The clinicopathological and molecular features of sinusoidal large B-cell lymphoma.

We report 17 cases of sinusoidal large B-cell lymphoma (SLBCL). Clinical, morphologic, immunophenotypic, and molecular features were detected and analyzed. All cases showed an obvious sinusoidal growth pattern, usually associated with residual atrophic lymphoid tissue. All tumors contained large pleomorphic lymphoid cells and one or more prominent nucleoli, with abundant amphophilic cytoplasms; 15/17 cases showed anaplastic morphologic features. The patient age ranged from 43 to 80 years (median 57 years), and 7 males and 10 females were included. Eleven of 15 (73.3%) patients had Ann Arbor stage III or IV disease, and 10/15 (66.6%) patients had an International Prognostic Index (IPI) score ≥3. Immunophenotypically, 16/17 (94.1%) cases displayed a nongerminal center B-cell (non-GCB) immunophenotype. Furthermore, 16/17 (94.1%) cases were positive for CD30, and p53 was expressed in 10/16 (62.5%) cases. In total, 12/14 (85.7%) cases expressed BCL2 and MYC simultaneously (double expression), and 11/14 (78.6%) cases showed PD-L1 positivity (6/11 had a PD-L1 tumor proportion score ≥50%). Cytogenetically, concurrent MYC and BCL2 and/or BCL6 abnormalities (break-apart or extra copy) were detected in 10/15 cases, and 7/13 (53.8%) cases harbored a PD-L1/L2 amplification. TP53 mutation was found in 7/13 (53.8%) cases by Sanger sequencing. Whole-exome and large-panel sequencing results revealed high mutation frequencies of TP53 (4/7), MYD88 (3/7), KMT2D (3/7), CREBBP (3/7), and PIM1 (3/7). Among the 13 patients with SLBCL treated with aggressive chemotherapy regimens, the median overall survival (OS) was 18 months, and the 2-year OS rate was 34.6%. The OS of patients with SLBCL was markedly worse than that of 35 control group patients with common diffuse large B-cell lymphoma (DLBCL) without sinusoidal features (P < 0.001). SLBCL may represent a specific type of DLBCL that has characteristic pathologic features. The cancer is aggressive in most clinical cases, and outcomes are poor. SLBCL and anaplastic DLBCL (A-DLBCL) have many overlapping clinicopathological and molecular features.

[IgG4-related lung disease:a clinical analysis and literature review].

OBJECTIVE: To summarize the clinical features, diagnosis and treatment experience of IgG4-related lung disease for the sake of improving clinical understanding of this disease and reducing the misdiagnosis and mistreatment rates. METHODS: To analyze the general situation, clinical manifestation, laboratory examination, histopathology, therapy and prognosis of 2 patients with IgG4-related lung disease, who were admitted in the department of respiratory diseases at Changhai Hospital. Publications related to IgG4 lung disease were reviewed. RESULTS: Both patients were male with elevated serum IgG4 level (2.25 g/L and 10 g/L respectively). In one patient, radiologic finding showed solid nodules in the lung with ileocecal involvement. He responded well to glucocorticoid. The other patient's computed tomography of lung demonstrated bronchovascular type. Glucocorticoid therapy was effective to both patients. A total of 69 cases with IgG4-related lung disease were reported worldwide, among whom 39 cases were admitted with chief complaints of respiratory symptoms. However, there were 41 cases suffering extra-pulmonary involvement. Serum IgG4 levels detected in 48 cases were significantly elevated (307-52 500 mg/L). The radiographic pattern of solid nodule type was the most frequent, accounting for 50.7% (35 cases). A total of 31 (44.9%) patients received glucocorticoid therapy with good response and prognosis. CONCLUSION: IgG4-related lung disease is a rare immunological disease lack of specific symptoms. Serum immunological examination, radiographic characteristics and histopathology should be comprehensively considered for diagnosis. Glucocorticoid is so far the most acceptable therapy with good response rate.

Prognostic significance of miR-34a and its target proteins of FOXP1, p53, and BCL2 in gastric MALT lymphoma and DLBCL.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL), which are the two most common types of gastric lymphomas, have different clinicopathological features and molecular characteristics with distinct clinical outcomes. Tumor suppressor miR-34a connects the p53 network with forkhead box protein 1 (FOXP1) and BCL2. Here, we investigated the prognostic value of these molecules in gastric MALT lymphoma and DLBCL for use in routine clinical practice. METHODS: Relative miR-34a expression was detected by quantitative reverse transcriptase-polymerase chain reaction in 20 cases of MALT lymphomas and 20 cases of DLBCLs. Tissue microarray, in situ hybridization, and immunohistochemistry analysis were used to examine the expression of miR-34a and its regulated genes, FOXP1, p53, and BCL2 proteins, in 64 patients with gastric MALT lymphoma and in 58 patients with DLBCL. Helicobacter pylori infection, overall survival (OS), and progression-free survival (PFS) were documented. RESULTS: The expression level of miR-34a was markedly decreased in MALT lymphomas and DLBCLs compared to normal gastric tissues and peripheral blood mononuclear cells. miR-34a was present in the cytoplasm and nucleus of lymphocytes. Its expression was significantly downregulated in MALT and DLBCL lymphoma tissues, as compared with normal lymphocytes. The expression level of miR-34a in DLBCL was lower than in MALT lymphoma. FOXP1 was found to be positive in 48%, p53 in 20%, and BCL2 in 68% of MALT lymphoma cases. The corresponding positive rates of these markers in DLBCL were 64, 57, and 52%, respectively. High expression of FOXP1, p53, and BCL2 was seen in stage III and IV of both types of lymphomas. FOXP1, p53, and BCL2 positivity was associated with poor OS with both lymphoma types but OS with DLBCL was significantly lower than with MALT lymphoma. CONCLUSIONS: Decreased miR-34a expression and increased FOXP1, p53, and BCL2 coexpression to predict a poor OS for MALT lymphoma and DLBCL patients could become very important prognostic markers in daily clinical work. Further investigation of these changes may be of prognostic significance in clinical practice.

Global contextual representation via graph-transformer fusion for hepatocellular carcinoma prognosis in whole-slide images.

Current methods of digital pathological images typically employ small image patches to learn local representative features to overcome the issues of computationally heavy and memory limitations. However, the global contextual features are not fully considered in whole-slide images (WSIs). Here, we designed a hybrid model that utilizes Graph Neural Network (GNN) module and Transformer module for the representation of global contextual features, called TransGNN. GNN module built a WSI-Graph for the foreground area of a WSI for explicitly capturing structural features, and the Transformer module through the self-attention mechanism implicitly learned the global context information. The prognostic markers of hepatocellular carcinoma (HCC) prognostic biomarkers were used to illustrate the importance of global contextual information in cancer histopathological analysis. Our model was validated using 362 WSIs from 355 HCC patients diagnosed from The Cancer Genome Atlas (TCGA). It showed impressive performance with a Concordance Index (C-Index) of 0.7308 (95% Confidence Interval (CI): (0.6283-0.8333)) for overall survival prediction and achieved the best performance among all models. Additionally, our model achieved an area under curve of 0.7904, 0.8087, and 0.8004 for 1-year, 3-year, and 5-year survival predictions, respectively. We further verified the superior performance of our model in HCC risk stratification and its clinical value through Kaplan-Meier curve and univariate and multivariate COX regression analysis. Our research demonstrated that TransGNN effectively utilized the context information of WSIs and contributed to the clinical prognostic evaluation of HCC.

A case of congenital bronchial atresia with tracheobronchial stenosis caused by emphysema: Successful management with thoracoscopic surgery.

Introduction: Congenital bronchial atresia (CBA), as a rare developmental abnormality of the lung, is usually asymptomatic and is accidently discovered in most cases. Currently, no standardized guidelines for the treatment or management of CBA have been established. Case presentation: A 22-year-old male soldier was referred to Shanghai Changhai Hospital, The First Affiliated Hospital of Naval Medical University due to chest tightness and shortness of breath after repeated strenuous activities. Contrast-enhanced computed tomography (CT) revealed an 18mm × 11mm solitary, well-circumscribed, and solid nodule with no enhancement in the right upper lobe (RUL), and emphysematous changes distributed throughout the RUL. A flexible bronchoscopic examination showed extrinsic compression stenosis in the bronchial opening of the right middle lobe (RML). After three-dimensional (3D) reconstruction CT and a multidisciplinary consultation, a diagnosis of CBA in the anterior segment (B3) of RUL was established. Subsequently, thoracoscopic right upper lobectomy was performed and resulted in an improved respiratory capacity 6 months after surgery. To date, the patient has good quality of life without any complication. Conclusion: This study underscores the role of bronchoscopy, 3D reconstruction CT, and a multidisciplinary consultation in the diagnosis of CBA, and highlights that a thoracoscopic intervention should be considered in such case.

Papillary renal neoplasm with reverse polarity: an observational study of histology, immunophenotypes, and molecular variation.

Background: Papillary renal neoplasm with reverse polarity (PRNRP) is a novel entity with unique clinicopathological characteristics, and only a small number of patients with PRNRP have been described. Methods: We retrospectively analyzed the data for nine patients with PRNRP and evaluated differences in the clinical, histomorphological, immunohistochemical, and molecular features; prognosis; and differential diagnosis of PRNRP from other renal tumors with papillary structure. Results: There were six males and three females aged 36 to 74 years (mean: 62.33 years; median: 68 years). All the tumors were solitary and ranged from 1 to 3.7 cm (mean: 2.17 cm; median: 2 cm), with three and six tumors arose in the left and right renal tract, respectively. Pathologically, PRNRP is a small, well-circumscribed neoplasm with predominant papillary formations. The lining epithelium is composed of a monolayer of cuboidal to low-columnar cells with low-grade nuclei arranged against the apical pole of the tumor cells. Edema, mucinous degeneration, and hyaline degeneration are found in the fibrovascular cores. Foamy macrophages, psammoma bodies, hemosiderin deposition, and infiltrative tumor boundaries were present in some patients. Immunohistochemically, all tumors showed diffuse positive staining for GATA3. Sanger sequencing confirmed the presence of KRAS mutation in seven patients. All patients had a good prognosis after surgery and were relapse free. Positive staining for GATA3 and negative staining for vimentin were the most significant markers for differentiating PRNRP from other renal tumors with analogous structure. Conclusions: These findings suggested that PRNRP is a distinctive subtype of renal tumor with specific pathological features and indolent behaviors that should be distinguished from other renal tumors, especially papillary renal cell carcinoma. A monolayer of tumor cells with an inverted nuclear pattern, positive staining for GATA3, and KRAS mutation are essential for pathological diagnosis. Owing to its satisfactory prognosis, the surveillance and follow-up of patients with PRNRP should be additionally formulated.

Outcomes of endoscopic submucosal dissection versus esophagectomy for poorly differentiated superficial esophageal squamous cell carcinoma: A 10-year cohort study.

BACKGROUNDS: The efficacy of endoscopic submucosal dissection (ESD) to treat poorly differentiated superficial esophageal squamous cell carcinoma (SESCC) is unclear. AIMS: To exploring the efficacy and prognosis of ESD treatment poorly differentiated SESCC compared with esophagectomy. METHODS: A retrospective cohort study was conducted, the data of poorly differentiated SESCC patients who received ESD or esophagectomy from Jan 2011 to Jan 2021 were analyzed. Overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and procedure-related variables were compared between ESD and esophagectomy group. RESULTS: 95 patients underwent ESD, while 86 underwent esophagectomy. No significant differences were found between the two groups in OS (P = 0.587), DSS (P = 0.172), and RFS (P = 0.111). Oncologic outcomes were also similar between the two groups in propensity score-matched analysis. For T1a ESCC, the rates of R0 resection, LVI or nodal metastasis and additional therapy were similar between ESD and esophagectomy groups. But for T1b ESCC, the rates of positive resection margin and additional therapy were significantly higher in ESD group than those in esophagectomy group. CONCLUSIONS: ESD is a minimally invasive procedure that has comparable oncologic outcomes with esophagectomy for treatment poorly differentiated T1a ESCC. However, ESD is not suitable for poorly differentiated T1b ESCC, additional surgery or radiochemotherapy should be required.

Prognostic Significance of Grade Discrepancy Between Primary Tumor and Venous Thrombus in Nonmetastatic Clear-cell Renal Cell Carcinoma: Analysis of the REMEMBER Registry and Implications for Adjuvant Therapy.

BACKGROUND: Further stratification of the risk of recurrence of clear-cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) will facilitate selection of candidates for adjuvant therapy. OBJECTIVE: To assess the impact of tumor grade discrepancy (GD) between the primary tumor (PT) and VTT in nonmetastatic ccRCC on disease-free survival (DFS), overall survival (OS), and cancer-specific survival (CSS). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective analysis of a multi-institutional nationwide data set for patients with pT3N0M0 ccRCC who underwent radical nephrectomy and thrombectomy. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS: Pathology slides were centrally reviewed. GD, a bidirectional variable (upgrading or downgrading), was numerically defined as the VTT grade minus the PT grade. Multivariable models were built to predict DFS, OS, and CSS. RESULTS AND LIMITATIONS: We analyzed data for 604 patients with median follow-up of 42 mo (excluding events). Tumor GD between VTT and PT was observed for 47% (285/604) of the patients and was an independent risk factor with incremental value in predicting the outcomes of interest (all p < 0.05). Incorporation of tumor GD significantly improved the performance of the ECOG-ACRIN 2805 (ASSURE) model. A GD-based model (PT grade, GD, pT stage, PT sarcomatoid features, fat invasion, and VTT consistency) had a c index of 0.72 for DFS. The hazard ratios were 8.0 for GD = +2 (p < 0.001), 1.9 for GD = +1 (p < 0.001), 0.57 for GD = -1 (p = 0.001), and 0.22 for GD = -2 (p = 0.003) versus GD = 0 as the reference. According to model-converted risk scores, DFS, OS, and CSS significantly differed between subgroups with low, intermediate, and high risk (all p < 0.001). CONCLUSIONS: Routine reporting of VTT upgrading or downgrading in relation to the PT and use of our GD-based nomograms can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression. PATIENT SUMMARY: We developed a tool to improve patient counseling and guide decision-making on other therapies in addition to surgery for patients with the clear-cell type of kidney cancer and tumor invasion of a vein.

Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study.

There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

[Analysis of Clinicopathologic Features of 9 Cases of 
SMARCA4-deficient Non-small Cell Lung Cancer].

BACKGROUND: SMARCA4-deficient non-small cell lung cancer (SMARCA4-dNSCLC) is a rare primary lung malignancy. These diseases are not listed separately in the 2021 World Health Organization (WHO) classification of lung neoplasms, but they have special morphological, immunophenotypic and molecular genetic characteristics. This study aims to improve understanding of SMARCA4-dNSCLC by discussing the clinicopathological features, diagonosis and differential diagnosis of the disease. METHODS: The clinical and imaging data of 9 cases of SMARCA4-dNSCLC diagnosed in Shanghai Changhai Hospital from January 2020 to March 2022 were collected. The clinicopathological features were analyzed by histological and immunohistochemical staining, and the literature was reviewed. RESULTS: The median age of 9 patients was 65 years old. Six men were smokers. The average maximum diameter of tumor was 3.3 cm. Six cases had been metastasized. The imaging showed that it was an infiltrating mass with unclear boundary and 3 cases invaded the pleura. Nine cases were diagnosed as SMARCA4-dNSCLC, which mainly showed three pathological forms including classic lung adenocarcinoma, mucinous adenocarcinoma and poorly differentiated carcinoma. Poorly differentiated tumor cells are epithelioid, syncytial or rhabdomyoid, the cytoplasm was rich, the cytoplasm could be completely transparent to eosinophilic, eosinophilic globules or small abscesses could be seen, showing solid flakes, with more inflammatory cells and flake necrosis in the stroma. Immunohistochemistry showed that SMARCA4 was negative in all cases and eight cases demonstrated cytokeratin 5.2 (CAM5.2) and cytokeratin 7 (CK7) was diffusely strongly positive, p40 was negative, thyroid transcription factor-1 (TTF-1) was negative in 6 cases, partially positive in 2 cases and diffusely positive in 1 case. CONCLUSIONS: SMARCA4-dNSCLC is a rare subtype of lung cancer with complex and diverse pathological morphology. The characteristic of immunohistochemical phenotype can assist in the diagnosis.

B2M mutation paves the way for immune tolerance in pathogenesis of Epstein-Barr virus positive diffuse large B-cell lymphomas.

This study focused genetic pathogenesis and tumor microenvironment of Epstein-Barr virus (EBV) positive diffuse large B-cell lymphomas (DLBCL) in patients without immunodeficiency. DNA samples from these cases were sequenced by next generation sequencing (NGS) using a selected gene panel. Results revealed that most gene mutations were not specific for EBV positive DLBCL. However, B2M (ß2-microglobulin) mutations were significantly increased and HLA-I or HLA-II expression was decreased in these cases, which was related to patient's poor outcome. B2M mutations and deregulation of B2M expression were further confirmed by Sanger sequencing and immunohistochemistry. Reducing the infiltration of CD8+ T lymphocytes, related to decreased expression of HLA-I or HLA-II was found in these patients. These results suggest that the mutations of B2M could cause the disruption of the expression and functions of this important subunit of HLA, leading to decreased expression of HLA-I or HLA-II and subsequently to reduce T lymphocyte infiltration in tumor tissues. The consequence of this event lessens the recognition and elimination of EBV+ tumor cells by host immunity and paves the way for the host immune tolerance to EBV+ tumor cells by evading immune recognition and escaping the T lymphocyte killing.

Rhabdoid glioblastoma: case report and literature review.

Rhabdoid glioblastoma is a recently described entity in which a glioblastoma is associated with a rhabdoid component. Although rhabdoid glioblastoma has not appeared in the new World Health Organization classification of tumors of the CNS, it has a specific morphological feature and highly aggressive clinic process. Up to now, there have been six cases of rhabdoid glioblastoma reported in the literature. We report rhabdoid glioblastoma in the right front temporal lobe from a 31-year-old Chinese man. This tumor consisted of rhabdoid tumor cells with an eccentric nucleus and an eosinophilic cytoplasm. The tumor had an area appearing to be glioblastoma with microvascular proliferation and necrosis, and lacked a primitive neuroectodermal tumor component, and a mesenchymal component. Vimentin, epithelial membrane antigen, GFAP and integrase interactor (INI-1) expression were found in the tumor cells. Genetic abnormalities which include monosomy or a deletion of chromosome 22 were not found in this tumor. After 3 months post-surgery, the tumor was widespread in leptomeningia and the patient died. In conclusion, rhabdoid glioblastoma is a rare glioblastoma with poor prognosis; the differential diagnosis contained other rhabdoid tumors. This case will contribute to the profile of rhabdoid glioblastoma with typical morphology and immunophenotype, genetic and clinic features.

Immunotherapy and Targeting the Tumor Microenvironment: Current Place and New Insights in Primary Pulmonary NUT Carcinoma.

Primary pulmonary nuclear protein of testis carcinoma is a rare and highly aggressive malignant tumor. It accounts for approximately 0.22% of primary thoracic tumors and is little known, so it is often misdiagnosed as pulmonary squamous cell carcinoma. No effective treatment has been formed yet, and the prognosis is extremely poor. This review aims to summarize the etiology, pathogenesis, diagnosis, treatment, and prognosis of primary pulmonary nuclear protein of testis carcinoma in order to better recognize it and discuss the current and innovative strategies to overcome it. With the increasing importance of cancer immunotherapy and tumor microenvironment, the review also discusses whether immunotherapy and targeting the tumor microenvironment can improve the prognosis of primary pulmonary nuclear protein of testis carcinoma and possible treatment strategies. We reviewed and summarized the clinicopathological features of all patients with primary pulmonary nuclear protein of testis carcinoma who received immunotherapy, including initial misdiagnosis, disease stage, immunohistochemical markers related to tumor neovascularization, and biomarkers related to immunotherapy, such as PD-L1 (programmed death-ligand 1) and TMB (tumor mutational burden). In the meanwhile, we summarized and analyzed the progression-free survival (PFS) and the overall survival (OS) of patients with primary pulmonary nuclear protein of testis carcinoma treated with PD-1 (programmed cell death protein 1)/PD-L1 inhibitors and explored potential population that may benefit from immunotherapy. To the best of our knowledge, this is the first review on the exploration of the tumor microenvironment and immunotherapy effectiveness in primary pulmonary nuclear protein of testis carcinoma.

Aggregative Perivascular Tumor Cell Growth Pattern of Primary Central Nervous System Lymphomas Is Associated with Hypoxia-Related Endoplasmic Reticulum Stress.

Primary central nervous system lymphomas (PCNSLs) often present a unique histopathological feature of aggregative perivascular tumor cells (APVT). Our previous studies showed that patients of PCNSL with APVTs exhibited poor long-term outcomes and increased expression of the endoplasmic reticulum stress (ERS) factor X-box-binding protein (XBP1). However, very little is known about molecular mechanism of the APVT formation in PCNSLs. The aim of this study is to determine if hypoxia-induced ERS is related to the APVT formation in PCNSLs. In this study, cell culture was used to observe the interplay between diffuse large B cell lymphoma (DLBCL) tumor cells and human brain microvascular endothelial cells (HBMECs) in different oxygen conditions. The expression of XBP1, CXCR and CD44 was manipulated by molecular cloning and siRNA technology. Mouse in vivo experiments and clinical studies were conducted to confirm our hypothesis. Our results showed that activated B-cell type-DLBCL cells easily migrated and invaded, and expressed high levels of XBP1 and stromal molecules CXCR4 and CD44 during hypoxia-induced ERS and dithiothreitol unfolded protein response (UPR). The gene upregulation (using overexpression vector) and downregulation (siRNA gene knock-out) in cultured cells and in mouse models further confirmed a close relation of the expression of XBP1, CXCR4, and CD44 with APVT formation, which is coincided with our clinical observation that increased expression of XBP1, CXCR4, and CD44 in the APVT cells in PCNSLs were associated with poor clinical outcomes. The results suggest that hypoxia-induced ERS and UPR might be associated with APVTs formation in PCNSL and its poor clinical outcomes. The results will help us better understand the progression of PCNSL with APVTs feature in daily pathological work and could be valuable for future target treatment of PCNSLs.

SAMHD1 Mutations and Expression in Mantle Cell Lymphoma Patients.

SAMHD1 (sterile alpha motif domain and histidine-aspartate domain-containing protein 1) is a deoxynucleoside triphosphate triphosphohydrolase regulating innate immune and modulating DNA damage signaling. It plays an important role in the development of some tumors. SAMHD1 was also reported as a barrier to cytarabine, a common chemotherapy drug for mantle cell lymphoma (MCL), and as a biomarker of grim prognosis for acute myelocytic leukemia (AML) patients. However, SAMHD1 expression and function in MCL have not been well-defined. In the present study, we evaluated SAMHD1 expression by immunohistochemistry and its gene structure by Sanger sequencing in MCL. Our results showed that SAMHD1 was positive in 36 (62.1%) patients. Importantly, SAMHD1-positive patients were associated with lower chemotherapy response rate (p = 0.023) and shorter overall survival (p = 0.039) than SAMHD1-negative cases. These results suggest that SAMHD1 is an adverse biomarker for MCL patients, which is due to the high expression of SAMHD1 and rapid cell proliferation. These findings were confirmed in an in vitro study using the siRNA technique. Silencing the SAMHD1 gene in the MCL cell line Jeko-1 significantly decreased cell proliferation and increased cell apoptosis. The MCL cell line with SAMHD1 knockdown showed lower Ki-67 proliferation index, higher caspase-3, and higher sensitivity to cytarabine. Furthermore, for the first time, four previously unreported missense mutations (S302Y, Y432C, E449G, and R451H) in exon 8 and exon 12 of the SAMHD1 gene were discovered by sequencing. The mutations had not been found to corelate with SAMHD1 protein expression detected by immunohistochemistry. The biological functions of this mutated SAMHD1 remain to be investigated.

An asymptomatic Moyamoya disease: autopsy case and literature review.

BACKGROUND: Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disorder. Patients diagnosed asymptomatic MMD should have no prior ischemic or hemorrhagic episode and no history of neurologic diseases. The incidence of asymptomatic MMD has turned out to be higher than previously thought due to better diagnosis with the increasing availability of magnetic resonance imaging or magnetic resonance angiography technology. However, the clinical symptoms of asymptomatic MMDs are still obscure. CLINICAL CASE: This report presents an asymptomatic MMD patient, who was a previously healthy 42-year-old-woman. The patient suffered from burst coma and started vomiting 3 hours before hospitalization. The patient died of the rupture of hemorrhage located on the right temporal lobe near the cortex. Autopsy revealed that the vascular networks were increased at the right postcentral gyrus and on the surface of the occipital lobe. CONCLUSIONS: As a small number of asymptomatic MMD patients have clinical symptoms, we must be aware of the possibility of MMD. The clinical symptoms of transient ischemic attack, ischemic stroke, or/and intracranial bleeding maybe the manifestation of this disease. Early recognition, accurate diagnosis and prompt treatment are vital to the survival of the patients with asymptomatic MMD.

Rupture of splenic artery aneurysm in pregnancy: a review of the literature and report of two cases.

BACKGROUND: Splenic artery aneurysms are an uncommon form of vascular disease, which have a significant potential for rupture, most commonly associated with pregnancy, typically presents as sudden, unexpected death. As a consequence, the initial recognition and diagnosis of splenic artery aneurysm rupture take place only at autopsy. CLINICAL CASES: This report presents 2 cases of sudden death resulting from splenic artery aneurysm in a pregnant woman and a postpartum woman, respectively. The former splenic artery aneurysm were measuring 1 cm in diameter and the latter splenic artery aneurysm 5.5 x 5 x 2 cm in size. Histologic examination of the both vessels wall showed severe morphologic changes of degeneration together with an attenuation of arterial internal elastica. CONCLUSIONS: To our knowledge, splenic artery aneurysm in pregnant woman is unusual vital disease. It is essential that obstetricians are alert to the prodromal and catastrophic symptoms of splenic artery aneurysm. Early recognition and prompt management, including early resected electively, are vital to the survival of both mother and fetus.