bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloid sarcoma mimicking as recurrent squamous cell carcinoma: What is the etiology?
Authors: Varghese I , Ahmed A A , mai B 
Published: October 2024

Abstract

Introduction/Objective
Myeloid sarcoma is an extramedullary malignancy of primitive myeloid cells and can occur during, preceding, or as a relapse of acute myeloid leukemia that occurs mostly in the soft tissue and skin.

Methods/Case Report
A 77-year-old white male with a history of oral squamous cell carcinoma status post resection (18 months ago) followed by radiation and chemotherapy (15 months prior), presented to the ear nose and throat clinic with increasing weakness and dizziness. He received two doses of Cisplatin and was currently on Pembrolizumab. On examination, there were two lesions in the oral cavity, one on the right gingivobuccal sulcus and a second on the left posterior mandibular ridge, suspicious for squamous cell carcinoma recurrence. Interestingly, the biopsy did not show evidence of recurrent squamous cell carcinoma but showed sheets of blasts that were positive for MPO, CD117, CD43, and CD68, consistent with myeloid sarcoma. Subsequent peripheral blood and bone marrow examinations showed acute myeloid leukemia.

Results (if a Case Study enter NA)
NA

Conclusion
Myeloid neoplasms post-cytotoxic therapy (MN-pCT) occur after radiation, alkylating agents, DNA topoisomerase II inhibitors, antimetabolites, and PARP1 inhibitors for a non-myeloid malignancy. Topoisomerase inhibitors are associated with MN-pCT after a latency period of 1 to 3 years; alkylating agents and radiation are associated with MN-pCT after a latency period of 5 to 7 years. Interestingly, this patient developed myeloid sarcoma in a previously irradiated area within 2 years. Cisplatin was discontinued after 2 doses due to side effect complications and is unlikely to be the culprit. Pembrolizumab is not considered to be a cytotoxic therapy and has not been reported to be associated with MN-pCT, however, the latency period for radiation-induced MN-pCT is unusually short in this patient and this raises the possibility of a Pembrolizumab-induced secondary myeloid neoplasm; additional investigation with other patients on this medication with second subsequent malignancies is required.
Nonimmune Hemolytic Anemia in Myelodysplastic Neoplasms (MDS) with U2AF1 Gene Mutation at S34 Hotspot: A Rare and Challenging Case Presentation
Authors: Li X , Krishnamurthy K , Sheikh F , Shi Y , Wang Y , Fang Y , Wang Q 
Published: October 2024

Abstract

Introduction/Objective
Hemolysis is recognized but not well understood in a subset of patients with myelodysplastic Neoplasms (MDS), largely through non-immune-mediated mechanisms. Lower survival rates are observed in MDS patients experiencing hemolysis. It is important to investigate the underlying mechanism including the molecular features of these cases. We hereby present a rare and challenging case of nonimmune hemolytic anemia in MDS with U2AF1 gene mutation at S34 hotspot.

Methods/Case Report
The patient is a 75-year-old male with past medical history of hypertension that presented with two weeks of 20 pounds weight loss, dyspnea on exertion and a syncopal event complicated with a parietal subarachnoid hemorrhage. Patient was found to have pancytopenia with severe anemia (hemoglobin 3.6 g/dl), reticulocytosis (reticulocyte 13.29%), decreased haptoglobin, while increased indirect bilirubin and lactate dehydrogenase. Spherocytes were detected in peripheral blood smear. With Coombs test being negative, all above are consistent with nonimmune hemolytic anemia. There is no evidence of paroxysmal nocturnal hemoglobinuria.
Bone marrow biopsy revealed trilineage hematopoiesis, many hypo-or mono-lobated dysplastic megakaryocytes and less than 5% blasts. Cytogenetics/FISH unveiled 5q deletion, 20q deletion and trisomy 8. Mutation in the U2AF1 gene at S34 hotpot is detected by next-generation sequencing. The overall findings are consistent with MDS with nonimmune mediated hemolysis.

Results (if a Case Study enter NA)
NA

Conclusion
Hemolysis, although uncommon in MDS, has a substantial impact on prognosis, treatment approaches and response. U2AF1 gene mutation is associated with poor outcomes in MDS patients. U2AF1 gene mutation at S34 hotpot is observed in 30% MDS patients with hemolysis in one recent report. Responses to erythropoiesis-stimulating agents and hypomethylating agents vary depending on different mutations, including U2AF1, SF3B1 and EZH2, with discrepancies across studies. Further investigation is warranted to elucidate the relationship between the molecular abnormalities and treatment response as well as prognosis in MDS patients with hemolysis.
Utility of Targeted Next Generation Sequencing (NGS) to Predict Hematologic Neoplasms with Germline Predisposition
Authors: Radova N , Miret E F , Gur H , Bizgarity P 
Published: October 2024

Abstract

Introduction/Objective
Hematologic neoplasms with germline predisposition are increasingly gaining clinical relevance as associated gene variants are emerging. These variants confer an increased risk for developing hematologic neoplasms as additional somatic aberrations accumulate. Recognition of germline predisposition is crucial to patient management as it would prompt genetic counseling and regular surveillance in affected patients and biological family members, as well as guide therapy, as many patients undergo allogeneic stem cell transplantation for which relatives are typically the preferred donors. Furthermore, these patients may respond differently to conventional therapies.
Clinical recognition of germline predisposition is challenging due to phenotypic heterogeneity and a lack of germline testing standards and resources. Next generation sequencing is routinely utilized to detect somatic variants associated with hematopoietic neoplasms. Molecular profiling may also potentially serve as a screening tool to suggest pathogenic germline variants.

Methods/Case Report
Comprehensive genomic profiling data was reviewed for 301 patients with known hematologic neoplasms. A somatic-germline-zygosity (SGZ) computational method classified variants by origin. Variants of unknown clinical significance were excluded. The final study showed 94 patients predicted to have germline variants. The variables analyzed include germline variants, concurrent mutations, diagnosis, sex, age, and ancestry.

Results (if a Case Study enter NA)
Acute myeloid leukemia was the most frequent diagnosis, followed by B-cell acute lymphoblastic leukemia, myeloproliferative neoplasms, myelodysplastic syndrome, and chronic myelomonocytic leukemia. The median patient age was 60 years, ranging from 6 months to 91 years. Male gender and European ancestry were proportionally greater. In this study, we identified 70 distinct genes with 145 germline pathogenic variants. The most common pathogenic germline variants were TET2, SRSF2, RUNX1, DNMT3A, and CHEK2.

Conclusion
In conclusion, SGZ computational methods can be used as a screening tool to predict possible germline mutations in hematologic malignancies, which will help guide treatment and improve patient and family outcomes
An unusual case of a de novo high-grade B cell neoplasm with MYC and BCL2 rearrangements, strong TdT expression, and BRAF V600E mutation
Authors: Asghar I A , Horwath M C , Zhang L , Abro B 
Published: October 2024

Abstract

Introduction/Objective
Aggressive de novo B cell neoplasms can rarely exhibit overlapping features of B- lymphoblastic leukemia/lymphoma (B-ALL) and high-grade B cell lymphoma (HGBL) making their definitive classification challenging. The distinction between mature and immature B cell neoplasms is critical as treatment approaches differ. We report a unique case of an aggressive B cell neoplasm that not only posed diagnostic difficulties but was also found to harbor a BRAF V600E mutation, an unusual finding in such cases.

Methods/Case Report
A 33-year-old man without any significant past medical history presented for evaluation of a large tonsil mass and diffuse lymphadenopathy. The tonsil was excised, and histologic examination showed a diffuse atypical infiltrate composed of medium to large monomorphic lymphoid cells with high-grade cytology. By immunohistochemistry, the atypical cells were positive for CD19, CD79a, CD22, PAX5, CD10 (strong), CD45 (strong), BCL2, MYC, and TdT (strong). Ki67 showed a high proliferation index (80%). The atypical cells were negative for CD20, CD34, CD1a, CD30, Cyclin D1, T cell markers, myeloid markers, HHV8, and EBER. Flow cytometry detected a CD10 positive B cell population that was negative for CD20, CD34, and surface light chain expression. Fluorescence in-situ hybridization (FISH) detected BCL2 and MYC rearrangements. Staging marrow showed diffuse involvement by a neoplastic infiltrate with similar features to those observed in the tonsil. Chromosome analysis showed a complex karyotype. The patient was treated with two cycles of da-EPOCH-R. A neck lymph node biopsy two months later showed persistent disease. Next-generation sequencing (NGS) on this sample demonstrated a BRAF V600E mutation at 31% allele frequency. A mutation-specific BRAF-VE1 immunostain was diffusely positive.

Results (if a Case Study enter NA)
NA

Conclusion
This was a diagnostically challenging case of a de novo B-cell lineage neoplasm with high-grade features, MYC and BCL2 rearrangements, and strong diffuse TdT expression. There is limited literature on mutational profiles and prognostic data for such cases, and whether they are best classified (and treated) as HGBL or B-ALL remains challenging and controversial. In our case, we also discovered an unexpected finding of a BRAF V600E mutation, which has not been reported in similar cases in the existing literature and could serve as a potential therapeutic target. Additional reporting and genetic profiling of such cases may help further elucidate their biology and guide treatment protocols.
Not All Therapy-Related Neoplasms are Myeloid: A Case Report of Rare B-ALL With t(5;14) Following Alkylating Agent Treatment
Authors: Patel R , Cortes P , Freeman J 
Published: October 2024

Abstract

Introduction/Objective
Most therapy-related hematologic neoplasms are myeloid (t-MN). Although not recognized as a distinct entity in the WHO classification of hematologic neoplasms, therapy-related acute lymphoblastic leukemia (t- ALL) cases have been previously reported. ALL incidence increases with any previous malignancy and is higher in those with previous treatment, supporting the concept of therapy-related ALL. B lymphoblastic leukemia/lymphoma (B- ALL) with t(5:14) is a rare subtype of the ALL (&lt;1%) harboring a IL-3/IGH gene translocation. We present the first case of B-ALL with t(5;14) following treatment with alkylating agents for breast carcinoma.

Methods/Case Report
A 79-year-old female received docetaxel, carboplatin, trastuzumab, pertuzumab, Herceptin and radiotherapy for an invasive ductal breast carcinoma. Two years later, she developed progressive pancytopenia requiring a bone marrow biopsy.

Results (if a Case Study enter NA)
The bone marrow aspirate smears demonstrated B-ALL with 25% blasts, limited neutrophilic maturation, moderate erythroid dysplasia, and decreased megakaryocytes with occasional atypical forms. On the biopsy, atypical megakaryocytes and lymphoblasts were positive for TP53 immunohistochemical stain. On flow cytometry, blasts were positive for CD19, cCD79a, CD22, CD10, TdT, and HLA-DR and only 6% were positive for CD34. Next generation sequencing showed TP53 and NRAS mutation. Karyotyping revealed 46, XX, t (5;14) (q33; q13) and trisomy 21.

Conclusion
B-ALL with t (5;14); IGH/IL3 fusion has not been previously reported following treatment with alkylating agents. The presence of morphologic myeloid dysplasia developing after chemotherapy with alkylating agents support causality being therapy related rather than an independent process. The case expands the breadth of known therapy- related hematologic neoplasms and raises questions regarding the mechanisms of leukemogenesis.
Epstein Barr Virus Positive Mucocutaneous Ulcer versus Classic Hodgkin Lymphoma: Challenges in Diagnosis
Authors: Hamdan H , Chinchanikar S , Irfan A , Mateescu V , Lankachandra K 
Published: October 2024

Abstract

Introduction/Objective
Epstein- Barr virus positive mucocutaneous ulcer (EBVMCU) is a clinicopathologic entity first identified in 2010. It occurs in patients with immunosuppression and presents as a well circumscribed ulceration on the oropharyngeal mucosa, skin or gastrointestinal tract. Infiltrates of atypical lymphoid cells that may have appearances similar to Diffuse Large B-cell Lymphoma (DLBCL) or Classic Hodgkin Lymphoma (CHL) are seen.

Methods/Case Report
A 41 year old male patient with history of HIV infection presented with hematochezia and rectal pain, underwent sigmoidoscopy and a large ulcerated mass was present at the anal verge. Polymorphic infiltrates of small lymphoid cells, eosinophils, granulocytes, plasma cells, histiocytes and scattered large atypical lymphoid cells, morphologically mimicking Reed-Sternberg cells were identified. The large atypical lymphoid cells were positive for CD30, MUM-1, BCL-6, EBER (EBV) and negative for CD3, CD15, CD20, CD45, CD79a, SOX-10. Based on lack of B-symptoms, no lymphadenopathy, superficial lesions, reduced CD4/CD8 ratio and specific location, EBVMCU was favored. Eight months later, he presented with night sweats, decreased appetite and inguinal lymphadenopathy. Lymph node excision displayed infiltrates of predominantly small lymphocytes, histiocytes, plasma cells and eosinophils. Foci of scattered large atypical cells morphologically compatible with Hodgkin/Reed Sternberg cells with focal necrosis were noted. The atypical cells were positive for CD30, PAX5 (weak), CD20 (subset), CD15 (focal), MUM-1 and EBV-EBER. CHL, Mixed Cellularity Subtype was diagnosed.

Results (if a Case Study enter NA)
NA

Conclusion
As a newer entity, we don’t know if EBVMCU can co-exist with or progress to CHL/DLBCL. Therefore, EBVMCU patients should undergo vigilant screening.
Straightforward, Highly Useful, Innovative and Cost-Effective Method with Potential to Improve Personalized Diagnosis: Sectioning of Prostatectomy Specimen with a Single Blade
Authors: Gandhi S , Petersen J M , Jhala D 
Published: October 2024

Abstract

Introduction/Objective
There is potential for devices with an adjustable base and a single blade to precisely cut parallel slices of a prostatectomy specimen at a set preferred thickness to improve pathology practice by standardizing the tissue for histological review, allowing for precise punch biopsies of the slices for molecular diagnostics for biobanking and personalized therapy. The current standard method of sectioning the prostate involves serially sectioning the prostatectomy specimen by hand with a sharp long knife, leading to uneven sections.

Methods/Case Report
A device with an adjustable base was developed at a regional Veteran Affairs Medical Center (VAMC) that consists of two sets of multiple, vertically arranged parallel and flat bars measuring 10 cm in height, 1.5 cm in width and 0.3 cm in thickness spaced 0.4 cm from each other, resembling a comb with flat teeth. After inking, orientation, and removal of the seminal vesicles and apex and base margins, the prostatectomy specimen is immobilized between the two combs and sliced in parallel from apex to base to produce parallel consistent prostate slices. The ability to obtain punch biopsies from precise areas of the prostate was reviewed.

Results (if a Case Study enter NA)
The device results in uniform 4 mm thick oriented smooth specimen slices of good quality with minimal distortion. The device allows for the obtaining of punch biopsies taken at precise locations of the prostate corresponding to specific imaging locations (highly useful for biobanking or obtaining diagnostic tissue for molecular diagnostics for personalized therapy). The adjustable nature of the device and single blade gives the device flexibility in the specimen.

Conclusion
This device with an adjustable base and single blade allows for safe and precise parallel slicing. This is highly useful obtaining diagnostic standardized tissue, for obtaining biobank specimens and for obtaining material of precise location for molecular studies to guide the personalized therapy of tumors.
Addressing HLA Laboratory Vacancy Challenges: Insights from a Survey-Based Analysis
Authors: Kudika C , Gebhart C , Hitchman K , Fisher P R 
Published: October 2024

Abstract

Introduction/Objective
Laboratory vacancies pose significant challenges to institutions across diverse sectors.
Understanding the landscape of these vacancies is crucial for developing effective strategies on how best to address them. The American Society of Histocompatibility & Immunogenetics (ASHI) Laboratory Professionals Recruitment Initiative (LPRI) was created to help address these issues by promoting and raising awareness of Histocompatibility and Immunogenetics (HLA) labs. This poster presents findings from a comprehensive survey conducted among various types of institutions to explore the prevailing dynamics surrounding HLA laboratory job vacancies. The primary purpose of this study is to provide a comprehensive overview of the HLA laboratory job vacancy landscape, including current vacancy rates, time taken to fill vacancies, and the perceived underlying causes attributed to these vacancies.

Methods/Case Report
The ASHI LPRI developed structured survey was administered to HLA laboratories represented in different service sectors, including hospital based, reference, organ procurement and independent laboratories. The survey collected data on the type of institution, current laboratory job vacancy rates, average time taken to fill vacancies, and perceived primary causes for vacancies. Data analysis was conducted to identify patterns and insights into the HLA laboratory vacancy challenges.

Results (if a Case Study enter NA)
The majority of respondents were from hospital-based or independent HLA laboratories, with few identifying as reference or organ procurement laboratories. Licensure or required certification was not a restricting factor in filling the vacancies. Vacancy rates for the varying institutions range between 10%- 25% with few reporting greater than 25% vacancy rate. A majority (54%) report their vacancies remain open for &gt; 6 months. Predominant vacancy perpetuation was most attributed to lack of applicants (58%) and insufficient pay offered (41%).

Conclusion
The findings of this study offer valuable insights into the complexities surrounding laboratory job vacancies in the clinical HLA space. Understanding the underlying causes and dynamics of these vacancies is essential for developing targeted strategies to mitigate the problem. By addressing these challenges, institutions can enhance workforce stability and ensure optimal laboratory operations. This poster serves as a foundation for further research and policy interventions aimed at addressing laboratory vacancy challenges.
Severe Congenital Neutropenia with ELANE gene mutation, on G-CSF therapy; a case report
Authors: Hanan A , Altaf S , Safdar J , Khan A , Sheikh-Fayyaz S 
Published: October 2024

Abstract

Introduction/Objective
Severe congenital neutropenia (SCN) is a genetic syndrome characterized by a deficiency of mature neutrophils in the bone marrow and peripheral blood. The disease is caused by various gene mutations, with ELANE gene mutations accounting for 50% to 60% of cases.

Methods/Case Report
We report a case of a 12-year-old male patient with severe congenital neutropenia, positive for the ELANE gene mutation. He has a history of recurrent infections and unexplained fevers since childhood. He has been receiving G-CSF treatment for ten years but is now exhibiting a diminished response to it. Analysis of the bone marrow biopsy reveals trilineage hematopoiesis, maturing myeloid with a rise in eosinophils, maturing erythroid, megakaryocytes normal in number and morphology with significantly reduced iron reserves in normocellular bone marrow. On immunostaining, CD34, CD14, or CD117 stains were negative. Neither monocytes nor granulocytes were CD56 positive. Increased monocyte counts coincide with partial CD14 loss. Lymphocytes make up 10% of all cells and consist of Polytypic B-cells, natural killer cells, and a heterogeneous population of T-cells with a normal CD4 to CD8 ratio. Hence, myelodysplastic syndrome was ruled out.

Results (if a Case Study enter NA)
NA

Conclusion
This case report provides valuable insights into the limited knowledge of congenital neutropenia with ELANE mutation on G-CSF therapy. It highlights the importance of ruling out Myelodysplastic syndrome in patients with severe congenital neutropenia and ELANE gene mutation treated with G-CSF therapy.
Case Report: Emergence of de novo Donor-Specific HLA antibodies post Pneumococcal & Varicella Zoster Vaccinations in Waitlisted Renal Transplant Candidate
Authors: Kakodkar P , Webster D , Pearce T , Wu F , Mostafa A , Johnston B , Shekari N 
Published: October 2024

Abstract

Introduction/Objective
In renal transplant waitlisted patients, vaccination series remains to be the standard of care for infection prevention. There is a need to investigate if any of these vaccines or their adjuvant components can induce de novo donor-specific antibodies (dnDSA) against human leukocyte antigens (HLA). These novel anti-HLA antibodies in renal transplant waitlisted patients can result in a positive flow cell crossmatch (FCXM) associated with an increased risk of renal transplant rejection.

Methods/Case Report
We present a 59-year-old renal transplant waitlisted patient who has had multiple negative T- cell and B-cell FCXM with no detection of dnDSA at baseline. We detected de-novo anti-HLA antibodies after he received pneumococcal conjugate (Pneum-C-13) and recombinant zoster vaccine (RZV). After vaccination, FCXM was positive for both T-cells and B-cells. HLA class I antibodies (A1, 23, 24, 80; B44, 45, 76) showed a panel reactive antibody (PRA) of 51%. Epitope analysis highlighted 166DG and 166ES as shared epitopes responsible for the entire specificity. The A1 dn-DSA had a mean fluorescence intensity (MFI) of 1800 and with shared A80 epitope MFI was 15,000 contributing to the strong positivity observed in T-cell and B-cell FCXM. New onset A1, and B44 DSA predicted high risk for transplant rejection with his sibling. His planned live donor renal transplant was halted and had to instead enter the kidney-paired donor program wherein he received his transplantation after 16 months.

Results (if a Case Study enter NA)
NA

Conclusion
Allosensitization risk secondary to RZV or Pneum-C-13 vaccines or their adjuvant components in renal transplant waitlisted patients must be considered as a potential risk for transplant rejection. Future studies can utilize monitoring of HLA-specific memory B-cells to provide crucial insights into the primary mechanism of action of dn-DSA anti-HLA antibody formation and suggest interventions to mitigate this memory B-cell activation.