Extranodal NK/T-cell lymphoma (ENKTL), nasal type, may be of NK or T-cell origin; however, the proportion of T-ENKTLs and whether they are of αβ or γδ type remains uncertain. To elucidate the cell of origin and detailed phenotype of ENKTL and assess any clinicopathologic associations, 67 cases of ENKTL from Thailand were investigated, together with 5 γδ enteropathy-associated T-cell lymphomas (EATLs) for comparison. In all, 70% of the ENKTL were T-cell receptor (TCR) β,γ and, in cases tested, δ negative (presumptive NK origin); 5% were TCR γδ, 3% were TCR αβ, 1% were TCR αβ/γδ, and 21% were indeterminate. Out of 17 presumptive NK-ENKTLs tested, 3 had clonal TCR rearrangements. All cases were EBV and TIA-1; >85% were positive for CD3, CD2, granzyme B, pSTAT3, and Lsk/MATK; and all were CD16. Presumptive NK-ENKTLs had significantly more frequent CD56 (83% vs. 33%) and CXCL13 (59% vs. 0%) but less frequent PD-1 (0% vs. 40%) compared with T-ENKTLs. Of the NK-ENKTLs, 38% were Oct-2 compared with 0% of T-ENKTLs, and 54% were IRF4/MUM1 compared with 20% of T-ENKTLs. Only αβ T-ENKTLs were CD5. Intestinal ENKTLs were EBV and had significantly more frequent CD30, pSTAT3, and IRF4/MUM1 expression but less frequent CD16 compared with γδ EATL. Significant adverse prognostic indicators included a primary non-upper aerodigestive tract site, high stage, bone marrow involvement, International Prognostic Index ≥2, lack of radiotherapy, Ki67 >40%, and CD25 expression. The upper aerodigestive tract ENKTLs of T-cell origin compared with those of presumptive NK origin showed a trend for better survival. Thus, at least 11% of evaluable ENKTLs are of T-cell origin. Although T-ENKTLs have phenotypic and some possible clinical differences, they share many similarities with ENKTLs that lack TCR expression and are distinct from intestinal γδ EATL.
BackgroundExtranodal NK/T-cell lymphoma, nasal type (ENKTL) is not common worldwide, but it is the most common T- and NK-cell lymphomas in many Asian countries. Immunophenotypic profiles were studied based on limited series. The authors, therefore, studied on ENKTL according to characterize immunophenotypic profiles as well as the distribution of EBV subtype and LMP-1 gene deletion.MethodsBy using tissue microarray (TMA), immunohistochemical study and EBV encoded RNA (EBER) in situ hybridization were performed. T-cell receptor (TCR) gene rearrangement, EBV subtyping, and LMP-1 gene deletion were studied on the available cases.ResultsThere were 22 cases eligible for TMA. ENKTL were positive for CD3 (91%), CD5 (9%), CD7 (32%), CD4 (14%), CD56 (82%), TIA-1 (100%), granzyme B (95%), perforin (86%), CD45 (83%), CD30 (75%), Oct2 (25%), and IRF4/MUM1 (33%). None of them was positive for βF1, CD8, or CD57. TCR gene rearrangement was negative in all 18 tested cases. EBV was subtype A in all 15 tested cases, with 87% deleted LMP-1 gene. Cases lacking perforin expression demonstrated a significantly poorer survival outcome (p = 0.008).ConclusionsThe present study demonstrated TIA-1 and EBER as the two most sensitive markers. There were a few CD3 and/or CD56 negative cases noted. Interestingly, losses of CD45 and/or CD7 were not uncommon while Oct2 and IRF4/MUM1 could be positive in a subset of cases. Based on the present study in conjunction with the literature review, determination of PCR-based TCR gene rearrangement analysis might not be a useful technique for making diagnosis of ENKTL.
These findings indicate that ANs either do not express or express very low levels of the analysed proangiogenic growth factors. We conclude that tumour angiogenesis is not likely to be a relevant mechanism of AN growth and might therefore not be a suitable anticancer therapy target.
Patients with tumors larger than 18 mm in diameter and who are younger than 50 years of age sustain an enhanced risk for fast-growing tumors because of these lesions' enhanced proliferative activity. For these patients the authors recommend active therapy.
Objective/Hypothesis: Paragangliomas are heavily vascularized tumors, and the expression of VEGF (vascular endothelial growth factor) has been reported. The aim of our study was to extend the available database of VEGF expression in paraganglioma, to add correlated data concerning vessel density and proliferative activity, and to draw conclusions concerning the mechanisms resulting in tumor vascularization and growth. Study Design: Semiquantitative histopathologic examination of paraganglioma specimens obtained from surgical cases. Methods: Paraffin-embedded paragangliomas were analyzed by immunohistochemistry. Fourteen consecutive samples were hybridized with VEGF-, CD31- and Ki67-specific antibodies, and visualized by diaminobenzidine staining. Vessel density was determined by counting CD31-positive vessels and proliferation by quantification of Ki67-positive cells. Results: Ten out of 14 samples were positive for VEGF. In this group, vessel density was up to 5 times as high and proliferative activity was about twice as high as in the VEGF-negative group. Conclusions: We observed higher CD31 and Ki67 counts in VEGF-positive tumors, but statistical significance could not be assessed due to low sample numbers. These data might suggest a contribution of VEGF secreted by paragangliomas to tumor vascularization and possibly proliferation. The clinical impact of VEGF expression analysis has to be proven in future studies.
Inflammation of the nose and paranasal sinus or rhinosinusitis (RS) is a significant global health problem that is both very common and very costly to treat. Previous reports reveal variability in histology and mechanism of inflammation in patients with chronic rhinosinusitis with and without polyp (CRScNP and CRSsNP, respectively). There are various methods and hypothesis that try to explain this variability. Accordingly, the aim of this study was to investigate the incidence of each type of sinonasal inflammation among patients diagnosed with CRScNP or CRSsNP using transcription factor analysis (TFA). This study included mucosa specimens from nose/paranasal sinuses from patients with chronic rhinitis (CR), CRSsNP, or CRScNP that were obtained at the Department of Otorhinolaryngology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during the June 2009 to May 2012 study period. TFA was employed to measure the following transcription factors: T-box transcription factor (T-bet) for Th1, GATA binding protein 3 (GATA-3) for Th2, retinoic acid-related orphan receptor C (RORC) for Th17, and forkhead box P3 (FOXP3) for Treg. Forty-one subjects (22 males, 19 females) were enrolled, with a mean age of 45.93 ± 13 years. Twenty-six patients were diagnosed with CRScNP, 7 with CRSsNP, and 8 with CR (controls). The majority of CRScNP specimens (76.9%) had eosinophil count greater than 100 cells/high-power field (HPF). Mean eosinophil count was 930.08 ± 1,399 cells/HPF (range: 17–5,570). Th2 transcription factor (GATA-3) was statistically significantly higher in the CRScNP group than in the CRS and control groups (p < 0.001); whereas, Treg transcription factor (FOXP3) was statistically significantly lower in the CRScNP group than in the CRSsNP and control groups (p < 0.001). The transcription factors for Th1 and Th17 (T-bet and RORC, respectively) were not significantly different among the three groups. The result of transcription factor analysis revealed hyperfunction of Th2 in patients with CRScNP, which might result in hypereosinophilic infliltration in the polyps. One explanation for this finding is the decreased activity of Treg. Although environment-host interaction is the most probable hypothesis, the etiology of aberrant adaptive immunity needs to be elucidated.
Background: Thailand’s fourth and fifth waves of coronavirus disease 19 (COVID-19) started in July and December 2021, respectively, and greatly overloaded the nation’s public health system. The massive imbalance between health resources and patient demand for services was one of the most significant challenges hampering the country’s response to the catastrophic COVID-19 pandemic. Hospital-based facilities were overwhelmed with an exponential rise in new patient numbers, with a rapidly growing backlog of patients with delayed care or even acceptance within the healthcare system. In response, “outpatient self-isolation” (SI), “home-based isolation” (HI), and “community-based isolation” (CI) strategies were adopted to stabilize COVID-19 cases with mild to moderate symptoms. We present the lessons learned from the system management of HI by drawing on the experiences gained at a university hospital that provided patient-to-professional remote support during the pandemic. The vast majority of patients were assigned to HI immediately after being diagnosed with COVID-19. This system enabled remote consultation, needed medications, and survival-kit supplies to be initiated and delivered to patients’ homes. Conclusion: Our investigation indicates that the HI teleconsultation system was a productive approach to COVID-19 management. It allowed a prompt response to patients’ needs and provided timely access to medical support, especially for patients with mild to moderate symptoms.
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