title: Marginal zone lymphoma-derived interfollicular diffuse large B-cell lymphoma harboring 20q12 chromosomal deletion and missense mutation of BIRC3 gene: a case report.
abstract: BACKGROUND
  Diffuse large B-cell lymphoma (DLBCL) typically leads to effacement of the nodal architecture by an infiltrate of malignant cells. Rarely (<1%), DLBCL can present with an interfollicular pattern (DLBCL-IF) preserving the lymphoid follicles. It has been postulated that DLBCL-IF is derived from marginal zone B cells and may represent a large-cell transformation of marginal zone lymphoma (MZL), however no direct evidence has been provided to date. Here we describe a rare case of a diagnostically challenging DLBCL-IF involving a lymph node in a patient with a prior history of lymphadenopathy for several years and MZL involving skin.
  
  
  METHODS
  A 53-year old man presented to our Dermatology Clinic due to a 1-year history of generalized itching, fatigue of 2-3 month's duration, nausea and mid back rash that was biopsied. PET (positron emission tomography)/CT (computed tomography) was performed and revealed inguinal, pelvic, retroperitoneal, axillary, and cervical lymphadenopathy. The patient was referred to surgery for excisional biopsy of a right inguinal lymph node. Diagnostic H&E stained slides and ancillary studies were reviewed for the lymph node and skin specimens. B-cell clonality by PCR and sequencing studies were performed on both specimens. We demonstrate that this patient's MZL and DLBCL-IF are clonally related, strongly suggesting that transformation of MZL to DLBCL had occurred. Furthermore, we identified a novel deletion of the long arm of chromosome 20 (del(20q12)) and a missense mutation in BIRC3 (Baculoviral IAP repeat-containing protein 3) in this patient's DLBCL that are absent from his MZL, suggesting that these genetic alterations contributed to the large cell transformation.
  
  
  CONCLUSIONS
  To our knowledge, this is the first report providing molecular evidence for a previously suspected link between MZL and DLBCL-IF. In addition, we describe for the first time del(20q12) and a missense mutation in BIRC3 in DLBCL. Our findings also raise awareness of DLBCL-IF and discuss the diagnostic pitfalls of this rare entity.
authors.affiliation: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 7 E Gates Pavilion, 3400 Spruce Street, Philadelphia, 19104-4283, PA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hatem
authors.affiliation: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 7 E Gates Pavilion, 3400 Spruce Street, Philadelphia, 19104-4283, PA, USA.
authors.forename: April M
authors.initials: AM
authors.lastname: Schrank-Hacker
authors.affiliation: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 7 E Gates Pavilion, 3400 Spruce Street, Philadelphia, 19104-4283, PA, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Watt
authors.affiliation: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 7 E Gates Pavilion, 3400 Spruce Street, Philadelphia, 19104-4283, PA, USA.
authors.forename: Jennifer J D
authors.initials: JJ
authors.lastname: Morrissette
authors.affiliation: Department of Dermatology, University of Pennsylvania, Philadelphia, 19104, PA, USA.
authors.forename: Adam I
authors.initials: AI
authors.lastname: Rubin
authors.affiliation: Department of Dermatology, University of Pennsylvania, Philadelphia, 19104, PA, USA.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Medicine, University of Pennsylvania, Philadelphia, 19104, PA, USA.
authors.forename: Sunita D
authors.initials: SD
authors.lastname: Nasta
authors.affiliation: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 7 E Gates Pavilion, 3400 Spruce Street, Philadelphia, 19104-4283, PA, USA.
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.affiliation: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 7 E Gates Pavilion, 3400 Spruce Street, Philadelphia, 19104-4283, PA, USA. Agata.Bogusz@uphs.upenn.edu.
authors.forename: Agata M
authors.initials: AM
authors.lastname: Bogusz
mesh_terms: D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D014408:Biomarkers, Tumor / Q000032:analysis; D002872:Chromosome Deletion; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases
keywords: Diffuse large B-cell lymphoma (DLBCL) with deletion 20q(del(20q)); Interfollicular diffuse large B cell lymphoma (DLBCL-IF); Marginal zone lymphoma