Ultrastructural characteristics of malignant non-Hodgkin's lymphoma in baboons

The ultrastructure of 29 malignant non-Hodgkin's lymphomas of baboons including prolymphocytic lymphoplasmacytic, lymphoblastic, and immunoblastic malignant lymphomas is described. The ultrastructure of the cells of B-cell malignant lymphomas is characterized by a more developed strands system of rough endoplasmic reticulum in the tumor cell cytoplasm and the presence of structural abnormalities in the protein synthesis in some B-cell malignant lymphoma cells in the form of Russell's and Dutcher bodies. Analogous baboon and human tumors were shown to have a high degree of cell ultrastructure similarity. Rare forms of baboon malignant non-Hodgkin's lymphomas including a large-cell variant of T-cell lymphoblastic lymphoma with large multilobated nuclei and a variety of B-cell lymphoma with an intermediate degree of cell differentiation have been found. Malignant lymphoma of large multilobated T-cell type and lymphoma of the intermediate lymphocytic type occur rarely in human pathology too.     

Non-Hodgkin's lymphoma, multilobated B-cell type: report of nine cases with immunohistochemical and immunoultrastructural evidence for a follicular center cell derivation

The clinical, pathologic, and immunologic features in nine cases of non-Hodgkin's lymphoma of the multilobated B-cell type are described. Clinical and phenotypic heterogeneity was observed in these B-cell neoplasms. A probable follicular center cell derivation for these cytologically unusual B-cell lymphomas is supported by antecedent histories of follicular center cell neoplasms in three cases; a focal nodular pattern in one case; the demonstration of peanut lectin (PNA) receptors, a marker for follicular center cells, on neoplastic multilobated B cells; and immunoultrastructural studies of nonneoplastic tonsillar cells that identified and characterized rare multilobated cells, immunoreactive for B1, B2, and Ia membrane antigens, a phenotype consistent with follicular center-type cells. Comparison of B- and T-cell multilobated lymphomas revealed that only immunologic studies accurately discriminated between these neoplasms.     

Malignant lymphoma of mucosa-associated lymphoid tissue

Lymphomas of the gastrointestinal tract, salivary glands, lung and thyroid are grouped together as tumours arising in mucosa-associated lymphoid tissue. The great majority of them are of B-cell origin but distinctive T-cell lymphomas are also recognized in the gastrointestinal tract. These lymphomas tend to remain localized for prolonged periods but, whereas the B-cell group respond favourably to local therapy, the T-cell group are associated with severe morbidity and their overall prognosis is extremely poor. Accepted histological classifications of non-Hodgkin's lymphomas are difficult to apply to these tumours. In this paper their morphological features are reviewed; recent findings based on immunohistochemistry and DNA analysis are presented; and the biological behaviour of these tumours is discussed insofar as they offer insight into mucosal immunological mechanisms.     

Critical assessment of four monoclonal antibodies reactive with B-cells in formalin-fixed paraffin-embedded tissues

Four commercially available monoclonal antibodies, MB1, MB2, LN1 and LN2, were studied to determine their sensitivity and specificity for the diagnosis of B-cell lymphomas when used on formalin-fixed paraffin-embedded tissues. In addition to 125 cases of immunologically characterized non-Hodgkin's lymphoma, a range of normal tissues, reactive lymphoid proliferations, Hodgkin's disease and granulocytic sarcomas were also studied. MB1 was found to give positive results in 53.6% of B-cell lymphomas, but the staining was sometimes weak and patchy; there was also cross-reaction with 1.8% of T-cell lymphomas. MB2 reacted with 88.4% of B-cell lymphomas and the reaction was often strong and diffuse, but it showed cross-reaction with 18.2% of T-cell lymphomas. LN1 and LN2 gave positive staining of 44.9 and 46.4% of B-cell lymphomas respectively, and the results appeared to be inferior to that obtained in B5-fixed tissues; staining was sometimes weak and focal, and they also gave false-positive results in a few cases of T-cell lymphoma. This study shows that MB1, LN1 and LN2 are fairly but not entirely specific for B-cells in the non-Hodgkin's lymphomas, but are not very sensitive when applied to formalin-fixed tissues. MB2 shows a high sensitivity but only moderate specificity. Therefore, when these antibodies are used to determine the immunophenotype of malignant lymphomas, the B-cell nature can be predicted with great confidence only when two, preferably three or more, of the antibodies give positive results. The potential applications of these antibodies are discussed.     

Pediatric primary bone lymphoma-diffuse large B-cell lymphoma: morphologic and immunohistochemical characteristics of 10 cases

Most primary bone lymphomas (PBLs) are diffuse large B-cell lymphomas (DLBCLs). Pediatric PBL-DLBCL has a favorable prognosis but remains poorly characterized. Herein, 10 such cases are detailed. They involved 11- to 20-year-old males with bone lesions that were often painful. They were diagnosed often after months to years of symptoms, suggesting an indolent disease. All were successfully treated with chemotherapy with or without radiotherapy (0.5- to 24-year followup). Biopsy revealed that the lymphomas were paratrabecular or diffuse and were medium- to large-sized with round to irregular nuclei, dispersed chromatin, indistinct to small nucleoli, and abundant cytoplasm. Other features included varying levels of necrosis, cytoplasmic retraction, and myeloid hyperplasia. All cases marked as mature B cells, and most were CD10+ (7/10). Typical centroblastic morphologic features with nucleoli were rare, multilobated nuclei were uncommon, and CD10 negativity did not predict poor prognosis, unlike in the adult PBL-DLBCL. These findings suggest that pediatric and adult PBL-DLBCLs are distinct entities.     

Ploidy, proliferative activity, cluster differentiation antigen expression and clinical remission in highgrade non-Hodgkin''s lymphoma

Using a large range of monoclonal antibodies to specific cluster differentiation antigens the phenotypes of a series of high-grade non-Hodgkin's lymphomas of B- and T-cell type were investigated. Cell ploidy and proliferative fraction were assessed by fluorescent staining of DNA and flow cytometry and data on the incidence of complete clinical remission were obtained. With the exception of some lymphoblastic lymphomas, high-grade B-cell lymphomas normally expressed the pan B-cell antigens CD19 and CD22 but only immunoblastic lymphomas consistently expressed the pan B marker CD20. Variable, generally weak expression of CD21 was observed whilst CD23 expression was most prevalent in rapidly proliferative cases and in Burkitt's and centroblastic lymphomas. A rapidly proliferative, multilobated B-cell lymphoma displayed phenotypic properties intermediate between centroblastic and immunoblastic lymphomas. The T-cell lymphomas generally showed low proliferative activity and expression of CD4 prevailed over CD8. Most cases also showed CD2 and CD5 positivity with some also showing CD3 and CD7 expression. Patients with rapidly proliferative diploid or DNA aneuploid tumours obtained complete remission more readily than patients with lowly proliferative diploid tumours. An excess of early deaths occurred among T-cell cases.     

Clinicopathological analysis of 143 primary malignant lymphomas in the small and large intestines based on the new WHO classification

AIM: To study the clinicopathological and immunohistochemical features of 143 cases of primary small and large intestinal non-Hodgkin's lymphoma (NHL) in Japanese patients who presented between 1981 and 2000. METHODS AND RESULTS: The new World Health Organization (WHO) classification was used to classify NHL. The patients included 109 males and 34 females, with an average age of 54.1 years. Tumour sites were as follows: ileocaecal (n = 51, 35.7%), ileum (n = 29, 20.3%), rectum (n = 13, 9.1%), and duodenum (n = 11, 7.7%). Macroscopically, 124 cases (86.7%) were classified as tumorous type, 12 (8.4%) as diffuse infiltration type (erosion, superficial ulceration), five (3.5%) as polyposis type, and only two cases (1.4%) as ulceration type. Immunohistochemically, 122 lesions (85.3%) were of B-cell phenotype and 21 lesions (14.7%) were of T-cell phenotype. According to the WHO classification, of the B-cell lymphomas, 84 cases (68.9%) were large cell, 16 (13.1%) were Burkitt, 10 (8.2%) were marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT), and seven (5.7%) were mantle cell tumours. Among the T-cell lymphomas, 15 (71.4%) were of unspecified type, two (9.5%) were natural killer type, two were anaplastic large-cell lymphomas, one was lymphoblastic, and one was an adult T-cell leukaemia lymphoma. The survival rate for T-cell lymphomas was poorer than for B-cell lymphomas. Among the B-cell lymphomas, mantle cell lymphoma tended to have a poorer prognosis, whereas MALT lymphomas had a better prognosis than other B-cell tumour types. CONCLUSIONS: Our retrospective study of patients with primary malignant lymphomas in the small and large intestines has illustrated the clinical features and outcomes of patients with this disease.     

BIOMED-2聚合酶链反应Ig基因重排对成熟非霍奇金B细胞淋巴瘤诊断的价值

目的 探讨BIOMED-2聚合酶链反应(PCR)在成熟非霍奇金B细胞淋巴瘤(B-NHL)诊断中的价值.方法 收集成熟B-NHL组织标本72例,其中弥漫性大B细胞淋巴瘤37例,黏膜相关淋巴组织结外边缘区淋巴瘤35例为研究对象,并以反应性增生病变25例作为对照.提取以上组织的DNA,并以PCR来检测其完整性和可扩增性,选取质量合格的DNA.85.6%(83/97)的样品DNA长度>300 bp,其中60例成熟B-NHL和23例反应性增生可用于BIOMED-2 PCR检测免疫球蛋白重链(IgH)和kappa轻链(IgK)基因重排的克隆性.结果 利用BIOMED-2 PCR检测的60例成熟B-NHL中,57例存在Ig基因的克隆性重排,其检测敏感性为95%,23例反应性增生病例中未出现Ig基因的克隆性重排,其检测特异性为100%.结论 BIOMED-2 PCR适用于石蜡包埋组织.该方法具有很高的敏感性和特异性,对成熟B-NHL诊断的辅助价值很高.     

Primary non-Hodgkin's lymphoma of the intestine: a morphological, immunohistochemical and clinical study of 31 Chinese cases

Thirty-one cases of primary non-Hodgkin's lymphoma of the intestine were investigated. Twenty-one were of B-cell and 10 of T-cell origin. The B-cell lymphomas comprised two cases of low-grade B-cell lymphoma of mucosaassociated lymphoid tissue (MALT), one of centroblastic/centrocytic type, three of high-grade B-cell lymphoma coexisting with a low-grade B-cell lymphoma of MALT, nine of centroblastic, three of immunoblastic and three of Burkitt type. Of the T-cell lymphomas, eight were of pleomorphic medium-to large-sized cell type and two of large cell anaplastic type. All the B-cell lymphomas expressed CD20 (L26) and/or Ki-B5; in six there was monotypic immunoglobulin light chain restriction. Membrane positivity for CD45RO (UCHL1) was observed in the 10 cases of T-cell lymphoma, but the tumour cells did not express monocyte-macrophage markers. Clinically, the patients with T-cell lymphomas were usually young males with constitutional symptoms and their prognosis was significantly worse than those of patients with intestinal B-cell lymphoma.     

Differential expression of the HECA-452 antigen (cutaneous lymphocyte associated antigen, CLA) in cutaneous and non-cutaneous T-cell lymphomas

The monoclonal antibody HECA-452 identifies an antigen that is primarily expressed on high endothelial venules, the preferred site of lymphocyte extravasation in lymphoid tissues, and also on a subpopulation of myelomonocytic cells and some T-cells. We investigated the expression of the HECA-452 antigen, also called the cutaneous lymphocyte associated antigen, in primary cutaneous and primary non-cutaneous T-cell non-Hodgkin's lymphomas. The tumour cells of cutaneous T-cell non-Hodgkin's lymphomas were positive in 53% of cases, while only 5% of the non-cutaneous lymphomas were positive. These differences were also present in morphologically identical tumours. Thus, the tumour cells in six out of 10 primary cutaneous anaplastic large cell T-cell lymphomas were positive, while they were positive in none of 24 primary non-cutaneous anaplastic large cell T-cell lymphomas. In general, primary cutaneous and primary nasal T-cell non-Hodgkin's lymphomas were devoid of HECA-452 positive high endothelial venules, whereas most nodal T-cell non-Hodgkin's lymphomas contained HECA-452 positive high endothelial venules. These observations suggest that the HECA-452 antigen might be related to a skin-associated type of lymphoid tissue and to lymphomas originating in the skin. However, the results of HECA-452 expression in secondary sites, and the clinical data of the primary cutaneous large cell lymphomas did not support the concept that HECA-452 is functionally involved in homing to the skin, or that loss of the HECA-452 antigen is related to tumour progression of primary cutaneous T-cell lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gastrointestinal lymphomas of T- and B-cell types.

Gastrointestinal lymphomas comprise a group of distinctive clinicopathological entities of B- or T-cell type, with primary gastrointestinal Hodgkin's disease being extremely uncommon. Most low-grade B-cell gastrointestinal lymphomas are of mucosa-associated lymphoid tissue (MALT) type, so called because they recapitulate the features of MALT rather than those of lymph nodes. Paradoxically, however, most MALT lymphomas arise in the stomach, which normally contains no organized lymphoid tissue. Gastric MALT lymphomas appear to arise in MALT acquired as a reaction to infection of the stomach by Helicobacter pylori and their growth can be inhibited by eradication of this organism from the stomach. Low-grade MALT lymphomas, which usually have a very favorable clinical course, may undergo high-grade transformation but high-grade diffuse large B-cell lymphomas may also arise de novo. Immunoproliferative small intestinal disease (IPSID) is a special form of MALT lymphoma characterized by synthesis of alpha heavy-chain immunoglobulin and a restricted geographic distribution. Other B-cell lymphomas that tend to arise in the gastrointestinal tract include mantle cell lymphoma, which presents as lymphomatous polyposis, Burkitt's lymphoma, and B-cell lymphomas associated with immunodeficiency states. Enteropathy (celiac disease)-associated T-cell lymphoma (EATL) is the most common primary gastrointestinal T-cell lymphoma This is a clinically aggressive tumor that arises from the intraepithelial T-cell population.     

BCL10 expression in normal and neoplastic lymphoid tissue. Nuclear localization in MALT lymphoma

BCL10 is an apoptotic regulatory molecule identified through its direct involvement in t(1;14)(p22;q32) of mucosa-associated lymphoid tissue (MALT) lymphoma. We examined BCL10 protein expression in various normal tissues and B-cell lymphomas by immunohistochemistry of formalin-fixed and paraffin-embedded tissues using mouse BCL10 monoclonal antibodies. BCL10 protein was expressed in lymphoid tissue but not in 21 various other tissues with the exception of breast. In normal B-cell follicles, the protein was expressed abundantly in the germinal center B cells, moderately in the marginal zone, but only weakly in the mantle zone B cells. Irrespective of their stage of B-cell maturation, BCL10 was predominantly expressed in the cytoplasm. In contrast, each of the four MALT lymphomas with t(1;14)(p22;q32) showed strong BCL10 expression in both the nucleus and cytoplasm. Twenty of 36 (55%) MALT lymphomas lacking the translocation exhibited BCL10 expression in both the nucleus and cytoplasm although at a much lower level, whereas the remaining 16 cases displayed only cytoplasmic BCL10. Unlike MALT lymphoma, both follicular and mantle cell lymphomas generally displayed BCL10 expression compatible to their normal cell counterparts. Our results show differential expression of BCL10 protein among various B-cell populations of the B-cell follicle, indicating its importance in B-cell maturation. The subcellular localization of BCL10 was frequently altered in MALT lymphoma in comparison with its normal cell counterparts, suggesting that ectopic BCL10 expression may be important in the development of this type of tumor.     

Immunohistological characterization of malignant lymphomas of the Waldeyer''s ring other than the nasopharynx

Among extranodal lymphomas, the Waldeyer's ring is the second most frequently involved site after the gastrointestinal tract. Fresh tissue from 23 consecutive cases of malignant lymphoma of the faucial tonsil, palate and base of tongue were studied histologically and with a panel of 25 monoclonal antibodies. Twenty cases were primary Waldeyer's ring lymphoma, and all were found to express B-cell phenotype. Most cases were classified as diffuse centroblastic lymphoma, polymorphic subtype, in which there were immunoblast-like, centrocyte-like and/or multilobated centroblasts. All except one case expressed all three B-cell lineage antigens CD19, CD20 and CD22, but they showed inconsistent expression of the B-cell antigens CD9 and CD24. Four cases lacked surface immunoglobulin. Six cases expressed interleukin-2 receptor, suggesting that they were composed of highly activated B-cells. Three cases represented relapse in the tonsil or tongue in patients with known malignant lymphoma in other sites; one case expressed T-cell and two cases B-cell phenotype (both of which also expressed interleukin-2 receptor). The clinical features and immunohistological findings suggest that Waldeyer's ring lymphomas, other than those of the nasopharynx, share some of the characteristics of 'mucosa-associated lymphoid tissue' lymphomas. In contrast, nasopharyngeal lymphomas are more related to nasal lymphomas, and are almost exclusively peripheral T-cell neoplasms.     

Cadherins in reactive lymph nodes and lymphomas: high expression in anaplastic large cell lymphomas

Using a polyclonal pan-cadherin antibody and a monoclonal E-cadherin antibody (HECD-1) we have investigated cadherin expression in lymphomas and reactive lymph nodes. Routinely processed tissue from nine reactive lymph nodes and 48 lymphomas (six T-cell, six high-grade B-cell, 15 low-grade B-cell, 13 anaplastic large cell and eight Hodgkin's disease) were immunostained. The reactive cases showed pan-cadherin membrane associated staining of endothelium and epithelioid granulomas. No staining of lymphoid cells was seen. Pan-cadherin immunostaining was present in three of six T-cell lymphomas, two of six high-grade B-cell lymphomas, 12 of 13 anaplastic large cell lymphomas and three of eight cases of Hodgkin's disease. No staining of low-grade B-cell lymphomas was identified with the pan-cadherin antibody. E-cadherin was not detected in any of the lymphomas that showed pan-cadherin expression. The frequent and strongest cadherin expression in anaplastic large cell is noteworthy. The tumour cells of this lymphoma subtype are characterized by copious cytoplasm and a cohesive appearance, features which impart a superficial resemblance to carcinoma cells. Since cadherin molecules are known to have major morpho-regulatory functions our data suggests that the expression of cadherin molecules by anaplastic large cell lymphomas may play an important role in determining their characteristic epithelioid phenotype.     

Lymphoma of the breast. A clinicopathologic study of primary and secondary cases

BACKGROUND: Primary lymphomas of the breast are rare, accounting for 1.7% to 2.2% of extranodal lymphomas and 0.38% to 0.7% of all non-Hodgkin lymphomas. Although secondary breast lymphomas are also rare, they represent the largest group of metastatic tumors of the breast. OBJECTIVES: To investigate the clinicopathologic and immunophenotypic characteristics of breast lymphomas, the relative frequency of primary and secondary mammary lymphomas, and in selected cases, the role of gene rearrangement analysis in diagnosis and staging of these lymphomas. RESULTS: We conducted a retrospective review of 22 cases of breast lymphoma diagnosed at William Beaumont Hospital, Royal Oak, Mich, during a 30-year period (1963-1994). Eleven of the 22 cases fulfilled the criteria for primary breast lymphoma; these cases represented 0.6% of all non-Hodgkin lymphomas seen in our hospital. Of the 11 cases, 5 were diffuse large B-cell lymphomas, 2 were follicle center lymphomas, 2 were marginal zone B-cell lymphomas (mucosa-associated lymphoid tissue type), 1 was a lymphoplasmacytoid lymphoma, and 1 was a peripheral B-cell neoplasm, unclassified. Using a panel of immunohistochemical stains (CD45RO, CD45RA, CD43, CD3, CD20, CD30, CD68, and HLA-DR), 8 cases demonstrated unequivocal B-cell phenotype and 3 cases had equivocal or weak staining patterns for B-cell markers. We identified no cases of T-cell lymphoma. Of 7 cases that had bone marrow biopsies for staging, 3 were positive morphologically for bone marrow involvement. Molecular analysis of B- and T-cell gene rearrangement was used to exclude bone marrow involvement in one case with bone marrow lymphoid aggregates and to confirm negativity in a case that was morphologically negative. Of the 11 secondary breast lymphomas, 5 were diffuse large B-cell lymphomas; 1 was diffuse large B-cell, primary mediastinal subtype; and 5 were follicle center lymphomas. CONCLUSIONS: Breast lymphomas represented 1.2% of all non-Hodgkin lymphomas in this study; the frequency of primary and secondary cases was equal. In both groups, right breast lesions were predominant, and the most frequent morphologic type was diffuse large B-cell lymphoma. Gene rearrangement analysis is helpful in selected cases to rule out bone marrow involvement, especially in older patients, in whom lymphoid aggregates are common.     

Primary malignant lymphomas of the central nervous system: a histological and immunohistological study of 12 cases

Paraffin sections of surgical and autopsy material from 12 cases of primary non-Hodgkin's lymphomas of the central nervous system were examined for histopathological diagnosis and for the demonstration of cytoplasmic immunoglobulins. According to the Kiel classification, there were five cases of lymphoplasmacytoid polymorphous lymphoma, five of immunoblastic lymphoma, one of lymphoblastic lymphoma of convoluted cell type. There was also one of the recently described multilobated lymphoma. An immunohistological study of light and heavy chains by peroxidase-antiperoxidase (PAP) technique and avidin-biotin complex (ABC)technique was performed. Intracellular immunoglobulins were demonstrated in seven cases: four cases were classified as immunoblastic lymphomas and three cases as lymphoplasmacytoid lymphomas. Negative immunoglobulin staining was observed in five cases: two lymphoplasmacytoid lymphomas, one immunoblastic, one lymphoblastic of convoluted cell type and one multilobated. A 'monoclonal' pattern of immunoglobulin staining was detected in six cases. One case, classified as immunoblastic lymphoma, showed 'bitypic' staining for kappa and lambda chains. It was concluded that primary CNS non-Hodgkin's lymphomas of the present series showed morphological and immunohistological features similar to those of malignant lymphomas arising in extraneural sites. In particular, the presence in our series of a multilobated lymphoma, as a primary CNS tumour, is emphasized.     

T-cell lymphomas of the stomach: Morphological and immunological studies characterizing two cases of T-cell lymphoma

Summary Using cytochemical, electron microscopic and immunohistochemical techniques in 20 primary malignant lymphomas of the stomach, we found 18 B-cell and 2 T-cell lymphomas. Primary T-cell lymphoma in the stomach has not been previously reported. The T cells in both cases were reminiscent of T immunoblasts with prominent nucleoli and a basophilic cytoplasm. Case 1 showed a cytological relationship to pleomorphic T-cell lymphoma, large cell type. Case 2 contained in addition some cells not previously described in T-cell lymphomas, resembling immature plasma cells with abundant rough endoplasmic reticulum. Focal positivity to acid phosphatase and dipeptidylaminopeptidase IV suggests the T-cell nature of both lymphomas. In both cases the tumour cells were OKT 11 and OKT 4 positive, and negative for OKT 8. Thus, both cases represent high-grade malignant T-cell lymphomas which correspond phenotypically to T-helper cell lymphoma. Case 2 revealed a further immunohistochemical peculiarity: atypical immunoblasts reacted positively with Ki-1 antibody. Thus, it is a Ki-1 lymphoma of T-cell type.     

B-cell and T-cell lymphomas of the breast: clinical--pathological features of 53 cases

Breast involvement by non-Hodgkin lymphomas is rare. We studied the morphological, immunophenotypical, and clinical features of 53 cases of malignant lymphomas involving the breast in a population of Brazilian patients. Most of the cases were of B-cell phenotype. Four of the patients with primary breast lymphomas had T-cell lymphomas, 3 had CD30-positive anaplastic large cell lymphomas, and 1 had panniculitis-like T-cell lymphoma. Most patients presented with an incidental breast mass. Secondary breast lymphoma was seen in 19 patients and most commonly occurred as part of widespread nodal disease. Two patients presented with bilateral breast involvement. The most prevalent histological subtype was also diffuse large B-cell lymphoma, followed by follicular lymphoma. This study shows that the broad morphological and immunophenotypical spectrum of malignant lymphoma of the breast occurring in a large series of Brazilian patients has many similarities with that seen in Western countries, with a higher proportion of high-grade lymphomas in both primary and secondary cases.