1.       Introduction 

Endometriosis is a common, chronic, oestrogen-dependent disease affecting about 5-20 % of women of reproductive age [1]. It is defined as the presence of endometrium outside the uterine corpus [2,3] and usually affects organs such as ovaries (endometriomas), fallopian tubes, uterus, urinary bladder, rectosigmoideum, uterosacral ligaments, the pouch of Douglas, and peritoneum [4,5]. Intestinal involvement by endometriosis occurs in 3-37 % of patients. The lower rectosigmoid colon is most commonly involved (up to 73 % of cases), followed by the rectovaginal septum, terminal ileum, caecum, and the appendix [6]. Superficial intestinal disease in the form of serosal implants usually causes no symptoms, but bulky, deeply invasive disease can cause real problems. Spontaneous perforation of intestinal endometriosis is a very rare complication that occurs more frequently in pregnancy [7,8]. 

2.       Case Report 

4.1.              Case Presentation 

A 20-year-old female, gravida 0, para 0, was admitted to the surgical unit with acute and worsening anorexia, vomiting and abdominal pain that she has been complaining about for three months. The abdominal pain was mainly located at the right lower quadrant and right epigastrium. The patient also complained of dysmenorrhea however complete gynaecological ultrasound examination was unremarkable. Esophagogastroduodenoscopy (EGD), c-reactive protein (CRP) and white blood cells (WBC) remained within normal ranges. As no obvious etiology of her symptoms was identified, the patient was eventually referred for a psychiatric evaluation. Her symptoms persisted and she later underwent diagnostic laparoscopic evaluation. Endometriosis of the vesico-uterine pouch, right ovarian fossa, right sacrouterine ligament and Allen-Masters syndrome were identified (Figures 1A,B). The appendix, sigmoid colon and rectum did not show any signs of inflammation, infection nor other structural abnormalities. For classification of endometriosis, the revised American Society for Reproductive Medicine (rASRM) score (stage IV) was used. Two months later the patient underwent deperitonealization of the posterior compartment, bilateral ureterolysis and revision of the sacrouterine ligaments.

On the fourth postoperative day the patient was discharged home in a stable condition without complaints of hematochezia. On the eighth postoperative day the patient was presented to the hospital with cramping abdominal pain, rectal and vaginal bleeding. Ultrasound showed pelvic haematoma consistent with postoperative changes. CRP was 130 mg/l, WBC 16,500 and procalcitonin was negative. Computer tomography (CT) scan of the abdomen and pelvis confirmed haematoma in the pelvic cavity and the patient was found to have distended sigmoideum. Flexible sigmoidoscopy was unrevealing due to poor bowel preparation. Later, the patient clinically deteriorated with worsening leukocytosis, fevers and increasing abdominal pain suggesting acute abdomen and therefore underwent repeat laparoscopic evaluation. The findings included a pelvic abscess and secondary inflammation of the rectosigmoideum (Figures 1C,D). No evidence of bowel perforation was reported. Further deterioration of the patient’s clinical status and the development of sepsis and stercoral peritonitis required emergent exploratory laparotomy. A small perforation of the anterior rectal wall and acute pelviperitonitis was identified. Low anterior resection of the rectosigmoid colon with protective ileostomy was indicated. Three months later the patient underwent revision and reconstruction of the rectosigmoideum and is currently without symptoms. 

3.       Pathology 

Three separate specimens were evaluated at the department of pathology: rectosigmoid colon resection specimen, 18 cm in the length (1), colon resection rings (2) and appendix (3). Macroscopically, regressive and inflammatory changes including one 8 mm perforation were detected in the colon resection specimen. Overall 31 tissue sections were stained with hematoxylin-eosin and extensively investigated. Cardinal histologic finding represented discrete endometriotic lesions in the submucosa, muscular layer and serosa of the rectum associated with full thickness bowel wall necrosis and acute inflammation (Figures 2A,B). This finding was confirmed by using immunohistochemistry - both stromal and glandular immunopositivity for oestrogen and progesterone receptors (ER, PR) (Figure 2C), only stromal immunopositivity for CD10 (Figure 2D), only glandular immunopositivity for cytokeratin 7 (CK7) and stromal and glandular immunonegativity for cytokeratin 20 (CK20). The final diagnosis was of deep infiltrating endometriosis (DIE) of the rectum causing perforation and fibrinous-purulent peritonitis.

4.       Discussion

Intestinal endometriosis typically involves areas where the peritoneum is irregularly folded, such as the rectovaginal septum, rectum, and sigmoid colon [1,6]. Most cases occur during surgical intervention or is revealed incidentally by pathological examinations of tissues removed for other surgical indications [9].

The symptoms of gastrointestinal tract involvement by endometriosis are nonspecific and depend on the severity and location of the disease. Superficial intestinal endometriosis may be asymptomatic or cause cyclical spastic pain [10]. When endometriosis invades the bowel wall deeply, it causes a scarring and retraction and can form a mass lesion which partially obstructs the bowel wall [11]. In such cases symptoms include constipation, diarrhoea, melena, rectal bleeding, tenesmus and meteorism. Perforation of the colon by endometriosis is very rare. When searching the literature, a total 31 cases of bowel perforation due to intestinal endometriosis were found - 12 cases of perforation of the small bowel, 16 of the large bowel and 3 of the appendix. The first case report was published in 1931 by Haufler in a 30-year old women with jejunal perforation due to rupture of an endometriotic cyst during the sixth month of pregnancy [12]. Most recently, Marujo et al in 2017 described a case of transmural perforation of the rectum wall by the left fallopian tube in a patient with DIE. A 38-year-old women, nulliparous, with a history of primary infertility, complained of chronic pelvic pain, dysmenorrhea, dyspareunia, dyschezia and occasional rectal bleeding. On gynaecological examination a painful retrocervical nodule and elastic mass on the left adnexal area was revealed. Given the clinical suspicion of DIE the patient was initially treated with hormonal contraceptives. In magnetic resonance imaging (MRI) rectal endoluminal formation was described; a biopsy taken during colonoscopy revealed an inflammatory polyp of the colon. Consequently, as a result of symptoms and the presence of lesions compatible with DIE of the rectovaginal septum with probable intestinal infiltration, the patient was proposed for surgery. During adhesiolysis it was found that the rectum was pierced by the tube. Histological examination showed tubal endometriosis; involvement of the excised rectal segment by endometriosis was not described [13]. We have a few comments on this case. We disagree with the strategy that a conservative approach should be the first-choice treatment (in this clinical context). Currently, many papers approve a strategy of the complete removal of bulky deeply invasive disease by laparoscopy in trained centers followed by in vitro fertilization (IVF) in the case of sterility or hormonal treatment [14-18]. It is commonly accepted that the division on the deep and superficial endometriosis is an anachronism because endometriosis is a systemic disease, which in the form of DIE, does not show any respect to the organ borders, melting all concerned tissue in one bulk consisting of an active part of endometriosis, inflammatory tissue and hyalinisation respectivelly. Pathological findings of the resected specimens are therefore regionally heterogeneous and a large number of sections are required to determine the correct diagnosis. We would recommend a second-look histopathological examination of the resected rectal specimen focusing on the area of the perforation. In our opinion, piercing is a very dubious mechanism of the rectal penetration and we lack a competent commentary from the pathologist on this subject.

Our case is interesting from two points of view, clinical as well as pathological. Desinterpretation of abdominal symptomatology, initially treated by a psychiatrist and not surgically. Macroscopically, endometriosis involved the lesser pelvis, not the bowel, caused by inapparent lesions of inactive endometriosis and absence of fibrous adhesions within the lesser pelvis. Microscopically, discrete small lesions of endometriosis, in contrast with the cases of extensive transmural involvement that have been published to date, and absence of decidualized stromal cells. Spontaneous perforation of the rectum occurred after a simple surgical procedure - peritonectomy, without any manipulation with the bowel (e.g. rectal shaving) and with no use of coagulation devices, i.e. monopolar or bipolar.

The pathophysiology of bowel perforation secondary to endometriosis is not clear. Generally, two mechanisms are considered. Firstly, endometriosis involving the intestinal tract may weaken the bowel wall while, for one, the elasticity of the endometriotic tissue is impaired and causes a loss of elasticity and second, in the case of pregnancy, the whole endometriotic tissue is decidualised so that the elasticity of the tissue vanishes completely. Secondly, the intestine becomes a part of a convolute consisting of the uterus, adnexa and fibrous tissue (frozen pelvis) and is under tension of adhesions secondary to peristalsis. Both of these phenomenona together may compromise the intestinal wall integrity and result in perforation, especially during pregnancy [11].

Intestinal endometriosis is difficult to diagnose because of the lack of characteristic symptoms. In the paper published in 2007, FU et al. recommend that intestinal endometriosis should be considered when a reproductive woman who had a history of pelvic endometriosis developed a cyclical bowel discomfort [10]. Diagnostic laparoscopy is suggested in the case of chronic nonspecific abdominal pain. In the case of asymptomatic superficial intestinal endometriosis, we recommend, in accordance with some authors, follow-up without any treatment. Resection of the involved bowel segment remains the treatment of choice for patients with intestinal endometriosis since the effect of gonadotropin-releasing hormone (GnRH) analogs and progestin is limited; also for patiens with symptoms of obstruction or bleeding, and if malignancy cannot be excluded [7,18-20].

The peritoneal implantation of endometrium by retrograde menstruation, vascular dissemination or the possible metaplasia of peritoneal cells are still the most accepted etiological theories of endometriosis. Intestinal endometriosis may be found in all the layers of the bowel wall, but predominantly involves the extra mucosal layers. Most endometriomas are ill-defined serosal and subserosal nodules that are rarely larger than 5 cm. On the cut surface, the spectrum of colors is quite broad, ranging from black through brown to red and white [21]. Microscopically, they consist of endometrioid glands and stroma that are often accompanied by fibrosis in the adjacent bowel wall. Sometimes only endometrioid-type stroma, including a variety of changes such as decidua, pseudodecidua, smooth-muscle metaplasia, fibroblastic metaplasia and sarcoma, are present. Such lesions are referred to as stromal endometriosis and are thought to be most likely due to limited sampling [22]. In these cases a broad differential diagnosis must be considered including gastrointestinal stromal tumor and benign nerve sheath tumor [23].

From a histopathological point of view, it is necessary to differentiate between colorectal adenocarcinoma and endometriosis. Chen et al. in 2015 described a case report of a 39-year-old women with rectal mucosal endometriosis primarily misinterpreted as adenocarcinoma. Initial colonoscopy showed a rectal mass with ulceration and circum wall involvement. A combination of all the histological features (irregular glands with mucin depletion, nuclear stratification, subtile subnuclear vacuoles and spindle cells with abundant pink cytoplasm and unclear boundary in the stroma), was subjectively interpreted as dysplastic glands in desmoplastic setting with primary rectal adenocarcinoma being raised first. Subsequently, immunohistochemical examination with positivity for CK7, ER and CD10 identified the essence of ectopic endometrium [24]. As shown in this case, the distinction between adenocarcinoma and endometriosis can be particularly challenging in mucosal biopsy specimens, mostly due to the limited amount of tissue present, misinterpreting of the reactice glandular changes and, because the endometrial tubules tend to be separated from their stroma, secondary to trauma from the biopsy procedure [23,25]. Routine light microscopy is usually sufficient to make the correct diagnosis. Malignancy is excluded by lack of significant cellular atypia, low mitotic activity and an absence of a desmoplastic stromal reaction. Diagnosis of colonic endometriosis can be confirmed by using immunohistochemistry. In this context, we have recently described, as a first, a case of pelvic lymph node endometriosis with aberrant immunophenotype with complete loss of oestrogen and progesterone receptor expression of endometrioid glands mimicking metastasis of adenocarcinoma [26]. Thus, it is important to keep in mind that final interpretation must always be carried out within the context of the morphological findings.

Laparoscopy and laparotomy often considered as the gold standard for diagnosing pelvic endometriosis may be insufficient in the case of inactive endometriosis. As in the paper published in 2014 by Galazis et al., no active endometriosis of the bowell wall was seen during laparoscopy and laparotomy [27]. Definitive diagnosis is thus reached only by the histological examination. In our case, initially, we found only regressive and inflammatory changes including one perforation of the bowell wall. Due to unclear pathogenesis of these changes, we submitted another 15 sections of the resected colon. Then we found endometriotic lesions in the submucosa, muscular layer and subserosa of the bowel wall in 3 hematoxylin and eosin stained slides. Generally, in a non-neoplastic bowel resection specimen, it is necessary to submit representative sections of the proximal and distal margins and any focal lesions. We also recommend to sample all areas of the bowel by submitting sections at regular 5-cm intervals. Therefore extensive examination of the resection specimen is essential for proper diagnosis.

5.       Conclusion

Intestinal endometriosis should be considered in the differential diagnosis of any gastrointestinal or abdominal symptoms of every women. It is difficult to diagnose and may mimic other disease, including neoplasm. Simultaneous gynaecological symptoms increase the risk of intestinal involvement by endometriosis and diagnostic laparoscopy should be considered. The patients should be closely followed up after the operation.

We also want to emphasize the need for extensive pathological examination of the resected specimens which is essential for a proper diagnosis. This report is believed to be the first case of spontaneous rectal perforation secondary to endometriosis in non-pregnant women.

Figures 1(A-D): Intraoperative laparoscopic images. A, B: Initial diagnostic laparoscopy showing endometriosis of the lesser pelvis – vesico-uterine pouch, right ovarian fossa, right sacrouterine ligament, Allen Masters syndrome. C, D: Laparoscopic revision of the abdominal cavity on the 8th postoperative day - pelvic haematoma and rectosigmoiditis.

Figures 2(A-D): Intestinal endometriosis, immunohistochemical expression of oestrogen receptors and CD10 in intestinal endometriosis. A, B: Discrete endometriotic lesion and florid regressive and inflammatory changes in the subserosa of the bowel wall (hematoxylin-eosin staining, original magnification x100, x200). C: Oestrogen receptors stain both endometrial gland and endometrial stromal cells (immunohistochemistry, original magnification x200). D: CD10 stains a few endometrial stromal cells adjacent to the gland in the muscular layer of the bowel wall, confirming the diagnosis of intestinal endometriosis (immunohistochemistry, original magnification x200).

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