Inguinal endometriosis, a rare entity of which surgeons should be aware: clinical aspects and long-term follow-up of nine cases

Introduction Inguinal endometriosis is a rare disease and often misdiagnosed for other, more common groin pathology. We present nine cases of women with inguinal endometriosis with long-term follow-up.

In this retrospective case series, the Dutch PALGA system was searched for all patients diagnosed with extrapel- vic endometriosis located in the groin in the OLVG hospital, Amsterdam, between 2000 and 2016. Relevant information regarding pre- and postoperative characteristics and symptoms was collected. Follow-up consisted of a telephone call from the attending surgeon.

None of the patients had a history of pelvic endometriosis. Typically, they presented with a right-sided swelling in the groin. Preoperative ultrasound and MRI were in most cases inconclusive. In one of two patients fna indicated endometriosis. In only three patients the surgeon considered the diagnosis endometriosis preoperatively. Surgical removal was effective with no reported complications. A coexisting hernia sac was resected in four cases, and there was a suspicion of a persistent processus vaginalis (canal of Nuck) in three, suggesting that a persistent processus vaginalis is possibly an important key to the pathogenesis. In none of the cases there was an indication for mesh implantation. One patient was later diagnosed with pelvic endometriosis.

Follow-up by a gynecologist is advised to check for intra-abdominal disease and inform patients on fertility perspective. Surgeons should be aware of the possibility of inguinal endometriosis in fertile women with a lump in the groin.

Inguinal hernia · Endometriosis · Groin · Processus vaginalis

Endometriosis is defined as the presence of endometrial gland cells and stroma outside the uterine cavity. Endo- metriosis is a common benign inflammatory disease with a reported prevalence of 1.2–1.5%, with a peak prevalence between the age of 35 and 44, usually situated within the pelvis [1]. Extrapelvic endometriosis is less common, but can involve nearly all organs [2]. Inguinal endometriosis is rare with a reported incidence of < 1% of patients with endometriosis [3 –6]. It is defined as endometriosis in the inguinal canal, either in a hernia sac, surrounding the round ligament or in a persistent processus vaginalis (PPV). A PPV, a small invagination of the parietal peritoneum, is also known as the persistent canal of Nuck. Due to its location in the groin, symptomatic patients are often presented to a general surgeon rather than a gynecolo- gist. Because of its rare and uncommon presentation, endo- metriosis of the groin is frequently clinically misdiagnosed as a lymph node, cyst of Nuck, femoral or inguinal hernia or a lipoma [7–9]. Inguinal endometriosis is prone to diag- nostic uncertainty, which possibly leads to multiple and expensive preoperative imaging. The disease itself remains enigmatic because inguinal endometriosis grows outside the pelvic peritoneal cavity and, intriguingly, preferably in the * M. P. Simons [email protected] 1 Department of Surgery, Flevoziekenhuis, Almere, The Netherlands 2 Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands 3 Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands 4 Department of Obstetrics and Gynecology, OLVG, Amsterdam, The Netherlands 5 Department of Surgery, OLVG, Oosterpark 9, 1091 AC Amsterdam, The Netherlands 882 Hernia (2018) 22:881–886 1 3 right inguinal canal. Several theories have been proposed, including but not limited to metaplasia of mesothelium, ret- rograde menstruation and seeding into a hernia or PPV, oxi- dative stress and inflammation, auto-immune dysfunction, apoptosis suppression and regeneration of stem cells [10]. However, none of them fully elucidate its pathogenesis [4 , 6, 11, 12]. Only a limited number of cases have been reported in contemporary literature. We present clinical aspects of nine individual cases of inguinal endometriosis with their long- term follow-up, and considerations on its diagnosis, treat- ment and pathogenesis are discussed.

We searched the Dutch PALGA system, a nationwide histo- pathology and cytopathology data network and archive, for patients who were diagnosed with extrapelvic endometrio- sis located in the groin in the OLVG hospital, Amsterdam, between 2000 and 2016 [13]. Furthermore, we identified all female patients treated for an inguinal hernia in the same time period to estimate the incidence of the inguinal endo- metriosis in this patient group at our hospital. For all patients that had received surgical treatment for endometriosis in the groin, the following data were col- lected: age, relevant medical history, initial symptoms, location of the swelling, preoperative imaging, preopera- tive fine needle aspiration (fna) and pathology results, type of primary surgery, pathology results of the resected tissue and results of short-term follow-up. After current inclusion, patients received follow-up from the attending surgeon by a semi-structured telephone call. If required or requested by the patient they also received evaluation by a gynecologist .

A total of nine women were included. In the same period in our hospital, 592 female patients were operated for a hernia or swelling in the groin giving an estimated incidence of 9/592 (1.5%). The mean age of women included in this study was 32.5 years (range 27–43 years) at the time of operation. All patients presented with a swelling in the groin (Table 1). Three patients presented with complaints of cyclical pain solely in the groin and one with cyclical pain in the lower abdomen radiating to the groin. Physical examination revealed a swelling in the right groin in seven patients, and in two on the left side. Time of complaints prior to surgery varied from 1 month up to 2 years. None of the patients had a history of pelvic endometriosis. In seven patients an ultrasound (US) of the groin was performed. In only one patient this was suggestive for endometriosis. In four patients an MRI was performed additionally to the US. None of the MRI’s offered the (dif- ferential) diagnosis of endometriosis. Preoperative imaging was suggestive for an inguinal hernia in three patients. Pre- operative diagnostic fna was performed in two patients. In one patient the cytology report showed endometriosis, for one patient fna was inconclusive. Peroperatively, an endometrial cyst was suspected in five patients. Four patients had an inguinal hernia. Three patients did not have an inguinal hernia with a hernia sac; however, a PPV was described or suspected. In two patients, there was no documentation of the operation and, therefore, no details of per-operative findings are known. Following the diagnosis endometriosis of the groin, only three of nine women were seen by a gynecologist for evalu- ation. One woman had complaints of dysmenorrhea and superficial dyspareunia. Diagnostic laparoscopy confirmed pelvic endometriosis according to the American Fertility Society classification (AFS) I–II. Others had no (known) history of endometriosis and no pelvic endometriosis was found. Five women were nulliparous, in two parity was unknown. At short-term follow-up, the remaining patients had no complaints related to the operation or a possible recurrence of disease. Telephone follow-up was attempted in all patients. Three women were lost to follow-up due to change of con- tact details and unknown current address. Follow-up of six patients, with an average of 6 years (range 2–9 year), revealed that none had recurrence of disease (i.e. inguinal endometriosis). Five patients had complaints of dysmenor - rhea, possibly related to endometriosis. These patients had not consulted a physician with these complaints. Nonethe- less, only one of these patients received follow-up and treat- ment for endometriosis and subfertility by a gynecologist. All patients contacted by telephone would appreciate follow- up by a gynecologist.

In this case series, we report nine women treated for an inguinal swelling containing inguinal endometriosis, of which six were successfully contacted for long-term follow- up. Our case series gives insight into relevant preoperative and postoperative aspects. Swelling in the right side of the female groin, in particular a painful swelling with cyclic symptoms related to menstrua- tion, must guide the diagnosis towards inguinal endometrio- sis. However, in many cases symptoms are not recognized as such, resulting in incorrect clinical preoperative diagnosis of other, more common, groin pathology such as inguinal or femoral hernia, lymph nodes, a cyst of Nuck or swellings arising from structures in the skin such as cysts and lipomas 883Hernia (2018) 22:881–886 1 3 [8]. Three out of nine cases were diagnosed preoperatively, which is consistent with reported numbers in literature of less than 50% [ 11]. This might be due to the uncommon location of the endometriosis, the non-cyclic pain pattern in a number of patients [4, 14, 15] or inconclusive results from imaging [5, 7, 8, 16–18]. In case of a swelling in the groin of unknown etiology, preoperative imaging might be helpful to identify underly - ing pathology. Nonetheless, surgery is often inevitable. In our series non-invasive imaging (ultrasound and MRI) had a very low sensitivity. The exact sensitivity of a MRI in ingui- nal endometriosis is unknown. Ultrasound can be helpful to roughly differentiate between inguinal hernia, enlarged lymph nodes and cyst/masses, but further classification of lesions is complex [19]. Although MRI is a helpful diag- nostic tool for pelvic endometriosis (sensitivity of 90% and specificity of 98%) [6 , 12], for extrapelvic endometriosis familiarity with the disease might be a more important factor for the correct diagnosis [19]. It is argued that once there is a suspicion for inguinal endometriosis, fna is an appropri- ate diagnostic test [12, 14]. Fna was conclusive in one out of two patients, a comparable result with previous studies in inguinal-, abdominal- or scar endometriosis [20, 21]. We do believe that when inguinal endometriosis is included in the differential diagnosis, an ultrasound is first choice for diagnostic purpose. If this is inconclusive and an inguinal hernia is excluded, fna could be a cost-effective workup to ascertain the diagnosis and rule out other significant disease. Table 1 Clinical characteristics of nine patients with inguinal endometriosis Characteristics pre- and postoperative and current status at follow-up US ultrasound, PA pathological anatomy, fna fine needle aspiration Patient age at diagnosis parity Year of surgery pri- mary/secondary side of the body Complaints Physical examination Preoperative diagnosis Follow-up 28 years Unknown 2011 Primary Right side Swelling and pain in the groin Reducible inguinal swelling US + MRI: hypointens anomaly, no inguinal hernia Seen by doctor: com- plaints of back pain with unknown etiology, no endometriosis found Cyclical pain around scar 36 years Nulliparous 2010 Primary Left side Swelling in groin and cyclical abdominal pain, radiating to the groin Reducible inguinal swelling 1–2 cm, valsalva+ US: hernia inguinalis or endometriosis Lost to follow-up 43 years Unknown 2013 Primary Right side Swelling in the groin Swelling in groin US + MRI: leiomyoma Not seen by doctor Numb feeling around scar Irregular menstrual cycle 27 years Nulliparous 2015 Primary Right side Swelling in the groin Swelling in groin US: atypical lymph node or sebaceous cyst fna: endometriosis Not seen by doctor No complaints 30 years Nulliparous 2008 Primary Right side Swelling and cyclical pain in the groin Swelling in groin Not mentioned Lost to follow-up 32 years Nulliparous 2010 Recurrent hernia Left side Swelling groin and cyclical abdominal pain Swelling in groin US + MRI: bursitis, cyst of Nuck, bursa or lymph node Seen by doctor: exten- sive follow-up with gynecologist Endometrioses grade 1–2, fertility problems 29 years Vaginal birth C-section 2010 Primary Rigth side Swelling in the groin Reducible inguinal/ medial swelling, valsalva + US: inguinal or medial hernia Lost to follow-up 36 years Unknown 2008 Primary Right side Swelling in the groin Swelling in groin US: cyst of Nuck Not seen by doctor Less complaints since gestation 32 years Unknown 2008 Primary Right side Swelling and cyclical pain in the groin Swelling in groin US + MRI: presumably incarcerated seba- ceous cyst in hernia inguinalis fna: inconclusive Not seen by doctor Mild complaints, irregu- lar cycle since 1 year 884 Hernia (2018) 22:881–886 1 3 Although an MRI could be considered indicated to identify groin pathology, in our series we do not deem an additional MRI of additive value to diagnose inguinal endometriosis. The exact etiology of endometriosis is not clear. Although retrograde menstruation can explain how endometrial gland cells are found outside the uterine cavity, this does not com- pletely explain why or how endometrium ends up in the groin and in other organs that are not in contact with the abdominal cavity. Two theories of embryological origin have been described, but none is proven. The first concerns the metaplasia of coelomic mesothelial cells and the second seeding via an open route (Hernia or PPV) into the groin. Both theories require a short explanation of the embryologi- cal development of the groin, which is complex. Epithelial cells of the uterus (endometrium) and the Fal- lopian tubes are formed in the embryo after differentiation of the epithelial cells of the Müllerian tube. These tubes are formed by invagination of mesothelial cells, forming the parietal peritoneum and covering the urogenital ridges. During the fetal period, the peritoneal cavity will extend in the inguinal canal along the gubernaculum, forming the round ligament and creating the processus vaginalis. The processus vaginalis runs from the abdominal cavity to the labium majus. Normally the processus vaginalis obliterates in the first year of life [6]. In both men and women there is a chance that this does not happen, leaving a PPV or remnants of the early peritoneal cells in the inguinal canal. These cells have the same embryological source as the endometrium cells covering the lumen of the uterus and, therefore, the cells of the (microscopic) processus vaginalis can give rise to endometrial cells by metaplasia. The second theory of inguinal endometriosis is based on the presence of the PPV [6 , 12, 22], creating a pathway for endometrial cells to seed through this canal. A PPV can be difficult to identify during surgery. It can be a very small defect, with a lumen only identifiable by microscope. A coexisting hernia sac has been found in several other stud- ies [5, 6, 23], and also in our series we found a hernia sac in three patients. In addition, in four others there was a fibrotic extension to the internal ring or a continuation of the struc- ture into the abdominal cavity (following the round liga - ment). These are all suggestive for a PPV. Both theories are rarely mentioned in previous reviews describing inguinal endometriosis [6, 12], but have been described in the etiol- ogy of mesothelial cyst adjacent to the round ligament [9 , 24–26]. Our series shows that in most cases (seven out of nine patients) the swelling is on the right side. This is in line with earlier reviews [3, 5, 6, 27]. The exact etiology for the right-sided preference is unknown but it is argued that the sigmoid has a preventive role in seeding on the left ingui- nal side [3 , 4, 18, 28]. Alternatively, it is hypothesized that as the right processus vaginalis in men obliterates later in childhood, this might be the same with the right processus vaginalis in women; however, this has not been proven. Furthermore, some studies plead for an asymmet- rical right-sided lymphatic drainage [4 , 5], explaining the favorable side of endometriosis in the right inguinal canal, but this has not been proven either. Primary treatment of inguinal endometriosis relies on complete surgical excision of the lesion to avoid sub- sequent recurrence [29]. In all patients in our series, open excision was performed and sufficient, as none of the patients had complaints of the groin after surgery at short-term and long-term follow-up. Although reports have shown that for some sites of inguinal endometriosis a laparoscopic excision is advisable, this should only be recommended in cases where an inguinal indirect hernia is present, making it possible to pull the lesion out of the inguinal canal. Mesh implantation might be indicated in case of large defects after surgical resection of the endo- metriosis and hernia sac; however, this was not consid- ered necessary in our cases. Per-operative inspection of the lesion remains most important, as complete excision has a preventive role in the recurrence of endometriosis. Also, in cases where the etiology is unknown there is a very small risk of a malignancy [30]. Secondary to excision, we recommend follow-up by a gynecologist. Inguinal endometriosis has been shown to be associated with pelvic endometriosis, although num - bers differ between various studies [ 3, 5, 6]. In our series, only one patient had mild endometriosis at laparoscopy, and others had no (known) history of endometriosis and negative results at physical examination. Intriguingly, five women were nulliparous, and two coped with subfertility, with several fertility treatments. Subfertility has been men- tioned in most studies on inguinal endometriosis [4 , 23], so women should be examined for pelvic endometriosis and be informed on future fertility perspectives. There are some limitations in this study. Due to its ret- rospective design, preoperative diagnostics were not stand- ardized which is of importance considering the interpreta- tion of the reported pain in our patients. The existence of preoperative symptoms, in particular cyclical pain, could be omitted in the charts for various reasons, such as insuf- ficient anamnesis or documentation, but also because of the absence of (cyclic) pain; it is a remarkable but well- documented phenomenon that in patients with endome- triosis symptoms are poorly related to the stage of the disease [31], and pain even can be absent. In addition, two operative charts were missing and follow-up could only be completed in six out of nine patients. Furthermore, due to the rarity very little is investigated thoroughly. 885Hernia (2018) 22:881–886 1 3

The presence of endometriosis should be considered in fer - tile women with a painful swelling in the groin. Surgeons should be aware of this rare diagnosis and pay attention to gynecological complaints. Gynecological evaluation should have an important role in the pre- and postopera- tive diagnosis. Compliance with ethical standards Conflict of interest NW declares no conflict of interest. NS declares no conflict of interest. KDJ declares no conflict of interest. PVK declares no conflict of interest. MS declares no conflict of interest. Ethical approval This article did not require ethical approval according to Dutch Law. Human and animal rights Human and/or animal rights were not vio- lated. Informed consent Patients were contacted by phone by the surgical team that had performed the operation. If contacted and included, informed consent was given by the participants during the phone call.

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