54 research outputs found
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CD117 expression in diffuse large B-cell lymphomas: Fact or fiction?
CD117 (KIT) is expressed in a variety of hematopoietic neo- plasms but there are a paucity of data regarding its expres- sion in diffuse large B-cell lymphomas (DLBCL). The purpose of the present paper was to describe the authorsâ experience of two CD117+ DLBCL (one of follicle center-cell origin and one nasal EpsteinâBarr virus (EBV)â plasmablas- tic lymphoma associated with lytic bone lesions), as deter- mined by tissue immunohistochemistry and flow cytometry. The CD117 expression in DLBCL was further evaluated using tissue microarrays and seven additional plasma- blastic lymphomas, using two commercially available anti-CD117 antibodies (Ab-1, Oncogene and A4502, Dako- Cytomation). Membranous ± cytoplasmic staining was seen with Ab-1 in 24/65 (37%) DLBCL, including 21/56 microarray DLBCL, two index cases, and 1/7 additional plasmablastic lymphomas, with persistent staining in 13% of microarray DLBCL despite preincubation with KIT peptide. However, A4502 had only membranous staining of the index cases and one additional EBVâ plasmablastic lymphoma with medullary disease. The present study suggests that (i) CD117 expression can be detected sporadically in DLBCL of follicle center-cell origin and a subset of plasmablastic lymphomas; (ii) staining for CD117 might help in identifying EBVâ plasmablastic lymphomas associated with bone mar- row involvement; and (iii) CD117 antibodies should be care- fully validated prior to use, because non-specific staining, as observed with Ab-1, could lead to false-positive results
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Nodular pattern of bone marrow infiltration: frequent finding in immunosuppression-related EBV-associated large B-cell lymphomas
Different patterns of bone marrow (BM) infiltration by diffuse large B cell lymphomas (DLBCL) have been described. A pure nodular pattern is uncommon, and the pathologic features, as well as the clinical correlates of DLBCL manifesting this pattern in the BM have not been well characterized. We evaluated BM biopsies involved by large B cell lymphomas diagnosed at our institute over an 11-year period to assess the morphology, phenotype, cytogenetic abnormalities, and clinical features of cases associated with a nodular pattern. A distinct nodular pattern of BM involvement was noted in 14 out of 55 (25%) cases. Although both EBV+ and EBVâDLBCL with this pattern were identified, a pure nodular pattern was significantly more common in EBV+ DLBCL compared to EBVâ DLBCL (8/9, 89% versus 6/46, 13%; P=0.00002). The majority of EBV+ DLBCL associated with a nodular pattern had distinctive morphologic features (polymorphic cellular infiltrate and pleomorphic cytology), and CD30 expression was more commonly observed in this group (P=0.0163). All EBV+ DLBCL and two out of six (33%) EBVâ DLBCL had nongerminal center phenotypes. No recurrent cytogenetic abnormalities were detected in either group. Importantly, all EBV+ DLBCL occurred in individuals with immune dysfunction (organ transplant recipients, HIV infection) or in those >50 years of age. Our study indicates a much higher predilection for EBV+ DLBCL to involve the marrow in a nodular pattern compared to EBVâ cases and highlights similarities in the morphologic pattern of BM involvement by previously recognized subsets of immunodeficiency-related EBV + lymphomas and the newer entity of âEBV+ DLBCL of the elderly.
Indolent Small Intestinal CD4+ T-cell Lymphoma Is a Distinct Entity with Unique Biologic and Clinical Features
Enteropathy-associated T-cell lymphomas (EATL) are rare and generally aggressive types of peripheral T-cell lymphomas. Rare cases of primary, small intestinal CD4+ T-cell lymphomas with indolent behavior have been described, but are not well characterized. We describe morphologic, phenotypic, genomic and clinical features of 3 cases of indolent primary small intestinal CD4+ T-cell lymphomas. All patients presented with diarrhea and weight loss and were diagnosed with celiac disease refractory to a gluten free diet at referring institutions. Small intestinal biopsies showed crypt hyperplasia, villous atrophy and a dense lamina propria infiltrate of small-sized CD4+ T-cells often with CD7 downregulation or loss. Gastric and colonic involvement was also detected (nâ=â2 each). Persistent, clonal TCRÎČ gene rearrangement products were detected at multiple sites. SNP array analysis showed relative genomic stability, early in disease course, and non-recurrent genetic abnormalities, but complex changes were seen at disease transformation (nâ=â1). Two patients are alive with persistent disease (4.6 and 2.5 years post-diagnosis), despite immunomodulatory therapy; one died due to bowel perforation related to large cell transformation 11 years post-diagnosis. Unique pathobiologic features warrant designation of indolent small intestinal CD4+ T-cell lymphoma as a distinct entity, greater awareness of which would avoid misdiagnosis as EATL or an inflammatory disorder, especially celiac disease
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Aggressive presentation of breast implant-associated ALK-1 negative anaplastic large cell lymphoma with bilateral axillary lymph node involvement
We recently encountered a unique case of breast silicone implant-associated ALK-1 negative anaplastic large cell lymphoma (ALCL) in a female with a remote history of breast carcinoma, which presented as a sinusoidal infiltrate in an axillary lymph node (LN) and had a highly complex karyotype
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Cytogenetic analysis of B-cell posttransplant lymphoproliferations validates the World Health Organization classification and suggests inclusion of florid follicular hyperplasia as a precursor lesion
Cytogenetic abnormalities in B-cell posttransplant lymphoproliferative disorders (PTLD) have not been well characterized. We thus performed cytogenetic analysis of 28 cases of B-cell PTLD, 1 infectious mononucleosis (IM)âlike lesion, 9 polymorphic PTLD, 17 monomorphic PTLD, and 1 classical Hodgkin lymphoma (HL), and correlated the karyotypic findings with the phenotype, Epstein- Barr virus infection status, and clinical outcome. Karyotypes of 19 cases of posttransplant florid follicular hyperplasia (FFH) were also analyzed. Informative karyotypes were obtained in 20 (71.4%) of 28 PTLDs and 18 (94.7%) of 19 FFHs. Clonal karyotypic abnormalities were detected in 13 (65%) of 20 PTLDs, including 9 (75%) of 12 monomorphic PTLDs, 2 (33.3%) of 6 polymorphic PTLDs, 1 IM-like lesion, and 1 HL, and 2 (11.1%) of 18 FFHs. Recurrent chromosome breaks at 1q11-21 (n = 6, including 1 FFH), 14q32 (n = 3, including 1 FFH), 16p13 (n = 3), 11q23-24 (n = 2), and 8q24 (c-MYC) (n = 2); gains of chromosome 7 (n = 4), X (n = 3), 2 (n = 3), 12 (n = 2); and loss of chromosome 22 (n = 2, including 1 IM- like lesion) were identified. The presence of cytogenetic abnormalities did not correlate with PTLD phenotype, Epstein-Barr virus infection, or clinical outcome. We describe novel karyotypic aberrations in PTLD and report clonal cytogenetic abnormalities in posttransplant FFH and an IM-like lesion for the first time. Our findings provide validation of the current World Health Organization classification of PTLD and also suggest incorporation of FFH as the earliest recognizable precursor of PTLD
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Pediatric ALK+ Anaplastic Large Cell Lymphoma With t(3;8)(q26.2;q24) Translocation and c-myc Rearrangement Terminating in a Leukemic Phase
Pediatric ALKâpositive anaplastic large cell lymphoma (ALK+ ALCL) is usually associated with a favorable prognosis. ALK+ ALCL associated with a leukemic phase is uncommon, but has been associated with an aggressive clinical course and unfavorable prognosis. Overexpression of câmyc has been shown to be a consistent finding in ALK+, but not ALKânegative ALCL (ALKâ ALCL), and the câmyc gene is considered a downstream target of deregulated ALK signaling. We describe a pediatric ALK+ ALCL with a leukemic phase at relapse. Similar to other rare cases described in the literature, it followed an aggressive clinical course despite multiple regimens of chemotherapy and bone marrow transplantation. Lymphoma cells showed aberrant ALK expression and câmyc overexpression. In addition to the characteristic t(2;5)(p23;q35) translocation, a t(3;8)(q26.2;q24) translocation was also present, and câmyc gene rearrangement was confirmed by FISH analysis. The findings in this case demonstrate the association of peripheral blood leukemic involvement and aggressive clinical course, and suggest that other factors, such as câmyc rearrangement, may be responsible for the aggressive clinical behavior in ALK+ ALCL
Lymphoid follicle colonization by Bcl-2bright+CD10+ B-cells (âfollicular lymphoma in situâ) at nodal and extranodal sites can be a manifestation of follicular homing of lymphoma
Follicular lymphoma (FL) in situ (FLIS) was first described and proposed as a distinct entity associated with an indolent clinical course in 2002. To gain further insight into the biology of this enigmatic lymphoproliferation, we analyzed morphologic, phenotypic, cytogenetic and molecular features of tissue specimens manifesting a pattern of follicular colonization by Bcl-2bright+CD10+ B-cells and associated lymphomas from 13 adults and evaluated their clinical outcomes. We observed this immunoarchitectural pattern in lymph nodes (n = 8), at extranodal sites (n = 4), or at both locations (n = 1) at diagnosis. All except 3 cases showed concomitant bright CD10 expression. Six (46%) patients had synchronous and 2 (15%) developed metachronous B-cell lymphomas, with 5 representing high-grade lymphomas. The Bcl-2bright+CD10+ B-cells colonizing reactive follicles and synchronous lymphomas were clonally related in 4/5 (80%) cases analyzed and 5/6 (83%) displayed BCL2 translocations. Two cases exhibited complex karyotypes in both components; a genetic âtriple hitâ was detected in one instance and 2 copies of t(14,18) were observed in a lymph node biopsy lacking evidence of lymphoma from an individual with stage 4 disease, suspected on imaging, who subsequently displayed a mantle zone/perifollicular infiltrate of Bcl-2bright+CD10+ B-cells in the adenoids. Our findings suggest that bright Bcl-2, and often bright CD10 expression, by B-cells colonizing reactive follicles might represent a phenomenon related to follicular homing of lymphoma, rather than being an attribute of preneoplastic FL precursors. Furthermore, due to the relatively high frequency of overt lymphomas observed, complete staging workup is recommended for patients exhibiting a Bcl-2bright+CD10+ B-cell follicular colonization pattern on biopsy
MYC Protein Expression in Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System
Primary diffuse large B-cell lymphoma of the central nervous system (CNS DLBCL) is a rare, aggressive subtype of DLBCL, the biology of which is poorly understood. Recent studies have suggested a prognostic role of MYC protein expression in systemic DLBCL, but little is known about the frequency and significance of MYC protein expression in CNS DLBCL. Hence, we investigated MYC protein expression profiles of CNS DLBCL and assessed the relationship between MYC expression and a variety of histopathologic, immunophenotypic, genetic, and clinical features. Fifty-nine CNS DLBCL diagnosed at our institution over the past 13 years were evaluated. The majority of cases (80%) showed centroblastic morphology, and 12 (20%) displayed a perivascular pattern of infiltration. According to the Hans criteria, 41 (69%) cases had a non-germinal center B-cell and 18 (31%) had a germinal center B-cell cell-of-origin (COO) phenotype. Mean MYC protein expression was 50% (median: 50%, range: 10-80%). Forty-three cases (73%) showed MYC overexpression (â„40%), and 35 (60%) showed MYC/BCL2 coexpression. MYC overexpression was seen in the single case harboring MYC translocation and in the cases showing increased copies of MYC (27%); however, no significant difference in mean MYC expression was seen between groups harboring or lacking MYC aberrations. In our series, age was associated with a significantly increased risk of death, and the perivascular pattern of infiltration was associated with a significantly increased risk of disease progression. Neither MYC expression (with or without BCL2 coexpression) nor other variables, including COO subtype were predictive of clinical outcome. Our findings indicate that the proportion of CNS DLBCL overexpressing MYC is higher compared to systemic DLBCL, and MYC overexpression appears to be independent of genetic MYC abnormalities. Thus, MYC expression and other immunophenotypic markers used for prognostication of systemic DLBCL might not apply to CNS DLBCL due to differences in disease biology
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Diffuse large B-cell lymphoma with TEL/ETV6 translocation
Cytogenetic abnormalities of chromosome 12p involving the TEL/ETV6 gene are observed in a variety of hematopoietic neoplasms including acute leukemias, myelodysplastic syndromes, and myeloproliferative disorders. Karyotypic aberrations, including rearrangements, deletions, and amplifications of chromosome 12p, have been documented in B-cell non-Hodgkin lymphoma; however, rearrangements targeting TEL have rarely been reported. Here we describe a diffuse large B- cell lymphoma that had a complex karyotype including t(9;12)(q22;p13), which was confirmed by fluorescence in situ hybridization to represent rearrangement of TEL. Additional cytogenetic abnormalities included t(3;14)(q27;q32) involving the variant, alternative breakpoint region of the BCL6 gene and del(6)(q13q23), resulting in the loss of 1 allele of BLIMP1. This case reiterates the importance of correlating morphologic and phenotypic findings with the results of cytogenetic analysis to avoid errors in diagnosing hematologic neoplasms and highlights the rare association of B-cell non- Hodgkin lymphoma with aberrations of TEL
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