Marginal zone lymphoma-derived interfollicular diffuse large B-cell lymphoma harboring 20q12 chromosomal deletion and missense mutation of BIRC3 gene: a case report

Abstract

BackgroundDiffuse 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.Case presentationA 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.ConclusionsTo 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.

Deletion 20q12 is associated with histological transformation of nodal marginal zone lymphoma to diffuse large B‐cell lymphoma

“…As previously stated, HT of MZL is an extremely rare event: 3‐5% of ∼3% of all NHL implies <100 cases per annum in the US. Nevertheless, we sought to perform further cytogenetic analysis of matched cases of MZL transforming to DLBCL; including the original case reported . Remarkably, we found a significant association of del(20q12) in matched pairs of DLBCL cases transformed from NMZL, compared to an equivalent number of unmatched DLBCL cases.…”

“…Although rarely associated with lymphoma, del(20q12) has been reported in a case of aggressive NMZL . We recently described a case of DLBCL harboring del(20q12) in a patient with a history of MZL involving lymph nodes and skin . Polymerase chain reaction of IgG variable regions from the DLBCL and an original skin biopsy were clonally related, strongly suggesting that transformation of MZL to DLBCL had occurred.…”

EBV-Negative Monomorphic B-Cell Posttransplant Lymphoproliferative Disorder with Marked Morphologic Pleomorphism and Pathogenic Mutations in ASXL1, BCOR, CDKN2A, NF1, and TP53

“…DNA was extracted from FFPE small bowel tumor tissue and analyzed for clonality as described previously [ 11 ]. Briefly, PCR amplification was performed with two sets of fluorescently labeled primers (InVivoScribe Technologies) that hybridize to a conserved V-framework, framework 2 (FR2), and framework 3 (FR3) regions and the conserved J-region of immunoglobulin heavy chain (IGH) gene.…”

“…Mutational analysis of FFPE tissue samples was performed by the University of Pennsylvania at the Center for Personalized Diagnostics as described previously [ 11 ]. The genes sequenced were part of a custom, targeted next-generation sequencing amplicon panel testing for 68 hematologic malignancy-associated genes (ABL1, ASXL1, ATM, BCOR, BCORL1, BIRC3, BRAF, CALR, CBL, CDKN2A, CEBPA, CSF1R, CSF3R, DDX3X, DNMT3A, ETV6, EZH2, FAM5C, FBXW7, FLT3, GATA2, GNAS, HNRNPK, IDH1, IDH2, IL7R, JAK2, KIT, KLHL6, KRAS, MAP2K1, MAPK1, MIR142, MPL, MYC, MYCN, MYD88, NF1, NOTCH1, NOTCH2, NPM1, NRAS, PDGFRA, PHF6, POT1, PRPF40B, PTEN, PTPN11, RAD21, RIT1, RUNX1, SETBP1, SF1, SF3A1, SF3B1, SMC1A, SRSF2, STAG2, TBL1XR1, TET2, TP53, TPMT, U2AF1, U2AF2, WT1, XPO1, ZMYM3, and ZRSR2) (TruSeq Custom Amplicon, Illumina Inc.) based on previously described analyses [ 12 , 13 ].…”

Cytoplasmic and Nuclear Functions of cIAP1

“…Non-canonical NF-κB signaling is essential for the activation, survival and differentiation of immune cells such as B-cells, macrophages and dendritic cells. Deletion of cIAP1 and cIAP2 in mice maintained B-cells survival and maturation independent of BAFF-R stimulation [ 91 ], and can account for B-cell transformation [ 94 , 95 , 96 ]. We demonstrated that cIAP1-mediated degradation of TRAF2 is essential for the full activity of macrophages in response to CD40 stimulation [ 45 ].…”