Scholars@Duke
Chad Michael McCall

Chad Michael McCall

Adjunct Assistant Professor in the Department of Pathology
Pathology
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Selected Publications

Breast cancer exploits neural signaling pathways for bone-to-meninges metastasis.

Journal Article Science · June 21, 2024 The molecular mechanisms that regulate breast cancer cell (BCC) metastasis and proliferation within the leptomeninges (LM) are poorly understood, which limits the development of effective therapies. In this work, we show that BCCs in mice can invade the LM ... Full text Link to item Cite

Lymphoma genetics

Chapter · March 8, 2024 Genetics plays a crucial role in the classification and treatment of non-Hodgkin lymphoma. Various techniques, including conventional cytogenetics, fluorescence in-situ hybridization, and next-generation sequencing, have significantly contributed to our un ... Full text Cite

Expression of CD6 in Aggressive NK/T-cell Neoplasms and Assessment as a Potential Therapeutic Target: A Bone Marrow Pathology Group Study

Journal Article Clinical Lymphoma, Myeloma and Leukemia · January 1, 2024 Background: Aggressive NK/T-Cell neoplasms are rare hematological malignancies characterized by the abnormal proliferation of NK or NK-like T (NK/T) cells. CD6 is a transmembrane signal transducing receptor involved in lymphocyte activation and differentia ... Full text Cite

Bone marrow Ki-67 index is of prognostic value in newly diagnosed multiple myeloma.

Journal Article Eur J Haematol · September 2023 BACKGROUND: Ki-67 is an index of proliferative activity and is an established predictive and prognostic marker in multiple malignancies. However, its prognostic relevance in multiple myeloma (MM) is unclear. We investigated the relationship between Ki-67 e ... Full text Link to item Cite

Clinical insights from Wolman disease: Evaluating infantile hepatosplenomegaly.

Journal Article Am J Med Genet A · November 2022 There is a broad differential diagnosis of infantile hepatosplenomegaly, with some etiologies being debilitating and treatable. A structured approach to history, examination, and laboratory and radiographic findings is important in diagnosis. Herein, we pr ... Full text Link to item Cite

A multiple instance learning approach for detecting COVID-19 in peripheral blood smears.

Journal Article PLOS Digit Health · August 2022 A wide variety of diseases are commonly diagnosed via the visual examination of cell morphology within a peripheral blood smear. For certain diseases, such as COVID-19, morphological impact across the multitude of blood cell types is still poorly understoo ... Full text Open Access Link to item Cite

CloneRetriever: An Automated Algorithm to Identify Clonal B and T Cell Gene Rearrangements by Next-Generation Sequencing for the Diagnosis of Lymphoid Malignancies.

Journal Article Clin Chem · November 1, 2021 BACKGROUND: Clonal immunoglobulin and T-cell receptor rearrangements serve as tumor-specific markers that have become mainstays of the diagnosis and monitoring of lymphoid malignancy. Next-generation sequencing (NGS) techniques targeting these loci have be ... Full text Link to item Cite

Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Fidelity of Diagnosis Using WHO Criteria.

Journal Article Clin Lymphoma Myeloma Leuk · May 2021 PURPOSE: Diagnosing primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is challenging because it is a clinicopathologic entity that shares characteristics with other lymphomas and lacks pathognomonic features. We sought to investigate the fidelity ... Full text Link to item Cite

CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma.

Journal Article Blood Cancer J · June 17, 2020 The diffuse variant of follicular lymphoma (dFL) is a rare variant of FL lacking t(14;18) that was first described in 2009. In this study, we use a comprehensive approach to define unifying pathologic and genetic features through gold-standard pathologic r ... Full text Link to item Cite

Myeloid neoplasms in the setting of sickle cell disease: an intrinsic association with the underlying condition rather than a coincidence; report of 4 cases and review of the literature.

Journal Article Mod Pathol · December 2019 Myeloid neoplasms occasionally occur in patients with sickle cell disease, and the underlying connection between the two diseases is unclear. Herein, we retrospectively analyzed four cases of sickle cell disease patients who developed myeloid neoplasm. Age ... Full text Link to item Cite

Sequential development of human herpes virus 8-positive diffuse large B-cell lymphoma and chronic myelomonocytic leukemia in a 59 year old female patient with hemoglobin SC disease.

Journal Article Pathol Res Pract · December 2019 Hematolymphoid neoplasms, including lymphoma and myeloid neoplasms, can occur in patients with sickle cell disease (SCD) or equivalent hemoglobinopathy, but an underlying connection between the two conditions has yet to be fully determined. Herein, we repo ... Full text Link to item Cite

Whole Exome and Transcriptome Sequencing in 1042 Cases Reveals Distinct Clinically Relevant Genetic Subgroups of Follicular Lymphoma.

Journal Article Blood · November 13, 2019 DISCLOSURES: Koff: Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; Lymphoma Research Foundation: Research Funding; American Association for Cancer Research: Research Funding. Leppä:Roche: Honoraria, Research Funding; Takeda: Hono ... Full text Link to item Cite

Targeting High Mobility Group Box-1 (HMGB1) Promotes Cell Death in Myelodysplastic Syndrome.

Journal Article Clin Cancer Res · July 1, 2019 PURPOSE: Myelodysplastic syndrome (MDS) is associated with a dysregulated innate immune system. The purpose of this study was to determine whether modulation of the innate immune system via high mobility group box-1 (HMGB1) could reduce cell viability in M ... Full text Link to item Cite

Systematic Dissection of the Metabolic-Apoptotic Interface in AML Reveals Heme Biosynthesis to Be a Regulator of Drug Sensitivity.

Journal Article Cell Metab · May 7, 2019 Crosstalk between metabolic and survival pathways is critical for cellular homeostasis, but the connectivity between these processes remains poorly defined. We used loss-of-function CRISPR/Cas9 knockout screening to identify metabolic genes capable of infl ... Full text Link to item Cite

Idiopathic orbital inflammation with bone destruction and extension into the paranasal sinuses.

Journal Article Surv Ophthalmol · 2019 Idiopathic orbital inflammation developed in the right orbit of a woman in her mid-thirties, causing tearing, photophobia, diplopia, altered depth perception, proptosis, and pain on eye movements. Computed tomography disclosed a mass involving the intracon ... Full text Link to item Cite

Beneath the Retinal Pigment Epithelium: Histopathologic Findings in Metastatic Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type.

Journal Article Ocul Oncol Pathol · November 2018 PURPOSE: To report a case of extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type metastatic to the space beneath the retinal pigment epithelium (RPE) with coincident paraneoplastic lymphoma-associated retinopathy. METHODS: Findings of clinical a ... Full text Link to item Cite

Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.

Journal Article Cold Spring Harb Mol Case Stud · October 2018 Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little i ... Full text Link to item Cite

Expanding the Spectrum of EBV-positive Marginal Zone Lymphomas: A Lesion Associated With Diverse Immunodeficiency Settings.

Journal Article Am J Surg Pathol · October 2018 Traditionally low-grade B-cell lymphomas have been excluded from the category of monomorphic posttransplant lymphoproliferative disorders. However, recent reports identified Epstein-Barr virus-positive (EBV) extranodal marginal zone lymphomas (MZL), almost ... Full text Link to item Cite

Breast cancer exploits neural signaling pathways for bone-to-meninges metastasis.

Journal Article Science · June 21, 2024 The molecular mechanisms that regulate breast cancer cell (BCC) metastasis and proliferation within the leptomeninges (LM) are poorly understood, which limits the development of effective therapies. In this work, we show that BCCs in mice can invade the LM ... Full text Link to item Cite

Lymphoma genetics

Chapter · March 8, 2024 Genetics plays a crucial role in the classification and treatment of non-Hodgkin lymphoma. Various techniques, including conventional cytogenetics, fluorescence in-situ hybridization, and next-generation sequencing, have significantly contributed to our un ... Full text Cite

Expression of CD6 in Aggressive NK/T-cell Neoplasms and Assessment as a Potential Therapeutic Target: A Bone Marrow Pathology Group Study

Journal Article Clinical Lymphoma, Myeloma and Leukemia · January 1, 2024 Background: Aggressive NK/T-Cell neoplasms are rare hematological malignancies characterized by the abnormal proliferation of NK or NK-like T (NK/T) cells. CD6 is a transmembrane signal transducing receptor involved in lymphocyte activation and differentia ... Full text Cite

Bone marrow Ki-67 index is of prognostic value in newly diagnosed multiple myeloma.

Journal Article Eur J Haematol · September 2023 BACKGROUND: Ki-67 is an index of proliferative activity and is an established predictive and prognostic marker in multiple malignancies. However, its prognostic relevance in multiple myeloma (MM) is unclear. We investigated the relationship between Ki-67 e ... Full text Link to item Cite

Clinical insights from Wolman disease: Evaluating infantile hepatosplenomegaly.

Journal Article Am J Med Genet A · November 2022 There is a broad differential diagnosis of infantile hepatosplenomegaly, with some etiologies being debilitating and treatable. A structured approach to history, examination, and laboratory and radiographic findings is important in diagnosis. Herein, we pr ... Full text Link to item Cite

A multiple instance learning approach for detecting COVID-19 in peripheral blood smears.

Journal Article PLOS Digit Health · August 2022 A wide variety of diseases are commonly diagnosed via the visual examination of cell morphology within a peripheral blood smear. For certain diseases, such as COVID-19, morphological impact across the multitude of blood cell types is still poorly understoo ... Full text Open Access Link to item Cite

CloneRetriever: An Automated Algorithm to Identify Clonal B and T Cell Gene Rearrangements by Next-Generation Sequencing for the Diagnosis of Lymphoid Malignancies.

Journal Article Clin Chem · November 1, 2021 BACKGROUND: Clonal immunoglobulin and T-cell receptor rearrangements serve as tumor-specific markers that have become mainstays of the diagnosis and monitoring of lymphoid malignancy. Next-generation sequencing (NGS) techniques targeting these loci have be ... Full text Link to item Cite

Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Fidelity of Diagnosis Using WHO Criteria.

Journal Article Clin Lymphoma Myeloma Leuk · May 2021 PURPOSE: Diagnosing primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is challenging because it is a clinicopathologic entity that shares characteristics with other lymphomas and lacks pathognomonic features. We sought to investigate the fidelity ... Full text Link to item Cite

CREBBP and STAT6 co-mutation and 16p13 and 1p36 loss define the t(14;18)-negative diffuse variant of follicular lymphoma.

Journal Article Blood Cancer J · June 17, 2020 The diffuse variant of follicular lymphoma (dFL) is a rare variant of FL lacking t(14;18) that was first described in 2009. In this study, we use a comprehensive approach to define unifying pathologic and genetic features through gold-standard pathologic r ... Full text Link to item Cite

Myeloid neoplasms in the setting of sickle cell disease: an intrinsic association with the underlying condition rather than a coincidence; report of 4 cases and review of the literature.

Journal Article Mod Pathol · December 2019 Myeloid neoplasms occasionally occur in patients with sickle cell disease, and the underlying connection between the two diseases is unclear. Herein, we retrospectively analyzed four cases of sickle cell disease patients who developed myeloid neoplasm. Age ... Full text Link to item Cite

Sequential development of human herpes virus 8-positive diffuse large B-cell lymphoma and chronic myelomonocytic leukemia in a 59 year old female patient with hemoglobin SC disease.

Journal Article Pathol Res Pract · December 2019 Hematolymphoid neoplasms, including lymphoma and myeloid neoplasms, can occur in patients with sickle cell disease (SCD) or equivalent hemoglobinopathy, but an underlying connection between the two conditions has yet to be fully determined. Herein, we repo ... Full text Link to item Cite

Whole Exome and Transcriptome Sequencing in 1042 Cases Reveals Distinct Clinically Relevant Genetic Subgroups of Follicular Lymphoma.

Journal Article Blood · November 13, 2019 DISCLOSURES: Koff: Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; Lymphoma Research Foundation: Research Funding; American Association for Cancer Research: Research Funding. Leppä:Roche: Honoraria, Research Funding; Takeda: Hono ... Full text Link to item Cite

Targeting High Mobility Group Box-1 (HMGB1) Promotes Cell Death in Myelodysplastic Syndrome.

Journal Article Clin Cancer Res · July 1, 2019 PURPOSE: Myelodysplastic syndrome (MDS) is associated with a dysregulated innate immune system. The purpose of this study was to determine whether modulation of the innate immune system via high mobility group box-1 (HMGB1) could reduce cell viability in M ... Full text Link to item Cite

Systematic Dissection of the Metabolic-Apoptotic Interface in AML Reveals Heme Biosynthesis to Be a Regulator of Drug Sensitivity.

Journal Article Cell Metab · May 7, 2019 Crosstalk between metabolic and survival pathways is critical for cellular homeostasis, but the connectivity between these processes remains poorly defined. We used loss-of-function CRISPR/Cas9 knockout screening to identify metabolic genes capable of infl ... Full text Link to item Cite

Idiopathic orbital inflammation with bone destruction and extension into the paranasal sinuses.

Journal Article Surv Ophthalmol · 2019 Idiopathic orbital inflammation developed in the right orbit of a woman in her mid-thirties, causing tearing, photophobia, diplopia, altered depth perception, proptosis, and pain on eye movements. Computed tomography disclosed a mass involving the intracon ... Full text Link to item Cite

Beneath the Retinal Pigment Epithelium: Histopathologic Findings in Metastatic Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type.

Journal Article Ocul Oncol Pathol · November 2018 PURPOSE: To report a case of extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type metastatic to the space beneath the retinal pigment epithelium (RPE) with coincident paraneoplastic lymphoma-associated retinopathy. METHODS: Findings of clinical a ... Full text Link to item Cite

Further evidence for the involvement of EFL1 in a Shwachman-Diamond-like syndrome and expansion of the phenotypic features.

Journal Article Cold Spring Harb Mol Case Stud · October 2018 Recent evidence has implicated EFL1 in a phenotype overlapping Shwachman-Diamond syndrome (SDS), with the functional interplay between EFL1 and the previously known causative gene SBDS accounting for the similarity in clinical features. Relatively little i ... Full text Link to item Cite

Expanding the Spectrum of EBV-positive Marginal Zone Lymphomas: A Lesion Associated With Diverse Immunodeficiency Settings.

Journal Article Am J Surg Pathol · October 2018 Traditionally low-grade B-cell lymphomas have been excluded from the category of monomorphic posttransplant lymphoproliferative disorders. However, recent reports identified Epstein-Barr virus-positive (EBV) extranodal marginal zone lymphomas (MZL), almost ... Full text Link to item Cite

Leukaemia hijacks a neural mechanism to invade the central nervous system.

Journal Article Nature · August 2018 Acute lymphoblastic leukaemia (ALL) has a marked propensity to metastasize to the central nervous system (CNS). In contrast to brain metastases from solid tumours, metastases of ALL seldom involve the parenchyma but are isolated to the leptomeninges, which ... Full text Link to item Cite

Chronic Myeloid Leukemia Following Treatment for Primary Neoplasms or Other Medical Conditions.

Journal Article Am J Clin Pathol · July 31, 2018 OBJECTIVES: Therapy-related chronic myeloid leukemia (CML) has been reported, but its clinical presentation and pathologic features have not yet been well characterized. METHODS: Twenty-one cases of CML following treatment for primary diseases were collect ... Full text Link to item Cite

Ocular involvement in neurolymphomatosis.

Journal Article Am J Ophthalmol Case Rep · June 2018 PURPOSE: To describe the ophthalmic symptoms and histopathological findings in a case of primary neurolymphomatosis (NL). OBSERVATIONS: A man in his 60s with a prior diagnosis of chronic inflammatory demyelinating polyneuropathy developed facial numbness, ... Full text Link to item Cite

Lineage Switch Between B-Lymphoblastic Leukemia and Acute Myeloid Leukemia Intermediated by "Occult" Myelodysplastic Neoplasm: Two Cases of Adult Patients With Evidence of Genomic Instability and Clonal Selection by Chemotherapy.

Journal Article Am J Clin Pathol · August 1, 2017 OBJECTIVES: Lineage switch occurs in rare leukemias, and the mechanism is unclear. We report two cases of B-lymphoblastic leukemia (B-ALL) relapsed as acute myeloid leukemia (AML). METHODS: Retrospective review of clinical and laboratory data. RESULTS: Com ... Full text Link to item Cite

Diagnosis of Capnocytophaga canimorsus Sepsis by Whole-Genome Next-Generation Sequencing.

Journal Article Open Forum Infect Dis · September 2016 We report the case of a 60-year-old man with septic shock due to Capnocytophaga canimorsus that was diagnosed in 24 hours by a novel whole-genome next-generation sequencing assay. This technology shows great promise in identifying fastidious pathogens, and ... Full text Open Access Link to item Cite

Dormant breast cancer micrometastases reside in specific bone marrow niches that regulate their transit to and from bone.

Journal Article Sci Transl Med · May 25, 2016 Breast cancer metastatic relapse can occur years after therapy, indicating that disseminated breast cancer cells (BCCs) have a prolonged dormant phase before becoming proliferative. A major site of disease dissemination and relapse is bone, although the cr ... Full text Link to item Cite

The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms.

Journal Article Am J Surg Pathol · May 2015 The 2010 World Health Organization (WHO) classification recommends that pancreatic neuroendocrine tumors (PanNETs) be graded on the basis of the mitotic rate and Ki67 index, with grade 2 (G2) PanNETs defined as having a mitotic rate of 2 to 20 mitotic figu ... Full text Link to item Cite

False positives in multiplex PCR-based next-generation sequencing have unique signatures.

Journal Article J Mol Diagn · September 2014 Next-generation sequencing shows great promise by allowing rapid mutational analysis of multiple genes in human cancers. Recently, we implemented the multiplex PCR-based Ion AmpliSeq Cancer Hotspot Panel (>200 amplicons in 50 genes) to evaluate EGFR, KRAS, ... Full text Link to item Cite

Grading of well-differentiated pancreatic neuroendocrine tumors is improved by the inclusion of both Ki67 proliferative index and mitotic rate.

Journal Article Am J Surg Pathol · November 2013 The grading system for pancreatic neuroendocrine tumors (PanNETs) adopted in 2010 by the World Health Organization (WHO) mandates the use of both mitotic rate and Ki67/MIB-1 index in defining the proliferative rate and assigning the grade. In cases when th ... Full text Link to item Cite

Iatrogenic Exserohilum infection of the central nervous system: mycological identification and histopathological findings.

Journal Article Mod Pathol · February 2013 An outbreak of fungal infections has been identified in patients who received epidural injections of methylprednisolone acetate that was contaminated with environmental molds. In this report, we present the mycological and histopathological findings in an ... Full text Link to item Cite

Serotonin expression in pancreatic neuroendocrine tumors correlates with a trabecular histologic pattern and large duct involvement.

Journal Article Hum Pathol · August 2012 Pancreatic neuroendocrine tumors with prominent stromal fibrosis are often clinically, radiographically, and grossly indistinguishable from ductal adenocarcinoma. We recently described a small series of fibrotic pancreatic neuroendocrine tumors that expres ... Full text Link to item Cite

Flow cytometric findings in hemophagocytic lymphohistiocytosis.

Journal Article Am J Clin Pathol · May 2012 Hemophagocytic lymphohistiocytosis (HLH) is an often fatal hyperinflammatory syndrome. HLH may be inherited, but it more commonly arises secondary to Epstein-Barr virus (EBV) or other infections, hematologic malignancies, or rheumatologic diseases. We iden ... Full text Link to item Cite

Human immunodeficiency virus type 1 Vpr-binding protein VprBP, a WD40 protein associated with the DDB1-CUL4 E3 ubiquitin ligase, is essential for DNA replication and embryonic development.

Journal Article Mol Cell Biol · September 2008 Damaged DNA binding protein 1, DDB1, bridges an estimated 90 or more WD40 repeats (DDB1-binding WD40, or DWD proteins) to the CUL4-ROC1 catalytic core to constitute a potentially large number of E3 ligase complexes. Among these DWD proteins is the human im ... Full text Link to item Cite

Arabidopsis DDB1-CUL4 ASSOCIATED FACTOR1 forms a nuclear E3 ubiquitin ligase with DDB1 and CUL4 that is involved in multiple plant developmental processes.

Journal Article Plant Cell · June 2008 The human DDB1-CUL4 ASSOCIATED FACTOR (DCAF) proteins have been reported to interact directly with UV-DAMAGED DNA BINDING PROTEIN1 (DDB1) through the WDxR motif in their WD40 domain and function as substrate-recognition receptors for CULLIN4-based E3 ubiqu ... Full text Link to item Cite

DDB1 functions as a linker to recruit receptor WD40 proteins to CUL4-ROC1 ubiquitin ligases.

Journal Article Genes Dev · November 1, 2006 Cullins assemble the largest family of ubiquitin ligases by binding with ROC1 and various substrate receptors. CUL4 function is linked with many cellular processes, but its substrate-recruiting mechanism remains elusive. We identified a protein motif, the ... Full text Link to item Cite

Recruiting substrates to cullin 4-dependent ubiquitin ligases by DDB1.

Journal Article Cell Cycle · January 2005 The ubiquitin-proteasome system is the major pathway by which cells target proteins for degradation in a specific manner. The E3 ubiquitin ligase, which brings targeted proteins (substrates) and activated ubiquitin in close proximity, enabling covalent con ... Full text Link to item Cite

Targeted ubiquitination of CDT1 by the DDB1-CUL4A-ROC1 ligase in response to DNA damage.

Journal Article Nat Cell Biol · October 2004 Cullins assemble a potentially large number of ubiquitin ligases by binding to the RING protein ROC1 to catalyse polyubiquitination, as well as binding to various specificity factors to recruit substrates. The Cul4A gene is amplified in human breast and li ... Full text Link to item Cite

Frameshifts and deletions during in vitro translesion synthesis past Pt-DNA adducts by DNA polymerases beta and eta.

Journal Article DNA Repair (Amst) · December 5, 2002 DNA polymerases beta (pol beta ) and eta (pol eta ) are the only two eukaryotic polymerases known to efficiently bypass cisplatin and oxaliplatin adducts in vitro. Frameshift errors are an important aspect of mutagenesis. We have compared the types of fram ... Full text Link to item Cite