Bio

Clinical Focus


  • Anatomic Pathology
  • Pathology
  • Hematopathology

Academic Appointments


Administrative Appointments


  • Associate Director, Stanford Society of Physician Scholars (2010 - 2012)
  • Member, College of American Pathologists (CAP) Cancer Biomarker Reporting Committee (CBRC) Hematopathology (2013 - Present)
  • Associate Member, Stanford Cancer Institute (2013 - Present)

Honors & Awards


  • Research Scholar, College of American Pathologists (2012)

Professional Education


  • Board Certification: Hematology, American Board of Pathology
  • Residency:Stanford Hospital and Clinics (2012) CA
  • Fellowship:Stanford Hospital and Clinics (2011) CA
  • BA, Princeton, Molecular Biology (2000)
  • Medical Education:Harvard Medical School (2008) MA
  • Medical Education (HST), Massachusetts Institute of Technology, MA (2008)
  • PhD, Harvard, Cell and Developmental Biology (2006)
  • Board Certification, American Board of Pathology, Hematology (2012)
  • Board Certification, American Board of Pathology, Anatomic Pathology (2012)

Research & Scholarship

Current Research and Scholarly Interests


My research is focused on the pathologic classification and understanding of hematopoietic diseases; in recent years I have focused attention on T-cells, both neoplastic and reactive, myeloid neoplasms and other diseases such as Castleman Disease using standard phenotyping as well as newer technologies.

Publications

Journal Articles


  • Indolent T-lymphoblastic Proliferation With Disseminated Multinodal Involvement and Partial CD33 Expression. The American journal of surgical pathology Ohgami, R. S., Sendamarai, A. K., Atwater, S. K., Liedtke, M., Fleming, M. D., Natkunam, Y., Warnke, R. A. 2014

    Abstract

    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

  • E-Cadherin Is a Specific Marker for Erythroid Differentiation and Has Utility, in Combination With CD117 and CD34, for Enumerating Myeloblasts in Hematopoietic Neoplasms. American journal of clinical pathology Ohgami, R. S., Chisholm, K. M., Ma, L., Arber, D. A. 2014; 141 (5): 656-64

    Abstract

    Objectives E-cadherin, epithelial calcium-dependent cell adhesion protein, has been identified as a marker of immature erythroid precursors in recent years. However, the specificity of E-cadherin in bone marrow specimens for erythroblasts vs myeloblasts or other early hematopoietic precursors in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) has not been fully elucidated. Methods We analyzed 105 cases of AML and MDS to evaluate the specificity of E-cadherin. Results Of 84 cases of AML, including cases with megakaryocytic, erythroid, monocytic, and granulocytic differentiation, all five acute erythroleukemia cases were positive, as well as one case of megakaryoblastic leukemia that showed coexpression of glycophorin A. In addition, we demonstrate that a panel of three markers, E-cadherin, CD117, and CD34, is effective in identifying lineage-specific myeloblasts in cases of MDS where left-shifted erythroid hyperplasia may complicate morphologic assessment of myeloblasts. Conclusions In marrow specimens, E-cadherin is a useful marker for erythroid differentation.

    View details for DOI 10.1309/AJCP8M4QQTAZPGRP

    View details for PubMedID 24713736

  • Profound plasmacytosis in a patient with dengue. International journal of hematology Ewalt, M. D., Abeynayake, J., Waggoner, J. J., Pinsky, B. A., Ohgami, R. S. 2013; 98 (5): 518-519

    View details for DOI 10.1007/s12185-013-1452-3

    View details for PubMedID 24114365

  • STAT3 mutations are frequent in CD30+ T-cell lymphomas and T-cell large granular lymphocytic leukemia. Leukemia Ohgami, R. S., Ma, L., Merker, J. D., Martinez, B., Zehnder, J. L., Arber, D. A. 2013; 27 (11): 2244-2247

    View details for DOI 10.1038/leu.2013.104

    View details for PubMedID 23563237

  • TdT(+) T-lymphoblastic Populations Are Increased in Castleman Disease, in Castleman Disease in Association With Follicular Dendritic Cell Tumors, and in Angioimmunoblastic T-cell Lymphoma AMERICAN JOURNAL OF SURGICAL PATHOLOGY Ohgami, R. S., Zhao, S., Ohgami, J. K., Leavitt, M. O., Zehnder, J. L., West, R. B., Arber, D. A., Natkunam, Y., Warnke, R. A. 2012; 36 (11): 1619-1628

    Abstract

    T-lymphoblastic lymphoma is an aggressive neoplasm requiring prompt clinical treatment. Conversely, indolent T-lymphoblastic proliferation mimics T-lymphoblastic lymphoma but consists of a proliferation of non-neoplastic TdT+ T cells, requiring no treatment. Recently, we identified several cases of indolent T-lymphoblastic proliferations in extrathymic lymphoid tissues: 1 in a patient suffering from Castleman disease (CD) associated with a follicular dendritic cell sarcoma/tumor, 1 in a patient with a history of angioimmunoblastic T-cell lymphoma (AITL), and 1 in association with acinic cell carcinoma. Interestingly, in the case of the patient with a history of AITL, these TdT+ T cells were seen in multiple anatomic sites over the span of 5 years. Here we review these 3 cases and extend our findings by demonstrating that TdT+ T-lymphoblastic populations are increased in lymph nodes of patients with CD (P=0.011), CD in association with follicular dendritic cell tumors, and AITL (P<0.01) compared with other T-cell or B-cell lymphomas or reactive lymph nodes. Finally, analysis of 352 nonhematolymphoid tumors including carcinomas, melanomas, and sarcomas demonstrates that TdT+ T cells are not increased in these tumors. Our studies not only present several detailed cases of indolent T-lymphoblastic proliferations, but also correlate these populations with specific hematologic diseases.

    View details for DOI 10.1097/PAS.0b013e318264e223

    View details for Web of Science ID 000310059600004

    View details for PubMedID 23060347

  • DNA methylation analysis of ALOX12 and GSTM1 in acute myeloid leukaemia identifies prognostically significant groups BRITISH JOURNAL OF HAEMATOLOGY Ohgami, R. S., Ma, L., Ren, L., Weinberg, O. K., Seetharam, M., Gotlib, J. R., Arber, D. A. 2012; 159 (2): 182-190

    Abstract

    To determine the role of DNA methylation in the progression of acute myeloid leukaemia (AML), we analysed the methylation status of ALOX12, GSTM1, HS3ST2 and FZD9 in 127 AML patients. Aberrant methylation of ALOX12 was associated with the subcategory AML with myelodysplasia-related changes (P=00439) and specifically with megakaryocytic dysplasia (P=00003). An association between HS3ST2 and AML patients with favourable cytogenetic risk was identified (P=00469). In univariate and multivariate analysis, methylation of GSTM1 was associated with worse overall survival (OS) and disease-free survival (DFS), with hazard ratios of 257 and 186, respectively. Furthermore, the significance of methylation of GSTM1 in predicting poor prognosis was maintained within the subcategories of AML not otherwise specified (NOS), AML with intermediate cytogenetic risk and normal karyotype AML. Finally, patients with both GSTM1 and ALOX12 methylated, demonstrated worse outcomes when all AML patients were assessed (OS; P=0000411) as well as within AML NOS (DFS; P=00023), AML with intermediate cytogenetic risk (OS; P=00104) and normal karyotype AML (OS; P=000636). This study implicates methylation of specific genes in the classification and prognostication of AML and suggests that the morphological feature of multilineage dysplasia may be a surrogate marker of gene methylation in at least a subset of AML cases.

    View details for DOI 10.1111/bjh.12029

    View details for Web of Science ID 000309242000009

    View details for PubMedID 22924777

  • Refining the diagnosis of T-cell large granular lymphocytic leukemia by combining distinct patterns of antigen expression with T-cell clonality studies LEUKEMIA Ohgami, R. S., Ohgami, J. K., Pereira, I. T., Gitana, G., Zehnder, J. L., Arber, D. A. 2011; 25 (9): 1439-1443

    Abstract

    T-cell large granular lymphocytic (LGL) leukemia is a complex diagnosis, requiring persistent clonal expansions of LGLs, and cytopenias. Often the diagnosis is unclear as non-clonal expansions of LGLs commonly occur in reactive conditions. To better understand T-LGL leukemia, we performed a comprehensive clinicopathologic analysis of 85 patients with LGL expansions. Interestingly, distinct CD8+(dim)/CD57+ populations, seen by flow cytometry, were significantly associated with clonal T-LGL leukemia (P < 0.001) as well as neutropenia (median absolute neutrophil count (ANC) 1.45 vs 3.19 10(9)/l; P = 0.0017). Furthermore, cases with distinct CD8+(dim)/CD57+ populations and monoclonal T cells had even lower ANCs (median ANC 1.41 10(9)/l; P = 0.001) compared with cases without these dual criteria. Additionally, complete or partial loss of CD5 expression was independently associated with clonal T-LGL leukemia (P<0.001) and neutropenia (median ANC 1.41 vs 2.70 10(9)/l; P = 0.002). This study describes specific immunophenotypic parameters to better define clonal cases of T-LGL leukemia associated with significant neutropenia.

    View details for DOI 10.1038/leu.2011.107

    View details for Web of Science ID 000294665400008

    View details for PubMedID 21617700

  • Indolent T-Lymphoblastic Proliferation (iT-LBP): A Review of Clinical and Pathologic Features and Distinction from Malignant T-Lymphoblastic Lymphoma ADVANCES IN ANATOMIC PATHOLOGY Ohgami, R. S., Arber, D. A., Zehnder, J. L., Natkunam, Y., Warnke, R. A. 2013; 20 (3): 137-140

    Abstract

    In recent years, a new pathologic entity has emerged: indolent T-lymphoblastic proliferation (iT-LBP). iT-LBPs share immunophenotypic similarities with T-lymphoblastic lymphoma; however, T-lymphoblastic proliferations are clinically indolent, and unlike the malignant counterpart, these expansions of nonclonal terminal deoxynucleotidyl transferase (TdT)+ T cells do not require treatment. Here we review the clinical and pathologic features, which are required for an accurate diagnosis of an iT-LBP. We demonstrate specific criteria can be used to accurately diagnose iT-LBP, notably: (1) confluent groups of TdT+ T cells in a biopsy specimen, (2) relative preservation of surrounding normal lymphoid architecture, (3) TdT+ T cells without morphologic atypia, (4) absence of thymic epithelium, (5) nonclonal TdT+ T cells, (6) immunophenotype of developmentally normal immature thymic T cells, and (7) clinical evidence of indolence (follow-up >6 mo without progression).

    View details for DOI 10.1097/PAP.0b013e31828d17ec

    View details for Web of Science ID 000317588700001

    View details for PubMedID 23574769

  • Challenges in Consolidated Reporting of Hematopoietic Neoplasms Surgical Pathology Clinics Ohgami, R. S., Arber, D. A. 2013
  • The Efficacy of HGAL and LMO2 in the Separation of Lymphomas Derived From Small B Cells in Nodal and Extranodal Sites, Including the Bone Marrow AMERICAN JOURNAL OF CLINICAL PATHOLOGY Younes, S. F., Beck, A. H., Ohgami, R. S., Lossos, I. S., Levy, R., Warnke, R. A., Natkunam, Y. 2011; 135 (5): 697-708

    Abstract

    We studied the efficacy of 2 germinal center B-cell markers, HGAL and LMO2, in the separation of lymphomas derived from small B cells, particularly follicular lymphoma (FL) and marginal zone lymphoma occurring in nodal, extranodal, splenic, and bone marrow sites using immunohistochemical analysis for CD10, BCL6, BCL2, HGAL, and LMO2. Our results showed that HGAL and LMO2 are sensitive and specific markers for detecting FL in nodal and extranodal sites. In contrast, all markers were down-regulated in FL infiltrates in the bone marrow. CD10 and HGAL were expressed in a subset of FLs in the bone marrow and were highly correlated with each other and with CD21, a marker of follicular dendritic cells. We conclude that HGAL and LMO2 should be considered in immunohistochemical panels used for the routine workup of lymphomas derived from small B cells. In the bone marrow, staining for HGAL or CD10 can be helpful in making a diagnosis of FL, although they are absent in a subset of cases.

    View details for DOI 10.1309/AJCP7Z2BIBUNQPLZ

    View details for Web of Science ID 000289743400007

    View details for PubMedID 21502424

  • PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from Heal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma MODERN PATHOLOGY Sangoi, A. R., Ohgami, R. S., Pai, R. K., Beck, A. H., McKenney, J. K., Pai, R. K. 2011; 24 (3): 412-424

    Abstract

    PAX (paired box) genes encode a family of transcription factors that regulate organogenesis in a variety of organs. Very little is known about the role of PAX8 in endocrine cell development and the expression of PAX8 in neuroendocrine tumors. The purpose of this study was to analyze PAX8 immunohistochemical expression in gastroenteropancreatic and pulmonary well-differentiated neuroendocrine tumors to determine whether PAX8 can reliably distinguish pancreatic neuroendocrine tumors from neuroendocrine tumors of other anatomic sites and other pancreatic non-ductal neoplasms. In total, 221 well-differentiated neuroendocrine tumors were evaluated: 174 primary neuroendocrine tumors (66 pancreatic, 31 ileal, 21 pulmonary, 20 gastric, 17 rectal, 11 appendiceal, and 8 duodenal) and 47 neuroendocrine tumors metastatic to the liver (31 pancreatic, 11 ileal, 2 pulmonary, 2 duodenal, and 1 rectal). Fifteen solid-pseudopapillary neoplasms and six acinar cell carcinomas of the pancreas were also evaluated. PAX8 was positive in 49/66 (74%) primary pancreatic neuroendocrine tumors. PAX8 expression did not correlate with World Health Organization categorization, grade, size, functional status, or the presence of liver or lymph node metastasis. PAX8 expression was identified in 0/31 (0%) ileal, 0/21 (0%) pulmonary, 2/20 (10%) gastric, 5/17 (29%) rectal, 1/11 (9%) appendiceal, and 6/8 (75%) duodenal neuroendocrine tumors. PAX8 was positive in 4/15 (27%) solid-pseudopapillary neoplasms of the pancreas, whereas all acinar cell carcinomas (0/6) lacked immunoreactivity. Among liver metastases, only pancreatic neuroendocrine tumors (20/31, 65%) were PAX8 positive, whereas no cases of ileal (0/11), pulmonary (0/2), duodenal (0/2), and rectal (0/1) neuroendocrine tumor metastases were PAX8 positive. PAX8 is expressed in primary and metastatic pancreatic well-differentiated neuroendocrine tumors, and its expression can reliably distinguish pancreatic from ileal and pulmonary well-differentiated neuroendocrine tumors. Duodenal neuroendocrine tumors and a subset of rectal, gastric, and appendiceal neuroendocrine tumors may also express PAX8. PAX8 expression can distinguish pancreatic neuroendocrine tumors from acinar cell carcinomas, but its utility in distinguishing neuroendocrine tumors from solid-pseudopapillary neoplasms is limited.

    View details for DOI 10.1038/modpathol.2010.176

    View details for Web of Science ID 000287986600009

    View details for PubMedID 20890270

  • Diagnosing PNH in the era of FLAER Blood K, H., R, O. S., D, A. A., A, A., St, C. 2011; [e-letter]
  • Structure of the membrane proximal oxidoreductase domain of human Steap3, the dominant ferrireductase of the erythroid transferrin cycle PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Sendamarai, A. K., Ohgami, R. S., Fleming, M. D., Lawrence, C. M. 2008; 105 (21): 7410-7415

    Abstract

    The daily production of 200 billion erythrocytes requires 20 mg of iron, accounting for nearly 80% of the iron demand in humans. Thus, erythroid precursor cells possess an efficient mechanism for iron uptake in which iron loaded transferrin (Tf) binds to the transferrin receptor (TfR) at the cell surface. The Tf:TfR complex then enters the endosome via receptor-mediated endocytosis. Upon endosomal acidification, iron is released from Tf, reduced to Fe(2+) by Steap3, and transported across the endosomal membrane by divalent metal iron transporter 1. Steap3, the major ferrireductase in erythrocyte endosomes, is a member of a unique family of reductases. Steap3 is comprised of an N-terminal cytosolic oxidoreductase domain and a C-terminal heme-containing transmembrane domain. Cytosolic NADPH and a flavin are predicted cofactors, but the NADPH/flavin binding domain differs significantly from those in other eukaryotic reductases. Instead, Steap3 shows remarkable, although limited homology to FNO, an archaeal oxidoreductase. We have determined the crystal structure of the human Steap3 oxidoreductase domain in the absence and presence of NADPH. The structure reveals an FNO-like domain with an unexpected dimer interface and substrate binding sites that are well positioned to direct electron transfer from the cytosol to a heme moiety predicted to be fixed within the transmembrane domain. Here, we discuss possible gating mechanisms for electron transfer across the endosomal membrane.

    View details for DOI 10.1073/pnas.0801318105

    View details for Web of Science ID 000256378100015

    View details for PubMedID 18495927

  • The Steap proteins are metalloreductases BLOOD Ohgami, R. S., Campagna, D. R., McDonald, A., Fleming, M. D. 2006; 108 (4): 1388-1394

    Abstract

    Iron and copper are essential for all organisms, assuming critical roles as cofactors in many enzymes. In eukaryotes, the transmembrane transport of these elements is a highly regulated process facilitated by the single electron reduction of each metal. Previously, we identified a mammalian ferrireductase, Steap3, critical for erythroid iron homeostasis. Now, through homology, expression, and functional studies, we characterize all 4 members of this protein family and demonstrate that 3 of them, Steap2, Steap3, and Steap4, are not only ferrireductases but also cupric reductases that stimulate cellular uptake of both iron and copper in vitro. Finally, the pattern of tissue expression and subcellular localization of these proteins suggest they are physiologically relevant cupric reductases and ferrireductases in vivo.

    View details for DOI 10.1182/blood-2006-02-003681

    View details for Web of Science ID 000239698800047

    View details for PubMedID 16609065

  • nm1054: a spontaneous, recessive, hypochromic, microcytic anemia mutation in the mouse BLOOD Ohgami, R. S., Campagna, D. R., Antiochos, B., Wood, E. B., Sharp, J. J., Barker, J. E., Fleming, M. D. 2005; 106 (10): 3625-3631

    Abstract

    Hypochromic, microcytic anemias are typically the result of inadequate hemoglobin production because of globin defects or iron deficiency. Here, we describe the phenotypic characteristics and pathogenesis of a new recessive, hypochromic, microcytic anemia mouse mutant, nm1054. Although the mutation nm1054 is pleiotropic, also resulting in sparse hair, male infertility, failure to thrive, and hydrocephaly, the anemia is the focus of this study. Hematologic analysis reveals a moderately severe, congenital, hypochromic, microcytic anemia, with an elevated red cell zinc protoporphyrin, consistent with functional erythroid iron deficiency. However, serum and tissue iron analyses show that nm1054 animals are not systemically iron deficient. From hematopoietic stem cell transplantation and iron uptake studies in nm1054 reticulocytes, we provide evidence that the nm1054 anemia is due to an intrinsic hematopoietic defect resulting in inefficient transferrin-dependent iron uptake by erythroid precursors. Linkage studies demonstrate that nm1054 maps to a genetic locus not previously implicated in microcytic anemia or iron phenotypes.

    View details for DOI 10.1182/blood-2005-01-0379

    View details for Web of Science ID 000233187700052

    View details for PubMedID 15994289

  • Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells NATURE GENETICS Ohgami, R. S., Campagna, D. R., Greer, E. L., Antiochos, B., McDonald, A., Chen, J., Sharp, J. J., Fujiwara, Y., Barker, J. E., Fleming, M. D. 2005; 37 (11): 1264-1269

    Abstract

    The reduction of iron is an essential step in the transferrin (Tf) cycle, which is the dominant pathway for iron uptake by red blood cell precursors. A deficiency in iron acquisition by red blood cells leads to hypochromic, microcytic anemia. Using a positional cloning strategy, we identified a gene, six-transmembrane epithelial antigen of the prostate 3 (Steap3), responsible for the iron deficiency anemia in the mouse mutant nm1054. Steap3 is expressed highly in hematopoietic tissues, colocalizes with the Tf cycle endosome and facilitates Tf-bound iron uptake. Steap3 shares homology with F(420)H(2):NADP(+) oxidoreductases found in archaea and bacteria, as well as with the yeast FRE family of metalloreductases. Overexpression of Steap3 stimulates the reduction of iron, and mice lacking Steap3 are deficient in erythroid ferrireductase activity. Taken together, these findings indicate that Steap3 is an endosomal ferrireductase required for efficient Tf-dependent iron uptake in erythroid cells.

    View details for DOI 10.1038/ng1658

    View details for Web of Science ID 000233045200028

    View details for PubMedID 16227996

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