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Uterine PEComas often present a diagnostic challenge as they share morphological and immunohistochemical features with smooth muscle tumors. Herein we evaluated a series of 19 uterine PEComas to compare the degree of melanocytic marker expression with their molecular profile. Patients ranged from 32–77 (median 48) years, with six tumors classified as malignant based on the modified gynecologic-specific prognostic algorithm. All patients with malignant PEComas were alive with disease or dead of disease at last follow-up, while all those of uncertain malignant potential were alive and well (median follow-up, 47 months). Seventeen of 19 (89%) PEComas harbored either a TSC1 or TSC2 alteration. One of the two remaining tumors showed a TFE3 rearrangement, but the other lacked alterations in all genes evaluated. All showed at least focal (usually strong) positivity for HMB-45, with 15/19 (79%) having >50% expression, while the tumor lacking TSC or TFE3 alterations was strongly positive in 10% of cells. Melan-A and MiTF were each positive in 15/19 (79%) tumors, but staining extent and intensity were much more variable than HMB-45. Five of six (83%) malignant PEComas also harbored alterations in TP53, ATRX, or RB1, findings not identified in any tumors of uncertain malignant potential. One malignant PEComa was microsatellite-unstable/mismatch repair protein-deficient. In summary, TSC alterations/TFE3 fusions and diffuse (>50%) HMB-45 expression are characteristic of uterine PEComas. In morphologically ambiguous mesenchymal neoplasms with myomelanocytic differentiation, especially those with metastatic or recurrent disease, next-generation sequencing is recommended to evaluate for TSC alterations; as such, patients can be eligible for targeted therapy.

SummaryER and PR regulate growth and differentiation in normal ovaries and fallopian tubes and in HGSC transformation and progression. Higher PR expression was associated with improved survival outcomes, while high ER expression was associated with worse survival in patients with HGSC. Here, we show that patients with ER+PR+ tumors have longer overall survival and confirm the role of PR as a prognostic marker of survival and response to chemotherapy. Gene expression analysis demonstrated up-regulation of the ATM signaling pathway in the ER+PR+ subgroup when compared to ER+PR− tumors. Up-regulation of interferon alpha, beta and gamma signaling, and antigen presentation pathways were identified in ER+PR− compared to ER−PR+. In summary, this study elucidated that the genomic and transcriptomic signatures related to ER/PR status in HGSC have clinical prognostic value.

Heatmap of protein functions

The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: (i) benign gynecologic disease (controls, n = 11), (ii) low-grade endometrial carcinoma (n = 30), and (iii) high-grade endometrial carcinoma (n = 20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign versus carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications.Significance:The vaginal microbiome reliably segregates not just benign gynecologic condition from endometrial cancer, but also predicts cancer grade and histology. Patterns of microbial abundance and gene expression should be increasingly considered as a factor in the evolution of precision medicine approaches, especially as they relate to cancer screening, disease pathogenesis, and patient-centered outcomes.

Heatmap of abundance values

Additional statistical methods

Biomarker discovery by histology

Individual Specimen Reads

Analysis of Confounders

Functional pathway analysis

Microbial alpha diversities

Microbial abundance by histotype

Herein we evaluated a series of 21 embryonal rhabdomyosarcomas of the uterine corpus (ucERMS), a rare neoplasm, to characterize their morphology, genomics, and behavior. Patients ranged from 27 to 73 (median 52) years and tumors from 4 to 15 (median 9) cm, with extrauterine disease noted in two. Follow-up (median 16 months) was available for 14/21 patients; nine were alive and well, four died of disease, and one died from other causes. Most tumors (16/21) showed predominantly classic morphology, comprised of alternating hyper- and hypocellular areas of primitive small cells and differentiating rhabdomyoblasts in a loose myxoid/edematous stroma. A cambium layer was noted in all; seven had heterologous elements (six with fetal-type cartilage) and eight displayed focal anaplasia. The remaining five neoplasms showed only a minor component (

The human microbiome has been strongly correlated with disease pathology and outcomes, yet remains relatively underexplored in patients with malignant endometrial disease. In this study, vaginal microbiome samples were prospectively collected at the time of hysterectomy from 61 racially and ethnically diverse patients from three disease conditions: (i) benign gynecologic disease (controls, n = 11), (ii) low-grade endometrial carcinoma (n = 30), and (iii) high-grade endometrial carcinoma (n = 20). Extracted DNA underwent shotgun metagenomics sequencing, and microbial α and β diversities were calculated. Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Differential abundance was calculated, and machine learning utilized to assess the predictive value of bacterial abundance to distinguish grade and histology. Both α- and β-diversity were associated with patient tumor grade. Four vaginal CST were identified that associated with grade of disease. Different histologies also demonstrated variation in CST within tumor grades. Using supervised clustering algorithms, critical microbiome markers at the species level were used to build models that predicted benign versus carcinoma, high-grade carcinoma versus benign, and high-grade versus low-grade carcinoma with high accuracy. These results confirm that the vaginal microbiome segregates not just benign disease from endometrial cancer, but is predictive of histology and grade. Further characterization of these findings in large, prospective studies is needed to elucidate their potential clinical applications. Significance: The vaginal microbiome reliably segregates not just benign gynecologic condition from endometrial cancer, but also predicts cancer grade and histology. Patterns of microbial abundance and gene expression should be increasingly considered as a factor in the evolution of precision medicine approaches, especially as they relate to cancer screening, disease pathogenesis, and patient-centered outcomes.

Teratomas are tumors of germ cell origin, and in the female genital tract are subclassified as immature or mature based on the presence or absence, respectively, of immature elements. Somatic tumors may also develop in association with teratomas, and most commonly include thyroid tumors, carcinoids and carcinomas. We report herein 2 rare forms of gynecologic teratomas: 1 case of immature teratoma of the uterus and 1 case of a benign follicular hamartoma arising in association with mature cystic teratoma of the ovary.

Objective Mutations in the MAP kinase pathway (KRAS, NRAS, BRAF) are common in low grade serous ovarian carcinoma (LGSOC). The effect of these and other mutations on RNA transcription in this disease is poorly understood. Our objective was to describe patterns of somatic mutations and gene transcription in a racially diverse population with LGSOC. Methods Utilizing an institutional tumor registry, patients with LGSOC were identified and charts were reviewed. RNA was extracted from available tumor tissue. Commercial tumor profiling results were analyzed with PanCancer pathway nanoString mRNA expression data. Along with nanoString n-Solver software, Chi-squared, Fishers Exact, and Cox proportional hazards models were used for statistical analysis, with significance set at p Results 39 patients were identified—20% Black, 43% Hispanic, and 36% non-Hispanic White. 18 patients had commercial somatic DNA test results, and 23 had available tumor tissue for RNA extraction and nanoString analysis. The most common somatic alterations identified was KRAS (11 patients, 61%), followed by ERCC1 and TUBB3 (9 each, 50%). KRAS mutations were less common in smokers (14.3% vs 90.9%, p = 0.002). RNA expression analysis demonstrated a greater than two-fold decrease in expression of HRAS in tumors from older patients (p = 0.04), and a greater than two-fold decrease in the expression of HRAS in recurrent tumors (p = 0.007). No significant differences were seen in somatic testing results, RNA expression analysis, or progression free survival between different racial and ethnic cohorts. Conclusions Somatic deficiencies in ERCC1, TUBB3, and KRAS are common in LGSOC in a population of minority patients. HRAS demonstrates decreased expression in tumors from older patients and recurrent tumors.

Verruciform proliferations of the vulva unrelated to HPV infection are rare. The term differentiated exophytic vulvar intraepithelial lesion (DEVIL) was recently proposed for these lesions, which harbor recurrent PIK3CA mutations. It is still unclear whether DEVIL is related to verrucous carcinoma, a neoplasm characterized by persistence and local recurrence but nil risk of distant spread. Specimens identified using the words “verruciform” and “verrucous” were reviewed. Diagnosis of DEVIL required verruciform acanthosis, hyper and/or parakeratosis, hypogranulosis, cytoplasmic pallor, and bland nuclei. Verrucous carcinoma required, in addition, discontinuous, bulbous, puzzle-like nests in the stroma. A targeted next-generation sequencing using a custom 11-gene panel was performed. Eighteen specimens corresponding to ten patients with DEVIL and/or verrucous carcinoma were included. Median age at presentation was 66 years for DEVIL and 70 years for verrucous carcinoma. A similar spectrum of prevalent mutations was found in both lesions involving HRAS, PIK3CA, and BRAF. DEVIL preceded verrucous carcinoma and/or was diagnosed concurrently or in subsequent follow-up in five patients. In four of these, the same mutation was identified in DEVIL and synchronous or metachronous carcinoma. All cases showed wild-type 53 staining and lacked pathogenic TP53 mutations. DEVIL is a rare form of squamous proliferation characterized by prevalent PIK3CA and HRAS mutations. Its temporal relationship with verrucous carcinoma and their shared mutational profile in some patients suggest that DEVIL is a precursor of verrucous carcinoma. Moreover, given their morphologic and molecular overlap and the nil risk of verrucous carcinoma for distant spread, it is conceivable that DEVIL and verrucous carcinoma represent a spectrum of the same entity.

Primary sarcomas of the lung are extremely uncommon. A diverse group of round cell sarcomas has been reported to originate in this location, including Ewing sarcoma, desmoplastic small round cell tumor, rhabdomyosarcoma, and poorly differentiated synovial sarcoma. The rarity of these tumors presents a potential pitfall; without careful study, they may easily be misidentified as the significantly more common poorly differentiated carcinoma. While histomorphology is a key aspect of correctly identifying a sarcoma, ancillary testing has become increasingly important in making a definitive diagnosis, as more and more recurrent genetic alterations are discovered and new entities are defined. We present three cases of primary round cell sarcomas of the lung that proved diagnostically challenging, describe the features and ancillary testing that led to the correct diagnoses, and discuss classic and evolving entities among sarcomas with round cell morphology.

BackgroundThe vaginal microbiome is an underexplored environment which may yield insights about endometrial cancer (EC) pathophysiology and serve as an early marker of disease. Our objective was to evaluate the preoperative vaginal microbiome in women undergoing hysterectomy for benign conditions and EC to identify patterns which could segregate benign disease from EC, and to assess if the microbiome distinguishes low-grade (LG) from high-grade (HG) histologies.MethodsVaginal microbiome samples were prospectively collected at the time of hysterectomy, and clinicopathologic data collected. Extracted DNA underwent shotgun metagenomics sequencing. Microbial diversity was calculated using the Shannon Index (α-diversity) and PERMANOVA (β-diversity). Hierarchical clustering was used to describe community state types (CST), which were then compared by microbial diversity and grade. Machine learning was utilized to assess the predictive value of grade and histology based on relative bacterial abundance.Results61 patients participated: 1) benign gynecologic disease (n=11), 2) LG EC (n=30), and 3) HG EC (n=20). 40 (62.5%) were White, 22 (34.3%) were Black, and 37 (57.8%) were Hispanic. Both α- and β-diversity were associated with tumor grade (p□=□0.026 and p□=□0.035, respectively). Four CST were identified that associated with grade of disease (p=0.036). Different histologies demonstrated variation in CST even within tumor grades (p=0.017). Markers at the species level informed models that predicted benign vs cancer (AUC 0.878), HG versus benign (AUC=0.803), and HG versus LG (AUC=0.771) with high accuracy.ConclusionsThe vaginal microbiome segregates benign disease from EC, and is predictive of histology and grade, suggesting it may be an effective tool for screening.

Besides BRCA1 and BRCA2, several other inheritable mutations have been identified that increase ovarian cancer risk. Surgical excision of the fallopian tubes and ovaries reduces ovarian cancer risk, but for some non-BRCA hereditary ovarian cancer mutations the benefit of this intervention is unclear. The fallopian tubes of women with hereditary ovarian cancer mutations provide many insights into the early events of carcinogenesis and process of malignant transformation. Here we review cancer pathogenesis in hereditary cases of ovarian cancer, the occurrence of pre-invasive lesions and occult carcinoma in mutation carriers and their clinical management.

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ObjectiveOvarian cancer in Black women is common in many West African countries but is relatively rare in North America. Black women have worse survival outcomes when compared to White women. Ovarian cancer histotype, diagnosis, and age at presentation are known prognostic factors for outcome. We sought to conduct a preliminary comparative assessment of these factors across the African diaspora.MethodsPatients diagnosed with ovarian cancer (all histologies) between June 2016-December 2019 in Departments of Pathology at 25 participating sites in Nigeria were identified. Comparative population-based data, inclusive of Caribbean-born Blacks (CBB) and US-born Blacks (USB), were additionally captured from the International Agency for Research on Cancer and Florida Cancer Data Systems. Histology, country of birth, and age at diagnosis data were collected and evaluated across the three subgroups: USB, CBB and Nigerians. Statistical analyses were done using chi-square and student’s t-test with significance set at pResultsNigerians had the highest proportion of germ cell tumor (GCT, 11.5%) and sex-cord stromal (SCST, 16.2%) ovarian cancers relative to CBB and USB (p=0.001). CBB (79.4%) and USB (77.3%) women were diagnosed with a larger proportion of serous ovarian cancer than Nigerians (60.4%) (pConclusionThere is significant variation in age of diagnosis and distribution of ovarian cancer histotype/diagnosis across the African diaspora. The etiology of these findings requires further investigation.

Introduction Variability in endometrial cancer (EC) risk and outcomes exist, with Black women disproportionately negatively affected related to White women. The biologic etiologies of these observations are poorly understood. Our objective was to describe the somatic mutations of the tumor genome and compare them to RNA expression in self-identified Black and White women diagnosed with EC. Methods Women with newly diagnosed EC and undergoing hysterectomy were recruited prospectively. Fresh tumors obtained at the time of surgery were flash-frozen, underwent DNA and RNA extraction and were submitted for whole exome sequencing (WES) analysis (DNA) or bulk RNA sequencing analysis. Differentially expressed genes between racial groups and tumor grade were calculated using Deseq2. Genomic ancestry was determined using ADMIXTURE. Chi-square and Mann Whitney U tests were used for analyses, with a threshold for significance of p14% African ancestry. The remaining 13 (26.5%) patients had admixed European and Native American ancestry, with Citation Format: Alex P. Sanchez-Covarrubias, Ramlogan Sowamber, Leah Dodds, Andre Pinto, Sophia George, Matthew Schlumbrecht. Endometrial cancer genomics varies by race [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C052.

Recognising metastatic gastrointestinal and pancreatobiliary tumours to gynaecological sites may be challenging, as primary Mullerian tumours can demonstrate similar histological features. Endocervical adenocarcinomas can be of gastric and intestinal types, endometrial lesions may show gastrointestinal phenotype, and finally, mucinous tumours with secondary involvement of the ovaries may mimic primary neoplasms. The aim of this review is to address selected neoplastic entities of the gynaecological tract with gastric and intestinal differentiation and provide helpful clinical and pathological parameters for the diagnosis. A brief overview of metastatic tumours originating from the gastrointestinal and pancreaticobiliary tracts is also provided, including the most common pathological features.

The cubic-plus-association (CPA) equation of state (EoS) is unable to correctly describe the vapor–liquid critical behavior of pure fluids and mixtures because of its classical behavior. In fact, the traditional parametrization procedure (i.e., matching the saturated pressure and liquid density curves far from the critical point) causes an overprediction of the critical pressures and temperatures of pure components. Besides, the deviations with respect to experimental data are even larger for systems containing hydrogen-bonding species, in comparison to systems composed of nonassociating molecules. To improve the representation of the thermodynamic properties of fluids in near-critical regions with CPA, we have applied White’s recursive procedure to introduce density fluctuations in the classical model, allowing the correct description of the nonanalytical behavior of real fluids close to the critical point. The resulting model (i.e., the crossover CPA (CCPA) EoS) is capable of accurately representing the phase behavior of fluids, specifically normal alkanes and alcohols, carbon dioxide, and water as well as some of their binary mixtures, far away from and close to the critical region. This is shown by the comparison of the results obtained from CCPA and classical EoS with the experimental data.

SMAD4 is a tumor suppressor gene that plays a role in cancer initiation and progression. A few studies have explored the value of immunohistochemistry for SMAD4 in gynecologic neoplasms, mainly in the ovary. However, literature is sparse when it comes to other sites such as endometrium and cervix, as well as in benign and borderline ovarian mucinous neoplasms. The aim of this study was to assess the expression of SMAD4 in various gynecologic tumors. We selected primary gynecologic tumors comprising a spectrum of neoplasms showing mucinous differentiation. Few cases of metastatic tumors were also included. A total of 103 cases were retrieved, including tumors of ovarian origin (13 mucinous adenocarcinomas, 9 mucinous borderline tumors, 19 mucinous cystadenomas, and 3 mucinous tumors arising from teratomas), 36 of endometrial origin (23 endometrioid adenocarcinomas with mucinous differentiation and 13 mucinous adenocarcinomas), 17 cases of cervical carcinoma (16 of usual type and 1 of gastric type), and 6 metastatic adenocarcinomas to ovary. SMAD4 immunohistochemistry was retained in most primary tumors, except in 3 endocervical adenocarcinomas (2 usual-type, 1 gastric-type) and in one mucinous carcinoma arising from an ovarian teratoma. Of the 6 metastatic cases, 4 showed SMAD4 loss. In summary, retained expression of SMAD4 was seen in 95.8% of primary gynecologic neoplasms. These results can be of utility when dealing with mucinous lesions for which metastatic origin is suspected. Loss of SMAD4 expression virtually excludes primary tumors of endometrial or ovarian origin, but is of less utility when evaluating carcinomas involving the cervix.

The entity "pericytoma with t(7;12)" was described as a rare, distinct perivascular myoid neoplasm provisionally classified within the family of myopericytic tumors that demonstrates t(7;12)(p22;q13) translocation with resultant ACTB-GLI1 fusion and biologically was felt to behave in an indolent fashion. However, a recent study showed that tumors with this and similar translocations may have variable morphology and immunohistochemical phenotype with inconsistent myopericytic characteristics and a propensity for metastasis, raising questions regarding the most appropriate classification of these neoplasms. Herein, we report 3 additional patients with tumors harboring t(7;12) and ACTB-GLI1 fusion. The tumors arose in adults and involved the proximal tibia and adjacent soft tissues, scapula and adjacent soft tissues, and ovary. All tumors were composed of round-to-ovoid cells with a richly vascularized stroma with many small, delicate, branching blood vessels, where the neoplastic cells were frequently arranged in a perivascular distribution. Both tumors involving bone showed histologic features of malignancy. By immunohistochemistry, all tested tumors were at least focally positive for smooth muscle actin (3/3) and CD99 (patchy) (2/2), with variable staining for muscle-specific actin (2/3), S100 protein (1/3), epithelial membrane antigen (2/3), and pan-keratin (1/3); all were negative for desmin and WT1 (0/3). The 2 patients with bone tumors developed metastases (27 and 84 mo after diagnosis). Whether these tumors are best classified as malignant myopericytoma variants or an emerging translocation-associated sarcoma of uncertain differentiation remains to be fully clarified; however, our study further documents the potential for these tumors to behave in an aggressive fashion, sometimes over a prolonged clinical course.

In this work, two crossover procedures were applied to the Soave-Redlich-Kwong (SRK) equation of state (EoS) in order to describe the thermodynamic behavior of hydrocarbons from far away up to close to the critical point. The first one is based on a renormalization group theory method, which uses a recursive procedure originally proposed by White and coworkers (Salvino and White, J. Chem. Phys. 96 (1992) 4559–4568). The second one incorporates the scaling laws close to the critical point into the cubic EoS, and was developed by Kiselev (Kiselev, Fluid Phase Equilibria, 147 (1998) 7–23). The classical and crossover SRK EoS are applied to describe the phase behavior of pure n-alkanes (from methane to n-decane), and the comparison with experimental data indicates that the non-mean-field models are superior to the classical one for the representations of vapor-liquid coexistence data, isothermal pressure-density data and critical properties. Additionally, a thorough comparison of the two crossover approaches is done indicating the advantages and disadvantages of each approach.

Wilms tumor (WT) is an uncommon malignant neoplasm that occurs predominantly in the kidney of pediatric patients; its extrarenal counterpart is exceedingly rare. We present the case of an adult female diagnosed with uterine WT. Following hysterectomy due to a uterine mass, histopathologic examination demonstrated a triphasic malignancy composed of epithelial, stromal, and blastemal elements. The characteristic morphologic features, which were supported by immunohistochemical analysis, were diagnostic of WT of the uterus. A summary of the main clinicopathologic parameters, along with a review of all previously reported cases, are described.

Uterine PEComas often present a diagnostic challenge as they share morphological and immunohistochemical features with smooth muscle tumors. Herein we evaluated a series of 19 uterine PEComas to compare the degree of melanocytic marker expression with their molecular profile. Patients ranged from 32-77 (median 48) years, with six tumors classified as malignant based on the modified gynecologic-specific prognostic algorithm. All patients with malignant PEComas were alive with disease or dead of disease at last follow-up, while all those of uncertain malignant potential were alive and well (median follow-up, 47 months).Seventeen of 19 (89%) PEComas harbored either a TSC1 or TSC2 alteration. One of the two remaining tumors showed a TFE3 rearrangement, but the other lacked alterations in all genes evaluated. All showed at least focal (usually strong) positivity for HMB-45, with 15/19 (79%) having50% expression, while the tumor lacking TSC or TFE3 alterations was strongly positive in 10% of cells. Melan-A and MiTF were each positive in 15/19 (79%) tumors, but staining extent and intensity were much more variable than HMB-45. Five of six (83%) malignant PEComas also harbored alterations in TP53, ATRX, or RB1, findings not identified in any tumors of uncertain malignant potential. One malignant PEComa was microsatellite-unstable/mismatch repair protein-deficient.In summary, TSC alterations/TFE3 fusions and diffuse (50%) HMB-45 expression are characteristic of uterine PEComas. In morphologically ambiguous mesenchymal neoplasms with myomelanocytic differentiation, especially those with metastatic or recurrent disease, next-generation sequencing is recommended to evaluate for TSC alterations; as such, patients can be eligible for targeted therapy.

We present a rare case pulmonary metastasis of an early stage endometrial cancer nearly 20 years after curative surgical resection. Our patient had a remote history of hysterectomy for endometrial cancer in 1998 and later had Stage 1B right upper lobe lung cancer treated with lobectomy and adjuvant chemotherapy in 2014. She was found to have an enlarging nodule in the left upper lobe in 2018, which was thought to be another primary lung cancer. She underwent left upper lobe segmentectomy for an intraoperative diagnosis of adenocarcinoma by diagnostic wedge resection of the lung nodule. Final pathologic examination of the resected tumor demonstrated an endometrial adenocarcinoma. It is important for thoracic surgeons to remain vigilant, keeping secondary lung cancer in the differential diagnosis for patients with complex oncologic histories.

Objectives: Uterine serous carcinoma (USC) is a rare but aggressive histologic variant of endometrial cancer that accounts for less than 10% of cases but 80% of endometrial cancer deaths. Initial treatment strategies have remained largely unchanged over the years, with the mainstay of treatment being primary cytoreductive surgery (PCS) followed by adjuvant chemotherapy with or without tailored radiotherapy. More recent strategies have incorporated the use of neoadjuvant chemotherapy (NAC) in certain cases with bulky nodal disease or stage IV disease. This study compares survival outcomes between PCS and neoadjuvant chemotherapy followed by an interval cytoreductive surgery (ICS). Methods: Retrospective data spanning 7 years was collected for patients with stage III or IV USC in a large academic institution. PCS was categorized as initial surgical treatment for stage III or IV disease. This was further stratified into microscopic and bulky disease at the time of surgery. ICS was defined as initial treatment with NAC with interval cytoreductive surgery. Overall survival (OS) and progression free survival (PFS) were calculated for each group with Kaplan-Meier estimation and analyzed using the Chi-Square test. Results: Forty-seven patients were identified to have stage III or IV disease at the time of diagnosis. 35 patients underwent PCS and 12 underwent ICS. The PCS and ICS groups were matched for race, age and BMI. Among the PCS patients, 52% had bulky disease. OS was 82.1 months compared to 40.1 months for PCS and ICS respectively (p=0.23). PFS of PCS patients was 42.9 months compared to 18.1 months of ICS patients (p=0.03). PCS of non-bulky disease, PCS of bulky disease and ICS had OS of 82.1, 40.9, and 31.8 months respectively (p=0.47) while PFS was 42.9, 19.6 and 13.8 months for PCS of non-bulky disease, PCS of bulky disease and ICS respectively (p=0.02). For patients with non-bulky disease and bulky disease, OS was 82.1 vs 40.1 months respectively (p=0.23) while PFS was 42.9 and 18.1 months respectively (p=0.32). Patients with bulky disease who had PCS had an OS of 40.9 months compared to 31.8 months for ICS (p=0.86) and PFS of 19.7 months vs 13.9 months (p=0.13). Conclusions: While no statistical difference in OS was observed between the groups, there was a significant improvement in PFS in the PCS patients compared to ICS patients. PFS was significantly longer after PCS regardless of bulky disease. PFS appears to favor PCS over ICS. This study is limited by the small sample size. Additional studies are needed to better determine optimal treatment strategies for patients with advance stage USC.

Papillary squamous cell carcinoma is a rare variant of squamous cell carcinoma, histologically characterized by thin or broad papillae lined by epithelium showing the features of high-grade squamous intraepithelial lesion. Given the exophytic nature of these neoplasms, the diagnosis, assessment and quantification of invasion may be difficult in small biopsies. The goal of this study was to determine the presence and extent of cervical stromal invasion by comparing biopsy samples with excisional specimens in a cohort of patients diagnosed with papillary squamous cell carcinoma. Cases were identified from the surgical pathology files between the years 2003 and 2018 and only cases in which the patients underwent an excisional procedure following the diagnostic biopsy were included. Eighteen cases were identified. Patients age ranged 21 to 72 yr (mean: 46.2 yr). Review of the initial, presurgical biopsies showed that 17/18 (94%) patients had no evidence of stromal invasion. In the surgical excision specimens (2 cone biopsies, 1 loop electrosurgical excision procedure, and 15 hysterectomies), 13 cases (76.5%) showed invasive squamous cell carcinoma. Tumor sizes ranged 1.0 to 6.1 cm; stromal invasion ranged in depth 0.2 to 2.2 cm (median: 1.2), and in horizontal length 0.3 to 4.0 cm (median: 2.01). Papillary squamous cell carcinoma is a rare variant of squamous cell carcinoma of the cervix that may impose some diagnostic difficulties in small biopsies. Our findings demonstrated that the significant majority of cases might only show the presence of invasive cancer in excisional samples. Awareness of this data is important to guide proper management and avoid under-treatment.

The use of Unmanned Aerial Vehicles (UAVs) to perform complex tasks is very common today. The private transport sector will soon experience a significant change with the arrival of a new concept, the electric Vertical Take-Off and Landing (eVTOL) aircraft. These autonomous vehicles will, at first, be used in conjunction with other manned aircraft. That implies that the eVTOL aircraft will have to use the current civil airspace, where the aviation authorities require full compliance with the regulations that apply to General Aviation. This paper proposes a complete prototype of a Collision Avoidance System (CAS) for VTOL UAVs using civil airspace under the regulations of the Visual Flight Rules (VFR). The entire study corresponding to this CAS was implemented and tested in micro quadcopters that have the premise of bringing results with an experimental value that can grant proof of concept to the entire system.

Background Heart transplant is the gold standard therapy for patients with advanced heart failure. Over 5,500 heart transplants are performed every year worldwide. Cardiac allograft vasculopathy (CAV) is a common complication post-heart transplant which reduces survival and often necessitates heart retransplantation. Post-transplant follow-up requires serial coronary angiography and endomyocardial biopsy (EMB) for CAV and allograft rejection screening, respectively; both of which are invasive procedures. This study aims to determine whether osteopontin (OPN) protein, a fibrosis marker often present in chronic heart disease, represents a novel biomarker for CAV. Methods Expression of OPN was analyzed in cardiac tissue obtained from patients undergoing heart retransplantation using immunofluorescence imaging (n = 20). Tissues from native explanted hearts and three serial follow-up EMB samples of transplanted hearts were also analyzed in five of these patients. Results Fifteen out of 20 patients undergoing retransplantation had CAV. 13/15 patients with CAV expressed nuclear OPN. 5/5 patients with multiple tissue samples expressed nuclear OPN in both 1 st and 2 nd explanted hearts, while 0/5 expressed nuclear OPN in any of the follow-up EMBs. 4/5 of these patients had an initial diagnosis of dilated cardiomyopathy (DCM). Conclusion Nuclear localization of OPN in cardiomyocytes of patients with CAV was evident at the time of cardiac retransplant as well as in patients with DCM at the time of the 1 st transplant. The results implicate nuclear OPN as a novel biomarker for severe CAV and DCM.

Thrombocytosis (platelets &ge, 400K) is a common hematologic finding in gynecologic malignancies and associated with worse outcomes. Limited data exist on the prognostic capability of thrombocytosis in women with high-grade endometrial cancer (EC). Our objective was to describe the associations between elevated platelets at diagnosis, clinicopathologic features, and survival outcomes among women with high-grade, non-endometrioid EC. A review of the institutional cancer registry was performed to identify these women treated between 2005 and 2017. Sociodemographic, clinical, and outcomes data were collected. Analyses were performed using chi-square tests, Cox proportional hazards models, and the Kaplan&ndash, Meier method. A total of 271 women were included in the analysis. A total of 19.3% of women had thrombocytosis at diagnosis. Thrombocytosis was associated with reduced median overall survival (OS) compared with those not displaying thrombocytosis (29.4 months vs. 60 months, p &lt, 0.01). This finding was most pronounced in uterine serous carcinoma (16.4 months with thrombocytosis vs. 34.4 months without, p &lt, 0.01). While non-White women had shorter median OS for the whole cohort in the setting of thrombocytosis (29.4 months vs. 39.6 months, p &lt, 0.01), among those with uterine serous carcinoma (USC), this finding was reversed, with decreased median OS in White women (22.1 vs. 16.4 months, p = 0.01). Thrombocytosis is concluded to have negative associations with OS and patient race.

Background: Caribbean immigrants represent one of the largest groups of minorities in the United States (US), yet are understudied. Racial and ethnic disparities among women with ovarian cancer have been reported, but not in immigrant populations. Our objective was to evaluate differences in the clinicopathologic features and survival outcomes of Caribbean-born (CB) immigrants with ovarian cancer, with special focus on the influence of race and ethnicity on these measures.Methods: A review of the institutional cancer registry was performed to identify women with known nativity treated for epithelial ovarian cancer between 2005 and 2017. Sociodemographic, clinical, and outcomes data were collected. Analyses were done using chi-square, Cox proportional hazards models, and the Kaplan-Meier method, with significance set at p < 0.05.Results: 529 women were included in the analysis, 248 CB and 281 US-born (USB). CB women were more likely to have residual disease after debulking surgery (31.2 vs. 16.8%, p = 0.009) and be treated at a public facility (62.5 vs. 33.5%, p < 0.001). Black CB women less frequently received chemotherapy compared to White CB women (55.2 vs. 82.2%, p = 0.001). Among all CB women, Hispanic ethnicity was independently associated with improved survival when adjusting for other factors (HR 0.61 [95% CI 0.39–0.95], p = 0.03). White Hispanic CB women had a median overall survival (OS) of 59 months while Black, non-Hispanic CB women had a median OS of 24 months (log-rank p = 0.04).Conclusion: Among Caribbean-born women with ovarian cancer, Hispanic ethnicity is significantly associated with improved survival outcomes, regardless of race.

Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the presumptive site of origin of HGSC. Precancerous lesions are primarily found in the distal fallopian tube (fimbria), near the ovary relative to the proximal tissue (ampulla), nearer to the uterus. The proximity of the fimbria to the ovary and the link between ovulation, through follicular fluid release, and ovarian cancer risk led us to examine transcriptional responses of fallopian tube epithelia (FTE) at the different anatomical sites of the human fallopian tube. Gene expression profiles of matched FTE from the fimbria and from premenopausal women resulted in differentially expressed genes (DEGs): CYYR1, SALL1, FOXP2, TAAR1, AKR1C2/C3/C4, NMBR, ME1 and GSTA2. These genes are part of the antioxidant, stem and inflammation pathways. Comparisons between the luteal phase (post-ovulation) to the follicular phase (pre-ovulation) demonstrated greater differences in DEGs than a comparison between fimbria and fallopian tube anatomical differences alone. This data suggests that cyclical transcriptional changes experienced in pre-menopause are inherent physiological triggers that expose the FTE in the fimbria to cytotoxic stressors. These cyclical exposures induce transcriptional changes reflective of genotoxic and cytotoxic damage to the FTE in the fimbria which are closely related to transcriptional and genomic alterations observed in ovarian cancer.

Verruciform proliferations of the vulva unrelated to HPV infection are rare. The term differentiated exophytic vulvar intraepithelial lesion (DEVIL) was recently proposed for these lesions, which harbor recurrent PIK3CA mutations. It is still unclear whether DEVIL is related to verrucous carcinoma, a neoplasm characterized by persistence and local recurrence but nil risk of distant spread. Specimens identified using the words "verruciform" and "verrucous" were reviewed. Diagnosis of DEVIL required verruciform acanthosis, hyper and/or parakeratosis, hypogranulosis, cytoplasmic pallor, and bland nuclei. Verrucous carcinoma required, in addition, discontinuous, bulbous, puzzle-like nests in the stroma. A targeted next-generation sequencing using a custom 11-gene panel was performed. Eighteen specimens corresponding to ten patients with DEVIL and/or verrucous carcinoma were included. Median age at presentation was 66 years for DEVIL and 70 years for verrucous carcinoma. A similar spectrum of prevalent mutations was found in both lesions involving HRAS, PIK3CA, and BRAF. DEVIL preceded verrucous carcinoma and/or was diagnosed concurrently or in subsequent follow-up in five patients. In four of these, the same mutation was identified in DEVIL and synchronous or metachronous carcinoma. All cases showed wild-type 53 staining and lacked pathogenic TP53 mutations. DEVIL is a rare form of squamous proliferation characterized by prevalent PIK3CA and HRAS mutations. Its temporal relationship with verrucous carcinoma and their shared mutational profile in some patients suggest that DEVIL is a precursor of verrucous carcinoma. Moreover, given their morphologic and molecular overlap and the nil risk of verrucous carcinoma for distant spread, it is conceivable that DEVIL and verrucous carcinoma represent a spectrum of the same entity.

Objectives Lymphoepithelioma-like carcinoma (LELC) of the uterine cervix is a rare tumor. The goal of this study was to evaluate a series of cases of cervical LELC and to investigate possible association with human papillomavirus (HPV) and/or Epstein-Barr virus (EBV). Methods Immunohistochemistry for p63, p16, human leukocyte antigen-D related (HLA-DR), and B-cell lymphoma 2 (BCL-2); in situ hybridization (ISH) for EBV and HPV; and polymerase chain reaction (PCR) genotyping were performed. Mismatch repair (MMR) studies and PD-L1 status were obtained. Results We found eight cases of LELC. Tumors demonstrated sheets of cells containing vesicular nuclei, amphiphilic cytoplasm, and dense peri- and intratumoral lymphocytic infiltrates. All tumors stained for p63, p16, and HLA-DR; two also stained for BCL-2. When combining ISH and PCR results, seven tumors were HPV positive; they were all Epstein-Barr encoding region negative. All cases were MMR intact, and most overexpressed PD-L1. Conclusions This study shows that cervical LELCs are associated with HPV and not EBV.

Carcinosarcomas of the gynecologic tract, also known as malignant mixed Müllerian tumors, are aggressive neoplasms with a high recurrence rate and poor prognosis. Despite advances in adjuvant therapies in recent years, the prognosis of these tumors has not improved. In fact, there are currently no consensus guidelines for the treatment of these neoplasms and the search for targetable biomarkers has not been successful so far. Programmed death-ligand 1 (PD-L1) has emerged as a potential target for therapeutics in a number of malignant tumors, including melanoma, lung, and colorectal cancer. In normal conditions, PD-L1 is thought to promote immune homeostasis via a number of pathways, but mainly through downregulation of cytotoxic T cells. In some human neoplasms, however, overexpression of PD-L1 by tumor cells has been observed, which can modulate the immune system to allow cancer cells to evade host response. As this marker could potentially be a therapeutic target for these tumors, the immunohistochemical expression of PD-L1 in a group of carcinosarcomas was evaluated in the present study.Twenty-nine cases of gynecologic carcinosarcomas were analyzed, corresponding to tumors originating from the uterus (25), ovary (2), fallopian tube (1), and pelvic epithelium (1). Immunohistochemistry for PD-L1 was performed on paraffin sections and the staining results were assessed semiquantitatively in both epithelial and mesenchymal components of each tumor.Positive membranous staining for PD-L1 was detected in 25/29 tumors (86%). The epithelial components were strongly positive in 19/29 (65%) and weakly positive in 6/29 tumors (21%). The mesenchymal elements were strongly positive in 8/29 (27%) and weakly positive in 3/29 tumors (10%). With exception of 1, all tumors with positive sarcomatous components had staining of the carcinomatous element. Four tumors were negative for PD-L1 in both components.This study shows that PD-L1 is expressed by the majority of carcinosarcomas, predominantly in the epithelial components. This is particularly important as most locoregional recurrences and distant metastases are of epithelial origin. This finding may serve as a basis for possible therapeutic approaches using antibodies that have already shown significant value in a number of other malignant tumors.

Focused-electron-beam-induced deposition (FEBID) constitutes a direct-writing maskless technique, which has been employed to prepare nanodots, nanolines, as well as laminar and even three-dimensional nanostructures with potential in many technological fields. Here, we report direct-writing of functional nanostructures with the HFeCo3(CO)12 bimetallic carbonyl precursor. The metal content as well as the magnetotransport properties of Fe–Co–C–O deposits were reproducibly tuned upon ex situ postgrowth annealing at 100, 200, and 300 °C in a high-vacuum system. The atomic composition obtained by energy-dispersive X-ray spectroscopy (EDX) analysis revealed that carbonyl groups release during annealing, although principally sole oxygen is released from the deposits, yielding an atomic ratio of Co:Fe:C:O = 52:17:22:9 with respect to the atomic composition of as-grown Co:Fe:C:O = 41:13:26:20. Interestingly, the amorphous carbon contained in the as-grown material turns into graphite nanocrystals with an average siz...

There is a complex connection between diabetes mellitus and pancreatic carcinoma, whereby it has been a target of many studies. The new-onset diabetes may be a symptom caused by occult pancreatic cancer, but the most important question remains when to think about it. We present a case report of a 72-year-old female with a new-onset diabetes mellitus, initially diagnosed with no associated complications. However, a few months later, glycemic index was uncontrolled despite optimized therapy. It led to further study and a pancreatic carcinoma was discovered. With this case we intend to raise awareness that new-onset diabetes could be a hint for a hidden disease, especially when glycemic index is difficult to control despite optimized therapy. For that reason, physicians must be aware of the intrinsic relationship between diabetes and pancreatic carcinoma.