Pathology Trainee Redeployment and Education During the COVID-19 Pandemic: An Institutional Experience.

Pathology training programs throughout the United States have endured unprecedented challenges dealing with the ongoing coronavirus disease 2019 pandemic. At Houston Methodist Hospital, the Department of Pathology and Genomic Medicine planned and executed a trainee-oriented, stepwise emergency response. The focus was on optimizing workflows among areas of both clinical and anatomic pathology, maintaining an excellent educational experience, and minimizing trainee exposure to coronavirus disease 2019. During the first phase of the response, trainees were divided into 2 groups: one working on-site and the other working remotely. With the progression of the pandemic, all trainees were called back on-site and further redeployed within our department to meet the significantly increased workload demands of our clinical laboratory services. Adjustments to trainee educational activities included, among others, the organization of a daily coronavirus disease 2019 virtual seminar series. This series served to facilitate communication between faculty, laboratory managers, and trainees. Moreover, it became a forum for trainees to provide updates on individual service workflows and volumes, ongoing projects and research, as well as literature reviews on coronavirus disease 2019-related topics. From our program's experience, redeploying pathology trainees within our department during the coronavirus disease 2019 pandemic resulted in optimization of patient care while ensuring trainee safety, and importantly, helped to maintain continuous high-quality education through active involvement in unique learning opportunities.

The Prevalence and Role of Hemoglobin Variants in Biometric Screening of a Multiethnic Population: One Large Health System's Experience.

OBJECTIVES: To characterize and quantitate hemoglobin (Hb) variants discovered during biometric hemoglobin A1c (HbA1c) analyses in a large multiethnic population with a focus on the effect of variants on testing method and results. METHODS: In total, 13,913 individuals had their HbA1c measured via ion-exchange high-performance liquid chromatography. Samples that had a variant Hb detected or HbF fraction more than 25% underwent variant Hb characterization and confirmation by gel electrophoresis. RBC indices were also evaluated for possible concomitant thalassemia. RESULTS: Of the 13,913 individuals evaluated, 524 (3.77%) had an Hb variant. The prevalence of each variant was as follows: HbS trait (n = 396, 2.85%), HbSS disease (n = 4, 0.03%), HbC trait (n = 85, 0.61%), HbCC disease (n = 2, 0.01%), HbSC disease (n = 5, 0.04%), HbE trait (n = 18, 0.13%), HbD or G trait (n = 9, 0.06%), HbS ß-thalassemia + disease (n = 1, 0.01%), hereditary persistence of HbF (n = 2, 0.01%), and HbMontgomery trait (n = 1, 0.01%). Concomitant α-thalassemia was detected in 20 (3.82%) of the 524 individuals with an Hb variant. CONCLUSIONS: This study represents one of the largest epidemiologic investigations into the prevalence of Hb variants in a North American metropolitan, multiethnic workforce and their dependents and reinforces the importance of method selection in populations with Hb variants.

Investigating the Abscopal Effects of Radioablation on Shielded Bone Marrow in Rodent Models Using Multimodality Imaging.

The abscopal effect is the response to radiation at sites that are distant from the irradiated site of an organism, and it is thought to play a role in bone marrow (BM) recovery by initiating responses in the unirradiated bone marrow. Understanding the mechanism of this effect has applications in treating BM failure (BMF) and BM transplantation (BMT), and improving survival of nuclear disaster victims. Here, we investigated the use of multimodality imaging as a translational tool to longitudinally assess bone marrow recovery. We used positron emission tomography/computed tomography (PET/CT), magnetic resonance imaging (MRI) and optical imaging to quantify bone marrow activity, vascular response and marrow repopulation in fully and partially irradiated rodent models. We further measured the effects of radiation on serum cytokine levels, hematopoietic cell counts and histology. PET/CT imaging revealed a radiation-induced increase in proliferation in the shielded bone marrow (SBM) compared to exposed bone marrow (EBM) and sham controls. T2-weighted MRI showed radiation-induced hemorrhaging in the EBM and unirradiated SBM. In the EBM and SBM groups, we found alterations in serum cytokine and hormone levels and in hematopoietic cell population proportions, and histological evidence of osteoblast activation at the bone marrow interface. Importantly, we generated a BMT mouse model using fluorescent-labeled bone marrow donor cells and performed fluorescent imaging to reveal the migration of bone marrow cells from shielded to radioablated sites. Our study validates the use of multimodality imaging to monitor bone marrow recovery and provides evidence for the abscopal response in promoting bone marrow recovery after irradiation.

Detection of malignancy in body fluids: a comparison of the hematology and cytology laboratories.

CONTEXT: Body fluids submitted to the hematology laboratory for cell counts may also be examined for the presence of malignancy. Previous studies evaluating the hematology laboratory's performance at detecting malignancy in body fluids have reached conflicting conclusions. OBJECTIVE: To investigate the hematology laboratory's ability to detect malignancy in body fluids by comparison with cytology. DESIGN: Retrospective analysis of 414 body fluid samples during an 18-month period, with introduction of new quality assurance measures after the first 210 cases. If no concurrent cytology was ordered, results were compared with recent previous and/or subsequent cytologic, histologic, or flow cytometric diagnoses. RESULTS: Of the initial 210 cases, the hematology laboratory detected 3 of 13 malignancies diagnosed by concurrent cytology (23% sensitivity), with no false-positives (100% specificity). Malignancy was not identified on retrospective review of the hematology slides in the 10 discrepant cases. After the initial study, educational sessions on morphology for the medical technologists and a more thorough hematology-cytology correlation policy were implemented. The subsequent 204 hematology laboratory cases had increased sensitivity for the detection of malignancy (60%; 6 of 10). Definitive features of malignancy were seen in only one discrepant hematology laboratory slide on retrospective review. This case had not been flagged for hematopathologist review. None of the discrepancies before or after implementation of the additional quality assurance measures impacted patient care. CONCLUSIONS: Body fluid processing by the hematology laboratory is not optimized for the detection of malignancy. Concurrent cytologic examination is critical for the detection of malignancy, and needs to be considered as cost-saving measures are increasingly implemented.

Histological changes and risk factor associations in type 2 atherosclerotic lesions (fatty streaks) in young adults.

OBJECTIVES: The purpose of this study was to investigate which histological changes associated with risk factors could contribute to the progression from the initial atherosclerotic lesions including fatty streaks to the advanced lesions. METHODS: We examined the associations of histomorphometric findings in the determined anatomical sites of mid-thoracic aortas (TAs) and left anterior descending coronary arteries (LADs) with major risk factors for atherosclerosis, using a young autopsied series from the the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. The histological classification by the American Heart Association was graded for 1013 TAs and 1009 LADs. Histometric study, including immunohistochemistry, was performed in type 2 lesions (fatty streaks) of TAs from 59 subjects and LADs from 45 ones. RESULTS: For the progression from the initial lesions into the advanced atherosclerotic lesions, the most effective lipid profiles were low plasma HDL-C in TA and elevated serum non-HDL-C in LAD. This lipid profile of each artery correlated with number or density of intimal smooth muscle cell-derived foam cells, respectively. The serum concentration of non-HDL-C correlated with macrophage foam cells in TAs. Hypertension and hyperglycemia were associated with increase of intimal area and/or collagen content in both arteries, but not with either types of foam cell proliferation. Smoking correlated with increased collagen content in TAs. CONCLUSION: There were histologically different ways of progressing from fatty streaks to advanced atherosclerotic lesions depending on the risk factors. For the atherosclerosis progression from type 2 lesions to advanced lesions, increase in number of smooth muscle cell-derived foam cells could be an important indicator.

Harmonic scalpel versus flexible CO2 laser for tongue resection: a histopathological analysis of thermal damage in human cadavers.

BACKGROUND: Monopolar cautery is the most commonly used surgical cutting and hemostatic tool for head and neck surgery. There are newer technologies that are being utilized with the goal of precise cutting, decreasing blood loss, reducing thermal damage, and allowing faster wound healing. Our study compares thermal damage caused by Harmonic scalpel and CO2 laser to cadaveric tongue. METHODS: Two fresh human cadaver heads were enrolled for the study. Oral tongue was exposed and incisions were made in the tongue akin to a tongue tumor resection using the harmonic scalpel and flexible C02 laser fiber at various settings recommended for surgery. The margins of resection were sampled, labeled, and sent for pathological analysis to assess depth of thermal damage calculated in millimeters. The pathologist was blinded to the surgical tool used. Control tongue tissue was also sent for comparison as a baseline for comparison. RESULTS: Three tongue samples were studied to assess depth of thermal damage by harmonic scalpel. The mean depth of thermal damage was 0.69 (range, 0.51 - 0.82). Five tongue samples were studied to assess depth of thermal damage by CO2 laser. The mean depth of thermal damage was 0.3 (range, 0.22 to 0.43). As expected, control samples showed 0 mm of thermal damage. There was a statistically significant difference between the depth of thermal injury to tongue resection margins by harmonic scalpel as compared to CO2 laser, (p = 0.003). CONCLUSION: In a cadaveric model, flexible CO2 laser fiber causes less depth of thermal damage when compared with harmonic scalpel at settings utilized in our study. However, the relevance of this information in terms of wound healing, hemostasis, safety, cost-effectiveness, and surgical outcomes needs to be further studied in clinical settings.

Trp53 negatively regulates autoimmunity via the STAT3-Th17 axis.

Emerging evidence suggests that the tumor suppressor p53 is also a crucial regulator for many physiological processes. Previous observations indicate that p53 suppresses inflammation by inhibiting inflammatory antigen-presenting cells. To investigate the potential role of p53 in autoimmune effector T cells, we generated p53(null)CD45.1 mice by crossing p53(null)CD45.2 and CD45.1 mice. We demonstrate that p53(null)CD45.1 mice spontaneously developed autoimmunity, with a significant increase in IL-17-producing Th17 effectors in their lymph nodes (4.7 ± 1.0%) compared to the age-matched counterparts (1.9 ± 0.8% for p53(null)CD45.2, 1.1 ± 0.2% for CD45.1, and 0.5 ± 0.1% for CD45.2 mice). Likewise, p53(null)CD45.1 mice possess highly elevated serum levels of inflammatory cytokines IL-17 and IL-6. This enhanced Th17 response results largely from an increased sensitivity of p53(null)CD45.1 T cells to IL-6-induced STAT3 phosphorylation. Administration of STAT3 inhibitor S31-201 (IC50 of 38.0 ± 7.2 µM for IL-6-induced STAT3 phosphorylation), but not PBS control, to p53(null)CD45.1 mice suppressed Th17 effectors and alleviated autoimmune pathology. This is the first report revealing that p53 activity in T cells suppresses autoimmunity by controlling Th17 effectors. This study suggests that p53 serves as a guardian of immunological functions and that the p53-STAT3-Th17 axis might be a therapeutic target for autoimmunity.

Heparin cofactor II in atherosclerotic lesions from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study.

Heparin cofactor II (HCII) is a serine protease inhibitor (serpin) that has been shown to be a predictor of decreased atherosclerosis in the elderly and protective against atherosclerosis in mice. HCII inhibits thrombin in vitro and HCII-thrombin complexes have been detected in human plasma. Moreover, the mechanism of protection against atherosclerosis in mice was determined to be the inhibition of thrombin. Despite this evidence, the presence of HCII in human atherosclerotic tissue has not been reported. In this study, using samples of coronary arteries obtained from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, we explore the local relationship between HCII and (pro)thrombin in atherosclerosis. We found that HCII and (pro)thrombin are co-localized in the lipid-rich necrotic core of atheromas. A significant positive correlation between each protein and the severity of the atherosclerotic lesion was present. These results suggest that HCII is in a position to inhibit thrombin in atherosclerotic lesions where thrombin can exert a proatherogenic inflammatory response. However, these results should be tempered by the additional findings from this, and other studies, that indicate the presence of other plasma proteins (antithrombin, albumin, and alpha(1)-protease inhibitor) in the same localized region of the atheroma.

The effect of age and other atherosclerotic risk factors on carotid artery blood velocity in individuals ranging from young adults to centenarians.

To evaluate the effect of age and other risk factors for atherosclerosis on arterial blood velocity, carotid arteries in 179 healthy individuals ranging from 21 to 102 years old were examined using color Doppler ultrasonography. Velocity in common and internal carotid arteries decreased consecutively from young adults to very elderly people except for peak internal carotid artery velocity. Peak common carotid artery velocity in the elderly (> or = 65 years old) people was inversely associated with age and diastolic blood pressure and directly associated with pulse pressure. Minimum velocity of common carotid artery was inversely correlated with age and diastolic blood pressure in the elderly people. In elderly group, peak internal carotid artery velocity correlated only with serum high-density lipoprotein cholesterol. Minimum internal carotid artery velocity correlated inversely with systolic blood pressure in adults and diastolic blood pressure in elderly people. Blood velocity in the very elderly population approaches the critical level for thrombogenesis.

Bilateral infiltrating renal inflammatory pseudotumor responsive to corticosteroid therapy.

Inflammatory pseudotumor (IPT) is a quasi-neoplastic lesion that most commonly involves the lung, but has been shown to occur in nearly every tissue type. Renal involvement is very uncommon. We report the second case of IPT ever published presenting as bilateral infiltrating renal masses. Although most renal IPTs were treated with nephrectomy, our patient was managed successfully with conservative steroid treatment, thereby avoiding the alternative of dialysis or kidney transplantation.

Histological topographical comparisons of atherosclerosis progression in juveniles and young adults.

BACKGROUND: The histologically topographic comparisons on atherosclerosis progression among three anatomical sites, mid-thoracic and lower abdominal aorta and left anterior descending coronary artery (LAD) were performed using a young population (age 15-34 years) from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. METHODS AND RESULTS: The histological classification based on the American Heart Association grading scheme showed that in the thoracic aorta type 2 lesions (numerous macrophage foam cells with fine particles but no pools of extracellular lipid) appeared in the first 10-year age group, with no significant change in prevalence in the next 10 years. Lesions greater than type 2 were rarely seen in the thoracic aorta. Although type 2 lesions appeared later in the LAD than in the aorta, the lesions within the LAD progressed rapidly to more advanced lesions (types 4 and 5) or atheroma. Lesion development in the abdominal aorta was intermediate to lesion development in the thoracic aorta and the LAD. CONCLUSIONS: The most striking topographic difference on lesion progression among the three anatomical sites was the vulnerability of type 2 lesions to progress into advanced lesions. The histology study, including immunohistochemistry limited to the type 2 lesions suggested that lesion progression was related to the intimal thickness and the amount of collagen but not to the number of macrophage foam cells.

Poorly differentiated carcinoma arising in a Warthin's tumor of the parotid gland: pathogenesis, histopathology, and surgical management of malignant Warthin's tumors.

Warthin's tumor is a benign lymphoepithelial neoplasm representing 10 per cent of all parotid gland tumors. Malignant transformation of a Warthin's tumor is an extremely rare event. We report a case of a patient with poorly differentiated carcinoma arising from a Warthin's tumor, as well as review the pathogenesis, histopathology, and surgical management of malignant Warthin's tumors.

Overexpression of SOCS3 is associated with decreased survival in a cohort of patients with de novo follicular lymphoma.

The prognostic significance of SOCS3 protein expression was determined in de novo follicular lymphomas (FL) with t(14;18) and bcl-2 overexpression. Presentation lymph nodes from 82 FL patients for whom clinical information was available were immunohistochemically segregated into SOCS3-positive (n = 42) or -negative (n = 40) cohorts, and overall survival (OS) was analysed. SOCS3-positive FL patients had a median OS of 10 years compared with 22 years in SOCS3-negative patients (P = 0.001, log rank test). After adjusting for Follicular Lymphoma International Prognostic Index subgroups, SOCS3 overexpression remained an independent predictor of decreased OS (P < 0.001). These findings suggest that overexpression of SOCS3 may be an independent poor prognostic variable in patients with de novo FL.

Elevated serum C-reactive protein levels and advanced atherosclerosis in youth.

OBJECTIVE: To determine the associations among serum C-reactive protein (CRP) concentration, age, sex, risk factors for coronary heart disease (CHD), and atherosclerosis in young people. METHODS AND RESULTS: In 1244 subjects 15 to 34 years of age, we measured gross atherosclerotic lesions in the right coronary artery (RCA) and abdominal aorta (AA) and American Heart Association (AHA) lesion grade in the left anterior descending (LAD) coronary artery; serum CRP, lipoprotein cholesterol, and thiocyanate (for smoking) concentrations; intimal thickness of renal arteries (for hypertension); glycohemoglobin (for hyperglycemia); and body mass index (for obesity). Serum CRP levels increased with age, were higher in women than in men, and were positively related to obesity and hyperglycemia. Serum CRP > or =10 mg/L was associated with more extensive gross raised lesions in the RCA after age 25 and in the AA after age 30. Serum CRP > or =3 was associated with a greater prevalence of AHA grade 5 lesions in the proximal LAD coronary artery after age 25. The associations of CRP with lesions were independent of the traditional CHD risk factors. CONCLUSIONS: Serum CRP level is independently associated with advanced atherosclerosis in young persons.

Risk scores predict atherosclerotic lesions in young people.

BACKGROUND: Atherosclerosis begins in childhood and progresses through young adulthood to form the lesions that cause coronary heart disease. These preclinical lesions are associated with coronary heart disease risk factors in young persons. METHODS: The Pathobiological Determinants of Atherosclerosis in Youth study collected arteries and samples of blood and other tissues from persons aged 15 to 34 years who died of external causes and underwent autopsy in forensic laboratories. We measured the coronary heart disease risk factors and atherosclerotic lesions in the coronary arteries (CAs) (n = 1117) and the abdominal aorta (n = 1458). RESULTS: We developed risk scores, normalized so that a 1-unit increase was equivalent to a 1-year increase in age, to estimate the probability of advanced atherosclerotic lesions in the CAs and the abdominal aorta from age, sex, serum lipoprotein concentrations, smoking, hypertension, obesity, and hyperglycemia. Odds ratios for a 1-unit increase in the risk scores were 1.18 (95% confidence interval, 1.14-1.22) for the CAs and 1.29 (95% confidence interval, 1.23-1.35) for the abdominal aorta. These risk scores had good discrimination (c-indexes: 0.78 for the CAs and 0.84 for the abdominal aorta) and were calibrated. The presence of abdominal aortic lesions increased the likelihood of having CA lesions. CONCLUSION: Risk scores calculated from traditional coronary heart disease risk factors provide a tool for identifying young individuals with a high probability of having advanced atherosclerotic lesions.

Smoking is associated with advanced coronary atherosclerosis in youth.

Smoking is linked to atherosclerosis and coronary heart disease (CHD) in older adults. However, evidence that smoking affects coronary atherosclerosis in young people is incomplete. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Study collected arteries, blood, and other tissues from persons 15 to 34 years of age dying of external causes and autopsied in forensic laboratories. Lesions in the proximal left anterior descending coronary arteries (LAD) from 1127 subjects were graded microscopically according to the American Heart Association criteria. Among individuals with advanced lesions (Grade 4 or 5), smokers had a greater prevalence of Grade 5 lesions than non-smokers (odds ratio 9.61, 95% confidence interval 2.34-39.57), a difference suggesting that smoking accelerates the transition from Grade 4 to Grade 5 lesions. This association occurred among both men and women, and among persons with and without other CHD risk factors. The difference in qualities of advanced lesions suggests that smoking possibly accelerates the transition from Grade 4 to Grade 5 lesions by promoting thrombosis and accretion on the intimal surface of the plaque.