bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictive value of ABO blood type with Carcinoembryonic antigen in a Nigerians population with preoperative Colorectal Cancer
Authors: Nwadike C N , Nnodim J , Anyagwa M K , Edward U , Ogbuokiri D K , Umeh O N , Duru M K
Published: October 2020

Introduction/Objective

Earlier studies speculated possible link between ABO blood type and risk of malignancies.

Given recent increase in Colorectal cancer (CRC) cases in Nigeria amidst poor facilities for early diagnosis, unraveling measures for prevention and prognosis become critical options. This study aims at assessing the predictive association of ABO blood types with preoperative Carcinoembryonic antigen (CEA) levels and some markers of gut immunostasis among southern Nigerian population with CRC.

Methods

The retrospective study evaluated 200 patients, scheduled for resection surgery for CRC between July, 2018 and September 2019 in Federal medical center Yenegoa, Nigeria. The relationship between the ABO blood types and CEA, interleukins, IL(6 and 8,) and Short chain fatty acids, SCFA (butyrate and propionate) were evaluated preoperatively using immunoturbidimetric assay, ELISA, and GC-MS respectively. The mean age of the patients was 51 years. The distribution of the ABO blood types in the patients were 60 (30.1%) for A, 50 (25%) for B, 79 (39.5%) for O, and 11 (5.5%) for AB. Patients with CEA levels <5 ng/mL, 6-30 ng/mL, and >30 ng/mL were classified as CEA Group 1, group 2 and group 3 respectively. Patient’s blood types, demographic characteristics and tumor locations, were recorded. SPSS, 22 was employed for data analysis.

Results

We determined a significant correlation between CEA levels and IL 6 in different blood types of CRC patients. No significant correlation was observed between CEA and gender. Blood type A showed significant increase in mean levels of CEA and IL 6 when compared to blood type B and O. No significant difference was observed in the mean SCFA levels among different blood types.

Conclusion

ABO blood type demonstrated significant prognostic value with CEA in colorectal cancer, with blood type A being most unfavorable.
Applying The Best Practice For Internal Quality Control (IQC) Management, Consolidation And Review Process In Sidra Medicine Clinical Chemistry Division
Authors: Asinas J M
Published: October 2020

Introduction/Objective

The management of internal quality control (IQC) in Sidra Medicine Clinical Chemistry Division has been evaluated in order to promote a more consolidated and efficient process of IQC management. The statistical data produced from Cerner QC Module are transferred to IQC review templates consisting of formulas to auto- calculate parameters such as multiple of expected QC failure frequency and desirable comparison limit between analyzers. The IQC review and documentation process using the in-house excel template requires several hours to complete, hence a faster and more efficient IQC management module is required. The main objective of this study is to improve the initial IQC management set up, work flow and review procedures and to implement Biorad Unity Real Time (URT) program to develop a more efficient IQC management system.

Methods

The URT software has been recently configured and implemented to consolidate and streamline IQC management. URT is built through Sidra Medicine IT Enterprise level which allows multiple users to login. IQC data are downloaded using scripts from Cerner which are filtered through Biorad Unity Connect (UC) software. Additional quality tools are also explored such as various user defined statistical reports, IQC analysis using peer reviewed total allowable error (TeA) and assignment of the most appropriate Westgard rules. Determination of sigma metrics and uncertainty of measurement is also performed using the URT application.

Results

The generation of any IQC report is less cumbersome and time consuming as compared with the previous process. However, some user defined formulas in the IQC templates are not found on the URT reports. The URT Levey Jennings chart are also more user friendly and directly compares the daily IQC data with Unity inter-laboratory peers enabling the production of instant and monthly reports through QCNet site when assay investigation is required and for IQC report documentation.

Conclusion

The combination of Cerner IQC, Unity Real-time, QCNet Inter-laboratory reports and in house IQC templates produce a high level and very detailed IQC review which effectively evaluate assay performance to assist on IQC troubleshooting and root cause analysis to be able to apply the most appropriate corrective actions.
Vendor-Recommended Protocol Is Not Adequate To Verify Analyzer Performance After Probe Replacement
Authors: Fathima S , Gallegos A F , Kumar V
Published: October 2020

Introduction/Objective

To verify performance after probe replacement on Siemens ADVIA® 1800 analyzer, the vendor recommends running 2 levels of quality control (QC) for each analyte; however, this approach provides only a snapshot of analyzer performance. Additional experiments were conducted to determine if the vendor-recommended protocol adequately verifies analyzer performance.

Methods

Serum from 20 random patients was mixed, centrifuged at 1000 g for 10 min, and supernatant prepared (PPS). Intra-assay precision was assessed by analyzing 20 replicates of 2 levels of QC, and PPS for the following indicator assays (total allowable error [TEa] in parentheses): alanine aminotransferase (20%), calcium (6%), creatinine (15%), immunoglobulin G (25%), and sodium (5 mEq/L). Inter-assay precision over past 30 days was calculated from the values (90 – 114) of 2 levels of QC. Violation of 13s QC rule is most commonly used for detecting critical error (error > TEa). We used TEa/4 and TEa/3 as the acceptability criteria for intra- and inter-assay precision. Inter-assay precision was also compared to the precision claim by the vendor. Bias between the mean of QC values from intra- and inter- assay precision was calculated and TEa/4 used as the acceptability criterion.

Results

Intra-assay precision for both levels of QC for all analytes was acceptable. Intra-assay precision (5.48%) for only alanine aminotransferase in the PPS was unacceptable, indicating that patient matrix may impact precision for certain analytes. Inter-assay precision (2.24%) for level 1 QC for calcium was unacceptable. For all analytes, inter- assay precision compared to vendor’s claim was found to be significantly higher (32% - 405%). The bias was unacceptable for level 3 QC for sodium (-2.11).

Conclusion

Increased imprecision and/or bias may be observed if either probe replacement or alignment was not appropriate; or the verification protocol was not adequate. This study demonstrates the need to conduct experiments beyond vendor-recommended protocol to ensure production of clinically acceptable results.
Paris System Has A Higher Cytohistologic Correlation And Reproducibility Than Traditional Urine Cytology Method
Authors: Mendoza R P , Haidary T , Gupta R
Published: October 2020

Introduction/Objective

The major limitation of urine cytology is the lack of consensus regarding the terminology and diagnostic criteria that should be used for urothelial atypia. The main goal of the newly proposed Paris System for Reporting Urine Cytology is to concentrate primarily on the detection of high grade urothelial carcinoma while minimizing the detection of low grade lesions. This study aimed to apply the criteria and categories of the Paris system in retrospectively collected urine cytology specimens and assess histologic correlation and reproducibility.

Methods

Two senior pathologists independently reviewed retrospectively collected urine cytology specimens strictly following the Paris system criteria for categorization. Cytologic diagnosis were compared with previous cytology result and histologic diagnosis.

Results

A total of 67 patients were included in the study. The mean age is 65.8 years (36-89 years), majority were males (73.1%) and African American (89.6%). Urine cytology using traditional method showed mostly atypical results (58.2%), followed by reactive (26.9%), high-grade urothelial carcinoma (11.9%) and suspicious (3.0%). On the other hand, the Paris system had more negative results (62.7%), followed by atypical (19.4%), high-grade urothelial carcinoma (11.9%) and lastly suspicious (6.0%). All of negative cases (18 out of 18) and majority of HGUC cases (7 out of 8) were concordant between the two cytology methods. Traditional urine cytology method only yielded 71.4% histologic concordance, while 100% Paris system results were concordant with bladder histology. Majority of the atypical cases using traditional method were converted to negative, and a few atypical cases were converted to suspicious and high-grade. All results using Paris system were concordant between two general pathologists.

Conclusion

Using the Paris system in analyzing urine cytology resulted to higher cytohistologic concordance than traditional method. Majority of atypical cases from traditional method were converted to more definitive categories. The cytopathologic analyses from two general pathologists applying the criteria of Paris system had superior reproducibility. Applying the Paris system, therefore, can significantly improve the performance of urine cytopathology.
Case Series: Seventeen Year Institutional Review of Placental Chorangiomas
Authors: Kousar A , Takeda K , Rizvi A , Sutton A , Geisinger K
Published: October 2020

Introduction/Objective

Chorangioma is a rare tumor occurring in less than 0.5 - 1% of all pregnancies. Small chorangiomas (< 4cm) are mostly asymptomatic and incidental. Large chorangiomas (> 4 cm) may be associated with various fetal complications and complicated pregnancies. The aim of our study is to assess the ultrasound detection rate of these lesions.

Methods

A retrospective study of chorangioma cases seen at Vidant Medical Center between 2003 to 2019 was conducted. Size of the lesion, detection on prenatal imaging, gestational weeks at delivery, maternal age and pregnancy related fetal and maternal complications were analyzed.

Results

A total of 25761 placentas were examined from 2003 to 2019 in Vidant Medical Center. Out of these only thirty-nine cases (0.15%) of chorangioma were found. 41% of these women were above 30 years of age. 36 patients were non-Hispanic. 92.3 % (36 cases) of these lesions were less than 4cm and 7.6 %(3 cases) were above 4 cm, with only one recent case of 7.0 cm in greatest dimension. 92% of the total patients presented with complicated pregnancies. Preeclampsia, preterm delivery, gestational hypertension and intrauterine growth retardation were among the most common complications observed. 3 patients presented with oligohydramnios. Interestingly, none of the lesions were detected on prenatal ultrasound.

Conclusion

Large chorangiomas(>4 cm) are rare but are known to be associated with adverse fetal outcomes. Our seventeen year institutional review shows the largest chorangioma to be 7 cm in greatest dimension. Regular ultrasound monitoring is required to pick up these benign lesions early and prevent adverse outcomes. A retrospective review is needed to determine why the lesions in our study were not detected radiographically.
Alterations of Hemoglobin Fractionation in a Sickle Cell Disease Patient on Voxelotor Therapy
Authors: Karimi S S , Ni H , Hsu L L
Published: October 2020

Introduction/Objective

Voxelotor is a molecule that allosterically binds to the alpha-chain of hemoglobin, resulting in increased oxygen affinity. This allosteric inhibition leads to prevention of hemoglobin polymerization and sickling of red blood cells in response to low oxygen tension. Voxelotor has been used to treat patients with Sickle Cell Disease (SCD) and recent literature indicates it may contribute to complex hemoglobin fractionation (HF) elution patterns. We report a novel case of a SCD patient on concurrent Hydroxyurea, Voxelotor and chronic RBC exchange transfusion treatment and discuss the implications of these three treatment modalities on HF and monitoring of SCD.

Methods

A 17-year-old female with SCD complicated by frequent vaso-occlusive crisis, and avascular necrosis managed with chronic RBC exchange and Hydroxyurea. Her HF prior to initiation of Voxelotor treatment showed 3.2% HbA2, 51% HbA, 6.0% HbF, and 41% HbS. Voxelotor therapy was initiated at 1500mg/day and HF was performed 10 days later. Whole blood was collected and subjected to High Performance Liquid Chromatography (HPLC) with reflex to RBC solubility and Capillary Electrophoresis.

Results

HF performed post-Voxelotor therapy revealed positive sickle solubility with a complex pattern of 2.7% HbA2, 49.2% HbA, 5.3% HbF, 15.7% HbS, 0% HbC, and two additional peaks of a 6.3% peak in the window-D region (retention time of 4.34) and 20.8% of an atypical Hb peak pattern (at the retentuin time of 4.18). The results reflected a complex HF of a HbSS patient on concurrent chronic RBC exchange transfusion, hydroxyurea therapy, and Voxelotor treatment. Post Voxelotor-therapy HF revealed a reduction in HbS from 41% to 15.7% with the emergence of two additional peaks. Chronic RBC exchange transfusion and Hydroxyurea treatment account for the observed fractionation of HbA and HbF, respectively. Based on recent literature, we attribute the emergence of the two additional peaks to Voxelotor therapy. All three therapies led to reduction in HbS.

Conclusion

Routine HF serves as an essential modality in diagnosis and monitoring of SCD. Voxelotor treatment alters the HF profile and may cause difficulty for interpretation. With the emergence of novel therapies, it is imperative for clinicians to provide medication information to clinical laboratories and pathologists to be fully aware of the effects of current treatments to correctly interpret and monitor SCD.
Leukemia Cutis in a Patient with Rare Indolent T-Prolymphocytic Leukemia - A Case Report and Review of the Literature
Authors: Da Silva Lameira F , Wang K , Rinker E , Jetly R
Published: October 2020

Introduction/Objective

T-cell prolymphocytic leukemia (T-PLL) is rare, comprising 2% of mature lymphocytic leukemias in adults. Clinical course is usually aggressive, however, 20-30% patients can have an indolent early phase. Most patients present with extensive disease with peripheral blood lymphocytosis, hepatosplenomegaly, and lymphadenopathy. T-PLL has a higher incidence in patients with ataxia-telangiectasia.

Methods

We present a case of a 67-year old man with history of somatic mutation of ataxia-telangiectasia gene (ATM) and multiple malignancies, including melanoma, skin and laryngeal squamous cell carcinomas, adrenal adenoma and spindle cell lung tumor (diagnosed on biopsy), who developed leukemia cutis during an indolent phase of T-PLL.

Results

Initial diagnosis of T-PLL was on routine complete blood count when patient had mild atypical lymphocytosis (5.5 x 109/L). Flow-cytometry immunophenotyping detected CD4 + 8 positive mature T-cells with no aberrant loss of T- cell antigens, and molecular studies confirmed clonal T-cell receptor beta and gamma gene rearrangements. T-PLL associated leukemia cutis was diagnosed on a leg skin nodule biopsy 10 months later. Subsequent bone marrow biopsy demonstrated low level involvement by T-PLL. The patient’s T-PLL followed an indolent trajectory for three years and treatment was withheld until symptomatic presentation. Rapid disease progression was heralded with emergence of widespread T-PLL leukemia cutis, rapidly increasing lymphocytosis, extensive lymphadenopathy, splenomegaly and increasing LDH levels.

Conclusion

Skin involvement is reportedly identified in 20% to 50% of T-PLL cases in some series. Skin manifestations can be heterogenous with a broad clinical differential. T-PLL associated leukemia cutis may not be recognized owing to the overall low incidence and in skin lesions appearing during an undiagnosed indolent early phase of T-PLL.We highlight the importance of accurate evaluation of non-specific skin lesions in early detection of T- PLL. Being aware of this diagnosis and early engagement in an interdisciplinary approach may allow for better outcomes of this aggressive malignancy.
Nodular Lymphocyte Predominant Hodgkin Lymphoma: A Rare Case with Fan Pattern E
Authors: Ozluk E , Wei E
Published: October 2020

Introduction/Objective

Growth patterns of nodular lymphocyte predominant Hogdkin lymphoma (NLPHL) has been further described by Fan et all. Pattern E is T cell/histiocyte rich large B-cell lymphoma-like and is quite rare. The treatment usually may follow large B cell lymphoma protocol instead of Hodgkin lymphoma regimen.

Methods

Here we report a patient with NLPHL pattern E. Patient was a 25 years-old African American man who initially presented with generalized lymphadenopathy.

Results

Biopsy of the axillary lymph node revealed effaced lymph node architecture by a malignant neoplasm in a diffuse and vaguely nodular pattern. In the background of a diffuse infiltrate, there were small to medium sized lymphocytes, numerous atypical large cells with irregular, basophilic nucleoli, and variable cytoplasm. The large cells focally sheeted out. Many histiocytes were also seen in the background. The large atypical cells were positive for CD20, BOB-1, OCT2, BCL-2 (focally), BCL-6, PAX5, and MUM-1, and IgD, whereas negative for BCL-1, CD10, CD15, CD30. CD2, CD3, CD4, CD5, CD7, CD8 highlighted numerous T cells with mild cytological atypia, forming rosettes around the large atypical cells. T cells were negative for ALK-1, CD1a, TdT with increased Ki-67 proliferation index around 35%. Although the surrounding T cells appear atypical in morphology, flow cytometric analysis showed predominantly reactive T-cells with no loss of T-cell associated antigens. PCR analysis showed a producible peak in a single IgH reaction. However, the fragment size of the peak observed did not meet the criteria. T-cell gene rearrangement by TCR gamma and TCR beta PCR was negative for monoclonal T-cells. BCL-1, BCL-2, and BCL-6 FISH panel were negative for gene rearrangements. Based on these findings the diagnosis was made at stage IV. Patient started treatment with R-CHOP therapy with subsequent relapse. Patient has been placed on RICE chemotherapy with partial response.

Conclusion

NLPHL Pattern E type should be differentiated from classical Hodgkin lymphoma, diffuse large B-cell lymphoma and peripheral T cell lymphoma because the treatment greatly differs from those with higher stage and tendency for recurrence. It is the pathologist role to lead the clinician and render a correct histopathologic diagnosis.
A Challenging Diagnosis of Acute Myeloid Leukemia with Myelodysplasia Related Changes in the Setting of Ayurvedic Supplements and B12 Deficiency
Authors: Goff R , Levyq R
Published: October 2020

Introduction/Objective

Bone marrow findings of myelodysplastic changes can be associated with vitamin or mineral deficiencies (B12, folic acid or copper), infections, inflammatory disorders, exposure to toxins, heavy metals, zinc excess, recent radio- or chemotherapy, or myeloid neoplasms including myelodysplasia (MDS) and acute myeloid leukemia (AML). We present a case of a 32 year old Indian woman who presented with fatigue and weakness. She has a history of vitamin B12 deficiency and has been taking Ayurvedic supplements. This clinical history is very important because studies have shown that vitamin B12 deficiency has led to incorrect diagnoses of AML and/or MDS. Additionally, Ayurvedic supplements can contain a variety of heavy metals which can contribute to myelodysplastic changes.

Results

A complete blood count and peripheral smear analysis showed pancytopenia with rare blasts. A bone marrow core biopsy with ancillary testing was performed to evaluate for a hematologic malignancy. Vitamin B12 testing and heavy metal analysis was necessary to reach a final diagnosis. Flow cytometric analysis of the marrow identified 19.5% CD34 positive myeloblasts. The aspirate and core are hypercellular with increased blasts (17% on aspirate and 20-25% on core biopsy) with trilineage dyspoiesis. AML panel by fluorescence in situ hybridization showed no abnormalities. Heavy metal analysis shows no increase in lead, cadmium, mercury and arsenic levels. Recent vitamin B12 tests show results within normal range secondary to successful replacement. Ultimately, chromosome analysis identifies t(3;12)(q26,p13) involving ETV6/MECOM characteristic of a very poor prognosis in MDS or AML. Molecular AML panel identified BCOR and PTPN11 gene mutations which are associated with more aggressive disease and a poor prognosis in myeloid neoplasms.

Conclusion

This case had multiple possible causes of myelodysplastic changes and it was necessary to exclude these factors before yielding the final diagnosis of Acute Myeloid Leukemia with myelodysplastic related changes which demonstrated a rare translocation t(3;12) ETV6/MECOM which has a poor prognosis.
Pediatric Patient With Neurological And Leukemic Peripheral Blood Involvement By Small Cell Variant Of ALK- Positive Anaplastic Large Cell Lymphoma (ALCL): Case Study
Authors: Reddy A C , Reddy K S
Published: October 2020

Casestudy

Anaplastic large cell lymphoma (ALCL), is a T-cell lymphoma typically consisting of large lymphoid cells including characteristic horseshoe- shaped hallmark cells. The rare small cell morphological variant of ALCL may pose a challenge in diagnosis, especially when the initial presentation is unusual.

Results

Our patient, a 7-year-old girl presented with a headache. A complete blood count showed leukocytosis and anemia. The smear was reported to have segmented neutrophils, reactive lymphocytes, and monocytes. A spinal tap was performed and flow analysis identified a minute aberrant T cell population (0.3% of total), positive for CD3, CD4, bright CD7; negative CD5, CD8 in the CSF sample. The peripheral blood sample was reviewed again; some small- medium atypical lymphocytes, with irregular nuclear contours and cytoplasmic azurophilic granules were noted. Flow immunophenotyping displayed an aberrant T cell population positive for CD45, CD2, CD3, bright CD7, CD4, CD13; negative CD30, TdT CD5, CD8, CD117, CD34; consistent with T cell lymphoma/leukemia. A cell block prepared from peripheral blood sample showed blood with numerous atypical cells with irregular nuclei positive for ALK, CD30, CD3, CD4, CD7; negative CD5 and CD8. A diagnosis of leukemic ALK(+) ALCL was rendered, though classic hallmark cells were difficult to see. A marrow biopsy showed interstitial and sinusoidal pattern of mainly small to medium-sized cells with irregular nuclei. Molecular study revealed ALK gene alteration showing characteristic NPM1-ALK fusion. The patient underwent a bone bone marrow transplantation but recently relapsed with a submandibular lymph hode biopsy showing the presence of many larger ALCL cells.

Conclusion

Correct clinical diagnosis of the small-cell variant of ALCL is often challenging as the scarce “hallmark cells” are scattered and difficult to recognize. While leukemic peripheral blood involvement is rare in ALCL, an association has been reported with small-cell variants, which may be a potential explanation for the poor prognosis and aggressive nature of small-cell variant ALCL. A meticulous examination of peripheral blood smears, comprehensive immunophenotypic studies, and early bone marrow and lymph node/tissue biopsy are needed to facilitate diagnosis.
Immune Modulation and CMV Reactivation In Sepsis-Induced Immunosuppression
Authors: Lambe G R , Kapadia F N , Khodaiji S , Rodrigues C
Published: October 2020

Introduction/Objective

Sepsis is a global health priority and is often accompanied by a transient immune paralysis, associated with impairment in innate and adaptive immunity leading to progressive immunosuppression and higher susceptibility to secondary infections. Reactivation of Cytomegalovirus (CMV) occurs frequently and has been associated with adverse outcomes even in immunocompetent patients, with sepsis. Study objective was to evaluate the association between incidence of CMV reactivation and immune alteration in sepsis-induced immunosuppression in patients with prolonged sepsis.

Methods

Prospective observational study, which included consecutive patients admitted to hospital ICU, with severe sepsis and length of stay > 48 hours. Patients with other causes of immune-suppression and anti-CMV treatment were excluded. Blood samples were collected on enrolment and further weekly until 21 days or death/discharge.

Quantification of CMV viremia was done using RT-PCR (qPCR). Markers used to evaluate immune suppression using Flow Cytometry were i) lymphocyte subsets (CD3+,CD19+,CD16+CD56+,CD4+,CD8+ and regulatory T cells - CD25+ CD127-), ii) surface receptor expression of HLA-DR on monocytes, and Programmed Death marker expression (PD-1) on T lymphocyte, iii) Measurement of pro-inflammatory(IL-6,TNF-a,IFN-g) and anti-inflammatory cytokines(IL-4,IL-10) by Cytometric Bead Array (CBA) assay.

Results

A total of 25 CMV IgG positive patients and 11 healthy controls were analyzed. CMV reactivation occurred in 20 patients. Median time for reactivation was 7 days. Patients with CMV reactivation had significant T-cell lymphopenia (p<0.01). PD-1 expression on both CD4+ and CD8+ T cells in these patients was markedly elevated as compared to non-reactive group. HLA-DR expression was significantly low on monocytes in all sepsis patients (p<0.01) vs healthy controls; however it did not show any significant correlation. Levels of IL-6 showed marked elevation from day 7 while, IL-10 was observed to be significantly higher from day 0 in CMV reactivated group as compared to the CMV non-reactive group of patients.

Conclusion

Our study evidence suggests that monitoring lymphocyte subsets, PD-1expression on T lymphocyte, and levels of IL-6/IL-10 using flow cytometry, may serve as indicators for reactivation of CMV. Individualized immune therapy such as PD-1 receptor blockade drugs can be used to optimize treatment of patients with severe sepsis.
Importance of the Second Opinion in Surgical Breast Pathology and Its Therapeutic Implications
Authors: Ibarra A , Baksai K , Vial M
Published: October 2020

Introduction/Objective

Histopathological diagnosis determines surgical management and complementary therapies in patients with breast cancer. There has been reported significant diagnostic divergences, between 7.8 and 26%, and in tumor markers between 3.4 and 41%. We evaluate the agreement between diagnoses of general pathologists and specialists of our center, in which serious discrepancies could have therapeutic repercussions.

Methods

Method: A retrospective study from 2012 to 2019. The cases were classified in benign and malignant. The atypical lesions were included with benign. Major disagreements were considered when there was a change in diagnosis from benign to malignant or vice versa, variation from intraepithelial to microinvasive carcinomas, infiltrating to intraductal carcinomas or vice versa. When necessary, we repeat routine stains and/or immunostains, or add new immunostains.

Material: 295 cases. 294 women and 1 man. 228 biopsies and 67 immunostains of prognostic-predictive factors.

Results

We found diagnostic differences in 46/295 cases (15.6%). Major discrepancies in 32 cases (10.8%). In morphological diagnoses 11/228 (4.8%) and in immunodeterminations 20/67 (29.9%). In diagnostic changes, they highlighted 3 cases of ductal carcinoma in situ (DCIS) to benign, 2 cases of benign lesions to DCIS, 1 benign to invasive ductal carcinoma (IDC), 1 DCIS to IDC and 1 IDC to DCIS.

Conclusion

We found serious diagnostic divergences in 32 of 295 cases, 10.8%, which could have varied the therapeutic approach. In morphological interpretation 4.8% and in immunohistochemical results 29.9%. This should motivate multidisciplinary teams to routinely use the second opinion in surgical breast disease
Increased Fecal Calprotectin Levels in Crohn’s Disease Correlate with Elevated Serum Th1- and Th17-Associated Cytokines
Authors: Kamel Y S
Published: October 2020

Introduction/Objective

Patient-reported symptoms and endoscopic disease activity do not correlate well in Crohn’s disease (CD). This warrants the need for reliable biomarkers to early detect active intestinal inflammation. Currently, the fecal calprotectin level is the most commonly used biomarker for inflammatory activity in CD. However, the diagnostic accuracy of the fecal calprotectin level is not fully efficacious and diagnosis may be further improved by the identification of other biomarkers for active CD. Here, we studied the association of a variety of serum disease markers with fecal calprotectin levels in CD patients.

Methods

39 CD patients were included and subdivided into ‘normal’ (defined as < 200 mg/kg feces) and ‘increased’ (defined as > 200 mg/kg feces) fecal calprotectin level groups. Serum levels of 37 different cytokines, chemokines and markers for angiogenesis and vascular injury were quantified by an electrochemiluminescence multiplex assay (V- PLEX Human Biomarker 40-Plex Kit of Meso Scale Discovery ®). Correlations between individual biomarkers and the fecal calprotectin level were assessed using Spearman’s correlation coefficient (ρ).

Results

A highly significant positive correlation was observed between the pro-inflammatory serum cytokines IFN-γ and CRP and fecal calprotectin levels (P < 0.01). Moreover, fecal calprotectin levels showed a significant positive correlation with IL-6, TNF-β, SAA and IL-17A (P < 0.05).

Conclusion

We show that a positive correlation exists between multiple serum Th1- and Th17-associated cytokines and the fecal calprotectin level. These cytokines and CRP may serve as additional biomarkers for determining disease activity and evaluating treatment response in CD. Ultimately, this may result in more efficient treatment of active disease in CD patients and prevention of complications.
Diagnostic Accuracy & Pathology Revised Reports: Evidence-Based Guideline Development
Authors: Spiczka A , Waibel L , Garcia E , Kundu I , Garris R , Jacobs J , Brown A
Published: October 2020

Introduction/Objective

Diagnostic errors in pathology may have adverse impact on patient outcomes and are often rectified through revised reports (RR). Improving patient outcomes with accurate RR is a tangible yet challenging benefit to assuring continuous quality improvement (CQI). Assessment and elevation of RR optimization requires counterbalance of workflow complexity in the diagnostic reporting domain. Implications inform best-practice guidelines for pathology RR and exemplify improved patient outcomes by driving down negative impacts from diagnostic errors.

Methods

A “Survey for RR in Pathology: Reality & Best Practices” was sent via email to relevant stakeholders. The 8-item survey was designed by the National Pathology Quality Registry team & ASCP’s Institute for Science, Technology & Policy. The model included quantitative and qualitative feedback to probe current experiences with RR. The survey was open April 1-30, 2019, via Key Survey and used snowball sampling.

Results

Key results illuminate necessity for RR standardization. Survey findings represent 172 respondents. Ninety- two percent of respondents indicated report accuracy as a major indication for optimizing RR practices & positively impacting patient care. Pathology practices assure appropriate RR by notifying a care provider when a change in diagnosis necessitates RR (89%) & 86% of respondents indicate delineation of RR types (e.g. addenda, amendment). Still 54% of respondents see inappropriate RR use with lack of notification to care providers and 48% indicate no delineation of RR types. This balance-counterbalance highlights deviations from optimized RR and a need for guidelines. Effects on patient care or impact to a patient’s treatment plan was indicated by 43% who affirmed stratification of diagnostic discrepancies as major vs. minor. Solely focusing on changes in diagnosis (benign vs. malignant) was heralded by 19% of respondents as a reason to categorize diagnostic discrepancies. Forty-two percent of respondents indicate data-driven CQI in the RR domain.

Conclusion

Identified RR practice gaps decrease diagnostic accuracy, confirming the need for optimal RR guidelines. RR guidelines should focus on standardized nomenclature; active dialogue between laboratory team & clinical care partners; streamlined workflows to assure accuracy; & valuing transparency to derive improved patient outcomes based on high-quality diagnostic pathology RR.
Comparison of Manual and Digital Assessment of KI-67 in Neuroendocrine Tumors
Authors: Raju B S , Quinton M , Hassell L
Published: October 2020

Introduction/Objective

Proliferative activity is an essential prognostic and treatment indicator for neuroendocrine tumors (NET). Ki-67 proliferation index, if reported by unaided microscopic estimation on hot-spot locations could lead to variability and inconsistencies. This study aims to compare the Ki-67 assessment of NETs by visual estimation versus automated digital image analysis (Roche iCoreo/Virtuoso).

Methods

212 patients with Ki-67-graded GI NETs (117 G1; 61 G2; 34 G3) from 2010 to 2019 were reassessed using digital image analysis quantification of hot spot areas of at least 500 cells (average 800 cells). Revised tumor grades were assigned according to the European Neuroendocrine Tumor Society guidelines and the 2010 World Health Organization classification and compared to initially reported grade.

Results

We found 75% concordance for G1, with 22% of cases upgraded to G2 and 3% of cases upgraded to G3. For G2, there was 70.5% agreement, with 13.1% of cases downgraded to G1 and 16.4% upgraded to G3. For G3, there was 100% agreement, (kappa=0.64, overall). Retrospective review of discordant G3 cases revealed cases with known metastasis, small fragments of tissue, or polyps. Scanning and scoring required approximately 10 minutes per case.

Conclusion

Our data shows the time/effort difference of visually estimating versus automated digital analysis may lead to significant classification errors in these tumors. Although digital analysis has limitations, including tumor heterogeneity, misidentification of tumor cells, and poor immunostaining which could require manual counting by a pathologist, this rigor should be reinforced and explicitly stated to increase accuracy and reproducibility of grading.
Monitoring Of IGF-1 Levels In Type 2 Diabetic Patients With Macro And Microvascular Complications
Authors: Wasim H , Abdelmonem M , Samir S , Salah A
Published: October 2020

Introduction/Objective

Introduction: Type-2 diabetes have a risk factor of multiple complications such as coronary artery diseases (CAD), premature atheroscalerosis and diabetic retinopathy. IGF-1 is regulated by a balance of hormones such as growth hormone and insulin. It is important that circulating IGF1 in serum has normal levels to maintain glucose metabolism.

Objectives: Monitoring of IGF-1levels in T2DM with macrovascular complications (CVD) and microvascular complications (retinopathy).

Methods

Subjects and methods: The collection of samples started in June 2018 and ended in December 2018. A total of 114 subjects were enrolled in this study; 98 clinically diagnosed T2D patients who were recruited from the outpatient clinic of the National Institute for Diabetes and Endocrinology “NIDE”, in addition to 16 healthy comparable control subjects (without diabetes). The subjects divided into 3 groups. Group 1; a population of 44 T2D patients with macrovascular complications (28 females and 16 males), the mean age was 57.4 years. Group 2; a population of 54 T2D patients with microvascular complicatios (34 females and 20 males), the mean age was 59.1 years. Group 3; a population of 16 healthy subjects (12 female and 4 males), the mean age was 59.2 years. Levels of FBS, C-peptide, HbA1c, Lipid profile, lipoprotein(a), hs-CRP and microalbuminurea were measured in all subjects. Seum concentration of IGF-1 was measured by commercially immunoenzymatic ELIZA method.

Results

It was found that serum concentration of IGF-1 decreased in diabetic patients groups compared to the control one. The mean±SD of group 1, group 2 and group 3 were (332.2±152.2), (316.9 ±142.2) and (625.4 ± 257.7) respectively.

Conclusion

It was observed that there was a negative correlation between serum IGF-1 levels in T2D patients compared to the control group. Also, it was found that T2D patients with microvascular complications had lower IGF-1 levels than patients with macrovascular ones. It seems that IGF-1 strongly involved in the incidence and pathogenesis of T2DM complications.
Performance Assessment on Buffy Coat Examination for Human Granulocytic Anaplasmosis Diagnosis
Authors: Ye Q , Li H , Wang G
Published: October 2020

Introduction/Objective

Anaplasma phagocytophilum is an obligate gram-negative intracellular bacterium that causes human granulocytic anaplasmosis (HGA). The diagnostic tests for HGA include buffy coat examination, culture, PCR, and serology. In our lab, suspected patient will be subjected to buffy coat examination, and the result will be further confirmed with PCR. The aim of the study is to assess the epidemiology of HGA diagnosed at WMC during 06/2014- 08/2019, and as well as the performance accuracy of buffy coat examination as compared to PCR.

Methods

The results of buffy coat examination and in house HGA PCR from 06/2014 to 08/2019 were collected from SoftLAB and SoftMOL, respectively.

Results

A total of 1,057 blood specimens were tested by buffy coat examination from 06/2014-08/2019; among them, 658 specimens were also analyzed by HGA PCR assay (Fig. 1). Positivity for buffy coat examination and PCR was 2.6% and 6.1%, respectively. Overall, using PCR as reference diagnostic method, 42 new HGA cases were identified.

The number of new HGA cases varied among years from 2 to 15, with year of 2017 having the greatest number of total cases (Fig. 2). Further analyzing new HGA cases by months reveal HGA starts in April and ends in December, and peaks at June and July (Fig. 3).

When comparing buffy coat result to PCR, 17 positive buffy coat tests were confirmed positive in PCR test, and 619 negative buffy coat tests were also consistent with negative PCR test result. However, 21 cases which were initially negative in buffy coat examination were positive in PCR tests. On the other hand, 1 positive buffy coat examination case was negative in PCR (table 1). Overall, using PCR as a reference test, the sensitivity and specificity of buffy coat examination are 44.7% and 99.8%, respectively.

Conclusion

Buffy coat examination has high specificity but low sensitivity in detecting HGAcompared to PCR. Low sensitivity is most likely due to variable presence of intracytoplasmic aggregates of HGA in peripheral blood neutrophils and technically incompetency of testing personnel. Overall, it is a good test for laboratory confirmation of clinically suspected HGA cases. We suggest clinicians to add HGA PCR to all the buffy coat examination to avoid missing potential HGA diagnosis. Moreover, more training and competency on testing personnel may improve the sensitivity of buffy coat exam for diagnosis of HGA.
Legionella Test Reporting at a Regional Veteran Affairs Medical Center
Authors: Petersen J M , Jhala D
Published: October 2020

Introduction/Objective

The appropriate reporting and monitoring of legionella antigen and culture test volumes and results is a veteran affairs quality assurance regulatory requirement. Legionnaires disease incidence has been noted to be increasing in the United States, and it has also been documented that health care facilities are especially high- risk settings for the transmission of Legionella bacteria from the building water systems to the occupants. However, studies of Legionella test epidemiology for non-veteran hospitals is sparse in the literature. To provide perspective, here we report the total legionella antigen and culture tests from quarter 1 2016 to quarter 4 2019 to provide a regional perspective.

Methods

Quality assurance data on both the total number of Legionella antigen and culture tests and the recorded number of positive cases were reviewed from quarter 1 2016 to quarter 4 2019 and tabulated. This data is collected routinely as per veteran affairs regulatory directives.

Results

There were a total of 1613 legionella antigen tests and 1287 legionella cultures. None of the Legionella cultures were positive during the study period. Nonetheless, there were 3 positive urinary antigen tests for a total calculated percentage of 0.00002%.

Conclusion

The presence of positive Legionella antigen tests at a regional veteran affairs medical center indicates that a robust quality assurance program is tremendous benefit to monitoring Legionella at a major medical institution in order to prompt action to prevent hospital-based spread.
An Emerging Infection: Streptococcal Toxic Shock-Like Syndrome Caused By Group B Streptococcus (GBS), Streptococcus Agalactiae
Authors: Rajack F , Afsari A , Ramadan A M , Naab T J
Published: October 2020

Introduction/Objective

Streptococcus agalactiae, Group B Streptococcus (GBS), is a major cause of neonatal sepsis and infections in pregnant women. However, incidence of invasive GBS infections has more than doubled in the last two decades with highest risk in adults 65 years or older. Other risk factors are diabetes, malignancy, and immunocompromised state. Bacteremia and skin soft tissue infections are the most common invasive infections in nonpregnant adults. Rarely GBS infection has a fulminating pyrogenic exotoxin-mediated course characterized by acute onset, multiorgan failure, shock, and sometimes death, referred to as toxic shock-like syndrome.

Methods

A 77-year-old hypertensive female with uncontrolled type 2 diabetes mellitus and a history of bilateral foot ulcers presented to the hospital in probable septic shock. Clinical diagnosis of necrotizing fasciitis was made and she underwent bilateral lower limb amputations.

Results

Grossly soft tissue appeared gray. Microscopically fascia was necrotic without neutrophils present and Gram stain revealed sheets of Gram positive cocci. These findings reflected histopathologic Stage III necrotizing fasciitis, which is associated with 47% mortality. Autopsy showed a similar histology of Stage III necrotizing fasciitis involving the surgical stump. Erythema and desquamation of the upper limbs bilaterally and multi-organ failure met the clinical picture of Streptococcal Toxic Shock Syndrome (STSS) and fulfilled the criteria for TSS due to Group A Streptococcus (GAS), defined by The Working Group on Severe Streptococcal Infections.

Conclusion

Group B Streptococcal Toxic Shock-Like Syndrome may have a similar outcome to STSS caused by GAS and other pathogens and, in limited studies, mortality has been 30% or greater.
Assessment of Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF- MS) for Accurate Bacterial Identification in Clinical Labs
Authors: Abdel-Rahman M , Azab M S , Meibed M , El-Kholy A , Elmetwalli A W
Published: October 2020

Introduction/Objective

On behalf of the diagnostic Medical Laboratory rapid, and accurate identification of bacteria with their one-to-one anti-microbial susceptibility outlines is of ultimate importance for the management of infected patients. Contemporary microbial identification methods employed in routine clinical diagnostic laboratories relies on the use of conventional phenotypic methods. Phenotypic methods are time consuming with minimum turn-around times of at least 24 hrs and in many occurrences of 48hrs. With the intention of accelerate laboratory processes the MALDI-TOF MS was familiarized. MALDI-TOF MS is established on proteomic profiling and permits for rapid identification of bacteria. This technology has not been widely used in Egypt, but has been regularly used in Europe for the past few years.

Methods

Two hundred forty three positive non duplicate blood cultures were accrued over a period of six months. Experimental aliquots were taken from excess sample material that was collected as part of routine clinical care. 105 were positive for Gram negative bacilli, 123 were positive for Gram positive cocci, 3 positive for Gram positive bacilli, and 7 were positive for yeast. MALDI-TOF identification was compared to conventional identification. Conventional identification consisted of a combination of MALDI-TOF identification of a subcultures colony by direct smear, biochemical reactions, Vitek 2, and molecular identification.

Results

Ninety seven of the one hundred and five blood cultures positive for Gram negative bacilli were monomicrobial. The majority of these were identified as Escherichia coli by conventional methods, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa. Eighty-four of these monomicrobial cultures were identified by MALDI-TOF to the species level. Eighty-one of the eighty-four were concordant with the conventional identification (96.4%).

Conclusion

The MALDI-TOF proved to be useful for the rapid and reliable identification of g-ve bacteria from the clinical specimens. The difference in turnaround time for bacterial identification was significant between MALDI-TOF MS and VITEK 2 with minimal preparation for the blood cultures.
A Rare Case of Chronic Myeloid Leukemia with t(3;9;22) 3-way Translocation
Authors: Elzamly S , Padilla O , McAlice M , Gohar M , Gaur S , Tonk S , Chavali S
Published: October 2020

Introduction/Objective

Chronic Myeloid Leukemia (CML) is a myeloproliferative neoplasm originating from malignant clonal proliferation of a pluripotent hematopoietic stem cell. CML is characterized by a reciprocal translocation between chromosomes 9 and 22, t(9;22)(q34;q11), that gives rise to an abnormal chromosome 22 called the Philadelphia (Ph) chromosome. The translocation results in the formation of a chimeric BCR-ABL1 fusion gene, which is the molecular hallmark of the disease. However, 5-10% of CML patients present with additional chromosomal abnormalities which is often considered a sign of clonal evolution, genetic instability, and is generally thought to portend a poor prognosis.

Methods

We present a case of CML with a rare 3- way translocation, t(3;9;22)(q21;q34;q11.2), who achieved a major molecular response on imatinib for 18 months. A review of the literature and Mitelman database search is presented focusing on the prognostic implications of this 3 way translocation in the era of tyrosine kinase inhibitors starting in 2001 till now.

Results

Twenty seven cases were reported, but the patient therapeutic response to imatinib and clinical outcome were only reported in 11 cases. Nine cases achieved a cytogenetic remission while the remaining two cases had an adverse outcome.

Conclusion

Taken in conjunction with the favorable outcome in our patient, we suggest that t(3;9;22) is not an adverse prognostic factor in the era of tyrosine kinase inhibitors.