Comparison of the Clinical Validity of Droplet Digital PCR to ARMS-PCR for BRAF V600E Mutation Detection in Thyroid Nodules.

OBJECTIVES: Droplet digital PCR (ddPCR) has been reported to have a superior validity over PCR with amplification-refractory mutation system (ARMS-PCR) for detecting the BRAF V600E mutation in thyroid nodule fine-needle aspiration (FNA) samples using cytological diagnosis as the reference. However, the added value of ddPCR on surgical decision-making remains to be illustrated when the technique is combined with FNA cytology. METHODS: A total of 277 consecutive patients with thyroid nodules were subjected to FNA cytology and BRAF V600E testing with ARMS-PCR. Within this patient cohort, 90 patients underwent surgical intervention with pathological diagnosis available. BRAF V600E testing with ddPCR was performed retrospectively using FNA frozen DNA specimens. The clinical validity and utility of ddPCR in comparison with ARMS-PCR were compared using surgical pathology as the reference. RESULTS: Overall, 101 BRAF V600E mutations were detected by ddPCR, including five ARMS negative patients, four of whom were confirmed to have papillary thyroid cancer (PTC) by surgical pathology. Of the 90 patients with surgical pathology, which is considered the gold standard, ddPCR BRAF V600E testing yielded a sensitivity of 91.3% and specificity of 100% for PTC diagnosis, higher than that of ARMS (sensitivity 83.1%, specificity 100%). However, ddPCR only identified one more candidate patient for surgical intervention than ARMS when the techniques were combined with cytology. CONCLUSIONS: This study highlighted the superior performance of ddPCR over ARMS in BRAF V600E detection from thyroid nodule FNA samples. Further studies are needed to evaluate the cost-effectiveness of replacing ARMS-PCR with ddPCR for surgical decision-making.

Gastrointestinal Lymphoma in Southwest China: Subtype Distribution of 1,010 Cases Using the WHO (2008) Classification in a Single Institution.

UNLABELLED: The gastrointestinal tract (GIT) is the most common anatomic site of extranodal non-Hodgkin lymphoma (NHL) involvement. The classification criteria of lymphoma have changed in recent decades, and few large-sample studies regarding subtype analysis of lymphoma have been performed in this site. AIM: Therefore, the present study was conducted to analyze the histological subtype distribution of the GIT. METHOD: All patients in a single institution with a diagnosis of primary NHL in the GIT were enrolled between January 2007 and April 2014. The patients were categorized according to the WHO (2008) classification of tumors of hematopoietic and lymphoid tissue. RESULT: A total of 1,010 eligible cases diagnosed as NHL were collected in this study. The male:female ratio was 1.7:1 and the median age was 55 years. The percent of patients with lymphoma involvement in the stomach was 52% (n = 522), and the remaining 48% (n = 484) had intestinal tract involvement. Histologically, diffuse large B cell lymphoma (DLBCL) was the most common subtype in all of the GIT lymphoma cases, and was also the most common subtype in cases involving the stomach (78%) and the intestinal tract (53%). The incidence of DLBCL and mucosa-associated lymphoid tissue lymphoma in the stomach was significantly higher than the incident in the intestinal tract (p < 0.01). T and NK cell lymphoma was significantly more common in the intestinal tract than in the stomach (p < 0.01). Extranodal NK/T cell lymphoma nasal type (ENKTL-N) was the most common subtype of T and NK cell lineage lymphoma in GIT and was also the second most common intestinal tract-involved lymphoma. CONCLUSION: DLBCL was the most frequent lymphoma in the stomach and in the intestinal tract. T and NK cell lineage lymphoma had a higher occurrence in the intestinal tract than in the stomach. ENKTL-N was the most frequent subtype of lymphoma derived from NK/T cell lineage, and was the second most common lymphoma among all intestinal tract lymphomas.

[Diffuse large B-cell lymphoma with aberrant expression of CD56: a clinicopathologic and immunohistochemical study].

OBJECTIVE: To study the clinicopathologic features and significance of aberrant CD56 expression in diffuse large B-cell lymphoma (DLBCL). METHODS: The clinical and pathologic profiles of 10 cases of DLBCL with aberrant expression of CD56 were investigated. Immunohistochemical staining, in-situ hybridization for Epstein-Barr virus encoded RNA and gene rearrangement for IgH and Igκ were carried out. RESULTS: There were 6 male and 4 female patients. The medium age of patients was 46 years. All of them presented with extranodal lymphoma involvement, with gastrointestinal tract being the commonest site (5/10). Histologic examination showed that most of the atypical lymphoid cells were centroblast-like and demonstrated a diffuse growth pattern. Apoptosis and necrosis were identified in some cases. Immunohistochemical study showed that the tumor cells were positive for CD20 or CD79α and aberrantly expressed CD56. Five cases had the GCB phenotype while the remaining cases had the non-GCB phenotype, according to Hans classification. Bcl-6 was positive in most cases (9/10). All cases showed a high proliferation index by Ki-67. The tumor cells were negative for CD3ε, CD138 and granzyme B. In-situ hybridization for Epstein-Barr virus encoded RNA was performed in 7 cases and none of them showed positive signals. IgH gene rearranged bands were detected in 4 cases (4/6) and Igκ was detected in 3 cases (3/6). Follow-up data were available in 8 patients. Two patients died of disease progression within 5 to 13 months after diagnosis and the other 6 patients were alive 8 to 60 months after therapy. CONCLUSIONS: DLBCL with aberrant expression of CD56 is rare. Most of them present with extranodal involvement, show high frequency of bcl-6 expression and high proliferation index. The patients often have good response to chemotherapy.

[Plasmablastic lymphoma: a clinicopathologic analysis of 11 cases with review of literature].

OBJECTIVE: To investigate the clinicpathologic features and diagnosis of plasmablastic lymphoma (PBL). METHODS: Eleven cases of PBL were collected and followed up, with review of the literature. HIV and EBV status and their relationships with the tumor were specially compared as well. RESULTS: In the current cohort, 10 patients were serologically HIV negative; the male to female ratio was 8 to 3, and the median age was 57 years. Ten cases showed extranodal involvement and one case was nodal based. At presentation, five patients had mid-facial involvement, including sinonasal area (3 cases) and oral cavity (2 cases). Histologically, six were PBL of oral mucosa type, and five were PBL with plasmacytic differentiation. In all cases, the neoplastic cells expressed CD138 and MUM-1, and were negative for CD20 and CD3ε; the median Ki-67 index was 80%. Five cases were EBER1/2 in situ hybridization positive. IgH or/and Igκ gene rearrangement was detected in all five cases examined. CONCLUSIONS: Most patients were no congenital or acquired immunodeficiency in the retrospective study. Of the died patients, EBER1/2 in situ hybridization were negative and their disease staging were Ⅳ, The neoplastic cells were immunoblastic or plasmablastic, sometimes the plasmacytoid cell can be seen and the neoplastic cell had mature plasma cell phenotype, the pathologic diagnosis of the lymphoma is still controversial now. Differentiate with plasma cell neoplasm is difficult, it is necessary to accumulate more cases for advanced study and observation in the future.

Soluble epoxide hydrolase is involved in the development of atherosclerosis and arterial neointima formation by regulating smooth muscle cell migration.

Epoxyeicosatrienoic acids (EETs) have beneficial effects on cardiovascular disease. Soluble epoxide hydrolase (sEH) metabolizes EETs to less active diols, thus diminishing their biological activity. sEH inhibitors can suppress the progression of atherosclerotic lesions in animal models. However, the regulation of sEH in vascular smooth muscle cells (VSMCs) and role of sEH in patients with atherosclerosis have not been evaluated. We hypothesize that sEH in VSMCs plays a pivotal role in atherosclerosis and injury-induced neointima formation. In this study, sEH expression in human autopsy atherosclerotic plaque was determined by immunohistochemistry. In cultured rat and human VSMCs, the phenotypic switching marker and sEH expression induced by platelet-derived growth factor-BB (PDGF-BB) were examined by Western blot analysis. Carotid-artery balloon injury was performed after adenovirus-mediated overexpression of sEH or oral administration of a potent sEH inhibitor in Sprague-Dawley rats. sEH was highly expressed in VSMCs of the intima and media within human atherosclerotic plaque. In vitro, PDGF-BB upregulated the expression in VSMCs after transcription and promoted cell proliferation and migration; the latter effect could be largely attenuated by an sEH inhibitor. Adenovirus-mediated overexpression of sEH could mimic the effect of PDGF-BB and induce VSMC proliferation and migration. In vivo, the sEH inhibitor led to a significant decrease in injury-induced neointima formation in a rat carotid-artery injury model. These data establish the effect of sEH expression on atherosclerotic progression and vascular remodeling after injury, thus identifying a novel integrative role for sEH in VSMC phenotypic modulation and migration. Blocking sEH activity may be a potential therapeutic approach for ameliorating vascular occlusive disease.

Multiparametric MR-based feature fusion radiomics combined with ADC maps-based tumor proliferative burden in distinguishing TNBC versus non-TNBC.

Objective.To investigate the incremental value of quantitative stratified apparent diffusion coefficient (ADC) defined tumor habitats for differentiating triple negative breast cancer (TNBC) from non-TNBC on multiparametric MRI (mpMRI) based feature-fusion radiomics (RFF) model.Approach.466 breast cancer patients (54 TNBC, 412 non-TNBC) who underwent routine breast MRIs in our hospital were retrospectively analyzed. Radiomics features were extracted from whole tumor on T2WI, diffusion-weighted imaging, ADC maps and the 2nd phase of dynamic contrast-enhanced MRI. Four models including the RFFmodel (fused features from all MRI sequences), RADCmodel (ADC radiomics feature), StratifiedADCmodel (tumor habitas defined on stratified ADC parameters) and combinational RFF-StratifiedADCmodel were constructed to distinguish TNBC versus non-TNBC. All cases were randomly divided into a training (n= 337) and test set (n= 129). The four competing models were validated using the area under the curve (AUC), sensitivity, specificity and accuracy.Main results.Both the RFFand StratifiedADCmodels demonstrated good performance in distinguishing TNBC from non-TNBC, with best AUCs of 0.818 and 0.773 in the training and test sets. StratifiedADCmodel revealed significant different tumor habitats (necrosis/cysts habitat, chaotic habitat or proliferative tumor core) between TNBC and non-TNBC with its top three discriminative parameters (p <0.05). The integrated RFF-StratifiedADCmodel demonstrated superior accuracy over the other three models, with higher AUCs of 0.832 and 0.784 in the training and test set, respectively (p <0.05).Significance.The RFF-StratifiedADCmodel through integrating various tumor habitats' information from whole-tumor ADC maps-based StratifiedADCmodel and radiomics information from mpMRI-based RFFmodel, exhibits tremendous promise for identifying TNBC.

Interference KRT17 reverses doxorubicin resistance in triple-negative breast cancer cells by Wnt/ß-catenin signaling pathway.

BACKGROUND: Triple-negative breast cancer (TNBC) is a subtype of breast cancer with the highest degree of malignancy and is easily resistant to drugs due to the lack of hormone receptors. Research on the resistance mechanisms in TNBC is particularly important. Keratin 17 (KRT17) is highly expressed in TNBC. Anthracycline doxorubicin (Dox) is a commonly used chemotherapeutic drug for early stage triple-negative breast cancer. OBJECTIVE: This study investigated the role of KRT17 in TNBC-Dox resistance. METHODS: Immuno-histochemical staining, qPCR, western blotting (WB), and immunofluorescence were used to detect the expression of KRT17 in TNBC-Dox-resistant patients and in TNBC-Dox-resistant MDA-MB-468 and MDA-MB-231. the effect of KRT17 on the proliferation and migration in KRT17 knockdown of TNBC-Dox-resistant cells was determined by the CCK8, clone formation, transwell invasion and wound healing assays were used to determine. RESULTS: KRT17 was highly expressed in the TNBC-Dox-resistant cells. Knockdown of KRT17 significantly reduced the IC50s of TNBC-Dox-resistant and parental strains and also reduced the proliferation and invasion abilities of TNBC-Dox-resistant cell lines. KRT17 regulated the Wnt/ß-catenin signaling pathway. The inhibitory effect of KRT17 knockdown on the proliferation and migration of TNBC-Dox-resistant cells was reversed by an activator of the Wnt signaling pathway. CONCLUSION: KRT17 can inhibit the Wnt/ß-catenin signaling pathway, thereby reducing the proliferation and invasion ability of TNBC-Dox-resistant cells.

Preoperative prediction model for macrotrabecular-massive hepatocellular carcinoma based on contrast-enhanced CT and clinical characteristics: a retrospective study.

Objective: To investigate the predictive value of contrast-enhanced computed tomography (CECT) imaging features and clinical factors in identifying the macrotrabecular-massive (MTM) subtype of hepatocellular carcinoma (HCC) preoperatively. Methods: This retrospective study included 101 consecutive patients with pathology-proven HCC (35 MTM subtype vs. 66 non-MTM subtype) who underwent liver surgery and preoperative CECT scans from January 2017 to November 2021. The imaging features were evaluated by two board-certified abdominal radiologists independently. The clinical characteristics and imaging findings were compared between the MTM and non-MTM subtypes. Univariate and multivariate logistic regression analyses were performed to investigate the association of clinical-radiological variables and MTM-HCCs and develop a predictive model. Subgroup analysis was also performed in BCLC 0-A stage patients. Receiver operating characteristic (ROC) curves analysis was used to determine the optimal cutoff values and the area under the curve (AUC) was employed to evaluate predictive performance. Results: Intratumor hypoenhancement (odds ratio [OR] = 2.724; 95% confidence interval [CI]: 1.033, 7.467; p = .045), tumors without enhancing capsules (OR = 3.274; 95% CI: 1.209, 9.755; p = .03), high serum alpha-fetoprotein (AFP) (≥ 228 ng/mL, OR = 4.101; 95% CI: 1.523, 11.722; p = .006) and high hemoglobin (≥ 130.5 g/L; OR = 3.943; 95% CI: 1.466, 11.710; p = .009) were independent predictors for MTM-HCCs. The clinical-radiologic (CR) model showed the best predictive performance, achieving an AUC of 0.793, sensitivity of 62.9% and specificity of 81.8%. The CR model also effectively identify MTM-HCCs in early-stage (BCLC 0-A stage) patients. Conclusion: Combining CECT imaging features and clinical characteristics is an effective method for preoperatively identifying MTM-HCCs, even in early-stage patients. The CR model has high predictive performance and could potentially help guide decision-making regarding aggressive therapies in MTM-HCC patients.

Evaluation of molecular receptors status in breast cancer using an mpMRI-based feature fusion radiomics model: mimicking radiologists' diagnosis.

Objective: To investigate the performance of a novel feature fusion radiomics (RFF) model that incorporates features from multiparametric MRIs (mpMRI) in distinguishing different statuses of molecular receptors in breast cancer (BC) preoperatively. Methods: 460 patients with 466 pathology-confirmed BCs who underwent breast mpMRI at 1.5T in our center were retrospectively included hormone receptor (HR) positive (HR+) (n=336) and HR negative (HR-) (n=130). The HR- patients were further categorized into human epidermal growth factor receptor 2 (HER-2) enriched BC (HEBC) (n=76) and triple negative BC (TNBC) (n=54). All lesions were divided into a training/validation cohort (n=337) and a test cohort (n=129). Volumes of interest (VOIs) delineation, followed by radiomics feature extraction, was performed on T2WI, DWI600 (b=600 s/mm2), DWI800 (b=800 s/mm2), ADC map, and DCE1-6 (six continuous DCE-MRI) images of each lesion. Simulating a radiologist's work pattern, 150 classification base models were constructed and analyzed to determine the top four optimum sequences for classifying HR+ vs. HR-, TNBC vs. HEBC, TNBC vs. non-TNBC in a random selected training cohort (n=337). Building upon these findings, the optimal single sequence models (Rss) and combined sequences models (RFF) were developed. The AUC, sensitivity, accuracy and specificity of each model for subtype differentiation were evaluated. The paired samples Wilcoxon signed rank test was used for performance comparison. Results: During the three classification tasks, the optimal single sequence for classifying HR+ vs. HR- was DWI600, while the ADC map, derived from DWI800 performed the best in distinguishing TNBC vs. HEBC, as well as identifying TNBC vs. non-TNBC, with corresponding training AUC values of 0.787, 0.788, and 0.809, respectively. Furthermore, the integration of the top four sequences in RFF models yielded improved performance, achieving AUC values of 0.809, 0.805 and 0.847, respectively. Consistent results was observed in both the training/validation and testing cohorts, with AUC values of 0.778, 0.787, 0.818 and 0.726, 0.773, 0.773, respectively (all p < 0.05 except HR+ vs. HR-). Conclusion: The RFF model, integrating mpMRI radiomics features, demonstrated promising ability to mimic radiologists' diagnosis for preoperative identification of molecular receptors of BC.

Comprehensive analysis of competitive endogenous RNAs network: Identification and validation of prediction model composed of mRNA signature and miRNA signature in gastric cancer.

Gastric cancer (GC), one of the most lethal malignant tumors, is highly aggressive with a poor prognosis, while the molecular mechanisms underlying it remain largely unknown. Although advanced imaging techniques and comprehensive treatment facilitate the diagnosis and survival of some GC patients, the precise diagnosis and prognosis are still a challenge. The present study used publicly available gene expression profiles from The Cancer Genome Atlas and Gene Expression Omnibus datasets including mRNA, micro (mi)RNA and circular (circ)RNA of GC to establish a competing endogenous RNA network (ceRNA). Further, the present study performed least absolute shrinkage and selector operator regression analysis on the hub RNAs to establish a prediction model with mRNA and miRNA. The ceRNA network contained 109 edges and 56 nodes and the visible network contains 13 miRNAs, 9 circRNAs and 34 mRNAs. The five mRNA-based signature were CTF1, FKBP5, RNF128, GSTM2 and ADAMTS1. The area under curve (AUC) value of the diagnosis training cohort was 0.9975. The prognosis of the high-risk group (RiskScore >4.664) was worse compared with that of the low-risk group (RiskScore ≤4.664; P<0.05) in the training cohort. The five miRNA-based signature were miR-145-5p, miR-615-3p, miR-6507-5p, miR-937-3p and miR-99a-3p. The AUC value of the diagnosis training cohort was 0.9975. The prognosis of the high-risk group (RiskScore >1.621) was worse compared with that of the low-risk group (RiskScore ≤1.621; P<0.05) in the training cohort. The validation cohorts indicated that both five mRNA and five miRNA-based signatures had strong predictive power in diagnosis and prognosis for GC. In conclusion, a ceRNA network was established for GC and a five mRNA-based signature and a five miRNA-based signature was identified that enabled diagnosis and prognosis of GC by assigning patient to a high-risk group or low-risk group.

Case report: Acute Talaromyces marneffei mediastinitis in an HIV-negative patient.

Talaromyces marneffei (T. marneffei) is one of the most important opportunistic human pathogens endemic in Southeast Asia. Talaromycosis, which was once regarded as an opportunistic infectious disease in patients with acquired immunodeficiency syndrome, is being increasingly reported in HIV-negative populations. Since T. marneffei infection can be localized or disseminated, patients may present with a variety of symptoms. However, mediastinal infection attributed to T. marneffei is extremely rare. We report the case of a 32-year-old female who manifested a large mediastinal mass and was eventually diagnosed as acute T. marneffei mediastinitis. The patient was HIV-negative and had no direct contact with intermediate hosts. We successfully managed to treat the patient with inhaled amphotericin B deoxycholate and observed lesion absorption in subsequent CT examinations. To our knowledge, this is the first published case of T. marneffei mediastinitis and first use of inhaled antifungal monotherapy on patients with T. marneffei infection.

Prediction of Microvascular Invasion in Hepatocellular Carcinoma With a Multi-Disciplinary Team-Like Radiomics Fusion Model on Dynamic Contrast-Enhanced Computed Tomography.

OBJECTIVE: To investigate microvascular invasion (MVI) of HCC through a noninvasive multi-disciplinary team (MDT)-like radiomics fusion model on dynamic contrast enhanced (DCE) computed tomography (CT). METHODS: This retrospective study included 111 patients with pathologically proven hepatocellular carcinoma, which comprised 57 MVI-positive and 54 MVI-negative patients. Target volume of interest (VOI) was delineated on four DCE CT phases. The volume of tumor core (V tc ) and seven peripheral tumor regions (V pt , with varying distances of 2, 4, 6, 8, 10, 12, and 14 mm to tumor margin) were obtained. Radiomics features extracted from different combinations of phase(s) and VOI(s) were cross-validated by 150 classification models. The best phase and VOI (or combinations) were determined. The top predictive models were ranked and screened by cross-validation on the training/validation set. The model fusion, a procedure analogous to multidisciplinary consultation, was performed on the top-3 models to generate a final model, which was validated on an independent testing set. RESULTS: Image features extracted from V tc +V pt(12mm) in the portal venous phase (PVP) showed dominant predictive performances. The top ranked features from V tc +V pt(12mm) in PVP included one gray level size zone matrix (GLSZM)-based feature and four first-order based features. Model fusion outperformed a single model in MVI prediction. The weighted fusion method achieved the best predictive performance with an AUC of 0.81, accuracy of 78.3%, sensitivity of 81.8%, and specificity of 75% on the independent testing set. CONCLUSION: Image features extracted from the PVP with V tc +V pt(12mm) are the most reliable features indicative of MVI. The MDT-like radiomics fusion model is a promising tool to generate accurate and reproducible results in MVI status prediction in HCC.

Treatment Effect of a Vascular-Disrupting Agent Dynamically Monitored by DWI: An Animal Experimental Study.

Objective: To investigate the treatment effect of a vascular-disrupting agent, M410, using diffusion-weighted imaging in a rabbit model of hepatic VX2 tumor. Methods: 28 New Zealand white rabbit models with VX2 liver tumors were established and were randomly divided into M410 (intravenous injection of M410 at a dose of 25 mg/kg every three days) and control (intravenous injection of saline every three days) groups. Conventional and diffusion-weighted imaging (DWI) were acquired on a 3.0 T MR unit at baseline, 4 h, d 1, d 4, d 7, and d 14 posttreatment. B-value with 700 (s/mm2) was chosen during DWI examinations. Tumor volume and apparent diffusion coefficient (ADC) values of the entire tumor and solid component of the tumor at every time point were measured. Two randomly chosen rabbits from each group were sacrificed for H&E staining and CD34 immunohistochemical assessments at each time point. An independent sample t-test was used to assess differences in tumor sizes and ADC values of the entire tumor and solid component of tumors between two groups, with P < 0.05 considered statistically significant. Result: There was no significant difference in tumor volume between the two groups at baseline, 4 h, and d 1. With time, the tumors in the control group grew significantly faster than those in the M410 group, and the average ADC values of the M410 group were lower than those of the control group at d 1 and higher than those of the control group at d 4; as such, there were statistical differences between the two groups at these two time points but not at the other four time points. The following pathological results reflected the underlying morphological changes and vascular alterations. Conclusions: M410 performed well in inhibiting the growth of the hepatic VX2 tumor which could be noninvasively monitored by DWI metrics.

Multiphase Contrast-Enhanced CT-Based Machine Learning Models to Predict the Fuhrman Nuclear Grade of Clear Cell Renal Cell Carcinoma.

OBJECTIVE: To investigate the predictive performance of different machine learning models for the discrimination of low and high nuclear grade clear cell renal cell carcinoma (ccRCC) by using multiphase computed tomography (CT)-based radiomic features. MATERIALS AND METHODS: A total of 137 consecutive patients with pathologically proven ccRCC (including 96 low-grade [grade 1 or 2] and 41 high-grade [grade 3 or 4] ccRCC) from January 2011 to January 2019 were enrolled in this retrospective study. Target region of interest (ROI) delineation followed by texture extraction was performed on a representative slice with the largest section of the tumor on the four-phase (unenhanced phase [UP], corticomedullary phase [CMP], nephrographic phase [NP] and excretory phase [EP]) CT images. Fifteen concatenations of the four-phase features were fed into 176 classification models (built with 8 classifiers and 22 feature selection methods), the classification performances of the 2640 resultant discriminative models were compared, and the top-ranked features were analyzed. RESULTS: Image features extracted from the unenhanced phase (UP) CT images demonstrated a dominant classification performance over features from the other three phases. The discriminative model "Bagging + CMIM" achieved the highest classification AUC of 0.75. The top-ranked features from the UP included one shape-based feature and five first-order statistical features. CONCLUSION: Image features extracted from the UP are more effective than other CT phases in differentiating low and high nuclear grade ccRCC based on machine learning-based classification modeling.

Tracheal Lymphoepithelioma-Like Carcinoma on FDG PET/CT.

Lymphoepithelioma-like carcinoma (LELC) in the trachea is an extremely rare disease. We present a case of a 64-year-old man with FDG-avid tracheal LELC on F-FDG PET/CT. Despite its rarity, LELC in the trachea should be considered as one of the possibilities in patients with a hypermetabolic mass in the trachea. If LELC in the trachea is suspected, F-FDG PET/CT is a useful tool for initial staging.

PET/CT-based bone-marrow assessment shows potential in replacing routine bone-marrow biopsy in part of patients newly diagnosed with extranodal natural killer/T-cell lymphoma.

PURPOSE: This study aimed to determine the potential of positron emission tomography/computed tomography (PET/CT) in replacing routine bone-marrow biopsies (BMB) in newly diagnosed extranodal natural killer/T-cell lymphoma (ENKTCL). METHODS: Newly diagnosed patients underwent PET/CT imaging and routine BMB to assess bone/bone marrow involvement (BMI). Clinical stage and treatment plan were determined, and survival was compared. RESULTS: In a total of 101 patients, 78 were diagnosed as stage I/II and 23 as stage III/IV without using the BMB results. No BMB-positive patients were identified in stages I/II, and therefore, the BMB results did not alter the stage and treatment choice in any patients. The sensitivity and specificity of focal skeletal PET/CT lesion(s) in assessing BMI was 100% and 92.8%, respectively, taking routine BMB as the reference standard. The overall survival (OS) and progression-free survival (PFS) of BMB-positive patients was significantly inferior (P = 0.0011 and 0.0465, respectively, in advanced-stage patients; both P < 0.0001 in all patients), and this was corroborated by the PET/CT findings (P = 0.0006 and 0.0116, respectively, in advanced-stage patients; both P < 0.0001 in all patients). CONCLUSIONS: Based on the results, PET/CT demonstrated satisfactory predictive performance in terms of staging and prognosis in ENKTCL. BMB did not influence staging and treatment in newly diagnosed ENKTCL, and routine non-targeted BMB is not obligatory for early stage patients undergoing PET/CT. Targeted BMB is recommended to confirm BMI in advanced-stage patients.

Pulmonary inflammatory myofibroblastic tumor versus IgG4-related inflammatory pseudotumor: differential diagnosis based on a case series.

BACKGROUND: Pulmonary inflammatory myofibroblastic tumor (IMT) has been considered as a synonym for inflammatory pseudotumor (IPT) for a long time. Recent studies have indicated that IMT and IgG4-related IPT are distinct diseases. However, no consensus criteria have been recommended. Here we propose a set of criteria for the differential diagnosis. METHODS: Twenty-six archived IMT and IgG4-related IPT samples were examined for histological characteristics and the expression of IgG, IgG4, SMA and ALK-1. Based on our proposed criteria, we reclassified the cases into either IMT or IgG4-related IPT group and compared the clinicopathological features, laboratory findings, overall survivals (OS) and disease-free survivals between groups to validate the effectiveness and dependability of the diagnostic criteria. RESULTS: The average age of IgG4-related IPT group was higher than IMTs (48.82 vs. 39.22 years, P=0.031). In IMT group, tumors were characterized by bigger tumor sizes (3.47 vs. 2.22 cm, P=0.007), diffuse and total destroyed alveoli (88.89% vs. 17.65%, P=0.002), fewer lymphoid follicles (1.6/HPF vs. 3.0/HPF, P=0.045) and lower expression of IgG (74.7/HPF vs. 149.1/HPF; P<0.001). As an exclusion criterion of IgG4-related IPT, ALK-positivity was correlated with the higher cytological atypia (mean 3.7/HPF, P<0.001) and lesser lymphoid follicles (mean 1.2/HPF, P=0.021). And it's the first study to show the liner positive correlation between the lymphocytes + plasma cells count and IgG4-positive plasma cells count in these lesions (r=0.914, P<0.001). The negative correlation between the IgG4-positive plasma cells count and the expression of ALK-1 are reported for the first time as well (rs=-0.632, P=0.001). However, despite two patients with recurrence or metastasis were divided into IMT group, only borderline values were detected in the survival analysis (OS 88.89% vs. 100%, P=0.197, DFS 77.78% vs. 100.00%; P=0.056). CONCLUSIONS: The significant differences of clinicopathological characteristics between the IMTs and IgG4-related IPTs indicated that a combination of lymphocytes + plasma cells count, cytological atypia, IgG4 and ALK-1 staining will be helpful in differential diagnosis.

High Frequency of Bone Marrow Involvement in Intravascular Large B-Cell Lymphoma.

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. Thirteen cases of IVLBCL with a median age of 56 years were analyzed retrospectively. Nonspecific symptoms such as fever and hepatosplenomegaly were the most common manifestations, and the bone marrow was usually involved in 8/13 (61.5%) cases. All tumors expressed CD20, and 12/13 (92.3%) of the tumors exhibited a nongerminal center phenotype by Hans algorithm. CD5 was expressed in 3/12 (25%) of the tumors. MYC was negative in all cases, and BCL2 was positive in 10/12 (83.3%) cases. Cytogenetic analysis revealed 5 cases that did not have rearrangements in either the MYC or the BCL2 gene. No association with Epstein-Barr virus was found. Seven of 11 patients received chemotherapy. The median survival time was 6 months. Patients with hemophagocytic syndrome had poor prognoses. Our study demonstrates that IVLBCL has a poor clinical outcome with a high frequency of bone marrow involvement and that the MYC gene may not play an important role in the poor prognosis of IVLBCL.

Clinicopathologic Characterization of Aggressive Natural Killer Cell Leukemia Involving Different Tissue Sites.

Aggressive natural killer cell leukemia (ANKL) is a rare disease with an extremely aggressive clinical course. The etiology of ANKL is unclear with few genetic/epigenetic aberrations described to date. Moreover, misdiagnosis of ANKL is a frequent problem. Clinicopathologic characteristics of 35 retrospective cases of ANKL were investigated with the aim of improving diagnosis and to find the genetic/epigenetic aberrations associated with ANKL etiology. Because of the relatively low number of leukemic cells in the peripheral blood and bone marrow, diagnosis of ANKL can be missed; therefore, it is important to perform biopsy on solid tissues, if necessary. We describe the pathology of ANKL in the lymph nodes, bone marrow, spleen, liver, and skin, with focus on diagnosis and differentiated diagnosis. We observed young male predominance in our cohort, and the clinical course was more aggressive than reported previously. Low lactate dehydrogenase (<712 IU/L), chemotherapy or L-asparaginase administration were found to be associated with more favorable outcomes. SH2 domains of STAT5B and STAT3 also were screened for the presence of activating mutations. Moreover, CpG island methylation status of HACE1, a candidate tumor-suppressor gene, was determined in ANKL samples. We observed activating STAT5B mutations (1/5) and hypermethylation of HACE1 (3/4) in ANKL cases, suggesting that these aberrations may contribute to ANKL pathogenesis.

Clinicopathological study of pulmonary extranodal nature killer/T-cell lymphoma, nasal type and literature review.

OBJECTIVES: Malignant tumors of the lung are predominantly derived from epithelial tissue, such as squamous cell carcinoma and adenocarcinoma, while pulmonary lymphatic and hematopoietic tumor is relatively rare. Extranodal NK/T-cell lymphoma (ENKTL), nasal type, originates in nasal and extra-nasal sites anatomically. This distinct non-Hodgkin lymphoma is endemic and is characterized by a highly aggressive clinical course and dismal survival outcome. Extra-nasal ENKTL, especially pulmonary ENKTL, is rare compared with nasal type ENKTL and has received relatively little attention. Therefore, this study was conducted to assess the clinicopathological features of pulmonary ENKTL and to promote awareness of this malignancy. MATERIALS AND METHODS: All cases of ENKTL, nasal type diagnosed from January 2008 to June 2014 in our institution were collected, and those with pulmonary involvement were selected for further study. The eligible cases were analyzed retrospectively: medical recordings, imaging manifestations, pathological features, immunophenotypes, EBER1/2 hybridizations in situ and other related literatures were reviewed. RESULTS AND CONCLUSIONS: A total of 1105 cases were diagnosed as ENKTL, nasal type, in this period, and 8 cases (7.2‰) had lung involvement. Seven cases had core biopsy, and for 1 case, a resected tissue specimen was available. The group was composed of 6 men and 2 women (gender ratio 3:1) with ages ranging from 19 to 44 (average age of 33.5) years. In this group, 2 cases were secondary and 5 cases were primary. The clinical symptoms and computed tomography (CT) manifestations were nonspecific. Histologically, the neoplasms presented angiocentric and angiodestructive growth patterns with different degrees of inflammatory response and necrosis. The neoplastic cell sizes were heterogeneous with spectra of small to large or mixed-composition types. For the immunophenotypes, all cases were positive for CD3ɛ and cytotoxic granule (granzyme B or TIA-1). The positive ratios of CD56 and CD30 were 6/8 and 4/5 respectively. All 8 cases showed positive in situ hybridization for Epstein-Barr virus-encoded small RNA (EBER). TCR-γ gene rearrangement was tested in 4 cases, and only 1 of these cases was monoclonal. Laboratory testing demonstrated that the whole blood was decreased while the average level of LDH was elevated. Six bone marrow biopsy specimens were negative and showed no neoplastic cells infiltration. For treatment, 4 individuals accepted chemotherapy and 1 patient underwent localized tumor resection surgery. The follow-up information was available for 6 patients, 1 of whom was alive and the other 5 cases survived shortly between 20 days and 4 months. ENKTL, nasal type of lung is very rare, and the diagnosis is challenging due to nonspecific clinical symptoms and imaging results. The diagnosis of pulmonary ENKTL should be based on comprehensive clinical, imaging, histopathological and molecular examination. More effective treatment strategies are required for this disease.