Age-dependent phenotypes of ovarian endometriomas

Abstract

Purpose: To analyze the characteristics of the ovarian endometrioma (OE) across the life span of a woman. In the past, the OE has traditionally been viewed as a single, monolithic disease. Today, there are emerging data indicating that OE phenotypes differ according to the age of the woman.

Method: A narrative review of original articles on OE indexed by PubMed.

Results: When appearing in infancy and early adolescence, OE may be the consequence of endometrial cells retrogradely shed with neonatal uterine bleeding. The post-menarcheal variant, manifesting itself during full adolescence, is singularly frequent in the presence of vaginal or uterine outflow obstructive anomalies. The typical and most frequent adult phenotype is characterized by increasing fibrosis and a tendency to progress; its mere presence exerts a detrimental effect on the surrounding healthy ovarian tissue. In postmenopause, an old lesion may be reactivated in the presence of exogenous or endogenous estrogens, or even be produced ex novo; rarely, it can spread to a variety of organs and structures and even degenerate causing malignancies.

Conclusions: Given the existence of these variants, it is important to agree on management guidelines that take into consideration these different phenotypes.

Keywords: adolescence; adulthood; neonatal uterine bleeding; ovarian endometrioma; postmenopause; premenarche.

FIGURE 1

Full section of the ovary of a 57‐year‐old woman with an endometrioma (left) and its schematic view (right). Adhesions are visible above the cavity; this is surrounded in succession by thickened invaginated cortex, U‐shaped medulla, and the remainder of the cortex. Below is the broad ligament. Reprinted with permission from Hughesdon

FIGURE 2

Natural history of endometriotic lesions (adapted from Ref.142). This diagram sketches, in broad strokes, the progression of endometriotic lesions, which interact with various mediators and players in their microenvironment, such as estrogen (E2), hypoxia, platelets, various immune cells, and sensory nerve fibers, through epithelial‐mesenchymal transition (EMT), endothelial‐mesenchymal transition (EndoMT), fibroblast‐to‐myofibroblast transdifferentiation (FMT), mesothelial‐mesenchymal transition (MMT), smooth muscle metaplasia (SMM), and type 2 immunity, leading ultimately to fibrosis. In addition, pain or infertility resulting from endometriosis may also induce stress, depression, and anxiety, resulting in the activation of the hypothalamic‐pituitary‐adrenal (HPA) and sympatho‐adreno‐medullary (SAM) axes, which, in turn, release copious amount of catecholamines. When these catecholamines reach the endometriotic lesions, adrenaline β2 receptor (ADRB2) would be activated, causing further progression of endometriosis. The progression of endometriosis would cause increased nerve fiber density within or surrounding the lesions (hyperinnervation) and as the fibrogenesis progresses, result in reduced vascular density and progesterone receptor (PR) expression, causing more pain and making lesions resistant to drug treatment. Note that all these players in the lesional microenvironment could engage in crosstalk through various mechanisms (the arrows). ADRB2, adrenaline β2 receptor; E2, estrogen; EMT, epithelial‐mesenchymal transition; EndoMT, endothelial‐mesenchymal transition; FMT, fibroblast‐to‐myofibroblast transdifferentiation; MMT, mesothelial‐mesenchymal transition; PR, progesterone receptor; SMM, smooth muscle metaplasia

FIGURE 3

Hydrolaparoscopic approach to the ovarian endometrioma. Transvaginal hydrolaparoscopy for reconstructive surgery of non‐fibrotic ovarian endometrioma up to 3 cm in diameter. (A) Disconnection of adhesions between ovary and pelvic side wall at the site of invagination; (B) Ovariolysis and exploration of what lies beneath the surface with sharp microscissors; (C) The “chocolate” content appears, clearly indicating the presence of an underlying endometrioma; (D) The endometrioma is further incised with the use of a bipolar needle to an opening of approximately 15 mm in diameter. Image taken after washing out the chocolate content; (E, F) Inside view, clearly showing the presence of red cobblestone‐like ectopic endometrium, well differentiated at pathology (red arrows) and concentrated mostly behind the site of invagination and retraction. With a 5‐Fr biopsy forceps, biopsies can easily be taken under direct visual control; (G) Endometriotic implants (blue arrows) inside the endometrioma superficially spread on a white background of inverted ovarian cortex; (H & I) End result of a conservative “minimally invasive” ablative surgery with a 5‐Fr bipolar probe or a 1000 fiber of a 15‐W diode laser under direct visual control, minimizing the damage to the cortex, that is, preserving ovarian reserve to a maximal extent. Reprinted with permission from Benagiano et al.

FIGURE 4

Assessment of ovarian endometriomas by ovarioscopy. (A) In younger women, the wall of the endometriotic cyst has the same marble‐white or yellowish appearance as the outer cortex and is lined by a thin highly vascularized mucosa. (B) By contrast, the lining of older cysts typically appears darker, fibrotic, and devascularised. Reprinted with permission from Brosens et al.

FIGURE 5

Appearance at positron emission tomography‐computed tomography (PET/CT) with [¹⁸F]‐fluorodeoxyglucose (FDG) of an abdominal mass found in a 69‐year‐old woman. The four images show a predominantly cystic mass arising from the pelvis. (A) Axial view. (B) Same axial image as appearing at fused FDG PET‐CT. (C) Fused sagittal FDG PET‐CT image. (D) Fused axial FDG PET‐CT image. Initially, a diagnosis was posed of a primary ovarian malignancy with ascites and diffuse peritoneal carcinomatosis. At surgery, however, a large tumor (25 cm in diameter) containing a solid area and chocolate‐like material was found. At histology, bilateral endometriomas were found, but no malignant cells. Peritoneal deposits consisted of a florid histiocytic reaction, with foreign body‐type giant cells and cholesterol clefts. Reprinted with permission from Agarwal Sharma et al.