南口 早智子

Glomerular diseases with organized deposits can be classified into various etiologies. A diagnostic algorithm based on clinical and pathological findings has been proposed. However, some cases cannot be diagnosed using existing algorithms. Here, we report the case of a 77-year-old man diagnosed with membranoproliferative glomerulonephritis (MPGN) with striated ultrastructural deposits, microfilament-like substructures with straight bands arranged in parallel in the subendothelial space by two sequential renal biopsies. His examinations and clinical findings were incompatible with known glomerular diseases with organized deposits. Dialysis was initiated 10 months after the second biopsy procedure. Furthermore, we report the first mass spectrometry analysis of laser micro-dissected glomeruli with striated ultrastructural deposits, which revealed significant levels of fibrinogen and fibronectin. Immunostaining was positive for fibrinogen, fibrin, and fibronectin in the subendothelial space. These findings suggest that the deposits were composed of a fibrin-fibronectin complex, and that accumulation of these fibrin-fibronectin complexes possibly induced endothelial injury, leading to MPGN. We also reviewed the literature on the clinical and pathological characteristics of the four cases with striated ultrastructural deposits. Our investigation showed that all patients had the MPGN pattern and striated ultrastructural deposits in the subendothelial space, and all underwent hemodialysis within 3 years after renal biopsy. Clinicians should be aware of the findings of glomerulonephritis with striated ultrastructural deposits since this disease may be a new entity and has a poor prognosis.  .

BACKGROUND/AIMS: Pathological evaluation is crucial for diagnosing biliary lesions and determining appropriate treatment strategies. However, tissue sampling via the transpapillary route can be difficult. In this study, we aimed to assess the efficacy and safety of a novel tapered-tip sheath system for tissue sampling from biliary strictures. METHODS: This single-center, randomized, parallel-group clinical trial included patients aged 20 to 85 years admitted to Kyoto University Hospital for biliary strictures. The patients were randomly assigned (1:1) to a new or conventional method group. The primary outcome was technical success of biopsy at the target bile duct using the assigned method, as determined in accordance with the intention-to-treat principle. Adverse events were assessed in all eligible patients. RESULTS: Fifty-six patients were assessed for eligibility between September 2020 and March 2023; 50 patients were enrolled. The patients were randomly divided into the new (n=25) method group and the conventional (n=25) method group. Technical success was achieved in 96.0% (24/25) and 48.0% (12/25) of patients in the new and conventional method groups, respectively (risk ratio, 2.00; 95% confidence interval [CI], 1.32 to 3.03; risk difference, 48.0%; 95% CI, 27.0% to 69.0%; p<0.001). Adverse events occurred in 4.0% (1/25) and 36.0% (9/25) of patients in the new and conventional method groups, respectively (risk ratio, 0.11; 95% CI, 0.02 to 0.81; risk difference, -32.0%; 95% CI, -52.3% to -11.7%; p=0.005). CONCLUSIONS: The novel tapered-tip sheath system is a promising option for precisely and safely delivering biopsy forceps to target sites, thereby facilitating the diagnosis of biliary strictures.

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.

INTRODUCTION: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disease that can affect nearly every organ system, including blood vessels and the kidney. IgG4-related vascular lesions mainly involve the aorta, and the dominant renal manifestation is tubulointerstitial nephritis (TIN). Here, we report a case of IgG4-RD demonstrating extensive abdominal periarteritis and membranous nephropathy (MN). CASE PRESENTATION: The patient was a 71-year-old man with peptic ulcer who developed nephrotic syndrome, with a low serum albumin level (1.8 g/dL), massive urinary protein (6.1 g/day), and high serum IgG4 level (435 mg/dL). Computed tomography images revealed soft tissue mass around the medium-sized abdominal arteries. Renal pathological findings showed MN and focal infiltration of numerous IgG4-positive cells in the interstitium. The findings of high serum IgG4 levels, periarteritis, and focal inflammation with rich IgG4-positive plasma cells led to the diagnosis of IgG4-RD. We chose low-dose steroid therapy to prevent the recurrence of the peptic ulcer and aneurysm formation in the affected arteries, which can occur with medium to high doses of prednisolone. We successfully controlled IgG4-related periarteritis and kidney disease without relapse or complications. CONCLUSION: The varied clinical manifestations of IgG4-RD sometimes make the diagnosis challenging. However, clinicians should diagnose IgG4-RD based on serological, radiological, and pathological evaluations because, without appropriate therapy, IgG4-RD can lead to irreversible organ failure caused by swelling, obstruction, or fibrosis of the organs.

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.

UNLABELLED: 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.

UNLABELLED: 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.

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.

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.

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.

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.

There have been no reported cases of neuroendocrine carcinoma (NEC) of the cervix with pagetoid spread (Pag-S). A 44-year-old woman came to our department because of abnormal cytology that persisted immediately after a radical hysterectomy for NEC of the cervix. A mapping biopsy in a large area from the vaginal wall to the vulva revealed that synaptophysin/Ki-67-positive tumor cells were scattered within the epithelium in multiple areas, suggesting a wide Pag-S of NEC. Because tumor cells were found beyond the vaginal wall, the anterior pelvic exenteration was performed. Since we could pathologically confirm the complete resection and no distant metastases were detected, no adjuvant therapy was performed. Four years have passed since the initial treatment without any tumor recurrence. It is known that the prognosis of NEC of the cervix that invades beyond the cervix is poor; however, if there is a Pag-S pattern, a radical surgical treatment can be considered.

Tumor-infiltrating lymphocytes (TILs) are associated with improved survival in patients with epithelial ovarian cancer. However, the evaluation of TILs has not been applied to routine clinical practice due to reproducibility issues. We 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. We demonstrated that patients with a higher density of intraepithelial TILs had a significantly prolonged overall survival (OS) and progression-free survival (PFS) in multiple cohorts. Based on the density of intraepithelial and stromal TILs, we classified patients 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 (CYT) and T-cell-inflamed gene-expression profile (GEP) scores, whereas immune-excluded subgroup had higher expression of interferon-γ and programmed death 1 receptor (PD-1) signaling pathway. Our established evaluation method provides detailed and comprehensive quantification of intraepithelial and stromal TILs throughout hematoxylin and eosin (H&E)-stained slides, and has potential for clinical application for personalized treatment of patients with ovarian cancer.

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.

Context.— Endocervical adenocarcinoma is divided into human papillomavirus (HPV)–associated (HPVA) and HPV-independent (HPVI) in the 5h edition of the World Health Organization (WHO) tumor classification launched in 2020. However, the validity of the morphological 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.

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 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.

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.

Abstract 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 (&lt; 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.

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.

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.

Abstract 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 β₂-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.