Summary. t(11;18)(q21;q21), the most frequent chromosomal aberration of mucosa‐associated lymphoid tissue (MALT) lymphoma, occurs in 30% of gastric patients.Although the translocation is often associated with an ‘aggressive’ course, it has not been described in transformed MALT lymphomas. We screened 15 gastric MALT lymphomas [three with concurrent or subsequent high‐grade transformation and 11 diffuse large B‐cell lymphomas (DLBCLs)] in Chinese patients for t(11;18). t(11;18) was found in 9/15 (60%) MALT lymphomas, but not in any DLBCLs. One patient, with subsequent high‐grade transformation, showed the translocation in low‐ and high‐grade lesions. t(11;18) was frequent in Chinese gastric MALT lymphomas and unusually one transformed lymphoma carried the translocation.
Mantle cell lymphomas (MCL) frequently show a vaguely follicular growth pattern. This phenomenon is thought to result from the colonization of reactive B-cell follicles by tumour cells. In view of the unique property of the germinal centre environment, antigen stimulation may play a role in the expansion of the tumour. To assess this, we have examined ongoing Ig mutations, which are genetic markers of B cells in persistent response to antigen stimulation, in five MCLs including two cases derived from the gastrointestinal tract known as lymphomatous polyposis (LP). We have specifically analysed Ig ongoing mutations in tumour cells from multiple lesions in one case and in tumour cells microdissected from colonized follicles in two cases. The consensus Ig VB sequences in four MCLs were identical, or almost identical (three cases 100%, one case 99% homology), to the published germlines, which in each case were those frequently employed by autoantibodies. The consensus Ig VH sequence in the remaining case displayed 95.5% homology to the closest published germline. This may represent derivation from an unknown VH germline or a rare instance of somatic mutations. Extensive sequencing of the rearranged Ig genes revealed ongoing mutations within the tumour clone in two cases: one was a LP with multiple lesions of the gastrointestinal tract and the other was a nodal MCL in which tumour cells from colonized follicles were analysed. Our results indicate that MCLs are derived from pre-germinal centre B cells, possibly autoreactive B-cell clones. The ongoing mutations identified suggest a possible involvement of antigen stimulation in the clonal expansion of a proportion of MCLs.
AIM--To establish a simple and reliable polymerase chain reaction (PCR) methodology for random amplification of whole genomic DNA from limited histopathological samples. METHODS--Trace amounts of genomic DNA extracted from fresh tissue and individual lymphoid follicles microdissected from archival paraffin wax tissue sections were amplified using a two-phase PCR protocol with random hexamers as primers (RP-PCR). The randomly amplified DNA samples were used as templates for specific PCR amplifications. To check the fidelity of the RP-PCR, products of the specific PCR amplifications were further analysed by single stranded conformation polymorphism (SSCP) or sequencing. RESULTS--Using a minute fraction of RP-PCR template pool, multiple PCR analyses, including those for beta globin gene, p53 gene (exon 5-6, exon 7, exon 8-9 and exon 7-9), and rearranged immunoglobulin heavy chain gene fragments (VH framework 3 to JH and VH framework 2 to JH) were successfully performed. No artefactual mutations were identified in the products of these specific PCR reactions by SSCP or sequencing when compared with the products from the original DNA. CONCLUSION--This method is simple and reliable, and permits multiple genetic analyses when only a limited amount of tissue is available.
We describe the morphologic, immunohistologic, and genotypic characteristics of 13 cases of true histiocytic lymphomas. Six cases presented with primary gastrointestinal involvement, five with lymphadenopathy, the other sites involved being the bone marrow and the skin. The neoplastic cells displayed large abundant eosinophilic cytoplasm, occasionally vacuolated with folded or bizarre-shaped nuclei with prominent nucleoli. Mitotic figures were numerous. Multinucleated cells were common. The pattern of growth was usually diffuse and noncohesive. Spindle cell sarcoma-like areas were evident in five cases, with a prominent foam cell component in four cases. All cases expressed histiocyte-associated markers (CD68, lysozyme, α-1-antitrypsin), CD45 or CD45RO, and were negative for CD1a, epithelial, and B- and T-cell lineage-specific markers. Reactivity for S-100 was observed in a variable proportion of cells in 11 cases. The proliferation fraction varied from 3 to 88%. Genotypic analysis for T-cell receptor or immunoglobulin gene rearrangement demonstrated a germline configuration in all cases. We demonstrate that true histiocytic lymphoma is a rare distinctive pathologic entity that may be defined by immunohistochemical criteria and that recognition among histiocytic disorders is important for clinical and prognosis reasons.
Summary The clinical and histological presentations of angioimmunoblastic T‐cell lymphoma (AITL) often mimic an infectious process. Epstein–Barr virus (EBV) and human herpes virus (HHV6) are known to be associated with AITL, but whether these viral infections play a role in its pathogenesis is unclear. It also remains to be investigated whether there might be other viruses associated with AITL. We first screened 26 well‐characterised cases of AITL for herpesvirus by polymerase chain reaction (PCR) with universal primers and found evidence of only EBV and HHV6B infection. Subsequent PCR using virus‐specific primers demonstrated EBV and HHV6B infection in 40/49 biopsies (36/42 cases) and 21/49 biopsies (19/42 cases) of AITL respectively with both viral infections found in 17/49 specimens (15/42 cases). Importantly, simultaneous infection with both viruses was found only in specimens showing histological pattern II ( n = 2) or III ( n = 15). Interestingly, among specimens containing both viruses, there was a tendency towards an inverse correlation between the EBV and HHV6B viral load as shown by quantitative PCR. In specimens positive only for EBV, the viral load was significantly higher in specimens with histological pattern III than those with pattern II. High EBV load was also significantly associated with B‐cell monoclonality. Double EBV encoded small RNA (EBER) in situ hybridisation and immunohistochemistry indicated that EBV‐infected B cells had a late postgerminal centre immunophenotype. Our results demonstrate an association between EBV and HHV6B infection and the histological progression of AITL, suggesting that these viruses may play a role in the pathogenesis of this lymphoma.
A simple microdissection technique involving the use of a drawn‐out glass pipette was developed for isolation of defined cell subsets from tissue sections. Using this technique and the polymerase chain reaction (PCR), clonally rearranged immunoglobulin (Ig) heavy chain genes were reliably amplified in single neoplastic follicles or few hundreds of tumour cells isolated from archival haematoxylin and eosin or immunostained sections of B‐cell lymphomas. A polyclonal nature was consistently demonstrated in reactive lymphoid follicles or interfollicular reactive B‐cells within the same lymphoma sections. Microdissection of lymphoma cells from within foci of chronic inflammation improved the resolution of tumour‐specific PCR products by reducing amplification of background polyclonal B‐cell sequences. The combination of microdissection and PCR techniques, therefore, provides an important tool for the investigation of B‐cell lymphomas and also allows simple and specific access for other molecular genetic analyses of different cell subsets on tissue sections.
Abstract Genotypic analysis has led to the implication of certain oncogenes in the pathogenesis of specific groups of non‐Hodgkin's lymphoma. Rearrangements of c‐myc are associated with Burkitt's lymphoma and of bcl‐2 with centroblastic/centrocytic lymphoma. Rearrangement of bcl‐1 has yet to be associated with a specific group of lymphoma. In this study DNA from 62 cases of low grade B‐cell lymphoma, classified using the Kiel classification, were analysed by Southern blotting and hybridization with probes to bcl‐1, bcl‐2, and c‐myc. Rearrangements of bcl‐2 were found in a proportion of centroblastic/centrocytic lymphoma comparable to other published studies. Rearrangement of c‐myc was not found in any case studied. Bcl‐1 rearrangement was found in 2/9 cases of B‐CLL, and 3/6 cases of centrocytic lymphoma. This incidence of bcl‐1 rearrangement in centrocytic lymphoma suggests that it is a characteristic change. No rearrangement of bcl‐1, bcl‐2 or c‐myc was found in any case of lymphoma of mucosa associated lymphoid tissue (MALT), providing further evidence that, in spite of having a similar morphology to some other groups of low grade B‐cell lymphoma, lymphomas of MALT comprise a distinct entity.
We describe two patients with low‐grade and one patient with mixed low‐ and high‐grade B‐cell lymphoma of mucosa associated lymphoid tissue (MALT) type arising in the large intestine. In each patient the lesion occurred as a single polyp. Two patients presented with rectal bleeding and in one the lesion was discovered incidentally. The bone marrow was uninvolved in all three cases but in the patient with mixed low‐ and high‐grade lymphoma involvement of mesenteric lymph nodes and liver was found. CT scan revealed no lymphadenopathy or splenomegaly in any of the patients. Two patients remain well 9 and 24 months respectively after polypectomy whereas the patient with mixed low‐ and high‐grade lymphoma died 7 days after hemicolectomy due to cardiac failure. These previously undescribed solitary polypoid MALT lymphomas can closely resemble both benign lymphoid polyposis of the colon and lymphomatous polyposis (mantle cell lymphoma). Because of their different behaviour accurate diagnosis of polypoid MALT lymphoma is important.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
