[Histiocytic sarcoma derived from the same origin as splenic marginal zone lymphoma revealed by exome analysis].

Histiocytic sarcoma (HS) is a rare aggressive hematological malignancy reported to occur secondary to B cell lymphoma. We report a case of HS secondary to splenic marginal zone lymphoma (SMZL) complicated by autoimmune hemolytic anemia (AIHA) in a 64-year-old man. He was referred to our department with anemia and was diagnosed as having AIHA. After starting treatment with prednisolone, atypical lymphocytes appeared in his blood tests, and a bone marrow biopsy revealed invasion by B cell lymphoma. A CT scan showed splenomegaly and a pancreatic mass, which confirmed the diagnosis of SMZL. The patient received bendamustine and rituximab as chemotherapy, which rapidly improved the anemia and splenomegaly and reduced atypical lymphocytes. However, left lumbar back pain appeared along with an increase in the pancreatic mass, and he died suddenly of acute renal failure. An autopsy revealed that the tumor had invaded several organs including the pancreas, and immunohistochemistry was positive for CD163, leading to the diagnosis of HS. Furthermore, the specimens of SMZL and HS were positive for IgH gene reconstitution, and exome analysis showed genetic abnormalities in 226 genes including CARD11, suggesting that the SMZL and HS had the same origin.

Hyperechogenicity and histopathological features of focal liver lesions.

The identification and accurate diagnosis of focal liver lesions are important in modern medicine, where diagnostic radiology plays an essential role. This review aimed to examine the hyperechogenicity and histopathological features of focal liver lesions. Hyperechogenic liver lesions can be either benign or malignant. Evidence shows that hyperechogenicity is caused by factors such as fat deposition, sinusoidal dilation, peliotic changes, and pseudoglandular patterns. Fat deposition is a common cause of increased echogenicity in hepatocellular carcinoma (HCC). Meanwhile, sinusoidal dilation and peliotic changes are more frequently observed in larger HCC nodules. Pseudoglandular patterns, characterized by the reflection of ultrasound waves at the walls of numerous acini, are associated with hyperechogenicity in well-to-moderately differentiated HCCs. Moreover, this review comprehensively examined the histological features that may cause hyperechogenic internal echoes in not only HCCs but also localized liver lesions (metastases of adenocarcinoma and neuroendocrine neoplasm, intrahepatic cholangiocarcinoma, cavernous hemangioma, focal nodular hyperplasia, and angiomyolipoma). To make an accurate diagnosis and provide appropriate management, it is important to understand the histopathological basis for hyperechogenicity in focal liver lesions. By maximizing the accuracy of imaging studies and enhancing the radiology-pathology correlation, unnecessary biopsies can be avoided, thereby reducing potential complications and mortality. This review can help facilitate the effective management of patients with focal liver lesions, thereby resulting in timely and appropriate treatment decision-making.

The white ring sign is useful for differentiating between fundic gland polyps and gastric adenocarcinoma of the fundic gland type.

Background and study aims Gastric adenocarcinoma of the fundic gland type (GA-FG) is characterized by an elevated lesion with vessel dilation exhibiting branching architecture (DVBA). However, this feature is also found in fundic gland polyps (FGPs), posing a challenge in their differentiation. In this study, we aimed to investigate the clinicopathological features of gastric elevated lesions with DVBA and assess the efficacy of the white ring sign (WRS) as a novel marker for distinguishing between FGPs and GA-FGs. Methods We analyzed 159 gastric elevated lesions without DVBA and 51 gastric elevated lesions with DVBA, further dividing the latter into 39 in the WRS-positive group and 12 in the WRS-negative group. The clinicopathological features, diagnostic accuracy, and inter-rater reliability were analyzed. Results Univariate and multivariate analyses for gastric elevated lesions with DVBA identified the histological type consistent with FGPs and GA-FGs, along with the presence of round pits in the background gastric mucosa, as independent predictors. FGPs were present in 92.3% (36/39) of the WRS-positive group and GA-FGs were observed in 50.0% (6/12) of the WRS-negative group. WRS positivity and negativity exhibited high diagnostic accuracy, with 100% sensitivity, 80.0% specificity, and 94.1% accuracy for FGPs, and 100% sensitivity, 86.7% specificity, and 88.2% accuracy for GA-FGs. Kappa values for WRS between experts and nonexperts were 0.891 and 0.841, respectively, indicating excellent agreement. Conclusions WRS positivity and negativity demonstrate high diagnostic accuracy and inter-rater reliability for FGPs and GA-FGs, respectively, suggesting that WRS is a useful novel marker for distinguishing between FGPs and GA-FGs.

Efficacy of endoscopic surveillance for pharyngeal mucosa during endoscopic resection for pharyngeal carcinoma: a multicenter prospective study.

INTRODUCTION: Since patients with pharyngeal squamous cell carcinoma (SCC) often have multiple pharyngeal lesions, evaluation of pharyngeal lesions before endoscopic resection (ER) is important. However, detailed endoscopic observation of the entire pharyngeal mucosa under conscious sedation is difficult. We examined the usefulness of endoscopic surveillance with narrow band imaging (NBI) and lugol staining for detection of pharyngeal sublesions during ER for pharyngeal SCC under general anesthesia (endoscopic surveillance during treatment; ESDT). METHODS: From January 2021 through June 2022, we examined 78 patients who were diagnosed with superficial pharyngeal SCC and underwent ER. They underwent the ESDT and for patients who were diagnosed with new lesions of pharyngeal SCC or high-grade dysplasia (HGD) that were not detected in the endoscopic examination before treatment, ER were performed simultaneously for new lesions and the main lesions. The primary endpoint of this study was the detection rate of new lesions of pharyngeal SCC or HGD in the ESDT. RESULTS: Fifteen of the 78 patients were diagnosed as having undetected new pharyngeal lesions in the ESDT and 10 (12.8%) (95% CI 6.9-22.2%) were histopathologically confirmed to have new lesions of pharyngeal SCC or HGD. Among the 13 lesions of SCC or HGD, 8 were found by NBI observation; however, 5 were undetectable using NBI but detectable by lugol staining. All of the 13 lesions had endoscopic findings of pink color sign on lugol staining. CONCLUSIONS: Endoscopic surveillance for pharyngeal sublesions during ER for pharyngeal SCC is feasible and useful.

Branch-duct Intraductal Papillary Mucinous Neoplasm with Rapidly Developing Intracystic Xanthogranulomatous Nodules.

We herein report a case of a branch-duct intraductal papillary mucinous neoplasm (IPMN) with rapidly developing intracystic xanthogranulomatous nodules. A unilocular cystic lesion without a mural nodule was found in the pancreatic tail of a 69-year-old man. Ten months later, multiple mural nodules emerged unexpectedly within the cyst, and the patient underwent distal pancreatectomy. Based on immunohistochemical studies and a molecular analysis, we diagnosed him with branch-duct IPMN of the gastric immunophenotype. Fragility of the pancreatic duct mucosa and consequent exposure of the wall to pancreatic juice might have caused marked granulation nodule formation in the cyst lumen.

Inference of core needle biopsy whole slide images requiring definitive therapy for prostate cancer.

BACKGROUND: Prostate cancer is often a slowly progressive indolent disease. Unnecessary treatments from overdiagnosis are a significant concern, particularly low-grade disease. Active surveillance has being considered as a risk management strategy to avoid potential side effects by unnecessary radical treatment. In 2016, American Society of Clinical Oncology (ASCO) endorsed the Cancer Care Ontario (CCO) Clinical Practice Guideline on active surveillance for the management of localized prostate cancer. METHODS: Based on this guideline, we developed a deep learning model to classify prostate adenocarcinoma into indolent (applicable for active surveillance) and aggressive (necessary for definitive therapy) on core needle biopsy whole slide images (WSIs). In this study, we trained deep learning models using a combination of transfer, weakly supervised, and fully supervised learning approaches using a dataset of core needle biopsy WSIs (n=1300). In addition, we performed an inter-rater reliability evaluation on the WSI classification. RESULTS: We evaluated the models on a test set (n=645), achieving ROC-AUCs of 0.846 for indolent and 0.980 for aggressive. The inter-rater reliability evaluation showed s-scores in the range of 0.10 to 0.95, with the lowest being on the WSIs with both indolent and aggressive classification by the model, and the highest on benign WSIs. CONCLUSION: The results demonstrate the promising potential of deployment in a practical prostate adenocarcinoma histopathological diagnostic workflow system.

Optical biopsy for esophageal squamous cell neoplasia by using endocytoscopy.

BACKGROUND: Endocytoscopy (ECS) enables microscopic observation in vivo for the gastrointestinal mucosa; however, there has been no prospective study in which the diagnostic accuracy of ECS for lesions that have not yet undergone histological diagnosis was evaluated. We conducted a surveillance study for patients in a high-risk group of esophageal squamous cell carcinoma (ESCC) and evaluated the in vivo histological diagnostic accuracy of ECS. METHODS: This study was a multicenter prospective study. We enrolled 197 patients in the study between September 1, 2019 and November 30, 2020. The patients first underwent white light imaging and narrow band imaging, and ultra-high magnifying observation was performed if there was a lesion suspected to be an esophageal tumor. Endoscopic submucosal dissection (ESD) was later performed for lesions that were diagnosed to be ESCC by ECS without biopsy. We evaluated the diagnostic accuracy of ECS for esophageal tumorous lesions. RESULTS: ESD was performed for 37 patients (41 lesions) who were diagnosed as having ESCC by ECS, and all of them were histopathologically diagnosed as having ESCC. The sensitivity [95% confidence interval (CI)] was 97.6% (87.7-99.7%), specificity (95% CI) was 100% (92.7-100%), diagnostic accuracy (95% CI) was 98.9% (94.0-99.8%), positive predictive value (PPV) (95% CI) was 100% (91.4-100%) and negative predictive value (NPV) (95% CI) was 98.0% (89.5-99.7%). CONCLUSIONS: ECS has a high diagnostic accuracy and there were no false positives in cases diagnosed and resected as ESCC. Optical biopsy by using ECS for esophageal lesions that are suspected to be tumorous is considered to be sufficient in clinical practice.

A Deep Learning Model for Cervical Cancer Screening on Liquid-Based Cytology Specimens in Whole Slide Images.

Liquid-based cytology (LBC) for cervical cancer screening is now more common than the conventional smears, which when digitised from glass slides into whole-slide images (WSIs), opens up the possibility of artificial intelligence (AI)-based automated image analysis. Since conventional screening processes by cytoscreeners and cytopathologists using microscopes is limited in terms of human resources, it is important to develop new computational techniques that can automatically and rapidly diagnose a large amount of specimens without delay, which would be of great benefit for clinical laboratories and hospitals. The goal of this study was to investigate the use of a deep learning model for the classification of WSIs of LBC specimens into neoplastic and non-neoplastic. To do so, we used a dataset of 1605 cervical WSIs. We evaluated the model on three test sets with a combined total of 1468 WSIs, achieving ROC AUCs for WSI diagnosis in the range of 0.89-0.96, demonstrating the promising potential use of such models for aiding screening processes.

A deep learning model for breast ductal carcinoma in situ classification in whole slide images.

The pathological differential diagnosis between breast ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) is of pivotal importance for determining optimum cancer treatment(s) and clinical outcomes. Since conventional diagnosis by pathologists using microscopes is limited in terms of human resources, it is necessary to develop new techniques that can rapidly and accurately diagnose large numbers of histopathological specimens. Computational pathology tools which can assist pathologists in detecting and classifying DCIS and IDC from whole slide images (WSIs) would be of great benefit for routine pathological diagnosis. In this paper, we trained deep learning models capable of classifying biopsy and surgical histopathological WSIs into DCIS, IDC, and benign. We evaluated the models on two independent test sets (n= 1382, n= 548), achieving ROC areas under the curves (AUCs) up to 0.960 and 0.977 for DCIS and IDC, respectively.

Absent X-linked inhibitor of apoptosis protein expression in T cell blasts and causal mutations including non-coding deletion.

BACKGROUND: X-linked inhibitor of apoptosis protein (XIAP) deficiency is one of inborn errors of immunity characterized by recurrent hemophagocytic lymphohistiocytosis and refractory inflammatory bowel disease (IBD), mimicking Crohn's disease. The aim of this study is to make an accurate diagnosis of XIAP deficiency based on genetic and XIAP expression studies and to investigate endoscopic findings shared by patients with this disease. METHODS: Four male patients with recurrent hemophagocytic lymphohistiocytosis and long-term refractory IBD were studied for the diagnosis of XIAP deficiency. Endoscopic findings of the four patients were also studied in parallel. RESULTS: These four patients were diagnosed with XIAP deficiency based on the absent XIAP expression in cultured T-cell blasts. Sequence analysis of the responsible gene, XIAP, demonstrated two novel nonsense mutations of p.Gln114X and p.Glu25X, and a previously reported nonsense mutation of p.Arg381X. Although no mutations in the coding region were detected in the fourth patient, further studies demonstrated a novel 2,199 bp deletion encompassing non-coding exon 1, presumably affecting transcription and stability of XIAP mRNA. All of the patients eventually underwent hematopoietic stem cell transplantation, leading to a complete or partial remission of IBD. These four patients shared an endoscopic finding of multiple wide and longitudinal ulcers with straight and non-raised edge in the colon. CONCLUSIONS: X-linked inhibitor of apoptosis protein expression in T-cell blasts could facilitate the diagnosis of this disease, especially with causal mutations in non-coding regions.

Thymic Adenocarcinoma with Positivity for Thyroid Transcription Factor-1 and a BRAF V600E Mutation.

Thymic adenocarcinomas are rare. We herein report for the first time a case of thymic adenocarcinoma with positivity for thyroid transcription factor-1 (TTF-1) and a BRAF V600E mutation. A 50-year-old woman had persistent suffocation and chest pain. Computed tomography revealed a 42×28-mm tumor in the anterior mediastinum. The patient underwent tumor resection using video-assisted thoracoscopic surgery. Histopathological findings showed thymic papillary adenocarcinoma, Masaoka stage II. Immunohistochemically, the tumor was positive for TTF-1. A sequencing analysis revealed a BRAF V600E mutation. The patient underwent postoperative radiotherapy and was in good health without recurrence at five months after resection.

Gastric Signet-Ring Cell Carcinoma That Presented as an Elevated Lesion due to Fibromuscular Obliteration in the Lamina Propria.

The widespread use of Helicobacter pylori eradication therapy in recent years has reduced the H. pylori infection rate, indicating that gastric cancer cases diagnosed in the future may be H. pylori-naïve. The typical endoscopic presentation of signet-ring cell carcinoma, which accounts for the majority of H. pylori-naïve gastric cancer cases, is a discolored, flat, or depressed lesion; it is rarely presented as an elevated lesion. In this study, we treated a patient with elevated signet-ring cell carcinoma in an H. pylori-naïve stomach. Histopathological testing after endoscopic submucosal dissection showed proliferation of fibromuscular tissue in the tumor, which may have caused the formation of the elevated lesion.