Background and Aims Pathological examination is commonly used to diagnose immune checkpoint inhibitor (ICI)-related myocarditis. However, well-organized clinicopathological evidence remains limited. In this study, we aimed to investigate the pathological and clinical characteristics of myocarditis to enhance understanding.Methods This multicentre retrospective observational study included 38 patients diagnosed with or suspected of having ICI-related myocarditis. Patients were stratified using the pathological grading system proposed by Palaskas et al. Lymphocyte infiltration was assessed using both global and hot-spot (hotspot) methods. Immunohistochemistry was performed for lymphocytes, macrophages, and inflammatory markers, including human leucocyte antigen-DR isotype (HLA-DR), programmed death-ligand 1 (PD-L1), granzyme B, and tenascin C.Results An increased infiltration of CD3, CD4, CD8-positive T cells, and CD68 and CD163-positive macrophages was observed with higher pathological grades. HLA-DR and tenascin C (clone 4F10) were sensitive markers of inflammation, whereas PD-L1 and tenascin C (clone 4C8) were more specific for high-grade inflammation. Global assessment more accurately predicted myocarditis-related mortality than hotspot assessment, although both methods similarly predicted fulminant myocarditis and major adverse cardiac events. Two patients presented with suspected ICI-mediated non-inflammatory left ventricular dysfunction (NILVD), with minimal myocardial inflammation.Conclusions Pathological grading using both global and hotspot assessment is valuable for the diagnosis and risk stratification of ICI-related myocarditis. As low-grade inflammation is not uncommon, supplementary markers such as HLA-DR, granzyme B, tenascin C, and PD-L1 may aid diagnosis. Furthermore, ICI-mediated NILVD may encompass cases of low-grade myocarditis.

OBJECTIVE:In the differential diagnosis between uterine fibroids and uterine sarcomas, real-world magnetic resonance imaging (MRI) diagnostic information is scarce; furthermore, high diagnostic sensitivity is important in clinical practice. We previously developed a diagnostic algorithm to detect uterine sarcoma with high sensitivity using simple MRI images and serum lactate dehydrogenase (LDH) levels. In this multicenter study, we investigated the preoperative diagnosis of sarcoma in the real world and further validated the usefulness of our diagnostic algorithm. METHODS:Of 154 uterine sarcomas and 154 uterine fibroids treated at 15 centers between January 2006 and December 2020, 139 sarcomas (16 smooth muscle tumors of uncertain malignant potential) and 141 fibroids with diffusion-weighted imaging information were included in the analysis. The diagnostic algorithm was validated by 3 radiologists who were blinded to the clinical information and pathologic diagnoses and who read the MRIs. RESULTS:The sensitivity/specificity of preoperative diagnosis was 77.7%/92.9% for the preoperative report; 92.1%/72.3% for algorithm A; and 82.0%/85.8% for algorithm B (McNemar's test p<0.05). Comparison of overall survival rates among 3 groups (Group 1: negative A, Group 2: positive A and negative B; Group 3: positive B) using algorithms A and B showed p=0.012. On multivariate analysis, stage, and serum LDH level were independent prognostic factors. CONCLUSION:MRI is useful for preoperative diagnosis of uterine sarcoma, and the sarcoma diagnostic algorithm presented in this study is an option for diagnosing sarcoma with greater sensitivity. This information should be shared with patients.

Intra-abdominal epithelioid neoplasm with EWSR1/FUS::CREB fusions is an emerging entity characterized by a broad age distribution, epithelioid morphology, variable epithelial marker expression, prominent lymphoplasmacytic infiltration, and systemic inflammation. A few ovarian cases have been reported. We describe a 63-yr-old woman who presented with anemia and elevated C-reactive protein. She underwent surgery for a 14-cm right ovarian mass. Grossly, the tumor was solid with cystic change and hemorrhage, and had a light tan cut surface. Histologically, it consisted of uniform sheets of epithelioid cells with ample pale eosinophilic cytoplasm, divided by fibrotic septa with dense lymphoplasmacytic infiltration. Immunohistochemically, the tumor was positive for EMA, WT1, and vimentin; focally positive for CAM5.2; and negative for AE1/AE3, estrogen and progesterone receptors, PAX8, sex cord markers, desmin, HMB45, and Melan A. The Ki-67 labeling index was 20%. The differential diagnoses, including poorly differentiated carcinoma, sex cord-stromal tumors, perivascular epithelioid cell tumor, and inflammatory myofibroblastic tumor, were considered. Whole-genome sequencing revealed a FUS::CREM gene fusion. Based on clinicopathologic and genomic features, the tumor was classified as an ovarian example of EWSR1/FUS::CREB fusion-associated epithelioid neoplasm. Inflammation-related laboratory abnormalities resolved postoperatively. No adjuvant therapy was administered, and the patient remained disease-free at 12 mo. This represents the third reported ovarian tumor with FUS::CREM fusion and the seventh adnexal tumor with EWSR1/FUS::CREB family fusion. Prognostic information on these adnexal tumors is limited, but given the aggressive nature of analogous extra-adnexal and testicular tumors, cautious management and further studies are warranted.

OBJECTIVE:To validate the clinical utility of the Silva classification (a risk-stratification system based on invasion pattern for HPV-associated cervical adenocarcinoma; HPVA) using Japanese cohort data; and to determine how HPV-independent adenocarcinoma (HPVI) should be positioned relative to Silva-classified HPVA. METHODS:We retrospectively analyzed 264 cases of surgically treated FIGO 2008 stage I-II cervical adenocarcinoma from eight institutions participating in the KAMOGAWA Study. Tumors were classified as HPVA or HPVI. HPVA cases were further categorized as low-risk or high-risk using the binary Silva classification, which incorporates invasion pattern and lymphovascular space invasion. Outcome measures included lymph node metastasis, disease-free survival (DFS), and overall survival (OS). RESULTS:Of the 264 cases, 27 % were classified as low-risk HPVA, 49 % as high-risk HPVA, and 23 % as HPVI. Lymph node metastasis was observed in 0 %, 12 %, and 38 % of cases, respectively (p < 0.001). The 5-year DFS was 98 %, 83 %, and 53 %, and the 5-year OS was 100 %, 97 %, and 63 % (both p < 0.001). Multivariable analysis showed that low-risk HPVA was associated with longer DFS (HR 0.12, 95 % CI 0.015-0.87) and HPVI was associated with shorter DFS (HR 2.76, 95 % CI 1.44-5.30), after adjusting for tumor size (≤2 cm, 2-4 cm, >4 cm) and age. Tumor size >4 cm, but not ≤2 cm was an independent prognostic factor. CONCLUSIONS:The three-tier system combining the histotype and binary Silva classification outperformed tumor size in prognostic stratification. The low-risk group showed excellent outcomes, supporting the potential for conservative management such as uterine preservation after conization.

Recent next-generation sequencing (NGS) studies have shown that synchronous endometrial and ovarian cancers (SEOCs) are often derived from the same clone. However, the clonal relationship in Lynch syndrome remains unclear. A 45-year-old woman was diagnosed with grade 2 endometrial endometrioid carcinoma and an ovarian yolk sac tumor with clear cell carcinoma. Genetic testing revealed different MLH1 variants in the endometrial and ovarian cancers, and peripheral blood analysis identified an exon 5 deletion in MLH1, confirming Lynch syndrome. The somatic variants in the tumors were distinct. A review of the literature found six cases of SEOC in Lynch syndrome with NGS-based clonal analysis, four of which (67%) showed independent cancers with different somatic profiles. These findings suggest that, unlike sporadic SEOC, synchronous cancers in Lynch syndrome are more likely to arise from separate clones.

Background: The prognosis for recurrent ovarian cancer is poor, but a small percentage of patients can be cured. The aim of this study was to clarify the criteria for being cured and the characteristics of cured cases. Methods: Ovarian cancer cases at 2 university hospitals and 8 community hospitals were analyzed to identify patients who were considered cured after complete remission (CR) following recurrence. Analyses of the tumors were performed and included BRCA1/2 mutation analysis. Results: Of the 157 cases of recurrence, 21 (13%) showed no evidence of disease (NED). NED cases had a lower rate of ascites at the initial diagnosis, longer disease-free survival, a higher rate of solitary lesions, and a higher rate of secondary debulking surgery. All CR cases except for one showed no further recurrence when DFS reached 4 years, which was considered a criterion for being cured. The case of relapse occurred after long-term treatment with bevacizumab. Furthermore, 19.4% of the CR cases achieved 4-year DFS, which represents 9.3% of the cases of recurrent ovarian cancer and 2.3% of all cases of ovarian cancer. BRCA mutation analysis of the tumor was possible in 17 of the 30 cases of recurrent ovarian cancer that achieved a 4-year DFS. Pathogenic variants of BRCA were found in 5 of the 11 cases of high-grade serous carcinoma. Conclusions: Approximately 10% of patients with recurrent ovarian cancer achieved a 4-year DFS and were mostly cured. The curing of cases not involving high-grade serous carcinoma (HGSC) was unrelated to the presence of pathogenic BRCA variants.

Endometrial cancer is generally associated with a favorable prognosis when detected at an early stage and treated appropriately, especially in young women receiving fertility-sparing therapy. However, rare cases may exhibit unexpected aggressive progression driven by novel genetic alterations.A 38-year-old woman was diagnosed with stage IA endometrial endometrioid carcinoma grade 1, based on pathologic examination by endometrial curettage, magnetic resonance imaging, and computed tomography scans. The tumour progressed systemically during fertility-sparing treatment and she died on day 112. Pathologic examination of the liver metastasis revealed that the tumour was morphologically different from the endometrial tumour and was oestrogen receptor-negative, chromogranin A-positive, and synaptophysin-positive on immunohistochemistry, leading to the diagnosis of neuroendocrine carcinoma. Gene panel testing identified TMEM178B-BRAF fusion and subclonal PIK3CA mutations in the liver metastasis, in addition to ARID1A and CTNNB1 mutations that were shared with the endometrial tumour. This is the first report of an endometrioid carcinoma transforming into a high-grade neuroendocrine tumour associated with TMEM178B-BRAF fusion.

As endovascular therapy for ischemic stroke has advanced, we are getting increasing opportunities to study cerebral thromboemboli histologically. These opportunities have not been fully exploited, but some reports suggest that thromboemboli retrieved from cancer patients with stroke are platelet-richer than those from non-cancer patients. Nonbacterial thrombotic endocarditis (NBTE) is an important cause of ischemic stroke in cancer patients. In this study, we analyzed 20 autopsy cases of NBTE (13 of which had advanced cancer), along with cases of cerebral embolism associated with atrial fibrillation (AF, n = 11) and infective endocarditis (IE, n = 7). The histological features of NBTE vegetations (n = 20) were fairly consistent among cases: they were overwhelmingly platelet-dominant and spatially homogeneous, containing few erythrocytes or inflammatory cells. They were little organized, if at all, and were not associated with valvular destruction. Cerebral emboli associated with NBTE (n = 7) were also platelet-dominant. Intracardiac thrombi/vegetations and cerebral emboli associated with AF and IE, in contrast, contained variable amounts of platelets and erythrocytes. NBTE vegetations/emboli, compared with AF thrombi/emboli, had significantly higher %platelet area (intracardiac vegetations/thrombi: 70 ± 15 % vs 33 ± 20 %, p < 0.001; cerebral emboli: 65 ± 16 % vs 25 ± 22 %, p < 0.001) and lower %erythrocyte area (vegetations/thrombi: 9 ± 7 % vs 61 ± 21 %, p < 0.001; emboli: 20 ± 11 % vs 70 ± 9 %, p < 0.001). These results suggest that some platelet-rich thrombi retrieved during mechanical thrombectomy for ischemic stroke in cancer patients are likely to have originated from NBTE. Clinical diagnosis of NBTE is often difficult, but histological analysis of retrieved thrombi may help identify this underdiagnosed condition.

BACKGROUND:B7-H3 and delta-like ligand 3 (DLL3) are novel therapeutic targets in extensive-stage small cell lung cancer (ES-SCLC). We aimed to assess the impact of B7-H3 and DLL3 expression on the tumor immune microenvironment (TME) and on the therapeutic efficacy of programmed cell death-ligand 1 (PD-L1) blockade for ES-SCLC. PATIENTS AND METHODS:A total of 146 ES-SCLC patients who received platinum-based chemotherapy either with (Chemo + ICI cohort) or without (Chemo cohort) an immune checkpoint inhibitor was analyzed. Progression-free survival (PFS) and overall survival (OS) were evaluated in each cohort according to B7-H3 or DLL3 expression status as detected by immunohistochemistry. The relation of B7-H3 or DLL3 expression to characteristics of the TME was assessed by immune-related gene expression profiling (irGEP). RESULTS:In the Chemo + ICI cohort, patients with high B7-H3 expression showed a shorter PFS (median of 4.3 vs. 5.4 months; HR of 2.11 with a 95 % Cl of 1.08-4.10; P = 0.03) and OS (median of 8.4 vs. 14.2 months; HR of 1.83 with a 95 % CI of 0.91-3.69; P = 0.09) than those with low B7-H3 expression. In the Chemo cohort, there was no apparent difference in survival outcomes between the high and low B7-H3 expression groups. The irGEP analysis revealed that the effector function of CD8+ T cells was impaired in tumors with high B7-H3 expression. No clear association was apparent between therapeutic efficacy and DLL3 expression status. CONCLUSIONS:High B7-H3 expression may serve as a resistance mechanism for PD-L1 antibody therapy by promoting T cell dysfunction in ES-SCLC.

Cell adhesion molecule 1 (CADM1), an immunoglobulin superfamily member, is expressed in endometrial glandular cells highly during the proliferative phase but lowly during the secretory phase. Previously, a CADM1-targeting antibody-drug conjugate (ADC) was generated, in which a humanized anti-CADM1 ectodomain antibody h3E1 was linked with monomethyl auristatin E (h3E1-MMAE ADC). The present study aimed at probing whether this ADC could be useful for the treatment of endometrial neoplasm. Firstly, immunohistochemistry for CADM1 was conducted on proliferative-phase endometrium (n = 13), endometrial hyperplasia (n = 35), and endometrioid carcinoma at various stages (n = 166). CADM1 immunostaining intensity was highest in atypical endometrial hyperplasia and endometrioid carcinoma confined within the endometrium and was decreased stepwise as the carcinoma stage progressed. Next, h3E1-MMAE ADC was examined for its cytotoxicity in vitro using human endometrial adenocarcinoma cell lines expressing CADM1; HEC-1B, HEC-50B, JHUM-3, and OMC-2. The ADC killed these cells in a dose-dependent manner with half maximal inhibitory concentration (IC50) of 12.02 nM for HEC-1B and 2.04 nM for HEC-50B. Collectively, h3E1-MMAE ADC may serve as a noninvasive alternative to simple hysterectomy in the treatment of endometrioid carcinoma confined within the endometrium.

Background:Immunotherapy with immune checkpoint inhibitors (ICIs) enhances the host immune reaction against tumour cells by inhibiting intrinsic down-regulators of the T cell-mediated immune response. Although the advent of ICIs has dramatically changed oncology, ICIs may also trigger an overactivation of T cells against non-cancerous tissues, leading to off-target immune-related adverse events (irAEs). Case summary:A 64-year-old man with a history of seven courses of atezolizumab, an ICI, for small-cell lung cancer and coronavirus disease 2019 (COVID-19) was admitted to the hospital complaining of acute chest pain. Transthoracic echocardiography showed preserved ejection fraction (EF), but electrocardiography indicated precordial ST-elevations and marked increases in biomarkers for myocardial injury were observed. Emergent cardiac catheterization showed no significant coronary stenosis. On the fifth hospital day, EF decreased to 25% and pericardial effusion occurred. Endomyocardial biopsy was immediately performed, and prednisolone (60 mg/day) was administered. Troponin I level rapidly reduced, ST changed, and EF improved. Histological examinations demonstrated CD8-predominant T lymphocytic infiltration with myocardial cell injury, consistent with irAE-myocarditis. Discussion:In irAEs, myocarditis is the most common and severe cardiac manifestation with a high mortality. Even at 20 weeks after the initial ICI treatment, irAE-myocarditis occurs and the clinical presentation may mimic ST-elevation myocardial infarction. The histopathological findings suggested the high possibility of irAE-myocarditis rather than COVID-19-induced myocarditis, but COVID-19 has possibly played a role in the development of late-onset irAE-myocarditis. This educational case implies the importance of immediate recognition of irAE even after stable ICI treatment.

A 69-year-old multiparous postmenopausal woman had undergone bilateral total hip arthroplasty 17 years ago. Computed tomography showed a mature teratoma of 10 cm in the pelvis. Subsequently, she presented with symptoms of hoarseness and weight loss, along with evidence of malignant transformation of the same tumor in the pelvis and multiple enlarged lymph nodes. Bilateral adnexectomy was performed via laparotomy, yet peritoneal dissemination persisted. The ovarian tumor’s histopathological diagnosis was mature teratoma with squamous cell carcinoma. Additionally, the mediastinal lymph nodes biopsy revealed poorly differentiated carcinoma. Comprehensive genomic profiling testing of the ovarian tumor showed pathogenic variants of TP53 and PTEN, a high tumor mutational burden, homologous recombination deficiency and the absence of human papilloma virus. The similar genomic testing of the mediastinal tumor revealed three variants of uncertain significance that were common to the ovarian tumor. However, no variants of TP53 or PTEN were identified. Following surgery, she demonstrated a partial response to six cycles of conventional paclitaxel and carboplatin. She then received maintenance treatment with niraparib; however, disease progression subsequently occurred. The patient was treated with pembrolizumab and is currently receiving treatment with a partial response. Previous reports have demonstrated the efficacy of immune checkpoint inhibitors in 5 out of 6 cases of malignant transformation of mature teratomas, and this treatment appears to be a promising strategy.

Aim: To investigate the role of pentraxin 3 (PTX3) in atherosclerotic disease progression and plaque destabilization, as well as in coronary restenosis after directional coronary atherectomy (DCA). Materials and methods: PTX3 contents of early and advanced atherosclerotic lesions of the aorta obtained at autopsy were determined by ELISA and Western blot. Also, coronary plaques of patients with acute coronary syndrome (ACS) or stable angina pectoris (SAP) obtained by DCA were analyzed by immunohistochemistry for PTX3. The effects of PTX3 on smooth muscle cells (SMCs) and thrombogenesis were investigated with cultured human coronary artery SMCs and a flow chamber system, respectively. Results: Advanced atherosclerotic lesions contained a significantly larger amount of PTX3 than early lesions (ELISA: 9.96 +/- 2.77 ng/100 mg tissue, n = 8 vs 0.24 +/- 0.18 ng/100 mg tissue, n = 6, P = 0.0097). Also, ACS plaques contained a significantly larger amount of PTX3 than SAP plaques (PTX3 immunohistochemistry-- positive area percentage: 2.88 +/- 0.53 %, n = 22 vs 0.67 +/- 0.27 %, n = 23, P = 0.0009). Curiously, the patients who would remain free of post-DCA restenosis (n = 19) had plaques with a significantly higher PTX3 immunohistochemistry-positive area percentage than those who would develop restenosis (n = 12) (2.32 +/- 0.49 % vs 0.49 +/- 0.17 %, P = 0.002). In the mechanistic part of the study, PTX3 inhibited SMC proliferation and migration. PTX3 also inhibited platelet thrombus formation in the condition simulating arterial blood flow. Conclusions: PTX3 is increased in advanced (vs early) atherosclerotic lesions and unstable (vs stable) coronary plaques. The inhibitory effects of PTX3 on SMCs and thrombogenesis suggest that intraplaque PTX3 might have atheroprotective effects.

Introduction: Immune checkpoint inhibitors have recently been approved for the treatment of early -stage NSCLC in the perioperative setting on the basis of phase 3 trials. However, the characteristics of such patients who are susceptible to recurrence after adjuvant chemotherapy or who are likely to benefit from postoperative immunotherapy have remained unclear. Methods: This biomarker study (WJOG12219LTR) was designed to evaluate cancer stem cell markers (CD44 and CD133), programmed death-ligand 1 (PD -L1) expression on tumor cells, CD8 expression on tumor -infiltrating lymphocytes, and tumor mutation burden in completely resected stage II to IIIA NSCLC with the use of archived DNA and tissue samples from the prospective WJOG4107 trial. Tumors were classified as inflamed or noninflamed on the basis of the PD -L1 tumor proportion score and CD8 & thorn; tumorinfiltrating lymphocyte density. The association between each potential biomarker and relapse -free survival (RFS) during adjuvant chemotherapy was assessed by KaplanMeier analysis. Results: A total of 117 patients were included in this study. The median RFS was not reached (95% confidence intervals [CI]: 22.4 mo -not reached; n = 39) and 23.7 months (95% CI: 14.5 -43.6; n = 41) in patients with inflamed or noninflamed adenocarcinoma, respectively (log -rank p = 0.02, hazard ratio of 0.52 [95% CI: 0.29 -0.93]). Analysis of the combination of tumor inflammation category and TP53 mutation status revealed that inflamed tumors without TP53 mutations were associated with the longest RFS. Conclusions: PD -L1 expression on tumor cells, CD8 & thorn; T cell infiltration, and TP53 mutation status may help identify patients with early -stage NSCLC susceptible to recurrence after adjuvant chemotherapy. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

Four subtypes of ovarian high-grade serous carcinoma (HGSC) have previously been identified, each with different prognoses and drug sensitivities. However, the accuracy of the classification depended on the assessor’s experience. This study aimed to develop a universal algorithm for HGSC-subtype classification using deep learning techniques. An artificial intelligence (AI)-based classification algorithm, which replicates the consensus diagnosis of pathologists, was formulated to analyze the morphological patterns and tumor-infiltrating lymphocyte counts for each tile extracted from whole slide images of ovarian HGSC available in The Cancer Genome Atlas (TCGA) dataset. The accuracy of the algorithm was determined using the validation set from the Japanese Gynecologic Oncology Group 3022A1 (JGOG3022A1) and Kindai and Kyoto University (Kindai/Kyoto) cohorts. The algorithm classified the four HGSC-subtypes with mean accuracies of 0.933, 0.910, and 0.862 for the TCGA, JGOG3022A1, and Kindai/Kyoto cohorts, respectively. To compare Mesenchymal Transition (MT) with non-MT groups, overall survival analysis was performed in the TCGA dataset. The AI-based prediction of HGSC-subtype classification in TCGA cases showed that the MT group had a worse prognosis than the non-MT group (p = 0.017). Furthermore, Cox proportional hazard regression analysis identified AI-based MT subtype classification prediction as a contributing factor along with residual disease after surgery, stage, and age. In conclusion, a robust AI-based HGSC-subtype classification algorithm was established using virtual slides of ovarian HGSC.

Uterine angioleiomyoma is benign tumor that composed of smooth muscle cells and thick-walled vessels. It is a very rare condition reported to present as lower abdominal mass, accompanied by dysmenorrhea and hypermenorrhea. However, its clinical presentation is not known. We report the case of a 44-year-old Japanese woman who developed severe anemia with disseminated intravascular coagulation without obvious external bleeding. The patient had a huge abdominal mass of over 20 cm in size, which was thought to be a uterine tumor. She received daily blood transfusions and her condition improved rapidly after she underwent hysterectomy. Pathological examination of the tumor revealed spindle-shaped cells with little atypia and mitosis, and numerous large vessels with smooth muscle and thrombus in the vessels. Uterine angioleiomyoma was identified as the cause of the coagulation abnormality. CCND2 and AR gene amplification was detected in the tumor. Uterine tumors that present with coagulopathy despite a clinical course suggestive of benign disease should undergo differential diagnosis for uterine angioleiomyoma.

Introduction: The PACIFIC regimen of consolidation therapy with the programmed cell death-ligand 1 inhibitor durvalumab after definitive concurrent chemoradiation therapy has become a standard of care for individuals with unresectable stage III NSCLC. Nevertheless, approximately half of the treated patients experience disease progression within 1 year, with the mechanisms of treatment resistance being poorly understood. We here performed a nationwide prospective biomarker study to explore the resistance mechanisms (WJOG11518L:SUBMARINE). Methods: A total of 135 patients with unresectable stage III NSCLC who received the PACIFIC regimen were included for comprehensive profiling of the tumor microenvironment by immunohistochemistry, transcriptome analysis, and genomic sequencing of pretreatment tumor tissue and flow cytometric analysis of circulating immune cells. Progression-free survival was compared on the basis of these biomarkers. Results: The importance of preexisting effective adaptive immunity in tumors was revealed for treatment benefit regardless of genomic features. We also identified CD73 expression by cancer cells as a mechanism of resistance to the PACIFIC regimen. Multivariable analysis of immunohistochemistry data with key clinical factors as covariables indicated that low CD8 thorn tumor-infiltrating lymphocyte density and the high CD73 thorn cancer cells were independently associated with poor durvalumab outcome (hazard ratios 1/4 4.05 [95% confidence interval: 1.17-14.04] for CD8 thorn tumor-infiltrating lymphocytes; 4.79 [95% confidence interval: 1.12-20.58] for CD73). In addition, whole-exome sequencing of paired tumor samples suggested that cancer cells eventually escaped immune pressure as a result of neoantigen plasticity. Conclusions: Our study emphasizes the importance of functional adaptive immunity in stage III NSCLC and implicates CD73 as a promising treatment target, thus providing insight forming a basis for development of a new treatment approach in NSCLC. (c) 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Background: This study aimed to establish an evaluation method for detecting uterine sarcoma with 100% sensitivity using MRI and serum LDH levels. Methods: One evaluator reviewed the MRI images and LDH values of a total of 1801 cases, including 36 cases of uterine sarcoma and 1765 cases of uterine fibroids. The reproducibility of the algorithm was also examined by four evaluators with different imaging experience and abilities, using a test set of 61 cases, including 14 cases of uterine sarcoma. Results: From the MRI images and LDH values of 1801 cases of uterine sarcoma and uterine fibroids, we found that all sarcomas were included in the group with a high T2WI and either a high T1WI, an unclear margin, or high LDH values. In addition, when cases with DWI were examined, all sarcomas had high DWI. Among the 36 sarcoma cases, the group with positive findings for T2WI, T1WI, margins, and serum LDH levels all had a poor prognosis (p = 0.015). The reproducibility of the algorithm was examined by four evaluators and the sensitivity of sarcoma detection ranged from 71% to 93%. Conclusion: We established an algorithm to distinguish uterine sarcoma if tumors in the myometrium with low T2WI and DWI are present.