bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Case of Ambiguous Lineage Acute Leukemia Posing Diagnostic Challenge
Authors: Rahman M , Huq Ronny F , Islam H 
Published: November 2022

Abstract

Introduction/Objective
N/A.

Methods/Case Report
Acute leukemias with ambiguous lineage encompass those leukemias that show no clear evidence of differentiation along a single lineage and account for less than 4% of all cases of acute leukemias and often poses diagnostic dilemma. We present a challenging case of an ambiguous lineage acute leukemia in a previously healthy 27-year-old male, who presented to the ED with acute fever, dyspnea on exertion, nausea and vomiting. A complete blood count (CBC) showed a white blood cell count of 323 × 109/L, Hemoglobin of 3.3 g/dl, Platelet count of 44 × 109/L and a differential count of Neutrophil: 11, Lymphocyte: 31, Monocyte: 02, Band Neutrophil:1, Myelocyte :1, Blast: 54. Bone marrow aspirate smears revealed a heterogenous population of small to large sized blasts comprising 83% of cellularity. They expressed scant to moderate basophilic cytoplasm, high N/C ratio, round to irregular nuclear contour, finely granular chromatin and some with nucleoli. Other lineages were markedly suppressed. Flow cytometric analysis revealed an abnormal blast population (~80% of total) expressing CD34, HLA-DR, Tdt (subset), CD71 (dim) and CD38. In addition, the blasts expressed myeloid associated antigens CD13, MPO (smaller subset), as well as B-cell associated antigens CD19 (dim), cytoplasmic CD22 and cytoplasmic CD79a. They also expressed T-cell associated antigens, CD2, CD3 (smaller subset), CD5 (subset) and CD7 (subset) but negative for cytoplasmic CD3. This unusual pattern of expression posed a challenge as to what type of mixed phenotype leukemia it should be with variable expressions from all three lineage of myeloid, B- and T-cell. Further work-up showed, scattered blasts are also positive for MPO by cytochemical (on aspirate smear) and immunohistochemical stain (on core). The latter also showed negativity for CD3. Based on all these findings, this mixed phenotype acute leukemia (MPAL) was best categorized as MPAL (B/myeloid) over so called “Triphenotypic (B/T/myeloid) acute leukemia”. We considered expression of myeloid and B cell markers as more lineage defining in this case as compared to small subset expressing T lineage marker CD3. This case exemplifies the importance of multimodal comprehensive analysis of acute leukemia, especially in the setting of MPAL with expression of multi- lineage markers posing a diagnostic challenge.

Results (if a Case Study enter NA)
N/A.

Conclusion
N/A.
Concurrent IRF4 Rearrangements in a Patient with B Cell and T Cell Disorders
Authors: Bernhisel A , Siddon A , Katz S 
Published: November 2022

Abstract

Introduction/Objective
IRF4 is a regulatory protein which required at several stages of B and T cell development and differentiation. Rearrangements of the IRF4 chromosomal region have been detected in various B and T cell neoplasms including a distinct entity in the WHO tumor classification for diffuse large B cell lymphoma (DLBCL) with IRF4 rearrangement and another for an IRF4 rearranged subtype of the CD30-positive T cell lymphoproliferative disorder, lymphomatoid papulosis (LyP).

Methods/Case Report
We present the case of a 52-year-old man with a past medical history of treated Hodgkin disease in remission who now presents with a DLBCL of the tonsil as well a cutaneous LyP, both of which demonstrate the IRF4 gene rearrangement. Immunohistochemical stains support the morphologic diagnoses and the rearrangement is detected in both cases using fluorescence in situ hybridization (FISH).

Results (if a Case Study enter NA)
NA.

Conclusion
The detection of IRF4 translocation in two separate cell lineages may result from one of a handful of possible explanations that we explore. First, a mutation in a multipotent hematopoietic progenitor cell may give rise to common lymphoid progenitors which pass the mutation on to subsequent B and T differentiated lymphocytes. Second, de novo mutations may be occurring in both B and T cell lines leading to the mature lesions. Finally, it may be possible that one of the two lesions is not truly positive for IRF4 rearrangement, but rather the background B cells in the skin or T cells in the tonsil are the cells positive for the aberration. This is a unique case of a B and T cell lesion in the same patient which both possess the same rare genetic rearrangement. The implications on our understanding of the genetic development of such lesions is significant and may subsequently impact diagnosis and therapy going forward.
Utility of Repeated NGS Testing in Myeloid Diagnostic Work Up
Authors: Zhu Y , Aljuboori O , Zhou Y 
Published: November 2022

Abstract

Introduction/Objective
NGS is an integral component of diagnostic work-up of myeloid neoplasms, commonly applied at initial diagnosis and for assessment of treatment response. It is less clear how NGS should be repeated at disease follow-up when initial result is negative. In order to assess the utility of repeated NGS testing, we retrospectively analyzed results in patients with multiple tests.

Methods/Case Report
Myeloid NGS results were collected between 10/2017 and 4/2022 at University of Miami. The results were grouped by patients and arranged by collection date and finding of mutations. First, we identified patients with negative result or a single mutation of common CHIP gene TET2, DNMT3A, or ASXL1 (DAT) in the first available NGS test. Then we divided these patients into negative follow-up group, if all NGS results were the same as the initial test, and positive follow-up group, if any new mutations were detected. The NGS findings were correlated with clinical history and pathology diagnosis.

Results (if a Case Study enter NA)
Results from 876 patients were analyzed. A total of 362 patients underwent multiple NGS tests; among them, 84 were negative and 14 had a single DAT mutation in the first NGS test. Among the 98 patients, 21 (21.4%) were in the positive follow-up group, with median time-to-positive at 132 days; the other were in the negative follow-up group with median follow-up time at 258 days. Analysis of the patient history showed the positive follow-up group consists 16 patients who were in remission of high-grade myeloid neoplasm at the time of initial testing and relapsed at the time of detection of mutations, 4 patients who acquired alteration of uncertain significance after hematopoietic stem cell transplant, and 1 patient who acquired KRAS mutation corresponding to MDS developed 846 days after the initial testing.

Conclusion
Positive conversion in repeated NGS testing are mostly associated with relapsed myeloid neoplasm after chemotherapy.
A Novel Fusion Partner in a Case of Myeloid/Lymphoid Neoplasm with FGFR1 Rearrangement
Authors: Chakraborty S R , Ibrahim S , Johari V , Hunt J , Freeman J 
Published: November 2022

Abstract

Introduction/Objective
Myeloid/lymphoid neoplasms with rearrangement of FGFR1 are uncommon and heterogeneous group of hematological malignancies that may present as myeloproliferative neoplasm, acute myeloid leukemia, T or B lymphoblastic lymphoma/leukemia, or mixed phenotypic acute leukemia. Patients can present with lymphadenopathy, mediastinal mass, or systemic symptoms. Eosinophilia is common in peripheral blood or bone marrow. Several chromosomal rearrangements and fusion genes have been described with FGFR1 rearrangement and all of them encode an aberrant tyrosine kinase. Tyrosine kinase inhibitors may offer a prospective therapeutic approach although specific targeted therapies have yet to be established.

Methods/Case Report
We present a case of a 14-year-old male who presented with rapid neck pain and swelling. Imaging revealed a 15 x 8 x 6 cm neck mass extending into the anterior mediastinum. Laboratory evaluation revealed anemia, thrombocytopenia, and leukocytosis (41.7 K/mm3), with absolute eosinophilia and blasts of 50%. Flow cytometry of peripheral blood demonstrated a population of T-lymphoblasts comprising about 60% of the cellularity with dim CD45, cytoplasmic CD3, CD7, TdT, CD38, CD4, CD5, CD10, and CD15, supporting T-lymphoblastic leukemia/lymphoma. The patient received induction chemotherapy, and subsequent bone marrow biopsy showed morphologic remission. Six weeks from diagnosis, the patient developed a gluteal mass with an atypical T-cell infiltrate that was negative for TdT; and at 15 weeks from diagnosis, developed an enlarging abdominal mass, also with an atypical T-cell infiltrate also negative for TdT and CD1a. At that time molecular diagnostic studies of the abdominal wall mass discovered a previously unpublished ATG16L1-FGFR1 fusion, supporting myeloid/lymphoid neoplasm with FGFR1 rearrangement, T-lymphoblastic leukemia/lymphoma.

Results (if a Case Study enter NA)
NA.

Conclusion
Although a variety of translocations have been identified with FGFR1 rearrangement, the novel fusion partner ATG16L1 has not been previously reported. The case also illustrates an unusual extramedullary recurrence of the T-cell lymphoblastic leukemia/lymphoma with significant antigenic shift including loss of TdT and CD1a.
Peripheral Blood Flow Cytometry Outside of Recommended Indications: A Potential Source of Increased Healthcare Costs?
Authors: Ocampo Gonzalez F , Solarewicz J , Miller I J , Lopez-Hisijos N M 
Published: November 2022

Abstract

Introduction/Objective
Flow cytometry (FC) is a useful tool in the diagnosis of hematological conditions. Recommended indications for peripheral blood FC have been put forth by several groups, including the American Society for Clinical Pathology (ASCP) in its Choosing Wisely Initiative, and include neutropenia, absolute lymphocytosis, lymphadenopathy and splenomegaly, as well as follow-up for known hematological malignancies. Concerns exist that the use of peripheral blood flow cytometry outside of these indications can be associated with increased health costs.

Methods/Case Report
We performed a retrospective search for all peripheral blood flow cytometry studies performed at Rush University Medical Center in the period spanning January to June, 2021. We used the Query feature on Soft Computer’s SoftFlow (SCC Soft Computer, Florida). For all cases found the electronic health record was searched for information on the clinical indication, ordering service, history of hematological malignancies, and study results.

Results (if a Case Study enter NA)
286 peripheral blood flow cytometry studies were identified, of which 187 had negative findings and 99 were abnormal. 220 cases (77%) were ordered under recommended indications (by ASCP) while 66 cases (23%) were ordered outside of them. Of the studies ordered under recommended indications, 121 (55%) had abnormal findings, while 99 (45%) were negative. Of the studies ordered outside of recommended indications, 100% had negative findings; none of these cases showed a history of hematological malignancy on record. The most common non-recommended indications were isolated anemia (31 cases, 11%), isolated thrombocytopenia (16 cases, 5.5%), bicytopenia (15 cases, 5%) and coagulopathy (4 cases, 1.5%). 42 studies (65%) were ordered by the hematology/oncology service while 22 (35%) were ordered by the internal medicine and surgery services.

Conclusion
A quarter of the peripheral blood flow cytometry studies in the selected period were performed outside of recommended indications, with negative results in 100% of them. Collectively, single or bicytopenias were the most common non-recommended indication. The majority of these studies were ordered by the hematology/oncology service, with only a third coming from others. Some possible causes for these inappropriate requests include ordering studies as a battery instead of a step-wise approach, and concern for missing an incipient/occult condition.
Immunoglobulin G4-Related Disease (IgG4-RD) Mimicking Hyaline Vascular Castleman Disease
Authors: Karimi S S , Fidai S 
Published: November 2022

Abstract

Introduction/Objective
Immunoglobulin G4-related disease (IgG4-RD) is a newly emerging immune-mediated fibroinflammatory disease characterized by increased IgG-4+ plasma cells. In soft tissue and visceral organs, the IgG4+ plasma cells often accompany a storiform pattern of fibrosis with obliterative phlebitis. In lymph nodes, rare cases have been described in the literature mimicking Multicentric Castleman Disease.

Methods/Case Report
Herein, we present a case of a 59-year-old male with history of lung adenocarcinoma status post resection one year prior, who presented with several months of unintentional weight loss and worsening of cervical lymphadenopathy. CT scan of the neck demonstrated extensive cervical lymphadenopathy. Incidentally, patient had traveled to a foreign country and had a positive QuantiFERON result. Clinical suspicion was either nodal metastatic disease or TB infection. An excisional biopsy of the left cervical lymph node was performed. Microscopic examination revealed numerous hyperplastic follicles with significant hyaline deposition, concentrically thickened mantle zones, radially penetrating vessels, increased interfollicular vascularity and plasmacytosis; morphologic features commonly associated with Hyaline-Vascular Castleman Disease (HVCD). Additionally, plasmacytosis within germinal center was identified. Immunohistochemical stains demonstrated significant IgG4+ plasma cells (approaching 108/HPF) within the germinal centers. All plasma cells were polytypic.

Results (if a Case Study enter NA)
N/A.

Conclusion
Commonly described patterns for IgG4-RD in the literature are multicentric Castleman disease (MCD)-like, whereas, in our case, we present intrafollicular plasma cell proliferation pattern of IgG4-RD with classic background features of HVCD. Accurate diagnosis and distinction between these two entities is imperative for prognostication, treatment and clinical management of IgG4-RD.
A Rare Case of Anaplastic Lymphoma Kinase-Positive Large B-Cell Lymphoma Involving Epidural Tissue
Authors: Satia S , Lam J 
Published: November 2022

Abstract

Introduction/Objective
Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK-positive LBCL) is a rare, aggressive type of non-Hodgkin’s B-cell lymphoma with characteristic rearrangements and overexpression of ALK. Diagnosis of ALK-positive LBCL is challenging because of its rarity and uncharacteristically low expression of B- lineage antigens usually needed for diagnosis of B-cell lymphomas. In this report, we describe a case of ALK-positive large B cell lymphoma involving epidural soft tissue in a young adult.

Methods/Case Report
29 year old presented to emergency department with a two week history of back pain and a three day history of worsening numbness and weakness in the lower extremities. MRI of the thoracic spine showed an epidural soft tissue mass posterior to T5, T6 and T7 vertebral bodies with abnormal signal in the T6 spinous process. Histological examination from the epidural mass revealed sheets of atypical lymphoid cells with abundant pale cytoplasm and round vesicular nuclei with prominent single to occasional multiple nucleoli. Immunohistochemical stains demonstrated neoplastic cell positivity for ALK, VS38c, CD138, EMA, MUM1, CD45, PAX5 and MCK. They were negative for CD3, CD20, CD19, CD79a, CD30, CD2, CD117, SOX10, HMB45, cytokeratin, synaptophysin and chromogranin. These overall findings were consistent with ALK-positive large B-cell lymphoma.

Results (if a Case Study enter NA)
NA.

Conclusion
ALK-positive large B-cell lymphoma is a non-Hodgkin lymphoma associated with high morbidity and mortality. Absence of reliable B-cell marker expression in this B-cell lymphoma requires recognition of morphological findings to order confirmatory testing such as immunohistochemical stains for CD138 and ALK. This particular case also showed an unusual anatomic presentation in epidural tissue.
A Two Part Case Series on Acquired Hemophilia A
Authors: Dailey D S 
Published: November 2022

Abstract

Introduction/Objective
Acquired Hemophilia A is a rare condition with an incidence of 1 per 1.5 million per year. The average age at presentation is 74 years. It is due to spontaneous production of IgG autoantibodies that target endogenous factor viii. This disease should be considered when a patient presents with bleeding, an abnormal prolongation of activated partial thromboplastin time and /or no prior personal or family history of bleeding. Autoimmune disorders and malignancy are common associations. Pregnancy and surgery are common presenting scenarios.

Methods/Case Report
Case 1: 71 year old female with a history of deep venous thrombosis, and rheumatoid arthritis. Patient presented to the emergency department with a hemoglobin of 4.7 and coagulation studies showed a prolonged partial thromboplastin time of 119 seconds. Imaging revealed retroperitoneal bleeding. A mixing study showed no correction of partial thromboplastin time. The patient was treated with packed red blood cell transfusions until hemodynamically stable. Further coagulation studies revealed a factor VIII activity of 3L and factor VIII inhibitor level of 103 bethesda units. This confirmed suspicion of an acquired factor VIII inhibitor associated with the patient’s rheumatoid arthritis as the source of abnormal lab values and bleeding. Patient was treated with recombinant factor VIIa, novoseven, along with continuous prednisone and cyclophosphamide. Case 2: 82 year old male with history of IgG Kappa Monoclonal Gammopathy of Undetermined Significance. Patient presented with gastrointestinal bleeding and 4g/Dl hemoglobin. He received 5 units of packed red blood cells. Sigmoidoscopy revealed a rectal ulcer causing lower gastrointestinal bleeding. An advanced coagulation study revealed factor VIII activity of 1%, and inhibitor levels of 17 bethesda units. Patient was started on prednisone initially, followed by cyclophosphamide. However, bleeding continued. He was treated with 6 units of recombinant factor VIIa and packed red blood cell transfusions as required to keep hemoglobin levels at 7g/Dl. He was continued on prednisone at an increased dosage and discharged.

Results (if a Case Study enter NA)
NA.

Conclusion
Acquired Hemophilia A is a rare disease. It should be suspected anytime there is unprecedented bleeding and/or unexplained prolongation of partial thromboplastin time. It is diagnosed with factor VIII panel, including inhibitor. Treatment includes immunosuppresants, intravenous immunoglobulins, and recombinant factor VIIa.
Artificial Intelligence with CBC Based Morphometric Parameters Aimed Toward Effective Diagnostic Practices for Dysplasia Associated Hematological Malignancies
Authors: Haider R 
Published: November 2022

Abstract

Introduction/Objective
The diagnosis and classification of dysplasia associated hematological neoplasms is dominated by morphology. Current round of study made use of potential ‘fingerprints’ among routinely generated diagnostic data particularly morphological and immature fraction-related (morphometric) parameters produced during routine complete blood count (CBC) testing in hemat-oncology department through artificial intelligence predictive modeling.

Methods/Case Report
Along conventional statistics, neural network models were trained on anonymized demographical, clinical and diagnostic data of total 1624 individuals with common hematological neoplasms. In addition, validation conducted on independent dataset. The frameworks were trained to differentiate hematological malignancies cases with various sub-entities of Dysplasia against Non-dysplastic group as a control cohort.

Results (if a Case Study enter NA)
Our predictive model attained greater precisions; percent incorrect prediction were remained 10.3 and 4.6 for training and testing phases, respectively along with a 95.4% negative predictive value (NPV). Moreover, higher accuracy (93.1%) was obtained during prospective validation in challenge of independent dataset. Model’s performance related metrics: the gain and lift chart, predictive-pseudo probability chart, and receiver operative curve (ROC) curve were noted as persuasive. Considering the sensitivity and specificity, area under the curve (AUC) values were also noted quite convincing; 0.954 for Non-dysplasia group while 0.994 for acute myeloid leukemia with dysplasia (AML-Dys) followed by 0.992, 0.988, 0.986, 0.984, 0.973, and 0.962 for chronic myelo- monocytic leukemia (CMML), refractory anemia with excess blast-I (RAEB-I), refractory anemia with excess blast-II (RAEB-II), refractory anemia with multi-lineage dysplasia (RCMD), Hypoplastic myelodysplastic syndrome (H-MDS), and refractory anemia with uni-lineage dysplasia (RCUD) respectively.

Conclusion
The negative predictive efficiency of our framework advocates its utility as a screening tool for the rapid expulsion of Dysplasia associated hematological neoplasms in hemat-oncology sections, aiding prompt care decisions.
Applying Deep Learning Cancer Subtyping Algorithms Trained on Physical Slides to Multiphoton Imaging of Unembedded Samples
Authors: Mahmood F , Robbins C J , Perincheri S , Torres R 
Published: November 2022

Abstract

Introduction/Objective
Deep learning algorithms on digital images of physical tissue slides have shown potential improvements in accuracy and precision of diagnostic interpretation of neoplastic histology. Clustering-constrained- attention multiple-instance learning (CLAM) is one such method that identifies diagnostic sub-regions to accurately classify whole slides. Often, algorithm performance degrades when deployed on datasets that differ from the original set and it is subject to physical slide preparation variability. New multiphoton imaging modalities have potential workflow and quality advantages over physical slides, producing images analogous to whole slide imaging (WSI) without cutting artifacts, but performance of existing algorithms trained on digitized physical slides and applied to multiphoton images remains completely unknown. Given this, we aimed to test the performance of CLAM algorithms for subtyping renal cell carcinoma (RCC) and lung cancer (LC) applied to pseudo-colored multiphoton WSI.

Methods/Case Report
Clinical RCC and LC surgical resection samples were processed and imaged by Clearing Histology with MulitPhoton microscopy (CHiMP, Applikate Technologies, Fairfield, CT), producing digital images of un- cut, un-embeded tissue to generate H&E-like optical slices. Multiphoton images were downscaled to 0.5 um/px to match algorithm target resolution. CLAM models for subtyping RCC (chromophobe, clear cell, papillary) and LC (squamous & adenocarcinoma) previously trained using TCGA and CPTAC whole slide images of physical slides were applied directly to CHiMP multiphoton images without adjustment. Reference cancer subtype classifications were provided from physical and digital slides.

Results (if a Case Study enter NA)
For the subtypes included during training, multiphoton WSIs of RCC and LC were accurately subtyped by the CLAM models without stain normalization nor network fine tuning producing high prediction levels. Subtypes not included during the training (namely oncocytoma for RCC) resulted in low scoring model predictions (below 0.85), indicating specificity of identification. Multiple slide levels improved interpretation of several difficult cases for CLAM predictions.

Conclusion
This preliminary data suggests that CLAM models trained on standard H&E WSIs for RCC and LC subtyping are applicable to pseudo-H&E multiphoton WSIs without domain adaptations. This implies that diagnostic histologic features have been learned by these CLAM models and are efficiently recognized in digital histology images produced via CHiMP.