Intraocular Lymphoma: Diagnostic Approach and Immunophenotypic Findings in Vitrectomy Specimens

AbstractContext.—Diagnosis and classification of primary intraocular lymphoma can be challenging because of the sparse cellularity of the vitreous specimens.Objective.—To classify and clinically correlate intraocular lymphoma according to the World Health Organization (WHO) classification by using vitrectomy specimens.Design.—Clinical history, cytologic preparations, flow cytometry reports, and outcome of 16 patients diagnosed with intraocular lymphoma were reviewed.Results.—The study group included 10 women and 6 men. The mean age of the patients was 63 years (range, 19–79 years). Eleven patients had central nervous system involvement and 6 patients had systemic involvement. All cases were adequately diagnosed and classified according to the WHO classification by using combination of cytologic preparations and 4-color flow cytometry with a limited panel of antibodies to CD19, CD20, CD5, CD10, and κ and λ light chains. The cases included 9 primary diffuse large B-cell lymphomas of the CNS type; 2 diffuse large B-cell lymphomas, not otherwise specified; 1 extranodal, low-grade, marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT); 1 precursor B-lymphoblastic lymphoma; and 3 peripheral T-cell lymphomas, not otherwise specified. Of note, all 11 cases of diffuse large B-cell lymphoma were CD10−. All the patients received systemic chemotherapy and radiation therapy. Only 4 patients were free of disease at last follow-up (range, 18 months to 8 years), with severe visual loss.Conclusions.—Intraocular lymphoma cases can be adequately classified according to the WHO classification. Diffuse large B-cell lymphoma, CD10− and most likely of non–germinal center B-cell–like subgroup, is the most common subtype of non-Hodgkin lymphoma in this site, in contrast to ocular adnexal lymphoma for which MALT lymphoma is the most common subtype.

Download Full-text

Grey Zone Lymphomas: Lymphomas with Intermediate Features

Advances in Hematology ◽

10.1155/2012/460801 ◽

2012 ◽

Vol 2012 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Sylvia Hoeller ◽

Christiane Copie-Bergman

Keyword(s):

B Cell ◽

Who Classification ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

World Health ◽

Grey Zone ◽

B Cell Lymphomas ◽

Large B Cell Lymphoma ◽

Large B Cell

The current classification of lymphoid neoplasms is based on clinical information, morphology, immunophenotype, and molecular genetic characteristics. Despite technical and scientific progress, some aggressive B-cell lymphomas with features overlapping between two different types of lymphomas remain difficult to classify. The updated 2008 World Health Organization (WHO) classification of Tumours of the Hematopoietic and Lymphoid Tissues has addressed this problem by creation of two new provisional categories of B-cell lymphomas, unclassifiable; one with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma and the second with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. We review here the diagnostic criteria of these two provisional entities and discuss new scientific findings in light of the 2008 WHO classification.

Download Full-text

Diagnosis of ‘double hit’ diffuse large B-cell lymphoma and B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma: when and how, FISH versus IHC

Hematology ◽

10.1182/asheducation-2014.1.90 ◽

2014 ◽

Vol 2014 (1) ◽

pp. 90-99 ◽

Cited By ~ 75

Author(s):

Steven H. Swerdlow

Keyword(s):

B Cell ◽

Burkitt Lymphoma ◽

Cell Lymphoma ◽

Clinical Importance ◽

B Cell Lymphoma ◽

B Cell Lymphomas ◽

Not Otherwise Specified ◽

Large B Cell Lymphoma ◽

Double Hit ◽

Large B Cell

Abstract Identification of large B-cell lymphomas that are “extra-aggressive” and may require therapy other than that used for diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), is of great interest. Large B-cell lymphomas with MYC plus BCL2 and/or BCL6 rearrangements, so-called ‘double hit’ (DHL) or ‘triple hit’ (THL) lymphomas, are one such group of cases often recognized using cytogenetic FISH studies. Whether features such as morphologic classification, BCL2 expression, or type of MYC translocation partner may mitigate the very adverse prognosis of DHL/THL is controversial. Classification of the DHL/THL is also controversial, with most either dividing them up between the DLBCL, NOS and B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma (BCLU) categories or classifying at least the majority as BCLU. The BCLU category itself has many features that overlap those of DHL/THL. Currently, there is growing interest in the use of MYC and other immunohistochemistry either to help screen for DHL/THL or to identify “double-expressor” (DE) large B-cell lymphomas, defined in most studies as having ≥40% MYC+ and ≥50%-70% BCL2+ cells. DE large B-cell lymphomas are generally aggressive, although not as aggressive as DHL/THL, are more common than DHL/THL, and are more likely to have a nongerminal center phenotype. Whether single MYC rearrangements or MYC expression alone is of clinical importance is controversial. The field of the DHL/THL and DE large B-cell lymphomas is becoming more complex, with many issues left to resolve; however, great interest remains in identifying these cases while more is learned about them.

Download Full-text

Diffuse Large B-Cell Lymphoma, Not Otherwise Specified: Discordance between Histology and Flow Cytometry in Bone Marrow Examination at Diagnosis

Blood ◽

10.1182/blood-2018-99-117041 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1718-1718

Author(s):

Fernando Martín Moro ◽

Miguel Piris-Villaespesa ◽

Monica Garcia Cosio ◽

Jesus Villarrubia ◽

Juan Marquet Palomanes ◽

...

Keyword(s):

Bone Marrow ◽

Flow Cytometry ◽

B Cell ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Survival Outcomes ◽

Not Otherwise Specified ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background: Bone marrow (BM) examination is essential in the staging of diffuse large B-cell lymphoma (DLBCL). The assessment of BM involvement includes both histology (gold-standard) and flow cytometry (FC), but few studies have compared BM biopsy (BMB) histologic findings with results of FC analysis of BM aspirate. Discordance between both techniques generates debate about the staging and the prognostic significance in these cases. Methods: We performed a retrospective single-center analysis of patients with DLBCL, not otherwise specified (NOS) diagnosed during a 4-year period (2014-2017). Patients were divided in three groups according to BM findings of BMB and FC at diagnosis. Standard FC was performed by 4-color flow panel until 2016 and by 8-color FC since then. We described main characteristics of each group at diagnosis and analyzed survival outcomes. We applied means of descriptive statistics and Pearson's chi-squared test, and analyzed survival outcomes according to Kaplan-Meier, using Cox regression for comparisons. Results: We analyzed 59 cases, which were divided in three groups: 40 cases (67.8%) presented both negative histology and FC (BMB-/FC-), 10 (16.9%) showed BM involvement using both histology and FC (BMB+/FC+) and 9 cases (15.3%) presented discordant results, all of them with negative histology and positive FC (BMB-/FC+). Clinical and biological characteristics of each group at diagnosis are presented in Table 1. Median infiltration by FC analysis of the BMB-/FC+ group was 0.8% (0.1-2.9) and 3/9 patients presented discordant immunophenotype of lymphoma cells between BM and node biopsy. If we considered BM infiltration as positive in all BMB-/FC+ cases, 4/9 (6.8% of all patients) would be upstaged. First-line treatment was homogeneous in all patients. With a median observation time of 18 months, progression-free survival (PFS) after 2 years was 67%, 22% and 22% with BMB-/FC-, BMB-/FC+ and BMB+/FC+, respectively (Figure 1A), with a multivariate hazard ratio (HR) of 1.9 (95% CI 1.2-2.9, p=0.004) and an univariate HR for FC+ (BMB-/FC+ and BMB+/FC+) vs FC- (BMB-/FC-) of 3.3 (95% CI 1.5-7.3, p=0.003). Two-year overall survival (OS) was 68%, 41% and 33% with BMB-/FC-, BMB-/FC+ and BMB+/FC+, respectively (Figure 1B); multivariate HR was 1.6 (95% CI 1.1-2.6, p=0.042) and univariate HR for FC+ vs FC- was 2.5 (95% CI 1.1-5.9, p=0.035). We found no significant difference between BMB-/FC+ and BMB+/FC+ in survival outcomes. Conclusions: In our series, the group with discordant BM infiltration (BMB-/FC+) presented worsen survival outcomes than BMB-/FC-. Such results should be validated in prospective studies because published series are retrospective and not focused specifically on DLBCL. BM infiltration detected by FC analysis but not by BMB could be considered as extranodal involvement at DLBCL NOS diagnosis. Disclosures García Gutiérrez: Novartis: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Research Funding, Speakers Bureau.

Download Full-text

Practical Applications in Immunohistochemistry: Evaluation of Diffuse Large B-Cell Lymphoma and Related Large B-Cell Lymphomas

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2014-0451-cp ◽

2015 ◽

Vol 139 (9) ◽

pp. 1094-1107 ◽

Cited By ~ 18

Author(s):

Dennis P. O'Malley ◽

Aaron Auerbach ◽

Lawrence M. Weiss

Keyword(s):

B Cell ◽

Who Classification ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

World Health ◽

Cell Of Origin ◽

B Cell Lymphomas ◽

Practical Applications ◽

Large B Cell Lymphoma ◽

Large B Cell

Context Diffuse large B-cell lymphoma is the most commonly diagnosed subtype of lymphoma worldwide. The current World Health Organization (WHO) classification includes several subtypes, based on a combination of clinical, immunohistochemical, and genetic differences. Immunohistochemical staining is essential in evaluating diffuse large B-cell lymphoma and many related large B-cell lymphomas and aggressive B-cell lymphomas. Objective To address different immunohistochemical features used for identification, subclassification, prognosis and in some cases, therapy, of diffuse large B-cell lymphoma and related lymphomas. Data Sources The information outlined in this review article is based on our experiences with routine cases, on the current WHO classification of hematopoietic and lymphoid tumors, and on a review of English-language articles published throughout 2014. Conclusions Features and diagnostic criteria of diffuse large B-cell lymphoma, aggressive variants of B-cell lymphomas, including Burkitt lymphoma and “double-hit” lymphomas, are discussed. Identification of cell of origin (germinal center type versus activated B-cell type) is discussed at length. Finally, practical approaches for diagnosis are discussed.

Download Full-text