- Anatomic and Clinical Pathology
- Hematopathology, flow cytometry, transfusion medicine
Clinical Assistant Professor, Pathology
Medical Director, Clinical Flow Cytometry, Stanford Hospital (2018 - Present)
PhD Training: University of California at Irvine School of Medicine Registrar (2002) CA
Board Certification: American Board of Pathology, Blood Banking/Transfusion Medicine (2017)
Fellowship: Stanford University Pathology Residency (2017) CA
Fellowship: Stanford University Pathology Residency (2016) CA
Board Certification: American Board of Pathology, Hematopathology (2016)
Residency: Stanford University Department of Pathology (2016) CA
Board Certification: American Board of Pathology, Anatomic and Clinical Pathology (2015)
Medical Education: University of California at Irvine School of Medicine Registrar (2010) CA
- Disseminated Pneumocystis jirovecii Infection with Osteomyelitis in a Patient with CTLA-4 Haploinsufficiency. Journal of clinical immunology 2020
Multiplexed single-cell morphometry for hematopathology diagnostics.
2020; 26 (3): 408–17
The diagnosis of lymphomas and leukemias requires hematopathologists to integrate microscopically visible cellular morphology with antibody-identified cell surface molecule expression. To merge these into one high-throughput, highly multiplexed, single-cell assay, we quantify cell morphological features by their underlying, antibody-measurable molecular components, which empowers mass cytometers to 'see' like pathologists. When applied to 71 diverse clinical samples, single-cell morphometric profiling reveals robust and distinct patterns of 'morphometric' markers for each major cell type. Individually, lamin B1 highlights acute leukemias, lamin A/C helps distinguish normal from neoplastic mature T cells, and VAMP-7 recapitulates light-cytometric side scatter. Combined with machine learning, morphometric markers form intuitive visualizations of normal and neoplastic cellular distribution and differentiation. When recalibrated for myelomonocytic blast enumeration, this approach is superior to flow cytometry and comparable to expert microscopy, bypassing years of specialized training. The contextualization of traditional surface markers on independent morphometric frameworks permits more sensitive and automated diagnosis of complex hematopoietic diseases.
View details for DOI 10.1038/s41591-020-0783-x
View details for PubMedID 32161403
Histology-Independent Signature Distinguishes Kikuchi-Fujimoto Disease/Systemic Lupus Erythematosus-Associated Lymphadenitis From Benign and Malignant Lymphadenopathies.
American journal of clinical pathology
Kikuchi-Fujimoto disease (KFD) and systemic lupus erythematosus (SLE) are benign entities with histologic features that raise concern about malignancy and infection. We searched for a histology-independent KFD/SLE signature relying on only immunophenotype and basic clinical characteristics.A histology-independent KFD/SLE signature was generated using 975 excised lymph nodes with flow immunophenotyping, including 16 cases of KFD/SLE. This signature was then evaluated in 1,198 fine-needle aspiration (FNA) specimens.The top flow cytometry discriminant for KFD/SLE was uniform CD38+ expression on CD19+ events. Immunohistochemistry demonstrated nodules of IgD+, IgM- B cells surrounding necrotizing and activated T-cell areas. A signature combining 6 flow cytometry criteria with age and sample site had a positive predictive value of 88% for KFD/SLE, which had a prevalence of 1.6%. All 4 signature-positive FNA cases with follow-up excision were KFD/SLE. At a second institution, 4 of 5 KFD/SLE cases passed the top discriminant.A flow cytometry signature combined with age and biopsy site identifies KFD/SLE independent of histology, suggesting a shared immune composition and independently confirming that KFD/SLE represents a distinct entity. Unexpectedly, an IgD+CD38+ small B-cell population is a distinctive feature of KFD/SLE, suggesting a possible pathologic role for anergic/autoreactive B cells.
View details for DOI 10.1093/ajcp/aqaa036
View details for PubMedID 32367142
- Flow Cytometry Signature for Kikuchi-Fujimoto/Lupus Lymphadenitis Derived From 975 Benign and Malignant Lymphadenopathies OXFORD UNIV PRESS INC. 2019: S105–S106
Rationale and Feasibility of Using a Standardized Screening Tube on the FACSCanto II and the FACSLyric
NATURE PUBLISHING GROUP. 2019
View details for Web of Science ID 000478081102317
- Target Antigen Downregulation and Other Mechanisms of Failure after Axicabtagene Ciloleucel (CAR19) Therapy AMER SOC HEMATOLOGY. 2018
- Phase I Experience with a Bi-Specific CAR Targeting CD19 and CD22 in Adults with B-Cell Malignancies AMER SOC HEMATOLOGY. 2018
- Elevated Axicabtagene Ciloleucel (CAR-19) Expansion By Immunophenotyping Is Associated with Toxicity in Diffuse Large B-Cell Lymphoma AMER SOC HEMATOLOGY. 2018
A reevaluation of erythroid predominance in Acute Myeloid Leukemia using the updated WHO 2016 Criteria
2018; 31 (6): 873–80
The 2016 WHO update changed the diagnostic criteria for myeloid neoplasms with erythroid predominance, limiting the diagnosis of acute myeloid leukemia to cases with ≥20% blasts in the bone marrow or peripheral blood. Although acute myeloid leukemia with ≥50% erythroid cells has historically been presumed to represent acute myeloid leukemia with myelodysplasia-related changes, this hypothesis has never been systematically examined. We sought to investigate the clinicopathologic, cytogenetic, and molecular features of acute myeloid leukemia with erythroid predominance to subclassify cases as defined by the 2016 WHO. We retrospectively identified patients with ≥50% erythroid precursors and either ≥20% bone marrow blasts or ≥20% peripheral blood blasts at the time of initial diagnosis at seven major academic centers. Laboratory and clinical data were obtained. Patients were then reclassified according to 2016 WHO guidelines. A matched control group was also obtained. We identified 146 patients with acute myeloid leukemia with erythroid predominance (62% M, average age: 62 y, range: 5-93 y). Of these, 91 were acute myeloid leukemia with myelodysplasia-related changes, 20 (14%) were therapy-related myeloid neoplasm, 23 (16%) acute myeloid leukemia, not otherwise specified, and ten acute myeloid leukemia with recurrent cytogenetic/molecular abnormalities. The bone marrow blast count ranged from 9-41%. There was no difference in survival for patients with erythroid predominance compared to patients with acute myeloid leukemia without erythroid proliferations. In a multivariable analysis, cytogenetic risk was the only significant predictor of survival. We find a significantly lower rate of FLT3 and RAS pathway alterations in acute myeloid leukemia with erythroid predominance compared to controls. Our study is one of the first to apply the 2016 WHO guidelines for classification of acute myeloid leukemia. We find acute myeloid leukemia with erythroid predominance is a heterogeneous group and that erythroid richness has no impact on overall survival.
View details for PubMedID 29403082
Occult Hemolytic Anemia Due to Anti-Mur in a Patient Receiving Blood from a Region with a Prominent Asian Donor Population
WILEY. 2017: 178A
View details for Web of Science ID 000409065000450
Myelodysplastic Syndrome, Unclassifiable (MDS-U) With 1% Blasts Is a Distinct Subgroup of MDS-U With a Poor Prognosis
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
2017; 148 (1): 49–57
Three situations qualify as myelodysplastic syndrome, unclassifiable (MDS-U): (1) refractory cytopenia with dysplasia and 1% blasts in peripheral blood (BL), (2) pancytopenia with unilineage dysplasia (Pan), and (3) persistent cytopenia, less than 5% bone marrow blasts, and less than 10% dysplastic cells and presence of MDS-defining cytogenetic abnormalities (CG). We compared the clinicopathologic features and mutational profiles for these three groups.MDS-U cases were reviewed at four major academic institutions. Targeted next-generation sequencing for genes implicated in myeloid neoplasms was performed in a subset of cases.Twenty-seven patients were identified (six MDS-U BL, 13 MDS-U Pan, and eight MDS-U CG). Clonal cytogenetic abnormalities were found in six of six, seven of 13, and eight of eight cases in MDS-U BL, Pan, and CG, respectively (P > .05). Overall, four of six patients with MDS-U BL progressed to acute myeloid leukemia; no MDS-U Pan or CG patients did. The rates of progression-free survival and mortality (overall survival) were significantly higher in MDS-U BL compared with Pan and CG (P < .001 for both).We find that MDS-U BL is a distinct subset of MDS-U with a poor prognosis, while MDS-U Pan and CG are relatively indolent. Evaluation of peripheral blood smears in patients with MDS is essential for accurate classification and prognosis.
View details for PubMedID 28927162
Oligomonocytic chronic myelomonocytic leukemia (chronic myelomonocytic leukemia without absolute monocytosis) displays a similar clinicopathologic and mutational profile to classical chronic myelomonocytic leukemia.
Chronic myelomonocytic leukemia is characterized by persistent absolute monocytosis (≥1 × 109/l) in the peripheral blood and dysplasia in ≥1 lineages. In the absence of dysplasia, an acquired clonal genetic abnormality is required or causes for reactive monocytosis have to be excluded. Oligomonocytic chronic myelomonocytic leukemia showing increased monocytes but no absolute monocytosis in the peripheral blood occurs occasionally. These cases are likely classified as myelodysplastic syndrome or myelodysplastic/myeloproliferative neoplasm, unclassifiable. A subset eventually develop overt chronic myelomonocytic leukemia. Better characterization of oligomonocytic chronic myelomonocytic leukemia is essential since the distinction between chronic myelomonocytic leukemia and myelodysplastic syndrome is clinically relevant. We identified 44 cases of oligomonocytic chronic myelomonocytic leukemia (≥10% peripheral blood monocytes with absolute monocyte count of 0.5-1 × 109/l) and 28 consecutive chronic myelomonocytic leukemia controls. Clinicopathologic features were compared and mutation analysis was performed. Oligomonocytic chronic myelomonocytic leukemia patients were significantly younger (median age of 65 vs 72). They had lower WBC and absolute neutrophil count, while the monocyte percentage, hemoglobin and platelet counts were similar in the two groups. The myeloid to erythroid ratio was predominantly decreased or normal, compared with the characteristic increase in chronic myelomonocytic leukemia (P=0.006). 38% of patients progressed to overt chronic myelomonocytic leukemia (median: 12 months). The overall percentage of mutations was significantly lower in oligomonocytic chronic myelomonocytic leukemia. However, the most frequent mutations in both groups were the 'signature' chronic myelomonocytic leukemia mutations in ASXL1, TET2 and SRSF2. Mutations in CBL were found exclusively in overt chronic myelomonocytic leukemia. In conclusion, we demonstrate clinical and genetic similarities between overt chronic myelomonocytic leukemia and oligomonocytic chronic myelomonocytic leukemia. The findings suggest that at least a subset of oligomonocytic chronic myelomonocytic leukemia represents early phase 'dysplastic type' chronic myelomonocytic leukemia.
View details for DOI 10.1038/modpathol.2017.45
View details for PubMedID 28548124
- Focusing on frequent ASXL1 mutations in myeloid neoplasms, and considering rarer ASXL2 and ASXL3 mutations. Current medical research and opinion 2017: 1-2
c-Myc Protein Expression Distinguishes Plasma Cell Myeloma from Solitary Plasmacytoma and Is Associated with Aggressive Morphologic Features
NATURE PUBLISHING GROUP. 2017: 368A
View details for Web of Science ID 000394467302052
A Retrospective Study of 305 Cases of Angioimmunoblastic T-Cell Lymphoma with Emphasis on Rare Lymphoplasmacytic and Plasma Cell Proliferations
NATURE PUBLISHING GROUP. 2017: 367A–368A
View details for Web of Science ID 000393724401748
Acute Myeloid Leukemia with Erythroid Predominance: Are All Cases MDS-Related?
NATURE PUBLISHING GROUP. 2017: 362A
View details for Web of Science ID 000394467302031
Myelodysplastic Syndrome, Unclassifiable (MDS-U) with 1% Blasts Is a Distinct Subgroup of MDS-U with a Poor Prognosis
NATURE PUBLISHING GROUP. 2016: 361A
View details for Web of Science ID 000370302502434