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1.
Cytopathology ; 31(2): 106-114, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31943445

RESUMO

OBJECTIVE: We assessed whether intraoperative squash cytology could provide surgeons with a qualitative diagnosis of brain lesions when frozen section diagnosis is equivocal. METHODS: The study included 51 lesions that were diagnosed intraoperatively as equivocal brain tumour on the basis of frozen section. We retrospectively classified the lesions into five groups according to the final histopathological diagnoses (I: malignant lymphomas; II: diffuse astrocytic and oligodendroglia tumours; III: pituitary adenomas, IV: metastatic carcinomas; V: others). We assessed the squash cytology features of Groups I-IV and of the specific lesion types, and compared features among the groups. RESULTS: The four groups differed in a range of salient cytomorphological features: lymphoglandular bodies in Group I (eight of nine cases), cytoplasmic fibrillary processes in Group II (six of eight cases), low-grade nuclear atypia in Group III (seven of seven cases), and large nuclei (approximately 80 µm2 ) and nuclear crush artefacts in Group IV (seven of nine cases). CONCLUSION: Findings of lymphoglandular bodies on intraoperative squash cytology can be considered characteristic of malignant lymphomas, while cytoplasmic fibrillary processes indicate diffuse astrocytic and oligodendroglial tumours. We conclude that squash cytology could yield a qualitative intraoperative diagnosis in over 25% of cases for which frozen section yields a diagnosis of equivocal brain tumour.

2.
Esophagus ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980976

RESUMO

BACKGROUND: Vasohibins (VASH), which are angiogenesis regulators, consist of Vasohibin-1 (VASH1) and Vasohibin-2 (VASH2). VASH1 is an angiogenesis inhibitor, while VASH2 is a proangiogenic factor. Patients with esophageal squamous cell carcinoma (ESCC) with high tumor expression levels of VASH1 and VASH2 have been reported to show a poor prognosis. The clinical significance of VASH concentrations in the blood of patients with ESCC has not yet been investigated. METHODS: Plasma samples from 89 patients with ESCC were analyzed, and the relationships between the plasma VASH concentrations and the clinicopathological factors of the patients were evaluated. Immunohistochemical examination (IHC) of the resected tumor specimens for VASH was performed in 56 patients, and the correlation between the plasma VASH concentrations and tumor expression levels of VASH was analyzed. RESULTS: The patient group with high plasma concentrations of VASH1 showed a higher frequency of lymph node metastasis (P = 0.01) and an invasive growth pattern (P = 0.05). Furthermore, poorly differentiated cancer occurred at a higher frequency in the patient group with high plasma concentrations of VASH2 (P < 0.01). High tumor expression levels of VASH1 were encountered more frequently in the patient group with high plasma concentrations of VASH1 (P = 0.03), and high tumor expression levels of VASH2 were encountered more frequently in the patient group with high plasma concentrations of VASH2 (P = 0.04). CONCLUSIONS: In patients with ESCC, high plasma concentrations were associated with poor clinical outcomes for both VASH1 and VASH2. We propose that results indicate that plasma VASH1 and VASH2 are useful biomarkers in patients with ESCC.

3.
Pathol Int ; 70(1): 31-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31823459

RESUMO

To address the diagnostic performance of scratch-imprint cytology (SIC), in this study we compared intraoperative diagnoses of pulmonary lesions between SIC and frozen section histology (FSH) for accuracy with respect to the final pathological diagnosis. We histologically divided 206 pulmonary lesions (resected surgically) into two groups (benign and malignant) and compared each intraoperative diagnosis by SIC and FSH with the final pathological diagnoses. We also examined the radiological existence of pure ground-glass opacity (GGO) nodules in each group. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 91.5%, 100%, 100%, 63.6%, and 92.6%, respectively for SIC, and 98.2%, 100%, 100%, 92.1% and 98.5%, respectively, for FSH. Thus, we concluded that diagnosis by SIC is reliable for malignancy, but not for benign lesions. All pure GGO nodules (19; 9.2%) were noninfectious and malignant with a high accuracy of FSH diagnosis (100%), in comparison with those of low accuracy with a SIC diagnosis (57.9%). SIC can be an appropriate intraoperative diagnostic tool where multiple cytotechnologists observe intraoperative SIC preparations scratched evenly across the whole lesion including the peripheral area of the mass.

4.
Pathol Int ; 70(2): 84-91, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31855317

RESUMO

Pancreatic neuroendocrine tumors (PanNETs) are rare, and prediction of aggressive characteristics, such as recurrence and metastasis and prognosis of PanNETs remain difficult. Nectins are cell adhesion molecules that regulate the formation of adherens and tight junctions. In this study, we investigated the clinicopathological significance of nectin-3 expression in patients with PanNETs. Immunohistochemical analysis of nectin-3 expression was performed on 78 cases of PanNET. Low nectin-3 expression in the membrane (positive ratio ≤25%) was observed in 62 cases (79.5%) and was significantly correlated with larger tumor size (>20 mm; P = 0.003), G2/G3 tumors (P = 0.025), higher Ki67 labeling index (≥3%; P = 0.009), lymphatic involvement (P = 0.047), advanced pT-factor (T2-T4; P = 0.003), lymph node metastasis (P = 0.006), advanced Union for International Cancer Control/American Joint Committee on Cancer-stage (Stage II-IV; P = 0.001), advanced ENETS stage (Stage IIa-IV; P = 0.001), nonfunctioning tumors (P = 0.002), and a shorter disease-free survival (P = 0.019). However, there was no significant correlation between nectin-3 expression in the membrane and/or cytoplasm and the clinicopathological parameters. The present results suggest that decreased nectin-3 expression in the membrane is associated with increased tumor aggressiveness of PanNETs. Clinically, immunohistochemical analysis of nectin-3 may help predict tumor aggressiveness for PanNETs.

5.
Genes (Basel) ; 10(12)2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31810328

RESUMO

Renal cell carcinoma (RCC) is associated with various genetic alterations. Although whole-genome/exome sequencing analysis has revealed that nuclear genome alterations are associated with clinical outcomes, the association between nucleotide alterations in the mitochondrial genome and RCC clinical outcomes remains unclear. In this study, we analyzed somatic mutations in the mitochondrial D-loop region, using RCC samples from 61 consecutive patients with localized RCC. Moreover, we analyzed the relationship between D-loop mutations and NADH dehydrogenase subunit 1 (MT-ND1) mutations, which we previously found to be associated with clinical outcomes in localized RCC. Among the 61 localized RCCs, 34 patients (55.7%) had at least one mitochondrial D-loop mutation. The number of D-loop mutations was associated with larger tumor diameter (> 32 mm) and higher nuclear grade (≥ ISUP grade 3). Moreover, patients with D-loop mutations showed no differences in cancer-specific survival when compared with patients without D-loop mutations. However, the co-occurrence of D-loop and MT-ND1 mutations improved the predictive accuracy of cancer-related deaths among our cohort, increasing the concordance index (C-index) from 0.757 to 0.810. Thus, we found that D-loop mutations are associated with adverse pathological features in localized RCC and may improve predictive accuracy for cancer-specific deaths when combined with MT-ND1 mutations.

6.
Sci Rep ; 9(1): 19369, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852956

RESUMO

Gangliosides, a group of glycosphingolipids, are known to be cell surface markers and functional factors in several cancers. However, the association between gangliosides and pancreatic ductal adenocarcinoma (PDAC) has not been well elucidated. In this study, we examined the expression and roles of ganglioside GM2 in PDAC. GM2+ cells showed a higher growth rate than GM2- cells in the adherent condition. When GM2- and GM2+ cells were cultured three-dimensionally, almost all cells in the spheres expressed GM2, including cancer stem cell (CSC)-like cells. A glycolipid synthesis inhibitor reduced GM2 expression and TGF-ß1 signaling in these CSC-like cells, presumably by inhibiting the interaction between GM2 and TGFß RII and suppressing invasion. Furthermore, suppression of GM2 expression by MAPK inhibition also reduced TGF-ß1 signaling and suppressed invasion. GM2+ cells formed larger subcutaneous tumors at a high incidence in nude mice than did GM2- cells. In PDAC cases, GM2 expression was significantly associated with younger age, larger tumor size, advanced stage and higher histological grade. These findings suggest that GM2 could be used as a novel diagnostic and therapeutic target for PDAC.

8.
Respir Res ; 20(1): 263, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752884

RESUMO

BACKGROUND: Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years. METHODS: From our hospital database, 1,699 patients, registered as lung cancer between 1st Mar 2004 and 30th Apr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13th Feb 2017. RESULTS: There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response. CONCLUSIONS: Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV. This study was retrospectively registered on 16th Jun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).

9.
J Thorac Dis ; 11(9): 3776-3784, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31656650

RESUMO

Background: Esophageal cancer is one of the most malignant gastroenterological cancers. To improve the treatment outcomes of patients with esophageal squamous cell carcinoma (ESCC), a biomarker capable of predicting the malignant potential of the cancer cells is needed. The aim of the present study was to investigate the relationship between the expression pattern of insulin-like growth factor II m-RNA-binding protein 3 (IMP3), a promising cancer testis antigen for peptide vaccine therapy, in ESCC tumors and the outcomes of patients with ESCC. Methods: One hundred and seventy patients with ESCC who underwent a radical transthoracic esophagectomy between 2003 and 2005 at Tokai University Hospital were investigated. IMP3 expression was immunohistochemically analyzed using sections from surgically resected tumor specimens and metastatic lymph nodes. Results: Of the 170 patients, 160 patients (94%) exhibited IMP3 positivity in the cytoplasm of their cancer cells (IMP3-positive group), while 10 patients (6%) were IMP3-negative (IMP3-negative group). No significant difference in the overall survival curves were observed between the IMP3-positive and IMP3-negative groups. When the survival analysis was confined to the 160 IMP3-positive patients, however, an invasive front-type IMP3 expression pattern (IF-type) was seen in 46 patients (29%) and a diffuse-type pattern (D-type) was seen in 114 patients (71%). A multivariate analysis also showed that an IF-type was a prognostic factor (HR =1.618, P=0.049). The overall survival curve for patients with an IF-type was significantly worse than that of D-type patients (P=0.001). Conclusions: An IF-type pattern of IMP3 expression might predict a poor outcome in patients with ESCC.

10.
Nat Metab ; 1(8): 775-789, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31579886

RESUMO

The humoral immune response demands that B cells undergo a sudden anabolic shift and high cellular nutrient levels which are required to sustain the subsequent proliferative burst. Follicular lymphoma (FL) originates from B cells that have participated in the humoral response, and 15% of FL samples harbor point, activating mutations in RRAGC, an essential activator of mTORC1 downstream of the sensing of cellular nutrients. The impact of recurrent RRAGC mutations in B cell function and lymphoma is unexplored. RRAGC mutations, targeted to the endogenous locus in mice, confer a partial insensitivity to nutrient deprivation, but strongly exacerbate B cell responses and accelerate lymphomagenesis, while creating a selective vulnerability to pharmacological inhibition of mTORC1. This moderate increase in nutrient signaling synergizes with paracrine cues from the supportive T cell microenvironment that activates B cells via the PI3K-Akt-mTORC1 axis. Hence, Rragc mutations sustain induced germinal centers and murine and human FL in the presence of decreased T cell help. Our results support a model in which activating mutations in the nutrient signaling pathway foster lymphomagenesis by corrupting a nutrient-dependent control over paracrine signals from the T cell microenvironment.

11.
Clin Transl Immunology ; 8(8): e1074, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417675

RESUMO

Objectives: Infiltration of macrophages through the tyrosine kinase receptor CSF1R is a poor prognosis factor in various solid tumors. Indeed, these tumors produce CSF1R ligand, macrophage colony-stimulating factor (M-CSF) or interleukin-34 (IL-34). However, the significance of these cytokines, particularly, the newly discovered IL-34 in haematological malignancies, is not fully understood. We therefore analysed the role of IL-34 in diffuse large B-cell lymphoma (DLBCL), the most common subtype of malignant lymphoma. Methods: We analysed formalin-fixed paraffin-embedded lymphoma tissues of 135 DLBCL patients for the expression of IL-34 and the number of macrophages, and the survival of these patients. The expression of IL-34 in DLBCL cell lines and the activity of IL-34 to induce the migration of monocytic cells were also characterised. Results: Several lymphoma tissues showed a clear IL-34 signal, and such signal was detectable in 36% of patients. DLBCL cell lines also expressed IL-34. Interestingly, the percentage of IL-34+ patients in the activated B-cell subtype was significantly higher than that in the germinal centre B-cell subtype. More interestingly, IL-34+ patients showed shorter survival periods and higher number of macrophages in lymphoma tissues. The recruitment of monocytes is likely the first step for the higher macrophage density in the IL-34+ lymphoma tissues. Indeed, IL-34 induced the migration of monocytic cells. Conclusion: Our results raise the possibility that IL-34 in lymphoma tissues of DLBCL patients recruits monocytes, leading to the higher number of macrophages in the tissues and poor prognosis of patients. IL-34 may be an additional therapeutic target of DLBCL.

13.
Ann Vasc Dis ; 12(2): 256-259, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31275488

RESUMO

The diagnosis of pulmonary artery sarcoma (PAS) is challenging, and its definitive diagnosis is mainly confirmed using specimens obtained during surgery or autopsy. Endovascular catheter biopsy was performed in five patients with suspected PAS to establish a definitive diagnosis. Aspiration biopsy was performed in all patients, and forceps biopsy was performed in one patient. Three patients were diagnosed with PAS, and no definitive diagnosis was obtained in two patients with squamous cell lung carcinoma with pulmonary artery infiltration. Endovascular catheter biopsy is helpful in the diagnosis of PAS and should be performed when a tumor is suspected.

14.
Br J Ophthalmol ; 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31201167

RESUMO

AIMS: To investigate morphological changes in type VI collagen in the human trabecular meshwork associated with the rho kinase inhibitor ripasudil. METHODS: This cross-sectional study evaluated the effects of ripasudil eye drop administration (RA) or no ripasudil eye drop administration (NRA) in patients with primary open-angle glaucoma (POAG; age range 60-80 years) who underwent conventional outflow reconstruction between December 2015 and September 2016 at Tokai University Hachioji Hospital. The juxtacanalicular tissue was removed and imaged using transmission electron microscopy. Type VI collagen comprises cross-banded aggregates with transverse bands 30 nm apart repeating every 105 nm. The transverse bands are called the outer rod-like region (ORR) and the intervals are called the inner rod-like region (IRR). The waveform intensity in the type VI collagen was analysed in electron micrographs using Fourier transformation to detect the IRR and ORR borders. RESULTS: Ten eyes of 10 patients were included (n=5/group). The baseline characteristics did not differ significantly between groups. ORR width was significantly smaller in the RA group (37.85±3.43 nm) than in the NRA group (50.62±5.23 nm, p<0.05), whereas IRR width was significantly greater in the RA group (70.68±10.84 nm) than in the NRA group (58.19±5.34 nm, p<0.05). Morphological changes in the type VI collagen total width tended to correlate with the duration of ripasudil administration (r=0.9, p=0.08). CONCLUSIONS: Ripasudil administration in patients with POAG induced morphological changes in type VI collagen. Patients with POAG administered RA had a significantly smaller ORR width and a significantly greater IRR width than patients with POAG not administered RA.

15.
Urol Oncol ; 37(10): 711-720, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31174957

RESUMO

BACKGROUND AND OBJECTIVE: We assessed the aggressiveness of localized renal cell carcinoma (N0M0 RCC) with rhabdoid differentiation (RD) after partial or radical nephrectomy. METHODS: A total of 604 patients with N0M0 RCC who had undergone partial or radical nephrectomy at a single institution were included in this study. Clinicopathological and outcome data on recurrence-free survival (RFS), cancer-specific survival (CSS), and time to recurrence (TTR) were analyzed using Kaplan-Meier methods, log-rank test, univariate and multivariable Cox proportional hazard models, and concordance index. We also evaluated the RFS and CSS in a propensity score-matched cohort to reduce inherent differences. Among the 604 patients, RD was identified in RCC specimens from 24 patients. RESULTS: At the median postoperative follow-up period of 53 months, 58 patients (12 with RD) showed recurrence and 26 patients (7 with RD) had died from RCC. Multivariate analyses showed that RD was an independent risk factor of RFS (hazard ratio 2.81; P = 0.0266) and CSS (hazard ratio 5.18; P = 0.00182). By RD adding to standard risk factors, the concordance indices for RFS and CSS increased 0.77 to 0.79, and 0.76 to 0.79, respectively. Subgroup analysis showed that the presence of RD in RCC specimens was more important for predicting poor RFS and CSS in the early pathological tumor category (≤pT2) subgroup compared to in the advanced tumor category (≥pT3) subgroup. Patients with RD showed a significantly shorter TTR than patients with RCC without RD (7.5 vs. 18 months: P = 0.0150). The propensity score-matched cohort included 24 patients with RD and 24 without RD, of which patients RD showed significantly shorter RFS than those without RD (P = 0.0026). CONCLUSIONS: In summary, the aggressiveness of N0M0 RCC with RD increased the risk of postoperative recurrence, particularly in the early pathological stage. The short TTR also demonstrated the aggressiveness of RCC with RD.

16.
Ann Diagn Pathol ; 41: 51-56, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132652

RESUMO

Splenic epidermoid cyst (SEC) is a rare condition. We aimed to evaluate the immunohistochemical profiles of the epithelial lining of SECs. A total of 7 SEC cases were analyzed: 2 cases involved a monolayered epithelial lining and 5 cases involved a multilayered epithelial lining. Among the multilayered SECs, the superficial/luminal layer showed mucin 4 (MUC4), cytokeratin 5/6 (CK5/6), and CK7 expression in 5 cases (100%); MUC1, carcinoembryonic antigen (CEA), CA19-9, and thrombomodulin expression in 4 cases (80%); Wilms' tumor-1 (WT-1) and Hector Battifora mesothelial-1 (HBME-1) expression in 2 cases (40%), but it did not express p63 or D2-40. The basal layer expressed MUC1, CK5/6, p63, and thrombomodulin in 5 cases (100%); CK7 and WT-1 in 4 cases (80%); D2-40 in 3 cases (60%); CA19-9 and HBME-1 in 2 cases (40%) and MUC4 in 1 case (20%) but it did not express CEA. The analysis showed that all cases of multilayered SECs were negative for MUC2, MUC5AC, MUC6, CK20, calretinin, uroplakin-II, and uroplakin-III. Both cases of monolayered SECs expressed CK5/6, CK7, HBME-1, WT-1, and thrombomodulin but not MUC2, MUC4, MUC5AC, MUC6, p63, CEA, CK20, CA19-9, D2-40, uroplakin-II, or uroplakin-III. One case of monolayered SEC expressed MUC1 and calretinin. Our findings indicate that monolayered SECs have mesothelial-like characteristics, whereas multilayered SECs have glandular and squamous-like characteristics besides mesothelial-like characteristics. Furthermore, monolayered SECs may develop from mesothelial inclusion and monolayered SECs develop squamous and glandular metaplasia, which results in multilayered SECs.

17.
Pathol Int ; 69(5): 260-271, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30990953

RESUMO

We aimed to characterize the mucosal immune microenvironment and immune checkpoint of Ulcerative colitis (UC) by immunohistochemistry with correlation to prognosis: requirement of second-line steroid-therapy within the 2-years after diagnosis (SR). A series of 72 cases included 56 UC, 43 non-SR (with first-line treatment 5-ASA) and 13 SR, 11 infectious colitis and 5 normal colonic biopsies. Normal mucosa was characterized by low infiltrates but high BTLA and TNFRSF14. Compared to normal, UC had increased pan-immune-markers of CD3, CD8, FOXP3, PD-1, CD68, CD16, CD163, PTX3 and CD11C but had decreased BTLA (P < 0.05); by GSEA analysis comparable results were found in an independent UC gene-expression-data set (GSE38713). Compared to infectious, UC had higher CD4, CD8, PTX3 and CD11C but lower BTLA (P < 0.05). Compared to non-SR, SR had lower FOXP3 + Tregs (Odds-Ratio = 0.114, P = 0.002), PD-1 (OR = 0.176, P = 0.002) and CD163/CD68 M2-ratio (OR, 0.019, P = 0.019) but higher CD68 + pan-macrophages (OR = 6.034, P = 0.002). Higher Baron endoscopic and Geboes histologic disease activity scores also correlated with SR. In summary, UC was characterized by increased pan-immune-markers, normal TNFRSF14 and low BTLA. SR had increased CD68 + pan-macrophages but lower immune inhibitors of FOXP3 + Tregs, PD-1 and CD163/CD68 M2-macrophage ratio. In conclusion, alterations of the immune homeostasis mechanisms are relevant in the UC pathogenesis and steroid-requiring situation.

18.
Pathol Int ; 69(4): 211-218, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30990957

RESUMO

We aimed to propose a biosafety algorithm for the protection of pathology staff during intraoperative examinations of pulmonary lesions when working with cytological imprints and/or frozen sections for the intraoperative diagnosis of pulmonary lesions. We examined 148 pulmonary surgical tissues obtained intraoperatively for imprint cytology (IC) and for frozen sectioning and compared the diagnoses against the final pathological diagnoses. We analyzed concordance and non-concordance rates and then used the data to produce a biosafety algorithm. The diagnostic sensitivity, specificity, positive predictive value, negative predictive value and accuracy of scratch-IC were 91%, 100%, 100%, 50% and 92%, respectively, and those of frozen sectioning were 99%, 100%, 100%, 96% and 99%, respectively. Our data indicate that frozen sectioning is unnecessary if scratch-IC yields a 'malignant' diagnosis but recommended with a 'benign' diagnosis. When a scratch-IC preparation deemed inadequate for a diagnosis or an abscess, the pathologist must consult the surgeon concerning the possibility of granuloma with caseous necrosis and should ask the surgeon to be prepared for a frozen section. If granuloma with caseous necrosis is found in the frozen section, the pathologist must immediately communicate the information to entire staff and perform a PCR test before making a permanent section.


Assuntos
Algoritmos , Granuloma/diagnóstico , Abscesso Pulmonar/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Contenção de Riscos Biológicos , Citodiagnóstico , Feminino , Secções Congeladas , Granuloma/patologia , Granuloma/cirurgia , Humanos , Cuidados Intraoperatórios , Abscesso Pulmonar/patologia , Abscesso Pulmonar/cirurgia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Manejo de Espécimes
19.
J Clin Exp Hematop ; 59(1): 1-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30918139

RESUMO

The microenvironment influences the behavior of follicular lymphoma (FL) but the specific roles of the immunomodulatory BTLA and TNFRSF14 (HVEM) are unknown. Therefore, we examined their immunohistochemical expression in the intrafollicular, interfollicular and total histological compartments in 106 FL cases (57M/49F; median age 57-years), and in nine relapsed-FL with transformation to DLBCL (tFL). BTLA expression pattern was of follicular T-helper cells (TFH) in the intrafollicular and of T-cells in the interfollicular compartments. The mantle zones were BTLA+ in 35.6% of the cases with similar distribution of IgD. TNFRSF14 expression pattern was of neoplastic B lymphocytes (centroblasts) and "tingible body macrophages". At diagnosis, the averages of total BTLA and TNFRSF14-positive cells were 19.2%±12.4STD (range, 0.6%-58.2%) and 46.7 cells/HPF (1-286.5), respectively. No differences were seen between low-grade vs. high-grade FL but tFL was characterized by low BTLA and high TNFRSF14 expression. High BTLA correlated with good overall survival (OS) (total-BTLA, Hazard Risk=0.479, P=0.022) and with high PD-1 and FOXP3+Tregs. High TNFRSF14 correlated with poor OS and progression-free survival (PFS) (total-TNFRSF14, HR=3.9 and 3.2, respectively, P<0.0001), with unfavorable clinical variables and higher risk of transformation (OR=5.3). Multivariate analysis including BTLA, TNFRSF14 and FLIPI showed that TNFRSF14 and FLIPI maintained prognostic value for OS and TNFRSF14 for PFS. In the GSE16131 FL series, high TNFRSF14 gene expression correlated with worse prognosis and GSEA showed that NFkB pathway was associated with the "High-TNFRSF14/dead-phenotype".In conclusion, the BTLA-TNFRSF14 immune modulation pathway seems to play a role in the pathobiology and prognosis of FL.


Assuntos
Linfoma Folicular/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico , Receptores Imunológicos/metabolismo , Membro 14 de Receptores do Fator de Necrose Tumoral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/química , Linfócitos B/patologia , Transformação Celular Neoplásica , Feminino , Humanos , Fatores Imunológicos , Linfoma Folicular/mortalidade , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Linfócitos T/química
20.
J Clin Exp Hematop ; 59(1): 34-39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30918142

RESUMO

Composite lymphoma (CL) is defined as the occurrence of two distinct types of lymphoma within the same patient. Most cases of CL involve Hodgkin and non-Hodgkin lymphomas or two distinct types of B-cell lymphomas; true CL is a composite B-cell and T-cell lymphoma, and is rare. We herein report a case involving concurrent extranodal NK/T-cell lymphoma, nasal-type and diffuse large B-cell lymphoma, which has not been previously reported. As the mechanisms and treatments of composite B-cell and T-cell lymphomas are unclear, further studies are required to improve the prognosis.


Assuntos
Linfoma Composto/patologia , Linfoma Extranodal de Células T-NK/patologia , Linfoma Difuso de Grandes Células B/patologia , Neoplasias Nasais/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Invasividade Neoplásica
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