Clinical Associate Professor, Pathology
Medical Director, Point-of-Care Testing license, Stanford Medical Outpatient Center (2008 - Present)
Co-Director, Flow Cytometry, Stanford Hospital Clinical Lab (2005 - Present)
Honors & Awards
Senior CP Faculty Teaching Award, Stanford Pathology residents (2009)
B.S., Duke University, Zoology (1981)
M.D., Duke University, School of Medicine (1985)
Current Research and Scholarly Interests
I am interested in optimizing the process of diagnosing leukemias, lymphomas and other hematolymphoid neoplasms, particularly by the use of diagnostic flow cytometry. One goal is to develop flow data analysis processes that function as interactive tools, allowing pathologists to query rich diagnostic data sets in real time.
- Independent Studies (5)
- An integrated flow cytometry analysis of 286 mature B cell neoplasms identifies CD13 as a useful marker for diagnostic subtyping INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY 2018; 40 (6): 715–20
An integrated flow cytometry analysis of 286 mature B cell neoplasms identifies CD13 as a useful marker for diagnostic subtyping.
International journal of laboratory hematology
INTRODUCTION: CD13 is a myeloid associated antigen, which may be expressed by a subset of B cell lymphomas; however, the significance of its expression along with other B cell associated antigens is not well characterized.METHODS: Two hundred and eighty-six mature B cell neoplasms with flow cytometric analysis performed at the time of diagnosis were identified. Expression of CD13, CD45, CD19, CD20, CD5, CD10, CD38, CD22, CD23, FMC7, and kappa and lambda light chains was assessed for each case and correlated with clinicopathologic features.RESULTS: CD13 expression was associated specifically with cases of lymphoplasmacytic lymphoma (LPL) (16/26)- and FMC7-positive chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (11/30). No cases of follicular lymphoma (FL) expressed CD13 (0/48). Across all B cell neoplasms, CD13 expression positively correlated with FMC7 co-expression and kappa light chain restriction and negatively correlated with CD10 co-expression and lambda light chain restriction. No significant association of CD13 with overall or disease free survival in B cell neoplasms was seen.CONCLUSION: CD13 expression is present more often in LPL- and FMC7-positive CLL/SLL than other mature B cell lymphoma subtypes and absent in cases of FL and may be a useful feature for diagnostic subtyping.
View details for PubMedID 30066366
Normative data for flow cytometry immunophenotyping of benign lymph nodes sampled by surgical biopsy.
Journal of clinical pathology
To create clinically relevant normative flow cytometry data for understudied benign lymph nodes and characterise outliers.Clinical, histological and flow cytometry data were collected and distributions summarised for 380 benign lymph node excisional biopsies. Outliers for kappa:lambda light chain ratio, CD10:CD19 coexpression, CD5:CD19 coexpression, CD4:CD8 ratios and CD7 loss were summarised for histological pattern, concomitant diseases and follow-up course.We generated the largest data set of benign lymph node immunophenotypes by an order of magnitude. B and T cell antigen outliers often had background immunosuppression or inflammatory disease but did not subsequently develop lymphoma.Diagnostic immunophenotyping data from benign lymph nodes provide normative ranges for clinical use. Outliers raising suspicion for B or T cell lymphoma are not infrequent (26% of benign lymph nodes). Caution is indicated when interpreting outliers in the absence of excisional biopsy or clinical history, particularly in patients with concomitant immunosuppression or inflammatory disease.
View details for DOI 10.1136/jclinpath-2017-204687
View details for PubMedID 28916595
Cell Signaling-Based Classifier Predicts Response to Induction Therapy in Elderly Patients with Acute Myeloid Leukemia
2015; 10 (4)
Single-cell network profiling (SCNP) data generated from multi-parametric flow cytometry analysis of bone marrow (BM) and peripheral blood (PB) samples collected from patients >55 years old with non-M3 AML were used to train and validate a diagnostic classifier (DXSCNP) for predicting response to standard induction chemotherapy (complete response [CR] or CR with incomplete hematologic recovery [CRi] versus resistant disease [RD]). SCNP-evaluable patients from four SWOG AML trials were randomized between Training (N = 74 patients with CR, CRi or RD; BM set = 43; PB set = 57) and Validation Analysis Sets (N = 71; BM set = 42, PB set = 53). Cell survival, differentiation, and apoptosis pathway signaling were used as potential inputs for DXSCNP. Five DXSCNP classifiers were developed on the SWOG Training set and tested for prediction accuracy in an independent BM verification sample set (N = 24) from ECOG AML trials to select the final classifier, which was a significant predictor of CR/CRi (area under the receiver operating characteristic curve AUROC = 0.76, p = 0.01). The selected classifier was then validated in the SWOG BM Validation Set (AUROC = 0.72, p = 0.02). Importantly, a classifier developed using only clinical and molecular inputs from the same sample set (DXCLINICAL2) lacked prediction accuracy: AUROC = 0.61 (p = 0.18) in the BM Verification Set and 0.53 (p = 0.38) in the BM Validation Set. Notably, the DXSCNP classifier was still significant in predicting response in the BM Validation Analysis Set after controlling for DXCLINICAL2 (p = 0.03), showing that DXSCNP provides information that is independent from that provided by currently used prognostic markers. Taken together, these data show that the proteomic classifier may provide prognostic information relevant to treatment planning beyond genetic mutations and traditional prognostic factors in elderly AML.
View details for DOI 10.1371/journal.pone.0118485
View details for Web of Science ID 000353017000002
View details for PubMedID 25884949
View details for PubMedCentralID PMC4401549
Indolent T-lymphoblastic Proliferation With Disseminated Multinodal Involvement and Partial CD33 Expression.
American journal of surgical pathology
2014; 38 (9): 1298-1304
Although indolent T-lymphoblastic proliferations (iT-LBP) are rare, this diagnosis should be excluded in any patient with an extrathymic proliferation of immature TdT+T cells. Unlike T-lymphoblastic leukemia/lymphoma, patients with iT-LBP do not require chemotherapy. We report a case of iT-LBP with disseminated multinodal involvement in an otherwise healthy 49-year-old woman. Multiple lymph node biopsies were performed over the course of several months demonstrating persistent and anatomically diffuse involvement. Over 18 months, and without therapy, she has remained healthy, and her lymphadenopathy significantly improved. No bone marrow or peripheral blood involvement was ever identified. Atypical T cells showed an immunophenotypic spectrum of T-cell antigen expression with partial CD33 on a subset of T cells detected by both flow cytometry and immunohistochemistry. Both T-cell clonality and Human Androgen Receptor Assay (HUMARA) studies, performed on lymph node biopsy specimens, were negative. This case represents the first detailed clinical, morphologic, molecular, and immunophenotypic description of disseminated multinodal involvement by nonclonal iT-LBP with partial CD33 expression on T cells.
View details for DOI 10.1097/PAS.0000000000000197
View details for PubMedID 24618611
Expression of the Activating Receptor, NKp46 (CD335), in Human Natural Killer and T-Cell Neoplasia.
American journal of clinical pathology
2013; 140 (6): 853-866
Objectives To evaluate the expression of CD335 (NKp46), an activation receptor that is selectively expressed on natural killer (NK) cells. Methods We assessed CD335's potential utility as a diagnostic marker in 657 cases by flow cytometry and 410 cases by immunohistochemistry. Results We observed that CD335 was highly specific for NK cells in nonneoplastic tissues. Moreover, 61 (90%) of 68 of NK cell neoplasms demonstrated CD335 expression, whereas B-cell, myelomonocytic, and plasma cell neoplasms lacked expression. Notably, 16 (20%) of 82 mature T-cell neoplasms, particularly T-cell large granular lymphocytic leukemia, mycosis fungoides, and ALK+ anaplastic large cell lymphoma, aberrantly expressed CD335. Conclusions Collectively, these data support the diagnostic utility of CD335 in evaluating hematopoietic malignancies and suggest that CD335 could be a useful target for selective immunotherapy in patients with mature NK and T-cell neoplasms.
View details for DOI 10.1309/AJCPWGG69MCZOWMM
View details for PubMedID 24225754
The PEBP2 beta MYH11 fusion created by Inv(16)(p13;q22) in myeloid leukemia impairs neutrophil maturation and contributes to granulocytic dysplasia
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
1998; 95 (20): 11863-11868
Chromosomal translocations involving the genes encoding the alpha and beta subunits of the Pebp2/Cbf transcription factor have been associated with human acute myeloid leukemia and the preleukemic condition, myelodysplasia. Inv(16)(p13;q22) fuses the gene encoding the beta subunit of Pebp2 to the MYH11 gene encoding a smooth muscle myosin heavy chain (Smmhc). To examine the effect of the inv(16)(p13;q22) on myelopoiesis, we used the hMRP8 promoter element to generate transgenic mice expressing the Pebp2betaSmmhc chimeric fusion protein in myeloid cells. Neutrophil maturation was impaired in PEBP2betaMYH11 transgenic mice. Although the transgenic mice had normal numbers of circulating neutrophils, their bone marrow contained increased numbers of immature neutrophilic cells, which exhibited abnormal characteristics. In addition, PEBP2betaMYH11 inhibited neutrophilic differentiation in colonies derived from hematopoietic progenitors. Coexpression of both PEBP2betaMYH11 and activated NRAS induced a more severe phenotype characterized by abnormal nuclear morphology indicative of granulocytic dysplasia. These results show that PEBP2betaMYH11 can impair neutrophil development and provide evidence that alterations of Pebp2 can contribute to the genesis of myelodysplasia.
View details for Web of Science ID 000076222200065
View details for PubMedID 9751756
View details for PubMedCentralID PMC21731
A PMLRAR alpha transgene initiates murine acute promyelocytic leukemia
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
1997; 94 (6): 2551-2556
The malignant cells of acute promyelocytic leukemia (APL) contain a reciprocal chromosomal translocation that fuses the promyelocytic leukemia gene (PML) with the retinoic acid receptor alpha gene (RAR alpha). To test the hypothesis that the chimera PMLRAR alpha plays a role in leukemogenesis, we expressed a PMLRAR alpha cDNA in myeloid cells of transgenic mice. PMLRAR alpha transgenic mice exhibited impaired neutrophil maturation early in life, which progressed at a low frequency over the course of several months to overt APL. Both the preleukemic state and the leukemia could be transplanted to nontransgenic mice, and the transplanted preleukemia could progress to APL. The APL recapitulated features of the human disease, including a response to retinoic acid. Retinoic acid caused the leukemic cells to differentiate in vitro and in vivo, eliciting remissions of both the preleukemic state and APL in mice. Our results demonstrate that PMLRAR alpha impairs neutrophil differentiation and initiates the development of APL. The transgenic mice described here provide an apparently accurate model for human APL that includes clear evidence of tumor progression. The model should be useful for exploring the molecular pathogenesis of APL and the mechanisms of the therapeutic response to retinoic acid, as well as for preclinical studies of therapeutic regimens.
View details for Web of Science ID A1997WP33400084
View details for PubMedID 9122233
View details for PubMedCentralID PMC20126