Brent Tan

All Publications

• Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States. Pediatric transplantation Tajima, T., Martinez, O. M., Bernstein, D., Boyd, S. D., Gratzinger, D., Lum, G., Sasaki, K., Tan, B., Twist, C. J., Weinberg, K., Armstrong, B., Desai, D. M., Mazariegos, G. V., Chin, C., Fishbein, T. M., Tekin, A., Venick, R. S., Krams, S. M., Esquivel, C. O. 2024; 28 (4): e14763

  Abstract

  Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis.The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis.The uni-/multivariable competing risk analyses revealed the combination of EBV-seropositive donor and EBV-naïve recipient (D+R-) was a significant risk factor for PTLD development (sub-hazard ratio: 2.79 [1.34-5.78], p = .006) and EBV DNAemia (2.65 [1.72-4.09], p < .001). Patients with D+R- were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations (p = .02). Patients with monomorphic/polymorphic PTLD (n = 21) had significantly more EBV DNAemia than non-PTLD patients (p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias (p < .001), within 6-month post-transplant. Among non-liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant (p = .01).D+R- is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow-up of EBV viral load within 6-month post-transplant, especially for patients with D+R- and/or non-liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.

  View details for DOI 10.1111/petr.14763

  View details for PubMedID 38682750

• Circulating lobular breast carcinoma cells. International journal of laboratory hematology Tan, B., Oak, J. 2024

  View details for DOI 10.1111/ijlh.14295

  View details for PubMedID 38658384

• p53 immunohistochemistry as an ancillary tool for rapid assessment of residual disease in TP53-mutated acute myeloid leukemia and myelodysplastic syndromes. American journal of clinical pathology Brar, N., Lawrence, L., Fung, E., Zehnder, J. L., Greenberg, P. L., Mannis, G. N., Zhang, T. Y., Gratzinger, D., Oak, J., Silva, O., Kurzer, J., Tan, B., Menke, J. R., Fernandez-Pol, S. 2024

  Abstract

  Measurable residual disease flow cytometry (MRD-FC) and molecular studies are the most sensitive methods for detecting residual malignant populations after therapy for TP53-mutated acute myeloid leukemia and myelodysplastic neoplasms (TP53+ AML/MDS). However, their sensitivity is limited in suboptimal aspirates or when the immunophenotype of the neoplastic blasts overlaps with erythroids or normal maturing myeloid cells. In this study, we set out to determine if p53 immunohistochemistry (IHC) correlates with MRD-FC and next-generation sequencing (NGS) in the posttherapy setting and to determine the utility of p53 IHC to detect residual disease in the setting of negative or equivocal MRD-FC.We retrospectively identified 28 pre- and posttherapy bone marrow biopsy specimens from 9 patients with TP53+ AML/MDS and a p53 overexpressor phenotype by IHC (strong 3+ staining at initial diagnosis). Next-generation sequencing and/or MRD-FC results were collected for each specimen.Using a threshold of more than ten 2-3+ cells in any one 400× field, p53 IHC detected residual disease with a sensitivity of 94% and a specificity of 89%. The threshold used in this study showed a high degree of concordance among 6 blinded pathologists (Fleiss κ = 0.97).Our study suggests that p53 IHC can be used as a rapid tool (within 24 hours) to aid in the detection of residual disease that may complement MRD-FC or NGS in cases in which the flow cytometry immunophenotype is equivocal and/or the bone marrow aspirate is suboptimal.

  View details for DOI 10.1093/ajcp/aqae034

  View details for PubMedID 38643353

• CD38 and BCL2 expression guides treatment with daratumumab and venetoclax in tagraxofusp-refractory blastic plasmacytoid dendritic cell neoplasm (BPDCN) featuring dynamic loss of CD123. Leukemia research Hu, X., Ediriwickrema, A., Saleem, A., Tan, B., Pemmaraju, N., Mannis, G. N. 2024; 139: 107479

  View details for DOI 10.1016/j.leukres.2024.107479

  View details for PubMedID 38492495

• Identification of T-cell Acute Lymphoblastic Lymphoma/Leukemia Using TRBC1 Expression by Immunohistochemical Methods De Lancy, S., Herring, M., Fernandez-Pol, S., Tan, B. ELSEVIER SCIENCE INC. 2024: S1388

  View details for Web of Science ID 001302363405024

• The clinical, molecular, and prognostic features of the 2022 WHO and ICC classification systems for myelodysplastic neoplasms. Leukemia research Khanna, V., Lu, R., Kumar, J., Molina, A., Stehr, H., Spiteri, E., Spinner, M., Silva, O., Fernandez-Pol, S., Tan, B., Greenberg, P. L. 2023; 136: 107433

  Abstract

  Myelodysplastic neoplasms (MDS) are clonal disorders of bone marrow failure exhibiting a variable risk of progression to acute myeloid leukemia. MDS exhibit certain prognostic genetic or cytogenetic abnormalities, an observation that has led to both the pathologic reclassification of MDS in the 2022 World Health Organization (WHO) and International Consensus Classification (ICC) systems, as well as to an updated prognostic schema, the Molecular International Prognostic Scoring System (IPSS-M). This single-institution study characterized the molecular patterns and clinical outcomes associated with the 2022 WHO and ICC classification schemas to assess their clinical utility. Strikingly, with the exception of one individual, all 210 patients in our cohort were classified into analogous categories by the two pathologic/diagnostic schemas. Most patients (70%) were classified morphologically while the remaining 30% had genetically classified disease by both criteria. Prognostic risk, as assessed by the IPSS-M score was highest in patients with MDS with biallelic/multi-hit TP53 mutations and lowest in pts with MDS-SF3B1. Median leukemia-free survival (LFS) was shortest for those with MDS with biallelic/multi-hit TP53 (0.7 years) and longest for those with MDS with low blasts (LFS not reached). These data demonstrate the clear ability of the 2022 WHO and ICC classifications to organize MDS patients into distinct prognostic risk groups and further show that both classification systems share more similarities than differences. Incorporation of the IPSS-M and IPSS-R features provide additive prognostic and survival components to both the WHO and ICC classifications, which together enhance their utility for evaluating and treating MDS patients.

  View details for DOI 10.1016/j.leukres.2023.107433

  View details for PubMedID 38154193

• Lupus erythematosus cells in a bone marrow aspirate. Journal of hematopathology Zhang, J., Tan, B., Fernandez-Pol, S. 2023; 16 (4): 247-248

  Abstract

  A teenage girl presented with fevers of unknown origin and pancytopenia. Complete blood count showed anemia (hemoglobin, 9.0 g/dL), neutropenia (1.7 × 109/L), and thrombocytopenia (66 × 109/L). The bone marrow was hypocellular with left shifted hematopoiesis and myeloid hypoplasia. Aspirate smears were notable for a prominent population of neutrophils with crescentic nuclei that engulfed blue amorphous material (Fig. 1 panels A and B, Wright-Giemsa, magnification × 1000). The trephine biopsy showed similar cells with crescentic nuclei and eosinophilic material (Fig. 1 panels C and D, hematoxylin and eosin × 400). Flow cytometry was negative for an abnormal population. EBV by in situ hybridization and parvovirus immunohistochemistry were negative. Subsequent serologic testing was positive for ANA (1:1280), low C3/C4, anti-dsDNA, anti-SM and anti-B2GP1. A kidney biopsy demonstrated findings consistent with class III lupus nephritis.

  View details for DOI 10.1007/s12308-023-00561-8

  View details for PubMedID 38175431

• Lupus erythematosus cells in a bone marrow aspirate JOURNAL OF HEMATOPATHOLOGY Zhang, J., Tan, B., Fernandez-Pol, S. 2023

  View details for DOI 10.1007/s12308-023-00561-8

  View details for Web of Science ID 001092021900001

• 311.2: Risk factors for Epstein-Barr virus DNAemia in pediatric transplantation: A multicenter study in the United States. Transplantation Tajima, T., Bernstein, D., Boyd, S. D., Gratzinger, D., Lum, G., Sasaki, K., Tan, B., Weinberg, K., Armstrong, B., Brown, M., Chin, C., Desai, D., Fishbein, T. M., Mazariegos, G., Robien, M. A., Tekin, A., Twist, C. J., Venick, R. S., Krams, S. M., Martinez, O. M., Esquivel, C. O. 2023; 107 (10S1): 71-72

  View details for DOI 10.1097/01.tp.0000993400.94644.c0

  View details for PubMedID 37845955

• Rapid Deployment of Whole Slide Imaging for Primary Diagnosis in Surgical Pathology at Stanford Medicine Responding to Challenges of the COVID-19 Pandemic ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE Rojansky, R., Jhun, I., Dussaq, A. M., Chirieleison, S. M., Nirschl, J. J., Born, D., Fralick, J., Hetherington, W., Kerr, A. M., Lavezo, J., Lawrence, D. B., Lummus, S., Macasaet, R., Montine, T. J., Ryan, E., Shen, J., Shoemaker, J., Tan, B., Vogel, H., Waraich, P., Yang, E., Young, A., Folkins, A. 2023; 147 (3): 359-367

  View details for DOI 10.5858/arpa.2021-0438-OA)

  View details for Web of Science ID 000958483400012

• Epstein-Barr virus-associated post-transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States Tajima, T., Bernstein, D., Boyd, S. D., Gratzinger, D., Lum, G., Sasaki, K., Tan, B., Twist, C. J., Weinberg, K., Robien, M. A., Brown, M., Armstrong, B., Desai, D., Mazariegos, G., Chin, C., Fishbein, T. M., Tekin, A., Venick, R. S., Martinez, O. M., Krams, S. M., Esquivel, C. O. WILEY. 2023

  View details for Web of Science ID 001002465500078

• Mutations In Latent Membrane Protein 1 of Epstein-Barr Virus are Associated with Increased Risk for Post-Transplant Lymphoproliferative Disorder in Children. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Martinez, O. M., Krams, S. M., Robien, M. A., Lapasaran, M. G., Arvedson, M. P., Reitsma, A., Balachandran, Y., Harris-Arnold, A., Weinberg, K., Boyd, S. D., Armstrong, B., Trickey, A., Twist, C. J., Gratzinger, D., Tan, B., Brown, M., Chin, C., Desai, D. M., Fishbein, T. M., Mazariegos, G. V., Tekin, A., Venick, R. S., Bernstein, D., Esquivel, C. O. 2023

  Abstract

  Epstein-Barr virus (EBV)+ post-transplant lymphoproliferative disorder (PTLD) results in significant morbidity and mortality in pediatric transplant recipients. Identifying individuals at increased risk of EBV+ PTLD could influence clinical management of immunosuppression and other therapies, improving post-transplant outcomes. A seven-center prospective, observational clinical trial of 872 pediatric transplant recipients evaluated the presence of mutations at position 212 and 366 of EBV latent membrane protein 1 (LMP1) as an indicator of risk for EBV+ PTLD (Clinical Trials: NCT02182986). DNA was isolated from peripheral blood of EBV+ PTLD cases and matched controls (1:2 nested case-control), and the cytoplasmic tail of LMP1 sequenced. Thirty-four participants reached the primary endpoint of biopsy-proven EBV+ PTLD. DNA was sequenced from 32 PTLD cases and 62 matched controls. Both LMP1 mutations were present in 31/32 PTLD cases (96.9%) and in 45/62 matched controls (72.6%) (p=0.005, OR=11.7, 95% CI 1.5, 92.6). The presence of both G212S and S366T carries a nearly 12-fold increased risk for development of EBV+ PTLD. Conversely, transplant recipients without both LMP1 mutations carry a very low risk of PTLD. Analysis of mutations at positions 212 and 366 of LMP1 can be informative in stratifying patients for risk of EBV+ PTLD.

  View details for DOI 10.1016/j.ajt.2023.02.014

  View details for PubMedID 36796762

• LymphoML: An interpretable artificial intelligence-based method identifies morphologic features that correlate with lymphoma subtype Shankar, V., Yang, X., Krishna, V., Tan, B., Silva, O., Rojansky, R., Ng, A., Valvert, F., Briercheck, E., Weinstock, D., Natkunam, Y., Fernandez-Pol, S., Rajpurkar, P., Hegselmann, S., Parziale, A., Shanmugam, D., Tang, S., Asiedu, M. N., Chang, S., Hartvigsen, T., Singh, H. JMLR-JOURNAL MACHINE LEARNING RESEARCH. 2023: 528-558

  View details for Web of Science ID 001221195600031

• Correlation of Mutational Profiles and Cytogenetics with Morphologic Dysplasia in Myelodysplastic Syndromes Kumar, J., Khanna, V., Lu, R., Stehr, H., Spinner, M. A., Silva, O., Fernandez-Pol, S., Oak, J. S., Greenberg, P. L., Tan, B. AMER SOC HEMATOLOGY. 2022: 4053-4055

  View details for DOI 10.1182/blood-2022-160237

  View details for Web of Science ID 000893223204027

• Characterization of Clinical, Molecular, and Prognostic Features of the WHO 2022 Classification System for Myelodysplastic Neoplasms (MDS) Khanna, V., Lu, R., Kumar, J., Stehr, H., Spinner, M. A., Silva, O., Fernandez-Pol, S., Oak, J. S., Tan, B., Greenberg, P. L. AMER SOC HEMATOLOGY. 2022: 6955-6957

  View details for DOI 10.1182/blood-2022-165841

  View details for Web of Science ID 000893223206427

• Histiocytic Sarcoma With CCND1 Gene Rearrangement Clonally Related and Transdifferentiated From Mantle Cell Lymphoma. American journal of clinical pathology Kumar, J., Al-Kawaaz, M., Martin, B. A., Hegazi, M. M., Tan, B., Gratzinger, D. 2022

  Abstract

  OBJECTIVES: Histiocytic neoplasms demonstrate shared gene translocations and clonal immunoglobulin gene rearrangements in cases of associated B-cell lymphomas. However, the evolution of these related disease processes remains largely uncertain, especially in the setting of a prior mantle cell lymphoma.METHODS: We describe a unique case of a histiocytic sarcoma that transdifferentiated from blastoid mantle cell lymphoma after extensive therapy. Cytogenic and molecular studies were performed and provided evidence for clonal progression.RESULTS: We present the first reported case of a patient with blastoid mantle cell lymphoma harboring a CCND1 rearrangement that progressed despite multiple therapeutic regimens and ultimately transdifferentiated into histiocytic sarcoma. The histiocytic sarcoma demonstrated a CCND1 rearrangement and targeted next-generation sequencing showed a pathogenic variant in NRAS, a gene involved in the RAS/MAPK pathway, known to play a role in the pathogenesis of histiocytic sarcomas. TP53, NOTCH2, CREBBP, and NFKBIE variants were also identified, which are often seen in B-cell lymphomas, while rarely described in histiocytic sarcoma.CONCLUSIONS: To our knowledge, this is the first report to provide evidence for clonal evolution of histiocytic sarcoma from blastoid mantle cell lymphoma based on cytogenic and molecular findings. The patient's protracted therapeutic course may have acted as an evolutionary driver promoting this transdifferentiation process.

  View details for DOI 10.1093/ajcp/aqac087

  View details for PubMedID 35964234

• Rapid Deployment of Whole Slide Imaging for Primary Diagnosis in Surgical Pathology at Stanford Medicine. Archives of pathology & laboratory medicine Rojansky, R., Jhun, I., Dussaq, A. M., Chirieleison, S. M., Nirschl, J. J., Born, D., Fralick, J., Hetherington, W., Kerr, A. M., Lavezo, J., Lawrence, D. B., Lummus, S., Macasaet, R., Montine, T. J., Ryan, E., Shen, J., Shoemaker, J., Tan, B., Vogel, H., Waraich, P. S., Yang, E., Young, A., Folkins, A. 2022

  Abstract

  Stanford Pathology began stepwise subspecialty implementation of whole slide imaging (WSI) in 2018 soon after the first US Food and Drug Administration approval. In 2020, during the COVID-19 pandemic, the Centers for Medicare & Medicaid Services waived the requirement for pathologists to perform diagnostic tests in Clinical Laboratory Improvement Amendments (CLIA)-licensed facilities. This encouraged rapid implementation of WSI across all surgical pathology subspecialties.To present our experience with validation and implementation of WSI at a large academic medical center encompassing a caseload of more than 50 000 cases per year.Validation was performed independently for 3 subspecialty services with a diagnostic concordance threshold above 95%. Analysis of user experience, staffing, infrastructure, and information technology was performed after department-wide expansion.Diagnostic concordance was achieved in 96% of neuropathology cases, 100% of gynecologic pathology cases, and 98% of immunohistochemistry cases. After full implementation, 8 high-capacity scanners were operational, with whole slide images generated on greater than 2000 slides per weekday, accounting for approximately 80% of histologic slides at Stanford Medicine. Multiple modifications in workflow and information technology were needed to improve performance. Within months of full implementation, most attending pathologists and trainees had adopted WSI for primary diagnosis.WSI across all surgical subspecialities is achievable at scale at an academic medical center; however, adoption required flexibility to adjust workflows and develop tailored solutions. WSI at scale supported the health and safety of medical staff while facilitating high-quality patient care and education during COVID-19 restrictions.

  View details for DOI 10.5858/arpa.2021-0438-OA

  View details for PubMedID 35802938

• Mutations in latent membrane protein 1 of Epstein Barr virus are associated with increased risk of post-transplant lymphoproliferative disorder Martinez, O. M., Krams, S. M., Robien, M., Lapasaran, M. M., Arvedson, M., Reitsma, A., Weinberg, K., Boyd, S., Armstrong, B., Twist, C., Gratzinger, D., Tan, B., Trickey, A., Sever, M., Brown, M., Bernstein, D., Esquivel, C., CTOC 06 Investigators WILEY. 2022

  View details for Web of Science ID 000783167500008

• Gelatinous transformation of the bone marrow in a previously healthy male presenting with pancytopenia. British journal of haematology Zhang, J., Tan, B. 2022

  View details for DOI 10.1111/bjh.18007

  View details for PubMedID 35128636

• Host microRNAs are decreased in pediatric solid-organ transplant recipients during EBV+ Post-transplant Lymphoproliferative Disorder. Frontiers in immunology Sen, A., Enriquez, J., Rao, M., Glass, M., Balachandran, Y., Syed, S., Twist, C. J., Weinberg, K., Boyd, S. D., Bernstein, D., Trickey, A. W., Gratzinger, D., Tan, B., Lapasaran, M. G., Robien, M. A., Brown, M., Armstrong, B., Desai, D., Mazariegos, G., Chin, C., Fishbein, T. M., Venick, R. S., Tekin, A., Zimmermann, H., Trappe, R. U., Anagnostopoulos, I., Esquivel, C. O., Martinez, O. M., Krams, S. M. 2022; 13: 994552

  Abstract

  Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation. Predisposing factors include primary Epstein-Barr virus (EBV) infection, reactivation of EBV in recipient B cells, and decreased T cell immunity due to immunosuppression. In our previous studies EBV infection was demonstrated to markedly alter the expression of host B cell microRNA (miR). Specifically, miR-194 expression was uniquely suppressed in EBV+ B cell lines from PTLD patients and the 3'untranslated region of IL-10 was determined to be targeted by miR-194. Although EBV has been shown to regulate host miR expression in B cell lymphoma cell lines, the expression of miRs in the circulation of patients with EBV-associated PTLD has not been studied. The objective of this study was to determine if changes in miR expression are associated with EBV+ PTLD. In this study, we have shown that miR-194 is significantly decreased in EBV+PTLD tumors and that additional miRs, including miRs-17, 19 and 106a are also reduced in EBV+PTLD as compared to EBV-PTLD. We quantitated the levels of miRs-17, 19, 106a, 155, and 194 in the plasma and extracellular vesicles (EV; 50-70 nm as determined by nanoparticle tracking analysis) from pediatric recipients of solid organ transplants with EBV+ PTLD+ that were matched 1:2 with EBV+ PTLD- pediatric transplant recipients as part of the NIH-sponsored Clinical Trials in Organ Transplantation in Children, (CTOTC-06) study. Levels of miRs-17, 19, 106a, and 194 were reduced in the plasma and extracellular vesicles (EV) of EBV+ PTLD+ group compared to matched controls, with miRs-17 (p = 0.034; plasma), miRs-19 (p = 0.029; EV) and miR-106a (p = 0.007; plasma and EV) being significantly reduced. Similar levels of miR-155 were detected in the plasma and EV of all pediatric SOT recipients. Importantly, ~90% of the cell-free miR were contained within the EV supporting that EBV+ PTLD tumor miR are detected in the circulation and suggesting that EVs, containing miRs, may have the potential to target and regulate cells of the immune system. Further development of diagnostic, mechanistic and potential therapeutic uses of the miRs in PTLD is warranted.

  View details for DOI 10.3389/fimmu.2022.994552

  View details for PubMedID 36304469

• Angioimmunoblastic T-cell lymphoma diagnosed from pleural fluid by integration of morphologic, immunophenotypic, and molecular findings. Diagnostic cytopathology Tan, B., Martin, B., Fernandez-Pol, S. 2021

  Abstract

  An 88-year-old man with end-stage renal disease on hemodialysis presented with shortness of breath and was found to have lower extremity edema and bilateral pleural effusions on a chest X-ray. A therapeutic and diagnostic thoracentesis was performed, and cytologic examination revealed atypical mononuclear cells. Based on this, flow cytometry was performed on the pleural fluid, along with immunostains on the cellblock and a next-generation sequencing (NGS) panel. A definitive diagnosis of angioimmunoblastic T-cell lymphoma (AITL) was made based on demonstrating an atypical T follicular helper cell population expressing CD10, BCL6, CXCL13, CD200, CD57, and PD1, and detection of pathogenic variants in RHOA, IDH2, and TET2. This case represents the first reported case where a primary diagnosis of AITL was made on a body fluid specimen and highlights how immunophenotyping and NGS can provide a definitive diagnosis of AITL on a cytologic specimen.

  View details for DOI 10.1002/dc.24861

  View details for PubMedID 34449978

• Human Germinal Center-associated Lymphoma (HGAL) Is a Reliable Marker of Normal and Neoplastic Follicular Helper T Cells Including Angioimmunoblastic T-Cell Lymphoma. The American journal of surgical pathology Koo, M., Zhang, J., Tan, B., Kurzer, J., Gratzinger, D., Zhao, S., Suarez, C., Lossos, I. S., Warnke, R. A., Natkunam, Y. 2021

  Abstract

  The diagnosis of angioimmunoblastic T-cell lymphoma (AITL) is complex and requires the demonstration of a T-follicular helper (TFH) phenotype. Immunophenotypic markers that detect the TFH phenotype are highly variable, thereby necessitating the use of 3 to 5 TFH markers to substantiate a TFH phenotype. We tested the utility of germinal center markers human germinal center-associated lymphoma (HGAL) and LIM-domain only 2 (LMO2) in detecting a TFH phenotype. We compared their staining to that of 6 TFH markers in current use, PD-1, ICOS, CXCL13, SAP, CD10, and BCL6, in a cohort of 23 AITL. Our results show that although both markers can detect a TFH phenotype, HGAL was superior to LMO2 in the percent of cells stained and the intensity of staining, 2 variables used to generate H-scores. Using H-scores as the metric, HGAL was most comparable to BCL6 among the currently used TFH markers and was more sensitive than CXCL13, SAP, CD10, and LMO2. PD-1 and ICOS emerged as the most robust of the 8 markers tested in this study in detecting a TFH phenotype. We conclude that HGAL is a reliable marker of TFH cells and can aid in the diagnosis of lymphomas of TFH derivation, particularly in the recognition of early patterns of AITL.

  View details for DOI 10.1097/PAS.0000000000001852

  View details for PubMedID 34907996

• Reactive Eosinophil Proliferations in Tissue and the Lymphocytic Variant of Hypereosinophilic Syndrome. American journal of clinical pathology King, R. L., Tan, B., Craig, F. E., George, T. I., Horny, H., Kelemen, K., Orazi, A., Reichard, K. K., Rimsza, L. M., Wang, S. A., Zamo, A., Quintanilla-Martinez, L. 2020

  Abstract

  OBJECTIVES: The 2019 Society for Hematopathology and European Association for Haematopathology Workshop reviewed the spectrum of neoplastic, nonneoplastic, and borderline entities associated with reactive eosinophilia in tissue.METHODS: The workshop panel reviewed 46 cases covered in 2 workshop sessions.RESULTS: The 46 cases were presented with their consensus diagnoses during the workshop. Reactive eosinophilia in lymph nodes and other tissues may be accompanied by or be distinct from peripheral blood eosinophilia. Reactive etiologies included inflammatory disorders such as Kimura disease and IgG4-related disease, which may show overlapping pathologic features and reactions to infectious agents and hypersensitivity (covered in a separate review). Hodgkin, T-cell, and B-cell lymphomas and histiocytic neoplasms can result in reactive eosinophilia. The spectrum of these diseases is discussed and illustrated through representative cases.CONCLUSIONS: Reactive eosinophilia in lymph nodes and tissues may be related to both nonneoplastic and neoplastic lymphoid proliferations and histiocytic and nonhematolymphoid processes. Understanding the differential diagnosis of reactive eosinophilia and the potential for overlapping clinical and pathologic findings is critical in reaching the correct diagnosis so that patients can be treated appropriately.

  View details for DOI 10.1093/ajcp/aqaa227

  View details for PubMedID 33367482

• B-lymphoblastic leukemia arising in a patient with chronic neutrophilic leukemia. Blood advances Boddy, C. S., Tan, B. T., Aoki, J. 2020; 4 (21): 5389–92

  View details for DOI 10.1182/bloodadvances.2020003109

  View details for PubMedID 33147336

• Acute myeloid leukemia with NPM1 and FLT3 ITD mimicking acute promyelocytic leukemia. Blood Pepper, M. n., Tan, B. n. 2020; 136 (12): 1467

  View details for DOI 10.1182/blood.2020007198

  View details for PubMedID 32941638

• Myeloid Cell Nuclear Differentiation Antigen (MNDA) Positivity in Primary Follicles: Potential Pitfall in the Differential Diagnosis With Marginal Zone Lymphoma. Applied immunohistochemistry & molecular morphology : AIMM Manohar, V., Peerani, R., Tan, B., Gratzinger, D., Natkunam, Y. 2019

  Abstract

  Myeloid cell nuclear differentiation antigen (MNDA) is an immunohistochemical marker that is used to distinguish marginal zone lymphomas (MZLs) from other small B-cell lymphomas. An index case that showed MNDA staining in primary follicles prompted the current study to evaluate whether MNDA expression is widespread in primary follicles and to address whether it poses a potential diagnostic pitfall. Of the 15 cases with primary follicles identified by a search of the laboratory information system, 7 had positive MNDA staining. In all cases, there was weak nuclear staining similar to what is typical of MNDA staining in MZLs. All cases showed intense nuclear signal in myeloid lineage cells such as neutrophils, which served as positive internal controls. The histologic and cytologic features of primary follicles and MZLs showed overlapping features, particularly in small biopsies. Our results indicate that weak nuclear MNDA staining can act as a potential pitfall in the evaluation of small B-cell lymphomas. Correlation with other immunohistochemical markers that are useful in the workup of small B-cell lymphomas, as well as those that outline immunoarchitectural features of lymphoid follicles, is suggested when both entities are part of the differential diagnosis. Our results underscore the need for caution in the interpretation of weak nuclear MNDA staining in the evaluation of small B-cell lymphomas.

  View details for PubMedID 30640752

• Prospective Analysis of EBV plus PTLD in a Multi-Center Study of Pediatric Transplant Recipients Martinez, O. M., Krams, S. M., Lapasaran, M., Boyd, S. D., Bernstein, D., Twist, C., Weinberg, K., Gratzinger, D., Tan, B., Armstrong, B., Ikle, D., Brown, M., Robien, M., Esquivel, C. O. LIPPINCOTT WILLIAMS & WILKINS. 2018: S319

  View details for Web of Science ID 000444541200511

• Implementation of Epic Beaker Clinical Pathology at Stanford University Medical Center AMERICAN JOURNAL OF CLINICAL PATHOLOGY Tan, B. T., Fralick, J., Flores, W., Schrandt, C., Davis, V., Bruynell, T., Wilson, L., Christopher, J., Weber, S., Shah, N. 2017; 147 (3): 261-272

  Abstract

  To provide an account of implementation of the Epic Beaker 2014 clinical pathology module at Stanford University Medical Center and highlight strengths and weaknesses of the system.Based on a formal selection process, Stanford selected Epic Beaker to replace Sunquest as the clinical laboratory information system (LIS). The rationale included integration between the LIS and already installed Epic electronic medical record (EMR), reduction in the number of systems and interfaces, and positive patient identification (PPID). The build was significantly customized and included a first of its kind Epic-to-Epic interface. This was due to the clinical laboratory serving two hospitals (pediatric and adult) with independent instances of Epic.Test turnaround times showed improvement from historical baselines, mostly because of the implementation of PPID. PPID also resulted in significant reduction in mislabeled specimens.Epic 2014 Beaker clinical pathology is a viable LIS with adequate functionality for a large academic center. Strengths include PPID and integration with the EMR. Integration provides laboratory users with ready access to the patient's relevant clinical history to assist releasing of results and gives physician and nurse providers sophisticated add-on ordering and specimen collection workflows. Areas that could use further development include specimen aliquoting, quality control reporting, and maintenance tools.

  View details for DOI 10.1093/AJCP/AQW221

  View details for Web of Science ID 000397109200002

  View details for PubMedID 28395051

• Primary lymphoma of bone in the pediatric and young adult population. Human pathology Chisholm, K. M., Ohgami, R. S., Tan, B., Hasserjian, R. P., Weinberg, O. K. 2017; 60: 1-10

  Abstract

  Primary lymphoma of bone (PLB) accounts for 3% to 7% of primary neoplasms of bone and must be distinguished from more common bone tumors in the pediatric population such as osteosarcoma, Ewing sarcoma, and other small round blue cell tumors. In this study, pathology databases from 4 institutions were queried for PLB in individuals 1 to 21 years old. A total of 54 cases of PLB were identified, including 41 diffuse large B-cell lymphomas (DLBCL, 76%), 8 B-lymphoblastic lymphomas (BLL, 15%), 3 anaplastic large cell lymphomas (ALCL, 6%), and 2 low-grade follicular lymphomas (4%). The male/female ratio was 1.8:1 and median age was 16 years (range, 2-21). Patients with DLBCL were significantly older (P<.001), and patients with ALCL and BLL were significantly younger (P=.050 and P=.008, respectively) when compared with the other patients. Due to necrosis, crush artifact, and/or insufficient material, 30% of cases required multiple biopsies for diagnosis. The femur, tibia, pelvic bones, humerus, and vertebrae were most commonly involved. DLBCL patients had significantly more solitary bone involvement (P=.001), whereas BLL had significantly more polyostotic involvement (P<.001). Of the 37 patients with outcome data, all had no evidence of disease on last follow-up. This largest pediatric series of PLB identifies DLBCL as the most frequent subtype and documents rarer occurrences of BLL, ALCL, and follicular lymphomas. The differential diagnosis of bone neoplasms in pediatric patients, including those with necrosis, should include PLB.

  View details for DOI 10.1016/j.humpath.2016.07.028

  View details for PubMedID 27554207

• Hemophagocytic lymphohistiocytosis as a paraneoplastic syndrome associated with ovarian dysgerminoma. Gynecologic oncology reports Nosratian-Baskovic, M., Tan, B., Folkins, A., Chisholm, K. M., Dorigo, O. 2016; 17: 38-41

  Abstract

  •Ovarian dysgerminoma associated with paraneoplastic fever, cytopenia and splenomegaly•Complete symptom resolution resulted from tumor resection and medical management•Non-hematolymphoid neoplasms are part of differential diagnosis in secondary HLH.

  View details for DOI 10.1016/j.gore.2016.05.013

  View details for PubMedID 27354999

  View details for PubMedCentralID PMC4909829

• Validation of Digital Whole Slide Imaging System for Breast Sentinel Lymph Node Touch Prep Analysis: A Single Institution Experience Hoffmann, J., McGinnis, L., Mafnas, C. T., Ziskin, J., Folkins, A. K., Allison, K., West, R. B., Higgins, J. P., Kambham, N., Long, S. R., Tan, B. NATURE PUBLISHING GROUP. 2016: 496A

  View details for Web of Science ID 000369270703125

• Initial Validation of Whole Slide Imaging (WSI) for Use in Frozen Section Consultation at Stanford University Fernandez-Pol, S., Carneal, E., Rumery, M., Samghabadi, P., Tan, B. NATURE PUBLISHING GROUP. 2016: 494A

  View details for Web of Science ID 000369270703118

• Initial Validation of Whole Slide Imaging (WSI) for Use in Frozen Section Consultation at Stanford University Fernandez-Pol, S., Carneal, E., Rumery, M., Samghabadi, P., Tan, B. NATURE PUBLISHING GROUP. 2016: 494A

  View details for Web of Science ID 000370302503439

• Validation of Digital Whole Slide Imaging System for Intraoperative Breast Sentinel Lymph Node Touch Prep Analysis: A Single Institution Experience Hoffmann, J., McGinnis, L., Mafnas, C. T., Ziskin, J., Folkins, A. K., Allison, K., West, R. B., Higgins, J. P., Kambham, N., Long, S. R., Tan, B. NATURE PUBLISHING GROUP. 2016: 496A

  View details for Web of Science ID 000370302503446

• Cellular morphology of BRAF V600E-positive Langerhans cell histiocytosis BLOOD Satpathy, A. T., Tan, B. T. 2015; 126 (15): 1857-1857

  View details for DOI 10.1182/blood-2015-07-656900

  View details for Web of Science ID 000365451500021

  View details for PubMedID 26734696

• Angioimmunoblastic T Cell Lymphoma: An Unusual Presentation of Posttransplant Lymphoproliferative Disorder in a Pediatric Patient ACTA HAEMATOLOGICA Kraus, T. S., Twist, C. J., Tan, B. T. 2014; 131 (2): 95-101

  Abstract

  Posttransplant lymphoproliferative disorders (PTLD) are a potentially life-threatening complication of immunosuppression in transplant recipients. The majority of cases are Epstein-Barr virus-associated lesions of B cell origin. T cell PTLD is rare, particularly in pediatric patients. We present an unusual case of monomorphic T cell PTLD with features of angioimmunoblastic T cell lymphoma in an 8-year-old heart transplant patient, presenting with cranial nerve palsy. © 2013 S. Karger AG, Basel.

  View details for DOI 10.1159/000353783

  View details for Web of Science ID 000331488500006

  View details for PubMedID 24157860

• Evaluation of the Beckman Coulter UniCel DxH 800, Beckman Coulter LH 780, and Abbott Diagnostics Cell-Dyn Sapphire Hematology Analyzers on Adult Specimens in a Tertiary Care Hospital AMERICAN JOURNAL OF CLINICAL PATHOLOGY Tan, B. T., Nava, A. J., George, T. I. 2011; 135 (6): 939-951

  Abstract

  We evaluated the new Beckman Coulter DxH 800 hematology analyzer (Beckman Coulter, Miami, FL) vs the Abbott Diagnostics Cell-Dyn Sapphire (Abbott Diagnostics, Santa Clara, CA) and Beckman Coulter LH 780 hematology analyzers using 430 adult specimens. The DxH 800 provided a CBC and differential that correlated well with those of the Sapphire and LH 780, with most parameters showing correlation coefficients (r) of more than 0.97. In the instrument vs 400-cell manual differential comparison, all 3 instruments showed similar and acceptable accuracy to the reference method except for nucleated RBC (NRBC) enumeration, in which the DxH 800 and Sapphire outperformed the LH 780. We also compared clinical efficiency by determining whether flagged specimens showed abnormalities on a peripheral blood smear as defined by International Council for Standardization in Haematology criteria. The efficiency, sensitivity, and specificity of the DxH 800 were 77.0%, 87.1%, and 73.0%, respectively, compared with the Sapphire at 75.8%, 93.5%, and 68.8%, respectively, and LH 780 at 66.1%, 93.5%, and 55.3%, respectively.

  View details for DOI 10.1309/AJCP1V3UXEIQTSLE

  View details for PubMedID 21571967

• Evaluation of the Beckman Coulter UniCel DxH 800 and Abbott Diagnostics Cell-Dyn Sapphire Hematology Analyzers on Pediatric and Neonatal Specimens in a Tertiary Care Hospital AMERICAN JOURNAL OF CLINICAL PATHOLOGY Tan, B. T., Nava, A. J., George, T. I. 2011; 135 (6): 929-938

  Abstract

  We evaluated the new UniCel DxH 800 hematology analyzer (Beckman Coulter, Miami, FL) vs the Cell-Dyn Sapphire (Abbott Diagnostics, Santa Clara, CA) using 156 pediatric specimens in Microtainer tubes (Becton Dickinson, Franklin Lakes, NJ). The CBC and differential showed good interinstrument correlation, including WBCs (r = 0.995), RBCs (r = 0.992), hemoglobin (r = 0.998), mean corpuscular volume (r = 0.988), platelets (r = 0.997), neutrophils (r = 0.988), lymphocytes (r = 0.984), monocytes (r = 0.815), eosinophils (r = 0.840), basophils (r = 0.049), and nucleated RBCs (NRBCs; r = 0.906). In the instrument vs 400-cell manual differential comparison, the DxH 800 and Sapphire showed comparable performance for nearly all parameters except for NRBCs, for which the DxH 800 correlated better (r = 0.989) than the Sapphire (r = 0.906). We also compared clinical efficiency by determining whether flagged specimens showed abnormalities on a peripheral blood smear as defined by International Council for Standardization in Haematology criteria. The efficiency of the DxH 800 was 78.0% vs the Sapphire at 68.1%. Both instruments showed identical sensitivity (91.1%), but the specificity for the DxH 800 (71.9%) was higher than that of the Sapphire (57.3%).

  View details for DOI 10.1309/AJCP2EXNSLGGRVSQ

  View details for PubMedID 21571966

• Anti-CD47 Antibody Synergizes with Rituximab to Promote Phagocytosis and Eradicate Non-Hodgkin Lymphoma CELL Chao, M. P., Alizadeh, A. A., Tang, C., Myklebust, J. H., Varghese, B., Gill, S., Jan, M., Cha, A. C., Chan, C. K., Tan, B. T., Park, C. Y., Zhao, F., Kohrt, H. E., Malumbres, R., Briones, J., Gascoyne, R. D., Lossos, I. S., Levy, R., Weissman, I. L., Majeti, R. 2010; 142 (5): 699-713

  Abstract

  Monoclonal antibodies are standard therapeutics for several cancers including the anti-CD20 antibody rituximab for B cell non-Hodgkin lymphoma (NHL). Rituximab and other antibodies are not curative and must be combined with cytotoxic chemotherapy for clinical benefit. Here we report the eradication of human NHL solely with a monoclonal antibody therapy combining rituximab with a blocking anti-CD47 antibody. We identified increased expression of CD47 on human NHL cells and determined that higher CD47 expression independently predicted adverse clinical outcomes in multiple NHL subtypes. Blocking anti-CD47 antibodies preferentially enabled phagocytosis of NHL cells and synergized with rituximab. Treatment of human NHL-engrafted mice with anti-CD47 antibody reduced lymphoma burden and improved survival, while combination treatment with rituximab led to elimination of lymphoma and cure. These antibodies synergized through a mechanism combining Fc receptor (FcR)-dependent and FcR-independent stimulation of phagocytosis that might be applicable to many other cancers.

  View details for DOI 10.1016/j.cell.2010.07.044

  View details for PubMedID 20813259

• The Frequency of Immunoglobulin Heavy Chain Gene and T-Cell Receptor gamma-Chain Gene Rearrangements and Epstein-Barr Virus in ALK(+) and ALK(-) Anaplastic Large Cell Lymphoma and Other Peripheral T-Cell Lymphomas JOURNAL OF MOLECULAR DIAGNOSTICS Tan, B. T., Seo, K., Warnke, R. A., Arber, D. A. 2008; 10 (6): 502-512

  Abstract

  We previously identified a relatively high frequency of B-cell proliferations along with simultaneous T-cell receptor gamma-chain gene (TRG) and immunoglobulin heavy chain gene (IGH) rearrangements in a series of angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified. Here, we report on a series of 74 peripheral T-cell lymphoma (PTCL) cases composed entirely of specific PTCL subtypes, including 28 cases of ALK+ anaplastic large-cell lymphoma (ALCL), 35 cases of ALK- ALCL, and 11 cases that represent other specific PTCL subtypes. We performed IGH and TRG gene rearrangement studies and in situ hybridization for Epstein-Barr virus (EBV) to determine the frequency of IGH clonality and to investigate the relationship between EBV, clonality, and associated B-cell proliferations. Using BIOMED-2 PCR assays, we detected TRG clones in 64 of 74 (86%) cases and IGH clones in 6 of 74 (8%) cases, with all IGH-positive cases exhibiting a concurrent TRG clone. Despite the detection of occasional IGH clones, there was no correlation between IGH clonality and EBV, and B-cell proliferations were not identified in any of the cases. These findings suggest that other factors contribute to IGH clonality and demonstrate that, in the absence of an associated B-cell proliferation, IGH clonality occurs infrequently (8%) in specific PTCL subtypes.

  View details for DOI 10.2353/jmoldx.2008.080054

  View details for Web of Science ID 000260533600007

  View details for PubMedID 18832464

  View details for PubMedCentralID PMC2570633

• The Wilms' tumor gene WT1-GFP knock-in mouse reveals the dynamic regulation of WT1 expression in normal and leukemic hematopoiesis LEUKEMIA Hosen, N., Shirakata, T., Nishida, S., Yanagihara, M., Tsuboi, A., Kawakami, M., Oji, Y., Oka, Y., Okabe, M., Tan, B., Sugiyama, H., Weissman, I. L. 2007; 21 (8): 1783-1791

  Abstract

  The Wilms' tumor gene WT1 is overexpressed in most of human leukemias regardless of disease subtypes. To characterize the expression pattern of WT1 during normal and neoplastic hematopoiesis, we generated a knock-in reporter green fluorescent protein (GFP) mouse (WT1(GFP/+)) and assayed for WT1 expression in normal and leukemic hematopoietic cells. In normal hematopoietic cells, WT1 was expressed in none of the long-term (LT) hematopoietic stem cells (HSC) and very few (<1%) of the multipotent progenitor cells. In contrast, in murine leukemias induced by acute myeloid leukemia 1 (AML1)/ETO+TEL/PDGFbetaR or BCR/ABL, WT1 was expressed in 40.5 or 38.9% of immature c-kit(+)lin(-)Sca-1(+) (KLS) cells, which contained a subset, but not all, of transplantable leukemic stem cells (LSCs). WT1 expression was minimal in normal fetal liver HSCs and mobilized HSCs, both of which are stimulated for proliferation. In addition, overexpression of WT1 in HSCs did not result in proliferation or expansion of HSCs and their progeny in vivo. Thus, the mechanism by which expansion of WT1-expressing cells occurs in leukemia remains unclear. Nevertheless, our results demonstrate that the WT1(GFP/+) mouse is a powerful tool for analyzing WT1-expressing cells, and they highlight the potential of WT1, as a specific therapeutic target that is expressed in LSCs but not in normal HSCs.

  View details for DOI 10.1038/sj.leu.2404752

  View details for Web of Science ID 000248170100021

  View details for PubMedID 17525726

• The cancer stem cell hypothesis: a work in progress LABORATORY INVESTIGATION Tan, B. T., Park, C. Y., Ailles, L. E., Weissman, I. L. 2006; 86 (12): 1203-1207

  Abstract

  There is a growing body of evidence that supports the idea that malignant tumors are initiated and maintained by a population of tumor cells that share similar biologic properties to normal adult stem cells. This model, the cancer stem cell (CSC) hypothesis, is based on the observation that tumors, like adult tissues, arise from cells that exhibit the ability to self-renew as well as give rise to differentiated tissue cells. Although the concept of the CSC is not entirely new, advances made over the past two decades in our understanding of normal stem cell biology in conjunction with the recent application of these concepts to experimentally define CSCs have resulted in the identification of CSCs in several human malignancies.

  View details for DOI 10.1038/labinvest.3700488

  View details for Web of Science ID 000242442400001

  View details for PubMedID 17075578

• The frequency of B- and T-cell gene Rearrangements and Epstein-Barr virus in T-cell lymphomas - A comparison between angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified with and without associated B-cell proliferations JOURNAL OF MOLECULAR DIAGNOSTICS Tan, B. T., Warnke, R. A., Arber, D. A. 2006; 8 (4): 466-475

  Abstract

  We report on a series of 58 cases of angioimmunoblastic T-cell lymphoma (AILT) and 59 cases of peripheral T-cell lymphoma, unspecified (PTCL-NOS). Subsets of cases from both diagnostic groups were complicated by associated B-cell proliferations, and we performed B- and T-cell clonality studies and in situ hybridization for Epstein-Barr virus (EBV) to investigate the relationship between B-cell proliferation, B-cell clonality, and EBV. Using multiplex polymerase chain reaction assays based on the BIOMED-2 collaborative study, we detected TCRgamma T-cell clones in 78 and 81% of AILT and PTCL-NOS cases, respectively, and IGH B-cell clones in 34 and 35% of AILT and PTCL-NOS cases, respectively. The majority of cases contained EBV-positive cells, including 50% of AILT and 57% of PTCL-NOS cases, and cases with B-cell proliferations were more often EBV-positive. Although a relatively high rate of B-cell clonality has been shown for AILT, our findings for PTCL-NOS differ from previous reports in that B-cell clonality was relatively frequent. Overall, a positive B-cell clone correlated, in part, with the presence of a B-cell proliferation but not with EBV. Our findings demonstrate that B-cell clonality is a common finding in AILT and PTCL-NOS, and its presence should not negate the diagnosis established by morphologic, immunophenotypic, and clinical findings.

  View details for DOI 10.2353/jmoldx.2006.060016

  View details for Web of Science ID 000240256600010

  View details for PubMedID 16931587

  View details for PubMedCentralID PMC1867616