Dual-Energy Computed Tomography Virtual Noncalcium Imaging of Intracranial Arteries in Acute Ischemic Stroke: Differentiation Between Acute Thrombus and Calcification.

OBJECTIVE: Hyperdense artery sign (HAS) on noncontrast brain computed tomography (CT) indicates an acute thrombus within the cerebral artery. It is a valuable imaging biomarker for diagnosing large-vessel occlusion; however, its identification may be challenging with the presence of vascular calcification. Dual-energy CT virtual noncalcium (VNCa) imaging using a 3-material decomposition algorithm is helpful for differentiating between calcification and hemorrhage. This study aimed to clarify the potential of VNCa imaging for differentiating HAS from vascular calcification. METHODS: Patients with acute ischemic stroke and large-vessel occlusion identified on MR angiography, who also underwent noncontrast dual-energy CT, were included. The 80 kV/Sn 140 kV mixed images, with a weighting factor of 0.4, were considered 120 kVp-equivalent images. Postprocessing using a 3-material decomposition algorithm to differentiate between calcium (Ca), cerebrospinal fluid, and hemorrhage was performed via a commercially available 3-dimensional workstation. A mixed image, VNCa image, color-coded Ca image, and color-coded Ca image with VNCa image overlay (color-coded Ca-overlay image) were obtained, and axial reconstruction with a 1-mm slice thickness was performed for each image type. Two experienced neuroradiologists conducted imaging evaluations in consensus. RESULTS: Thirty-four patients (mean age, 76.0 years; 21 male and 13 female patients) were included. The mixed and VNCa images revealed an HAS (indicating an acute clot) corresponding to the large-vessel occlusion site in 30 patients. Among them, the VNCa and color-coded Ca-overlay images enabled clear differentiation between the acute thrombus and adjacent vessel wall calcification in 5 patients. Among the other 4 patients, the VNCa, Ca-overlay, and Ca images identified calcified cerebral emboli in the M1 segment in 1 patient. For the other 3 patients, no high attenuation corresponding to magnetic resonance angiography findings was observed in any of the mixed, VNCa, Ca-overlay, or Ca images. CONCLUSIONS: VNCa and color-coded Ca-overlay images obtained via dual-energy brain CT enabled differentiation of acute thrombus from vessel wall calcification and calcified cerebral emboli in patients with acute ischemic stroke.

Paratesticular cellular angiofibroma: a case report.

INTRODUCTION: Paratesticular cellular angiofibroma is a rare benign mesenchymal tumor. The optimal management is surgical resection due to the difficulty of preoperative accurate diagnosis. CASE PRESENTATION: A 51-year-old Japanese male visited our hospital complaining of asymptomatic left scrotal swelling. Physical examination revealed a nontender elastic paratesticular mass (5.5 cm in diameter). Although testicular germ cell tumor was ruled out clinically, the possibility of malignant potential remained for the tumor. Since the patient consented to complete resection, a transinguinal radical orchiectomy was performed. The pathological diagnosis revealed cellular angiofibroma. The patient recovered without perioperative complications, and no apparent recurrence was observed at 5 years after surgery. CONCLUSION: The pathological findings were compatible for cellular angiofibroma. The tumor was successfully resected, and no apparent recurrence was observed at 5 years after surgery.

A Phase II Clinical Trial to Study the Safety of Triamcinolone after Endoscopic Radial Incision and Cutting Dilatation for Benign Stenosis of the Lower Gastrointestinal Tract: A Study Protocol.

BACKGROUND: Lower gastrointestinal tract stenosis is commonly diagnosed and is typically treated with surgery or endoscopic balloon dilation (EBD). Radial incision and cutting (RIC) is a novel treatment approach that has several benefits compared with EBD and surgery. Although RIC has demonstrated a high technical success rate and has been shown to improve subjective symptoms, previous studies revealed that restenosis after RIC remain unsolved. Herein, we report the design of a prospective, multicenter, single-arm, interventional, phase II trial to evaluate the safety of local triamcinolone acetonide (TA) administration and its feasibility in preventing restenosis after RIC for lower gastrointestinal tract stenosis. METHODS: The major inclusion criteria are age 20-80 years and the presence of benign stenosis in the lower gastrointestinal tract accessible by colonoscope. We will perform RIC followed by local administration of TA to 20 participants. The primary outcome is the safety of local TA administration, which will be assessed by determining the frequency of adverse events of special interest. The secondary outcomes are the technical success rate of RIC, duration of procedure, improvement in subjective symptoms, and duration of hospitalization. The outcomes, improvement in subjective symptoms, and long-term results will be evaluated using descriptive statistics, Student's t-test, and Kaplan-Meier curve, respectively. DISCUSSION: This explorative study will provide useful information regarding the safety of TA administration after RIC, which may contribute to further investigations.

Brain metastases in patients with salivary duct carcinoma: A retrospective study.

BACKGROUND: Salivary duct carcinoma (SDC) is a high-grade adenocarcinoma with a 5-year survival rate of 40%. Although drug therapy has improved patients' prognosis, the impact of brain metastasis (BM) remains poorly understood. We aimed to retrospectively examine the incidence of BM in patients with SDC (n = 464) and develop a tool to estimate their prognoses. METHODS: We retrospectively examined 464 patients with SDC enrolled in a multicenter study. We investigated the incidence of BM, overall survival (OS) rates, and factors affecting prognosis in patients with BM. We also developed an SDC-graded prognostic assessment (GPA) score for disease prognostication. RESULTS: Sixty-five (14%) patients had BM. The median OS (mOS) was 13.1 months. On univariate and multivariate analyses, factors such as Eastern Cooperative Oncology Group Performance Status >1, human epidermal growth factor receptor 2-negative status, and locoregional uncontrolled disease were associated with poor OS. SDC-GPA scores according to the prognostic factors were 0, 1, 2, and 3 points, and mOS estimates were 50.5, 16.1, 3.9, and 1.2 months, respectively (p < 0.001). CONCLUSION: The SDC-GPA score emerged as a useful prognostication tool for patients with BM.

Bilateral long ureteral strictures were successfully replaced by ileum in inverse seven configuration: A case report.

INTRODUCTION AND IMPORTANCE: Ureteral stricture is a potential postoperative complication of pelvic surgery. Repair is performed in the intraoperative or postoperative phase for various reasons. Ileal reconstruction of ureter is considered for extensive and bilateral ureteral injuries. CASE PRESENTATION: A 44-year-old female presented to the hospital where she had undergone hysterectomy two months prior, with acute renal failure due to bilateral hydronephrosis. Radiological examination revealed bilateral distal ureteral stricture measuring 5 cm in length. After failed balloon-dilation, ileal reconstruction was successfully performed without perioperative complications; and she has remained free from hydronephrosis with normal renal function for four years. CLINICAL DISCUSSION: Ileal interposition can be used for reconstruction of long lengths or bilateral ureteral injuries. High success rates and low rates of complication have been reported, and the long-term outcome was also acceptable. Apparent ureteral injury was not observed in our case; however, narrowing of ureteral lumen due to submucosal and sub-adventitial edema was observed as a possible cause of strictures. Although, some minor occult injuries during hysterectomy, including thermal effect, ischemia or physical damage due to traction on the ureters were suggested, we were unable to conclusively determine the etiology. CONCLUSION: Ileal ureter replacement is a useful reconstruction, and the inverse seven configuration is suitable for long bilateral strictures of distal ureter.

Targeting cholesterol biosynthesis for AT/RT: comprehensive expression analysis and validation in newly established AT/RT cell line.

Atypical teratoid/rhabdoid (AT/RT) is a rare and highly malignant tumor of the central nervous system (CNS). It is most commonly found in children less than 5 years of age and is associated with inactivation of loss of function of SMARCB1/INI1. An experimental model for AT/RT is necessary to develop new and effective therapies. We established a patient-derived new cell line (MZ611ATRT), which showed loss of BAF-47. MZ611ATRT genetically features somatic heterozygous deletion of SMARCB1 and single nucleotide deletion of the residual allele, exon 5 ([c.541delC]), resulting in a stop codon at codon 954 by frameshift. We assessed the RNA-sequencing data of the other two AT/RT cell lines with forced expression of SMARCB1 available from public databases. We found SMARCB1 overexpression significantly down-regulates the expression of a group of enzymes related to cholesterol biosynthesis. Simvastatin was highly sensitive against MZ611ATRT cells and induced apoptosis (IC50 was 3.098 µM for MZ611ATRT, 41.88uM for U-87 MG, 23.34uM for IOMM-Lee, and 18.12uM for U-251 MG.). Pathways involved in cholesterol biosynthesis may be new targets for adjuvant therapy of AT/RT.

Non-contrast dual-energy CT using X-map for acute ischemic stroke: region-specific comparison with simulated 120-kVp CT and diffusion-weighted MR images.

PURPOSE: X-map is a non-contrast dual-energy CT (DECT) application to identify acute ischemic stroke (AIS). Our aim was to verify region-specific characteristics of early ischemic changes (EIC) on X-map compared with simulated 120-kVp mixed-CT image and DWI. METHODS: Fifty AIS patients who underwent DECT and DWI were enrolled (mean age, 76 years; 34 men, 16 women). All datasets including mixed-CT image, X-map, and DWI were transformed into a standard brain atlas with 11 × 2 ROIs based on the ASPECTS + W system. ROIs with EIC on DWI, mixed-CT image, and X-map were defined as DWI-positive, mixed-CT-positive, and X-map-positive, and those with normal finding were DWI-negative, mixed-CT-negative, and X-map-negative respectively, in visual assessment by two neuroradiologists in consensus. RESULTS: EIC on X-maps were visually relevant to those on the other images: of 221 ROIs with mixed-CT-positive and X-map-positive, 198 (89.6%) were DWI-positive. X-map revealed moderate diagnostic accuracy for AIS compared with DWI in ROC curve analysis (AUC = 0.732). X-map identified EIC in deep white matter more sensitively than mixed-CT image: of 15 ROIs with mixed-CT-negative and X-map-positive in W segments, 14 (93.3%) were DWI-positive. X-map often showed EIC in cortical regions that were not detected on the other images: of 67 ROIs with mixed-CT-negative and X-map-positive in I and M1-M6 segments, 47 (70.1%) were DWI-negative. CONCLUSIONS: X-map is useful to detect EIC, especially in deep white matter, and may also provide additional information in acute ischemic lesions where DWI cannot be detected.

Buffer-free CAS assay using a diluted growth medium efficiently detects siderophore production and microbial growth.

Siderophores are iron chelators and low-molecular-weight compounds secreted by various microorganisms under low-iron conditions. Many microorganisms produce siderophores in the natural environment as iron is an essential element for many of them. CAS assays are widely used to detect siderophores in cultures of various microorganisms; however, it is necessary to improve their sensitivity for the efficient application to fastidious microorganisms. We developed a simple, high-throughput CAS assay employing a buffer-free CAS reagent and diluted growth medium (10% dR2A) in a 96-well microplate. Using a diluted growth medium in agar plates suitable for iron-restricted conditions supported siderophore production by microorganisms from activated sludge. A buffer-free CAS reagent combined with a diluted growth medium revealed that these microorganisms tended to produce more siderophores or iron chelators than microorganisms under iron-rich conditions. Moreover, this buffer-free CAS assay easily and efficiently detected not only siderophore production but also the growth of fastidious microorganisms.

Multicenter prospective phase II trial of concurrent chemoradiotherapy with weekly low-dose carboplatin for cisplatin-ineligible patients with advanced head and neck squamous cell carcinoma.

BACKGROUND: The optimal chemotherapy regimen in concurrent chemoradiotherapy (CCRT) for cisplatin-ineligible head and neck squamous cell carcinoma (HNSCC) has not been established. We aimed to evaluate the feasibility, efficacy, and safety of CCRT with weekly low-dose carboplatin for the treatment of advanced HNSCC in patients who are cisplatin-ineligible. METHODS: This prospective phase II study enrolled adult patients (age ≥ 20 years) with HNSCC receiving whole-neck irradiation including bilateral levels II-IV and who were aged (≥ 75-year-old patients with 40 mL/min estimated glomerular filtration rate [eGFR] or better) or had renal dysfunction (< 75-year-old patients with 30-60 mL/min eGFR). Carboplatin was administered weekly (area under the plasma concentration-time curve = 2.0) for up to seven cycles during concurrent radiotherapy (70 Gy/35 Fr). The primary endpoint was the completion rate of CCRT. Secondary endpoints included overall response rate and incidence of adverse events. RESULTS: Among the 30 patients enrolled, 28 were men. The median age was 73.5 years. Seventeen patients were < 75 years whereas 13 were ≥ 75 years old. The completion rate of CCRT was 90%. The overall response rate was 90%. Grade 3 adverse events that occurred in 10% or more patients were oral/pharyngeal mucositis (47%), leukocytopenia (20%), and neutropenia (10%). Grade 4 adverse events occurred in one patient (elevation of alanine aminotransferase level). No treatment-related deaths occurred. CONCLUSION: CCRT with weekly low-dose carboplatin is a promising treatment option, with favorable feasibility, efficacy, and acceptable toxicity, for patients who are cisplatin-ineligible with advanced HNSCC. CLINICAL TRIAL REGISTRATION NUMBER: jRCTs031190028.

A case of multifocal sclerosis angiomatoid nodular transformations of the spleen occurring after partial splenic infarction with transcatheter arterial embolization for splenic artery aneurysm.

A 48-year-old woman underwent transcatheter arterial embolization (TAE) for a splenic artery aneurysm, which resulted in a partial splenic infarction in the middle lobe. Five years after TAE, a 20-mm diameter mass in the noninfarcted area of the spleen was detected on imaging, which grew to 25 mm in diameter after 6 months. MRI after gadolinium administration showed a 35 × 34 mm mass within the superior pole and 15 × 12 mm mass within the inferior pole. The patient underwent laparoscopic splenectomy and had an uneventful postoperative recovery. No evidence of recurrence was observed during the 2-year follow-up period after surgery. The mass was pathologically confirmed to be sclerosing angiomatoid nodular transformation (SANT) of the spleen. While some studies hypothesize that SANT is a response to vascular injury or trauma, to the best of our knowledge, there have been no previous reports of SANT occurring after procedures directly affecting splenic blood flow. Additionally, multifocal SANTs are reported to be very rare, accounting for only 4.7% of all reported SANTs of the spleen. We highlight a rare course of SANT of the spleen and discuss the possible relationship between blood flow abnormalities and the appearance of SANT.

Coronavirus disease 2019 in a patient with pulmonary fibrosis and emphysema: An autopsy report.

Various diseases (e.g., hypertension and diabetes) are risk factors for the exacerbation of coronavirus 2019 (COVID-19). Patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) tend to develop severe COVID-19. Patients with severe COVID-19 present with acute respiratory distress syndrome (ARDS), and many COVID-19-related ARDS survivors eventually develop fibrosis. However, the appropriate management of patients with COVID-19 and ILD and post-COVID-19 ILD remains unclear. Thus, a better understanding of the pathology that exacerbates COVID-19 in patients with ILD is needed. We report the autopsy results of a patient with COVID-19 and combined pulmonary fibrosis and emphysema, whose lung organization and fibrosis progressed after the acute phase of infection. Histopathological findings suggest that fatal pulmonary fibrosis persists after the negative conversion of SARS-CoV-2. Elucidating the cause of death by autopsy may help determine therapeutic strategies in patients with COVID-19 and ILD. Vaccination and early administration of anti-inflammatory drugs or antifibrotic agents may be crucial for preventing disease progression and fatal lung fibrosis. This report aims to clarify the histopathological features of COVID-19 in patients with ILD via autopsy and discuss treatment strategies.

Hepatic and lung methotrexate-associated polymorphic lymphoproliferative disorders arising during postoperative follow-up of renal cell carcinoma: a case report.

INTRODUCTION: Methotrexate induces lymphoproliferative disorders on rare occasions; however, its pathogenesis remains unknown. A clinical diagnosis based on imaging studies alone is often difficult. CASE PRESENTATION: A 57-year-old Japanese woman was referred to our department for the evaluation of multiple lung and hepatic nodules that developed during methotrexate treatment for rheumatoid arthritis. Since she had a history of nephrectomy for localized renal cell carcinoma, multiple lung and hepatic metastases were initially considered. However, pathological diagnosis of the lung nodules (needle biopsy) revealed methotrexate-associated polymorphic-type lymphoproliferative disorders. After methotrexate discontinuation, continuous smooth shrinkage of the lung and liver lymphoproliferative disorders was observed. CONCLUSION: Methotrexate-associated lymphoproliferative disorders should be considered in the event of newly appearing neoplastic lesions, even during follow-up for renal cell carcinoma, if methotrexate is being administered.

Sternal closure with sandwiched three-piece bioresorbable mesh reduces postoperative hemorrhage: a retrospective study.

BACKGROUND: Median sternotomy is the most performed procedure in cardiac surgery; however, sternal displacement and bleeding remains a problem. This study aimed to investigate whether sternal reconstruction using a sandwiched three-piece bioresorbable mesh plate can prevent postoperative sternal displacement and bleeding more than a bioresorbable pin. METHODS: Patients (n = 218) who underwent median sternotomy were classified according to whether a sandwiched three-piece bioresorbable mesh plate and wire cerclage (group M, n = 109) or a bioresorbable pin and wire cerclage (group P, n = 109) were used during sternal reconstruction. The causes of postoperative sternal displacement and bleeding with computed tomography data were analyzed and compared between the groups. RESULTS: The preoperative patient characteristics did not significantly differ between the groups. However, the evaluation of sternal and substernal hematoma on postoperative day 5 using computed tomography showed sternal displacement in 4 (4%) and 22 (20%) patients, and substernal hematoma in 17 (16%) and 41 (38%) patients in groups M and P, respectively; this difference was significant. Furthermore, the amount of bleeding at 6 h postoperatively was lower in group M than in group P (235 ± 147 vs. 284 ± 175 mL, p = 0.0275). Chest reopening, intubation time, and length of intensive care unit and hospital stays did not differ between the groups. The evaluation of substernal hematoma based on computed tomography yielded a significantly lower for group M than for group P, revealing that the mesh plate was an independent predictor of substernal hematoma prevention. CONCLUSION: Sternal fixation with a three-piece bioresorbable mesh plate could prevent postoperative sternal displacement, bleeding, and substernal hematoma more than sternal fixation with a pin.

Protective effect of hydroxychloroquine on infections in patients with systemic lupus erythematosus: an observational study using the LUNA registry.

Objectives: Infection is a leading cause of death in patients with systemic lupus erythematosus (SLE). Alt hough hydroxychloroquine (HCQ) has been reported to inhibit infection, evidence from Asian populations remains insufficient. We investigated this effect in Japanese SLE patients. Methods: Data from the Lupus Registry of Nationwide Institutions were used in this study. The patients were ≥20 years old and met the American College of Rheumatology (ACR) classification criteria revised in 1997. We defined "severe infections" as those requiring hospitalization. We analyzed the HCQ's effect on infection suppression using a generalized estimating equation (GEE) logistic regression model as the primary endpoint and performed a survival analysis for the duration until the first severe infection. Results: Data from 925 patients were used (median age, 45 [interquartile range 35-57] years; female, 88.1%). GEE analysis revealed that severe infections were significantly associated with glucocorticoid dose (odds ratio [OR] 1.968 [95% confidence interval, 1.379-2.810], p<0.001), immunosuppressants (OR 1.561 [1.025-2.380], p=0.038), and baseline age (OR 1.043 [1.027-1.060], p<0.001). HCQ tended to suppress severe infections, although not significantly (OR 0.590 [0.329-1.058], p=0.077). Survival time analysis revealed a lower incidence of severe infections in the HCQ group than in the non-HCQ group (p<0.001). In a Cox proportional hazards model, baseline age (hazard ratio [HR] 1.029 [1.009-1.050], p=0.005) and HCQ (HR 0.322 [0.142-0.728], p=0.006) were significantly related to incidence. Conclusion: HCQ may help extend the time until the occurrence of infection complications and tends to decrease infection rates.

Rare solitary pituitary metastasis of maxillary ameloblastic carcinoma: illustrative case.

BACKGROUND: Ameloblastic carcinoma (AC) is a rare odontogenic carcinoma with histological features resembling ameloblastoma. Metastasis to distant organs and direct expansion into the skull base structures are associated with a poor clinical outcome. This rare case of AC metastasis to the pituitary gland presented without local recurrence at the primary focus of the maxilla. OBSERVATIONS: A 47-year-old man had a 2-year history of AC in the right maxilla. Computed tomography for his regular checkup incidentally demonstrated pituitary tumor, rapidly growing over 2 months. He presented with the recent onset of panhypopituitarism and visual field defect. Magnetic resonance imaging showed a large, irregularly shaped intrasellar and suprasellar lesion with chiasmal compression. Endoscopic endonasal transsphenoidal surgery was performed for decompression of the optic apparatus to avoid intracranial spread. Histopathology confirmed metastatic AC, and a genetic panel test confirmed BRAF V600E mutation. Stereotactic radiotherapy (SRT) with the CyberKnife system was administered to the residual tumor. Remarkable tumor shrinkage was obtained, and panhypopituitarism was resolved 12 months later. LESSONS: A multidisciplinary treatment strategy including maximal safe resection to avoid dissemination in combination with SRT may be crucial for local control with the preservation of pituitary and visual functions in patients with solitary pituitary metastatic AC.

A case of hyperammonemia occurring during treatment of metastatic renal cell carcinoma with axitinib.

Introduction: Although the incidence of hyperammonemia as an adverse event of tyrosine kinase inhibitors is quite low, several cases of tyrosine kinase inhibitor associated hyperammonemia have been reported. We report a case of hyperammonemia, that occurred during combined treatment with axitinib and pembrolizumab in a metastatic renal cell carcinoma patient without hepatic disorder or liver metastases. Case presentation: A 77-year-old Japanese woman was diagnosed with metastatic renal cell carcinoma and was treated with pembrolizumab and axitinib. Both agents were subsequently discontinued due to hyperammonemia with hypothyroidism. After recovery, the patient resumed single-agent therapy with axitinib. However, hyperammonemia and hypothyroidism occurred again, suggesting axitinib-inducible adverse event. After nephrectomy, a lower dose of axitinib was restarted and continued safely for residual metastases under prophylactic treatment with aminoleban, lactulose, and levothyroxine. Conclusion: The rare occurrence of hyperammonemia should be considered during treatment with VEGFR- targeted tyrosine kinase inhibitor including axitinib, and supportive prophylactic medication may be useful.

Pleomorphic adenoma of the trachea: A case report.

INTRODUCTION AND IMPORTANCE: Although pleomorphic adenoma is the most common type of parotid gland tumor, its occurrence in the trachea is rare. Here, we describe a successfully resected pleomorphic adenoma of the trachea in a woman with severe respiratory failure that had been preoperatively misdiagnosed as asthma. CASE PRESENTATION: A 69-year-old woman presented to the emergency department with symptoms of worsening dyspnea and subsequent loss of consciousness. She had a history of progressively worsening wheezing and stridor over the course of 2-years and had been diagnosed with asthma. Arterial blood gas sample analysis indicated type II respiratory failure. A chest computed tomographic scan revealed a tumor in the trachea, which was almost completely obstructing the lower tracheal lumen. The tumor was located just above the carina. To alleviate airway constriction and achieve complete resection, carinal resection with reconstruction was performed. The postoperative diagnosis was pleomorphic adenoma of the trachea. CLINICAL DISCUSSION: Pleomorphic adenoma is a rare tracheal tumor that may present with obstructive airway symptoms that mimic asthma. CONCLUSION: Tracheal tumors should be considered in patients with chronic respiratory symptoms that do not improve with medication.

Spontaneous malignant transformation of trigeminal schwannoma: consideration of responsible gene alterations for tumorigenesis-a case report.

Malignant peripheral nerve sheath tumors (MPNSTs) arising from the trigeminal nerves are extremely rare (only 45 cases, including the present case, have been published) and have been reported to develop de novo from the peripheral nerve sheath and are not transformed from a schwannoma or neurofibroma. Here, we report a case of MPNSTs of the trigeminal nerve caused by the malignant transformation of a trigeminal schwannoma, with a particular focus on genetic considerations. After undergoing a near-total resection of a histologically typical benign schwannoma, the patient presented with regrowth of the tumor 10 years after the primary excision. Histopathologic and immunochemical examinations confirmed the recurrent tumor to be an MPNST. Comprehensive genomic analyses (FoundationOne panel-based gene assay) showed that only the recurrent MPNST sample, not the initial diagnosis of schwannoma, harbored genetic mutations, including NF1-p.R2637* and TP53-p.Y234H, candidate gene mutations associated with malignant transformation. Moreover, the results of reverse transcription polymerase chain reaction showed that the fusion of SH3PXD2A and HTRA1, which has been reported as one of the responsible genetic aberrations of schwannoma, was detected in the recurrent tumor. Taken together, we could illustrate the accumulation process of gene abnormalities for developing MPNSTs from normal cells via schwannomas.

Prognostic value and clinicopathological roles of the tumor immune microenvironment in salivary duct carcinoma.

Salivary duct carcinoma (SDC) is an aggressive type of salivary gland carcinoma. Recently, immunotherapies targeting immune checkpoints, including PD1, PD-L1, CTLA4, and LAG3, have had a considerable prognostic impact on various malignant tumors. The implementation of such immune checkpoint inhibitor (ICI) therapies has also been attempted in cases of salivary gland carcinoma. The tumor immune microenvironment (TIME) is implicated in tumorigenesis and tumor progression and is closely associated with the response to ICI therapies. However, the TIME in SDC has not been fully explored. We examined the immunohistochemical expression of CD8, FOXP3, PD1, PD-L1, CTLA4, LAG3, and mismatch repair (MMR) proteins, tumor-infiltrating lymphocytes (TILs), and microsatellite instability (MSI) status in 175 cases of SDC. The associations between these TIME-related markers and the clinicopathological factors and prognosis were evaluated. An elevated expression of CD8, FOXP3, PD1, CTLA4, and LAG3 was associated with more aggressive histological features and an advanced N and/or M classification, elevated Ki-67 index, and poor prognosis. Furthermore, cases with a high PD-L1 expression exhibited more aggressive histological features and adverse clinical outcomes than those with a low expression. Alternatively, there was no significant correlation between TILs and clinicopathological factors. No SDC cases with an MSI-high status or MMR deficiency were found. The coexistence of both an immunostimulatory and immunosuppressive TIME in aggressive SDC might play a role in the presence of T-cell exhaustion. The contribution of multiple immune escape pathways, including regulatory T cells and immune checkpoints, may provide a rationale for ICI therapy, including combined PD1/CTLA4 blockade therapy.