Mantle cell lymphoma: prognostic capacity of the Follicular Lymphoma International Prognostic Index.

The International Prognostic Index (IPI) is the most commonly used prognostic model for mantle cell lymphoma (MCL). However, the prognostic value of the IPI is limited. The recently published Follicular Lymphoma International Prognostic Index (FLIPI) is built on variables, which are pertinent to MCL. This study was conducted to evaluate the prognostic value of FLIPI in a population-based series of 93 patients with MCL diagnosed in a 7-year period. End points of the study were response to therapy, overall survival, and disease-free survival (DFS) according to the IPI and FLIPI. Applied to the whole series, the FLIPI identified three risk groups with markedly different outcome with 5-year overall survival rates of 65%, 42%, and 8% respectively. Notably, the high-risk group comprised 53% of patients. In contrast, the IPI only allocated 16% of cases to the high-risk group and had a lower overall predictive capacity. When both the FLIPI and IPI were included in a multivariate analysis, only the FLIPI was related to survival. Multivariate analysis of DFS also identified the FLIPI, and not the IPI, as independently significant. Thus, in the present study, the FLIPI was superior as a prognostic model compared with the IPI and can therefore be recommended as a clinical prognostic index for MCL.

Frequent alteration of MDM2 and p53 in the molecular progression of recurring non-Hodgkin's lymphoma.

AIMS: Recurrence of non-Hodgkin's lymphoma with or without transformation is often associated with increased clinical drug resistance and poor prognosis indicating molecular progression. The study addresses the currently poorly understood molecular mechanisms underlying relapsing non-Hodgkin's lymphoma. METHODS AND RESULTS: We have analysed sequential biopsies from 42 non-Hodgkin's lymphoma patients immunohistochemically for p53 alterations (based on p53 and p21Waf1 expression), as well as for expression of MDM2, p27Kip1 and cyclin D3. Relapse of follicle centre lymphoma was associated with p53 alterations as 5/6 (83%) follicle centre lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. Of these cases, three showed transformation to diffuse large B-cell lymphoma. p53 alteration was also associated with relapse of de novo diffuse large B-cell lymphoma and T-cell non-Hodgkin's lymphoma, as 2/5 (40%) diffuse large B-cell lymphomas and 3/9 (33%) T-cell non-Hodgkin's lymphomas with normal p53 at diagnosis showed p53 alterations at relapse. No indolent non-Hodgkin's lymphoma case showed MDM2 over-expression at diagnosis, whereas 4/5 (80%) transformed diffuse large B-cell lymphomas developed MDM2 over-expression. CONCLUSION: Our data are consistent with the notion that p53 alterations are important for the histological transformation of follicle centre lymphoma. However, the data also suggest that relapsing follicle centre lymphomas without overt transformation often have p53 alterations and increased risk of transformation, and that relapse of de novo diffuse large B-cell lymphomas and T-cell non-Hodgkin's lymphomas is associated with p53 alterations. Furthermore, our results are consistent with an association of MDM2 over-expression with histological transformation of both follicle centre lymphoma and marginal zone B-cell lymphoma.

Cyclin D3 expression in non-Hodgkin lymphoma. Correlation with other cell cycle regulators and clinical features.

Cyclin D3 is the most widely expressed D-type cyclin and can be rate limiting for G1/S transition. To study the expression of cyclin D3 in non-Hodgkin lymphoma, samples from 198 previously untreated patients with lymphoma from a prospectively collected, population-based lymphoma registry were analyzed immunohistochemically for cyclin D3 expression. In 43 lymphomas (21.7%), cyclin D3 was overexpressed. T-cell lymphomas more frequently overexpressed cyclin D3 than B-cell lymphomas. Furthermore, cyclin D3-overexpressing indolent lymphomas were associated with higher proliferation rate, higher p21Waf1 expression, lower p27Kip1 expression, and altered p53. Cyclin D3 overexpression identified a subgroup of patients with indolent B-cell lymphoma with adverse clinical features: patients were older, more frequently had "B" symptoms and extranodal involvement, and were more frequently in the high-intermediate or high-risk International Prognostic Index groups. At univariate analysis of indolent lymphomas, cyclin D3 overexpression was associated significantly with poor overall survival and poor relapse-free survival. The statistical significance was retained on multivariate analysis of overall survival and relapse-free survival. Our results suggest that cyclin D3 is expressed differentially among lymphoma subtypes and that overexpression might identify a subpopulation of patients with indolent lymphoma with adverse clinical features and poor outcome.

[Quality development at a medical department]. / Kvalitetsudvikling på medicinsk afdeling.

Organization on medical wards have an impact on patient continuity, both regarding contact with physicians and nurses. Highest continuity was found in teams with approximately 20 beds. Members ought to spend most of their time in the team. This was found to be especially important for the internal medical specialists. The amount of blood samples taken was lowest in the team with the highest patient-specialist continuity. Teams with or without continuity had the same high level of patient satisfaction.

Frequent disruption of the RB1 pathway in diffuse large B cell lymphoma: prognostic significance of E2F-1 and p16INK4A.

In the present study, we analysed 34 de novo diffuse large B cell lymphoma (DLCL) from a population-based lymphoma registry for alterations of the RB1 pathway at the genetic (RB1 and CDK4) and protein (pRb, cyclin D1, cyclin D3, CDK4, and E2F-1) level. The results were correlated with the data from our previous studies of CDKN2A deletion and hypermethylation, other p53 pathway components, p27Kip1 expression, and proliferation, as well as with clinical outcome, including prognosis. We found aberrant pRb expression in four (12%) of 34 DLCLs. One of these had a point mutation in intron 3 10 bp downstream of exon 3 generating a novel splice signal. Seven tumours (21%) showed cyclin D3 overexpression, including all three thyroid lymphomas (P = 0.006). Cyclin D3 overexpression and p16INK4A/pRb aberrations were mutually exclusive, supporting an oncogenic role for cyclin D3 in DLCL. p16INK4A inactivation, cyclin D3 overexpression, or aberrant pRb expression was identified in 18 of 34 DLCLs (53%). Combining these results with our previous p53 pathway studies showed that 82% of the de novo DLCLs had alterations of these pathways, and that both pathways were altered in 13 cases (38%). Low E2F-1 expression was associated with treatment failure (P = 0.020), and multivariate analysis of overall survival identified both low E2F-1 expression (relative risk = 6.9; P = 0.0037) and p16INK4A inactivation (relative risk = 3.3; P = 0.0247) as independent prognostic markers. These data support a role of E2F-1 as tumour suppressor gene in lymphoma and strongly suggest that the RB1 and p53 pathways are important in the development of de novo DLCL. Furthermore, low E2F-1 expression and p16INK4A inactivation may serve as prognostic markers for patients with this type of lymphoma.

Non-Hodgkin's lymphoma subtypes over time in an unselected population of 646 patients: a study of clinico-pathological data and incidence based on a review using the REAL-classification.

Biopsies from 646 consecutive unselected cases of non-Hodgkin's lymphoma from a Danish population-based registry were reclassified according to the REAL classification 1) to study the distribution of subtypes over time, and 2) to correlate a number of clinical parameters with the various subtypes. Two cohorts from 1986 and 1992, of 292 and 354 cases, respectively, were studied. From 1986 to 1992 diffuse large B-cell lymphoma showed a change in incidence of + 43.1%, as opposed + 2.5% for all other subtypes combined (p = 0.05), suggesting that the increasing general incidence of non-Hodgkin's lymphoma is due primarily to an increasing incidence of diffuse large B-cell lymphoma. A higher rate of cell proliferation was associated with an increasing chance of having extranodal disease. For the various subgroups there was good agreement between survival and the International prognostic index.

Oncoprotein MDM2 overexpression is associated with poor prognosis in distinct non-Hodgkin's lymphoma entities.

MDM2 is an oncoprotein involved in the regulation of p53. MDM2 exerts its tumorigenic potential through p53-dependent and -independent mechanisms. It is frequently overexpressed in various malignancies. Little is known about the prognostic value of MDM2 expression in non-Hodgkin's lymphomas (NHL). We analyzed MDM2 expression immunohistochemically in 188 NHL cases from a prospective population-based NHL registry. The aim was to identify MDM2 expression profiles in various histological NHL subtypes and analyze whether MDM2 expression correlated with clinical variables and p53 status. MDM2 overexpression was present in 42 (22%) of 188 cases. The frequency was highest in aggressive/very aggressive NHL (P < .0001). Furthermore, within follicle center lymphomas, MDM2 overexpression was associated with higher-grade disease (P = .008). MDM2 overexpression was not related to a phenotype indicating altered p53. In univariate analysis MDM2 overexpression associated with short survival in follicle center lymphomas (P = .0256), extranodal marginal zone lymphomas (P < .0001), and mantle cell lymphomas (P = .0047). The relation to poor prognosis was maintained in a Cox regression analysis including known prognostic factors (relative risk 5.5, P = .0022). The results of the present study suggest that MDM2 may play a role in lymphomagenesis and lymphoma progression through p53-independent mechanisms, and that MDM2 overexpression identifies a small fraction of follicle center lymphomas, extranodal marginal zone lymphomas, and mantle cell lymphomas with poor prognosis.

Disrupted p53 function as predictor of treatment failure and poor prognosis in B- and T-cell non-Hodgkin's lymphoma.

Mutation of the p53 gene has been associated with treatment failure and poor outcome in various malignancies. It has been suggested that immunohistochemical analysis of p53 and p21Waf1, a downstream target, can be used to screen for p53 gene mutations. We determined the value of immunohistochemical screening for p53 gene mutations as a prognostic marker in a population-based group of B- and T-cell non-Hodgkin's lymphomas (NHLs). On the basis of p53 gene mutation status and immunohistochemically detected p53 and p21Waf1 expression in 34 lymphomas, we established an immunophenotype (delta p53) correlating with p53 gene mutation. The immunohistochemical analysis was extended to encompass 199 lymphomas from a population-based registry and was correlated with clinical parameters. Delta p53 showed 100% concordance with p53 gene mutation and was detected in 42 cases (21%). Multivariate analysis of advanced stage lymphomas showed that delta p53 was independently associated with treatment failure (relative risk, 3.8; P = 0.001). Delta p53 predicted poor survival when analyzing all patients (P = 0.0001), as well as B-cell (P = 0.04) and T-cell NHL (P = 0.000002). In multivariate analysis, delta p53 (relative risk, 2.2; P = 0.001) maintained prognostic significance. The impact on prognosis of delta p53 was highly significant in the low-intermediate-risk group (P = 0.00002). Comparing survival of the aggressive lymphoma patients in this group showed that the 8 delta p53 patients died within 1 year, whereas the median survival of the 28 non-delta p53 patients was 36 months. These results suggest that immunohistochemically assessed p53 status may predict treatment response and outcome in B- and T-cell NHL patients.

Clinical significance of cyclin-dependent kinase inhibitor p27Kip1 expression and proliferation in non-Hodgkin's lymphoma: independent prognostic value of p27Kip1.

The cyclin-dependent kinase inhibitor p27Kip1 is a negative cell cycle regulator linking extracellular growth-regulatory signals to the cell cycle machinery in G1. We investigated the pattern and prognostic value of p27Kip1 expression in a population-based group of 203 non-Hodgkin's lymphoma (NHL) patients. The expression of p27Kip1 was identified by immunohistochemistry and correlated with Ki-67 expression and clinical features. Correlation with outcome was determined using uni- and multivariate analysis stratified by clinical grade. Except for very aggressive NHL, there was a negative correlation between p27Kip1 and Ki-67 expression. Low expression of p27Kip1, defined as nuclear p27Kip1 expression in <40% of malignant cells, was predictive of poor survival in indolent and aggressive NHL. However, even in this regard, very aggressive lymphomas behaved differently as those with low p27Kip1 expression tended to do better. Likewise, a high proliferation rate (Ki-67 >40%) was associated with poor survival in indolent and aggressive lymphomas. Multivariate analysis using the proportional hazards model showed that only p27Kip1, and not Ki-67, maintained independent prognostic significance in indolent and aggressive lymphomas (relative risk = 2. 0; P = 0.0095). The low cost and simplicity of this standard immunohistochemistry analysis makes p27Kip1 a promising and suitable prognostic marker in routine diagnostic laboratories in a standard diagnostic panel.

Chromosome aberrations in adult Hodgkin disease in a Danish population-based study.

During a 6-year period, 31 patients with Hodgkin disease (HD) were analyzed for chromosome aberrations on lymphoid tissue. We obtained metaphases in 87% (27/31). The number of cells analyzed per case ranged from 17 to 31 (median 25), and the number of abnormal mitoses was between 1 and 17 (median 6). Chromosome aberrations were found in 59% (16/27). Numerical aberrations involved all chromosomes. The most frequently gained chromosomes were numbers 2 and 9, and the most frequently lost were numbers 10, 16, 21, 22, and X. Chromosomes most frequently involved in structural aberrations were numbers 1 and 6. The most frequent subgroups were nodular sclerosis (NS) (n = 16) and mixed cellularity (MC) (n = 10). Six NS patients and 8 patients with MC showed an abnormal clone. For the NS patients with an abnormal karyotype, 4 of 6 had a gain of chromosome 2, and all had structural aberrations of chromosome 1. Of the 6 MC patients, where a partial analysis was possible, 4 had a gain of chromosome 9, 2 had structural aberrations involving chromosome 6 and 2 of chromosome 14. In 1 case a translocation normally associated with non-Hodgkin lymphoma (NHL) was found (t[11;14]), whereas other translocations characteristic of NHL, such as t(8;14), t(14;18), and t(2;5) were not observed. A review of the literature on cytogenetic investigations in HD performed on lymphoid tissue showed that the most frequently gained or lost chromosomes were 1, 2, 5, 9, and 12 for NS and 2, 5, and 9 for MC. The most frequently affected chromosomes in structural aberrations were 1 and 6 for NS, and 1, 7, and 14 for MC. Involvement of chromosome 1, 6, and 14 in structural aberrations is characteristic of lymphoid neoplasms, as are the most frequently involved bands (1p36, 6q21-q26, 14q11, and 14q32) further supporting a B- or T-cell origin of the neoplastic cell in HD. The high hyperploidy seen in HD is not a frequent observation in NHL. Although certain chromosome aberrations seem to be characteristic of HD as opposed to NHL, specific nonrandom aberrations have yet to be identified. The rather low number of abnormal mitoses found in most HD cases underlies the importance of analyzing a large number of metaphases.

Aberrations of the p53 pathway components p53, MDM2 and CDKN2A appear independent in diffuse large B cell lymphoma.

The two gene products of the CDKN2A gene, p16 and p19ARF, have recently been linked to each of two major tumour suppressor pathways in human carcinogenesis, the RB1 pathway and the p53 pathway. p16 inhibits the phosphorylation of the retinoblastoma gene product by cyclin D-dependent kinases, whereas p19ARF targets MDM2, a p53 inhibitory protein, for degradation. A deletion of CDKN2A would therefore disturb both pathways. To explore the p53 pathway genes as a functional unit in diffuse large B cell non-Hodgkin's lymphomas (DLCL), we wanted to see whether there exists mutually exclusiveness of aberrations of CDKN2A, MDM2 and p53, since this has not been analysed previously. We investigated 37 DLCL for aberrations of p15, p16, p19ARF, MDM2, and p53 at the epigenetic, genetic and/or protein levels. Homozygous deletion of CDKN2A was detected in seven (19%) of 37 tumours, and another three cases were hypermethylated at the 5' CpG island of p16. No point mutations were found in CDKN2B or CDKN2A. Immunohistochemical staining of formalin-fixed, paraffin-embedded tissue for p16 confirmed these results, as all tumours with alterations of CDKN2A were p16 immunonegative. We found p53 mutations in eight (22%) cases and MDM2 overexpression in 16 (43%) tumours. Twenty-three (62%) tumours had alterations of one or more p53 pathway components (p53, p19ARF and MDM2). Furthermore, 7/9 (78%) p16-immunonegative tumours showed co-aberration of p53 and/or MDM2. The lack of correlation between these aberrations suggests that DLCL acquire additional growth advantage by inactivating both of these critical regulatory pathways.

CB/CC diffuse lymphoma: a distinct subtype of non-Hodgkin's lymphoma? A study of 1593 patients from a Danish population-based registry. Danish LYFO Study Group.

Between 1983 and 1993, 3165 cases of non-Hodgkin's lymphoma (NHL) were reported to the West Danish Lymphoma Registry (LYFO). Out of these, 148 (4.7%) were of the CB/CC diffuse subtype according to the Kiel classification. However, in the new European-American NHL consensus classification (REAL, 1994), CB/CC diffuse lymphoma was categorized as a provisional subtype only. In the LYFO material, death-probability curves show a significantly shorter survival in CB/CC diffuse than in CB/CC follicular. In order to detect further possible differences between CB/CC diffuse and other NHL subtypes, a number of clinical parameters at presentation were analyzed in a subset of five types of lymphoma. This subset included 148 cases of CB/CC diffuse, 435 cases of CB/CC follicular, 667 cases of CB diffuse, 202 cases of CC diffuse, and 131 cases of peripheral T-cell lymphoma. Using logistic regression analysis, significant differences could be demonstrated between CB/CC diffuse and the four other subtypes as regards sex ratio, age distribution, and sites of both nodal and extranodal involvement. These findings indicate that CB/CC diffuse has a distinct clinical phenotype and imply the existence of real biological differences between CB/CC diffuse and other subtypes of lymphoma.

In B-cell chronic lymphocytic leukaemia chromosome 17 abnormalities and not trisomy 12 are the single most important cytogenetic abnormalities for the prognosis: a cytogenetic and immunophenotypic study of 480 unselected newly diagnosed patients.

Of 560 consecutive, newly diagnosed untreated patients with B CLL submitted for chromosome study, G-banded karyotypes could be obtained in 480 cases (86%). Of these, 345 (72%) had normal karyotypes and 135 (28%) had clonal chromosome abnormalities: trisomy 12 (+12) was found in 40 cases, 20 as +12 alone (+12single), 20 as +12 with additional abnormalities (+12complex). Other frequent findings included abnormalities of 14q, chromosome 17, 13q and 6q. The immunophenotype was typical for CLL in 358 patients (CD5+, Slg(weak), mainly FMC7-) and atypical for CLL in 122 patients (25%) (CD5-, or Slg(strong) or FMC7+). Chromosome abnormalities were found significantly more often in patients with atypical (48%) than in patients with typical CLL phenotype (22%) (P < 0.00005). Also +12complex, 14q+, del6q, and abnormalities of chromosome 17 were significantly more frequent in patients with atypical CLL phenotype, whereas +12single was found equally often in patients with typical and atypical CLL phenotype. The cytomorphology of most of the +12 patients was that of classical CLL irrespective of phenotype. In univariate survival analysis the following cytogenetic findings were significantly correlated to a poor prognosis: chromosome 17 abnormalities, 14q+, an abnormal karyotype, +12complex, more than one cytogenetic event, and the relative number of abnormal mitoses. In multivariate survival analysis chromosome 17 abnormalities were the only cytogenetic findings with independent prognostic value irrespective of immunophenotype. We conclude that in patients with typical CLL immunophenotype, chromosome abnormalities are somewhat less frequent at the time of diagnosis than hitherto believed. +12single is compatible with classical CLL, and has no prognostic influence whereas chromosome 17 abnormalities signify a poor prognosis. In patients with an atypical CLL immunophenotype, chromosome abnormalities including +12complex, 14q+, del 6q and chromosome 17 are found in about 50% of the patients, and in particular chromosome 17 abnormalities suggest a poor prognosis.

Clonal chromosome aberrations in myeloid leukemia after styrene exposure.

OBJECTIVES: The purpose of the study was to determine the risk of myeloid leukemia subclassified according to clonal chromosome aberrations in styrene-exposed workers. METHODS: A nested case-referent study was carried out on 19 myeloid leukemia patients, of which 12 showed clonal chromosome aberrations, and 57 referents ascertained within the Danish reinforced plastics industry and similar industries with no styrene exposure. RESULTS: A 2.5-fold increased risk for myeloid leukemia with clonal chromosome aberrations (95% confidence interval 0.2-25.0) was found among workers of companies with styrene exposure. CONCLUSIONS: The results suggest that styrene may cause leukemia through a clastogenic effect. But similar findings could also have been found if the exposure was associated with a specific subtype of leukemia prone to develop the chromosome aberrations in question. Due to the few observations and the lack of detailed exposure data, additional studies are needed to corroborate or refute the present suggestive findings.

Primary non-Hodgkin's lymphoma of the thyroid gland: a population based study.

During a 9-year-period, 50 cases of primary non-Hodgkin's lymphoma (NHL) of the thyroid gland were reported to a population-based lymphoma registry covering western Denmark giving an incidence of 2.06 x 10(-6) cases per year. The male:female ratio was 1:4, and the mean age was 72.8 years for women and 62.8 years for men. On histomorphological reclassification 83% of the cases showed a high grade and 17% a low grade morphology, 98% had a B-phenotype and 2% a T-phenotype. In at least 33 of the cases, primary NHL of the thyroid gland was preceded by Hashimoto's thyroiditis and at least 25 of the patients had a high grade NHL which was transformed from Hashimoto's thyroiditis through a low grade B-cell lymphoma of MALT type. The most frequent presenting symptoms were goitre (100%), hoarseness (57%), stridor/dyspnoea (55%) and dysphagia (45%); thirty-six percent of the patients were hypothyroid at the time of diagnosis. Seventy-six percent of the patients had localized disease (stages 1-2) and 24% had disseminated lymphoma (stages 3-4). Five year survival was 34.5% and 5 year cause-specific survival 46.2%. The following factors were associated with a poor prognosis: stage 3-4 disease, elevated S-urate, presence of hoarseness and age > 66 years. Morphological subtype did not correlate significantly with survival.

Chronic pancreatitis.

Chronic pancreatitis is a serious disease with many yet unsolved problems, e.g. pathogenesis, cause of pain and treatment. Danish gastroenterologists have for many years participated actively in the investigation of the disease and have produced many internationally recognized results, especially regarding secretion physiology and pathophysiology, epidemiology, cause of pain and characterization of the secondary diabetes mellitus. In the past 25 years more than 60 Danish papers about chronic pancreatitis have been published in international, reviewed journals. Furthermore six theses on subjects related to chronic pancreatitis have been produced. In this article the Danish contribution to the literature on chronic pancreatitis during the past 25 years is reviewed.

Characterization of add(1)(p36) in non-Hodgkin lymphomas by fluorescence in situ hybridization.

Chromosome rearrangements involving chromosome I, band p36, are among the most common aberrations in non-Hodgkin lymphomas (NHL). We have studied nine cases of NHL with add(1)(p36) using fluorescence in situ hybridization (FISH) from a series of 205 cases. Five were follicular low-grade NHL and four were follicular or diffuse high-grade NHL. Three of the five cases with follicular low-grade NHL did not contain the 14;18 translocation. The extra material on the add(1)(p36) in these three cases was derived from chromosome segment 2q31-qter; in one it was observed as a sole clonal rearrangement. In the two remaining cases, with t(14;18), the add(1)(p36) consisted of material from chromosome arms 3q and 17q, respectively. In the four cases of high-grade NHL, the material added on to Ip36 was derived from chromosomes 6, 9, 17, and 19, respectively. Using a Ip36-specific probe, DIS94, we showed a deletion on the add(1) in one of the cases with low-grade NHL, whereas no loss was observed in one of the cases with high-grade NHL. Our study indicates that cytogenetically similar add(1)(p36) are found in both high- and low-grade NHL, and the breakpoint on Ip36 as well as the origin of translocated material may vary.

Non-Hodgkin's lymphoma of the gastrointestinal tract: a population-based analysis of incidence, geographic distribution, clinicopathologic presentation features, and prognosis. Danish Lymphoma Study Group.

PURPOSE: To evaluate incidence, time trends, geographic distribution, clinicopathologic presentation features, and prognostic factors for survival and relapse in gastrointestinal (GI) non-Hodgkin's lymphomas (NHLs). PATIENTS AND METHODS: Over a 9-year period (1983 to 1991), 2,446 new NHL cases were recorded in a Danish population-based NHL registry (Danish Lymphoma Study Group [LYFO]). Of these, 306 (12.5%) were GI NHL (175 gastric, 109 intestinal, and 22 both sites). LYFO registry data were used for incidence rate (IR) assessment, and time-trend and geographic distribution analysis. Relative risk (RR) values for survival and relapse were identified by multivariate analysis. RESULTS: The mean annual, age-standardized IRs for gastric and intestinal NHL were 0.71/10(5) and 0.48/10(5) per year, respectively. Age-specific IRs for both localizations showed an exponential increase as a function of age. Time-trend analysis for the period 1983 to 1991 showed stable IRs for both localizations. Intestinal NHL was more frequent in males (male-to-female ratio, 2.0 v 1.3), and had a higher occurrence of disseminated disease, constitutional symptoms, high-grade histology, and T-cell phenotype (10% v 2%). Gastric NHL had more low-grade cases (38% v 19%), and almost all were of the mucosa-associated lymphoid tissue (MALT) type. The cause-specific 5-year survival rate was 63% for gastric NHL and 49% for intestinal NHL. The Musshoff staging system was an excellent discriminator between truly localized (stage I and II1) and disseminated cases (stage II2 to IV), particularly for gastric NHL, for which no survival difference was found between surgically and conservatively stage localized cases. CONCLUSION: (1) No increase in the incidence of GI NHL was found over a 9-year observation period; (2) nonrandom spatial distribution of new GI NHL cases was observed; (3) factors that significantly increased the risk of death in gastric cases were presence of B symptoms (RR = 3.3), clinical stage is more than II1 (RR = 3.0), age more than 72 years (RR = 2.4), and elevated serum lactate dehydrogenase (s-LDH) level (RR = 2.0); and factors that increased the risk of death in intestinal cases were presence of B symptoms (RR = 3.2), age more than 58 years (RR = 2.8), and clinical stage more than I (RR = 2.1); (4) factors that significantly increased the risk of relapse in gastric cases were male sex and no radiotherapy in primary treatment; and in intestinal cases were T-cell phenotype and no surgery in primary treatment; (5) surgical staging, as opposed to thorough noninvasive staging, did not improve staging accuracy and final outcome in localized gastric NHL.

[Non-Hodgkin lymphoma in the elderly]. / Non-Hodgkin's lymfom hos aeldre.

Within a seven year period, 1597 newly diagnosed cases of non-Hodgkins lymphoma (NHL) were included in a Danish population-based NHL-register. Of these, 602 (38%) were aged 70 or older (age range 70-94, median: 76.8) and represented the population defined as "elderly" patients in the present study. Their average annual incidence rate was 35.7/10(5), as compared to 6.6/10(5) for patients aged < 70 (overall annual incidence: 9.5/105). Localised cases (stage I and II) and extranodal manifestations were more frequent among elderly patients. The most common sites of extranodal involvement were stomach (21% of all extranodal cases) and bone marrow (16%). Histologically, follicular centroblastic/centrocytic cases were found to be less frequent (p < 0.01) in elderly patients as compared to their younger counterparts (< 70 years), who on the other hand had a lower occurrence of diffuse centroblastic cases (p < 0.01). Overall seven year survival for the elderly patient population was 35% (median: 1.7 years), and for patients aged < 70 it was 57%. This difference persisted after correction for apparently NHL-unrelated deaths (52% vs. 66% respectively, p < 0.0001). The following poor prognostic factors for elderly patients were identified by multivariate analysis: hepatic involvement, presence of B-symptoms, high-grade histology and elevated s-LDH. The corresponding relative risk values were respectively 2.4, 2.2, 1.9 and 1.6.

Chromosome painting as a supplement to cytogenetic banding analysis in non-Hodgkin's lymphoma.

Chromosomal in situ suppression (CISS) hybridization with biotin labeled chromosome-specific libraries was performed on short-term cultures from five cases of non-Hodgkin's lymphoma (NHL). The painting analysis proceeded in three stages. First-stage CISS hybridization was done with libraries specific for chromosomes that seemed to be lost or rearranged as judged by banding analysis. Second-stage CISS included hybridization with probes specific for chromosomes that, because of banding pattern similarities, were considered to be likely candidates to have contributed unidentified chromatin blocks in the abnormal karyotype. The third and final stage was a confirmation hybridization with a library specific for the chromosome that, at the stage two analysis, was found to have donated the previously unknown chromosomal segment. The aberrant chromosomes were often more complex than the banding analysis had led us to believe. Among the rearrangements whose nature was determined by CISS hybridization were two add(1)(p36) which, in both cases, were shown to be a der(1)t(1;2)(p36;q31). This study illustrates the potential use of chromosome painting in resolving karyotypic uncertainties in NHL, and it shows that new cytogenetic subgroups may emerge when classical banding analysis is supplemented with fluorescence in situ hybridization techniques.