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Background: Chemotherapy is crucial for hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and its survival benefits may outweigh adverse events. Oncotype DX (ODX) assesses this balance; however, it is expensive. Using nomograms to identify cases requiring ODX may be economically beneficial. We aimed to identify clinicopathological variables that correlated with the recurrence score (RS) and develop a nomogram that predicted the RS., Methods: We included 457 patients with estrogen receptor-positive, HER2-negative breast cancer with metastases in fewer than four axillary lymph nodes who underwent surgery and ODX at our hospital between 2007 and 2023. We developed nomograms and internally validated them in 310 patients who underwent surgery between 2007 and 2021 and validated the model's performance in 147 patients who underwent surgery between 2022 and 2023., Results: Logistic regression analysis revealed that progesterone receptor (PgR) level, histological grade (HG), and Ki67 index independently predicted the RS. A nomogram was developed using these variables to predict the RS (area under the curve [AUC], 0.870; 95% confidence interval [CI], 0.82-0.92). The nomogram was applied to the model validation group (AUC, 0.877; 95% CI, 0.80-0.95). When the sensitivity of the nomogram was 90%, the model was able to identify 52.3% low-RS and 41.2% high-RS cases not requiring ODX., Conclusions: This was the first nomogram model developed based on data from a cohort of Japanese women. It may help determine the indications for ODX and the use of nomogram to identify cases requiring ODX may be economically beneficial., (© 2024. The Author(s).)

We experienced three cases of a fever and subsequent severe, prolonged gross hematuria after COVID-19 vaccination. A kidney biopsy revealed immunoglobulin A (IgA) nephropathy, and electron microscopy showed two types of podocytopathy (podocyte damage): loss of foot processes from the glomerular basement membrane and foot process effacement. Mesangial interposition was also present in cases 1 and 3 but not in case 2. Podocytopathy is known to be a cause of proteinuria; however, the reactions to COVID-19 vaccination described here suggest that it may also be related to hematuria in IgA nephropathy.

A 62-year-old man with a history of diabetes mellitus was hospitalised with numbness of lower limbs, bullous lesions of the whole body, kidney dysfunction, presence of eosinophils, and elevated antineutrophil cytoplasmic antibodies to myeloperoxidase and anti-bullous pemphigoid 180 antibodies and was diagnosed with mononeuritis multiplex. Kidney and muscle biopsies showed vasculitis with fibrinoid necrosis, whereas skin biopsies showed only blister formation between the epidermis and dermis; a high eosinophilic infiltrate was present in all three tissues. These findings led to a diagnosis of eosinophilic granulomatosis with polyangiitis combined with allergic bullous lesions. Immunohistological examination indicated cytolytic eosinophils and extracellular traps, suggesting the presence of eosinophil extracellular trap cell death (eosinophil ETosis) in diseased tissue., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background: MRI is expected to be a valuable tool for evaluating disease activity in immunoglobulin G4 (IgG4)-related tubulointerstitial nephritis (IgG4-TIN). However, the correlation between MRI findings and renal histopathological findings remains to be elucidated., Purpose: This study aimed to clarify the correlation between MRI findings and renal histopathological findings in IgG4-TIN., Method: This retrospective cross-sectional study investigated 26 patients with biopsy-proven IgG4-TIN who underwent simultaneous percutaneous kidney biopsies and abdominal MRI examinations at Toranomon Hospital or Toranomon Hospital Kajigaya between December 2007 and November 2022. We reviewed kidney biopsy specimens and scored the degree of inflammatory cell infiltration and interstitial fibrosis. We assessed abdominal MRI, specifically examining T1WI, T2WI, and DWI, for the presence of abnormal signals in the inferior pole of the kidney on the side where the kidney biopsy was performed. Spearman's correlation coefficient test was conducted to examine the relationship between the images and histological findings., Result: For T1WI, eight cases showed a positive low-intensity signal, and 18 cases were negative. For T2WI, 19 cases were positive for a low-intensity signal, and seven cases were negative. In DWI, 23 cases were positive for a high-intensity signal, and one was negative. T1WI low-intensity signal and T2WI low-intensity signal were significantly correlated with interstitial fibrosis score (correlation coefficient 0.52 and 0.64). DWI revealed IgG4-TIN detected IgG4-TIN lesions with the highest sensitivity; however, the correlation with inflammatory cell infiltration score was not significant., Conclusion: Low-intensity signal on T2WI is useful for predicting the degree of fibrosis in IgG4-TIN., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

A 62-year-old man with type 2 diabetes was admitted because of a decrease in estimated glomerular filtration rate from 72 to 17.5 mL/min/1.73 m 2 in 10 years and development of widespread bullous skin lesions. His hemoglobin A1c level had been maintained at 6.0-7.0% for 10 years with a dipeptidyl peptidase (DPP)-4 inhibitor. Skin biopsy showed typical bullous pemphigoid, and kidney biopsy showed tubulointerstitial nephritis with eosinophilic infiltration and glomerular endothelial cell proliferation. After discontinuing the DPP-4 inhibitor, skin lesions improved, and renal decline slowed. This case indicates that DPP-4 inhibitors can cause not only skin lesions but also renal disease., (© 2023. The Author(s).)

A kidney biopsy was performed in a 64-year-old woman with type 2 diabetes mellitus and less than 1 g of proteinuria who rapidly progressed to end-stage renal failure after approximately 2 years of treatment with two dipeptidyl peptidase 4 (DPP-4) inhibitors for type 2 diabetes mellitus. The biopsy revealed not only a coincidental diagnosis of renal cell carcinoma, which was not evident on pre-biopsy computed tomography, but also severe thrombotic microangiopathy (TMA)-like glomerular endothelial cell damage in the noncancerous areas. These results suggest that DPP4 inhibitors may have been involved in two kidney diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kurihara, Sawa, Sumida, Ikuma, Oba, Mizuno, Sekine, Yamanouchi, Hasegawa, Suwabe, Urakami, Kono, Kinowaki, Ohashi, Yamaguchi and Ubara.)

A man with polycystic kidney disease and a history of renal transplantation at the age of 55 years developed seronegative rheumatoid arthritis (RA) at the age of 68 years. Treatment with a biological derivative led to remission; however, the patient relapsed 2 years later. After being switched to baricitinib, the patient again achieved remission. After 2 years, when the patient was aged 72 years, RA recurred, and the right native kidney became enlarged due to the presence of a large tumor. Surgical nephrectomy was performed, and the tumor was classified as renal cell carcinoma (RCC), not otherwise specified. The cancer tissue comprised sarcomatoid and rhabdoid cells with marked neutrophil infiltration, and the tumor cells were positive for interleukin-6. The patient, aged 73 years, experienced a resolution of joint pain following surgical intervention; however, they died because of systemic metastases ~10 weeks post-operation. Based on the clinical course, the RA-like lesions and subsequent RCC were considered to represent a paraneoplastic syndrome., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

A 49-year-old Japanese woman was admitted to our hospital with weight loss of 15 kg, nephrotic-range proteinuria (4.5 g/g.Cre), and hematuria over a 6-month period. She had received two doses of the coronavirus disease 2019 (COVID-19) vaccine one year before the onset of the disease, after which the estimated glomerular filtration rate increased. Laboratory tests and other tests led to a diagnosis of hyperthyroidism, and a kidney biopsy showed thrombotic microangiopathy-like glomerular microangiopathy comprising mainly glomerular endothelial cell damage. Thiamazole (30 mg) was started for the hyperthyroidism. Three months later, the thyroid function normalized, and two months later, the proteinuria and hematuria disappeared, suggesting that COVID-19 vaccination and these events were related.

A 68-year-old man with type 2 diabetes mellitus was admitted with decreased renal function. He had high IgG4 (1070 mg/dL) and hypocomplementemia (CH50, 25 U/mL). Kidney biopsy showed tubulointerstitial nephritis with IgG4-positive plasma cell infiltration. Four years later, a second kidney biopsy revealed a new manifestation of membranous nephropathy and tubulointerstitial nephritis with exacerbated fibrosis formation. Six years later, the patient developed bullous pemphigoid, which was thought to be caused by DPP4 inhibitors, so DPP4 inhibitor treatment was discontinued. The use of DPP4 inhibitors correlated with changes in renal function, and the patient was diagnosed with IgG4-related kidney disease related to DPP4 inhibitors., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

A 35-year-old woman was admitted for the examination of lower leg edema and proteinuria. A kidney biopsy showed membranous nephropathy (MN) with fine granular deposits of IgG along the glomerular capillary and poor spike formation, differing from primary MN in the presence of positive IgG3 and C1q. Lupus nephritis was excluded because serum complement and anti-dsDNA antibody, anti-Smith antibody, and anti-cardiolipin antibody tests were negative. The serological test for syphilis was positive, as was the Treponema pallidum hemagglutination test. The patient was diagnosed with syphilis, and the proteinuria disappeared with antibiotic treatment. In MN with positive IgG3 and C1q, syphilis nephropathy may be a differential diagnosis.

We report on a 53-year-old Japanese man diagnosed with gastric Burkitt's monomorphic post-transplant lymphoproliferative disorder (B-PTLD) after endoscopy for gastric discomfort 28 months after the patient underwent renal transplantation in Ethiopia. Serum Epstein-Barr virus (EBV) tests were negative before transplantation, but the tumor cells collected from a gastric biopsy showed positive EBV-encoded small RNAs (EBER) at B-PTLD onset. Intensive treatment started with R(rituximab)-CHOP therapy and continued with DA-EPOCH-R therapy has been effective, and relapse has not yet occurred. Burkitt lymphoma has a poor prognosis, but B-PTLD may be effectively treated with high-dose chemotherapy. This is a rare case of gastric B-PTLD in a Japanese patient.

Introduction: This study aimed to analyze the clinical course of TAFRO syndrome in patients through extended follow-up, focusing on recurrent cases and long-term remission., Methods: This was a retrospective case series study. We assessed the clinical course of patients diagnosed with TAFRO syndrome between January 2012 and September 2022 at Toranomon Hospital or Toranomon Hospital Kajigaya, excluding those patients who died during the initial hospitalization., Results: Twelve patients were included. Baseline characteristics, laboratory findings, treatment modalities, and outcomes were assessed. During the median follow-up period of 1474 days, two patients experienced recurrence following a reduction in tocilizumab (TCZ) dose, whereas two achieved remission for >400 days without TCZ treatment. The remaining eight patients maintained remission under the continued TCZ therapy. Recurrence diagnosis was complicated by the non-simultaneous presentation of the five manifestations of TAFRO syndrome. The patients who experienced recurrence showed milder manifestations and faster recovery than the initial onset. Glomerular endotheliopathy was evident in kidney biopsies during recurrence, which was similar to the initial presentation. In a case where only inflammation preceded other manifestation, a kidney biopsy was pivotal in distinguishing TAFRO syndrome relapse from other inflammatory conditions such as infection. Pretreatment serum IL-6 levels were within the reference range only in patients who experienced long-term remission without TCZ treatment., Conclusions: This is the first study to perform kidney biopsies on recurrent TAFRO cases, highlighting recurrence after TCZ dosage reduction, non-simultaneous manifestation of symptoms, the utility of kidney biopsies in recurrence diagnosis, and potential non-IL-6 pathogenesis factors. Pretreatment serum IL-6 levels may help identify patients suitable for maintenance therapy without TCZ. Further investigation is warranted to identify stratified treatment approaches based on individual etiologic factors., Competing Interests: The authors declare that they have no competing or conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Poststreptococcal acute kidney glomerulonephritis (PSAGN) has been seen in adults in recent years, especially in patients with type 2 diabetes mellitus, and the renal prognosis has not always been good. There have been cases of PSAGN in which complete remission was not achieved and hematuria and proteinuria persisted, leading to end-stage renal disease. Previous reports showed that the patients subjected to PSAGN have an underlying defect in regulating the alternative pathway of complement, and they identified that antibodies to the C3 convertase, C3 nephritic factors (C3NeF), are involved. C3NeF stabilizes C3 convertase, sustains C3 activation, and causes C3 glomerulonephritis (C3GN). On the other hand, factor H is a glycoprotein that suppresses the overactivation of the alternative pathway by decaying the C3 convertase. Anti-factor H (aFH) antibodies interfere with factor H and cause the same activation of the alternative pathway as C3NeF. However, a limited number of reports describe the clinical course of C3GN with aFH antibodies. We encountered a 49-year-old Japanese man with type 2 diabetes mellitus. He was referred to our hospital because of his elevated serum creatinine, proteinuria, hematuria, and developed edema on both legs. He was diagnosed as PSAGN at the first kidney biopsy, and his renal function improved and edema and hematuria disappeared, but proteinuria persisted after 5 months. He was diagnosed as C3GN at the second kidney biopsy. In our case, no C3NeF was detected. However, a high titer of aFH antibodies was detected in stored serum from the initial presentation, providing a unified diagnosis of aFH antibody-positive C3GN secondary to PSAGN. He progressed to end-stage renal disease (ESRD) and hemodialysis was started. The persistence of high levels of aFH autoantibodies may have caused C3GN secondary to PSAGN due to activating the alternative complement pathway, which eventually worsened the nephropathy and led to ESRD., (© 2023. The Author(s).)

A 28-year-old woman with a 5-year history of untreated hypertension was admitted for respiratory distress, hemoptysis, and retinopathy. Computed tomography showed diffuse plaques in both lung fields. Acute kidney injury, hemolytic anemia, and thrombocytopenia were noted. Kidney biopsy showed thrombosis with fibrinoid necrosis and edematous intimal thickening and luminal narrowing of the small renal artery, indicating thrombotic microangiopathy; the majority of glomeruli were collapsed. After 8 weeks of treatment with antihypertensive drugs, serum creatinine decreased to 1.0 mg/dL, and the patient recovered. In the absence of any other underlying disease, malignant nephrosclerosis associated with a hypertensive emergency was diagnosed., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

A 63-year-old man with polycystic kidney disease underwent kidney transplantation from his wife. Nine years later, after the first and second doses of the COVID-19 vaccination, he developed proteinuria, hematuria, and elevated C-reactive protein. Kidney biopsy 7 months after the initial appearance of proteinuria showed immunoglobulin (Ig)-G granular stain, predominantly IgG1, and spike formation in the glomerular basement membrane. Electron microscopy revealed mainly subepithelial deposits, which corresponds to membranous nephropathy (MN) stage 3 of the Ehrenreich-Churg classification indicating chronic disease, but it also showed electron-dense deposits and endothelial damage. Because a kidney biopsy was performed 1 h after renal transplantation and a biopsy of the patient's native kidney showed intact glomeruli, atypical de novo posttransplant membranous nephropathy (MN) was diagnosed, and a close relationship with COVID-19 vaccination was assumed. Clinicians should consider the involvement of COVID-19 vaccination in de novo posttransplant MN with unclear pathogenesis., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

A 58-year-old woman with rheumatoid arthritis was diagnosed with methotrexate-associated Hodgkin lymphoma. After receiving several chemotherapy regimens, she started nivolumab treatment. Two weeks later, she was hospitalized with worsening finger, wrist, and elbow joint pain. A synovial biopsy of the wrist joint showed villous synovial proliferation and linear infiltration of CD68-/CD3-positive T cells (with more CD8 than CD4 T cells) but no CD20-positive B cells or CD138-positive macrophages. These findings corresponded to synovitis associated with immune-related adverse events, which are induced mainly by T cells and are different from typical rheumatoid arthritis (RA), in which B cells play a central role.

A 37-year-old man with autosomal polycystic kidney disease (ADPKD) was admitted to our hospital with a liver volume of 8,000 cm 3 . Hepatic arterial embolization was performed using a microcoil but was ineffective. Eight years later, the hepatomegaly progressed to liver failure and death. At autopsy, the liver weighed 21.5 kg, and the entire liver had been replaced by cysts; in the few remaining areas of liver parenchyma, microscopic, small cysts of various sizes and fibrosis were evident, with only a few normal hepatocytes observed. Hepatic arterial branches developed; however, the portal vein could not be observed.

Pancreatic neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are rare pancreatic malignant tumors, and comprehensive gene analyses are scarce. In this study, six NECs and six MiNENs were collected, immunohistochemistry for synaptophysin, chromogranin A, INSM1, Ki-67, and Rb was conducted, and KRAS mutational status was examined. Among these cases, comprehensive gene expression analysis of oncogene pathways using nCounter® were performed with six NECs and four MiNENs, and those data were compared with that of three pancreatic ductal adenocarcinomas (PDACs), with that of three normal pancreatic ducts, and with each other. By dividing NEC and MiNEN cases into KRAS-mutated group and KRAS-wild group, the difference of clinicopathological data and gene expression profiling data were examined between the two groups. Compared to the data of normal pancreatic epithelium, all 13 cancer-related pathways were upregulated in PDAC, MiNEN, and NEC group with more upregulation in this order. Compared to the data of PDAC, genes of DNA Damage repair pathway was most upregulated both in NECs and MiNENs. Regarding the difference between KRAS-mutated and KRAS-wild groups, several genes were differentially expressed between the two, where MMP7 was the upregulated gene with highest p-value and NKD1 was the downregulated gene with highest p-value in KRAS-mutated group. From the extent of upregulation of 13 pathways, MiNEN was considered more progressed stage than PDAC, and NEC was considered more progressed than MiNEN. From the comparison of KRAS-mutated and KRAS-wild NECs and MiNENs, several differentially expressed genes were identified in this study., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

A 48-year-old woman visited our hospital because of bilateral lacrimal gland enlargement. Her serum immunoglobulin G4 (IgG4) level was high, and positron emission tomography-computed tomography showed significant positive findings in the bilateral lacrimal gland. A biopsy revealed a considerable increase in IgG4/CD138, leading to a diagnosis of IgG4-related dacryoadenitis. The disease did not respond to steroid therapy, so treatment was started with baricitinib because of exacerbation of the original atopic dermatitis and dacryoadenitis after the second dose of the coronavirus disease 2019 (COVID-19) vaccine. Baricitinib was effective for resolving both dermatitis and dacryoadenitis, and steroids were able to be discontinued. The IgG4 level also improved.

Objectives: Cardiac amyloidosis (CA) is the most crucial determinant of amyloid light-chain (AL) amyloidosis patients' prognosis. We attempted cardiac involvement prediction by 12‑lead electrocardiograph (ECG) and echocardiography (UCG) in AL amyloidosis patients., Materials and Methods: Fifty patients with histologically confirmed AL amyloidosis underwent gadolinium-enhanced magnetic resonance imaging (Gd-MRI), and CA was assessed using late gadolinium enhancement. ECG and UCG parameters were measured on admission. Fisher's linear discriminant analysis was used to create a model for predicting CA using the ECG and UCG parameters., Results: Prediction by five ECG parameters [QTc(B), QRS-T-angle, III-QRS, aVF-QRS, and V3-R] showed the best performance. Average sensitivity and specificity in the modeling sets, utilizing a linear discriminator based on these five variables, were 99.2 % and 96.8 % and in validation sets, 94.2 % and 90.3 %, respectively. In addition, we tested this model on an additional 26-patient cohort and survival analysis using the Kaplan-Meier method, and significant differences between CA positively predicted and negatively predicted patients were observed., Conclusion: Here, we suggest the application of a condensed classical multivariate statistical technique for the diagnosis of CA. It can be used as a guide to invasive endomyocardial biopsy for those in whom Gd-MRI is contraindicated and as a guide for repeat Gd-MRI in follow-up of AL amyloidosis., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Recurrence and metastasis are resistant to multimodal treatments, and are the major causes of death in breast cancer. Accumulating evidence suggests that the IL17RB signaling pathway plays a key role in progression and metastasis of breast cancer. Clinical significance of the IL17RB positivity in tumor tissues has been also reported as a poor prognostic factor in breast cancer. However, the molecular mechanisms underlying the poor prognosis of patients with IL17RB + breast cancer, particularly the immunological aspects, remain to be fully elucidated, and elimination of the IL17RB + tumors has not been practically achieved in clinical settings. In this study, we identified a distinct molecular mechanism underlying the intractability of the IL17RB + tumors through tumor biological and immunological investigation using mouse and human breast cancer cells transduced with il17rb gene. IL17RB overexpression in tumor cells confers cancer stemness, including high invasive and self-renewal abilities, and high resistance to CDK4/6 inhibitors that have been considered as a promising agent for treating breast cancer despite the limited efficacy. In the mice implanted with the IL17RB + tumors, IL25 + macrophages (Møs) are expanded locally in tumor tissues and systemically in spleen, and promote the IL17RB + tumor progression directly by intensifying the tumor functions, and indirectly via impairment of anti-tumor effector CTLs and NK cells utilizing the secreted IL25. Blocking IL25 with the specific mAb, however, interferes the adverse events, and successfully elicits significant anti-tumor efficacy in combination with CDK4/6 inhibitors providing better survival in murine mammary tumor models. These results suggest that the IL25 + Mø is a key determinant of building the solid treatment resistance of the IL17RB + breast cancer. Targeting the IL17RB-IL25 axis may be a promising strategy to improve clinical outcomes in the treatment of breast cancer patients, particularly with IL17RB + tumors., Competing Interests: None., (AJCR Copyright © 2023.)

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used to treat type 2 diabetes (T2D). Lowering blood glucose is expected also to reduce the progression of diabetic nephropathy. We experienced a patient with T2D who achieved good glycemic control with a DPP-4 inhibitor but experienced rapid deterioration of renal function. Therefore, we performed a retrospective study of similar patients treated at our hospital., Methods: Out of 56 patients with biopsy-proven diabetic nephropathy who underwent native kidney biopsy at Toranomon Hospital from January 2018 through December 2022, we selected 22 patients who had been receiving DPP-4 inhibitors for at least 9 months at the time of kidney biopsy. Of these patients, we evaluated 16 diagnosed with class IIa diabetic nephropathy according to Tervaert's pathologic classification. The yearly estimated glomerular filtration rate (eGFR) slope in the 16 patients was arranged from the highest to the lowest slope. Ten patients with a large eGFR slope had thrombotic microangiopathy (TMA)-like lesions characterized by glomerular endothelial cell proliferation and GBM duplication on kidney biopsy (group A), whereas the remaining 6 patients did not have TMA-like lesions (group B)., Results: Group A had a median (interquartile range [IQR]) eGFR of 18.2 (16.2, 26.2) and a yearly median (IQR) eGFR slope of -11.2 (-17.6, -9.2) mL/min/1.73 m 2 after of DPP-4 administration, whereas group B had a median (IQR) eGFR of 31.5 (21.9, 34.8) mL/min/1.73 m 2 and a yearly median (IQR) eGFR slope of -1.6 (-3.1, -0.3). Renal function declined significantly more rapidly in group A than in group B, and proteinuria was higher in group A than in group B (median [IQR], 3.4 [2.6, 4.4] g/day vs 0.8 [0.4, 1.3] g/day, respectively). Five patients in group A progressed to dialysis during follow-up, but none of the patients in group B did. Median (IQR) hemoglobin A1c was 6.2 % (6.0 %, 6.6 %) in group A and 5.8 % (5.7 %, 6.6 %) in group B., Conclusion: DPP-4 inhibitors promote vascular endothelial regeneration, but when this effect occurs in the glomerulus, glomerular endothelial cell proliferation leads to TMA-like lesions, which may cause an increase in proteinuria and rapid decline in renal function., Competing Interests: Declaration of competing interest The authors declare no competing financial interests and no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

We experienced a 36-year-old man with lupus nephritis and antiphospholipid syndrome (APS) who received a donor kidney from his father. Twenty-two months after transplantation, at a time of poor adherence to immunosuppressants and warfarin, the patient developed sudden graft loss due to hemolytic uremic syndrome with rapid deterioration of renal function, thrombocytopenia, and hemolytic anemia. A kidney biopsy showed thrombotic microangiopathy (TMA) related to platelet thrombus formation; however, there was no recurrence of lupus and no findings suggestive of post-transplant rejection, so acute TMA associated with APS was thought to be the cause of the graft loss. This case highlights the importance of instructing patients with lupus nephritis to adhere to treatment with warfarin, a therapeutic drug for APS.

We performed 3 kidney biopsies in a 71-year-old man. At the first biopsy, we made the diagnosis of immunoglobulin G4 (IgG4)-related interstitial nephritis characterized by the simultaneous presence of IgG4-positive plasma cells and characteristic fibrosis with a bird's-eye pattern. At the second biopsy, rather than finding fibrosis as a post-inflammatory scar, we noted that steroid treatment had caused the simultaneous disappearance of IgG4-positive plasma cells and fibrosis and had restored the normal tubular structure. The third biopsy showed the recurrence of the disease with inflammatory cells accompanied by fibrosis. These findings suggest that IgG4-positive plasma cells and fibrosis occur simultaneously.

A 16-year-old Japanese girl developed a fever, thrombocytopenia, and renal dysfunction. Treatment was started with steroids, but cervical lymphadenopathy and ascites developed. A lymph node biopsy indicated TAFRO syndrome. The patient's renal function deteriorated, and dialysis was started. Refractory hypertension and subsequent encephalopathy developed. Treatment was started with an anti-IL-6 receptor antibody and an anti-CD20 monoclonal antibody. A kidney biopsy showed malignant nephrosclerosis-like microangiopathy and glomerular collapse due to narrowing of the small arteries. The majority of TAFRO syndrome cases are adult-onset, with glomerular microangiopathy. To our knowledge, this is the first report of adolescent-onset TAFRO syndrome presenting with malignant nephrosclerosis-like lesions associated with hypertension.

An 84-year-old woman with IgG4-related disease presented with jaundice and liver dysfunction after coronavirus disease 2019 (COVID-19) vaccination. Serum IgG4 levels were elevated. Diagnostic imaging showed no stenotic lesions in the bile ducts. A liver biopsy was performed because of the enlarged liver. Infiltration of IgG4-positive plasma cells, which accounted for approximately 74% of total plasma cells, was found in the portal area, but there was no evidence of periportal hepatitis, and inflammatory cell infiltration into the lobular space was minimal. IgG4-related hepatopathy was diagnosed. The patient achieved spontaneous remission with no treatment and only follow-up and remains under observation at the time of writing.

We encountered an 86-year-old Japanese woman who presented with proteinuria (0.4 g/day) and hematuria (red blood cell sediment >100/high-power field), a decreased renal function (serum creatinine, 1.51 mg/dL), and elevated myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) levels (231 IU/mL) during treatment of rheumatoid arthritis with abatacept (a cytotoxic T-lymphocyte-associated antigen 4 agent) and adalimumab (a tumor necrosis factor-α agent). A kidney biopsy showed pauci-immune necrotizing glomerulonephritis, and ANCA-associated vasculitis was diagnosed. Treatment with tocilizumab (an interleukin 6 receptor antibody) monotherapy resulted in the improvement of renal findings and normalization of rheumatoid arthritis disease activity and serum ANCA levels. Tocilizumab can also suppress ANCA-associated vasculitis.

Background: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare RCC subtype, and FH-deficient RCC may be misdiagnosed as another type of RCC, such as type 2 papillary RCC or collecting duct carcinoma. FH and 2-succinocysteine (2SC) are useful diagnostic markers for FH-deficient RCC and can be measured using immunohistochemistry (IHC)., Case Report: A 30-year-old female with 3-month history of fatigue and left-flank mass was diagnosed with a 20×13×10 cm left-side renal mass with massive inferior vena cava (IVC) tumor thrombus that extended into the right atrium. She underwent nephrectomy and IVC thrombectomy, and a pathological diagnosis of type 2 papillary RCC was made. Four months after the surgery, computed tomography scan showed multiple liver metastases not observed immediately after surgery. Systemic treatment with sorafenib was initiated; however, she did not respond and died 3 months after treatment. Subsequent re-review of hematoxylin and eosin-stained sections indicated morphologic characteristics consistent with FH-deficient RCC, and IHC staining was negative for FH but positive for 2SC, indicating a diagnosis of FH-deficient RCC. Further immunological analyses revealed the loss of HLA-class I, b2 microglobulin, and HLA-DR antigens in cancer cells. In addition, a few CD8-positive cytotoxic T cells and CD163-positive tumor-associated macrophages were noted., Conclusion: An immunosuppressive tumor microenvironment that facilitates cancer immune evasion might be associated with the rapid progression and poor prognosis in our patient. Further investigation of the tumor immune microenvironment in patients with FH-deficient RCC is warranted., Competing Interests: All Authors have no conflicts of interest to declare in relation to this study., (Copyright 2023, International Institute of Anticancer Research.)

Background: Invasive lobular carcinoma (ILC) grows diffusely in a single-cell fashion, sometimes presenting only subtle changes in preoperative imaging; therefore, axillary lymph node (ALN) metastases of ILC are difficult to detect using magnetic resonance imaging (MRI). Preoperative underestimation of nodal burden occurs more frequently in ILC than in invasive ductal carcinoma (IDC), however, the morphological assessment for metastatic ALNs of ILC have not fully been investigated. We hypothesized that the high false-negative rate in ILC is caused by the discrepancy in the MRI findings of ALN metastases between ILC and IDC and aimed to identify the MRI finding with a strong correlation with ALN metastasis of ILC., Method: This retrospective analysis included 120 female patients (mean ± standard deviation age, 57.2 ± 11.2 years) who underwent upfront surgery for ILC at a single center between April 2011 and June 2022. Of the 120 patients, 35 (29%) had ALN metastasis. Using logistic regression, we constructed prediction models based on MRI findings: primary tumor size, focal cortical thickening (FCT), cortical thickness, long-axis diameter (LAD), and loss of hilum (LOH)., Results: The area under the curves were 0.917 (95% confidence interval [CI] 0.869-0.968), 0.827 (95% CI 0.758-0.896), 0.754 (95% CI 0.671-0.837), and 0.621 (95% CI 0.531-0.711) for the FCT, cortical thickness, LAD, and LOH models, respectively., Conclusions: FCT may be the most relevant MRI finding for ALN metastasis of ILC, and although its prediction model may lead to less underestimation of the nodal burden, rigorous external validation is required., (© 2023. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Immune checkpoint inhibitors (ICIs) have recently improved the prognosis of various cancers. By contrast, some immune-related adverse events (irAEs) caused by ICIs are fatal and have become problematic. The pathogenesis of irAEs remains unknown and must be elucidated to establish biomarkers. This study investigated plasma cytokine, chemokine, and anti-CD74 autoantibody levels in patients with renal cell carcinoma (RCC) and analyzed their association with irAEs. In a discovery cohort of 13 patients, plasma levels of chemokine (C-X-C motif) ligand (CXCL) 1, IL-17A, IL-1β, IL-6, IL-8, CXCL10, MCP-1, and TNFα were measured at baseline and post-dose 1. Only CXCL10, at post-dose 1 but not at baseline, was significantly associated with grade 2 or higher irAEs (P = 0.0413). Plasma CXCL10 levels were then measured at baseline and post-dose 1 in an extended cohort of 43 patients with RCC who received ICI-based treatment. Higher plasma CXCL10 levels both at baseline and post-dose1 were significantly associated with the occurrence of grade 2 or higher irAEs (P = 0.0246 and 0.0137, respectively). Plasma CXCL13 levels, which we measured in a previous study, were significantly higher in patients with grade 2 or higher irAEs at baseline but not at post-dose 1 (P = 0.0037 and 0.052, respectively). No significant association between plasma anti-CD74 autoantibody level and both irAE pneumonitis and any grade 2 or higher irAE was observed. In conclusion, plasma CXCL10 is significantly associated with the occurrence of irAEs in patients with RCC treated with ICIs. CXCL10 is a potential predictive and on-treatment biomarker for irAEs., (© 2023 The Societies and John Wiley & Sons Australia, Ltd.)

Objective: We occasionally observed internal mammary lymph node metastases of breast cancer in a clinical setting. However, unlike a standard treatment in axillary metastasis, surgical resection for internal mammary lymph node metastasis is not prevalent because of unclear safety and benefits. Thus, we aimed to evaluate the diagnostic ability and clinical outcomes of positron emission tomography/computed tomography and video-assisted thoracoscopic surgery., Methods: We retrospectively investigated 34 patients with breast cancer with abnormal 18F-fluorodeoxyglucose uptake in internal mammary lymph nodes, at a single centre, between January 2015 and June 2022 and identified 11 female patients (mean age ± SD, 51.5 ± 12.9 years) who underwent video-assisted thoracoscopic surgery resection. Positron emission tomography/computed tomography was used to determine the clinical stage. We reviewed the surgical pathology of eleven and two patients who underwent direct-view internal mammary lymph node resection to calculate the positive predictive value of positron emission tomography/computed tomography., Results: Ipsilateral fluorodeoxyglucose accumulation was observed, with an average maximum standardized uptake value of 8.9 (range, 3.1-24.0). No perioperative complications occurred, and all patients who underwent video-assisted thoracoscopic surgery alone were discharged from the hospital on post-operative day 2 or 3. The estimated positive predictive value was 80%. All patients were alive, and seven of nine patients with metastasis were relapse-free, at a mean follow-up period of 17.9 months (range, 1-51). However, two patients had recurrence at 16 and 14 months after surgery for internal mammary lymph node relapse., Conclusions: Radiotherapy is the standard treatment for suspected internal mammary lymph node metastasis detected using positron emission tomography/computed tomography; however, we could safely perform minimally invasive video-assisted thoracoscopic surgery resection, leading to a definite pathological diagnosis., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

A 72-year-old man was admitted for examination of proteinuria (9.14 g/day) and leg edema. Essential thrombocythemia (ET) was diagnosed because of thrombocytosis (platelet count, 57.9×10 4 /μL), elevated megakaryocytes in bone marrow biopsy, and JAK2 V617 mutation. Kidney biopsy led to a diagnosis of focal segmental glomerulosclerosis (FSGS) cellular variant (characterized by glomerular capillaries filled with swollen endothelial cells containing foam cells) in 6 glomeruli, FSGS tip variant in 5 glomeruli, and additional FSGS variants in other glomeruli. Affected glomeruli had anti-CD61 antibody staining-positive megakaryocyte infiltrations. ET mayinduce FSGS because megakaryocyte infiltration increases intraglomerular pressure, resulting in hypertension and proteinuria.

Systemic lupus erythematosus was diagnosed in a patient at 43 years old. When proteinuria recurred at 57 years old, the first kidney biopsy was performed, and class IV-G (A) +V lupus nephritis was diagnosed. The prednisolone dose was increased to 40 mg/day, and cyclosporine A was introduced. After 1 year, proteinuria had decreased to 0.1 g/day. Prednisolone was discontinued three years later, and cyclosporine A was continued. Thereafter, proteinuria did not reoccur. At 67 years old, a second kidney biopsy showed complete remission of lupus nephritis. Cyclosporine A enabled permanent discontinuation of glucocorticoids in a patient with lupus nephritis.

A 66-year-old man was admitted to our hospital because of a low-grade fever and arthralgia. The symptoms started on the third day after influenza vaccine administration and persisted for two months. Serum creatinine was 1.0 mg/dL; C-reactive protein, 16.1 mg/dL; and myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA), 4,170 IU/mL. A kidney biopsy showed crescentic glomerulonephritis with fibrinoid necrosis of small arteries. Microscopic polyangiitis was diagnosed. After five months of steroid pulse therapy and rituximab administration, the patient entered remission. There have been very few reports of this condition after influenza vaccine administration.

A 42-year-old Japanese woman was admitted for the evaluation of proteinuria. She had a history of four habitual abortions and valvular heart disease, including severe mitral regurgitation and moderate tricuspid regurgitation. A kidney biopsy showed fibrointimal thickening of interlobular arteries, fibrin thrombosis, and associated focal segmental sclerosis. Although the standard test for antiphospholipid (aPL) antibodies was negative, the patient was diagnosed with antiphospholipid syndrome (APS)-related disease by testing for phosphatidylserine dependent anti-prothrombin anticardiolipin antibody, a non-criterial aPL antibody. A kidney biopsy may lead to a diagnosis of APS in patients with negative laboratory test findings for APS.

We evaluated kidney histology in a 43-year-old woman with autosomal dominant tubulointerstitial kidney disease subtype hepatocyte nuclear factor 1β. Magnetic resonance imaging showed multiple cysts in the renal medullary area, and computed tomography showed hypoplasia of the pancreatic body and tail. A kidney biopsy showed thinning of the cortex, size reduction of glomerular tuft area, proximal tubule clustering, fibrosis around the tubules, loss of peritubular capillaries, and multilayered epithelial cells of cortical collecting ducts; this last finding was consistent with so-called medullary dysplasia specific to congenital disease, in which the renal pelvic epithelial cells enter the collecting duct.

A 37-year-old Japanese man was admitted to our hospital for evaluation of severe hypertension and visual impairment. His serum creatinine was 4.16 mg/dL. Plasma renin activity was normal (2.7 ng/mL/h), but plasma aldosterone concentration was elevated (27.2 ng/dL). A kidney biopsy showed concentric subendothelial edematous thickening of the arterioles (onion skin pattern) with luminal narrowing or obstruction, and malignant nephrosclerosis was diagnosed. Antihypertensive therapies, including an angiotensin II receptor blocker and spironolactone, were administered and effectively preserved kidney function and normalized blood pressure. This case indicates that hyperaldosteronemia in the presence of normal renin levels might also cause malignant hypertension., (© 2022. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

A 43-year-old Japanese woman with rheumatoid arthritis treated by infliximab and methotrexate for 11 years was admitted for proteinuria and purpura. A kidney biopsy revealed endothelial damage-dominant nephritis with IgA deposition. Infliximab and methotrexate were discontinued, and tocilizumab was started; however, proteinuria persisted. Therefore, tocilizumab was discontinued, and oral prednisolone and methylprednisolone pulse therapy were administered. After 6 months, urinary protein was less than 0.1 g/day, and purpura subsided. To our knowledge, this is the first case of endothelial damage-dominant nephritis related to IgA vasculitis involving the skin and kidney after long-term use of infliximab and methotrexate.

Background: The aim of this study is to evaluate the efficacy of radical nephrectomy with thrombectomy and to identify the prognostic factors for patients with renal cell carcinoma (RCC) and inferior vena cava tumor thrombus (IVCTT). The role of the neutrophil-to-lymphocyte ratio (NLR), which has been reported to be a useful prognostic predictor for various solid cancers, was also investigated., Methods: Fifty-five patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy in our hospital were retrospectively analyzed. The relationship between clinical characteristics and surgical outcome was examined using the Kaplan-Meier method. Univariate and multivariate analyses were carried out to determine the prognostic factors., Results: The median follow-up time after surgery was 44.2 months. Twenty-seven patients died of RCC, and 4 died of other disease at last follow-up. There were no patients with postoperative pulmonary embolism (PE) or deaths from PE. The median cancer-specific survival (CSS) and overall survival (OS) were 81.0 (95% confidence interval [CI]: 42.0-103.2) and 69.0 (95% CI: 34.3-81.5) months, respectively. Significant prognostic factors for CSS were distant metastasis (p = 0.045) and NLR ≥ 2.9 (p = 0.009). The only independent predictor for OS was the NLR ≥ 2.9 (p = 0.034)., Conclusions: A high preoperative NLR level was an independent poor prognostic factor influencing CSS and OS of patients with RCC and IVCTT who underwent radical nephrectomy and thrombectomy. The NLR may be an available biomarker that helps with preoperative risk stratification., Competing Interests: Declaration of competing interest The authors declare no potential financial and non-financial conflicts of interest associated with this manuscript., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

A 35-year-old woman was treated with chemotherapy for leukemia. One year later, allogeneic hematopoietic stem cell transplantation (HSCT) was performed with umbilical cord blood. After nine months, she developed a spiking fever, sore throat, arthralgia, pleural effusion, hyperferritinemia, and persistent generalized pruritic erythema. A skin biopsy showed dyskeratotic cells in the epidermis, neutrophil infiltration in the epidermis and upper dermis, and neutrophils in the parakeratotic layer. Treatment with tocilizumab was effective. Adult-onset Still's disease (AOSD)-like disease related to graft versus-host disease (GVHD) after HSCT was suspected. Abnormal immune states related to GVHD may cause AOSD-like disease with more severe skin lesions than usual.

A 32-year-old man was admitted for the evaluation of proteinuria (5.69 g/day). A light microscopic examination showed markedly dilated glomerular capillary loops with vacuolated areas in many glomeruli, and vacuolated areas were seen on peritubular capillaries in the tubulointerstitium. When electron microscopy specimens prepared by pre-fixation with glutaraldehyde and post-fixation with osmium tetroxide were used for oil red staining, the deposition was confirmed on the affected areas. A genetic analysis of apoE showed that the lipoprotein glomerulopathy was due to apoE-Sendai (Arg145Pro, p.R163P) heterozygosity, which was found in not only the patient but also his mother and twin brother.

Background: Solitary fibrous tumors (SFT) are uncommon mesenchymal neoplasms which can arise in any anatomical location. Pleural SFTs have been most frequently documented; however, breast SFT is an exceedingly rare entity and seldom present in male breast, with only 8 previously reported cases. Recently, STAT6 immunostaining was considered to be a definitive marker of SFT, however, no case of the male breast SFT showing STAT6 positivity preoperatively has been reported., Methods and Results: We describe a case of breast SFT in a 73-year-old male patient with a 12-month history of a palpable breast mass. The only associated clinical symptom was bilateral gynecomastia. An ultrasound scan examination revealed an oval, well-circumscribed and hypoechoic mass with hypervascularity. A core-needle biopsy was performed, and microscopic examination with immunohistochemistry confirmed the diagnosis of SFT. He underwent a complete surgical resection with clear margins, and there were no signs of high cellularity, remarkable mitotic activity, pleomorphism, hemorrhage or necrosis., Conclusion: A perioperative immunohistochemical evaluation for diffuse and intense nuclear expression of STAT6 was helpful to distinguish SFT from myofibroblastoma. We, herein, describe the first case of SFT in a male breast, confirmed by STAT6 immunostaining positivity. We also conducted a literature review of all previous cases of breast SFTs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Rectal neuroendocrine neoplasms can induce liver metastasis. However, few reports exist on the associated long-term recurrence rates. We report a case of liver metastasis identified 15 years after rectal neuroendocrine neoplasm resection., Case Presentation: A 50-year-old woman was on semi-annual follow-up after undergoing mastectomy for breast cancer (pT1N0M0) and low anterior resection for grade 1 rectal neuroendocrine neoplasm (pT1b, ly1, v1). Fifteen years postoperatively, a 7-mm hyperechoic mass was identified at liver segment 6. Magnetic resonance imaging revealed a slight growth of the mass. Positron emission tomography/computed tomography revealed radiotracer accumulation in the lesion. Laparoscopic hepatectomy was performed. The histopathological diagnosis was grade 2 neuroendocrine neoplasm. The pathological findings and clinical course indicated the tumor originated in the rectum., Conclusions: Our findings highlight the need to reassess the optimal postoperative follow-up period for patients with rectal neuroendocrine neoplasm., (© 2022. The Author(s).)

We encountered a 77-year-old Japanese man who presented with nephrotic-range proteinuria 20 days after receiving ramucirumab treatment for metastatic sigmoid colon cancer. A kidney biopsy showed two characteristic histological findings. The first finding was podocyte injury with cellular crescent-like formation, although focal segmental glomerulosclerosis (FSGS) (collapsing variant) according to the Columbia classification may have been a more appropriate name for this injury, as hypertrophy and hyperplasia of epithelial cells, presumably resulting from podocyte injury, were seen between Bowman's capsule and the glomerular basement membrane (GBM); these changes appeared to be due to the collapse of the GBM rather than to GBM destruction with fibrinoid necrosis. The second finding was endotheliopathy characterized by prominent mesangial interposition via enlargement of the mesangial matrix with mesangiolysis. Proteinuria and renal dysfunction subsided after discontinuation of ramucirumab. Bevacizumab has been reported to induce glomerular microangiopathy with endothelial damage and swelling six months after treatment, but in this case, ramucirumab may have induced focal segmental glomerulosclerosis (FSGS) collapsing variant and glomerular microangiopathy with endotheliopathy via mesangial damage within 1 month. We believe that the damage to the glomerular podocyte and endothelial cells via mesangial damage secondary to ramucirumab in our patient was a different type of glomerular microangiopathy than the endothelial cell damage with enlargement of the subendothelial space caused by bevacizumab.