Monocytoid B-cell lymphoma: morphological variants and relationship to low-grade B-cell lymphoma of the mucosa-associated lymphoid tissue

Twenty-eight cases of monocytoid B-cell lymphoma of lymph nodes and 16 lymph node metastases of primary gastric lymphomas, mostly low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type were investigated morphologically and immunohistochemically. Both groups showed the same morphological and immunohistochemical features: diagnostically important sites of infiltration were the sinuses and the marginal zones. The tumour cells were either medium-sized or small. The cytoplasm stained grey with Giemsa and was sometimes rather pale. In imprints the grey colour of the cytoplasm was a characteristic feature. The medium-sized cell type was more frequent; in one third of the cases it was combined with a prominent lymphoplasmacytic component from the same clone, and it resembled the monocytoid B-cells of the sinuses. The small cell type was less common, was not combined with a lymphoplasmacytic component and more closely resembled marginal zone cells. The difference was underlined by the negative reaction with the monoclonal antibody Ki-B3 in the small cell type, which, conversely, was positive in the medium-sized cell type and in the monocytoid B-cell reaction of the sinuses. Both of these cell types, however, showed a granular reaction with the new monoclonal antibody Ki-Mlp. The morphological and immunohistochemical parallels are arguments in favour of the assumption that monocytoid B-cell lymphoma is the nodal equivalent of low-grade B-cell lymphoma of MALT type. This is further supported by the fact that in nine of our 28 cases of monocytoid B-cell lymphoma, lymphomas were found simultaneously or subsequently in organs of the MALT. Monocytoid B-cell lymphoma must be differentiated from an infiltration that occurs in the form of clusters of monocytoid B-cells in other low-grade B-cell lymphomas, especially in immunocytoma with a high content of epithelioid cells.     

Primary B cell lymphoma of the thyroid and its relationship to Hashimoto's thyroiditis

Twenty-one cases were selected from 236 thyroidectomies with a diagnosis of Hashimoto's disease for detailed clinicopathologic study on the basis of "early" changes in three cases and an unusually heavy lymphoplasmacytic infiltrate in 18 cases. These cases were studied in conjunction with ten cases of high-grade non-Hodgkin's lymphoma of the thyroid. Immunoglobulin light chain restriction was demonstrated in five cases of Hashimoto's thyroiditis and the diagnosis was accordingly changed to low-grade lymphoma. All ten high-grade lymphoma cases were of B phenotype and light chain restriction could be demonstrated in eight of them. The study revealed close homology between the lymphoplasmacytic infiltrate in Hashimoto's thyroiditis and normal mucosa-associated lymphoid tissue (MALT). Like lymphomas of mucosal sites, thyroid lymphoma appears to be derived from the parafollicular ("centrocyte-like") B cells. The high-grade thyroid lymphomas appear to be derived from low-grade tumors. There were close histologic, immunohistologic, and clinical similarities between low- and high-grade non-Hodgkin's lymphomas of the thyroid and those appearing in mucosal sites. This study confirms the close association between Hashimoto's thyroiditis and B cell lymphoma of the thyroid gland and suggests that this tumor belongs to the group of non-Hodgkin's lymphomas derived from MALT.     

Lack of PAX5 rearrangements in lymphoplasmacytic lymphomas: reassessing the reported association with t(9;14)

A t(9;14)(p13;q32) involving the PAX5 and IGH genes has been described in association with lymphoplasmacytic lymphoma. Although often described as common, the incidence of this translocation in nodal lymphoplasmacytic lymphoma has never been investigated. Recent studies of patients with Waldenstr?m's macroglobulinemia (often corresponding to marrow-based lymphoplasmacytic lymphoma) have failed to identify the t(9;14). These studies have suggested that either nodal and marrow-based lymphoplasmacytic lymphomas have distinct pathogenetic mechanisms or that the t(9;14) is less frequent in lymphoplasmacytic lymphoma than was believed previously. We therefore analyzed a series of nodal or other extramedullary lymphoplasmacytic lymphomas for the presence of the t(9;14) with paraffin section interphase fluorescence in situ hybridization. We developed a BAC contig probe spanning all previously described PAX5 breakpoints and validated this assay with the KIS-1 cell line that expresses a t(9;14). Analysis with the PAX5 probe showed a lack of PAX5 rearrangements in all cases that were analyzed successfully. Similarly, analysis by an IGH fluorescence in situ hybridization probe showed no evidence of translocations involving the IGH locus. These findings indicate that the t(9;14) is at least uncommon in lymphoplasmacytic lymphoma and should no longer be considered a characteristic finding in this type of lymphoma as defined by World Health Organization criteria.     

Sequential malt lymphomas of the stomach, small intestine, and gall bladder.

Low grade lymphomas of mucosa associated lymphoid tissue (MALT) are indolent neoplasms that, although tending to remain localised for many years, may spread to other mucosal sites. A 53 year old woman treated by total gastrectomy for low grade MALT lymphoma of the stomach developed a recurrence in the small bowel 18 years later, and a further recurrence involving the gall bladder after three years in complete clinical remission after chemotherapy. In situ hybridisation showed that the small intestine and gall bladder recurrences had the same pattern of light chain restriction. Tumour from all three sites was shown to be derived from a single clone by the demonstration of an identical immunoglobulin heavy chain gene rearrangement by the polymerase chain reaction. The case illustrates the propensity of MALT lymphomas to "home" to mucosal sites and gives an insight into their behavior over an extended follow up.     

Neoplastic plasma cells in follicular lymphomas

Summary Six cases of follicular lymphoma contained an abundant plasma cell component. With immunoperoxidase techniques, this was found to demonstrate monotypic cytoplasmic marking for either K or L Ig light chain in five cases, and for IgA heavy chain only in one case. A histogenetic relationship between follicular center cells and plasma cells was suggested by cell forms morphologically intermediate between these two types and by monotypic plasma cells in the neoplastic follicles. The progressive differentiation of follicular center cells into Ig-secreting cells in these cases is likely to be the result of an alteration of the immunoregulatory mechanisms that usually block the differentiation of follicular lymphomas.Four of our patients presented with disseminated disease, three had extranodal presentation and four manifested serum paraproteins. Their median survival was 40 months; two of them died of disease. The published data and our own suggest that follicular lymphoma with plasmacytic differentiation is a malignancy of intermediate grade, with survival and clinical features closer to lymphoplasmacytic/lymphoplasmacytoid lymphoma (LP immunocytoma) than to follicular lymphoma.Dedicated to Professor Dr. Karl Lennert, on the occasion of his 65th birthday     

Crystal-storing histiocytosis: a disorder occurring in plasmacytic tumors expressing immunoglobulin kappa light chain

Intracellular immunoglobulin crystal formation within plasma cells is an uncommon finding in multiple myeloma and other lymphoplasmacytic tumors. We present 12 cases of plasmacytic tumors with prominent crystal formation, including myeloma (5 cases), lymphoplasmacytic lymphoma (6 cases), and a nonneoplastic plasma cell proliferation. In all cases, crystal formation was associated with the proliferation of variable numbers of histiocytes containing similar inclusions. These cases showed a variety of appearances, sometimes obscuring the underlying plasma cell tumor and raising the differential diagnosis of a storage disorder, hemophagocytosis, or a mesenchymal lesion. In cases of lymphoplasmacytic lymphoma, patients typically presented with marked paraproteinemia and symptoms of hyperviscosity. Crystal-storing histiocytosis was not associated with other immunoglobulin deposition disorders, including amyloidosis, Mott cell tumors, or kappa-light chain deposition. In our cases and those previously reported, we found an overwhelming association of crystal-storing histiocytosis (CSH) with tumors expressing immunoglobulin kappa light chain with no consistent association with a particular heavy chain. These results suggest that CSH results from the ingestion of crystals produced by plasma cell tumors that either overproduce kappa light chain or express a structurally aberrant molecule. CSH persists in the marrow and other sites throughout the course of the disease and in our series was not highly associated with development of the adult Fanconi syndrome or rapid clinical deterioration.     

原发性骨恶性淋巴瘤临床病理及免疫表型观察

目的：观察原发性骨恶性淋巴瘤（PLB）的临床病理及免疫表型特征。方法：对8例PLB进行临床病理学观察及免疫组织化学染色（ABC法）。结果：8例PLB平均年龄51岁。X线片示溶骨性破坏或伴有骨质疏松;组织学观察均为弥漫性非霍奇金淋巴瘤（NHL）,大细胞性4例,中心细胞性2例、混合细胞性（中心细胞－中心母细胞）和淋巴交细胞样各1例;免疫化显示B细胞6例、T细胞2例。结论：PLB好于50岁左右,X线片主要表现为溶骨性破坏和骨质疏松。病理类型为弥漫性NHL,细胞形态主要是大细胞,免疫表型则以B细胞多见,免疫化有助于PLB的鉴别诊断。     

Combined analysis of T cell receptor gamma and immunoglobulin heavy chain gene rearrangements at the single-cell level in lymphomas with dual genotype

By prospectively studying immunoglobulin heavy chain gene (IgH) and T cell receptor gamma (TCRgamma) gene rearrangements in 398 lymphoma cases, a dual genotype was observed in 13% of B cell and 11% of T cell lymphomas. According to histological subtype, the highest incidence was observed for mantle cell lymphomas (32%) and lymphoplasmacytic lymphoma (21%) among B cell lymphomas, and for angioimmunoblastic lymphoma (AILT) (46%) and Sézary syndrome (SS) (50%) among T cell lymphomas. To determine whether the dual genotype corresponds to the presence of two distinct monoclonal populations or to the presence of both rearrangements within the same lymphoma cells, single-cell microdissection was used after immunohistochemistry and a single-cell combined IgH and TCRgamma gene analysis was designed after a whole-genome amplification step. This protocol was applied to the study of two nodal B cell lymphomas (one diffuse large B cell lymphoma and one mantle cell lymphoma) and two cutaneous T cell lymphomas (one AILT and one SS). Two cases (SS and mantle cell lymphoma) were true bigenotypic lymphomas, as both IgH and TCRgamma monoclonal rearrangements were detected in the same cells. Conversely, in the diffuse large B cell lymphoma and AILT cases, large CD22+ single cells exhibited only the monoclonal IgH rearrangement but not the TCRgamma gene that was detected in CD3+ single cells. Such an approach allows the identification of true bigenotypic lymphoma among dual genotypic lymphoma. Specific genetic alterations may be further amplified from microdissected cryopreserved material, such as the t(11;14) breakpoint detected in bigenotypic B cells of the mantle cell lymphoma case.     

Histological and immunohistochemical studies on primary gastrointestinal lymphomas.

To study the characteristics and histogenesis of the malignant lymphomas derived from the gastrointestinal mucosa, histologic and immunohistochemical analyses were performed on a series of 28 malignant lymphomas of the gastrointestinal tract. By cytomorphologic classification, there were two small lymphocytic lymphomas, one small cleaved cell lymphoma, two mixed small cleaved and large cell lymphomas, 17 large cell lymphomas, one small noncleaved cell lymphoma, three immunoblastic lymphomas, and two lymphoblastic lymphomas. This distribution of histologic types was compatible with that of nodal lymphoma. The lymphomas with poor prognostic histology (23 cases) outnumbered those with favorable prognosis (five cases). Three of 28 cases (one in the stomach and two in the small intestine) had cytologic features consistent with centrocytoid cell lymphoma of the mucosa associated lymphoid tissue and were large cell lymphomas. Immunophenotypically, 23 cases expressed B-cell markers (82.1%) and three cases reacted with T-cell markers. Two cases did not react with either T-cell or B-cell markers. True histiocytic lymphomas were not identified. Gastric lymphomas (nine cases) and colorectal lymphomas (three cases) were of B-lymphocyte origin whereas T-cell lymphomas were noted in the small intestine (two cases) and ileocecal region (one case). Three cases of centrocytoid lymphoma were of B-lymphocyte origin. Histologically B-cell lineage lymphomas were evenly distributed on various histologic subtypes but all T-lineage lymphomas belonged to the large cell type. The two cases with undetermined phenotype were lymphoblastic lymphomas histologically. This study showed that the primary GIT lymphomas, mostly of B-cell lineage, were not cytomorphologically distinctive from the nodal lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)     

Paraffin-immunohistochemical Analysis of 26 Non-Hodgkin's Malignant Lymphomas n the Endemic Area of Human T-cell Leukemia Virus Type 1

A study was conducted to evaluate the usefulness of paraffin immunohistochemistry for histopathological classification of non Hodgkin's malignant lymphomas (NHML). The phenotypes of lymphoma cells and other cells were examined using 11 monoclonal and 3 polyclonal antibodies by the ABC method on paraffin-embedded tissue sections of 226 cases of NHML, comprising 94 B cell lymphomas (B ML) and 132 T cell lymphomas (T-ML). In 219 NHML cases (96.8%), lymphoma cells reacted with more than one of these antibodies. A set of MB 1, Mx pan B, L26, LN 1, LN 2 and antiimmunoglobulin light chain antibodies characterized each subtype of B MLs, categorized according to the Kiel classification. Mantle-zone lymphoma (MzML) was added as one subtype. L26 stained the largest number of B MLs (82.8%). B cell chronic lymphocytic leukemia (B CLL) was labeled most frequently by MB 1. MzML was characterized by reactivity of lymphoma cells with LN 2 and by the appearance of monoclonal immunoglobulin light chain along the cell membrane. Follicle center cell lymphomas were stained by LN 1 and LN 2, although a small number of proliferating cells were labeled by LN 1 in B CLL, MzML and the im-munocytoma lymphoplasmacytic/cytoid variant. MT 1 and/or UCHL-1 showed various degrees of reactivity with the cell membranes of lymphoma cells in 94.8% of T-MLs. Among the T cell pleomorphic lymphomas of Suchi and Lennert, the adult T cell leukemia/lymphoma type, defined by stippled heterochromatin distribution and peculiar huge cells, reacted selectively (p<0.05) with anti phospho-kinase C antibody. Anaplastic large cell T-ML reacted with a set of Ber H2, LN 2 and Leu Ml. In T zone lymphomas without hyperplastic follicles, angioimmuno-blastic lymphadenopathy with dysproteinemia type T-ML, lymphoepithelioid cell lymphomas and some pleomorphic lymphomas comprising clear large lymphoma cells, there were many intermingling B cells, and their constitution varied. In some lymphoblastic lymphomas of both the T cell and B cell type, phenotypes of T cells and B cells were expressed. Consequently, it was shown that paraffin immunohistochemistry was useful for the practical histopathological diagnosis of NHML even in the area where human T cell leukemia virus type 1 is endemic.     

Primary intestinal lymphomas

Summary The histology and immunohistology of twenty-seven malignant non-Hodgkin's lymphomas of the intestinal tract were studied. Nine of these cases were in the small intestine, ten in the ileocaecal region, two in the appendix and four in the large intestine. In one case, several locations in the gastrointestinal tract were involved. The so-called Kiel-Classification was applied. We have found thirteen lymphomas with low grade (lymphocytic, lymphoplasmacytic, centrocytic, centroblastic/centrocytic) and fourteen with high grade of malignancy (centroblastic, lymphoblastic, immunoblastic). For most of the lymphoplasmacytic and immunoblastic lymphomata a monoclonal pattern of intracellular immunoglobulin (IgM/kappa) was identified by the immunoperoxidase method. Tumour cells of lymphocytic, centrocytic, centroblastic/centrocytic, centroblastic and lymphoblastic lymphomas were always Ig-negative. The immunoperoxidase technique helped considerably in distinguishing between (monoclonal) malignant lymphomas and (polyclonal) lympho- or immunoproliferative processes.Six out of twenty-seven malignant lymphomas had developed from immuno-inflammatory diseases of the gut. Four of these were complications of coeliac disease. One had developed from a malabsorptive dermatitis herpetiformis Duhring, and one from a complication of a long-standing ulcerative colitis. In two patients with coeliac sprue and malabsorptive dermatitis herpetiformis Duhring respectively the ulcerating small intestinal lymphomas were initially misinterpreted as benigne ulcerative non-granulomatous jejunitis. The evidence from the literature summarized suggests strongly that the benign non-granulomatous jejunoileitis, lymphomatous ulcer, intestinal pseudolymphoma and malignant lymphoma, when associated with villous atrophy of adjacent mucosa and malabsorption symptoms, are all one condition, namely, malignant lymphoma.This study was supported by a grant from the Deutsche Forschungsgemeinschaft (Ot 53/4-6)     

肺粘膜相关型淋巴瘤与肺炎性假瘤临床病理及免疫组化研究

目的 :探讨肺粘膜相关型淋巴瘤和肺炎性假瘤的病理特征及相互关系。方法 :对 9例肺粘膜相关型淋巴瘤和 6例肺炎性假瘤进行临床病理及免疫组化研究。结果 :男性多见 ,平均年龄 5 8岁 ,干咳、胸闷、胸痛为主要症状。病理形态 :肺粘膜相关型淋巴瘤 9例 ,细胞类型 ,CCL细胞性 6例、小淋巴细胞性 2例 ,淋巴浆细胞性 1例。肺炎性假瘤 6例。免疫组化证实 ,肺粘膜相关型淋巴瘤 9例LCA 、L2 6 、IgM、κ或λ呈单克隆性 ,6例炎性假瘤显示多克隆性。 结论 :两者临床鉴别困难 ,病理诊断须依靠免疫组化才能鉴别 ,两者均应以手术治疗为主。     

Marginal zone lymphomas with plasmacytic differentiation and related disorders

Marginal zone lymphomas of all types (nodal, splenic, and extranodal mucosa-associated lymphoid tissue [MALT]) may show plasmacytic differentiation. Distinguishing marginal zone lymphomas from other small B-cell lymphomas with plasmacytic differentiation, especially lymphoplasmacytic lymphoma, or from plasma cell neoplasms may be challenging. Marginal zone lymphomas with plasmacytic differentiation were discussed in 2 sessions of the 2009 Society for Hematopathology/European Association for Haematopathology Workshop. Session 4 focused on nodal marginal zone lymphomas, including cases exhibiting classic features and cases displaying atypical phenotypes. The difficulties of classification of cases with increased numbers of large cells were also discussed. Session 5 examined nonnodal marginal zone lymphomas and related entities, including splenic marginal zone lymphoma, MALT lymphoma, γ heavy chain disease, and cryoglobulin-associated lymphoproliferative disorders. These cases illustrate the importance of clinical data and, in some cases, phenotypic and cytogenetic findings in appropriately applying the 2008 World Health Organization criteria.     

Follicular lymphomas of the gastrointestinal tract. Pathologic features in 31 cases and bcl-2 oncogenic protein expression.

The gastrointestinal tract is the most common site for extranodal lymphomas, but follicular lymphomas involving the gut are rare. To study their pathologic features and bcl-2 expression, 31 follicular lymphomas of the GI tract were reviewed and unstained paraffin sections from 24 of the cases were immunohistochemically stained using a monoclonal antibody for the peptide product of the proto-oncogene bcl-2. The most common site of lymphoma involvement was the small intestine, especially the terminal ileum. Gastric lymphomas tended to present clinically with symptomatic ulcers and small intestinal lesions presented with obstruction. Five cases involving the terminal ileum or colon had a gross appearance of multitudinous mucosal polyps and were considered to represent examples of "multiple lymphomatous polyposis." Enhanced expression of the bcl-2 oncogenic protein was detectable in lymphoma cells in 75% of cases and at lower levels in normal lymphoid cells in most cases. Small cleaved or mixed cell lymphomas were more likely to show enhanced expression than were large cell cases. Reactive germinal centers showed no bcl-2 staining. It is concluded that follicular GI lymphomas are associated with distinctive pathological features. In their tendency to express bcl-2, these neoplasms resemble their lymph node-based counterparts. Immunohistochemical staining for enhanced bcl-2 expression is of potential diagnostic utility in distinguishing between follicular lymphoma and follicular lymphoid hyperplasia in the gastrointestinal tract. The relevance of the results to lymphoma of mucosa-associated lymphoid tissue (MALT) is discussed.     

Small B-cell lymphomas of the lymph nodes and spleen: practical insights to diagnosis and pathogenesis.

As defined in the proposed World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues, the small B-cell lymphomas include B-cell chronic lymphocytic leukemia / small lymphocytic lymphoma, mantle cell lymphoma, follicular lymphoma, marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, nodal marginal zone lymphoma, lymphoplasmacytic lymphoma, and splenic marginal zone B-cell lymphoma. These neoplasms are recognized mostly on the basis of their histopathologic features, but ancillary studies are useful in confirming and sometimes making the diagnosis. Clinically, the small B-cell lymphomas of lymph nodes and spleen (but not those of MALT type) are usually disseminated at diagnosis and considered incurable. With the exception of mantle cell lymphoma, however, they are generally indolent. The small B-cell lymphomas are among the best examples of how malignant lymphomas can be related to the normal immune system. Although uncertainties exist, these lymphomas are generally considered the neoplastic equivalents of normal B-cell compartments. From a molecular perspective, mantle cell and follicular lymphomas are the best characterized. In both cases, there are characteristic chromosomal translocations involving the immunoglobulin heavy chain and the cyclin D1 or bcl-2 genes, respectively, that are probably followed by additional molecular events leading to overt neoplasia. Variable proportions of the small B-cell lymphomas undergo transformation that might be associated with abnormalities in tumor suppressor genes / cell cycle regulatory proteins. After a brief review of normal B-cell development, the major small B-cell lymphomas (except for those of MALT type) will be discussed in terms of their morphologic features, immunophenotype (including paraffin-section immunostaining), genotype, karyotype, and clinical features, including disease evolution.     

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.     

Prevalence of EBV RNA in sinonasal and Waldeyer's ring lymphomas.

A high incidence of a T cell phenotype of sinonasal lymphomas in other Asian countries has been associated with a high incidence of Epstein Barr virus (EBV) infection. We analyzed 13 sinonasal and 18 Waldeyer''s ring lymphomas for the prevalence of EBV encoded RNA (EBER) using a sensitive and specific in situ hybridization. In addition, we examined the relationship of histologic findings and immunophenotype as well as the location of the lymphomas to the presence of EBV. The EBER was detected in each of 12 sinonasal lymphomas with a T cell immunophenotype. One B cell sinonasal lymphoma was EBER negative. Four of 18 Waldeyer''s ring lymphomas were positive for EBER, including two T cell lymphomas. Two of 16 B cell Waldeyer''s ring lymphomas were EBER positive. Morphologically, 11 of 20 diffuse large cell lymphomas, 2 diffuse mixed small and large cell lymphomas, 2 of 4 immunoblastic lymphomas and 1 lymphoplasmacytic lymphoma were EBER positive. Four follicular large cell lymphomas were EBER negative. A characteristic angiocentric or angiodestructive pattern was found in most T cell lymphomas and EBER positive cases. These findings indicate that EBV infection is more strongly associated with the T cell immunophenotype, angiocentric pattern and sinonasal location of the lymphoma.     

Genomic analysis of marginal zone and lymphoplasmacytic lymphomas identified common and disease-specific abnormalities

Lymphoplasmacytic lymphomas and marginal zone lymphomas of nodal, extra-nodal and splenic types account for 10% of non-Hodgkin lymphomas. They are similar at the cell differentiation level, sometimes making difficult to distinguish them from other indolent non-Hodgkin lymphomas. To better characterize their genetic basis, we performed array-based comparative genomic hybridization in 101 marginal zone lymphomas (46 MALT, 35 splenic and 20 nodal marginal zone lymphomas) and 13 lymphoplasmacytic lymphomas. Overall, 90% exhibited copy-number abnormalities. Lymphoplasmacytic lymphomas demonstrated the most complex karyotype (median=7 copy-number abnormalities), followed by MALT (4), nodal (3.5) and splenic marginal zone lymphomas (3). A comparative analysis exposed a group of copy-number abnormalities shared by several or all the entities with few disease-specific abnormalities. Gain of chromosomes 3, 12 and 18 and loss of 6q23-q24 (TNFAIP3) were identified in all entities. Losses of 13q14.3 (MIRN15A-MIRN16-1) and 17p13.3-p12 (TP53) were found in lymphoplasmacytic and splenic marginal zone lymphomas; loss of 11q21-q22 (ATM) was found in nodal, splenic marginal zone and lymphoplasmacytic lymphomas and loss of 7q32.1-q33 was found in MALT, splenic and lymphoplasmacytic lymphomas. Abnormalities affecting the nuclear factor kappa B pathway were observed in 70% of MALT and lymphoplasmacytic lymphomas and 30% of splenic and nodal marginal zone lymphomas, suggesting distinct roles of this pathway in the pathogenesis/progression of these subtypes. Elucidation of the genetic alterations contributing to the pathogenesis of these lymphomas may guide to design-specific therapeutic approaches.     

Malignant lymphoma with eosinophilia of the gastrointestinal tract

Lesions of the gastrointestinal tract with massive tissue eosinophilia may present a difficult diagnostic problem. In a series of 250 gastrointestinal lymphomas drawn from the files of St Bartholomew's and St Mark's Hospitals there were 28 cases of a lymphoma with distinctive histological features, characterized by a massive tissue eosinophilia. Two of these tumours were present in the stomach and 26 in the small intestine. Eight of the latter were associated with coeliac disease. On low power examination a zoning phenomenon was regularly seen and fissuring ulceration, with perforation and fistula formation, was a common finding. The tumour cells were large and pleomorphic with irregular nuclear morphology and prominent nucleoli. Eosinophils were the predominant inflammatory cell associated with the lymphoma but plasma cells, epithelioid histiocytes and small lymphocytes were also present. Vascular changes were prominent. Involved lymph nodes showed gross expansion of the paracortex by tumour. Immunohistochemical studies showed that this lymphoma was probably of T-cell origin.     

Carcinoma of the urinary bladder with a lymphomatous appearance

We present the first report of bladder carcinoma that demonstrates a mixture of two distinct histological patterns resembling malignant lymphoma. The patient was a 79-year-old man. One of the histological patterns was a diffuse growth of monomorphic carcinoma cells, and the other was a dense lymphoplasmacytic infiltrate, obscuring the carcinoma. The tumor cells showing both patterns expressed cytokeratin and epithelial membrane antigen, but not lymphoid markers. Careful immunohistochemical evaluation should be done when diagnosing urinary bladder carcinomas resembling lymphomas (other than primary lymphomas).