bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric glomus tumor mimicking neuroendocrine tumor on fine needle aspiration: a diagnostic pitfall
Authors: Khan J , Cramer H M , Dave N , Segura S
Published: November 2023

Introduction/Objective

Glomus tumors (GT) are mesenchymal neoplasms of modified smooth muscle that most commonly affect subungual regions of distal extremities. Although they can occur everywhere in the body, gastric involvement is rare. Gastric GT is usually benign but given the overlapping morphologic and immunohistochemical features with other gastric mesenchymal tumors, GT is commonly misdiagnosed.

Methods/Case Report

We present two cases of gastric GT initially diagnosed as well-differentiated neuroendocrine tumor (WDNT), G1 on fine needle aspiration (FNA). A 57-year-old female presented with an incidental 1.5 cm gastric submucosal lesion discovered on endoscopy performed for esophageal food impaction. The second case is of a 73- year-old male with a 1.7 cm submucosal lesion found on endoscopy for reflux. Both lesions were located in the gastric antrum. FNA showed clusters of relatively uniform cells with moderate cytoplasm, round nuclei, and stippled chromatin. Tumor cells were focally positive for synaptophysin, while negative for CK7, CD117, DOG-1, and chromogranin. Ki-67 proliferative index was <3%. A diagnosis of WDNT, G1 was made. Subsequent partial gastrectomy showed a submucosal epithelioid neoplasm composed of cells with eosinophilic to clear cytoplasm, and distinct cellular membranes. Focally dilated, tumor-associated thin-walled vessels were noted.

Immunohistochemically, the tumor was positive for SMA, calponin, and synaptophysin, and negative for CK AE1/AE3 and chromogranin, supporting the diagnosis of gastric GT.

Results (if a Case Study enter NA)

N/A

Conclusion

The rarity of gastric GT, combined with the morphological and immunohistochemical similarity with WDNT, led to diagnostic pitfalls in these cases. With the increased detection and sampling of incidental gastric lesions, cytopathologists should be aware of this uncommon tumor and its mimics, and as such, expand their differential diagnoses.
Selpercatinib-induced hepatotoxicity: A rare case report
Authors: Liang G , Lin J , Zhang D
Published: November 2023

Introduction/Objective

Selpercatinib (Retevmo) is a highly selective rearranged during transfection (RET) kinase inhibitor indicated for treatment of solid tumors with RET gene mutation or fusion, such as medullary thyroid carcinoma or non-small cell lung carcinoma. Among selpercatinib’s side effects, severe hepatotoxicity was only seen in 3% of the patients. Here we report a case of selpercatinib-induced hepatotoxicity, which has not been well characterized before.

Methods/Case Report

The patient was a 56-year-old female who had medullary thyroid carcinoma with RET M918T mutation (pT3aN1b) status post total thyroidectomy. Recurrence occurred and selpercatinib treatment was initiated. Then the patient complained of mouth sores, tongue sensitivity, and lower extremity cramping. The dosage was reduced to half. The magnetic resonance imaging on day 67 of selpercatinib treatment showed heterogeneous enhancement in the right hepatic lobe, compatible with parenchymal liver disease/hepatitis, trace perihepatic ascites, and mild splenomegaly. On day 71, liver function abnormalities were detected (ALK 315 IU/L, ALT 745 IU/L, AST 899 IU/L, total bilirubin 7.7 mg/dL). Workups including autoimmune hepatitis serology, viral hepatitis, or other infections were all negative. She had no history of other drug use. On day 72, a liver biopsy was performed that demonstrated mild to moderate portal lymphocyte-predominant mixed inflammation with interface activity. The lobules showed marked inflammation with hepatocyte disorganization, acidophil bodies, hepatocyte dropout, and rare lipogranulomas. Bile duct injury and patchy canalicular cholestasis were also noted. Trichrome stain showed focal bridging fibrosis.

Overall, the histologic findings were acute and chronic hepatitis pattern injury, favor selpercatinib-induced hepatotoxicity. Selpercatinib was discontinued. All liver enzymes gradually returned to normal levels on day 169.

Results (if a Case Study enter NA)

NA

Conclusion

Our study suggests that screening patients for abnormal liver function tests prior to and monitoring periodically during selpercatinib treatment is necessary. Based on the severity of hepatotoxicity, withholding, reducing the dose, or permanently discontinuing selpercatinib is recommended.
Impact of Online Tumor Board Simulation for Optimizing Testing and Treatment of Patients with BRAFV600E- mutant Metastatic Colorectal Cancer
Authors: Kelly M , Beumer K
Published: November 2023

Introduction/Objective

Approximately 10% of patients with metastatic colorectal cancer (mCRC) have BRAF genetic mutations, 90% of which result in a V600E substitution. Although there are targeted therapies available, there has been confusion about new and emerging testing and treatment options for BRAFV600E-mutant mCRC.

Methods/Case Report

To meet these needs, ASCP designed a 60-minute, self-paced, CME/CMLE online tumor board simulation to: increase knowledge, skills, and competence of pathologists and laboratory professionals to ensure patients with mCRC are appropriately and efficiently tested for BRAF mutations in accordance with NCCN guidelines, and enable pathologists to guide medical oncologists in the appropriate diagnosis, testing, and treatment of patients with mCRC. In the simulation, an expert pathologist and oncologist presented patient cases involving BRAFV600E-mutant mCRC. Learners answered questions designed to help them carefully consider the nuances of each case, building their knowledge and skills related to the detection and optimal management of patients with BRAF-mutant mCRC.

Results (if a Case Study enter NA)

250+ learners have participated, with results demonstrating greater understanding of the NCCN guidelines for molecular testing of patients with mCRC, the clinicopathologic characteristics of BRAF-mutant mCRC. The tumor board simulation also increased awareness of strategies for improving turnaround times in biomarker testing for patients with mCRC, as well as current and emerging treatment options for BRAFV600E-mutant mCRC, which were two of the main goals of the education.

Conclusion

This project advanced knowledge, skills, and competence among pathologists and laboratory professionals, particularly those in community practice, to help ensure that patients who may be eligible for new and emerging therapies for BRAFV600E-mutant mCRC receive effective, optimized, and timely biomarker testing and treatment. The education may be useful to learners who want an increased understanding of BRAF mutations and their role in treatment selection.
Cystic pheochromocytoma: a rare variant of adrenal gland tumor case report
Authors: Zhong X , Kokabee M , Sham S , Grasso M , Unger P
Published: November 2023

Introduction/Objective

Pheochromocytoma is the primary adrenal medullary tumor in adults. Patients usually present with sustained or sporadic hypertension. The tumors are almost always solid. Cystic pheochromocytoma (CP) is extremely rare with only a few cases reported in the literature. Patients with CP may be asymptomatic and normotensive and be diagnosed incidentally on imaging or intraoperatively.

Methods/Case Report

We report a case of an 82-year-old male with a large CP who presented with back pain. The patient was hypertensive preoperatively (140/85 mmHg). Imaging showed a 5.4 cm complex right adrenal mass that could not be further classified. Labs showed markedly increased 24hr urine normetanephrine (1342 ug/24hr). The patient was presumed to have a pheochromocytoma and was preoperatively treated with an alpha-blocker. At surgery an 8.0 cm multiloculated cystic adrenal mass was removed, and grossly the specimen consisted of a brown, multicystic mass filled with brown liquid. Histology revealed the septa to contain nests of polygonal cells with vacuolated to basophilic granular cytoplasm with moderate nuclear pleomorphism . Immunohistochemical staining was positive for synaptophysin, chromogranin and S-100, which confirmed the diagnosis of CP. Patient’s postoperative blood pressure was 130/60 mmHg.

Results (if a Case Study enter NA)

NA

Conclusion

Cystic pheochromocytoma has to be in the differential for a retroperitoneal cystic mass in order that clinicians, radiologists as well as pathologists undertake proper patient management and diagnosis.
Diagnostic role and prognostic impact of PSAP immunohistochemistry: A tissue microarray study on 31,358 cancer tissues from 127 different tumor types
Authors: Tribian L S , Lennartz M , Blessin N C , Kind S , Viehweger F , Menz A , Burandt E , Sauter G , Simon R , Kluth M , Bernreuther C
Published: November 2023

Introduction/Objective

Prostatic specific acid phosphatase (PSAP) protein is produced in prostate epithelial cells and it is used as an immunohistochemical marker for prostate cancer. However, studies have reported PSAP expression to occur in various other tumor entities as well.

Methods/Case Report

Prostatic specific acid phosphatase (PSAP) protein is produced in prostate epithelial cells and it is used as an immunohistochemical marker for prostate cancer. However, studies have reported PSAP expression to occur in various other tumor entities as well.

Results (if a Case Study enter NA)

In prostate cancer, PSAP staining was seen in 100% of Gleason 3 + 3, 95.5% Gleason 4 + 4, 93.8% recurrent prostate cancer under androgen deprivation therapy, 91.0% Gleason 5 + 5 and 31.2% small cell neuroendocrine prostate cancer. Reduced PSAP staining was strongly linked to high pT stage, high Gleason grade, lymph node metastasis, early PSA-recurrence (p<0.0001 each),high androgen receptor expression and TMPRSS2:ERG fusions. In multivariate analyses, low PSAP expression was able to predict PSA recurrence independent of pre- and postoperative prognostic markers in ERG negative cancers. In extra-prostatic cancers, PSAP immunostaining was only seen in 3 of 94 (3.2%) neuroendocrine tumors of the pancreas and in 1 of 129 (0.8%) diffuse type gastric adenocarcinomas.

Conclusion

A positive PSAP immunostaining is highly specific for prostate cancer and reduced PSAP expression is associated with an aggressive prostate cancer phenotype. The independent association of reduced PSAP expression with poor prognosis in ERG negative prostate cancer makes PSAP measurement a candidate marker for prognostic multiparameter panels for prostate cancer.
Fine Needle Aspiration and Core Biopsy of Liver Mass as First Time Diagnosis of Sarcomatoid Anaplastic Thyroid Carcinoma, A Rare Malignancy Presenting at an Unexpected Body Site
Authors: Kamashki A , Rivera M , Sturgis C
Published: November 2023

Introduction/Objective

Anaplastic thyroid carcinoma (ATC) is a fatal malignancy. We report an unusual case of a patient with ATC whose chief complaint and clinical history were listed as “jaundice and liver mass” without mention of disease in the neck.

Methods/Case Report

A 66-year-old female presented to the emergency department with worsening “yellow-green skin discoloration” for a few weeks. She also reported worsening dyspnea and recent dysphagia with solid foods, fatigue, abdominal pain and recent hemoptysis. Physical examination revealed conjunctival icterus, jaundice, a tender neck mass, right upper chest wall tenderness and palpable lymphadenopathy in the lower neck. Assessment notes indicated inability to carry out self-care and being bedridden, even though she reported having been active, swimming and cycling, up to one month before her presentation.

Computed tomography studies confirmed findings compatible with widespread malignancy with mass lesions in her

liver, lungs, adrenals, kidneys, neck, pancreas, gallbladder, and brain. Mild anemia, hemoglobin 10.5g/dL, mild leukocytosis, leukocytes 17,000/mm3, were confirmed. Bilirubin was 15µmol/L, and hepatic enzymes were elevated. An ultrasound-guided liver biopsy was performed and evaluated for cytologic features, histologic features and pattern of immunoreactivity. The combined cytomorphologic and histologic features were those of a pleomorphic sarcomatoid high-grade malignancy with variably spindled to epithelioid morphology and associated necrosis.

Immunohistochemical studies performed on sections from the accompanying core biopsy confirmed the malignant cells to be positive with CK-AE1/AE3, CK 7, TTF-1, GATA3, PAX8, SATB2, and BRAF V600E. The malignant cells were nonreactive with CK 20, thyroglobulin, calcitonin, napsin, CDX2, PCEA, and ER.

The combined clinical setting, imaging findings, cytomorphology, histomorphology and ancillary testing results together allowed for a specific diagnosis of metastatic anaplastic thyroid carcinoma. The patient was referred for palliative care services and died within a few days of diagnosis.

Results (if a Case Study enter NA)

NA

Conclusion

Metastatic disease from a sarcomatoid ATC, as diagnosed in this case, is an important differential diagnosis to keep in mind when an elderly patient presents with multisite metastases from an undefined primary source. Clinical, radiological and laboratory correlations are of paramount importance in correlating with cytomorphology/histomorphology and in helping to determine the best panel of IHC studies to consider.
A Skin Inflammatory Myofibroblastic Tumor Penetrates Through Skull To The Dura: A Case Report
Authors: Xian L , Wei E
Published: November 2023

Introduction/Objective

Inflammatory myofibroblastic tumor (IMT) is currently accepted to be a true neoplasm with a wide spectrum of biological behavior, varying from benign lesions to the rare tumors which are multifocal and prone to recurrence. IMT is characterized by a proliferation of myofibroblastic spindle cells with an inflammatory infiltrate. It was first described in the lung and later on reported in various sites such as stomach, intestine, spleen, bone. Here we report a rare IMT case in that the tumor penetrates through skull and extends to the dura.

Methods/Case Report

A 29-year-old female presented with a slowly progressive upper head scalp mass of one-year duration. Magnetic resonance imaging showed a soft tissue mass that extended through the skull and into the dura. Patient denies headache, syncopal episodes, neck pain, back pain, radicular symptoms, weakness, ataxia, nausea, vomiting, bladder or bowel incontinence, saddle anesthesia, or changes from baseline hearing, vision, or speech.

Grossly, serial sectioning of the scalp skin specimen revealed a well-circumscribed mass lesion with white, firm, and homogeneous cut surface, with no hemorrhage or necrosis identified. The lesion measured 7.0 x 6.5 x 1.7 cm in greatest dimension. The lesion involved the deep margin and extended to the skull and dura. On histopathological examination, the lesion was composed of variable admixture of spindle cells with eosinophilic cytoplasm and inflammatory cells comprising of plasma cells and lymphocytes. The spindle cells were positive for smooth muscle actin, CD10 (partial), and negative for AE1/AE3, ALK–1, CD34, CD68, CD117, Desmin, Myogenin, p53, S-100, and SOX-10. The Ki-67 showed a spindle cell proliferation index at about 2%. The patient successfully went through surgery and was followed up without complications.

Results (if a Case Study enter NA)

NA

Conclusion

Our case showed a rare IMT case harboring histologically benign features like low cellularity, minimal nuclear atypia, and low proliferative index, but demonstrating locally very aggressive biological behaviors. Complete surgical resection and close follow up are suggested to avoid recurrence. Further studies are needed in this field to design in-depth investigation for accurate diagnosis and better clinical outcomes.
Like, Share, and Follow! Analysis of the Use of Social Media by Pathology Residency Programs
Authors: Khatskevich K , Baker T , Hartman C , Cha J , Nguyen A , Mason A
Published: November 2023

Introduction/Objective

To establish the patterns of social media usage across Facebook, Twitter, and Instagram for pathology residency programs and departments from January 2018 to August 2022. To our knowledge, this is the first study of its kind focused on pathology residency programs.

Methods/Case Report

A list of pathology residency programs was compiled from National Resident Matching Program data. Websites for pathology residencies and major social media platforms were searched for pathology program accounts. The date of creation, number of followers, and number of likes were tracked for each program’s account(s). Each post between January 2018 and August 2022 was categorized according to the content (i.e resident life, education, research announcements, etc.), the number of likes, comments, and shares. Data collection is ongoing with future plans to compare posts and social media popularity between programs based on residency program size, prestige, and geographic location.

Results (if a Case Study enter NA)

Preliminarily 86 residency programs and 110 social media accounts were identified. There was an increase in social media posts between 2018 and 2022 with Twitter being the most utilized platform. The most commonly posted content category was pathology education, particularly on Twitter. Programs can use this information to create education-based posts or expand on existing teaching programs through social media. While educational posts had the most likes on Facebook, posts focused on the MATCH (the process in which medical students are accepted into a residency program) garnered the most likes on Twitter and Instagram.

Conclusion

A closer look into how residency programs are using social media and the relative success of posts could be used to increase visibility of residency programs as the resident recruitment process continues to be conducted virtually. The prevalence and popularity of education-focused posts shows that social media is an effective platform to teach pathology and is well received by viewers. Future research can focus on how pathology residency social media posts may have impacted residents, students, and other social media consumers on their decision to apply or to attend a program and/or interest in pathology.
Chronic Myeloid Leukemia Presenting with Mixed Phenotype B/Myeloid Blast Phase: A Diagnostic Challenge
Authors: Rivera D , Shirai S , Moosvi A , Wahed M A , Armstrong J A
Published: November 2023

Introduction/Objective

Chronic myeloid leukemia (CML) is typically identified in chronic phase, however about 5% of cases present in a more advanced phase. In blast phase (BP), the blasts are most commonly of myeloid lineage, less commonly lymphoid, and rarely mixed lineage cases are encountered. A mixed phenotype at presentation raises the possibility of a de novo mixed phenotype acute leukemia (MPAL) with BCR::ABL1 fusion and requires careful correlation with ancillary studies to confirm the diagnosis.

Methods/Case Report

The patient is a 60-year-old man who presented with leukocytosis, anemia, normal platelet count, and blasts identified on peripheral blood smear examination. A bone marrow biopsy demonstrated hypercellular marrow and a dimorphic population of large and small blasts, comprising nearly 70% of cellularity. Flow cytometry demonstrated distinct myeloid and B-lymphoid blast populations, both of which expressed CD13 and TdT. Interphase fluorescence in situ hybridization (FISH) showed the BCR::ABL1 fusion in more than 90% of nuclei, including segmented nuclei, and conventional cytogenetic studies showed t(9;22)(q34.1;q11.2) in 19 of 20 metaphases.

Molecular studies demonstrated the minor BCR::ABL1 p190 transcript, as well as ASXL1 and dual RUNX1 mutations. The discrepant number of BCR::ABL1 positive cells by FISH and conventional cytogenetic studies compared to the proportion of blasts, and its presence in segmented nuclei, enabled a diagnosis of CML with mixed phenotype blast phase despite absence of features such as basophilia or significant granulocytic left shift.

Results (if a Case Study enter NA)

NA

Conclusion

We share this case of CML in mixed phenotype blast phase to highlight the importance of careful evaluation in distinguishing this rare presentation from de novo MPAL, particularly with BCR::ABL1 fusion. Features such as a disproportionate number of nuclei or metaphases carrying the t(9;22) translocation on FISH or conventional cytogenetic studies and the presence of BCR::ABL1 in mature granulocytes can be helpful when other morphologic features of CML are absent.
Angioimmunoblastic T-Cell Lymphoma with Concurrent EBV Viremia: A Challenging Case
Authors: Ak S , Wang W , Wahed M A , Armstrong J A
Published: November 2023

Introduction/Objective

Angioimmunoblastic T-cell lymphoma (AITL) represents only 1-2% of all non-Hodgkin lymphomas but is one of the most common non-cutaneous T-cell lymphomas. Although typically associated with latent Epstein Barr Virus (EBV) infection, recent studies have demonstrated the presence and prognostic impact of EBV viremia at the time of diagnosis. Here, we present a case of AITL in which the diagnosis was complicated by EBV viremia.

Methods/Case Report

A 41-year-old male presented to our hospital with generalized abdominal pain, diffuse lymphadenopathy, hepatomegaly, ascites, and diffuse body wall edema. A recent retroperitoneal lymph node biopsy reportedly demonstrated features suggesting an infectious process, and EBV PCR revealed a viral load of 141,050 copies/mL.

A left axillary lymph node was excised, which demonstrated vascular proliferation and diffuse architectural effacement by a polymorphous infiltrate including variably sized lymphocytes with moderate to abundant clear cytoplasm, and occasional admixed neutrophils, plasma cells, and eosinophils. Immunohistochemical staining demonstrated an atypical CD4-positive, CD7-negative T-cell population in a vaguely nodular distribution, expressing Bcl-6, PD-1, ICOS, and CXCL13 without definite CD10 expression. CD21 immunostaining demonstrated markedly expanded follicular dendritic cell meshworks in a distribution similar to the atypical T-cell population. No B-cell or cytotoxic T-cell proliferation was seen, and in situ hybridization for EBV-encoded RNA (EBER ISH) demonstrated only scattered EBV- positive cells. Taken together, these findings supported a diagnosis of AITL over an atypical reaction to EBV infection. Next-generation sequencing demonstrated mutations in TET2, IDH2, and RHOA, further confirming the diagnosis.

Results (if a Case Study enter NA)

NA

Conclusion

AITL manifests with a diverse range of clinical symptoms and pathological features and may mimic infection. Additionally, acute EBV infection is well-known to mimic various lymphomas and has rarely been reported to mimic AITL. We present this case to raise awareness of the concurrent presentation of AITL with EBV viremia and to highlight features that may be helpful in distinguishing between the two.
Expression of PD-L1 in human placenta and retained product of conception of early pregnancy loss
Authors: Singh K K
Published: November 2023

Introduction/Objective

Immune surveillance evasion and impeding rejection by the maternal immune response system are elemental in sustaining foetal development. The exact mechanism behind this paradoxical immune response remains unclear. Since the trophoblast directly interacts with the maternal immune-environment, these cells must have some contribution to local immunosuppression. The programmed death-1 receptor and its ligands (PD- 1/PDL1)illustrates a novel regulatory-costulatory pathway that plays a major role in establishing peripheral tolerance. It was recently proved that PDL1 is expressed at the feto-maternal interface is necessary for maintaining feto-maternal tolerance.

We undertook this study to determine the expression-pattern of PD-L1 in formalin-fixed paraffin embedded tissues of human placentas in third trimester and retained product in early spontaneous abortions.

Methods/Case Report

Clinical history were recorded. The H&E sections of 40 placenta & 20 RPOC cases were examined. After evaluation appropriate sections were selected for IHC examination using anti-PD-L1 antibodies of Lab-vision and Biogenic

Results (if a Case Study enter NA)

Main focus of study was to see expression of PD-L1 at feto-maternal interface. 30 out of 40 third-trimester placenta expressed PD-L1 immunohistochemistry (13, 11 and 6 cases showed intense, fair and weak positivity respectively on outer surface of syncytiotrophoblast). 2 out of 20 early pregnancy loss cases in 11 & 9wk gestation expressed PD-L1 positivity.

Conclusion

Fetal cells in direct contact with maternal blood villous syncytiotrophoblast are major source of PD-L1 at the maternal-fetal interface and may utilize these immuno-suppressive mechanisms to ensure tolerance of conceptus. Failure to adapt this mechanism can lead to pregnancy loss.
Comparative study of total antibody titer against SARS-CoV-2 spike protein between male and female COVID- 19 patients of different age groups in UAE
Authors: Rashid Z , Ullah R , Yousaf M , Rajabudeen A , Ur Rehman M , Sajjad Naqvi S , Ul Ain Q , Ammad M , Arshad N , Al Yafei Z , Noorul Hasan T , Hussain A
Published: November 2023

Introduction/Objective

Currently, there is increasing evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes men to experience more serious symptoms and have a higher mortality rate than women, but the associations between gender and age groups are still elusive. This study aimed to examine the associations with age, gender, and clinical parameters of total antibody responses against the spike protein of SARS- CoV-2 after infection in UAE population.

Methods/Case Report

In this study, spike protein antibody titer estimation for COVID-19 positive individuals (n = 1070) was determined. A cross-sectional study design was planned in which patients were divided into nine groups (based on their age) and further subdivided into two groups based on their genders (9 x 2). Serum was collected from the patients after 17 days of diagnosis as COVID-19 positive by RT-PCR method. Concentrations of SARS-CoV-2 Total antibody (COV2T) were measured by chemiluminescent immunoassay using ADVIA Centaur® XPT systems.

We used a mixed effects model to investigate the potential associations of antibodies by bootstrapping t-tests of the putative effects of gender and age of the individuals.

Results (if a Case Study enter NA)

There were significant differences (P< 0.05) between males and females for SARS-CoV-2 total antibody reactivity. Total 645 (50.4%) male were found reactive compared to 425 (31.2%) female. Noteworthy, the group having middle-aged (41-50 years) participants depicted a higher antibody titer in both males and female against SARS-CoV-2. A significant decrease in titers also observed with different age groups. Highest number of reactive individuals were observed in 41-50 years age group (31%), followed by 31-40 years (27.34%), 51- 60 years (15.21%) and 21-30 years (13.04%). Same pattern of number of reactive individuals was found in male and female of different age group. Moreover, despite there being a weak significant positive association between age and total antibody titre in male patients, while there was no significant correlation between gender and age for the antibody response.

Conclusion

In a nutshell, total antibody (COV2T) reactivity was found significantly associated with male group and that was highest in 41-50 years age group, irrespective of the gender. These findings are crucial to treat and care for male and female patients infected with COVID-19 at hospitals.
Breaking Barriers in Pathology Education: Embracing the Straight Path to Reform
Authors: Saxena R , Shaw A , Skildum A
Published: November 2023

Introduction/Objective

The field of pathology and preclinical education is undergoing significant changes, with a shift towards student-centered approaches that emphasize self-directed learning. One such approach is case-based learning, which promotes active engagement and critical thinking. Technological advancements, such as digital pathology and radiology, offer several advantages in facilitating case-based learning.

Methods/Case Report

In this study, we implemented a unique educational strategy that combined digital pathology and radiology resources with case-based learning and team-based learning methodologies. Our approach involved designing and delivering modules, and subsequently collecting feedback from participants.

Results (if a Case Study enter NA)

Significant findings indicate that the integration of digital pathology and radiology has been highly appreciated by students. The majority of students acknowledged that it effectively aligned with the learning objectives. The survey responses also revealed the successful integration of early holistic pedagogy, the development of team-working skills, and the delivery of authentic and challenging clinical problems. These outcomes greatly contributed to achieving the desired learning outcomes.

Conclusion

The utilization of digital pathology and radiology resources, alongside well-designed modules, has proven successful in providing long-term access to educational materials and optimizing the presentation and systematization of the learning environment. Our innovative case-based study design, complemented by team-based learning, addresses the current demands of pathology concepts and modern curricula, facilitating a seamless transition into the clinical years. This approach holds great promise for enhancing the effectiveness of pathology education.
Correlation Between Large-Scale Health System Operational Parameters and Laboratory Test Utilization
Authors: Zhou Y , Windham A K , Staker C , Whitted M , Brimhall B , Podichetty A
Published: November 2023

Introduction/Objective

The extent of correlation between clinical laboratory test utilization and large-scale operational parameters would be helpful to adjust for these parameters when benchmarking utilization.

Methods/Case Report

We compared clinical laboratory and imaging utilization over 3 years (2019-2021) for adult patients hospitalized for specific surgical, medical, and obstetrics diagnoses at multiple academic hospitals (N=58; 625,436 hospitalizations) ranging in size from 250-1300 hospital beds. We queried the Vizient Clinical Data Base with permission from Vizient, Inc.® employing Medicare Severity Diagnosis Related Groups (MSDRG), used by the US Centers for Medicare and Medicaid Services (CMS), to identify hospitalizations for gastrointestinal (GI) surgery (MSDRG triplet 329/330/331), sepsis (MSDRG triplet 870/871/872), and vaginal delivery (MSDGR triplet 805/806/807). We stratified patients within each diagnostic group for comorbid conditions and complications into high, moderate, and low severity groups. We compared mean laboratory tests and Resource Intensity Weight (RIW) per hospitalization and hospital day. The RIW is based on the CMS Ambulatory Payment Classification (APC) weights.

We measured correlation of laboratory utilization with hospital bed size as well as annual discharges (sepsis group), surgical procedures (GI surgery group), births (vaginal delivery group), and diagnosis-specific discharges.

Results (if a Case Study enter NA)

For sepsis hospitalizations, there were small significant (p<.01) negative correlations (r2 0.05-0.16) between laboratory utilization, measured as test numbers or RIW, and diagnosis-specific discharges for low and moderate severity groups; there was no significant correlation with either bed size or overall annual discharges. There were no consistent correlations of laboratory utilization with bed size, annual surgical procedures, or diagnosis-specific discharges for GI surgery patients. Hospitalizations for vaginal delivery demonstrated small negative correlations between laboratory utilization and bed size, annual births, and diagnosis- specific discharges.

Conclusion

For specific diagnostic groups, laboratory utilization (tests as well as laboratory RIW) exhibited negative correlations with large-scale hospital operational parameters. These correlations were typically weak with varying statistical significance. The findings suggest that laboratory test utilization efficiency may require evaluation of individual health systems on a case-by-case basis.
Blood Products Wastage in Benghazi Hospitals, Libya: The Rate and Causes
Authors: Abdelmonem M , Mansour N , Dughman N A , Wasim H
Published: November 2023

Introduction/Objective

Introduction: Despite the rising demand for blood and blood products, supplies are limited. Limiting blood wastage may compensate for fewer donors. This study examines blood waste in Benghazi. A close look at blood and blood product distribution can reveal areas of frequent wastage and the primary factors contributing of blood waste. This would aid in the development of waste prevention programs and raise awareness of the issue. Physicians, laboratory professionals and nurses can follow blood transfusion guidelines.

Objectives: This study aimed to determine the rate of blood products wastage and identify the causes of Wastage in Benghazi hospitals in Libya.

Methods/Case Report

Materials and Methods: Data for this retrospective study describes the blood components utilization or waste for two years: 2015 and 2016 were obtained from hospital blood bank records of all public and private hospitals that Benghazi central blood bank supply with blood and blood components. Descriptive statistical methods analyzed the data.

Results (if a Case Study enter NA)

Results: In 2015 and 2016, Benghazi central blood bank supplied hospitals with 73511 units of blood. 35107(47.8%) were transfused. Wasted or discarded 33318(45.4)units. No data was available for 5086 units(6.8%).

The most frequently wasted component was PRBCs(87%) followed by platelets(8%) and FFP(6%).

The major cause of wastage for PRBCs is over-ordering (70.2%) followed by outdated units(18.5%), Returned after 30 minutes of issue (0.6%), Kept more than 3daysand expired(0.6%) and Issued to other hospitals(10.1%).

The main cause of wastage for platelets is over-ordering (89%), and inappropriate ordering is the most common cause of waste of FFP(85%).

PRBCs waste was mostly found in the surgical department, mainly obstetric(24%). For platelets, waste was mostly found in the hematology department(32%). for FFP, waste was mostly found in ER(47.1%).

Conclusion

The main cause of blood and blood component wastage is the unnecessary ordering of blood products. The most blood component discarded is PRBCs. Physicians are the most responsible for blood and blood component wastage. The blood ordering pattern needs to be revised, and the over-ordering of blood and blood component should be minimized. Medical staff must be educated to reduce blood wastage. Every hospital should implement a hospital transfusion committee to develop local guidelines and policies to monitor the rational use of blood and blood component.
Racial Disparity in Antibody Against A rare High Prevalence Antigen; (Anti-Inb)
Authors: Abdelmonem M , Ngo N , Cai W , Yunce M , Papakonstantino K , Jurado C , Virk M S , Lee J , Chang S , Yoshizuka S , Cabungan M
Published: November 2023

Introduction/Objective

Introduction: Ina antigen is very rare except in Iranian and Arab populations (10.6% and 11.8%, respectively). In 1973, Badkere et al. identified this antigen in about 3% of Indians from Bombay. Inb is a very high-prevalence antigen. It is prevalent in 99.9% of Caucasians and blacks, 96% of Indians and South Asians, and 90% of Iranians and Arabs. The Indian blood group system also has two other very high prevalence antigens: INFI and INJA. Indian blood group resides in CD44 glycoprotein that binds to hyaluronate of extracellular matrix. CD44 is an adhesion molecule in lymphocytes, monocytes, and other tumor cells, but its function in RBC is unknown. Ina and Inb are sensitive to proteolytic enzyme treatments and destroyed by disulfide bond-reducing agents 2-aminoethyl isothiouronium bromide (AET) and dithiothreitol (DTT).

Methods/Case Report

Case study: An 11-year-old female of South-East Indian descent with a history of intractable epilepsy was admitted for surgical treatment for epilepsy. Her antibody screen was positive, and her plasma reacted with all cells in PEG AHG except for the auto control. Ficin and DTT-treated cells weakened the reactivity. Suspecting a high-frequency antibody, the patient's plasma was tested against a series of cells in the rare donor cell inventory, including O Bombay cell and Inb-cell considering the patient's ethnicity. With Inb-negative cells, the plasma tested negative. All major alloantibodies from this rare donor cell were ruled out except for anti-C, anti-E, anti-K, and anti-S due to the availability of the rare cell.

Results (if a Case Study enter NA)

NA

Conclusion

Antigen Inb has a high prevalence in all populations. The rare phenotype In(b–) has been observed in approximately 2 of 700 Indian blood donors. A patient may be advised to undergo an autologous transfusion. Fortunately, the patient's procedures were uncomplicated, so a blood transfusion was unnecessary. Awareness on the part of blood bank staff regarding the variability of the blood group phenotype and the unpredictability of Anti-Inb may aid in improving patient care. To prevent further exposure, it is recommended that patients with rare antibodies carry an Antibody ID card indicating the rare antibody they possess.Inb antigen blood donors are under represented in the general donors pool. It is recommended to develop a systematic recruitment for Inb antigen donors
Financial Analysis of Transfusion Therapy: A Focus on Liquid Plasma and Fresh Frozen Plasma
Authors: Alazawi S , Saad A , Jain D , Alzaiem F , Ballouk C , Nash T
Published: November 2023

Introduction/Objective

Fresh Frozen Plasma (FFP) is widely used in transfusions, but its short shelf life once thawed (5 days) can lead to wastage. Liquid Plasma (LQP), on the other hand, doesn't require thawing and, thus, has a longer shelf life (26 days), but also more expensive. Our project examines the cost-effectiveness of LQP versus FFP, with a focus on the waste resulting from FFP units expiration at our institution.

Methods/Case Report

Our methodology involves a comprehensive review of existing literature, focusing on the utility and advantages of liquid plasma incorporation in transfusion protocols, and strategies to mitigate the wastage of Fresh Frozen Plasma (FFP). We conducted a detailed evaluation of FFP usage and wastage data in 2022 at a level one trauma center in the Detroit metropolitan area, specifically pertaining to trauma and trauma activation cases.

Results (if a Case Study enter NA)

In 2022, our institution collectively consumed 2,595 units of Fresh Frozen Plasma (FFP). Of these, 1,024 units, or 39%, were wasted, and only 1,571 units, or 61%, were actually utilized. The average cost per unit of FFP was $40.8, resulting in a total expenditure of $105,876.

If the hospitals had used liquid plasma (LQP) instead of FFP, and assuming no wastage with LQP, the total cost would have been $88,133 (given the average cost of $56.1 per unit of LQP).

This implies that by switching to LQP from FFP, and by eliminating the wastage, the hospitals could have achieved a combined saving of $17,745 in 2022.

Conclusion

Our findings highlight the urgent need for more efficient plasma usage. Despite the higher cost of LQP per unit, the increased waste associated with FFP contributes to higher overall costs for hospitals, making liquid plasma a potentially more cost-effective option when considering waste reduction.
Phosphatidylethanol as a biomarker to assess alcohol exposure in women of reproductive age using retrospective data from a reference laboratory
Authors: Mathewson Nicole , Johnson-Davis Kamisha
Published: November 2023

Alcohol consumption during pregnancy may cause fetal alcohol spectrum disorder (FASD), which is a preventable disorder. Prenatal alcohol exposure during the first trimester of pregnancy is deemed most disruptive to the developing fetus. Pregnant women may be screened for alcohol use through self-reported measures. These subjective methods are known to underreport drug use. Therefore, a reliable method to detect and monitor alcohol use during pregnancy is needed. Phosphatidylethanol (PEth) is a specific biomarker associated with alcohol consumption that can be used to differentiate social drinking from heavy alcohol use. The predominant PEth homologues are PEth 16:0/18:1 (POPEth) and PEth 16:0/18:2 (PLPEth), which account for 37-46% and 26-28% of the total PEth homologues, respectively. PEth can reflect alcohol intake up to several days to weeks after consumption. The aim of this study is to investigate the prevalence of positive PEth samples in women of reproductive age to determine whether testing for PEth should be assessed in a three-month checkup in pregnant women. The first objective is to perform a retrospective study on the direct alcohol biomarker, PEth, to evaluate the true positivity rates of alcohol use in females and in women of reproductive age (14 - 44 years old) using retrospective data analysis from a reference laboratory. The initial data analysis demonstrated the positivity rate of PEth in females (N = 66,306) to be 32% for POPEth and 28% for PLPEth. Further retrospective data analysis of PEth in women of reproductive age (N = 19,366) was performed and the positivity rate of PEth in this population was quite similar between the ages of 27 to 40 years old, at around 35%. The data shows that the positivity rate of PEth in women of reproductive age (~35%) is slightly above the positivity rate for all females (~30%). These percentages are significantly higher than what is reported in the 2020 National Survey on Drug Use and Health (NSDUH). The NSDUH reported that 10.6% of pregnant women used alcohol in the past month. The second objective is to conduct a laboratory study where we will measure PEth concentrations by mass spectrometry using residual whole blood specimens from females in an OB/GYN clinic and compare the positivity rates to those determined by the retrospective analysis. This study will provide the opportunity to educate women of reproductive age on drinking during pregnancy and the long-term effects of alcohol use.
Caffeine, Lorazepam, and Morphine Use in Neonatal Intensive Care Unit Population and Potential Relevance of Pharmacogenomics
Authors: Falekun Seyi , Mankouski Anastasiya , Solorzano Chelsea , Floyd Ivah , Rau Carrie , Margraf Rebecca , Del Angel Sergio , Brunelli Luca , McMillin Gwendolyn
Published: November 2023

Medications are critical for managing acutely ill infants in neonatal intensive care unit (NICU). Tailoring therapies to individual differences in response and dose requirements might help improve outcomes. However, tools for optimizing pharmacotherapy remain limited. In this retrospective study, we explored the potential utility of pharmacogenetics for commonly prescribed NICU medications. All patients admitted to our local NICU March-December, 2022 were eligible for inclusion in the study. In infants who received at least three doses of one or more medications, we extracted DNA from residual EDTA blood collected for routine clinical care according to IRB-approved study protocols. Demographic, pharmacy, and clinical information was recorded retrospectively. Targeted pharmacogenetics testing was performed with a custom TaqMan OpenArray and a QuantStudio 12K Flex (ThermoFisher Scientific) with DNA normalized to 50 ng/mL. Results were analyzed using Genotyper Software version 1.3 and allele calls were made based on the combination of variants detected and consensus nomenclature. For drugs administered to at least 30 NICU patients, pharmacogenes were evaluated for variant allele frequency and potential clinical relevance. Of the 132 patients enrolled, 81 were male. Average length of stay was 47 days. Of the 64 different medications prescribed to at least one infant, for 15 of them are described clinical annotations with specific pharmacogenes by the PharmGKB and/or Clinical Pharmacogenetics Implementation Consortium. Of those 15 medications, three were administered at least three times to at least 30 infants: caffeine (n=102), morphine (n=56), and lorazepam (n=31). The associated pharmacogenes were CYP1A2 (caffeine); CYP3A4, OPRM1, COMT, ABCB1 (morphine); and UGT2B15 (lorazepam). Relevant to the rate of clearance of caffeine, rs2069514 (CYP1A2) was heterozygous in 18% of patients, and homozygous in 5%. Relevant to the rate of clearance of morphine, CYP3A4*22 was heterozygous in 5%. The common variants associated with response to morphine, c.472G>A (COMT) and c.118A>G (OPRM1) were heterozygous in 43% and 26%, and were homozygous in 22% and 8%, respectively. The transporter variant ABCB1*2 was heterozygous in 6% and homozygous in 11%. Relevant to the rate of clearance of lorazepam, UGT2B15*2 (rs1902023) was heterozygous in 45%, and homozygous in 31%. Correlation of pharmacogenetic results to specific clinical phenotypes is currently in progress. Pharmacogenetic variants relevant to commonly prescribed medications in the NICU are prevalent. Further clinical correlation of pharmacogenetic results may help inform selection and dosing of medications for critically ill NICU infants. This research may also facilitate detection and definition of new drug-gene associations unique to this patient population.