Specific Histopathological Findings Research Articles

Interpreting Histopathology Reports of Temporal Artery Biopsies Positive for Giant Cell Arteritis (GCA): A Single-Center Retrospective Study.

The gold standard for diagnosing giant cell arteritis (GCA) is temporal artery biopsy (TAB). However, specific histopathologic findings on biopsy reports are rarely considered in the context of the patient's clinical presentation. The purpose of this study was to analyze the correlation of specific biopsy findings with the clinical presentation of patients with GCA. Retrospective chart review of patients with a clinical and histopathologic diagnosis of GCA at a single tertiary care neuro-ophthalmology practice from January 2014 to September 2023. Histopathologic findings on TAB were recorded for each patient, along with clinical history, examination, and treatment. Continuous variables were reported as mean values with standard deviations (SD), while categorical variables were described as percentages. Correlation coefficients with P-values were used to evaluate the relationship between biopsy findings and clinical data. A total of 53 patients were included. TAB specimens ranged in length from 0.6 to 3.4 cm, with a statistically significant correlation coefficient between specimen length and total number of positive findings on the biopsy report. A positive correlation coefficient that approached statistical significance was found between the presence of lymphocytes in the biopsy and permanent vision loss (R = 0.253, P-value 0.054), which occurred in 27 patients. Patients were treated with steroids prebiopsy for an average of 9 days; there was no statistically significant correlation between the duration of steroid treatment and the presence of specific histopathologic findings other than involvement of the intima. The results of this study demonstrate that (1) longer temporal artery biopsy specimens are significantly correlated with a higher number of findings on biopsy reports; (2) the presence of arterial stenosis, eosinophils, and lymphocytes correlated with permanent vision loss or degree of vision loss; and (3) the duration of steroid treatment had a significant inverse correlation with intimal involvement but did not affect other histopathologic findings seen with GCA. This retrospective observational study provides clinicians with an approach to understanding the nuances of the histopathologic findings on their patient's TAB report.

Evidence based treatment for lupus nephritis: present perspectives and challenges.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease known for its high heterogeneity among individuals, which affects various organs including the kidneys. Lupus nephritis (LN) is a frequent and life-threatening manifestation of the disease, with up to 50% of patients developing kidney involvement. Classification of renal involvement in lupus is based on specific histopathological findings, guiding therapeutical decisions. Immunosuppressive therapy, particularly glucocorticoids combined with cyclophosphamide or mycophenolate mofetil, has been the mainstay of treatment for many years, while rates of complete remission have not changed dramatically. Despite advancements in therapy, in an important proportion of patients LN leads to end-stage kidney disease (ESKD). Emerging therapies including belimumab, voclosporin, and obinutuzumab offer promising results in improving renal outcomes, especially in refractory or relapsing disease. Maintenance therapy is crucial to prevent disease flares and preserve renal function. Supportive measures including lifestyle modifications and non-immunosuppressive pharmacological interventions are nowadays also essential in managing LN. This review emphasizes recent advances of therapy and challenges regarding treatment optimization with strategies to improve long-term outcomes.

An Exuberant Case of Ulceronodular-Rupioid (Malignant) Syphilis in an HIV Patient: A Proposal for New Diagnostic Criteria.

We report the case of a 28-year-old male with uncontrolled human immunodeficiency virus (HIV) infection who presented with extensive ulcerated lesions with dark lamellated crusting on his face, torso, and limbs. The patient had a rapid plasma reagin (RPR) titer of 1:512, indicative of syphilis. A skin biopsy revealed granulomata surrounded by lymphocytes, histiocytes, and plasma cells, with spirochetes visible on immunohistochemical staining. The patient's rash resolved with hyperpigmented scarring after penicillin and doxycycline treatment. This severe form of secondary syphilis has been termed malignant syphilis, lues maligna, ulceronodular syphilis, or rupioid syphilis. We propose a single descriptive name for this entity, ulceronodular-rupioid syphilis. In 1969, Fisher proposed criteria for malignant syphilis based on lesion appearance, histopathologic findings, high RPR values, and rapid response to treatment. We found that the Fisher criteria were imprecise with respect to specific histopathologic findings, the quantitation of RPR values, and what constitutes rapid response to treatment. Thus, we examined an additional 74 cases from the literature and propose new diagnostic criteria based on rash appearance, histopathologic characteristics, non-treponemal and treponemal test positivity, and response to therapy. We also found that uncontrolled viremia, and not a low CD4 count, is a major risk factor for ulceronodular-rupioid syphilis in HIV patients.

Portosinusoidal Vascular Disorder: A Heretofore Unrecognized Manifestation of Sickle Cell Disease?

Portosinusoidal vascular disorder (PSVD) is a recently proposed histopathologic entity that encompasses a spectrum of often subtle hepatic microvascular lesions and related microarchitectural abnormalities. Clinical manifestations may arise years after histologic diagnosis and include extrahepatic portal vein thrombosis and portal hypertension. While the histopathologic features of PSVD have been associated with numerous clinical conditions, most notably prothrombotic/vasculopathic disorders, PSVD has not yet been described in sickle cell disease. This gap is striking given the central role of microvascular dysfunction in sickle cell disease and well-described patterns of hepatic injury and dysfunction in this population. This case series is the first to explore the prevalence and pathogenesis of PSVD in sickle cell disease. Forty-one diagnostically adequate liver biopsies from patients with sickle cell disease were identified across the archives of 5 tertiary medical centers. All biopsies exhibited at least 1 histopathologic feature associated with PSVD (mean 3.8 features/case). Overall, 90.2% of patients met the criteria for a diagnosis of PSVD based on the presence of specific histopathologic and/or clinical findings. Immunohistochemical stains for von Willebrand factor, CD34, and glutamine synthetase were performed on 36 cases (87.8%). Aberrant (centrilobular sinusoidal) CD34 and von Willebrand factor staining was present in 97.2% and 86.1% of cases, respectively. Glutamine synthetase reactivity was at least mildly decreased in zone 3 hepatocytes in 52.8% of cases. We posit that chronic erythrocyte sickling results in dysfunction and remodeling of the portal microvasculature, culminating in regression of zone 3 hepatocytes. The presence of PSVD may explain, at least in part, the hepatic dysfunction observed in this patient population. These patients may also benefit from extended clinical surveillance for portal hypertension and other complications. While subtle and prone to overdiagnosis, the features of PSVD should be carefully considered when interpreting liver biopsies from patients with sickle cell disease.

Single cell RNA sequencing sheds light on infiltrating T cells in idiopathic inflammatory myopathies.

Idiopathic inflammatory myopathies (IIM), also referred to as "myositis," are a group of heterogeneous autoimmune disorders characterised by muscle weakness, atrophy and progressive reduced mobility (Lundberg etal, 2021). IIM represent a significant health burden in adult populations, affecting individuals at a mean ageof 50 with an estimated prevalence of 2.9-34 per 100,000 (Dobloug etal, 2015; Svensson etal, 2017). IIM encompass several subtypes including dermatomyositis, immune-mediated necrotising myopathy, inclusion-body myositis, antisynthetase syndrome and polymyositis, which are characterised by specific clinical features, histopathological findings and autoantibody status (Pinal-Fernandez etal, 2020).

Intrauterine life to adulthood: a potential risk factor for chronic kidney disease.

Multiple risk factors for chronic kidney disease (CKD), one of the major causes of morbidity and mortality in the adult population globally, have been identified, including older age, male gender, family history, smoking, diabetes mellitus, hypertension, ischaemic heart diseases and various medications. Preterm delivery, affecting >10% of the newborns in the USA, is a global concern with increasing incidence in recent decades. Preterm birth has been linked to multiple medical comorbidities such as diabetes mellitus, hypertension and cardiovascular diseases, while its association with CKD has recently been investigated. Prematurity and intrauterine growth restriction (IUGR) have been associated with an increased risk for CKD, specific histopathological examination findings and CKD-associated risk factors such as diabetes mellitus, hypertension and dyslipidaemia. In this narrative review, our aim is to evaluate and summarize the association between the risk for CKD and prematurity, low birthweight and IUGR along with potential underlying pathophysiological mechanisms.

History of Various Classifications of Gastritis

Gastritis is common worldwide. The combination of Helicobacter pylori (H. pylori) infection with background gastritis, including atrophic gastritis or intestinal metaplasia is implicated as an important etiopathogenetic contributor to gastric cancer. Since the gastritis classification proposed by Schindler, research has focused on classification of gastritis for accurate diagnosis and prediction of prognosis. Advances in endoscopic technology have enabled more accurate visualization of the gastric mucosa and ‘targeted’ biopsies with the emergence of newer classifications based on visual findings (Kimura-Takemoto classification) and more specific histopathological findings using targeted biopsies (Whitehead classification). Following the discovery of H. pylori, it is mandatory to consider its role as an important contributor to gastritis. Therefore, it was necessary to redefine the classification of gastritis and arrive at a consensus, which led to the establishment of an international consensus classification, referred to as the Sydney system. However, the Sydney system alone cannot predict the gastric cancer risk, and scoring systems such as the Operative Link for Gastritis Assessment and the Operative Link on Gastritis Assessment based on Intestinal Metaplasia were proposed. These systems are based on histopathological findings observed in endoscopic biopsy specimens. However, availability of high-definition images following technological advances has facilitated the emergence of a visual classification, the Kyoto classification. In contrast to the Sydney system, the Kyoto classification is based exclusively on interpretation of visual findings and focuses on detection of H. pylori infection and gastric cancer prediction. In this review, we summarize the history and background of the various classifications of gastritis.

Associations Between Kidney Histopathologic Lesions and Incident Cardiovascular Disease in Adults With Chronic Kidney Disease

Histologic lesions in the kidney may reflect or contribute to systemic processes that may lead to adverse cardiovascular events. To assess the association between kidney histopathologic lesion severity and the risk of incident major adverse cardiovascular events (MACE). This prospective observational cohort study included participants without a history of myocardial infarction, stroke, or heart failure from the Boston Kidney Biopsy Cohort recruited from 2 academic medical centers in Boston, Massachusetts. Data were collected from September 2006 and November 2018, and data were analyzed from March to November 2021. Semiquantitative severity scores for kidney histopathologic lesions adjudicated by 2 kidney pathologists, a modified kidney pathology chronicity score, and primary clinicopathologic diagnostic categories. The main outcome was the composite of death or incident MACE, which included myocardial infarction, stroke, and heart failure hospitalization. All cardiovascular events were independently adjudicated by 2 investigators. Cox proportional hazards models estimated associations of histopathologic lesions and scores with cardiovascular events adjusted for demographic characteristics, clinical risk factors, estimated glomerular filtration rate (eGFR), and proteinuria. Of 597 included participants, 308 (51.6%) were women, and the mean (SD) age was 51 (17) years. The mean (SD) eGFR was 59 (37) mL/min per 1.73 m2, and the median (IQR) urine protein to creatinine ratio was 1.54 (0.39-3.95). The most common primary clinicopathologic diagnoses were lupus nephritis, IgA nephropathy, and diabetic nephropathy. Over a median (IQR) of 5.5 (3.3-8.7) years of follow-up, the composite of death or incident MACE occurred in 126 participants (37 per 1000 person-years). Compared with the reference group of individuals with proliferative glomerulonephritis, the risk of death or incident MACE was highest in individuals with nonproliferative glomerulopathy (hazard ratio [HR], 2.61; 95% CI, 1.30-5.22; P = .002), diabetic nephropathy (HR, 3.56; 95% CI, 1.62-7.83; P = .002), and kidney vascular diseases (HR, 2.86; 95% CI, 1.51-5.41; P = .001) in fully adjusted models. The presence of mesangial expansion (HR, 2.98; 95% CI, 1.08-8.30; P = .04) and arteriolar sclerosis (HR, 1.68; 95% CI, 1.03-2.72; P = .04) were associated with an increased risk of death or MACE. Compared with minimal chronicity, greater chronicity was significantly associated with an increased risk of death or MACE (severe: HR, 2.50; 95% CI, 1.06-5.87; P = .04; moderate: HR, 1.66; 95% CI, 0.74-3.75; P = .22; mild: HR, 2.22; 95% CI, 1.01-4.89; P = .047) in fully adjusted models. In this study, specific kidney histopathological findings were associated with increased risks of CVD events. These results provide potential insight into mechanisms of the heart-kidney relationship beyond those provided by eGFR and proteinuria.

Risk Reassessment of Differentiated Thyroid Cancer in Ahvaz, Iran: A Cross-sectional Retrospective Study.

Accurate evaluation of response to treatment in differentiated thyroid cancer (DTC) is the sine qua non of preventing over-treatment in low-risk patients and implementing appropriate interventions in high-risk individuals. This study aimed to assess the response to therapy in DTC patients based on dynamic stratification method. In this cross-sectional study, 154 medical records of subjects with DTC (with at least 6 months after total thyroidectomy) and referred to endocrinology clinics in Ahvaz, Iran, from April 2020 to May 2021 were examined. Patients were stratified according to a dynamic risk stratification system (informed by their specific clinical, histopathological, and ultrasonography findings, and other diagnostic imagines) into four groups: Excellent response (ER), indeterminate response (IR), biochemical incomplete response (BIR), and structural incomplete response (SIR). For a mean follow-up period of 28.59 months, excellent response to treatment was observed in 92 patients (59.7%), indeterminate response to treatment was found in 32 patients (20.8%), biochemical incomplete response was detected in 2 patients (1.3%), and structural incomplete response was seen in 28 patients (18.2%). In the group with low risk of recurrence, ER and IR were observed in 79.2% and 15.6% of the patients, respectively (P < 0.0001). In the group with an intermediate risk of recurrence, ER was found in 32% of the patients, while IR and SIR + BIR were seen in 34% and 34% of the patients, respectively (P < 0.0001). No cases of ER or IR were observed in the group with high risk (P = 0.001). In sum, response to treatment significantly varied based on dynamic risk stratification, with ER being highest in the low-risk group, less likely in moderate risk group, and undetected in the high-risk group.

Update on the Diagnosis of Behçet's Disease.

Behçet's disease (BD) is a systemic inflammatory disease with unknown etiology. It is characterized by recurrent mucocutaneous lesions and major organ disease such as ocular, neurologic, vascular, and gastrointestinal manifestations. The diagnosis of BD is mainly based on clinical manifestations after ruling out other potential causes. There are no specific laboratory, histopathologic, or genetic findings for the diagnosis of BD. The International Study Group (ISG) criteria set is still the most widely used set for the diagnosis. The main limitation of this criteria set is the lack of major organ manifestations such as vascular, neurologic, and gastrointestinal involvement. The ICBD 2014 criteria are more sensitive, especially in early disease. However, patients with such as spondyloarthritis can easily meet this criteria set, causing overdiagnosis. Diagnosing BD can be a big challenge in daily practice, especially in patients presenting with only major organ involvement such as posterior uveitis, neurologic, vascular, and gastrointestinal findings with or without oral ulcers. These patients do not meet ISG criteria and can be diagnosed with "expert opinion" in countries with high BD prevalence. The pathergy test is the only diagnostic test used as diagnostic or classification criteria for BD. Our recent studies showed that common femoral vein (CFV) thickness measurement can be a valuable, practical, and cheap diagnostic tool for BD with sensitivity and specificities higher than 80% for the cut-off value of 0.5 mm. However, the diagnostic accuracy of CFV measurement should be investigated in other disease groups in the differential diagnosis of BD and in also different ethnic populations.

Malignant complications of celiac disease: a case series and review of the literature

BackgroundCeliac disease is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Diagnosis is based on evaluating specific autoantibodies and histopathologic findings of duodenal biopsy specimens. The only therapy for celiac disease is a gluten-free diet. Celiac disease can be complicated by malnutrition, other autoimmune diseases, refractoriness to treatment, and gastrointestinal tumors. This article presents seven cases of malignancies in patients with celiac disease. Its objective is to raise awareness of the malignant complications of celiac disease, leading to earlier diagnosis and improved outcomes.Case presentationSeven cases of malignant complications of celiac disease occurred among 190 patients followed at the Department of Internal Medicine and Gastroenterology, University Hospital Brno from 2014 to 2021. We describe these cases and the presentation, diagnostic process, course, management, and outcomes for each, along with proposed potential risk factors of malignant complications. There was one Caucasian man who was 70 years old and six Caucasian women who were 36, 46, 48, 55, 73, and 82 years old in our cohort. Of the seven cases of malignancies in our cohort, four patients were diagnosed with small bowel adenocarcinoma, one with diffuse large B-cell lymphoma, one with carcinoma of the tongue, and one with colorectal carcinoma.ConclusionsMalignancies occurred in 3.7% of patients followed up for celiac disease. Awareness of the malignant complications of celiac disease, risk factors, presentation, and disease course could lead to earlier diagnosis and improved outcomes.

Severe Antenatal Hypertrophic Cardiomyopathy Secondary to ACAD9-Related Mitochondrial Complex I Deficiency

Introduction: Antenatal presentation of hypertrophic cardiomyopathy (HCM) is rare. We describe familial recurrence of antenatal HCM associated with intrauterine growth restriction and the diagnostic process undertaken. Methods: Two pregnancies with antenatal HCM were followed up. Biological assessment including metabolic analyses, genetic analyses, and respiratory chain study was performed. We describe the clinical course of these two pregnancies, antenatal manifestations as well as specific histopathological findings, and review the literature. Results: The assessment revealed a deficiency in complex I of the respiratory chain and two likely pathogenic variations in the ACAD9 gene. Discussion and Conclusion: Antenatal HCM is rare and a diagnosis is not always made. In pregnancies presenting with cardiomyopathy and intrauterine growth restriction, ACAD9 deficiency should be considered as one of the potential underlying diagnoses, and ACAD9 molecular testing should be included among other prenatal investigations.

Usefulness of Urinary Biomarkers for Assessing Bladder Condition and Histopathology in Patients with Interstitial Cystitis/Bladder Pain Syndrome.

This study investigated the usefulness of urinary biomarkers for assessing bladder condition and histopathology in patients with interstitial cystitis/bladder pain syndrome (IC/BPS). We retrospectively enrolled 315 patients (267 women and 48 men) diagnosed with IC/BPS and 30 controls. Data on clinical and urodynamic characteristics (visual analog scale (VAS) score and bladder capacity) and cystoscopic hydrodistention findings (Hunner’s lesion, glomerulation grade, and maximal bladder capacity (MBC)) were recorded. Urine samples were utilized to assay inflammatory, neurogenic, and oxidative stress biomarkers, including interleukin (IL)-8, C-X-C motif chemokine ligand 10 (CXCL10), monocyte chemoattractant protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), eotaxin, IL-6, macrophage inflammatory protein 1 beta (MIP-1β), regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 8-isoproatane, and total antioxidant capacity. Further, specific histopathological findings were identified via bladder biopsy. The associations between urinary biomarker levels and bladder conditions and histopathological findings were evaluated. The results reveal that patients with IC/BPS had significantly higher urinary MCP-1, eotaxin, TNF-α, PGE2, 8-OHdG, and 8-isoprostane levels than controls. Patients with Hunner’s IC (HIC) had significantly higher IL-8, CXCL10, BDNF, eotaxin, IL-6, MIP-1β, and RANTES levels than those with non-Hunner’s IC (NHIC). Patients with NHIC who had an MBC of ≤760 mL had significantly high urinary CXCL10, MCP-1, eotaxin, IL-6, MIP-1β, RANTES, PGE2, and 8-isoprostane levels and total antioxidant capacity. Patients with NHIC who had a higher glomerulation grade had significantly high urinary MCP-1, IL-6, RANTES, 8-OHdG, and 8-isoprostane levels. A significant association was observed between urinary biomarkers and glomerulation grade, MBC, VAS score, and bladder sensation. However, bladder-specific histopathological findings were not well correlated with urinary biomarker levels. The urinary biomarker levels can be useful for identifying HIC and different NHIC subtypes. Higher urinary inflammatory and oxidative stress biomarker levels are associated with IC/BPS. Most urinary biomarkers are not correlated with specific bladder histopathological findings; nevertheless, they are more important in the assessment of bladder condition than bladder histopathology.

S2600 Gastric Mucormycosis: A Case of a Rare Infectious Cause of Upper GI Bleeding

Introduction: Gastric mucormycosis is a rare clinical entity that mandates upper endoscopic evaluation and specific histopathologic findings for a diagnosis. Due to its non-specific clinical presentation, it poses a diagnostic challenge for providers. We present a case of gastric mucormycosis in a critically ill and immunosuppressed patient that was discovered in the setting of evaluation of upper gastrointestinal bleeding. Case Description/Methods: A 66-year-old man with a history of a kidney transplant two years prior, with a recent diagnosis of post-transplant lymphoproliferative disorder (PTLD) and who had recently undergone an initial round of R-CHOP chemotherapy four weeks prior was admitted to the hospital with altered mentation and neutropenia. His hospital course was prolonged with multiple cardiac arrests in the setting of septic shock from his profound neutropenia. He was noted to have dark blood from his nasogastric tube and a concomitant drop in his hemoglobin, for which the Gastroenterology service was consulted. He underwent urgent upper endoscopic evaluation and was found to have both significant clot in his stomach and an ulcerated fungating lesion along the greater curvature of the stomach which was biopsied. Pathology results showed fungal organisms with special GMS stain showing morphologic features consistent with mucormycosis. The Infectious Diseases service was urgently consulted and he was started on triple anti-fungal therapy with amphotericin, micafungin and posaconazole. Otolaryngology evaluated the patient due to these endoscopic findings, with laryngoscopy negative for head and neck involvement of this infection. Surgery was consulted for evaluation of subtotal gastrectomy, but he was deemed an unsuitable surgical candidate. The patient eventually succumbed to this and passed away during his hospitalization. Discussion: Gastric mucormycosis is a rare infection that often manifests in the setting of immunosuppression as seen in solid organ transplant recipients or in patients with diabetes. The most often clinical manifestation is upper gastrointestinal bleeding, and thus endoscopic evaluation is part of the work-up to exclude other diseases that could mimic its presentation. This diagnosis often results in fatal outcomes, so early recognition is critical for both medical management with anti-fungal therapy, along with surgical management given the high failure rate of medical management alone for this diagnosis.

Dengue infection triggered immune mediated necrotizing myopathy in children: a case report and literature review

BackgroundImmune-mediated necrotizing myopathy (IMNM) is a subgroup of idiopathic inflammatory myopathies manifesting with progressive weakness, elevated serum creatine kinase (CK) levels, and necrotizing myopathic features on muscle biopsy. There is a paucity of data on the clinical presentation of IMNM in children. We report a paediatric patient who developed anti-3-hydroxy-3-methylglutaryl-CoA reductase (anti-HMGCR)-positive necrotizing myopathy after recent dengue infection.Case presentationA previously healthy 9-year-old boy presented with acute proximal muscle weakness after recovery from dengue infection. Five days after the fever subsided, he could not stand from a squatting position. He denied having skin rash, arthritis, or other systemic features. He had marked elevation of CK level of 30,833 mg/dL and was put on steroid therapy. The patient initially responded to oral prednisolone, however the weakness persisted and muscle enzymes increased as steroids were decreased. He was then referred to our hospital for further assessment. Subsequent investigation revealed anti-HMGCR positivity along with specific histopathological findings consistent with IMNM. The patient was treated with six cycles of intravenous immunoglobulin (IVIG) monthly, then followed by a gradual taper of prednisolone and oral methotrexate weekly with complete recovery in motor power.ConclusionsOur report presents a child with clinical manifestations of IMNM which can be categorized as acute onset of muscle weakness following dengue infection. Two key points supporting a diagnosis in this case are clinical response after immunosuppressive therapy and absence of rashes found in juvenile dermatomyositis.

Reactive granulomatous dermatitis as a clinically relevant and unifying term: a retrospective review of clinical features, associated systemic diseases, histopathology and treatment for a series of 65 patients at Mayo Clinic.

Reactive granulomatous dermatitis (RGD) is an umbrella term used to describe interstitial granulomatous dermatitis (IGD), palisaded neutrophilic and granulomatous dermatitis (PNGD), and interstitial granulomatous drug eruption (IGDR). The aim of this study was to describe systemic associations of RGD, explore possible associations between histopathologic findings and systemic RGD associations and determine clinical relevance of RGD subtypes. We retrospectively studied clinical and histopathologic characteristics of patients with RGD from 1990 through 2020. Of 65 patients with RGD (41 women, 24 men; median age at diagnosis, 62 years), 37 had IGD, 26 had PNGD, and 2 had IGDR. Fifty patients (76.9%) had an associated systemic condition; rheumatologic conditions were identified for 34 (52.3%) patients. The associated systemic condition occurred before RGD in approximately 75% of patients. Statistical analyses did not show significant associations between specific subtypes of RGD and systemic diseases or treatment response, and specific histopathologic findings were not predictive of an associated systemic disease. Although most patients with RGD had an associated systemic condition, subtypes of RGD did not correlate with systemic associations, lending support to the use of the umbrella term RGD.

Clinicopathologic Associations in a Large International Cohort of Patients With Giant Cell Arteritis

In addition to aiding in diagnosis, histopathologic findings from temporal artery biopsy (TAB) specimens in giant cell arteritis (GCA) may be valuable for their associations with clinical features of the disease. This study was undertaken to compare histopathologic findings on TAB with biopsy interpretation and demographic, clinical, and imaging features at time of diagnosis. Patients with a clinical diagnosis of GCA who had a TAB were selected from an international, multicenter observational cohort of vasculitis. Associations between demographic, clinical, radiographic, and histopathologic features were identified using bivariate testing and multivariate regression modeling. Of 705 patients with GCA who underwent TAB, 69% had histopathologic evidence of definite vasculitis. Specific histopathologic findings included the presence of giant cells (51%), fragmentation of the internal elastic lamina (41%), intimal thickening (33%), and predominantly mononuclear leukocyte infiltration (32%). Histopathologic interpretation of definite vasculitis was independently associated with giant cells (odds ratio [OR] 151.8 [95% confidence interval (95% CI) 60.2-551.6]), predominantly mononuclear leukocyte infiltration (OR 11.8 [95% CI 5.9-24.9]), and fragmentation of the internal elastic lamina (OR 3.7 [95% CI 1.9-7.4]). A halo sign on temporal artery ultrasound and luminal damage of large arteries on angiography were significantly associated with presence of giant cells (OR 2.6 [95% CI 1.1-6.5] and OR 2.4 [95% CI 1.1-5.2], respectively). Specific histopathologic findings were associated with older age, but no associations were identified with vision loss or other clinical features. Histopathologic findings in GCA are strongly associated with the clinical diagnosis of GCA but have a limited role in identifying patterns of disease.

Anti-HLA DQ Antibodies Are Associated with Chronic Lung Allograft Dysfunction in a Pediatric Lung Transplant Population

<h3>Purpose</h3> Chronic lung allograft dysfunction (CLAD) limits long term survival after lung transplantation. Antibody mediated rejection (AMR) has been associated with earlier CLAD development, but studies are limited in children. Clinical AMR can exist on a spectrum from subclinical to definite AMR based on the presence of anti-HLA donor specific antibodies (DSA), allograft dysfunction, and histopathologic findings, with DSA development first to appear. This study aims to describe the relationship of elevated DSA with clinical outcomes in a single center pediatric lung transplant population. <h3>Methods</h3> This was a single center, retrospective study. Pediatric bilateral lung transplant recipients were included from 2002-2020 if they had longitudinal HLA and lung function data for at least 6 months after transplantation. Preliminary analyses with chi-squared or Fisher's exact test for categorical variables and ANOVA or Kruskal-Wallis for continuous variables were used. DSA were detected with single-antigen bead arrays, and elevated DSA was defined as a mean fluorescence intensity level above 500. <h3>Results</h3> 34 patients were included: 19 with elevated DSA and 15 without. Most patients had subclinical AMR (n=10) without allograft dysfunction and two patients had definite AMR, based on the 2018 Banff consensus statement. The proportion of patients who developed CLAD was significantly higher in the elevated DSA group and had an earlier onset of CLAD. Average graft longevity and rates of acute cellular rejection, while not significant, trended towards shorter survival and higher rates of rejection in the elevated DSA group. All persistently elevated DSA were directed against HLA Class II DQ (6 of 14 patients) epitopes. Survival analysis and the significance of different HLA antigens remains ongoing. <h3>Conclusion</h3> The development of persistently elevated HLA Class II DQ DSA is associated with CLAD and likely decreased survival in the pediatric lung transplant population.

Sinonasal Schwannoma: Retrospective Review of Cases from 1997-2016 at A Tertiary Referral Centre

Sinonasal schwannomas (SNS) are benign neoplasms of peripheral nerve sheaths within sinonasal cavities and little is known about them. We aim to expand current literature by analysing all cases of SNS at the National University of Malaysia Medical Centre (UKMMC). There were five females and one male in this study. Mean age was 52.3±2.1 years (range 42-75). The mean tumour size was 3.6cm±0.1 (range 1.50-5.90cm). Tumours originated from outside the sinonasal cavities (n=4) and inside (n=2). Extension was present in five patients. The sinonasal cavity most frequently involved is the maxillary sinus (n=3). Clinical presentation corresponded to site of involvement with facial numbness being the most common presentation. All histopathologically diagnosed cases showed regions of Antoni A, Antoni B, Verocay Bodies and immunoreactivity with S100 protein. Four patients underwent Functional Endoscopic Sinus Surgery (FESS). The presentation of SNS corresponds to their site. Site of involvement is more informative than the site of origin. Endoscopy, CT scans and MRIs are helpful in facilitating an accurate diagnosis. SNS show specific histopathological findings and its main treatment is FESS.

A Pattern-based Pathology Approach to Very Early-onset Inflammatory Bowel Disease: Thinking Beyond Crohn Disease and Ulcerative Colitis.

Very early-onset inflammatory bowel disease (VEO-IBD), IBD diagnosed in children younger than 6 years old, is phenotypically and genetically distinct from older onset IBD. Monogenic and digenic causative defects, particularly in primary immunodeficiency and intestinal epithelial barrier genes, have been identified in a subset of patients with VEO-IBD allowing for targeted therapies and improved outcomes. However, these findings are the minority, thus strategies to correctly diagnose patients, including identification of specific histopathologic findings with correlating clinical and laboratory features may provide critical and necessary insight into mechanisms of disease pathogenesis and subsequent therapeutic options. In this article, we review the pathologic findings seen in patients with VEO-IBD and outline a pattern-based approach to diagnosis using examples from primary immunodeficiencies with gastrointestinal manifestations.