bluuebunny/crossref_metadata_2025 huggingface dataset:
First Reported Case of a Well-Differentiated Neuroendocrine Tumor (WDNET) Arising Within Diffuse Ganglioneuromatosis (DGN) in a Patient With Neurofibromatosis Type 1 (NF-1)
Authors: Cox Brian , Balzer Bonnie , Dhall Deepti , Guindi Maha , Gangi Alexandra , Larson Brent
Published: September 2019

Case Report

A 51-year-old female with NF-1 underwent flexible sigmoidoscopy, which revealed a 1.8-cm mass in the upper rectum. The noncircumferential mass was located predominantly at the posterior rectal wall and was suspicious for a neurofibroma. The biopsy revealed a WDNET arising in a ganglioneuroma that extended to the edges of the biopsy tissue. The patient underwent a segmental resection, and sections revealed residual grade 1 WDNET intimately admixed with DGN. The area of DGN also showed multifocal microscopic clusters of neuroendocrine cells limited to the lamina propria.

Discussion

NF-1 involves the gastrointestinal tract in 10% to 25% of affected individuals. DGN is a poorly circumscribed, frequently transmural gastrointestinal lesion composed of spindled and ganglion cells that may be seen in PTEN hamartomatous tumor syndrome, multiple endocrine neoplasia syndrome type 2B, and (less commonly) NF-1. Though malignant transformation of neurofibromas to malignant peripheral nerve sheath tumors is well documented in NF-1, malignant transformation of DGN is extremely rare. To our knowledge, this is the first reported case of a WDNET arising in DGN.

In addition to being the first reported case of WDNET in this setting, this is the first case to describe microscopic neuroendocrine cell nests in DGN. Similar proliferations have been described in the setting of inflammatory bowel disease, termed microcarcinoid or neuroendocrine cell micronests, which are not thought to have malignant potential. However, given the presence of these microscopic neuroendocrine cell nests within the larger DGN lesions and adjacent to the WDNET, we hypothesize that in the setting of NF-1, microscopic neuroendocrine cell clusters may serve as a precursor of WDNET. While this is a rare situation, these novel findings should prompt careful examination for WDNET and microscopic neuroendocrine cell nests in future cases of DGN.
An Autopsy Case of Severe Nonimmune Hydrops Fetalis Secondary to Premature Closure of the Foramen Ovale
Authors: Gao Guofeng , Tovar Jason , Raven Katherine
Published: September 2019

Hydrops fetalis is a condition in the fetus characterized by excessive fluid accumulation within the fetal extravascular compartments and body cavities occurring prenatally. Nonimmune hydrops fetalis is the predominant (>85%) cause of all affected individuals (cardiovascular is the leading etiological category). Herein we present an autopsy case of severe nonimmune hydrops fetalis. The decedent was delivered from a blood type A Rh-positive mother. The overall autopsy findings are diffuse subcutaneous edema, significant ascites, pleural effusion, and pericardial effusion. The major autopsy finding is the premature closure of the foramen ovale of the heart, in addition to enlarged heart and liver. Premature closure of the foramen ovale may occur at any stage of pregnancy and may be due to multiple causes and has been reported as a cause of hydrops fetalis. It is well known that the foramen ovale is the shortcut through which the fetal heart provides oxygenated blood to preferential organs, mainly the brain and the heart itself, and normally closes at birth. The timing of the premature closure of the foramen ovale in fetus is critical: its closure late during pregnancy has been associated with right heart failure, while its closure very early during pregnancy frequently results in a hypoplastic left heart due to decreased blood flow, with an aneurysm consistently bulging into the left atrium, which ultimately leads to right heart failure. Both, if uncorrected in time, can ultimately lead to hydrops fetalis and fetal death. Other structural abnormalities, like pulmonary vascular disease/irreversible pulmonary hypertension, and enlarged edematous placenta, may further aggravate obstruction to venous return to fetal heart, setting up a vicious cycle. In summary, the newborn baby died of complications of nonimmune hydrops fetalis due to the premature closure of the foramen ovale of the heart.
Six-Year Experience (2013-2018) With College of American Pathologists Programs at King Hussein Cancer Center in Jordan
Authors: Bohisi Salah , Sughayer Maher , Alsalahat Heba
Published: September 2019

Objectives

Proficiency testing (PT) includes interlaboratory comparisons that are organized regularly to assess the performance of individual laboratories for specific tests or measurements and it is used to monitor laboratories’ continuing performance.

Background

The College of American Pathologists (CAP) requires laboratories to participate in PT programs and to perform the investigation and root cause analysis for unsatisfactory PT results, which is valuable to improve the laboratory performance.

Methods

The data were extracted from the CAP PT results of the laboratory from 2013 to 2018 in the areas of Biochemistry, Immunology, Hematology, Microbiology, Anatomic Pathology and Cytology, and Blood Bank. The data were PT scores and consisted of values between 0 and 100, representing the percentage of correct response for each analyte.

Results

There were 211 analytes (502 event) in 2018, 215 analytes (547 event) in 2017, 204 analytes (531 event) in 2016, 210 analytes (519 event) in 2015, 228 analytes (443 event) in 2014, and 158 analytes (528 event) in 2013 that were covered by CAP PT surveys in different laboratory areas. Over the 6 years of experience, there were 57 (1.86%) unsatisfactory results for all PT events. It was seen that the rates of unsatisfactory results in that period were gradually decreased with each year of experience, which was 1.1% (2018), 1.6% (2017), 1.9% (2016), 1.5% (2015), 2.4% (2014), and 2.6% (2013). The top 3 reasons for unacceptable results were random error, analytical error, and procedural error, which accounted for 21.0% random error (2013 (9%), 2014 (4%), 2015, 2016, 2017, & 2018 (2%)), 19.3% analytical error (2013 (2%), 2014 (5%), 2015 (5%), 2016 (3.5%), 2017 (2%), & 2018 (1.8%)), and 17.5% procedural error (2013 (4%), 2014 (4%), 2015 (0%), 2016 (2%), 2017 (5%), & 2018 (3.5%)).

Conclusion

The proficiency testing performance showed a trend of improvement from 2013 to 2018, which contributed to the improvement of laboratory performance and declining the unacceptable results that affected positively on patient test performance.
Evaluation of Quality Control in Clinical Chemistry and Hematology Using Sigma Metrics
Authors: Njeru Carol
Published: September 2019

Objectives

The aim of this study was to evaluate clinical chemistry and hematology laboratory performance using six sigma metrics.

Methods

Clinical chemistry data and hematology data were analyzed from Bungoma Referral Hospital. Five parameters from renal and liver function tests were studied over a period of 6 months (December 2016 to May 2017). Data from IQC and EQA participation were used. The analytes were plasma creatinine, aspartate transaminase (AST), alanine transaminase (ALT), total serum protein, and total and direct bilirubin. Hematology parameters, namely white blood cell count (WBC), red blood cell count (RBC), and hemoglobin (Hb) levels, were studied. Data from IQC and EQA participation were used. Sigma metrics was calculated using total allowable error as per CLIA recommendations. Bias was calculated from HUQAS EQA participation while coefficient of variation was calculated from IQC data collected during the abovementioned months.

Results

Clinical chemistry had sigma metrics below 3; the highest sigma value was 2.01 while the lowest sigma value was 0.85. Hematological parameters had sigma levels above 3. The highest sigma value was 7.21 while the lowest sigma value was 3.87. Only one level of sigma was below 4.

Conclusion

Clinical chemistry analytes had sigma levels less than 3; method performance improvement with stringent internal quality control and correct setting of control limits need to be applied. Application of sigma metrics in addition to daily internal quality control can identify analytical deficits and improvement in clinical laboratories. Most hematological parameters had sigma levels above 3. The highest sigma value was 7.21 while the lowest sigma value was 3.87. Only one level of sigma was below 4.
Evaluating Percentage-Based Reporting of Glucose-6-Phosphate Dehydrogenase (G6PD) Enzymatic Activity in a National Reference Laboratory: Assessment of Patient Eligibility for Plasmodium vivax Radical Cure Therapy
Authors: Calvaresi Emilia , Genzen Jonathan
Published: September 2019

Objectives

The World Health Organization recommends measurement of G6PD activity prior to initiation of 8-aminoquinolones for the treatment of P vivax malaria. An estimated 400 million people worldwide have G6PD deficiency, making them susceptible to hemolysis under oxidative stress. A new single-dose therapy (radical cure) for malaria with tafenoquine is contraindicated in patients with <70% normal G6PD activity due to its prolonged circulating half-life. However, most clinical laboratories report G6PD activity in units g/Hb or units/1012 RBC and do not provide percentage of normal activity, making potential eligibility determination challenging.

Methods

Using an IRB-exempt protocol, a limited data set of consecutive G6PD quantitative results was retrieved from the clinical laboratory’s enterprise data warehouse. Laboratory testing of these specimens was previously performed at 37°C using an automated enzymatic assay (Pointe Scientific) configured on a cobas c501 chemistry analyzer (Roche Diagnostics). Data were assembled to include adults age 18 to 89 years and excluded repeat results from the same patients as well as outliers.

Conclusion

The final data set included 52,216 results (female, 55.9%, n = 29,173; male, 44.1%, n = 23,043) from 47 US states. An adjusted male median (100% G6PD activity) was derived using an approach proposed by the Bangkok Workshop guidelines (Domingo et al., Malaria Journal, 2013), modified to more accurately differentiate bimodal peaks in population G6PD histograms. The laboratory-specific, adjusted male median was 12.7 U g/Hb and was similar to peak values derived from alternative curve-fitting approaches. Applying this median to gender-specific data sets, 5.4% of males and 3.8% of females were found to have <70% of normal activity (<8.9 U g/Hb). This study demonstrates the feasibility of percentage-based G6PD result reporting in adults; further studies will query percentage-based reporting in pediatric populations. Population-based medians will vary based on G6PD assay type and temperature and should be established by laboratories prior to percentage-based reporting.
Parallel Comparison of Cancer Antigen 15.3 and Cancer Antigen 27.29 in Breast Cancer
Authors: Wei Qing , Cao Liyun , Hardy Robert
Published: September 2019

Objectives

Mucins are large and complex glycoproteins expressed by several epithelial tissues. The expression of MUC1 mucin is upregulated in breast cancer and the protein is released in high amounts in patients’ blood. Cancer antigens (CA) 15.3 and CA 27.29, which measure different epitopes of MUC1 protein, are useful biomarkers for postoperative surveillance and therapy monitoring of advanced breast cancer. The aim of this study was to compare CA 15.3 assay and CA 27.29 assay by using paired patient samples.

Methods

The study was performed in 523 patient samples. CA 15.3 was measured by a sandwich assay on Beckman Coulter UniCel® DxI 800. CA 27. 29 was measured by a competitive immunoassay on Siemens ADVIA Centaur System.

Results

On Deming regression, the slope was 0.310 with an intercept of 8.6 and correlation coefficient of 0.951. The mean bias between the two assays was –39.2 (–56.6%). The agreement of the two methods was 89% (n = 467), among which, 12% (n = 62) were positive for both CA 15.3 and CA 27.29 (above the upper limit of the reference range), and 77% (n = 405) were negative for both assays (within the reference range). The disagreement was 11% (n = 56), which showed positive CA 27.29 and negative CA 15.3. The correlation coefficient between CA 15.3 and CA 27.29 is 0.9085 when both are positive and 0.6315 when both are negative. The bias is –238.9 (–84.7%) when both are positive and –8.5 (–52.4%) when both are negative. Paired t tests showed significant difference (P < .001) between the CA 15.3 and CA 27.29 in both positive samples and both negative samples.

Conclusion

In summary, there is a good correlation between CA 15.3 tested on Beckman Coulter UniCel® DxI 800 and CA 27.29 on ADVIA Centaur System. However, with the negative bias, they should not be used interchangeably.
Human Immunodeficiency Virus–Positive Patient Presenting With Acute Renal Failure and Hypercalcemia Diagnosed With Sarcoidosis
Authors: Dehghani Amir , Yousefi Elham , Alshal Mohamed , Xie Qiang , Zuretti Alejandro
Published: September 2019

Objectives

A 42-year-old African American man with a history of HIV infection on highly active antiretroviral therapy (HARRT) presented with excessive thirst, polydipsia, polyuria, weight loss, and abnormal kidney function tests. Physical examination was normal.

Methods

The patient workup results were as follows: calcium 13.8 mg/dL (8.4-10.3 mg/dL), ACE 88 U/L (8-52 U/L), PTH 7.34 pg/mL (14-72 pg/mL), 1,25 (OH)2 vitamin D 125 pg/mL (19.9-79.3 pg/mL), BUN 38 mg/dL (6-20 mg/dL), Cr 2.42 mg/dL (0.4-1.2 mg/dL), glucose 87 mg/dL (70-99 mg/dL), CD4 count 303/μL (544-1,894/μL). Chest CT scan showed diffuse pulmonary nodules with mediastinal and bilateral hilar lymphadenopathy. A transbronchial biopsy was performed.

Results

Biopsy revealed noncaseating granuloma and Schaumann bodies. AFB and GMS stains were negative for micro-organisms. These findings were compatible with sarcoidosis. The patient received prednisone and showed significant improvement in his renal function (creatinine: 1.23 mg/dL) and calcium level (9.12 mg/dL).

Conclusion

CD4+ T lymphocytes have a crucial role in the formation of sarcoid granulomas. However, HIV infection is characterized by a profound loss of the CD4+ T-lymphocytes. Therefore, sarcoidosis in HIV-positive patients is rare. The development of sarcoidosis usually occurs when a significant increase in CD4+ T-cell count induced by HAART has taken place. Pulmonary involvement and symptoms are responsible for the majority of the morbidity and mortality in sarcoidosis. Renal involvement is significantly less common than respiratory symptoms.

This patient was one out of two HI- positive cases of sarcoidosis among 200 patients who were diagnosed with sarcoidosis in our three major affiliated hospitals from 2000 to 2019. This case is unique and rare both in terms of unusual presentation of renal failure and hypercalcemia and also the co-occurrence of sarcoidosis in an HIV-positive patient while the CD4 count is lower than the normal limit.
Prevalence, Demographic Patterns, and Outcome of Childhood Malignancies in a Tertiary Hospital in Nigeria: A 15-Year Retrospective Study
Authors: Otokiti Oluwakemi , Temiye Edamisan
Published: September 2019

Objectives

Childhood cancers are increasingly recognized as a cause of childhood morbidity and mortality following improvement in immunization programs and sanitation against communicable diseases. With improvement in health care, better survival outcomes have been reported in childhood cancers worldwide. However, mortality associated with childhood cancers remains high in developing countries. This study aims to determine the prevalence, demographic characteristics, and outcome of childhood cancers seen in Lagos University Teaching Hospital, Lagos, Nigeria.

Methods

A retrospective study analyzed 749 cases of childhood malignancies between 2003 and 2017. Data on gender, age at diagnosis, diagnosis, and outcome were extracted using a data extraction proforma. Data were analyzed using SPSS v23. P value of .05 was considered statistically significant.

Results

Median age at diagnosis was 4.75 years with a male to female ratio of 1.3:1. Highest prevalence was noticed with hematological malignancies (41%), Wilm’s tumor (18%), retinoblastoma (13%), and soft tissue tumors (6.5%) and lowest prevalence with testicular cancers (0.3%). Apart from liver malignancy, males had a higher incidence in all malignancies. Median age at diagnosis was 12 years for nasopharyngeal carcinoma, 11 years for bone cancers, 8 years for gynecological cancers, 6 years for hematological cancers, and 0.47 years for testicular cancers. Overall mortality rate was 30%, and a significant number (53%) were lost to follow-up (discharged against medical advice, defaulted, financial burden, medical tourism). Hematological malignancies had the highest mortality rates, with Wilm’s tumor having best survival chances (lowest mortality).

Conclusion

Prevalence patterns mirror what was obtained in other centers (Jos, Ife, and Ibadan). A mortality rate of 30% is significant. Financial burden, religious beliefs, delay in presentation, and ignorance are major hindrances to health care and might contribute significantly to overall mortality and outcome. More needs to be done concerning childhood cancers.
Diagnostic Efficacy of Cytological Preparations With Rapid Onsite Evaluation Compared With Thinprep Without Onsite Evaluation in Diagnosing Pancreatic Solid Masses
Authors: Chang Qing , Gimenez Cecilia , Reddy Kalpana
Published: September 2019

Objectives

The diagnostic efficacy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic solid masses varies widely depending on the presence of rapid onsite evaluation (ROSE) and the type of cytology preparations. The present study aims to compare the diagnostic efficacy of cytology smears (CS) and cell block (CB) with ROSE versus Thinprep slides (TpS) with CB without ROSE in diagnosing pancreatic solid masses.

Methods

Performed retroprospective review of 56 patients (2017-2018) with surgically confirmed pancreatic neoplasms including cytology preparation type and comparison of diagnostic efficacies.

Results

Out of 56 patients who underwent surgical resection, 30 patients were diagnosed with pancreatic ductal adenocarcinoma (PDAC) and 26 with pancreatic neuroendocrine tumor (PNET) or solid pseudopalliary neoplasm (SPN). Out of 30 surgically removed PDACs, 20 patients had prior cytology specimens while 10 had surgical core biopsies. Of the 20 cytology specimens, 12 patients had ROSE with concurrent CS and CB, and all cases were diagnosed as positive. Out of the 8 patients without ROSE, 3 patients (1 with bile duct brush, 2 with TpS and CB) were diagnosed as positive. The diagnostic efficacy was 100% (12/12) in patients with ROSE and CS compared to 37.5% (3/8) in patients without ROSE. In 26 non-PDAC cases, 21 patients had cytology specimens and 5 had surgical biopsies. Seventeen cases with ROSE and immunohistochemical stains (IHC) on CB were diagnosed as positive, while 4 cases without ROSE and IHC received atypical diagnoses, resulting in a decreased diagnostic efficacy from 100% (17/17) to 0% (0/4).

Conclusion

ROSE with CS and CB are superior to TpS and CB in diagnosing solid pancreatic masses. ROSE with IHC on CB is crucial for diagnosing PNET and SPN, while CS and CB are important for PDAC diagnosis.
Infusing CURE Into the Medical Laboratory Science Curriculum
Authors: Johnson Deborah , Barham Beverly
Published: September 2019

Introduction

One of the challenges for Medical Laboratory Science (MLS) educators in a university-based program can be providing meaningful research experiences for all students. The availability of research positions for undergraduate MLS students in individual research labs is limited or not available, often due to time constraints within the MLS course schedule or other variables in the students’ lives outside of academe.

Methods

This study introduced a CURE (course-based undergraduate research experience) into a junior-level MLS microbiology course, where all students in the junior cohort participated in the same research agenda during the same semester. The objective was to provide equal access and an equitable experience for each MLS student in the cohort. The research question was determined with input from students and instructors and had application within the microbiology course where it was being infused. The study protocol was designed during class time and most tasks were completed in class as well. From a pedagogical perspective, the CURE model is designed around five basic parameters, including (1) use of multiple scientific practices, (2) the outcome is unknown, (3) there is a broader relevance or importance beyond this classroom experience, (4) collaboration is essential among students and instructors, and (5) iteration is built into the process.

Conclusion

We found this CURE resulted in useful data for both students and other outside stakeholders. This differs from basic inquiry models where students participate in the protocol, including interpretation of the data, but the answer or outcomes are already known by the instructors. While the learning curve for students and instructors can be steep when infusing a CURE into an already heavy content course, the rewards of providing equal access and an equitable experience for the entire cohort are well worth the additional time spent preparing for this challenge.
Experience With a Research and Innovation Office to Support Laboratory Medicine and Pathology Research
Authors: Beinborn Julie , Saling Kenneth , Reed Katelyn , Ibrahim Mohamed , Feldman Andrew
Published: September 2019

Objectives

Translational research in laboratory medicine and pathology is transforming health care based on recent quantum advances in omics technologies, computational science, and precision medicine. However, high-volume clinical settings where this research may be most effective often have significant constraints on faculty time that challenge productivity. The objective of this study was to assess our experience with a new resource designed to address this challenge.

Methods

In September 2016, we established the Research and Innovation Office (RIO) in the Department of Laboratory Medicine and Pathology, Mayo Clinic–Rochester. The goal was to provide infrastructure to unburden faculty from performing administrative, organizational, and operational tasks related to research. Over 30 months, we solicited faculty input into desired services, conducted surveys on utility and ease of use, and tracked metrics, including faculty participation, numbers of projects, and publications.

Results

Faculty members were highly satisfied with the range of services, ease of use, and service-oriented approach of RIO. Initial services included project organization, institutional process support (eg, IRB protocol management), biospecimen requests and handling, and data management. Based on early feedback, patient consenting, budget support, and manuscript assistance were added as additional services. Total RIO staff increased from 6 to 10 during in the first 30 months. Over this time, 97 of 160 faculty members (60%) utilized RIO services in over 1,000 discrete project requests. Annual departmental publications increased by 50% during this time.

Conclusion

Faculty time is a critical element for translational research productivity in laboratory medicine and pathology departments. Numerous tasks previously performed by faculty could be managed effectively by a team of research facilitators that unburdened constraints on research time and led to high levels of faculty engagement, satisfaction, and productivity. This model may promote advances in transformative laboratory medicine and pathology research in high-volume clinical settings.
Utilization of Apple iPads in Student Clinical Rotations to Improve Safety and Streamline Information Access
Authors: Harrison Jenica , Perkins Lisa , Nadder Teresa
Published: September 2019

Introduction

American Society for Microbiology, Guidelines for Biosafety in Teaching Laboratories (2012) state that educators must use best practices to minimize risk of biohazard contamination to students. Integrating mobile digital devices into Medical Laboratory Science (MLS) programs’ clinical training is potentially one means of reducing this risk. Historically, student assignments and evaluations for clinical rotations were in paper format. The purpose of this pilot project was to ascertain attitudes from students and clinical educators on using mobile devices as a laboratory bench-side educational tool during clinical rotations.

Methods

In this prospective study, three senior-level MLS students used Apple iPads (Apple, Inc; Cupertino, CA) in concert with Google Drive (Google; Mountain View, CA) in lieu of paper manuals during Hematology and Transfusion Medicine clinical rotations at Virginia Commonwealth University Health in fall 2018. Two VCUH clinical educators from these laboratories also participated. All participants were trained on usage and access of electronic material on the iPads as well as proper cleaning of the devices. As a comparison, student participants used paper clinical manuals during their Chemistry and Microbiology rotations. In addition, the clinical educators used paper versions of clinical manuals during four of five student rotations that occurred in fall 2018. Prestudy surveys were used to assess attitudes toward mobile devices. Focus groups, for students and clinical educators, separately, were conducted after completion of the clinical rotations.

Conclusions

The results of the study indicate that advantages of employing mobile devices include improvement of safety by eliminating transfer of paper worksheets from laboratory to the outside, ability to electronically monitor students’ progress through clinical laboratory rotations, and ease of accessibility to electronic references at the bench-side. Moving forward, the study will expand to include additional disciplines and students as well as employment of styli and DocuSign (DocuSign, Inc.; San Francisco, CA).
Predicting the Optimal Maintenance Dose of Warfarin (Marevan) Based on Multiple Influential Factors
Authors: Elsafty Ahmed , Gumenyak Maryana , Agranovsky Elena
Published: September 2019

Introduction

Although there are new anticoagulant drugs, warfarin is useful after surgery. The safety margin of warfarin is narrow, requiring precise dosing to avoid unpredicted bleeding and thrombophilia/embolisms. The initial dose is adjusted depending on the prothrombin time–international normalized ratio (PT-INR) level to establish the maintenance dose. The monitored adjustment may take several days.

Objective

To formulate a valid and reliable equation that indicates the daily maintenance dose of warfarin “Marevan” to achieve closest PT-INR levels to the targets.

Methods

Studies were conducted on 150 adult patients treated with daily doses of warfarin “Marevan” for different therapeutic/prophylactic indications with variable PT-INR results (1.15-12.7). The samples were drawn at least 2 days after the drug initial administration. Laboratory tests were analyzed using fully automated machines with reviewed quality control and preanalytical precautions. A continuous multiple regression analysis was undertaken. The dependent variable was the daily warfarin “Marevan” dose in milligrams. The independent variables included PT-INR, serum albumin concentration, patient age, hematocrit, height, weight, and estimated total plasma albumin amount. A review of the clinical history and disease category was undertaken and paired with the findings to validate and discover the equation’s limitations.

Results

Multiple regression analysis revealed significant results (multiple r > 0.8 with minimal two-sided P values). A reliable equation was developed to predict the warfarin “Marevan” dose, which mostly achieves a PT-INR level of 3.0 or any targeted level. The equation encompassed almost two-thirds of all potential variables, including the effect of other drugs’ interaction. Clinically, the equation was applicable to cases with coexisting lupus thrombophilia, severe anemia, or renal or liver diseases. In the presence of moderate or severe cold agglutinins, the equation predicted underestimated doses.

Conclusion

Predicted warfarin “Marevan” dose = + 45.9505 + (0.770598 × PT.INR) – (5.67861 × Serum.Albumin.Concentration) – (0.0933151 × Patient.Age.In.Years) + (0.507168 × Hematocrit) – (0.296932 × Height.In.Centimeters) – (0.21711 × Weight.In.Kilograms) + (0.290377 × Estimated.Total.Plasma.Albumin.Amount).
Metastatic CD138+ Lobular Breast Carcinoma Mimicking a Plasma Cell Neoplasm
Authors: Canevari Margaux , Wells Justin , Pryor Eric
Published: September 2019

We present a case of an 85-year-old female who received a bone marrow biopsy for concern over myelodysplastic symptoms and was subsequently diagnosed with a CD138-positive metastatic lobular breast carcinoma that mimicked a plasma cell neoplasm. Her medical history included endometrial serous adenocarcinoma (pT1a N0), severe mitral regurgitation, and atrial fibrillation. She presented with a 3-month history of thrombocytopenia (60,000/mcL) and a down-trending macrocytic anemia (nidus hemoglobin: 6-7 g/dL) that prompted a bone marrow biopsy. The aspirate smears were aparticulate and hemodiluted, while the touch preparations revealed a homogeneous population of large, plasmacytoid cells. These were again seen filling the medullary cavity on the bone marrow biopsy with eccentrically placed nuclei containing nucleoli and abundant eosinophilic cytoplasm. The cells were CD138, cytokeratin 7 and 8/18, mammoglobulin, and GATA-3 positive. They were cytokeratin 20, TTF-1/Napsin, PAX-8, and uroplakin negative. Further testing revealed the cells to be estrogen receptor positive (strong, 90%+), progesterone negative, HER2 negative, p120 positive (strong cytoplasmic), and E-cadherin negative. The patient’s prior serous adenocarcinoma histomorphology was not consistent with the plasmacytoid cells. Prior literature revealed a case report on a metastatic lobular carcinoma to bone marrow and discussion on the morphologic similarities, but the case was CD138 negative. This case highlights that CD138 can be positive in certain carcinomas, some of which can have a plasmacytoid morphology. Suspicion should be raised in an elderly female population.
Immunophenotypic Analysis of Peripheral T-Cell Lymphomas: A Single-Center Retrospective Review of Flow Cytometric Analysis
Authors: Abbott Daniel , Kroft Steven , Hintzke Maria , Carrillo-Polanco Luis , Cunningham Ashley , Astle John , Leventaki Vasiliki , Harrington Alexandra
Published: September 2019

Background

Peripheral T-cell lymphomas (PTCLs) are heterogenous, mature T-cell neoplasms that are a diagnostic challenge, requiring a combination of morphologic assessment and ancillary studies. Flow cytometry (FC) is a tool used routinely in lymphoma diagnosis; however, most analyses are limited to B-cell evaluation and pathologists generally lack experience evaluating for PTCL. We aimed to describe the immunophenotypic aberrancies observed by FC in PTCL.

Design

PTCLs with FC were collected, excluding primary leukemic processes. Four- and eight-color FC data were reanalyzed with the following antigens (when available): CD2, CD3, CD4, CD5, CD7, CD8, CD30, CD45, CD45RO, CD56, and CD57. Lymphoma cells were compared to normal T cells and an isotype control. Antigen expression was defined as >20%.

Results

Thirty-eight cases were analyzed (29 males, 9 females, 6-86 years, median 62 years), including 29 PTCLs NOS, 4 angioimmunoblastic T-cell lymphomas (AITLs), 3 anaplastic large cell lymphomas, 1 δγ-TCL, and 1 hepatosplenic TCL from 15 bone marrows, 14 lymph nodes, 6 bloods, 2 fluids, and 1 skin. Twenty cases were CD4+, 4 were CD8+, 3 were dual +, and 10 were dual –. Thirty-seven cases (97%) showed global aberrant antigen patterns, median 4 aberrancies/case (1-8). Lymphoma cells accounted for 0.07% to 68% (median 2.6%) of total events. Aberrant CD7 expression was present in 34 of 38 (89%) and was underexpressed in 22 of 34 (65%). CD3 and CD5 were aberrant in 79% of cases each, with two-thirds showing underexpression. CD2 and CD45RO were aberrant in two-thirds of PTCLs, with overexpression in 61% and 92% of those cases, respectively. One AITL showed no aberrancies.

Conclusions

Nearly all PTCLs show immunophenotypic aberrancy compared to normal T cells. Most commonly, PTCL showed aberrant underexpression of CD7, CD3, and CD5 and overexpression of CD2 and CD45RO. Our data support FC panels with CD2, CD3, CD4, CD5, CD7, CD8, and CD45RO to optimize recovery of aberrant T cells.
A 62-Year-Old African American Woman With Stable Lymphadenopathy Over 5 Years
Authors: El Achi Hanadi , Glass William , Velazquez Miriam , Hu Zhihong
Published: September 2019

The patient is a 62-year-old African American female with medical history of Plummer Vinson syndrome and CT scan in 2014 showing lymphadenopathy of the porta hepatis. Needle core biopsy of enlarged lymph nodes revealed sheets of polytypic plasma cells with no aberrant B or T cells or granulomas or hyaline-like depositions identified. The findings were suspicious for unicentric Castleman disease. In 2019, the patient presented with chronic fatigue without other systemic symptoms. Contrast CT revealed persistent retroperitoneal lymphadenopathy and calcified granulomas in the liver, spleen, and lung. Excision of portal and celiac nodes showed preserved nodal architecture with mild mantle zone expansion and marked hyaline-like deposition in the follicles. Sheets of mature plasma cells and focally increased vasculatures were seen in the interfollicular areas. Focally frequent nonnecrotizing granulomas were noted. Occasional giant cells and rare asteroid bodies were identified in the granulomas. Immunohistochemistry stain workup revealed normal distribution of the B and T lymphocytes. CD138 stain highlighted marked increased plasma cells and HHV8 was negative. Immunofluorescence microscopy for kappa and lambda did not show monoclonality; IgA was positive in <10% of plasma cells; special stain for Congo red and serum amyloid associated protein (SSA) IHC stain were strongly positive in the follicles. The overall findings are consistent with reactive lymphadenopathy with interfollicular polytypic plasmacytosis, noncaseating granuloma formation, and reactive amyloidosis. The features of mantle zone hyperplasia and polytypic plasmacytosis are suggestive of HHV8-negative/idiopathic unicentric Castleman disease. This case possibly represents an example of concurrent amyloidosis, sarcoidosis, and idiopathic unicentric Castleman disease. Given that SSA was recently reported to have a pathogenic role in granulomatous inflammation of sarcoidosis through sustained inflammatory reaction, the possibility of increased SSA triggering sarcoidoisis in this patient can be considered. However, the exact pathogenesis of these concurrent findings needs further investigation and clarification.
Atypical Plasmablastic Lymphoma Presenting as a Perianal Mass in a 19-Year-Old Male
Authors: Ding Daniel , Wang Jun
Published: September 2019

Objectives

To describe a case of plasmablastic lymphoma with an atypical immunophenotype in an unusual location.

Methods

We received this specimen for routine processing after the patient underwent an incision and drainage surgery. The specimen was sent to hematopathology for workup of lymphoma. We then ordered several special stains and molecular tests to confirm our diagnosis of plasmablastic lymphoma.

Results

Histologic examination of the tissue reveals sheets of large plasmablastic cells with eccentrically located round nuclei, prominent nucleoli, and cartwheel chromatin. Frequent apoptotic bodies and mitotic figures are present. Immunohistochemistry shows strong, diffuse positivity for leukocyte common antigen CD45, CD10, plasmacytic markers (MUM1, CD79a) and negativity for B-cell markers (CD20, PAX5) and CD138. The Ki-67 proliferation index is very high (>90%) and Epstein-Barr virus encoded small RNA (EBER) in situ hybridization is diffusely positive. Molecular FISH testing for aggressive B-cell lymphoma genetic abnormalities is positive for MYC gene rearrangement in 68% of nuclei and the loss of one copy of the BCL2 gene on chromosome 18 in 64% of nuclei.

Conclusion

This case of plasmablastic lymphoma is unique due to its atypical presentation as a perianal mass in a young patient with undiagnosed HIV. Usually, this lymphoma presents as an oral lesion in an older patient with HIV. In addition, immunohistochemistry showed an unusual immunophenotype (CD138–, MUM1+, CD45+, CD10+). Most plasmablastic lymphomas are CD138+, MUM1+, and CD45– but this specimen is CD138–, MUM1+, and CD45+. Further testing shows EBER positivity, a positive HIV test, and MYC gene rearrangement, which confirms our diagnosis of a plasmablastic lymphoma. Of note, genetic analysis also reveals a loss of one copy of the BCL2 gene on chromosome 18 in 64% of nuclei.
Comparing Efficacy of Low Dose Cytoreduction and Manual Exchange Blood Transfusion in Managing Hyperleukocytosis: A Case Report
Authors: Otokiti Oluwakemi , Ogbenna Ann , Bolarinwa Abiola , Olatinwo Adejoke
Published: September 2019

Objectives

Hyperleukocytosis is defined as white cell count greater than 100,000 cells/mm3. Symptomatic hyperleukocytosis (leukostasis) is a medical emergency and can complicate hematological malignancies. It is commoner in myeloid leukemia but can occur in extremely high-count lymphoid leukemia causing tumor lysis syndrome and death. Immediate management is hydration, cytoreduction, and leukapheresis. In a developing country without leukapheresis, how effective is manual exchange blood transfusion compared to low-dose cytoreduction? We present a case of chronic lymphocytic leukemia with severe hyperleukocytosis, comparing response to different treatment modalities in the absence of leukapheresis.

Case Summary

A 57-year-old woman with complaints of a vaginal protrusion and an incidental finding of a splenomegaly with moderate anemia. Hemogram showed a white cell count of 301,000 cells/mm3, and blood film revealed a chronic lymphocytic leukemia. She had two cycles of cyclophosphamide, vincristine, and prednisolone and presented 8 months later with worsening leukocytosis of 697,000 cells/mm3, severe anemia, dizziness, headaches, fatigue, and hyperkalemia. Two manual exchange blood transfusions insignificantly decreased count by 40,000 cells/mm3 with slight reduction of hyperkalemia. She had low-dose cytoreduction with weekly vincristine and prednisolone. White cell count reduced from 653,000 cells/mm3 to 467,000 cells/mm3 with normal electrolytes. She was then commenced on cyclophosphamide, mini-hydroxorubicin, vincristine, and prednisolone. There was a steady decline in counts with improvement in hematological parameters and overall well-being.

Conclusion

Due to nonavailability of leukapheresis, we attempted a manual exchange without a significant decrease in white cell count. However, with low-dose cytoreduction, there was a considerable decrease in white blood cell count and improvement of electrolyte with no tumor lysis syndrome, and it was more affordable. Therefore, in a resource-poor setting, using low-dose cytoreduction might be cheaper, safer, and more effective than exchange blood transfusion in managing hyperleukocytosis.
Synoptic Versus Narrative Reporting of Prostate Biopsies at a Tertiary Healthcare Institution: Challenges, Successes, and Expectations
Authors: Orah Nnamdi , Charles Anunobi
Published: September 2019

Objectives

Cancer pathology reports are expected to contain all information required for patient management and disease surveillance. Moreover, reports for patients with prostate cancer have become increasingly complex with the addition of more pathological details. This study aimed to compare narrative and synoptic prostate cancer reports for core needle biopsies received at a tertiary hospital in Nigeria in order to determine which form was most complete according to international standards.

Methods

This study was conducted from January 2010 to December 2015 at the Lagos University Teaching Hospital, Lagos, Nigeria. All malignant prostate cancer histopathology reports received during this period were analyzed for the presence of important clinicopathological parameters, including the numbers of cores taken and those involved by the tumor, percentage of tumor involvement, Gleason score, and the presence of high-grade prostatic intraepithelial neoplasms (HGPINs) and perineural and lymphovascular invasion.

Results

A total of 83 reports were reviewed, of which 27 were in narrative and 56 in synoptic format. The documentation of clinicopathological characteristics in narrative reports was significantly incomplete compared to synoptic reports in recording the number of cores (33.3% versus 96.4%), number of cores involved by the tumor (11.1% versus 94.6%), percentage of cores involved by the tumor (3.7% versus 100.0%), and the presence of HGPINs (7.4% versus 100.0%) and perineural (59.3% versus 98.2%) and lymphovascular (48.1% versus 100.0%) invasion (P < .001 each).

Conclusion

Synoptic reports of malignant prostate cancer biopsies received at the Lagos University Teaching Hospital were found to contain more complete information than narrative reports.
Implementation of Whole-Slide Imaging as a Pathology Teaching Tool and for Institutional Tumor Boards: A Resident’s Experience
Authors: Mishra Ashish , Tuthill J Mark
Published: September 2019

Objectives

This presentation will describe our experience implementing and utilizing whole-slide imaging (WSI) as a teaching tool for the pathology residents in Henry Ford Hospital, Detroit, as well as our initial efforts to use WSI at institutional tumor boards.

Methods

Glass slides were scanned for practice over several weeks to determine basic operation, system performance, and workflow processes. Experience quickly showed that the scanner could be used to improvement quality and efficiency of weekly unknown slide conference. Informatics lecture and luncheon meeting topics as well as a grand-rounds presentation on novel ways to use WSI were shared with residents and other members of the department. This resulted in marked increased interest. Soon interest grew from attending physicians to use WSI for a subset of tumor boards. The same processes and procedures used for scanning slides for unknown conference were applied.

Results

In October 2016, an unknown slide conference was presented using WSI. The reaction to the quality of the histopathology system usage was excellent: nuclear contours and nucleoli were clear; navigation was easy; response time was excellent, with no screen lag. Residents and attending loved the new format. Since then, the unknown conference has been presented monthly using WSI. In November 2016, we started presenting cases on WSI in the GYN tumor board. Some had no idea that this was even technically possible. All GYN weekly tumor boards are now presented using WSI.

Conclusion

Whole-slide imaging is a useful tool for teaching and presentation purposes. It can be easily implemented and integrated into our day-to-day pathology practice and resident training. The reluctance to use WSI is initially high among pathologists, but enthusiasm increases once implemented into regular practice. WSI provides for efficiencies and ease of collaboration in both educational and clinical case review settings such as institutional tumor boards.
The Value of Monitoring Requisition Forms in the Laboratory
Authors: Ebare Kingsley , Lanceta Joel , Restivo JeanneAnn , Opitz Lynne
Published: September 2019

Objectives

Insufficient or extraneous information on requisition forms may delay turnaround time and become a source of error in diagnosis. Monitoring the completeness and accuracy of clinical information in the requisition forms provided to pathologists is a potential target in laboratory quality improvement, but its effectiveness is currently not known. Here, we describe a pilot study at our institution’s anatomic pathology laboratory to determine the effect of monitoring the completeness of information filled in the requisition forms by clinicians.

Methods

We randomly selected and reviewed records in each quarter from August 2017 to January 2019. All records were obtained from one hospital site and included requisition forms for specimens from inpatient and outpatient surgical operating rooms. The percentage of incomplete or improperly filled forms was tracked each quarter and feedback is provided to clinicians with insufficient information in the forms.

Results

A total of 70 requisition forms from 7 quarters were reviewed. Five different physicians were responsible for all the requisition forms without complete information. One physician was responsible for 33.3% of all requisition forms with incomplete information. Commonly recurring missing information in requisition forms were preoperative diagnosis (40%), postoperative diagnosis (35%), type of procedure (15%), and indications for procedure (10%). There was a remarkable improvement on completion of requisition forms from 60% at the beginning of the review period to 100% at the end of the review period (P < .0001).

Conclusion

Long-term review of requisition forms submitted to the laboratory and provisional feedback to clinicians are associated with sustainable improvement on information provided to pathologists to ensure specimen identification, integrity, and accurate interpretation.
Choosing Wisely: Persistent Amylase Concurrent With Lipase Testing at Multiple Academic Health Systems
Authors: Ritter Jacob , Ghirimoldi Federico , Manuel Laura , Moffett Eric , Shireman Paula , Brimhall Bradley
Published: September 2019

Objectives

Choosing Wisely is a multidisciplinary effort to reduce unnecessary tests and procedures. Evidence-based guidelines advocate using serum lipase to diagnose acute pancreatitis; concurrent amylase and lipase tests provide minimal benefit compared to either alone. Serial measurements after the first elevated test are ineffective for tracking disease course. Our study determined the number of concurrent amylase/lipase tests and unnecessary serial tests to examine adherence to Choosing Wisely recommendations at four academic health systems. We also identified provider-ordering patterns and quantified the variable and total costs of unnecessary tests.

Methods

We analyzed deidentified laboratory data from four academic health systems in the Greater Plains Collaborative for all serum amylase and lipase tests from 2017, including results, timing, and patient-encounter location. We defined concurrent tests occurring within a 24-hour period and unnecessary serial inpatient measurements occurring after the first elevated result.

Conclusion

While the majority of providers adhered to Choosing Wisely recommendations obtaining 58,693 lipase-only tests, 85.8% of amylase tests were obtained in parallel with lipase (20,771 concurrent tests; amylase only, 3,447; total amylase tests, 24,218). Encounter location revealed concurrent rates of 43%, 32%, and 5% for ambulatory, inpatient, and emergency department settings, respectively. Ambulatory clinics from multiple services obtained concurrent tests, with Family Medicine obtaining 48%. Services with order sets containing both amylase and lipase were associated with higher rates of concurrent testing. Inpatient unnecessary serial testing resulted in 413 amylase and 1,266 lipase tests occurring in 33% and 31% of inpatient encounters for amylase and lipase, respectively. Unnecessary amylase and lipase tests resulted in $31,195 variable costs and in $86,297 total costs. Targeted education to clinicians/services ordering unnecessary amylase/lipase tests and revising order sets could decrease costs and improve quality of care by decreasing the volume and frequency of blood draws. Funded by UL1TR002645 and the Greater Plains Collaborative.