Tumor immune microenvironment characteristics of papillary thyroid carcinoma are associated with histopathological aggressiveness and BRAF mutation status.

BACKGROUND: Papillary thyroid carcinoma (PTC) follows an indolent course; however, up to 30% of patients develop recurrent disease requiring further treatment. Profiling PTC immune complexity may provide new biomarkers for improved risk prediction. METHODS: Immune complexity profiles were quantitatively evaluated by multiplex immunohistochemistry (mIHC) in archived tissue sections from 39 patients with PTC, and were assessed for correlations with aggressive histopathological features based on the presence of lymphovascular invasion and/or extrathyroidal extension, and BRAF V600E mutational status. RESULTS: mIHC revealed two distinct immune clusters stratifying patients: a lymphoid-inflamed group (higher CD8+ T cells, reduced dendritic and mast cells) and a myeloid/hypo-inflamed group that correlated with aggressive pathological features. BRAF mutation was not associated with aggressive pathological features but did correlate with increased mast cell density. CONCLUSIONS: Distinct immune microenvironments exist in PTC correlating with pathological aggressiveness. Immune-based biomarkers associated with possible tumor-immune interactions may be used for risk stratification.

Robust Cell Detection and Segmentation for Image Cytometry Reveal Th17 Cell Heterogeneity.

Image cytometry enables quantitative cell characterization with preserved tissue architecture; thus, it has been highlighted in the advancement of multiplex immunohistochemistry (IHC) and digital image analysis in the context of immune-based biomarker monitoring associated with cancer immunotherapy. However, one of the challenges in the current image cytometry methodology is a technical limitation in the segmentation of nuclei and cellular components particularly in heterogeneously stained cancer tissue images. To improve the detection and specificity of single-cell segmentation in hematoxylin-stained images (which can be utilized for recently reported 12-biomarker chromogenic sequential multiplex IHC), we adapted a segmentation algorithm previously developed for hematoxlin and eosin-stained images, where morphological features are extracted based on Gabor-filtering, followed by stacking of image pixels into n-dimensional feature space and unsupervised clustering of individual pixels. Our proposed method showed improved sensitivity and specificity in comparison with standard segmentation methods. Replacing previously proposed methods with our method in multiplex IHC/image cytometry analysis, we observed higher detection of cell lineages including relatively rare TH 17 cells, further enabling sub-population analysis into TH 1-like and TH 2-like phenotypes based on T-bet and GATA3 expression. Interestingly, predominance of TH 2-like TH 17 cells was associated with human papilloma virus (HPV)-negative status of oropharyngeal squamous cell carcinoma of head and neck, known as a poor-prognostic subtype in comparison with HPV-positive status. Furthermore, TH 2-like TH 17 cells in HPV-negative head and neck cancer tissues were spatiotemporally correlated with CD66b+ granulocytes, presumably associated with an immunosuppressive microenvironment. Our cell segmentation method for multiplex IHC/image cytometry potentially contributes to in-depth immune profiling and spatial association, leading to further tissue-based biomarker exploration. © 2019 International Society for Advancement of Cytometry.

Pediatric primary Sjögren syndrome presenting with bilateral ranulas: A case report and systematic review of the literature.

CONTEXT: Primary Sjögren syndrome is uncommon in children, and the standard clinical criteria used in diagnosis of adult Sjögren syndrome will miss many children with the disease. Floor of mouth ranulas have not been described in Sjögren syndrome. OBJECTIVE: This study aims to describe a novel presentation of juvenile primary Sjögren syndrome, and to present a comprehensive systematic review of the literature regarding the presentation and diagnosis of Sjögren syndrome in children. DATA SOURCES: Ovid MEDLINE. STUDY SELECTION: A MEDLINE literature search was performed using the following search terms: primary, Sjögren, disease, and children. Results were limited to human subjects and articles written in English between 1981 and 2014. Applicable articles were reviewed and qualitatively summarized. DATA EXTRACTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRIMA). RESULTS: Initial MEDLINE search yielded 146 articles, 80 of which were excluded as not clinically pertaining to Sjögren syndrome. An additional 25 were excluded due to lack of pediatric-specific data. Systematic review of the literature revealed no reports of ranula in association with Sjögren syndrome. 6 papers were manually included from review of reference lists of included articles. Our review indicated that recurrent parotitis is the most commonly reported presenting symptom in children, followed by ocular and oral symptoms, musculoskeletal, and renal symptoms. Compared to adults, children are less likely to present with dry eyes and mouth. LIMITATIONS: All studies were retrospective chart reviews, case series or case reports. CONCLUSION: This is the first report of a child presenting with floor of mouth ranulas in association with Sjögren syndrome. While recurrent parotitis is the most common presentation in children, other salivary gland and extra-salivary manifestations may be seen, and the clinician must maintain a high index of suspicion for underlying Sjögren syndrome.

Osteocutaneous radial forearm free flap in nonmandible head and neck reconstruction.

BACKGROUND: The osteocutaneous radial forearm free flap (RFFF) is a versatile flap primarily used to reconstruct composite defects involving the mandible. The purpose of this study was to describe our experience with this flap for nonmandible reconstruction. METHODS: All patients undergoing nonmandible osseous reconstruction with free-tissue transfer were reviewed. Patients with osteocutaneous RFFF reconstructions were evaluated. The retrospective review of all osteocutaneous RFFFs was performed from 1998 to 2014. RESULTS: One hundred forty-two nonmandible osseous reconstructions were performed. Twenty-five patients underwent nonmandible osteocutaneous RFFF reconstruction. Eleven patients failed previous nonmicrovascular reconstruction. Reconstruction was for defects of the: palatomaxillary complex (n = 15), orbitomaxillary complex (n = 4), nasomaxillary complex (n = 4), larynx (n = 1), and clavicle (n = 1). There were no flap compromises. Postoperative complications included: 2 partial intraoral dehiscences; 1 recipient-site infection; and 1 seroma. Eight reconstructions required secondary procedures to improve functional and/or cosmetic outcomes. CONCLUSION: The osteocutaneous RFFF is a robust flap that can be used to reconstruct composite defects involving bone and soft-tissue beyond the mandible.

Long-Term Outcomes of Radiofrequency Ablation of the Inferior Turbinates.

Radiofrequency ablation of the inferior turbinates (RFAIT) is a minimally invasive surgical technique that reduces turbinate size and decreases nasal obstruction. Few studies have assessed long-term outcomes of this procedure using standardized, symptom-specific evaluation instruments. The primary aim of this study is to assess the long-term effectiveness of RFAIT using a standardized, symptom-specific evaluation instrument. An additional outcome evaluated is the effect of RFAIT on therapeutic CPAP pressures in centimetres of water pressure (cwp) and overall CPAP use. Patients who had received RFAIT >14 months previously were identified via retrospective chart review and underwent a telephone interview with several questions to include the Nasal Obstruction Symptom Evaluation (NOSE) scale. Additionally, data regarding therapeutic pressures for continuous positive pressure devices (CPAP) and CPAP use was obtained for patients using these devices as treatment for obstructive sleep apnoea. The average NOSE scale score for the 40 patients who completed the NOSE scale questionnaire in our study was 6.35 ± 3.98 (0-20 scale). Crusting and mild, self-resolving epistaxis were the most common complications in the perioperative period. In general, unforeseen complications occurred in <13 % of patients. The mean therapeutic CPAP pressures reduced from 11.4 ± 2.7 to 10.1 ± 3.2 cwp, p = 0.085. This study supports that radiofrequency ablation of the inferior turbinates has low complication rates, is well-tolerated, may decrease therapeutic CPAP pressures, and provides symptomatic improvement that is sustained >14 months post-procedure.

Inferior turbinate classification system, grades 1 to 4: development and validation study.

OBJECTIVES/HYPOTHESIS: To develop a validated inferior turbinate grading scale. STUDY DESIGN: Development and validation study. METHODS: Phase 1 development (alpha test) consisted of a proposal of 10 different inferior turbinate grading scales (>1,000 clinic patients). Phase 2 validation (beta test) utilized 10 providers grading 27 standardized endoscopic photos of inferior turbinates using two different classification systems. Phase 3 validation (pilot study) consisted of 100 live consecutive clinic patients (n = 200 inferior turbinates) who were each prospectively graded by 18 different combinations of two independent raters, and grading was repeated by each of the same two raters, two separate times for each patient. RESULTS: In the development phase, 25% (grades 1-4) and 33% (grades 1-4) were the most useful systems. In the validation phase, the 25% classification system was found to be the best balance between potential clinical utility and ability to grade; the photo grading demonstrated a Cohen's kappa (κ) = 0.4671 ± 0.0082 (moderate inter-rater agreement). Live-patient grading with the 25% classification system demonstrated an overall inter-rater reliability of 71.5% (95% confidence interval [CI]: 64.8-77.3), with overall substantial agreement (κ = 0.704 ± 0.028). Intrarater reliability was 91.5% (95% CI: 88.7-94.3). Distribution for the 200 inferior turbinates was as follows: 25% quartile = grade 1, 50% quartile (median) = grade 2, 75% quartile = grade 3, and 90% quartile = grade 4. Mean turbinate size was 2.22 (95% CI: 2.07-2.34; standard deviation 1.02). Categorical κ was as follows: grade 1, 0.8541 ± 0.0289; grade 2, 0.7310 ± 0.0289; grade 3, 0.6997 ± 0.0289, and grade 4, 0.7760 ± 0.0289. CONCLUSIONS: The 25% (grades 1-4) inferior turbinate classification system is a validated grading scale with high intrarater and inter-rater reliability. This system can facilitate future research by tracking the effect of interventions on inferior turbinates. LEVEL OF EVIDENCE: 2c.