Diffuse large B cell lymphoma expressing the natural killer cell marker CD56

The expression of the natural killer (NK) cell antigen, CD56, in hematological malignancies is rare. However, there are several reports that some hematological malignancies, such as T/NK cell lymphoma, multiple myeloma (MM) and acute myeloid leukemia (AML), express this molecule. In B cell non-Hodgkin's lymphomas (NHL), however, very limited number of cases have been reported to express CD56 molecule. Although one study has recently described that half of microvillous B cell lymphoma (MVL), an uncommon subset of large cell lymphoma, expressed CD56, there have been no reports about most common type of B-NHL, diffuse large B cell lymphoma (DLBL) other than a mention of weak CD56 expression in one of 83 DLBL. We herein presented the first case of diffuse large B cell lymphoma expressing CD56 clearly. The immunophenotype determined by immunostaining and flow cytometric analysis was CD10+, CD19+, CD20+, CD45RO-, CD3- and CD56+. On immunohistochemical study, neither bcl-2 nor TIA-1 was positive for tumor cell. Monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was detected, and the sequence analysis of the variable region of IgH (VH) suggested that this tumor was derived from antigen selected post germinal center B cell. Conventional combination chemotherapy (CHOP) was administered, and the patient has still been in complete remission for 10 months.     

Expression of lymphocyte homing receptor antigen in non-Hodgkin's lymphoma.

In man, lymphocyte binding to high endothelial venules (HEVs) involves specific 85-95 kd cell surface glycoprotein(s) recognized by the monoclonal antibodies Hermes-1 and Hermes-3. These putative "homing receptor" molecule(s) are believed to play an important role in the normal regulation of lymphocyte circulation. To investigate the possibility that homing receptors also play a role in the biology of lymphoid malignancies, the authors studied over 300 cases of non-Hodgkin's lymphoma by immunohistologic staining with Hermes-1 and -3, antibodies that define two distinct epitopes on the gp 85-95 putative homing receptor molecules. Furthermore, they directly compared expression of the Hermes-3 antigen with clinical extent of disease in 57 patients with diffuse large cell lymphoma. They found that staining of the various subtypes of lymphoma was heterogeneous, and in general correlated with patterns of expression seen in benign lymphoid populations. Essentially all normal lymphoid populations examined, except germinal center B cells and most cortical thymocytes, bear a high level of homing receptor antigen. Similarly, nearly all peripheral T-cell lymphomas, diffuse small cell lymphomas of B lineage, and plasma cell tumors were positive for homing receptor antigen (95%, 97%, and 100%, respectively). Small noncleaved cell, follicular, and diffuse large cell lymphomas of B lineage, tumors having morphologic or immunologic features resembling germinal center cells, frequently failed to express Hermes-defined epitopes (81%, 41%, 25% Hermes-3-, respectively). Antigen expression in T-lymphoblastic lymphomas strongly correlated with immunophenotypic subtypes: only 8% of CD4+/CD8+ were Hermes-1+ versus 86% of CD4-/CD8- and 43% of CD4+/CD8-. Hermes-3 expression by cases of diffuse, large cell lymphoma which showed generalized lymph node involvement (a pattern strongly suggestive of HEV-mediated spread; 100% Hermes-3+, mean intensity 3.4) was higher than that of cases with localized or multifocal, contiguous involvement (consistent with lymphatic spread; 69% Hermes-3+, mean intensity 2.2), but these differences did not achieve statistical significance. The results indicate that homing receptor antigen expression, although perhaps necessary for wide-spread blood-borne lymphoma dissemination to lymphoid sites, is not in and of itself sufficient to predict such behavior in this subtype of lymphoid malignancy.     

Immunoreactivity of CD99 in non-Hodgkin's lymphoma: unexpected frequent expression in ALK-positive anaplastic large cell lymphoma

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.     

Expression of Vimentin and Epithelial Membrane Antigen in Human Malignant Lymphomas

Immunoreactivity with monoclonal antibodies against the intermediate filament protein, vimentin, and epithelial membrane antigen (EMA) was examined in 330 cases of lymphoma (317 non-Hodgkin's and 13 Hodgkin's lymphomas), 12 reactive lymph nodes and mononuclear cells of the peripheral blood using either indirect immunoperox-idase staining or the avidin-biotin immunoperoxidase complex technique. The cell origin of each tumor was established using a panel of monoclonal antibodies against lymphocyte differentiation antigens. There were 41 T cell, 247 B cell and 29 undetermined lymphomas, and 13 cases of Hodgkin's disease in the series. Vimentin was expressed in 24 T-cell lymphomas (58.5%) and 60 B cell lymphomas (24.2%). This difference in frequency was statistically significant. Vimentin expression in follicular lymphomas was less frequent than in diffuse B-cell lymphomas. In diffuse lymphomas, small and medium cell types were more reactive with anti-vimentin than large cell types. Reed-Sternberg cells (R-S cells) in Hodgkin's disease were positive for vimentin in 11 cases (84.6%). The frequency of EMA reactivity in lymphomas was low, particularly in T cell lymphomas. No positive cases were found among follicular lymphomas. In diffuse non Hodgkin's lymphomas, EMA was expressed only in mixed and large cell types, but never in smaller ones. In conclusion, monoclonal antibodies against vimentin and EMA appear to be of limited usefulness for the diagnosis of non Hodgkin's lymphomas, but anti vimentin antibody may be used as an adjunct to the diagnosis of R-S cells in Hodgkin's disease.     

鼻及咽部非霍奇金淋巴瘤158例临床特点及其与EB病毒感染的关系

目的探讨鼻及咽部原发性非霍奇金淋巴瘤（NHL）的临床特点、免疫表型及其与EB病毒感染的关系。方法对158例鼻及咽部原发性NHL进行了HE和免疫组织化学SP法（CD3、CD20、CD56、CD57）检查,按WHO2001年《造血和淋巴组织肿瘤的病理学和遗传学》标准进行分类;并对其中99例进行了EBER-1原位杂交的检测。结果158例鼻及咽部原发性NHL中,原发于鼻腔84例（53．2％）,扁桃体39例（24．7％）,咽部35例（22．1％）。结外鼻型NK／T细胞淋巴瘤101例（63．9％）、非特异性外周T细胞淋巴瘤23例（14．6％）,B细胞淋巴瘤34例（21．5％）。99例EBER-1原位杂交结果显示阳性率：结外鼻型NK／T细胞淋巴瘤为98．6％（70／71）,而非特异性外周T细胞淋巴瘤为66．7％（8／12）,B细胞淋巴瘤为43．8％（7／16）。结论鼻及咽部NHL中结外鼻型NK／T细胞淋巴瘤最为多见,与EB病毒密切相关,其病理诊断需结合其免疫表型特征及肿瘤部位。     

CD10 expression in peripheral T-cell lymphomas complicated by a proliferation of large B-cells.

CD10 expression by the neoplastic T cells in angioimmunoblastic T-cell lymphoma was recently described. As cases of peripheral T-cell lymphoma, unspecified, fail to show similar CD10 expression, this feature helps discriminate between these two entities, particularly in cases exhibiting morphologic overlap. Given these findings, we studied CD10 expression in a subtype of peripheral T-cell lymphoma known as peripheral T-cell lymphoma complicated by a proliferation of large B cells and compared it with angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation. A total of 33 cases were identified including peripheral T-cell lymphoma complicated by a proliferation of large B cells (10), angioimmunoblastic T-cell lymphoma (10) and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (13). Diagnoses were established by hematoxylin and eosin (H&E) stain, immunohistochemistry and/or molecular findings (polymerase chain reaction for T-cell receptor-gamma gene rearrangement). Two of 10 cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells showed aberrant CD10 expression (20%) compared to 9/10 cases of angioimmunoblastic T-cell lymphoma (90%) and 8/13 of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation (62%). One case each of angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation showed a rare, but not unequivocal, CD10+ atypical cell. Four cases of angioimmunoblastic T-cell lymphoma with a large B-cell proliferation were CD10 negative. Of the 2 CD10+ peripheral T-cell lymphoma complicated by a proliferation of large B cells, one had no H&E or IHC features of angioimmunoblastic T-cell lymphoma and showed only a rare positive cell. The second case, a lung biopsy, exhibited diffuse CD10 tumor cell positivity. The predominant staining pattern in the CD10+ cases was characterized by scattered, mostly individual, morphologically neoplastic cells. A rare case showed clusters of positive cells. Our data indicate that only 20% of cases of peripheral T-cell lymphoma complicated by a proliferation of large B cells show CD10 expression by the neoplastic T cells in contrast to angioimmunoblastic T-cell lymphoma and angioimmunoblastic T-cell lymphoma with a large B-cell proliferation which exhibit CD10 staining in 90 and 62% of cases, respectively. This finding does not reach statistical significance with a P-value of 0.57 (Fisher's exact test). As these entities appear to be biologically distinct and may portend different overall survivals, CD10 expression may serve as an additional discriminating criterion.     

Gastrointestinal malignant lymphomas in Macedonia

The gastrointestinal tract including oral cavity is the most common location of extranodal lymphomas. In this retrospective study, the histomorphological, immunohistochemical and clinical features of 21 Macedonian cases with diagnosed malignant lymphomas were investigated. The series included 15 males and 6 females, mean age 44 (4-78) years. The most common locations were hard palate (n = 7), gastric site (n = 5), small intestinal wall (n = 2), large intestinal wall (n = 5), and lingual root (n = 2). All cases were B cell lymphomas, 23.8% of them low grade B cell lymphoma of mucosa associated lymphoid tissue, 4.7% mantle cell lymphoma, 47.6% diffuse large cell lymphoma, and 23.8% Burkitt type lymphoma. There was no T cell lymphoma. Most of the cases were positive for CD20 and CD79a. Monoclonality was confirmed by light chain restriction, except for nine cases where it failed due to poor tissue preservation. The fact that eight cases were in the clinically advanced third and fourth stage implied a conclusion that not only primary non-Hodgkin's lymphomas but also secondary lesions could invade the gastrointestinal tract. Immunohistochemical staining was helpful in differentiation between benign and malignant infiltration in low grade lymphomas, and in distinguishing diffuse large cell lymphomas from undifferentiated epithelial neoplasms.     

Application of a T cell receptor antibody beta F1 for immunophenotypic analysis of malignant lymphomas

One hundred sixty-five non-Hodgkin's lymphomas (101 B, 63 T, one histiocytic) were immunostained with an antibody (beta F1) reactive with a common framework determinant on the beta-subunit of the T cell receptor (TCR). beta F1 stained T lymphomas exclusively, including 53% of peripheral T cell lymphomas but only 33% of T lymphoblastic lymphomas. When expression of beta F1 and CD3 were considered together, 4 types of T lymphoma were delineated: 1) beta F1+CD3+; 2) beta F1+CD3-; 3) beta F1-CD3+, and 4) beta F1-CD3-. The first represented lymphomas with classical T immunophenotype. The second might represent T lymphomas with aberrant loss of CD3 expression. The third might represent T lymphomas with a putative second TCR or cases with an immature phenotype expressing cytoplasmic CD3 only. The fourth type included cases that may be derived from natural killer cells instead of T cells, cases of T lymphoma with aberrant loss of both beta F1 and CD3, and some cases of immature T cell (lymphoblastic) lymphoma. beta F1-CD3- lymphomas exhibited a remarkable predilection for the nasal region. beta F1 is useful in studying T cell lymphomas and distinguishing a novel immunophenotype frequently expressed by nasal lymphomas.     

bcl-10蛋白异常表达对黏膜相关淋巴组织结外边缘区B细胞淋巴瘤的诊断价值

目的探讨bcl-10蛋白表达对黏膜相关淋巴组织结外边缘区B细胞淋巴瘤（MALT淋巴瘤）的诊断价值。方法收集140例不同部位的MALT淋巴瘤,包括胃38例、眼眶35例、肠16例、皮肤15例、涎腺15例、肺14例、甲状腺3例、其他部位4例。对照：10例扁桃体反应性滤泡增生（RFH）、5例眼眶的淋巴组织增生和143例非MALT淋巴瘤、不同类型的非霍奇金淋巴瘤（NHL）,包括20例NK／T细胞淋巴瘤、20例滤泡性淋巴瘤（FL）、20例间变性大细胞淋巴瘤（ALCL）、20例淋巴结内弥漫大B细胞淋巴瘤（DLBCL）、10例原发胃DLBCL、13例淋巴结边缘区淋巴瘤（NMZL）、12例套细胞淋巴瘤（MCL）、11例脾脏边缘区淋巴瘤（SMZL）、6例血管免疫母细胞性T细胞淋巴瘤（AITL）、6例外周T细胞淋巴瘤（PTCL）、3例B．小淋巴细胞淋巴瘤（B-SLL）、1例淋巴浆细胞性淋巴瘤（LPL）和1例浆细胞瘤。免疫组织化学EnVision法检测bcl-10蛋白;免疫组织化学双标记法检测CD20与bcl-10的共表达。结果在扁桃体RFH中,bel-10蛋白呈中等强度表达于生发中心B细胞质中,套细胞不表达,边缘区细胞和副皮质区T细胞呈弱表达。在眼眶淋巴组织增生中,2例bel-10阴性,3例主要呈淋巴滤泡生发中心B细胞质阳性,与扁桃体RFH的表达类似。在非MALT淋巴瘤的其他类型NHL中,除3例（3／10）原发胃DLBCL呈胞核阳性外,其余均未见胞核表达;在不同NHL中的胞质阳性分别为：结内（12／20）和胃（7／10）DLBCL、FL和ALCL（16／20）、PTCL（5／6）、AILT（6／6）、NMZL（13／13）、SMZL（11／11）、B-SLL（3／3）和浆细胞瘤（1／1）,11例MCL呈胞质可疑阳性,20例NK／T细胞淋巴瘤和1例LPL阴性;在部分淋巴瘤中可见肿瘤性细胞表达而反应性小淋巴细胞不表达：MALT淋巴瘤之bcl-10的总表达率为92．1％（129／140）,其中54．3％（76／140）胞质阳性,37．9％（53／140）胞核阳性;但不同部位之胞核阳性率有所不同。在MALT淋巴瘤中,bcl-10蛋白核强表达最常见于眼眶（25．7％,9／35）;除出现异常bcl-10胞核表达外,约20％有反应性滤泡的病例呈生发中心失表达。双标记显示bcl-10阳性细胞为CD20阳性细胞,但CD20阳性细胞多于bcl-10阳性细胞。结论（1）淋巴细胞增生性病变中bcl-10蛋白普遍表达,细胞质表达可出现在多数NHL和反应性增生中,但在淋巴瘤中呈肿瘤细胞表达而反应性细胞不表达,提示bcl-10异常可能与部分淋巴瘤的形成有关;（2）细胞核内bcl-10异常表达主要见于MALT淋巴瘤;眼眶、肺等部位的胞核强阳性和生发中心阴性的特殊模式,对MALT淋巴瘤的诊断及其与反应性病变的鉴别诊断有一定辅助意义。     

Identification of tumours with the CD43 only phenotype during the investigation of suspected lymphoma: a heterogeneous group not necessarily of T cell origin

AIMS: CD43 is usually employed as a T cell marker in the immunophenotypic work-up of suspected cases of non-Hodgkin's lymphoma (NHL). In this setting, tumours expressing CD43 in the absence of other T or B cell markers (CD43 only phenotype) are rare. We present four cases with this aberrant phenotype seen at our institution. METHODS: The CD43 only phenotype was defined as expression of CD43 in the absence of expression of B cell markers CD20 and CD79a, and T cell markers CD3 and CD5, on initial immunohistochemistry performed on biopsies of suspected NHL. Combinations of further immunohistochemistry, flow cytometry, cytogenetic analysis and molecular studies were used to enable further diagnosis and lineage assignment. RESULTS: The four cases were subsequently diagnosed as: one case of extramedullary acute myeloid leukaemia, one case of null cell anaplastic large-cell lymphoma, and two cases of extranodal diffuse large B cell lymphoma. None were demonstrated to be of T cell origin. CONCLUSIONS: Our series further confirms the lack of specificity of CD43 expression for T cell lineage. Documentation of the CD43 only phenotype in suspected cases of NHL therefore requires further investigation to both correctly diagnose and clarify lineage of these tumours.     

淋巴瘤患者HBV感染标志物及其DNA定量的实验室调查与分析

目的 探讨霍奇金淋巴瘤、非霍奇金淋巴瘤、弥漫性大B细胞淋巴瘤和T淋巴母细胞淋巴瘤患者HBV感染标志物和HBV DNA的表达情况.方法 选取近5年淋巴瘤科1779例住院病人,其中霍奇金淋巴瘤(Hodgkin's lymphoma,HL) 160例,非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL) 1590例,弥漫性大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL) 16例,T淋巴母细胞淋巴瘤(T cell lymphoblasts lymphoma,T-LBL) 13例.健康查体者作为正常对照组(normal control group,NCG),共12890名,男性8450名,女性4440名.采用电化学发光法测定乙型肝炎病毒抗原和抗体;采用TaqMan实时荧光定量PCR方法测定乙型肝炎病毒DNA.结果 霍奇金淋巴瘤、非霍奇金淋巴瘤、弥漫性大B细胞淋巴瘤和T淋巴母细胞淋巴瘤的HBsAg、HBeAg的阳性率高于显著高于正常对照组;霍奇金淋巴瘤和非霍奇金淋巴瘤的HBcAb阳性率显著高于正常对照组;霍奇金淋巴瘤、非霍奇金淋巴瘤和弥漫性大B细胞淋巴瘤的HBsAb阳性率低于正常对照组;说明HBV携带者对HBV的免疫力较低,发生恶性淋巴瘤的风险较大.乙型肝炎病毒具有嗜淋巴细胞和嗜肝细胞的特性,淋巴瘤患者HBsAg携带率是正常对照组的4.1 ～10.9倍;霍奇金淋巴瘤和非霍奇金淋巴瘤患者HBV DNA的阳性率是正常对照组的2.2 ～8.3倍.结论 HBV感染与淋巴瘤的发生具有很强的相关性,患者血清的HBV抗原、抗体和DNA水平可能是淋巴瘤患者致病和HBV再激活的重要因素.对于用化疗药物或免疫抑制剂治疗的淋巴瘤患者,应定期对其肝功能和乙肝标志物进行检测.若出现肝功异常或HBV再激活等情况,应立即评估患者病情,及时调整治疗方案.     

肠道原发性非霍奇金淋巴瘤32例的临床与病理学分析

目的研究肠道原发性非霍奇金淋巴瘤(NHL)的临床表现、病理特点及预后因素。方法复习32例肠道原发性NHL的临床资料、大体标本、HE切片及免疫组织化学染色结果,按2001年WHO淋巴造血系统肿瘤的标准重新进行分类。结果B细胞性NHL 21例,其中弥漫大B型15例,套细胞型2例,滤泡型1例,Burkitt淋巴瘤1例,黏膜相关淋巴组织淋巴瘤2例。T细胞NHL 10例(其中肠病相关型NHL2例和非肠病相关型NHL8例),组织细胞NHL1例。诊断时,9例为Ⅰ～Ⅱ期,23例为Ⅲ～Ⅳ期。随访4—168个月,死亡15例。B细胞NHL死亡率为7／21例(33％),T细胞NHL的死亡率为8／10。Ⅱ期死亡2例,均为T细胞NHL。Ⅲ-Ⅳ期死亡13例,占死亡数的86．6％。Cox多因素分析显示,最重要的预后因素是肿瘤的分期及肿瘤类型(分期P=0．002、肿瘤类型P=0．032)。结论肠道原发性NHL以弥漫大B型最多见。以结肠最多见,其次为小肠和回盲部,直肠最少。就诊时65．6％为Ⅲ-Ⅳ期患者。比较同期T、B细胞NHL,T细胞NHL预后差,死亡率高。分期越高预后越差,黏膜相关淋巴组织淋巴瘤等恶性度较低的淋巴瘤预后较好。     

间变性大细胞淋巴瘤形态学及免疫表型观察

目的：探讨间变性大细胞淋巴瘤（ALCL）的形态学和免疫表型特征。方法：对6例ALCL和2例弥温性大B细胞淋巴瘤（DLBCL）进行形态学和免疫组织化学染色（ABC法）观察。结果：6例ALCL中，普通型2例、淋巴组织细胞型2例、ALK－变型2例，均可见单型性或多形性的标志性大细胞。普通型和ALK－变型大细胞沿淋巴窦内生长，而淋巴组织细胞型大细胞则呈散在分布；2例DLBCL形态上颇似ALCL；6例ALCL均为T细胞，CD30＋，儿童患者共同表达ALK＋和EMA＋，年长者则ALK－和EMA－。2例DLBCL均为B细胞，ALK＋、CD30－和EMA－。结论：不论何型ALCL，均可见CD30＋的标志性大细胞，淋巴窦内生长多见于普通型和ALK－变型。ALCK均为T细胞，儿童常有ALK和EMA共同表达，年长者则ALK和EMA－。DLBCL的免疫表型不同于ALCL。     

Expression of vimentin and epithelial membrane antigen in human malignant lymphomas

Immunoreactivity with monoclonal antibodies against the intermediate filament protein, vimentin, and epithelial membrane antigen (EMA) was examined in 330 cases of lymphoma (317 non-Hodgkin's and 13 Hodgkin's lymphomas), 12 reactive lymph nodes and mononuclear cells of the peripheral blood using either indirect immunoperoxidase staining or the avidin-biotin immunoperoxidase complex technique. The cell origin of each tumor was established using a panel of monoclonal antibodies against lymphocyte differentiation antigens. There were 41 T-cell, 247 B-cell and 29 undetermined lymphomas, and 13 cases of Hodgkin's disease in the series. Vimentin was expressed in 24 T-cell lymphomas (58.5%) and 60 B-cell lymphomas (24.2%). This difference in frequency was statistically significant. Vimentin expression in follicular lymphomas was less frequent than in diffuse B-cell lymphomas. In diffuse lymphomas, small and medium cell types were more reactive with anti-vimentin than large cell types. Reed-Sternberg cells (R-S cells) in Hodgkin's disease were positive for vimentin in 11 cases (84.6%). The frequency of EMA reactivity in lymphomas was low, particularly in T-cell lymphomas. No positive cases were found among follicular lymphomas. In diffuse non-Hodgkin's lymphomas, EMA was expressed only in mixed and large cell types, but never in smaller ones. In conclusion, monoclonal antibodies against vimentin and EMA appear to be of limited usefulness for the diagnosis of non-Hodgkin's lymphomas, but anti-vimentin antibody may be used as an adjunct to the diagnosis of R-S cells in Hodgkin's disease.     

Clusterin expression in malignant lymphomas: a survey of 266 cases.

Clusterin expression has been reported to be characteristic of systemic anaplastic large cell lymphoma and usually negative in cutaneous anaplastic large cell lymphoma as well as other lymphoma types. We surveyed clusterin expression using immunohistochemical methods in 266 cases of non-Hodgkin's lymphoma and Hodgkin's disease to further assess the diagnostic utility of this marker. Clusterin immunostaining was observed in 40 of 49 (82%) systemic anaplastic large cell lymphomas and 12 of 29 (41%) cutaneous anaplastic large cell lymphomas. Clusterin also was expressed in 5 of 43 (12%) diffuse large B-cell lymphomas (4 of 5 CD30+), 1 of 14 (7%) peripheral T-cell lymphomas, 1 of 32 (3%) cases of nodular sclerosis Hodgkin's disease, and 1 case of mycosis fungoides in large cell transformation. Clusterin was negative in all other neoplasms assessed including follicular lymphoma of all grades (n = 24), mantle cell lymphoma (n = 13), marginal zone B-cell lymphoma (n = 12), precursor T-cell or B-cell lymphoblastic leukemia/lymphoma (n = 10), mixed cellularity Hodgkin's disease (n = 8), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 7), Burkitt lymphoma (n = 7), mycosis fungoides (n = 4), nodular lymphocyte predominant Hodgkin's disease (n = 3), lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (n = 2), and plasmacytoma (n = 2). We conclude that clusterin is a marker of anaplastic large cell lymphoma and that addition of clusterin to antibody panels designed to distinguish systemic anaplastic large cell lymphoma from classical Hodgkin's disease is useful. However, clusterin is also positive in a substantial subset of cutaneous anaplastic large cell lymphomas, a smaller subset of diffuse large B-cell lymphomas, and rarely in cases of peripheral T-cell lymphoma and nodular sclerosis Hodgkin's disease.     

Follicular large cell lymphoma. An immunophenotype study.

The authors investigated 17 cases of follicular large cell lymphoma using monoclonal antibodies applied to frozen sections. The neoplastic cells in 11 cases (65%) showed evidence of immunoglobulin expression similar to the reported percentage of immunoglobulin expressing diffuse large cell lymphomas and lower than seen in low grade follicular lymphomas. All cases showed expression of the B lineage markers T015, B1, and 4G7, and HLA-DR. CALLA was present in all but 1 case, similar to that reported for follicular lymphomas, and much higher than reported for diffuse large cell lymphoma. Approximately one-half of the cases showed weak expression of Tac, 5 cases expressed B2 (C3d), and 3 cases expressed T05 (C3b). Variable expression was seen for the Ki-67 antigen. A CR4/23+, B2+, T05+ dendritic population was identified in all cases. An interfollicular host T-cell infiltrate was noted, mainly phenotypic helper cells. This study demonstrates that follicular large cell lymphoma has immunologic similarities to both diffuse large cell lymphoma and the low grade follicular lymphomas.     

HLA-DR expression in B-cell non-Hodgkin's malignant lymphomas: a multiparameter flow cytometry study

Ten cases of reactive follicular hyperplasia and 31 cases of B-cell non-Hodgkin's malignant lymphoma were studied using multiparameter flow cytometry. A bimodal distribution for HLA-DR expression, but not for surface immunoglobulin or B cell-specific antigens CD19 and CD20, was observed commonly in mixed cell type and infrequently in non-mixed cell type B-cell malignant lymphomas. On the basis of HLA-DR distribution alone, 31 cases of B-cell malignant lymphomas of low, intermediate, and high grades could be separated into mixed and non-mixed cell types, with only two misclassifications (P = 0.0001). Exceptionally, one case of malignant lymphoma, follicular and diffuse, mixed-cell type had a unimodal HLA-DR distribution, and one case of malignant lymphoma, diffuse, large noncleaved cell type had a bimodal HLA-DR distribution. In all cases of malignant lymphoma, follicular, mixed-cell type studied, low HLA-DR was correlated with small cells, and high HLA-DR was correlated with large cells. In contrast, HLA-DR expression and cell size were not as directly correlated in cases of malignant lymphoma, diffuse, mixed-cell type. These observations suggest that most, but not all, cases of B-cell malignant lymphomas of the mixed cell type can be separated from other B-cell lymphomas on the basis of HLA-DR distribution.     

The Leukocyte Semaphorin CD100 Is Expressed in Most T-Cell, but Few B-Cell, Non-Hodgkin’s Lymphomas

The 150-kd transmembrane protein CD100 is the first semaphorin protein shown to be expressed in lymphoid tissue. CD100 is present in the interfollicular T cell zones and is also expressed by B cells in the germinal centers of secondary lymphoid follicles, but not in the mantle zones. The CD100 molecule was recently cloned, and CD100 transfectants were shown to induce homotypic aggregation of human B cells and improve their viability in vitro, suggesting that CD100 may play a role in lymphocyte aggregation and germinal center formation. We studied the expression of CD100 in 138 clinical cases representing a range of lymphoproliferative disorders, to determine whether this molecule is expressed in these neoplastic processes. In general, we found CD100 expression to be common in peripheral T-cell non-Hodgkin’s lymphomas but rare in B-cell non-Hodgkin’s lymphomas. CD100 expression was not detectable in low-grade B-cell non-Hodgkin’s lymphomas, including cases of small lymphocytic lymphoma (18 cases), marginal zone lymphoma (10 cases), and mantle cell lymphoma (10 cases), as might be expected for these neoplasms that are not of follicular center cell origin. Surprisingly, we found that the vast majority of follicular lymphomas (37 of 40 cases) as well as diffuse large-cell lymphomas of B-cell type (35 cases) did not express CD100. The neoplastic cells in 3 of 11 cases of predominantly large-cell-type follicular lymphoma did express CD100. In contrast, all five cases of high-grade, small non-cleaved (Burkitt-like) B-cell lymphoma were immunoreactive for CD100 expression, as were 18 of 20 cases (90%) of malignant T cell neoplasms. Northern blot analysis of CD100 expression correlated with immunohistochemical findings. Absence of expression of CD100 by neoplastic follicular center B cells is a common feature in follicular lymphomas, but expression of CD100 by T cells is maintained in T-cell lymphoproliferative disorders.     

Angiotropic lymphoma occurring in a lacrimal sac oncocytoma

This report describes a case of angiotropic variant of diffuse large B cell lymphoma within a benign oncocytoma of the lacrimal sac. The occurrence of this rare lymphoma within a benign neoplasm has not been documented previously. An 87 year old woman presented with a swelling over the area of the left lacrimal sac, which histological examination revealed to be an oncocytoma. Many small blood vessels within the tumour were filled with large cytologically atypical cells, which stained positively for leucocyte common antigen and a B cell antigen, CD20, confirming the presence of a large B cell non-Hodgkin's lymphoma of angiotropic type. Angiotropic lymphoma is a very rare and usually highly aggressive variant of non-Hodgkin's lymphoma, which classically involves the central nervous system and skin, but has been described within most organs. Its occurrence within a benign neoplasm is probably coincidental, although a close association between oncocytic epithelium and normal lymphoid cells is recognised in Warthin's tumour of salivary and lacrimal glands.