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PubMed2006

Relationship between classic Hodgkin lymphoma and overlapping large cell lymphoma investigated by comparative expressed sequence hybridization expression profiling.

There is a diagnostic grey zone between classic Hodgkin lymphoma (cHL) and some non-Hodgkin lymphoma (NHL), including primary mediastinal B cell lymphoma, diffuse large B cell lymphoma, and anaplastic large cell lymphoma. They all have some morphological and/or phenotypic features in common. To investigate this, we undertook an expression profiling study of these lymphomas using comparative expressed sequence hybridization. This technique detects chromosomal regions that are differentially expressed between a test and a reference tissue in a manner similar to comparative genomic hybridization, and is particularly suitable when the number of informative biopsies is limited. Using this approach, we identified a unique expression profile for all lymphoma types investigated. Unsupervised hierarchical cluster analysis of the acquired data showed that cHL separates from all investigated NHLs, including ALCL-like HL. Moreover, anaplastic lymphoma kinase (ALK)-negative ALCL clustered in a separate branch together with ALCL-like HL. Thus, analysing the neoplastic cells concurrently with their microenvironment, ALK-negative ALCL and ALCL-like HL seem to be related to each other, while cHL constitutes a separate lymphoma entity.

Adolescent↗
PubMed1987

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

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.

Adolescent↗
PubMed2001

[Increasing incidence and mortality of non-Hodgkin lymphomas. An epidemiological review of recent studies on risk factors for non-Hodgkin lymphoma].

BACKGROUND: Non-Hodgkin's lymphoma (NHL) are among the small number of malignant tumors with markedly increasing incidence and mortality rates in the recent past. This trend is particularly obvious in industrialized countries. The causes of the observed increase remain unclear. METHODS: We conducted a Medline search to identify case control and cohort studies on medical, biological and selected environmental risk factors of non-Hodgkin's lymphoma published between 1992 and 1998. Methodological aspects and results of identified studies are presented in tabular form. We furthermore discuss the role of various risk factors for the observed trends in non-Hodgkin's lymphoma. RESULTS: We identified a total of 64 studies. Iatrogenic immunosuppression as well as numerous diseases associated with an impaired immune system have clearly been recognized as etiological factors for non-Hodgkin's lymphoma. However, they can explain only a small percentage of the rate increases of non-Hodgkin's lymphoma. Similarly, the HIV/AIDS epidemic in Germany is responsible only for a small proportion of the rising figures of non-Hodgkin's lymphoma; other viral agents are currently being associated with a few distinct subtypes of non-Hodgkin's lymphoma. Smoking and nutritional factors are weakly or not at all associated with non-Hodgkin's lymphoma and can not account for the disease trends. CONCLUSION: The observed secular rise in incidence and mortality of non-Hodgkin's lymphoma can only partly be explained. New epidemiologic studies should focus on risk factors associated with the function of the immune system and on possible interactions between different etiological factors.

Case-Control Studies↗
PubMed2001

Outcome of patients with non-Hodgkin's lymphoma of the stomach after gastrectomy: clinicopathologic study and reclassification according to the revised European-American lymphoma classification.

BACKGROUND: The best treatment for patients with non-Hodgkin's lymphoma (NHL) of the stomach is still uncertain. The revised European-American lymphoma (REAL) classification has helped to define new, potentially more appropriate classification schemes for gastric lymphomas. METHODS: Fifty-one resected gastric lymphomas were reclassified according to the REAL classification, and the efficacy of multimodal treatment was examined retrospectively. The principal treatment plan consisted of: (1) surgical resection of the stomach with lymph node dissection, followed by (2) systemic chemotherapy, mainly using the cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) regimen. RESULTS: According to the Ann Arbor classification, 27 patients had stage IE, 19 had stage IIE, and 5 had stage IV NHL. Using the REAL classification, we diagnosed diffuse large B-cell lymphoma (DLBL) in 23 patients, marginal zone B-cell (low-grade mucosa-associated lymphoid tissue [MALT]-type) lymphoma in 22, follicle center lymphoma in 4, mantle cell lymphoma in 1, and peripheral T-cell lymphoma in 1 patient. Nine of the 51 patients relapsed, and 8 patients with DLBL died of cancer. Survival rates at 5 years after surgery were 96.0% for stage IE, 83.3% for stage IIE, and 87.0% for all patients. Univariate analysis indicated that the tumor histology (according to the REAL classification), depth of invasion, degree of nodal involvement, Ann Arbor staging, and chemotherapy had an impact on patient outcome (P = 0.0018; P = 0.0002; P = 0.0308; P = 0.0016, and P = 0.0118, respectively). CONCLUSIONS: These data reveal that gastric NHL, especially of the low-grade MALT-type, often remains localized and has a good prognosis after surgery. The REAL classification was useful for classifying new categories of NHL, including the MALT-type, in the clinical setting, and for determining the optimal treatment modality for gastric NHL.

Female↗
PubMed1986

Cytogenetic and immunohistochemical analysis of lymphoepithelioid cell lymphoma (Lennert's lymphoma): further substantiation of its T-cell nature.

In 1968 a special variant of Hodgkin's disease, epithelioid cellular lymphogranulomatosis--later on termed lymphoepithelioid cell lymphoma/Lennert's lymphoma--was defined. There are increasing indicators that Lennert's lymphoma is of T-cell origin. Seven cases of Lennert's lymphoma are studied with cytogenetic as well as immunohistochemical techniques. Six of them have cytogenetic abnormal clones always including aberrations of chromosome No. 3 (+3, break in q22, dup q22----q24). In all cases band 3q22 is either broken or duplicated. Immunohistochemically it is clearly demonstrated that the proliferating cells are of T-cell nature (Ki67+, Leu4+, Leu1+). Under consideration in the literature it can be stated in conclusion that (1) lymphoepithelioid cell lymphoma (Lennert's lymphoma) with aberrations has to be designated as malignant lymphoma, (2) immunohistochemical double labeling proved the T-cell nature of this lymphoma, (3) there are remarkable similarities between the chromosomal patterns of lymphoepithelioid cell lymphoma, lymphogranulomatosis X/angioimmunoblastic lymphadenopathy and probably Hodgkin's disease: many normal mitoses and abnormalities of chromosome No. 3, especially trisomy. It is discussed that abnormalities of chromosome No. 3 involving band q22 are an indicator of a common genetic background of these lymphomas.

Adult↗
PubMed2000

B cell lymphomas of C57L/J mice; the role of natural killer cells and T helper cells in lymphoma development and growth.

The Hodgkin's-like Type B neoplasms which arise spontaneously in aging C57L mice (25% incidence at 21 months of age) were first reported over 40 years ago, but since then relatively little has been published about these lymphomas. Based on previous studies in SJL mice, we investigated the phenotypic and functional properties of C57L-derived lymphomas in relation to Mtv29-encoded vSAg expression by the tumor cells, and their ability to stimulate TCR Vbeta-restricted T cells. The cell surface phenotype of the C57L lymphomas indicates a B cell origin (sIg(+), MHC II(+)). These B lymphoma cells also express co-stimulatory molecules [B7-1 (CD80) and HSA (CD24)], and stimulate marked proliferation of syngeneic CD4(+) T cells. C57L B lymphoma cells exhibit Mtv-encoded mRNA by northern analysis, and also stimulate IL-2 production from Vbeta16(+) T cell hybrids, suggesting a role for Mtv 29 in this syngeneic T cell response. After transfer to syngeneic recipients, primary C57L lymphomas grow slowly, if at all. However, tumor growth is greatly accelerated by pretreatment of C57L recipients with anti-asialo GM1 antibody (but not anti-CD8 mAb), suggesting that NK cells play a major role in inhibiting lymphoma growth. If, in addition to anti-asialo GM1, the mice are also pretreated with anti-CD4 mAb, tumor growth is markedly inhibited, indicating that the lymphoma-responsive syngeneic CD4(+) T cells promote tumor growth. Therefore, although the vSAg-induced response stimulated by vSAg29 expressing lymphoma cells in syngeneic TCR Vbeta-restricted CD4(+) T cells is an important etiologic factor in this type of B cell neoplasm both in C57L and in SJL mice, the final outcome of the spontaneous neoplastic process appears strongly influenced by endogenous NK activity in aging mice.

Animals↗
PubMed1984

Cytophotometric measurements of the DNA in Hodgkin lymphomas and non-Hodgkin lymphomas.

In smear preparation of lymph nodes excised from 36 patients with a malignant lymphoma the DNA content was estimated in different tumor cells following Feulgen staining by means of quantitative cytophotometric measurements. The tumors investigated included 11 Hodgkin lymphomas and various types of Non-Hodgkin lymphomas (altogether 25). Whereas the small lymphoid cells found in Hodgkin lymphomas show a diploid DNA content with a wide scattering, in the large mononuclear reticular cells (Hodgkin cells) as well as in Sternberg's giant cells only aneuploid DNA values are seen lying in the hyperdiploid, hypertetraploid and hyperoctoploid regions. DNA stemlines are found in the aneuploid regions, but in some cases they are missing. This indicates that we are dealing with malignant tumor cells. In Non-Hodgkin lymphomas with a low grade of malignancy (centrocytic-centroblastic lymphoma, centrocytic lymphoma, CLL) an aneuploid DNA content is found particularly in the large cells (centroblasts, lymphoblasts) with or without a DNA stemline. These cells must be considered as primary malignant tumor cells. In the immunoblastic lymphoma of high malignancy only aneuploid tumor cells are present showing a particularly intense DNA content in the large immunoblasts, whereas a DNA stemline is usually missing. The range of aneuploid values, the number of polyploid tumor cells and the presence or absence of a DNA stemline are important criterions in determining the degree of malignancy. By means of cytophotometric measurements of the DNA content in the tumor cells of malignant lymphomas it is possible to assertain the degree of malignancy and to establish an objective prognosis.

DNA, Neoplasm↗
PubMed2005

Kaposi's sarcoma-associated herpesvirus/human herpesvirus type 8-positive solid lymphomas: a tissue-based variant of primary effusion lymphoma.

Kaposi's sarcoma-associated herpesvirus (KSHV), also termed human herpesvirus type 8, is consistently identified in Kaposi's sarcoma, primary effusion lymphoma (PEL), and multicentric Castleman's disease. Here we report four cases of KSHV-bearing solid lymphomas that occurred in AIDS patients (cases 1 to 3) and in a human immunodeficiency virus (HIV)-seronegative person (case 4). The patients presented extranodal masses in the abdomen (cases 1, 3, and 4) or skin (case 2), and nodal involvement, together with Kaposi's sarcoma (case 3). The gastrointestinal tract was involved in two patients (cases 1 and 3). The patients did not develop a lymphomatous effusion. KSHV was detected in the tumor cells of all cases by immunohistochemistry and by polymerase chain reaction. Epstein-Barr virus was detected in two of the HIV-related cases. All KSHV-positive solid lymphomas exhibited PEL-like cell morphology. To investigate the relationship of these disorders to PEL and to other AIDS-associated diffuse large cell lymphomas, KSHV-positive solid lymphomas were tested for the expression of a set of genes that were previously shown by gene profiling analysis to define PEL tumor cells. The results showed that expression of this set of genes in KSHV-positive lymphomas is similar to that of PEL but distinct from KSHV-negative AIDS-associated diffuse large cell lymphomas. Because pathobiological features of KSHV-positive solid lymphomas closely mimic those of PEL, our results suggest that KSHV-positive solid lymphomas should be considered as a tissue-based variant of classical PEL, irrespective of HIV status.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Follicular lymphoma with marginal zone differentiation: cytogenetic findings in support of a high-risk variant of follicular lymphoma.

AIMS: The pathogenesis and clinical significance of marginal zone differentiation in follicular lymphoma remains to be determined, although genetic alterations are likely to be important determinants of both. We therefore report the cytogenetic findings in three cases of follicular lymphoma with marginal zone differentiation studied by routine karyotyping and in-situ hybridization. METHODS AND RESULTS: The morphology and immunophenotype of each case was typical of follicular lymphoma displaying marginal zone differentiation. Karyotyping, performed on GTL-banded preparations of cell cultures derived from fresh lymph node tissue, revealed a complex karyotype in all three cases, including t(14;18)(q32;q21) and abnormalities associated with progression and/or transformation of follicular lymphoma. In addition, trisomy 3 was found in one case and translocations between the q27-29 region of chromosome 3 and chromosome 2 in the other two cases; the latter was identified only in subclones derived from less complex stem lines possessing t(14;18). In-situ hybridization, performed on sections cut from routinely processed paraffin-embedded tissue blocks, localized cells possessing these abnormalities of chromosome 3 to both the follicular and marginal zone components of two lymphomas studied in this way. CONCLUSIONS: Trisomy 3 and alterations involving the q27-29 region of chromosome 3 are implicated in the pathogenesis of de novo marginal zone lymphoma. Their presence in the current cases indicates that they may also be responsible for marginal zone differentiation in follicular lymphoma when cells harbouring these genetic alterations are exposed to the appropriate microenvironment. Our findings are consistent with follicular lymphoma with marginal zone differentiation as a high-risk variant of follicular lymphoma.

Aged↗
PubMed2000

Primary gastric B-cell lymphoma: results of a prospective multicenter study. The German-Austrian Gastrointestinal Lymphoma Study Group.

BACKGROUND & AIMS: Appropriate management of primary gastric lymphoma is controversial. This prospective, multicenter study aimed to evaluate the accuracy of endoscopic biopsy diagnosis and clinical staging procedures and assess a treatment strategy based on Helicobacter pylori status and tumor stage and grade. METHODS: Of 266 patients with primary gastric B-cell lymphoma, 236 with stages EI (n = 151) or EII (n = 85) were included in an intention-to-treat analysis. Patients with H. pylori-positive stage EI low-grade lymphoma underwent eradication therapy. Nonresponders and patients with stage EII low-grade lymphoma underwent gastric surgery. Depending on the residual tumor status and predefined risk factors, patients received either radiotherapy or no further treatment. Patients with high-grade lymphoma underwent surgery and chemotherapy at stages EI/EII, complemented by radiation in case of incomplete resection. RESULTS: Endoscopic-bioptic typing and grading and clinical staging were accurate to 73% and 70%, respectively, based on the histopathology of resected specimens. The overall 2-year survival rates for low-grade lymphoma did not differ in the risk-adjusted treatment groups, ranging from 89% to 96%. In high-grade lymphoma, patients with complete resection or microscopic tumor residuals had significantly better survival rates (88% for EI and 83% for EII) than those with macroscopic tumor residues (53%; P < 0.001). CONCLUSIONS: There is a considerable need for improvement in clinical diagnostic and staging procedures, especially with a view toward nonsurgical treatment. With the exception of eradication therapy in H. pylori-positive low-grade lymphoma of stage EI and the subgroup of locally advanced high-grade lymphoma, resection remains the treatment of choice. However, because there is an increasing trend toward stomach-conserving therapy, a randomized trial comparing cure of disease and quality of life with surgical and conservative treatment is needed.

Adult↗
PubMed2002

High frequency of MALT lymphoma in a series of 14 cases of primary breast lymphoma.

This article reports the clinicopathologic and immunohistochemical findings of 14 cases fulfilling the criteria of Wiseman and Liao for primary lymphoma of the breast (PBL), with emphasis on the frequency of mucosa-associated lymphoid tissue (MALT) lymphomas. The tumors were reclassified according to the revised European-American classification of lymphoid neoplasms. Immunohistochemistry was used to assist in the classification and subtyping of PBL, to demonstrate lymphoepithelial lesions (LEL), and to assess estrogen/progesterone receptor expression. Nine tumors were classified as MALT lymphomas (seven low grade and two high grade), four as diffuse large cell lymphomas and one as follicle center lymphoma. Extensive lymphoid cell infiltration of mammary ducts and acini was also found in non-MALT lymphoma cases. None of the 14 cases expressed hormonal receptors. Primary lymphoma of the breast is a rare and morphologically heterogeneous entity. There is similarity on the clinicopathologic overall profile of the current series of patients and those previously reported, but we recorded a higher incidence of MALT lymphoma (64.3%). Immunohistochemistry is mandatory to identify "true" LEL because epithelial permeation by lymphoid cells can also be found in non MALT-type lymphomas.

Adult↗
PubMedDate not supplied

CD30 differential staining is useful in classifying lymphomas intermediate between Hodgkin's disease and anaplastic large cell (Ki1) lymphoma.

AIMS AND BACKGROUND: The authors analyzed the BerH2 reactivity patterns of the tumor cells in 23 Hodgkin's lymphomas (HD), in 13 CD30+ anaplastic large cell (Ki1) lymphomas (ALCL), in two HD with transition to secondary CD30+ ALCL, and in six additional lymphomas intermediate between HD and ALCL. METHODS: Paraffin blocks of formalin-fixed biopsies were immunostained. Immunostaining was modified by pronase digestion and by microwave assistance. RESULTS: Hodgkin-Reed-Sternberg (HRS) cells of all 23 Hodgkin's lymphomas were reactive for BerH2, but the reactivity patterns differed: after pronase digestion, HRS cells of 17/23 Hodgkin's lymphomas showed exclusively or at least predominantly cytoplasmic BerH2 reactivity, whereas only four Hodgkin's lymphomas presented with prominent membrane-bound positivity. Microwave processing in 16/23 Hodgkin's lymphomas induced membrane-bound BerH2 positivity in the HRS cells; a minority of five cases retained the distinct cytoplasmic pattern. In contrast, 10/13 ALCLs were characterized by membranous reactions, independent of whether pronase or microwave pretreatment had been applied. The CD30+ ALCLs secondary to HD also showed a tendency towards membranous positivity more than did the antecedent Hodgkin's lymphomas. In the HD/ALCL borderline group, 3/6 cases revealed cytoplasmic BerH2 patterns after pronase digestion and thus were more closely related to HD, whereas 2/6 cases reacted with membranous positivity as did the genuine ALCLs of our series. CONCLUSIONS: We conclude from these findings that the above modifications in CD30 immunostaining can be helpful in the characterization of lymphomas that constitute a continuous histomorphological as well as phenotypical spectrum between HD and ALCL.

Adult↗
PubMed1985

Morphological subclassification of follicular lymphoma: variability of diagnoses among hematopathologists, a collaborative study between the Repository Center and Pathology Panel for Lymphoma Clinical Studies.

A collaborative study between the Repository Center for Lymphoma Clinical Studies and the members of the lymphoma pathology subcommittee of the major cooperative oncology groups was undertaken in an effort to ascertain the reproducibility and the interobserver agreement for the cytologic diagnosis of follicular lymphomas. A group of 105 patients with follicular lymphomas were subclassified by seven hematopathologists according to two methods. In the first method, cases were subclassified according to the Rappaport, Lukes, and Collins, and Working Formulation systems. In these systems, follicular lymphomas are subclassified by estimation of the different cell populations without the actual counting of cells. With this method, great variability in diagnosis was noted. For example: (1) The consensus diagnosis was that of poorly differentiated lymphocytic lymphoma (PDL) in 39 cases, but among the individual pathologists the number of cases thus diagnosed ranged from 24 to 65; (2) In 40 cases, the consensus diagnosis was follicular lymphoma, mixed-cell type; however, all seven pathologists independently agreed on this subtype in only one case; (3) A major disagreement was noted in 39 cases (37%), in which both diagnostic extremes (small cleaved and large noncleaved) were expressed. In the second method, only precise counts of different cells were made, according to a modification of the method recommended by Berard. With this counting method, diagnoses were independently derived based on the counts provided by the seven pathologists for large cleaved, small noncleaved, and large noncleaved cells. The variability in the results was wide also with this second method. For example, the average number of large cells found by each pathologist was ascertained, and the ranges were determined. The average range was 28 cells, which was considered high. The same determinations were performed only for large noncleaved cells, and the range was found to be 15 cells, which was also considered high. When the diagnoses derived from counts of only large noncleaved cells were compared with the traditional, more subjective diagnoses, fairly close agreement was obtained. In summary, the great variability in diagnoses of follicular lymphomas among pathologists may be attributed to the difficulties inherent in accurate determination of cell size and of the precise percentages of different cells. Until solutions to these problems are developed, one can subclassify follicular lymphomas according to the Berard method or the estimation method.

Cell Count↗
PubMed1988

The Non-Hodgkin Lymphoma Pathologic Classification Project. Long-term follow-up of 1153 patients with non-Hodgkin lymphomas.

STUDY OBJECTIVE: To document the long-term prognosis of patients with non-Hodgkin lymphoma treated between 1971 and 1975 and to determine how the prognosis varies by histologic subtype and stage. SETTING: Three cancer referral centers in the United States and one center in Italy. PATIENTS: A consecutive sample of 1153 previously untreated patients with non-Hodgkin lymphoma. At the time of analysis, 71% of the patients had died and the median follow-up for patients still alive was 11.2 years. MEASUREMENTS AND MAIN RESULTS: The 10-year survival proportions were 45% (CI, 40% to 50%); 26% (CI, 22% to 30%); and 23% (CI, 18% to 30%) for patients with low-, intermediate-, and high-grade lymphomas, respectively. Patients with intermediate- and high-grade lymphomas were curable, but this was not apparent for patients with advanced stage low-grade lymphomas. For the low-grade follicular small cleaved and follicular mixed lymphomas, the Ann Arbor staging system distinguished the prognosis of patients with stage I disease from those with more extensive involvement. For the diffuse large cell and immunoblastic lymphomas, the Ann Arbor staging system distinguished long-term prognosis for patients with stage I disease from patients with stage II disease and those with more disseminated involvement. CONCLUSIONS: The probability of long-term survival for unselected patients with non-Hodgkin lymphoma can be substantial. Long-term prognosis depends on the histologic subtype of the tumor and the extent of dissemination. The Working Formulation for non-Hodgkin lymphomas is a simple and useful nomenclature for selecting treatment and reporting results. The Ann Arbor staging system is a useful but imperfect prognostic indicator.

Bone Marrow↗
PubMed2004

Lymphoma presenting as a parotid tumour: a population-based study of diagnosis, treatment and outcome on behalf of the Scotland and Newcastle Lymphoma Group.

AIMS: Lymphoma presenting as a parotid tumour is rare. Previous published studies have been small and have not characterised fully the nature of lymphoma presenting this way. We studied the clinical features, diagnosis, prognosis and treatment in a patient group identified from the Scotland and Newcastle Lymphoma Registry, which is a prospectively collected population-based register of consecutive cases of lymphoma since 1979. MATERIALS AND METHODS: The study includes all patients with a biopsy-proven lymphoma in the parotid gland as the first presentation of their disease. RESULTS: Of 136 cases identified, 128 had non-Hodgkin's lymphoma (representing 1.5% of the 8499 non-Hodgkin's lymphomas in the registry) and eight had Hodgkin's disease (0.3% of the 2716 cases registered). Female to male ratio was 1.3:1, and median age was 69 years (range 19-94 years). Fifty-six per cent of patients had stage I, 16% had stage II, 11 % had stage III and 17% had stage IV disease. Diagnostic method was recorded in 81 cases; 47 of these were by parotidectomy. Overall median survival was 90 months, with a 5-year survival of 54%, but there was substantial variation according to age, grade, stage and International Prognostic Index (IPI). Diagnosis was often made by unnecessary major facial surgery, which could be avoided in many cases. CONCLUSION: Treatment should be directed by standard practice for lymphoma according to stage and histological classification.

Adult↗
PubMed2006

Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma.

Follicular lymphoma is commonly transformed to a more aggressive diffuse large B-cell lymphoma (DLBCL). In order to provide molecular characterization of this histological and clinical transformation, comparative genomic hybridization was applied to 23 follicular lymphoma and 35 transformed DLBCL tumors from a total of 30 patients. The results were also compared with our published findings in de novo DLBCL. Copy number changes were detected in 70% of follicular lymphoma and in 97% of transformed DLBCL. In follicular lymphoma, the most common alterations were +18q21 (33%), +Xq25-26 (28%), +1q31-32 (23%), and -17p (23%), whereas transformed DLBCL most frequently exhibited +Xq25-26 (36%), +12q15 (29%), +7pter-q22 (25%), +8q21 (21%), and -6q16-21(25%). Transformed DLBCL showed significantly more alterations as compared to follicular lymphoma (P=0.0001), and the alterations -6q16-21 and +7pter-q22 were only found in transformed DLBCL but not in follicular lymphoma (P=0.02). Alterations involving +13q22 were significantly less frequent, whereas -4q13-21 was more common in transformed as compared to de novo DLBCL (P=0.01 and P=0.02, respectively). Clinical progression from follicular lymphoma to transformed DLBCL is on the genetic level associated with acquisition of increasing number of genomic copy number changes, with non-random involvement of specific target regions. The findings support diverse genetic background between transformed and de novo DLBCL.

Adult↗
PubMed1999

Bcl-6 protein expression by follicle center lymphomas. A marker for differentiating follicle center lymphomas from other low-grade lymphoproliferative disorders.

Low-grade lymphoproliferative disorders are a heterogeneous group of lymphoid neoplasms with wide variation in histologic features, immunologic phenotype, and molecular abnormalities. Subclassification of these disorders with small lymphocytic proliferation may be difficult on the basis of morphologic findings alone. The bcl-6 gene, originally cloned from a tumor with 3q27 translocation, is commonly expressed in large cell lymphomas. In humans, bcl-6 encodes for a Krüppel-type zinc finger protein and is believed to be important in germinal center formation. Bcl-6 protein is expressed mainly by follicle center cells and a few interfollicular T lymphocytes. We analyzed Bcl-6 expression with immunologic methods in common low-grade lymphoproliferative disorders as an aid to differentiation of tumors with follicle center origin. We analyzed Bcl-6 staining of formalin-fixed paraffin-embedded tissue from 72 indolent lymphomas including 31 grade I and II follicle center lymphomas (FCL). 13 small lymphocytic lymphomas (SLL), 12 mantle cell lymphomas (MCL), and 16 marginal zone lymphomas (MZL) including lymphomas of mucosa-associated lymphoid tissue and spleen. All of 31 FCL were positive for Bcl-6 expression. One of 13 SLL and 1 of 12 MCL were positive, whereas none of 16 MZL were positive. Bcl-6 was also detected in 5 of 5 FCL and 1 of 3 MZL but in no SLL or MCL by Western blot analysis in 14 cases with lymphoid disorders. Our study demonstrates that Bcl-6 expression is common in low-grade FCL but is rare in other indolent B-cell lymphoid disorders, and may be a useful adjunct in classification of indolent lymphomas.

Adult↗
PubMed2006

t(14;18)(q32;q21) involving IGH and MALT1 is uncommon in cutaneous MALT lymphomas and primary cutaneous diffuse large B-cell lymphomas.

BACKGROUND: t(14;18)(q32;q21) involving IGH and MALT1 has been demonstrated in cutaneous MALT lymphomas and in one case of primary cutaneous diffuse large B-cell lymphoma (DLBCL). However, the incidence of IGH/MALT1 translocations in these forms of cutaneous lymphoma remains unclear. METHODS: We performed paraffin section interphase fluorescence in situ hybridization (FISH) analysis using MALT1 and IGH break-apart probes on 16 cutaneous MALT lymphomas and 16 primary cutaneous DLBCL in order to assess the frequency of IGH/MALT1 translocations and to screen for other potential translocations involving the IGH or MALT1 loci. RESULTS: Translocations involving MALT1 were not detected in any of 16 cutaneous MALT lymphomas or 16 primary cutaneous DLBCL. Of the 12 MALT lymphomas that could be analyzed for an IGH translocation, all were negative. In contrast, four of the 13 cases (31%) of primary cutaneous DLBCL that could be analyzed for translocations involving IGH were positive. Subsequent FISH analysis demonstrated one of these to be an IGH/BCL2 translocation and one to be a CMYC/IGH translocation, while the translocation partners in the remaining two cases are currently unidentified. CONCLUSIONS: This study demonstrates that translocations involving MALT1, including IGH/MALT1, are uncommon in cutaneous MALT lymphomas and primary cutaneous DLBCL. Other translocations involving IGH also are not involved in the pathogenesis of at least most cutaneous MALT lymphomas. In contrast, primary cutaneous DLBCL may contain one of several IGH translocations in a minority of cases.

Adult↗