Endometriosis is one of the most common benign gynecological pathologies, characterized by the presence of heterotopic endometrial mucosa outside the uterine cavity. The locations are multiple, most commonly affecting the pelvic structures (ovaries, recto-vaginal space, urinary tract, peritoneum), along with extra-pelvic structures, such as the surgical scars, and very rarely umbilicus, lungs, or brain ^[1].

The exact cause of endometriosis is still unknown. Multiple mechanisms were suggested. The presence of retrograde menstruation, and coelomic metaplasia represent the basic pathogenic theories of the disease, besides vascular or lymphatic dissemination, immunological abnormalities, and iatrogenic dissemination ^[2]. Retrograde menstruation is a common phenomenon among women in reproductive age and is the most acknowledged theory of endometriosis. It postulates that during menstruation, endometrial fragments reach de abdominal cavity trough reversed flow and implant into the abdominal and pelvic structures, proliferate and develop ectopic endometrial implants ^[3]. Celomic metaplasia theory stands that the cells from the peritoneum structure are related to the Müllerian ducts and under specific circumstances may develop intro endometrial cells ^[4] and may represent the mechanism of endometriosis in prepubertal girls ^[5]. The presence of endometrial cell outside the peritoneal cavity may be explained by the lymphatic dissemination theory, that postulates that the endometrial cells travel via lymphatic vessels and veins to the lungs or diaphragm ^[3]. Hormonal factors and altered immunological response may stimulate the transformation of normal peritoneal cells into endometrial cells ^[5]. Studies showed that the leukocytes are unable to recognize the abnormal locations of the endometrial cell and potentate the disease ^[3]. The disease may be different women of reproductive age than in prepubertal girls due to low estrogen levels before puberty. Endometriosis may be caused by defective embryogenesis. This theory is based on findings of ectopic endometrial tissue in female fetuses and sustains those embryonic cells of the Wolffian or Mullerian ducts may persist and develop into endometriotic tissue that respond to estrogens ^[5]. The risk factors associated with endometriosis include early menarche, short menstrual cycle, menorrhagia, nulliparity, late menopause, and other conditions involving increased ovulatory cycles. Parity, oral contraceptives, prolonged breastfeeding, tubal ligation, and hysterectomy represent protective factors ^[6].

Endometriosis mainly affects women during the reproductive period, having a substantial negative impact on patients’ quality of life through the accompanying symptoms such as infertility and pelvic pain ^[1]. The clinical aspect is characterized by a significant variability of signs and symptoms. However, the common symptoms are dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility ^[1]. Laparoscopic exploration and histopathological confirmation of suspect lesions represent, the gold standard in diagnosing endometriosis ^[1].

This disease is characterized by lesions that vary in appearance, size, and location. Macroscopically, ectopic endometrial foci may present as superficial “gunpowder burn” lesions on the ovaries or the visceral or parietal serosa. The lesions may be white, red, brown, or blue. They often appear as nodules or small cysts that contain old bleeding areas, surrounded by various degrees of fibrosis. Atypical or “subtle” lesions are common and may occur in the form of red implants (vesicular, polypoid, petechiae, hemorrhagic, “flame-like”) and transparent blisters ^[7]. In particular, wrese canarchers find endometrioma on the ovary, like a cyst with a fibrous wall and a semi-fluid or dense, chocolate-like content. The malignant degeneration should be ruled out when the cyst presents wall nodules or intraluminal polypoid projections ^[7]. Deep, nodular infiltrative endometriosis extends >5 mm in the retroperitoneum and may affect uterosacral ligaments, vagina, bladder, ureters, or intestines. The lesions can also take the form of mucous or serous polypoid masses that imitate a neoplastic lesion ^[7].

Histopathological examination remains the foundation for the definitive diagnosis of endometriosis. The standard histological stains, Hematoxylin-Eosin (HE) and Masson’s trichrome (MT), highlight the endometrial tissue. It can be abnormally found either at the level of the myometrium or outside the uterine cavity. However, there are exceptions, including atypical endometriosis, in which the use of immunohistochemistry is necessary to establish an unequivocal diagnosis ^[8]. Microscopically, the pathology is characterized by the same tissue architecture as the uterine endometrium. The lesions consist of glandular structures surrounded by stroma, along with areas of fibrosis, old or new hemorrhages, and macrophages loaded with hemosiderin ^[7].

In addition, cellular atypia of various grades may be discovered, granting a premalignant potential for these lesions ^[8]. Although it is a benign pathology, endometriosis has common characteristics with malignant processes. Hence, endometrial lesions can penetrate adjacent tissues (deep infiltrative endometriosis) and be associated with neoplasms’ evolution ^[7]. There is a robust association between ovarian cancer and endometriosis. Common genetic mutations were discovered at the origin of both pathologies. Therefore, endometriosis-associated ovarian cancers comprise a heterogeneous group of neoplasms with a frequently favorable prognosis, including clear cell carcinoma (CCC), endometrioid carcinoma (EC), and borderline seromucous tumors (TBSM), which develop concomitantly with the endometriotic process. The diagnosis of malignant lesions established in the absence of secondary neoplasms involve identifying the structure affected by endometriosis, the neoplastic process, and the benign–malignant transition on the tissue ^[8].

Endometrial implants may respond to hormonal changes depending on certain factors such as the amount of stroma surrounding the glands, the degree of vascularization, and the degree of fibrosis ^[8].

Summarizing, the microscopic investigation of endometriosis transformations represents a hot topic in the field, with significant applicability, especially for cases with atypical clinical and imaging features and possible malignant transformation.