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CONTEXT: The recent WHO 2022 Classification of pituitary tumours identified a novel group of 'plurihormonal tumours without distinct lineage differentiation (WDLD)'. By definition, these express multiple combinations of lineage commitment transcription factors, in a monomorphous population of cells. OBJECTIVES: To determine the expression of stem cell markers (SOX2, Nestin, CD133) within tumours WDLD, immature PIT-1 lineage and acidophil stem cell tumours, compared with committed cell lineage tumours. METHODS: Retrospective evaluation of surgically resected pituitary tumours from St Vincent's Hospital, Sydney. Patients were selected to cover a range of tumour types, based on transcription factor and hormone immunohistochemistry. Clinical data was collected from patient files. Radiology reports were reviewed for size and invasion. Samples were analysed by immunohistochemistry and RT-qPCR for SF-1, PIT-1, T-PIT, SOX2, Nestin and CD133. Stem cell markers were compared between tumours WDLD and those with classically "mature" types. RESULTS: On immunohistochemistry, SOX2 was positive in a higher proportion of tumours WDLD compared with those meeting WHO lineage criteria, 7/10 v 10/42 (70 v 23.4%, p = 0.005). CD133 was positive in 2/10 tumours WDLD but 0/41 meeting lineage criteria, P = 0.003. On RT-qPCR, there was no significant difference in relative expression of stem cell markers (SOX2, CD133, Nestin) between tumours with and WDLD. CONCLUSIONS: Our study is the first to biologically characterise pituitary tumours WDLD. We demonstrate that these tumours exhibit a higher expression of the stem cell marker SOX2 compared with other lineage-differentiated tumours, suggesting possible involvement of stem cells in their development.
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Diferenciação Celular , Linhagem da Célula , Nestina , Neoplasias Hipofisárias , Fatores de Transcrição SOXB1 , Humanos , Fatores de Transcrição SOXB1/metabolismo , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , Estudos Retrospectivos , Diferenciação Celular/fisiologia , Feminino , Nestina/metabolismo , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Adulto , Antígeno AC133/metabolismo , Biomarcadores Tumorais/metabolismo , Idoso , Células-Tronco/metabolismo , Células-Tronco/patologiaRESUMO
BACKGROUND: Eosinophilic chronic rhinosinusitis is an often treatment-resistant inflammatory disease mediated by type-2 cytokines, including interleukin (IL)-5. Mepolizumab, a monoclonal antibody drug targeting IL-5, has demonstrated efficacy and safety in inflammatory airway disease, but there is negligible evidence on direct tissue response. The study's aim was to determine the local effect of mepolizumab on inflammatory biomarkers in sinonasal tissue of eosinophilic chronic rhinosinusitis patients. METHODS: Adult patients with eosinophilic chronic rhinosinusitis received 100mg mepolizumab subcutaneously at four-weekly intervals for 24 weeks in this prospective phase 2 clinical trial. Tissue eosinophil counts, eosinophil degranulation (assessed as submucosal eosinophil peroxidase deposition by immunohistochemistry) and cytokine levels (measured in homogenates by immunoassay) were evaluated in ethmoid sinus tissue biopsies collected at baseline and at weeks 4, 8, 16 and 24. RESULTS: Twenty patients (47.7 ± 11.7 years, 50% female) were included. Sinonasal tissue eosinophil counts decreased after 24 weeks of treatment with mepolizumab (101.64 ± 93.80 vs 41.74 ± 53.76 cells per 0.1 mm2 ; p = .035), eosinophil degranulation remained unchanged (5.79 ± 2.08 vs 6.07 ± 1.20, p = .662), and type-2 cytokine levels increased in sinonasal tissue for IL-5 (10.84 ± 18.65 vs 63.98 ± 50.66, p = .001), IL-4 (4.48 ± 3.77 vs 9.38 ± 7.56, p = .004), IL-13 (4.02 ± 2.57 vs 6.46 ± 3.99, p = .024) and GM-CSF (1.51 ± 1.74 vs 4.50 ± 2.97, p = .001). CONCLUSION: Mepolizumab reduced eosinophils in sinonasal tissue, demonstrating that antagonism of IL-5 suppresses eosinophil trafficking. With reduced tissue eosinophils, a local type-2 inflammatory feedback loop may occur. The study exposes mechanistic factors which may explain incomplete treatment response.
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Interleucina-5 , Sinusite , Adulto , Feminino , Humanos , Masculino , Doença Crônica , Citocinas , Eosinófilos , Estudos Prospectivos , Sinusite/tratamento farmacológicoRESUMO
BACKGROUND: Prognostic cytological and molecular features of uveal melanoma have been well researched and are essential in management. Samples can be obtained in vivo through fine needle aspirate biopsy, vitrector cutter, forceps or post-enucleation for off-site testing. This study aims to examine cytological and chromosome microarray yields of these samples. METHODS: A retrospective cohort analysis of 119 uveal melanoma biopsies submitted to our laboratory. Samples included those taken in vivo (n = 57) and post-enucleation (n = 62). Patient and tumour features were collected including age, sex, primary tumour location, basal diameter and tumour height. Prognostic outcomes measured include cell morphology, chromosomal status and immunohistochemistry. RESULTS: Post-enucleation biopsies accounted for just over half of our samples (52%). Post-enucleation samples had a more successful genetic yield than in vivo biopsies (77% vs. 50%, p = 0.04) though there was no difference for cytological yields. There was no difference in cytological or microarray yields between instruments. The vitrector biopsy group had the smallest tumour thickness (5 mm vs. 10 mm [fine-needle aspirate biopsy], p = 0.003). There was a strong correlation between monosomy 3, BAP1 aberrancy and epithelioid cell type in post-enucleation samples (Tb = 0.742, p = 0.005). However, epithelioid morphology was not associated with either monosomy 3 (p = 0.07) or BAP1 aberrancy (p = 0.24) for in vivo biopsies. CONCLUSIONS: All three biopsy instruments provide similar cytological yields as post-enucleation sampling, although post-enucleation samples had a more successful chromosome microarray yield. Epithelioid cytomorphology alone is insufficient for prognostication in in vivo biopsies, immunohistochemistry would be a useful surrogate test.
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Neoplasias Uveais , Biópsia por Agulha Fina , Humanos , Melanoma , Monossomia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Neoplasias Uveais/diagnóstico , Neoplasias Uveais/genética , Neoplasias Uveais/metabolismoRESUMO
The cytokine IL-21 has been shown to influence immune responses through both costimulatory effects on effector T cells and opposing inhibitory effects on T regulatory cells (Tregs). To distinguish the effect of IL-21 on the immune system from that of its effect on Tregs, we analyzed the role of IL-21/IL-21R signaling in mice made genetically deficient in IL-2, which exhibit a deficit in IL-2-dependent Foxp3 regulatory T cells and suffer from a fatal multiorgan inflammatory disease. Our findings demonstrate that in the absence of IL-21/IL-21R signaling, Il2(-/-) mice retained a deficiency in Tregs yet exhibited a reduced and delayed inflammatory disease. The improved health of Il2(-/-)Il21r(-/-) mice was reflected in reduced pancreatitis and hemolytic anemia and this was associated with distinct changes in lymphocyte effector populations, including the reduced expansion of both T follicular helper cells and Th17 cells and a compensatory increase in IL-22 in the absence of IL-21R. IL-21/IL-21R interactions were also important for the expansion of effector and memory CD8(+) T cells, which were critical for the development of pancreatitis in Il2(-/-) mice. These findings demonstrate that IL-21 is a major target of immune system regulation.
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Anemia Hemolítica/imunologia , Subunidade alfa de Receptor de Interleucina-21/metabolismo , Interleucinas/metabolismo , Pancreatite/imunologia , Linfócitos T Reguladores/imunologia , Anemia Hemolítica/genética , Animais , Anticorpos/sangue , Formação de Anticorpos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Diferenciação Celular/imunologia , Fatores de Transcrição Forkhead/deficiência , Fatores de Transcrição Forkhead/genética , Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-21/genética , Interleucinas/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pancreatite/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/metabolismo , Células Th17/citologia , Células Th17/imunologia , Interleucina 22Assuntos
Adenoma , Tumores Neuroendócrinos , Doenças da Hipófise , Neoplasias Hipofisárias , Humanos , HipófiseRESUMO
Objectives Sellar pathologies are frequently found on imaging performed to investigate headache. However, both headache and incidental sellar lesions are common. Hence, this study prospectively examined headache prevalence, phenotype, and severity in patients with sellar pathologies and the impact of transsphenoidal surgery on headache. Methods Patients undergoing transsphenoidal resection of sellar lesions were consecutively recruited. At baseline, participants were defined as having headache or not and headache phenotype was characterized using validated questionnaires. Headache severity was assessed at baseline and 6 months postoperatively using the Headache Impact Test-6 (HIT-6) and Migraine Disability Assessment Score (MIDAS). Tumor characteristics were defined using radiological, histological, and endocrine factors. Primary outcomes included baseline headache prevalence and severity and headache severity change at 6 months postoperatively. Correlation between headache and radiological, histological, and endocrine characteristics was also of interest. Results Sixty participants (62% female, 47.1 ± 18.6 years) were recruited. Sixty-three percent possessed baseline headache. HIT-6 scores were higher in patients with primary headache risk factors, including younger age (R 2 = -0.417, p = 0.010), smoking history (63.31 ± 7.93 vs 54.44 ± 9.21, p = 0.0060), and family headache history (68.13 ± 7.01 vs 54.94 ± 9.11, p = 0.0030). Headaches were more common in patients with dural invasion (55.70 ± 12.14 vs 47.18 ± 10.15, p = 0.027) and sphenoid sinus invasion (58.87 ± 8.97 vs 51.29 ± 10.97, p = 0.007). Postoperative severity scores improved more with higher baseline headache severity (HIT-6: R 2 = -0.682, p < 0.001, MIDAS: R 2 = -0.880, p < 0.0010) and dural invasion (MIDAS: -53.00 ± 18.68 vs 12.00 ± 17.54, p = 0.0030). Conclusion Headaches in sellar disease are likely primary disorders triggered or exacerbated by sellar pathology. These may respond to surgery, particularly in patients with severe headache and dural invasion.
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We present a cohort review of TORS resection for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and its associated oncological outcomes spanning a 10-year period. A retrospective case series review was performed of patients undergoing primary surgical treatment for HPV-associated OPSCC through the St. Vincent's Head and Neck Cancer service from 2011 to 2022. The primary outcomes were to investigate complete resection of the primary tumour, rates of recurrence, and survival analysis. Secondary outcomes included complications, rates of adjuvant therapy, sites of recurrence and rates of percutaneous endoscopic gastrostomy (PEG). 184 patients underwent TORS-based therapy with neck dissection, and guideline-directed adjuvant therapy for HPV-associated OPSCC. Our median follow-up was 46 months. The positive margin rate on final histopathology analysis was 10.9%. Adjuvant therapy was indicated in 85 patients (46%). The local recurrence rate was 10.9% with the majority (80%) of patients recurring in the first 3 years since treatment. The disease-specific survival at 3 years was 98.6% and at 5 years was 94.4%. The 3-year and 5-year OS for the cohort was 96.7% and 92.5%, respectively. The presence of extranodal extension and positive margins were associated with increased risk of recurrence, whereas adjuvant therapy was found to be a protective factor for both overall recurrence and survival. Major complications occurred in 12 patients (6.5%), resulting in one death. This study has demonstrated that primary surgical therapy for HPV-associated OPSCC is a safe and effective treatment modality with low local recurrence and complication rates, and overall survival benefits.
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Neoplasias Orofaríngeas , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Recidiva Local de Neoplasia , Austrália/epidemiologia , Adulto , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/cirurgia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/virologia , Carcinoma de Células Escamosas/patologia , Margens de Excisão , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Esvaziamento Cervical/métodos , Idoso de 80 Anos ou maisRESUMO
Objective: Pituitary tumours comprise a pathologically and clinically diverse group of neoplasms. Classification frameworks have changed dramatically in the past two decades, reflecting improving understanding of tumour biology. This narrative review examines the evolution of pituitary tumour classification, from a clinical perspective. Results: In 2004, pituitary tumours were classified as 'typical' or 'atypical', based on the presence of markers of proliferation, Ki67, mitotic count and p53. In 2017, the new WHO marked a major paradigm shift, with a new focus on lineage-based classification, determined by transcription factor and hormonal immunohistochemistry. The terms 'typical' and 'atypical' were omitted, though the importance of proliferative markers Ki67 and mitotic count was acknowledged. The recent WHO 2022 classification incorporates further refinements, specifically recognising some less common types that may represent less well-differentiated tumours. Whilst 'high risk' tumour types have been identified, further work is still required to improve prognostication. Conclusions: Recent WHO classifications have marked significant progress in the diagnostic evaluation of pituitary tumours, though shortcomings and challenges remain for both clinicians and pathologists in managing these tumours.
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KEY POINTS: Culturable bacterial colonization is similar between type 2 CRS phenotypes Staphylococcus aureus coinfection is similar between eosinophilic CRS and CCAD Patients with CCAD were younger, consistent with current knowledge of the disease.
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Pólipos Nasais , Rinite , Sinusite , Humanos , Rinite/microbiologia , Sinusite/microbiologia , Fenótipo , Doença Crônica , Pólipos Nasais/microbiologiaRESUMO
BACKGROUND: Central compartment atopic disease (CCAD) and eosinophilic chronic rhinosinusitis (eCRS) are two clinical phenotypes of primary diffuse type 2 chronic rhinosinusitis (CRS) defined in the European Position Paper on Rhinosinusitis 2020 classification. Currently, the distinction between these subtypes relies on phenotypic features alone. OBJECTIVE: This study aimed to investigate whether eosinophil activation differed between CCAD and eCRS. METHODS: A cross-sectional study was conducted of adult patients presenting with CCAD and eCRS who had undergone functional endoscopic sinus surgery. Routine pathology results were obtained from clinical records. Eosinophils were counted on haematoxylin and eosin-stained formalin-fixed paraffin-embedded sinonasal tissue. Eotaxin-3, eosinophil peroxidase and immunoglobulin E levels were assessed using immunohistochemistry. RESULTS: 38 participants were included (51.7 ± 15.6 years, 47.4% female), of whom 36.8% were diagnosed with CCAD and 63.2% with eCRS. The eCRS group was characterised by older age (55.8 ± 16.3 vs 44.5 ± 11.8 years, p = 0.029), and on histology exhibited a higher degree of tissue inflammation (τb = 0.409, p = 0.011), greater proportion of patients with >100 eosinophils/high power field (87.5% vs 50%, p = 0.011), and higher absolute tissue eosinophil count (2141 ± 1947 vs 746 ± 519 cells/mm2, p = 0.013). Eotaxin-3 scores were higher in the eCRS group (5.00[5.00-6.00] vs 6.00[6.00-6.75], p = 0.015). Other outcomes were similar. CONCLUSIONS: Eosinophil and eotaxin-3 levels were elevated in eCRS compared with CCAD, suggesting a greater degree of eosinophil stimulation and chemotaxis. Patients with CCAD were younger. Future investigation and biomarkers may better distinguish CRS subpopulations.
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Eosinofilia , Pólipos Nasais , Rinite , Sinusite , Feminino , Masculino , Humanos , Quimiocina CCL26 , Rinite/diagnóstico , Rinite/cirurgia , Estudos Transversais , Eosinófilos , Eosinofilia/diagnóstico , Sinusite/diagnóstico , Sinusite/cirurgia , Doença Crônica , Pólipos Nasais/diagnósticoRESUMO
OBJECTIVES: To determine the clinical utility of assessment of tumour invasion, markers of proliferation, and the French clinicopathological classification in pituitary tumour prognostication. METHODS: This is a retrospective evaluation of adult patients undergoing pituitary surgery at Oxford University and St Vincent's Hospitals, between 1989 and 2016, with at least 12 months of clinical data. Invasion was assessed radiologically, proliferative markers (Ki67, mitotic count, p53) by immunohistochemistry. Tumours were graded according to the clinicopathological classification. Intra- and interlaboratory variability of histopathology reporting was evaluated. OUTCOMES: (1) Tumour recurrence (radiological or reintervention ≥12 months postoperatively) and/or (2) "aggressive behaviour" (≥4 interventions and/or invasive tumour with recurrence/reintervention between 12 and 24 months postoperatively). RESULTS: A total of 386 patients were included, age at surgery was 56 (interquartile range [IQR] 41-67) years, 54% were male, and median follow-up was 90 months (range 44-126). Tumours were predominantly clinically nonfunctioning (252, 65%), with overall 53% invasive, and 10% that demonstrated ≥2 proliferative marker positivity. Recurrence was predicted by invasiveness (hazards ratio [HR] 1.6 [1.10-2.37], P .02), elevated mitotic count (HR 2.17 [1.21-3.89], P .01), grade (2b vs 1a HR 2.32 [1.06-5.03], P .03), and absence of gross total resection (HR 3.70 [1.72-8.00], P .01). Clinically defined aggressiveness was associated with elevated Ki67, mitotic count, and invasiveness. Ki67 reporting methodologies showed moderate correlation across laboratories (Phi 0.620), whereas p53 reporting reproducibility was poor (Phi 0.146). CONCLUSIONS: Proliferative markers, including Ki67 and mitotic count, but not p53, are important in predicting the development of aggressive pituitary tumour behaviour.
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Neoplasias Hipofisárias , Adulto , Humanos , Masculino , Pré-Escolar , Feminino , Neoplasias Hipofisárias/patologia , Antígeno Ki-67 , Seguimentos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Recidiva Local de Neoplasia/patologiaRESUMO
BACKGROUND: Biologic therapy targeting type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) has greatly improved disease control but nonresponders exist in a proportion of patients in phase 3 trials and clinical practice. This study explores the serum and histologic changes in biologic treated CRSwNP that predict disease control. METHODS: A cross-sectional study was performed of patients with CRSwNP on biologics for their asthma, who underwent endoscopic sinus surgery while on biologic therapy. At the 6-month postoperative assessment, patients with poorly controlled CRSwNP while on biologic therapy were compared to patients who were controlled. Blood and mucosal samples taken at the time of surgery 6 months prior were assessed to predict disease control. RESULTS: A total of 37 patients were included (age 47.8 ± 12.4 years, 43.2% female). Those with poorly controlled disease had reduced tissue eosinophils (% >100 cells/high-powered field: 8.3% vs. 50.0%, p < 0.001) and increased serum neutrophils (5.2 ± 2.7 vs. 3.7 ± 1.1 × 109 cells/L, p = 0.02). Logistic regression analysis demonstrated that reduced tissue eosinophil was predictive for poorly controlled disease (OR = 0.21, 95% CI [0.05, 0.83], p = 0.03). Receiver-operating characteristic analysis showed that need for rescue systemic corticosteroid was predicted at a serum neutrophil cut-off level of 5.75 × 109 cells/L (sensitivity = 80.0%, specificity = 96.9%, AUC = 0.938, p = 0.002). CONCLUSION: Low tissue eosinophils and increased serum neutrophils while on biologics predict for poor response in the biological treatment of with CRSwNP. A serum neutrophil level of ≥5.75 × 109 cells/L predicts for poor response to current biologic therapy.
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INTRODUCTION: Flow cytometry (FCM) is widely used in the diagnosis of mature B-cell neoplasms (MBN), and FCM data are usually consistent with morphological findings. However, diffuse large B-cell lymphoma (DLBCL), a common MBN, is sometimes not detected by FCM. This study aimed to explore factors that increase the likelihood of failure to detect DLBCL by FCM. METHODS: Cases with a final diagnosis of DLBCL that were analysed by eight-colour FCM were retrospectively collated. Clinical, FCM, histopathological and genetic data were compared between cases detected and cases not detected by FCM. RESULTS: DLBCL cases from 135 different patients were analysed, of which 22 (16%) were not detected by FCM. In samples not detected by flow cytometry, lymphocytes were a lower percentage of total events (p = 0.02), and T cells were a higher percentage of total lymphocytes (p = 0.01). Cases with high MYC protein expression on immunohistochemistry were less likely to be missed by FCM (p = 0.011). Detection of DLBCL was not different between germinal centre B-cell (GCB) and non-GCB subtypes, not significantly affected by the presence of necrosis or fibrosis, and not significantly different between biopsy specimens compared to fine-needle aspirates, or between samples from nodal compared to extranodal tissue. CONCLUSION: The study identifies several factors which affect the likelihood of DLBCL being missed by FCM. Even with eight-colour analysis, FCM fails to detect numerous cases of DLBCL.
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Linfoma Difuso de Grandes Células B , Humanos , Estudos Retrospectivos , Citometria de Fluxo , Linfoma Difuso de Grandes Células B/patologia , Linfócitos B/patologia , Centro Germinativo/metabolismo , Centro Germinativo/patologia , PrognósticoRESUMO
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic disorder characterised by a germline mutation of the fumarate hydratase (FH) gene, in which affected individuals have a high likelihood of developing cutaneous leiomyomas, uterine leiomyomas and renal cell cancer (RCC). HLRCC-associated RCC is characterised by presentation at a younger age than the sporadic form, its aggressive nature and rapid metastatic potential. We present the case of a 50 year old woman with FH mutation, a history of early onset symptomatic uterine leiomyomas, and RCC with the first reported case of an isolated metastasis to the pituitary gland.
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BACKGROUND: Biologic therapies such as mepolizumab and benralizumab are currently utilised in the treatment of eosinophilic asthma, and are emerging in the management of eosinophilic chronic rhinosinusitis (eCRS). These biologics inhibit the interaction of IL-5 with its receptor, thus impairing cytokine signalling and eosinophil inflammation. Mepolizumab does so by targeting IL-5, whereas benralizumab targets the α chain of the IL-5 receptor. This study compares the sinonasal tissue response to anti-IL-5 biologic therapies in patients with eCRS. METHODS: A cross-sectional study of adult eCRS patients who had completed at least 2 cycles of biologic therapy and underwent endoscopic sinus surgery as part of their management were included. Sinonasal mucosal tissue biopsies were obtained intraoperatively and assessed with structured histopathological examination. Comparisons of tissue histopathology outcomes following treatment with mepolizumab or benralizumab were performed. RESULTS: 18 patients (age 49.6 ± 14.2 years, 47% female, 100% co-morbid asthma) were included in this study, comprising 10 patients managed with mepolizumab and 8 patients managed with benralizumab. Even after mepolizumab, the tissue had predominantly eosinophilic inflammation compared to benralizumab (90% v 0%, p < 0.01), which demonstrated a greater lymphoplasmacytic inflammation (10% v 75%, χ2(2) = 14.53, p < 0.01). Compared with benralizumab, mepolizumab had increased tissue eosinophil count (100% v 37.5% >10 eosinophils/HPF, τb = -8.47, p < 0.001) and more severe subepithelial oedema (80% v 37.5% severe, τb = -2.37, p = 0.02). CONCLUSION: Tissue histopathologic outcomes reflect the differing mechanism of action of mepolizumab and benralizumab in eCRS. Further analysis at the tissue level will provide further information to guide application of mAbs in type 2 inflammatory diseases.
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Antiasmáticos , Asma , Sinusite , Adulto , Antiasmáticos/uso terapêutico , Estudos Transversais , Eosinófilos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sinusite/tratamento farmacológicoRESUMO
Although the ectopic thyroid in adults is rarely symptomatic, biochemistry and imaging workup are essential. Treatment modality of choice is dependent on patient factors, institution factors and surgeon factors. The mainstay treatment involves hormone suppression treatment with exogenous thyroid hormone. If medical management is unsuccessful, surgical excision requires an experienced team including an anaesthetist and otolaryngologist. Anaesthetic considerations are important because intubation may be a potentially difficult procedure secondary to potential serious obstruction of the upper airway. We present a case report and narrative review of the literature regarding lingual thyroid workup and management.
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OBJECTIVE: The clinical utility and prognostic value of WHO 2017 lineage-based classification of pituitary tumours have not been assessed. This study aimed to (1) determine the clinical utility of transcription factor analysis for classification of pituitary tumours and (2) determine the prognostic value of improved lineage-based classification of pituitary tumours. METHODS: This was a retrospective evaluation of patients who underwent surgical resection of pituitary tumours at St Vincent's Public and Private Hospitals, Sydney, Australia between 1990 and 2016. Included patients were at least 18 years of age and had complete histopathological data, forming the 'histological cohort'. Patients with at least 12 months of post-surgical follow-up were included in the subgroup 'clinical cohort'. The diagnostic efficacy of transcription factor immunohistochemistry in conjunction with hormone immunohistochemistry was compared with hormone immunohistochemistry alone. The prognostic value of identifying 'higher-risk' histological subtypes was assessed. RESULTS: There were 171 patient tumour samples analyzed in the histological cohort. Of these, there were 95 patients forming the clinical cohort. Subtype diagnosis was changed in 20/171 (12%) of tumours. Within the clinical cohort, there were 21/95 (22%) patients identified with higher-risk histological subtype tumours. These were associated with tumour invasiveness (P = 0.050), early recurrence (12-24 months, P = 0.013), shorter median time to recurrence (49 (IQR: 22.5-73.0) vs 15 (IQR: 12.0-25.0) months, P = 0.005) and reduced recurrence-free survival (P = 0.031). CONCLUSIONS: Application of transcription factor analysis, in addition to hormone immunohistochemistry, allows for refined pituitary tumour classification and may facilitate an improved approach to prognostication.
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Imuno-Histoquímica , Neoplasias Hipofisárias/diagnóstico , Fatores de Transcrição/análise , Hormônio Adrenocorticotrópico/análise , Adulto , Idoso , Austrália , Estudos de Coortes , Feminino , Hormônio Foliculoestimulante/análise , Hormônio do Crescimento Humano/análise , Humanos , Hormônio Luteinizante/análise , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Hipofisárias/classificação , Neoplasias Hipofisárias/patologia , Prognóstico , Prolactina/análise , Estudos Retrospectivos , Tireotropina/análise , Fator de Transcrição Pit-1/análiseRESUMO
PURPOSE OF REVIEW: The current understanding of eosinophilic chronic rhinosinusitis (CRS) has developed rapidly over the past decades. Classification of CRS based on the inflammatory endotype more accurately reflects the underlying pathophysiology and better directs treatment. Corticosteroids and more recently biologic agents, target the eosinophil inflammatory that drives this subtype of CRS. Tissue sampling is not always accessible or available and surrogate markers are sought to define this endotype of CRS. The purpose of this review is to assess current systemic predictors of eosinophilic CRS (eCRS) diagnosis. RECENT FINDINGS: Blood eosinophils are a moderate surrogate predictor of eCRS. A blood eosinophil count of more than 0.24â×â10/l predicts eCRS with tissue eosinophilia of more than 10 eosinophils per high-power field. It has been further shown that a blood eosinophil count more than 0.45â×â10/l is associated with need for long-term systemic therapy following endoscopic sinus surgery. Other biomarkers reviewed include IgE, eosinophilic cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, IL-5, periostin, eotaxin-3 and IL-16. SUMMARY: There remains limited data surrounding the prognostic use of biomarkers in eCRS. However, peripheral eosinophilia best predicts the eosinophilic density that best predicts the eCRS phenotype. In addition, it is also prognostic of need for more intensive therapy. Simple haematoxylin and eosin stained sinus mucosa still remains the most reliable tissue for assessment and is more accessible than bronchial biopsies.
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Biomarcadores/sangue , Eosinófilos/patologia , Pólipos Nasais/diagnóstico , Rinite/diagnóstico , Sinusite/diagnóstico , Doença Crônica , Proteína Catiônica de Eosinófilo/sangue , Neurotoxina Derivada de Eosinófilo/sangue , Humanos , Imunoglobulina E/sangueRESUMO
The significant decrease in the incidence of cervical cancer in Australian women since the implementation of an organised approach to cervical screening through the National Cervical Screening Program (NSCP) can be largely attributed to high-quality cervical cytology reporting by Australian laboratories. Performance measures for Australian laboratories reporting cervical cytology are a well-established and an integral part of monitoring and maintaining this high standard by facilitating interlaboratory comparison of performance. This study summarises the aggregate data collected annually by Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) over the decade from 2009 until 30 November 2017, when the NCSP was revised and the cervical screening test replaced the Pap test as the primary mode of screening women for preinvasive disease. Overall, laboratories continued to perform to a high standard over this period. However, the introduction of a national school and GP based human papillomavirus (HPV) vaccination program in 2006 had a significant impact on the reporting of possible and definite high-grade abnormalities. In the renewed cervical screening program which commenced in December 2017 and which is based on HPV testing and reflex liquid-based cytology, new performance benchmarks will need to be developed when sufficient data have been collected.
Assuntos
Colo do Útero/patologia , Detecção Precoce de Câncer/normas , Laboratórios/normas , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Displasia do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/diagnóstico , Austrália , Colo do Útero/virologia , Citodiagnóstico , Feminino , Humanos , Teste de Papanicolaou , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Cobertura Vacinal , Esfregaço Vaginal , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
BACKGROUND: Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is well validated in the staging of pre-treatment head and neck squamous cell carcinoma (HNSCC), although the impact of human papilloma virus (HPV) status and node size on accuracy remains unclear. The aim of this study was to assess the diagnostic accuracy of PET/CT based on HPV status and node size and determine the effects of maximum standardized uptake value thresholds on sensitivity, specificity and positive predictive value. METHODS: A total of 38 patients with primary HNSCC were recruited. All patients underwent primary tumour resection and cervical node dissection following FDG-PET/CT. RESULTS: A total of 38 patients including 68 dissected necks, representing 353 nodal levels and a total of 2701 lymph nodes were included. Histopathological analysis revealed lymph node metastases in 4.3% (116/2701) of dissected lymph nodes. Forty-four percent of patients had HPV-positive tumours. Sixty-four percent of involved lymph nodes were <1 cm. The sensitivity and specificity for HPV-positive nodes were 67.2% and 99.3% versus 35.6% and 98.2% in HPV-negative nodes, respectively (P < 0.001). Mean maximum standardized uptake value in HPV-positive nodes was 6.3 versus 3.5 in HPV-negative nodes (P < 0.001). Sensitivity and specificity were 30.7% and 99.2% in <1 cm nodes versus 90.2% and 84.8% in ≥1 cm nodes, respectively (P < 0.001). CONCLUSION: FDG-PET/CT has significantly higher diagnostic accuracy in determining nodal metastases in HPV-positive HNSCC versus HPV-negative disease. Accuracy was lower in <1 versus ≥1 cm nodes.