Gynecologic Tract Research Articles

Endothelial Mitochondria Transfer to Melanoma Induces M2-Type Macrophage Polarization and Promotes Tumor Growth by the Nrf2/HO-1-Mediated Pathway.

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor's phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.

Perivascular epithelioid cell tumors (PEComas) of gynecological tract: preoperative diagnostic imaging challenge.

Perivascular epithelioid cell tumors (PEComas) of gynecological tract: preoperative diagnostic imaging challenge.

Impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in patients with soft tissue sarcoma: an analysis from the OnCovid registry.

To date, limited evidence exists on the impact of COVID-19 in patients with soft tissue sarcoma (STS), nor about the impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in this specific population. We described COVID-19 morbidity and mortality among patients with STS across 'Omicron' (15 December 2021-31 January 2022), 'Pre-vaccination' (27 February 2020-30 November 2020), and 'Alpha-Delta' phase (01 December 2020-14 December 2021) using OnCovid registry participants (NCT04393974). Case fatality rate at 28 days (CFR28) and COVID-19 severity were also described according to the SARS-CoV-2 vaccination status, while the impact of the receipt of cytotoxic chemotherapy within 4 weeks prior to COVID-19 on clinical outcomes was assessed with Inverse Probability of Treatment Weighting (IPTW) models adjusted for possible confounders. Out of 3820 patients, 97 patients with STS were included. The median age at COVID-19 diagnosis was 56 years (range: 18-92), with 65 patients (67%) aged < 65 years and most patients had a low comorbidity burden (65, 67.0%). The most frequent primary tumor sites were the abdomen (56.7%) and the gynecological tract (12.4%). In total, 36 (37.1%) patients were on cytotoxic chemotherapy within 4 weeks prior to COVID-19. The overall CFR28 was 25.8%, with 38% oxygen therapy requirement, 34% rate of complications, and 32.3% of hospitalizations due to COVID-19. CFR28 (29.5%, 21.4%, and 12.5%) and all indicators of COVID-19 severity demonstrated a trend toward a numerical improvement across the pandemic phases. Similarly, vaccinated patients demonstrated numerically improved CFR28 (16.7% versus 27.7%) and COVID-19 morbidity compared with unvaccinated patients. Patients who were on chemotherapy experienced comparable CFR28 (19.4% versus 26.0%, p = 0.4803), hospitalizations (50.0% versus 44.4%, p = 0.6883), complication rates (30.6% versus 34.0%, p = 0.7381), and oxygen therapy requirement (28.1% versus 40.0%, p = 0.2755) compared to those who were not on anticancer therapy at COVID-19, findings further confirmed by the IPTW-fitted multivariable analysis. In this study, we demonstrate an improvement in COVID-19 outcomes in patients with STS over time. Recent exposure to chemotherapy does not impact COVID-19 morbidity and mortality and SARS-CoV-2 vaccination confers protection against adverse outcomes from COVID-19 in this patient population.

Adipose Tissue Dysfunction Following Trauma and Hypoxia Increases the Risk of Post-Surgical Adhesion: Potential for Therapeutic Interventions

Post-surgical adhesion is a medical challenge, especially following abdominal and pelvic surgeries. This refers to the formation of fibrotic scars that form from connective tissue in the gynecological tract or abdominal cavity. Dysfunctional adipose tissue (AT) by surgical injuries and hypoxia increases the risk of post-surgical adhesion through different molecular mechanisms. Damage-associated molecular patterns (DAMPs) and Hypoxia-induced factor 1 alpha (HIF-1α) produced during surgery trauma and hypoxia induce AT dysfunction to promote inflammation, oxidative stress, metabolic alterations, and profibrotic pathways, which contribute to post-surgical adhesions. HIF-1α and DAMPs can be considered therapeutic targets to prevent AT dysfunction and diminish the formation of adhesions in obese patients undergoing abdominal or pelvic surgeries.

Extrapulmonary Neuroendocrine Carcinomas: Current Management and Future Perspectives.

Neuroendocrine carcinomas (NECs) are poorly differentiated and highly aggressive epithelial neuroendocrine neoplasms. The most common primary site is the lung, but they may arise in every organ. Approximately 37% of extrapulmonary NECs (EP-NECs) occur in the gastroenteropancreatic (GEP) tract, followed by the genitourinary (GU) system and gynecological tract. As a result of their rarity, there is scant evidence to guide treatment recommendations, and a multidisciplinary approach is essential for the management of such patients. Platinum-based chemotherapy currently represents the standard of care for EP-NECs of any site, mirroring the management of small-cell lung cancer (SCLC), but further approaches are still under investigation. Indeed, ongoing trials evaluating targeted therapies, immune checkpoint inhibitors (ICIs), and radionuclide therapy could provide potentially breakthrough therapeutic options. Given the relative dearth of evidence-based literature on these orphan diseases, the aim of this review is to provide an overview of the pathology and current treatment options, as well as to shed light on the most pressing unmet needs in the field.

Adenocarcinomas of the Gynecologic Tract Involving the Urinary Bladder: A Series of 16 Cases Potentially Mimicking Urothelial Malignancy.

There is limited literature describing gynecologic adenocarcinomas involving the urinary bladder and potential diagnostic pitfalls. To describe key features distinguishing metastatic (or extension of) gynecologic adenocarcinomas from urothelial carcinomas with glandular differentiation. Retrospective review of surgical pathology cases of gynecologic adenocarcinomas involving the bladder from 2 different institutions, retrieved from surgical pathology archives, was performed. Morphologic features were recorded, along with immunohistochemistry results when available. Electronic medical records were reviewed for clinical and radiographic information. Sixteen cases of gynecologic adenocarcinomas (9 endometrial endometrioid adenocarcinomas, 4 endometrial serous carcinomas, 2 high-grade tubo-ovarian serous carcinomas, and 1 cervical adenosquamous carcinoma) involving the bladder were identified. All included cases had mucosal involvement potentially mimicking primary bladder neoplasms, including 4 cases originally diagnosed as urinary carcinomas. Tumors expressed keratin 7 (12 of 13; 92%), PAX8 (11 of 12; 92%), estrogen receptor (11 of 15; 73%), p16 (8 of 11; 73%), progesterone receptor (8 of 14; 57%), GATA3 (5 of 12; 42%), and p63 (3 of 11; 27%); all tumors were negative for keratin 20 (0 of 12). Features supportive of Müllerian origin included prior history of gynecologic malignancy, lack of morphologic heterogeneity in nonendometrioid tumors, and immunophenotypic coexpression of PAX8 and estrogen receptor with absent GATA3. Potential pitfalls seen in a subset of cases included misleading radiologic and cystoscopic findings, replacement of the overlying urothelial mucosa by tumor mimicking precursor lesions, focal GATA3 and/or p63 positivity, and areas of squamous differentiation in tumors of endometrioid histology. A combination of clinical history, certain morphologic features, and proper selection of immunohistochemical stains is key for the correct diagnosis of secondary gynecologic adenocarcinomas involving the urinary bladder.

Neuroanatomical location of brain metastases from solid tumours based on pathology: An analysis of 511 patients with a comparison to the provided clinical history.

Brain metastases are a frequent occurrence in neuropathology practices. The literature on their neuroanatomical location is frequently derived from radiological analyses. This work examines brain metastases through the lens of pathology specimens. All brain surgical pathology reports for cases accessioned 2011-2020 were retrieved from a laboratory. Specimens were classified by neuroanatomical location, diagnosis and diagnostic category with a hierarchical free text string-matching algorithm (HFTSMA) and also subsequently audited. All reports classified as probable metastasis were reviewed by a pathologist. The provided history was compared to the final categorization by a pathologist. The cohort had 4,625 cases. The HFTSMA identified 854 cases (including metastases from a definite primary, metastases from primary not known and improperly classified cases). 514/854 cases had one definite primary site per algorithm and on report review 538/854 cases were confirmed as such. The 538 cases originated from 511 patients. Primaries from breast, gynecologic tract, and gastrointestinal tract not otherwise specified were most frequently found in the cerebellum. Kidney metastases were most frequently found in the occipital lobe. Lung, metastatic melanoma and colorectal primaries were most commonly found in the frontal lobe. The provided clinical history predicted the primary in 206 cases (40.3%), was discordant in 17 cases (3.3%) and non-contributory in 280 cases (54.8%). The observed distribution of the metastatic tumours in the brain is dependent on the primary site. In the majority (54.8%) of cases, the provided clinical history was non-contributory; this suggests surgeon-pathologist communication may have the potential for optimization.

Gynaecological Causes of Acute Pelvic Pain: Common and Not-So-Common Imaging Findings.

In female patients, acute pelvic pain can be caused by gynaecological, gastrointestinal, and urinary tract pathologies. Due to the variety of diagnostic possibilities, the correct assessment of these patients may be challenging. The most frequent gynaecological causes of acute pelvic pain in non-pregnant women are pelvic inflammatory disease, ruptured ovarian cysts, ovarian torsion, and degeneration or torsion of uterine leiomyomas. On the other hand, spontaneous abortion, ectopic pregnancy, and placental disorders are the most frequent gynaecological entities to cause acute pelvic pain in pregnant patients. Ultrasound (US) is usually the first-line diagnostic technique because of its sensitivity across most common aetiologies and its lack of radiation exposure. Computed tomography (CT) may be performed if ultrasound findings are equivocal or if a gynaecologic disease is not initially suspected. Magnetic resonance imaging (MRI) is an extremely useful second-line technique for further characterisation after US or CT. This pictorial review aims to review the spectrum of gynaecological entities that may manifest as acute pelvic pain in the emergency department and to describe the imaging findings of these gynaecological conditions obtained with different imaging techniques.

Can Volume-Based MRI-Guided Planning for Interstitial Gynecologic Brachytherapy Overcome Clinicopathologic Risk Factors for Fistula Formation?

Tumor and patient factors requiring an interstitial (IS) approach for gynecologic tract brachytherapy (BT) may be associated with high morbidity despite the conformality maximizing effect of ISBT. We reviewed outcomes from a diverse, high-volume center to evaluate the association of clinical features and planning parameters with toxicity, with the hypothesis that MRI-guided volume-based planning mitigates clinicopathologic risk factors associated with treatment related fistula (TRF) after ISBT. We retrospectively reviewed patients treated with Syed-based ISBT at a single institution from 2014-2019. Fisher's exact was used for group comparison with p<0.05. Kaplan-Meier method was used to estimate local control (LC), overall survival (OS), and fistula-free survival (FFS). Cox regression was used for univariate (UVA) and multivariate analysis (MVA) to estimate hazard ratios (HR). Collinearity was assessed using variable inflation factor and Pearson's correlation. A total of 54 patients (median age 58 [IQR 46-67], 54% Caucasian, 39% African American, 15% Hispanic) treated with ISBT (89% MRI-guided) with median follow-up 32 months had initial (89%) or recurrent (11%) disease from cervical (70%), vaginal (15%), urethral (6%), and other cancers. At presentation 5.5% had clinically evident fistula. There was radiographic rectal and bladder involvement in 22.0% and 19.2%, respectively. 89% received concurrent chemotherapy and 98% received EBRT prior to ISBT with a cumulative median high-risk CTV (HRCTV) dose 80.8 Gy (IQR 76.8-84.3), bladder D2cc 84.3 Gy (IQR 75.8-89.0), and rectal D2cc 73.8 Gy (IQR 67.7-80.0 Gy). All 7 patients who developed a TRF (rectovaginal in 6/7 and vesicovaginal in 5/7) were former or current smokers, had primary cervical cancer, and received chemotherapy. Management included surgical intervention in 6 (85.7%). LC, OS, and FFS at 2-years was 89.3% (95% CI 75.9-95.4%), 87.8% (95% CI 66.9-89.8%), and 85.2% (95% CI 69.9-93.1%), respectively. On UVA, current smoking (HR 4.60, 95% CI 1.02-20.74), BT bladder D2cc (HR 1.63, 95% CI 1.07-2.47) and BT rectal Dmax (HR 1.30, 95% CI 1.07-1.58) predicted for increased risk of TRF. Most factors were non-significant including Charlson Comorbidity Index, age, BMI, surgical history, extent of vaginal involvement, race, HRCTV volume and number of needles used. No patients with radiographic bladder or rectal invasion developed TRF. On MVA, only smoking status (HR 14.05, 95% CI 1.48-133.1) remained significant. 0% of never (0/26), 20% of former (3/15) and 31% of current (4/13) smokers developed fistulas from toxicities (p<0.05). In patients with locally advanced cancers of the gynecologic tract treated with MRI-guided volume-based ISBT, smoking was the only factor predictive of TRF formation, occurring primarily in cervical cancer patients. This highlights the importance of smoking cessation during treatment and appropriately counseling patients at high risk for this morbidity.

GSOR08 Presentation Time: 12:35 PM: Use of Superflab during Interstitial Brachytherapy for Highly Locally Advanced Cancer of the Gynecological Tract to Minimize Toxicity

GSOR08 Presentation Time: 12:35 PM: Use of Superflab during Interstitial Brachytherapy for Highly Locally Advanced Cancer of the Gynecological Tract to Minimize Toxicity

Gynecological Fistulae-Has Anything Changed in the Diagnosis and Treatment over the Last Decade? A Narrative Literature Review.

Gynecological fistulae are a rare but severe complication of radiation therapy, pelvic surgery, prolonged labor, cesarean deliveries, or inflammatory bowel diseases. A gynecological fistula is an abnormal pathway formed between the urinary and gynecological tract, most commonly located between the urinary bladder and vagina. Vesico-uterine and vesicovaginal fistulae are an important health issue, common in women of reproductive age in developing countries with limited access to obstetrical care. Various surgical techniques have been described for VVF repair, depending on the location, severity, and cause of the fistula and the surgeon's experience. The purpose of our review was to evaluate the present state of knowledge about the prevalence and treatment of gynecological fistulae. The PubMed scientific database was searched for original articles on the subject of gynecological fistulae that had been published between 2013 and 2023.

Low-level expression of human Epidermal growth Factor Receptor-2 (HER2) in High-Grade Mullerian Tumors: Implications for therapy decision making

IntroductionReclassification of HER2-negative breast cancers to HER2 low-level expression allowed targeted anti-HER2 therapy in about 60% of patients, improving outcome. The high recurrence rates and often dismal outcomes with current therapies of high-grade Mullerian carcinomas, offers opportunity to explore anti-HER2 therapies in the gynecologic tract carcinomas. We investigated HER2 low expression as currently defined in breast carcinomas. MethodsWe reviewed all high-grade Mullerian cancers between 2016 and 2021, where HER2 by IHC and/or FISH tests were available. Additional clinical information was recorded, and statistical analysis was performed using SPSS (version 27). ResultsForty (49.4%) tumors were endometrial, 20 (24.7%) ovarian, 16 (19.8%) fallopian tubal, and 5 (6.2%) primarily peritoneal. Overall, 17 (21.0%) were HER2 positive (IHC 3+/IHC 2+/FISH amplified), 31 (38.3%) HER2 low (IHC 1+/2+/FISH non-amplified), and 30 (37.0%) were HER2 negative (IHC = 0). HER2 low expression was noted in 15% ovarian, 25% fallopian tubal, 53% endometrial, and 60% peritoneal tumors; 34% and 21% of serous carcinomas, 63% and 13% of carcinosarcomas, and 67% and 33% of endometrioid carcinomas were HER2 low and HER2 positive respectively. HER2 negative and HER2 low expression had a significant association with primary tumor location (p = 0.001); endometrium and peritoneal tumors were more likely to be HER2 low and HER2 negative. During a mean follow-up of 13.2 months (range: 1–34), 5% of the patients were deceased. ConclusionsBased on the current HER2-low recommendations in the breast, about one-third of patients with high-grade Mullerian carcinomas might qualify for anti-HER2 therapy with a potential for improved progression-free and overall survival.

Bi-allelic Dicer1 mutations in the gynecologic tract of mice drive lineage-specific development of DICER1 syndrome-associated cancer.

DICER1 is an RNase III enzyme essential for microRNA (miRNA) biogenesis through cleaving pre-miRNA hairpins. Germline loss-of-function DICER1 mutations underlie the development of DICER1 syndrome, a rare genetic disorder that predisposes children to cancer development in organs such as lung, gynecologic tract, kidney, and brain. Unlike classical tumor suppressors, the somatic "second hit" in DICER1 syndrome-associated cancers does not fully inactivate DICER1 but impairs its RNase IIIb activity only, suggesting a noncanonical two-hit hypothesis. Here, we developed a genetically engineered conditional compound heterozygous Dicer1 mutant mouse strain that fully recapitulates the bi-allelic DICER1 mutations in DICER1 syndrome-associated human cancers. Crossing this tool strain with tissue-specific Cre strains that activate Dicer1 mutations in gynecologic tract cells at two distinct developmental stages revealed that embryonic bi-allelic Dicer1 mutations caused infertility in females by disrupting oviduct and endometrium development and ultimately drove cancer development. These multicystic tubal and intra-uterine tumors histologically resembled a subset of DICER1 syndrome-associated human cancers. Molecular analysis uncovered accumulation of additional oncogenic events (e.g. aberrant p53 expression, Kras mutation, and Myc activation) in murine Dicer1 mutant tumors and validated miRNA biogenesis defects in 5P miRNA strand production, of which loss of let-7 family miRNAs was identified as a putative key player in transcriptomic rewiring and tumor development. Thus, this DICER1 syndrome-associated cancer model recapitulates the biology of human cancer and provides a unique tool for future investigation and therapeutic development.

Histopathological Findings in Hernia Sacs: A Clinical and Pathological Review.

Routine histopathological examination of hernia sac in adults remains a controversial topic. We undertook a retrospective study to assess possible clinical benefits of pathological examination of hernia sac specimens. Our pathology database between 1992 and 2020 was searched for adult specimens submitted as hernia sac. The clinical and pathological data of patients with abnormal histopathological findings were reviewed. There were 5424 hernia sac specimens (3722 inguinal, 1625 umbilical, and 77 femoral), 32/5424 (0.59%) with malignancies (28 epithelial and 4 lymphoid) and 25/32 were located in the umbilical region. Twelve out of twenty-five malignancies (48%) presented as primary clinical manifestations of the diseases (5 GI tract carcinomas, 5 gynecological tract carcinomas, and 2 lymphoid neoplasms); and 13/25 (52%) specimens were involved by previously known tumors (8 gynecological carcinomas, 3 colon carcinomas, 1 breast carcinoma, and 1 lymphoma). Among the 7 inguinal hernia sacs with malignancies, 3 (42.9%) were primary presentations of the tumors (2 prostatic carcinomas, 1 pancreatic carcinoma), and 4 (57.1%) were previously known tumors (2 ovarian carcinomas, 1 colon carcinoma, 1 lymphoid). Benign lesions were 12/5424 (0.22%), including 7 adrenal rests, 4 endometriosis, and 1 inguinal sarcoidosis. The incidence of hernia sacs with malignancies was 32/5424 (0.59%), most commonly from nearby organs in gynecological tract. However distant metastases from breast were also present. Near half of the hernia sac with malignancies (15/32, 47%) presented as the first clinical manifestation. Routine histopathological examination of hernia sac in adults is recommended, since it may provide important clinical information.

Diagnostic utility of PRAME immunohistochemistry in PEComa family of tumors and morphologic mimics with emphasis on the gynecologic tract

Perivascular epithelioid cell tumors (PEComas), rare mesenchymal tumors with myomelanocytic differentiation, can be a diagnostic challenge, often requiring a panel of immunohistochemicalmarkers. Preferentially expressed antigen in melanoma (PRAME) is a relatively new antigen with utility in diagnosing melanomas. This study aimed to survey PRAME expression patterns in the PEComa family of tumors and morphologic mimics. Twenty cases of PEComas and 27 non-PEComas (10 leiomyosarcomas, 3 smooth muscle tumors of uncertain malignant potential [STUMPs], 11 leiomyomas, 1 uterine inflammatory myofibroblastic tumor [IMT], and 2 low-grade endometrial stromal sarcomas [LGESSs]) were stained with PRAME and compared to previously performed HMB45 and Melan-A stains, when available. Tumors showing no or barely perceptible PRAME staining at 10× were considered negative. Tumors were considered positive if there was full nuclear staining evident at 10× in at least one 10× field. Diffuse staining was defined as positivity in at least 80% of tumor nuclei. Overall, PRAME was expressed in 70% of PEComas, with diffuse positivity in 60%. However, PRAME was not specific for PEComas, with immunopositivity in the majority (70%) of uterine leiomyosarcoma cases, though negative in STUMP, leiomyoma, IMT, and LGESS cases. PRAME sensitivity was 70% and specificity was 74%, while HMB45 was more sensitive (90%) and specific (100%), but only 15% of PEComas showed diffuse staining. Melan-A staining was less common than HMB45 or PRAME, with only 18.8% sensitivity but 100% specificity. Among gynecologic PEComas, PRAME was expressed in 75% overall and enriched among malignant cases (85.7% positive). As part of an immunohistochemical panel, PRAME could be useful in the workup of PEComa cases. In the future, PRAME-specific immunotherapies may be beneficial in treating patients with malignant PEComas.

Neuroendocrine Neoplasms of the Gastrointestinal Tract versus Neuroendocrine Neoplasms of the Gynaecological Tract-Comparison of the Risk Factors and Non-Surgical Treatment Efficacy.

Neuroendocrine tumours of the gastrointestinal tract are rare. The incidence has increased in recent years due to improvements in diagnostic methods for detecting these lesions. These tumours have a poor prognosis, especially when detected at an advanced stage. The basis of the treatment is resection, and non-surgical treatments are also standard in the treatment process. The situation is similar in even rarer neuroendocrine tumours of the reproductive tract, which are associated with an equally poor prognosis. In this article, we focus on learning about the risk factors (including genetic mutations) that increase the risk of the disease and comparing the effectiveness of non-surgical treatments-chemotherapy, radiotherapy, peptide receptor radionuclide therapy, somatostatin analogues, and immunotherapy. The efficacy of these treatments varies, and immunotherapy appears to be a promising form of treatment; however, this requires further research.

Peritumoural Oedema as a Predictor of Overall Survival for Patients with Posterior Fossa Metastases.

To analyse the relationship between peritumoural oedema volume and tumour volume in relation to the impact of metastatic posterior fossa tumour survival rates. An observational study. Umraniye Training and Research Hospital, İstanbul, Turkey, from 2011-2021. Fifty-six cancer patients who had been operated upon for cerebellar metastases were analysed retrospectively. To investigate the effect of oedema on survival, patients with a single cerebellar metastasis were evaluated retrospectively. Those patients had a single metastasis located in the cerebellum and did not receive radiotherapy or corticosteroids before surgery. OsiriX MD DICOM viewer was used to calculate the volumes of the tumour and the oedema using fluid-attenuated inversion recovery (FLAIR) and contrast-enhanced magnetic resonance imaging (MRI). The patients were separated into two groups, and the cut-off limit for the oedema to-tumour ratio was set to two. Survival analysis was performed on the two groups. When the primary sites of the tumours were evaluated, 60.7% were located in the lungs (n = 34), 10.7% were located in the breasts (n = 6), 10.7% were located in the gastrointestinal tract (n = 6), 7.1% were located in the renal region (n = 4), 5.4% were located in the gynaecologic tract (n = 3), and 5.4% were located in other parts of the body (n = 3). A univariate analysis showed that overall survival duration was significantly longer in the subgroup with breast cancer (83.3%) and in those patients with a peritumoural oedema volume to tumour volume ratio of less than two (27.6%, p <0.05). Negative prognostic factors were lung cancer and high peritumoural oedema volume. Significant peritumoural oedema was linked to a poor prognosis for cancer patients with a single cerebellar metastasis, especially with lung cancer as the primary source. Cerebellar metastases, Cerebellum, OsiriX MD, Tumour volume.

A few issues I have with peritoneal pathology

An unintended consequence of being a gynaecologic pathologist is secondarily becoming a peritoneal pathologist. Often, when considering differential diagnoses in the gynaecologic tract one must include numerous primary peritoneal diseases and vise versa. Determining the nature of borderline tumour ‘implants’, the origin of tumours involving the ovaries and mesothelial tumours that can mimic gynaecologic entities are all exercises that surgical pathologists must commonly undertake. This talk will review several of these considerations and highlight potential diagnostic pitfalls when dealing with lesions of the abdomen and pelvis.

Rare Primary Fallopian Tube Grade 2 Neuroendocrine Tumor: A Case Report With Review of Literature.

Neuroendocrine neoplasms commonly arise from the gastrointestinal tract and lungs. Less commonly, they may occur in the gynecologic tract, typically within the ovary of a mature cystic teratoma. Primary neuroendocrine neoplasms of the fallopian tube are exceptionally rare and only a total of 11 cases have been reported in the literature. We describe the first case to our knowledge of a primary grade 2 neuroendocrine tumor of the fallopian tube in a 47-yr-old female. In this report, we describe the case's unique presentation, review the published literature on primary neuroendocrine neoplasms of the fallopian tube, discuss the treatment options, and speculate on their origin and histogenesis.

High-Grade Sarcomas with Myogenic Differentiation Harboring Hotspot PDGFRB Mutations

PDGFRB-activating mutations have been reported in pediatric myofibroma and myofibromatosis. However, recurrent gain-of-function PDGFRB mutations have not been documented in sarcomas with myogenic differentiation. Driven by occasional sarcomas harboring PDGFRB mutations, we investigated their prevalence and clinicopathologic and genomic features in a large cohort of sarcomas. An institutional targeted DNA next-generation sequencing database was searched for sarcomas with myogenic differentiation harboring hotspot PDGFRB gene alterations. Among 3300 patients with sarcomas, 21 (0.6%) patients were identified (17 women, 4 men) with an age range of 35 to 88 years. The site distribution included 13 gynecologic tract (12 uteri, 1 vagina), 4 bone and soft tissue, and 4 viscera. All except 1 were high grade. Most patients were diagnosed as sarcomas with myogenic differentiation based on partial staining for 1 or more muscle markers, whereas 6 were labeled as leiomyosarcoma (LMS). Most tumors showed monomorphic spindle morphology, with either heterogeneous features of myofibroblastic and smooth muscle differentiation or an undifferentiated phenotype. Hormone receptors were negative in all uterine cases. PDGFRB immunostaining in all cases tested was strong and diffuse, whereas PDGFRA was negative/focal. The most frequent PDGFRB mutations were exon 12 (43%), exon 14 (N666K/S/T) (38%), and exon 18 (D850Y/H/V or insertion/deletion) (19%). The most frequent co-existing genetic alterations (26% to 37%) occurred in CDKN2A/B, TP53, TERT, and MED12. Moreover, PDGFRB-mutant sarcomas had an overall distinct genomic landscape compared with both uterine and soft tissue LMS control groups. These tumors were associated with a highly aggressive clinical course, with frequent distant metastases (81%) and death (76%), regardless of anatomic location, and worse overall survival compared with the 2 LMS control groups. This is the first study documenting recurrent hotspot PDGFRB alterations in high-grade sarcomas, which show a predilection for uterine location and myogenic differentiation that fall short of the diagnostic criteria for LMS. Further studies are needed to investigate the therapeutic potential of kinase inhibitors in this group of tumors.