Cancers

The Imaging of Primary Fallopian Tube Carcinoma: A Literature Review

Primary Fallopian tube carcinomas (PFTCs) are rare malignancies that are often misclassified as ovarian cancers due to overlapping clinical and pathological features. This frequent misdiagnosis contributes to the under-recognition of PFTCs, which account for a larger proportion of pelvic malignancies than historically reported. The central aim of this literature review is to highlight the critical importance of and methods for achieving an early diagnosis of Fallopian tube cancer, to improve patient outcomes. We classify benign and malignant fallopian tube neoplasms and evaluate the essential role of clinical evaluation and advanced imaging techniques, considering especially ultrasound, MRI, and PET-CT, in achieving an accurate and timely diagnosis. While histopathology remains the gold standard, imaging is pivotal for differentiating benign from malignant tubal lesions. This review details clinical manifestations, diagnostic pitfalls, and the necessity of a multidisciplinary approach to management. We conclude that advancing early detection through refined diagnostic criteria is essential to guiding effective, patient-specific therapeutic interventions.

Imaging Evaluation of Ovarian Masses in a Pediatric Population: A Comprehensive Overview

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.

Calreticulin—From the Endoplasmic Reticulum to the Plasma Membrane—Adventures of a Wandering Protein

Calreticulin (CRT) is a 46 kDa highly conserved protein initially identified as calregulin, a prominent Ca2+-binding protein of the endoplasmic reticulum (ER). Subsequent studies have established that CRT functions in the ER’s protein folding response and Ca2+ homeostatic mechanisms. An ER retention signal on the carboxyl terminus of CRT suggested that CRT was restricted to the ER. However, the identification of CRT in the nucleus and cytosol has established that CRT is a multi-compartmental, multifunctional protein. CRT also plays an important role in cancer progression. Most recently, CRT was identified on the cell surface and shown to be a potent ‘eat-me’ signal that plays a key role in the uptake of apoptotic and viable cancer cells by phagocytes. Elevated CRT exposure on the outer leaflet of cancer cells has been linked with anticancer immunity and superior therapeutic outcomes in patients with non-small cell lung carcinoma, colorectal carcinoma, acute myeloid leukemia, ovarian cancer, and high-grade serous carcinomas. Mutations in the CRT gene have been identified in a subset of patients with myeloproliferative neoplasms. The most recent studies from our laboratory have revealed a new and significant function for extracellular CRT as a plasminogen receptor. This discovery has profound implications for our understanding of the role of CRT in myeloproliferative neoplasms, specifically, essential thrombocythemia.

Range of Resection in Endometrial Cancer—Clinical Issues of Made-to-Measure Surgery

Endometrial cancer (EC) poses a significant health issue among women, and its incidence has been rising for a couple of decades. Surgery remains its principal treatment method and may have a curative, staging, or palliative aim. The type and extent of surgery depends on many factors, and the risks and benefits should be carefully weighed. While simple hysterectomy might be sufficient in early stage EC, modified-radical hysterectomy is sometimes indicated. In advanced disease, the evidence suggests that, similarly to ovarian cancer, optimal cytoreduction improves survival rate. The role of lymphadenectomy in EC patients has long been a controversial issue. The rationale for systematic lymphadenectomy and the procedure of the sentinel lymph node biopsy are thoroughly discussed. Finally, the impact of the molecular classification and new International Federation of Gynecology and Obstetrics (FIGO) staging system on EC treatment is outlined. Due to the increasing knowledge on the pathology and molecular features of EC, as well as the new advances in the adjuvant therapies, the surgical management of EC has become more complex. In the modern approach, it is essential to adjust the extent of the surgery to a specific patient, ensuring an optimal, made-to-measure personalized surgery. This narrative review focuses on the intricacies of surgical management of EC and aims at summarizing the available literature on the subject, providing an up-to-date clinical guide.

Human Papillomaviruses and Malignant Neoplasms of the Female Upper Reproductive Tract: A Comprehensive Review of the Literature

Malignancies of the female upper reproductive tract, especially endometrial and ovarian cancers, generate a significant burden for women worldwide. The possible etiopathogenetic role of chronic human papillomavirus (HPV) infection in the carcinogenesis of the female upper genital tract is neither clearly established not completely understood. Therefore, we performed a literature review, using the PubMed and SCOPUS electronic databases, of the prevalence of HPV DNA in endometrial, primary fallopian tube, ovarian, and primary peritoneal cancers, as well as uterine sarcomas. The present investigation covered 35 studies from different countries on various continents. Overall, the prevalence of HPV was approximately 15% in all the above cancers. HPV DNA was isolated from 11%, 0%, 0%, and 14% of endometrial carcinomas, uterine sarcomas, primary fallopian tube cancers, and ovarian malignant neoplasms, respectively. No relevant studies on primary peritoneal cancers were retrieved. The predominant HPV strain from tumors of the upper female reproductive tract, regardless of the tumor site, was HPV-16, followed by HPV-18. The HPV DNA identified was exclusively from subtypes HPV-6, HPV-11, HPV-16, HPV-18, and HPV-33, which are responsible for the development of not only cervical cancer, but also condylomata acuminata. The findings of the present review indicate that HPV vaccination might prove to be a useful strategy in the prevention of HPV-related carcinomas of the upper genital tract in women.

Gonadal Teratomas: A State-of-the-Art Review in Pathology

Teratomas are neoplasms arising from germ cells and encompass tissues derived from two or more embryonic germ layers, including ectoderm, mesoderm, and endoderm. These tumours typically localize along the midline or in paramedian positions and can manifest as gonadal (20%) or extragonadal (80%) entities. Although gonadal teratomas are uncommon, they represent the predominant type of gonadal tumour in the paediatric population. They comprise approximately 20–25% of all ovarian tumours in females and about 3–5% of all testicular tumours in males. Ovarian teratomas exhibit a higher incidence in early childhood and adolescence, whereas testicular teratomas are more prevalent during the first three months of life and between the ages of 15 and 19. While the majority of paediatric gonadal teratomas are benign, malignant or mixed variants may also arise, necessitating more aggressive therapeutic interventions.

Trends in Mortality Due to Malignant Neoplasms of Female Genital Organs in Poland in the Period 2000–2021—A Population-Based Study

The aim of this study is to assess mortality trends due to malignant neoplasms of female genital organs (MNFGOs) in Poland between 2000 and 2021. For the purpose of the study, the authors used data on all deaths of Polish female inhabitants due to MNFGO between 2000 and 2021, obtained from the Statistics Poland database. The standardised death rates (SDR), potential years of life lost (PYLL), annual percentage change (APC) and average annual percentage change (AAPC) were calculated. Between the years 2000 and 2021, 138,000 women died due to MNFGOs in Poland. Of this number, 54,975 (39.8%) deaths were caused by ovarian cancer, 37,487 (27.2%) by cervix uteri cancer, and 26,231 (19.0%) by corpus uteri cancer. A decrease in mortality due to cervix uteri cancer (APC = −2.4%, p < 0.05) was the most favourable change that occurred in the period 2000–2021, while the least favourable change was an increase in mortality due to corpus uteri cancer for the period 2005–2019 (APC = 5.0%, p < 0.05). SDRs due to ovarian cancer showed a decreasing trend between 2007 and 2021 (APC = −0.5%, p < 0.05). The standardised PYLL index due to cervical cancer was 167.7 per 100,000 women in 2000 and decreased to 75.0 in 2021 (AAPC = −3.7, p < 0.05). The number of lost years of life due to ovarian cancer decreased from 143.8 in 2000 to 109.5 in 2021 (AAPC = −1.3, p < 0.05). High values of death rates due to MNFGO in Poland, compared to other European countries, show that there is a need to promote preventive programmes and continue to monitor changes in mortality.

Relevance of Molecular Pathology for the Diagnosis of Sex Cord–Stromal Tumors of the Ovary: A Narrative Review

Ovarian sex cord–stromal tumors (SCSTs) account for 8% of all primary ovarian neo-plasms. Accurate diagnosis is crucial since each subtype has a specific prognostic and treatment. Apart from fibrosarcomas, stromal tumors are benign while sex cord tumors may recur, sometimes with a significant time to relapse. Although the diagnosis based on morphology is straightforward, in some cases the distinction between stromal tumors and sex cord tumors may be tricky. Indeed, the immunophenotype is usually nonspecific between stromal tumors and sex cord tumors. Therefore, molecular pathology plays an important role in the diagnosis of such entities, with pathognomonic or recurrent alterations, such as FOXL2 variants in adult granulosa cell tumors. In addition, these neoplasms may be associated with genetic syndromes, such as Peutz–Jeghers syndrome for sex cord tumors with annular tubules, and DICER1 syndrome for Sertoli–Leydig cell tumors (SLCTs), for which the pathologist may be in the front line of syndromic suspicion. Molecular pathology of SCST is also relevant for patient prognosis and management. For instance, the DICER1 variant is associated with moderately to poorly differentiated SLCTS and a poorer prognosis. The present review summarizes the histomolecular criteria useful for the diagnosis of SCST, using recent molecular data from the literature.

Prospective Real-World Gynaecological Cancer Clinical Registry with Associated Biospecimens: A Collaborative Model to Promote Translational Research between GEICO and the Spanish Biobank Network.

Patient registries linked to biorepositories constitute a valuable asset for clinical and translational research in oncology. The Spanish Group of Ovarian Cancer Research (GEICO), in collaboration with the Spanish Biobank Network (RNBB), has developed a multicentre, multistakeholder, prospective virtual clinical registry (VCR) associated with biobanks for the collection of real-world data and biological samples of gynaecological cancer patients. This collaborative project aims to promote research by providing broad access to high-quality clinical data and biospecimens for future research according to the needs of investigators and to increase diagnostic and therapeutic opportunities for gynaecological cancer patients in Spain. The VCR will include the participation of more than 60 Spanish hospitals entering relevant clinical information in harmonised electronic case report forms (eCRFs) in four different cohorts: ovarian, endometrial, cervical, and rare gynaecological cancers (gestational trophoblastic disease). Initial data for the cases included till December 2021 are presented. The model described herein establishes a real-world win-win collaboration between multicentre structures, promoted and supported by GEICO, that will contribute to the success of translational research in gynaecological cancer.

Molecular Biomarkers in Borderline Ovarian Tumors: Towards Personalized Treatment and Prognostic Assessment

Borderline Ovarian Tumours (BOTs) are a heterogenous group of ovarian neoplasms which have increased mitotic activity but lack stromal invasion. We performed a narrative review of the literature, aiming to identify prognostic molecular biomarkers that can potentially be used for treatment personalisation. We identified and discussed BRAF/KRAS, Cancer Antigen 125 (Ca 125), Calprotectin, p16ink4a, and Microsatellite instability (MSI) as the most studied biomarkers related to BOTs. Overall, BRAF and KRAS mutations are associated with earlier-stage and favourable prognosis; KRASmt may indicate extraovarian disease in serous BOT (sBOT). Ca125, the only currently clinically used biomarker, can be assessed pre-operatively and has an established role in post-operative surveillance, especially when it is raised pre-operatively or a high potential for malignant transformation is suspected post-operatively. p16ink4a expression trends could also indicate the malignant transformation of the tumour. Calprotectin has an inferior specificity to Ca125 and is not yet established as a biomarker, whilst there is very limited evidence available for MSI. As new evidence is coming along with artificial intelligence platforms, these biomarkers can be integrated and used towards the development of a precision model for treatment stratification and counselling in women diagnosed with BOTs.

Influence of Age on Treatment and Prognosis in Ovarian Cancer Patients

Background: Ovarian cancer, particularly in advanced stages, requires cytoreductive surgery followed by chemotherapy. A significant proportion of patients are elderly, yet older women are often treated with non-standard regimens despite a lack of consistent evidence linking age to prognosis. The aim of this study is to assess age-specific differences in treatment and survival outcomes for ovarian cancer in women aged 70 years or older. Methods: This retrospective study included ovarian cancer patients treated at the Hospital del Mar, Barcelona, between 2016 and 2022. Patients were stratified into two groups: <70 and ≥70 years. Clinical and pathological data were analyzed, and hazard ratios (HR) for overall survival (OS) and disease-free survival (DFS) were calculated using Cox proportional hazards regression models. Multivariate analysis was performed to compare outcomes. Results: A total of 110 patients were included (73 <70 years, 37 ≥70 years). Among the older group, 80.5% were diagnosed at advanced stages (III–IV), compared to 63% in the younger group (p = 0.012). Patients aged ≥70 were more likely to undergo interval surgery (p = 0.053) and receive non-standard treatment (p = 0.023). Complete cytoreduction was achieved in 95.8% of younger patients versus 81.3% of older patients (p = 0.024). Age ≥70 did not significantly impact DFS (p = 0.091), but OS was significantly worse in the older group (44.4% vs. 67.2%, p = 0.014). Conclusions: Older women (≥70 years) with ovarian cancer are more likely to be diagnosed at advanced stages, receive non-standard treatment, and achieve suboptimal cytoreduction compared to younger patients. While DFS was similar across age groups, older age was associated with worse OS, highlighting the need for age-tailored treatment strategies.

The Evolving Molecular Landscape of Uterine Mesenchymal Tumors: Diagnostic and Therapeutic Implications

Uterine mesenchymal tumors encompass a diverse and diagnostically challenging group of neoplasms, including smooth muscle tumors, endometrial stromal tumors (ESS), perivascular epithelioid cell tumors (PEComas), inflammatory myofibroblastic tumors (IMTs), uterine tumor resembling ovarian sex cord tumor (UTROSCT), along with many other relatively rare entities. Traditionally classified by histomorphology and immunophenotype, these tumors are now increasingly defined by recurrent genetic alterations that refine diagnosis and elucidate tumorigenesis. For example, leiomyosarcomas display complex genomic instability with frequent TP53, RB1, and ATRX mutations. Low grade-ESS are characterized by JAZF1::SUZ12 and other related fusions, whereas high-grade tumors harbor YWHAE::NUTM2 or ZC3H7B::BCOR fusions, and BCOR internal tandem duplication (ITD) alterations. PEComas frequently contain TSC1 or TSC2 mutations, leading to aberrant activation of the mTOR pathway. Beyond their diagnostic utility, these molecular signatures increasingly inform prognosis and highlight potential therapeutic targets, including CDK4/6 inhibition, PI3K/AKT/mTOR blockade, and immunotherapy. This review summarizes the evolving molecular landscape of uterine mesenchymal tumors, underscoring the value of integrating molecular testing into clinical practice to enhance diagnostic precision and enable personalized management of these rare yet clinically significant neoplasms.

Mutations in the Serine/Threonine Kinase BRAF: Oncogenic Drivers in Solid Tumors

Since their discovery in 2002, BRAF mutations have been identified as clear drivers of oncogenesis in several cancer types. Currently, their incidence rate is nearly 7% of all solid tumors with BRAF V600E constituting approximately 90% of these diagnoses. In melanoma, thyroid cancer, and histiocytic neoplasms, BRAF hotspot mutations are found at a rate of about 50%, while in lung and colorectal cancers they range from 3% to 10% of reported cases. Though present in other malignancies such as breast and ovarian cancers, they constitute a small portion of diagnoses (<1%). Given their frequency along with advancements in screening technologies, various methods are used for the detection of BRAF-mutant cancers. Among these are targeted next-generation sequencing (NGS) on tumor tissue or circulating tumor DNA (ctDNA) and immunohistochemistry (IHC)-based assays. With advancements in detection technologies, several approaches to the treatment of BRAF-mutant cancers have been taken. In this review, we retrace the milestones that led to the clinical development of targeted therapies currently available for these tumors.

Novel Targeted Agents in Advanced and Recurrent Low-Grade Serous Ovarian Cancer: A Silver Lining in the Therapy of a Chemoresistant Disease?

Low-grade serous ovarian carcinoma (LGSOC) is a rare subtype of epithelial ovarian cancer, characterized by a unique molecular background and specific clinical behavior. A growing body of molecular data underscores LGSOC as a distinct disease entity; however, clinical evidence on the optimal treatment regimens for LGSOC remains limited due to the low incidence of the disease. Consequently, treatment recommendations for LGSOC are still often derived from findings on the more common high-grade serous ovarian carcinoma (HGSOC) and typically focus on radical cytoreductive surgery and platinum-based chemotherapy. Since LGSOCs typically exhibit only limited responsiveness to platinum-based chemotherapy, the clinical management of advanced and recurrent LGSOCs remains a significant therapeutic challenge and often results in limited treatment options and suboptimal outcomes. Recent advances in molecular profiling and the identification of new, promising targets, such as the mitogen-activated protein kinase (MAPK) pathway, offer hope for improving both the prognosis and health-related quality of life in affected patients. Given the high unmet clinical need to establish new therapeutic standards beyond cytotoxic chemotherapy, this review aims to summarize the most promising molecular targets and emerging targeted agents.