperitoneal or anterior to the small bowel or colon. Splenic tissue may be present at both ends of the cord or stud the cord throughout its length. The discontinuous type of splenogonadal fusion has no connection between the spleen and splenogonad. The splenic tissue appears within the tunica albuginea or scrotum, or along the vascular pedicle. Splenogonadal fusion probably results from early fusion of the spleen and gonad during embryonic development, perhaps as the result of inflammation or adhesions. The spleen develops during the fourth and fifth weeks of gestation, and rotates into proximity with the urogenital fold and developing gonadal mesoderm. During the eighth to tenth weeks, the gonads migrate caudally, probably accompanied by a portion of the spleen in cases of splenogonadal fusion. The limb buds and mandible are developing at the same time, accounting for the close association of splenogonadal fusion with peromelia and micrognathia. Preoperative diagnosis of splenogonadal fusion by splenic scan may avoid unnecessary orchiectomy. Splenogonadal fusion and accessory spleen are important to consider when splenic ablation is needed.

Adrenal Heterotopia and Renal Ectopia Adrenal cortical tissue may be present anywhere along the route of descent of the testis from the abdomen to the scrotum.25 It is usually an incidental finding at inguinal herniorrhaphy or epididymoorchiectomy, present in 1% to 3% of children undergoing such operations.26-28 Adrenal cortical tissue has been identified in inguinal hernia sac, spermatic cord (Fig. 14.2), epididymis, and rete testis.29 It may present as a palpable tumor, and appears as small, round-to-oval, 1 to 5 mm in diameter, yellow-orange nodules, usually near the inguinal ring. The lesions almost always consist of adrenal cortical tissue resembling zona glomerulosa and fasciculata. Rarely they contain medullary tissue. Involution during childhood is the rule, but exceptional cases persist and become functional, rarely harboring neoplasms or developing into “tumors” in the adrenogenital syndrome and Nelson syndrome; rare cases occur in adults.29 Removal of functional rests may result

Splenogonadal Fusion Splenogonadal fusion is a rare congenital anomaly in which there is fusion of the splenic and gonadal anlage.23 About 100 cases have been reported, usually on the left side (98%) in men (95%). Patients may present with nontender scrotal mass or intestinal obstruction, but most cases are discovered incidentally at autopsy

Fig. 14.2 Heterotopic adrenal cortical tissue in the left spermatic cord forming a discrete yellow-orange nodule.

C H A P T E R 14

in adrenal insufficiency. Ectopic renal tissue has rarely been observed in the scrotum, consisting of tubules and immature glomeruli.

€llerian Remnants Wolffian and Mu Numerous embryonic remnants are found in the paratesticular area, including the appendix testis (hydatid of Morgagni), appendix epididymis, paradidymis, and vasa aberrantia. Precise classification of cystic remnants may be challenging.30,31

Appendix Testis (Hydatid of Morgagni) The appendix testis is attached to the surface of more than 90% of testes at autopsy; ultrasound examination found an incidence rate of 44%.32 This structure is located at the superior pole of the testis adjacent to the epididymis. Grossly it varies from 2 to 4 mm, appearing as a polypoid or sessile nodular excrescence. Microscopically it consists of a fibrovascular core of loose connective tissue covered by simple cuboidal or low columnar m€ ullerian-type epithelium that is in continuity with the tunica vaginalis at the base. The fibrovascular core may contain tubular inclusions lined by similar cuboidal epithelium. Torsion of the appendix testis may be painful and mimic testicular torsion, and is the most common cause of acute scrotum in children.33,34 The severity of the acute inflammatory cell infiltrates is associated with longer duration of symptoms and clinical evidence of torsion of the testicular appendages.35 No other association was detected between the pattern or degree of acute inflammatory cell infiltrate and any other clinicopathologic variable that may indicate pyogenic infection. No bacteria or fungal elements were identified. Marked lymphatic dilation may be the only histologic finding to indicate the presence of early torsion in cases of scrotal pain secondary to torsion of the appendix testis. Appendix Epididymis (Vestigial Caudal Mesonephric Collecting Tubule) The appendix epididymis is present in about 35% of testicles examined at autopsy; ultrasound examination found an incidence rate of 18%.32 Grossly it is a pedunculated spherical cystic or elongate structure arising from the anterosuperior pole of the head of the epididymis. Microscopically it is lined by cuboidal to low columnar epithelium that may be ciliated and show secretory activity. The wall consists of loose connective tissue and is covered by flattened mesothelial cells that are continuous with the visceral tunica vaginalis. The appendix epididymis may become dilated by serous fluid and, when enlarged, may mimic a tumor. Torsion may occur, sometimes in cryptorchidism. Paradidymis (Organ of Giraldes) This wolffian duct embryonic remnant consists of clusters of tubules lined by cuboidal to low columnar epithelium within the connective tissue of the spermatic cord, superior to the head of the epididymis.36 Vasa Aberrantia (Organ of Haller) Vasa aberrantia are wolffian duct remnants that appear as clusters of tubules that are histologically similar to the paradidymis. They arise within the groove between the testis and epididymis. Torsion of the vas aberrans is rare.37

Spermatic Cord and Testicular Adnexa

837

Other Lesions Associated With the Epididymis Other rare epididymal lesions have been described, including epididymal cyst, duplication, and ectopic epididymal tissue associated with inguinal hernia. Cyst and duplication may arise from the caudal vasa aberrantia. Walthard Rest The remnant Walthard rest, probably of m€ ullerian origin, consists of solid and cystic nests of uniform epithelial cells with ovoid nuclei and characteristic longitudinal grooves.

Hernia Sac Specimens: Glandular Inclusions Versus Vas Deferens or Epididymis Herniorrhaphy in children is surgically challenging, particularly in strangulated hernia sac, accounting for the vulnerability of the epididymis and vas deferens that may be inadvertently transected during the procedure. This problem is compounded by the diagnostic difficulty in classifying glandular inclusions in hernia sacs; a challenging problem in young children is separating these structures and embryonic remnants before puberty. Benign glandular inclusions in inguinal herniorrhaphy specimens may represent M€ ullerian remnants, wolffian remnants, transected vas deferens, or transected epididymis. It is critical to make this distinction due to the potential impact on reproductive function and medicolegal issues.38-41 Disruption of one vas deferens may generate antisperm antibodies. Classification of glandular inclusions is often subjective; in one study, interobserver agreement was reported in only 44% to 52% of cases.39 Epididymis typically has a well-formed concentric muscular coat, whereas embryonic remnants lack a muscular coat but have a mantle of fibrous tissue. Some have advocated the use of Masson trichrome stain and muscle-specific actin to make this distinction, but this has been refuted by others as inconclusive.39 Comparative analysis reveals that the combination of glandular diameter (with special attention to patient age, recognizing possible changes with advancing development) and histochemical and immunohistochemical stains (trichrome, muscle-specific actin, and CD10) should allow distinction in most cases (Table 14.2). Reliance on light microscopic features alone may be misleading.38 Should inguinal hernia repair specimens be routinely submitted for histopathologic examination? One study of 456 specimens from 371 patients younger than 20 years revealed four unexpected cases with epididymal tissue (1%), leading the authors to conclude that pathologic study was an unnecessary expense.42 In a study of almost 1500 inguinal herniorrhaphies, the authors found vas deferens in 0.13% of cases (Table 14.2).43 Another report of more than 7000 consecutive pediatric herniorrhaphies found incidence rates of 0.23% vas deferens, 0.3% epididymis, and 0.41% embryonal rests.39 Inguinal hernia characteristically shows cremasteric muscle fiber hypertrophy that accounts for the palpable thickening of the spermatic cord (see later Hamartoma [Smooth Muscle Hyperplasia] section).44

Cystic Fibrosis Cystic fibrosis is a genetic abnormality that often affects the testicular adnexa, resulting in infertility due to agenesis or atresia of mesonephric structures or anomalies of the testes (see Chapter 12). Patients with congenital bilateral absence of vas

838 CHA P T E R 14

TABLE 14.2

Spermatic Cord and Testicular Adnexa

Glandular Inclusions in Herniorrhaphies: Comparative Features

Embryonic remnants

Vas deferens Epididymis

Incidence in Herniorrhaphies (%)

Mean Diameter (mm)

Immunophenotype

1.540 2.6282 2.939 6.041 0.1640 0.2339 0.1640 0.3039 0.8842

0.1740 0.20282

Muscle-specific actin negative; CD10 negative-38

0.638 1.2-1.4 (age, 4 months)40 0.20282

Muscle-specific actin positive in wall; CD10 positive+38 Muscle-specific actin positive in wall; CD10 positive+ in epithelium38

“Celes” and Cysts

Hematocele (Hematoma) Hematocele refers to the accumulation of blood in the space between the parietal and visceral tunica vaginalis, often in association with hydrocele (Fig. 14.3). Long-standing hematocele becomes calcified and fibrotic, with numerous hemosiderin-laden macrophages. The causes of hematocele are like those for hydrocele. Idiopathic hematoma arising in the spermatic cord or epididymis may be mistaken for neoplasm.48

Hydrocele This mesothelial-lined cyst results from accumulation of serous fluid between the parietal and visceral tunica vaginalis of the testis (Fig. 14.3). There are two variations of spermatic cord hydrocele: the “encysted” variety that does not communicate with the peritoneal cavity, caused by defective closure at both proximal and distal ends of processus vaginalis; and the “funicular” variety that does communicate with the peritoneal cavity, caused by defective closure of only the distal end of tunica vaginalis. The encysted type can be confused with an inguinal mass (lymphadenopathy, hernia) and a primary tumor of the cord.45,46 Congenital hydrocele occurs when a patent processus vaginalis within the spermatic cord communicates with the peritoneal cavity. The prevalence of congenital hydrocele is about 6% at birth and 1% in adulthood. Most cases of hydrocele are idiopathic, but they may be associated with inguinal hernia, scrotal trauma, epididymoorchitis, or tumors of the testis or paratesticular region. Possible causes of idiopathic hydrocele include excessive secretion within the testicular tunics by parietal mesothelial cells, decreased reabsorption, and congenital absence of efferent lymphatics. Hydrocele is lined by a single layer of cuboidal or flattened mesothelial cells, sometimes with prominent atypia, with underlying connective tissue stroma. The luminal fluid is usually clear and serous unless complicated by infection or hemorrhage. The surface is often covered by fibrinous adhesions and inflammation, and subepithelial chronic inflammation and fibrosis may be present. In some cases progressive fibrosis narrows or obliterates the cyst lumen, creating adhesions and multiple cysts. Spermatocele may rupture into the hydrocele sac. Contralateral hydrocele, commonly seen in cases of neonatal testicular torsion, is of minimal clinical significance and does not warrant formal inguinal exploration for treatment, thereby minimizing the potential of contralateral spermatic cord injury in the neonate.47

Varicocele Varicocele is a mass of dilated tortuous veins of the internal testicular vein and pampiniform venous plexus of the spermatic cord that occurs posterior and superior to the testis, sometimes extending into the inguinal ring (Fig. 14.3). The venous plexus normally empties into the internal spermatic vein near the internal inguinal ring; poor drainage and progressive dilatation and elongation result from incompetent valves of the left internal spermatic vein that empties into the renal vein. The right internal spermatic vein is less likely to be involved with varicocele because it drains directly into the inferior vena cava and has a lower probability of having incompetent valves. Varicocele results from many conditions, but most cases are idiopathic. Unilateral varicocele in older men may indicate the presence of a renal tumor that has invaded the renal vein and occluded the spermatic vein drainage. Varicocele is associated with maternal exposure to diethylstilbestrol. Patients with varicocele sometimes present with testicular pain associated with sexual activity. Longstanding varicocele may result in testicular damage in some males, causing testicular atrophy with impaired sperm production and decreased Leydig cell function, whereas in others the varicocele may seemingly cause no ill effects. In adult men, varicocele is frequently present and surgically correctable, yet the measurable benefits of surgical repair are slight.49 Although occurring more commonly in infertile men than fertile men, only 20% of those with varicocele will suffer from fertility problems. Most varicoceles found in adolescents are detected during routine medical examination, and it is difficult to predict which adolescent presenting with a varicocele will ultimately show diminished testicular function in adolescence or adulthood. As in adults, the mainstay of treatment for varicocele in adolescents is surgical correction. Treatment consists of ligation of the internal spermatic vein at the level of the internal inguinal ring and does not usually yield a pathologic specimen for analysis.

deferens often have cystic fibrosis, although this finding may occur in patients without cystic fibrosis.

Nonneoplastic Diseases of the Spermatic Cord and Testicular Adnexa

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839

Fig. 14.3 (A) Hydrocele. (B) Encapsulated hematocele. (C) Varicocele. (D) Spermatocele.

Microscopic changes in the pampiniform plexus with varicocele include vascular wall thickening, segmental obliteration, medial hypertrophy of longitudinal smooth muscle fibers, fragmentation of the internal elastic lamina, and occasional occlusive thrombi.50,51 Compared with control group without varicocele, affected patients have significant thickening of the tunica adventitia and tunica media of the spermatic veins (control versus varicocele: tunica adventitia 0.22  0.10 mm versus 0.35  0.08 mm, respectively; tunica media: 0.09  0.04 mm versus 0.25  0.05 mm, respectively).52

Spermatocele (Acquired Epididymal Cyst) Spermatocele is a dilatation of an efferent ductule in the region of the rete testis or caput epididymis.53 The inner lining consists of a single layer of cuboidal to flattened epithelial cells that are often ciliated. The wall is composed of fibromuscular soft tissue, often with chronic inflammation, and the cyst may be unilocular or multilocular (Fig. 14.3).54 Spermatocele is distinguished from hydrocele by the presence of spermatozoa within the cyst fluid (Fig. 14.4), a distinction that can be made by aspiration cytology. Torsion is a rare complication of spermatocele.55,56 Benign papilloma may arise within the epithelial lining of spermatocele. The papillae contain fibrovascular cores lined by a single

layer of columnar epithelium with vacuolated cytoplasm. The epithelium appears cytologically benign, and there is no evidence of subepithelial invasion.

Mesothelial Cyst Mesothelial cyst arises within the tunica vaginalis, tunica albuginea, or, less commonly, the epididymis and spermatic cord. The cyst may be single or multiple, measuring up to 2.5 cm in diameter, and lined by a single layer of uniform cuboidal to flattened attenuated mesothelial cells. Mesothelial cyst of the tunica vaginalis arises from the connective tissue of the tunica. There may be nodular or diffuse proliferation of mesothelial cells, sometimes with squamous metaplasia. This cyst is probably an embryonic remnant or an inclusion of vaginalis mesothelium resulting from inflammation, trauma, or neoplasm, similar to mesothelial cyst of the tunica albuginea. Mesothelial cyst of the tunica albuginea most often occurs in men older than 40 years, but all ages are affected. It is usually located anterior and lateral to the testis, measuring up to 4 cm in diameter. The cyst is filled with clear or blood-tinged serous fluid, and the lining consists of typical mesothelial cells with a wall composed of hyalinized fibrous tissue. Unilocular and multilocular mesothelial cyst of the spermatic cord is rare and probably arises

840 CHA P T E R 14

Spermatic Cord and Testicular Adnexa

Fig. 14.4 Spermatocele with sperm granuloma. (A) Caput epididymis with dilated efferent ductules filled with abundant spermatozoa. (B) Abundant extravasation of sperm (lower right) rimmed by macrophages (upper left).

from embryonic mesothelial remnants such as the processus vaginalis.57

Epidermoid Cyst (Epidermal Cyst) Epidermoid cyst is common in the testis, comprising about 1% of testicular tumors, but may also rarely arise in the paratesticular area and epididymis.58 Epidermoid cyst consists of a lining of benign keratinizing squamous epithelium and a wall composed of fibrous connective tissue, often with inflammation. Diligent search is required to exclude the presence of adnexal structures or teratomatous elements. Paratesticular epidermoid cyst may arise from squamous metaplasia of wolffian duct structures, displacement of squamous epithelium from the scrotal skin to paratesticular structures during embryogenesis, squamous metaplasia of mesothelial cyst, or monomorphic epidermal development of a teratoma. Epidermoid cyst in the paratesticular area does not recur after surgical excision. Some consider this tumor to be a cholesteatoma when it arises in the epididymis.

Cystic transformation of the rete testis and epididymis is common in men undergoing dialysis for chronic renal insufficiency. Histologic changes include columnar transformation of the epithelium, accumulation of calcium oxalate crystals, fibrosis, and giant cell reaction.62-64 Other causes of cystic transformation include mechanical obstruction of the epididymis by tumor or trauma, ischemia, hormonal alterations such as those in cirrhosis, or cryptorchidism.65 Patients with cryptorchidism display changes in the rete testis referred to in one report as dysgenetic rete testis; changes included metaplastic epithelium with columnar or large cuboidal cells, rete testis hypoplasia, combined hypoplasia and cystic dysplasia, or adenomatous hyperplasia.10,66 These findings may result from a primary abnormality of the rete testis or incomplete pubertal maturation. A rare case was reported of a 35-year-old with a seminal vesicle cyst that extended through the inguinal canal.67

Inflammatory and Reactive Diseases

Dermoid Cyst (Mature Teratoma) Dermoid cyst most often involves the testis and paratesticular structures, but may occur in the spermatic cord and, rarely, in the testicular tunics.59 This cyst measures up to 4 cm in diameter and contains soft, cheesy, yellow-white amorphous material with or without hair and calcifications. The cyst is lined by keratinized squamous epithelium, and the wall contains typical dermal adnexal structures such as pilosebaceous units, although these may be difficult to identify without thorough sectioning. Dermoid cyst does not recur or metastasize after excision.

Epididymitis Epididymitis may be acute or chronic, depending on the inciting agent and the duration of infection.68 It usually occurs in association with orchitis or after trauma but rarely is an isolated finding. Most cases result from retrograde spread by vesicoepididymal urine reflux, but hematogenous and lymphatic spread account for some. Congenital anomalies such as ureteral ectopia may cause epididymitis in infants. The surgical pathologist rarely receives specimens of these diseases. Urethral and epididymal smears and cultures are useful in identifying the causative infectious agent.

Simple Cyst and Cystic Dysplasia of the Rete Testis Simple cyst of the rete testis is rare and is typically unilocular, up to 1 cm in diameter, lined by normal rete testis tubular epithelium, and bulges into the testis proper. When multilocular, it is often associated with epididymal cysts.60 Cystic dysplasia of the rete testis is a benign congenital lesion of newborns and young boys that is frequently associated with ipsilateral renal agenesis and dysplasia.61 It clinically mimics testicular cancer. Long-term follow-up for possible recurrence is recommended.

Acute Epididymitis

Patients with acute epididymitis usually present with unilateral painful enlargement of the epididymis, more commonly on the right side, often involving the testicle (50% of cases have epididymoorchitis) and vas deferens (Fig. 14.5). The epididymis is thickened, congested, and edematous, with white fibrinopurulent exudate in the tubules and stroma. Microabscesses and fistulae may occur, but rupture is uncommon. The tubules may be damaged or destroyed by the inflammation, sometimes with squamous metaplasia and regenerative changes.

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TABLE 14.3

841

Comparison of Bacterial and Chlamydial Epididymitis Bacterial Epididymitisa

Chlamydial Epididymitis

59.8 (39-79) Yes

42.8 (22-74) Infrequent

Frequent Yes

Infrequent No

Yes

No

Yes Yes Yes Histiocytes

Minimal Minimal Minimal Epithelial cells

Clinical Features Patient age (range), y Pain

Laboratory Features Pyuria Elevated erythrocytic sedimentation rate Elevated C-reactive protein

Pathologic Features Tissue destruction Xanthogranuloma Abscess and necrosis Cytoplasmic location of antigens

Fig. 14.5 Acute Epididymitis With Associated Testicular Infarction.

Acute epididymitis is commonly caused by bacteria. Coliforms account for most cases in children, whereas Neisseria gonorrhoeae and Chlamydia trachomatis are most frequent in young men, and Escherichia coli and Pseudomonas predominate in older men.69 Other bacteria that may cause acute epididymitis include Klebsiella, Staphylococcus, Streptococcus pneumoniae, Neisseria meningitidis, Aerobacter aerogenes, and Haemophilus influenzae. The epididymis is a reservoir for N. gonorrhoeae, and although infection may be asymptomatic, microabscesses and edema are common, usually without extensive necrosis. The round cytoplasmic inclusions of C. trachomatis are difficult to identify in routinely stained sections, and immunohistochemical stains, culture, or genotypic studies are usually required for diagnosis. Clinical and histopathologic findings allow separation of some cases of chlamydial and bacterial epididymitis (Table 14.3).70 C. trachomatis–positive cases are clinically indolent, with minimally destructive periductal and intraepithelial inflammation and epithelial regeneration.71 Lymphoepithelial complexes and squamous metaplasia are sometimes present. E. coli–positive cases are characterized by scrotal pain, pyuria, leukocytosis, and highly destructive epididymitis with abscesses and xanthogranulomas. Viral causes of acute epididymitis include mumps and cytomegalovirus, like those causing orchitis (see Chapter 12). Mumps epididymitis, present in 85% of cases of mumps orchitis, occurs before testicular involvement, usually appearing as unilateral scrotal swelling after parotiditis. The epididymis shows vascular congestion, edema, and interstitial lymphocytic inflammation; neutrophils are usually not a prominent feature. Cytomegaloviral epididymitis may occur in patients with AIDS or those receiving immunosuppression for transplantation.72,73 In endemic areas such as India, parasitic infection by Wuchereria bancrofti preferentially involves intrascrotal juxtatesticular lymphatic vessels, with nests of microfilaria with a mean diameter of 0.3 cm2 observable by ultrasonography.74,75 These infections form epididymal and spermatic cord nodules that contain larvae (microfilariae), eggs, and adult worms, visible in cytologic smears. Early diagnosis and treatment prevents the more severe manifestation

a Usually Escherichia coli. Modified from Hori S, Tsutsumi Y. Histologic differentiation and bacterial epididymitis: nondestructive and proliferative versus destructive and abscess forming — immunohistochemical and clinicopathologic findings. Hum Pathol 1995;26:402–407.

of the disease, lymphatic filariasis. Traumatic acute epididymitis is characterized by vascular congestion, petechial hemorrhages, and hematocele. Drugs such as amiodarone may also cause epididymitis.76 Chronic Epididymitis

Although many cases of acute epididymitis resolve, some become chronic. The epididymis in chronic epididymitis is indurated and scarred, with cystically dilated tubules, marked fibrosis, chronic inflammation, and sperm granulomas; similar changes may account for the “late vasectomy syndrome” in which patients report pain many months or years after vasectomy.77 The epithelium shows reactive or metaplastic changes, often with cytoplasmic vacuolization and lumenal hyaline aggregates. Epididymitis nodosa, a proliferative lesion of the epididymis, may result from chronic inflammation or trauma, reminiscent of vasitis nodosa.78 Coarse granular cytoplasmic changes appear in the epididymis in the setting of ductal obstruction. Calcification is common in chronic epididymitis, and there may be a foreign body giant cell reaction. Xanthogranulomatous epididymitis may also occur. Special stains for bacteria and fungi may be of value. Specific causes of chronic epididymitis include tuberculosis, leprosy, malakoplakia, sarcoidosis, and sperm granuloma. The epididymis is the reservoir for tuberculous involvement in the male genital tract, with secondary testicular involvement and other local sites of involvement in about 80% of cases; 40% of cases of renal tuberculosis are accompanied by epididymal infection. Patients usually present with painless scrotal swelling, but other signs and symptoms include unilateral or bilateral mass, infertility, and scrotal fistula.79,80 Caseating granulomatous inflammation is prominent, with fibrous thickening and enlargement of the epididymis and adjacent structures (Fig. 14.6). Rarely miliary tuberculosis causes small punctate white lesions. One case of bilateral tuberculous epididymoorchitis followed intravesical bacillus Calmette–Guerin therapy for urothelial carcinoma of the

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eosinophilia; scrotal and penile elephantiasis results from lymphatic obstruction.90 Human papillomavirus was identified by polymerase chain reaction in dysplastic squamous metaplastic epithelium of the epididymis in a 39-year-old man.91 Young syndrome is characterized by the association of sinobronchial disease and azoospermia resulting from bilateral epididymitisassociated obstruction in the distal ductuli efferentes.92,93 Idiopathic granulomatous epididymitis is a rare but significant finding at autopsy or during surgery (less than 1% incidence rate), arising in the caput epididymis.94 This lesion contains zonal necrosis of efferent ducts with epithelial damage and regeneration. Macrophages are plentiful, as are cholesterol crystals, foreign body–type giant cells, and spermatozoa. Sperm Granuloma Fig. 14.6 Tuberculosis of the Epididymis and Testis.

bladder.81 The auramine-rhodamine stain is preferred over the Ziehl–Neelsen stain because of its greater sensitivity (60% positive in aspiration smears).82 Fine needle aspiration cytology was diagnostic in 67% of patients with tubercular epididymitis or epididymoorchitis, with epithelioid cell granulomas with caseation.82 Lepromatous leprosy frequently involves the epididymis, usually after testicular involvement, but rarely spreads to the vas deferens. Patients report painful scrotal swelling, and the epididymis and testis are thickened and enlarged. The inflammation consists chiefly of perivascular and perineural lymphocytic infiltrates, often with sheets of macrophages that contain acid-fast bacilli set in a dense sclerotic stroma. Sterility results from testicular azoospermia rather than epididymal blockage. The dartos muscle of the testicular tunics shows a predilection for lepromatous myositis. Malakoplakia of the epididymis is uncommon, usually occurring with testicular involvement.83 Patients are asymptomatic or present with painful scrotal swelling or hydrocele. The histologic findings are similar to malakoplakia at other sites. Sarcoidosis involves the genital tract in about 5% of cases at autopsy but is rarely symptomatic. The epididymis is the most common site of genital involvement.84-86 Patients present with painful or painless scrotal swelling that is bilateral in about 33% of cases. Nonnecrotizing granulomatous inflammation is typical, similar to involvement at other sites. The main differential diagnostic consideration is sperm granuloma, but extravasated sperm are absent in sarcoidosis. Epididymitis may also result from other fungi,12 bacteria, parasites, and viruses. Candida albicans epididymoorchitis with candiduria is rare, usually after instrumentation of the urinary tract.87 Histoplasma capsulatum creates necrotizing inflammation and abscesses that mimic sperm granuloma; typical silver-stained 2to 4-μm fungal spores are usually present.88 Coccidioides immitis produces necrotizing and nonnecrotizing granulomas of the epididymis and prostate; silver-stained fungal spherules measuring about 100 μm in diameter contain numerous endospores. Systemic Blastomyces dermatitidis involves the epididymis in up to 30% of systemic cases, producing microabscesses that contain silverstained budding fungal spores up to 15 μm in diameter with thick refractile capsules.89 Other causes of epididymitis include Paracoccidioides brasiliensis, Actinomyces, Sporothrix schenckii, Schistosoma haematobium, Treponema pallidum, typhoid, brucellosis, rickettsia, and hydatid cyst. The degenerating worms of W. bancrofti filariasis produce granulomas, often with prominent tissue and blood

Sperm granuloma is an exuberant foreign body giant cell reaction to extravasated sperm and occurs in up to 42% of patients after vasectomy and 2.5% of routine autopsies.95 Patients may have no symptoms but often present with a history of pain and swelling of the upper pole of the epididymis, spermatic cord, and, rarely, testis. Others have a history of trauma, epididymitis, and orchitis. In some cases sperm granuloma mimics testicular or spermatic cord tumor. Sperm granuloma appears as a solitary yellow nodule or multiple small indurated nodules measuring up to 3 cm in diameter. Foreign body–type granulomas are present, with necrosis in the early stages and progressive fibrosis in late stages (Fig. 14.4). Extravasated sperm are often present in large numbers, but are quickly engulfed by macrophages (referred to as spermiophages) and eventually disappear. Yellow-brown ceroid pigment, a lipid degradation product of sperm, may persist. Vasitis nodosa occurs in about one-third of cases of sperm granuloma. Disruption of the tubules and extravasation of sperm results in sperm granuloma, but isolated sperm may be present in the interstitium without significant inflammation. Ligation vasectomy accounts for most cases of sperm granuloma, whereas cauterization vasectomy rarely results in granuloma. Secondary oxalosis with crystal deposition from chronic renal failure may be accompanied by sperm granuloma.63 Experimental injection of ceroid pigment produces granulomatous inflammation, suggesting that destruction of sperm initiates the process. An autoimmune process has been proposed but is not favored.

Vasitis and Vasitis Nodosa Inflammation of the vas deferens (vasitis, or deferentitis) usually occurs in association with epididymitis or posterior urethritis.96 Vasitis nodosa is a benign ductular proliferation that produces nodular and fusiform enlargement of the vas deferens, often after vasectomy. It resembles salpingitis isthmica nodosa and clinically mimics sperm granuloma. In vasitis nodosa the vas deferens may be more than 1 cm in diameter, with diffuse enlargement or rounded indurated masses punctuated by small lumens. The ductular proliferation is prominent and may be mistaken for metastatic prostatic adenocarcinoma. Chronic inflammation and fibrosis are always observed, although in variable amounts, and are sometimes accompanied by muscular hyperplasia of the wall. The ductules vary from discrete, round, acinar structures to plexiform masses of irregular acini. The cells are cuboidal or low columnar, with a moderate amount of pale granular cytoplasm, central large nuclei with uniform chromatin, and single enlarged nucleoli. Cilia may be present. Perineural invasion is common and often extensive, and may be mistaken for malignancy; benign vascular invasion may

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also occur. Sperm granulomas are present in about 50% of cases, and sperm are often present in the acinar lumens of vasitis nodosa. As the number of sperm granulomas declines, the amount of ceroid pigment increases, resulting from lipid breakdown products of spermatozoa. A histologically similar process may occur in the epididymis (epididymitis nodosa). Vasitis nodosa is a benign reactive process. Trauma or surgery results in epithelial rupture with release of sperm into the soft tissues of the vas deferens, invariably invoking a prominent fibroinflammatory response. However, some cases have no history of trauma and are idiopathic. Funiculitis (Inflammation of the Spermatic Cord)

Inflammation of the spermatic cord, or funiculitis, often accompanies vasitis, usually as the result of direct extension from the vas deferens, but isolated involvement may occur by hematogenous spread from other sites of inflammation.97,98 Funiculitis appears as painful enlargement of the spermatic cord. Tuberculous funiculitis is rare, presenting as multiple large, discrete masses or diffuse thickening with typical necrotizing granulomatous inflammation.99 Perforation of an incarcerated hernia may cause extravasation of fecal contents and vegetable fibers, resulting in an exuberant foreign body giant cell reaction in the cord. Sclerosing endophlebitis and thrombosis of the pampiniform plexus may accompany funiculitis, resulting in necrosis and gangrene. Recent reports described diabetes-associated, Actinomyces-infected xanthogranulomatous funiculitis and Dirofilaria repens–induced chronic funiculitis and epididymitis.69,100 S. haematobium–induced funiculitis can be diagnosed by semen analysis in infected men.101 An unusual incidental finding during hernia repair in a 70-year-old was incarcerated colonic diverticulum with fecalith that was “parasitized” onto the spermatic cord.102

Meconium-Induced Inflammation Prenatal or antenatal perforation of the colon may cause meconium leakage through the patent processus vaginalis into the scrotum, resulting in foreign body giant cell reaction, chronic inflammation, and scarring; this is referred to as meconium periorchitis, meconium granuloma, or meconium vaginalitis.103 Fewer than 30 cases have been reported, rarely in association with cystic fibrosis. Grossly the tunica vaginalis contains a single mass or is studded with numerous orange or green nodules composed of chronically inflamed myxoid stroma, sometimes containing bile, cholesterol, or lanugo hairs within histiocytes. Hydrocele is often present. Vasculitis Vasculitis may be part of systemic vasculitis or may exist as singleorgan/isolated vasculitis; the distinction is important because in other forms of single-organ vasculitis, surgical therapy alone may be curative. Isolated epididymal or spermatic cord vasculitis is rare and usually occurs in men presenting with a mass in the absence of systemic symptoms and normal laboratory results.104,105 In most patients with isolated vasculitis, neoplasm is initially suspected, and vasculitis is an unexpected finding. After surgical removal, isolated vasculitis does not require systemic therapy. Systemic vasculitides may affect the epididymal and testicular vessels, sometimes resulting in hydrocele or swelling of the affected structures.106 Polyarteritis nodosa is observed in these vessels at autopsy in 80% of affected patients, although clinical involvement is rare.107,108 There are no histopathologic differences between systemic vasculitis and most forms of isolated necrotizing vasculitis of testicular and epididymal tissue.105

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Other Nonneoplastic Diseases Torsion of the Spermatic Cord and Embryonic Remnants Torsion of the spermatic cord results in hemorrhagic infarction of the testis (see Chapter 12), as well as thrombosed veins surrounded by fat necrosis with cystic cavities bounded by wavy hyaline membranes.109-111 Torsion of embryonic remnants is a much rarer event that may clinically mimic torsion of the cord. Torsion of a hernia sac is rare, presenting as acute scrotum in children.112 Torsion is a common abnormality of the appendix testis. Patients report acute scrotal pain, often after vigorous exercise. About 90% of patients are boys between 10 and 12 years of age, accounting for the most common cause of acute scrotum in children, but men of all ages are affected. Typical histologic features of torsion are present, including severe congestion, edema, and hemorrhagic infarction. Severe acute inflammation is associated with longer duration of symptoms.35 Bilateral involvement is rare.113 Torsion of the appendix epididymis is much less common than of the appendix testis, and the histologic findings are similar. Torsion of the vasa aberrantia is rare, with fewer than 10 reported cases. Calculi and Calcification Acute and chronic epididymitis and vasitis predispose to calculus formation usually in the epididymis, vas deferens, and scrotum (Fig. 14.7). The calculi are brown and composed of phosphates and carbonates, measuring up to 1 cm in diameter. Their occurrence in varicocele veins has been referred to as “varicolithiasis.”114 Idiopathic mural calcification of the vas deferens occurs in up to 15% of males with diabetes. These deposits in the smooth muscle are focal and variable in appearance, rarely with osseous metaplasia. Inflammation-induced calcifications are scattered throughout the smooth muscle, usually associated with chronic inflammation and fibrosis. Myositis ossificans has also been reported forming a spermatic cord tumor, as has heterotopic ossification.115,116 Osseous metaplasia of the epididymis occurs sporadically of in association with fibrous pseudotumor, sometimes forming a mass that may be mistaken for a neoplasm. Microscopically it consists of trabecular bone set in connective tissue stroma.

Fig. 14.7 Idiopathic scrotal and epididymal calcinosis in an otherwise healthy 37-year-old man forming a multinodular mass measuring 3 cm in greatest dimension.

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Neoplasms Benign Neoplasms and Pseudotumors A variety of unusual tumors and tumor-like proliferations arise in the paratesticular region, often of uncertain histogenesis. Because of the rarity of many of these benign tumors, they may be erroneously considered malignant.

Lipoma Lipoma is the most common paratesticular tumor, accounting for up to 90% of spermatic cord tumors (Fig. 14.8).117 Lipoma usually occurs in adults, but may be seen at all ages. Grossly it is a circumscribed, unencapsulated mass of lobulated yellow adipose tissue, measuring up to 30 cm in diameter and weighing as much as 3.2 kg.118 The microscopic appearance is similar to lipoma at other sites, consisting of mature adipose tissue. Variants include angiolipoma, hibernoma, fibrolipoma, fibromyxolipoma, myxolipoma, and myxoid myolipoma (Fig. 14.9). Lipoma was identified in 23% of hernia repairs; of these, 51% were associated with indirect hernia, 17% with direct hernia, 1% with pantaloon and femoral hernia, and 31% without hernia.119 Autopsy study with careful inguinal dissection revealed 75% with discrete masses of adipose tissue within the inguinal canal, and the majority of lipomas measured more than 4 cm in length with pedunculation and a bulbous distal tip.120

Fig. 14.8 Lipoma of the Cord Dwarfing the Testis.

Fig. 14.9 Chondrolipoma of the paratestis arising in a 53-year-old. The mass was 3 cm in diameter, circumscribed, and composed chiefly of mature fat and cartilage with scant fibrous connective tissue.

Adenomatous Hyperplasia Adenomatous hyperplasia of the rete testis and epididymis consists of a poorly circumscribed tubular or tubulopapillary proliferation of uniform benign cuboidal to low columnar epithelial cells with back-to-back crowding; there is no stromal invasion or other features of malignancy. This lesion is a frequent finding in the undescended testis and is considered benign.121 Adenomatoid Tumor (Benign Nonpapillary Mesothelioma) Adenomatoid tumor is the most common tumor of the epididymis and cord, and second in frequency only to lipoma in the paratesticular area; it accounts for about one-third of nonlipoma paratesticular tumors.122,123 It also arises in the tunica vaginalis or tunica albuginea, and may be present in association with hydrocele. Adenomatoid tumor is usually seen in men between 20 and 50 years of age, but has been reported in those as old as 79 years; rare cases occur in childhood.124 Patients often present with a painless scrotal mass, but some lesions are found incidentally at epididymoorchiectomy or autopsy. Adenomatoid tumor consists of a firm, circumscribed, solid mass, measuring up to 2 cm in greatest dimension, and usually arising in the head of the epididymis or rarely in the lower pole of the epididymis, testicular tunics, or spermatic cord. The cut surface is homogeneous and white-gray. The characteristic microscopic findings are irregular tubules, cell nests, and solid trabeculae of cuboidal to flattened epithelioid or endothelioid cells (Fig. 14.10).125 The tumor cells are eosinophilic, with variably sized cytoplasmic vacuoles. In some cases excessive vacuolization creates thin strands of cytoplasm spanning lumina; alternatively, it creates a signet ring cell pattern. Nuclei are small and vesicular with inconspicuous nucleoli. The stroma contains fibroblasts, blood vessels, and smooth muscle. Focal stromal hyalinization may be present, and the tumor may infiltrate the testis. Adenomatoid leiomyoma consists of adenomatoid tumor in association with prominent smooth muscle. Tumor cell cytoplasm contains hyaluronidase-sensitive acid mucopolysaccharides, similar to mesothelioma. Immunohistochemistry reveals cytoplasmic staining for cytokeratin in most cases, focal luminal surface staining for epithelial membrane antigen in some cases, and negative staining for carcinoembryonic antigen, vimentin, factor VIII–related antigen, and Ulex europaeus

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inflammation. Reactive mesothelial hyperplasia has also been described in association with hydrocele, hematocele, inguinal hernia sac, and fibrous pseudotumor. Reactive hyperplasia consists of solid nests, tubules, simple papillae, or small cysts of cytologically benign mesothelium set in a fibrous stroma, often appearing beneath the surface mesothelium. Mild cytologic atypia may be present, and squamous metaplasia is rarely seen. Histologic mimics include benign papillary mesothelioma, malignant mesothelioma, and metastatic adenocarcinoma. Benign papillary mesothelioma has more complex papillary architecture. Malignant mesothelioma is also architecturally complex, often with nuclear atypia, increased mitotic activity, and stromal infiltration. Metastatic adenocarcinoma usually shows severe nuclear abnormalities that stand in contrast with the adjacent surface mesothelium; stains for neutral or hyaluronidase-resistant mucin may also be of value, with negative staining suggesting adenocarcinoma rather than mesothelioma.

Fig. 14.10 Adenomatoid Tumor of the Epididymis. (A) Grossly the tumor was a firm white-gray mass. (B) Anastomosing tubules lined by cells with small nuclei and punctuated by thin-walled vessels.

agglutinin 1, although focal staining for factor VIII has been occasionally reported. Proliferative activity by MIB1 staining is less than 1%, and the tumor is diploid.126 Ultrastructural studies reveal mesothelial differentiation including slender microvilli, intermediate filaments adjacent to the nuclei, intracellular canaliculi, desmosomes, basal lamina, and transition forms with features of both typical mesothelial cells and stromal spindle cells. Mesothelial origin is likely for adenomatoid tumor because of the anatomic continuity between the surface mesothelium of the tunica vaginalis and tumor cells in some cases, as well as identification of rare cases of adenomatoid tumor in the retroperitoneum. The mesothelial theory of histogenesis has displaced earlier theories, including endothelial origin, mesonephric origin, and m€ ullerian origin. Despite the potential for local invasion, adenomatoid tumor is benign, with no metastatic potential. Intraoperative frozen section diagnosis allows local resection with preservation of the epididymis and testis. This tumor may recur if incompletely excised but does not recur after complete excision.

Hamartoma (Smooth Muscle Hyperplasia) Separation of smooth muscle hamartoma (tumor-like overgrowth of normal tissue) and hyperplasia may be difficult and perhaps arbitrary, according to a study of 16 cases in which there was predominantly concentric periductal, perivascular, or interstitial proliferation of muscle fascicles.127 Hamartoma of the spermatic cord may be composed chiefly of smooth muscle or fibrous connective tissue. One case of hamartoma of the rete testis arose as a testicular mass in a 2-year-old. The tumor consisted of a disorganized cluster of tubules embedded in a loose connective tissue stroma. The tubules were lined by cells that were cytologically similar to normal rete testis. Another case of smooth muscle hyperplasia of the rete testis arose in association with multilocular cyst and myxoid stroma with scattered Leydig cells mimicking Leydig cell tumor.128 Reactive Mesothelial Hyperplasia Reactive mesothelial hyperplasia appears as a small solid nodule of mesothelial cells that is usually microscopic and clinically asymptomatic. It probably arises as a result of mechanical irritation or

Benign Papillary Mesothelioma Benign papillary mesothelioma is a rare tumor of the tunica vaginalis that usually appears in young men.129,130 Grossly it consists of a hydrocele sac with papillary or adenomatous excrescences and cystic or solid areas. Microscopically there are complex papillae covered by cuboidal, columnar, or flattened mesothelial cells with large vesicular nuclei and glassy eosinophilic cytoplasm (Fig. 14.11). There is no significant nuclear atypia. Psammoma bodies are often present. Careful search should be made to determine whether the papillary lining of the tumor is in continuity with the mesothelium of the adjacent tunica vaginalis. The tumor contains hyaluronidase-sensitive mucin, and ultrastructural study reveals mesothelial differentiation. Multicystic mesothelioma rarely arises in the spermatic cord.131 Papillary Cystadenoma of the Epididymis Papillary cystadenoma of the epididymis is a benign tumor that accounts for about one-third of all primary epididymal tumors; one case was located in the spermatic cord.132 It occurs in men between 16 and 81 years of age (mean, 36 years). More than 50 cases have been reported.133 About two-thirds of cases of papillary cystadenoma of the epididymis occurs in patients with von Hippel-Lindau syndrome, and are more frequently bilateral in this syndrome.134 Other manifestations of von Hippel-Lindau syndrome include hemangioblastoma of the cerebellum, cerebrum, spinal cord, retina, pancreas, and urinary bladder; meningioma; syringomyelia; paraganglioma; renal cell carcinoma; pheochromocytoma; islet cell tumor; adrenal cortical adenoma; and a variety of cysts of the liver, kidney, adrenal, and pancreas. Somatic von Hippel–Lindau mutations are present in some, but not all, cases.135 About 40% of cases of papillary cystadenoma of the epididymis are bilateral, and these appear as cystic masses in the head of the epididymis that measure up to 6 cm in diameter. The cut surface is gray-brown with yellow foci, and the tumor often contains cyst fluid that varies from clear and colorless to yellow, green, or bloodtinged (Fig. 14.11). Microscopically, papillary cystadenoma consists of dilated ducts lined by papillae with a single or double layer of cuboidal to low columnar epithelium (Fig. 14.11).136 The cells have characteristic clear glycogen-filled cytoplasm with secretory droplets and cilia at the surface. The papillary cores and cyst walls consist of fibrous connective tissue that may be hyalinized or inflamed. This appearance may be mistaken for metastatic renal cell carcinoma.135

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Fig. 14.11 Papillary Cystadenoma of the Epididymis. (A) Grossly the tumor consisted of a papillary mass. (B) Cystic space containing wellformed papillae. This 35-year-old man had a history of von Hippel-Lindau syndrome, including bilateral renal cell carcinoma and cerebellar and retinal hemangioblastomas. (C) Another case of papillary cystadenoma from a patient without a history of von Hippel-Lindau syndrome. (A and B, courtesy Dr. Bernd Scheithauer, Rochester, Minnesota.)

The cells stain with soybean agglutinin lectin and are immunoreactive for low- and intermediate-weight cytokeratins CAM5.2 and AE1/AE3, epithelial membrane antigen, α1-antitrypsin, α1-antichymotrypsin, and vimentin.135,137 Rare cases of mucinous subtype of papillary cystadenoma have been reported, including one case with intestinal-type goblet cells.138 There was no significant cytologic atypia, and the neoplastic cells displayed immunoreactivity for carcinoembryonic antigen, cytokeratin 20, CDX2, epithelial membrane antigen, and CD15; they were negative for PAX8 and Wilms tumor 1 protein.138

Fibrous Pseudotumor (Nodular and Diffuse Fibrous Proliferation) Fibrous pseudotumor encompasses a wide variety of fibroproliferative lesions of the testicular tunics, epididymis, and spermatic cord.139-141 This lesion has been referred to as chronic periorchitis, proliferative funiculitis, fibrous proliferation of the tunics, fibroma, nonspecific paratesticular fibrosis, nodular fibrous periorchitis, nodular fibropseudotumor, inflammatory pseudotumor,

reactive periorchitis, and pseudofibromatous periorchitis.142,143 Early cases of spermatic cord and epididymal fibroma were probably fibrous pseudotumors. This nonneoplastic fibroinflammatory reactive lesion clinically mimics testicular and paratesticular neoplasm, especially when it encases the testis and manifests grossly as indurated testis. Patients are typically in the third decade of life, but age ranges from 7 to 95 years. It usually involves the tunics and may be associated with hydrocele, hematocele, or both. Less commonly the epididymis or spermatic cord are involved. A history of epididymoorchitis, trauma, or inflamed hydrocele is often elicited.144 Fibrous pseudotumor is a nodular or diffuse thickening of firm white tissue, measuring up to 9.5 cm in diameter, often with focal yellow calcifications (Fig. 14.12). Histologically it consists of granulation tissue with chronic inflammation, but long-standing tumors contain only paucicellular hyalinized fibrous connective tissue with calcification and ossification. Sclerosing lipogranuloma-like changes may be present. The condition is considered reactive. Resection of the tumor, perhaps with the tunica vaginalis, is curative, but it is frequently difficult

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Fig. 14.12 Fibrous Pseudotumor of the Testicular Tunics.

Fig. 14.13 Leiomyoma of the Vas Deferens.

to confirm the benign nature of the process preoperatively, and orchiectomy is often used.144 One case was associated with lipoma and diffuse mast cell infiltration of unknown significance.145 Based on similarities to other fibroinflammatory disorders characterized by infiltrates of IgG4-expressing plasma cells and included under the heading of IgG4-mediated diseases, Bosmuller and colleagues investigated the plasma cell distribution and immunoglobulin isotypes in paratesticular fibrous pseudotumor.146 They found that all three of their cases contained a high number of IgG4-positive plasma cells, with an IgG4/IgG ratio of 44% to 48%, suggesting that paratesticular fibrous pseudotumor belongs to the growing list of IgG4-related diseases, including retroperitoneal fibrosis, sclerosing pancreatitis and cholangitis, Riedel thyroiditis, and sclerosing sialadenitis. The differential diagnosis includes solitary fibrous tumor, idiopathic fibromatosis, neurofibroma, and leiomyoma.

Melanotic Neuroectodermal Tumor of Infancy (Progonoma; Retinal Anlage Tumor) Rare cases of melanotic neuroectodermal tumor of infancy have arisen in the head of the epididymis and paratestis.156-159 Patients range in age from newborn to 24 months (mean, 7 months). The tumor is a solitary, circumscribed, solid blue-brown or black mass, measuring up to 3 cm in diameter. Microscopically it consists of cells with uniform round nuclei and abundant melanin granules lining small cystic spaces of variable size. Smaller round cells with hyperchromatic nuclei, prominent nucleoli, and minimal cytoplasm are observed within lumen spaces and the stroma. Tumor cells resemble neuroblasts and may form glomeruloid bodies, sometimes surrounded by a fibrous matrix set in a collagenous stroma. Melanotic neuroectodermal tumor of infancy may replace the epididymis, but there are no reports of testicular or spermatic cord invasion. No recurrences of metastases have been identified at this site, but the number of cases is small, and the length of follow-up is limited; some speculate that this tumor has the potential for local recurrence and lymph node involvement.

Leiomyoma Reports of the relative frequency of leiomyoma to adenomatoid tumor of the epididymis vary from 1:1 to 1:9.147,148 Men with genital leiomyoma range in age from 25 to 81 years (mean, 48 years).149 Hydroceles or hernia sacs are identified in up to 21% of cases, and up to 39% of cases of leiomyoma are bilateral.150,151 Leiomyoma appears as a round, firm, gray-white mass, measuring up to 8 cm in diameter; the cut surface is homogeneous and whorled and bulges from the adjacent soft tissues (Fig. 14.13). It has typical microscopic features of leiomyoma, including interlacing fascicles of spindled smooth muscle cells with few or no mitotic figures. Tumor cells are immunoreactive for vimentin, desmin, and smooth muscle actin.152 Rare cases of leiomyoma with bizarre nuclei have been described.153 Angioleiomyoma has also been reported.154 Spermatic cord leiomyoma may clinically mimic irreducible inguinal hernia without scrotal involvement.155 Surgical excision of epididymal leiomyoma is curative. Differential diagnostic considerations include smooth muscle hyperplasia, low-grade leiomyosarcoma, and solitary fibrous tumor. The number of mitotic figures is the most reliable criterion for making this separation, but quantitative reporting in smooth muscle tumor of the epididymis and spermatic cord has not been validated. Leiomyoma is less common in the spermatic cord than the epididymis, with fewer than 20 reported cases. Patient age is similar.

Brenner Tumor Brenner tumor of the testicular tunics is rare, occurring in men between 37 and 61 years of age. The tumors are small, usually less than 3 cm in diameter, and appear as solid masses with smooth external surfaces and typical histologic features of Brenner tumors elsewhere. Brenner tumor may share a common histogenesis with adenomatoid tumor or Walthard cell rest. Gonadal Stromal Tumor Gonadal stromal tumor accounts for up to 3% of testicular tumors, and rare extratesticular examples have been reported. Embryogenesis of the testis can account for extratesticular nests of germ cells and stromal cells. Microscopic foci of gonadal interstitial cells are occasionally observed in extratesticular sites such as the spermatic cord and epididymis in orchiectomy specimens removed for other reasons, and these may account for gonadal stromal tumor at such sites. Other Benign Tumors Other rare benign paratesticular tumors and tumor-like conditions include mucinous adenoid tumor, pleomorphic adenoma, desmoid, neurofibroma, pheochromocytoma/paraganglioma, blue nevus, and hemangioma of the testicular tunics.160-168 Lymphangiectasia,

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Fig. 14.14 Angiomyofibroblastoma-like Tumor (Cellular Angiofibroma). A 48-year-old man presented with a small, 1.2-cm-diameter, oval, tan rubbery mobile mass near the left epididymis. The tumor is a variably cellular proliferation of tapered uniform spindled cells containing numerous small- to medium-sized irregularly ectatic vessels, patchy red cell extravasation, and fine collagenous stroma (A to C). Scattered epithelioid-appearing stromal cells are seen, but no necrosis or mitotic activity is observed. (D) Tumor cells exhibit immunoreactivity for vimentin, muscle-specific actin (shown), and smooth muscle actin; negative immunostains include progesterone receptors, estrogen receptors, CD34, desmin, and S100 protein.

arteriovenous malformation, lymphangioma, hemangioma, angiomyolipoma, angiomyofibroblastoma, angiomyofibroblastoma-like tumor (cellular angiofibroma) (Fig. 14.14), and neurofibroma may arise in the spermatic cord or epididymis.169-177 There have been rare case reports of granular cell tumor, paratesticular myxoma, carcinoid, solitary fibrous tumor, extratesticular Leydig cell tumor, and rhabdomyoma of the spermatic cord and epididymis.178-187 Aggressive angiomyxoma of the spermatic cord was reported in two 13-yearold boys, appearing as a benign myxoid tumor immunoreactive for vimentin and smooth muscle actin.188-190 Another case arose in an 82-year-old that was also positive for vimentin but negative for actin, desmin, and CD34.191 Four cases of aggressive angiomyxoma contained estrogen and progesterone immunoreactivity in the majority, similar to cases in women.192 Fibrous hamartoma of infancy occasionally arises in the scrotum or spermatic cord, and usually requires surgical excision for diagnosis.193

Malignant Neoplasms Spermatic cord sarcoma accounts for 2% of all urologic tumors; it is usually treated initially with surgery and has a poor prognosis.194

The most common histologic types are liposarcoma (46%), leiomyosarcoma (20%), malignant fibrous histiocytoma (13%), and rhabdomyosarcoma (9%). The median age of diagnosis for rhabdomyosarcomas was 26.3 years, whereas for others it was 64.7 years.195 According to Rodriguez et al., worse outcome was observed with undifferentiated tumor grade, distant disease, positive lymph nodes, and leiomyosarcoma or malignant fibrous histiocytoma cell histology.195 Other reports described the following adverse outcome variables: patient age, performance status, size, grade depth of invasion, and surgical margin status.196,197

Liposarcoma The most common sarcoma of the paratesticular region in adults is spermatic cord liposarcoma.198-201 Mean patient age is about 63 years (range, 16 to 90 years).202 Grossly liposarcoma is a lobulated mass of yellow tissue ranging from 3 to 50 cm (mean, 12 cm) that often resembles lipoma (Fig. 14.15).202,203 Microscopically the most common pattern is well-differentiated liposarcoma (lipoma-like liposarcoma), often with prominent sclerosis or abundant myxoid stroma.204,205 Myxoid/round cell liposarcoma and dedifferentiated/pleomorphic liposarcoma may also occur.202,206-210

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Fig. 14.15 Liposarcoma of the Spermatic Cord. (A) Grossly the tumor consisted of a multinodular mass of firm tan tissue. (B) Delicate fibrosis and increased cellularity were observed within adipose tissue.

Well-differentiated liposarcoma displayed immunoreactivity for MDM2 in 95% of cases and CDK4 in 78%.200,205 Cytogenetics in 13 cases showed ring and giant marker chromosomes; fluorescence in situ hybridization revealed amplification of 12q13 to 12q15 in all cases evaluated.205,211 Paratesticular liposarcoma is treated by radical orchiectomy with high ligation of the spermatic cord.199 Hemiscrotectomy may be required in cases with inadequate surgical resection margins to avoid local recurrence. Lymphadenectomy is usually not indicated, especially with well-differentiated and myxoid liposarcoma. The role of radiation therapy and chemotherapy is uncertain, but they are commonly employed. The majority of patients with paratesticular liposarcoma treated by resection with negative surgical margins are clinically free of tumor, and those with welldifferentiated liposarcoma have a prolonged course, sometimes with late recurrence.202 In a surgical series, Bachmann et al. reported 100% disease-free survival rate at 3 years after radical resection and 64% overall survival at 4.5 years.212 However, 23% of patients with liposarcoma experience local recurrence and less than 10% experience development of metastases, invariably in those with dedifferentiated or high-grade liposarcoma. Dedifferentiated liposarcoma (DDL) may be pure low grade (14% of cases) or pure or mixed high grade (86%).213 Mixed patterns are common and may coexist with osteosarcoma and leiomyosarcoma. Low-grade DDL may have fibrosarcoma, myxofibrosarcoma, or inflammatory-like patterns, whereas high-grade DDL may display undifferentiated pleomorphic sarcoma-like, myxofibrosarcoma, fibrosarcoma, and myxofibrosarcoma-like patterns. Osseous metaplasia may also occur.214 DDL occurs at a median age of 71 years (range, 43 to 90 years) and has a median size of 10.9 cm (range, 3 to 30 cm). Most are high grade, with occasional cases mixed with osteosarcoma or leiomyosarcoma. Recurrence is common, developing at a median of 24 months (range, 2 to 180 months). Size, grade, and margin status are not predictive of recurrence. Fluorescence in situ hybridization reveals amplification of MDM2 in the majority of cases.215 The differential diagnosis of well-differentiated liposarcoma includes sclerosing lipogranuloma and lipoma. Myxoid liposarcoma should be distinguished from rhabdomyosarcoma and myxoid malignant fibrous histiocytoma. Pleomorphic liposarcoma may be difficult to distinguish from other types of high-grade sarcoma.

A rare case of DDL and contralateral angiolipoma has been described in a 60-year-old man.216

Rhabdomyosarcoma Paratesticular rhabdomyosarcoma may arise in the testicular tunics, epididymis, or spermatic cord. When the tumor is large or locally invasive, the exact site of origin cannot be determined. Rhabdomyosarcoma is the most common sarcoma of the paratesticular area in children, with a peak incidence at about 9 years, although it may occur at any age.217-220 Grossly, rhabdomyosarcoma is an encapsulated white-gray mass with focal hemorrhage and cystic degeneration that measures up to 20 cm in diameter. Most are embryonal rhabdomyosarcoma, consisting of small, round cells with dark nuclei, scant cytoplasm, and variable numbers of cells showing myoblastic differentiation. The connective tissue stroma may be myxoid. Alveolar, botryoid, and pleomorphic patterns have rarely been observed at this site.218 Rhabdomyosarcoma usually spreads to retroperitoneal lymph nodes, and patients without distant metastases are treated by radical inguinal orchiectomy with high ligation of the spermatic cord and ipsilateral or bilateral retroperitoneal or pelvic lymphadenectomy. Retroperitoneal lymphadenectomy can be avoided after radical inguinal orchiectomy when radiologic studies such as computerized tomography are negative. The extent of lymphadenectomy determines the likelihood of postoperative fertility. Locally invasive rhabdomyosarcoma that involves the skin or arises with clinically suspicious inguinal lymph nodes is treated by orchiectomy, scrotectomy, and inguinal lymphadenectomy. Long-term survival rates of greater than 80% are observed in patients receiving adjuvant radiation therapy and combination chemotherapy. Leiomyosarcoma Leiomyosarcoma is more common in the spermatic cord than in the epididymis, with more than 125 reported cases.221-224 It arises in patients of all ages, with a peak in the sixth and seventh decades of life; more than 80% of patients are older than 40 years.202,225,226 Grossly, leiomyosarcoma is a solid gray-tan, 2 to 9 cm in diameter mass involving the intrascrotal portion of the spermatic cord, scrotal subcutis and dartos muscle, epididymis, or testicular tunics.227 It

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consists of a spindle cell proliferation with typical features of leiomyosarcoma at other sites. Features that conclusively separate low-grade leiomyosarcoma and leiomyoma are lacking, although the presence of necrosis, a high number of mitotic figures, nuclear pleomorphism, and marked cellularity suggest malignancy. Most cases are high grade at diagnosis, although this has been refuted.227 Paratesticular leiomyosarcoma is treated by radical inguinal orchiectomy. The role of retroperitoneal lymphadenectomy is uncertain and is usually not recommended because of the propensity of leiomyosarcoma for hematogenous spread rather than lymphatic spread. Adjuvant radiation therapy and chemotherapy are considered palliative. Leiomyosarcoma may recur locally and metastasize, and about one-third of patients die of metastases. Survival rates after treatment are 75% and 50% at 5 and 10 years, respectively.228 Enucleation was undertaken in one patient with good long-term results.229

Malignant Mesothelioma Paratesticular malignant mesothelioma is uncommon, with fewer than 300 reported cases. Most occur in the tunica vaginalis, with very few in the spermatic cord and epididymis.230-233 Mean patient age is about 55 years and ranges from 12 to 84 years. Primary peritoneal malignant mesothelioma may present as a mass in an inguinal hernia. The most common presenting symptom is either hydrocele of unknown origin or intrascrotal mass. Malignant mesothelioma of the tunica vaginalis may appear in pipe fitters after asbestos exposure, raising the possibility of asbestos as a contributory factor, similar to pleural and peritoneal mesothelioma, and may account for an estimated 30% to 40% of cases.231 Bilateral mesothelioma of the tunica vaginalis occurs rarely. Grossly, malignant mesothelioma appears as multiple friable cystic and solid masses and small nodules studding the lining of a hydrocele sac, hernia sac, or the peritoneum (Fig. 14.16). Continuity between the tumor and adjacent mesothelium of the tunica vaginalis may be apparent, and there may be invasion of adjacent structures.

Histologically paratesticular malignant mesothelioma is similar to mesothelioma at other sites and may be epithelial, spindle cell, or biphasic, with a wide morphologic spectrum (Fig. 14.16). The epithelial pattern is most common, accounting for about 75% of cases, and may be mixed with papillary, tubular, and solid areas. Spindle cells predominate in the sarcomatous pattern and may merge perceptively with solid epithelioid nests. Tumor cells are cuboidal or flattened, with variable amounts of eosinophilic cytoplasm and atypical vesicular nuclei, often with prominent nucleoli. Mitotic figures are usually present. One case mimicked adenomatoid tumor because of the presence of small tubular and microcystic glands lined by flattened epithelioid cells and vague signet ring cells set in a myxofibrous stroma.234 The combination of calretinin, cytokeratin 5/6, and thrombomodulin appears to be useful in separating epithelioid mesothelioma from metastatic carcinoma; these markers are also positive in benign and reactive mesothelium.235 Few cases have been identified or suspected preoperatively on cytologic examination. Malignant mesothelioma is aggressive, with potential for late recurrence or metastasis. It recurs locally along the vas deferens or in the pelvis, and usually spreads by lymphatic routes to pelvic, retroperitoneal, or distant lymph nodes. Radical inguinal orchiectomy is recommended with high ligation of the spermatic cord at the internal inguinal ring. Hemiscrotectomy or hemiscrotal irradiation may be useful to avoid local recurrence when transscrotal incision is made. Primary retroperitoneal lymphadenectomy is often used in patients with clinical or radiologic evidence of lymphatic metastases or in those without distant metastases. The utility of adjuvant chemotherapy is uncertain. About one-half of patients remain free of tumor up to 18 years after treatment. The predominance of the epithelial or spindle cell component determines the differential diagnostic considerations. Epithelial malignant mesothelioma may be mistaken for reactive mesothelial hyperplasia, adenomatoid tumor, benign papillary mesothelioma, adenocarcinoma of the epididymis, paratesticular m€ ullerian serous tumor, and metastatic adenocarcinoma. Paratesticular mesothelioma

Fig. 14.16 Malignant Mesothelioma of the Tunica Vaginalis. (A) Grossly the tumor consisted of a large exophytic papillary mass. (B) Micropapillations are lined by flattened to cuboidal tumor cells. (Courtesy Dr. Jan Kennedy, Atlanta, Georgia.)

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should be suspected in cases with in situ mesothelioma in the adjacent tunics, typical tubulopapillary architecture, and a lack of extrascrotal involvement. Spindle cell malignant mesothelioma should be distinguished from the variety of soft tissue sarcomas that arise at this site. Biphasic mesothelioma may be confused with stromal fibrosis, synovial sarcoma, and carcinosarcoma.

Papillary Serous Tumor of M€ ullerian Epithelium (Benign and Malignant) Rarely m€ ullerian epithelial tumors (also referred to as ovarian-type epithelial tumors) arise in the testis and paratesticular structures, perhaps from embryonic remnants such as the appendix testis.156,236 One case arose in the torsed appendix testis of a young boy.237 Some early reports of adenocarcinoma of the testicular appendages apparently represent papillary serous tumor of m€ ullerian epithelium or malignant mesothelioma. Papillary serous tumor of low malignant potential may occur in the tunica vaginalis, testis, spermatic cord, and epididymis and is grossly, microscopically, and immunohistochemically identical to its ovarian counterpart.126,238 Patients range in age from 6 to 77 years (mean, 56 years) and present with an apparent testicular tumor. Proliferative activity by MIB1 staining ranges from 1% to 10% (mean, 5.5%), and most are diploid. Radical orchiectomy is the treatment of choice, and the tumor does not recur or metastasize after complete resection.126 Papillary serous carcinoma typically consists of invasive papillae lined by serous cuboidal or columnar cells with eosinophilic cytoplasm, frank nuclear anaplasia, and abundant psammoma bodies.239 Cancer cells display immunoreactivity for broad-spectrum keratin AE1/AE3. S100 protein, epithelial membrane antigen, and BerEP4; variable positive staining is seen with Leu M1, B72.3, CEA, PLAP, and vimentin. Serum concentration of CA-125 is elevated in some patients. Cancer tends to recur within 5 to 7 years. The differential diagnosis of serous tumor of m€ ullerian epithelium includes papillary cystadenoma of the epididymis, benign papillary mesothelioma, malignant mesothelioma, adenocarcinoma of the rete testis or epididymis, and metastatic adenocarcinoma. Adenocarcinoma of the Epididymis Fewer than 30 cases of epididymal adenocarcinoma have been reported.8,240-243 Mean patient age is 44 years (range, 5 to 78 years). The tumors measure up to 9 cm in diameter and may be multicystic or solid. About one-half are associated with hydrocele. Microscopically there are typical features of adenocarcinoma including papillary, glandular, mucinous, and solid undifferentiated patterns; clear cells often predominate.244 Squamous cell carcinoma may also be admixed. The main differential diagnostic consideration is metastatic renal cell carcinoma.245 Nearly one-half of reported patients experience development of metastases. Treatment is uncertain, but surgery and chemotherapy are most often used. Palliative radiation therapy has no apparent durable effect on cancer progression.246 Malignant Fibrous Histiocytoma Fewer than 40 reported cases of malignant fibrous histiocytoma involving the spermatic cord and paratesticular area have been reported.247-250 Most cases occur in patients older than 50 years. Grossly the tumor is solid gray or yellow-white, has a whorled cut surface, and measures up to 10 cm in diameter. Histologic patterns include myxoid, inflammatory, and pleomorphic malignant

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fibrous histiocytoma; the storiform-pleomorphic pattern accounted for more than 80% of reported cases.248 About one-third of patients with malignant fibrous histiocytoma experience local recurrence or distant metastases. The treatment of choice is radical inguinal orchiectomy with high ligation of the spermatic cord. The value of adjuvant therapy is unknown, although one patient was cancer-free 6 years after adjuvant radiation therapy.251 Tumor size did not predict outcome.248

Other Sarcomas and Malignancies More than 60 cases of spermatic cord and epididymal fibrosarcoma have been described, but some of these probably represent other forms of sarcoma.252 Most occur in adults, but all ages may be affected. The gross and microscopic appearances of fibrosarcoma of the paratesticular area are similar to other sites. More than one-half of patients die of locally recurrent or metastatic tumor. Most types of sarcoma have been described in the paratesticular area including primary neuroblastoma, neurofibrosarcoma, angiosarcoma, chondrosarcoma, myxofibrosarcoma, and undifferentiated sarcoma (Fig. 14.17).253,254 Peripheral neuroectodermal tumor (extraskeletal Ewing sarcoma) also has been reported.255 Carcinosarcoma of the tunica vaginalis occurred after radiation therapy for prostate cancer.256 Paraganglioma with malignant features was recently described.257 Germ Cell Tumor A variety of germ cell tumors have been described in the paratesticular area including seminoma, embryonal carcinoma, and teratoma; rare cases may be burned out and pose a diagnostic challenge.258 The epididymis is more commonly involved than the spermatic cord, but germ cell tumor at either site is rare. The demographic and pathologic features of paratesticular germ cell tumor are like those of the testis. These tumors probably arise from misplaced germinal elements. Contiguous subepithelial spread of seminoma along the vas deferens was reported in a 56-year-old man.259 Malignant Lymphoma and Hematopoietic Neoplasms Malignant lymphoma is the most common tumor of the testis in men older than 50 years, yet paratesticular lymphoma is uncommon.260 Rare cases of primary epididymal or spermatic cord lymphoma have been described.260-264 Secondary lymphoma has been described in all sites of the paratesticular area, invariably in association with testicular involvement. Occlusion of spermatic cord vessels by lymphoma may result in testicular ischemia.265 Plasmacytoma of the epididymis and spermatic cord has also been reported.266 Metastases Metastases to the paratesticular area are rare, and usually arise from the prostate, kidney, lung, and stomach, and other sites.267-273 Renal primary should always be considered in clear cell carcinoma at this site; misdiagnoses include Sertoli cell tumor, Sertoli-Leydig cell tumor, and clear cell cystadenoma of the epididymis.274 Rare cases have originated from colonic adenocarcinoma (Fig. 14.18), pancreatic adenocarcinoma, esophageal squamous cell carcinoma, urothelial carcinoma, ileal carcinoid, Wilms tumor, and malignant melanoma.275-281 Patients with paratesticular metastases usually have a poor outcome. References are available at expertconsult.com

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Fig. 14.17 High-Grade Spindle Cell Sarcoma. (A) Circumscribed, tan-white, nodular, 2.5-cm-diameter, paratesticular mass attached to the inferior pole without invasion. (B) The fascicular pattern is composed of plump spindle cells with pleomorphic nuclei and tumor giant cells. (C) There is brisk mitotic activity with rare abnormal mitotic figures. (D) Tumor cells display diffuse intense cytoplasmic immunoreactivity for vimentin, myo-D1 (shown), and myoglobulin; focal staining for calponin, smooth muscle actin, and muscle-specific actin; and negative staining for pankeratin, CD34, CD68, CD99, S100 protein, caldesmon, and desmin.

Fig. 14.18 Hernia Sac Containing Multiple Nodules of Metastatic Colonic Adenocarcinoma.

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References 1. Srigley JR. The paratesticular region: histoanatomic and general considerations. Semin Diagn Pathol. 2000;17:258–269. 2. Lioe TF, Biggart JD. Tumours of the spermatic cord and paratesticular tissue. A clinicopathological study. Br J Urol. 1993;71:600–606. 3. Sajjad Y. Development of the genital ducts and external genitalia in the early human embryo. J Obstet Gynaecol Res. 2010;36:929–937. 4. Han CH, Kang SH. Epididymal anomalies associated with patent processus vaginalis in hydrocele and cryptorchidism. J Korean Med Sci. 2002;17:660–662. 5. De Miguel MP, Marino JM, Martinez-Garcia F, Nistal M, Paniagua R, Regadera J. Pre- and post-natal growth of the human ductus epididymidis. A morphometric study. Reprod Fertil Dev. 1998;10: 271277. 6. Raymond AS, Shur BD. A novel role for SED1 (MFG-E8) in maintaining the integrity of the epididymal epithelium. J Cell Sci. 2009;122:849–858. 7. Oliva E, Young RH. Paratesticular tumor-like lesions. Semin Diagn Pathol. 2000;17:340–358. 8. Jones EC, Murray SK, Young RH. Cysts and epithelial proliferations of the testicular collecting system (including rete testis). Semin Diagn Pathol. 2000;17:270–293. 9. Sharp SC, Batt MA, Lennington WJ. Epididymal cribriform hyperplasia. A variant of normal epididymal histology. Arch Pathol Lab Med. 1994;118:1020–1022. 10. Butterworth DM, Bisset DL. Cribriform intra-tubular epididymal change and adenomatous hyperplasia of the rete testis—a consequence of testicular atrophy? Histopathology. 1992;21:435–438. 11. Coyne JD. Eosinophilic granular cell change of Sertoli cells and of epididymal columnar cells. Histopathology. 2004;44:86–87. 12. Oshima S, Okayasu I, Uchima H, Hatakeyama S. Histopathological and morphometrical study of the human epididymis and testis. Acta Pathol Jpn. 1984;34:1327–1342. 13. Kuo T, Gomez LG. Monstrous epithelial cells in human epididymis and seminal vesicles. A pseudomalignant change. Am J Surg Pathol. 1981;5:483–490. 14. Bromberg WD, Kozlowski JM, Oyasu R. Prostate-type gland in the epididymis. J Urol. 1991;145:1273–1274. 15. Nistal M, Iniguez L, Paniagua R. Pitted pattern in the human epididymis. J Reprod Fertil. 1990;89:655–661. 16. Nistal M, Iniguez L, Paniagua R, Regadera J. Diverticula of the ductus epididymis in men. J Urol. 1986;136:1224–1227. 17. Shah VI, Ro JY, Amin MB, Mullick S, Nazeer T, Ayala AG. Histologic variations in the epididymis: findings in 167 orchiectomy specimens. Am J Surg Pathol. 1998;22:990–996. 18. Jayaram N, Ramaprasad AV, Chethan M, Sujay RP. Tumours and tumour-like conditions of the para-testicular region—a study of morphological features. Indian J Pathol Microbiol. 1998;41: 287–295. 19. Weiske WH, Salzler N, Schroeder-Printzen I, Weidner W. Clinical findings in congenital absence of the vasa deferentia. Andrologia. 2000;32:13–18. 20. Wagenknecht LV, Lotzin CF, Sommer HJ, Schirren C. Vas deferens aplasia: clinical and anatomical features of 90 cases. Andrologia. 1983;15 Spec No: 605–613. 21. Conley GR, Sant GR, Ucci AA, Mitcheson HD. Seminoma and epididymal cysts in a young man with known diethylstilbestrol exposure in utero. JAMA. 1983;249:1325–1326. 22. Koff WJ, Scaletscky R. Malformations of the epididymis in undescended testis. J Urol. 1990;143:340–343. 23. Pendse AK, Mathur PN, Sharma MM, Gupta OP. Splenic-gonadal fusion. Br J Surg. 1975;62:624–628. 24. Fan R, Faught PR, Sun J, Meldrum KK. Hepatogonadal fusion. J Pediatr Surg. 2012;47:e5–e6. 25. Habuchi T, Mizutani Y, Miyakawa M. Ectopic aberrant adrenals with epididymal abnormality. Urology. 1992;39:251–253.

Spermatic Cord and Testicular Adnexa

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26. Oguzkurt P, Oz S, Kayaselcuk F. Ectopic adrenal tissue: an incidental finding during inguinoscrotal operations in children. Hernia. 2002;6:62–63. 27. Savas C, Candir O, Bezir M, Cakmak M. Ectopic adrenocortical nodules along the spermatic cord of children. Int Urol Nephrol. 2001;32:681–685. 28. Vaos G, Zavras N, Boukouvalea I. Ectopic adrenocortical tissue along the inguinoscrotal path of children. Int Surg. 2006;91:125–128. 29. Mullhaupt G, Mordasini L, Gramann T, Ertel V, Schmid HP, Abt D. Ectopic adrenocortical tissue in the spermatic cord in a 44-year-old man. Urol Case Rep. 2014;2:169–170. 30. Schned AR, Seremetis GM, Rous SN. Paratesticular multicystic mass of Wolffian, probably paradidymal, origin. Am J Clin Pathol. 1994;101:543–546. 31. Nistal M, Iniguez L, Paniagua R, Redondo E, Regadera J. Tubular embryonal remnants in the human spermatic cord. Urol Int. 1987;42:260–264. 32. Kantarci F, Ozer H, Adaletli I, Mihmanli I. Cystic appendix epididymis: a sonomorphologic study. Surg Radiol Anat. 2005;27:557–561. 33. Skorpil M, Silseth C, Berne M. [Torsion of the hydatid of Morgagni—a hereditary disease? The most common cause of acute scrotum in children]. Lakartidningen. 1999;96:1320–1322. 34. Aworanti O, Awadalla S. An unusual cause of acute scrotum in a child. Ir Med J. 2014;107:327–328. 35. Rakha E, Puls F, Saidul I, Furness P. Torsion of the testicular appendix: importance of associated acute inflammation. J Clin Pathol. 2006;59:831–834. 36. Wollin M, Marshall FF, Fink MP, Malhotra R, Diamond DA. Aberrant epididymal tissue: a significant clinical entity. J Urol. 1987;138: 1247–1250. 37. Virdi JS, Conway W, Kelly DG. Torsion of the vas aberrans. Br J Urol. 1990;66:435. 38. 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. 39. 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. 40. Popek EJ. Embryonal remnants in inguinal hernia sacs. Hum Pathol. 1990;21:339–349. 41. 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. 42. Miller GG, McDonald SE, Milbrandt K, Chibbar R. Routine pathological evaluation of tissue from inguinal hernias in children is unnecessary. Can J Surg. 2003;46:117–119. 43. Partrick DA, Bensard DD, Karrer FM, Ruyle SZ. Is routine pathological evaluation of pediatric hernia sacs justified? J Pediatr Surg. 1998;33:1090–1092 discussion 1093-1094. 44. Brisson P, Patel H, Feins N. Cremasteric muscle hypertrophy accompanies inguinal hernias in children. J Pediatr Surg. 1999;34: 1320–1321. 45. Busigo JP, Eftekhari F. Encysted spermatic cord hydroceles: a report of three cases in adults and a review of the literature. Acta Radiol. 2007;48:1138–1142. 46. Manimaran D, Karthikeyan TM, Khan DM. Encysted spermatic cord hydrocele in a 60-year-old, mimicking incarcerated inguinal hernia: a case report. J Clin Diagn Res. 2014;8:153–154. 47. Kaefer M, Agarwal D, Misseri R, et al. Treatment of contralateral hydrocele in neonatal testicular torsion: is less more? J Pediatr Urol. 2016;12:306.e1–306.e4. 48. Nistal M, Martin L, Paniagua R. Idiopathic hematoma of the epididymis: presentation of three cases. Eur Urol. 1990;17:178–180. 49. Chiba K, Ramasamy R, Lamb DJ, Lipshultz LI. The varicocele: diagnostic dilemmas, therapeutic challenges and future perspectives. Asian J Androl. 2016;18:276–281.

852.e2 CHA P T E R 14

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50. Gioffre L. [Structure of the venous wall of the pampiniform plexus in idiopathic varicocele]. G Chir. 2001;22:213–216. 51. Tanji N, Fujiwara T, Kaji H, Nishio S, Yokoyama M. Histologic evaluation of spermatic veins in patients with varicocele. Int J Urol. 1999;6:355–360. 52. Aldemir M, Isik E, Ozgun G, Onen E, Okulu E, Kayigil O. Comparison of spermatic vein histology in patients with and without varicocele. Andrologia. 2011;43:341–345. 53. Mavrov K, Takov R, Tsvetkov D. [Clinico-morphological studies of epididymal cysts]. Khirurgiia (Sofiia). 1990;43:56–61. 54. Yagi H, Igawa M, Shiina H, Shigeno K, Yoneda T, Wada Y. Multilocular spermatocele: a case report. Int Urol Nephrol. 2001;32:413–416. 55. Takimoto K, Okamoto K, Wakabayashi Y, Okada Y. Torsion of spermatocele: a rare manifestation. Urol Int. 2002;69:164–165. 56. Jassie MP, Mahmood P. Torsion of spermatocele: a newly described entity with 2 case reports. J Urol. 1985;133:683–684. 57. Nistal M, Iniguez L, Paniagua R. Histological classification of spermatic cord cysts in relation to their histogenesis. Eur Urol. 1987;13: 327–330. 58. Katergiannakis V, Lagoudianakis EE, Markogiannakis H, Manouras A. Huge epidermoid cyst of the spermatic cord in an adult patient. Int J Urol. 2006;13:95–97. 59. Skorniakov MS, Ramirez AC, Delgado MS, Duran AC, Bernal CS. Spermatic cord dermoid cyst as paratesticular mass. Case report and bibliographic review. Arch Esp Urol. 2011;64:991–994. 60. Brown DL, Benson CB, Doherty FJ, et al. Cystic testicular mass caused by dilated rete testis: sonographic findings in 31 cases. AJR Am J Roentgenol. 1992;158:1257–1259. 61. Wojcik LJ, Hansen K, Diamond DA, et al. Cystic dysplasia of the rete testis: a benign congenital lesion associated with ipsilateral urological anomalies. J Urol. 1997;158:600–604. 62. Nistal M, Jimenez-Heffernan JA, Garcia-Viera M, Paniagua R. Cystic transformation and calcium oxalate deposits in rete testis and efferent ducts in dialysis patients. Hum Pathol. 1996;27:336–341. 63. Coyne J, al-Nakib L, Goldsmith D, O’Flynn K. Secondary oxalosis and sperm granuloma of the epididymis. J Clin Pathol. 1994; 47:470–471. 64. Nistal M, Santamaria L, Paniagua R. Acquired cystic transformation of the rete testis secondary to renal failure. Hum Pathol. 1989; 20:1065–1070. 65. Nistal M, Mate A, Paniagua R. Cystic transformation of the rete testis. Am J Surg Pathol. 1996;20:1231–1239. 66. Nistal M, Jimenez-Heffernan JA. Rete testis dysgenesis. A characteristic lesion of undescended testes. Arch Pathol Lab Med. 1997;121:1259–1264. 67. Inoue K, Higaki Y, Yoshida H. Inguinal hernia of seminal vesicle cyst. Int J Urol. 2004;11:1039–1040. 68. Mikuz G, Damjanov I. Inflammation of the testis, epididymis, peritesticular membranes, and scrotum. Pathol Annu. 1982;17 (Pt 1): 101–128. 69. Nistal M, Gonzalez-Peramato P, Serrano A, Regadera J. Xanthogranulomatous funiculitis and orchiepididymitis: report of 2 cases with immunohistochemical study and literature review. Arch Pathol Lab Med. 2004;128:911–914. 70. Doble A, Taylor-Robinson D, Thomas BJ, Jalil N, Harris JR, Witherow RO. Acute epididymitis: a microbiological and ultrasonographic study. Br J Urol. 1989;63:90–94. 71. Ostaszewska I, Zdrodowska-Stefanow B, Darewicz B, et al. Role of Chlamydia trachomatis in epididymitis. Part II: Clinical diagnosis. Med Sci Monit. 2000;6:1119–1121. 72. Dalton AD, Harcourt-Webster JN. The histopathology of the testis and epididymis in AIDS—a post-mortem study. J Pathol. 1991;163:47–52. 73. McCarthy JM, McLoughlin MG, Shackleton CR, et al. Cytomegalovirus epididymitis following renal transplantation. J Urol. 1991;146:417–419.

74. Reddy GS, Das LK, Pani SP. The preferential site of adult Wuchereria bancrofti: an ultrasound study of male asymptomatic microfilaria carriers in Pondicherry, India. Natl Med J India. 2004;17:195–196. 75. Mondal SK. Incidental detection of filaria in fine-needle aspirates: a cytologic study of 14 clinically unsuspected cases at different sites. Diagn Cytopathol. 2012;40:292–296. 76. Gasparich JP, Mason JT, Greene HL, Berger RE, Krieger JN. Amiodarone-associated epididymitis: drug-related epididymitis in the absence of infection. J Urol. 1985;133:971–972. 77. Chen TF, Ball RY. Epididymectomy for post-vasectomy pain: histological review. Br J Urol. 1991;68:407–413. 78. Schned AR, Selikowitz SM. Epididymitis nodosa. An epididymal lesion analogous to vasitis nodosa. Arch Pathol Lab Med. 1986;110:61–64. 79. Segawa N, Abe H, Nishida T, Katsuoka Y. [Spermatic cord tuberculosis: a case report]. Hinyokika Kiyo. 2005;51:347–349. 80. Benjelloun A, Elktaibi A, Elharrech Y, Touiti D, Ghoundale O. Tuberculosis of the spermatic cord: case report. Urol Case Rep. 2014;2:176–177. 81. Muttarak M, Lojanapiwat B, Chaiwun B, Wudhikarn S. Preoperative diagnosis of bilateral tuberculous epididymo-orchitis following intravesical Bacillus Calmette-Guerin therapy for superficial bladder carcinoma. Australas Radiol. 2002;46:183–185. 82. Sah SP, Bhadani PP, Regmi R, Tewari A, Raj GA. Fine needle aspiration cytology of tubercular epididymitis and epididymo-orchitis. Acta Cytol. 2006;50:243–249. 83. Dieckmann KP, Henke RP, Zimmer-Krolzig G. Malacoplakia of the epididymis. Report of a case and review of the literature. Urol Int. 1995;55:222–225. 84. Esser R, Rothenberger KH. [Sarcoidosis of the spermatic cord and epididymus]. Aktuelle Urol. 2003;34:354–355. 85. Gazaigne J, Mozziconacci JG, Mornet M, Provendier B. Epididymal and renal sarcoidosis. Br J Urol. 1995;75:413–414. 86. Ryan DM, Lesser BA, Crumley LA, et al. Epididymal sarcoidosis. J Urol. 1993;149:134–136. 87. Jenkin GA, Choo M, Hosking P, Johnson PD. Candidal epididymo-orchitis: case report and review. Clin Infect Dis. 1998; 26:942–945. 88. Kauffman CA, Slama TG, Wheat LJ. Histoplasma capsulatum epididymitis. J Urol. 1981;125:434–435. 89. Seo R, Oyasu R, Schaeffer A. Blastomycosis of the epididymis and prostate. Urology. 1997;50:980–982. 90. Jungmann P, Figueredo-Silva J, Dreyer G. Bancroftian lymphangitis in northeastern Brazil: a histopathological study of 17 cases. J Trop Med Hyg. 1992;95:114–118. 91. Svec A, Urban M, Mikyskova I, Tachezy R. Human papillomavirus in squamous metaplastic epithelium with dysplasia of the epididymis detected by PCR method. Am J Surg Pathol. 1999;23:1437–1438. 92. Matsuda T, Horii Y, Nishimura K, Amitani R, Matsui Y, Yoshida O. Young’s syndrome: report of two Japanese cases. Urol Int. 1991;47:53–56. 93. Handelsman DJ, Conway AJ, Boylan LM, Turtle JR. Young’s syndrome. Obstructive azoospermia and chronic sinopulmonary infections. N Engl J Med. 1984;310:3–9. 94. Nistal M, Mate A, Paniagua R. Granulomatous epididymal lesion of possible ischemic origin. Am J Surg Pathol. 1997;21:951–956. 95. McDonald SW. Cellular responses to vasectomy. Int Rev Cytol. 2000;199:295–339. 96. Warner JJ, Kirchner FK, Jr., Wong SW, Dao AH. Vasitis nodosa presenting as a mass of the spermatic cord. J Urol. 1983;129: 380–381. 97. Tsurusaki T, Maruta N, Iwasaki S, Iwasaki K, Saito Y. Idiopathic bilateral panniculitis of the spermatic cord in an elderly male patient. J Urol. 2000;164:1657–1658. 98. Sallami S, Chelif M, Horchani A. Pseudo-tumoral proliferative funiculitis of the spermatic cord. Tunis Med. 2012;90:333.

C H A P T E R 14

99. Tanaka M, Tsumatani K, Mibu H, Saka T. [Genital tuberculosis occurring in the spermatic cord: a case report]. Hinyokika Kiyo. 2002;48:753–755. 100. Pampiglione S, Rivasi F, Angeli G, et al. Dirofilariasis due to Dirofilaria repens in Italy, an emergent zoonosis: report of 60 new cases. Histopathology. 2001;38:344–354. 101. Durand F, Brion JP, Terrier N, Pinel C, Pelloux H. Funiculitis due to Schistosoma haematobium: uncommon diagnosis using parasitologic analysis of semen. Am J Trop Med Hyg. 2004;70:46–47. 102. Grigor T, Ahmad S. Parasitised large intestinal diverticulum of the spermatic cord. BMJ Case Rep. 2014;2014:bcr2014206115. 103. Heydenrych JJ, Marcus PB. Meconium granulomas of the tunica vaginalis. J Urol. 1976;115:596–598. 104. Kessel A, Toubi E, Golan TD, Toubi A, Mogilner JG, Jaffe M. Isolated epididymal vasculitis. Isr Med Assoc J. 2001;3:65–66. 105. Hernandez-Rodriguez J, Tan CD, Koening CL, Khasnis A, Rodriguez ER, Hoffman GS. Testicular vasculitis: findings differentiating isolated disease from systemic disease in 72 patients. Medicine (Baltimore). 2012;91:75–85. 106. Al-Arfaj A. Limited Wegener’s granulomatosis of the epididymis. Int J Urol. 2001;8:333–335. 107. Hashiguchi Y, Matsuo Y, Torii Y, et al. Polyarteritis nodosa of the epididymis. Abdom Imaging. 2001;26:102–104. 108. Kameyama K, Kuramochi S, Kamio N, Akasaka Y, Higa I, Hata J. Isolated periarteritis nodosa of the spermatic cord presenting as a scrotal mass: report of a case. Heart Vessels. 1998;13:152–154. 109. Nistal M, Gonzalez-Peramato P, Paniagua R. Lipomembranous fat necrosis in three cases of testicular torsion. Histopathology. 2001;38:443–447. 110. Sirvent JJ, Bernat R, Navarro MA, Rodriguez Tolra J, Garcia B, Salvado MT. [Spermatic cord torsion: morphologic and functional study, with special reference to the Leydig cells]. Actas Urol Esp. 1988;12:443–448. 111. Nistal M, Paniagua R, Gonzalez-Peramato P, Reyes-Mugica M. Perspectives in pediatric pathology, chapter 19. Testicular torsion, testicular appendix torsion, and other forms of testicular infarction. Pediatr Dev Pathol. 2016;19:345–359. 112. Matsumoto A, Nagatomi Y, Sakai M, Oshi M. Torsion of the hernia sac within a hydrocele of the scrotum in a child. Int J Urol. 2004;11:789–791. 113. Mumtaz FH, Khan MA, Morgan RJ. Synchronous bilateral torsion of the appendix testis. Urol Int. 1998;60:128–129. 114. Kilciler M, Saglam M, Sumer F, Ozgok Y, Soydan H, Erduran D. Lithiasis in varicocele veins: “varicolithiasis.” J Urol. 2002;168:630. 115. Ozgur A, Tarcan T, Simsek F, Ahiskali R. An unusual tumor of the spermatic cord: myositis ossificans. Arch Esp Urol. 2003;56:1072–1074. 116. Demirci D, Ekmekcioglu O, Inci M, Akgun H. Heterotopic ossification of the spermatic cord. Int Urol Nephrol. 2003;35:513–514. 117. Montgomery E, Buras R. Incidental liposarcomas identified during hernia repair operations. J Surg Oncol. 1999;71:50–53. 118. Greeley DJ, Jr., Sullivan JG, Wolfe GR. Massive primary lipoma of the scrotum. Am Surg. 1995;61: 954-955. 119. Lilly MC, Arregui ME. Lipomas of the cord and round ligament. Ann Surg. 2002;235:586–590. 120. Heller CA, Marucci DD, Dunn T, Barr EM, Houang M, Dos Remedios C. Inguinal canal “lipoma”. Clin Anat. 2002;15:280–285. 121. Cooper K, Govender D. Adenomatous hyperplasia of the rete testis in the undescended testis. J Pathol. 1990;162:333–334. 122. Racioppi M, D’Addessi A, Di Pinto A, et al. Three consecutive cases of adenomatoid tumour of the epididymis: histological considerations and therapeutical implications. Review of the literature. Arch Ital Urol Androl. 1996;68:115–119. 123. Tammela TL, Karttunen TJ, Makarainen HP, Hellstrom PA, Mattila SI, Kontturi MJ. Intrascrotal adenomatoid tumors. J Urol. 1991;146:61–65. 124. Liu W, Wu RD, Yu QH. Adenomatoid tumor of the testis in a child. J Pediatr Surg. 2011;46:E15–E17.

Spermatic Cord and Testicular Adnexa

852.e3

125. Perez-Campos A, Jimenez-Heffernan JA, Perez F, Vicandi B. Cytologic features of paratesticular adenomatoid tumor. Acta Cytol. 2004;48:457–458. 126. McClure RF, Keeney GL, Sebo TJ, Cheville JC. Serous borderline tumor of the paratestis: a report of seven cases. Am J Surg Pathol. 2001;25:373–378. 127. Barton JH, Davis CJ, Jr., Sesterhenn IA, Mostofi FK. Smooth muscle hyperplasia of the testicular adnexa clinically mimicking neoplasia: clinicopathologic study of sixteen cases. Am J Surg Pathol. 1999;23: 903-909. 128. Fridman E, Skarda J, Ofek-Moravsky E, Cordoba M. Complex multilocular cystic lesion of rete testis, accompanied by smooth muscle hyperplasia, mimicking intratesticular Leydig cell neoplasm. Virchows Arch. 2005;447:768–771. 129. Rosales Leal JL, Tallada Bunuel M, Espejo Maldonado E, et al. [Multicystic mesothelioma of the testicular tunica vaginalis]. Arch Esp Urol. 2003;56:1154–1157. 130. Xiao SY, Rizzo P, Carbone M. Benign papillary mesothelioma of the tunica vaginalis testis. Arch Pathol Lab Med. 2000;124:143–147. 131. Tobioka H, Manabe K, Matsuoka S, Sano F, Mori M. Multicystic mesothelioma of the spermatic cord. Histopathology. 1995;27:479–481. 132. Geenen RW, Bevers RF, Gielis C, Boon TA. Papillary cystadenoma located in the spermatic cord. J Urol. 1997;158:546. 133. Raimoldi A, Berti GL, Canclini L, et al. [Papillary cystadenoma of the epididymis. 2 case reports]. Arch Ital Urol Androl. 1997;69:309–311. 134. Handra-Luca A, Toublanc M, Richard S, Polivka M, BocconGibod L, Henin D. [Papillary cystadenoma of the epididymis revealing von Hippel-Lindau disease]. Ann Pathol. 2001;21:102–103. 135. Gilcrease MZ, Schmidt L, Zbar B, Truong L, Rutledge M, Wheeler TM. Somatic von Hippel-Lindau mutation in clear cell papillary cystadenoma of the epididymis. Hum Pathol. 1995; 26:1341–1346. 136. Calder CJ, Gregory J. Papillary cystadenoma of the epididymis: a report of two cases with an immunohistochemical study. Histopathology. 1993;23:89–91. 137. Kragel PJ, Pestaner J, Travis WD, Linehan WM, Filling-Katz MR. Papillary cystadenoma of the epididymis. A report of three cases with lectin histochemistry. Arch Pathol Lab Med. 1990;114:672–675. 138. Kim JY, Lee YT, Kang HJ, Lee CH. Primary mucinous cystadenoma of the spermatic cord within the inguinal canal. Diagn Pathol. 2012;7:139. 139. Polsky EG, Ray C, Dubilier LD. Diffuse fibrous pseudotumor of the tunica vaginalis testis, epididymis and spermatic cord. J Urol. 2004;171:1625–1626. 140. Yamashina M, Honma T, Uchijima Y. Myofibroblastic pseudotumor mimicking epididymal sarcoma. A clinicopathologic study of three cases. Pathol Res Pract. 1992;188:1054–1059. 141. Frazier AA. Extratesticular fibrous pseudotumor. Radiographics. 2015;35:1942. 142. Milanezi MF, Schmitt F. Pseudosarcomatous myofibroblastic proliferation of the spermatic cord (proliferative funiculitis). Histopathology. 1997;31:387–388. 143. Hollowood K, Fletcher CD. Pseudosarcomatous myofibroblastic proliferations of the spermatic cord (“proliferative funiculitis”). Histologic and immunohistochemical analysis of a distinctive entity. Am J Surg Pathol. 1992;16:448–454. 144. Tobias-machado M, Correa Lopes Neto A, Heloisa Simardi L, Borrelli M, Wroclawski ER. Fibrous pseudotumor of tunica vaginalis and epididymis. Urology. 2000;56:670–672. 145. Shintaku M, Ukikusa M. Proliferative funiculitis with a prominent infiltration of mast cells. Pathol Int. 2003;53:897–900. 146. Bosmuller H, von Weyhern CH, Adam P, Alibegovic V, Mikuz G, Fend F. Paratesticular fibrous pseudotumor—an IgG4-related disorder? Virchows Arch. 2011;458:109–113. 147. Yusim IE, Neulander EZ, Eidelberg I, Lismer LJ, Kaneti J. Leiomyoma of the genitourinary tract. Scand J Urol Nephrol. 2001;35:295–299.

852.e4 CHA P T E R 14

Spermatic Cord and Testicular Adnexa

148. Elmer EB, Levine R, Nolan J. Leiomyoma of spermatic cord with unusual features. Urology. 1989;33:236–237. 149. Bremmer F, Kessel FJ, Behnes CL, Trojan L, Heinrich E. Leiomyoma of the tunica albuginea, a case report of a rare tumour of the testis and review of the literature. Diagn Pathol. 2012;7:140. 150. Bruno S, Leone V, Mincione GP. Bilateral leiomyoma of the epididymis. Pathologica. 1993;85:129–133. 151. Fernandez A, Krishnamoorthy S, Muralitharan S, Johnson T, Ramanan V. Bilateral synchronous paratesticular leiomyoma—a rare entity. J Clin Diagn Res. 2017;11: PD05-PD06. 152. Kato Y, Hori J, Taniguchi N, Hashimoto H, Kaneko S, Yachiku S. [Solitary genital leiomyoma of the tunica dartos: a case report and review of the literature in Japan]. Hinyokika Kiyo. 2005;51:699–701. 153. Borri A, Nesi G, Bencini L, Pernice LM. Bizarre leiomyoma of the epididymis. A case report. Minerva Urol Nefrol. 2000;52:29–31. 154. Ghei M, Arun B, Maraj BH, Miller RA, Nathan S. Case report: angioleiomyoma of the spermatic cord: a rare scrotal mass. Int Urol Nephrol. 2005;37:731–732. 155. Koprivanac M, Billings SD, Khachaturov V, Morris-Stiff G. Inguinal canal spermatic cord leiomyoma presenting as an incarcerated inguinal hernia. BMJ Case Rep. 2017;2017. 156. Henley JD, Ferry J, Ulbright TM. Miscellaneous rare paratesticular tumors. Semin Diagn Pathol. 2000;17:319–339. 157. Toda T, Sadi AM, Kiyuna M, Egawa H, Tamamoto T, Toyoda Z. Pigmented neuroectodermal tumor of infancy in the epididymis. A case report. Acta Cytol. 1998;42:775–780. 158. Kobayashi T, Kunimi K, Imao T, et al. Melanotic neuroectodermal tumor of infancy in the epididymis. Case report and literature review. Urol Int. 1996;57:262–265. 159. Calabrese F, Danieli D, Valente M. Melanotic neuroectodermal tumor of the epididymis in infancy: case report and review of the literature. Urology. 1995;46:415–418. 160. Boto J, Boudabbous S, Lobrinus JA, Gourmaud J, Terraz S. Solitary neurofibroma of the spermatic cord: a case report. J Radiol Case Rep. 2015;9:19–28. 161. Garaffa G, Muneer A, Freeman A, et al. Paraganglioma of the spermatic cord: case report and review of the literature. Scient Wor J. 2008;8:1256–1258. 162. Gonzalez-Campora R, Galera-Davidson H, Vazquez-Ramirez FJ, Diaz-Cano S. Blue nevus: classical types and new related entities. A differential diagnostic review. Pathol Res Pract. 1994;190:627–635. 163. Jiang R, Chen JH, Chen M, Li QM. Male genital schwannoma, review of 5 cases. Asian J Androl. 2003;5:251–254. 164. Lai FM, Allen PW, Chan LW, Chan PS, Cooper JE, Mackenzie TM. Aggressive fibromatosis of the spermatic cord. A typical lesion in a “new” location. Am J Clin Pathol. 1995; 104:403–407. 165. Liokumovich P, Herbert M, Sandbank J, Schvimer M, Dolberg L. Cavernous hemangioma of spermatic cord: report of a case with immunohistochemical study. Arch Pathol Lab Med. 2002;126: 357–358. 166. Milathianakis KN, Karamanolakis DK, Mpogdanos IM, TrihiaSpyrou EI. Solitary neurofibroma of the spermatic cord. Urol Int. 2004;72:271–274. 167. Terada T. Pleomorphic adenoma of spermatic cord. Int Urol Nephrol 2015;47:1357–1359. 168. Young IE, Nawroz IM, Aitken RJ. Phaeochromocytoma of the spermatic cord. J Clin Pathol. 1999;52:305–306. 169. Kaido M, Iwai S, Ide Y, Koide O. Epididymal lymphangiectasis. J Urol. 1993;150:1251–1252. 170. Joshi MA, Gadhire M, Dhake A, Patil M. A diagnostic dilemma: arteriovenous malformation of spermatic cord presenting as irreducible inguinal swelling. J Postgrad Med. 2011;57:339–340. 171. Postius J, Manzano C, Concepcion T, Castro D, Gutierrez P, Banares F. Epididymal lymphangioma. J Urol. 2000;163:550–551. 172. Chetty R. Epididymal cavernous haemangiomas. Histopathology. 1993;22:396–398.

173. Castillenti TA, Bertin AP. Angiomyolipoma of the spermatic cord: case report and literature review. J Urol. 1989;142:1308–1309. 174. Siddiqui MT, Kovarik P, Chejfec G. Angiomyofibroblastoma of the spermatic cord. Br J Urol. 1997;79:475–476. 175. Canales BK, Weiland D, Hoffman N, et al. Angiomyofibroblastomalike tumors (cellular angiofibroma). Int J Urol. 2006;13: 177–179. 176. Aydin M, Uzuner H, Akgunes E, Bitkin A, Kadihasanoglu M. Cellular angiofibroma of the spermatic cord. Aktuelle Urol. 2017;48:159–160. 177. Wolfman DJ, Marko J, Gould CF, Sesterhenn IA, Lattin GE, Jr. Mesenchymal extratesticular tumors and tumorlike conditions: from the radiologic pathology archives. Radiographics. 2015; 35:1943–1954. 178. Ferrari M, Raber M, Capitanio U, et al. Leydig cell tumor of the spermatic cord in an adolescent affected by congenital adrenal hyperplasia. Int J Urol. 2012;19:954–956. 179. Fisher C, Bisceglia M. Solitary fibrous tumour of the spermatic cord. Br J Urol. 1994;74:798–799. 180. Han Y, Qiu XS, Li QC, et al. Epididymis rhabdomyoma: a case report and literature review. Diagn Pathol. 2012;7:47. 181. Kurzrock EA, Busby JE, Gandour-Edwards R. Paratesticular rhabdomyoma. J Pediatr Surg. 2003;38:1546–1547. 182. Lanzafame S, Leonardi R, Torrisi A. Extratesticular Leydig cell tumor of the spermatic cord. J Urol. 2004;171:1238–1239. 183. Maheshkumar P, Berney DM. Spermatic cord rhabdomyoma. Urology. 2000;56:331. 184. Matsunaga GS, Shepherd DL, Troyer DA, Thompson IM. Epididymal rhabdomyoma. J Urol. 2000;163:1876. 185. Wehner MS, Humphreys JL, Sharkey FE. Epididymal rhabdomyoma: report of a case, including histologic and immunohistochemical findings. Arch Pathol Lab Med. 2000;124:1518–1519. 186. Xambre L, Lages R, Cerqueira M, et al. [Solitary fibrous tumor. Two additional cases with urologic implications]. Actas Urol Esp. 2003;27:832–838. 187. Zeng L, Xia T, Kong X, Na Y, Guo Y. Primary carcinoid tumor of the epididymis. Chin Med J (Engl). 2001;114:544–545. 188. Malik A, Singh KJ, Mehta A. Aggressive angiomyxoma of the spermatic cord: A rare entity. Indian J Urol. 2009;25:137–139. 189. Minagawa T, Matsushita K, Shimada R, et al. Aggressive angiomyxoma mimicking inguinal hernia in a man. Int J Clin Oncol. 2009;14:365–368. 190. Carlinfante G, De Marco L, Mori M, Ferretti S, Crafa P. Aggressive angiomyxoma of the spermatic cord. Two unusual cases occurring in childhood. Pathol Res Pract. 2001;197:139–144. 191. Madrigal B, Veiga M, Vara A, et al. [An aggressive inguinal (parafunicular) angiomyxoma in a male patient]. Arch Esp Urol. 1999;52:785–788. 192. Idrees MT, Hoch BL, Wang BY, Unger PD. Aggressive angiomyxoma of male genital region. Report of 4 cases with immunohistochemical evaluation including hormone receptor status. Ann Diagn Pathol. 2006;10:197–204. 193. Sengar M, Mohta A, Manchanda V, Khurana N. Paratesticular fibrous hamartoma in an infant. Singapore Med J. 2012;53:e63–e65. 194. Trans-Atlantic RPS Working Group. Management of primary retroperitoneal sarcoma (RPS) in the adult: a consensus approach from the Trans-Atlantic RPS Working Group. Ann Surg Oncol. 2015;22:256–263. 195. Rodriguez D, Barrisford GW, Sanchez A, Preston MA, Kreydin EI, Olumi AF. Primary spermatic cord tumors: disease characteristics, prognostic factors, and treatment outcomes. Urol Oncol. 2014;32 (52):e19–e25. 196. Guttilla A, Crestani A, Zattoni F, et al. Spermatic cord sarcoma: our experience and review of the literature. Urol Int. 2013;90:101–105. 197. Radaelli S, Desai A, Hodson J, et al. Prognostic factors and outcome of spermatic cord sarcoma. Ann Surg Oncol. 2014;21:3557–3563. 198. Merimsky O, Terrier P, Bonvalot S, Le Pechoux C, Delord JP, Le Cesne A. Spermatic cord sarcoma in adults. Acta Oncol. 1999;38: 635–638.

C H A P T E R 14

199. Kodzo-Grey Venyo A, Deoleker M. Paratesticular liposarcoma of the spermatic cord: a case report and a review of the literature. West Afr J Med. 2011;30:447–452. 200. Tajima S, Koda K. Paratesticular dedifferentiated liposarcoma with prominent myxoid stroma: report of a case and review of the literature. Med Mol Morphol. 2017;50:112–116. 201. Panus A, Mesina C, Plesea IE, et al. Paratesticular liposarcoma of the spermatic cord: a case report and review of the literature. Rom J Morphol Embryol. 2015;56:1153–1157. 202. Montgomery E, Fisher C. Paratesticular liposarcoma: a clinicopathologic study. Am J Surg Pathol. 2003;27:40–47. 203. De Nardi P, Bissolati M, Cristallo M, Staudacher C. Recurrent giant liposarcoma of the spermatic cord. Urology. 2012;79:113–114. 204. Dundar M, Erol H, Kocak I, Kacar F. Liposarcoma of the spermatic cord. Urol Int. 2001;67:102–103. 205. Sioletic S, Dal Cin P, Fletcher CD, Hornick JL. Well-differentiated and dedifferentiated liposarcomas with prominent myxoid stroma: analysis of 56 cases. Histopathology. 2013;62(2):287–293. 206. Panagis A, Karydas G, Vasilakakis J, Chatzipaschalis E, Lambropoulou M, Papadopoulos N. Myxoid liposarcoma of the spermatic cord: a case report and review of the literature. Int Urol Nephrol. 2003;35:369–372. 207. Ikinger U, Westrich M, Pietz B, Mechtersheimer G, Schmidt C. Combined myxoid liposarcoma and angiolipoma of the spermatic cord. Urology. 1997;49:635–637. 208. Zozumi M, Nakai M, Matsuda I, et al. Paratesticular myxoid/round cell liposarcoma harboring type 3 DDIT3-FUS fusion gene: report of a very rare case. Pathol Res Pract. 2013;209:124–127. 209. Hornick JL, Bosenberg MW, Mentzel T, McMenamin ME, Oliveira AM, Fletcher CD. Pleomorphic liposarcoma: clinicopathologic analysis of 57 cases. Am J Surg Pathol. 2004;28:1257–1267. 210. Russell MJ, Flynt FL, Harroff AL, Fadare O. Dedifferentiated liposarcoma of the retroperitoneum with extensive leiomyosarcomatous differentiation and beta-human chorionic gonadotropin production. Sarcoma. 2008;2008:658090. 211. Hugar LA, Quiroga-Garza GM, Davies BJ, Hrebinko RL, Tran T, Jacobs BL. Molecular cytogenetics as a diagnostic aid for primary liposarcoma of the spermatic cord. Clin Genitourin Cancer. 2017;15: e83–e89. 212. Bachmann R, Rolinger J, Girotti P, et al. Liposarcoma of the spermatic cord: impact of final surgical intervention—an institutional experience. Int J Surg Oncol. 2016;2016:4785394. 213. Kryvenko ON, Rosenberg AE, Jorda M, Epstein JI. Dedifferentiated liposarcoma of the spermatic cord: a series of 42 cases. Am J Surg Pathol. 2015;39:1219–1225. 214. Chondros K, Heretis I, Papadakis M, et al. Dedifferentiated paratesticular liposarcoma with osseous metaplasia. Case Rep Urol. 2015;2015:965876. 215. Dantey K, Schoedel K, Yergiyev O, Bartlett D, Rao UN. Correlation of histological grade of dedifferentiation with clinical outcome in 55 patients with dedifferentiated liposarcomas. Hum Pathol. 2017;66:86–92. 216. Christodoulidou M, Khetrapal P, Edmunds L, Muneer A. Paratesticular liposarcoma and contralateral angiolipoma in a 60-year-old patient. BMJ Case Rep. 2015;2015:bcr2015212078. 217. Kizer WS, Dykes TE, Brent EL, Chatham JR, Schwartz BF. Paratesticular spindle cell rhabdomyosarcoma in an adult. J Urol. 2001;166:606–607. 218. Furlong MA, Mentzel T, Fanburg-Smith JC. Pleomorphic rhabdomyosarcoma in adults: a clinicopathologic study of 38 cases with emphasis on morphologic variants and recent skeletal musclespecific markers. Mod Pathol. 2001;14:595–603. 219. Perez Herms S, Castellanos Acosta R, Cortadellas Angel R, Guzman Fernandez A, Ballesteros Sampol JJ. [Paratesticular rhabdomyosarcoma. Report of 2 cases]. Actas Urol Esp. 1991;15:491–494. 220. Boudahna L, Benbrahim Z, Amaadour L, et al. Para testicular rhabdomyosarcoma in adults: three case reports and review of literature. Pan Afr Med J. 2014;19:279.

Spermatic Cord and Testicular Adnexa

852.e5

221. Watanabe J, Soma T, Kawa G, Hida S, Koisi M. Leiomyosarcoma of the spermatic cord. Int J Urol. 1999;6:536–538. 222. Weinshank LB, Kellner D, Nash I. Paratesticular leiomyosarcoma: case report and review. Conn Med. 2011;75:399–403. 223. Muduly DK, Kallianpur AA, Suryanarayana Deo SV, Shukla NK, Kapali AS, Yadav R. Primary leiomyosarcoma of epididymis. J Cancer Res Ther. 2012;8:109–111. 224. Dehghan A, Sami G, Eskandari N. Leiomyosarcoma of the spermatic cord in a seventy-five-year-old man. Nephrourol Mon. 2015;7:e24308. 225. Varzaneh FE, Verghese M, Shmookler BM. Paratesticular leiomyosarcoma in an elderly man. Urology. 2002;60:1112. 226. Galosi AB, Scarpelli M, Mazzucchelli R, et al. Adult primary paratesticular mesenchymal tumors with emphasis on a case presentation and discussion of spermatic cord leiomyosarcoma. Diagn Pathol. 2014;9:90. 227. Fisher C, Goldblum JR, Epstein JI, Montgomery E. Leiomyosarcoma of the paratesticular region: a clinicopathologic study. Am J Surg Pathol. 2001;25:1143–1149. 228. Llarena Ibarguren R, Azurmendi Sastre V, Martin Bazaco J, Villafruela Mateos A, Eizaguirre Zarza B, Pertusa Pena C. [Paratesticular leiomyosarcoma. Review and update]. Arch Esp Urol. 2004; 57:525–530. 229. Lopes RI, Leite KR, Lopes RN. Paratesticular leiomyosarcoma treated by enucleation. Int Braz J Urol. 2006;32:66–67. 230. Reynard JM, Hasan N, Baithun SI, Newman L, Lord MG. Malignant mesothelioma of the tunica vaginalis testis. Br J Urol. 1994;74:389–390. 231. Bisceglia M, Dor DB, Carosi I, Vairo M, Pasquinelli G. Paratesticular mesothelioma. Report of a case with comprehensive review of literature. Adv Anat Pathol. 2010;17:53–70. 232. Akin Y, Bassorgun I, Basara I, Yucel S. Malignant mesothelioma of tunica vaginalis: an extremely rare case presenting without risk factors. Singapore Med J. 2015;56:e53–e55. 233. Ahmed Z, Singh S, Mangal A, Mittal A. Primary malignant mesothelioma of the spermatic cord. BMJ Case Rep. 2016;2016: bcr2016214602. 234. Yang LH, Yu JH, Xu HT, et al. Mesothelioma of the tunica vaginalis testis with prominent adenomatoid features: a case report. Int J Clin Exp Pathol. 2014;7:7082–7087. 235. Cury PM, Butcher DN, Fisher C, Corrin B, Nicholson AG. Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura. Mod Pathol. 2000;13:107–112. 236. Kurian RR, Prema NS, Belthazar A. Paratesticular papillary serous cystadenocarcinoma—a case report. Indian J Pathol Microbiol. 2006;49:36–37. 237. Johnson DB, Sarda R, Uehling DT. Mullerian-type epithelial tumor arising within a torsed appendix testis. Urology. 1999;54:561. 238. McCluggage WG, Shah V, Nott C, Clements B, Wilson B, Hill CM. Cystadenoma of spermatic cord resembling ovarian serous epithelial tumour of low malignant potential: immunohistochemical study suggesting Mullerian differentiation. Histopathology. 1996; 28:77–80. 239. Jones MA, Young RH, Srigley JR, Scully RE. Paratesticular serous papillary carcinoma. A report of six cases. Am J Surg Pathol. 1995;19:1359–1365. 240. Arocena Garcia Tapia J, Sanz Perez G, Diez-Caballero Alonso F, et al. [Epididymal carcinoma. Bibliographic review in reference to a case]. Arch Esp Urol. 2000;53:273–275. 241. Ganem JP, Jhaveri FM, Marroum MC. Primary adenocarcinoma of the epididymis: case report and review of the literature. Urology. 1998;52:904–908. 242. Jones MA, Young RH, Scully RE. Adenocarcinoma of the epididymis: a report of four cases and review of the literature. Am J Surg Pathol. 1997;21:1474–1480. 243. Yu CC, Huang JK, Chiang H, Chen MT, Chang LS. Papillary cystadenocarcinoma of the epididymis: a case report and review of the literature. J Urol. 1992;147:162–165.

852.e6 CHA P T E R 14

Spermatic Cord and Testicular Adnexa

244. Nistal M, Revestido R, Paniagua R. Bilateral mucinous cystadenocarcinoma of the testis and epididymis. Arch Pathol Lab Med. 1992;116:1360–1363. 245. Kurihara K, Oka A, Mannami M, Iwata Y. Papillary adenocarcinoma of the epididymis. Acta Pathol Jpn. 1993;43:440–443. 246. Chauhan RD, Gingrich JR, Eltorky M, Steiner MS. The natural progression of adenocarcinoma of the epididymis. J Urol. 2001;166:608–610. 247. Sethi S, Ashok S. Malignant fibrous histiocytoma of the spermatic cord. J Indian Med Assoc. 2003;101:599–600. 248. Lin BT, Harvey DA, Medeiros LJ. Malignant fibrous histiocytoma of the spermatic cord: report of two cases and review of the literature. Mod Pathol. 2002;15:59–65. 249. Bosch-Princep R, Martinez-Gonzalez S, Alvaro-Naranjo T, Castellano-Megias VM, Salvado-Usach MT, Marti-Mestre J. Fine needle aspiration and touch imprint cytology of a malignant fibrous histiocytoma of the spermatic cord. Case report. Acta Cytol. 2000;44:423–428. 250. Xu LW, Yu YL, Li GH. Malignant fibrous histiocytoma of the spermatic cord: case report and literature review. J Int Med Res. 2012;40:816–823. 251. Ikinger U, Westrich M, Bersch W, Bottinger K. Malignant fibrous histiocytoma of the epididymis. Case report and review of the literature. Urol Int. 1999;62:106–109. 252. Folpe AL, Weiss SW. Paratesticular soft tissue neoplasms. Semin Diagn Pathol. 2000;17:307–318. 253. Calonge WM, Heitor F, Castro LP, et al. Neonatal paratesticular neuroblastoma misdiagnosed as in utero torsion of testis. J Pediatr Hematol Oncol. 2004;26:693–695. 254. Ozkan B, Ozguroglu M, Ozkara H, Durak H, Talat Z. Adult paratesticular myxofibrosarcoma: report of a rare entity and review of the literature. Int Urol Nephrol. 2006;38:5–7. 255. Matsumoto H, Inoue R, Tsuchida M, Takahashi M, Naito K. Primitive neuroectodermal tumor of the spermatic cord. J Urol. 2002;167:1791–1792. 256. Viers CD, Lele SM, Kirkpatrick T, LaGrange CA. Carcinosarcoma of the Tunica Vaginalis Following Radiation Therapy for Localized Prostate Cancer. Urol Case Rep. 2017;13:140–142. 257. Kwon AY, Kang H, An HJ, et al. Spermatic cord paraganglioma with histologically malignant features. Urology. 2016;93:e7–e8. 258. Rzeszutko M, Rzeszutko W, Nienartowicz E, Jelen M. Paratesticular localization of burned out non-seminomatous germ cell tumor— NSGCT: a case report. Pol J Pathol. 2006;57:55–57. 259. Lockett CJ, Nandwani GM, Stubington SR. Testicular seminoma— unusual histology and staging with sub epithelial spread of seminoma along the vas deferans. BMC Urol. 2006;6:5. 260. Diakatou E, Haramis G, Kostopoulou A, Kakiopoulos G. Primary lymphoma of the spermatic cord: a case report and review of the literature. Indian J Pathol Microbiol. 2011;54:588–590. 261. Vega F, Medeiros LJ, Abruzzo LV. Primary paratesticular lymphoma: a report of 2 cases and review of literature. Arch Pathol Lab Med. 2001;125:428–432. 262. Novella G, Porcaro AB, Righetti R, et al. Primary lymphoma of the epididymis: case report and review of the literature. Urol Int. 2001;67:97–99. 263. Suzuki K, Sai S, Kato K, Murase T. [A case of malignant lymphoma of the epididymis]. Hinyokika Kiyo. 2000;46:291–293. 264. Monappa V, Kudva R, Ray S. Primary paratesticular lymphoma with testicular sparing: account of an unusual scrotal mass. J Clin Diagn Res. 2016;10:ED07–08.

265. Tranchida P, Bayerl M, Voelpel MJ, Palutke M. Testicular ischemia due to intravascular large B-cell lymphoma: a novel presentation in an immunosuppressed individual. Int J Surg Pathol. 2003;11:319–324. 266. Ferry JA, Young RH, Scully RE. Testicular and epididymal plasmacytoma: a report of 7 cases, including three that were the initial manifestation of plasma cell myeloma. Am J Surg Pathol. 1997;21:590–598. 267. Wiebe B, Warnoe H, Klarlund M, Jacobsen AK. Epididymal metastasis from prostatic carcinoma. Scand J Urol Nephrol. 1993;27:553–555. 268. Mabjeesh NJ, Bar-Yosef Y, Schreiber-Bramante L, Kaver I, Matzkin H. Spermatic vein tumor thrombus in renal cell carcinoma. Scient Wor J. 2004;4 Suppl 1: 192–194. 269. Mohammadi A, Makhdoomi K, Ghasemi-rad M. Metachronous metastasis to the spermatic cord from renal cell carcinoma presenting as a high scrotal mass: a case report. Cancer Imaging. 2011;11:163–165. 270. Pirola GM, Martorana E, Fidanza FA, et al. Rare metastatic sites of renal cell carcinoma: urethra and spermatic cord. Urologia. 2016;83:214–217. 271. Kaya C, Tanrikulu H, Yilmaz G, Aker F, Karaman MI. Spermatic cord metastasis as an initial manifestation of non-small cell carcinoma of the lung. Int J Urol. 2006;13:846–848. 272. Dutt N, Bates AW, Baithun SI. Secondary neoplasms of the male genital tract with different patterns of involvement in adults and children. Histopathology. 2000;37:323–331. 273. Hirano D, Ohkawa M, Hasegawa R, Okada N, Ishizuka N, Kusumi Y. Metastatic tumor of the spermatic cord in adults: a case report and review. Case Rep Urol. 2015;2015:747261. 274. Datta MW, Ulbright TM, Young RH. Renal cell carcinoma metastatic to the testis and its adnexa: a report of five cases including three that accounted for the initial clinical presentation. Int J Surg Pathol. 2001;9:49–56. 275. Salesi N, Fabi A, Di Cocco B, et al. Testis metastasis as an initial manifestation of an occult gastrointestinal cancer. Anticancer Res. 2004;24:1093–1096. 276. Ishibashi K, Chika N, Miyazaki T, et al. Spermatic cord metastasis from colon cancer: report of a case. Surg Today. 2011;41:418–421. 277. Zhou XC, Jiang Y. Colonic carcinoma metastatic to the left testis, epididymis & spermatic cord. Indian J Med Res. 2016;143: 836–837. 278. Jang JG, Jeong HY, Kim KS, et al. Metastatic spermatic cord tumor from colorectal cancer. Ann Coloproctol. 2015;31:202–204. 279. Matsutani T, Nomura T, Hagiwara N, et al. Laparoscopic diagnosis for spermatic cord metastasis from esophageal squamous cell carcinoma: report of a case. J Nippon Med Sch. 2015;82:304–307. 280. Issa MM, Kabalin JN, Dietrick DD, Reese J, Freiha FS. Spermatic cord metastasis from transitional cell carcinoma of the bladder. Urology. 1994;43:561–563. 281. Kajbafzadeh AM, Javan-Farazmand N, Baghayee A, Hedayat Z. Paratesticular metastasis from Wilms tumor: the possible routs of metastasis and literature review. J Pediatr Hematol Oncol. 2012;33:e347–e349. 282. Gomez-Roman JJ, Mayorga M, Mira C, Buelta L, Fernandez F, Val-Bernal JF. Glandular inclusions in inguinal hernia sacs: a clinicopathological study of six cases. Pediatr Pathol. 1994;14: 1043–1049.