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Purpose: The purposes of the study are to assess the diagnostic performance of preoperative imaging for staging factors in gastric-type endocervical adenocarcinoma (GEA) and to compare the performance for GEA with that of usual-type endocervical adenocarcinoma (UEA) among patients preoperatively deemed locally early stage (DLES) (< T2b without distant metastasis)., Materials and Methods: For this multi-center retrospective study, 58 patients were enrolled. All had undergone MRI with or without CT and FDG PET-CT preoperatively and had been pathologically diagnosed with GEA at five institutions. Based on the medical charts and radiological reports, the diagnostic performances of preoperative imaging for the International Federation of Gynecology and Obstetrics staging factors were assessed retrospectively. Next, the imaging performance was assessed in preoperatively DLES-GEA (n = 36) and DLES-UEA (n = 136, with the same inclusion criteria). The proportions of underestimation of GEA and UEA were compared using Fisher's exact test., Results: Imaging diagnostic performance for GEA was limited, especially for sensitivity: parametrial invasion, 0.49; vaginal invasion, 0.54; pelvic lymph node metastasis (PELNM), 0.48; para-aortic lymph node metastasis, 0.00; and peritoneal dissemination, 0.25. Among preoperatively DLES patients, the proportions of underestimation were significantly higher in GEA than in UEA; parametrial invasion, 35% vs. 5% (p < 0.01); vaginal invasion, 28% vs. 6% (p < 0.01); PELNM, 24% vs. 6% (p < 0.05); peritoneal dissemination, 6% vs. 0% (p < 0.05)., Conclusion: At present, preoperative imaging diagnostic performance for staging factors in GEA does not meet clinical expectations, especially for sensitivity. Among patients preoperatively DLES, the proportions of underestimation in GEA were significantly higher than in UEA. Future incorporation of approaches specifically emphasizing GEA is desirable to improve imaging performance., Competing Interests: Declaration. Conflict of interest: All authors have nothing to declare in this study. Ethical approval: The institutional review board of Kyoto University Hospital provided a unified approval of this multi-center retrospective study for both Kyoto University Hospital and National Cancer Center Hospital. The provision of samples and information was also approved by the institutional review board of other three university hospitals. Informed consent: Informed consent was waived in this retrospective study., (© 2024. The Author(s).)

Background: Recently, it has been shown that DNA methylation arrays and German Cancer Research Center (Deutsches Krebsforschungszentrum) methylation classifiers are useful aids in brain tumor diagnosis for cases in which histopathological diagnosis is difficult. However, not enough is known about diagnostic aids for intracranial liposarcoma (LPS)., Observations: An 18-year-old woman with a history of natural killer/T-cell lymphoma, which had been treated with a bone marrow transplant and total body irradiation at age 11 years, presented with diplopia. Magnetic resonance imaging revealed a brain tumor in the posterior left temporal lobe, which was removed by craniotomy. The tumor was initially diagnosed as pleomorphic xanthoastrocytoma through histopathological and DNA methylation examination. She also had a soft tissue tumor in her left thigh, which was removed. It contained spindle cells with oval nuclei and highly pleomorphic cells and was diagnosed as radiation-induced LPS. Histopathological re-examination of the brain tumor led to a final diagnosis of pleomorphic LPS., Lessons: In this report, the authors describe the case of a patient with an intracranial pleomorphic LPS that was initially classified as a pleomorphic xanthoastrocytoma by a DNA methylation classifier. Although DNA methylation classifiers are useful as diagnostic aids in cases in which definitive pathology is difficult to determine, there is a risk of misdiagnosis in some types of tumors. https://thejns.org/doi/10.3171/CASE24465.

Context.—: Endocervical adenocarcinoma is divided into human papillomavirus (HPV)-associated (HPVA) and HPV-independent (HPVI) in the 5th edition of the World Health Organization (WHO) tumor classification launched in 2020. However, the validity of the morphologic criteria used for biopsy specimens in real-world practice remains undetermined., Objective.—: To validate the utility of the 5th edition of the WHO classification for biopsy samples, focusing on its diagnostic criteria with the aid of ancillary studies., Design.—: We retrieved 217 cases of endocervical adenocarcinoma from 6 institutions, in which glass slides of both biopsy and resection specimens were available for review. Concordance between the biopsy and resection specimen diagnoses was evaluated. For discordant diagnoses, an algorithmic approach with ancillary studies proposed by the international group was applied to confirm their utility to improve the accuracy of biopsy diagnosis., Results.—: The biopsy diagnosis matched the resection specimen diagnosis in 197 cases (concordance rate, 91%; κ = 0.75). The concordance rate was significantly higher for HPVA than HPVI (95% versus 81%, P = .001). There were no significant differences in the proportions of HPVA and HPVI or the accuracy of biopsy diagnosis between the participating institutions. All 19 discordant cases with unstained glass slides available were accurately recategorized as HPVA or HPVI using HPV in situ hybridization; p16 immunohistochemistry was positive in 3 of 9 cases of gastric-type HPVI that were negative by in situ hybridization., Conclusions.—: The 5th edition of the WHO criteria for biopsy diagnosis of endocervical adenocarcinoma distinguishes HPVA from HPVI well when ancillary studies are adequately applied., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Background: Lynch syndrome (LS) is a hereditary cancer syndrome caused by pathogenic germline variants in mismatch repair (MMR) genes, which predisposes to various types of cancers showing deficient MMR (dMMR). Identification of LS probands is crucial to reduce cancer-related deaths in affected families. Although universal screening is recommended for colorectal and endometrial cancers, and age-restricted screening is proposed as an alternative, LS screening covering a broader spectrum of cancer types is needed. In the current study, we elucidated the rate of dMMR tumors and evaluated the outcome of LS screening in young-onset extra-colorectal LS-associated cancers., Methods: Immunohistochemistry for MMR proteins were retrospectively performed in a total of 309 tissue samples of endometrial, non-mucinous ovarian, gastric, urothelial, pancreatic, biliary tract, and adrenal cancers in patients < 50 years of age. Clinicopathological information and the results of genetic testing were obtained from medical charts., Results: There were 24 dMMR tumors (7.8%) including 18 endometrial, three ovarian, two urothelial, and one gastric cancer. Co-occurrence of colorectal cancer and family history of LS-associated cancers was significantly enriched in patients with dMMR tumors. Among the 16 patients with dMMR tumors who were informed of the immunohistochemistry results, five with endometrial and one with urothelial cancer were diagnosed as LS with positive pathogenic variants in MMR genes., Conclusions: We report the outcome of immunohistochemistry for MMR proteins performed in multiple types of young-onset extra-colorectal LS-associated cancers. Our study demonstrates the feasibility of a comprehensive LS screening program incorporating young-onset patients with various types of extra-colorectal LS-associated cancers., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

The staging of endometrial cancer is based on the International Federation of Gynecology and Obstetrics (FIGO) staging system according to the examination of surgical specimens, and has revised in 2023, 14 years after its last revision in 2009. Molecular and histological classification has incorporated to new FIGO system reflecting the biological behavior and prognosis of endometrial cancer. Nonetheless, the basic role of imaging modalities including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography, as a preoperative assessment of the tumor extension and also the evaluation points in CT and MRI imaging are not changed, other than several point of local tumor extension. In the field of radiology, it has also undergone remarkable advancement through the rapid progress of computational technology. The application of deep learning reconstruction techniques contributes the benefits of shorter acquisition time or higher quality. Radiomics, which extract various quantitative features from the images, is also expected to have the potential for the quantitative prediction of risk factors such as histological types and lymphovascular space invasion, which is newly included in the new FIGO system. This article reviews the preoperative imaging diagnosis in new FIGO system and recent advances in imaging analysis and their clinical contributions in endometrial cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 3., (© 2023 International Society for Magnetic Resonance in Medicine.)

SMARCA4-deficient tumors have been reported in various organs and are associated with a poor prognosis. SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) was first described in 2018. Conversely, loss of SMARCA4 (BRG1) expression, as observed by immunostaining, has been observed in several cases of undifferentiated endometrial carcinoma. SDUS has considerable morphologic overlap with undifferentiated endometrial carcinoma, while there are differences in their clinicopathological features. Here, we present two cases of SMARCA4-deficient uterine tumors in patients in their 20 s: SDUS ( Case 1 ) and undifferentiated endometrial carcinoma without SMARCA4 nuclear expression ( Case 2 ). Using comprehensive genome profiling, we found that both cases had SMARCA4 mutations, with tumor mutation burdens of 0 and 68 Muts/Mb, respectively. Case 1 had multiple lung metastases 9 months after surgery. We treated the patients with combination of an immune checkpoint inhibitor (pembrolizumab) and a multikinase inhibitor (lenvatinib), and the response to the treatment was stable. This study presents the first report on the response to immune checkpoint inhibitor and multikinase inhibitor in SDUS., Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-024-00721-2., Competing Interests: Conflict of interestThe authors declare no conflicts of interest related to this manuscript., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Mucinous borderline ovarian tumors (MBOTs) have a very low recurrence rate and a good prognosis, especially in the early stages, but some MBOTs occasionally recur with the progression to mucinous ovarian carcinomas (MOCs). Here, we present a case of MBOT that recurred as invasive MOC within 3 years. To examine the reason for the progression from MBOT to MOC, whole-exome sequencing of our case identified identical mutations and copy number alterations in KRAS , CDKN2A , and TP53 in both the MBOT and recurrent MOC. The recurrent MOC had a greater copy number alteration burden compared to the primary MBOT. These findings suggest that MBOT may have progressed to MOC via recurrence, wherein the increased burden of copy number alterations could be its key driver. It was also suggested that TP53 mutations already present in MBOT may contribute to the increased copy number alterations leading to MOC., Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-024-00722-1., Competing Interests: Conflict of interestThe authors declare no conflicts of interest related to this manuscript., (© The Author(s) under exclusive licence to The Japan Society of Clinical Oncology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Primary peritoneal cancer has characteristics similar to high-grade serous carcinomas of ovarian and fallopian tube origin. However, the relationship between endometriosis and primary peritoneal cancer is not well understood. This study focuses on a case of peritoneal cancer in a patient who had undergone hysterectomy and bilateral salpingo-oophorectomy 5 yr before. In addition to morphology, there was a positive for TP53 in immunohistochemistry and homologous recombination deficiency test, which were similar to high-grade serous carcinomas. However, WT1 was negative in the tumor, and extensive endometriosis coexisted. To reveal the clonal relationship between tumor and endometriosis, we dissected 3 sites each from the tumor and endometriosis and performed whole-exome sequencing analysis. As a result, we found that the tumors were of identical origin. Contrarily, no shared mutations were found in the 3 endometriosis sites. Furthermore, several shared mutations were found between the tumor and 1 endometriosis tissue, showing that the tumor and 1 ectopic endometrial gland originated from the same clone. This study indicates that several peritoneal cancers may be derived from endometriosis. We should consider the possibility of more diverse origins of peritoneal cancer than we speculated before., Competing Interests: K.Y. and M.M. receive grants from company DUMSCO Inc. S.O. is an editorial board member of Cancer Science. The remaining authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Aim: Recent evidence suggests that acute liver failure (ALF) in some patients may reflect a dysregulated immune response, and that corticosteroids improve survival of the native liver in ALF patients with high serum alanine aminotransferase levels, which are an indication of liver inflammation. However, it is unclear whether steroids are effective for pediatric acute liver failure (PALF). The aim of this retrospective case-control study is to examine whether steroid therapy for PALF accompanied by immune activation improves the survival of native liver and to identify factors that predict responses to steroid treatment., Methods: Of 38 patients with PALF treated at Kyoto University Hospital from February 2006 to August 2022, 19 receiving steroids who met the specific criteria for identifying the pathophysiology of immune activity in the liver (the "Steroid group"), and seven steroid-free patients who also met the criteria ("Nonsteroid group") were enrolled. Patients in the "Steroid group" were categorized as "responders" or "nonresponders" according to treatment outcome. Clinical and histological data were analyzed., Results: Survival of the native liver in the Steroid group was significantly higher than that in the Nonsteroid group (68% vs. 0%, respectively; p = 0.0052). Nonresponders were significantly younger, with higher Model for End-stage Liver Disease and pediatric end-stage liver disease scores, higher prothrombin time - international normalized ratio, and higher serum ferritin levels than responders. Massive hepatic necrosis was more common in nonresponders., Conclusion: Steroid therapy is effective for PALF patients with liver inflammation; however, liver transplantation should be prioritized for young children with ALF accompanied by severe coagulopathy or massive hepatic necrosis., (© 2024 The Author(s). Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

Tumor-infiltrating lymphocytes (TILs) are associated with improved survival in patients with epithelial ovarian cancer. However, TIL evaluation has not been used in routine clinical practice because of reproducibility issues. The current study developed two convolutional neural network models to detect TILs and to determine their spatial location in whole slide images, and established a spatial assessment pipeline to objectively quantify intraepithelial and stromal TILs in patients with high-grade serous ovarian carcinoma. The predictions of the established models showed a significant positive correlation with the number of CD8 + T cells and immune gene expressions. Patients with a higher density of intraepithelial TILs had a significantly prolonged overall survival and progression-free survival in multiple cohorts. On the basis of the density of intraepithelial and stromal TILs, patients were classified into three immunophenotypes: immune inflamed, excluded, and desert. The immune-desert subgroup showed the worst prognosis. Gene expression analysis showed that the immune-desert subgroup had lower immune cytolytic activity and T-cell-inflamed gene-expression profile scores, whereas the immune-excluded subgroup had higher expression of interferon-γ and programmed death 1 receptor signaling pathway. The established evaluation method provided detailed and comprehensive quantification of intraepithelial and stromal TILs throughout hematoxylin and eosin-stained slides. It has potential for clinical application for personalized treatment of patients with ovarian cancer., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare, recurrent oncogenic variant that constitutively activates EGFR in non-small-cell lung cancer. Herein, we report the case of a 70-year-old man with resectable colorectal adenocarcinoma who underwent surgery followed by adjuvant therapy. He relapsed with multiple liver metastases and received standard chemotherapy until his disease became refractory. Comprehensive genomic profiling of his postoperative colorectal cancer tissue revealed EGFR-KDD. He was treated with an EGFR tyrosine kinase inhibitor (TKI), afatinib and achieved a partial response (- 55%) after 8 weeks; however, he developed massive malignant ascites after 13 weeks. Osimertinib, another EGFR-TKI, controlled his tumors for 9 months. Patient-derived cancer organoids from his malignant ascites confirmed sensitivity to EGFR-TKIs. The findings suggest that EGFR-TKIs can be a potential treatment option for this molecular subgroup., (© The Author(s) 2024. Published by Oxford University Press.)

Objectives: To build preoperative prediction models with and without MRI for regional lymph node metastasis (r-LNM, pelvic and/or para-aortic LNM (PENM/PANM)) and for PANM in endometrial cancer using established risk factors., Methods: In this retrospective two-center study, 364 patients with endometrial cancer were included: 253 in the model development and 111 in the external validation. For r-LNM and PANM, respectively, best subset regression with ten-time fivefold cross validation was conducted using ten established risk factors (4 clinical and 6 imaging factors). Models with the top 10 percentile of area under the curve (AUC) and with the fewest variables in the model development were subjected to the external validation (11 and 4 candidates, respectively, for r-LNM and PANM). Then, the models with the highest AUC were selected as the final models. Models without MRI findings were developed similarly, assuming the cases where MRI was not available., Results: The final r-LNM model consisted of pelvic lymph node (PEN) ≥ 6 mm, deep myometrial invasion (DMI) on MRI, CA125, para-aortic lymph node (PAN) ≥ 6 mm, and biopsy; PANM model consisted of DMI, PAN, PEN, and CA125 (in order of correlation coefficient β values). The AUCs were 0.85 (95%CI: 0.77-0.92) and 0.86 (0.75-0.94) for the external validation, respectively. The model without MRI for r-LNM and PANM showed AUC of 0.79 (0.68-0.89) and 0.87 (0.76-0.96), respectively., Conclusions: The prediction models created by best subset regression with cross validation showed high diagnostic performance for predicting LNM in endometrial cancer, which may avoid unnecessary lymphadenectomies., Clinical Relevance Statement: The prediction risks of lymph node metastasis (LNM) and para-aortic LNM can be easily obtained for all patients with endometrial cancer by inputting the conventional clinical information into our models. They help in the decision-making for optimal lymphadenectomy and personalized treatment., Key Points: •Diagnostic performance of lymph node metastases (LNM) in endometrial cancer is low based on size criteria and can be improved by combining with other clinical information. •The optimized logistic regression model for regional LNM consists of lymph node ≥ 6 mm, deep myometrial invasion, cancer antigen-125, and biopsy, showing high diagnostic performance. •Our model predicts the preoperative risk of LNM, which may avoid unnecessary lymphadenectomies., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe drug eruption that causes multiple organ damage. The renal impairment in these patients usually improves with immunosuppressants, but subsequent infections often develop. We herein report a rare case of DRESS syndrome leading to hemodialysis and multiple infections with Pneumocystis pneumonia, cytomegalovirus and Aspergillus despite the administration of low-dose prednisolone. We also present a literature review of cases requiring dialysis after DRESS syndrome. In patients with chronic kidney disease, it is important to be alert for not only the development of DRESS syndrome but also subsequent infections.

Pancreatic solid pseudopapillary neoplasm (SPN) is a low-grade malignant neoplasm with a good prognosis. Clinically aggressive SPNs have rarely been reported but have not been analyzed in detail. In this study, we referred to this highly malignant type of SPN as high-grade SPN (HG-SPN) and compared its clinicopathological and genetic characteristics with conventional SPN (C-SPN) using immunohistochemistry and gene panel analyses. Five HG-SPNs and 15 C-SPNs were evaluated in this study. HG-SPNs share many pathologic characteristics: macroscopically, solid/cystic appearances, microscopically, pseudopapillary/pseudorosette pattern (100%), tumor cell loose cohesiveness (100%), thin/delicate vasculature (100%), tumor cell cytoplasmic vacuolization (100%), immunohistochemical positivity for β-catenin (nuclear expression) (100%), CD10 (80%), CD56 (80%), and vimentin (100%). Conversely, HG-SPNs showed distinct malignant features compared with C-SPNs: mean tumor size (11.7 vs. 2.9 cm, P <0.001); true necrosis (100% vs. 0%, P <0.001); high-grade nuclear atypia (100% vs. 0%, P <0.001); lymphatic and/or venous invasion (100% vs. 20%, P =0.004); mean mitotic count (4.38 vs. 0.05/high-power field, P <0.001); and mean Ki-67 labeling index (33.9% vs. 3.4%, P <0.001). All HG-SPN patients died of primary disease 3 to 36 months after surgery, while all C-SPN patients were alive without disease. Genetic studies have shown that all analyzed HG-SPNs have CTNNB1 mutations. Two HG-SPN cases showed RB1 mutations with altered immunohistochemical findings for RB1 and p16. Two HG-SPN cases had TP53 mutation and/or p53 overexpression. In conclusion, HG-SPNs show distinct malignant features and some genetic alterations that differ from C-SPNs, indicating the importance of differentiating between these 2 subtypes., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Primary diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) can be difficult to diagnose because of the limited amount of biopsy tissue. Here, we analyzed the utility of insulin-like growth factor II mRNA binding protein 3 (IMP3) immunohistochemistry (IHC) as an adjunctive diagnostic tool for CNS-DLBCL. IHC was performed on 57 biopsy samples (55 brain biopsy samples and two vitreous cell blocks) from 54 patients with CNS-DLBCL, including three biopsy samples initially diagnosed as negative or indeterminate for CNS-DLBCL. Additionally, IMP3 IHC was performed on 68 DLBCLs other than CNS-DLBCL and 12 inflammatory brain diseases. Cytoplasmic IMP3 expression was noted in ≥50% of tumor cells in 100% (57/57) of CNS-DLBCLs and 88.2% (60/68) of non-CNS-DLBCLs. In contrast, no IMP3-positive CD20-positive B cells were observed in the inflammatory brain disease (P < 0.0001). In conclusion, IMP3 is highly expressed in CNS-DLBCL. However, it is also expressed in other types of DLBCLs, making it less specific. Most CNS-DLBCL cases can be diagnosed without performing IHC for IMP3 expression, but it may be a useful adjunctive tool to differentiate from reactive lesions when tumor cells are few or deformed.

The number of patients with syphilis has been rapidly increasing. Without treatment, syphilis can damage various organs and become life-threatening. We herein report a 29-year-old woman diagnosed with neurosyphilis, acute hydrocephalus, syphilitic uveitis combined with hypertensive retinopathy, and malignant hypertensive nephropathy. To our knowledge, this is the first report of syphilis complicated with malignant hypertensive nephropathy proven by a renal biopsy. Neurosyphilis was successfully treated with intravenous penicillin G, and severe hypertension subsequently resolved. However, delayed medical examinations and complications of syphilitic uveitis and hypertensive retinopathy resulted in irreversible visual loss. To prevent irreversible organ damage, early treatment is essential.

Background: Adult non-neoplastic hyperinsulinemic hypoglycemia (ANHH), also known as adult-onset nesidioblastosis, is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. This disease is characterized by diffuse hyperplasia of pancreatic endocrine cells and is diagnosed by a pathological examination. While diagnostic criteria for this disease have already been proposed, we established more quantitative criteria for evaluating islet morphology., Methods: We measured the number, maximum diameter, total area, and circularity (representing how closely islets resemble perfect spheres) of islets contained in representative sections of ANHH (n = 4) and control cases (n = 5) using the NIS-Elements software program. We also measured the average cell size, percentage of cells with enlarged nuclei, and percentage of cells with recognizable nucleoli for each of three representative islets. We also assessed the interobserver diagnostic concordance of ANHH between five experienced and seven less-experienced pathologists., Results: There was no significant difference in the number, maximum diameter, or total area of islets between the two groups, even after correcting for these parameters per unit area. However, the number of islets with low circularity (< 0.71) per total area of the pancreatic parenchyma was significantly larger in ANHH specimens than in controls. We also found that the percentage of cells with recognizable nucleoli was significantly higher in the ANHH group than in the controls. There were no significant differences in the average cell size or the number of cells with enlarged nuclei between the groups. The correct diagnosis rate with the blind test was 47.5% ± 6.12% for experienced pathologists and 50.0% ± 8.63% for less-experienced pathologists, with no significant differences noted., Conclusions: Low circularity, which indicates an irregular islet shape, referred to as "irregular shape and occasional enlargement of islets" and "lobulated islet structure" in a previous report, is a useful marker for diagnosing ANHH. An increased percentage of recognizable nucleoli, corresponding to "macronucleoli in β-cells," has potential diagnostic value., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Ovarian serous borderline tumors (SBT) are typically unilateral and are primarily treated using hysterectomy and bilateral salpingooophorectomy (SO). However, most young patients prefer fertility-sparing surgeries (FSS) with tumorectomy or unilateral SO. Micropapillary morphology and invasive implants have been designated as histopathological risk indicators for recurrence or metastasis, but their clinical impact remains controversial because of limitations like diagnostic inconsistency and incomplete surgical staging., Methods: A nationwide multi-institutional population-based retrospective surveillance was conducted with a thorough central pathology review to reveal the clinical features of SBT. Of 313 SBT patients enrolled in the Japanese Society of Clinical Oncology's Surveillance of Gynecologic Rare Tumors, 289 patient records were reviewed for clinical outcomes. The glass slides of patients at stage II-IV or with recurrence or death were re-evaluated by three gynecological pathologists., Result: The 10-year overall and progression-free survival (PFS) rates were 98.6% and 92.3%. The median recurrence period was 40 months and 77.0% was observed in the contralateral ovary within 60 months. Patients aged ≤ 35 years underwent FSS more frequently and relapsed more (p < .001). A clinic-pathological analysis revealed diagnosis during pregnancy, FSS, and treatment at non-university institutes as well as advanced stage and large diameter were independent risk factors of recurrence. Among patients having pathologically confirmed SBTs, PFS was not influenced by the presence of micropapillary pattern or invasive implants., Conclusion: The recurrence rate was lower in this cohort than previous reports, but the clinical impacts of incomplete resection and misclassification of the tumor were still significant on the treatment of SBT., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Finding the ideal balance between efficacy and safety of immunosuppression is challenging, particularly in cases of severe TAFRO syndrome. We herein report a 60-year-old man diagnosed with grade 5 TAFRO syndrome mimicking hepatorenal syndrome that was successfully treated by glucocorticoid, tocilizumab, and cyclosporin despite virus infection. Furthermore, by examining 14 peer-reviewed remission cases, we revealed that the recovery periods among inflammation, renal dysfunction, and thrombocytopenia were quite different, with recovery from thrombocytopenia notably slow. All patients requiring dialysis were successfully withdrawn from dialysis, and the reversibility from kidney injury was good. This clinical information will help clinicians plan treatments and tailor the intensity of immunosuppression.

Ponatinib is a novel multi-tyrosine kinase inhibitor (TKI) with potent inhibitory activity against refractory chronic myeloid leukemia (CML). Despite its high clinical efficacy, ponatinib induces various adverse events due to its multi-target characteristic. However, renal complications associated with ponatinib are rare. A 76-year-old woman had a history of chronic myeloid leukemia (CML) resistant to imatinib and nilotinib. Our patient developed proteinuria and renal function deterioration during treatment with ponatinib but not with imatinib or nilotinib. We herein report the first case of a patient with secondary focal segmental glomerulosclerosis (FSGS) with partial glomerular collapse induced by ponatinib treatment.

The most common subtype of ovarian carcinoma associated with somatically derived yolk sac tumor (YST) is endometrioid carcinoma. Only two cases of ovarian mucinous carcinomas associated with YST have been reported; herein, we present three additional patients, along with a review of previous literature and our pathology archives to analyze the tumor prognosis. The patients' ages ranged from 38 to 53 years. Two patients had FIGO stage 1 tumors, and one patient had a stage 3 tumor. Two patients died of the disease within a year, and one patient survived with distant metastasis (32 months after surgery). In all three tumors, the YST-like component comprised less than 5% of the total tumor area. Together with the two previously reported mucinous carcinomas with a YST-like component, the prognosis of the five mucinous carcinomas with a YST-like component were compared with that of 19 conventional mucinous carcinomas resected at our hospital. The survival curves were estimated using the Kaplan-Meier method. As a result, the overall survival rate of patients with mucinous carcinomas with a YST-like component was significantly lower than that of patients with conventional mucinous carcinomas ( P  = .0014). Our study indicates that the presence of a YST-like component in mucinous carcinomas would be a strong prognostic indicator.

Background: Tubulointerstitial nephritis with IgM-positive plasma cells (IgMPC-TIN) is a newer disease about which there are many unclear points. Glucocorticoid therapy is effective in many cases of IgMPC-TIN; however, relapse during glucocorticoid tapering has been reported. Relapse and its treatment are poorly defined., Case Presentation: Case 1 was a 61-year-old man with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. He was diagnosed with IgMPC-TIN accompanied by Fanconi syndrome and distal renal tubular acidosis (d-RTA). Prednisolone (PSL; 30 mg daily, 0.45 mg/kg/day) treatment was highly effective, and PSL was gradually tapered and discontinued after 1 year. However, 1 month after PSL discontinuation, therapeutic markers were elevated. Therefore, PSL (10 mg daily, 0.15 mg/kg/day) was administered, and the markers indicated improvement. Case 2 was a 43-year-old woman referred for renal dysfunction and proteinuria. Laboratory data revealed that she had primary biliary cholangitis (PBC), d-RTA, and Fanconi syndrome. A renal biopsy showed accumulation of IgM-positive plasma cells in the tubulointerstitium without any glomerular changes. A diagnosis of IgMPC-TIN was made and the patient was started on PSL (35 mg daily, 0.6 mg/kg/day). Therapeutic markers decreased immediately and PSL was discontinued after 1 year. Three months later, the proteinuria and Fanconi syndrome worsened. PSL treatment was restarted (20 mg daily, 0.35 mg/kg/day) and markers indicated improvement. Case 3 was a 45-year-old woman with renal dysfunction and proteinuria. Tubulointerstitial nephritis and IgM-positive plasma cells were observed in a renal biopsy. The patient had PBC, Sjögren syndrome, d-RTA, and Fanconi syndrome, and the diagnosis of IgMPC-TIN was made. The patient was started on PSL (30 mg daily, 0.4 mg/kg/day) and disease markers decreased immediately. However, when PSL was tapered to 15 mg daily (0.2 mg/kg/day), the patient's serum IgM levels increased; therefore, we maintained the PSL at 15 mg daily (0.2 mg/kg/day)., Conclusion: We report three cases of relapsed IgMPC-TIN associated with reduction or discontinuation of glucocorticoid therapy. In these cases, elevation of serum IgM preceded that of other markers such as urinary β 2 -microglobulin, proteinuria, and glycosuria. We recommend monitoring serum IgM levels while tapering glucocorticoids; a maintenance dose of glucocorticoid should be considered if relapse is suspected or anticipated., (© 2023. The Author(s).)

Malignant gastrointestinal neuroectodermal tumors (GNETs) are mesenchymal tumors that typically arise in the digestive tract and harbor EWSR1::ATF1 or EWSR1::CREB1 fusions. We report a case of primary retroperitoneal GNET in a 38-year-old woman who presented with a month-long fever with increased serum IL-6 level. A right retroperitoneal mass of 7 cm consisting of diffuse sheets of small cells with a high nuclear-to-cytoplasmic ratio and scattered osteoclast-like multinucleated giant cells was confirmed apart from the digestive tract. Peripheral lymphoid cuff and focal pseudoangiomatous spaces were present, reminiscent of angiomatoid fibrous histiocytoma. The tumor cells were positive for S100 protein and SOX10 and negative for melanocytic markers. Fluorescent in situ hybridization revealed EWSR1 and CREM gene rearrangements, consistent with EWSR1::CREM fusion, which has never been reported in GNET. The patient lives with recurrent lesions for 8 months. This case was associated with several unusual features and contributes to the evolving GNET concept., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Next-generation sequencing (NGS)-based gene profiling can identify patients with pancreatic cancer with homologous recombinant repair gene pathogenic variants (HRRv). Several retrospective studies have reported a positive association between HRRv and the efficacy of platinum-based chemotherapy. However, this association remains to be validated in a prospective study. This multicenter, prospective, observational study included patients with histologically confirmed unresectable or recurrent pancreatic cancer who required systemic chemotherapy. Patients who were oxaliplatin-naïve patients were eligible. The HRRv status was measured using a College of American Pathologists-accredited NGS panel. One-year overall survival rate (1yr-OS%) was calculated after initiation of oxaliplatin-based chemotherapy and was set as the primary endpoint. Forty patients were enrolled between August 2018 and March 2020. The NGS success rate was 95% (38/40). HRRv was detected in 11 patients (27.5%). Oxaliplatin-based chemotherapy was administered to 9 of 11 patients with HRRv (81.8%) and 15 of 29 patients with non-HRRv (51.7%). The 1yr-OS% after initiation of oxaliplatin-based chemotherapy was 44.4% [95% confidence interval (CI) 13.7-71.9] and 57.1% (95% CI 28.4-78.0) in HRRv-positive and -negative cohorts, respectively. These data suggested that HRRv status alone could not be a potential predictive marker of oxaliplatin-based chemotherapy in patients with advanced pancreatic cancer. These results were in line with the results of a recent phase II study reporting the limited efficacy of poly(adenosine diphosphate-ribose) polymerase inhibitor in patients with pancreatic cancer who harbored HRRv other than BRCA. Future studies investigating patients with biallelic HRRv in the first-line setting are warranted.Trial registration UMIN000033655., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Most gastric cancers develop in inflamed gastric mucosa due to Helicobacter pylori infection, typically with metaplastic changes. However, the origins of gastric cancer remain unknown. Here, we present a case of intramucosal gastric carcinoma (IGC) and oxyntic gland adenoma (OGA) derived from spasmolytic polypeptide-expressing metaplasia (SPEM). Early gastric cancer adjacent to a polyp was found in the upper corpus of a 71-year-old woman without H. pylori infection and was endoscopically resected. Histological examination showed IGC and OGA, both of which had predominant MUC6 expression. Interestingly, gastric glands with enriched MUC6-positive mucous cells, referred to as SPEM, expanded between them. Whole-exome sequencing analysis revealed a truncating KRAS(G12D) mutation in IGC, OGA, and SPEM. In addition, TP53 and CDKN2A mutations and a loss of chromosome 17p were found in the IGC, whereas a GNAS mutation was observed in the OGA. These results indicated that IGC and OGA originated from the KRAS-mutated SPEM. © 2023 The Pathological Society of Great Britain and Ireland., (© 2023 The Pathological Society of Great Britain and Ireland.)

In post-liver transplant recipients, SARS-CoV-2 infection is a health threat, and novel messenger RNA vaccines such as Pfizer BioNTech BNT162b2 and Moderna mRNA-1273 are aggressively recommended. However, there are few reports on their adverse effects, some of which may be potentially fatal. We have experienced 2 post-liver transplant recipients with exacerbated chronic rejection after vaccination, one of whom had to undergo retransplant and the other who is still in the process of liver function without improvement. These alarming cases will be presented as case reports., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Early identification of placental insufficiency can lead to appropriate treatment selections and can improve neonates' outcomes. Possible contributions of magnetic resonance imaging (MRI) have been suggested., Purpose: To evaluate the prognostic capabilities of placental intravoxel incoherent motion (IVIM) parameters and T2-relaxation time, and their correlation with fetal growth and adverse outcomes, comparing umbilical artery (UmA) pulsatility index (PI)., Material and Methods: A total of 68 singleton pregnancies at 24-40 weeks of gestation underwent placental MRI and were reviewed retrospectively. UmA-PI was measured using Doppler ultrasound by obstetricians. IVIM parameters ( Dfast , Dslow , and f ) were calculated with a Bayesian model fitting. First, the associations between gestational age (GA) with placental IVIM parameters, T2-relaxation time, and placental thickness (PT) were evaluated. Second, IVIM parameters, T2 value (Z-score), PT (Z-score), and UmA-PI (Z-score) were compared between ( 1) those delivering small for gestational age (SGA) and appropriate for gestational age (AGA) neonates, ( 2) emergency cesarean section (ECS), and non-ECS, and ( 3) preterm birth and full-term birth., Results: Low birth weight was observed in 15/68 cases (22%). GA was significantly associated only with T2-relaxation time and PT. SGA was significantly associated with T2 value (Z-score), f , and UmA-PI (Z-score). In the ECS groups, T2 value (Z-score), f , and Dfast were significantly lower than those in non-ECS groups. All IVIM parameters and T2 values (Z-score) showed significantly lower scores in the preterm birth group., Conclusion: Placental f and T2 value (Z-score) had significant associations with low birth weight and clinical adverse outcomes and could be potential imaging biomarkers of placental insufficiency.

Background: Diagnosis of fetal growth restriction (FGR) entails difficulties with differentiating fetuses not fulfilling their growth potential because of pathologic conditions, such as placental insufficiency, from constitutionally small fetuses. The feasibility of placental MRI for risk stratification among pregnancies diagnosed with FGR remains unexplored., Purpose: To explore quantitative MRI features useful to identify pregnancies with unfavorable outcomes and to assess the diagnostic performance of visual analysis of MRI to detect pregnancies with unfavorable outcomes, among pregnancies diagnosed with FGR., Study Type: Retrospective., Population: Thirteen pregnancies with unfavorable outcomes (preterm emergency cesarean section or intrauterine fetal death) and 11 pregnancies with favorable outcomes performed MRI at gestational weeks 21-36., Field Strength/sequence: A 5-T, half-Fourier-acquired single-shot turbo spin echo (HASTE), spin-echo echo-planar imaging (SE-EPI) and T2 map derived from SE-EPI., Assessment: Placental size on HASTE sequences and T2 mapping-based histogram features were extracted. Three radiologists qualitatively evaluated the visibility of maternal cotyledon on HASTE and SE-EPI sequences with echo times (TEs) = 60, 90, and 120 msec using 3-point Likert scales: 0, absent; 1, equivocal; and 2, present., Statistical Tests: Welch's t-test or Mann-Whitney U test for quantitative features between the favorable and unfavorable outcome groups. Areas under the receiver operating curves (AUCs) of the three readers' visual analyses to detect pregnancies with unfavorable outcomes. A P value of <0.05 was inferred as statistically significant., Results: Placental size (major and minor axis, estimated area of placental bed, and volume of placenta) and T2 mapping-based histogram features (mean, skewness, and kurtosis) were statistically significantly different between the two groups. Visual analysis of HASTE and SE-EPI with TE = 60 msec showed AUCs of 0.80-0.86 to detect pregnancies with unfavorable outcomes., Data Conclusion: Placental size, histogram features, and visual analysis of placental MRI may allow for risk stratification regarding outcomes among pregnancies diagnosed with FGR., Evidence Level: 3 TECHNICAL EFFICACY: Stage 5., (© 2022 International Society for Magnetic Resonance in Medicine.)

Aim: The pathogenic mechanism of chronic abruption-oligohydramnios sequence (CAOS) remains unknown, and there are no objective standards for diagnosis on imaging or using pathological evidence. We aimed to reconsider and clarify the true pathology of CAOS by integrating clinical, magnetic resonance imaging (MRI) and histopathological findings of the placenta., Material and Methods: This is a case series of patients with CAOS managed at our hospital between 2010 and 2020. The clinical data of the patients, including MRI findings and placental pathology, were reviewed retrospectively., Results: A total of 18 patients were eligible. Preterm birth occurred in 17 (94%) cases; the median gestational age at delivery was 25. Three neonates (17%) died within two years, and 10 neonates (56%) developed chronic lung disease. MRI was performed in 13 cases and clearly showed intrauterine hematoma and hemorrhagic amniotic fluid. Pathologically, in all cases, retroplacental hematoma was not detected, and fetal membranes were extremely fragile and ragged. Shedding and necrosis of the amniotic epithelium was a characteristic finding, which was confirmed in 17 cases (94%). Diffuse chorionic hemosiderosis (DCH) was detected in all cases., Conclusions: The fundamental cause of CAOS is repeated intrauterine hemorrhage and subsequent subchorionic hematoma, which induces hemorrhagic amniotic fluid and DCH. Consequently, these factors result in the necrosis and weakening of the amnion. Therefore, the true pathology of CAOS is believed to be premature rupture of membranes rather than chronic abruption.

A 39-year-old man had an intracranial tumour without infiltration into the surrounding cerebral tissue. The tumour recurred seven times in 11 years but maintained a well-demarcated character. Histopathological examination of the 4th surgical specimens showed nests of tumour cells surrounding small blood vessels. The tumour cells harboured amphophilic cytoplasm and small round nuclei with fine chromatin, and perinuclear haloes and clear borders were frequently observed, which was unclassifiable histology. By the Deutsches Krebsforschungszentrum methylation classifier, the tumour was not classified into any of the methylation classes. mRNA sequencing identified a novel SREBF1::NACC1 gene fusion. This intracranial tumour could be a novel tumour entity with NACC1 rearrangement showing characteristic histological and diagnostic imaging findings., (© 2022 British Neuropathological Society.)

Tumors demonstrating deficient mismatch repair (dMMR) account for 12%-15% of colorectal cancers (CRCs), but their characteristics have not been fully elucidated. The aim of this study was to characterize dMMR CRCs in terms of clinicopathological findings and molecular alterations. Immunostaining for mismatch repair (MMR) proteins was performed to determine MMR status, and then MLH1 promoter methylation and genetic variants of 25 genes involved in colorectal carcinogenesis were analyzed by next-generation sequencing in dMMR tumors. Coexistence of precancerous lesions was histologically evaluated to characterize the type of precursors. Immunohistochemistry revealed 34 dMMR tumors in 492 CRCs. Among dMMR CRCs, there were 25 MLH1 methylation-positive, 16 BRAF V600E variant-positive, and 7 KRAS variant-positive tumors. Positive MLH1 methylation was associated with BRAF V600E, older age, and right-side tumor location. MLH1 methylated BRAF/KRAS wild-type tumors were distinct in that all 5 tumors possessed variants in ligand-independent WNT signaling genes including APC, AXIN2, and CTNNB1. Among 10 dMMR CRCs that presented with precancerous lesions, 4 BRAF variant-positive, 1 KRAS variant-positive, and 2 BRAF/KRAS wild-type MLH1 methylated tumors coexisted with serrated lesions, whereas 1 MLH1 methylated BRAF/KRAS wild-type tumor and 2 MLH1 unmethylated tumors accompanied conventional adenomas. The present study characterized distinct subgroups of dMMR CRCs based on molecular alterations including MLH1 methylation and variants in BRAF, KRAS, and ligand-independent WNT signaling genes. The existence of distinct precursor lesions including serrated lesion and conventional adenoma further illustrates the involvement of heterogeneous carcinogenetic pathways in the development of dMMR CRCs., (Copyright © 2022 Elsevier Inc. All rights reserved.)