bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma cell neoplasm with initial presentation as an ovarian mass: a rare case report
Authors: Shirai S , Wang W , Guo T , Buryanek J , Chen L
Published: November 2022

Introduction/Objective

Plasmacytoma is a discrete, solitary mass of neoplastic plasma cells. Extramedullary plasmacytoma (EMP) is a rare entity arising in tissues other than bone and it constitutes about 1% of all plasma cell neoplasms. Most cases of reported EMPs are in the upper aerodigestive tract (~80%). We present a very rare case with the initial presentation as an ovarian mass with metastasis into the peritoneal and pleural cavity.

Methods/Case Report

This is a 66-year-old female who presented with generalized abdominal pain, unexpected weight loss, and occasional fever and night sweats. Computed tomography (CT) scan of abdomen and pelvis showed an extensive metastatic disease including bilateral cardiophrenic angle lymphadenopathy, peritoneal spread encasing the bowel loops, bladder, and uterus as well as moderate right pleural effusion. The positron emission tomography (PET)-CT showed an ill-defined soft tissue density in the pelvis with hypermetabolism. The pelvic ultrasound showed a 2.6 x 2.2 x 1.1 cm hypoechoic mass in the left adnexa. The patient's serum cancer antigen (CA-125) was elevated at 123 U/mL and the post-thoracentesis chest x-ray was unremarkable with no acute osseous abnormalities. Other clinical data were not available.

Results (if a Case Study enter NA)

Cytopathologic evaluation of the pleural fluid showed abundant atypical cells with eccentrically located nuclei, scant to moderate cytoplasm with a paranuclear hof, frequent binucleation and mitoses. The cells ranged in size from small to large. Further immunohistochemical (IHC) analysis on the cell block showed that the tumor cells diffusely positive for CD138 and lambda light chain and negative for MOC31, BerEP4, calretinin, D2-40, WT1, HHV8, ALK1, and EBER in situ hybridization (ISH). The biopsy of the left adnexal mass showed a diffuse proliferation of tumor cells with frequent mitotic figures. The IHC analysis on the biopsy specimen showed tumor cells positive for CD79a and CD56 (weak) and negative for CD20 and PAX5. Kappa/lambda ISH analysis confirmed lambda light chain restriction of the tumor cells. These morphological and immunophenotypic features were consistent with plasma cell neoplasm.

Conclusion

The ovary is an unusual location to be involved by plasma cell neoplasm. We use this case to remind the pathologists and clinicians that ovarian plasmacytoma can be the initial presentation of the plasma cell neoplasm, although rare, and to aid the patients to receive an appropriate treatment. A thorough workup is needed to make an accurate diagnosis of this entity.
Spectrum of cervical cancer among women screened for cervical cancer in Nakuru County Referral Hospital Laboratory, Kenya
Authors: mokua G M
Published: November 2022

Introduction/Objective

Cervical cancer is the leading cause of cancer-related deaths in Kenya and the second most common cancer among females. However, the prevalence of this type of cancer at Nakuru county is not known. We sought to establish the spectrum of this cancer among women who were attended at Nakuru county referral Hospital between 2015-2019.

Methods/Case Report

A retrospective descriptive cross-sectional study was carried out among women screened for cervical cancer between January 2015 and December 2019. One thousand and thirty-one (1031) records were retrieved. Data extracted were analyzed using SPSS version 21. Approval to conduct the study was obtained from the hospital institutional review board;

Results (if a Case Study enter NA)

Among the 1,031 women whose records were reviewed, 81 (7.9%) had lesions, while 950 (92.1%) had no lesions. Results for pre-cancerous and cancerous according to age group were as follows: 15 – 25 years (3.4%), 26 – 35 (6.3%), 36 – 45 (10.1%), 46 – 55 (5.2%), 56 – 65 (8.9%), 66 – 75 (15.1%), 76 years and above (4.5%). Those who had HSIL were 4.9%, LSIL 2.3%, ASC-H 0.4% and ISCC 0.2% respectively.

Conclusion

The percentage for pre-cancerous and Cancerous lesions of women of younger age group between 15–25 years was low at 3.4% while percentage for older age group for pre-cancerous and Cancerous lesions was at 10.1%, 8.9% and 5.2% respectively. This necessitates the need for increased campaigns for cytology screening for cervical lesions. This would reduce morbidity and mortality associated with cancer of the cervix.
A Cost Comparison Modeling Analysis for Healthcare Access and Equity: Cost of COVID-19 Test Screening by Point of Care (POC) Versus Rapid Reverse Transcriptase Polymerase Chain Reaction (RT-PCR)
Authors: Petersen J M , Jhala A
Published: November 2022

Introduction/Objective

Testing platforms to detect COVID-19 infection include antigen-based point of care (POC) testing and reverse transcriptase polymerase chain reaction (RT-PCR) to detect viral ribonucleic acid (RNA). RT-PCR, generally considered the gold standard for diagnosis of COVID-19 infection, is capable of being used for mass population screening but may be more expensive. Alternatively, antigen based POC testing can not only produce results rapidly (15 minutes on some assays) but also may be less expensive. This reduced cost provides an argument that it may be economical to use POC testing for mass surveillance in asymptomatic or mildly symptomatic patients while reserving the more expensive gold standard RT-PCR testing for sensitivity for hospitalized and more significantly at risk or ill patients. However, cost modeling between the two modalities for mass screening is sparse, particularly for studies including the Veteran Affairs system that may have different costs from the general community retail pricing.

Methods/Case Report

Cost information reviewed at the regional VAMC included costs for the Alinity-m SARS-CoV-2 RT-PCR assay (Abbott, Chicago IL), the Cepheid Xpert-Xpress-CoV-2-Flu-RSV-Plus RT-PCR assay (Cepheid, Sunnyvale CA), and the BinaxNOW POC antigen-based assay (Abbott, Chicago IL). The median cost of RT-PCR testing in the community was obtained from the Peterson-KFF Health System Tracker. Publicly available quoted prices for selected POC assays in the community were reviewed for comparison.

Results (if a Case Study enter NA)

Test costs at the regional VAMC was $28.34 (Alinity-m), $68 (Cepheid), and $5 (BinaxNOW). These costs did not include technologist time or standard laboratory consumables that would be part of the standard overhead costs of running the laboratory. The median community RT-PCR assay price per the Peterson- KFF Health System Tracker was $148, and the Abbott’s quoted BinaxNOW price was $25. POC testing cost was 82% less than the cheapest RT-PCR assay available at the regional VAMC. This trend in being significantly cheaper holds true in the community whereby BinaxNOW testing was 83% cheaper. Publicly available quoted prices from other selected POC assays confirm this trend.

Conclusion

For a mass surveillance screening program, the use of POC assays would result in significant cost savings.
An Illustrative Model of Economically Utilizing Point of Care and Reverse Transcriptase Polymerase Chain Reaction Testing to Reduce Costs and Help Balance Supply and Demand
Authors: Petersen J M , Jhala A
Published: November 2022

Introduction/Objective

Both point of care (POC) antigen-based assays and reverse transcriptase polymerase chain reaction (RT-PCR) laboratory-based assays exist for diagnosis of COVID-19. COVID-19 RT-PCR tests are the gold standard based on their higher sensitivity. However, in this era of inflation and supply chain disruptions, the use of only RT-PCR tests would be more expensive and may be vulnerable to reagent supply chain shortages. Triage of resources of both test types is important in ensuring access and equity in testing distribution as well as ensuring economical RT-PCR testing access for sicker patients. A comparison of costs was explored by contrasting a model of cost effectively reserving RT-PCR tests for those with significant disease requiring hospitalization and using POC tests for those with mild disease (defined as at most mild symptoms not requiring hospitalization) versus universal provision of RT-PCR to all.

Methods/Case Report

Cost information from the regional Veteran Affairs Medical Center (VAMC), specifically for the Alinity-m (RT-PCR) and BinaxNOW (POC) by Abbott (Chicago IL), and from the community (median COVID-19 RT- PCR pricing obtained from the Peterson KFF Health System Tracker) were included. Based on this cost information, a model of 100 tested COVID-19 suspected patients was created. A percentage of mild disease not requiring hospitalization (81%) was utilized based on literature from early in the COVID-19 pandemic.

Results (if a Case Study enter NA)

The cost per test at VAMC factored in was $28.34 (Alinity-m) and $5 (BinaxNOW). The median community RT-PCR and POC price factored in was $148 and $25, respectively. From the model of 100 COVID-19 with a mild disease percentage of 81%, the total testing cost of including POC assays for mild cases vs. universal RT-PCR assays would be $943.46 vs. $2,834 at the VAMC and similarly $4,837 vs. $14,800 in the community for a 67% reduction in costs at both settings.

Conclusion

A model of testing including both POC and RT-PCR testing may be economical and critically help ensure triage of resources in this era of inflation and supply chain shortages.
An Autopsy Case Report of ARDS Caused by Tumor Lysis Syndrome in A Patient with Mantle Cell Lymphoma
Authors: Cai D , Onur P
Published: November 2022

Introduction/Objective

Acute respiratory distress syndrome (ARDS) is a type of respiratory failure caused by diffuse injury to surfactant-producing cells and fluid buildup in the alveoli. ARDS impairs lung's ability and is potentially fatal. Tumor lysis syndrome is an oncologic emergency mostly triggered by the initiation of chemotherapy causing life- threatening metabolic cascades even with preventable therapies.

Methods/Case Report

We report an autopsy case of a 71-year-old male who was referred to the Emergency Department with complaints of poor appetite, dizziness, nausea. He was found to have a white blood cell count over 1,000,000, with hemoglobulin of 7.7, platelet count of 95, uric acid 11.5, LDH 486. He was diagnosed with mantle cell lymphoma (MCL) involving peripheral blood and received Allopurinol for tumor lysis syndrome prophylaxis. He started to receive Rituximab. Soon after, he became lethargic and more hypoxemic and needed intubation. But he became pulseless and he did not recover.

Results (if a Case Study enter NA)

The autopsy revealed an extensive spread of the lymphoma to multi-organs, including the esophagus, spleen, liver, kidney, heart, prostate. Bone marrow and lymph nodes were diffusely infiltrated by atypical medium lymphocytes. Stains on lymph nodes show the atypical lymphocytes are positive for CD20, CD5, Cyclin D1, Bcl2, negative for CD23, Bcl6, with a Ki-67 proliferative index around 40%, consistent with MCL. The patient's lungs were heavy and microscopic examination confirmed ARDS.

Conclusion

We, here describe a patient with MCL who developed tumor lysis syndrome with Rituximab monotherapy and died of ARDS shortly after. It's rarely reported that tumor lysis syndrome results in fatal ARDS.
Automated Clinicopathologic Correlation Integrating Clinical Findings, Suspicions, Hematopathology Tests and Previous Records
Authors: Elsafty A M , Ahmed Y M
Published: November 2022

Introduction/Objective

Conducting clinicopathologic correlation (CPC) to provide comprehensive diagnosis, prognosis/risk assessment, follow up and/or recommendations is essential in Hematopathology. The clinical findings/suspicions and medical history contribute in building a personalized diagnosis and prognosis, while comparing with the previous records is required for specialized follow-ups and progression assessment. HIPAA violation liability and changeable medical guidelines limit the "freelance outsourcing" of Hematopathology assistance/second opinion. The proposed electronic Hematopathologist assistant could play this role perfectly, because automation in Hematopathology is easier when compared with other medical specialties. This is because only visual sense is needed for Hematopathology review/examination while automating more than one sense is needed in medicine and surgery.

Methods/Case Report

Scalable, customizable and fully controlled system is developed harnessing the state-of-the-art technologies. The user selects specific answers in smart hierarchical choice lists about specimen types, medical history, clinical findings and suspicions. Then, the available current and previous results of the performed diagnostic and prognostic test panels are needed to be entered and dated. These panels include quantitative and qualitative parameters of the complete blood count (CBC), smear review, flow cytometry, immunohistochemistry, cytogenetics and/or molecular studies. Zero harm to the patients privacy is achieved, there is no personal information entered or needed.

Results (if a Case Study enter NA)

Based on the entered results, detailed interpretation for each test panel is created to explain how the generated comprehensive CPC is built. Furthermore, the CPC is concluded in one line, this is an informative and summative title for the case. The system is also used as a triage advisor, it suggests the useful parameters to be triaged considering the choosing wisely recommendations and providing the potential percentage of resulting positive/abnormal in similar specific cases. All possible generated test panel interpretations, CPCs and case titles are reviewed and validated.

Conclusion

This system generates preliminary versions for the Hematopathologist to review, leading to productivity increase with no medical liability or feeling fatigued and stressed. This also helps to increase the profitability and cover the shortage.
Uncommon Variant of CD4+ T-cell Large Granular Lymphocytic Leukemia
Authors: Gao Y , Wang W , Chen L
Published: November 2022

Introduction/Objective

T-cell large granular lymphocytic leukemia (T-LGL) is a T-cell lymphoma with persistently increased large granular lymphocytes in peripheral blood. The majority of T-LGL is associated with CD8+ T-cells. However, the CD4+ variant is uncommonly seen.

Methods/Case Report

The patient is a 49-year-old female with a history of diabetes mellites and anemia who presented with shortness of breath, lower extremities edema, and fatigue. Physical examination showed a significantly distended abdomen. CBC results showed hemoglobin 6.9 g/dL, WBC 18.2 × 109/L with 88% lymphocytes, and PLT 190,000. The peripheral blood smear presented lymphocytosis with LGL cells, microcytic anemia, and increased target cells. Bone marrow biopsy showed lymphoid infiltrate as an intravascular pattern confirmed by immunochemical stains. A complete workup including flow cytometric, cytogenetics, and molecular studies was performed on the bone marrow. The lymphoma phenotype by flow shows positivity for CD2, CD3, CD4, CD5 (bright), CD7 (partial/dim), CD56, CD57 (majority), TCRαβ. T-cell gene rearrangement was detected and was further confirmed by PCR with the detection of clonal TCR beta gene rearrangements on molecular genetics analysis. However, STAT3 was not detected. The patient was diagnosed with CD4+ T-LGL leukemia.

Results (if a Case Study enter NA)

NA.

Conclusion

CD4+CD8- immunophenotype is an uncommon variant of T-LGL, which has a high incidence of activating STAT5B mutation, while CD8+CD4- T-LGLL tends to have STAT3 mutation. Clinically, those two subtypes behave similarly. Flow cytometry is the golden method to confirm the diagnosis. More research is needed to clarify the essence of CD4+ T-LGLL.
Gluteal Region Plasmablastic Lymphoma in a Crohn’s Disease Patient Treated with Anti-Tumor Necrosis Factor and Immunosuppressive Therapies: Report of a Rare Case with Literature Review
Authors: Sadough Shahmirzadi M , Fakhri N , Jetly R , Loganantharaj N
Published: November 2022

Introduction/Objective

Plasmablastic lymphoma (PBL) is rare, initially described in the oral cavity of HIV patients but can affect other extra-nodal sites and immunodeficiency states. We report an unusual case of PBL in an HIV negative Crohn’s disease (CD) patient with prior anti-tumor necrosis factor (TNF) and immunosuppressive therapies including prednisone.

Methods/Case Report

A 54-year-old man with recent bleeding from chronic gluteal wounds had CD (five years), a left-lower-quadrant diverting colostomy (three years) and treatment with adalimumab (three years), briefly with infliximab (discontinued after an infusion reaction) and chronic prednisone. Multiple perianal fistulous tracts were present and biopsied. Dermal diffuse infiltrate of pleomorphic plasmacytoid cells had prominent nucleoli, and an immunohistochemical profile as: CD20-/CD22-/CD30-/CD38-/CD45-/CD56+(weak, subset)/CD79a-/CD138+/EBV+(EBER-ISH)/HHV8-/kappa+/lambda-/MUM1+/PAX5-/Ki-67(70-80%) confirming PBL. Chemotherapy with bortezomib combined with etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin resulted in a good response.

Results (if a Case Study enter NA)

NA.

Conclusion

A meta-analysis found increased risk of non-Hodgkin lymphomas in CD treated with anti-TNFs, however, lymphoma subtypes were not specified. Seven cases of CD-associated PBL were found in the literature (from 2007). Of all cases 6 were men and 2 women with an average age 49 years (range 32-65), HIV negativity documented in five, involvement sites of gastrointestinal tract (5), perianal skin (2) and paravertebral soft tissue (1), and treatments with anti-TNFs (6), 6-mercaptopurine+budesonide (1) and salazosulfapyridine (1). The average intervals from CD and anti-TNFs to PBL were 14.5 years (range 5-30) and 17 months (range 4-36) respectively. Increased PBL risk may be related to the disease itself, anti-TNF/immunomodulator therapies, EBV reactivation, or other host-related factors. Investigations for potential risks of CD therapies can ensure their safe use in susceptible patients.
Alpha Heavy Chain Disease Post-Diffuse Large B-cell Lymphoma Remission: A Series of Two Cases
Authors: Aljumaili Z , Ahmed A , mai B , Wahed M
Published: November 2022

Introduction/Objective

Heavy chain disease is the production of abnormal monoclonal immunoglobulin heavy chains. Alpha heavy chain disease is typically identified in mucosa-associated lymphoid tissue lymphomas and is secreted due to chronic infection. The alpha heavy chain can manifest as hypogammaglobulinemia or a normal serum protein electrophoresis (SPEP). Broadband may appear in the alpha-2 or beta mobility regions.

Methods/Case Report

We describe two cases in which a monoclonal alpha heavy chain was detected in a 60-year-old female with diffuse large B-cell lymphoma (DLBCL) of the thoracic spine and a 71-year-old female with mediastinal DLBCL. Both patients achieved clinical and radiological remission.

Results (if a Case Study enter NA)

A distinct IgA band without an associated light chain was detected on the first patient's serum immunofixation essay (SIFE) one year later. For the second case, there was a distortion of the beta-2 region, elevated kappa free light chain (230.6 mg/dL), and a kappa to lambda free light chain ratio of 14.23, suggesting alpha heavy chain disease and a possible monoclonal gammopathy of unknown significance. Interestingly, even with a monoclonal IgA, the patients remained symptom-free, without any gastrointestinal manifestations, and concurrent PET scans show no recurrence.

Conclusion

To the best of our knowledge, these are the first two cases describing the presence of alpha heavy chain disease in association with DLBCL. The significance of alpha heavy chain secretion in patients with a history of DLBCL needs to be further assessed and we need to identify the possible presence of a non-clonally related paraprotein post-treatment for DLBCL.
High-Grade B-Cell Lymphoma with Effusion as the Initial presentation
Authors: Aljumaili Z , mai B , Ahmed A , Wang X , Zhang H , Hu Z
Published: November 2022

Introduction/Objective

Malignant effusion is usually caused by metastatic carcinoma. Lymphoma is often not included in the differential diagnoses. Here, we describe two cases of young females with no significant past medical history, presenting with fluid overload.

Methods/Case Report

The first case is a 41-year-old female with abdominal ascites and pleural effusion. Microscopic examination of the ascitic fluid showed intermediate to large lymphoid cells with irregular nuclear contours and fine chromatin. Flow cytometry showed CD10-positive lambda restricted B-cells. She had retropectoral mass biopsy showing sheets of intermediate to large-sized lymphoma cells with abundant apoptotic bodies and necrosis. The lymphoma cells are positive for CD20, CD10, BCL-2, BCL-6, and C-MYC (~50%,) while negative for TdT and cyclin D1. Proliferative index by Ki-67 stain is ~80%). Fluorescence in situ hybridization (FISH) analysis demonstrated rearrangements of BCL2/18q (80%) and MYC/8q (82%). The patient had a diagnosis of high-grade B-cell lymphoma with MYC and BCL-2 gene rearrangements. The second case is a 43-year-old woman with abdominal pain. She was diagnosed with acute cholecystitis and underwent cholecystectomy. Peritoneal fluid showed numerous neoplastic cells with irregular nuclei, prominent nucleoli, and cytoplasmic vacuoles. Flow cytometry demonstrated CD10-positive B-cells with lambda restriction. The cells were positive for CD10, CD20, BCL-2, BCL-6, and PAX5, and negative for CD34, cyclin D1, HHV-8, and TDT. EBER ISH was negative. The proliferation index by Ki67 stain was >90%. FISH studies showed MYC, BCL2 and BCL6 gene arrangements. Cytogenetic analysis revealed a complex karyotype. A diagnosis of HGBL with triple-hit rearrangements was rendered. Despite receiving aggressive chemotherapy, the patient expired 8.5 months after the diagnosis.

Results (if a Case Study enter NA)

NA.

Conclusion

HGBL is an aggressive and often stage IV disease. It should be considered in the differential diagnoses of malignant effusions. Flow cytometry and FISH analysis of the body fluid specimen are essential to reach an accurate diagnosis in a timely manner.
Essential Thrombocythemia Associated with Plasma Cell Neoplasm
Authors: Eltahir M , Barbieri A , Rivero G
Published: November 2022

Introduction/Objective

The co-occurrence of essential thrombocythemia (ET) and multiple myeloma (MM), two distinct entities with distinct cellular origin, is rare, with a limited number of cases reported.

Methods/Case Report

We report a case of a 63-year-old male who initially presented with thrombocytosis, splenomegaly and elevated LDH. A bone marrow examination showed hypercellularity (90%) with increased abnormal megakaryocytes, as well as a JAK2 V617F mutation, with overall features consistent with involvement by a myeloproliferative neoplasm (MPN), consistent with ET (versus early primary myelofibrosis (PMF)). Additionally, 6% kappa-restricted plasma cells were identified, consistent with involvement by a monoclonal gammopathy of undetermined significance (MGUS). The patient was subsequently treated with hydroxyurea. Four years later, he presented with evidence of paraproteinemia. IgG kappa monoclonal paraprotein was elevated at 3.4 g/dL. A repeat bone marrow examination showed hyper-cellularity (60%), including clusters of abnormal megakaryocytes and mild to moderate reticulin fibrosis. The previously identified kappa-restricted plasma cell population increased to approximately 40% of the total cellularity. Cytogenetic analysis showed a normal male karyotype (46,XY[20]), and a prognostic myeloma-FISH panel including 13q-/-13, 1q32/1q21, p53/NF1, CCND1/IgH t(11;14), FGFR3/IgH t(4;14), IgH/MAF t(14;16) and IgH/MAFB t(14;20) was negative for all tested abnormalities. The overall features were again consistent with involvement by an MPN and progression of the previously identified MGUS.

Results (if a Case Study enter NA)

NA.

Conclusion

Only a few cases of concurrent ET and MM have been previously reported in the literature, with most of these cases having a temporal association with alkylating agent therapy. However, MM development has also been reported in a patient with non-cytotoxic treatment of ET. In contrast, our patient was diagnosed with ET associated with MGUS at the initial diagnosis. Notably, the co-existence of early PMF with MM appears to be relatively more established. A large study showed that previous PMF was strongly associated with MM development (OR 24.3; 95% CI:2.9-201.5).
Case Series: Large B-cell Lymphoma with IRF4 Rearrangement Involving the Lung and the Tonsil in Two Different Patients
Authors: Abdulrahim A
Published: November 2022

Introduction/Objective

Large B-cell lymphoma (LBCL) with IRF4 rearrangement is a new entity described in the 2017 WHO classification. It is characterized by a monotonous proliferation of medium to large sized cells with strong expression of IRF4/MUM1 and IRF4 rearrangement. It accounts for only 0.05% of all diffuse LBCLs and affects predominantly children and young adult with median age of 12 years. The reported sites of disease include lymph nodes of head and neck, Waldeyer ring and gastrointestinal tract. Here, we report two cases of Large B-cell Lymphoma with IRF4 rearrangement in two female patients, 73-year old and 71-year old respectively. The first patient presented with a lung nodule, while the second presented with right palatine tonsillitis. Hematoxylin and Eosin staining, immunohistochemistry and Fluorescence In-Situ Hybridization were used to characterize the lesions. H&E stained sections of the lung nodule biopsy from the first patient showed diffuse proliferation of medium- to large-sized cells (Figures A and B). Immunohistochemistry shows tumor cells are positive for CD20 (figure C), CD10, BCL6, and IRF4/MUM1(figure D). FISH study shows that tumor cells carry the IRF4 rearrangement but are negative for MYC, BCL2, and BCL6 translocations. To the best of our knowledge, this is the first case of LBCL with IRF4 rearrangement reported involving the lung in an older patient. H&E stained sections of the right palatine tonsil from the second patient shows effacement of the normal architecture which is replaced by sheets of large lymphoid cells. Immunohistochemistry shows tumor cells positive for CD20, CD10, BCL-6, BCL-2, MUM-1, C-MYC, and Ki-67 (80%). FISH study shows that tumor cells carry the IRF4 rearrangement which is consistent with a diagnosis of LBCL with IRF4 rearrangement.

Methods/Case Report

NA.

Results (if a Case Study enter NA)

NA.

Conclusion

NA.
Automated Blasts and Plasma Cells Counting on Manually Prepared Bone Marrow Aspirate Smears, Closest Deep Learning Pipeline for Generalizability
Authors: Elsafty A M , Ahmed Y M
Published: November 2022

Introduction/Objective

Medical errors, liability and reduced productivity in Hematopathology labs stem from fatigue, stress and shortage. 5-35% of complete blood count specimens (at least 3 billion tests worldwide annually) compared to 100% of bone marrow aspirates require visual examination using microscopes or digital scanners. The deep learning technologies and growing digital scanners market empower for developing work-fit automated visual examination to assist the Hematopathologist.

Methods/Case Report

2.6K+ manually smeared and stained bone marrow aspirate slides were scanned using integrated cameras on microscopes with electronic/mechanical control units. On top of the intracellular and background staining/dyeing variations, new scanning-related variations in exposure, resolution/focus and stitching were noted inter-patches and intra-patches. This led to consensus loss and "carry over" during cells identification. A convolutional autoencoder with skip connection for restoring/normalizing the stain and resolution was developed using data simulating the entire variations and artifacts. Generation of dimensions and ground truths was performed just by drawing on cells borders using pens, this enabled to localize and segment 5K+ cells per day with almost 100% accuracy. To help with labelling, intracellular colors split and quantification were applied. The processed 1.72+ million cells for 14 different WBCs classes/types were used to train a U-net architecture for segmentation, a transfer learning with pre-trained network EfficientNetB0 with ImageNet for classification and YOLO for detection. A previously developed pipeline for RBCs counting was used to select the proper areas for counting on smears. New diverse datasets were used for testing. Results were validated against confirmatory tests including immunohistochemistry and flow cytometry.

Results (if a Case Study enter NA)

The five-by-two cross validations revealed minor performance fluctuations (+/- 1.05%) with significant averages normalization SSIM, detection mAP, segmentation IoU, and classification F1-score exceeded 0.96, 0.97, 0.98 and 0.97, respectively. This beta prototype finds the proper areas for counting, calculates the M:E ratio, collects and counts the differential. Sufficient qualitative abnormalities assessment needs more work.

Conclusion

Without normalization and at least 100K cell images for each class, there is no generalizability.
A Case of Near Total Rh(D) Expression Loss in a Sickle Cell Patient Following Aplastic Anemia and Development of a Transient Auto-Anti-D
Authors: Sadough Shahmirzadi M , Lawicki S
Published: November 2022

Introduction/Objective

Red blood cell (RBC) antigens are inherited traits and, and their expression is consistent throughout the life of most individuals. Changes in RBC antigen expression rarely occur in association with hematologic malignancies. We report a case of Rh(D) antigen change in a patient with sickle cell disease (HbSS) after developing aplastic anemia (AA).

Methods/Case Report

Patient is a 21-year-old female with HbSS who developed progressively worsening anemia and severe thrombocytopenia over 1 month requiring frequent RBC and platelet transfusions. She was initially treated for idiopathic thrombocytopenic purpura with no significant improvement. Bone marrow examination demonstrated severe AA; additional viral, rheumatological, and hematologic studies were all non-informative. Subsequently, she was treated with corticosteroids, cyclosporin, anti-thymocyte immunoglobin and eltrombopag with minimal improvement. She has been non-compliant with maintenance cyclosporine and continued to be transfusion dependent in the past 2.5 years. She had always strongly typed 4+ Rh(D) positive at immediate spin (IS) before this event, but approximately about 1.5 years after the AA diagnosis her reactions became weaker (2-3+ at IS). She had a short-lived auto-anti-D identified on one occasion which has never been re-identified, but she has had very weak Rh(D) typings since this time with negative reactions at IS and only microscopically positive reactions at the anti-human globulin phase. The same pattern of reaction is present across a variety of commercial anti-D reagents. Molecular analysis reveals a normal RHD*01 hemi- or homozygous allele and no mutations known to cause a weak or partial Rh(D) type. No other antigen change is detected, and her extended phenotype matches a recently obtained genotype. She has been treated as both type O+ and O- in the last year by different facilities and transfused both types of RBCs without incident.

Results (if a Case Study enter NA)

NA.

Conclusion

We believe this is the first reported case of decreased Rh(D) expression following aplastic anemia and a transient auto-anti-D.
Effects of Storage Temperature and Duration on Flow Cytometry Analysis of Bone Marrow Aspirate Samples
Authors: Chen C , Cevallos S , Zhou Y
Published: November 2022

Introduction/Objective

Multiparameter flow cytometry immunophenotyping is a powerful and indispensable tool in the diagnosis of hematologic malignancies, but its accuracy and precision are vulnerable to pre-analytical interferences. Acid-citrate-dextrose (ACD) is one of three main anticoagulants used for marrow collection. It offers better preservation and is commonly used for apheresis stem cell collection. However, ACD may alter the pH of short-draw samples. It is unclear how prolonged storage in ACD affects the results of flow cytometry testing. In this pre-analytical study, we characterized the effects of temperature and storage duration in bone marrow aspirate collected in ACD.

Methods/Case Report

Five bone marrow specimens were collected in ACD and stored at 4°C or room temperature (RT), respectively. Aliquots of specimens were tested at 24, 48, and 72 hours. A flow cytometry panel including CD19, CD33, CD34, CD38, CD45, CD138, and 7-AAD was used to identify lymphocytes, monocytes, granulocytes, myeloid blasts, hematogones, and plasma cells. Absolute cell count, percentage of leukocytes, percentage of membrane- compromised cells (7-AAD bright), and mean-fluorescent-intensities were measured for each subset. The results of each storage condition were compared to the results on the day of sample collection.

Results (if a Case Study enter NA)

We found that granulocytes and plasma cells are most vulnerable to delayed testing, especially when stored at RT. Myeloid blasts, hematogones, monocytes, and lymphocytes were largely stable within 48 hours at 4°C or RT, but their relative representation in total leukocytes was affected by the diminished granulocytes. Variations in surface marker expression of CD45, CD38, and CD138 in the plasma cell subset were also noticed. This effect was less profound at 4°C than RT.

Conclusion

We conclude that delayed testing of specimens collected in ACD within 72 hours does not significantly impact the results of flow cytometry testing for the commonly studied subsets, and 4°C may be a more robust and preferable method for storage.
“You Get What You Need”: Early Results of BloodTrack System on Reducing Inefficiencies in Blood Product Allocation
Authors: Hung S , Woddor N , Husami S , Fernandez X
Published: November 2022

Introduction/Objective

The preparation of blood products allocated for massive transfusion protocol (MTP) activation and surgical cases consumes much time and energy of blood bank technologists. Often, these blood products are returned to the blood bank unused. Clinicians may activate the MTP preemptively to ensure the availability of blood products in case they are needed. Most blood products ordered for surgeries are placed on hold and not transfused. These returned units require additional inspections before they can be made available again. To reduce these inefficiencies, we implemented the BloodTrack [Haemonetics, Boston, MA] system, wherein blood products are stored in remote refrigerators and made available to clinicians near the patients’ bedside. Besides safeguarding units placed on hold for surgeries, we hypothesized that BloodTrack would provide greater visibility of available products in the emergency department (ED), thus reducing the rate of preemptive MTP activations.

Methods/Case Report

From March 2022 onwards, BloodTrack refrigerators with OnDemand software were active in the ED, operating room (OR), and two intensive care (ICU) units. We educated ED, OR, and ICU nurses on the appropriate use of BloodTrack. MTP activations were recorded from August 2021 to June 2022. Data on units allocated to OR patients by BloodTrack were collected from software-generated logs. Data on units allocated to OR patients by BloodTrack were collected from software-generated logs.

Results (if a Case Study enter NA)

Since its introduction in March, BloodTrack has dispensed 92 red blood cell units, which represents 12% of the total 766 units assigned. The remainder of 674 units were unused, and represent substantial savings in time otherwise spent re-instating them. Moreover, the rates of preemptive MTP activations trended downwards, from 28% (32/113) in the 7 months prior to implementation, to 13% (3/24) after implementation.

Conclusion

In conclusion, our implementation of BloodTrack has led to reduced MTP activations, improved efficiency of our blood product allocation process, and developed interdisciplinary care team integration.
Review of Effective Use of the Departmental Electronic Occurrence System for the Patient Care Related Safety Events. A CMC VAMC Experience
Authors: Patel S , Jhala D
Published: November 2022

Introduction/Objective

Electronic patient safety event reporting (e-reporting) is an effective mechanism to learn from errors and enhance patient safety. The Pathology and Laboratory Medicine (P&LMS) has established an electronic occurrence reporting (EOR) program to detect occurrences in patient results prior to the release of results, procedures for the documentation of corrected results that have been released, and any deviation to standard operating procedures. Patient safety and its monitoring is improved by using the EOR reporting system in which healthcare workers can document and learn from incidents, and thus prevent potential medical errors. The authors explore the use of the EOR in the calendar year 2021 and its effective use.

Methods/Case Report

The EOR is available to all the employees of P&LMS. This EOR allows the recording of all information pertinent to the occurrence (including pre-analytical, analytical, and post analytical issues) and a variety of issues (i.e., safety events, notifications, recalls, correction of released results, changed, results, or any unexpected standard operating procedure deviation). The section supervisor will initiate an investigation including root causes and outcomes of the occurrence and propose corrective action, recommendations, and follow-up in the Occurrence Detection Database. This is also reviewed at the quality management meeting and by the sectional pathologist director. For quality assurance review, the EOR’s usage for January 1st, 2021, to December 31st, 2021, was reviewed.

Results (if a Case Study enter NA)

The EOR successfully allowed the full documentation of all 870 reported occurrences during the study period in an organized fashion allowing appropriate tracking and investigation for quality improvement. All reported occurrences were handled appropriately with organized data to ensure quality assurance and improvement.

Conclusion

The EOR is a highly effective, successful program in terms of monitoring and assisting in ensuring timely action is taken in real time for patient care. Electronic reporting and documentation of incidents should be well supported by continuous staff training, help, and feedback. The ERO plays an important role in the maintenance of Veteran Affairs’ position as a High Reliability Organization (HRO).
A Rare Case of Amyloid Light Chain Amyloidosis with Extensive Hepatic Involvement
Authors: Prakash V , Ajmal I , Daley W , Varshney N , Petrasek J
Published: November 2022

Introduction/Objective

Amyloid light chain (AL) amyloidosis is a life-threatening disease entity, with an incidence of 10–15 per million per year in the USA. Amyloidosis is caused by the extracellular deposition of insoluble fibrillary amyloid protein resulting in multiorgan damage. Though amyloidosis is primarily a systemic disease, 10%-20% of cases can be localized.

Methods/Case Report

We present a case of a 37-year-old male admitted with predominant hepatic manifestations, whose liver biopsy led to the diagnosis of amyloidosis. The patient presented with intermittent abdominal pain, weight loss, persistent hypoglycemia, hepatomegaly, and raised liver enzymes. Imaging studies showed hepatomegaly with a heterogeneous lace like appearance of the liver parenchyma. Liver biopsy revealed an extensive deposition of amyloid protein in peri-sinusoidal spaces. The amyloid protein is highlighted by crystal violet stain and revealed apple- green birefringence on polarized microscopy after Congo red staining. On further evaluation, elevated kappa and lambda free light chains with increased kappa-lambda ratio were identified by serum protein electrophoresis. Subsequent bone marrow aspirate and biopsy identified a monoclonal kappa positive plasma cell neoplasm with an amorphous eosinophilic infiltrate. Liquid chromatography-tandem mass spectrometry on bone marrow biopsy detected a peptide profile consistent with AL (kappa) type amyloid deposition.

Results (if a Case Study enter NA)

NA.

Conclusion

AL amyloidosis patients with predominant hepatic involvement have a worse prognosis. Rapid diagnosis and prompt clinical intervention prevents further organ damage. This case study aims to promote awareness of the unusual presentations of amyloidosis.
60-Year-Old Patient with Invasive Mold Infection Consequent to an Encounter with a Barnyard Animal
Authors: Puello Yocum B , Lavik J
Published: November 2022

Introduction/Objective

Lichtheimia and Scedosporium species are ubiquitous fungi associated with a range of clinical presentations. We report a complex soft tissue coinfection caused by Lichtheimia spp. and Scedosporium spp. following a puncture wound by a rooster spur.

Methods/Case Report

A 60-year-old immunosuppressed man with a history of heart transplant presented with a non-healing wound 2-months after sustaining a lower leg puncture secondary to a rooster spur. The patient was previously treated with Augmentin for presumed cellulitis without improvement. To characterize the ongoing disease process, the wound was sampled with tissue portions routed for both histopathologic review and culture. In short order, the biopsy demonstrated invasive hyaline pauciseptate fungal hyphae consistent with organisms of the Mucorales order. In congruence, culture rapidly revealed a mucoraceous mold, subsequently identified as a Lichtheimia spp. Thus, the patient was treated with liposomal amphotericin B. However, days later, a second fungus - a Scedosporium spp. - was isolated from the original specimen. Consequently, isavuconazonium sulfate therapy was added. Re-review of the initial biopsy enabled distinction of two populations of fungal hyphae plausibly representing both molds. Despite numerous debridements and optimal medical management, the patient was ultimately referred for amputation.

Results (if a Case Study enter NA)

NA.

Conclusion

When encountered in an immunocompromised host, providers understandably respond to an invasive mucoraceous mold with alarm followed by quick, decisive action. However, septate molds, such as the Scedosporium spp., can also be aggressive. Further, the presence of more than one invasive mold presents a treatment challenge as the mucormycetes may require surgery coupled with amphotericin B therapy; whereas, the a Scedosporium spp. may be wholly resistant to amphotericin B. This case illustrates the critical role that an alert pathologist plays in guiding management through integration of data from different diagnostic modalities. It also constitutes an emphatic reminder that an illness may be caused by more than one actionable, invasive fungus.
Investigation of Drug ResistantAcinetobacter baumannii Virulence Factors Implicated in Intracellular Survival Within Differentiated THP-1 Cells
Authors: Wheibe E , Connolly K , Grier J , Fiester S
Published: November 2022

Introduction/Objective

Acinetobacter baumannii is a nosocomial opportunistic pathogen that is usually associated with mucosal infections such as pneumonia, urinary tract infections or sepsis and less commonly with more severe illnesses such as meningitis, wound infection, or necrotizing fasciitis. Of late, A. baumanniihas been flagged by the CDC as an urgent threat due to multidrug-resistant properties it has acquired, making it a major concern to public health. Due to a sparsity of information on the virulence factors of immune evasion, it has been difficult to understand how this bacterium is able to gain a foothold and cause severe infections. We sought to study how necrotizing fasciitis-associated strains of A. baumannii interact with human macrophages to assess their capabilities in evasion of the host immune response.

Methods/Case Report

To this end, extensively drug resistant A. baumannii was isolated at two timepoints (strains NFAb-1 and NFAb-2) from a patient over the course of a lethal necrotizing fasciitis infection that led to sepsis. The intracellular survival of these two strains was compared with each other, as well as to the type strains, ATCC 19606 and ATCC 17978, within a human macrophage-differentiated monocyte cell line, THP-1. Survival studies were complemented with quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) to investigate expression of potential bacterial virulence factors, Catalase E (KatE), Phospholipase C (PLC), Outer membrane protein A (ompA), and Pilus A (PilA), that could contribute to immune evasion.

Results (if a Case Study enter NA)

The intracellular survival assay demonstrated enhanced survival and bacterial growth of NFAb-1 and NFAb-2 within macrophages compared to ATCC 19606 and 17978. Examining gene expression, KatE, PLC, and OmpA didn’t show any significant differences between the bacterial strains, while the PilA gene had much higher expression in NFAb-1 and NFAb-2 compared to ATCC 19606 and 17978.

Conclusion

This data establishes these nectrotizing fasciitis-causing A. baumannii strains are more likely to sruvivie a macrophage-mediatied immune response and expression of pilus-assocated genes may play a role in these interactions. our studies demonstrate a need to further investigate A. baumannii mechanisms of virulence to understand its ability to evade the immune response in hopes of understanding and combating infections.
Trending the Variants of SARS-CoV-2 in the Veteran Population: How Things Have Changed from Before to the Interesting Present
Authors: Petersen J M , Jhala D
Published: November 2022

Introduction/Objective

In both the past and for the foreseeable future, SARS-CoV-2 (the coronavirus that causes COVID-19 disease) will continue to evolve. This evolution has already and will lead to new variants that will then cause surges of infection. These outbreaks in the past with the variant responsible have previously been reported individually. However, a timeline perspective on the changing SARS-CoV-2 variant landscape is sparse in the literature, particularly for testing performed at a Veteran Affairs Medical Center (VAMC). The Veteran population has increased comorbidities compared to the general population leading to susceptibility to infection including SARS-CoV-2. Hence, it is of utmost importance to explore the trending variants of SARS-CoV-2 in the veteran population as this epidemiological information may help in preventing transmission, which remains key in the management of COVID-19.

Methods/Case Report

Samples from selected patients from March 2021 to June 2022 who tested positive for SARS- CoV-2 by reverse transcriptase polymerase chain reaction with a cycle threshold or number <30 (required for sequencing) were sent for SARS-CoV-2 sequencing analysis.

Results (if a Case Study enter NA)

There were a total of 19 VAMC patients who were sequenced during the entire study period (March 2021 to June 2022). From March to May 2021, there were 8 patients, from which 6 demonstrated Pango Lineage B.1.1.7, 1 demonstrated Pango Lineage B.1.526.1, and 1 demonstrated Pango Lineage B.1. Later in 2021 (August to October 2021), there were 4 patients all of which demonstrates the Delta variant; 2 of these 4 demonstrated the Delta subvariant Pango Lineage AY.25 and the other 2 demonstrated Pango Lineage AY.44. By May to June 2022, there were 7 patients, all of whom demonstrated infection by the Omicron variant. Interestingly, 6 of these 7 patients demonstrated the newly emerging subvariant BA.2.12.1 and the remaining 1 demonstrated BA.2.9.

Conclusion

SARS-CoV-2 has continued to evolve throughout the course of the pandemic, which has led to variants and subvariants that have predominated for a time to cause an outbreak only to be replaced later by a different strain. This timeline epidemiological perspective demonstrates that the Veteran population has also been affected by the variants that have led to outbreaks in the past within the general population.