Conventional diagnostic ultrasound images of the anatomy (as opposed to blood flow) reveal differences in the acoustic properties of soft tissues (mainly echogenicity but also, to some extent, ...attenuation), whereas ultrasound-based elasticity images are able to reveal the differences in the elastic properties of soft tissues (e.g., elasticity and viscosity). The benefit of elasticity imaging lies in the fact that many soft tissues can share similar ultrasonic echogenicities but may have different mechanical properties that can be used to clearly visualize normal anatomy and delineate pathologic lesions. Typically, all elasticity measurement and imaging methods introduce a mechanical excitation and monitor the resulting tissue response. Some of the most widely available commercial elasticity imaging methods are ‘quasi-static’ and use external tissue compression to generate images of the resulting tissue strain (or deformation). In addition, many manufacturers now provide shear wave imaging and measurement methods, which deliver stiffness images based upon the shear wave propagation speed. The goal of this review is to describe the fundamental physics and the associated terminology underlying these technologies. We have included a questions and answers section, an extensive appendix, and a glossary of terms in this manuscript. We have also endeavored to ensure that the terminology and descriptions, although not identical, are broadly compatible across the WFUMB and EFSUMB sets of guidelines on elastography (Bamber et al. 2013; Cosgrove et al. 2013).
The breast section of these Guidelines and Recommendations for Elastography produced under the auspices of the World Federation of Ultrasound in Medicine and Biology (WFUMB) assesses the clinically ...used applications of all forms of elastography used in breast imaging. The literature on various breast elastography techniques is reviewed, and recommendations are made on evidence-based results. Practical advice is given on how to perform and interpret breast elastography for optimal results, with emphasis placed on avoiding pitfalls. Artifacts are reviewed, and the clinical utility of some artifacts is discussed. Both strain and shear wave techniques have been shown to be highly accurate in characterizing breast lesions as benign or malignant. The relationship between the various techniques is discussed, and recommended interpretation based on a BI-RADS-like malignancy probability scale is provided. This document is intended to be used as a reference and to guide clinical users in a practical way.
The interaction between CD47 and signal‐regulatory protein‐α (SIRPα) inhibits phagocytosis, thus affecting the clinical outcomes of neoplastic diseases. Although CD47 upregulation is associated with ...poor prognosis in several malignancies, the effect of SIRPα expression and its coexpression with CD47 remains unclear. This study aimed to investigate the clinicopathologic effect of CD47 and SIRPα expression in diffuse large B‐cell lymphoma (DLBCL). Immunostaining of 120 biopsy samples showed that CD47 is primarily expressed in tumor cells, whereas SIRPα is expressed in nonneoplastic stromal cells, mostly macrophages. CD47high cases showed higher MYC protein expression and lower MYC translocation. The SIRPαhigh cases presented significantly shorter overall survival (OS) and progression‐free survival (PFS) than SIRPαlow cases in the activated B‐cell (ABC) subtype of DLBCL (P = .04 and P = .02, respectively). Both CD47high and SIRPαhigh presented significantly shorter OS and PFS than other cases among all DLBCL patients (P = .01 and P = .004, respectively), and the ABC type (P = .04 and P = .008, respectively) but not the germinal center B‐cell type. Both CD47high and SIRPαhigh yielded a constant independent prognostic value for OS and PFS in multivariate analysis (hazard ratio HR, 2.93; 95% confidence interval CI, 1.20‐7.43; P = .02; and HR, 2.87; 95% CI, 1.42‐5.85; P = .003, respectively). To the best of our knowledge, this is the first study to report that combinatorial CD47 and SIRPα expression is a potential independent prognostic factor for DLBCL. Evaluation of CD47 and SIRPα expression could be useful before CD47 blockade therapy.
This study investigated the clinicopathologic effect of CD47 and signal‐regulatory protein‐α (SIRPα) in diffuse large B‐cell lymphoma by immunohistochemical staining. CD47 and SIRPα coexpression is associated with a poor prognosis in the activated B‐cell type, but not in the germinal center B‐cell type.
Tumor location and immunity play important roles in the progression of colorectal cancer (CRC). This study aimed to investigate the differences in the immunosurveillance pattern between right‐ and ...left‐sided CRC and analyze their association with clinicopathologic features, including mismatch repair (MMR) status. We included surgically resected stage II/III CRC cases and evaluated the immunohistochemical findings of HLA class I, HLA class II, programmed cell death‐ligand 1 (PD‐L1), PD‐1, CTLA‐4, CD3, CD4, CD8, TIA‐1, T‐bet, GATA3, RORγT, Foxp3, and CD163. A total of 117 patients were included in the analyses; of these, 30 and 87 had right‐ and left‐sided cancer, respectively. Tumor immunity varied according to the tumor location in the overall cohort. Analysis of the tumors excluding those with DNA mismatch repair (MMR) deficiency also revealed that tumor immunity differed according to the tumor location. In right‐sided colon cancer (CC), high expression of Foxp3 (P = .0055) and TIA‐1 (P = .0396) were associated with significantly better disease‐free survival (DFS). High CD8 (P = .0808) and CD3 (P = .0863) expression tended to have better DFS. Furthermore, in left‐sided CRC, only high PD‐L1 expression in the stroma (P = .0426) was associated with better DFS. In multivariate analysis, high Foxp3 expression in right‐sided CC was an independent prognostic factor for DFS (hazard ratio, 7.6445; 95% confidence interval, 1.2091‐150.35; P = .0284). In conclusion, the immunosurveillance pattern differs between right‐ and left‐sided CRC, even after adjusting for MMR deficiency.
Comparison of Kaplan‐Meier curves of disease‐free survival (DFS) in each tumor location excluding DNA mismatch repair deficiency. In right‐sided colon cancer, high Foxp3 (P = .0055) and TIA‐1 expression (P = .0396) were associated with significantly better DFS. High CD8 (P = .0808) and CD3 (0.0863) expression showed a tendency towards better DFS. In left‐sided colorectal cancer, only high sPD‐L1 expression (P = .0426) was associated with better DFS.
Gefitinib (Iressa) and erlotinib (Tarceva), which target the epidermal growth factor receptor (EGFR), are approved for treatment of patients with advanced non-small cell lung cancer (NSCLC). Patients ...whose tumors harbor mutations in the EGFR gene, including delE746-A750 in exon 19 and L858R in exon 21, may benefit in particular from gefitinib treatment. However, acquired resistance to gefitinib has been a serious clinical problem, and further optimization is needed for application of EGFR-targeted drugs in lung cancer patients. In this study, we established gefitinib-resistant NSCLC cells from PC-9 cell line, which harbors the delE746-A750 mutation, by exposing the cell line to gefitinib for over 7 months. Gefitinib-resistant PC-9/GEFs cell lines showed a marked downregulation of PTEN expression and increased Akt phosphorylation. In revertant, gefitinib-sensitive clones (PC-9/Rev) derived from PC-9/GEF1-1 and PC-9/GEF2-1, PTEN expression, as well as sensitivity to gefitinib and erlotinib, was restored. Knockdown of PTEN expression using small interfering RNA specific for PTEN in PC-9 cells resulted in drug resistance to gefitinib and erlotinib. Nuclear translocation of the EGR1 transcription factor, which regulates PTEN expression, was shown to be suppressed in resistant clones and restored in their revertant clones. Reduced PTEN expression was also seen in tumor samples from a patient with gefitinib-refractory NSCLC. This study thus strongly suggests that loss of PTEN expression contributes to gefitinib and erlotinib resistance in NSCLC. Our findings reinforce the therapeutic importance of PTEN expression in the treatment of NSCLC with EGFR-targeted drugs.
A 30-year-old woman was diagnosed with T-lymphoblastic lymphoma (T-LBL) that harbored a clonal Epstein-Barr virus (EBV) genome. At relapse, axillary lymph node adenopathy, which was diagnosed as ...peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), was detected. Southern blot analyses of the T-cell receptor and EBV genome revealed that the T-LBL and PTCL-NOS were clonally identical. We previously showed that CD21 acted as an entry molecule that allowed EBV into the patient's T-LBL cells. Interestingly, the PTCL-NOS cells lacked CD21 expression. Our case suggests that EBV might infect immature CD21-positive T-cells, and CD21-negative PTCL-NOS might subsequently arise through phenotypic changes.
This is the first case of follicular T‐cell lymphoma (FTCL) presenting as methotrexate‐associated lymphoproliferative disorders (MTX‐LPDs). A 69‐year‐old man treated rheumatoid arthritis with ...methotrexate presented with cervical swelling, hoarseness and fever. Imaging studies revealed multiple lymphadenopathy and lymphoma was suspected. Lymph node biopsy was performed to confirm the diagnosis. Pathologically, the lymph node was composed of atypical lymphocytes with a follicular growth pattern and area of necrosis. Immunohistochemical examination showed the atypical lymphocytes were positive for CD3, CD4, programmed cell death protein 1, and inducible T‐cell co‐stimulator. These findings are consistent with FTCL. During hospitalization, the patient's fever subsided and cervical lymphadenopathy improved, probably due to discontinuation of MTX. Here we presented the first case of FTCL presenting as MTX‐LPDs. The T‐cell phenotype MTX‐LPDs are relatively rare and accounts for only 3.4%–6.3% of all MTX‐LPD cases. Therefore, detailed clinicopathological features have not been clarified sufficiently. It is hoped that similar cases should be accumulated and studied to better understand the clinical and pathological features of this condition.
Aims
T‐follicular helper (TFH) cells are effector T‐cells that are crucial for B‐cell selection and differentiation. T‐cell lymphomas derived from TFH cells have distinct characteristics. ...Additionally, in the World Health Organization (WHO) classification 5th edition, three lymphomas were introduced as independent disease entities with TFH cell origin. We aimed to investigate the clinicopathological features of adult T‐cell leukemia/lymphoma (ATLL) with a TFH phenotype (TFHP).
Methods and Results
We performed TFH immunohistochemistry analysis of five biomarkers for the biopsy specimen, with TFHP being indicated by a positive result for more than two markers. Among 75 cases of ATLL, 37.3% of them showed TFHP. Compared with cases of ATLL without TFHP, cases of ATLL with TFHP showed higher C‐reactive protein levels (p = 0.0219) and increased high endothelial venule proliferation (p = 0.024). However, there were no significant between‐group differences in overall survival as well as other clinical and morphological findings. Furthermore, there was no significant between‐group difference in TFH markers and FOXP3 expression.
Conclusion
Some patients with ATLL may present a TFHP, which should not preclude the diagnosis of ATLL. Although presenting a TFHP does not affect prognosis, it is important to identify cases of ATLL with a TFHP since it may inform future treatment strategies.
Adult T‐cell leukemia/lymphoma (ATLL) may present with T‐follicular helper (TFH) markers, and ATLL with TFH phenotype present high endothelial venule proliferation and higher C‐reactive protein levels than non‐TFH phenotype but does not affect the prognosis. It may be important to stratify treatment interventions for ATLL according to the presentation of THFP.
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