Plasma Cell Myeloma in Children and Young Adults: A Report of 4 Cases From a Single Institution and a Review of the Literature.

Plasma cell myeloma (PCM) is rare in children and young adults and therefore may be difficult to diagnose. Here we report the clinicopathologic findings of 4 patients under the age of 30 diagnosed with PCM at our institution and summarize the literature about 48 other cases of PCM in this age group. The male:female ratio was 1.2:1 and the number of cases increased with age. Children and young adults with PCM often present with a plasmacytoma and are less likely to have asymptomatic PCM than their adult counterparts. From the cases that reported ethnicity, the majority (55%) were non-white suggesting a possible ethnic predisposition to PCM in this age group. PCM should be included in the differential diagnosis of mass lesions, especially a destructive bony lesion, after more common causes have been ruled out in this age group. The optimal treatment for PCM in this patient population is unclear and conclusions into this are hampered by the paucity of cases and the lack of standardized follow-up.

Langerhans cell histiocytosis in acute leukemias of ambiguous or myeloid lineage in adult patients: support for a possible clonal relationship.

Four patients presented with acute leukemia of ambiguous or myeloid lineage in association with Langerhans cell histiocytosis and provide evidence suggesting a common origin of the two neoplasms. One patient had a non-constitutional trisomy 21 in both the leukemic blasts and the Langerhans cells indicative of a clonal relationship. A second case expressed CD2, CD13, and CD117 on both the Langerhans cells and the blasts suggesting a possible clonal relationship. All four cases exhibited geographic intermingling of the Langerhans cell histiocytosis and acute leukemia and shared unique features including extramedullary leukemia involving lymph nodes in all cases with Langerhans cell histiocytosis only present in sites involved by acute leukemia. T-cell antigen expression was present in all cases with one meeting criteria for mixed phenotype acute leukemia, T/myeloid, not otherwise specified. These findings support the concept that coexistent Langerhans cell histiocytosis and acute leukemia is clonally related in some cases. Furthermore, these cases of acute myeloid or acute leukemia of ambiguous lineage with Langerhans cell histiocytosis share some unique features suggesting a common underlying neoplastic hematopoietic stem cell.

A 3-way collision tumor of the upper respiratory tract: a composite of 2 immunophenotypically distinct mantle cell lymphomas and a plasmacytoma.

Composite lymphoma (CL) is composed of 2 or more morphologically and immunophenotypically distinct lymphomas in a single anatomical site. Here we report a unique CL of the upper respiratory tract in an elderly male patient. Morphologically, the lymphoma was composed of 2 distinct and well-demarcated areas consisting of monotonous small to medium-sized lymphocytes and sheets of mature-appearing plasma cells. Immunophenotyping by both flow cytometry and immunohistochemistry revealed that the small to medium-sized lymphocytes were composed of 2 distinct subpopulations sharing a CD5(+)/CD19(+)/CD20(+)/CD22(+)/CD23(-)/FMC-7(+)/cyclin D1(+) immunophenotype but with different immunoglobulin (Ig) light and heavy chain expression, consistent with 2 immunophenotypically distinct mantle cell lymphomas (MCLs); the plasma cells were composed of CD38(bright +)/CD138(+)/IgG kappa-restricted plasma cells, consistent with a plasmacytoma. Fluorescence in situ hybridization showed the t(11;14) translocation present in the lymphocyte region but absent in the plasma cell area. Ig heavy chain gene rearrangement studies on manually dissected populations showed 2 distinct patterns for the MCL and plasmacytoma. To our knowledge, this is the first report of a 3-way CL consisting of 2 immunophenotypically distinct MCLs and a plasmacytoma.

Immunophenotypic studies of monoclonal gammopathy of undetermined significance.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is a common plasma cell dyscrasia, comprising the most indolent form of monoclonal gammopathy. However, approximately 25% of MGUS cases ultimately progress to plasma cell myeloma (PCM) or related diseases. It is difficult to predict which subset of patients will transform. In this study, we examined the immunophenotypic differences of plasma cells in MGUS and PCM. METHODS: Bone marrow specimens from 32 MGUS patients and 32 PCM patients were analyzed by 4-color flow cytometry, using cluster analysis of ungated data, for the expression of several markers, including CD10, CD19, CD20, CD38, CD45, CD56 and surface and intracellular immunoglobulin light chains. RESULTS: All MGUS patients had two subpopulations of plasma cells, one with a "normal" phenotype [CD19(+), CD56(-), CD38(bright +)] and one with an aberrant phenotype [either CD19(-)/CD56(+) or CD19(-)/CD56(-)]. The normal subpopulation ranged from 4.4 to 86% (mean 27%) of total plasma cells. Only 20 of 32 PCM cases showed an identifiable normal subpopulation at significantly lower frequency [range 0-32%, mean 3.3%, p << 0.001]. The plasma cells in PCM were significantly less likely to express CD19 [1/32 (3.1%) vs. 13/29 (45%), p << 0.001] and more likely to express surface immunoglobulin [21/32 (66%) vs. 3/28 (11%), p << 0.001], compared to MGUS. Those expressing CD19 did so at a significantly lower level than in MGUS, with no overlap in mean fluorescence intensities [174 +/- 25 vs. 430 +/- 34, p << 0.001]. There were no significant differences in CD56 expression [23/32 (72%) vs. 18/29 (62%), p = 0.29], CD45 expression [15/32 (47%) vs. 20/30 (67%), p = 0.10] or CD38 mean fluorescence intensities [6552 +/- 451 vs. 6365 +/- 420, p = 0.38]. Two of the six MGUS cases (33%) with >90% CD19(-) plasma cells showed progression of disease, whereas none of the cases with >10% CD19(+) plasma cells evolved to PCM. CONCLUSION: MGUS cases with potential for disease progression appeared to lack CD19 expression on >90% of their plasma cells, displaying an immunophenotypic profile similar to PCM plasma cells. A higher relative proportion of CD19(+) plasma cells in MGUS may be associated with a lower potential for disease progression.

Quantification of marrow hematogones following autologous stem cell transplant in adult patients with plasma cell myeloma or diffuse large B-cell lymphoma and correlation with outcome.

In this retrospective study, we quantified the hematogone (normal B-lineage precursor) population by flow cytometric immunophenotyping in post-transplant bone marrow biopsy specimens from adult patients who received an autologous stem cell transplant for either plasma cell myeloma (n = 57) or diffuse large B-cell lymphoma (n = 73). The majority of patients (80%) had <5% marrow hematogones post-transplant. Extreme (>10%) hematogone percentages were quite rare, seen in only four patients, and were not associated with disease progression. There was a positive association between the post-transplant day and hematogone percentage within the first year after transplant, and a negative association thereafter. Plasma cell myeloma patients with ≥5% hematogones in any post-transplant flow cytometry study had a worse overall survival as did plasma cell myeloma patients with increased hematogones (as defined by percentile) at 100 days post-transplant. These findings require further study, ideally in a prospective study design.

Stability of leukemia-associated immunophenotypes in precursor B-lymphoblastic leukemia/lymphoma: a single institution experience.

Essentially all cases of precursor B-lymphoblastic leukemia/lymphoma (B-ALL) demonstrate multiple immunophenotypic aberrancies relative to normal maturing B-cell precursors (hematogones). The stability of these aberrancies has relevance to follow-up minimal residual disease analysis. We compared the immunophenotypes at diagnosis and relapse in 51 childhood and adult B-ALLs with flow cytometry (FC) using broad antibody panels. A total of 446 aberrancies were present at diagnosis (median, 9 per case; range, 2-14). All cases retained multiple aberrancies at relapse (median, 8 per case; range, 2-14). Antibody panels at relapse allowed assessment of 383 (85.9%) of the initial 446 aberrancies. Of these, 299 (78.1%) were persistent and 84 (21.9%) were lost at relapse. Overall, 73% of cases showed a loss of at least 1 aberrancy at relapse. However, new aberrancies were detected in 60% of cases. These findings suggest that FC is suitable for the detection of residual B-ALL, provided that follow-up studies are not too narrowly targeted.

Immunophenotypic differentiation between neoplastic plasma cells in mature B-cell lymphoma vs plasma cell myeloma.

Some non-Hodgkin lymphomas show marked plasmacytic differentiation. In such cases, it may be difficult to differentiate these lymphoma from plasmacytoma or myeloma, especially with limited diagnostic material. However, there may be immunophenotypic differences in the plasma cells in these disorders that distinguish them. This study characterizes the immunophenotypes of neoplastic plasma cells in 41 cases of B-lineage non-Hodgkin lymphoma and compares them with those in plasma cell myeloma. We found that plasma cells in lymphoma were significantly more likely to express CD19, CD45, and surface immunoglobulin and less likely to express CD56 than those in myeloma. We further show that CD 19 and CD56 expression can be used reliably to distinguish these entities. Myeloma-associated osseous lesions and solitary plasmacytoma of bone showed myeloma-like immunophenotypes. However, some extramedullary plasmacytomas showed lymphoma-like phenotypes, suggesting that, in reality, they may represent non-Hodgkin lymphomas with extensive plasmacytic differentiation.

Anaplastic large cell lymphoma: a flow cytometric analysis of 29 cases.

We report our experience with flow cytometric (FC) analysis of 29 cases of anaplastic large cell lymphoma (ALCL). Morphologic analysis of processed cytocentrifuged preparations demonstrated neoplastic cells in 28 cases. In 25 of these, an aberrant lymphoid population was detected by FC analysis. The majority showed high orthogonal light scatter, similar to monocytes or granulocytes. Of the antigens CD2, CD3, CD4, CD5, and CD7, 5 cases expressed 1, 8 expressed 2, 6 expressed 3, 3 expressed 4, and 3 expressed all 5. CD4 was expressed most commonly (20/25 [80%]), followed by CD2 (18/25 [72%]), CD3 (10/25 [40%]), and CD5 and CD7 (8/25 [32%] each). CD45 was expressed in 23 of 25 cases and CD13 in 7 of 9. Of 21 cases, 13 were anaplastic lymphoma kinase (ALK)+, all of which were CD4+, vs 5 of 8 ALK - cases (P = .042). Most ALCLs can be detected and characterized by multiparameter FC analysis. However, light scatter gating on typical lymphoid regions may yield false-negative results in a substantial number of cases.

Unusual extramedullary hematopoietic neoplasms in lymph nodes.

Myeloid, plasma cell, and lymphoblastic neoplasms are expected findings in bone marrow but are much less commonly diagnosed as primary processes in lymph nodes. The objective of this review is to aid pathologists in recognizing common hematopoietic neoplasms in the unusual setting of initial presentation in lymph nodes. Review of historical background and evolution of testing strategies is presented to improve understanding of the need for accurate diagnosis and classification using current nomenclature. The review is based on peer-reviewed literature and the personal experience of the authors. The University of Minnesota Medical Center, Fairview provides lymph node diagnostic consultation services for its busy oncology and therapeutic hematopoietic cell transplant divisions serving patients from around the globe. Although readily recognizable when they present in bone marrow, myeloid leukemia in the form of myeloid sarcoma, plasmacytoma, and lymphoblastic lymphoma can create diagnostic and classification challenges when they present as primary lymph node pathologies. Use of all diagnostic tools may be necessary to ensure accurate and reproducible diagnoses.

Relapsed Acute Promyelocytic Leukemia Lacks "Classic" Leukemic Promyelocyte Morphology and Can Create Diagnostic Challenges.

OBJECTIVES: Although current therapies for acute promyelocytic leukemia (APL), such as all- trans retinoic acid and arsenic trioxide, usually result in remission, some patients relapse. Early recognition of relapse is critical for prompt intervention. In this study, we systematically reviewed morphologic, immunophenotypic, and cytogenetic findings in paired diagnostic and relapsed APL cases and describe and quantify the changes in blast morphology at relapse. METHODS: By electronic database search, we identified eight paired diagnostic and relapsed APL cases for which peripheral blood or bone marrow smears were available for review. For two cases, diagnostic material was available for relapse after hematopoietic cell transplantation. RESULTS: Neoplastic hypergranular or microgranular promyelocytes with indented or bivalve nuclei predominated at diagnosis in all patients. Most patients had undifferentiated blasts at relapse and/or hypergranular blast equivalents with round to oval nuclei. Classic acute promyelocytic leukemia cells with bivalve nuclei and bundles of cytoplasmic Auer rods were easily identifiable in fewer than half of cases at diagnosis and rare to absent in all relapsed cases. CONCLUSIONS: Morphologic features of relapsed APL overlap with other types of acute myeloid leukemia, creating diagnostic challenges, especially if no history is available when relapsing patients seek treatment for care.

Differential methylation of genes that regulate cytokine signaling in lymphoid and hematopoietic tumors.

The perturbations of the cytokine signaling pathway play an important role in lymphoid/hematopoietic tumors. Aberrant promoter methylation is the major mechanism of gene silencing in tumors. We examined 150 lymphoid/hematopoietic tumors or potential premalignant specimens, 55 control specimens and 12 EBV-transformed B lymphoblastoid cultures and 10 lymphoma/leukemia (L/L) or multiple myeloma (MM) cell lines for the methylation (and, in cell lines, of the expression status) of three genes involved in the cytokine signaling pathway. The genes were: SHP1, a protein tyrosine phosphatase; SYK, a protein kinase; and SOCS1, a suppressor of cytokine signaling. Our major findings were: (1) one or more of the three genes was frequently methylated in L/L and MM cell lines and there was good concordance (90-100%) between methylation and loss of gene expression; (2) treatment of L/L cell lines with a demethylating agent resulted in re-expression of SHP1 protein and downregulation of phosphorylated STAT3 in L/L cell lines; (3) all 55 control specimens and the lymphoblastoid cultures were negative for methylation of the three genes; (4) non-Hodgkin's lymphomas (100%), and leukemias (94%) had almost universal methylation of SHP1 and relatively less frequent (<30%) methylation of SOCS1 and SYK; (5) MM and monoclonal gammopathy of unknown significance (MGUS) had infrequent methylation of SHP1 (<20%), and occasional methylation of SOCS1 and SYK; and (6) comparable methylation frequencies for SOCS1 were observed in MM and MGUS, suggesting that SOCS1 methylation is an early event in MM pathogenesis. At least one gene was methylated in 119 of 130 (93%) of the malignant and 12 of 20 (60%) of the MGUS samples. Our findings demonstrate that the perturbations of cytokine signaling via silencing of these three genes are almost universal in lymphoid/hematopoietic tumors but the patterns of gene methylated for L/L and plasma cell dyscrasias are different.

Differential usefulness of various markers in the flow cytometric detection of paroxysmal nocturnal hemoglobinuria in blood and bone marrow.

In this study, we examined the usefulness of various markers on blood cell populations in the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). We also evaluated bone marrow specimens, which generally are considered less suitable than blood owing to variable expression of glycosyl phosphatidylinositol (GPI)-linked antigens during hematopoietic cell differentiation. All 15 patients in our cohort had subpopulations of CD16/CD55-deficient granulocytes and CD14/CD55-deficient monocytes ("PNH clones"). The PNH clone size of granulocytes and monocytes was greater than that of erythrocytes or lymphocytes in the majority of the cases. It is interesting that CD59 showed limited usefulness for detecting PNH+ monocytes. Normal monocytes exhibited significantly dimmer CD59 expression than normal granulocytes. PNH-deficient monocytes expressed only marginally lower CD59, making it a less robust marker for highlighting PNH+ monocytes compared with CD14 or CD55. Finally, our study demonstrated the definitive usefulness of a limited combination of markers (CD16/CD55/CD45/CD14) in detecting GPI-deficient monocytes and granulocytes in bone marrow specimens submitted for flow cytometric evaluation of cytopenias.

Flow cytometric features of angioimmunoblastic T-cell lymphoma.

BACKGROUND: The immunophenotypic features of angioimmunoblastic T-cell lymphoma (AILT) have not been well described. METHODS: We retrospectively reviewed our institutional experience with the flow cytometric features of 16 cases of AILT. RESULTS: Multiparameter flow cytometry was able to identify a distinct population of immunophenotypically aberrant T cells in 15 of 16 cases. In 13 lymph node specimens, the neoplastic cells ranged from 1.9 to 87% (median 23%) of cells. The ratio of reactive to neoplastic T cells ranged from 0.01 to 20 (median 1.5); reactive T cells outnumbered neoplastic in 9/13 (69%) cases. The neoplastic populations expressed CD2, CD4, CD5, and CD45RO in all cases, lacked expression of CD8 and CD56 in all cases, and showed negative or dim surface CD3 in most cases. CD10 was expressed by the neoplastic populations in 11 of 14 cases at diagnosis; in 3 of these 11 only a subpopulation of the neoplastic cells was CD10(+). CD10 tended to be absent on neoplastic cells in staging bone marrows. The neoplastic population in all but one of the 15 positive cases possessed multiple immunophenotypic abnormalities and these were generally retained during the follow-up analyses of several cases. CONCLUSIONS: These results indicate the potential utility of flow cytometry in the diagnosis and follow-up of AILT.

Presence of simian virus 40 DNA sequences in human lymphoid and hematopoietic malignancies and their relationship to aberrant promoter methylation of multiple genes.

The simian polyoma virus SV40 has been detected in specific human tumors including non-Hodgkin's lymphomas, although a causative role for the virus has not been convincingly demonstrated. Aberrant methylation of CpG islands in promoter regions is a frequent method of silencing tumor suppressor genes (TSGs) in cancers and may be induced by oncogenic viruses. We investigated the relationship between the presence of SV40 or EBV DNA sequences and the methylation profiles for 10 TSGs in 90 cases of non-Hodgkin's lymphomas/leukemias and 56 control tissues. SV40 sequences were present in 33/90 (37%) non-Hodgkin's lymphomas/leukemias, and EBV was present in 11/42 (26%) of non-Hodgkin's lymphomas. We found a highly significant correlation between the presence of SV40 and methylation of seven genes (P values, 0.006 to <0.0001). In lymphomas, there was no relationship between EBV and methylation. Oncogenic viruses and methylation were rarely present in control tissues. We investigated methylation of the same 10 TSGs in peripheral blood mononuclear cells (PBMC) from a healthy volunteer infected with EBV or EBV and SV40. Promoter methylation of CDH1 and CDH13 were noted in dual SV40- and EBV-infected PBMC, and these two genes were also highly significantly correlated to the presence of SV40 sequences in tumors. SV40 infection also resulted in appearance of the lymphoma/leukemia-specific marker, methylated SHP1. Methylation was completely absent in uninfected and EBV-infected PBMC. Our results demonstrate that the presence of SV40 in hematological malignancies is associated with promoter methylation of TSGs and that in all probability, the virus plays a role in tumor pathogenesis.

Patients With a History of Chemotherapy and Isolated del(20q) With Minimal Myelodysplasia Have an Indolent Course.

OBJECTIVES: Isolated deletion (20q) is relatively common in myeloid neoplasms and has been rarely reported in cases of therapy-related myelodysplastic syndrome (MDS). Our aim was to characterize cases of isolated del(20q) in bone marrow biopsy specimens from patients with a history of chemotherapy with morphologic findings insufficient for a diagnosis of MDS. METHODS: In this retrospective study from one institution, we identified 22 patients with isolated del(20q) and no or minimal dysplasia and evaluated clinical and pathologic characteristics. RESULTS: Eleven of the patients had a history of chemotherapy for mostly lymphoproliferative disorders. There were no statistically significant differences in peripheral blood or bone marrow features between patients with a history of chemotherapy and those without. Three patients with a history of chemotherapy had died at last follow-up; cause of death was recurrent nonmyeloid neoplasm. None of the patients with a history of chemotherapy subsequently developed a high-grade myeloid neoplasm, whereas one of the patients who had not received prior chemotherapy developed refractory anemia with excess blasts 2. CONCLUSIONS: The presence of del(20q) as an isolated bone marrow cytogenetic abnormality in the absence of morphologic findings sufficient for a diagnosis of acute myeloid leukemia, myeloproliferative neoplasm, or MDS portends an indolent clinical course, regardless of previous exposure to chemotherapy.

Low blast count myeloid disorders with Auer rods: a clinicopathologic analysis of 9 cases.

Auer rods are a hallmark of acute myeloid leukemia but occasionally are seen in myelodysplastic syndromes (MDSs) or chronic myelomonocytic leukemia, rarely in cases with fewer than 5% blasts. The significance of this finding is unclear. We report 9 cases of this unusual phenomenon. All patients had cytopenias, isolated to a single lineage in 4. Circulating blasts were present in 8 cases (rare to 2.5%). Bone marrow blasts ranged from 0.4 to 4.9%; 1% to 32% of blasts contained Auer rods. There were variable degrees of dysplasia; 1 case closely mimicked refractory anemia with ringed sideroblasts. Cytogenetic studies in 8 cases showed clonal changes in 4. In 5 patients, acute myelogenous leukemia (AML) developed 6, 6, 5, 13, and 24 months after diagnosis; the patients subsequently died. Three patients died at 1, 1, and 8 months without progression to AML, and only 1 was alive at 10 months. MDSs with fewer than 5% blasts and Auer rods seem to be a heterogeneous group, but rapid progression to death or AML in most cases suggests that Auer rods signify an aggressive biology in MDSs with a low blast count.

Flow cytometric analysis of monocytes as a tool for distinguishing chronic myelomonocytic leukemia from reactive monocytosis.

To determine whether immunophenotypic features of monocytes are useful in differentiating chronic myelomonocytic leukemia (CMML) from reactive monocytosis, multiparameter flow cytometry was used to immunophenotype 20 bone marrow samples from patients with CMML, 10 normal marrow samples, and 20 marrow samples with reactive monocytosis. Monocytes in CMML exhibited aberrant antigen expression in all 20 cases. Abnormal antigen expression also was observed in monocytes in 11 of 20 reactive marrow samples. However, aberrant expression of 2 or more antigens was significantly less frequent in reactive monocytosis than in CMML (P = .002). CD56 expression with underexpression of a myeloid marker was unique to CMML monocytes. Subpopulations of monocytes with moderate levels of CD14 were present in all 3 groups. The proportion of CD14(moderate) monocytes was highest in CMML and was 20% or more in 13 of 20 CMML cases vs 3 of 20 reactive marrow samples (P = .003) and 2 of 10 normal marrow samples (P = .007). A combination of monocytosis with 2 or more immunophenotypic aberrancies with 20% or more of marrow monocytes showing moderate CD14 expression was 67% sensitive and 100% specific for CMML.

Zinc-induced copper deficiency: a report of three cases initially recognized on bone marrow examination.

Copper deficiency is a rare cause of sideroblastic anemia and neutropenia that often is not suspected clinically. The morphologic findings in bone marrow, while not pathognomonic, are sufficiently characteristic to suggest the diagnosis, leading to further testing to establish the correct diagnosis. Excess zinc ingestion is among the causes of copper deficiency. We present 3 cases of zinc-induced copper deficiency in which the diagnosis first was suggested on the basis of bone marrow examination. The first patient was a 47-year-old man with a debilitating peripheral neuropathy that had progressed during the previous 18 months, mild anemia, and severe neutropenia. The second was a 21-year-old man receiving zinc supplementation for acrodermatitis enteropathica in whom moderate normocytic anemia and neutropenia developed. The third patient was a 42-year-old man with anemia, severe neutropenia, and a peripheral neuropathy that had progressed during 8 months. The bone marrow findings in all cases suggested copper deficiency, which was confirmed by further laboratory testing and determined to be due to zinc excess. The morphologic features, clinical manifestations, differential diagnosis, and pathogenetic mechanisms are discussed.

CD5-positive B-cell neoplasms of indeterminate immunophenotype: a clinicopathologic analysis of 26 cases.

The flow cytometric classification of CD5-positive small B-cell neoplasms is dependent largely on the differential expression of CD23 and FMC-7. Occasional CD5-positive neoplasms with prominent co-expression of these antigens are encountered, precluding definitive immunophenotypic classification. The authors studied the clinicopathologic features of 26 neoplasms with this indeterminate immunophenotype. Available morphologic material was reviewed and analysis of CYCLIN D1 derangement was performed in selected cases by a combination of immunohistochemical, molecular, and cytogenetic techniques. Individual neoplasms were classified based on correlation of morphologic features and results of CYCLIN D1 studies. The neoplasms were classified into five categories: chronic lymphocytic leukemia (14 cases), "favor chronic lymphocytic leukemia" (3 cases), mantle cell lymphoma (3 cases), lymphoplasmacytic lymphoma (1 case), and unclassifiable (5 cases). Three of the unclassifiable neoplasms had morphologic features of mantle cell lymphoma, but CYCLIN D1 derangement could not be demonstrated. Neither relative expression of CD23 and FMC-7 nor intensity of CD20 or surface immunoglobulin expression was helpful in final classification. The authors conclude that CD5-positive small B-cell neoplasms with an indeterminate immunophenotype are a heterogeneous group, requiring additional studies for final classification. The majority (65%) appear to be chronic lymphocytic leukemia, with most of the remaining cases either definitively mantle cell lymphoma or unclassifiable.

The t(14;18) in diffuse large B-cell lymphoma: correlation with germinal center-associated markers and clinical features.

The clinical and biologic relevance of the t(14;18) and features of germinal center (GC) differentiation in diffuse large B-cell lymphoma (DLBCL) remain controversial. The authors examined the association of t(14;18) with GC-associated markers and clinical features in 44 de novo DLBCLs (22 nodal and 22 primary extranodal). CD10, bcl-2, and bcl-6 were expressed in 50%, 62%, and 54% of cases respectively. There were no significant differences in expression of these markers between nodal and extranodal cases. Coexpression of CD10 and bcl-6 was seen in 12 of 41 cases, and was more frequent in nodal than extranodal DLBCL (9 of 21 vs. 3 of 20; P = 0.05). A CD10+/bcl-6+ phenotype was not significantly associated with bcl-2 expression, stage, complete remission rate, or survival. The t(14;18) was found in 7 of 44 (16%) cases (6 nodal, 1 extranodal; P = 0.09). It was associated with a CD10+/bcl-6+ phenotype (5 of 7 vs. 7 of 27; P = 0.015) and a trend toward more frequent bcl-6 expression (6 of 7 vs. 15 of 34; P = 0.09), but no association with bcl-2 expression, CD10, clinical stage, complete remission, or survival. Among nodal or high-stage (III-IV) DLBCL, cases with the t(14;18) showed a trend toward decreased survival (P = 0.12).