Search Results (158)

(1) Background: Sertoli–Leydig cell tumors (SLCTs) are rare ovarian neoplasms that account for less than 0.5% of all ovarian tumors. They usually affect young women and often present with androgenic symptoms. We report a unique case of a 40-year-old woman diagnosed with both SLCT and clear cell papillary renal cell carcinoma (CCP-RCC), a rare tumor association with unclear pathogenesis. (2) Methods: Both tumors were treated surgically. The diagnostic workup included hormonal testing, imaging studies, and extensive genetic testing, including DICER1 mutation analysis and multiplex ligation-dependent probe amplification (MLPA), as well as the examination of a next-generation sequencing (NGS) panel covering ~280 cancer-related genes. (3) Results: Histopathologic examination confirmed a well-differentiated SLCT and CCP-RCC. No pathogenic variants in DICER1 were identified by WES or MLPA. No clinically relevant changes were found in the extended NGS panel either, so a known hereditary predisposition could be ruled out. The synchronous occurrence of both tumors without genomic alterations could indicate a sporadic event or as yet unidentified mechanisms. (4) Conclusions: This case highlights the importance of a multidisciplinary approach in the management of rare tumor compounds. The exclusion of DICER1 mutations and the absence of genetic findings adds new evidence to the limited literature and underscores the importance of long-term surveillance and further research into potential shared oncogenic pathways. Full article

Ovarian tumors are rare in the pediatric population, yet they are the most common type of malignancy in tumors of the female genital tract. Both non-neoplastic and neoplastic ovarian lesions are seen in children and adolescents. Most pediatric ovarian tumors are benign. Germ cell tumors constitute the majority of ovarian tumors in the pediatric cohort, and mature teratoma is the most prevalent histologic type. However, 3–8% % of ovarian tumors in children and adolescents are malignant. Accurate characterization of ovarian masses in the pediatric population is crucial to determine the appropriate treatment, which should be minimally invasive and focused on preserving fertility. Transabdominal US is the main imaging modality for the assessment of pediatric ovarian masses. MRI represents a valuable adjunct tool for the evaluation of sonographically indeterminate ovarian lesions. This technique is also recommended for tumor staging and follow-up. CT is often used in emergency situations or when there are contraindications for MRI. Imaging findings, along with clinical features and laboratory results, play a crucial role in the characterization of ovarian masses in the pediatric population. This narrative review was based on a comprehensive literature search of articles about imaging findings of ovarian masses in the pediatric population, published between 1977 and April 2025. Data were obtained from the PubMed database, using the following keywords: “imaging”, “ovarian tumors”, ovarian masses”, and “pediatric”. This article aims to provide an overview of the role of imaging in the assessment of ovarian masses in the pediatric age group. Full article

Background and Clinical Significance: Brenner tumors are rare epithelial tumors that can occur in both males and females. They consist of ovarian transition cells surrounded by dense fibrous tissue and can be classified as benign, borderline, or malignant. While most commonly found in the ovary, extraovarian Brenner tumors (EOBTs) have been reported in the uterus, vagina, broad ligament, and omentum. Case Presentation: A 71-year-old postmenopausal woman presented with a polypous formation on the upper third of the posterior vaginal wall, which was found at a routine health check. Macroscopically, the lesion appeared as a solid, polypoid mass with a yellowish-gray cut surface, measuring approximately 25 × 20 mm. Histological examination revealed a polypoid formation covered by stratified squamous epithelium, with a dense fibrous stroma (Van Gieson [VG]+) and tubular structures lined by clear epithelial cells. Parenchymal cells showed low proliferative activity, with Ki-67 expression in less than 5% of cells, also Cytokeratin (CK) 7/+/p63:/+/ CK AE1/AE3: /+/ Estrogen Receptor (ER): /+/ and Progesterone Receptor (PR)/−/; CK20/-/; p53/−/, Wilms’ Tumor (WT)-1/−/; Prostate-Specific Acid Phosphatase (PSAP)/−/. The final diagnosis was an extraovarian Brenner tumor. The patient was monitored for two months post-excision, with no signs of recurrence. Conclusions: EOBTs are extremely rarely seen and vaginal involvement is far less common. Due to their rarity, these tumors may be confused with other benign or malignant vaginal lesions. In order to differentiate EOBTs from other neoplasms, histological analysis is crucial due to their characteristic transitional-type epithelium and large fibrous stroma. Further studies are required to understand the origin and clinical behavior of EOBTs. Long-term monitoring should be performed to look for any recurrence or malignant change, even though benign Brenner tumors usually have a good prognosis. Awareness of EOBTs and their possible locations is essential for accurate diagnosis and appropriate management. Full article

Mesonephric-like adenocarcinoma (MLA) of ovaries is a new and rare neoplastic entity, recently classified by the World Health Organization. Its morphological and immunohistochemical profile is similar to primitive cervical mesonephric adenocarcinoma, but its origin has not been determined yet. Some authors believe that this neoplasm originates from Wolffian remnants in the ovarian hilum, while others suggest an origin from the Mϋllerian epithelium, followed by a mesonephric trans-differentiation. Starting from a recently diagnosed mismatch repair-deficient ovarian MLA, we try to further develop this line of research. A detailed molecular analysis of the studied tumor helps clarify our ideas. In fact, the typical KRAS mutation was not present. We found mutations in numerous other genes, which are rarely described in the literature or are already described in the endometrioid histotype. We reached some interesting conclusions, which, if supported by future studies, will clarify the true nature of these tumors, allowing for better stratification and a better therapeutic framework. Full article

Background and Objectives: Ovarian carcinosarcoma (OCS) is a rare gynecologic malignancy defined by both epithelial and mesenchymal components, generally associated with advanced clinical stage and poor outcomes. We present a 66-year-old patient initially presenting with right iliac vein thrombosis, ultimately diagnosed with OCS, and place these findings in context with a focused literature review from 2000 through to 2024. Methods: A comprehensive account of the patient’s clinical course—spanning diagnostic imaging, surgical pathology, neoadjuvant chemotherapy, and interval debulking—was combined with a review of the current data on OCS pathogenesis, treatment protocols, and outcomes. Results: The patient’s tumor showed predominantly sarcomatous histology (approximately 90%) with high-grade serous features, responded to platinum/taxane chemotherapy, and was resected to no visible residual disease. The updated literature indicates that the majority of OCS cases present at advanced stages (often exceeding 60%), with suboptimal cytoreduction closely tied to worse prognosis. Up to 64% of tumors may harbor homologous recombination deficiency, offering a rationale for PARP inhibitor therapy; nonetheless, five-year survival rarely surpasses 45% in most series. Conclusions: Despite its aggressive course, optimal debulking surgery plus platinum-based chemotherapy remain central in treating OCS. Emerging molecular insights highlight homologous recombination deficiency and BRCA mutations as potential therapeutic targets. Multidisciplinary care and future prospective studies are key to improving long-term outcomes in this challenging malignancy. Full article

Strumal carcinoid tumors of the ovary are rare neoplasms composed of an intimate mixture of thyroid and carcinoid tissues. Although various theories regarding their histogenesis have been proposed, evidence confirming the origin of the carcinoid component has been lacking. We report a case of a 40-year-old female with an ovarian strumal carcinoid arising in the background of a mature cystic teratoma. Morphological and immunohistochemical findings support the hypothesis that the carcinoid component originates from the thyroid follicular epithelium, undergoing neuroendocrine differentiation. A single-cell growth pattern was also identified, expanding the known histological spectrum of strumal carcinoids. Our case provides additional immunohistochemical support for the histogenetic origin of strumal carcinoids, offering new insights into their pathogenesis. Recognizing these distinct patterns of staining and unusual morphology is critical for accurate diagnosis and differentiation from metastatic disease. Full article

Background/Objectives: Mucinous ovarian carcinoma (MOC) is a rare and biologically distinct subtype of epithelial ovarian cancer, typically presenting at an early stage in younger women. Unlike high-grade serous carcinoma, MOC is characterized by unique molecular features—including frequent KRAS mutations and HER2 amplifications—and exhibits limited sensitivity to platinum-based chemotherapy. These differences highlight the need for individualized treatment strategies guided by molecular and histological profiling. This review aims to integrate current evidence on the clinical management of MOC with emerging insights into its molecular biology, with a focus on how these factors influence surgical decision-making, fertility preservation, and adjuvant therapy selection. Methods: We performed a comprehensive narrative review of the literature, synthesizing findings from retrospective cohorts, molecular studies, and clinical guidelines relevant to the surgical, reproductive, and therapeutic management of MOC. Results: Histologic subtype—expansile versus infiltrative—plays a critical role in guiding lymphadenectomy as lymph node metastases are rare (<1%) in expansile tumors but occur in up to 23% of infiltrative cases. Complete surgical staging remains essential for accurate prognostication, yet tailored approaches may reduce overtreatment in low-risk patients. Fertility-sparing surgery (FSS) appears safe in FIGO stage IA expansile MOC, with favorable reproductive outcomes, while higher-stage or infiltrative cases warrant caution. Given MOC’s chemoresistance, the role of adjuvant therapy in early-stage disease remains debated. Targeted strategies, including MEK inhibitors and HER2-directed therapies, are under investigation and may benefit selected molecular subgroups. Conclusions: MOC requires a nuanced, biomarker-informed approach. This review advocates for personalized, evidence-based management supported by multidisciplinary evaluation while underscoring the urgent need for prospective studies and biomarker-driven clinical trials. Full article

Background/Objectives: Ovarian germ cell tumors are rare, and determining prognostic factors is crucial for individualizing management strategies. We aimed to determine an optimal neutrophil-to-lymphocyte ratio (NLR) cut-off value for predicting survival outcomes in malignant ovarian germ cell tumors, and to evaluate the prognostic significance of NLR in these tumors. Methods: This retrospective cohort study included women diagnosed with malignant ovarian germ cell tumors who underwent surgery at Istanbul University-Cerrahpasa between 2000 and 2024. Patients with benign tumors; incomplete follow-up; inaccessible data; history of hematological or rheumatic diseases; inflammatory conditions such as diabetes mellitus, asthma, or renal failure; as well as those with acute/chronic infections or sepsis were excluded. Data collected included demographic characteristics, surgical and pathological findings, chemotherapy details, disease progression, survival outcomes, and laboratory values at preoperative, postoperative, and post-chemotherapy time points. The NLR was calculated and compared for overall survival and disease-free survival. Results: The study included 44 patients with a pathologically confirmed diagnosis of malignant ovarian germ cell tumors. The NLR cut-off value for survival prediction was determined as 3.69 using the ROC curve. The effect of preoperative NLR on overall survival was found to be significant. The median overall survival was significantly lower in the group with NLR ≥ 3.69 (153.2 months) compared to the group with NLR < 3.69 (234 months) (p = 0.010). However, there was no statistically significant difference in median disease-free survival between the NLR ≥ 3.69 group (159.3 months) and the NLR < 3.69 group (215 months). Conclusions: The preoperative NLR was found to have a significant impact on overall survival but not on disease-free survival. A cut-off value of 3.69 can be used to assess short survival time. Full article

Background and Clinical Significance: Paratubal Leydig cell nodules are rare incidental findings that present diagnostic challenges. Case Presentation: A 45-year-old female with a history of hypertension and diabetes mellitus presented with fever and chills following an episode of severe dysmenorrhea and menorrhagia. The patient reported heavy menstrual bleeding, persisting for 2–3 years. Physical examination revealed erythema of the perineum and whitish vaginal discharge, with no cervical lesions. Imaging revealed a 15 cm right ovarian cyst. Laboratory investigations showed elevated C-reactive protein (6.37 mg/L) and CA125 (88.82 U/mL) levels, whereas other tumor markers were within normal limits. A pelvic ultrasound revealed a retroverted uterus and a large ovarian mass suggestive of malignancy. The patient underwent a right salpingo-oophorectomy, during which a 15 cm ovarian tumor adherent to the right pelvic sidewall was excised. Histopathological examination revealed an endometriotic cyst with endometrial glandular epithelium positive for estrogen receptor and focal mucinous metaplasia. CD10-positive endometrial stromal cells and paratubal cysts were also observed. Additionally, a small Leydig cell tumor originated from the ovarian hilum was identified and confirmed by positive staining for inhibin, calretinin, and androgen receptors, as well as negative estrogen receptor staining. The postoperative recovery was uneventful, and at the five-week follow-up, the patient’s hormonal levels were normal, and there were no complications. Conclusions: This case highlights the importance of thorough histopathological evaluation in managing ovarian masses and the potential coexistence of benign and rare pathological entities, such as Leydig cell tumors. Full article

Background/Objective: Ovarian clear cell carcinomas (OCCCs) are a rare histological subtype of epithelial ovarian cancer characterized by resistance to platinum-based therapy. CDK8/19, a component of the regulatory CDK module associated with Mediator complex, has been implicated in transcriptional reprogramming and drug resistance in various solid tumors. Our study aimed to investigate the therapeutic potential of CDK8/19 kinase inhibition using selective inhibitors SNX631 and SNX631-6 in OCCC treatment, both as monotherapy and in combination with standard chemotherapeutics. Methods: CDK8 and Ki67 levels were evaluated via immunohistochemistry in benign, primary, and metastatic ovarian cancer tissues. The efficacy of SNX631 alone and in combination with cisplatin or paclitaxel was assessed in OCCC cell lines (ES-2, TOV-21-G, RMG-1). In vivo evaluation utilized xenograft models with subcutaneous and intraperitoneal delivery of the OCCC ES2 cells and oral delivery of SNX631-6, with the monitoring of tumor growth, metastatic spread, and survival. Results: CDK8 protein levels were elevated in OC tissues, particularly in OCCC primary and metastatic lesions compared to benign tissue. While CDK8/19 inhibition showed limited effects on in vitro cell proliferation, SNX631-6 demonstrated significant antitumor and anti-metastatic activity in vivo. Notably, SNX631-6 enhanced the efficacy of cisplatin, substantially inhibiting tumor growth and extending overall survival. Conclusions: Therapeutically achievable doses of CDK8/19 inhibitors may provide clinical benefit for OCCC patients by inhibiting tumor growth and reversing platinum resistance, potentially addressing a critical treatment challenge in this rare ovarian cancer subtype. Full article

DICER1 syndrome (DICERs) represents a tumor predisposition genetic syndrome, inherited in an autosomal dominant manner. Germline loss-of-function variants of the DICER1 gene lead to impaired processing of microRNA, gene expression, and increased risk of tumorigenesis. Although pleuropulmonary blastoma (PPB) is the hallmark of the syndrome, multiple extrapulmonary malignant and non-malignant conditions have also been described, including multinodular goiter (MNG) and sex-cord stromal tumors. MNG is one of the most common components and is associated with an increased risk of thyroid carcinoma. Sertoli–Leydig cell tumor (SLCT) represents the most prevalent type of sex-cord stromal tumor associated with the syndrome, whereas juvenile granulosa cell tumor (JGCT) is considered to be a very rare phenotype. They both may present with abdominal pain due to mass effect and menstrual irregularities in case of hormone production. Although they exhibit low rates of mortality, recurrence rates highly depend on the grade of malignancy. Herein, we report a novel pathogenic DICER1 variant associated with MNG, bilateral ovarian SLCT, and JGCT in a young Greek patient. Clinicians should be aware of a potential germline DICER1 variant when evaluating MNG in young patients, especially if it coexists with other neoplasms. Full article

Uterine tumors resembling ovarian sex-cord tumors (UTROSCTs) are among the rarest types of uterine tumors. Diagnosis of a UTROSCT is often challenging. Imaging techniques such as ultrasound and MRI are limited in distinguishing UTROSCTs as their appearance is usually suggestive of uterine leiomyoma or adenomyosis. Additionally, the value of a preoperative biopsy remains uncertain due to the heterogeneous composition of the tumor and the inadequacy of limited samplings. We present a rare case of UTROSCT in a 59-year-old woman and we have performed a narrative review of the literature on PubMed, Scopus, and Web of Science from 2000 to June 2024, identifying 133 cases. According to our review, at histological exam UTROSCTs are mainly composed of cells resembling ovarian sex-cord elements which are arranged in cords or trabeculae, typically with a mild cytologic atypia. The most expressed sex-cord differentiation markers include inhibin, calretinin, melan A, CD56, CD99, SF1, WT1, CD10, and FOXL2. For women who have completed their reproductive plans, a total hysterectomy with adnexectomy is an adequate treatment for tumors confined to the uterus. For younger patients who wish to preserve fertility, tumorectomy via hysteroscopy or laparoscopy is the preferred treatment option and the recurrence rates range from 5% to 30%. Treatments for recurrent disease include surgery, chemotherapy, and radiation therapy, often used in combination. Advancements in molecular profiling and immunohistochemistry will improve our ability to diagnose and manage this tumor. Such investigations will enhance prognostic stratification, facilitating more accurate predictions of biological behavior and recurrence risk. Full article

Background/Objectives: Immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have revolutionized cancer immunotherapy, however the clinical relevance of their soluble forms (sPD-1 and sPD-L1) remains less studied. Soluble PD-1 and PD-L1 have been implicated in tumor progression, prognosis, and treatment response across various malignancies. This study aims to provide a comprehensive analysis of sPD-1 and sPD-L1 levels in serum across diverse tumor types, including rare malignancies, and to evaluate their associations with clinicopathological characteristics and prognostic significance. Methods: In this study we analyzed sPD-1 and sPD-L1 levels in serum samples from 675 cancer patients representing a range of malignancies, including ovarian cancer, breast cancer, gastric cancer, colorectal cancer, renal cell carcinoma, and bone tumors. sPD-1 and sPD-L1 concentrations were measured using ELISA. Statistical analyses were performed to evaluate associations between soluble marker concentrations and clinicopathological factors, including tumor stage, size, histological subtype, and survival outcomes. Results: Elevated sPD-L1 levels were observed in several tumor types, including ovarian cancer, renal cell carcinoma, and gastric cancer, where they were associated with features of advanced disease, such as tumor size, stage, and metastases. In contrast, sPD-1 levels showed limited associations, with significant findings solely in gastric cancer and bone tumors, where levels correlated with histological subtype and differentiation. Prognostic analyses identified sPD-L1 as a marker of poor survival outcomes in ovarian cancer and bone tumors, while sPD-1 displayed no consistent prognostic significance. Conclusions: This study identifies the potential of sPD-L1 as a biomarker for tumor progression and prognosis across multiple malignancies. In contrast, sPD-1 showed limited clinical relevance, suggesting the importance of further investigation. These findings contribute to our understanding of soluble immune checkpoint proteins and their integration into personalized oncology strategies. Full article

Background and Clinical Significance: Borderline ovarian tumors (BOTs) are a rare diagnosis, especially in the adolescent population. This can make initial management and surveillance strategies difficult, given the limited guidelines and experience in this young age group. Case Presentation: We present two cases of recurrent serous BOTs diagnosed in adolescent patients. Both patients were initially treated with fertility-sparing surgery and followed with transabdominal pelvic ultrasounds. Secondary surgical debulking of recurrent disease with uterine preservation was successful in both patients with a long-term disease-free status. Conclusions: Although rare, BOTs can occur in adolescent patients and should be on the differential for ovarian masses in this age group. Fertility-sparing surgical techniques, reproductive endocrinology consultation, surveillance strategies, and hormone replacement therapy should all be taken into consideration when treating adolescent patients with BOTs. Full article

Malignant peripheral nerve sheath tumor (MPNST) is a rare but aggressive soft-tissue sarcoma characterized by poor response to therapy. The primary treatment remains surgical resection with negative margins. Nonetheless, in the setting of neurofibromatosis type 1 (NF1), the five-year survival rate is at 20–50%, with recurrence occurring in up to 50% of individuals. For patients with metastatic and unresectable disease, current treatment options include cytotoxic chemotherapy, which offers minimal benefit, and most patients die within five years of diagnosis. Despite advances in targeted therapy focusing on inhibiting Ras signaling and its downstream effectors, clinical trials report minimal clinical benefit, highlighting the need to explore alternative pathways in MPNST pathogenesis. Here, we discuss the role of the E3 ubiquitin ligase, UBR5, in cancer progression and immune modulation across various malignancies, including breast, lung, and ovarian cancer. We focus on mechanisms by which UBR5 contributes to tumorigenesis, focusing on its influence on tumor microenvironment and immune modulation. Additionally, we explore UBR5’s roles in normal tissue function, DNA damage response, metastasis, and therapeutic resistance, illustrating its multifaceted contribution to cancer biology. We discuss evidence implicating UBR5 in immune evasion and highlight its potential as a therapeutic target to enhance the efficacy of immune checkpoint blockade (ICB) therapy in MPNST, a tumor typically characterized by an immune cold microenvironment. We outline current immune-based strategies and challenges in MPNST management, ongoing efforts to shift the immune landscape in MPNST, and ultimately, we suggest that targeting UBR5 could be a novel strategy to potentiate ICB therapy-mediated anti-tumor immune response and clinical outcomes, particularly in MPNST patients with inoperable or metastatic disease. Full article