Search

Marginal zone B-cell lymphomas (MZBCLs) are non-Hodgkin lymphomas arising from postgerminal center marginal zone B cells. MZBCLs are subclassified into extranodal, nodal, and splenic MZBCLs. Primary nondural central nervous system (CNS) MZBCLs of the mucosa-associated lymphoid tissue (MALT) type are among the extranodal examples. Their clinicopathological features are not well characterized. Therefore, the clinicopathological features of 8 primary nondural CNS MZBCLs of the MALT type were assessed to establish their pathological diagnostic criteria. Histologically, all cases of primary nondural CNS MZBCLs of the MALT type showed perivascular expansive monotonous proliferation of small atypical B lymphoid cells with plasma cell differentiation, low Ki-67 labeling index, and minimal invasion from the perivascular space. In addition, no vascular changes such as glomeruloid changes, obliterative fibrointimal proliferation, and intramural lymphocytic infiltration were seen. These key histological characteristics should be considered when diagnosing cases that are suspected to be primary nondural CNS MZBCLs of the MALT type. Additionally, regarding PCR for the detection of immunoglobulin heavy variable gene and T-cell receptor γ gene rearrangements, the former is detected, but the latter is not detected in all cases. Therefore, PCR detection including sequence analysis should be added when diagnosing difficult cases based on the key histological characteristics., (© 2021 American Association of Neuropathologists, Inc. All rights reserved.)

Objectives: Lymphoid enhancer binding factor 1 (LEF1) is expressed in most cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and has shown utility in distinguishing CLL/SLL from other small B-cell lymphomas. LEF1 expression has not been systematically studied in CD5-positive marginal zone lymphomas (MZLs), lymphoplasmacytic lymphomas (LPLs), and follicular lymphomas (FLs). We evaluated whether these cases lacked LEF1, helping to distinguish them from CLL/SLL., Methods: MZLs, LPLs, and FLs expressing CD5 were retrospectively studied for expression of LEF1 by immunohistochemistry., Results: LEF1 was absent in 17 of 18 CD5-positive lymphomas including 13 MZLs (2 nodal, 3 splenic, and 8 mucosa-associated lymphoid tissue lymphomas), 3 LPLs, and 1 of 2 FLs. One grade 3A CD5-positive FL expressed LEF1 in a majority of tumor cells., Conclusions: LEF1 is not expressed in most CD5-positive MZLs and LPLs; therefore, it is a reliable marker for distinguishing them from CLL/SLL. LEF1 may be expressed in CD5-positive FLs., (© American Society for Clinical Pathology, 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To describe the clinicopathologic findings of seven patients with CD5-positive nodal marginal zone lymphoma (NMZL)., Methods: We searched cases of NMZL over a 10-year interval and identified seven cases of CD5-positive NMZL. The clinical, histologic, and immunophenotypic findings of this group were reviewed, and the frequency of dissemination in this group was compared with that of 66 patients with CD5-negative NMZL., Results: Other than CD5 expression, the histologic and immunophenotypic findings were typical of NMZL. Six (86%) of seven patients had lymphadenopathy above and below the diaphragm, and all six patients assessed had bone marrow involvement. In the CD5-negative group, 28 (42%) patients had lymphadenopathy above and below the diaphragm, and 36 (55%) had bone marrow involvement (P = .045 and P = .037, respectively). Six of seven patients were alive at last follow-up, with a median follow-up of 32 months (3-154 months)., Conclusions: CD5 expression in NMZL correlates with a higher frequency of dissemination, but patients have an indolent clinical course and excellent overall survival.

Objectives: To evaluate CD200 expression in B-cell proliferative disorders., Methods: We analyzed 180 recent specimens of B-cell neoplasms for CD200 expression by flow cytometric immunophenotypic analysis, which is better able to assess relative intensity of staining than immunohistochemical staining., Results: We found that hairy cell leukemia exhibits a high level of staining for CD200 in comparison to other B-cell lymphoproliferative disorders, including hairy cell leukemia-variant (HCL-V), marginal zone lymphoma, and lymphoplasmacytic lymphoma. We confirmed this observation by semiquantitative immunohistochemical staining., Conclusions: Assessment of the CD200 expression level is helpful to distinguish HCL from HCL-V and other B-cell lymphoproliferative disorders and in the differential diagnosis of B-cell neoplasms in general.

Objectives: To examine the immunoarchitectural patterns of the germinal center (GC)-associated markers CD10, BCL6, and LMO2 and their utility in the differential diagnosis of marginal zone lymphoma (MZL) vs follicular lymphoma (FL)., Methods: Forty-two cases of MZL involving lymph nodes and 88 cases of FL were examined., Results: Interfollicular staining for GC markers was uncommon in MZL but common in FL, including BCL2-positive and BCL2-negative cases. Two atypical patterns of intrafollicular GC staining were identified that were more common in MZL than in FL., Conclusions: Staining for LMO2 in addition to CD10 and BCL6 facilitates the detection of a GC phenotype in FL. Lymph nodes involved by MZL frequently show characteristic alterations of GC immunoarchitecture. Recognizing these altered patterns assists in the distinction between MZL and FL.

Detection of the integrin subunit CD103 is a useful diagnostic tool in the diagnosis of hairy cell leukemia (HCL). Currently, flow cytometric analysis (FC) and frozen section immunohistochemistry (IHC) represent the only available methods of detection. This study is the first to describe the successful use of a CD103 antibody to identify HCL and HCL-variant in paraffin sections of formalin- or Bouin solution- fixed specimens (n = 68) using an immunoperoxidase technique. In other B-cell lymphoproliferative disorders that morphologically may resemble HCL, including chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 32), mantle cell lymphoma (n = 23), lymphoplasmacytic lymphoma (n = 27), follicular lymphoma (n = 7), and marginal zone lymphoma (n = 13), lymphoid cells are nonreactive for CD103. In HCL, the CD103 staining pattern is predominantly membranous with delineation of delicate cytoplasmic projections. This CD103 antibody is an extremely valuable addition to the IHC panel for the diagnosis of HCL, especially in cases lacking FC analysis.

Background: Primary cutaneous B-cell lymphomas (PCBCL) are subdivided into the aggressive form, primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT) and two subtypes of indolent behaviour (primary cutaneous follicle centre lymphoma and primary cutaneous marginal zone B-cell lymphoma). The difference in clinical behaviour can be explained by the tumour cell itself, or the lymphoma microenvironment including the antitumour immune response., Objectives: To investigate the presence of regulatory T cells (Treg), CD4+CD25+FOXP3+, in the microenvironment of PCBCL in correlation with clinical outcome., Methods: Tumour specimens of 55 consecutive cases of PCBCL were blinded and analysed for FOXP3, CD4 and CD25 expression by immunohistochemistry. Confocal images were taken with a Leica SP5. Statistical analyses were performed to determine significance. The test was considered significant when P<0.05., Results: The CD4 and FOXP3 expression as well as the CD4/FOXP3 ratio were significantly increased in PCBCL of indolent behaviour in contrast to PCLBCL, LT (P=0.0002 for CD4, P<0.0001 for FOXP3 and P=0.0345 for FOXP3/CD4 ratio). CD25 expression did not differ in the three groups (P=0.9414). Within the group of patients with PCLBCL, LT we identified a subgroup with FOXP3+ tumour cells as demonstrated by CD20/FOXP3 double stainings. Patients with FOXP3+ PCLBCL, LT tumour cells showed a better prognosis on Kaplan-Meier analysis., Conclusion: High numbers of Treg in the lymphoma microenvironment correlate with a better prognosis in PCBCL. In PCLBCL, LT the presence of FOXP3+ tumour cells is beneficial for prognosis suggesting that FOXP3 expression of PCLBCL, LT tumour cells might serve as a tumour suppressor., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a mature B-cell neoplasm that typically follows an indolent clinical course. Amyloid deposition associated with MALT lymphoma is uncommon. We describe the clinical and pathologic features of 20 cases of MALT lymphoma and associated amyloid deposition across diverse primary sites. Frozen section immunofluorescence performed on 4 cases suggests that these deposits are a localized form of AL amyloid. Clinical follow-up was available for 15 patients. Amyloid deposits distant from the initial site occurred in 5 cases, always at sites also involved by the underlying lymphoma. No definitive evidence of systemic amyloidosis affecting the heart, kidneys, or liver was present in any patient. Given the generally indolent clinical behavior of MALT lymphomas with associated amyloid, we do not recommend extensive follow-up testing for systemic amyloidosis or more aggressive therapy than would be indicated for other MALT lymphomas of similar clinical stage.

We studied the efficacy of 2 germinal center B-cell markers, HGAL and LMO2, in the separation of lymphomas derived from small B cells, particularly follicular lymphoma (FL) and marginal zone lymphoma occurring in nodal, extranodal, splenic, and bone marrow sites using immunohistochemical analysis for CD10, BCL6, BCL2, HGAL, and LMO2. Our results showed that HGAL and LMO2 are sensitive and specific markers for detecting FL in nodal and extranodal sites. In contrast, all markers were down-regulated in FL infiltrates in the bone marrow. CD10 and HGAL were expressed in a subset of FLs in the bone marrow and were highly correlated with each other and with CD21, a marker of follicular dendritic cells. We conclude that HGAL and LMO2 should be considered in immunohistochemical panels used for the routine workup of lymphomas derived from small B cells. In the bone marrow, staining for HGAL or CD10 can be helpful in making a diagnosis of FL, although they are absent in a subset of cases.

Anetoderma is a rare condition, consisting of well-circumscribed areas of slack skin, in which dermal elastic fibres are destroyed or deficient. We present the case of a 45-year-old man with a 25-year history of deep nodules and plaques gradually progressing to areas of anetoderma. Histological examination found an infiltrate composed of neoplastic cells with lymphoplasmocytoid morphology. The cells were positive for CD20, CD38 and CD138, and there was a monoclonal kappa light chain gene rearrangement of plasma cells. A diagnosis of cutaneous marginal-zone B-cell lymphoma was made. The pathogenesis of anetoderma remains unknown, but it is possible that cytokines or other soluble factors produced by the infiltrating lymphocytes have a role in this process.

Nodal marginal zone lymphoma (NMZL) represents a rare and heterogeneous group that lacks markers specific for the diagnosis. We evaluated morphologic and immunoarchitectural features of 51 NMZLs, and the following immunostains were performed: CD20, CD21, CD23, CD5, CD3, CD43, CD10, Ki-67, BCL1, BCL2, BCL6, HGAL, and LMO2. Four immunoarchitectural patterns were evident: diffuse (38 [75%]), well-formed nodular/follicular (5 [10%]), interfollicular (7 [14%]), and perifollicular (1 [2%]). Additional features included a monocytoid component (36 [71%]), admixed large cells (20 [39%]), plasma cells (24 [47%]), compartmentalizing stromal sclerosis (13 [25%]), and prominent blood vessel sclerosis (10 [20%]). CD21 highlighted disrupted follicular dendritic cell meshwork in 35 (71%) of 49 cases, and CD43 coexpression was present in 10 (24%) of 42 cases. A panel of germinal center-associated markers was helpful in eliminating cases of diffuse follicle center lymphoma. Our results highlight the histologic and immunoarchitectural spectrum of NMZL and the usefulness of immunohistochemical analysis for CD43, CD23, CD21, BCL6, HGAL, and LMO2 in the diagnosis of NMZL.

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) can arise at any anatomic site, but involvement of the kidney is rare. We describe 10 cases of kidney MALT lymphoma, including 6 localized cases. No predisposing inflammatory conditions were identified, with the possible exception of coexistent renal Actinomyces infection in 1 case. We performed fluorescence in situ hybridization (FISH) using a malt1 break-apart probe in 7 cases. A malt1 gene rearrangement was identified in 1 case (14%). This case was further assessed by FISH using an IgH breakapart probe that showed IgH gene rearrangement. These results are suggestive of the t(14;18) involving malt1 and IgH. Immunostaining for NF-kappaB p65 showed nuclear positivity, consistent with NF-kappaB activation, in 3 of 5 cases assessed. Our results indicate that kidney MALT lymphomas share similarities with MALT lymphomas arising at other sites in that MALT lymphoma-associated translocations and NF-kappaB activation occur in a subset of cases.

The t(11;18)(q21;q21) API2/MALT1 translocation is a specific chromosomal abnormality in extranodal marginal B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) type, particularly in those occurring in the stomach and lungs. Identification of t(11;18) may aid in the diagnosis of MALT lymphoma and strongly predicts resistance of gastric MALT lymphoma to Helicobacter pylori eradication therapy. We developed a robust real-time reverse transcription-polymerase chain reaction (RT-PCR) procedure to efficiently detect t(11;18) in virtually all types of specimens used in routine diagnostic workups. We blindly tested 40 samples from 38 patients with gastric MALT lymphoma; 10 (25%) of 40 samples, or 8 (21%) of 38 patients were positive for t(11;18). In contrast, t(11;18) was not detected in 8 cases of gastric large B-cell lymphoma, 11 cases of chronic active gastritis, and 16 samples unrelated to lymphoma. Our findings suggest that real-time RT-PCR for t(11;18) may be a valuable tool with much relevance in the current clinical management scheme.

Waldenström macroglobulinemia (WM) and its associated hyperviscosity syndrome (HVS) are generally caused by lymphoplasmacytoid lymphoma or other small B-cell lymphoproliferative disorders. WM associated with extranodal marginal zone B-cell-mucosa-associated lymphoid tissue lymphoma (EMZL/MALT-type) has not been emphasized. We describe 4 men and 2 women (age, 40-79 years) with clinical and laboratory manifestations of WM and EMZL/MALT-type involving one or more sites: lung, pericardium/pleura, ocular adnexa, nasopharynx, minor salivary gland, glossopharyngeal fold, skin, and stomach. The following immunophenotypic patterns were observed: CD20+, 6; CD43+, 3; kappa light chain restriction, 5; and lambda light chain restriction, 1. All were negative for CD5, CD10, and cyclin D1 expression. A clonal paraproteinemia was present in each (IgM kappa, 4; IgM lambda, 1; biclonal IgM kappa/IgA kappa, 1). All 4 patients tested had elevated plasma viscosity; clinical HVS occurred in 3, and 2 required emergency plasmapheresis. These findings suggest that EMZL/MALT-type can cause WM and that the laboratory evaluation of EMZL/MALT-type should include serum protein electrophoresis/immunofixation, and plasma viscosity measurements and urine immunofixation in select cases. EMZL/MALT-type should be considered in the differential diagnosis in patients with clinicopathologic features of WM.

Low-grade lymphoproliferative disorders are a heterogeneous group of lymphoid neoplasms with wide variation in histologic features, immunologic phenotype, and molecular abnormalities. Subclassification of these disorders with small lymphocytic proliferation may be difficult on the basis of morphologic findings alone. The bcl-6 gene, originally cloned from a tumor with 3q27 translocation, is commonly expressed in large cell lymphomas. In humans, bcl-6 encodes for a Krüppel-type zinc finger protein and is believed to be important in germinal center formation. Bcl-6 protein is expressed mainly by follicle center cells and a few interfollicular T lymphocytes. We analyzed Bcl-6 expression with immunologic methods in common low-grade lymphoproliferative disorders as an aid to differentiation of tumors with follicle center origin. We analyzed Bcl-6 staining of formalin-fixed paraffin-embedded tissue from 72 indolent lymphomas including 31 grade I and II follicle center lymphomas (FCL). 13 small lymphocytic lymphomas (SLL), 12 mantle cell lymphomas (MCL), and 16 marginal zone lymphomas (MZL) including lymphomas of mucosa-associated lymphoid tissue and spleen. All of 31 FCL were positive for Bcl-6 expression. One of 13 SLL and 1 of 12 MCL were positive, whereas none of 16 MZL were positive. Bcl-6 was also detected in 5 of 5 FCL and 1 of 3 MZL but in no SLL or MCL by Western blot analysis in 14 cases with lymphoid disorders. Our study demonstrates that Bcl-6 expression is common in low-grade FCL but is rare in other indolent B-cell lymphoid disorders, and may be a useful adjunct in classification of indolent lymphomas.