Endometrioid adenofibroma of ovary - a literature review.

A 27-year-old female patient, with an unremarkable medical history, was admitted with a left ovarian cyst, diagnosed through ultrasound and magnetic resonance imaging (MRI). She had undergone hormone therapy, but without any improvement. On the abdominal examination, tenderness was noted in the left lower abdominal quadrant, though there were no signs of peritoneal irritation. Her menstrual cycles were regular, and she reported no abnormal vaginal discharge or pain during sexual intercourse. Upon admission, the patient’s general condition was stable, with no cardiorespiratory issues and no abnormalities detected during the rectal examination. The serum tumor marker results were as follows: carcinoembryonic antigen (CEA) at 1.10 μg/mL, a slightly elevated risk of ovarian malignancy algorithm (ROMA) score, and carbohydrate antigen 125 (CA 125) at 5.91 μg/mL. Pelvic MRI revealed a 6 cm cystic mass with mixed content and a small amount of peritoneal fluid, with no other pathological findings. The human papillomavirus (HPV) genotyping test returned negative. Based on these results, the patient underwent a laparoscopic left adnexectomy. Intraoperatively, a 6×4 cm ovarian tumor was identified, adhered to the pelvic region with some adhesions. The tumor was soft and slightly friable (Figure 1A , 1B ; Figure 2A , 2B ). A laparoscopic left ovariectomy was successfully performed. The patient completed the prescribed antibiotic course and was discharged without complications three days post-surgery. (A and B) Ovarian cyst confined within pelvic adhesions, resulting in the cyst being adhered to surrounding structures, making its removal more complex (A and B) Intraoperative visualization of an endometrioid adenofibroma cyst, characterized by its cystic structure and dense fibrous component, consistent with its typical histological presentation The macroscopic examination revealed a tumor measuring 5×4×3 cm with a smooth cystic wall and a gray-brown color. Upon sectioning, a 0.4 cm cystic area was observed, containing brown, creamy content. Pathological evaluation revealed ovarian parenchyma with the presence of an epithelial tumor proliferation composed of glandular structures with irregular contours, lined by endometrioid-like epithelium (Figures 3 , 4 ). In the epithelium, we distinguished low to moderate nuclear atypia, epithelial stratification (Figure 4 ), rare mitotic figures, and absence of necrosis. Focally, areas of crowded fusing glands as well as the presence of squamous morules (Figures 3 , 4 ) were noticed. Regarding the tumoral stroma there was a diffuse fibrous aspect (Figure 5 ), with no evidence of destructive stromal invasion. The performed immunohistochemical (IHC) tests showed: Wilms tumor protein 1 (WT1) negative in tumor cells, cluster of differentiation 10 (CD10) zonally positive in tumor cells, estrogen receptor (ER) positive in tumor cells (Figure 6 ), Ki67 focally positive up to 30% in tumor cells (Figure 7 ), p53 wild-type nuclear immunomarking in tumor cells, cytokeratin 7 (CK7) positive in tumor cells (Figure 8 ). Ovarian parenchyma. Epithelial tumor proliferation with irregular glandular structures (black arrow) and squamous morules (black asterisk). Hematoxylin–Eosin (HE) staining, ×100 Ovarian parenchyma. Epithelial tumor proliferation glandular structures lined by endometrioid-like epithelium with stratification and low-grade atypia (black arrow) and squamous morules (black asterisk). HE staining, ×200 Ovarian parenchyma. Fibrous stroma (black circle) of the epithelial tumor proliferation. HE staining, ×400 The tumor cells tested positive for estrogen receptors (ERs). Anti-ER antibody immunomarking, ×400 Ki67 showed focal positivity in up to 30% of the tumor cells. Anti-Ki67 antibody immunomarking, ×400 The tumor cells were positive for cytokeratin 7 (CK7). Anti-CK7 antibody immunomarking, ×400 The IHC tests correlated with the histological aspect advocate for borderline endometrioid tumor, associated ovarian adenofibroma, on the examined fragment. The patient was monitored for three years with MRI, during which no local recurrence or metastasis of the tumor was observed.

Age significantly influences the onset and progression of ovarian cancer. The majority of ovarian neoplasm cases are diagnosed postmenopausally, with a notably higher incidence observed in women over the age of 65 [ 9 ]. The relationship between age and the onset of ovarian cancer is multifaceted and not fully elucidated; however, studies consistently indicate that older patients generally experience a poorer prognosis and reduced survival rates compared to their younger counterparts [ 10 , 11 ]. The average age at diagnosis is typically between 50 and 79 years, depending on various factors, including subtype and clinical presentation [ 12 ]. Additionally, the early onset of menarche and menopause has not been shown to significantly affect the development of ovarian cancer lesions, according to most studies [ 12 ]. Although age is a critical determinant of prognosis, its impact may differ based on the histological subtype. High-grade serous carcinomas (HGSCs) are more frequently observed in older women, whereas other subtypes, such as germ cell tumors (GCTs), tend to be more prevalent in younger patients. In their study, Tung et al. propose that non-mucinous tumors are frequently associated with menstrual periods and ovulatory cycles, while other research has highlighted an inverse correlation between ovarian neoplasms and ovulatory cycles [ 13 , 14 , 15 ]. One study found that women who had not ovulated for an average of 8.7 years experienced a fourfold reduction in their risk of ovarian cancer, supporting the “incessant ovulation” theory [ 16 ]. According to this theory, continuous ovulatory cycles cause damage to the ovarian epithelium, leading to the development of cancerous lesions. Consequently, any factor that reduces the frequency of ovulatory cycles is considered a protective factor [ 17 ]. Nevertheless, Moorman et al. suggest that anovulatory states, such as those associated with pregnancy or the use of contraceptives, may contribute to an elevated risk of ovarian cancer development [ 18 ]. In their study, Ness et al. suggests that ovarian inflammation associated with pelvic inflammatory diseases contributes to the development of ovarian neoplasms [ 19 ], a finding supported by Jia et al., who argues that ovarian reparative damage and ovulation are critical factors in triggering ovarian cancer [ 20 ]. While Ness et al. have raised the possibility that genital infection with Chlamydia trachomatis may contribute to ovarian cancer lesions, Merritt’s study does not find a connection between this pathogen and ovarian cancer. Sampson’s study suggests that malignant ovarian lesions may result from the malignant transformation of endometriosis [ 21 ], while other research also highlights endometrial aging as a potential factor in the etiology of this pathology [ 22 ]. Ovarian cancer associated with endometriosis is typically diagnosed at a younger age and at an earlier stage [ 21 ]. However, Stewart et al. concluded that women with endometriosis have a three-fold increased risk of developing ovarian cancer [ 23 ]. According to the literature, tubal ligation is associated with a protective effect against ovarian cancer, leading to a 20% reduction in the incidence of invasive serous carcinoma, 32% for mucinous carcinoma, 42% for clear cell carcinoma, and 52% for endometrioid carcinoma (EC) [ 24 , 25 ]. The use of contraceptives, especially oral contraceptives, has been shown to reduce the risk of developing any type of ovarian cancer [ 12 ]. This protective effect is believed to result from ovulation suppression, which reduces ovarian epithelial damage. Long-term contraceptive use has been shown to lower incidence rates, with some studies indicating a lasting protective effect even after discontinuation. In contrast, ovulation-inducing medications, such as human menopausal gonadotropin (hMG), have been associated with ovarian damage and an increased risk of ovarian cancer [ 26 , 27 ]. These drugs stimulate multiple ovulations, potentially causing repeated trauma to the ovarian epithelium, thereby heightening the likelihood of neoplasm development. This risk is particularly pronounced in women undergoing prolonged fertility treatments. Furthermore, studies suggest that these medications may impact ovarian reserve and long-term ovarian health, although the overall risk remains an area of ongoing investigation. Mutations in tumor suppressor genes, particularly breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2), are commonly observed in ovarian tumors, with a risk of ovarian cancer rising to 10% by age 50 [ 14 , 28 , 29 ]. Inherited ovarian cancer accounts for 10–15% of cases associated with Lynch syndrome, which increases the risk of several cancers, including ovarian cancer. Non-mucinous types, particularly HGSCs, are most commonly observed in these patients and tend to be more aggressive [ 30 , 31 ]. Inherited ovarian cancer accounts for 10–15% of cases linked to Lynch syndrome, which is caused by mutations in mismatch repair (MMR) genes and increases the risk of multiple cancers, including ovarian, colorectal, endometrial, and gastric cancer. In Lynch syndrome patients, the lifetime risk of ovarian cancer is 6–8%, with HGSC being the most common and aggressive non-mucinous type [ 30 , 31 , 32 ]. One of the notable aspects of ovarian cancer associated with Lynch syndrome is that it is often diagnosed at earlier stages, with 82–84% of cases being identified in the early stages [ 30 ]. This early detection may be due to increased surveillance and genetic testing for individuals with Lynch syndrome. Despite the early diagnosis, the prognosis remains dependent on various factors, including the tumor grade, molecular characteristics, and treatment response. Studies in the literature suggest that daily fish consumption and excess cholesterol intake may elevate the risk of malignant ovarian lesions [ 33 , 34 ]. High cholesterol levels, especially from animal fats, are linked to inflammation and oxidative stress, which may promote tumorigenesis. Conversely, the consumption of milk, vegetables, vitamins, and beta-carotene offers protective effects against ovarian cancer due to their antioxidant, anti-inflammatory, and nutrient-rich properties that support ovarian health [ 35 ]. Diets high in saturated fats and low in fruits and vegetables may increase the risk of ovarian cancer by disrupting hormonal balance and immune function. Conversely, plant-based diets rich in antioxidants can boost immune response and reduce cancer risk, highlighting the role of balanced nutrition in prevention.

Ovarian neoplasms represent the third most prevalent gynecological malignancy globally, following cervical and endometrial cancers, and are associated with the poorest prognosis among female cancers. Epidemiological projections suggest a marked increase in ovarian cancer-related mortality by 2040 [ 1 , 2 ]. This unfavorable outlook is largely attributed to the frequent diagnosis at advanced stages, resulting from asymptomatic progression or the late onset of nonspecific symptoms. Furthermore, the absence of an effective population-wide screening strategy continues to hinder early detection and improved survival rates [ 1 ]. Histologically, ovarian tumors encompass a wide spectrum, with epithelial neoplasms being the most common, displaying significant heterogeneity in differentiation and biological behavior. Epidemiological data indicate that ovarian cancer incidence is highest among non-Hispanic white women, with 12 cases per 100 000 population. Hispanic women have an incidence rate of 10.3 per 100 000, whereas non-Hispanic Black women and Asian women exhibit lower rates of 9.4 and 9.2 per 100 000, respectively [ 3 ]. These disparities suggest the potential involvement of genetic, environmental, and socioeconomic factors in disease prevalence, warranting further investigation into population-specific risk profiles and access to early detection strategies. In 2022, there were 324 603 newly diagnosed cases of ovarian neoplasms worldwide [ 4 ]. The World Health Organization (WHO) reports over 250 000 ovarian cancer-related deaths annually [ 5 ]. Ovarian tumors can originate from epithelial, stromal, or germ cell tissues, with recent studies suggesting that the fallopian tube epithelium may be the primary source of high-grade serous ovarian carcinoma [ 6 , 7 ]. The clinical manifestations of ovarian neoplasms are often nonspecific, which complicates early diagnosis. The most commonly reported symptoms include abdominal pain (22%), which is often vague and may be mistaken for other conditions; the presence of lower abdominal masses (64%), which can sometimes be detected through physical examination or imaging; bloating (77%), commonly associated with gastrointestinal (GI) disturbances and often overlooked; GI symptoms such as altered intestinal transit (24%), which can mimic other digestive disorders; lumbar pain (45%), potentially radiating from pelvic or abdominal structures; and urinary issues (16–34%), including frequency or urgency, which may be attributed to other urological conditions [ 8 ]. Ovarian neoplasms include several histological subtypes, each with a unique pathogenesis and clinical presentation, further complicating early diagnosis. Understanding these variations is crucial for improving diagnostic accuracy and enhancing early intervention strategies [ 4 ].

EAs are rare benign tumors, representing only 1% of ovarian epithelial neoplasms, with 83% of cases occurring unilaterally [ 47 ]. In 90% of cases, these adenofibromas originate from the endometrium and cervical mucosa, while the remaining 10% arise from other regions of the uterus. Ovarian adenofibromas are exceptionally rare, with their occurrence in the ovary being even more uncommon [ 56 , 57 ]. Clinically, the expression of EA is non-specific, and clear symptoms are often absent. However, patients may experience abdominal pain in the hypogastrium, which can be either chronic or acute, typically due to torsion or intracystic/pericystic bleeding. Vaginal bleeding is rare, and when present, it can be intermittent or mild, which complicates the diagnostic process. In some cases, the tumor may be discovered incidentally during imaging for other conditions. On macroscopic examination, the EA can appear as either a solid or cystic mass, with a smooth cystic surface and a well-defined wall, often showing signs of fibrous tissue. The presence of fibrous components may also contribute to its differential diagnosis from other ovarian masses. Microscopically, adenofibroma is characterized by a fibrous stroma, in which tubular and cystic endometrioid glands of varying sizes are dispersed. These glands are lined with glandular epithelium, consisting of low cuboidal and columnar cells, along with areas of hyperplastic epithelium. The fibrous interstitium often shows a dense arrangement, and the cystic spaces may contain mucin or other secretory products. In certain cases, the glands display a distinctive branching pattern, which helps differentiate them from other ovarian neoplasms. The overall histological appearance reflects the benign nature of the tumor, although its cellular composition may vary in different areas. On MRI, the solid component of the tumor is identified by a distinct low T2 signal, which is significantly lower than that of muscle tissue [ 47 ]. Endometrioid tumors in the ovary share similarities with those observed in the uterine body, and several case reports have documented the presence of endometriosis within the EAs. The origin of these tumors is believed to be ovarian endometriosis, and they are more commonly located within the ovary itself rather than in paraovarian tissue. These tumors may display a range of radiological characteristics, which vary based on their size, cystic components, and the extent of solid tissue present. In some cases, associated hemorrhage or necrosis within the cystic areas may complicate the imaging appearance, making diagnosis challenging. Serous cystadenoma is the most prevalent type of ovarian tumor, and its differential diagnosis often includes EA [ 58 , 59 , 60 ]. Although both tumors may display ciliated epithelium and elongated papillary tubular glandular structures typical of serous gonadal fibromas, several crucial differences can help distinguish them. The absence of multiple cysts, combined with a more solid structure and the presence of specific glandular formations, points to endometrioid differentiation. EAs typically show a denser fibrous stroma and less cystic degeneration than serous cystadenomas, aiding in diagnosis [ 61 , 62 ]. In the HP differential diagnosis, distinguishing between ovarian EA and endometrioid adenocarcinoma is essential, as the latter is characterized by cytological atypia, mitotic activity, and invasive stromal infiltration. Adenofibromas, on the other hand, present a benign glandular architecture without invasion and are embedded in a dense fibrous stroma. Differentiation from granulosa cell tumors is also important, as these tumors can mimic adenofibromas due to their cystic-solid appearance. However, granulosa cell tumors often demonstrate characteristic Call–Exner bodies, nuclear grooves, and may secrete hormones, which are absent in adenofibromas. Imaging may reveal multilocular cystic lesions with intracystic hemorrhage and a ‘spongy’ appearance, but definitive diagnosis relies on immunohistochemistry and detailed histological evaluation [ 62 , 63 ]. Surgical intervention is the primary treatment option for EA, most often performed as a unilateral adnexectomy or localized tumor excision, especially in young patients where fertility preservation is a key consideration. Recurrence is rare following complete resection, but regular follow-up with imaging and clinical evaluation is recommended to monitor for potential relapse or development of associated endometrial pathology. EA is an epithelial ovarian tumor of uncertain incidence, typically lacking specific clinical symptoms and posing significant challenges for both preoperative and intraoperative diagnosis. However, definitive identification is achieved through IHC analysis [ 47 ]. The detection of a well-circumscribed, cystic, and heterogeneous pelvic mass on imaging may raise suspicion for an adenofibroma; however, a definitive diagnosis can only be established through comprehensive HP and IHC evaluation. Given the diagnostic challenges posed by its nonspecific clinical and radiological presentation, further advancement in clinical awareness and academic understanding of this rare tumor is essential for accurate identification and appropriate therapeutic decision-making. Predictive factors for recurrence include intraoperative tumor rupture and the presence of positive surgical margins identified on HP analysis, emphasizing the critical role of thorough pathological assessment [ 63 , 64 ]. Numerous studies highlight the importance of a second-look procedure, particularly in cases where the initial HP evaluation indicates a benign lesion, but subsequent IHC analysis reveals a BOT. BOTs metastasize to the omentum in approximately 39% of cases, and around 9% are associated with invasive peritoneal implants. In situations where the peritoneal cavity and surfaces were not thoroughly evaluated during the initial surgical procedure, a comprehensive secondary assessment is strongly recommended to ensure accurate staging and to guide appropriate management strategies [ 65 ]. Tumor recurrence is more commonly observed following conservative surgical approaches aimed at preserving fertility; however, such recurrences do not impact overall survival rates. BOTs are generally associated with a favorable prognosis [ 55 ]. Literature studies indicate that 50% of patients diagnosed with BOTs were able to achieve natural pregnancies, while 35% experienced infertility prior to surgery. However, postoperative peritoneal adhesions may develop, leading to infertility. Additionally, ovarian stimulation, commonly used in the medical treatment of infertility, has been associated with an increased likelihood of developing borderline tumors [ 66 , 67 ]. When BOTs recur following conservative surgery aimed at preserving fertility, a second-look surgery is recommended. If the patient no longer desires future pregnancies, bilateral adnexectomy is advised. For lesions located outside the ovary, cytoreductive surgery is recommended. The presence of residual tumors is a significant prognostic factor, with studies showing that favorable postoperative outcomes result in a decrease in mortality to 12%, compared to a 60% mortality rate in cases without favorable evolution following cytoreduction [ 68 , 69 ]. Histologically, EBTs are characterized by stromal invasion and the proliferation of confluent glands, typically not exceeding 5 mm in depth. These tumors are associated with an excellent prognosis, as they are generally confined to a single ovary, with metastases and recurrences occurring infrequently [ 69 , 70 , 71 ]. Some studies have suggested that fertility medications used in young women may elevate the risk of developing borderline tumors. However, due to short follow-up periods, limited sample sizes, and methodological limitations, these studies have not provided definitive conclusions. A Dutch study, however, found that the incidence of borderline tumors was twice as high in patients with a history of in vitro fertilization [ 72 ]. Fauvet et al. suggest that conservative surgical intervention aimed at preserving fertility should only be considered for patients under 40 years old and those with FIGO stage I tumors, as women over 40 typically do not achieve successful pregnancies [ 73 , 74 ]. Borderline tumors have low proliferation rates, are chemotherapy-resistant, and lack sufficient evidence for Tamoxifen efficacy, making it an unsuitable treatment [ 49 ]. This study is significant as it offers key insights into the diagnosis, treatment, and prognosis of EBOTs. It highlights the diagnostic challenges posed by these rare tumors, which often present non-specific symptoms, and stresses the importance of immunohistochemistry in confirming the diagnosis. The study also highlights the importance of careful surgical intervention and follow-up to prevent recurrence and manage fertility concerns, particularly in younger patients. Furthermore, it sheds light on the potential risks of fertility treatments and the role of conservative surgical options in preserving fertility while ensuring favorable long-term outcomes. The diagnosis of ovarian tumor disease triggers in more than half of cases depressive disorders accompanied by marked anxiety and the strange feeling of loss of sexual identity or the right to become a mother. Depression is associated with a significant increase in proinflammatory mechanisms, mechanisms that can precipitate rapid evolution of the ovarian tumor. Constantly high or continuously rising values of inflammatory markers [C-reactive protein (CRP)] may indicate evolutionary risks as well as the opportunity to use anti-inflammatory substances with “antidepressant-like effects” in the drug treatment of depression [ 74 ]. The persistence of proinflammatory markers at high values, the decrease in cerebral neuroprotection factors [brain-derived neurotrophic factor (BDNF)] and the appearance of suicidal ideation, especially in the context of unfavorable evolution of the tumor disease, may indicate suicidal risk [ 75 ].

Immunohistochemistry is essential for the accurate diagnosis of EBOTs due to non-specific symptoms and imaging findings. Conservative surgery, like unilateral adnexectomy, is effective, particularly for fertility preservation, with low recurrence rates. Postoperative adhesions may cause infertility, highlighting the need for careful follow-up in fertility-preserving cases. BOTs have a favorable prognosis, with recurrence and metastasis being rare, though certain factors can increase recurrence risk.

The authors declare that there is no conflict of interests.

Epithelial tumors constitute approximately 90% of ovarian cancer cases, with HGSC representing the most prevalent subtype, associated with the highest morbidity and mortality rates [ 34 , 36 ]. For many years, it was believed that these tumors originated from the ovarian surface epithelium; however, recent studies have shown that their origin is actually in the fallopian tubes, with a strong association to BRCA1 and BRCA2 mutations [ 17 , 37 ]. These mutations, which impair deoxyribonucleic acid (DNA) repair mechanisms, significantly increase the risk of developing HGSC, and individuals with BRCA mutations are at a much higher risk of ovarian and breast cancers. The discovery of the fallopian tube origin has led to a reevaluation of ovarian cancer prevention strategies. Prophylactic salpingectomy (removal of the fallopian tubes) is being explored as a potential preventive measure, especially in high-risk women with BRCA mutations. This has sparked new research into early detection and prevention of ovarian cancer, with a growing focus on molecular screening and genetic counseling. The understanding of the fallopian tube as the origin of these cancers has also opened new avenues for exploring biomarkers and treatment strategies that specifically target the molecular pathways involved in tumor development. Low-grade serous carcinoma is an infrequent variant of epithelial ovarian cancer typically diagnosed at a young age. It arises from benign tumor precursors and is characterized by slow progression and prolonged survival in contrast to HGSC [ 20 , 21 ]. Clear cell ovarian carcinoma, also a rare tumor, is often associated with endometrioid tumors and is more commonly found in the younger Asian population. It is typically diagnosed at an early stage but tends to be chemoresistant. This type of carcinoma is frequently linked to mutations in the AT-rich interaction domain 1A (ARID1A) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) genes [ 33 , 34 ]. Mucinous ovarian carcinoma (MOC) is an uncommon ovarian neoplasm, typically presenting as a large unilateral tumor mass filled with significant amounts of mucin. Due to its distinctive features, it is essential to differentiate this type of carcinoma from metastatic ovarian tumors, which may present similar clinical and imaging findings [ 37 , 38 ]. MOC often presents in younger women and can exhibit a relatively indolent course compared to other subtypes. However, it is known for its potential to metastasize to distant organs, complicating its diagnosis and treatment. One of the challenges in diagnosing MOC lies in its histological similarity to metastases from other GI tumors, such as those originating from the colon or appendix. Therefore, a thorough clinical workup, including imaging studies and pathological examination, is crucial for accurate diagnosis. Additionally, MOC is often associated with genetic mutations, including those related to the Kirsten rat sarcoma viral oncogene homolog (KRAS) and tumor protein p53 (TP53) genes, which may influence treatment decisions and prognosis. Sex cord stromal tumors (SCSTs) are infrequent ovarian neoplasms, representing approximately 7% of all ovarian cancer cases. They originate from stromal and primitive cells of the sexual cords and are classified into various subtypes, each distinguished by different histological characteristics [ 39 , 40 ]. These tumors encompass granulosa cell tumors, Sertoli–Leydig cell tumors, and fibromas, among others, and are frequently linked to specific clinical characteristics depending on their subtype. Although SCSTs generally exhibit a favorable prognosis, they are known to have the potential for recurrence, particularly if not detected early or if they are of a more aggressive subtype. Additionally, some of these tumors can secrete hormones, leading to the development of endocrine syndromes, such as precocious puberty, virilization, or postmenopausal bleeding, depending on the type of hormones produced. Hormone secretion can also complicate the clinical picture and make diagnosis more challenging. Despite their relatively favorable prognosis, treatment often involves surgical removal, and in some cases, additional therapies may be needed, particularly for more advanced or recurrent tumors. Genetic factors and molecular markers are progressively essential in comprehending the behavior of these tumors and personalizing treatment strategies. GCTs originate from germ cells and are predominantly found in young women, especially during their reproductive years. These tumors are characterized by the presence of large abdominal masses that may be detected through imaging or physical examination. They are divided into several subtypes, including dysgerminomas, immature teratomas, and yolk sac tumors, each with distinct histological features and clinical behavior [ 41 , 42 , 43 ]. Dysgerminomas are the most common GCTs and are often considered to be the ovarian counterpart of testicular seminomas. They are generally highly responsive to chemotherapy and have excellent prognosis. Immature teratomas, on the other hand, contain undifferentiated tissue and can behave more aggressively, often requiring a combination of surgery and chemotherapy for effective treatment. Yolk sac tumors are also rare but are characterized by their rapid growth and high potential for metastasis, making early diagnosis and intervention crucial [ 44 , 45 ]. Although GCTs present with diverse clinical features, they are typically treatable through surgery, chemotherapy, and/or radiation, depending on the tumor’s stage and type. The prognosis for young women with these tumors is generally favorable, especially when diagnosed at an early stage. However, close follow-up is essential due to the possibility of recurrence, especially for more aggressive subtypes. EC is frequently associated with endometriosis, accounting for 5–10% of ovarian neoplasms. It is characterized by a relatively low incidence of lymph node metastasis and is often associated with mutations in the BRCA1 and BRCA2 genes are known to significantly contribute to the development of various gynecological cancers. This type of carcinoma can also be diagnosed concurrently with endometrial carcinoma, with each tumor type presenting its own unique histological features, which may pose challenges in differential diagnosis. EC is often considered to have a more indolent course compared to other ovarian cancer subtypes, but it can still present with advanced-stage disease, particularly in cases that are diagnosed late. The coexistence of endometrial cancer is noteworthy, as it may indicate a shared pathophysiological pathway, such as hormonal influences or genetic mutations that predispose to the development of both cancers. While the prognosis for EC is generally better compared to HGSCs, it remains highly dependent on early detection and staging. Research into targeted therapies and the role of BRCA mutations in the management of this cancer is ongoing, with promising advancements in personalized treatment options. Endometrioid borderline tumors (EBTs) of the ovary are epithelial tumors considered to be an intermediate form between neoplasms and benign tumors. These tumors exhibit atypical endometrioid epithelium but lack stromal invasion. They represent a rare occurrence, comprising only 0.2% of epithelial ovarian tumors, and are typically associated with a favorable prognosis when diagnosed at an early stage. Borderline ovarian tumors (BOTs) are primarily classified into serous and mucinous types, which together comprise 95% of all cases. Rarer variants include endometrioid, clear cell, seromucinous, and borderline Brenner tumors [ 46 , 47 ]. The endometrioid subtype constitutes 2–3% of endometrioid tumors and is histologically characterized by atypical endometrioid glands or cysts embedded within fibrous stroma, without stromal invasion. These tumors may originate from either ovarian epithelial cells or endometriosis [ 46 , 48 ]. Their slow growth and indolent progression facilitate early detection, which often leads to a favorable prognosis following early intervention. For early-stage tumors with small sizes and no peritoneal involvement, the laparoscopic approach is considered the treatment of choice owing to its minimally invasive approach, reduced recovery time, and lower risk of complications [ 48 , 49 ]. This approach is particularly beneficial for preserving fertility, a crucial aspect for younger patients of reproductive age. In these cases, the preservation of the ovary and uterus is often a key consideration, allowing the patient to maintain future reproductive potential [ 49 , 50 ]. The current European Society of Gynecological Oncology (ESGO) Guidelines advocate for the preservation of the uterus if it remains intact and if ovarian tissue cannot be conserved, as long as there are no contraindications such as the presence of endometrial lesions in the uterus. In these cases, the potential for concurrent endometrial lesions or malignancy must be carefully assessed, as it may influence treatment strategies and the decision to preserve uterine tissue [ 48 , 51 , 52 ]. Furthermore, a multidisciplinary approach involving oncologists, gynecologists, and fertility specialists is essential to ensure optimal outcomes, balancing cancer treatment with fertility preservation. In 1929, Taylor first described ovarian epithelial tumors that exhibited characteristics intermediate positioned between benign and malignant neoplasms, these tumors are often referred to as “semimalignant”. These tumors were recognized as having the potential for both aggressive growth and the ability to remain relatively localized, distinguishing them from typical benign or malignant lesions. In 1971, the International Federation of Gynecology and Obstetrics (Fédération Internationale de Gynécologie et d’Obstétrique; FIGO) redefined these neoplasms as “carcinomas of low malignant potential”, underscoring their distinct pathobiological behavior and intermediate position between benign and overtly malignant ovarian tumors. In 1973, the WHO officially classified these tumors as ‘borderline tumors’, a term that better encapsulated their intermediate nature, indicating that while they exhibited some malignant features, they did not possess the invasive characteristics of full-blown carcinomas. Since then, BOTs have become an important category in gynecological oncology, with increasing recognition of their relatively favorable prognosis compared to high-grade malignant ovarian cancers. BOTs are now categorized into different histological subtypes, including serous, mucinous, and endometrioid, among others, which influence treatment approaches and patient outcomes. At present, these tumors are described using three terminologies interchangeably: borderline tumor, tumor of low malignant potential, and atypical proliferative tumor [ 46 , 53 ]. Regarding preoperative diagnosis, radiological findings are often inconclusive, the measurement of tumor markers yields unclear results, and histopathological (HP) examination can sometimes be inaccurate. However, immunohistochemistry provides definitive information for accurate diagnosis [ 54 ]. The incidence of BOTs has increased in recent years, likely due to advancements in HP diagnostic techniques and changes in the risk factors associated with the disease [ 54 ]. Endometrioid ovarian tumors constitute a rare group of neoplasms, predominantly affecting women during their reproductive years. In the 2020 classification by the WHO, these tumors are histologically divided into five categories: endometrioid cystadenoma, endometrioid adenofibroma (EA), EBT, endometrioid adenocarcinoma, and seromucinous carcinoma. Among these, endometrioid cystadenoma and EA are benign entities characterized by epithelial differentiation resembling endometrial tissue. EA is distinguished by a substantial fibrous stromal component, whereas endometrioid cystadenoma typically presents as a cystic lesion lined with benign endometrioid epithelium [ 47 , 55 ].