998 results on '"Medeiros, L. Jeffrey"'
Search Results
2. High-Grade B-Cell Lymphoma, Not Otherwise Specified: CNS Involvement and Outcomes in a Multi-Institutional Series.
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Epperla N, Zayac AS, Landsburg DJ, Bock AM, Nowakowski GS, Ayers EC, Girton MR, Hu M, Beckman AK, Li S, Medeiros LJ, Chang JE, Kurt H, Sandoval-Sus J, Ansari-Lari MA, Kothari SK, Kress A, Xu ML, Torka P, Sundaram S, Smith SD, Naresh KN, Karimi YH, Bond DA, Evens AM, Naik SG, Kamdar M, Haverkos BM, Karmali R, Farooq U, Vose JM, Rubinstein PG, Chaudhry A, and Olszewski AJ
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Little is known about the central nervous system (CNS) risk in high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS). Hence, we sought to describe the rates of baseline CNS involvement, risk of CNS recurrence after primary therapy, and management strategies in HGBL, NOS. In this multicenter retrospective study, we included 160 adults with newly diagnosed HGBL, NOS treated between 2016 and 2021 at 20 US institutions. Eleven patients (7%) had baseline CNS involvement at diagnosis (leptomeningeal=6, parenchymal=4, and both=1). Baseline CNS involvement was significantly associated only with MYC rearrangement (OR=3.5) and testicular (in men) or female pelvic (in women) involvement (OR=8.1). There was no significant difference in survival outcomes between HGBL, NOS patients with (median PFS=4 years) or without (median PFS=2.4 years) baseline CNS involvement (p=0.45). The cumulative incidence of CNS recurrence at 3 years was 11%. Patients with baseline CNS involvement were at the highest risk (48.5% versus 8% for those without baseline CNS involvement) and were excluded from the risk factors analysis for CNS recurrence. The risk for CNS recurrence was significantly associated with blood or bone marrow involvement, CD5 expression, non-GCB subtype, and DEL phenotype, however, high CNS-IPI was not. The prognosis of relapsed HGBL, NOS was poor, regardless of whether recurrence was systemic or limited to the CNS, and with currently available salvage strategies, including autologous transplantation and CAR T-cell modalities, almost all patients with CNS recurrence ultimately succumbed to their disease. These patients represent an unmet need and should be prioritized for experimental approaches., (Copyright © 2024 American Society of Hematology.)
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- 2024
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3. From the archives of MD Anderson Cancer Center: Composite mantle cell lymphoma and lymphoplasmacytic lymphoma involving bone marrow at presentation.
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Dimopoulos YP, Thakral B, Lin P, Toruner G, Zuo Z, Medeiros LJ, and Leventaki V
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Composite lymphoma, defined as two or more distinct well-defined entities involving the same anatomic site, is rare. Here we report a 79-year-old woman with composite mantle cell lymphoma (MCL) and lymphoplasmacytic lymphoma (LPL) involving bone marrow at the time of initial diagnosis. The patient presented with splenomegaly and lymphadenopathy and laboratory studies showed an elevated serum IgM level and IgM kappa paraprotein. Bone marrow evaluation showed concurrent involvement by MCL and LPL, supported by immunophenotypic studies that revealed two distinct aberrant B-cell populations. Next-generation sequencing analysis identified concurrent MYD88 and CXCR4 mutations and fluorescence in-situ hybridization showed CCND1 translocation, supporting the diagnosis of concomitant MCL and LPL. In conclusion, composite lymphoma can present in the bone marrow. The use of ancillary studies was essential in reaching the diagnosis in this case, as the results excluded the possibility of MCL lymphoma with plasmacytic differentiation, as well as other CD5- and CD10-negative small B-cell lymphomas., Competing Interests: Declaration of competing interest The authors declare no conflict of interest associated with this publication., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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4. Secondary acquisition of the Philadelphia chromosome in acute lymphoblastic leukemia.
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Shen Q, Jabbour EJ, Tang G, Fang H, Wang W, Short NJ, You MJ, Medeiros LJ, and Hu S
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- 2024
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5. Acute myeloid leukemia with mast cell differentiation is characterized by interstitial mast cells, complex karyotype, TP53 alterations and poor prognosis.
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Kim DH, Wang SA, Wang W, Tang G, Li S, Yin CC, Lin P, Konopleva M, You MJ, Miranda RN, Wang X, Wei Q, Medeiros LJ, and Xu J
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- Humans, Prognosis, Male, Female, Middle Aged, Mutation, Aged, Karyotype, Adult, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute pathology, Mast Cells pathology, Mast Cells metabolism, Tumor Suppressor Protein p53 genetics, Cell Differentiation
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- 2024
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6. Fifth Edition of the World Health Organization Classification of Tumors of the Hematopoietic and Lymphoid Tissues: Mature T-Cell, NK-Cell, and Stroma-Derived Neoplasms of Lymphoid Tissues.
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Miranda RN, Amador C, Chan JKC, Guitart J, Rech KL, Medeiros LJ, and Naresh KN
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- Humans, T-Lymphocytes immunology, T-Lymphocytes pathology, Lymphoid Tissue pathology, Lymphoid Tissue immunology, Stromal Cells pathology, Stromal Cells immunology, Hematologic Neoplasms pathology, Hematologic Neoplasms classification, Hematologic Neoplasms immunology, World Health Organization, Killer Cells, Natural pathology, Killer Cells, Natural immunology
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This review focuses on mature T cells, natural killer (NK) cells, and stroma-derived neoplasms in the fifth edition of the World Health Organization classification of hematolymphoid tumors, including changes from the revised fourth edition. Overall, information has expanded, primarily due to advancements in genomic understanding. The updated classification adopts a hierarchical format. The updated classification relies on a multidisciplinary approach, incorporating insights from a diverse group of pathologists, clinicians, and geneticists. Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract, Epstein-Barr virus-positive nodal T- and NK-cell lymphoma, and several stroma-derived neoplasms of lymphoid tissues have been newly introduced or included. The review also provides guidance on how the fifth edition of the World Health Organization classification of hematolymphoid tumors can be applied in routine clinical practice., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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7. T-Cell-Rich Hodgkin Lymphoma With Features of Classic Hodgkin Lymphoma and Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Borderline Category With Overlapping Morphologic and Immunophenotypic Features.
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El Hussein S, Fang H, Jelloul FZ, Wang W, Loghavi S, Miranda RN, Friedberg JW, Burack WR, Evans AG, Xu J, and Medeiros LJ
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- Humans, Male, Female, Middle Aged, Adult, T-Lymphocytes pathology, T-Lymphocytes immunology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Doxorubicin therapeutic use, Cyclophosphamide therapeutic use, Prednisone therapeutic use, B-Lymphocytes pathology, Reed-Sternberg Cells pathology, Vincristine therapeutic use, Diagnosis, Differential, Immunohistochemistry, Lymph Nodes pathology, Aged, Rituximab therapeutic use, Hodgkin Disease pathology, Hodgkin Disease diagnosis, Immunophenotyping
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Context.—: It is known that a subset of cases of classic Hodgkin lymphoma (CHL) with B-cell-rich nodules (lymphocyte-rich CHL) exhibits morphologic and immunophenotypic features that overlap with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), raising diagnostic difficulties that can be resolved in most cases by performing an adequate battery of immunohistochemical studies., Objective.—: To fully characterize cases of T-cell-rich Hodgkin lymphoma where a specific diagnosis of NLPHL (ie, pattern D) or CHL could not be made even after complete immunophenotypic investigation., Design.—: The clinical, immunomorphologic, and molecular (when applicable) presentation of 3 cases of T-cell-rich Hodgkin lymphoma was thoroughly investigated., Results.—: These 3 cases harbored lymphocyte-predominant-like and Hodgkin and Reed-Sternberg-like cells that partially expressed B-cell and CHL markers and were negative for Tiftein-Barr virus-encoded small RNA, in a T-cell-rich background with residual follicular dendritic cell meshworks; 1 case had frequent and the other 2 cases scant/absent eosinophils and plasma cells. Two patients with advanced-stage (III or IV) disease presented with axillary and supraclavicular lymphadenopathy, respectively, and without B symptoms. These patients underwent NLPHL-like therapeutic management with 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], vincristine sulfate [Oncovin], and prednisone) chemotherapy; both are in complete remission 7 years posttherapy. One patient presented with stage I disease involving an internal mammary lymph node without B-symptoms and was treated with surgical excision alone; this patient is also in complete remission 1 year later., Conclusions.—: These cases illustrate overlapping features of T-cell-rich NLPHL and CHL with neoplastic cells expressing both B-cell program and CHL markers. This underrecognized overlap has not been fully illustrated in the literature, although it portrays a therapeutic challenge. These neoplasms may deserve in-depth investigation in the future that may bring up diagnostic or theragnostic implications., (© 2024 College of American Pathologists.)
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- 2024
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8. From the archives of MD Anderson Cancer Center. Mesothelial/monocytic incidental cardiac excrescence with a review of the literature.
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Mallick J, Thakral B, Wei Q, and Medeiros LJ
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- Humans, Male, Aged, Monocytes pathology, Epithelium pathology, Epithelium metabolism, Antigens, CD metabolism, Immunohistochemistry methods, Atrial Appendage pathology, Antigens, Differentiation, Myelomonocytic metabolism, Diagnosis, Differential, Pericardial Effusion pathology, Pericardial Effusion diagnosis, CD68 Molecule, Aortic Valve Stenosis pathology, Aortic Valve Stenosis surgery, Aortic Valve Stenosis diagnosis
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Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare benign lesion composed of monocytes and mesothelial cells that is most often encountered during cardiothoracic surgery. We describe a case in a 71-year-old man with known aortic valve stenosis who presented with gradual onset dyspnea over a few weeks, made worse with minimal exertion. A transesophageal echocardiogram revealed severe aortic stenosis and mild pericardial effusion. The patient underwent aortic valve replacement, coronary artery bypass, and amputation of the left atrial appendage. Histological examination of a 0.8 cm blood clot received along with the atrial appendage showed an aggregation of bland cells with features of monocytes associated with small strands and nodules of mesothelial cells, fat cells, fibrin and a minute fragment of bone. Immunohistochemical analysis showed that the monocytic cells were positive for CD4 and CD68 (strong) and negative for calretinin and keratin. By contrast, the mesothelial cells were positive for calretinin and keratin and negative for all other markers. In sum, the morphologic and immunohistochemical findings support the diagnosis of MICE. Based on our review of the literature, about 60 cases of MICE have been reported previously which we have tabulated. We also discuss the differential diagnosis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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9. Low-grade histiocytic sarcoma with aggressive clinical behaviour: an unusual case with novel genetic mutations identified by whole genome sequencing.
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Chiu LJ, Huang WT, Wang MC, Medeiros LJ, and Chang KC
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- 2024
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10. Optical genome mapping improves the accuracy of classification, risk stratification, and personalized treatment strategies for patients with acute myeloid leukemia.
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Loghavi S, Wei Q, Ravandi F, Quesada AE, Routbort MJ, Hu S, Toruner GA, Wang SA, Wang W, Miranda RN, Li S, Xu J, DiNardo CD, Daver N, Kadia TM, Issa GC, Kantarjian HM, Medeiros LJ, and Tang G
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Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision-making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next-generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four with failed karyotyping. The most common additional alterations identified by OGM included chromoanagenesis (n = 23), KMT2A partial tandem duplication (n = 11), rearrangements involving MECOM (n = 7), NUP98 (n = 2), KMT2A (n = 2), JAK2 (n = 2), and other gene fusions in 17 patients, with 10 showing novel fusion gene partners. OGM also pinpointed fusion genes in 17 (11%) patients where chromosomal rearrangements were concurrently detected by OGM and CBA. Overall, 24 (15%) aberrations were identified exclusively by OGM and had the potential to alter AML classification, risk stratification, and/or clinical trial eligibility. OGM emerges as a powerful tool for identifying fusion genes and detecting subtle or cryptic cytogenomic aberrations that may otherwise remain undetectable by CBA., (© 2024 Wiley Periodicals LLC.)
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- 2024
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11. Cytoplasmic Lipid Droplets Predict Worse Prognosis in Diffuse Large B-Cell Lymphoma: Next-Generation Sequencing Deciphering Lipogenic Genes.
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Wang SH, Chiang PM, Su YY, Yu YT, Chen YP, Chen TY, Medeiros LJ, Chu CY, Chen PC, and Chang KC
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Burkitt lymphoma is characterized by high cell turnover and numerous cytoplasmic vacuoles that are demonstrated to be lipid droplets (LDs) decorated by adipophilin. By contrast, cytoplasmic vacuoles are variably observed in diffuse large B-cell lymphoma (DLBCL) and less well characterized. In this study, we first validated in DLBCL that cytoplasmic vacuoles are indeed LDs by Oil-red-O stain, Bodipy fluorescent stain, and electron microscopy. Second, in a cohort of DLBCL patients (n=52) we showed that LDs in effusional lymphoma cells were associated with a poorer prognosis (P=0.029, log-rank test) and higher International Prognostic Index (IPI) score (94% vs. 66%, P=0.026) than those without. Moreover, using adipophilin as a surrogate marker for LDs, we found in another cohort of biopsy specimen (n=85) that expression of adipophilin by lymphoma cells predicted a poorer prognosis (P=0.007, log-rank test) and higher IPI score (63% vs. 30%, P=0.005). In addition, whole exome sequencing of effusional DLBCL cells showed LD-positive DLBCL shared genetic features with the MCD (MYD88 and CD79B mutations) subtype and highlighted OSBPL10 and CUBN as the most frequently mutated genes involved in lipogenesis. Whole transcriptome analysis by comparing effusional DLBCL cells with versus without LDs showed upregulation of EHHADH, SLC1A1, CD96, INPP4B, and RNF183 relevant for lymphoma lipogenesis and upregulation of epithelial-mesenchymal transition and KRAS signaling pathways. Higher expression of EHHADH and CD96 were validated in LD-positive clinical samples and LD-rich cell lines than LD-poor cells along with the known lipogenic gene, FASN. Our findings highlight the roles of LDs and adipophilin expression in DLBCL, suggest that these markers may predict prognosis and show that lipogenic genes may be potential therapeutic targets., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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12. Radiotherapy in the treatment of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder.
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Wu SY, Damron EP, Xu J, Fang PQ, Dai J, Nair R, Malpica Castillo LE, Fayad LE, Torres-Cabala CA, Medeiros LJ, Vega F, Miranda RN, Duvic M, Pinnix CC, Dabaja BS, Iyer SP, Huen AO, and Gunther JR
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Background: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy., Objective: Our aim was to characterize treatment options for PCSM-LPD, with a focus on the role of radiotherapy., Methods: This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM-LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy., Results: All patients achieved a complete response (CR). Sixteen patients (35%) received focal radiotherapy, with a CR in 15 (94%). The CR rate following ultra-low-dose radiotherapy (4 Gy in 1-2 fractions) was 92%. There was no grade 3 toxicity after radiotherapy. Thirty patients were managed without radiotherapy, with excision and observation or steroids., Conclusion: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder has excellent outcomes, and management strategies may include observation following biopsy, steroids, or radiation. Ultra-low-dose radiotherapy results in excellent outcomes with limited toxicity and is effective for persistent lesions after steroidal therapy., (© 2024 the International Society of Dermatology.)
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- 2024
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13. Morphology, immunophenotype, and suggested diagnostic criteria of TCL1 family-negative T-prolymphocytic leukemia.
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Fang H, Wang SA, Beird HC, Tang Z, You MJ, Li S, Xu J, Hu S, Yin CC, El Hussein S, Lin P, Jelloul FZ, Vega F, Medeiros LJ, and Wang W
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Objectives: We sought to investigate the morphologic and immunophenotypic characteristics of TCL1 family-negative T-cell prolymphocytic leukemia (T-PLL)., Methods: Twenty cases of TCL1 family-negative T-PLL were studied., Results: The doubling time of leukemic cells ranged from less than 2 days to more than 5 years, with a median of 5.5 months. Leukemic cells were small to medium-sized, with round to irregular nuclei, variably condensed chromatin, and small amounts of agranular cytoplasm. A visible nucleolus was identified in 11 (55%) cases. Cytoplasmic blebs/protrusions were identified in all cases, but their occurrence was highly variable from case to case. Bone marrow biopsy showed an interstitial pattern in 90% of cases and a diffuse pattern in the remaining 10% of cases. Flow cytometric immunophenotypic analysis showed that the leukemic cells in all cases were CD4 positive; 3 (15%) also showed concurrent CD8 expression. All cases were positive for CD2 and CD5. Surface CD3 and CD7 were positive in 19 of 20 (95%) cases, and all CD3-positive cases expressed the T-cell receptor αβ. Compared with prototypic T-PLL cases, these 2 groups shared many immunophenotypic findings, except CD8 and CD26, both of which were more commonly expressed in prototypic T-PLL cases., Conclusions: TCL1 family-negative T-PLL cases have morphologic and immunophenotypic features that are similar to prototypic T-PLL. They are characterized by neoplastic proliferation of small to medium-sized mature T cells with CD4-positive T-cell receptor αβ phenotype. Tumor cells frequently maintain pan-T antigen expression. Recognizing these morphologic and immunophenotypic features will aid in accurately diagnosing this rare subset of T-PLL., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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14. Advancing Diagnostic Accuracy and Quality of Patient Care Through the Implementation of a Flow Cytometry Quality Assurance Program.
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Wang D, Fang H, Ok CY, Jorgensen JL, Medeiros LJ, Wang W, and Wang SA
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Context.—: Flow cytometry immunophenotypic analysis plays an important role in the diagnosis, classification, and disease monitoring of hematologic neoplasms. The interpretation of flow cytometry testing can be challenging., Objective.—: To explore ways to improve diagnostic accuracy and in turn enhance the quality of patient care., Design.—: A flow cytometry quality assurance (QA) program was developed. Cases from various complex flow cytometry panels were randomly selected and cross-reviewed. The outcomes of the QA review were categorized into 3 groups: complete agreement, minor discrepancy, and major discrepancy. Each discrepancy underwent a process of documentation, discussion, and resolution. Here we summarize our 3 years of experience with this program., Results.—: In total, 6166 cases were evaluated; 6028 cases (97.7%) showed complete concordance, 120 cases (2.0%) showed minor discrepancies, and 18 cases (0.3%) showed major discrepancies. Among the top 5 panels evaluated, the panel evaluating mature T-cell abnormalities showed the highest rate of discrepancy, whereas the panel for evaluation of myelodysplastic syndromes showed the lowest discrepancy rate. When analyzing the trends of concordance and discrepancy over time, we observed a statistically significant decrease in discrepancy rate over time, from 4% at the beginning of the 6-month period to 1.5% in the final 6-month period., Conclusions.—: The overall concordance rate was 97.7%. The remaining 2.3% of cases showed discrepancies that required a correction, underscoring the value and necessity of having a QA program. The overall discrepancy rates exhibited a gradual decline over time, indicative of the positive impact of the QA program on enhancing diagnostic competency and accuracy over time., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)
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- 2024
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15. Multicolor flow cytometric immunophenotyping is highly sensitive and specific in identifying aberrant mast cells in the diagnostic workup of systemic mastocytosis.
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Nwogbo OV, Fang H, Wang W, Xu J, Miranda RN, Bose P, Ok CY, Jorgensen JL, Medeiros LJ, and Wang SA
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- Humans, Middle Aged, Female, Male, Adult, Aged, Sensitivity and Specificity, Aged, 80 and over, Young Adult, Adolescent, Immunophenotyping methods, Mastocytosis, Systemic diagnosis, Mastocytosis, Systemic pathology, Mastocytosis, Systemic immunology, Flow Cytometry methods, Mast Cells pathology, Mast Cells immunology
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Objectives: Flow cytometric immunophenotyping (FCI) is a fast and sensitive method for characterizing hematolymphoid neoplasms. It is not widely used in the workup of systemic mastocytosis (SM), in part because of the technical challenges and in part because the utility of FCI in assessing mast cells is not well understood. The objectives of this study were to assess the diagnostic utility of FCI in establishing a diagnosis of SM and distinguishing SM from nonneoplastic mast cells and to examine the immunophenotypic findings among SM subtypes., Methods: We performed FCI on bone marrow samples suspicious for SM using a panel consisting of CD2, CD25, CD30, CD45, CD117, and HLA-DR., Results: The cohort included 88 SM cases: 67 without an associated hematologic neoplasm (AHN) (PureSM) and 21 with an AHN (SM-AHN). We also assessed 40 normal/reactive controls. Overall, FCI was adequate for interpretation in 87 of 88 (99%) cases and detected at least 1 immunophenotypic aberrancy in 100% of SM cases. CD2, CD25, and CD30 were positive in 78%, 98%, and 90% of SM cases vs 0%, 13%, and 13% of cases with normal/reactive mast cells (P < .0001 for all). Two or 3 abnormalities were observed in 92% of SM cases but not in normal/reactive mast cells. Among SM cases, SM-AHN showed statistically significant less CD2 (38% vs 91%, P < .0001) and less co-expression of all 3 aberrant markers (CD2, CD25, and CD30 positive in 38% vs 86% of cases; P < .0001) than PureSM. Immunohistochemical analysis showed consistently weaker or focal expression of CD2, CD25, and CD30 than FCI, with CD2 and CD30 being falsely negative in 40% and 50% cases, respectively. A KIT D816V mutation was detected in 67% of PureSM cases and 76% of SM-AHN cases., Conclusions: Flow cytometric immunophenotyping is a quick, sensitive, high-yield tool for evaluating the immunophenotype of mast cells. An abnormal FCI finding should prompt careful histologic evaluation and sensitive KIT D816V mutation testing to address the possibility of SM. CD2, CD25, and CD30 are important markers for the detection of immunophenotypic aberrancy of mast cells, and their frequencies of aberrancy differ across SM subtypes., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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16. Potential genetic mechanisms driving B/myeloid conversion in patients with follicular lymphoma and Langerhans cell neoplasms.
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Tashakori M and Medeiros LJ
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- Humans, B-Lymphocytes pathology, B-Lymphocytes metabolism, Langerhans Cells pathology, Mutation, Myeloid Cells pathology, Myeloid Cells metabolism, Lymphoma, Follicular genetics, Lymphoma, Follicular pathology, Cell Transformation, Neoplastic genetics
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Transformation of follicular lymphoma (FL) to a Langerhans cell (LC) neoplasm is extremely uncommon. The shared IGH::BCL2 rearrangement is a robust finding in most transformed tumors underscoring that the cell of origin is perhaps a pre-B cell harboring IGH::BCL2 with the propensity to undergo further genetic alterations in the germinal centers of lymph nodes: does IGH::BCL2 in pre-B cells set off a plasticity cell state? Do FL and LC neoplasms develop separately through a common progenitor or via a multistep process of transdifferentiation or dedifferentiation/redifferentiation? Here, we review the literature and relevant cases presented in the Society for Hematopathology/European Association of Haematopathology 2021 Workshop to better understand this rare and complex phenomenon. We discuss clinical data, clonal relationship, and the mutational profile of these tumors and review proposed mechanisms of B/myeloid conversion based on in vitro and in vivo models.
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- 2024
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17. The Spectrum of Non-neoplastic Changes Associated With Breast Implants: Histopathology, Imaging, and Clinical Significance.
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Marques-Piubelli ML, Lyapichev KA, Fnu A, Adrada B, Stewart J, Hunt KK, Clemens MW, Iyer S, Wu Y, El Hussein S, Xu J, Ok CY, Li S, Pierson DM, Ferrufino-Schmidt MC, Nahmod KA, Yoga A, Hunsicker L, Evans MG, Resetkova E, Qiu L, Khanlari M, Garces SA, Bueso-Ramos CE, Medeiros LJ, and Miranda RN
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- Humans, Female, Predictive Value of Tests, Breast Neoplasms pathology, Breast Neoplasms surgery, Clinical Relevance, Breast Implants adverse effects, Lymphoma, Large-Cell, Anaplastic pathology, Lymphoma, Large-Cell, Anaplastic etiology, Breast Implantation adverse effects, Breast Implantation instrumentation
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Breast implant-associated anaplastic large cell lymphoma has been recognized as a distinct entity in the World Health Organization classification of hematolymphoid neoplasms. These neoplasms are causally related to textured implants that were used worldwide until recently. Consequently, there is an increased demand for processing periprosthetic capsules, adding new challenges for surgeons, clinicians, and pathologists. In the literature, the focus has been on breast implant-associated anaplastic large cell lymphoma; however, benign complications related to the placement of breast implants occur in up to 20% to 30% of patients. Imaging studies are helpful in assessing patients with breast implants for evidence of implant rupture, changes in tissues surrounding the implants, or regional lymphadenopathy related to breast implants, but pathologic examination is often required. In this review, we couple our experience with a review of the literature to describe a range of benign lesions associated with breast implants that can be associated with different clinical presentations or pathogenesis and that may require different diagnostic approaches. We illustrate the spectrum of the most common of these benign disorders, highlighting their clinical, imaging, gross, and microscopic features. Finally, we propose a systematic approach for the diagnosis and handling of breast implant specimens in general., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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18. From the archives of MD Anderson Cancer Center: Monomorphic epitheliotropic intestinal T-cell lymphoma: A case with an unusual immunophenotype and discussion of differential diagnosis.
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Dcunha NJ, Wei Q, Thakral B, and Medeiros LJ
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- Humans, Male, Biomarkers, Tumor metabolism, Biomarkers, Tumor analysis, Diagnosis, Differential, Intestinal Neoplasms diagnosis, Intestinal Neoplasms pathology, Lymphoma, T-Cell diagnosis, Lymphoma, T-Cell pathology, Aged, Immunophenotyping methods
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Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare and aggressive T-cell neoplasm associated with poor survival. We report a case of MEITL that presented as an ulcerated mass in the jejunum with perforation. Microscopic examination showed that the neoplasm involved the full thickness of the intestinal wall, extended into the mesentery, and was composed of monomorphic, small to medium-size cells. Immunohistochemical analysis showed that the neoplastic cells were positive for T-cell receptor (TCR) delta, CD3, CD7, CD8 (small subset), BCL-2 and TIA-1, and negative for TCR beta, CD4, CD5, CD10, CD20, CD30, CD34, CD56, CD57, CD99, ALK, cyclin D1, granzyme B, MUM1/IRF4, and TdT. The Ki-67 proliferation index was approximately 50 %. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER ISH) was negative. Next-generation sequencing (NGS) analysis showed mutations involving SETD2 and STAT5B. The patient was treated with aggressive chemotherapy and consolidative autologous stem cell transplant and had clinical remission, but relapsed after about one year. Retreatment led to another one-year interval of clinical remission, but at last follow up the patient has relapsed disease involving the ileum and colon. We also discuss the differential diagnosis of MEITL., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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19. STAT5B mutations in myeloid neoplasms differ by disease subtypes but characterize a subset of chronic myeloid neoplasms with eosinophilia and/or basophilia.
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Yin CC, Tam W, Walker SM, Kaur A, Ouseph MM, Xie W, K Weinberg O, Li P, Zuo Z, Routbort MJ, Chen S, Medeiros LJ, George TI, Orazi A, Arber DA, Bagg A, Hasserjian RP, and Wang SA
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- Humans, Male, Female, Middle Aged, Aged, Adult, Myeloproliferative Disorders genetics, Myeloproliferative Disorders diagnosis, Aged, 80 and over, High-Throughput Nucleotide Sequencing, Myelodysplastic Syndromes genetics, Myelodysplastic Syndromes diagnosis, STAT5 Transcription Factor genetics, Mutation, Eosinophilia genetics, Eosinophilia pathology, Basophils pathology, Basophils metabolism
- Abstract
STAT5B has been reported as a recurrent mutation in myeloid neoplasms with eosinophilia, but its overall frequency and importance across a spectrum of myeloid neoplasms are largely unknown. We conducted a multicenter study on a series of 82 myeloid neoplasms with STAT5B mutations detected by next-generation sequencing. The estimated frequency of STAT5B mutations in myeloid neoplasms was low, <0.5%, but mutations were detected in all categories of such neoplasms, including myelodysplastic syndrome (MDS, 28%), acute myeloid leukemia (AML, 26%), myelodysplastic/myeloproliferative neoplasm (MDS/MPN, 18%), Philadelphia chromosome-negative classic MPN (12%), systemic mastocytosis (1%), and, with a notably high frequency, chronic eosinophilic leukemia, not otherwise specified (CEL-NOS, 15%). STAT5B mutations occurred preferentially in the SH2 domain (95%), involved 12 different codons, with the N642H hotspot being the most common (78%). Co-mutations were present in all cases and clonal hierarchy analysis showed that STAT5B mutations tended to be subclonal in AML, MPN, and MDS, but frequently dominant/co-dominant in CEL-NOS (83%), followed by MDS/MPN (40%). Across the group, eosinophilia and/or basophilia were common (41%), frequently observed in cases in which STAT5B mutations were detected at initial diagnosis (P<0.0001), with a high variant allele frequency (median 42.5%, P=0.0001), as a dominant/ co-dominant clone (P<0.0001), involving the canonical N642H (P=0.0607), and associated with fewer co-mutations (P=0.0009). Our data show that the characteristics and importance of a STAT5B mutation differ among myeloid neoplasms, but if present as a dominant mutation and detected at initial diagnosis, it appears to be a driver mutation in a subgroup of chronic myeloid neoplasms, preferentially promoting a proliferation of eosinophils and basophils.
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- 2024
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20. Integrative immunophenotypic and genetic characterization of acute myeloid leukemia with CBFB rearrangement.
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Sameeta F, Wang SA, Tang Z, Khoury JD, Fang H, Wang D, Xu J, Li S, Hu Z, Hu S, Jorgensen JL, Medeiros LJ, and Wang W
- Abstract
Objectives: We sought to characterize the immunophenotype of acute myeloid leukemia (AML) with CBFB rearrangement and correlate the results with cytogenetic and molecular data., Methods: Sixty-one cases of AML with CBFB rearrangement were evaluated., Results: The sample population consisted of 33 men and 28 women, with a median age of 49 years. Flow cytometry immunophenotypic analysis showed that myeloblasts were positive for CD34 and CD117 in all cases, and myeloperoxidase was positive in 52 of 55 (95%) cases. The most common abnormalities included decreased CD38 in 90%, increased CD13 in 85%, increased CD123 in 84%, and decreased HLA-DR in 84% of cases. Monocytes were increased, with a mature immunophenotype, and accounted for 23.7% of total cells. Among 60 cases with available karyotype, inv(16)(p13.1q22) was most common in 50 (83%) cases, followed by t(16;16) (p13.1;q22) in 6 (10%). Type A CBFB::MYH11 transcript was most common, detected in 84% of cases. Mutational analysis showed mutations of NRAS in 37%, FLT3 in 25%, and KIT in 24% of cases. Comparing cases with type A vs non-type A transcripts, blasts in type A cases more frequently exhibited CD64 positivity and increased CD13 levels while showing a lower frequency of CD7 and CD56 expression. Trisomy 22 and mutations in KIT, NF1, and TET2 were identified only in cases with type A transcript., Conclusions: Myeloblasts of AML with CBFB rearrangement are positive for CD34, CD117, and myeloperoxidase. These neoplasms most frequently carry inv(16)(p13.1q22) and type A fusion transcript. NRAS mutation was the most common mutation. Some immunophenotypic and genetic correlations occurred with different types of transcripts., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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21. Fifth Edition of the World Health Organization Classification of Tumors of the Hematopoietic and Lymphoid Tissues: Acute Lymphoblastic Leukemias, Mixed-Phenotype Acute Leukemias, Myeloid/Lymphoid Neoplasms With Eosinophilia, Dendritic/Histiocytic Neoplasms, and Genetic Tumor Syndromes.
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Choi JK, Xiao W, Chen X, Loghavi S, Elenitoba-Johnson KS, Naresh KN, Medeiros LJ, and Czader M
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- Humans, Eosinophilia pathology, Eosinophilia genetics, Histiocytic Disorders, Malignant genetics, Histiocytic Disorders, Malignant pathology, Hematologic Neoplasms genetics, Hematologic Neoplasms pathology, Hematologic Neoplasms classification, Phenotype, World Health Organization, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma pathology, Precursor Cell Lymphoblastic Leukemia-Lymphoma classification
- Abstract
This manuscript represents a review of lymphoblastic leukemia/lymphoma (acute lymphoblastic leukemia/lymphoblastic lymphoma), acute leukemias of ambiguous lineage, mixed-phenotype acute leukemias, myeloid/lymphoid neoplasms with eosinophilia and defining gene rearrangements, histiocytic and dendritic neoplasms, and genetic tumor syndromes of the 5th edition of the World Health Organization Classification of Tumors of the Hematopoietic and Lymphoid Tissues. The diagnostic, clinicopathologic, cytogenetic, and molecular genetic features are discussed. The differences in comparison to the 4th revised edition of the World Health Organization classification of hematolymphoid neoplasms are highlighted., (Copyright © 2024. Published by Elsevier Inc.)
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- 2024
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22. TP53 mutation is frequent in mantle cell lymphoma with EZH2 expression and have dismal outcome when both are present.
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Kim DH, Siddiqui S, Jain P, Wang M, Thakral B, Li S, Miranda R, Vega F, Medeiros LJ, and Ok CY
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- Humans, Male, Female, Middle Aged, Aged, Aged, 80 and over, Adult, DNA Mutational Analysis, Immunohistochemistry, Ki-67 Antigen analysis, Ki-67 Antigen metabolism, Cell Proliferation, Enhancer of Zeste Homolog 2 Protein genetics, Enhancer of Zeste Homolog 2 Protein analysis, Lymphoma, Mantle-Cell genetics, Lymphoma, Mantle-Cell pathology, Lymphoma, Mantle-Cell mortality, Tumor Suppressor Protein p53 genetics, Mutation, Biomarkers, Tumor genetics, Biomarkers, Tumor analysis
- Abstract
Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and p53 mutant pattern by immunohistochemistry. Comparative analysis disclosed that EZH2 expression correlates with high Ki-67 proliferation rate irrespective of TP53 mutation. Aggressive histology is associated with EZH2 expression or TP53 mutation, possibly via independent mechanisms. p53 mutant pattern is due to TP53 mutation. MCL patients with EZH2 expression or TP53 mutation show inferior outcome and when both are present, patients have dismal outcome., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest directly related to the topic of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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23. Recurrent lymphoid and myeloid relapses due to treatment cessations reveal natural history of Ph-positive B-ALL and pose a diagnostic challenge.
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Hu S, Jabbour EJ, Hu CY, Tang G, Wang W, Medeiros LJ, and Bueso-Ramos C
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- Humans, Chronic Disease, Withholding Treatment, Neoplasm Recurrence, Local, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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- 2024
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24. Fifth Edition of the World Health Classification of Tumors of the Hematopoietic and Lymphoid Tissues: B-cell Neoplasms.
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Medeiros LJ, Chadburn A, Natkunam Y, and Naresh KN
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- Humans, World Health Organization, Pathologists, Lymphoma, B-Cell pathology, Hematologic Neoplasms pathology
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We review B-cell neoplasms in the 5th edition of the World Health Organization classification of hematolymphoid tumors (WHO-HEM5). The revised classification is based on a multidisciplinary approach including input from pathologists, clinicians, and other experts. The WHO-HEM5 follows a hierarchical structure allowing the use of family (class)-level definitions when defining diagnostic criteria are partially met or a complete investigational workup is not possible. Disease types and subtypes have expanded compared with the WHO revised 4th edition (WHO-HEM4R), mainly because of the expansion in genomic knowledge of these diseases. In this review, we focus on highlighting changes and updates in the classification of B-cell lymphomas, providing a comparison with WHO-HEM4R, and offering guidance on how the new classification can be applied to the diagnosis of B-cell lymphomas in routine practice., (Copyright © 2024 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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25. Frequent expression of PD-L1 in BLS-type diffuse large B-cell lymphoma: implications for aggressiveness and immunotherapy.
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Yang CF, Yu YT, Wang SH, Chen YP, Chen TY, Hsu CY, Medeiros LJ, and Chang KC
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- Humans, B7-H1 Antigen metabolism, Prognosis, Herpesvirus 4, Human, Immunotherapy, Tumor Microenvironment, Epstein-Barr Virus Infections pathology, Lymphohistiocytosis, Hemophagocytic, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
BLS-type diffuse large B-cell lymphoma (DLBCL) denotes an uncommon, aggressive variant of DLBCL presenting initially in bone marrow, liver and spleen without lymphadenopathy or mass lesion. Patients with BLS-type DLBCL present frequently with haemophagocytic syndrome which often leads to early patient demise. Programmed death ligand 1 (PD-L1) plays a negative regulatory role on effector T cells and is an important target of immunotherapy. Assessment of PD-L1 expression in BLS-type DLBCL may carry therapeutic implications and provide mechanistic insights. Standard immunohistochemical analysis for PD-L1 was performed in seven cohorts for this study: (1) DLBCL-not otherwise specified (NOS) (n=201); (2) Epstein-Barr virus (EBV)-positive DLBCL (n=26); (3) thymic (primary mediastinal) DLBCL (n=12); (4) intravascular LBCL (n=3); (5) high-grade B-cell lymphoma, NOS (n=12); (6) BLS-type DLBCL (n=37); and (7) systemic DLBCL involving bone marrow (n=28). We found that PD-L1 was positive in 12.9% of DLBCL-NOS cases, 46.2% of EBV-positive DLBCL, 91.7% of thymic LBCL, none of intravascular LBCL, 8.3% of high-grade B-cell lymphoma-NOS, and 56.8% of BLS-type DLBCL. By comparison, only 14.3% of bone marrow cases involved by systemic DLBCL were positive for PD-L1 (p<0.001). Interestingly, BLS-type DLBCL more frequently showed activated B-cell phenotype (86.5% vs 65.2%, p=0.010), a high Ki-67 proliferative index (97.1% vs 63.3%, p<0.001), MYC overexpression (90.9% vs 56.2%, p=0.023), presence of haemophagocytic syndrome (86.5% vs 4.0%, p<0.001), and poorer overall survival (p<0.001) than DLBCL-NOS. These data suggest that the poor prognosis of BLS-type DLBCL may be explained by both extrinsic tumour microenvironment factors and intrinsic genetic factors of tumour cells, such as PD-L1-associated inactivation of anti-tumour immunity for the former, and MYC pathway activation-related aggressiveness for the latter., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)
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- 2024
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26. EBV-positive Nodal T-Cell and NK-Cell Lymphoma: A Study of 26 Cases Including a Subset With Strong CD30 Expression Mimicking Anaplastic Large Cell Lymphoma.
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Yu F, Wang J, Ke Z, Zhang Y, Xu L, Zhang H, Huang K, Cheng F, Yang H, Wang L, Wang Z, Shou L, Yu W, Fang H, Medeiros LJ, and Wang W
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- Male, Humans, Female, Middle Aged, Herpesvirus 4, Human genetics, Killer Cells, Natural pathology, Lymph Nodes pathology, Lymphoma, Large-Cell, Anaplastic pathology, Epstein-Barr Virus Infections pathology
- Abstract
Epstein-Barr virus (EBV)-positive nodal T-cell and NK-cell lymphoma is a rare neoplasm of cytotoxic T-cell or NK-cell lineage. Here, we report 26 cases affecting 14 men and 12 women with a median age of 52 years. All patients presented with disease involving multiple lymph nodes, and 20 of 22 (91%) fully staged patients had advanced Ann Arbor stage disease. Spleen, liver, and bone marrow were involved in 70%, 50%, and 52% of cases, respectively. These patients had a dismal prognosis with a median survival of 30 days. Histologically, lymph nodes were replaced by lymphoma in a diffuse pattern. Lymphoma cells were variable in size and large cell morphology was seen in 62% of cases. The neoplastic cells were CD4-/CD8- in 14 (54%) cases and CD4-/CD8+ in 12 (46%) cases. CD56 was positive in 14 (54%) cases. CD30 was positive in 20 (77%) cases; a strong and diffuse pattern was observed in 14 (54%) cases, mimicking, in part, anaplastic large cell lymphoma (ALCL). CD30 expression was associated with younger age and large cell morphology. In summary, EBV+ nodal T-cell and NK-cell lymphoma is an aggressive disease with a poor prognosis. These neoplasms are heterogeneous at the morphologic and immunophenotypic levels. Diffuse and strong expression of CD30 could potentially lead to a misdiagnosis of ALCL if EBV evaluation is not performed. Distinguishing between EBV+ nodal T-cell and NK-cell lymphoma from ALCL is important because treatment strategy and prognosis differ. CD30 expression offers a potential therapeutic target for patients with this aggressive disease., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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27. ALK-positive histiocytosis of external auditory canal in a 3-year-old boy.
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Wang SH, Huang HY, Medeiros LJ, and Chang KC
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- Male, Humans, Child, Preschool, Receptor Protein-Tyrosine Kinases, Ear Canal, Histiocytosis diagnosis
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- 2024
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28. Predictive and prognostic molecular biomarkers in lymphomas.
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Iorgulescu JB, Medeiros LJ, and Patel KP
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- Humans, Prognosis, Mutation, Lymphoma diagnosis, Lymphoma genetics, Lymphoma pathology, Lymphoma, B-Cell diagnosis
- Abstract
Recent advances in molecular diagnostics have markedly expanded our understanding of the genetic underpinnings of lymphomas and catalysed a transformation in not just how we classify lymphomas, but also how we treat, target, and monitor affected patients. Reflecting these advances, the World Health Organization Classification, International Consensus Classification, and National Comprehensive Cancer Network guidelines were recently updated to better integrate these molecular insights into clinical practice. We summarise here the molecular biomarkers of lymphomas with an emphasis on biomarkers that have well-supported prognostic and predictive utility, as well as emerging biomarkers that show promise for clinical practice. These biomarkers include: (1) diagnostic entity-defining genetic abnormalities [e.g., B-cell acute lymphoblastic leukaemia (B-ALL) with KMT2A rearrangement]; (2) molecular alterations that guide patients' prognoses (e.g., TP53 loss frequently conferring worse prognosis); (3) mutations that serve as the targets of, and often a source of acquired resistance to, small molecular inhibitors (e.g., ABL1 tyrosine kinase inhibitors for B-ALL BCR::ABL1, hindered by ABL1 kinase domain resistance mutations); (4) the growing incorporation of molecular measurable residual disease (MRD) in the management of lymphoma patients (e.g., molecular complete response and sequencing MRD-negative criteria in multiple myeloma). Altogether, our review spans the spectrum of lymphoma types, from the genetically defined subclasses of precursor B-cell lymphomas to the highly heterogeneous categories of small and large cell mature B-cell lymphomas, Hodgkin lymphomas, plasma cell neoplasms, and T/NK-cell lymphomas, and provides an expansive summary of our current understanding of their molecular pathology., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)
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- 2024
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29. Diagnostic utility of immunohistochemistry in detection of NPM1 mutations in acute myeloid leukemia with a patchy distribution.
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Wei Q, Wang SA, Loghavi S, Fang H, Medeiros LJ, and Wang W
- Abstract
Nucleophosmin 1 ( NPM1 ) mutations occur in approximately one-third cases of adult de novo acute myeloid leukemia (AML). Identification of NPM1 mutations is important for classification, risk stratification, tailored therapy, and monitoring minimal residual disease. Mutational analysis is widely used for detecting NPM1 mutations. Immunochemistry assessing abnormal cytoplasmic localization of NPM1 protein has been used as a surrogate marker for NPM1 mutations. We present a case of AML with mutated NPM1 that was missed by sequencing analysis but detected by immunohistochemistry. This case highlights the value of immunohistochemistry in identifying NPM1 mutations in a subset of AML cases., Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (© 2024 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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30. Optical genomic mapping is a helpful tool for detecting CCND1 rearrangements in CD5-negative small B-cell lymphoma: Two cases of leukemic non-nodal mantle cell lymphoma.
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Quesada AE, Hu S, Li S, Toruner GA, Wei Q, Loghavi S, Ok CY, Jain P, Thakral B, Nwogbo OV, Kim D, Iyer SP, You MJ, Medeiros LJ, and Tang G
- Subjects
- Adult, Humans, Lymphocytes pathology, Genomics, Cyclin D1 genetics, Lymphoma, Mantle-Cell pathology, Lymphoma, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell pathology
- Abstract
Optical genome mapping (OGM) is a new DNA-based technology which provides comprehensive examination of the entire genome. We report two patients who presented with splenomegaly and leukocytosis with lymphocytosis including villous lymphocytes. Neither patient had lymphadenopathy. Bone marrow evaluation showed involvement by small B-cell lymphoma in a sinusoidal and interstitial distribution, and immunophenotypic analysis showed that the neoplastic cells were positive for B-cell markers and cyclin D1 but were negative for SOX11 and CD5. Initially, the clinicopathologic features in both patients were thought to be suspicious for hairy cell leukemia variant or splenic marginal zone lymphoma. However, OGM detected CCND1 rearrangement: t(2;11)/IGK::CCND1 in one case and t(11;14)/IGH::CCND1 in the other case. These cases illustrate the valuable role OGM can play in establishing the diagnosis of MCL. Case 1 also contributes to the paucity of literature on the rare occurrence of IGK::CCND1 in MCL., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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31. SOX11+ Large B-Cell Neoplasms: Cyclin D1-Negative Blastoid/Pleomorphic Mantle Cell Lymphoma or Large B-Cell Lymphoma?
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Li S, Tang G, Jain P, Lin P, Xu J, Miranda RN, Cheng J, Yin CC, You MJ, Wang ML, and Medeiros LJ
- Subjects
- Adult, Humans, Cyclin D1 genetics, In Situ Hybridization, Fluorescence, Immunohistochemistry, SOXC Transcription Factors genetics, Lymphoma, Mantle-Cell metabolism, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Large or blastoid B-cell neoplasms that are SOX11+ are a diagnostic dilemma and raise a differential diagnosis of cyclin D1-negative blastoid/pleomorphic mantle cell lymphoma (MCL) versus diffuse large B-cell lymphoma (DLBCL) or blastoid high-grade B-cell lymphoma (HGBL) with aberrant SOX11 expression. Here we report a study cohort of 13 SOX11+ large/blastoid B-cell neoplasms. Fluorescence in situ hybridization analysis was negative for CCND1 rearrangement in all 13 cases; 1 of 8 (12.5%) cases tested showed CCND2 rearrangement and 2 (25%) cases had extracopies of CCND2. Gene expression profiling showed that the study group had a gene expression signature similar to cyclin D1+ blastoid/pleomorphic MCL but different from DLBCL. Principal component analysis revealed that the cohort cases overlapped with cyclin D1+ blastoid/pleomorphic MCL but had minimal overlap with DLBCL. All patients in the cohort had clinicopathologic features similar to those reported for patients with cyclin D1+ MCL. We also performed a survey of SOX11 expression in a group of 85 cases of DLBCL and 24 cases of blastoid HGBL. SOX11 expression showed a 100% specificity and positive predictive value for the diagnosis of MCL. Overall, the results support the conclusion that large or blastoid B-cell neoplasms that are positive for SOX11 are best classified as cyclin D1-negative blastoid/pleomorphic MCL, and not as DLBCL or blastoid HGBL. We also conclude that SOX11 is a specific marker for the diagnosis of MCL, including cyclin D1-negative blastoid/pleomorphic MCL cases and should be performed routinely on blastoid/large B-cell neoplasms to help identify potential cases of cyclin D1-negative blastoid/pleomorphic MCL., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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32. Fifth Edition of the World Health Classification of Tumors of the Hematopoietic and Lymphoid Tissue: Myeloid Neoplasms.
- Author
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Loghavi S, Kanagal-Shamanna R, Khoury JD, Medeiros LJ, Naresh KN, Nejati R, and Patnaik MM
- Subjects
- Humans, World Health Organization, Myeloproliferative Disorders diagnosis, Myeloproliferative Disorders genetics, Myeloproliferative Disorders pathology, Myelodysplastic Syndromes genetics, Leukemia, Myeloid, Acute genetics, Hematologic Neoplasms diagnosis
- Abstract
In this manuscript, we review myeloid neoplasms in the fifth edition of the World Health Organization classification of hematolymphoid tumors (WHO-HEM5), focusing on changes from the revised fourth edition (WHO-HEM4R). Disease types and subtypes have expanded compared with WHO-HEM4R, mainly because of the expansion in genomic knowledge of these diseases. The revised classification is based on a multidisciplinary approach including input from a large body of pathologists, clinicians, and geneticists. The revised classification follows a hierarchical structure allowing usage of family (class)-level definitions where the defining diagnostic criteria are partially met or a complete investigational workup has not been possible. Overall, the WHO-HEM5 revisions to the classification of myeloid neoplasms include major updates and revisions with increased emphasis on genetic and molecular drivers of disease. The most notable changes have been applied to the sections of acute myeloid leukemia and myelodysplastic neoplasms (previously referred to as myelodysplastic syndrome) with incorporation of novel, disease-defining genetic changes. In this review we focus on highlighting the updates in the classification of myeloid neoplasms, providing a comparison with WHO-HEM4R, and offering guidance on how the new classification can be applied to the diagnosis of myeloid neoplasms in routine practice., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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33. Origin of the terms 'water pot' and 'starry sky' in Burkitt lymphoma.
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Zhang DD, Medeiros CG, Liang M, and Medeiros LJ
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- Humans, Terminology as Topic, Burkitt Lymphoma pathology
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- 2024
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34. Aleukemic Chronic Myeloid Leukemia Without Neutrophilia and Thrombocytosis: A Report From the BCR::ABL1 Pathology Group.
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Rivera D, Cui W, Gao J, Peker D, Zhang QY, Dewar R, Qiu L, Konoplev S, Hu Z, Sasaki K, Hu AY, E S, Liu M, Fang H, Wang W, Tang G, Apperley JF, Hochhaus A, Cortes JE, Khoury JD, Medeiros LJ, Jabbour E, and Hu S
- Subjects
- Humans, In Situ Hybridization, Fluorescence, Leukocytosis, Fusion Proteins, bcr-abl genetics, Protein Kinase Inhibitors therapeutic use, Leukemia, Myelogenous, Chronic, BCR-ABL Positive diagnosis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive genetics, Leukemia, Myelogenous, Chronic, BCR-ABL Positive pathology, Thrombocytosis genetics, Eosinophilia
- Abstract
Chronic myeloid leukemia (CML) is characterized by leukocytosis with left-shifted neutrophilia, basophilia, eosinophilia, and variable thrombocytosis. However, extremely rare cases of patients with CML without significant leukocytosis and thrombocytosis (aleukemic phase [ALP] CML, or CML-ALP) have been reported. Due to its rarity and limited awareness, there remains a significant knowledge gap concerning the pathologic diagnosis, disease progression, and optimal patient management and outcomes. In this multi-institutional study, we investigated 31 patients with CML-ALP. Over half (54.8%) of patients had a history of or concurrent hematopoietic or nonhematopoietic malignancies. At time of diagnosis of CML-ALP, approximately 26.7% of patients exhibited neutrophilia, 56.7% had basophilia, and 13.3% showed eosinophilia. The median number of metaphases positive for t(9;22)(q34;q11.2) was 15, with a median of 38.5% of interphase nuclei positive for BCR::ABL1 by fluorescence in situ hybridization. The median BCR::ABL1 level was 26.14%. Remarkably, 14 (45.2%) patients were initially misdiagnosed or not diagnosed before karyotype or fluorescence in situ hybridization information for BCR::ABL1 became available. Twenty-five patients received tyrosine kinase inhibitors (TKIs). One patient developed blast crisis while on TKI treatment 8 months after initial diagnosis. With a median follow-up time of 46.1 months, 20 of 22 patients who received TKI therapy and had detailed follow-up information achieved complete cytogenetic remission or deeper, 15 achieved major molecular remission or deeper, and 10 achieved molecularly undetectable leukemia. In conclusion, given the frequent occurrence of prior or concurrent malignancies, aleukemic presentation, and low level of t(9;22)(q34;q11.2)/BCR::ABL1, misdiagnosis or delayed diagnosis is common among these patients. While these patients generally respond well to TKIs, rare patients may develop blastic transformation. It is therefore important for pathologists and hematologists to be aware of this highly unusual presentation of CML to ensure timely diagnosis and appropriate management., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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35. Genetics and pathologic landscape of lineage switch of acute leukemia during therapy.
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Zhou T, Curry CV, Khanlari M, Shi M, Cui W, Peker D, Chen W, Wang E, Gao J, Shen Q, Xie W, Jelloul FZ, King RL, Yuan J, Wang X, Zhao C, Obiorah IE, Courville EL, Nomura E, Cherian S, Xu ML, Burack WR, Liu HX, Jabbour EJ, Takahashi K, Wang W, Wang SA, Khoury JD, Medeiros LJ, and Hu S
- Subjects
- Humans, Acute Disease, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute pathology
- Published
- 2024
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36. Unicentric Castleman Disease: Illustration of Its Morphologic Spectrum and Review of the Differential Diagnosis.
- Author
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El Hussein S, Evans AG, Fang H, Wang W, and Medeiros LJ
- Subjects
- Humans, Diagnosis, Differential, Plasma Cells pathology, Castleman Disease diagnosis, Castleman Disease pathology, Dendritic Cell Sarcoma, Follicular, Multiple Myeloma diagnosis
- Abstract
Context.—: Unicentric Castleman disease (UCD) is a dynamic entity with a wide spectrum of morphologic findings. UCD can be further subdivided into hyaline-vascular and mixed/plasmacytic variants. Hyaline-vascular UCD has both follicular and interfollicular (stromal) changes, and occasionally these lesions show a skewed representation of either the follicular or stromal compartments. Plasmacytosis is usually minimal in the hyaline-vascular variant. The mixed/plasmacytic variant of UCD is composed of sheets of plasma cells often associated with a variable number of follicles with regressive changes., Objective.—: To illustrate the differential diagnosis of UCD, as it is quite broad and includes lymphomas, plasma cell neoplasms, stromal neoplasms such as follicular dendritic cell sarcoma and vascular neoplasms, immunoglobulin G4-related disease, infections, and other rare lesions. An additional objective is to enhance awareness of the morphologic features of UCD in excisional and in small core-needle biopsy specimens, the latter of which may inadvertently target follicle- or stroma-rich areas, causing diagnostic challenges., Data Sources.—: In this review, we provide readers a concise illustration of the morphologic spectrum of UCD that we have encountered in our practice and a brief discussion of entities in the differential diagnosis., Conclusions.—: UCD exhibits a broad spectrum of morphologic changes, and awareness of these morphologic variations is key to avoid misdiagnosis., (© 2024 College of American Pathologists.)
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- 2024
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37. Detection of clinically actionable gene fusions by next-generation sequencing-based RNA sequencing of non-small cell lung cancer cytology specimens: A single-center experience with comparison to fluorescence in situ hybridization.
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Diks J, Tang Z, Altan M, Anderson S, Chen H, Rashid A, Yang RK, Routbort MJ, Patel KP, Toruner GA, Medeiros LJ, Tang G, Luthra R, and Roy-Chowdhuri S
- Subjects
- Humans, Protein-Tyrosine Kinases genetics, Anaplastic Lymphoma Kinase genetics, RNA, In Situ Hybridization, Fluorescence methods, Proto-Oncogene Proteins genetics, High-Throughput Nucleotide Sequencing methods, Gene Fusion, Sequence Analysis, RNA, Gene Rearrangement, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung genetics, Lung Neoplasms diagnosis, Lung Neoplasms genetics
- Abstract
Background: Genomic profiling is needed to identify actionable alterations in non-small cell lung cancer (NSCLC). Panel-based testing such as next-generation sequencing (NGS) is often preferred to interrogate multiple alterations simultaneously. In this study, we evaluate the utility of an RNA-based NGS assay to detect genomic alterations in NSCLC cytology specimens and compare these results to fluorescence in situ hybridization (FISH) testing., Methods: A retrospective review was performed of 264 NSCLC cytology specimens that were concurrently tested for gene fusions by RNA-based NGS and ALK, RET, and/or ROS1 by FISH., Results: Genomic alterations were detected in 29 cases by NGS, including ALK, RET, ROS1, NTRK, NUTM1, and FGFR3 fusions and MET exon 14 skipping alterations. Of the 20 cases with ALK, RET, and ROS1 fusions detected by NGS, 16 (80%) were concordant with the corresponding FISH results. Three cases showed discordance, where EML4::ALK (n = 2) and SLC34A2::ROS1 (n = 1) fusions were not detected by the corresponding FISH assay; one case with EZR::ROS1 was inadequate for FISH. No gene fusions were detected in 181 cases by NGS and 54 cases failed testing. The concordance rates for detecting ALK, RET, and ROS1 fusions using NGS and FISH were 97%, 100%, and 99.5%, respectively., Conclusion: RNA-based NGS can be used to detect gene fusions in NSCLC cytology cases with high concordance with FISH results. However, RNA-based NGS may have high failure rates and therefore a low threshold for reflexing inadequate cases to an orthogonal testing method is essential for comprehensive genomic profiling., (© 2023 American Cancer Society.)
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- 2024
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38. Outcomes of patients with blastoid and pleomorphic variant mantle cell lymphoma.
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Gerson JN, Handorf E, Villa D, Gerrie AS, Chapani P, Li S, Medeiros LJ, Wang M, Cohen JB, Churnetski M, Hill BT, Sawalha Y, Hernandez-Ilizaliturri FJ, Kothari S, Vose JM, Bast M, Fenske T, Rao Gari SN, Maddocks KJ, Bond D, Bachanova V, Kolla B, Chavez J, Shah B, Lansigan F, Burns T, Donovan AM, Wagner-Johnston N, Messmer M, Mehta A, Anderson JK, Reddy N, Kovach AE, Landsburg DJ, Glenn M, Inwards DJ, Ristow K, Karmali R, Kaplan JB, Caimi PF, Rajguru S, Evens A, Klein A, Umyarova E, Pulluri B, Amengual JE, Lue JK, Diefenbach C, Fisher RI, and Barta SK
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- Adult, Humans, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Risk Assessment, Progression-Free Survival, Lymphoma, Mantle-Cell therapy, Lymphoma, Mantle-Cell drug therapy
- Abstract
Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma; data indicate that blastoid and pleomorphic variants have a poor prognosis. We report characteristics and outcomes of patients with blastoid/pleomorphic variants of MCL. We retrospectively studied adults with newly diagnosed MCL treated from 2000 to 2015. Primary objectives were to describe progression-free survival (PFS) and overall survival (OS). Secondary objectives included characterization of patient characteristics and treatments. Of the 1029 patients with MCL studied, a total of 207 neoplasms were blastoid or pleomorphic variants. Median follow-up period was 82 months (range, 0.1-174 months); median PFS was 38 months (95% confidence interval [CI], 28-66) and OS was 68 months (95% CI, 45-96). Factors associated with PFS were receipt of consolidative autologous hematopoietic transplantation (auto-HCT; hazard ratio [HR], 0.52; 95% CI, 0.31-0.80; P < .05), MCL International Prognostic Index (MIPI) intermediate (HR, 2.3; 95% CI, 1.2-4.3; P < .02) and high (HR, 3.8; 95% CI, 2.0-7.4; P < .01) scores, and complete response to induction (HR, 0.29 (95% CI, 0.17-0.51). Receipt of auto-HCT was not associated with OS (HR, 0.69; 95% CI, 0.41-1.16; P = .16) but was associated with MIPI intermediate (HR, 5.7; 95% CI, 2.5-13.2; P < .01) and high (HR, 10.8; 95% CI, 4.7-24.9; P < .01) scores. We report outcomes in a large cohort of patients with blastoid/pleomorphic variant MCL. For eligible patients, receipt of auto-HCT after induction was associated with improved PFS but not OS. Higher MIPI score and auto-HCT ineligibility were associated with worse survival., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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39. Non-V600E BRAF mutation in hairy cell leukemia variant.
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Vijayanarayanan A, Wang SA, Garces S, Saluja K, Medeiros LJ, and Thakral B
- Abstract
Competing Interests: All the authors have no disclosures or conflict of interest.
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- 2023
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40. Optical Genome Mapping Helps to Identify BCR::JAK2 Rearrangement Arising from Cryptic Complex Chromosomal Aberrations: A Case Report and Literature Review.
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Vanjari N, Tang G, Toruner GA, Wang W, Thakral B, Zhao M, Dave BJ, Khoury JD, Medeiros LJ, and Tang Z
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- Humans, In Situ Hybridization, Fluorescence, Disease Progression, Chromosome Mapping, Janus Kinase 2 genetics, Chromosome Aberrations, Myeloproliferative Disorders genetics
- Abstract
We report a case of myeloproliferative neoplasm, not otherwise specified (MPN-NOS)-transformed AML with BCR::JAK2 rearrangement. Chromosomal analysis indicated a simple abnormal karyotype 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2). Fluorescence in situ hybridization (FISH) using a BCR/ABL1/ASS1 probe set suggested a possible BCR rearrangement and a reflex JAK2 breakapart probe indicated JAK2 rearrangement, most likely partnered with BCR . Optical genome mapping (OGM) analysis confirmed BCR::JAK2 derived through an inv(9)(p24p13) after a t(9;22)(p13;q11.2) in this case. Due to the complexity of chromosomal aberrations, disruption and/or rearrangement of other genes such as KIF24::BCR , JAK2::KIF24/UBAP1, and CDK6:SOX9 were also identified by OGM. Although the functionality and clinical importance of these novel rearrangements were unknown, disruption of these genes might be associated with a poorer response to chemotherapy and disease progression. We also reviewed all cases with BCR::JAK2 rearrangement reported in the literature. In conclusion, a suspected t(9;22)/ BCR::JAK2 rearrangement warrants further characterization with genomic assays such as OGM, whole chromosome sequencing, and RNA sequencing to explore other gene disruptions and/or rearrangements.
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- 2023
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41. Cytogenetic Profile in Monoclonal Gammopathy of Undetermined Significance, Smoldering and Symptomatic Multiple Myeloma: A Study of 1087 Patients with Highly Purified Plasma Cells.
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Tang G, Wu Y, Lin P, Toruner GA, Hu S, Li S, Qazilbash MH, Orlowski RZ, Ye C, Xu J, Nahmod KA, Medeiros LJ, and Tang Z
- Abstract
The aim of this study was to examine the cytogenetic profiles of plasma cell neoplasms (PCNs) at various disease stages, encompassing 1087 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory/relapsed multiple myeloma (RRMM). Fluorescence in situ hybridization (FISH) analyses were conducted on highly purified plasma cell samples, revealing that 96% of patients exhibited at least one cytogenetic abnormality. The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM, largely driven by 1q gain, del(17p), MYC -rearrangement ( MYC -R), del(1p), and tetraploidy. Elevated frequencies of high-risk cytogenetics (59%), 1q gain (44%), and del(17p) (23%), as well as the presence of subclones (48%), were particularly notable in RRMM cases. IGH::CCND1 was observed in 26% of the cases, with no apparent variations across races, ages, or disease groups. Concurrent chromosomal analysis with FISH revealed that the incidence of abnormal karyotypes was strongly correlated with the extent of neoplastic plasma cell infiltration, genomic complexity, and the presence of specific abnormalities like del(17p) and MYC -R. Approximately 98% of the cases with abnormal karyotypes were complex, with most featuring five or more abnormalities. Chromosome 1 structural abnormalities were the most prevalent, found in 65% of cases. The frequent presence of subclones and composite karyotypes underscored the genomic heterogeneity and instability in this cohort.
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- 2023
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42. "Oncocytoid Renal Cell Carcinomas After Neuroblastoma" Represent TSC -mutated Eosinophilic Solid and Cystic Renal Cell Carcinomas : Association With Prior Childhood Malignancy and Multifocality With Therapeutic Implications.
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Argani P, Medeiros LJ, Matoso A, Baraban E, Lotan T, Pawel BR, McKenney JK, Mehra R, Falzarano SM, Pallavajjalla A, Lin MT, Patel S, Rawwas J, Bendel AE, Gagan J, and Palsgrove DN
- Subjects
- Child, Humans, Cathepsin K, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Transcription Factors, TOR Serine-Threonine Kinases genetics, Glycoproteins, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology, Neuroblastoma genetics, Neuroblastoma therapy, Cysts, Cerebellar Neoplasms
- Abstract
The concept of oncocytoid renal cell carcinoma in patients who have survived neuroblastoma as a distinct biologic entity has been controversial since its original description in 1999. This is in part because similar oncocytoid renal cell carcinomas have been described in association with other pediatric cancers, and also because other renal cell carcinoma subtypes (such as MiT family translocation renal cell carcinoma) have been described in children who have survived neuroblastoma. We identified an index case of a child who survived medulloblastoma and developed multifocal bilateral oncocytoid renal cell carcinomas with morphology and immunophenotype compatible with eosinophilic solid and cystic renal cell carcinoma (ESC RCC) and demonstrated that both neoplasms harbored distinctive mutations in the TSC1/TSC2 genes. Remarkably, the child's remaining bilateral multifocal renal neoplasms completely responded to MTOR inhibitor therapy without need for further surgery. To confirm our hypothesis that oncocytoid renal cell carcinomas after childhood cancer represent ESC RCC, we obtained formalin-fixed paraffin-embedded tissue blocks from 2 previously published cases of oncocytoid renal cell carcinoma after neuroblastoma, confirmed that the morphology and immunophenotype was consistent with ESC RCC, and demonstrated that both cases harbored somatic TSC gene mutations. Both expressed markers previously associated with neoplasms harboring TSC gene mutations, glycoprotein nonmetastatic B, and cathepsin K. Of note, one of these patients had 2 ESC RCC which harbored distinctive TSC2 mutations, while the background kidney of the other patient had multiple small cysts lined by similar oncocytoid cells which showed loss of TSC2 protein. We then reviewed 3 of 4 cases from the original 1999 report of oncocytoid renal cell carcinomas after neuroblastoma, found that all 3 demonstrated morphology (including basophilic cytoplasmic stippling) that is characteristic of ESC RCC, showed that all 3 overexpressed glycoprotein nonmetastatic B, and showed that both cases with adequate material demonstrated loss of TSC2 protein and expressed cytokeratin 20 and cathepsin K by immunohistochemistry. In summary, "oncocytoid renal cell carcinomas after neuroblastoma" represent ESC RCC which are often multifocal in patients who have survived childhood cancer, likely representing an incompletely characterized tumor predisposition syndrome. MTOR-targeted therapy represents an effective therapeutic option for such patients to preserve functional nephrons., Competing Interests: Conflicts of Interest and Source of Funding: Supported in part by: Dahan Translocation Carcinoma Fund (P.A.) and Joey’s Wings (P.A.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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43. Corrigendum to "Epstein-Barr-virus-positive large B-cell lymphoma associated with breast implants: an analysis of eight patients suggesting a possible pathogenetic relationship." [Modern Pathology 34 (2021) 2154-2167].
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Medeiros LJ, Marques-Piubelli ML, Sangiorgio VFI, Ruiz-Cordero R, Vega F, Feldman AL, Chapman JR, Clemens MW, Hunt KK, Evans MG, Khoo C, Lade S, Silberman M, Morkowski J, Pina EM, Mills DC, Bates CM, Magno WB, Sohani AR, Sieling BA, O'Donoghue JM, Bacon CM, Patani N, Televantou D, Turner SD, Johnson L, MacNeill F, Wotherspoon AC, Iyer SP, Malpica LE, Patel KP, Xu J, and Miranda RN
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- 2023
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44. The Clinicopathologic Features and Molecular Signatures of Blastoid High-Grade B Cell Lymphoma, Not Otherwise Specified.
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Qiu L, Lin P, Khanlari M, Xu J, Cohen EN, Garces S, Miranda RN, Wang W, Fang H, Bueso-Ramos CE, Medeiros LJ, and Li S
- Subjects
- Humans, Gene Rearrangement, Proto-Oncogene Proteins c-myc genetics, Biomarkers, Tumor genetics, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-6 genetics, Lymphoma, B-Cell pathology, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
A small subset of high-grade B-cell lymphoma (HGBL) with blastoid morphology remains poorly understood. We assessed 55 cases of blastoid HGBL, not otherwise specified (NOS) and compared their clinicopathologic characteristics with those of 81 non-blastoid HGBL-NOS and 62 blastoid HGBL with MYC and BCL2, with or without BCL6 rearrangements (double/triple-hit lymphoma [D/THL]). Patients with blastoid HGBL-NOS showed similar clinicopathologic features to patients with blastoid D/THLs and non-blastoid HGBL-NOS, except more frequently with a history of low-grade B-cell lymphoma, bone marrow involvement, and BCL2 rearrangement (P < .05) compared to the latter. MYC rearrangement (MYC-R), detected in 40% of blastoid HGBL-NOS, was associated with aggressive clinicopathologic features and poorer overall survival, even worse than that of blastoid D/THL (P < .05). Transcriptome profiling revealed a distinct gene expression pattern with differentially expressed genes enriched in MYC and P53-targeted genes in MYC-R blastoid HGBL-NOS. Fifty-two percent of blastoid HGBL-NOS had a double hit-like signature, similar to non-blastoid HGBL-NOS (P = .73). The overall survival of the blastoid HGBL-NOS group was similar to that of the blastoid D/THL group but appeared poorer than that of its non-blastoid counterparts (P = .07). Taken together, blastoid HGBL-NOS is an aggressive B-cell lymphoma that shares overlapping clinicopathologic and genetic features with non-blastoid HGBL-NOS. MYC-R in patients with blastoid HGBL-NOS identifies a highly aggressive subgroup with distinct aggressive clinicopathologic features, unique molecular signatures, and a dismal clinical outcome., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2023
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45. Introduction to the Fifth Edition of the World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues.
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Naresh KN and Medeiros LJ
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- Humans, Lymphoid Tissue pathology, World Health Organization, Hematologic Neoplasms pathology, Lymphoma genetics, Lymphoma pathology, Neoplasms genetics
- Abstract
The World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues has been the internationally accepted standard for over 20 years. The fifth edition of the WHO Classification (WHO-HEM5) is a multidisciplinary effort by pathologists, clinicians and other specialists that builds upon the revised fourth edition published in 2017. Entities in WHO-HEM5 are organized hierarchically. There are several changes in WHO-HEM5 from the previous edition, including addition of new entities, deletion of some entities and recognition or revision of some subtypes reflecting scientific developments and clinical advances during the past few years. Essential and desirable criteria for each entity are included. Here we introduce WHO-HEM5. Four reviews will follow that emphasize important aspects of the classification., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
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- 2023
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46. From the archives of MD Anderson Cancer Center: Plasmablastic lymphoma presenting as a kidney mass in an immunocompetent patient: Case report and literature review.
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Gietzen R, Muthukumarana V, Bhargava P, Vozniuk D, Thakral B, Medeiros LJ, and Lyapichev KA
- Subjects
- Male, Humans, Aged, Herpesvirus 4, Human, Plasma Cells pathology, Plasmablastic Lymphoma diagnosis, Plasmablastic Lymphoma pathology, Epstein-Barr Virus Infections pathology, Multiple Myeloma pathology, Lymphadenopathy, HIV Infections
- Abstract
Background: Plasmablastic lymphoma (PBL) is a rare, aggressive large B-cell lymphoma with plasmablastic or immunoblastic morphology and a terminally differentiated B-cell immunophenotype. PBL often presents at extranodal sites, commonly the oral cavity of immunocompromised patients with human immunodeficiency virus (HIV) and/or Epstein-Barr virus (EBV) infection. Cases of PBL arising outside the oral cavity in previously healthy immunocompetent patients are rare., Case Report: We report a 65-year-old HIV- and EBV-negative man who presented with abdominal pain, fatigue, and vomiting. Imaging studies showed a 30 × 18 cm bulky lobulated mass located within the left kidney with surrounding para-aortic lymphadenopathy. Serum and urine protein electrophoresis revealed a monoclonal gammopathy of IgA lambda type. Biopsy of the mass showed PBL. Bone marrow lumbar puncture evaluations also showed evidence of PBL. The patient was treated with chemotherapy and radiation with initial improvement; however, he died 14 months after initial diagnosis., Conclusions: Based on our literature review, this case of PBL is one of the few reported to present as a kidney mass in immunocompetent, HIV- and EBV-negative patient. Distinguishing PBL from plasma cell myeloma (PCM) can be challenging. Knowledge of clinical features including presence of CRAB (hypercalcemia, renal failure, anemia, bone lesions) or bone marrow infiltration by mature clonal plasma cells is helpful to establish a diagnosis of PCM. Genetic features of PCM (typical translocations or mutations) also can be helpful in distinguishing plasmablastic transformation of PCM and from PBL. The case we report also highlights the need for more studies to identify specific immunohistochemical and molecular markers to improve PBL diagnosis in immunocompetent patients., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)
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- 2023
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47. TdT-positive high-grade B-cell lymphoma with BCOR and IDH1 mutations.
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Yu YT, Lin KY, Chen YP, Chen YL, Medeiros LJ, and Chang KC
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- Humans, Mutation, Proto-Oncogene Proteins genetics, Repressor Proteins genetics, Isocitrate Dehydrogenase genetics, Lymphoma, B-Cell genetics
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- 2023
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48. High-grade B-cell lymphoma, not otherwise specified: a multi-institutional retrospective study.
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Zayac AS, Landsburg DJ, Hughes ME, Bock AM, Nowakowski GS, Ayers EC, Girton M, Hu M, Beckman AK, Li S, Medeiros LJ, Chang JE, Stepanovic A, Kurt H, Sandoval-Sus J, Ansari-Lari MA, Kothari SK, Kress A, Xu ML, Torka P, Sundaram S, Smith SD, Naresh KN, Karimi YH, Epperla N, Bond DA, Farooq U, Saad M, Evens AM, Pandya K, Naik SG, Kamdar M, Haverkos B, Karmali R, Oh TS, Vose JM, Nutsch H, Rubinstein PG, Chaudhry A, and Olszewski AJ
- Subjects
- Humans, Middle Aged, Rituximab therapeutic use, Retrospective Studies, Prednisone therapeutic use, Vincristine therapeutic use, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-myc genetics, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Etoposide, Lactate Dehydrogenases, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics
- Abstract
In this multi-institutional retrospective study, we examined the characteristics and outcomes of 160 patients with high-grade B-cell lymphoma, not otherwise specified (HGBL-NOS)-a rare category defined by high-grade morphologic features and lack of MYC rearrangements with BCL2 and/or BCL6 rearrangements ("double hit"). Our results show that HGBL-NOS tumors are heterogeneous: 83% of patients had a germinal center B-cell immunophenotype, 37% a dual-expressor immunophenotype (MYC and BCL2 expression), 28% MYC rearrangement, 13% BCL2 rearrangement, and 11% BCL6 rearrangement. Most patients presented with stage IV disease, a high serum lactate dehydrogenase, and other high-risk clinical factors. Most frequent first-line regimens included dose-adjusted cyclophosphamide, doxorubicin, vincristine, and etoposide, with rituximab and prednisone (DA-EPOCH-R; 43%); rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 33%); or other intensive chemotherapy programs. We found no significant differences in the rates of complete response (CR), progression-free survival (PFS), or overall survival (OS) between these chemotherapy regimens. CR was attained by 69% of patients. PFS at 2 years was 55.2% and OS was 68.1%. In a multivariable model, the main prognostic factors for PFS and OS were poor performance status, lactate dehydrogenase >3 × upper limit of normal, and a dual-expressor immunophenotype. Age >60 years or presence of MYC rearrangement were not prognostic, but patients with TP53 alterations had a dismal PFS. Presence of MYC rearrangement was not predictive of better PFS in patients treated with DA-EPOCH-R vs R-CHOP. Improvements in the diagnostic criteria and therapeutic approaches beyond dose-intense chemotherapy are needed to overcome the unfavorable prognosis of patients with HGBL-NOS., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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49. Recurrent Somatic Copy Number Alterations and Their Association with Oncogene Expression Levels in High-Grade Ovarian Serous Carcinoma.
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Esplen HP, Yang RK, Kalia A, Tang Z, Tang G, Medeiros LJ, and Toruner GA
- Abstract
Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome Atlas Pan Cancer dataset (OSC, TCGA, PanCancer Atlas) to identify cancer-related genes in HGOSC. We then investigated any association between highly correlated cancer genes and clinicopathological parameters, including age of diagnosis, disease stage, overall survival (OS), and progression-free survival (PFS). A total of 772 genes with recurrent SCNAs were observed. SCNA and mRNA expression levels were highly correlated for 274 genes; 24 genes were classified as a Tier 1 gene in the Cancer Gene Census in the Catalogue of Somatic Mutations in Cancer (CGC-COSMIC). Of these, 11 Tier 1 genes had highly correlated SCNA and mRNA expression levels: TBL1XR1 , PIK3CA , UBR5 , EIF3E , RAD21 , EXT1 , RECQL4 , KRAS , PRKACA , BRD4 , and TPM4 . There was no association between gene amplification and disease stage or PFS. EIF3E , RAD21 , and EXT1 were more frequently amplified in younger patients, specifically those under the age of 55 years. Patients with tumors carrying PRKACA , BRD4 , or TPM4 amplification were associated with a significantly shorter OS. RECQL4 amplification was more frequent in younger patients, and tumors with this amplification were associated with a significantly better OS.
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- 2023
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50. Follicular lymphoma and diffuse large B-cell lymphoma with BCL2 and IRF4 rearrangements in adult patients.
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Yuan J, Liu H, Hu S, Miranda RN, Xu X, Bayerl MG, Artymiuk CJ, Berg H, King RL, Shi M, He R, Viswanatha D, Medeiros LJ, and McPhail ED
- Subjects
- Humans, Gene Rearrangement, In Situ Hybridization, Fluorescence, Proto-Oncogene Proteins c-bcl-2 genetics, Aged, Lymphoma, Follicular genetics, Lymphoma, Follicular pathology, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) with concurrent BCL2 and IRF4 rearrangements are rare. It is unclear whether such cases should be classified as large B- cell lymphoma with IRF4 rearrangement or FL/DLBCL-not otherwise specified. We identified 5 adult patients (FL, N = 3 and FL/DLBCL, N = 2) with concurrent BCL2 and IRF4 rearrangements. The median age at presentation was 77 years, and three patients presented with advanced stage disease. Both nodal and extranodal sites were involved and involvement was not limited to head and neck region. With a median follow-up of 18 months, 1 patient died and 4 patients were alive, including 3 who received chemotherapy and 1 who was observed. The neoplasms were histologically heterogeneous, including grade 2 and 3 FL and DLBCL. Four cases coexpressed CD10, BCL6, BCL2 and MUM1/IRF4. The Ki67 labelling index ranged from 20% to 95%. In 4 patients, the percentage of cells with BCL2 rearrangement was equal to or slightly greater than the cells harboring IRF4 rearrangement. Two cases underwent next generation sequencing tailored for lymphoid neoplasms. Both lacked mutations involving IRF4 and NF-kB pathway genes that are frequently detected in large B-cell lymphoma with IRF4 rearrangement, and one case showed DLBCL-EZH2 type mutations, including KMT2D and BCL2 mutations, similar to 2 previously reported DLBCL with BCL2 and IRF4 rearrangements. Adults with FL and FL/DLBCL with BCL2 and IRF4 rearrangements display clinicopathologic and mutational features more akin to FL and DLBCL and should not be characterized as large B-cell lymphoma with IRF4 rearrangement., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
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