Renal Endometriosis Mimicking Cystic Renal Tumor: Case Report and Literature Review

Background: Endometriosis mainly affects female pelvic tissues and organs, and the presence of endometriosis in the kidney is extremely rare. Case Presentation: We report a case of a 48-year-old woman who presented with intermittent hematuria. She was found to have a cystic mass on renal ultrasonography, and contrast-enhanced computed tomography (CT) showed slight enhancement of the cystic wall and septa. These findings were indicative of cystic renal tumor. The patient subsequently underwent partial right nephrectomy. Histopathology revealed endometriosis of the right renal parenchyma. The patient recovered well and had no evidence of a recurrent renal mass at the 3 months' follow up. Conclusion: The possibility of renal endometriosis should be considered in a female patient with a cystic renal mass and clinical symptoms related to the menstrual cycle.


INTRODUCTION
Endometriosis is a common disease occurring in women of reproductive age. Most lesions occur in the reproductive system (1), and endometriosis of the kidneys is rare (2). Because of the insufficient knowledge of renal endometriosis, it can be easily misdiagnosed. Herein, we report our experience with renal endometriosis with the goal of increasing the scholarly awareness of this rare entity.

CASE PRESENTATION
A 48-year-old married woman presented to our hospital with intermittent gross hematuria for 3 months. She had regular menstrual cycle of 28 days without pain around her waist line or abdominal pain and no history of gynecologic surgery. She denied a family history of cancer, endometriosis, genetic and psychosocial diseases.
There was no obvious mass on the palpation of the bilateral kidney area, and no percussion pain. An ultrasound of the urinary system was recommended first. Conventional ultrasound examination was performed under standardized settings using Toshiba ultrasound systems (Aplio500, Tokyo, Japan) (ultrasound transducer: PVT-375BT, frequency 3.5 MHz). Ultrasonography showed a cystic mass in the lower pole of the right kidney with septa and well-circumscribed. The thickness of the cystic mass wall is about 4 mm. Doppler color flow imaging showed a small signal in the wall of the mass, but no blood flow was detected in the cystic part. Contrast-enhanced computed tomography (CT) of the kidney was then performed. It showed a heterogeneous hypodense mass in the lower pole of the right kidney, measuring ∼1.8 × 1.5 × 1.4 cm (Figure 1). The mass was polycystic, with slight enhancement of the wall and septa and no enhancement of the cystic area. Contrast filling of the mass was not observed during the excretory phase. The right lower pole of the kidney was partially depressed, and there was some local thinning of the renal cortex. Given the slight enhancement of the mass, the possibility of cystic renal tumor could not be ruled out, and surgical resection was planned. Laparoscopic right renal mass resection was subsequently performed at our hospital on the 7th day after her menstruation. After successful anesthesia, the surgeon opened the lateral retroperitoneum under laparoscopy, pushed the colon away and opened the Gerota's fascia, then carefully dissociated the right kidney. The right lower pole of the kidney was partially irregular and contracted. A well-demarcated cystic tumor with the size of 2.5 × 2.0 × 2.0 cm could be seen at the lower pole of the right kidney after surgical incision, which involved the renal parenchyma but had clear boundaries, and the mass was easily peeled off. The mass composed of brown central area showed several branching cavities, with 5 mm wide homogenous light-yellow zone at its periphery. Perioperatively, the tumor was confined to the right kidney without extracapsular invasion, which did not encroach on the perirenal fat sac or surrounding organs. The mass was completely resected, with an ∼0.5 cm margin of normal renal tissue. The resected mass had a diameter of ∼1.5 cm. There were several capsular spaces containing brown fluid, and the cut surface of the mass was yellowish. Microscopic examination confirmed the diagnosis of renal endometriosis characterized by endometrial glands and embedded stromal cells (Figure 2). Immunohistochemical analysis revealed that the stromal cells and epithelial cells were positive for estrogen receptor (ER), progestin receptor (PR), and vimentin, which further supported the diagnosis of renal endometriosis. Histopathology was reviewed by two senior pathologists separately, without any atypia. The patient recovered well after the surgery, and there were no obvious space-occupying lesions by ultrasonography in the kidney at the 3 months followup. The patient is very satisfied with the treatment of this disease.
The mechanism of extragenital endometriosis remains controversial. The main theories can be categorized as migratory, embryonic, and immunologic, these theories have been discussed in previous literature (43, 44, 46, 48, 50-54, 56, 57). Migratory theories propose that retrograde menstruation, lymphovascular metastasis, and direct extension allow the endothelial cells to transplant into ectopic sites (46, 48, 50-54, 56, 57). Embryonic theories suggest that endometriosis results from metaplastic changes of Wolffian, Mullerian, and occasionally peritoneal (celomic) structures (43,44,46,48,50,51,53,54). Immunologic theories suggest that a suboptimal immune response may result in ectopic endometrial implantation (46,(50)(51)(52)(53)(54). In these literatures, Bazaz-Malik et al., Dutta et al., and Cheng et al. believe that the pathogenesis of their cases of renal endometriosis is rationally explained by embryonic theory (44,48,53). The qualitative features of Bosniak III cystic masses: cystic masses with one or more thick or irregular enhancing walls or septa without nodular enhancement. The Bosniak Classification, version 2019 defines "thick" as 4 mm or thicker (58). In our case, the thickness of the cystic mass wall is 4 mm and with enhancement. It was classified as Bosniak III according to Bosniak Classification of Cystic Renal Masses, Version 2019 (58). Approximately 50% of Bosniak III masses are malignant (59). The imaging features of multilocular cystic renal neoplasm of low malignant potential are different from benign renal cystic masses. In general, necrosis of carcinoma tends to be central, with a thickened solid peripheral "rind" and a central ill-defined area of non-enhancement (60). Different imaging modalities may have some roles in the diagnosis of renal endometriosis. Shedding of the ectopic endometrium may result in a heterogeneous mass density on CT scan (52). The hyperplastic fibromuscular tissue surrounding the lesion is unevenly enhanced and may show protrusion into the central part (49). The continuous proliferation of muscle fibers around the lesion can distort the surrounding renal parenchyma and change the shape of the kidney. Unlike the CT scan, MRI can show renal pelvis compression or displacement. Mixed cystic-solid masses with fibromuscular hyperplasia and residual blood will produce heterogeneous MRI signals (49). The location, size, and composition (solid vs. cystic) of a renal mass can also be visualized using ultrasound. Ultrasound color Doppler flow imaging can demonstrate blood flow signals in the wall and septa. Ultrasound can also be used to facilitate tissue diagnosis. Ultrasound-guided fine needle aspiration (FNA) biopsy is an accurate and minimally invasive method that can greatly help in the diagnosis of endometriosis. To date, three cases of renal endometriosis have been confirmed by FNA (45,47,48). Ultrasound is very useful for detecting endometriosis in the uterus and ovary (61), and most importantly, it is cheap, especially suitable for developing countries.
Pain and hematuria are often intermittent and associated with the menstrual cycle in patients with renal endometriosis. Our patient had no abdominal pain, but her hematuria was cyclical and corresponded to her menstrual cycle. This important information was overlooked at the time of her initial presentation.
The histopathology of renal endometriosis is characterized by endometrial glands and stromal cells involving renal cortex and medulla (62). Immunohistochemical analysis shows stromal cell and epithelial cell positivity for CD10, ER, and PR (62). In our case, the stromal cells and epithelial cells were positive for ER, PR, and vimentin, which further supported the diagnosis of renal endometriosis.
As there are no treatment guidelines for renal endometriosis because of its rarity (51), the treatment should be based on the patient's clinical symptoms, characteristics of the lesion, and the patient's reproductive plans (41). Although renal endometriosis is a benign lesion, surgical treatment is usually considered due to its invasiveness (63). The feasibility of laparoscopic management is now widely proven and may reduce the length of hospital stay (64). Asymptomatic patients with multiple small lesions unchanged during subsequent imaging examinations generally do not require any definitive therapy for renal lesions (54). Hormone therapy, such as GnRH agonists and oral contraceptives, can be used for symptom management (45,48,51). Hormonal treatment reduces the pain in the short-term follow up and is the best treatment for patients of reproductive age (64).

CONCLUSION
We report a patient who presented with a single small cystic kidney mass and was found to have endometriosis. Although imaging can be helpful, the final diagnosis of endometriosis relies on histopathologic findings. The possibility of renal endometriosis should be considered in a female patient with a cystic renal mass and clinical symptoms related to the menstrual cycle.

DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

ETHICS STATEMENT
Written informed consent was obtained from the participant for the publication of this case report. Ethical approval was given by the Medical Ethics Committee of our hospital.

AUTHOR CONTRIBUTIONS
YY and YH diagnosed the patient. All authors wrote and revised the manuscript.

FUNDING
This study was supported by grants from the Scientific Research Project of the Educational Department of Liaoning Province (ZF2019023) and 345 Talent Project.