Endometriosis With Cystic Degeneration: A Rare Disease of Males

Introduction

Endometriosis has traditionally been defined as the presence of endometrial tissue outside the uterus, and it affects as much as 10% of women worldwide. ¹ In women, multiple theories have been postulated regarding its origin, including retrograde menstruation, ectopic endometrial tissue, coelomic metaplasia, and hematogenous spread or lymphatic spread.^2,3 In men, endometriosis is extremely rare, and only 17 cases have been previously reported in the English literature. ⁴ In this article, we describe the clinicopathologic features of 2 cases of endometriosis occurring in the testis of male patients.

Case Presentation

Case 1

The patient is a 50-year-old male with no significant past medical history who presented with a right testicular mass. Orchiectomy was performed and the specimen showed a 2-cm intratesticular cyst, abutting the tunica albuginea without macroscopic extension. The cyst contained brown fluid with necrotic debris. Microscopic examination showed a cystic lesion with dilated/elongated tubules and glands lined by endometrioid-type epithelium surrounded by spindled endometrial-type stroma. Focal chronic inflammation and epithelial denudation were present. Numerous hemosiderin-laden macrophages were present within the spindle cell stroma. The lesion was predominantly intratesticular; however, a minute focus of endometrioid-type glands with spindled stroma was located within the tunica albuginea (Figure 1). The surrounding testicular structures were histologically unremarkable. No germ cell neoplasia was identified. Immunohistochemically, the stroma was positive for CD10 and negative for estrogen receptor (ER). Progesterone receptor (PR) immunostain was not performed; however, despite the negative ER, the morphologic features and CD10 stromal positivity were diagnostic of endometriosis with cystic degeneration.

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Figure 1.

(A-D) Cystic lesion with intramural glands lined by endometrioid-type epithelium surrounded by spindled stroma. Chronic inflammation and abundance of hemosiderin-laden macrophages within the stroma are seen (hematoxylin–eosin; A and B, 20×; C and D, 40×).

Case 2

The patient was a 43-year-old male with a body mass index of 27 kg/m² and no significant past medical history or hormonal exposure, who presented with an enlarging paratesticular mass. The mass was followed-up for 5 years before it started to increase dramatically in size from 1.9 cm to 5.2 cm. Intraoperatively, the mass was adjacent to the epididymis. An excision with frozen section was performed. Grossly, it showed a cystic mass with tan-pink partially hemorrhagic lining and smooth external surface. Microscopic examination showed a cystic lesion lined by low columnar to cuboidal epithelium with minimal degree of nuclear atypia. In some areas, the epithelial cells appeared to have mucinous cytoplasm surrounded by spindle cell stroma resembling endometrial stroma. Numerous hemosiderin-laden macrophages were present within the spindle cell stroma. The adjacent epididymis was histologically unremarkable. Immunohistochemically, the epithelial and stromal cells were positive for ER and PR, while the stromal cells were positive for CD10 (Figure 2). The final diagnosis was endometriosis with cystic degeneration.

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Figure 2.

(A, B) Intramural glands lined by endometrioid-type epithelium and surrounded by spindled stroma (hematoxylin-eosin, 20×). (C, D) Diffuse staining of the epithelial and stromal cells with progesterone receptor and estrogen receptor immunostains (EP1 and PR1; Dako Corp), respectively; and stromal cells with CD10 immunostains (56C6; Dako Corp).

Discussion

Endometriosis is a benign lesion that is far more common in women. It was first described in 1860 by Von Rokitanski et al. ⁵ Since the description, multiple theories have been proposed to help understanding its development. The current acceptable theories are the following: metaplastic theory, dispersion theory, transplantation theory, and induction theory. According to the metaplasia theory, the development of endometriosis is the result of a continuous differentiation of mesothelial cells of the peritoneum under the effect of inflammatory or hormonal factors. The second theory is the dispersion of endometrial cells through the lymphatic or blood vessels. These theories can explain the development of endometriosis in distant organs and the extrapelvic endometriosis, respectively. The transplantation theory is supported by the presence of endometriosis in the peritoneal cavity, as a result of retrograde menstruation. Last is the induction theory, in which an induction of embryological remnants under prolonged hormonal stimulation leads to its development.^6-9 In men, it is extremely rare with only a few cases reported in the literature. Multiple risk factors have been postulated to trigger its development in males, most prominently prolonged hormonal exposure, mostly estrogen, in the setting of liver cirrhosis or as part of treatment of prostatic adenocarcinoma. ⁴ Such exposure supports the origin of endometriosis from embryologic remnants (the induction theory). Although none of our patients had a history of hormonal treatment or significant medical condition, the majority of cases reported in the literature supports this theory. The second patient in our series is overweight. The correlation between patients’ weight and endometriosis remains to be uncovered, despite being the only risk factor reported in 2 previous cases.^4,10

Briefly looking at the reported cases, pain was the most common presenting symptom, followed by hematuria. ⁴ Three cases were discovered incidentally during surgery or histologic evaluation of another tumor.^10-12 It was most commonly reported along the genitourinary tract system, although one case was reported in the abdominal wall. ¹³ The average age of presentation was 59.7 years (range = 40-83 years). In our series, both lesions presented as mass lesions, necessitating intervention to exclude malignant diagnosis. However, the second case was managed by simple excision after discovering the banal nature during frozen section. Both patients were younger than the average age, 43 and 50 years, although both occurred within the same reported age range.

The diagnosis of endometriosis is usually straightforward in women; however, the rarity of the disease in men makes the diagnosis challenging especially when it presents as a testicular mass. As in women, the diagnosis of endometriosis requires the presence of 2 of the following 3 features: presence of endometrial glands, endometrial stroma, and/or hemosiderin-laden macrophages. Immuno-histochemical staining is helpful in confirming the diagnosis. It was performed in less than half of the reported cases, and the most helpful stains were CD10, ER, and PR. The use of these stains is adjunct to the hematoxylin-eosin diagnosis and it should not substitute it. A study by Haga et al reported positive staining for ER in 88.1%, PR in 100%, and CD10 in 88.1% in women. ¹⁴ In our study, both cases were morphologically consistent with endometriosis. While both were positive for CD10, the first case was negative for ER stain. The differential diagnosis should include other relatively common scrotal intratesticular and extratesticular lesions such as germ cell tumors, mainly prepubertal or postpubertal teratoma, and ovarian-type Müllerian cystadenoma. Most of germ cell tumors occur in a younger population, and serum markers are usually elevated. An adjacent germ cell neoplasia in situ component is almost always present in postpubertal-type teratoma. Prepubertal teratoma occurs in a much younger age group and shows tissue arrangements mimicking organs. Ovarian-type Müllerian cystadenoma usually presents as a cyst lined by simple columnar to cuboidal cells, occasionally ciliated, resembling its ovarian counterpart. Other benign cysts including benign epididymal cysts and cysts of Müllerian remnants should also be considered.

In conclusion, although endometriosis is an extremely rare lesion in men, it should be considered in the differential diagnosis of patients presenting with banal-appearing cystic lesion, especially within or adjacent to the genitourinary tract system. Such alertness will guide the appropriate clinical management and avoid unnecessary surgical intervention.