Grading of minor salivary gland immuno-histopathology post-allogenic hematopoietic cell transplantation

Objectives: The oral cavity commonly displays mucosal lichenoid lesions and salivary gland dysfunction, which are considered different chronic Graft-versus-Host Disease (cGVHD) patho-physiology's. However, diagnostics of salivary gland (sg-)cGVHD are limited. The objectives of the current study are to evaluate the minor salivary gland (MSG) histo-immunopathological profiles post allogenic hematopoietic cell transplantation based on sg-cGVHD criteria. Design: Histopathology was characterized according to two published grading strategies. Firstly, the National Institute of Health (NIH) assessed peri-ductal/acinar infiltration, exocytosis, damage, and fibrosis, and a points-based grading scheme was established (0-16 points, Grade (G) 0 to IV). Second, a modified Sjo center dot gren's Syndrome focus-score with parenchymal damage was also adapted, (0-10 points, Score 0 to 2). 146 MSG biopsies from 79 patients were compared, using the his-topathological specific criteria for sg-cGVHD pathology. Quantitative immunohistochemistry for T-cells (CD4, CD8), B-cells (CD19, CD20), monocytic cells (CD68) and dendritic cells (CD1a) were also assessed. Results: The large-scale cohort validated the use of both grading schemes. GIII-GIV and score 2 signified a histopathological diagnosis of "likely" sg-cGVHD. Immunopathological severity was associated with increased T-cells (CD4 and CD8) and monocytic (CD68) infiltrate, with minimal involvement of B-cells (CD19 and CD20), and Langerhans cells (CD1a). Conclu-sions: Both schemes were verified as being suitable for histological grading to improve assess-ment and diagnosis of sg-cGVHD. The NIH cGVHD grading appears to be more beneficial for research purposes, including final diagnostics of "no/inactive", "possible" or "likely" cGVHD. The study highlights the intricacies of sg-cGVHD pathology; and the need for standardized assessment to improve patient management associated to sg-cGVHD

Quantitative chromogenic immunohistochemical image analysis in cellprofiler software.

Visual grading of chromogenically stained immunohistochemical (IHC) samples is subjective, time consuming, and predisposed to considerable inter- and intra-observer variations. The open-source digital analysis software, CellProfiler has been extensively used for fluorescently stained cells/tissues; however, chromogenic IHC staining is routinely used in both pathological and research diagnostics. The current investigation aimed to compare CellProfiler quantitative chromogenic IHC analyses against the gold standard manual counting. Oral mucosal biopsies from patients with chronic graft-versus-host disease were stained for CD4. Digitized images were manually counted and subjected to image analysis in CellProfiler. Inter-observer and inter-platform agreements were assessed by scatterplots with linear regression and Bland-Altman plots. Validation comparisons between the manual counters demonstrated strong intra-observer concordance (r(2) = 0.979), particularly when cell numbers were less than 100. Scatterplots and Bland-Altman plots demonstrated strong agreement between the manual counters and CellProfiler, with the number of positively stained cells robustly correlating (r(2) = 0.938). Furthermore, CellProfiler allowed the determination of multiple variables simultaneously, such as area stained and masking to remove any nonstained tissue and white gaps, which also demonstrated reliable agreement (r(2) = >0.9). CellProfiler demonstrated versatility with the ability to assess large numbers of images and allowed additional parameters to be quantified. CellProfiler allowed rapid high processing capacity of chromogenically stained chronic inflammatory tissue that was reliable, accurate, and reproducible and highlights potential applications in research diagnostics

Oral health in patients scheduled for hematopoietic stem cell transplantation in the Orastem study.

Despite advances in transplant medicine, prevalence of complications after hematopoietic stem cell transplantation (HSCT) remains high. The impact of pre-HSCT oral health factors on the incidence and severity of complications post-HSCT is poorly understood. The aim of this prospective, observational study was to analyze oral health in patients planned for HSCT. Patients ≥18 years requiring HSCT were included from five sites between 2011-2018. General health, oral findings and patient-reported symptoms were registered in 272 patients. Oral symptoms around disease onset were reported by 43 patients (15.9%) and 153 patients (58.8%) reported oral complications during previous chemotherapy. One third of patients experienced oral symptoms at the oral examination before conditioning regimen and HSCT. In total, 124 (46.1%) patients had dental caries, 63 (29.0%) had ≥one tooth with deep periodontal pockets, 147 (75.0%) had ≥one tooth with bleeding on probing. Apical periodontitis was observed in almost 1/4 and partially impacted teeth in 17 (6.3%) patients. Oral mucosal lesions were observed in 84 patients (30.9%). A total of 45 (17.4%) of 259 patients had at least one acute issue to be managed prior to HSCT. In conclusion, oral symptoms and manifestations of oral disease were prevalent in patients planned for HSCT. The extent of oral and acute dental diseases calls for general oral screening of patients pre-HSCT

Basic oral care for hematology–oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT)

PURPOSE: Hematology-oncology patients undergoing chemotherapy and hematopoietic stem cell transplantation (HSCT) recipients are at risk for oral complications which may cause significant morbidity and a potential risk of mortality. This emphasizes the importance of basic oral care prior to, during and following chemotherapy/HSCT. While scientific evidence is available to support some of the clinical practices used to manage the oral complications, expert opinion is needed to shape the current optimal protocols. METHODS: This position paper was developed by members of the Oral Care Study Group, Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) and the European Society for Blood and Marrow Transplantation (EBMT) in attempt to provide guidance to the health care providers managing these patient populations. RESULTS: The protocol on basic oral care outlined in this position paper is presented based on the following principles: prevention of infections, pain control, maintaining oral function, the interplay with managing oral complications of cancer treatment and improving quality of life. CONCLUSION: Using these fundamental elements, we developed a protocol to assist the health care provider and present a practical approach for basic oral care. Research is warranted to provide robust scientific evidence and to enhance this clinical protocol.Sharon Elad ... Richard M. Logan ... et al

Basic oral care for hematology-oncology patients and hematopoietic stem cell transplantation recipients: a position paper from the joint task force of mascc/isoo and ebmt

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