A case of laparoscopic lymphadenectomy for adenocarcinoma of unknown primary incidentally detected as a solitary enlarged lymph node along the common hepatic artery.

BACKGROUND: Even in cancer of unknown primary (CUP), which is rare clinical condition, solitary anterosuperior lymph node (LN) along the common hepatic artery (No.8a LN) enlargement diagnosed as metastatic adenocarcinoma has never been reported. CASE PRESENTATION: A 68-year-old Japanese male, with a history of early gastric cancer that had been completely treated by endoscopic submucosal dissection 26 years ago, was detected a single enlarged nodule along the common hepatic artery, No.8a LN, incidentally by computed tomography performed for monitoring of interstitial pneumonia. Endoscopic ultra-sound-guided fine needle aspiration revealed that this nodule was adenocarcinoma suggestive of metastasis, but other imaging studies, including upper and lower gastrointestinal endoscopy, positron emission tomography, and ultrasonography did not detect any primary cancer. We have finally diagnosed as the LN metastasis of CUP and performed laparoscopic lymphadenectomy for this tumor. The tumor was approximately 5 cm in size, was in close proximity to the pancreas, and involved part of the right gastric artery and vein. LNs in the No.5 and No.8a areas, including this tumor, were dissected laparoscopically, and radical resection was achieved. The patient had no postoperative complication and was discharged on postoperative day 10. Immunohistopathological findings revealed that the tumor was poorly differentiated adenocarcinoma, and different from the histology of gastric cancer resected 26 years ago, although the tumor was suggestive of gastrointestinal origin. Imaging studies performed 2 and 6 months after discharge also did not reveal a primary site. CONCLUSION: We reported a case of solitary No.8a LN adenocarcinoma of CUP. For diagnostic and therapeutic purposes, radical resection is recommended for single enlarged intra-abdominal LN of CUP.

Remarkable remission of symptomatic dermatomyositis after curative breast cancer surgery.

Dermatomyositis (DM) is an autoimmune disease that causes proximal muscle weakness in the extremities leading to severe immobility and dysphagia. Approximately 20% of patients with DM are positive for anti-TIF-1γ antibody and frequently accompanied by malignant tumors. Although DM remission after tumor resection has been reported, the indications for surgery in patients with severe DM are unknown. Herein, we report a case of a 79-year-old Japanese woman who presented with breast cancer and anti-TIF-1γ antibody-positive DM. She became bedridden shortly after DM onset. Although pulsed steroid therapy, intravenous immunoglobulin, tacrolimus, and endocrine therapy with fulvestrant did not improve her symptoms, tumor resection with axillary lymph node dissection resulted in complete remission of the DM after 8 months. Immunohistochemistry revealed high expression of TIF-1γ in cancer cells, both in the primary tumor and axillary lymph nodes. Since the serum levels of anti-TIF-1γ antibody decreased after the surgery, the existence of breast cancer with TIF-1γ expression may have contributed to the worsening of DM. The present case suggests that curative surgery should be considered as a treatment option even if the patient has severe symptoms, such as immobility and dysphagia. Careful discussions with patients and multidisciplinary collaboration are essential to make surgery feasible, particularly for those with severe symptomatic DM.

Expression of FOXI1 and POU2F3 varies among different salivary gland neoplasms and is higher in Warthin tumor.

PURPOSE: Salivary gland tumors are histologically diverse. Ionocytes and tuft cells, rare epithelial cells found in normal salivary glands, might be associated with salivary tumors. Here, we explored the expression of FOXI1 and POU2F3, master regulators of ionocytes and tuft cells, respectively, for common salivary neoplasms using immunohistochemistry. METHODS: We analyzed normal salivary tissues and nine salivary gland tumors; Warthin tumors (WT), pleomorphic adenomas (PA), basal cell adenomas, and oncocytomas were benign, whereas mucoepidermoid, adenoid cystic, acinic cell, salivary duct carcinomas, and polymorphous adenocarcinomas were malignant. RESULTS: Normal salivary glands contained a few FOXI1- and POU2F3-positive cells in the ducts instead of the acini, consistent with ionocytes and tuft cells, respectively. Among the benign tumors, only WTs and PAs consistently expressed FOXI1 (10/10 and 9/10, respectively). The median H-score of WTs was significantly higher than that of PAs (17.5 vs. 4, P = 0.01). While WTs and PAs harbored POU2F3-positive cells (10/10 and 9/10, respectively), the median H-score was higher in WTs than in PAs (10.5 vs 4, respectively). Furthermore, WTs exhibited a unique staining pattern of FOXI1- and POU2F3-positive cells, which were present in luminal and abluminal locations, respectively. Whereas none of the malignant tumors expressed FOXI1, only adenoid cystic carcinoma consistently expressed POU2F3 (5/5), with a median H-score of 4. CONCLUSION: The expression patterns of the characteristic transcription factors found in ionocytes and tuft cells vary among salivary gland tumor types and are higher in WT, which might be relevant for understanding and diagnosing salivary gland neoplasms.

Impact of Vascular Access Flow Suppression Surgery on Cervical Artery Circulation: A Retrospective Observational Study.

Vascular access (VA) flow suppression surgery augments VA flow resistance and can increase other circulation flows hindered by high-flow VA. However, whether VA flow suppression surgery affects cervical circulation has rarely been reported. We aimed to determine the effect of VA flow suppression surgery on the cervical circulation in patients with high-flow VA. This single-center, retrospective, observational study included 85 hemodialysis patients who underwent VA flow suppression surgery at the Kanno Dialysis and Access Clinic between 2009 and 2018. Blood flow in the VA, bilateral vertebral arteries, and common carotid artery was measured before and after VA flow suppression surgery. The VA flow decreased from 1548 mL/min to 693 mL/min postoperatively. The flow of the vertebral artery on the VA side increased from 55 mL/min to 81 mL/min. The flow in the bilateral common carotid arteries also increased. Patients whose symptoms improved postoperatively showed better improvement in the vertebral artery on the VA side. VA flow suppression surgery in patients with high-flow VA increases the flow of the vertebral artery on the VA side and of the bilateral common carotid arteries. High-flow VA can hinder the vertebral and common carotid circulation.

Hemoglobin Glycation Index: A Novel Risk Factor for Incident Chronic Kidney Disease in an Apparently Healthy Population.

CONTEXT: Chronic kidney disease (CKD) is a worldwide health problem. Recent literature has shown an association of hemoglobin glycation index (HGI) and CKD in patients with dysglycemia. OBJECTIVE: The aim of this study was to reveal the impact of HGI as a predictor for incident CKD in the general population. METHODS: CKD was defined as dipstick proteinuria or estimated glomerular rate (eGFR) < 60 mL/min/1.73 m2. Impact of HGI on incident CKD was assessed using the data from CKD-free health examinees (N = 23 467, 4.1% with diabetes) followed for a mean of 5.1 years: Cox proportional hazards model was employed with multivariate adjustment for age, systolic blood pressure, eGFR, fasting plasma glucose, body mass index, log[alanine aminotransferase], log[triglycerides], high-density lipoprotein cholesterol, platelet counts, smoking, and sex. Elevated level of HGI in subjects with CKD was ascertained after propensity score matching of another group of health examinees (N = 2580, 7.6% with diabetes). RESULTS: In the former group, CKD developed in 2540 subjects and HGI was the second most robust predictor for CKD, following low eGFR. With adjustment for the 11 covariates, the hazard ratio of HGI (95% CI) for CKD was 1.293 (1.238 to 1.349) (P < .0001). The population attributable risk of HGI for CKD was 4.2%. In the latter group, among 708 subjects matched 1:1 for 9 covariates, HGI was significantly elevated in subjects with CKD (median [interquartile range] -0.208 [-0.504 to -0.156] vs -0.284 [-0.582 to 0.052], P = .03). CONCLUSION: HGI was a novel risk factor for CKD in the general population.

Pathological snapshots of thymic epithelial tumors with invasion into neighboring structures: preparing for the forthcoming revision of the TNM classification.

Treatment decision-making of thymic epithelial tumors (TETs) after surgery is based on the pathological stage. Currently, most institutions use both the Masaoka-Koga system and the 8th edition of the tumor, node, metastasis (TNM) classification. Because these two systems separate each stage according to the same concept, namely, the "levels" of tumor extension, precise pathological evaluation of the presence or absence of tumor invasion into stage-defining structures is necessary. This review provides representative pathological snapshots of tumors invading neighboring structures to provide references that might be helpful to readers; the snapshots will cover features that correspond to those of "locally advanced TETs", the topic of this series. Tumor subtype, whether thymoma or thymic carcinoma, is another factor influencing treatment decisions. Accumulating evidence has indicated that most thymomas and thymic carcinomas have biologically distinct features. Representative results were achieved by a study conducted as part of The Cancer Genome Atlas (TCGA) project, and subsequent studies with the help of the TCGA data have further reported on these distinctive features. Here, we also introduce newly recognized features of TETs, mainly focusing on the difference between epithelial-rich thymomas and thymic squamous cell carcinoma. The new (9th) edition of the TNM classification will be launched in January 2024. Therefore, sharing current pathological features of TETs will help readers, not only in their daily practice but also in preparing for the upcoming classification system.

Serum sulfatide level is associated with severe systemic vasculitis with kidney involvement.

Sulfatides are a type of sulfated glycosphingolipid that are secreted with lipoproteins into the serum. These molecules are involved in the inflammatory pathway of vessels in addition to coagulation and platelet aggregation. Previous studies have proposed that sulfatides play a pivotal role in regulating inflammation-related disorders. Systemic vasculitis (SV) diseases are generally caused by autoimmune diseases and often involve kidney vasculitis, which may lead to rapidly progressive kidney dysfunction and end-stage kidney disease. Our earlier pilot study revealed that the level of serum sulfatides (SSs) was significantly decreased in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), a representative disease-causing SV with kidney involvement (SVKI), especially in patients exhibiting active crescentic findings on kidney biopsy. To further explore the clinical significance of an association between SS and SVKI, we analyzed and compared the SS level of patients with various SVKI diseases in this retrospective cohort study. Among patients admitted to our hospital between 2008 and 2021, we ultimately enrolled 26 patients with IgA vasculitis (IgAV), 62 patients with AAV, and 10 patients with anti-glomerular basement membrane disease (GBM) as examples of SVKI diseases, as well as 50 patients with IgA nephropathy (IgAN) and 23 donors for living kidney transplantation as controls. The mean ± standard deviation SS level in the donor, IgAN, IgAV, AAV, and GBM groups was 8.26 ± 1.72, 8.01 ± 2.21, 6.01 ± 1.73, 5.37 ± 1.97, and 2.73 ± 0.99 nmol/mL, respectively. Analysis of patients in the SVKI disease group showed that those with the crescentic class kidney biopsy finding exhibited a significantly lower SS level than did those with other class biopsy features. Additionally, the SS level had a higher detection ability for SVKI patients with crescentic class kidney biopsy findings (area under the receiver operating characteristic curve 0.90, 95% confidence interval 0.82-0.99) than did several other predictor candidates. Our results indicate that the SS level is decreased in more severe SVKI diseases and may be associated with active glomerular lesions in SVKI kidney biopsy samples.

Association between doubly labelled water-calibrated energy intake and objectively measured physical activity with mortality risk in older adults.

BACKGROUND: Physical activity or biomarker-calibrated energy intake (EI) alone is associated with mortality in older adults; the interaction relationship between the combined use of both factors and mortality has not been examined. We evaluated the relationship between mortality and calibrated EI and step counts in older adults. METHODS: This prospective study included 4,159 adults aged ≥65 years who participated in the Kyoto-Kameoka study in Japan and wore a triaxial accelerometer between 1 April and 15 November 2013. The calibrated EI was calculated based on a previously developed equation using EI biomarkers. The step count was obtained from the accelerometer ≥ 4 days. Participants were classified into the following four groups: low EI (LEI)/low step counts (LSC) group (EI: <2,400 kcal/day in men and <1,900 kcal/day in women; steps: <5,000 /day), n = 1,352; high EI (HEI)/LSC group (EI: ≥2,400 kcal/day in men and ≥1,900 kcal/day in women; steps: <5,000 /day), n = 1,586; LEI/high step counts (HSC) group (EI: <2,400 kcal/day in men and < 1,900 kcal/day in women; steps: ≥5,000 /day), n = 471; and HEI/HSC group (EI: ≥2,400 kcal/day in men and ≥1,900 kcal/day in women; steps: ≥5,000 /day), n = 750. Mortality-related data were collected until 30 November 2016. We performed a multivariable Cox proportional hazard analysis. RESULTS: The median follow-up period was 3.38 years (14,046 person-years), and 111 mortalities were recorded. After adjusting for confounders, the HEI/HSC group had the lowest all-cause mortality rate compared to other groups (LEI/LSC: reference; HEI/LSC: hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.41-1.23; LEI/HSC: HR: 0.59, 95% CI: 0.29-1.19; and HEI/HSC: HR: 0.10, 95% CI: 0.01-0.76). No significant interaction was observed between the calibrated EI and steps with mortality. The spline model showed that 35-42 kcal/100 steps/day of EI/100 steps was associated with the lowest mortality risk. CONCLUSIONS: HR mortality risk was lowest at 35-42 kcal/100 steps/day, suggesting that very high (≥56 kcal) or low (<28 kcal) EI/100 steps are not inversely associated with mortality. Adherence to optimal EI and adequate physical activity may provide sufficient energy balance to explain the inverse association with mortality among older Japanese adults.

Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens.

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

A Case of Biphenotypic Adnexal Carcinoma With Bowenoid and Basaloid Features: Focus on the Expression of SOX9 and Wnt Signaling Pathway Molecules, Including CDX2.

ABSTRACT: An 87-year-old woman presented with a pedunculated nodule of 1.2 × 1.2 × 0.6 cm on her left cheek. Microscopic examination of the lesion revealed bowenoid and rosette-like basaloid components, resembling Bowen disease and neuroendocrine carcinoma, respectively. Immunohistochemically, both components were positive for Wnt signaling pathway molecules-nuclear/cytoplasmic beta-catenin, lymphoid enhancer binding factor 1 (LEF1), and caudal type homeobox 2 (CDX2)-and the adnexal marker SRY-box transcription factor 9 (SOX9). Unlike neuroendocrine tumors and basal cell carcinomas, the basaloid component in the present case was negative for chromogranin A, INSM1, synaptophysin, and p40. Previously reported cases of similar CDX2-positive lesions were diagnosed as squamous cell carcinoma with enteric adenocarcinomatous differentiation and basaloid cutaneous carcinoma with a primitive cytomorphology. However, the lesion in the present case was simultaneously positive for SOX9, indicating adnexal differentiation. In particular, the expression of multiple Wnt signaling pathway molecules indicates follicular differentiation despite the absence of morphological follicular features, such as shadow cells. Moreover, shared immunopositivity for SOX9, CDX2, nuclear/cytoplasmic beta-catenin, and LEF1 by both bowenoid and basaloid components indicated that the bowenoid component did not represent Bowen disease but a part of the adnexal tumor, and that the basaloid component was not a tumor-to-tumor metastasis. After complete excision, no recurrence has been observed for 5 months. The findings of the present case expand the histological spectrum of cutaneous adnexal tumors with follicular immunophenotypic differentiation.

A Rare Case of Donor-Origin Intrahepatic Cholangiocarcinoma After Liver Transplantation for Hepatocellular Carcinoma: A Case Report.

BACKGROUND: Tumors may develop in the grafted liver after liver transplantation for hepatocellular carcinoma, most of which are hepatocellular carcinoma recurrences and are rarely of donor origin. We report a rare case of donor-origin intrahepatic cholangiocarcinoma in a liver allograft after liver transplantation for hepatocellular carcinoma. METHODS: A man in his 60s underwent liver transplantation for hepatocellular carcinoma with hepatitis C virus cirrhosis. The donor was a braindead woman in her 60s who had no history of malignancy. RESULTS: Three years and 5 months after liver transplantation, a tumor developed in the allograft. Computed tomography scans showed a 40-mm tumor that was atypical for hepatocellular carcinoma. Tumor biopsy was most suggestive of intrahepatic cholangiocarcinoma. Fluorescence in situ hybridization of the tumor showed an XX signal pattern, suggesting that it originated from the donor liver. Whole exome sequencing analysis strongly suggested that the tumor was an intrahepatic cholangiocarcinoma derived from the donor. CONCLUSIONS: Although donor-origin cancer after liver transplantation is extremely rare, it should be considered for adequate treatment.

Histogenetic and disease-relevant phenotypes in thymic epithelial tumors (TETs): The potential significance for future TET classification.

Thymic epithelial tumors (TETs) encompass morphologically various subtypes. Thus, it would be meaningful to explore the expression phenotypes that delineate each TET subtype or overarching multiple subtypes. If these profiles are related to thymic physiology, they will improve our biological understanding of TETs and may contribute to the establishment of a more rational TET classification. Against this background, pathologists have attempted to identify histogenetic features in TETs for a long time. As part of this work, our group has reported several TET expression profiles that are histotype-dependent and related to the nature of thymic epithelial cells (TECs). For example, we found that beta5t, a constituent of thymoproteasome unique to cortical TECs, is expressed mainly in type B thymomas, for which the nomenclature of cortical thymoma was once considered. Another example is the discovery that most thymic carcinomas, especially thymic squamous cell carcinomas, exhibit expression profiles similar to tuft cells, a recently discovered special type of medullary TEC. This review outlines the currently reported histogenetic phenotypes of TETs, including those related to thymoma-associated myasthenia gravis, summarizes their genetic signatures, and provides a perspective for the future direction of TET classification.

Bacterial Community Shifts during Polyp Bail-Out Induction in Pocillopora Corals.

Polyp bail-out constitutes both a stress response and an asexual reproductive strategy that potentially facilitates dispersal of some scleractinian corals, including several dominant reef-building taxa in the family Pocilloporidae. Recent studies have proposed that microorganisms may be involved in onset and progression of polyp bail-out. However, changes in the coral microbiome during polyp bail-out have not been investigated. In this study, we induced polyp bail-out in Pocillopora corals using hypersaline and hyperthermal methods. Bacterial community dynamics during bail-out induction were examined using the V5-V6 region of the 16S-rRNA gene. From 70 16S-rRNA gene libraries constructed from coral tissues, 1,980 OTUs were identified. Gammaproteobacteria and Alphaproteobacteria consistently constituted the dominant bacterial taxa in all coral tissue samples. Onset of polyp bail-out was characterized by increased relative abundance of Alphaproteobacteria and decreased abundance of Gammaproteobacteria in both induction experiments, with the shift being more prominent in response to elevated temperature than to elevated salinity. Four OTUs, affiliated with Thalassospira, Marisediminitalea, Rhodobacteraceae, and Myxococcales, showed concurrent abundance increases at the onset of polyp bail-out in both experiments, suggesting potential microbial causes of this coral stress response. IMPORTANCE Polyp bail-out represents both a stress response and an asexual reproductive strategy with significant implications for reshaping tropical coral reefs in response to global climate change. Although earlier studies have suggested that coral-associated microbiomes likely contribute to initiation of polyp bail-out in scleractinian corals, there have been no studies of coral microbiome shifts during polyp bail-out. In this study, we present the first investigation of changes in bacterial symbionts during two experiments in which polyp bail-out was induced by different environmental stressors. These results provide a background of coral microbiome dynamics during polyp bail-out development. Increases in abundance of Thalassospira, Marisediminitalea, Rhodobacteraceae, and Myxococcales that occurred in both experiments suggest that these bacteria are potential microbial causes of polyp bail-out, shedding light on the proximal triggering mechanism of this coral stress response.

An exploratory study for tuft cells in the breast and their relevance in triple-negative breast cancer: the possible relationship of SOX9.

BACKGROUND: Breast cancer is highly heterogeneous, suggesting that small but relevant subsets have been under-recognized. Rare and mainly triple-negative breast cancers (TNBCs) were recently found to exhibit tuft cell-like expression profiles, including POU2F3, the tuft cell master regulator. In addition, immunohistochemistry (IHC) has identified POU2F3-positive cells in the normal human breast, suggesting the presence of tuft cells in this organ. METHODS: Here, we (i) reviewed previously identified POU2F3-positive invasive breast cancers (n = 4) for POU2F3 expression in intraductal cancer components, (ii) investigated a new cohort of invasive breast cancers (n = 1853) by POU2F3-IHC, (iii) explored POU2F3-expressing cells in non-neoplastic breast tissues obtained from women with or without BRCA1 mutations (n = 15), and (iv) reanalyzed publicly available single-cell RNA sequencing (scRNA-seq) data from normal breast cells. RESULTS: Two TNBCs of the four previously reported invasive POU2F3-positive breast cancers contained POU2F3-positive ductal carcinoma in situ (DCIS). In the new cohort of invasive breast cancers, IHC revealed four POU2F3-positive cases, two of which were triple-negative, one luminal-type, and one triple-positive. In addition, another new POU2F3-positive tumor with a triple-negative phenotype was found in daily practice. All non-neoplastic breast tissues contained POU2F3-positive cells, irrespective of BRCA1 status. The scRNA-seq reanalysis confirmed POU2F3-expressing epithelial cells (3.3% of all epithelial cells) and the 17% that co-expressed the other two tuft cell-related markers (SOX9/AVIL or SOX9/GFI1B), which suggested they were bona fide tuft cells. Of note, SOX9 is also known as the "master regulator" of TNBCs. CONCLUSIONS: POU2F3 expression defines small subsets in various breast cancer subtypes, which can be accompanied by DCIS. The mechanistic relationship between POU2F3 and SOX9 in the breast warrants further analysis to enhance our understanding of normal breast physiology and to clarify the significance of the tuft cell-like phenotype for TNBCs.

Sessile serrated lesions with dysplasia: is it possible to nip them in the bud?

The serrated neoplasia pathway constitutes an "alternative route" to colorectal cancer (CRC), and sessile serrated lesions with dysplasia (SSLDs) are an intermediate step between sessile serrated lesions (SSLs) and invasive CRC in this pathway. While SSLs show indolent growth before becoming dysplastic (> 10-15 years), SSLDs are considered to rapidly progress to either immunogenic microsatellite instable-high (MSI-H) CRC (presumably 75% of cases) or mesenchymal microsatellite stable (MSS) CRC. Their flat shapes and the relatively short window of this intermediate state make it difficult to detect and diagnose SSLDs; thus, these lesions are potent precursors of post-colonoscopy/interval cancers. Confusing terminology and the lack of longitudinal observation data of serrated polyps have hampered the accumulation of knowledge about SSLDs; however, a growing body of evidence has started to clarify their characteristics and biology. Together with recent efforts to incorporate terminology, histological studies of SSLDs have identified distinct dysplastic patterns and revealed alterations in the tumor microenvironment (TME). Molecular studies at the single-cell level have identified distinct gene alterations in both the epithelium and the TME. Mouse serrated tumor models have demonstrated the importance of TME in disease progression. Advances in colonoscopy provide clues to distinguish pre-malignant from non-malignant-SSLs. Recent progress in all aspects of the field has enhanced our understanding of the biology of SSLDs. The aim of this review article was to assess the current knowledge of SSLDs and highlight their clinical implications.

A case of vasculogenic mesenchymal tumor in the mediastinum: whole-exome sequencing reveals origin from pre-existing germ cell tumor.

Vasculogenic mesenchymal tumor (VMT), a primitive mesenchymal neoplasm enriched by various-sized atypical vessels, is a new entity that develops in mediastinal germ cell tumors (GCTs) with yolk sac tumor (YST) components after chemotherapy. Notably, patients with VMT in the residual GCT have increased risk of developing sarcomas or hematopoietic malignancies. Here, we report a late-teenage male patient with residual teratoma and high-grade VMT after chemotherapy for a mediastinal mixed GCT, including YST. Whole-exome sequencing revealed biallelic inactivation of TP53 and extensive copy number alterations that suggested whole-genome doubling. The biopsy tissue of the mixed GCT before chemotherapy exhibited overlapping genetic alterations to those in the VMT. Immunohistochemical analyses of the VMT showed that the abnormal vessels were positive for cytokeratin, glypican 3, EZH2, and IMP3. The findings that VMT inherits the genetic alterations of pre-existing mixed GCT and exhibits a partly YST-like immunophenotype might contribute to its clinical aggressiveness.

Inhibition of RANKL Expression in Osteocyte-like Differentiated Tumor Cells in Giant Cell Tumor of Bone After Denosumab Treatment.

Giant cell tumors of bone (GCTBs) are locally aggressive tumors with the histological features of giant cells and stromal cells. Denosumab is a human monoclonal antibody that binds to the cytokine receptor activator of nuclear factor-kappa B ligand (RANKL). RANKL inhibition blocks tumor-induced osteoclastogenesis, and survival, and is used to treat unresectable GCTBs. Denosumab treatment induces osteogenic differentiation of GCTB cells. In this study, the expression of RANKL, special AT-rich sequence-binding protein 2 (SATB2, a marker of osteoblast differentiation), and sclerostin/SOST (a marker of mature osteocytes) was analyzed before and after treatment with denosumab in six cases of GCTB. Denosumab therapy was administered a mean of five times over a mean 93.5-day period. Before denosumab treatment, RANKL expression was observed in one of six cases. After denosumab therapy, spindle-like cells devoid of giant cell aggregation were RANKL-positive in four of six cases. Bone matrix-embedded osteocyte markers were observed, although RANKL was not expressed. Osteocyte-like cells were confirmed to have mutations, as identified using mutation-specific antibodies. Our study results suggest that treatment of GCTBs with denosumab results in osteoblast-osteocyte differentiation. Denosumab played a role in the suppression of tumor activity via inhibition of the RANK-RANKL pathway, which triggers osteoclast precursors to differentiate into osteoclasts.

Dose-response relationship between daily step count and prevalence of sarcopenia: A cross-sectional study.

OBJECTIVES: Daily step counts are an easy-to-understand indicator of physical activity; however, there is limited evidence regarding the optimal daily step count to prevent sarcopenia. This study examined the dose-response relationship between daily step count and the prevalence of sarcopenia and explored the optimal dose. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: The study included 7949 community-dwelling middle-aged and older adults (aged 45-74 years) from Japan. MEASUREMENTS: Skeletal muscle mass (SMM) was assessed using bioelectrical impedance spectroscopy, and muscle strength was quantified through handgrip strength (HGS) measurement. Participants who exhibited both low HGS (men: <28 kg, women: <18 kg) and low SMM (lowest quartile in each sex-specific category) were defined as having sarcopenia. Daily step counts were measured for 10 days using a waist-mounted accelerometer. To examine the association between daily step count and sarcopenia, a multivariate logistic regression analysis was performed, adjusting for potential confounding factors such as age, sex, body mass index, smoking status, alcohol consumption, protein intake, and medical history. The odds ratios (ORs) and confidence intervals (CIs) were calculated based on the daily step counts categorized into quartiles (Q1-Q4). Finally, a restricted cubic spline curve was fitted to further investigate the dose-response relationship between daily step count and sarcopenia. RESULTS: The prevalence of sarcopenia in the overall participants was 3.3 % (259/7949 participants), with a mean daily step count of 7292 ± 2966 steps. Expressed in quartiles, the mean daily step counts were 3873 ± 935 steps in Q1, 6025 ± 503 steps in Q2, 7942 ± 624 steps in Q3, and 11,328 ± 1912 steps in Q4. The prevalence of sarcopenia in each quartile of daily step count was 4.7 % (93/1987 participants) in Q1, 3.4 % (68/1987 participants) in Q2, 2.7 % (53/1988 participants) in Q3, and 2.3 % (45/1987 participants) in Q4. The ORs and 95 % CIs adjusted for covariates demonstrated a statistically significant inverse association between daily step count and sarcopenia prevalence (P for trend <0.01), as follows: Q1, reference; Q2, 0.79 (95 % CI: 0.55-1.11); Q3, 0.71 (95 % CI: 0.49-1.03); Q4, 0.61 (95 % CI: 0.41-0.90). The restricted cubic spline curve indicated that the ORs leveled off at approximately 8000 steps per day, and no statistically significant decrease in ORs was observed for daily step counts above this threshold. CONCLUSIONS: The study found a significant inverse association between daily step count and the prevalence of sarcopenia, with the association plateauing when the daily step count exceeded approximately 8000 steps. These findings suggest that 8000 steps per day may be the optimal dose to prevent sarcopenia. Further intervention and longitudinal studies are needed to validate the results.

Big insulin-like growth factor 2-producing multiple solitary fibrous tumors treated with debulking surgery: A case report.

Background: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome caused by a tumor-producing high molecular weight form of insulin-like growth factor 2 (IGF2) known as big IGF2. The only curative treatment for this condition is surgical resection of the responsible tumors. However, this may not be feasible in cases with multiple metastases at diagnosis of NICTH, and no standard treatment strategy for multiple tumors has been established. The effects of pharmacological therapies including somatostatin analogs are often inefficient and remain difficult to predict. Case description: A 68-year-old man was admitted to our hospital due to impaired consciousness and severe hypoglycemia. His medical history included diagnosis of a left temporal solitary fibrous tumor (SFT) at the age of 48 years, after which local recurrent and metastatic tumors were repeatedly resected. Four years before admission, multiple intraabdominal and subcutaneous tumors were detected and, being asymptomatic, were managed conservatively. Laboratory exam on admission demonstrated hypoglycemia accompanied with low serum insulin and IGF1 levels. Computed tomography (CT) scan revealed multiple intraabdominal and subcutaneous tumors increasing in size. Serum big IGF2 was detected on immunoblot analysis, and he was diagnosed as NICTH. In addition, tumor uptake was observed on 68Ga-labelled 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe1-Tyr3-octreotide positron emission tomography/CT (DOTATOC-PET/CT). Since larger tumor is more suspicious about responsible producibility of big IGF2, we planned to resect large ones preferentially and reduce the amounts of residual tumors. Debulking surgery was performed by removing eleven intraabdominal tumors; the hypoglycemia was then completely corrected. Histological analyses revealed the resected tumors to be metastases of SFT having somatostatin receptor 2 expression. In immunoblot analysis, the resected tumors were found to be positive for big IGF2; serum big IGF2 was undetectable after surgery. Conclusion: We present a case of NICTH with multiple metastatic SFTs. We strategically performed debulking surgery, which led to remission of hypoglycemia. This result demonstrates a pioneering practical solution for NICTH cases with multiple tumors. In addition, in cases of SFTs presenting with NICTH, positivity of DOTATOC-PET/CT as well as single-dose administration of octreotide may be predictive of the efficacy of somatostatin-based therapy.

Evaluation of breast lesions based on modified BI-RADS using high-resolution readout-segmented diffusion-weighted echo-planar imaging and T2/T1-weighted image.

PURPOSE: To evaluate the diagnostic performance of a non-contrast magnetic resonance imaging (MRI) protocol combining high-resolution diffusion-weighted images (HR-DWI) using readout-segmented echo planar imaging, T1-weighted imaging (T1WI), and T2-weighted imaging (T2WI), using our modified Breast Imaging-Reporting and Data System (modified BI-RADS). METHODS: Two experienced radiologists, blinded to the final pathological diagnosis, categorized a total of 108 breast lesions (61 malignant and 47 benign) acquired with the above protocol using the modified BI-RADS with a diagnostic decision tree. The decision tree included subcategories of category 4, as in mammography (categories 2, 3, 4A, 4B, 4C, and 5). These results were compared with the pathological diagnoses. RESULTS: The area under the ROC curve (AUC) was 0.89 (95% confidence interval [CI]: 0.83-0.95) for reader 1, and 0.89 (95% CI: 0.82-0.96) for reader 2. When categories 4C and above were classified as malignant, the sensitivity, specificity, and accuracy were 73.8%, 93.6%, and 82.4%, for reader 1; and 82.0%, 89.4%, and 85.2% for reader 2, respectively. CONCLUSION: Our results suggest that using HR-DWI, T1WI/T2WI analyzed with a modified BI-RADS and a decision tree showed promising diagnostic performance in breast lesions, and is worthy of further study.