Publications by authors named "Huan-You Wang"

90 Publications

Cutaneous intralymphatic anaplastic lymphoma kinase-negative anaplastic large-cell lymphoma arising in a patient with multiple rounds of breast implants.

J Cutan Pathol 2020 Dec 12. Epub 2020 Dec 12.

Division of Blood and Marrow Transplant, Department of Medicine, University of California San Diego Health System, La Jolla, California, USA.

Primary cutaneous anaplastic large-cell lymphoma and breast implant-associated ALCL (BIA-ALCL) are rare subtypes of anaplastic lymphoma kinase (ALK)-negative ALCLs originating from skin and breast implants, respectively. Herein, we report a unique case of cutaneous ALK-negative ALCL occurring in the skin of left medial breast from a patient with multiple rounds of bilateral breast implants and a history of breast carcinoma. The lymphoma cells are entirely confined to the lymphatic channels in the dermis, and the patient has no other areas of skin abnormality, no lymphadenopathy, peri-implant fluid accumulation, or masses from the bilateral capsules of implants. The differential diagnosis and its relationship with breast implants are further explored.
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http://dx.doi.org/10.1111/cup.13936DOI Listing
December 2020

Extramedullary early T-cell precursor acute lymphoblastic lymphoma presenting as blast crisis of CML.

Blood 2020 Aug;136(9):1112

University of California San Diego Health System.

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http://dx.doi.org/10.1182/blood.2020006326DOI Listing
August 2020

Epstein-Barr Virus-negative Marginal Zone Lymphoma as an Uncommon Form of Monomorphic Posttransplant Lymphoproliferative Disorder.

Am J Surg Pathol 2020 10;44(10):1340-1352

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD.

Monomorphic posttransplant lymphoproliferative disorders have been defined as lymphoid or plasmacytic proliferations that fulfill criteria for one of the B-cell or T/NK-cell neoplasms recognized in immunocompetent hosts in the current WHO Classification. Low-grade B-cell neoplasms have historically been excluded from this category, although rare reports of marginal zone lymphoma (MZL) have been described. We report 9 cases of posttransplant Epstein-Barr virus-negative MZL, all arising in solid organ transplant recipients (4 renal, 3 liver, 1 cardiac, and 1 liver, pancreas, and small bowel). Seven were extranodal MZL of mucosa-associated lymphoid tissue type, all of which had gastrointestinal involvement (4 colon, 1 duodenum, 1 stomach, and 1 oropharynx/base of tongue). Notably, the preferential involvement of intestine distinguishes posttransplant extranodal MZL from sporadic cases. Immunoglobulin light-chain restriction was seen in all cases, with polymerase chain reaction showing a monoclonal pattern in 7 of 8 cases with successful amplification of polymerase chain reaction products. A clonally unrelated recurrence was seen in one case. Next-generation sequencing identified recurrent mutations previously reported in MZL in 3/5 cases. MZL was diagnosed at least 1 year after solid organ transplant (median time to presentation, 84 mo; range, 13 to 108 mo). The median age was 44 (range, 9 to 73 y); the male: female ratio was 5:4. The mean follow-up was 33.4 months, with an indolent clinical course observed. A subset responded to reduction in immunosuppression and anti-CD20 therapy alone. These data support the designation of Epstein-Barr virus-negative MZL as an uncommon form of monomorphic posttransplant lymphoproliferative disorders.
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http://dx.doi.org/10.1097/PAS.0000000000001514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492423PMC
October 2020

An IgA plasmacytoma: a rare and distinct form of plasmacytoma.

Blood 2020 04;135(17):1505

University of California San Diego Health System.

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http://dx.doi.org/10.1182/blood.2020004978DOI Listing
April 2020

B-cell lymphomas associated with breast implants: Report of three cases and review of the literature.

Ann Diagn Pathol 2020 Jun 28;46:151512. Epub 2020 Mar 28.

Department of Medicine, Hematology/Oncology Division, University of California Irvine (UCI) Medical Center, Orange, CA, United States of America. Electronic address:

Since the first reported case in 1997, over 600 women with breast implant-associated anaplastic large cell lymphoma (BI ALCL) have been reported. BI ALCL is a CD30-positive T-cell lymphoma that carries clonal T-cell receptor gene rearrangements, and a subset of cases harbors mutations in the JAK-STAT signaling pathway. Rarely, other histologic types of lymphoma have been reported in association with breast implants, including fewer than 10 cases of B-cell origin. Here, we describe three additional patients with B-cell lymphoma occurring around breast implants. Two of these patients developed extranodal marginal zone lymphoma in the peri-implant capsule, one of which had a concurrent ALCL within the superficial lining of the capsule. The third patient presented with diffuse large B-cell lymphoma inside the breast parenchyma surrounding her implant. Determining the etiology and risk factors for the development of B-cell lymphomas associated with breast implants remains challenging, given the wide spectrum of histologic features and the rarity of these neoplasms. Ultimately, we document three new cases of B-cell lymphoma arising around breast implants and highlight their clinical and pathologic features in order to expand our understanding of this rare disease presentation.
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http://dx.doi.org/10.1016/j.anndiagpath.2020.151512DOI Listing
June 2020

Machine Learning of Discriminative Gate Locations for Clinical Diagnosis.

Cytometry A 2020 03 5;97(3):296-307. Epub 2019 Nov 5.

Department of Computer Science, University of California, Irvine, California.

High-throughput single-cell cytometry technologies have significantly improved our understanding of cellular phenotypes to support translational research and the clinical diagnosis of hematological and immunological diseases. However, subjective and ad hoc manual gating analysis does not adequately handle the increasing volume and heterogeneity of cytometry data for optimal diagnosis. Prior work has shown that machine learning can be applied to classify cytometry samples effectively. However, many of the machine learning classification results are either difficult to interpret without using characteristics of cell populations to make the classification, or suboptimal due to the use of inaccurate cell population characteristics derived from gating boundaries. To date, little has been done to optimize both the gating boundaries and the diagnostic accuracy simultaneously. In this work, we describe a fully discriminative machine learning approach that can simultaneously learn feature representations (e.g., combinations of coordinates of gating boundaries) and classifier parameters for optimizing clinical diagnosis from cytometry measurements. The approach starts from an initial gating position and then refines the position of the gating boundaries by gradient descent until a set of globally-optimized gates across different samples are achieved. The learning procedure is constrained by regularization terms encoding domain knowledge that encourage the algorithm to seek interpretable results. We evaluate the proposed approach using both simulated and real data, producing classification results on par with those generated via human expertise, in terms of both the positions of the gating boundaries and the diagnostic accuracy. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.
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http://dx.doi.org/10.1002/cyto.a.23906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079150PMC
March 2020

Cutaneous composite small lymphocytic lymphoma and primary cutaneous follicle center lymphoma.

Blood 2019 08;134(8):717

University of California San Diego Health System.

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http://dx.doi.org/10.1182/blood.2019001287DOI Listing
August 2019

Hippo kinase loss contributes to del(20q) hematologic malignancies through chronic innate immune activation.

Blood 2019 11;134(20):1730-1744

Moores Cancer Center.

Heterozygous deletions within chromosome 20q, or del(20q), are frequent cytogenetic abnormalities detected in hematologic malignancies. To date, identification of genes in the del(20q) common deleted region that contribute to disease development have remained elusive. Through assessment of patient gene expression, we have identified STK4 (encoding Hippo kinase MST1) as a 20q gene that is downregulated below haploinsufficient amounts in myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). Hematopoietic-specific gene inactivation in mice revealed Hippo kinase loss to induce splenomegaly, thrombocytopenia, megakaryocytic dysplasia, and a propensity for chronic granulocytosis; phenotypes that closely resemble those observed in patients harboring del(20q). In a JAK2-V617F model, heterozygous Hippo kinase inactivation led to accelerated development of lethal myelofibrosis, recapitulating adverse MPN disease progression and revealing a novel genetic interaction between these 2 molecular events. Quantitative serum protein profiling showed that myelofibrotic transformation in mice was associated with cooperative effects of JAK2-V617F and Hippo kinase inactivation on innate immune-associated proinflammatory cytokine production, including IL-1β and IL-6. Mechanistically, MST1 interacted with IRAK1, and shRNA-mediated knockdown was sufficient to increase IRAK1-dependent innate immune activation of NF-κB in human myeloid cells. Consistent with this, treatment with a small molecule IRAK1/4 inhibitor rescued the aberrantly elevated IL-1β production in the JAK2-V617F MPN model. This study identified Hippo kinase MST1 (STK4) as having a central role in the biology of del(20q)-associated hematologic malignancies and revealed a novel molecular basis of adverse MPN progression that may be therapeutically exploitable via IRAK1 inhibition.
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http://dx.doi.org/10.1182/blood.2019000170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856986PMC
November 2019

SOHO State of the Art Updates and Next Questions: The Conundrum in Assessing the Therapy Response of Patients With Chronic Lymphocytic Leukemia.

Clin Lymphoma Myeloma Leuk 2019 06 29;19(6):321-325. Epub 2019 May 29.

Division of Hematology/Oncology, UC San Diego Moores Cancer Center, La Jolla, CA. Electronic address:

In 2018, the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) updated the guidelines for diagnosis, indications for treatment, response assessment, and supportive management of patients with chronic lymphocytic leukemia. Included were definitions for response, which incorporated consideration of the significance of minimal residual disease. Here we discuss the clinical significance of complete response or partial response, as defined in the 2018 iwCLL guidelines, and the relative value of assessing for minimal residual disease.
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http://dx.doi.org/10.1016/j.clml.2019.05.013DOI Listing
June 2019

Acute myeloid leukaemia evolving from essential thrombocythaemia with marked KMT2A amplification as a homogenously staining region.

Br J Haematol 2019 08 28;186(4):509. Epub 2019 May 28.

Division of Laboratory and Genomic Medicine, Departments of Pathology, University of California San Diego Health Sciences, La Jolla, CA, USA.

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http://dx.doi.org/10.1111/bjh.15985DOI Listing
August 2019

Activity of brentuximab vedotin in AIDS-related primary effusion lymphoma.

Blood Adv 2019 03;3(5):766-768

Division of Hematology/Oncology, UC San Diego Moores Cancer Center, La Jolla, CA.

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http://dx.doi.org/10.1182/bloodadvances.2018026351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418491PMC
March 2019

and expression predicts Richter syndrome in chronic lymphocytic leukemia patients.

Blood 2018 11 21;132(20):2179-2182. Epub 2018 Sep 21.

Department of Cancer Biology and Medical Genetics and.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. It is characterized by the accumulation of CD19/CD5 lymphocytes and can have variable outcomes. Richter syndrome (RS) is a lethal complication in CLL patients that results in aggressive B-cell lymphomas, and there are no tests to predict its occurrence. Because alterations in microRNA expression can predict the development and progression of several cancers, we investigated whether dysregulation of specific microRNAs can predict RS in CLL patients. Thus, we compared microRNA expression levels in samples from 49 CLL patients who later developed RS with samples from 59 CLL patients who did not. We found that high expression of or low expression of can predict ∼50% of RS with a false positive rate of ∼9%. We found that CLL patients predicted to develop RS show either an increase of expression (∼20-fold) or a decrease of expression (∼21-fold) compared with CLL patients that are not predicted to develop RS. Thus, and can be valuable predictor markers of RS and have the potential to provide physicians with information that can indicate the best therapeutic strategy for CLL patients.
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http://dx.doi.org/10.1182/blood-2018-04-845115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238191PMC
November 2018

JAK2 double minutes with resultant simultaneous amplification of JAK2 and CD274 in a therapy-related myelodysplastic syndrome evolving into an acute myeloid leukaemia.

Br J Haematol 2019 05 21;185(3):566-570. Epub 2018 Aug 21.

Division of Laboratory and Genomic Medicine, Department of Pathology, University of California San Diego, La Jolla, CA, USA.

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http://dx.doi.org/10.1111/bjh.15538DOI Listing
May 2019

Prevalence of PDL1 Amplification and Preliminary Response to Immune Checkpoint Blockade in Solid Tumors.

JAMA Oncol 2018 09;4(9):1237-1244

Division of Hematology/Oncology, Department of Medicine, University of California, San Diego, La Jolla.

Importance: Copy number alterations in programmed cell death ligand 1 (PDL1 or CD274), programmed cell death 1 ligand 2 (PDCD1LG2 or PDL2), and Janus kinase 2 (JAK2) genes (chromosome 9p24.1) characterize Hodgkin lymphoma, resulting in high response rates to programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) blockade. The prevalence and utility of PDL1 amplification as a response biomarker to PD-1/PD-L1 blockade are unknown in other tumors.

Objectives: To examine the prevalence of PDL1 amplification and its utility as a response biomarker to PD-1/PD-L1 blockade in solid tumors.

Design, Setting, And Participants: This retrospective study (October 1, 2012, to October 1, 2017) used a deidentified tumor database from a commercial company and annotated clinical records from a subset of patients treated at a university tertiary referral center. The study analyzed 118 187 tumors from the deidentified database, including a clinically annotated subgroup of 2039 malignant tumors.

Interventions: Comprehensive genomic profiling was performed on all samples to determine PDL1 amplification, microsatellite instability, and tumor mutational burden (TMB). A subset of patients was treated with PD-1/PD-L1 blockade.

Main Outcomes And Measures: The prevalence of PDL1 amplification was determined among 118 187 patient samples that underwent next-generation sequencing. Solid tumors treated with checkpoint blockade were evaluated for response and progression-free survival (PFS).

Results: Of the 118 187 deidentified tumor samples, PDL1 amplifications were identified in 843 (0.7%), including more than 100 types of solid tumors. Most PDL1-amplified tumors (84.8%) had a low to intermediate TMB. PDL1 amplification did not always correlate with high-positive PD-L1 expression by immunohistochemical analysis. Six of 9 patients (66.7%) from 1 center with PDL1-amplified solid tumors had objective responses after checkpoint blockade administration. The median PFS among all treated patients was 15.2 months. Responders included 1 patient with glioblastoma (PFS, ≥5.2 months), 2 patients with head and neck squamous cell cancer (PFS, ≥9 and 15.2 months), 2 patients with metastatic basal cell cancer (PFS, 3.8 and ≥24.1 months), and 1 patient with urothelial cancer (PFS, ≥17.8 months).

Conclusions And Relevance: The results of this study suggest that PDL1 amplification occurs in a small subset of malignant tumors. Additional large-scale, prospective studies of PDL1-amplified cancers are warranted to confirm the responses to checkpoint blockade described herein, even in the absence of microsatellite instability, high PD-L1 expression, and a high TMB.
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http://dx.doi.org/10.1001/jamaoncol.2018.1701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139049PMC
September 2018

JAK2 V617F mutation in plasma cell-free DNA preceding clinically overt myelofibrosis: Implications for early diagnosis.

Cancer Biol Ther 2018 08;19(8):664-668

a Center for Personalized Cancer Therapy and Division of Hematology and Oncology, Department of Medicine , University of California San Diego Moores Cancer Center , La Jolla , CA , USA.

A 52 year-old man with Erdheim-Chester Disease (ECD) (a non-Langerhans polyostotic sclerosing histiocytosis) had next-generation sequencing (NGS) performed as part of his diagnostic workup. In addition to the tissue BRAF V600E mutation that is found in over 50% of ECD cases, he was also found to have a JAK2 V617F alteration in cell-free circulating tumor DNA (ctDNA) (liquid biopsy). The latter was thought to be an "incidental" finding, perhaps due to clonal hematopoiesis (though this usually occurs in older individuals), as his blood counts were normal and he had no splenomegaly. Approximately 13 months after the ctDNA test showing JAK2 V617F, he developed anemia, thrombocytopenia, and splenomegaly. Marrow biopsy then showed megakaryocytic atypia and markedly increased marrow fibrosis, consistent with WHO grade 2 of 3 myelofibrosis. Therefore, the patient was determined to have ECD with a typical BRAF V600E mutation, as well as primary myelofibrosis, with the latter diagnosis manifesting clinically over one year after the JAK2 V617F was first detected in ctDNA. He recently was started on the JAK2 inhibitor ruxolitinib. This case demonstrates that genomic alterations detected by liquid biopsy for evaluation of specific malignancies already present may serve as an early harbinger of hematological disease.
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http://dx.doi.org/10.1080/15384047.2018.1450120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067874PMC
August 2018

An anaplastic T-cell lymphoma mimicking classical Hodgkin lymphoma.

Blood 2018 03;131(11):1262

National Institutes of Health.

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http://dx.doi.org/10.1182/blood-2017-12-819987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855023PMC
March 2018

CAMKs support development of acute myeloid leukemia.

J Hematol Oncol 2018 02 27;11(1):30. Epub 2018 Feb 27.

Departments of Physiology and Developmental Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX, 75390, USA.

Background: We recently identified the human leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse ortholog-paired Ig-like receptor (PirB) as receptors for several angiopoietin-like proteins (Angptls). We also demonstrated that PirB is important for the development of acute myeloid leukemia (AML), but exactly how an inhibitory receptor such as PirB can support cancer development is intriguing.

Results: Here, we showed that the activation of Ca (2+)/calmodulin-dependent protein kinases (CAMKs) is coupled with PirB signaling in AML cells. High expression of CAMKs is associated with a poor overall survival probability in patients with AML. Knockdown of CAMKI or CAMKIV decreased human acute leukemia development in vitro and in vivo. Mouse AML cells that are defective in PirB signaling had decreased activation of CAMKs, and the forced expression of CAMK partially rescued the PirB-defective phenotype in the MLL-AF9 AML mouse model. The inhibition of CAMK kinase activity or deletion of CAMKIV significantly slowed AML development and decreased the AML stem cell activity. We also found that CAMKIV acts through the phosphorylation of one of its well-known target (CREB) in AML cells.

Conclusion: CAMKs are essential for the growth of human and mouse AML. The inhibition of CAMK signaling may become an effective strategy for treating leukemia.
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http://dx.doi.org/10.1186/s13045-018-0574-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828341PMC
February 2018

Composite morphologically and immunohistochemically distinct classical and pleomorphic mantle cell lymphomas.

Blood 2018 01;131(3):372

University of California San Diego Health System.

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http://dx.doi.org/10.1182/blood-2017-09-807230DOI Listing
January 2018

Automated Analysis of Clinical Flow Cytometry Data: A Chronic Lymphocytic Leukemia Illustration.

Clin Lab Med 2017 12;37(4):931-944

Department of Informatics, J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA 92037, USA.

Flow cytometry is used in cell-based diagnostic evaluation for blood-borne malignancies including leukemia and lymphoma. The current practice for cytometry data analysis relies on manual gating to identify cell subsets in complex mixtures, which is subjective, labor-intensive, and poorly reproducible. This article reviews recent efforts to develop, validate, and disseminate automated computational methods and pipelines for cytometry data analysis that could help overcome the limitations of manual analysis and provide for efficient and data-driven diagnostic applications. It demonstrates the performance of an optimized computational pipeline in a pilot study of chronic lymphocytic leukemia data from the authors' clinical diagnostic laboratory.
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http://dx.doi.org/10.1016/j.cll.2017.07.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766345PMC
December 2017

PAX5-Negative Classical Hodgkin Lymphoma: A Case Report of a Rare Entity and Review of the Literature.

Case Rep Hematol 2017 4;2017:7531729. Epub 2017 Oct 4.

Department of Pathology and Laboratory Medicine, University of California, Davis, Davis, CA, USA.

Classical Hodgkin lymphoma (CHL) is recognized as a B-cell neoplasm arising from germinal center or postgerminal center B-cells. The hallmark of CHL is the presence of CD30 (+) Hodgkin and Reed-Sternberg (HRS) cells with dim expression of PAX5. Nearly all of the HRS cells are positive for PAX5. However, a small minority of HRS cells may lack PAX5 expression, which can cause a diagnostic dilemma. Herein we describe two cases of PAX5-negative CHL and review of the English literature on this very rare entity. It is crucial to be aware of this phenomenon, which in some cases may lead to misdiagnosis and may ultimately adversely affect patient's management.
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http://dx.doi.org/10.1155/2017/7531729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646291PMC
October 2017

Exuberant nodal proliferation of mature plasmacytoid dendritic cells in a patient with chronic myelomonocytic leukemia.

Blood 2017 09;130(11):1387

Mayo Clinic.

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http://dx.doi.org/10.1182/blood-2017-04-779017DOI Listing
September 2017

CD5/SOX-11 mantle cell lymphoma with concomitant monotypic plasmacytic differentiation.

Blood 2016 10;128(14):1904

University of California San Diego Health Sciences System.

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http://dx.doi.org/10.1182/blood-2016-06-724757DOI Listing
October 2016

Diagnostic Algorithm of Common Mature B-Cell Lymphomas by Immunohistochemistry.

Arch Pathol Lab Med 2017 Sep 13;141(9):1236-1246. Epub 2017 Jun 13.

Context: - Different types of mature B-cell lymphomas, including plasma cell neoplasms, exhibit distinct immunohistochemical profiles, which enable them to be correctly diagnosed. However, except for rare examples of lymphoma-specific immunohistochemistry, such as cyclin D1 in mantle cell lymphoma and annexin A1 in hairy cell leukemia, immunohistochemical profiles of mature B-cell lymphomas overlap and lack specificity.

Objectives: - To systemically review immunohistochemical features associated with commonly encountered mature B-cell lymphomas based on the presence or absence of CD5 and CD10; to review the immunophenotypic profile of plasma cells derived from plasma cell myelomas and B-cell lymphomas; and to review a group of rare, aggressive B-cell lymphomas with antigen expression features of plasma cells.

Data Sources: - Published and PubMed-indexed English literature was reviewed.

Conclusions: - Although the presence or absence of CD5 and CD10 expression should be included in the initial immunohistochemistry screening panel for mature B-cell lymphomas, appropriate and judicial use of other B-cell antigens is necessary to ensure correct diagnoses. Furthermore, although the status of CD5 and CD10 expression is associated with certain prototypes of B-cell lymphomas, their expression is not specific. Plasma cells from plasma cell neoplasias and B-cell lymphomas exhibit overlapping but relatively distinct immunophenotypes; thus, a panel of immunohistochemical markers (CD19, CD45, CD56, and CD117) can be employed for their proper identification. Lastly, CD138 staining results are almost always positive in a group of aggressive B-cell lymphomas with plasmablastic features, including plasmablastic plasma cell myeloma, plasmablastic lymphoma, and ALK-1 large B-cell lymphoma.
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http://dx.doi.org/10.5858/arpa.2016-0521-RADOI Listing
September 2017

Cyclin D1-negative blastoid mantle cell lymphoma exhibiting cleaved to bilobated cytomorphology.

Blood 2017 05;129(19):2711

University of California San Diego.

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http://dx.doi.org/10.1182/blood-2017-02-766485DOI Listing
May 2017

Large B-cell lymphoma variant of Richter transformation originates in pseudoproliferation centers of small lymphocytic lymphoma.

Authors:
Huan-You Wang

Blood 2017 05;129(18):2592

University of California, San Diego.

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http://dx.doi.org/10.1182/blood-2017-02-766857DOI Listing
May 2017

PD-L1 and Notch1 expression in KSHV/HHV-8 and EBV associated germinotropic lymphoproliferative disorder: case report and review of the literature.

Pathology 2017 Jun 24;49(4):430-435. Epub 2017 Apr 24.

Department of Pathology and Laboratory Medicine, Hofstra North Shore-LIJ School of Medicine, Lake Success, NY, United States.

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http://dx.doi.org/10.1016/j.pathol.2017.03.003DOI Listing
June 2017

A CD34-negative -rearranged B-lymphoblastic lymphoma aberrantly expresses CD3 and CD5.

Blood 2017 03;129(10):1403

University of California San Diego.

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http://dx.doi.org/10.1182/blood-2016-10-745620DOI Listing
March 2017

mTOR activity in AIDS-related diffuse large B-cell lymphoma.

PLoS One 2017 13;12(2):e0170771. Epub 2017 Feb 13.

Division of Clinical Pathology, Department of Pathology, University of California, San Diego, La Jolla, CA, United States of America.

Background: Patients infected with HIV have a significantly increased risk of developing non-Hodgkin lymphomas despite the widespread use of HAART. To investigate mTOR pathway activity in acquired immunodeficiency syndrome (AIDS) related diffuse large B-cell lymphoma AR-DLBCL, we used immunohistochemistry to examine the presence of the phosphorylated 70 ribosomal S6 protein-kinase (p70S6K), an extensively studied effector of mTOR Complex 1 (mTORC1) and the phosphorylated phosphatase and tensin homolog (pPTEN), a negative regulator of mTORC1 pathway.

Materials And Methods: We evaluated tissue samples from 126 patients with AR-DLBCL. Among them, 98 samples were from tissue microarrays (TMAs) supplied by the Aids and Cancer Specimen Resource (ACSR), the remaining 28 samples were from cases diagnosed and treated at the University of California, San Diego (UCSD). The presence of p70S6K was evaluated with two antibodies directed against the combined epitopes Ser235/236 and Ser240/244, respectively; and additional monoclonal anti-bodies were used to identify pPTEN and phosphorylated proline-rich Akt substrate of 40kDa (pPRAS40). The degree of intensity and percentage of cells positive for p70S6K and pPTEN were assessed in all the samples. In addition, a subgroup of 28 patients from UCSD was studied to assess the presence of pPRAS40, an insulin-regulated activator of the mTORC1. The expression of each of these markers was correlated with clinical and histopathologic features.

Results: The majority of the patients evaluated were males (88%); only two cases (1.6%) were older than 65 years of age. We found high levels of both p70S6K-paired epitopes studied, 48% positivity against Ser235/236 (44% in ACSR and 64% in UCSD group), and 86% positivity against Ser240/244 (82% in ACSR and 100% in UCSD group). We observed more positive cells and stronger intensity with epitope Ser240/244 in comparison to Ser235/236 (p<0.0001). The degree of intensity and percentage of cells positive for pPTEN was positively correlated with p70S6K levels (p = 0.016 for 235/236 and p = 0.007 for 240/244). High levels of pPRAS40 were observed in the majority of the cases evaluated (64.3%), but no correlation was found with either pPTEN (p = 0.9) or p70S6K (p = 0.9) levels.

Conclusion: AR-DLBCL frequently contain p70S6K, a main downstream effector of the mTOR pathway. The presence of p70S6K is positively correlated with pPTEN, an inactive form of PTEN, which makes mTORC1 activated. The presence of p70S6K was independent of HIV viral load or CD4 (+) counts. These results suggest that the mTOR pathway is active in the majority of AR-DLBCL, and p70S6K, particularly the Ser240/244 epitope immunohistochemistry is an excellent surrogate biomarker, which could be used to identify cases expected to be responsive to mTOR inhibitors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170771PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5305194PMC
August 2017

Diagnostic pitfall: primary effusion lymphoma with rare cytokeratin immunoreactivity.

Blood 2016 06;127(24):3102

University of California San Diego Health Sciences System.

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http://dx.doi.org/10.1182/blood-2016-01-692616DOI Listing
June 2016

Thoracic Extramedullary Hematopoiesis Mimicking Metastatic Cancer.

J Bronchology Interv Pulmonol 2016 Oct;23(4):343-346

*Division of Pulmonary, Critical Care, and Sleep Medicine †Department of Pathology ‡Division of Hematology-Oncology, University of California San Diego, La Jolla, CA.

Thoracic extramedullary hematopoiesis (EMH) is a rare manifestation in patients with myeloproliferative neoplasm. A 76-year-old woman with a long-standing history of polycythemia vera presented with a 2-month history of worsening dyspnea and left-sided wheezing. A chest computed tomography showed an ill-defined soft tissue mass encasing the left mainstem bronchus causing airway obstruction, associated with paratracheal and paraesophageal lymphadenopathy. Endobronchial ultrasound-guided fine needle aspiration of the soft tissue mass and mediastinoscopy with excisional biopsy of a paratracheal lymph node demonstrated EMH with increased myeloid blasts. A bone marrow biopsy confirmed postpolycythemic myelofibrosis consistent with progression of polycythemia vera to myelofibrosis. We describe the bronchoscopic management of a case of EMH presenting as a mediastinal mass, mimicking malignancy.
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http://dx.doi.org/10.1097/LBR.0000000000000296DOI Listing
October 2016