Scholars@Duke
Siby Nil Sebastian

Siby Nil Sebastian

Adjunct Professor of Pathology
Pathology
siby.s@duke.edu
Duke Box 3712, Durham, NC 27710
Room# 0212, Wadsworth Bldg, 2351, Erwin Rd, Durham, NC 27705

Selected Publications

Subcutaneous panniculitis-like T-cell lymphoma in a 25-year-old male patient with sickle cell disease.

Journal Article Pathol Res Pract · August 2019 Sickle cell disease (SCD) is a hereditary blood disorder that often has multiple comorbidities. Patients occasionally develop malignant neoplasms, but the risk of lymphoma in SCD is currently unknown. Here, we report a unique case of subcutaneous panniculi ... Full text Link to item Cite

Yield of Malignant Pleural Effusion for Detection of Oncogenic Driver Mutations in Lung Adenocarcinoma.

Journal Article J Bronchology Interv Pulmonol · April 2019 BACKGROUND: Pleural fluid can be used to assess targetable mutations in patients with lung adenocarcinoma. The primary objective of this study was to assess the yield of pleural fluid cytology for targetable oncogenic mutations (EGFR, KRAS, BRAF, ALK, and ... Full text Link to item Cite

CD3-positive diffuse large B-cell lymphoma relapses as CD3-negative large B-cell lymphoma: Loss of aberrant antigen expression in B-cell lymphoma after chemotherapy.

Journal Article Pathol Res Pract · October 2018 Aberrant expression of CD3 on diffuse large B-cell lymphoma (DLBCL) is rare, and its mechanism and biological significance are currently unclear. Herein we report a case of Epstein-Barr virus-negative, CD3-positive DLBCL in a 53 year-old male, who had a re ... Full text Link to item Cite

Epstein-Barr virus-negative diffuse large B cell lymphoma with aberrant expression of CD3 and other T cell-associated antigens: report of three cases with a review of the literature.

Journal Article Ann Hematol · October 2016 Expression of CD3 on a mature B cell neoplasm, such as diffuse large B cell lymphoma (DLBCL), is extremely rare. When it is present, it will cause diagnostic confusion since the classification of lymphoid neoplasms is largely based on immunophenotyping to ... Full text Link to item Cite

A Proof-of-Concept Case Study for Personalized Noninvasive Prenatal Diagnosis: Can We Put It to Work?

Journal Article J Mol Diagn · September 2015 This commentary highlights the article by van den Oever et al that describes a new method of prenatal diagnosis of single-mutation disorders. ... Full text Link to item Cite

Acquisition of CD30 and CD15 accompanied with simultaneous loss of all pan-T-cell antigens in a case of histological transformation of mycosis fungoides with involvement of regional lymph node: an immunophenotypic alteration resembling classical Hodgkin lymphoma.

Journal Article Am J Dermatopathol · March 2015 : Acquired expression of CD30 is frequently noted in histological transformation of mycosis fungoides (MF), but simultaneous gain of CD15 accompanied with loss of pan-T-cell antigens are extremely rare. We report an unusual case of transformed MF with such ... Full text Link to item Cite

T-cell prolymphocytic leukemia in a 63-year-old female with a pre-existing T-cell large granular lymphocytic leukemia: metachronous T-cell leukemias with discordant subset restrictions (CD4 versus CD8) and distinct clonal identities.

Journal Article Pathol Res Pract · December 2014 A 55-year-old female with T-cell large granular lymphocytic leukemia (T-LGL) (CD8+) was initially treated with anti-thymocyte globulin and then cyclosporine due to anemia/neutropenia. While the severity of cytopenia varied with the therapy, the T-LGL persi ... Full text Link to item Cite

Metachronous/concomitant B-cell neoplasms with discordant light-chain or heavy-chain isotype restrictions: evidence of distinct B-cell neoplasms rather than clonal evolutions.

Journal Article Hum Pathol · October 2014 Metachronous/concomitant B-cell neoplasms with distinct morphology are usually considered clonally related. We retrospectively analyzed 4 cases of metachronous/concomitant B-cell neoplasms with discordant light-chain/heavy-chain restrictions. The primary d ... Full text Link to item Cite

Composite lymphoid neoplasm of B-cell and T-cell origins: a pathologic study of 14 cases.

Journal Article Hum Pathol · April 2014 We retrospectively analyzed 14 composite lymphoma/lymphoid neoplasms (CL) of B-cell/T-cell origins. These consisted of a spectrum of T-cell neoplasms in combination with different B-cell lymphomas/leukemias, with peripheral T-cell lymphoma and diffuse larg ... Full text Link to item Cite

Composite lymphoma of mycosis fungoides and cutaneous small B-cell lymphoma in a 73-year-old male patient.

Journal Article Hum Pathol · April 2013 Composite lymphoma of T-cell and B-cell type is uncommon, and the one occurring primarily on skin is extremely rare. Herein, we report a unique case of composite lymphoma of mycosis fungoides and cutaneous small B-cell lymphoma in a 73-year-old male patien ... Full text Link to item Cite

Gene rearrangements testing

Journal Article Modern Clinical Molecular Techniques · 2013 © 2012 Springer Science+Business Media, LLC. All rights reserved.The B- and T-cell gene rearrangement test is one of the hallmarks of the molecular pathology diagnostic laboratories. Historically done with Southern blot and now adopted by many laboratories ... Full text Cite

Inherited lipemic splenomegaly and the spectrum of apolipoprotein E p.Leu167del mutation phenotypic variation.

Journal Article J Clin Lipidol · 2013 OBJECTIVE: We review disorders associated with splenomegaly and dyslipidemia with an emphasis on the APOE p.Leu167del mutation. Recent studies suggest that this rare mutation may present more often without splenomegaly in patients with familial combined hy ... Full text Link to item Cite

A malignant lymphoma with histological features and immunophenotypic profile intermediate between EBV-positive diffuse large B-cell lymphoma and EBV-positive classical Hodgkin lymphoma in a 67-year-old female: a "gray zone" lymphoma associated with Epstein-Barr virus in the elderly.

Journal Article Pathol Res Pract · June 15, 2012 Epstein-Barr virus (EBV) can be associated with both classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma of the B-cell type, particularly in immunodeficient patients or elderly individuals. While polymorphic variants of EBV-positive large B-cell lymp ... Full text Link to item Cite

Molecular detection of circulating Sezary cells in patients with mycosis fungoides: could it predict future development of secondary Sezary syndrome? A single-institution experience.

Journal Article Leuk Lymphoma · May 2012 While the majority of patients with early-stage mycosis fungoides (MF) have an excellent prognosis, a few cases progress to secondary Sezary syndrome (sSS), which carries a dismal clinical outcome. We retrospectively analyzed 135 cases of MF/SS and correla ... Full text Link to item Cite

Primary cutaneous, composite, Epstein-Barr virus-associated, diffuse large B-cell lymphoma and peripheral T-cell lymphoma.

Journal Article Am J Dermatopathol · October 2011 T-cell lymphomas have a broad spectrum of cutaneous involvement. Several subtypes of T-cell lymphomas are associated with Epstein-Barr virus (EBV)-driven lymphoproliferative processes. We present a case of a composite, primary, cutaneous, EBV-associated, d ... Full text Link to item Cite

Donor cell-derived leukemias/myelodysplastic neoplasms in allogeneic hematopoietic stem cell transplant recipients: a clinicopathologic study of 10 cases and a comprehensive review of the literature.

Journal Article Am J Clin Pathol · April 2011 We report 10 cases of donor cell leukemia (DCL). All cases except the case of chronic lymphocytic leukemia had anemia, neutropenia, and/or thrombocytopenia when DCL was diagnosed. Eight cases with sex-mismatched hematopoietic stem cell transplant (HCT) sho ... Full text Link to item Cite

Sequential development of histiocytic sarcoma and diffuse large b-cell lymphoma in a patient with a remote history of follicular lymphoma with genotypic evidence of a clonal relationship: a divergent (bilineal) neoplastic transformation of an indolent B-cell lymphoma in a single individual.

Journal Article Am J Surg Pathol · March 2011 Follicular lymphoma (FL) often transforms to diffuse large B-cell lymphoma (DLBCL) during its protracted clinical course. Rarely, histiocytic sarcoma (HS) occurs secondary to or concurrent with FL, although the biological relationship between these 2 morph ... Full text Link to item Cite

Pseudo-Pelger-Huët anomaly induced by medications: a clinicopathologic study in comparison with myelodysplastic syndrome-related pseudo-Pelger-Huët anomaly.

Journal Article Am J Clin Pathol · February 2011 Pseudo-Pelger-Huët anomaly (PPHA) has been documented in association with transplant medications and other drugs. This iatrogenic neutrophilic dysplasia is reversible with cessation or adjustment of medications but is frequently confused with myelodysplast ... Full text Link to item Cite

Concurrent classical Hodgkin lymphoma and plasmablastic lymphoma in a patient with chronic lymphocytic leukemia/small lymphocytic lymphoma treated with fludarabine: a dimorphic presentation of iatrogenic immunodeficiency-associated lymphoproliferative disorder with evidence suggestive of multiclonal transformability of B cells by Epstein-Barr virus.

Journal Article Hum Pathol · December 2010 A small fraction of patients with chronic lymphocytic leukemia/small lymphocytic lymphoma develop Epstein-Barr virus-positive B-cell lymphoproliferative disorders. These Epstein-Barr virus-B-cell lymphoproliferative disorders are thought to be related to i ... Full text Link to item Cite

Donor cell leukemia in umbilical cord blood transplant patients: a case study and literature review highlighting the importance of molecular engraftment analysis.

Journal Article J Mol Diagn · July 2010 Donor cell neoplasms are rare complications of treatment regimens that involve stem cell transplantation for hematological malignancies, myelodysplastic processes, or certain genetic or metabolic disorders. We report a case of donor cell leukemia in a pedi ... Full text Open Access Link to item Cite

Histiocytic sarcoma arising in indolent small B-cell lymphoma: report of two cases with molecular/genetic evidence suggestive of a 'transdifferentiation' during the clonal evolution.

Journal Article Leuk Lymphoma · May 2010 The biologic relationship between small B-cell lymphoma and histiocytic sarcoma (HS) when occurring in the same patient remains unclear, though recent data suggest a possible 'transdifferentiation' from follicular lymphoma (FL) to HS. We investigated the c ... Full text Link to item Cite

Regional rearrangements in chromosome 15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene.

Journal Article Hum Mol Genet · November 1, 2007 Production of appropriate quantities of estrogen in various tissues is essential for human physiology. A single gene (CYP19), regulated via tissue-specific promoters, encodes the enzyme aromatase, which catalyzes the key step in estrogen biosynthesis. Arom ... Full text Link to item Cite

Detection of the JAK2 V617F mutation by LightCycler PCR and probe dissociation analysis.

Journal Article J Mol Diagn · July 2006 A point mutation in the JAK2 gene, a member of the tyrosine kinase family, was recently identified and shown to be associated with several myeloproliferative disorders. Several studies identified the same JAK2 point mutation (1,849G>T), resulting in the su ... Full text Link to item Cite

Posttransplant lymphoproliferative disorder after umbilical cord blood transplantation in children.

Journal Article Am J Surg Pathol · March 2006 Reported are 7 cases of posttransplant lymphoproliferative disorder (PTLD) arising in children who received umbilical cord blood transplantation (UCBT). There were 4 females and 3 males with a median age of 3 years (range, 1-16 years). All 7 patients recei ... Full text Link to item Cite

Posttransplant lymphoproliferative disorder after umbilical cord blood transplantation in children

Journal Article American Journal of Surgical Pathology · 2006 Reported are 7 cases of posttransplant lymphoproliferative disorder (PTLD) arising in children who received umbilical cord blood transplantation (UCBT). There were 4 females and 3 males with a median age of 3 years (range, 1-16 years). All 7 patients recei ... Full text Cite

Molecular and cytogenetic characterization of a novel rearrangement involving chromosomes 9, 12, and 17 resulting in ETV6 (TEL) and ABL fusion.

Journal Article Cancer Genet Cytogenet · February 2005 We performed chromosome analysis on the bone marrow of a patient with BCR/ABL negative chronic myelogenous leukemia (CML). By interphase fluorescence in situ hybridization (FISH), an extra ABL signal was present in interphase nuclei and appeared to be loca ... Full text Link to item Cite

Molecular and cytogenetic characterization of a novel translocation t(4;22) involving the breakpoint cluster region and platelet-derived growth factor receptor-alpha genes in a patient with atypical chronic myeloid leukemia.

Journal Article Genes Chromosomes Cancer · May 2004 We report a case of BCR-ABL-negative atypical chronic myeloid leukemia (CML) with translocation t(4;22) (q12;q11.2) juxtaposing the breakpoint cluster region (BCR) and platelet-derived growth factor receptor-alpha (PDGFRA) genes. The patient was a 57-year- ... Full text Link to item Cite

Estrogen up-regulates cyclooxygenase-2 via estrogen receptor in human uterine microvascular endothelial cells.

Journal Article Fertil Steril · May 2004 OBJECTIVE: To investigate the effects of 17beta-estradiol (E(2)) on cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) synthesis in primary human uterine microvascular endothelial cells (HUMEC). DESIGN: Prospective study. SETTING: Basic re ... Full text Link to item Cite

Organization of the human aromatase p450 (CYP19) gene.

Journal Article Semin Reprod Med · February 2004 The human CYP19 (p450arom) gene is located in the 21.2 region on the long arm of chromosome 15 (15q21.2). This gene spans a region that consists of a 30 kb coding region and a 93 kb regulatory region ( approximately 123 kb total length). Its regulatory reg ... Full text Link to item Cite

WT1 and DAX-1 regulate SF-1-mediated human P450arom gene expression in gonadal cells.

Journal Article Mol Cell Endocrinol · October 31, 2003 Binding activity of steroidogenic factor-1 (SF-1) to promoters of the majority of steroidogenic genes in response to gonadotropins is a critical mechanism that regulates steroidogenesis in gonads. Thus, the modulation of SF-1 action may be essential for th ... Full text Link to item Cite

The human CYP19 (aromatase P450) gene: update on physiologic roles and genomic organization of promoters.

Journal Article J Steroid Biochem Mol Biol · September 2003 The human CYP19 (P450arom) gene is located in the chromosome 15q21.2 region and is comprised of a 30 kb coding region and a 93 kb regulatory region. The Internet-based Human Genome Project data enabled us to elucidate its complex organization. The unusuall ... Full text Link to item Cite

Induction of cyclooxygenase-2 in human endometrial stromal cells by malignant endometrial epithelial cells: evidence for the involvement of extracellularly regulated kinases and CCAAT/enhancer binding proteins.

Journal Article J Mol Endocrinol · August 2003 We previously reported that human malignant endometrial epithelial cell conditioned medium (MECM) up-regulated cyclooxygenase (COX)-2 mRNA and protein levels in human normal endometrial stromal cells (ESC). Here we showed that pretreatment with a selective ... Full text Link to item Cite

Estrogen excess associated with novel gain-of-function mutations affecting the aromatase gene.

Journal Article N Engl J Med · May 8, 2003 BACKGROUND: Gynecomastia of prepubertal onset may result from increased estrogen owing to excessive aromatase activity in extraglandular tissues. A gene in chromosome 15q21.2 encodes aromatase, the key enzyme for estrogen biosynthesis. Several physiologic ... Full text Link to item Cite

Cloning and characterization of a novel endothelial promoter of the human CYP19 (aromatase P450) gene that is up-regulated in breast cancer tissue.

Journal Article Mol Endocrinol · October 2002 Intratumoral expression of aromatase P450 (P450arom) promotes the growth of breast tumors via increased local estrogen concentration. We cloned a novel 101-bp untranslated first exon (I.7) that comprises the 5'-end of 29-54% of P450arom transcripts isolate ... Full text Link to item Cite

WT1 and DAX-1 inhibit aromatase P450 expression in human endometrial and endometriotic stromal cells.

Journal Article J Clin Endocrinol Metab · September 2002 The orphan nuclear receptor steroidogenic factor-1 (SF-1) induces the expression of Müllerian inhibiting substance (MIS) and many steroidogenic genes, including aromatase P450 (P450arom). Dosage-sensitive sex reversal adrenal hypoplasia congenita critical ... Full text Link to item Cite

Up-regulation of cyclooxygenase-2 expression and prostaglandin synthesis in endometrial stromal cells by malignant endometrial epithelial cells. A paracrine effect mediated by prostaglandin E2 and nuclear factor-kappa B.

Journal Article J Biol Chem · July 19, 2002 We investigated the regulation of prostaglandin production in normal endometrial stromal cells (ESC) by malignant endometrial epithelial cells. We found that cyclooxygenase (COX)-2 mRNA and protein levels and prostaglandin (PG)E(2) production in ESC were s ... Full text Link to item Cite

Vascular endothelial growth factor up-regulates cyclooxygenase-2 expression in human endothelial cells.

Journal Article J Clin Endocrinol Metab · July 2002 We investigated the effects of vascular endothelial growth factor (VEGF) on cyclooxygenase-2 (COX-2) expression and prostaglandin E(2) (PGE(2)) synthesis in human microvascular endothelial cells (HMEC-1). Treatment of HMEC-1 with VEGF resulted in a dose- a ... Full text Link to item Cite

Interleukin-1beta elevates cyclooxygenase-2 protein level and enzyme activity via increasing its mRNA stability in human endometrial stromal cells: an effect mediated by extracellularly regulated kinases 1 and 2.

Journal Article J Clin Endocrinol Metab · July 2002 We investigated the regulation of PG production in human endometrial stromal cells (ESC) by IL-1beta. We found that cyclooxygenase-2 (COX-2) mRNA and protein levels and PGE(2) production in ESC were significantly increased by IL-1beta. COX-2 mRNA, protein, ... Full text Link to item Cite

Estrogen production and metabolism in endometriosis.

Journal Article Ann N Y Acad Sci · March 2002 Aromatase activity is absent in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis, which gives rise to strikingly high levels of aromatase activity in this tissue. Both aromatase expression and activity are stimulated by P ... Full text Link to item Cite

Mechanisms of excessive estrogen formation in endometriosis.

Journal Article J Reprod Immunol · 2002 Estrogen is produced in a number of human tissues including the ovary, placenta and extraglandular sites such as adipose tissue, skin and the brain. Aromatase is the key enzyme that regulates estrogen formation in these tissues. Aromatase activity is not d ... Full text Link to item Cite

Role of aromatase in endometrial disease.

Journal Article J Steroid Biochem Mol Biol · December 2001 Aromatase is the key enzyme for estrogen biosynthesis. It is normally expressed in the human ovary, skin, adipose tissue and brain. Aromatase activity is not detectable in normal endometrium. In contrast, aromatase is expressed aberrantly in endometriosis ... Full text Link to item Cite

The human gene for the type III isozyme of hexokinase: structure, basal promoter, and evolution.

Journal Article Arch Biochem Biophys · November 1, 2001 The structure of the gene for the Type III isozyme of human hexokinase is nearly identical to that of previously characterized genes for other isozymes of hexokinase. The most striking difference is that the 5'-untranslated sequence and the initial coding ... Full text Link to item Cite

Malignant breast epithelial cells stimulate aromatase expression via promoter II in human adipose fibroblasts: an epithelial-stromal interaction in breast tumors mediated by CCAAT/enhancer binding protein beta.

Journal Article Cancer Res · March 1, 2001 Expression of aromatase P450 (P450arom), which catalyzes the formation of estrogens, is aberrantly increased in adipose fibroblasts surrounding breast carcinomas, giving rise to proliferation of malignant cells. Aromatase in human adipose tissue is primari ... Link to item Cite

Anabolic function of the type II isozyme of hexokinase in hepatic lipid synthesis.

Journal Article Biochem Biophys Res Commun · April 21, 2000 The mRNA encoding the Type II isozyme of hexokinase was markedly elevated in livers of transgenic mice overexpressing the transcriptionally active nuclear form of sterol regulatory element binding protein-1a (nSREBP-1a), but not in transgenic mice overexpr ... Full text Link to item Cite

Characterization of the rat type III hexokinase gene promoter. A functional octamer 1 motif is critical for basal promoter activity.

Journal Article J Biol Chem · October 29, 1999 A 1532-base pair 5'-flanking region of the gene encoding rat type III hexokinase has been cloned and sequenced. The total sequence includes positions -1548 to -17 (A of the translational start ATG as position +1). Using luciferase reporter constructs trans ... Full text Link to item Cite

Allosteric regulation of type I hexokinase: A site-directed mutational study indicating location of the functional glucose 6-phosphate binding site in the N-terminal half of the enzyme.

Journal Article Arch Biochem Biophys · February 15, 1999 The Type I isozyme of mammalian hexokinase has evolved by a gene duplication-fusion mechanism, with resulting internal duplication of sequence and ligand binding sites. However, 1:1 binding stoichiometry indicates that only one of these is available for bi ... Full text Link to item Cite

Stimulation of brain hexokinase gene expression by recombinant brain insulin-like growth factor in C6 glial cells.

Journal Article Exp Cell Res · January 10, 1999 Glycolysis is essential for cerebral energy generation. Hence, expression and regulation of gene-encoding brain hexokinase (HK I), the exclusive brain glucose phosphorylating enzyme, can be a critical step in this process. The present study demonstrates th ... Full text Link to item Cite

Expression of two type II-like tumor hexokinase RNA transcripts in cancer cell lines.

Journal Article Tumour Biol · 1998 To maintain an elevated glycolytic rate, cancerous or proliferating cells alter the expression pattern of rate limiting glycolytic enzymes. Since glucose phosphorylation is the first step in glycolysis, hexokinase (HK), the first rate limiting glycolytic e ... Full text Link to item Cite

Chromosomes with high gene density are preferentially repaired in human cells.

Journal Article Mutagenesis · November 1997 It is known that DNA repair is heterogeneous in human cells since open chromatin, active genes and their transcribed strands are preferentially repaired. It is thus expected that DNA repair is clustered in chromosomes with high gene density. We have employ ... Full text Link to item Cite

Insulin-like growth factor I induces tumor hexokinase RNA expression in cancer cells.

Journal Article Biochem Biophys Res Commun · June 18, 1997 Increased glycolysis is a characteristic of cancer cells. Though less efficient in energy production, it ensures continuous supply of energy and phosphometabolites for biosynthesis enabling metastatic and less vascularized cancer cells to proliferate even ... Full text Link to item Cite