Blastic mantle cell leukemia: a previously undescribed form.

The leukemic phase of mantle cell lymphoma (mantle cell leukemia) is defined as an absolute lymphocyte count of greater than 4,000/microliter and characterized by the presence of relatively small, slightly irregular lymphocytes in the peripheral blood. Although a variant of mantle cell lymphoma with blastic morphsology exists and has been previously well described, a blastic morphologic variant of mantle cell leukemia has not been described. We report such a case in a 74-year-old male who presented with splenic rupture and an elevated white blood cell (WBC) count. The diagnosis was based on flow cytometric immunophenotyping and the cytomorphology of the peripheral blood.     

Interleukin 3 is a growth factor for human follicular B cell lymphoma

More than one-half of adults with non-Hodgkin's B cell lymphomas present with low-grade follicular lymphomas. These tumor cells are found in close association with follicular T lymphocytes and dendritic cells, suggesting that the surrounding cells may play a role in the support of follicular tumors. Supernatants from activated human peripheral blood lymphocytes were found to promote the in vitro proliferation of follicular tumor cells. This effect was entirely due to interleukin 3 (IL-3), a factor generally thought to cause the growth and differentiation of immature hematopoietic cells. IL-3 receptors were detected on fresh isolates of all primary follicular cell tumors examined. These findings suggest that follicular cell tumors may be dependent in vivo on IL-3 and that therapies directed against IL-3, its receptor, or the T cells that produce it may be effective treatment for follicular lymphoma.     

AIDS-related lymphoma diagnosed by flow cytometry of a pleural effusion

We have presented a case in which flow cytometry of pleural fluid was applied in the diagnosis of an AIDS-related lymphoma. Flow cytometric evaluation of malignant effusions is a less invasive means of diagnosing these neoplasms than tissue biopsy.     

Clinical significance of monoclonal B cells in cerebrospinal fluid

BACKGROUND: Morphologically malignant lymphocytes in the cerebrospinal fluid (CSF) are highly suggestive of central nervous system involvement by lymphoid malignancy. Although flow cytometry is increasingly used to detect a monoclonal B-cell population in the CSF, the significance of this finding in the absence of morphologically identifiable malignant cells is unknown. METHODS: We reviewed CSF flow cytometric results in 32 patients studied at a single institution over 5 years and identified patients who had monoclonal B-cells in the CSF. Clinical presentation and course were reviewed. RESULTS: Twelve patients had a monoclonal B-cell population in the CSF, but only three had clinical evidence of malignant CNS disease. Of the other nine patients, 4 had nonmalignant neurologic disease and five had a lymphoproliferative disorder: chronic lymphocytic leukemia (n = 4) and mantle cell lymphoma (n = 1). In patients who had chronic lymphocytic leukemia and mantle cell lymphoma, the monoclonal B-cell population was small and had an immunophenotype identical to that of circulating malignant B cells. None of these nine patients developed clinical evidence of malignant CNS involvement during follow-up. CONCLUSION: In patients who have indolent B-cell malignancies, the presence of monoclonal B cells in the CSF may not be diagnostic of clinically significant CNS involvement by a lymphoid malignancy.     

Malignant lymphoma of the small intestine

The clinicopathologic features of malignant lymphoma of the small intestine were reviewed. Genetically, characteristic chromosomal translocations have been identified in several B-cell lymphomas, such as t (11 ; 18)/API2-MALT1 in MALT lymphoma, t (14 ; 18)/IGH-BCL2 in follicular lymphoma, or t (3 ; 14)/BCL6-IGH in diffuse large B-cell lymphoma (DLBCL). Histologically, DLBCL is most frequently observed, and T-cell lymphoma and follicular lymphoma are more frequent in small intestinal cases than in gastric cases. Macroscopically, small intestinal lymphomas are classified as polypoid, ulcerative (including stricturing, non-stricturing and aneurysmal forms on radiography), multiple lymphomatous polyposis, diffuse, or other types. A significant correlation is observed between these macroscopic/radiographic and histologic types. The therapeutic strategy, such as surgery, chemotherapy, antibiotics or watch-and-wait, should be determined based on the disease extent, histologic type, and clinical stage.     

Utility of flow cytometry in subtyping composite and sequential lymphoma.

Composite lymphoma (CL) is defined as more than one distinct lymphoma variant occurring in the same anatomic site, and sequential lymphoma (SL) is defined as different lymphoma variants occurring at different sites or at different times in the same patient. The utility of flow cytometry immunophenotyping in evaluating CL and SL has only been investigated in a few single-case studies. To further define the utility of flow cytometry in evaluating these tumors, records were searched at two institutions. Cases representing high-grade progression of low-grade lymphoma were excluded. For each CL/SL, clinical data was obtained and morphology was evaluated in routinely processed H&E-stained tissue sections. Tumor components were subtyped using revised European-American classification (REAL) criteria. Follicle center components were graded using modified Rappaport criteria. Immunophenotype was determined using two-color flow cytometry and paraffin-section immunostains. Four cases were identified. Case 1, nodal follicle center, follicular, grade III plus marginal zone CL, showed two discrete populations of monoclonal B-cells that differed in their expression of CD10. Case 2, cutaneous lymphoplasmacytoid lymphoma followed by mesenteric non-Hodgkin's lymphoma (lymphoplasmacytoid plus follicle center, follicular, grade III) plus Hodgkin's disease CL, showed CD5-/CD10-/CD19+/kappa+ cells by flow cytometry in both tissue samples. The Hodgkin's disease component showed CD3-/CD15-/CD20-/CD30+ Reed-Sternberg cell variants in paraffin-section immunostains. Case 3 represented nodal follicle center lymphoma, follicular, grade I (CD3-/CD5-/CD10-/CD19+/kappa+) followed by cutaneous anaplastic large T-cell lymphoma (CD2+/CD4+/CD5+/CD19- cells with partial expression of CD3 and CD7). Case 4 represented cutaneous follicle center lymphoma, follicular, grade I (CD5-/CD10+/CD19+/CD23+/lambda+) followed by bone marrow B-cell small lymphocytic lymphoma (CD5+/CD10-/CD19+/CD23+/kappa+). Results show that flow cytometry is a potentially useful adjunct in characterizing CL and SL.     

Diminished expression of CD19 in B-cell lymphomas

BACKGROUND: CD19 is expressed on most B-cell lymphomas; however, the frequency and types of B-cell lymphomas with low-level expression of CD19 are not well characterized. METHODS: We reviewed flow cytometric histograms specifically for decreased CD19 expression on 349 cases analyzed by the Flow Cytometry Laboratory at University Hospitals of Cleveland (Cleveland, Ohio). Results of flow cytometry were correlated with the morphologic diagnosis. RESULTS: Of the cases reviewed, 125 (36%) showed a visible decrease in CD19 expression compared with normal B lymphocytes. Decreased CD19 expression was noted in 79% of follicular lymphomas (27 of 34), 36% of small lymphocytic lymphomas/chronic lymphocytic leukemias (82 of 228), 31% of mantle cell lymphomas (4 of 13), 24% of diffuse large B-cell lymphomas (8 of 33), and 13% of marginal zone B-cell lymphomas/lymphoplasmacytoid lymphomas (4 of 30) and was not observed in any Burkitt lymphoma (0 of 5) or hairy cell leukemia (0 of 6). Decreased CD19 expression was significantly more frequent in follicular lymphomas than in other lymphoma subtypes (P < 0.001). No significant difference was observed in the frequency of decreased CD19 expression based on histologic grade of follicular lymphoma. CONCLUSIONS: Diminished expression of CD19 expression occurs frequently in B-cell lymphomas, in particular follicular lymphoma, and may be helpful in identifying B-cell lymphoma cells in complex cell mixtures such as bone marrow specimens.     

Phenotyping renal leukocyte subsets by four-color flow cytometry: characterization of chemokine receptor expression

To investigate mechanisms of cell-mediated injury in renal inflammatory disease it is critical to determine the surface phenotype of infiltrating renal leukocyte subsets. However, the cell-specific expression of many leukocyte receptors is difficult to characterize in vivo. Here, we report a protocol based on flow cytometry that allows simultaneous characterization of surface receptor expression on different subsets of infiltrating renal leukocytes. The described technique combines an adapted method to prepare single cell suspensions from whole kidneys with subsequent four-color flow cytometry. We recently applied this technique to determine the differential expression of murine chemokine receptors CCR2 and CCR5 on infiltrating renal leukocyte subsets. In this article, we summarize our current findings on the validity of the method as compared with immunohistology and in situ hybridization in two murine models of nonimmune (obstructive nephropathy) and immune-mediated (lupus nephritis) inflammatory renal disease. Flow cytometry analysis revealed an accumulation of CCR5-, but not CCR2-positive lymphocytes in inflamed kidneys, compared to the peripheral blood. Particularly renal CD8+ cells expressed CCR5 (79% in obstructed kidneys, 90% in lupus nephritis). In both models, infiltrating renal macrophages were positive for CCR2 and CCR5. These data corresponded to immunohistological and in situ hybridization results. They demonstrate that flow cytometric analysis of single cell suspensions prepared from inflamed kidneys is a rapid and reliable technique to characterize and quantify surface receptor expression on infiltrating renal leukocyte subsets.     

Detection of bone marrow infiltration of lymphoma cells by fluorescence in situ hybridization

BACKGROUND: It is sometimes difficult to detect the bone marrow infiltration of lymphoma cells, because lymphoma cells are not distinguishable from normal lymphocytes due to the similarity of their phenotype. METHODS: Bone marrow involvement of 17 samples of 15 patients with follicular lymphoma, whose lymphoma cells were confirmed to harbor the translocation of chromosome14q32, were examined by microscopic analysis of bone marrow smear and biopsy, flow cytometorical analysis (FCM), chromosomal analysis of G-banding and fluorescence in situ hybridization (FISH). FISH was performed using a probe, which detects the split of IGH gene on 14q32. RESULTS: The positivity of FISH was highest among these methods and FISH was able to detect the bone marrow involvement in one case who was defined as negative by bone marrow biopsy. CONCLUSIONS: FISH can be used for detection of bone marrow involvement of malignant lymphoma that carries chromosomal rearrangement involving 14q32.     

Use of Color Doppler Ultrasonography for the Prediction of Malignancy in Follicular Thyroid Neoplasms

Objective. The purpose of this systematic review was to obtain summary estimates of the diagnostic accuracy of color Doppler ultrasonography (CDU) in predicting malignancy in thyroid follicular neoplasms (FNs). Methods. We searched Medical Subject Headings together with the search terms “follicular,” “thyroid,” and “Doppler” in the MEDLINE, Web of Science, and Excerpta Medica databases as well as the Latin American and Caribbean Health Sciences Literature database, after which we performed manual searches of the reference lists to locate additional studies. There were no language restrictions. We included studies that assessed the diagnostic accuracy of CDU in identifying malignancy in thyroid FNs. The assessments of the quality and extraction of data were performed by 3 independent reviewers. Results. We included 4 studies, which collectively evaluated 457 thyroid FNs, 67 of which had been classified as malignant based on the evaluation of surgical biopsy samples. Moderate, rich, predominant, or exclusive internal flow on CDU of thyroid FNs was considered indicative of malignancy. The overall sensitivity of CDU was 85% (95% confidence interval [CI], 74%–93%), with an overall specificity of 86% (95% CI, 82%–89%). The overall prevalence was 14.7%, and the positive and negative predictive values were 51% and 97%, respectively. The positive likelihood ratio was 6.07, and the negative likelihood ratio was 0.18. Conclusions. Predominant internal flow seen on CDU is associated with malignancy of thyroid FNs. Absence of internal flow or predominantly peripheral flow indicates a low probability of thyroid FN malignancy.     

Benign, atypical and malignant lymphoproliferative disorders in rheumatoid arthritis patients

Lymphadenopathy, which may be associated with systemic symptoms, is frequently associated with rheumatoid arthritis (RA). Reactive non-neoplastic tissue comprises the majority of the lymph node lesions. However, several cohort studies have demonstrated that RA has an increased risk of non-Hodgkin's lymphomas (NHLs). Since the early 1990s, an atypical or malignant lymphoproliferative disorders (LPD) in patients immunosupressed with methtorexate (MTX) therapy for RA has been emphasized, namely MTX-associated LPDs. Epstein-Barr virus (EBV) has received attention in connection with the etiology of RA. The present review describes the clinicopathologic and immunohistochemical findings of reactive, atypical and malignant LPDs associated with RA along with the presence or absence of EBV in LPDs using the in situ hybridization (ISH) method. The majority of reactive lymph node lesions exhibit reactive follicular hyperplasia with interfollicular polyclonal plasmacytosis. Atypical LPDs rarely appears in RA patients. However, these cases occasionally pose difficult problems in the differential diagnosis from malignant lymphomas associated with RA or atypical and malignant LPDs showing RA-like clinicopathological findings. Clinicopathologically, three types of atypical LPDs have delineated, i.e. (i) resembling multicentric Castleman's disease (MCD); (ii) atypical paracortical hyperplasia with lymphoid follicles (APHLF) and; (iii) atypical lymphoplasmacytic immunoblastic proliferation. Malignant lymphoma associated with RA is characterized by; (i) predominance of elderly cases; (ii) usually female predominance, reflecting the sex ratio of RA; (iii) longstanding history of RA; (iv) relatively frequent advanced stage of disease; (v) majority of the patients had the B-cell phenotype; and (vi) an increased frequency of diffuse large B-cell lymphoma (DLBCL) in RA. It is unlikely that EBV is the causative agent of either reactive or atypical LPD. Among malignant lymphomas, EBV-associated lymphoma comprised only a small fraction of all NHLs in the general RA patient population.     

Patient-specific vaccine therapy for non-Hodgkin lymphoma

Follicular non-Hodgkin lymphoma (NHL) is an indolent, or slow-growing, malignant disease of the lymphoid tissue, which usually responds to initial therapy. However, the disease is characterized by multiple relapses and remissions, eventually causing death. Several effective therapies are available, but improvement of overall survival in patients with follicular NHL has not been demonstrated. Stimulation of the immune system to recognize malignant lymphoma cells as foreign has been demonstrated as a viable treatment option for patients with follicular NHL. Patient-specific vaccine therapy is a new form of active immunotherapy being studied for NHL. Clinical trials have shown a benefit for patients receiving this type of therapy. This article will provide a foundation for nurses caring for patients receiving patient-specific vaccine therapy.     

原发性中枢神经系统恶性淋巴瘤bcl—2蛋白的表达

运用免疫组化SP法，观察18例中枢神经系统B细胞淋巴瘤（经LCA、L26、UCHL1、GFAP标记和电镜检查证实）bcl-2蛋白的表达。结果表明：13例滤泡中心性淋巴瘤bcl-2蛋白阳性，1例淋巴浆细胞淋巴瘤bcl－2蛋白阳性，总阳性率77．8％。我们认为bcl－2基因产物高表达介导的细胞凋亡障碍与中枢神经系统淋巴瘤的发生有关。并且bcl-2蛋白在中枢神经系统小圆细胞肿瘤的鉴别诊断中，不失为一种较为简便、可靠的技术，值得推广。     

体重指数与恶性淋巴瘤关系病例对照研究的Meta分析

目的采用Meta分析的方法探讨体重指数(BMI)与恶性淋巴瘤的关系。方法计算机检索Web of Science、PubMed、EMbase、CNKI、WanFang Data、VIP和CBM等国内外数据库,检索时间均从建库至2011年4月,查找BMI与恶性淋巴瘤发病关系的病例对照研究。由两位研究者按照纳入与排除标准进行资料提取和质量评价后,采用RevMan 5.0软件对各研究进行数据合并与分析。结果共纳入7个病例对照研究,合计8 416例恶性淋巴瘤患者和14 760例非恶性淋巴瘤的其他患者。7个纳入研究的质量评分均在4分以上,说明质量较可靠。Meta分析结果显示:低BMI人群的OR合并值为0.8[695%C(I0.79,0.95),P=0.003],超重人群的OR合并值为1.0[495%CI(0.98,1.11),P=0.16],肥胖人群的OR合并值为1.22[95%CI(1.04,1.43),P=0.01];对病理类型进行分层分析后发现,在弥漫性大B细胞淋巴瘤中肥胖者OR合并值为1.33[95%CI(1.18,1.50),P<0.000 01],而是否肥胖在滤泡性淋巴瘤和小淋巴细胞淋巴瘤/淋巴细胞白血病发生情况的亚组分析中,其差异无统计学意义。结论本Meta分析结果显示低BMI是恶性淋巴瘤的保护性因素,而肥胖是恶性淋巴瘤尤其是弥漫性大B细胞淋巴瘤发病的危险因素。     

Lymphomatoid papulosis

In this review, we discuss the clinical and histologic features of lymphomatoid papulosis, a cutaneous disorder characterized by recurrent eruptions of self-healing papules and small nodules with histologic findings suggestive of malignant lymphoma. Possible causes of this peculiar disease are discussed in the light of recent investigation. Recognition is important to avoid misdiagnosis and overly aggressive therapy, but it should be remembered that a small number of cases have been reported to progress to malignant lymphoma.     

Clinicopathological features of malignant lymphoma in Japan: the Miyagi Study

The Miyagi Study is an epidemiological study of malignant lymphoma, including immunological and genetic analyses, constructed by a population-based registration system covering Miyagi prefecture, Japan. A total of 1,552 newly diagnosed cases in Miyagi between 2002 and 2008 were enrolled in this study; 75% were B-cell lymphomas, 19% were T-cell and natural killer-cell (T/NK-cell) lymphomas, and 5% were Hodgkin's lymphomas. The most frequent subtype of B-cell lymphoma is diffuse large B-cell lymphoma, followed by follicular lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (51%, 24% and 8%, respectively). Thus, follicular lymphoma accounts for 18.2% of newly diagnosed cases in Miyagi; unexpectedly, its frequency is similar to that reported in Western countries. The common subtypes of T/NK-cell lymphoma are peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma, and adult T-cell leukemia/lymphoma (30%, 15% and 14%, respectively). Most of the data are similar to those reported in Asian countries, except for follicular lymphoma. We also analyzed the CD20 expression in B-cell lymphomas by flow cytometry for the cell membrane expression and by immunohistochemistry for the cytoplasmic expression. The cell membrane expression of CD20 protein may determine the susceptibility of B-cell lymphomas to anti-CD20 antibody therapy. The lack of CD20 expression was confirmed by both methods in 4 cases of 585 newly diagnosed cases (0.7%) and in 5 of 67 recurrent cases (7.5%). Furthermore, 23 cases (6.5%) showed the discrepancy of CD20 expression between both methods. The Miyagi Study has revealed the latest epidemiological features of malignant lymphoma in Japan.     

淋巴结细针穿刺标本的流式细胞术分析

目的 评价淋巴结细针穿刺标本流式细胞术分析方法在诊断淋巴结病变,以及在恶性淋巴瘤和淋巴结反应性增生鉴别诊断中的应用价值.方法 对99份疑为淋巴结病变的淋巴结针吸标本涂片进行常规细胞学分析,并结合病理活组织检查确诊分型.使用三色标记的流式细胞术方法分析针吸标本中各细胞免疫表型(CD3、CD3、CD4、CD5、CD10、CD19、CD20、CD23、CD45、K、λ、FMC7、 CD34),确定标本中各细胞组成及有无异常表型细胞.对于淋巴瘤病例,则按照WHO分型标准,根据免疫表型进一步确定其亚型,并对各类病例流式细胞术分型结果和细胞学结果进行比较.结果 99份标本中,细胞涂片检出淋巴瘤40例,转移癌29例,反应性增生、坏死、结核30例,有2例非霍奇金淋巴瘤(NHL)被误诊为反应性增生;对其中18例NHL进行了病理活组织检查,其中包括B淋巴细胞非霍奇金淋巴瘤(B-NHL)16例,T淋巴细胞非霍奇金淋巴瘤2例.流式细胞术分析结果显示,99份标本中检出淋巴瘤35例(淋巴母细胞淋巴瘤4例,T淋巴细胞病变1例,其余30例为B-NHL);有28份B-NHL检测到K或λ轻链限制性表达,其K:λ或λ:K大于3:1,B淋巴细胞所占比例为(73.2±27.2)%,其中26份能根据免疫标志物的表达确定其亚型.经病理活组织检查确定为B-NHL的16份标本中,仅2例滤泡淋巴瘤与流式细胞术分型结果不一致.对于反应性增生及转移癌等标本,流式细胞术分析未查见异常淋巴细胞,其k:λ或λ:k均小于3:1.结论 淋巴结细针穿刺标本的流式细胞术分析有助于淋巴结病变的诊断和鉴别诊断,并可确定NHL的亚型.     

A new system of diagnosis and classification--malignant lymphoma]

Malignant lymphoma is usually divided into Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) according to biological characteristics. Malignant lymphoma in Japan has such the characteristics as few incidence of HD, which is usually favorable in prognosis, and high incidence of NHLs, which have further distinctive features of less incidence of favorable follicular B cell lymphoma and of higher incidence of unfavorable diffuse T cell lymphoma including adult T cell leukemia/lymphoma (ATLL) in comparison with those in western countries. As a recent trend of progress in lymphoma diagnosis an introduction of immunological and molecular biological techniques has given an impact to the previous classification of malignant lymphoma based mainly on morphological criteria. Nowadays, the classification of pathologic type in HD seems to be settled in Rye classification. On the other hand in NHL the LSG classification has been well fixed in Japan and Working Formulation originated in USA has been well used internationally after a historical confusion. In this article a present state of working classification in malignant lymphoma is briefly described and discussed.     

伴有淋巴细胞浸润的子宫平滑肌瘤病理学观察

目的：分析伴有淋巴细胞浸润的子宫平滑肌瘤的病理学特征与诊断依据。方法：运用光镜、电镜和免疫组化技术，研究报道1例伴有淋巴细胞浸润的子宫平滑肌瘤，同时复习相关文献。结果：子宫平滑肌瘤间质中见到大量成熟的小淋巴细胞浸润，不侵犯周围子宫肌壁。大部分浸润淋巴细胞呈CD43、CD45RO、CD3和细胞毒性淋巴细胞标志物TIA－1、CD8阳性。电镜见浸润的淋巴细胞破坏邻近的平滑肌瘤细胞。结论：伴有淋巴细胞浸润的子宫平滑肌瘤是子宫平滑肌瘤的一种特殊类型，要注意与淋巴瘤鉴别。     

Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin''s lymphoma.

We report a case of untreated non-Hodgkin's lymphoma with histologic progression over 1 yr from a low-grade, small cleaved follicular center cell lymphoma to a high-grade, small noncleaved follicular center cell lymphoma. Both lymphomas had identical immunoglobulin (Ig) heavy-chain joining gene (JH), kappa light-chain joining gene, and bcl-2 gene rearrangements, indicating the clonal identity of the two tumors. The Ig heavy chain locus on one chromosome 14 was involved in an initial t(14; 18) translocation as shown by comigrating JH and bcl-2 rearrangements. However, the oncogene c-myc was in the germline configuration in the initial lymphoma but had one allele rearranged near the 3' end of exon I in the high-grade tumor; DNA sequence analysis was consistent with a chromosomal breakpoint at that site. The presence of the c-myc rearrangement in the high-grade tumor suggest a role for c-myc in the clonal evolution of the low-grade tumor into a more aggressive lymphoma. The coexistence of both bcl-2 gene and c-myc oncogene rearrangements in the same tumor is unusual, with only a few cases reported. Furthermore, this case is unique in the direct demonstration of the histologic and clinical progression of a human lymphoma associated with the sequential rearrangement of the bcl-2 gene and the c-myc oncogene.