Nasal T-cell lymphoma: a clinicopathological and immunophenotypic analysis of 13 cases

Thirteen cases of nasal lymphomas with T-cell or natural killer (NK)-cell phenotype were studied, with attention to clinical presentation and follow-up, the presence of Epstein-Barr virus (EBV) using in situ hybridization (EBER), the immunophenotype, and the presence of cytotoxic granules. All but two patients presented with stage I disease. In three cases local progression resulted in involvement of the central nervous system. When dissemination occurred, this was predominantly to extranodal localizations, in two cases to the skin. Response to therapy was highly variable, but patients treated with radiotherapy with or without additional chemotherapy had a better prognosis than patients treated with initial chemotherapy alone. All lymphomas were associated with EBV, and most cases howed cytotoxic features, ten of which were CD56 positive. In eight cases a T-cell origin was proven, but in five ases a possible NK-cell origin could not be excluded, No clinical differences were seen between true T-cell lymphomas and possible NK-cell neoplasms. Nasal T-cell lymphomas should be considered as a distinct clinicopathological entity, strongly associated with EBV, and with cytotoxic features in most cases. No prognostic parameters were detected to predict dissemination and response to therapy.     

原发性皮肤恶性淋巴瘤的临床病理和免疫组化研究

研究原发性皮肤恶性淋巴瘤的类型及临床病理特点,方法对４２例ＰＣＭＬ作了形态学观察,免疫表型标记和组织学分型。结果原发性皮肤Ｔ细胞性淋巴瘤（ＰＣＴＣＬ）占６９．０％,其中蕈样霉菌病占７．２％（ＭＦ）、血管中心性淋巴瘤占９．５％皮下指明脂膜炎样Ｔ细胞巴瘤占１９．０％,原发性皮肤Ｂ细胞性淋巴瘤（ＰＣＢＣＬ）占３１．０％;ＰＣＭＬ男女之比为２：１,中位年龄３７岁,ＰＣＴＣＬ的发病年龄小于ＰＣＢＣＬ（     

Nodal T/NK-cell lymphoma of nasal type: a clinicopathological study of six cases

Aims:  To investigate the clinicopathological features of six unusual cases of nodal CD56+ and Epstein–Barr virus (EBV)+ T/natural killer (NK)-cell lymphoma, a putative nodal counterpart of nasal NK/T-cell lymphoma (nodal T/NK-cell lymphoma of nasal type) in comparison with nasal NK/T-cell lymphoma with secondary lymph node involvement ( n  = 24) and peripheral T-cell lymphoma (PTCL) of cytotoxic molecule (CTM)+ and EBV+ type ( n  = 21).
Methods and results:  All cases of nodal T/NK-cell lymphoma of nasal type exhibited diffuse infiltration of pleomorphic medium-sized to large tumour cells, reminiscent of those in CTM+ EBV+ PTCL. The tumour cells had a typical phenotype of nasal NK/T-cell lymphoma: CD2+, CD3ε+, CD4−, CD5−, CD56+, T-cell intracellular antigen-1+, granzyme B+, perforin+ and EBV+. However, four of six cases demonstrated clonal T-cell receptor γ-gene rearrangement on polymerase chain reaction analysis, unlike nasal NK/T-cell lymphoma. Comparison of clinical parameters and overall survival among the three groups demonstrated only minor differences.
Conclusions:  Nodal T/NK-cell lymphoma may occupy the grey zone between extranodal nasal-type NK/T-cell lymphoma and nodal CTM+ PTCL in a spectrum of NK to T-cell lymphomas that are EBV+. The close relationship between NK/T-cell lymphomas and cytotoxic T-cell lymphomas was also substantiated.     

Composite marginal zone B-cell lymphoma and classical Hodgkin's lymphoma: a clinicopathological study of 12 cases

AIMS: Classical Hodgkin's lymphoma (cHL) rarely coexists as composite lymphoma with B-cell non-Hodgkin's lymphoma (B-NHL). We characterized 12 cases of composite marginal zone B-cell lymphoma (MZBL) and cHL by immunohistochemistry and molecular biology. METHODS AND RESULTS: Eight patients had gastric MZBL of mucosa-associated lymphoid tissue (MALT)-type, in five cases with a diffuse large B-cell lymphoma component. Concurrent cHL was observed either in the stomach wall, regional, or distant lymph nodes. One patient each had composite pulmonary/thyroid MZBL of MALT-type and cHL. In two cases, nodal composite MZBL and cHL was observed. cHL displayed features of mixed cellularity type in 10 cases, while in two cases only scattered Hodgkin- and Reed-Sternberg (H/RS) cells were noted. H/RS cells expressed CD30, multiple myeloma oncogene 1 protein (MUM1P), p53 (100%), CD15 (58%), CD20 (58%) and Epstein-Barr virus-associated LMP1 (50%). No t(11;18)(q21;q21) was detected in composite MZBL of MALT-type and cHL. CONCLUSIONS: MZBL and cHL may occur as composite lymphoma, possibly reflecting clonal lymphoma progression. Derivation from extranodal MZBL of MALT-type should be excluded in cases in which a diagnosis of primary extranodal cHL is considered.     

结外鼻型NK/T细胞淋巴瘤28例临床病理分析

目的：探讨结外鼻型NK/T细胞淋巴瘤( extranodal natural killer/T-cell lymphoma, nasal type, EN-NK/TCL)的临床病理学特征、诊断及鉴别诊断。方法应用免疫组化、EBER原位杂交技术检测28例EN-NK/TCL,依据WHO(2008)淋巴造血组织肿瘤分类进行临床病理学分析。结果28例EN-NK/TCL中,男性13例,女性15例,男女之比为1∶1．2,平均年龄46岁,中位年龄44．5岁。18例发生于鼻腔,5例发生于皮肤,扁桃体、上腭、舌根、肾上腺、胃各1例。临床主要表现为鼻塞,皮肤病变可表现为皮疹、溃疡、斑块或结节形肿物。可伴有B症状、淋巴结肿大,可累及多个部位。肿瘤细胞为小、中、大淋巴细胞或呈混合型,常见血管中心性或血管破坏的生长方式及坏死,多伴有炎细胞浸润。免疫表型：T细胞标志物( CD3ε最敏感)、CD56及细胞毒性标志物均阳性,原位杂交EBER呈阳性。10例获得随访,其中1例死亡。结论 EN-NK/TCL好发于上呼吸道,其次是皮肤。结合形态学、免疫表型及EBER原位杂交结果可确诊。     

Intravascular lymphomatosis: a clinicopathological study of two cases presenting as an interstitial lung disease

 

Aims:

Intravascular lymphomatosis is an uncommon type of non-Hodgkin's lymphoma characterized by intravascular proliferation of neoplastic lymphoid cells. Although the tumour is basically a systemic disease, eventually involving multiple organs, primary presentation in the lung is rare.  

Methods and results:

We describe the clinicopathological features of two patients with intravascular lymphomatosis presenting in the lung. One patient complained of fever, headache and chest pain; the other, of dyspnoea on exertion and headache. Both patients showed reticulonodular density on chest radiography and decreased diffusion capacity. Lung biopsy showed features characteristic of intravascular lymphomatosis. Malignant lymphoid cells were CD30 positive T-cells of anaplastic large cell type in one patient and B-cells of large cell type in the other. There was a poor response to chemotherapy and both patients died of the disease within 3 months of diagnosis.  

Conclusions:

These cases and 10 previous reports illustrate the need to include intravascular lymphomatosis in the differential diagnosis of interstitial lung disease.     

Mantle cell lymphoma: a clinicopathological study of 55 cases

A recently described unifying proposal for mantle cell lymphoma has led to the formulation of strict diagnostic criteria based on morphology, immunology and molecular data to define this specific entity. Previous studies were often based on broader definitions such as centrocytic lymphoma, intermediately differentiated lymphoma or mantle zone lymphoma and, therefore, included a variety of entities with some, but not all, features ascribed to the mantle cell lymphoma. Since the publication of the unifying proposal no comprehensive studies have been published to confirm and support it. We selected 55 cases of mantle cell lymphoma collected in our institution in order to evaluate the validity of the proposal and, by using strict criteria, we analysed the morphological features, their variations and the changes occurring in the course of the disease as well as its clinical behaviour. The analysis of this material demonstrates that mantle cell lymphoma affects predominantly elderly males presenting with an advanced stage of disease. Twenty-four out of 55 patients died with, or of, the disease with a median survival of 32 months, even though most of them received aggressive chemotherapy. In all cases the histological features were strikingly uniform and most cases had a diffuse growth pattern. The neoplastic cells corresponded to small cleaved cells with a minimal variation in shape and size from one case to the other. The phenotype of the neoplastic cells was remarkably constant with expression of several pan-B cell markers, IgM, IgD and CD5, and lack of CD10 and CD23. Sixteen cases, which were followed by consecutive biopsies, showed only slight morphological changes during the course of the disease and only four cases showed histological progression. Forty cases were documented by cytogenetics, of which 15 showed t(11; 14)(q13;q32). We examined 28 cases for DNA rearrangement of the BCL-1 locus; it was detected in 50% of the cases, with most breakpoints occurring at the major translocation cluster. This study demonstrates that when selection criteria are strictly applied, mantle cell lymphoma represents a disease entity with a uniform presentation, distinctive morphology, immunophenotype and a strong association with t(11;14)(q13;q32).     

原发性脑内淋巴瘤临床病理、免疫组化、基因重排分析

目的：研究脑内原发性恶性淋巴瘤临床病理、免疫且化及免疫性基因重排特征。方法：对６例脑原发性恶性淋巴瘤作了临床病理形态观察和免疫组化分析（Ｓ－Ｐ法）,并用ＰＣＲ技术单轮及半巢式扩增法进行了ＩｇＨ及ＴＣＲ－β基因重排检测。结果：６例皆为非霍奇金Ｂ细胞淋巴瘤。瘤细胞大部分是中心或中心母细胞型,常伴浆样分化,往往围绕血管排列。ＰＣＲ克隆性基因重排,ＩｇＨ单轮法（２／６例）阳性,半巢式（６／６例）阳性,ＴＣ     

Primary malignant lymphoma of the colon and rectum. A histopathological and immunohistochemical analysis of 45 cases with clinicopathological correlations

Primary colorectal lymphoma accounts for only about 0.2% of large intestinal malignancies. Management difficulties are compounded by a lack of consistent pathological reporting and by the use of numerous different classifications. Forty-five cases of primary colorectal lymphoma are included in this study. The presenting features are indistinguishable from those of colorectal cancer. Seven patients had a history of chronic ulcerative colitis but no other predisposing factors were identified. Immunohistochemical studies showed that all tumours were of B-cell phenotype. Most tumours were difficult to characterize using standard pathological classifications such as Kiel, except for the 11 cases of malignant (multiple) lymphomatous polyposis, which were morphologically diffuse centrocytic lymphomas. Twenty-nine lymphomas showed the morphological and immunohistochemical features associated with tumours arising in mucosa-associated lymphoid tissue. These tumours showed variable but often marked polymorphism and we have used the term polymorphic B-cell lymphoma to describe them. Consistency was achieved between three observers as to whether these tumours were low or high grade, and grade was found to be prognostically important. A modified Dukes staging system was adopted and there was a trend for early stage to give prognostic advantage. This study supports the view that surgery should be the primary treatment for localized lymphoma of the gastrointestinal tract with radiotherapy and/or chemotherapy for advanced cases and for malignant lymphomatous polyposis.     

脾脏非霍奇金淋巴瘤临床病理学研究

目的 探讨脾脏非霍奇金淋巴瘤(SNHL)的形态学特点、免疫表型及鉴别诊断。方法 对39例SNHL进行形态学观察及免疫组化ABC法分析，使用抗体包括CD3、CD45RO、CD56、CD79α、CD20、CD68、Mac387、CD5、CD10、bcl—2、CD23、CD43、cyclinD1、IgM、IgD等。结果 39例SNHL中有B细胞淋巴瘤(BCL)24例，包括小淋巴细胞性淋巴瘤(SLL)4例，套细胞淋巴瘤(MCL)4例，滤泡性淋巴瘤(FL)5例，边缘区淋巴瘤(MZL)6例，弥漫大B细胞性淋巴瘤(DLBCL)5例，其中2例为大多叶核细胞淋巴瘤。T细胞淋巴瘤(TCL)11例，其中肝脾T细胞淋巴瘤2例，非特异性TCL9例。组织细胞性淋巴瘤4例。结论 脾脏淋巴瘤病理类型多样，掌握其形态学特征，熟悉各类型的免疫表型的异同点对诊断与鉴别诊断有重要意义。     

Low-grade B-cell lymphomas of the splenic marginal zone: a clinicopathological and immunohistochemical study of 14 cases

We have studied 14 cases of low-grade, splenic marginal zone, B-cell non-Hodgkin's lymphoma. The clinical presentation in all cases was with splenomegaly and, in 10 cases, circulating neoplastic lymphoid cells in the peripheral blood with involvement of bone marrow. In all cases the splenic white pulp was hyperplastic with expansion of marginal zones and varying degrees of infiltration of germinal centres by neoplastic cells. The cells were a mixture of medium sized lymphocytes with moderate amounts of cytoplasm and finely dispersed nuclear chromatin, together with occasional blast cells with small nucleoli. Satellite red pulp aggregates of tumour cells centred on small epithelioid cell clusters were seen in all cases. These appear to be a characteristic and diagnostically important feature of splenic marginal zone lymphoma. The tumour cells expressed CD20, CD45RA, bcl-2 and the antigens detected by MB2. All cases expressed IgM with light chain restriction. In addition, IgD was expressed in four cases. The follicular dendritic cell network was disrupted in those follicles which were infiltrated by tumour cells. A network of stromal myoid cells, at the periphery of the marginal zone, identified by expression of α-smooth muscle actin, was preserved. Alpha-smooth muscle actin positive dendritic cells were also seen within and around satellite tumour nodules in the red pulp.     

乳腺粘膜相关型淋巴瘤临床病理观察

目的：探讨乳腺粘膜相关性淋巴瘤（MALT-ML）的病理特征。方法：对4例乳腺MALT-ML的手术根治及（或）活检标本做常规石蜡切片、HE染色和免疫组化ABC法标记。结果：4例乳腺MALT-ML中2例为CCL细胞型,1例为CCL细胞型向母细胞样转化,另1例炎单核样B细胞型。4例均显示B细胞单克隆性及滤泡克隆化和淋巴上皮病变。结论：乳腺MALT-ML有与其他部位MALT-ML相似的形态特征。     

睾丸原发性淋巴瘤17例临床病理分析

目的探讨睾丸原发性淋巴瘤(primary testicular lymphoma,PTL)的临床病理学特征。方法回顾性分析17例PTL的临床病理学特征。结果患者年龄37~81岁,中位年龄69岁;以睾丸无痛性肿大为主要临床表现;病变位于左侧6例,右侧10例,双侧1例;肿块最大径2~6 cm。组织学分型:17例PTL中16例(94%)为弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL),1例(6%)为结外NK/T细胞淋巴瘤(鼻型)。免疫表型提示16例DLBCL中14例为非生发中心B细胞样(non-germinal center B-cell-like,non-GCB)型,2例为生发中心B细胞样(germinal center B-cell-like,GCB)型;c-myc与BCL-2或BCL-6抗体共同阳性表达者(c-myc阳性率30%以上且BCL-2阳性率70%以上者)10例。对10例共表达病例行FISH检测,发现仅1例有MYC基因重排,未发现双重打击淋巴瘤(double-hit lymphoma,DHL)。EB病毒原位杂交检测除1例鼻型NK/T细胞淋巴瘤为阳性外均为阴性。Ann Arbor临床分期:Ⅰ+Ⅱ期15例(88%),Ⅲ+Ⅳ期2例(12%)。17例患者均行患侧睾丸根治性切除术,8例DLBCL患者行CHOP或R-CHOP方案化疗。结论 PTL发病率低,主要发生于老年人,最常见的组织学类型为DLBCL,以non-GCB型伴c-myc与BCL-2/BCL-6共表达为主,患者预后差。PTL中很少发现伴随MYC和BCL-2同时基因重排的DHL。PTL术前诊断困难,确诊需依靠病理组织学、免疫表型及分子病理学检查等。     

Peripheral T-cell lymphoma: a clinicopathological study of 41 cases and evaluation of the prognostic significance of the updated Kiel classification

A total of 41 non-cutaneous peripheral T-cell lymphomas were classified following the updated Kiel classification. Of these, 20 cases belonged to the low-grade group (T-cell chronic lymphocytic leukaemia, 3; lymphoepithelioid, 5; angioimmunoblastic, 4; pleomorphic small cell, 8) and 21 to the high grade group (pleomorphic medium and large cell, 11; immunoblastic, 3; large-cell anaplastic Ki-1 positive, 7). Seventy per cent showed a CD4+/CD8-phenotype, 39% a defective phenotype and 88% an activation phenotype. Eighty per cent had B-symptoms, 63% hepatomegaly, 48% splenomegaly and 26% had involvement of more than three lymphoid areas. Bone marrow was infiltrated in 34% central nervous system in 4%, lung in 12% and skin in 14.6%. Seventeen per cent presented with extranodal disease and 82.8% had stage III/IV disease. Hypergammaglobulinaemia was found in 29%, hypercalcaemia in 7%, raised LDH serum levels in 58% and HTLV-I antibodies in only one case. Of the 37 treated patients 18 (48%) achieved a complete remission, but 33% relapsed. Mortality was 59% and actuarial overall survival at 38 months was 0.32. In the comparison of the clinical, analytical and immunophenotypic variables and outcome between low and high grade groups, only the average of bone marrow infiltration in the low grade and stage I–II, presence of defective phenotypes and higher Ki-67 positivity in the high grade group were significantly different. In the statistical studies, extranodal prentation and the failure to achieve a complete remission were the only variables that influenced mortality; there weere no significant differences in the general features of the low and high grade groups and only minor differences were found in the immunoblastic and angioimmunoblastic subgroups. There were no differences in the actuarial survival between the low and high grade groups, among the subgroups of the Kiel classification, among stages I to IV, between patients with or without B-symptoms, with or without defective phenotypes, Ki-67 positivity over or under 60%, or among different CD4/CD8 phenotypes. The updated Kiel classification did not separate groups with a prognostic significance.     

鼻腔和鼻咽非霍奇金淋巴瘤EB病毒潜伏膜蛋白表达

目的；探讨鼻咽癌高发区人群鼻咽／鼻腔原发非霍奇金淋巴瘤（ＮＨＬ）与ＥＢ病毒（ＥＢＶ）感染的关系，方法：对４１例鼻咽和鼻腔ＮＨＬ进行免疫细胞学分型以及ＥＢＶ潜伏膜蛋白（ＬＭＰ１）检测。结果：发现（１）鼻咽／鼻腔ＮＨＬ的ＬＭＰ１检出率为４８．８％（２０／４１），（２）鼻咽ＮＨＬ的ＬＭＰ１检出率３７．９％（１１／２９），鼻腔７５％（９／１２），（３）Ｔ细胞性淋巴瘤ＬＭＰ１检出率６０％（１５／２５），Ｂ细     

B cell lymphoma with IRF4 rearrangement: A clinicopathological study of 13 cases

Interferon regulatory factor 4 (IRF4) rearrangement is commonly detected in patients with a range of lymphoproliferative malignancies, including myelomas, large B cell lymphomas and low-grade B cell neoplasms. However, IRF4 rearrangement is generally a relatively rare finding in these latter two cancer types. In the present article, we describe and summarize the clinicopathological and genetic features of 13 cases of B cell lymphoma with IRF4 rearrangement, including 12 cases of large B cell lymphoma and one case of low-grade lymphoma exhibiting such rearrangement. These cases were detected in six females and seven males between 14 and 71 years of age. From a morphological perspective, large B cell lymphoma tumors included in this analysis exhibited large neoplastic cells in diffuse or follicular patterns, while the case of low-grade lymphoma mainly composed of small lymphocytes. All analyzed cases exhibited a split in the IRF4 gene consistent with IRF4 translocation. Three of six analyzed large B cell lymphoma cases harbored IGLL5 mutations. Mutations in SAMHD1 were detected in the low-grade lymphoma with IRF4 rearrangement case. In summary, our results offer further insight into the morphological and molecular heterogeneity of cases of B cell lymphoma exhibiting IRF4 rearrangements.     

Histiocytic sarcoma (true histiocytic lymphoma): a clinicopathological study of 20 cases

Large-cell non-Hodgkin's lymphomas (T- and B-immunoblastic, centroblastic and true histiocytic lymphomas) have a heterogeneous clinical course. In the present study the clinical and morphological data of 20 cases of histiocytic sarcoma (true histiocytic lymphoma) are presented. Diagnosis was supported by immunohistochemistry, cytochemistry, rosette assays and/or electron microscopy. Although the follow-up was relatively short (up to 144 months, mean 26 months), the clinical data differed clearly from the series of large-cell non-Hodgkin lymphomas, recorded in the literature. Differences were found in age distribution with a peak in the third decade, in organ involvement showing a preference for skin, gastrointestinal tract and bone, and in response to therapy. In general, histiocytic sarcoma appears to have a more favourable response to therapy and clinical course than the other large-cell lymphomas (T- and B-immunoblastic and centroblastic lymphomas). Moreover, preliminary observations in the group of histiocytic sarcomas suggested that the presence of lysozyme and/or 5-nucleotidase and the absence of alpha 1-antitrypsin in the cytoplasm is associated with a better response to therapy and favourable clinical course.     

Malignant histiocytosis (true histiocytic lymphoma) clinicopathological study of 25 cases

Twenty-five cases originally diagnosed as malignant histiocytosis/true histiocytic lymphoma were reviewed according to both pathological and clinical criteria. Microscopically, they were characterized by large, pleomorphic tumour cells showing variable degrees of atypia and phagocytic activity. The growth more often appeared as diffuse, being limited to the sinuses in only two cases. Cytochemistry on touch imprints showed tumour cells strongly positive for acid phosphatase and alpha-naphthyl-acetate esterase in all the samples tested. Immunohistochemistry on paraffin embedded sections using specific antisera showed tumour cell positivity for lysozyme in 12 of 25 cases, for alpha 1-antitrypsin in 24 of 25 cases and for alpha 1-antichymotrypsin in all 25 cases. Immunophenotyping on frozen-sections in three cases displayed a clear-cut reactivity of the neoplastic cells with the monoclonal antibody OKM1. Clinically, the disease more often presented with B-symptoms, lymphadenopathy and mediastinal involvement. In the majority of the patients (18/25) it had a fatal and rapid course, despite therapy (median survival: 9 months; mean survival: 12 months). The presence of B-symptoms and bulky disease appeared as the only factors influencing the prognosis, both suggesting a more aggressive course of the tumour.