Primary Ovarian Tumors Research Articles

Ovarian Steroid Cell Tumor About a Case

Tumors of the sex cords and stroma of the ovary are relatively rare, accounting for around 8% of all primary ovarian tumors. Steroid cell tumors of the ovary are rare, accounting for less than 0.1% of all ovarian tumors. The majority of these tumors produce steroid hormones, and only 10-15% of patients are asymptomatic. Although steroid cell tumors are generally benign, there is a risk of malignant transformation. Surgery is the main treatment. We report a case of a steroid cell tumour of the left ovary discovered on anatomopathological examination of the left adnexectomy operative specimen in a 47-year-old hypertensive diabetic patient who clinically presented with virilism with severe hirsutism, muscular and clitoral hypertrophy and frontotemporal baldness, and biologically increased androgens without associated hypercorticism, and in whom an abdomino-pelvic scanner showed a left latero-uterine mass measuring 74x66x64 mm, pelvic MRI showed a polylobed left ovarian mass classified ORADS 5, measuring 53x65x87 mm. After histological confirmation of the diagnosis, the patient was taken back for total surgery with total hysterectomy, right adnexectomy, omentectomy, appendectomy, multiple peritoneal biopsies, with no signs of malignancy on histological examination, simple postoperative follow-up and our patient placed under surveillance.

Synchronous primary ovarian tumours in postmenopausal women: A rare case report and literature review

The reported incidence of synchronous primary cancers of genital tract is 1-2%, among this synchronous primary ovarian tumour is rarest. Herein, a postmenopausal woman, who had previously undergone abdominal hysterectomy, presented with vague lower abdominal pain persisting for six months. A computed tomography scan confirmed the presence of an 8.1 x 8.2 cm cyst on her right ovary. Despite her CA125 levels being normal, she was scheduled for laparoscopic cystectomy. During the surgery, the left ovary was found to be enlarged, prompting bilateral salpingo-oophorectomy. Histological analysis revealed a serous cystadenoma in the left ovary and a mucinous cystadenoma in the right ovary.Most reported synchronous ovarian tumors are malignant, with only a few cases of benign synchronous ovarian tumors documented in the literature. Early diagnosis and reporting of such cases are crucial for improving our understanding of synchronous ovarian neoplasms, which can impact management strategies and help prevent complications.

Clinicopathological and epigenetic differences between primary neuroendocrine tumors and neuroendocrine metastases in the ovary.

Currently, the available literature provides insufficient support to differentiate between primary ovarian neuroendocrine tumors (PON) and neuroendocrine ovarian metastases (NOM) in patients. For this reason, patients with a well-differentiated ovarian neuroendocrine tumor (NET) were identified through electronic patient records and a nationwide search between 1991 and 2023. Clinical characteristics were collected from electronic patient files. This resulted in the inclusion of 71 patients with NOM and 17 patients with PON. Histologic material was stained for Ki67, SSTR2a, CDX2, PAX8, TTF1, SATB2, ISLET1, OTP, PDX1, and ARX. DNA methylation analysis was performed on a subset of cases. All PON were unilateral and nine were found within a teratoma (PON-T+). A total of 78% of NOM were bilateral, and none were associated with a teratoma. PON without teratomous components (PON-T-) displayed a similar insular growth pattern and immunohistochemistry as NOM (p > 0.05). When compared with PON-T+, PON-T- more frequently displayed ISLET1 positivity and were larger, and patients were older at diagnosis (p < 0.05). Unsupervised analysis of DNA methylation profiles from tumors of ovarian (n = 16), pancreatic (n = 22), ileal (n = 10), and rectal (n = 7) origin revealed that four of five PON-T- clustered together with NOM and ileal NET, whereas four of five PON-T+ grouped with rectum NET. In conclusion, unilateral ovarian NET within a teratoma should be treated as a PON. Ovarian NET localizations without teratomous components have a molecular profile analogous to midgut NET metastases. For these patients, a thorough review of imaging should be performed to identify a possible undetected midgut NET and a corresponding follow-up strategy may be recommended.

DICER1-Related Tumor Predisposition: Identification of At-risk Individuals and Recommended Surveillance Strategies.

DICER1-related tumor predisposition increases risk for a spectrum of benign and malignant tumors. In 2018, the International Pleuropulmonary Blastoma (PPB)/DICER1 Registry published guidelines for testing and imaging-based surveillance of individuals with a known or suspected germline DICER1 pathogenic or likely pathogenic (P/LP) variant. One of the Registry's goals is to continue to refine these guidelines as additional data becomes available. Individuals were enrolled in the International PPB/DICER1 Registry, the International Ovarian and Testicular Stromal Tumor Registry, and/or the National Cancer Institute Natural History of DICER1 Syndrome study. Review of participant records identified 713 participants with a germline DICER1 P/LP variant from 38 countries. To date, 5 cases of type I and 29 cases of type Ir PPB have been diagnosed by surveillance in enrolled individuals. One hundred and three individuals with a germline P/LP variant developed a primary ovarian Sertoli-Leydig cell tumor (SLCT) at a median age of 14 years (range: 11 months-66 years); 13% were diagnosed under age 8 years, the current age of onset of pelvic surveillance. Additionally, 4% of SLCTs were diagnosed before the age of 4 years. Ongoing data collection highlights the role of lung surveillance in the detection of early PPB and suggests that imaging-based detection and early resection may decrease the risk of advanced PPB. DICER1-related ovarian tumors were detected before age 8 years, prompting the Registry to recommend earlier initiation of ovarian surveillance with pelvic ultrasound beginning at the time of detection of a germline DICER1 P/LP variant.

High-grade serous ovarian cancer development and anti-PD-1 resistance is driven by IRE1α activity in neutrophils

ABSTRACT High-grade serious ovarian cancer (HGSOC) is an aggressive malignancy that remains refractory to current immunotherapies. While advanced stage disease has been extensively studied, the cellular and molecular mechanisms that promote early immune escape in HGSOC remain largely unexplored. Here, we report that primary HGSO tumors program neutrophils to inhibit T cell anti-tumor function by activating the endoplasmic reticulum (ER) stress sensor IRE1α. We found that intratumoral neutrophils exhibited overactivation of ER stress response markers compared with their counterparts at non-tumor sites. Selective deletion of IRE1α in neutrophils delayed primary ovarian tumor growth and extended the survival of mice with HGSOC by enabling early T cell-mediated tumor control. Notably, loss of IRE1α in neutrophils sensitized tumor-bearing mice to PD-1 blockade, inducing HGSOC regression and long-term survival in ~ 50% of the treated hosts. Hence, neutrophil-intrinsic IRE1α facilitates early adaptive immune escape in HGSOC and targeting this ER stress sensor might be used to unleash endogenous and immunotherapy-elicited immunity that controls metastatic disease.

Imaging of Ovarian Metastases (OM) from Breast Cancer: A Review

The ovary is a common site of metastases from other primary malignancies, and 5-30% of ovarian cancers are metastatic malignancies [1-16]. The most common primary origins are the breast, colon, and stomach[24]. Although imaging cannot always differentiate between secondary and primary ovarian neoplasms, and pathologic confirmation is generally required, it is important to recognize suggestive imaging features on pelvic US, CT and MR imaging [5,8-10,16,18-20]. OM from breast cancers is frequently asymptomatic until the masses have grown to certain size, and the metastatic tumors are frequently manifested as bilateral, solid, hypervascular, small ovarian masses [2]. Even though the Immunohistochemistry plays a key role in distinguishing between primary ovarian tumors and OM, and it was also important for confirming the metastatic nature of the ovarian lesion and diagnosing the primary tumor, imaging is vital to guide radiologists to include metastases in their differential diagnosis for atypical adnexal masses and in some cases avoid unnecessarie mutilative surgery [2-24]. In this review i will analize the main radiology features of OM from breast cancer to direct the surgery planning including referral practice, selection of candidates for primary chemotherapy by demonstration of non resectable disease, and tissue sampling in case of peritoneal carcinomatosis.

High-grade serous ovarian cancer development and anti-PD-1 resistance is driven by IRE1α activity in neutrophils.

High-grade serous ovarian cancer (HGSOC) is an aggressive malignancy that remains refractory to current immunotherapies. While advanced stage disease has been extensively studied, the cellular and molecular mechanisms that promote early immune escape in HGSOC remain largely unexplored. Here we report that primary HGSO tumors program neutrophils to inhibit T cell anti-tumor function by activating the endoplasmic reticulum (ER) stress sensor IRE1α. We found that intratumoral neutrophils exhibited overactivation of ER stress response markers compared with their counterparts at non-tumor sites. Selective deletion of IRE1α in neutrophils delayed primary ovarian tumor growth and extended the survival of mice with HGSOC by enabling early T cell-mediated tumor control. Notably, loss of IRE1α in neutrophils sensitized tumor-bearing mice to PD-1 blockade, inducing HGSOC regression and long-term survival in ∼50% of treated hosts. Hence, neutrophil-intrinsic IRE1α facilitates early adaptive immune escape in HGSOC and targeting this ER stress sensor might be used to unleash endogenous and immunotherapy-elicited immunity that controls metastatic disease.

Dual Primary Endometrial and Ovarian Tumors - A Case Report

Dual Primary Endometrial and Ovarian Tumors - A Case Report

Correlation of PD-L1 expression with different clinico-pathological and immunohistochemical features of ovarian surface epithelial tumors.

Primary carcinoma of the ovary (OCs) are responsible for a significant number of deaths related to cancer, and have the highest rate of death related to cancers of the female reproductive organs. Programmed cell death 1 (PD1) protein, acts as an immune checkpoint, and has an important role in the down-regulation of the immune system by preventing the activation of T-cells, which will weaken the autoimmunity and increases self-tolerance. This study aimed at the evaluation of the immunohistochemical (IHC) expression of PD-L1 in various primary surface ovarian epithelial tumours and to test its correlation with different clinicopathological parameters together with the expression of a panel of P53, ER and PR. A set of 102 cases of primary ovarian surface epithelial neoplasms (benign, borderline and malignant) were collected to construct Tissue Microarray (TMA) using 3 tissue cores from each case. IHC for PD-L1, p53, PR and ER was performed. The expression of PD-L1 was evaluated in relation to some clinicopathological parameters and to the expression patterns of other markers. Expression of PD-L1 was detected in about 51% (n = 36) of malignant tumours. The malignant group significantly showed PD-L1 positivity compared to borderline and benign groups. The malignant tumours significantly showed PD-L1 and total p53 positivity in comparison to borderline group. Also, malignant tumours significantly showed higher combined positivity of PD-L1 and either PR or ER compared to borderline and benign lesions. No significant correlation was appreciated between PD-L1 expression and with any of the studied clinicopathological parameters. This study showed a significant PD-L1 expression in malignant primary surface epithelial tumours. Construction of a panel of IHC markers, including PD-L1, could have a potential value to define patients those would benefit from the addition of immunotherapy to the treatment plan.

Laparoscopic-Assisted Fertility-Sparing Surgery for Growing Teratoma Syndrome of the Ovary: Experience From a Tertiary Center

Study ObjectiveThe main objective is to evaluate the feasibility of laparoscopic fertility-sparing surgery in women with growing teratoma syndrome. DesignRetrospective cohort study. SettingChinese tertiary university hospital. PatientsPatients with growing teratoma syndrome who underwent fertility-sparing surgery between January 2015 and August 2023. InterventionsBaseline characteristics and surgical outcomes were evaluated, including clinical information, surgical procedures, operative time, intraoperative blood loss, complications, length of hospital stay, and follow-up information. Measurement and Main ResultsTwenty-six patients with ovarian growing teratoma syndrome underwent fertility-sparing surgery: 12 had laparoscopic surgery and 14 underwent laparotomic surgery. In the laparoscopic group, the median age of the patients during initial management of immature teratoma or mixed malignant ovarian germ cell tumor was 14.0 years (interquartile range: 13.0-24.5 years). Eleven patients were nulliparous. The primary ovarian tumor was pure immature teratoma in 10 patients and mixed ovarian germ cell tumor in 2 patients. Complete laparoscopic tumor resection was achieved in 11 patients. Patients in laparoscopic group had shorter median operative time (76.5 vs 180.0 minutes, p = 0.001), lower estimated blood loss (20.0 vs 400.0 ml, p < 0.001), decreased postoperative hospital stay (2.0 vs 7.0 days, p < 0.001), compared with laparotomic surgery. There was no conversion to laparotomy and no perioperative complications. Histological examination confirmed mature teratoma in all cases. During a median follow-up of 21.9 months (interquartile range: 7.6-44.9 months), 11 patients were alive without disease and 1 was alive with disease. One pregnancy was achieved postoperatively. ConclusionLaparoscopic fertility-sparing surgery may represent a feasible option in well-selected patients with ovarian growing teratoma syndrome. Surgery should be performed in gynecologic oncology centers by experienced staff trained in endoscopic procedures. More research and long-time follow-up are needed to determine the oncological outcomes and safety of laparoscopic surgery in this population.

Prediction of postoperative residual primary ovarian neoplasm or metastatic lesion close to rectum of serous ovarian carcinoma based on clinical and MR T1-DEI features.

The optimal primary debulking surgery outcome of serous ovarian carcinoma (SOC) is greatly affected by primary ovarian neoplasm or metastatic lesion close to the rectum. To study the risk factors affecting postoperative residual primary ovarian neoplasm or metastatic lesion close to the rectum of SOC. The clinical and MRI data of 164 patients with SOC eligible from institution A (training and test groups) and 36 patients with SOC eligible from institution B (external validation group) were collected and retrospectively analyzed. The clinical data included age, serum carbohydrate antigen 125 (CA-125), human epididymis protein 4, and neutrophil-to-lymphocyte ratio (NLR). Magnetic resonance imaging (MRI) data included ovarian mass distribution, maximum diameter of ovarian mass, ovarian mass features, degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion, and amount of ascites. A model was established using multivariate logistic regression. By univariate and multivariate logistic regressions, CA-125 (P = 0.024, odds ratio [OR] = 3.798, 95% confidence interval [CI] = 1.24-13.32), NLR (P = 0.037, OR = 3.543, 95% CI = 1.13-12.72), and degree of rectal invasion of the primary ovarian neoplasm or metastatic lesion (P < 0.001, OR = 37.723, 95% CI = 7.46-266.88) were screened as independent predictors. The area under the curve values of the model in the training, test, and external validation groups were 0.860, 0.764, and 0.778, respectively. The clinical-radiological model based on T1-weighted dual-echo MRI can be used non-invasively to predict postoperative residual ovarian neoplasm or metastasis close to SOC in the rectum.

Immunohistochemical expression of SATB2 and PAX8 in differentiating primary from metastatic ovarian mucinous neoplasms.

Accurate stratification of an ovarian mucinous neoplasm as primary or secondary is always challenging as they show overlapping histomorphological and immunohistochemical features. Immunohistochemical staining for SATB2 and PAX8 was performed on 80 cases of mucinous ovarian neoplasms subdivided into 53 primary [25 primary ovarian mucinous carcinomas (POMCs) and 28 mucinous borderline tumors (MBTs)] and 27 secondary (12 of colonic origin, 7 of appendiceal origin, and 8 of gastric origin). Expression was correlated with different clinicopathologic parameters. PAX8-positive immunostaining was detected in 38 out of 53 cases (71.69%) of primary ovarian mucinous neoplasms (POMNs) with null positivity in the secondary ovarian mucinous tumors (0/27). SATB2-positive expression was detected in 16 out of 27 cases (59.26%) of the secondary ovarian mucinous tumors. None of the studied POMNs showed any positive immunostaining for SATB2 (0/53). A profile of SATB2-/PAX8+ and SATB2+/PAX8- can be used to differentiate POMNCs from secondary ovarian mucinous tumors of GI origin, respectively, with 100% specificity. PAX8 expression is associated with some clinicopathologic parameters providing the basis for the possible usage of PAX8 as prognostic marker.

Incidence of metastatic tumors to ovary (Krukenberg) versus primary ovarian neoplasms associated with colorectal cancer surgery

BackgroundAn ovarian mass in the setting of colorectal cancer (CRC) can be concerning due to the uncertainty of it being metastatic disease or primary ovarian neoplasm, leading to different referral and treatment options. Our objective was to determine the incidence of ovarian metastasis compared to primary ovarian pathology in women diagnosed with CRC. MethodsWomen aged 18 years or older, diagnosed with CRC in 2014 were included. 806 records were screened for findings of an ovarian mass until 2023. Pathology was determined via resection, biopsy, or imaging with follow-up. ResultsForty women (5.0 %) had an ovarian mass; 11 at index surgery and 29 on follow-up. Median age at CRC diagnosis was 62.7 years. The incidence of Krukenberg tumour (KT) was 3.2 % accounting for 65 % of ovarian masses. Approximately 20 % presented with synchronous KTs (n = 5) and 53.8 % had synchronous peritoneal carcinomatosis (n = 14). On follow-up, KTs were found in 72.4 % of the patients (n = 21). The Overall Survival (OS) in the KT group was 7.8 % with median survival of 30.4 months. The median time to developing KTs was 20.8 months with 2-year disease-free survival of 19.2 %. Synchronous KT presentation was the only factor associated with worse OS on univariate and multivariate analysis (HR 7.23, 95 % CI 1.57–33.28, P < 0.05). ConclusionThe risk of developing KT in women with CRC is 3.2 %, of which most (72.4 %) present with metachronous disease within 2 years of CRC diagnosis. Initial evaluation by a gastrointestinal tumor group is warranted. SynopsisIn this multicenter study involving 806 women diagnosed with colorectal cancer, most ovarian masses that were detected during or following surgery are colorectal metastases and not primary ovarian pathology.

Gastrointestinal Stromal Tumors (GISTs) Mimicking Primary Ovarian Tumors or Metastasizing to the Ovaries: A Systematic Literature Review.

Background: Gastrointestinal stromal tumors (GISTs) are a rare neoplasm, sometimes mimicking primary ovarian tumors (OTs) and/or metastasizing to the ovaries (M-OT). We performed a systematic literature review (SLR) of OTs and M-OTs, investigating differences in recurrence-free and overall survival. Methods: Our SLR was performed according to PRISMA guidelines, searching in Pubmed, Scopus, and Web of Science databases from inception until 21 April 2024. Results: Overall, 59 OTs (Group 1) and 21 M-OTs (Group 2) were retrieved. The absence of residual disease after surgery was achieved significantly in a higher percentage of patients with Group 1 GISTs (91.5%) compared with Group 2 GISTs (57.1%). Chemotherapy was more frequently administered to Group 2 patients (33% vs. 0%). Recurrence and deaths for disease were significantly more frequent in Group 2 than Group 1 cases (54.5% vs. 6.8%, and 37.5% vs. 9.8%, respectively). Conclusions: GISTs can rarely mimic primary ovarian cancers or even more rarely metastasize to the ovaries. Group 1 GISTs occurred in younger women, were not associated with elevated tumor markers, and had a better prognosis. In contrast, Group 2 GISTs occurred in older women, may exhibit elevated tumor markers, and presented a worse prognosis. However, no significant statistical difference for survival between the two studied groups was detected. Computed tomography scans can define the size of GISTs, which correlate to stage and prognostic risk classes. The gold standard treatment is complete surgical resection, which was achieved in almost all cases of Group 1 GISTs and in half of Group 2. Histopathology and immunohistochemistry are essential for the final diagnosis and guide chemotherapy treatment.

Trastuzumab deruxtecan (DS-8201a), a HER2-targeting antibody-drug conjugate, demonstrates in vitro and in vivo antitumor activity against primary and metastatic ovarian tumors overexpressing HER2.

High-grade serous ovarian cancer (HGSOC) and ovarian clear cell carcinoma (CC), are biologically aggressive tumors endowed with the ability to rapidly metastasize to the abdominal cavity and distant organs. About 10% of HGSOC and 30% of CC demonstrate HER2 IHC 3 + receptor over-expression. We evaluated the efficacy of trastuzumab deruxtecan (T-DXd; DS-8201a), a novel HER2-targeting antibody-drug conjugate (ADC) to an ADC isotype control (CTL ADC) against multiple HGSOC and CC tumor models. Eleven ovarian cancer cell lines including a matched primary and metastatic cell line established from the same patient, were evaluated for HER2 expression by immunohistochemistry and flow cytometry, and gene amplification by fluorescence in situ hybridization assays. In vitro experiments demonstrated T-DXd to be significantly more effective against HER2 3 + HGSOC and CC cell lines when compared to CTL ADC (p < 0.0001). T-DXd induced efficient bystander killing of HER2 non-expressing tumor cells when admixed with HER2 3 + cells. In vivo activity of T-DXd was studied in HER2 IHC 3 + HGSOC and CC mouse xenograft models. We found T-DXd to be significantly more effective than CTL ADC against HER2 3 + HGSOC (KR(CH)31) and CC (OVA10) xenografts with a significant difference in tumor growth starting at day 8 (p = 0.0003 for KR(CH)31, p < 0.0001 for OVA10). T-DXd also conferred a survival advantage in both xenograft models. T-DXd may represent an effective ADC against primary and metastatic HER2-overexpressing HGSOC and CC.

Combining EHMT and PARP Inhibition: A Strategy to Diminish Therapy-Resistant Ovarian Cancer Tumor Growth while Stimulating Immune Activation.

Despite the success of Poly-ADP-ribose polymerase inhibitors (PARPi) in the clinic, high rates of resistance to PARPi presents a challenge in the treatment of ovarian cancer, thus it is imperative to find therapeutic strategies to combat PARPi resistance. Here, we demonstrate that inhibition of epigenetic modifiers Euchromatic histone lysine methyltransferases 1/2 (EHMT1/2) reduces the growth of multiple PARPi-resistant ovarian cancer cell lines and tumor growth in a PARPi-resistant mouse model of ovarian cancer. We found that combinatory EHMT and PARP inhibition increases immunostimulatory dsRNA formation and elicits several immune signaling pathways in vitro. Using epigenomic profiling and transcriptomics, we found that EHMT2 is bound to transposable elements, and that EHMT inhibition leads to genome-wide epigenetic and transcriptional derepression of transposable elements. We validated EHMT-mediated activation of immune signaling and upregulation of transposable element transcripts in patient-derived, therapy-naïve, primary ovarian tumors, suggesting potential efficacy in PARPi-sensitive disease as well. Importantly, using multispectral immunohistochemistry, we discovered that combinatory therapy increased CD8 T cell activity in the tumor microenvironment of the same patient-derived tissues. In a PARPi-resistant syngeneic murine model, EHMT and PARP inhibition combination inhibited tumor progression and increased Granzyme B+ cells in the tumor. Together, our results provide evidence that combinatory EHMT and PARP inhibition stimulates a cell autologous immune response in vitro, is an effective therapy to reduce PARPi resistant ovarian tumor growth in vivo, and promotes anti-tumor immunity activity in the tumor microenvironment of patient-derived ex vivo tissues of ovarian cancer.

The frequency and prognostic role of P53 and P16 immunoexpression in primary ovarian mucinous tumors

BackgroundPrimary ovarian mucinous tumors are uncommon. Factors leading to invasive progression and metastatic disease have not been fully delineated yet. The aim of this study is to determine the rates of p53 and p16 immunoexpressions in primary ovarian mucinous tumors, to investigate their relationship with clinicopathologic factors and their impact on prognosis and survival. MethodsSeventy-eight primary ovarian mucinous tumors (30 mucinous cystadenomas, 30 mucinous borderline tumors (MBOT), 18 mucinous carcinomas (MOC)) were evaluated immunohistochemically with p53 and p16 staining. The demographic, clinicopathological data, and postoperative follow-up findings of the patients were analyzed. ResultsMutation-type p53 staining was present in 1/30 (3.3 %) cystadenoma, 10/30 (33.3 %) MBOT and 9/18 (50 %) MOC (p = 0.001). p16 overexpression was detected in 3/30 (10.0 %) MBOT and 5/18 (27.8 %) MOC, but not in any cystadenoma (p = 0.04). The frequency of mutation-type p53 staining in MBOTs with microinvasion was higher (71.4 %) than in those without (28.6 %, p = 0.026). The frequencies of p16 or p53 mutations were similar in MBOTs with and without intraepithelial carcinoma, or mural nodule (p > 0.05). In MOCs with ovarian surface involvement, mutation-type p53 staining was detected in 66.7 % (6/9) and p16 overexpression in 55.6 % (5/9) of the cases. A significant difference was found between MOCs with or without ovarian surface involvement regarding the frequency of p16 overexpression (p = 0.029). Any relationship was not detected between survival and p53 and p16 expression in MOCs (p > 0.05). Conclusionp53 and p16 mutation rates were higher in MOCs compared to mucinous cystadenomas and MBOTs and suggest a relevant role in the development of primary ovarian mucinous carcinoma, however further studies are needed in this regard.

Characterization of innate lymphoid cell subsets infiltrating melanoma and epithelial ovarian tumors

ABSTRACT The innate lymphoid cell (ILC) family is composed of heterogeneous innate effector and helper immune cells that preferentially reside in tissues where they promote tissue homeostasis. In cancer, they have been implicated in driving both pro- and anti-tumor responses. This apparent dichotomy highlights the need to better understand differences in the ILC composition and phenotype within different tumor types that could drive seemingly opposite anti-tumor responses. Here, we characterized the frequency and phenotype of various ILC subsets in melanoma metastases and primary epithelial ovarian tumors. We observed high PD-1 expression on ILC subsets isolated from epithelial ovarian tumor samples, while ILC populations in melanoma samples express higher levels of LAG-3. In addition, we found that the frequency of cytotoxic ILCs and NKp46+ILC3 in tumors positively correlates with monocytic cells and conventional type 2 dendritic cells, revealing potentially new interconnected immune cell subsets in the tumor microenvironment. Consequently, these observations may have direct relevance to tumor microenvironment composition and how ILC subset may influence anti-tumor immunity.

Methods for assessing and removing non-specific photoimmunotherapy damage in patient-derived tumor cell culture models.

Tumor-targeted, activatable photoimmunotherapy (taPIT) has been shown to selectively destroy tumor in a metastatic mouse model. However, the photoimmunoconjugate (PIC) used for taPIT includes a small fraction of non-covalently associated (free) benzoporphyrin derivative (BPD), which leads to non-specific killing invitro. Here, we report a new treatment protocol for patient-derived primary tumor cell cultures ultrasensitive to BPD photodynamic therapy (BPD-PDT). Based on free BPD efflux dynamics, the updated invitro taPIT protocol precludes non-specific BPD-PDT by silencing the effect of free BPD. Following incubation with PIC, incubating cells with PIC-free medium allows time for expulsion of free BPD whereas BPD covalently bound to PIC fragments is retained. Administration of the light dose after the intracellular free BPD drops below the threshold for inducing cell death helps to mitigate non-specific damage. In this study, we tested two primary ovarian tumor cell lines that are intrinsically chemoresistant, yet ultrasensitive to BPD-PDT such that small amounts of free BPD (afew percent of the total BPD dose) lead to potent induction of cell death upon irradiation. The modifications in the protocol suggested here improve invitro taPIT experiments that lack invivo mechanisms of free BPD clearance (i.e., lymph and blood flow).

Carcinoid Heart Disease Associated with Primary Ovarian Carcinoid Tumor: A Rare Presentation

Primary ovarian carcinoid tumors, an extremely rare subset of ovarian malignancies (&lt;0.1% of cases), typically manifest with abdominal pain and bloating. The occurrence of carcinoid heart disease (CHD) without classic carcinoid syndrome features is exceptionally uncommon. We report a 54-year-old female presenting with dyspnea and edema over months, lacking typical carcinoid syndrome signs. Initial assessments diagnosed heart failure, supported by elevated NT-Pro BNP, echocardiographic right ventricular dilation, and pulmonary/tricuspid valve regurgitation (normal left ventricular function). Right heart catheterization showed normal pulmonary/right ventricular pressures. Subsequent investigations (computed tomography thorax abdomen pelvis, 5-hydroxyindole acetic acid levels) strongly suggested carcinoid disease, confirmed by an octreotide scan revealing an octreotide-secreting ovarian carcinoid tumor. Surgical intervention included tricuspid and pulmonary valve repair, total abdominal hysterectomy, and bilateral salpingo-oophorectomy. Primary ovarian carcinoid tumors, though rare, may lead to unexpected complications like CHD. Timely diagnosis and intervention are pivotal for optimizing patient outcomes in such cases.