*Review* **Pelvic Lymphadenectomy in Gynecologic Oncology—Significance of Anatomical Variations**

**Stoyan Kostov <sup>1</sup> , Yavor Kornovski <sup>1</sup> , Stanislav Slavchev <sup>1</sup> , Yonka Ivanova <sup>1</sup> , Deyan Dzhenkov <sup>2</sup> , Nikolay Dimitrov <sup>3</sup> and Angel Yordanov 4,\***


**Abstract:** Pelvic lymphadenectomy is a common surgical procedure in gynecologic oncology. Pelvic lymph node dissection is performed for all types of gynecological malignancies to evaluate the extent of a disease and facilitate further treatment planning. Most studies examine the lymphatic spread, the prognostic, and therapeutic significance of the lymph nodes. However, there are very few studies describing the possible surgical approaches and the anatomical variations. Moreover, a correlation between anatomical variations and lymphadenectomy in the pelvic region has never been discussed in medical literature. The present article aims to expand the limited knowledge of the anatomical variations in the pelvis. Anatomical variations of the ureters, pelvic vessels, and nerves and their significance to pelvic lymphadenectomy are summarized, explained, and illustrated. Surgeons should be familiar with pelvic anatomy and its variations to safely perform a pelvic lymphadenectomy. Learning the proper lymphadenectomy technique relating to anatomical landmarks and variations may decrease morbidity and mortality. Furthermore, accurate description and analysis of the majority of pelvic anatomical variations may impact not only gynecological surgery, but also spinal surgery, urology, and orthopedics.

**Keywords:** anatomical landmarks; anatomical variations; pelvic lymph nodes; gynecologic oncology; pelvic lymphadenectomy

#### **1. Introduction**

Pelvic lymph node dissection (PLND) is a common surgical procedure in gynecologic oncology [1]. The lymphatic system is the primary dissemination pathway for gynecological malignancies. PLND is applied for cancer staging, prognosis, surgical, and postoperative management [2,3]. PLND is performed for all types of gynecological malignancies to evaluate the extent of a disease and facilitate further treatment planning. Additionally, PLND is beneficial in cases where removing metastatic lymph nodes improves overall survival and disease-free survival [4]. Most studies examine the lymphatic spread, the prognostic, and therapeutic significance of pelvic lymph nodes. However, there are very few studies describing the possible surgical approach, dissection techniques and anatomical variations [5]. There is limited information and disagreement on lymph nodes location, groups, and overall number [6].

Moreover, a correlation between anatomical variations and PLND in the pelvic region has never been discussed in medical literature. Surgeons should be familiar with pelvic

**Citation:** Kostov, S.; Kornovski, Y.; Slavchev, S.; Ivanova, Y.; Dzhenkov, D.; Dimitrov, N.; Yordanov, A. Pelvic Lymphadenectomy in Gynecologic Oncology—Significance of Anatomical Variations. *Diagnostics* **2021**, *11*, 89. https://doi.org/ 10.3390/diagnostics11010089

Received: 28 November 2020 Accepted: 5 January 2021 Published: 7 January 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

anatomy and its variations to safely perform PLND. Learning the proper lymphadenectomy technique relating to anatomical landmarks and variations may decrease morbidity and mortality [7]. The present article aims to define, detail, and summarize the anatomic landmarks during PLND in gynecologic oncology. Furthermore, a summary of the most common anatomical variations (of nerves, vessels, ureters) and potential complications related to PLND in the pelvic region are clearly defined.

#### **2. Pelvic Lymph Nodes and Regions**

Knowledge of the anatomical localization of lymph node groups in the pelvis is essential for the effectiveness and safety of lymphadenectomy [8]. The pelvic lymph nodes and the connecting lymphatic channels communicate with the venous system; the lymphatic system embryologically develops from vascular plexuses, arising from the venous system [3]. The anatomical localization of the major groups and sub-groups of pelvic lymph nodes is summarized in Figures 1–3 [2,6,8–15].

**Figure 1.** Common iliac lymph nodes classification (open surgery). **1.** Lateral—between lateral part of CIV and medial part of psoas major muscle, **2.** medial—medial to CIV and CIA, **3.** middle—located in the lumbosacral fossa, **4.** subaortic—below aortic bifurcation, **5.** promontory—at the promontory. AA—abdominal aorta, IVC—inferior vena cava, RV—right renal vein, PMM—psoas major muscle, CIA—common iliac artery, CIV—common iliac vein, Cr—cranial, Ca—caudal, L—Left, R—right.

iliac artery, **2.** middle—medial to the EIA and lateral to the EIV, **3.** medial—medial to both external iliac vessels, **4.** obturator—around the obturator nerve and vessels, **5.** interiliac—at the level of CIA bifurcation, between the EIA and IIA. PMM—psoas major muscle, EIA—external iliac artery, EIV—external iliac vein, IIA—internal iliac artery, Ur—ureter, U—uterus, B—bladder, SRA—superior rectal artery, Pr—promontorium, R—rectum, L—left, r—right, Cr—cranial, Ca—caudal.

**Figure 3.** Internal iliac lymph nodes classification (embalmed cadaver—left hemipelvis). **1.** Anterior anterior to anterior division of internal iliac artery, **2.** lateral sacral—close to the paired lateral sacral arteries, **3.** gluteal—between superior gluteal and internal iliac artery, **4.** sacral (presacral)—along median sacral artery. CIA—common iliac artery, IIA—internal iliac artery, OA—obturator artery, UA—umbilical artery, IPA—internal pudendal artery, IGA—inferior gluteal artery, LSA—lateral sacral artery, ILA—iliolumbar artery, Pr—promontorium, S—sacrum.

Some authors include the subaortic and promontory lymph nodes in the medial common iliac lymph group; the obturator lymph nodes may also be considered as part of the medial external lymph group. Moreover, in some articles, anterior, lateral sacral, and gluteal internal lymph nodes are defined as junctional lymph nodes [8,10,12].

We present an anatomical classification of the pelvic lymph nodes rather than a clinical one. Although the anatomical classification is rather complex, it better defines the localization of the pelvic lymph nodes. Furthermore, the anatomical variations, significant for the PLND, are better described.

In medical literature and among surgeons, there are large variations and discrepancies in the nomenclature of the pelvic lymph node regions [2]. The present article and the majority of authors recognize the following pelvic lymph node regions: common iliac; external iliac; internal iliac; obturator; and sacral (or presacral) [5,7,12,13]. Some authors add parametrial, mesorectal, and interiliac regions, while others include tissue from the interiliac region to the external iliac and obturator regions and remove the tissue from the parametrial region together with the parametrium during radical hysterectomy [5,14,15].

#### **3. Selective PLND—Anatomical Landmarks and Techniques**

There are several surgical procedures related to dissection of pelvic lymph nodes: sentinel lymph node biopsy, pelvic lymph node sampling, selective lymphadenectomy and complete (systematic) PLND. The present article describes the systematic lymphadenectomy in which all pelvic lymph nodes, draining the pelvic organs, have been removed [1]. Cibula and Rustum presented detailed anatomic boundaries for five pelvic lymph node regions: external iliac, obturator, internal iliac, common iliac, and presacral region [5]. Anatomic boundaries of the common PLND are: ventral—common iliac artery bifurcations, dorsal—abdominal aorta bifurcation, lateral—psoas major muscle, medial—right-medial aspect of common iliac vessels, left-mesoureter [5]. Anatomic boundaries of the external and the internal PLND include common iliac artery bifurcation dorsally, the deep circumflex iliac vein ventrally, and the genitofemoral nerve of the psoas major muscle laterally. The medial border is the obliterated umbilical artery ventrally and the ureter dorsally (Figures 4 and 5) [1,7,15].

**Figure 4.** Common iliac lymph nodes dissection—anatomic boundaries (open surgery, right side). Dorsal—abdominal aorta bifurcation, ventral—common iliac artery bifurcation, medial—medial aspect of common iliac vessels (on the left side is mesoureter), lateral—psoas major muscle. AAB abdominal aorta bifurcation, PMM—psoas major muscle, CIAB—common iliac artery bifurcation, M—medial aspect of common iliac vessels on the right side (on the left side is mesoureter), IVC inferior vena cava, CIA—common iliac artery, CIV—common iliac vein.

**Figure 5.** External and internal iliac lymph nodes dissection—anatomic boundaries (open surgery left pelvic sidewall). CIAB—common iliac artery bifurcation, ON—obturator nerve, DCIV—deep circumflex iliac vein, GFN—genitofemoral nerve, PMM—psoas major muscle, EIA—external iliac artery, EIV—external iliac vein, OV—obturator vein. The medial border is the ureter dorsally and obliterated umbilical artery ventrally. In the figure, the ureter is stretched medially for better exposure of the visible structures.

#### **4. Systematic Open PLND—Surgical Technique and Steps**


#### **5. Anatomical Landmarks and Anatomical Variations, Related to Systematic PLND**

Anatomy of the pelvic ureter. Identification of the ureter is a necessary step during PLND for two reasons: to avoid injury and to serve as a medial landmark during PLND. The ureter is divided into abdominal, pelvic, and intramural segments [20]. According to Luschka's law, the left ureter crosses the iliac artery 1.5 cm below the common iliac artery bifurcation, while the right ureter crosses the iliac artery 1.5 cm above the bifurcation. Therefore, the ureter enters the pelvic cavity by crossing the common iliac artery on the left side and the external iliac artery on the right [21,22]. Hence, the left ureter is located laterally to the internal iliac artery, whereas the right ureter is located medially to the right internal iliac artery. Surgeons should fully understand the anatomical relation between the ureter and iliac vessels. As the ureter enters the true pelvis, it runs caudally and medially to the ovarian vessels, reaching the bladder on the posterior leaf of the broad ligament [23].

#### **6. Anatomical Variations of the Ureter, Related to PLND in Gynecologic Oncology (PLNDGO)**

There is a multitude of ureteral anomalies, but the following three groups are related to PLND in gynecologic oncology (PLNDGO):


(A) Ureteral multiplication is a longitudinal segmentation of the ureter into two or more tubes. Multiplication may be complete, incomplete, bilateral, and unilateral (Figure 6). Ureteral duplication is the most common type of multiplication and occurs more commonly in women than in men (4–5% of the population). Incomplete duplications tend to be unilateral and more common than complete, whereas complete duplications are often bilateral [24–26]. Unilateral ureteral duplication is more common on the right ureter than on the left (Figure 6) [25].

Surgical considerations. Ureteral multiplication increases the incidence of ureteral injury during PLND. Surgeons have to identify the course of the ureter as it crosses the pelvic brim and reaches the bladder. Injuries to the blood vessels of the ureters must be avoided, as duplicated ureters are usually contained within a single sheath and the associated blood supply could be interrupted [24,26]. Additionally, one of the duplicated ureters might be confused with vessel structures (artery most frequently), cut, and ligated during dissection. If intraoperatively, a suspicion of ureteral duplication arises, surgeons should observe the peristaltic activity of both ureters to differentiate this variation.

(B) Ureteral diverticulum is a rare urological congenital anomaly, classified into three subgroups: (1) abortive ureteral duplications, sharing the same embryogenesis as diverticula of the disordered ureteral budding; (2) true (congenital) diverticulum, characterized by the presence of all tissue layers of the normal ureter; and (3) false (required) diverticulum, which represents a mucosal herniation [27,28]. Ureteral diverticula are mainly asymptomatic, although urinary tract infection and ureteral stones causing obstruction could

appear. Papin and Eisendrath proposed and illustrated urethral diverticulum classification, which can be used clinically for PLNDGO (Figure 6) [29].

Surgical considerations. Ureteral diverticulum may also be confused with vascular structures. Ampullary diverticulum could mimic retroperitoneal cysts. In cases of retroperitoneal tumors in the pelvic region during PLNDGO, the ureter must be identified.

(C) Retro-iliac ureter (RIU) is a rare urological condition in which the ureter passes deep to the iliac vessels. Generally, the condition is diagnosed intraoperatively. Despite being a congenital anomaly, for the majority of patients the RIU first manifests itself as flank pain and symptoms of ureteral obstruction in their second or third decade of life. Coexisting anomalies are common: vaginal atresia, lumbosacral agenesis, or malrotation of the kidney. Surgical treatment consists of a dissection of the ureter and its anterior repositioning with a subsequent reimplantation in the bladder wall.

RIU is thought to originate as a result of embryologic defects: a defect in the mesonephric ureteral migration during arterial development, persistence of the embryologic primitive ventral root of the umbilical artery, between the aorta and distal umbilical artery, traps the ureter dorsally. The third hypothesis involves abnormal development of the iliac vessels from the anterior branch of the umbilical artery instead of the dorsal [30–32]. RIU is commonly located behind the common iliac artery, but other previously reported types have been described as a retro-common iliac vein, retro-external iliac artery/vein, and retrointernal iliac artery [30–32]. A bilateral RIU is a rare but possible variation (Figure 6) [30].

Surgical considerations. Although a rare anatomic variation, the RIU is of high importance. First, it is hard to be identified if the surgeon is not familiar with such a variation of the ureter. Second, it could be injured during an iliac lymph nodes dissection, especially if it is mistaken for a vascular structure. Finally, the RIU could not be the dorsomedial border of the PLND, as it has different location. In such cases, the lateral aspect of the rectum is considered as the dorsomedial border.

Anatomical variations of the ureter—conclusion of surgical considerations.

Ureteral injuries (UIs) occur approximately in 0.5–1% of all pelvic operations with gynecological operations accounting for 75% of these. UIs are more common during radical hysterectomy procedures combine with PLND. The incidence of UIs during PLND is 10%. It is believed that ureteral variations lead to an increased risk of UIs. There is consensus that a multiplication of the ureter is an independent risk factor for UIs during PLND. Benedetti-Panici et al. reported a prospective study, which included 309 consecutive patients with cervical, endometrial, and ovarian cancer treated with systematic aortic and PLND. Ureteral duplication was observed in four (1.6%) cases. Authors concluded that knowledge of ureteral anomalies is important in gynecological surgery, as the risk of UIs is elevated. Duplicated UIs during gynecological procedures are reported in medical literature. UIs may occur at the level of the infundibulopelvic ligament and deep in the pelvis, below the level of ischial spine, where the ureter lies lateral to the peritoneum of uterosacral ligament. Anatomical variations of the ureter are often associated with other congenital anomalies. Patients with known congenital anomalies or different types of syndromes should undergo preoperative imaging for careful surgical planning [33–39]. Postoperatively, a routine cystoscopy should be performed to rule out UIs [26].

**Figure 6.** Anatomical variations of the ureter related to pelvic lymph node dissection in gynecologic oncology (PLNDGO). (**A**) Duplicated ureter. (**A1**) complete duplication. (**A2**) incomplete duplication. (**B**) Ureteral diverticulum (Adapted from Papin and Eisendrath [29]). (**B1**) simple diverticulum, (**B2**) ampullary diverticulum, (**B3**) diverticulum ending in fibrous prolongation, (**B4**) multiple diverticulus. (**C**) Retroiliac ureter. (**C1**) Behind the common iliac artery, (**C2**) behind the common iliac vein, (**C3**) behind the external iliac artery, (**C4**) behind the external iliac vein, (**C5**) behind the internal iliac artery.

#### **7. Iliac Vessel Variations**

#### *7.1. Iliac Arteries*

As PLND is mainly a vascular dissection procedure, the anatomical variations of iliac vessels should be respected in order to avoid unnecessary hemorrhage or transfusion [40].

#### *7.2. Common Iliac Artery (CIA) Anatomy*

The abdominal aorta bifurcates anterolaterally to the left side of the fourth lumbar vertebral body and divides into the left and right common iliac arteries. They further divide into the external and internal iliac arteries at the level of the sacroiliac joint. The right CIA (5 cm) is frequently longer than its left counterpart (4 cm) [41].

#### *7.3. CIA Variations Related to PLNDGO*

CIA variations are relatively rare. Although the true incidence of CIA variations is not known, the most frequent anomaly is an absence of the CIA. It tends to be unilateral, predominantly to the right, even though bilateral agenesis of CIA has also been described [42–44]. In one of the cases, described by Shetty et al., the abdominal aorta was directly branching into external and internal iliac arteries at the level of the 4th–5th lumbar vertebra [43]. Dabydeen et al. described a case of congenital absence of the right CIA. In their article, the proximal part of the right external iliac artery was absent. The distal part and the right common femoral artery was reconstituted from the right inferior epigastric artery, deep circumflex iliac artery, and the contralateral common femoral artery [44]. Llauger et al. presented a case of atresia of the right CIA, associated with a large aberrant and anomalous artery, connecting both hypogastric arteries within the pelvis [45].

Rusu et al. observed the anomalous origin of the iliolumbar artery, which has not been reported before. The authors dissected 15 human adult cadavers (30 pelvic halves). The CIA appeared trifurcated due to a higher origin of the iliolumbar artery (originating from the CIA bifurcation) in 2.5% of cadavers [46]. In 8.75% of specimens, the iliolumbar artery originated from the CIA [46].

Surgical considerations. In cases of absent CIA, surgeons should be aware of collateral, anomalous, or aberrant arteries. Collateral arteries serve as an alternative blood source, compensating the absent CIA; they might be of atypical origin from the iliac system. Iliolumbar arteries, originating from the CIA or CIA bifurcation, may be damaged during a middle common iliac lymph nodes dissection of the lumbosacral fossa.

#### **8. External/Internal Iliac Artery Anatomy**

The external iliac artery (EIA) is a direct continuation of the CIA. It runs downwards, forwards in the iliac fossa, and reaches the lacuna vasorum under the inguinal ligament. The EIA has two branches: inferior epigastric artery and deep circumflex iliac artery. After crossing the mid-inguinal point, it continues as a common femoral artery. The internal iliac artery (IIA) arises from the CIA anterior to the sacroiliac joint. In the majority of the cases, the artery originates at the level of the L5–S1 intervertebral disc. The IIA descends posteriorly towards the superior border of the greater sciatic foramen where it divides into two branches: anterior and posterior [42,47,48]. The anterior and posterior branches of the IIA are illustrated in Figure 7.

**Figure 7.** The internal iliac artery (IIA) branches. OA—obturator artery, UA—obliterated umbilical artery, SVA—superior vesical artery, UA—uterine artery, VA—vaginal artery, MRA—middle rectal artery, IPA—internal pudendal artery, IGA—inferior gluteal artery, LSA—lateral sacral artery, SGA superior gluteal artery, ILA—iliolumbar artery.

#### **9. EIA Variations Related to PLNDGO**

Variations of the EIA are grouped into four categories [48,49]:


(A) Kawashima et al. reported a rare case of hypoplastic right EIA, which continued into the normal femoral artery by anastomoses formed with the enlarged obturator and deep circumflex iliac arteries [50]. Okamoto et al. reported a case of the CIA entering into the pelvic cavity without branching to the EIA. The artery passed behind the first sacral nerve and gave rise to each branch of the IIA in the pelvis [51]. In cases of EIA hypoplasia, an ipsilateral persistent sciatic artery may also be observed [49].

Surgical considerations. Cases of EIA hypoplasia and agenesis are of clinical significance due to the possible presence of a collateral pathway. PLND should be meticulous in order to preserve collateral and anomalous vessels.

(B) The EIA may directly originate from the abdominal aorta. The origin of the EIA could be posterior in the internal iliac fossa. The position of the EIA may differ to the external iliac vein (EIV) position. The EIA might be located superficially or medially to the EIV [48,49].

Surgical considerations. During an external iliac lymph nodes dissection, surgeons should be familiar with the EIA position differences to prevent iliac vessel injury. Safi et al. reported a case of EIA laparoscopic injury due to an anomalous position of the artery. The EIA was elongated and located posterior and medial to the EIV. They repaired the artery using a two-needle single-knot technique and continued the lymphadenectomy. Authors concluded that during PLND, both external iliac vessels should be exposed and visible to the surgeon, as the anatomical variations of the EIA increased the risk of injury [52].

(C) Morphological variations of the EIA are grossly classified in five groups: looped, tortuous, curved, twisted, and S-shaped EIA. Nayak et al. presented a cadaveric study of 48 hemipelvises. They observed morphological variations in nine (19%) of the hemipelvises [48]. Looped and tortuous EIA have been reported in other case studies [53,54]. We also observed morphological variations of EIA (Figure 8).

**Figure 8.** Morphological variations of the external iliac artery (EIA). (**A**) The EIA with an inward loop in the left hemipelvis. (**B**) The EIA with a gentle inward loop in the left hemipelvis. (C) 'S' shaped EIA in the right hemipelvis. EIA—external iliac artery, EIV—external iliac vein, IIA—internal iliac artery, PMM—psoas major muscle.

Surgical considerations. Knowledge of the EIA morphological variations is essential during an external iliac lymph nodes dissection. Particular attention should be paid during dissection of the lateral, middle, and medial external iliac lymph nodes. The risk of iatrogenic EIA lesions may increase as a result of existing morphological differences.

*Diagnostics* **2021**, *11*, 89

iliac artery (Figure 9) [55,56]. Nayak et al. reported duplication of the deep circumflex iliac artery and an additional large muscular branch, arising and descending laterally from the EIA [48]. The medial circumflex femoral artery and the profunda femoral artery could also arise from the EIA [42].

**Figure 9.** An aberrant obturator artery arising as a common trunk with the inferior epigastric artery (open surgery). EIA—external iliac artery, EIV—external iliac vein, AOA—aberrant obturator artery, ACOV—accessory obturator vein, ON—obturator nerve, OV—obturator vein, IEA—inferior epigastric artery, UMA—umbilical artery, FR—the deep femoral ring, OF—obturator foramen. Ca caudal, Cr—cranial, R—right, L—left.

Surgical considerations. An OA, arising from the EIA, is not a rare variation. The majority of OA origin variations are located at the distal part of the EIA.
