Recent studies have confirmed that EM is associated with a variety of etiologies, including genetics, epigenetics, metabolomics, immunological stress, and inflammatory disease. [6,7,8,9,10]. Several studies on the etiologies of ME are as follows: (a) Genetics has been shown to play a role in the etiology of ME after long-term family studies. In a recently published review, it was proposed that the pathogenesis of EM may be linked to genes , with related genes including metabolic regulation and DNA repair, inflammation and immune response, steroidogenesis and sex hormone receptor activity, tissue remodeling and neoangiogenesis, among others; (b) Some researchers have speculated that EM might be an epigenetic disorder. Evidence has shown that EMs have a unique epigenetic expression profile . Additionally, DNA methylation, histone modifications, and microRNAs played a role in modulating endometriotic cell proliferation, invasion, and strain. ; (c) Metabolomics research may provide serological diagnostic indicators or new biomarkers for EM. In Murgia F’s study, 1H-NMR analysis of serum samples from patients with and without ME revealed a decrease in tryptophan, an increase in glutamine and β-hydroxybutyric acid, and alterations in glutamine and glutamate metabolism, pyrimidine metabolism, nitrogen metabolism, and aminyl-trna biosynthetic pathways in patients with ME ; (d) Lipopolysaccharide (LPS) has been considered a marker of altered intestinal permeability and microbial translocation substitution. (e) Vigano et al. detected significantly higher plasma LPS levels in patients with EM than in healthy groups . Loss of gastrointestinal barrier integrity may contribute to elevated plasma LPS concentrations. Impaired small intestinal permeability in patients with ME leads to increased LPS translocation and chronic low-grade inflammation; (f) The immune response appears to play a key role in the pathogenesis of ME and there is several scientific evidence that the immune response can be modulated by microorganisms. Interestingly, D’alterio’s examination revealed a significant increase in negative bacteria, such as Mycobacterium and Aspergillus, in patients with ME. The results suggested that there may be significant differences in the microbiome profiles of patients with and without ME. ; (g) Laganà AS and colleagues found a significant increase in the number of macrophages in patients with EM, which may give rise to an early pro-inflammatory microenvironment and late pro-fibrotic activity . Additionally, it has been suggested that leukocytes and peritoneal inflammatory mediators may contribute to the microenvironment in which EMs occur and develop. .
The pathogenesis of ME has been well studied, but the mechanism of lymph node metastasis is unknown. The two existing hypotheses include Müller’s system of secondary chemotaxis and the lymphatic circulation theory of endometrial tissue metastasis. A recent study demonstrated that the potential for lymphangiogenesis and the density of lymphatic vessels in ME patients are elevated. In addition, EM causes impaired lymph node immune response and insufficient clearance of endometrial cells, resulting in EM metastasis. . EM lymph node metastasis was first reported by Li Volsi et al. in 1974, with rare subsequent reports. In 1996, Insabato et al. reported 3 cases of intestinal ME lymph node metastases . The exact prevalence of lymph node metastases in ME remains unfathomable due to the lack of epidemiological studies.
This report presents the case of a perimenopausal woman who had an elevated CA125 and an enlarged para-aortic lymph node after hysterectomy with bilateral salpingectomy with preservation of both ovaries and was ultimately diagnosed with endometriosis in a para-aortic lymph node. aortic. There are three previous reports in the literature (Table 1). In 2011 Beavis et al. reported the first case of ME of the para-aortic lymph nodes of a pregnant woman . The patient was a 25-year-old multiparous pregnant woman with a history of chronic pelvic pain and ovarian cystectomies for bilateral endometriomas. At the age of 19. During pregnancy, she underwent pelvic MRI due to central placenta previa and subchorionic hemorrhage, which revealed a large complex adnexal mass measuring 10.3 × 8.5 × 5.0 cm with areas of cystic degeneration and possible blood products, as well as a 2 cm left obturator lymph. The patient then underwent a caesarean of the lower segment at age 26+2 weeks of gestation due to vaginal bleeding and lack of adequate response to administration of uterine tocolytics for fetal maturity. The right para-aortic lymph node measured 2.4 cm at its greatest dimension, and microscopy revealed lymphatic tissue composed of endometrial glands surrounded by a cuff of endometrial stroma with decidual changes. Two years later, Escobar et al.  reported a case of left adnexal complex mass with elevated serum CA125 and enlarged para-aortic lymph node. Intraoperative frozen sections and postoperative pathology confirmed endometrioma of the left ovary and an enlarged para-aortic lymph node involved in ME. Recently, Christebull et al.  reported a case of primary infertility caused by ME, with an abnormally high CA125 level and an enlarged para-aortic lymph node approximately 3 cm in diameter. Histopathological examination revealed endometrial components in a para-aortic lymph node. Since lymph node resection in ovarian and peritoneal ME is extremely rare, it is unclear whether there are lymph node metastases in ovarian and peritoneal ME. In the prospective study by Tempfer et al. , 26 patients suspected of ovarian and peritoneal ME were included, and intraoperative staining and dissection of the sentinel lymph node were performed. Of the 26 patients, 23 had postoperative histopathological confirmation of ME. Of the 19 sentinel lymph nodes successfully sampled, 2 (11%) had sentinel lymph node involvement of endometrial cells. Immunohistochemistry of the samples suggested an endometrial stromal origin, with the presence of endometrioid cells in the pelvic sentinel lymph nodes.
Evaluation for the possibility of pelvic endometriosis involves a combination of clinical symptoms and imaging studies of signs. However, the gold standard for diagnosing pelvic endometriosis is laparoscopic visualization of the pelvis. There are no specific indicators for the preoperative diagnosis of para-aortic lymph node ME. MRI has specific predictive value for ME, but its accuracy and sensitivity need to be confirmed by further studies. Diagnosis of ME with lymph node involvement has limitations and more clinical cases are needed to enrich physician experience to improve diagnostic accuracy with tissue sample histopathology and immunohistochemical staining. As research progresses and more studies of lymph node involvement in EM appear in the literature, some researchers have questioned the malignant potential of EM. . Two main relationships have been proposed to describe between ME and ovarian carcinoma: (1) the coexistence of the two due to common risk factors and their influence; and (2) progressive transformation of endometrial cells into tumor cells. Although EMs are not malignant, they share similarities with cancer, such as cell infiltration, unrestricted growth, neovascularization, and reduced apoptosis. . Clear cell carcinoma of the ovary is often associated with ME. Molecular pathways linked to ARID1A mutations have been published suggesting progression of EM to endometriosis-associated ovarian cancer . Prior to this, research showed that ARID1A expression decreased in vaginal-rectal MEs and involved the pelvic sentinel nodes. Suggesting that the decrease could be associated with the malignant transformation of EM . Notably, in another study, 11 (42.3%) of 26 patients with colorectal ME had lymph node involvement. In addition, lymphovascular infiltration was demonstrated by immunohistochemistry in 4 (36.3%) of the 11 patients with lymphatic involvement and in 2 (13.3%) of the 15 patients without. . However, in a study by Rossini et al. , 140 patients with deeply infiltrating EM (one group of 70 patients had EMS lymph node involvement and another group of 70 patients without) were included, and there were no statistically significant differences in bowel obstruction. , the depth of invasion in the gut, and rate of disease recurrence between the two groups; only preoperative plasma CA125 levels were different, leading to the conclusion that lymph node involvement in ME does not accelerate disease progression. Deeply infiltrating EMs are similar to low-grade malignant mesenchymal sarcomas, but unlike them, EMs do not cause death.
The goal of surgery is to remove as much endometriosis as possible, and when there is a high risk of lymph node involvement and/or recurrence, removal of visible lesions alone may not be warranted. Resection of all visible lesions associated with drugs seems less effective than extensive surgery in reducing the risk of recurrence . Therefore, further research is needed to determine the best treatment protocol.
It is known that the incidence of lymph node involvement in ME is relatively rare and that a medical history may be grounds for suspicion of the diagnosis. There are no established preoperative serum tumor markers of lymph node involvement in extrapelvic EMS, and imaging studies tend to suggest the presence of malignancy. Histopathology and immunohistochemistry played a crucial role in establishing a diagnosis in this patient. Our report supports the concept that EM has the potential to invade and metastasize to lymph nodes via lymphatic vessels.