Clinical and ultrasound characteristics of deep endometriosis affecting sacral plexus

Objective To describe the sonomorphological changes and appearance of deep endometriosis (DE) affecting the nervous tissue of the sacral plexus (SP).

This was a retrospective study of symptomatic patients who underwent radical resection of histologically confirmed DE affecting the SP and who had undergone preoperative transvaginal sonography (TVS) between 2019 and 2023. Lesions were described based on the terms and definitions of the International Deep Endometriosis Analysis (IDEA), International Ovarian Tumor Analysis (IOTA) and Morphological Uterus Sonographic Assessment (MUSA) groups. A diagnosis of DE affecting the SP on TVS was made when the sonographic criteria of DE were visualized in conjunction with fibers of the SP and the presence of related symptoms corresponding to sacral radiculopathy. Clinical symptoms, ultrasound features and histological confirmation were analyzed for each patient included.

Twenty-seven patients with DE infiltrating the SP were identified in two contributing tertiary referral centers. Median age was 37 (range, 29–45) years and all patients were symptomatic and presented one or more of the following neurological symptoms: dysesthesia in the ipsilateral lower extremity (n = 17); paresthesia in the ipsilateral lower extremity (n = 10); chronic pelvic pain radiating in the ipsilateral lower extremity (n = 9); chronic pain radiating in the pudendal region (n = 8); and motor weakness in the ipsilateral lower extremities (n = 3). All DE lesions affecting the SP were purely solid tumors in the posterior parametrium in direct contact with, or infiltrating, the S1, S2, S3 and/or S4 roots of the SP. The median of the largest diameter recorded for each of the DE nodules was 35 (range, 18–50) mm. Echogenicity was non-uniform in 23 (85%) of the DE nodules, with all but one of these nodules containing hyperechogenic areas. The shape of the lesions was irregular in 24 (89%) cases. Only one lesion exhibited a lobulated form, with all other irregular lesions showing a spiculated appearance. An acoustic shadow was produced in 20 (74%) of the nodules, all of which were internal. On color or power Doppler examination, 21 (78%) of the nodules showed no signal (color score of 1). The remaining six (22%) lesions showed a minimal color content (color score of 2). According to pattern recognition, most DE nodules were purely solid, non-uniform, hypoechogenic nodules containing hyperechogenic areas, with internal shadows and irregular spiculated contours, and were poorly vascularized on color/power Doppler examination.

The ultrasound finding of a parametrial, unilateral, solid, non-uniform, hypoechogenic nodule with hyperechogenic areas and possible internal shadowing, as well as irregular spiculated contours, demonstrating poor vascularization on Doppler examination in proximity to or involving the structures of the SP, indicates DE affecting the SP. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. CONTRIBUTION What are the novel findings of this work? Deep endometriosis affecting the sacral plexus exhibits a distinct sonographic appearance on transvaginal ultrasound, in which lesions appear as unilateral, solid, non-uniform, hypoechogenic nodules containing hyperechogenic areas, with internal shadows, irregular spiculated contours, poor vascularization on color/power Doppler examination and a diameter of 2 cm or more. What are the clinical implications of this work? Transvaginal sonography is capable of diagnosing deep endometriosis affecting the sacral plexus, which may have implications for the planning of treatment strategies.

Deep endometriosis (DE) infiltrating the sacral plexus (SP) and SP roots is considered to be a severe form of DE in the posterior pelvic compartment1, 2. Perineural spread from the parametrium to the SP is a possible pathological pathway. However, the progression of the disease is largely unknown and this type of endometriosis is still considered rare3, with the prevalence of DE infiltrating the SP not yet reported4. The histological diagnosis of endometriosis is based on the presence of endometrial epithelium and/or stroma outside the uterine cavity, surrounded by fibrosis or muscular hyperplasia5. Endometriotic stroma contains a network of small vessels. Multiple layers of connective tissue surround the peripheral nerve fibers, with all the fascicles bound together by a thick layer called the epineurium6. This sheath of mesodermal origin contains fibroblasts, elastic fibers, Type-I and Type-III collagen and some adipocytes (Figure 1). During laparoscopic surgical dissection of the SP (neurolysis), the roots of the SP can be visualized only by opening the subperitoneal spaces and the fascia covering the SP1. The sacral nerve roots S1–S4 can be perceived as solitary solid white bands on the posterolateral wall of the pelvis. Large DE nodules in the posterior pelvic compartment can infiltrate the parametrium and penetrate the retroperitoneal space, compressing and infiltrating the inferior hypogastric plexus and S2–S4 sacral nerve roots in the form of infracardinal lesions3. These lesions may involve other pelvic visceral organs (e.g. rectum, ureter, vagina). DE nodules adhering to the pelvic side wall can infiltrate the roots of the sciatic nerve or the lumbosacral trunk and are referred to as supracardinal DE lesions3, 7. These lesions cause pain and sensory dysfunction, such as dermatome-associated dysesthesia and paresthesia of the lower extremities, and may also cause irritation of autonomous and pudendal nerve fibers arising from the S2–S4 sacral nerve roots (Figure 2). Until now, diagnosis of DE in this location was based on clinical signs and the results of magnetic resonance imaging (MRI)8. Recently, our group presented a technique to visualize the SP and its roots with transvaginal ultrasound (TVS)9. To the best of our knowledge, DE affecting the SP has not yet been studied with TVS. The aim of this study was to describe the clinical and sonographic characteristics of DE infiltrating the SP.

This was a retrospective descriptive study using data obtained from two tertiary referral centers for endometriosis (Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary and Department of Gynecology, Center for Endometriosis, Hospital St John of God, Vienna, Austria). From these databases, we identified 27 consecutive patients with a histological diagnosis of DE infiltrating the SP following surgery for symptomatic disease, who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 2019 and 2023, of whom 19 were from Budapest and eight were from Vienna. All women had been examined by TVS according to the systematic approach of the International Deep Endometriosis Analysis (IDEA) group10, using high-end ultrasound equipment, namely a 2–10-MHz transvaginal probe with three-dimensional option (Hera W9 and Hera W10, Samsung, Seoul, South Korea; Voluson E10, GE Healthcare, Zipf, Austria). Each author characterized the lesions from their own center based on patient records, ultrasound images, videoclips and ultrasound reports, according to the sonographic appearance of the lesion using the terminology of the IDEA, International Ovarian Tumor Analysis (IOTA) and Morphological Uterus Sonographic Assessment (MUSA) groups on a predefined ultrasound assessment form10-12. Data were recorded using a predefined protocol, including clinical information, sonographic characteristics, descriptions of the location of the lesion and its relation to surrounding nerves (either extrinsic compression or intrinsic infiltration) based on intraoperative findings, and final histology. DE affecting the SP was diagnosed when features of DE were visualized in the proximity of, and/or infiltrating, the sonographic structure of the sacral root S1, S2 or S3, as reported previously5, in the presence of symptoms corresponding to sacral radiculopathy. Typical symptoms of sacral radiculopathy are chronic pelvic pain or dysesthesia/paresthesia radiating to the perineum (S2–S4) and the ipsilateral lower limbs and corresponding dermatome, as well as weakness in the ipsilateral lower extremities (L5–S1), depending on the actual sacral root affected by DE. DE not only causes direct damage of the organs to a depth of at least 5 mm, but also causes secondary inflammation, reactive fibrosis and scarring. Nodules that reached the hyperechogenic outer edge of the nerve, the epineurium, and exerted traction on it were called extrinsic type. Lesions that extended through the epineurium into the fasciculi of the nerve were called intrinsic type. IOTA terms and definitions were developed originally for the description of adnexal tumors. For the purposes of this study, we used the IOTA terms to describe the type (solid or cystic) and color score of the lesion11. The intralesional vascular pattern was described using a semiquantitative color score of 1–4. A color score of 1 means that no color or power Doppler signals were detected in the tumor, a score of 2 means that a minimal amount of color Doppler signal (i.e. flow) was detected, a score of 3 means that a moderate amount was detected and a score of 4 means that an abundant amount of signal was detected. Color or power Doppler ultrasound was used to visualize the vascular architecture of the DE lesion, and low pulse-repetition frequency (0.3–0.6 kHz) and low wall filter (50–100 Hz) were used to enable the detection of as many blood vessels as possible. The gain was increased to the point of significant color noise and then slowly reduced until all artifacts disappeared. MUSA terminology was developed originally for describing myometrial lesions, including uterine smooth muscle tumors. DE is primarily a solid nodule and, therefore, MUSA terminology offered specific definitions that were used to describe the echogenicity of the solid DE lesions: uniform (hypoechogenic, isoechogenic or hyperechogenic); non-uniform with mixed echogenicity, hyperechogenic areas or cystic areas; and shadowing (edge, internal or fan-shaped)12. DE nodule shape was defined as regular (oval or round) or irregular (lobulated or spiculated). Oval lesions have a dominant long axis, while round nodules have long and short axes that are similar in length. Irregular shape means that the outer contour is lobulated or spiculated. DE lesions with a lobulated shape have a smooth, wavy external contour and intact capsule. DE nodules with a spiculated contour have spiky, blurred margins13. According to the dynamic ultrasonography steps of the IDEA approach, we evaluated soft markers of DE, such as site-specific tenderness and ipsilateral ovarian mobility10. By applying pressure between the uterus and ovary, we assessed if the ovary was fixed to the uterus medially, to the pelvic side wall laterally or to the uterosacral ligaments. To assess the status of the pouch of Douglas (POD), we used the real-time TVS-based ‘sliding sign’ for all patients. If the uterus was anteverted, gentle pressure was applied to the cervix using the transvaginal probe to assess whether the anterior rectum glided freely across the posterior surface of the cervix and posterior vaginal wall. If the anterior rectal wall did so, the sliding sign was considered to be positive. Then, one hand was placed over the patient's lower anterior abdominal wall in order to ballot the uterus between the palpating hand and the transvaginal probe (which was held in the other hand) to assess whether the anterior rectum glided freely over the posterior surface of the uterine fundus. If it did so, the sliding sign was also considered positive in this region. When the sliding sign was found to be positive in both of these anatomical regions (retrocervix and posterior uterine fundus), the POD was recorded as being not obliterated10. Other ultrasound techniques mentioned in the IDEA approach (e.g. transvaginal strain sonoelastography), if available, were also reported10, 14, 15. Using transvaginal strain sonoelastography, the stiffness of the nodules was compared with the stiffness of the intact nerve. A strain ratio of 2.0 served as a cut-off value for the optimal distinction. In most cases, an experienced sonographer can confidently and correctly evaluate lesions and make a differential diagnosis based on subjective evaluation of the grayscale ultrasound image with or without the added information of the color Doppler ultrasound examination results16. This process is called pattern recognition. In addition to the predefined protocol, the principal investigators (G.S. and G.H.) and two ultrasound examiners (I.M. and V.F.) reviewed all available digital ultrasound images and videoclips to identify possible ultrasound patterns characteristic of DE infiltrating the SP. The description agreed by the four observers based on pattern recognition was reported. The study data were evaluated by descriptive statistical methods. Continuous data are given as mean ± SD if normally distributed and median (range) if non-normally distributed. Categorical data are given as n (%). Statistical analysis was undertaken using STATISTICA software package (version 13.5.0.17; TIBCO Software Inc., Palo Alto, CA, USA).

Twenty-seven patients with DE affecting the SP were identified and verified histologically following surgical resection of the DE. Their median age was 37 (range, 29–45) years. Clinical characteristics of the patients are presented in Table 1. No known comorbidities were recorded. All patients underwent laparoscopic sacral neurolysis and resection of DE nodules. The median time between the onset of symptoms and surgery was 11 (range, 4–16) months. All patients exhibited unilateral DE with extrinsic or intrinsic involvement of the SP. Sixteen lesions were on the right side and 11 lesions were on the left side. All the patients were symptomatic and presented with one or more of the following neurological symptoms: dysesthesia in the ipsilateral lower extremity (n = 17); paresthesia in the ipsilateral lower extremity (n = 10); chronic pelvic pain radiating in the ipsilateral lower extremity (n = 9); chronic pain radiating in the pudendal region (n = 8); and motor weakness in the ipsilateral lower extremities (n = 3). | Characteristic | Value | |---|---| | Age (years) | 37 (29–45) | | Body mass index (kg/m2) | 24 ± 2.4 | | Gravidity | | | 0 | 19 (70) | | 1 | 3 (11) | | 2 | 4 (15) | | ≥ 3 | 1 (4) | | Parity | | | 0 | 20 (74) | | 1 | 3 (11) | | 2 | 3 (11) | | 3 | 1 (4) | - Data are given as median (range), mean ± SD or n (%). The sonographic characteristics of DE affecting the SP are presented in Table 2, which shows that all DE lesions affecting the SP were purely solid tumors (n = 27). The median of the largest diameter recorded for each DE nodule was 35 (range, 18–50) mm. The echogenicity was non-uniform in 23 (85%) of the DE nodules; of those, all but one contained hyperechogenic areas. The shape of the lesions was classified as irregular in 24 (89%); of those, only one lesion was lobulated and the rest were spiculated (Figure 3). In 20 (74%) of the nodules, an acoustic shadow was produced, all of which were internal (Figure 4). On color or power Doppler examination, 21 (78%) of the nodules showed no signal (Figure 5). The remaining six (22%) lesions manifested minimal color content (color score of 2). | Ultrasound finding | Value | |---|---| | Largest diameter of lesion (mm) | 35 (18–50) | | Type of lesion, solid | 27 (100) | | Lesion echogenicity | | | Uniform | | | Anechoic | 2 (7) | | Isoechogenic | 0 (0) | | Hypoechogenic | 2 (7) | | Non-uniform | | | Mixed | 0 (0) | | Non-uniform with cystic areas | 1 (4) | | Non-uniform with hyperechogenic areas | 22 (81) | | Acoustic shadowing | | | No | 7 (26) | | Edge | 0 (0) | | Internal | 20 (74) | | Fan-shaped | 0 (0) | | Color/power Doppler score* | | | 1 | 21 (78) | | 2 | 6 (22) | | 3 | 0 (0) | | 4 | 0 (0) | | Lesion shape | | | Regular | | | Oval | 3 (11) | | Round | 0 (0) | | Irregular | | | Spiculated | 23 (85) | | Lobulated | 1 (4) | | Relation with peripheral nerve | | | Intrinsic | 8 (30) | | Extrinsic | 19 (70) | | Ipsilateral ovarian immobility | 14 (52) | | Sliding sign between rectum and uterus | | | Positive | 17 (63) | | Negative | 10 (37) | | Site-specific tenderness | 27 (100) | - Data are given as median (range) or n (%). - Ultrasound findings are described using terms and definitions of International Ovarian Tumor Analysis11, Morphological Uterus Sonographic Assessment12 and International Deep Endometriosis Analysis10 groups and diagnosis was suggested by original ultrasound examiner. - * Color score: 1, no detectable blood flow; 2, minimal blood flow; 3, moderate blood flow; and 4, abundant blood flow. All 17 DE lesions for which information on strain elastography was available demonstrated hard stiffness compared with their surroundings (Figure 6). All DE nodules were located in the posterior parametrium in direct contact with the roots of the SP. In eight (30%) patients, the nodule was intrinsic, i.e. invasion and infiltration were diagnosed during surgery. The other lesions (n = 19) were extrinsic, i.e. DE affected the perineural tissue and appeared adherent to the neural structures, causing symptoms by traction and local irritation (Figure 7). The four observers evaluating the grayscale and color/power Doppler ultrasound images agreed in their description of DE affecting the SP and reached the following consensus to describe the 27 cases analyzed in this study: the most characteristic ultrasound appearance of a DE lesion affecting the SP in our series, using pattern recognition, was a purely solid, non-uniform, hypoechogenic nodule containing hyperechogenic areas, with internal shadows and irregular spiculated contours, that was poorly vascularized on color/power Doppler examination and in direct contact with the hyperechogenic epineurium of the nerves.

To date, the identification of DE nodules involving the SP on TVS has not been reported, making our study the first of its kind. The results of the present study suggest that diagnosis of DE in this rare location is feasible preoperatively using clinical signs and TVS. However, we support the additional use of MRI in women for whom surgery is considered and planned. Ultrasonographic features of endometriosis vary. Some DE nodules have organ-specific, distinct sonographic signs, for example, the ‘comet sign’ in the bowel17, 18. According to the literature summarized in the IDEA consensus statement, DE nodules tend to appear sonographically as solid, hypoechogenic to anechoic and irregular-shaped masses10. They may contain echogenic foci or small cystic spaces, which correspond to collections of detritus or blood. These lesions show mainly little or no blood flow on color Doppler and demonstrate high stiffness on elastography14, 15. In a recent case report, extrapelvic DE affecting the sciatic nerve was visualized by ultrasonography and described as a large, perineural, hypoechogenic, inhomogeneous lesion with an irregular contour engulfing the nerve19. The results of the present study support the sonographic characteristics described previously19. An interesting feature of the ultrasonographic appearance of DE nodules affecting the SP is that most of these lesions produced an acoustic shadow and a certain number of hyperechogenic foci. These features may be due to secondary scarring of the DE nodule or the presence of an epineurium of infiltrated nerves3. Only in exceptional cases did cystic areas appear in these lesions. A major difference between DE lesions and peripheral nerve sheath tumors (PNSTs) is that PNSTs originate from the nerve sheath cells. In contrast, DE nodules either adhere to the outside of the epineurium or wrap around it and may partly infiltrate the nerve. Therefore, DE nodules do not have a hyperechogenic rim. Benign PNSTs in the pelvis, such as schwannomas and neurofibromas, can be also identified with TVS20. However, these benign PNSTs are usually asymptomatic. The typical ultrasound appearance of a benign PNST is a solid, fusiform, hypoechogenic, non-uniform and poorly or moderately vascular tumor without acoustic shadowing. All benign PNSTs are well circumscribed by a hyperechogenic rim formed by the epineurium. Schwannomas are more inhomogeneous and show moderate vascularization. Ancient schwannomas may also show cystic areas. Neurofibromas are well-defined, homogeneously hypoechogenic and poorly vascularized tumors within hyperechogenic areas, in which nerve fibers can be seen entering and exiting the mass21. They demonstrate low-to-moderate stiffness on elastography (Figure 8). Malignant PNSTs are extremely rare and typically cause neurological symptoms. Their irregular spiculated borders, inhomogeneous irregular internal echogenicity and hyperechogenic rim due to the surrounding soft-tissue reaction may present a challenge for differential diagnosis. However, as they are richly vascularized21, color/power Doppler could be useful in the differential diagnosis between DE infiltrating the SP and malignant PNSTs. Other lesions of the SP, such as anterior sacral meningocele, present as a multilocular, thin-walled cyst on TVS22. All the patients in our study were of reproductive age. As only one of the patients was under 30 years of age (29 years) and only one of the nodules had a diameter of less than 20 mm (18 mm), we suspect that DE nodules affecting the SP may take a long time to develop. In the literature, the average age of patients operated on with laparoscopy for DE infiltrating the SP is also over 30 years1, 2. Further prospective studies should seek to clarify the natural history of DE nodules affecting the SP. Characteristic symptoms, like pain or paresthesia radiating to the perineum and the ipsilateral lower limbs and corresponding dermatome, i.e. sacral radiculopathy, may lead to the suspicion of disease23. However, a diagnosis cannot be made on the basis of these symptoms alone. A strength of our study is that it is the first of its kind to describe the ultrasound features of this rare type of DE in a clinically relevant number of patients and with a final diagnosis confirmed by radical resection and histology. A limitation of the study is its retrospective nature. However, to overcome this limitation, we used standardized terminology and a predefined ultrasound assessment form based on IOTA, MUSA and IDEA terms and definitions to describe the sonographic characteristics of the DE nodules, as well as exchanging and reviewing digital ultrasound images between four independent observers. In conclusion, clinical signs of sacral radiculopathy and the finding on TVS of a parametrial, unilateral, solid, non-uniform, hypoechogenic nodule with hyperechogenic areas, possible internal shadowing and irregular spiculated contours, demonstrating poor vascularization on Doppler examination, and in proximity to or involving the structures of the SP, reflect symptomatic DE affecting the SP. DATA AVAILABILITY STATEMENT The data that support the findings of this study are available from the corresponding author upon reasonable request.