Nodal non-Hodgkin's Lymphoma Research Articles

Late Relapse of Localized High-Grade Non-Hodgkin's Lymphoma: Clinical and Biological Features

Diffuse large cell lymphoma is the most common non-Hodgkin Lymphoma (NHL) that ranks among the most curable diffuse intermediate grade lymphomas. Most investigators have recognized that practically all patients with this cell type who are able to attain and maintain a complete response for 24 consecutive months are cured because late relapses seldom occur after this period of follow-up. However, relapses do occur late after the remission and the characteristics of patients who experience these relapses rarely have been studied especially for localized disease. From 1984 to 1996, three hundred and five patients aged more than 18 years were enrolled in a prospective multicenter study for primary treatment of localized stage I/II nodal and extra nodal high-grade NHL. The initial therapy consisted in three cycles of high dose CHOP regimen followed by involved field radiotherapy (40Gy). Of the 283 (93%) patients who obtained complete remission (CR), 36 (12.7%) patients relapsed more than 2 years after CR and 28 (9.8%) of them experienced relapse more than three years after CR. Clinical characteristics of patients at diagnosis are summarized in table 1. For the 28 patients who relapsed more than 3 years after diagnosis (group A), the median age was 55 years. There were 17 men and 11 women with predominant histology of diffuse large B cell lymphoma (n=15) and mixed small and large B-cell (n=6). Stage I disease was predominant (n=16) with normal LDH level (n=14). Extranodal disease was present in 11 patients. Most of the patients had no or one IPI risk factor at diagnosis (n=18). Relapses occurred after median CR duration of 84 (36–156) months. Seven patients (7/28; 25%) relapsed as a disseminated lymphoma and 17 of 21 patients who relapsed as a localized disease, relapsed at sites other than those of diagnosis. Only 4 patients relapsed at the same initial site of lymphoma. Nodal relapses remained the most frequent type of relapse (n=18; 64%). However, it is important to note that 10 patients experienced extranodal relapses especially in the central nervous system, the Waldeyer's ring and the gastrointestinal tract. Three patients had multiple extranodal localisations. All relapsed patients received chemotherapy alone (n=20) or followed by autologous stem cell transplantation (n=8). CR was obtained in 13 patients (13/23; 56%), and partial response in 1 patients. Chemotherapy failed in 5 patients and 4 patients deceased from toxicities. At the last follow-up, only 8 (8/24; 33%) patients are still alive and disease free (n=5) or in relapse (n=3). Sixteen patients deceased and lymphoma was the most frequent cause of death (13/24; 54%). In conclusion, late relapses in the setting of localized high grade NHL treated with short course of chemotherapy and involved field radiotherapy are frequent. Relapses occurred frequently at different sites from the initial presentation mostly nodal and extranodal localisations are frequent. The rate of cure for relapsed patients is low and death from lymphoma remains high. The role of novel therapeutic approaches with the addition of rituximab to chemotherapy with or without radiotherapy in preventing late relapses is awaited. More data will be presented at the meetingTable 1: clinical characteristics at diagnosis

Extranodal lymphoma: a comparative study

Background: The incidence of extranodal non-Hodgkin's lymphoma (NHL) is increasing worldwide. The epidemiology of NHL in the Middle East is largely unknown.Patients and methods: We evaluated all cases of NHL diagnosed at our institutions between 1998 and 2003 according to the site of presentation and their classification into primary nodal and primary extranodal NHL using strict criteria. Extranodal cases and early stage primary nodal cases were compared in terms of clinical characteristics and treatment outcomes.Results and discussion: There were 422 NHL cases diagnosed between January 1998 and December 2003, among which 97 cases (23%) were primary nodal, 132 (31%) were early nodal, and 193 (46%) were disseminated primary nodal. In general, there was a male preponderance of primary nodal cases (63% versus 44%; p=0·007). There was a higher prevalence of primary nodal cases in Arabs than in Asians: Kuwaiti Arabs, 50%; other Arabs, 46%; and Asians, 11%. There was a different distribution of histologic subtypes between primary nodal and extranodal NHL (p=0·001). The most common histologic subtype among extranodal cases was diffuse large B cell lymphoma, which accounted for 71% (69) of cases. The most common anatomic site involved was the gastrointestinal tract, which accounted for 45% of all cases. The difference in event-free survival between nodal and extranodal low-grade NHL was not statistically significant (p=0·17). Primary nodal high-grade lymphomas show an overall survival than the primary extranodal disease (p=0·003).Conclusion: We conclude that extranodal NHL is common among patients of Arabic descent. Diffuse large B cell lymphoma is the most common histologic subtype and often involves the gastrointestinal tract. Patients with aggressive primary extranodal NHL have lower overall survival than patients with early primary nodal disease.

Major Improvements in Survival in Hematologic Malignancies in the Early 2000s.

Background: Recent advances in the treatment of hematologic malignancies have led to improvements in response and survival in clinical trials for several conditions. Translation of these improvements to better survival on the population level should be monitored in as timely as possible a manner.Methods: We estimated trends in relative survival in patients with common hematologic malignancies in the United States between the years 2000 and 2004 using data from the Surveillance, Epidemiology, and End Results (SEER) program, employing the recently introduced technique of modeled period analysis to provide the most up-to-date and precise estimates of survival1. We calculated survival according to gender and age group as well as overall survival for each malignancy.Results: Major improvements in 5-year relative survivals were observed for nodal and extra-nodal non-Hodgkin lymphoma (NHL) (+8.3 and +7.1 percentage points, respectively, p<0.0001), acute myeloblastic leukemia (AML) (+4.8 percentage points, p=0.005), and chronic myelocytic leukemia (CML) (+15.9 percentage points, p<0.0001). Improvement in 10-year survivals were observed in nodal and extra-nodal (EN) NHL (+8.7 and +7.8 percentage points, p<0.0001), AML (+4.3 percentage points, p=0.009), CML (+16.2 percentage points, p<0.0001), and myeloma (+3.4 percentage points, p=0.01). Statistically significant improvements in 10-year survival were seen in both genders for NHL and CML, but were limited to women for MM and AML, although a trend towards improved survival was seen in men with these conditions as well. Improvements in prognosis were largely restricted to patients aged less than 65, except for NHL and CML. Patients over 65 with EN NHL actually had a greater improvement than younger patients, with increases of 6.0 and 8.5 percentage points, respectively for patients over and under 65. The single greatest improvement observed was in patients less than 65 with CML, who had a 25.2 percentage point improvement in 10-year relative survival between 2000 and 2004.Conclusions: Application of modeled period analysis to an examination of hematologic malignancies revealed profound improvements in survival in the 5 years between 2000 and 2004. Survival in CML has improved dramatically, and major improvements were also seen for survival in NHL, AML, and MM. A combination of new therapeutic options, improved supportive care, and wider application of recent advances is likely to be responsible for the improvements observed. Our results emphasize the importance of timely information about translation of therapeutic advances into clinical practice, such as can be provided by modeled period analysis. 1. Brenner H, Hakulinen T. Up-to-date and precise estimates of cancer patient survival: model-based period analysis. Am J Epidemiol. 2006; 164:689–696.10-year survival in hematologic malignanices in 2000 and 2004MalignancyNumber10-year survival (SE)-200010-yr survival (SE)-2004DifferenceP-valueHD998978.3 (1.2)81.8 (1.1)+3.50.12NHL-nodal40,12145.4 (0.9)54.1 (0.9)+8.7<0.0001NHL-EN19,44760.1 (1.4)67.9 (1.3)+7.80.00015MM17,33014.3 (0.9)17.7 (1.0)+3.40.01ALL222226.5 (2.8)33.2 (2.9)+6.70.14CLL12,88154.2 (2.0)56.6 (2.0)+2.40.45AML10,15315.0 (1.0)19.3 (1.2)+4.30.0085CML530822.4 (2.0)38.6 (2.4)+16.2<0.0001

Distribution and Pathology Characteristics of Non Hodgkin Lymphoma in Peru: A Study of 1014 Cases Using WHO Classification of Lymphoid Neoplasm.

BACKGROUND: The frequency of various subtypes of non-Hodgkin's lymphoma (NHL) differs in various regions worldwide.OBJECTIVE: To investigate the clinical and pathological features of non-Hodgkin's lymphoma (NHL) and to evaluate the applicability of the new WHO classification of lymphoid neoplasms.METHODS: According to the new WHO classification, a total of 1014 cases of non-Hodgkin's lymphoma diagnosed during the period 2002–2006 were reviewed and reappraised with their morphological, immunological and clinical characteristics in one general hospital from Lima, Peru. All cases corresponded >18 years old.RESULTS: There were 535 males and 479 females, mean age was 62.1 years (range 18 – 97 years) and the median was 64 years. B-cell neoplasms accounted for 763 cases (75.2%) and T/NK-cell neoplasms for 189 (18.6%). Sixty two cases (6.1%) were not classified. It was seen compared to that in the other Asian countries. Indolent lymphomas accounted for 17%, and aggressive ones for 83%. Among indolent lymphomas follicular grade I and II were the most common subset while MALT was second with low frequency. Among the aggressive lymphomas diffuse large cell lymphoma (DLCL) was the most common subtype, and accounted for 58.8% of all B cell lymphomas. Mantle and Burkitt lymphoma were very low incidence. Among the T cell lymphomas, peripheral T cell lymphomas, mycosis fungoides, Adult T Lymphoma/Leukemia (ATLL), T/NK nasal type Lymphoma were the most common subtypes. Nodal NHL occurred in 52% and extranodal in 48% of the cases. The more common extranodal presentation was stomach (14.1%), skin (8.1%), small intestine (2.9%) and nose (2.3%)CONCLUSIONS: The high incidence of T cell lymphomas, extranodal presentation and reduced frequency of indolent lymphoma in the current study is comparable to that reported from Asian countries.

Relapsing Polychondritis and Malignant Lymphoma

Relapsing polychondritis (RP) is associated with other rheumatic or autoimmune disease in about 30% of cases; however, an association with malignancy is rare with the exception of myelodysplastic syndrome (MDS). Observation Herein we report the first case, to our knowledge, of RP following splenic non-Hodgkin lymphoma (NHL), and we have reviewed all the previous well-documented reports that described the cases of RP associated with malignant lymphoma (ML). Our case and the review of reported cases showed that RP preceded ML in 2 cases, RP occurred after diagnosis and treatment of ML in 2 cases, and RP and ML occurred simultaneously in 1 case. The types of ML encountered were Hodgkin lymphoma, orbital mucosa associated lymphoid tissue type lymphoma, nodal NHL, and splenic NHL. From the frequent association of RP with MDS and, less frequently, with ML, we speculate that some RP cases may occur as a paraneoplastic condition of the concurrent hematological malignancies.

Rapidly increasing incidence of ocular non-Hodgkin lymphoma

A recent report suggesting that ocular adnexal non-Hodgkin lymphoma (NHL) may be related to Chlamydia psittaci infection underscores the need for reliable epidemiologic data for this malignancy. The authors examined population-based incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program. During 1992 to 2001 in the 12 SEER areas, ocular (that is eye and adnexa) NHL rates per 100,000 person-years for both genders were highest among Asians/Pacific Islanders, lower in Whites, and lower still in Blacks. Incidence increased with advancing age and showed little difference by gender, in contrast to other (extranodal and nodal) NHLs, which occurred predominantly in males. From 1975 to 2001, there was a rapid and steady increase in incidence of ocular NHL, with annual increases of 6.2% and 6.5% among White males and females, respectively, with no evidence of peaking. By contrast, other NHLs showed evidence of peaking in recent years. The distinctive patterns of ocular NHL call for further studies to identify risk factors and mechanisms, including the potential role of C. psittaci or other infections.—Hans E. Grossniklaus

Rapidly Increasing Incidence of Ocular Non-Hodgkin Lymphoma

A recent report suggesting that ocular adnexal non-Hodgkin lymphoma (NHL) may be related to Chlamydia psittaci infection underscores the need for reliable epidemiologic data for this malignancy. We examined population-based incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program. During 1992-2001 in the 12 SEER areas, ocular (i.e., eye and adnexa) NHL rates per 100,000 person-years for both sexes were highest among Asians/Pacific Islanders, lower in whites, and lower still in blacks. Incidence increased with advancing age and showed little difference by sex, in contrast to other (extranodal and nodal) NHLs, which occurred predominantly in males. From 1975-2001, there was a rapid and steady increase in incidence of ocular NHL, with annual increases of 6.2% and 6.5% among white males and females, respectively, with no evidence of peaking. By contrast, other NHLs showed evidence of peaking in recent years. The distinctive patterns of ocular NHL call for further studies to identify risk factors and mechanisms, including the potential role of C. psittaci or other infections.

Extranodal NHL- A retrospective review of clinico-pathologic features and outcome and comparison with nodal NHL. Single institution experience years: 1988–2004

17542 Background: Non-Hodgkin’s lymphoma (NHL) arising in an extra nodal (EN) site is not uncommon and its natural history and treatment is clearly characterized in the literature. Data on EN-NHL and comparison with N-NHL with relation to survival and prognostic factors is scarce in our part of the world. The primary objective of this study was to analyze the anatomic distribution, clinical features and outcome of DLBCL patients according to the primary site with applicability of International Prognostic Index (IPI). Methods: From 1988 to 2004, 557 patients were analyzed for the clinico-pathologic characteristics, treatment outcome and prognostic factors affecting overall survival. Results: Median age was 48.7 ± 15.3 years ; the M: F ratio was 2:1. The distribution according to the primary site was: lymph node, 322 cases (58%) of these 145 cases (44%) stage IV, 76 cases (23%) Stage III, 60 cases (18%) stage II and 47 cases(15%) stage I ; and EN sites, 235 (42%), including GIT (44%) followed by upper aerodigestive tract (19%), bones (08%), spine (05%), and 3% each as breast, CNS, testis,lungs. The median survival rate was 4.8 and 6.3 years in NL and ENL respectively vary according to primary site/stage of the lymphoma. In the univariate analysis age less than 60 years, early stage I-II, extra nodal involvement primarily gastric or bone, 0–1 extra nodal site, 0–1 PS, lack of B symptoms, normal LDH level has been associated with good prognosis. In the multivariate analysis age, PS, stage and level of LDH were the main variables to predict OS; no nodal or extranodal site maintained their prognostic value. Conclusion: Our data correspond with series from west increasing incidence extranodal lymphoma due to improved diagnostic techniques and superior results with chemotherapy by preserving the organ. Few patients with bowel obstruction or cord compression lymphoma required surgery for diagnosis or relief of symptoms. There is significant difference from western data in histologies DLBC-NHL is the most common histologies in our study. Overall survival patients with EN-NHL were similar to nodal NH-Lymphoma but largely depended on IPI. No significant financial relationships to disclose.

High Prevalence of SV40 Infection in Patients with Nodal Non-Hodgkin's Lymphoma But Not Acute Leukemia Independent of Contaminated Polio Vaccines in Taiwan

Recent studies have linked simian virus 40 (SV40) to non-Hodgkin's lymphoma (NHL), especially in countries in which people were exposed to contaminated polio vaccines prior to 1963. In Taiwan, nearly all children were not exposed to contaminated polio vaccine during this period; the relationship between SV40 infection and hematological malignancies is unclear and deserves to be studied. Using PCR amplification of SV40 large T antigen DNA, confirmed by Southern blot hybridization and sequence analysis, 91 frozen lymph nodes from NHL patients were examined. Thirteen (14.3 percent) showed positive for SV40. All other test samples, including diagnostic bone marrow from patients with acute leukemia, peripheral blood from 10 relatives of SV40 positive-patients and 91 age-matched normal volunteers, and 5 reactive hyperplastic lymphoid tissues, showed negative. These results may reflect that human-to-human transmission of SV40 is independent of contaminated polio vaccines; and SV40 is possibly associated with the development of NHL in Taiwan (p = 0.0001). Prospective studies are needed to determine the prevalence of SV40 infections in our and other human populations and to explore the means of transmission of the virus.

Cutaneous B-cell lymphoma: An emerging clinical entity

In recent years, cutaneous B-cell lymphoma (CBCL) has emerged as a clinicopathologic entity with a natural history distinct from nodal Non-Hodgkins lymphoma (NHL). However, given its rarity, population-based incidence and survival rates have not yet been documented, and single-institution reports have been unable consistently to identify prognostic factors and optimal treatment strategies.

MRI of neck nodes in non-Hodgkin's lymphoma of the head and neck.

The aim of this study is to describe the imaging features of neck nodes in non-Hodgkin's lymphoma (NHL). The MR scans of 61 patients undergoing staging of a primary extranodal NHL of the head and neck were reviewed retrospectively. Those MR images with nodal disease were assessed for (a) the pattern of nodal disease, (b) presence of nodal necrosis and (c) presence of extracapsular neoplastic spread (ENS) and nodal matting. The features of the nodal disease were analysed in relationship to the sites of the primary NHL (palatine tonsil (PT) n=23, nasal cavity (NC) n=24, nasopharynx (NP) n=6, other extralymphatic sites (OES) n=8), and histology (natural killer/T-cell (NK/T) n=26, diffuse large cell (DLC) n=24, other subtypes (OS) n=11). Nodal disease was present in 26 patients (43%) and occurred in NHL of the PT n=16 (70%), NP n=3 (50%), NC n=5 (21%) and OES n=2 (25%) and in DLC n=15 (63%), NK/T n=6 (23%) and OS n=5 (45%). Nodal disease was significantly more frequent in DLC than NK/T lymphomas (p=0.0053). Nodal disease spread in a contiguous fashion in 25 (96%) patients with nodes. Necrosis was present in 7 of 26 (27%) being present in DLC of the PT in 5, NK/T of the NP in one and NK/T of the NC in one. ENS and matting were present in 19 (73%) and 13 (50%) patients with nodes, respectively. ENS was found in DLC, NK/T, OS, NC, NP, PT, OES (11, 4, 4,1, 2, 14, 2, respectively) and matting was found in DLC, NK/T, OS, NC, NP, PT, OES (9, 3, 1, 0, 2, 10, 1, respectively). Nodal NHL spreads in a contiguous fashion and is most commonly associated with DLC lymphoma of the NP and PT in Waldeyer's ring. Extracapsular nodal spread is frequent and found in most histological subtypes especially those arising from Waldeyer's ring. Necrosis is more common than previously believed.

Salivary gland lymphomas

This tutorial focuses on malignant lymphomas and inflammatory conditions as potential precursors of primary malignant lymphomas in salivary glands. Salivary glands display a mucosa-associated lymphoid tissue and are often associated with intra- and periglandular lymph nodes. Inflammation of the glands may variably produce duct ectasia, lymphoepithelial lesions, atrophy, and fibrosis. Primary lymphomas of the salivary glands may develop on the basis of autoimmune sialadenitis and comprise most frequently marginal zone lymphomas, less often monocytoid lymphomas or other lymphoma entities. In a large proportion of cases, lymphoma infiltrates are attributable to extraglandular lymphomas either as a leukemic infiltrate with diffuse enlargement or as a localized manifestation of primary nodal non-Hodgkin lymphomas. Diagnosis is based on conventional histology and immunohistology.

Gastric T-cell lymphoma associated with hemophagocytic syndrome

BackgroundLymphoma-associated hemophagocytic syndrome (LAHS) occurs in mostly extra nodal non-Hodgkin's lymphoma. LAHS arising from gastrointestinal lymphoma has never been reported. Here we report a case of gastric T-cell lymphoma-associated hemophagocytic syndrome.Case presentationA 51-year-old woman presented with pain, redness of breasts, fever and hematemesis. Hematological examination revealed anemia. Gastroscopy revealed small bleeding ulcers in the stomach and the computed tomography scan showed liver tumor. She underwent total gastrectomy for gastrointestinal bleeding and the histopathology revealed gastric T-cell lymphoma. She continued to bleed from the anastomosis and died on the 8th postoperative day. Autopsy revealed it to be a LAHS.ConclusionsIf Hemophagocytic syndrome (HPS) occurs in lymphoma of the gastrointestinal tract, bleeding from the primary lesion might be uncontrollable. Early diagnosis and appropriate treatment are needed for long-term survival.

Selection of surrogate marker genes in primary central nervous system lymphomas for radio-chemotherapy by DNA array analysis of gene expression profiles

Primary central nervous system lymphomas (PCNSLs) are extra nodal B-cell non-Hodgkin's lymphomas with primary manifestation in the brain, and their incidence has been increasing among both immunocompetent and immunocompromised populations. Samples of oligodendroglioma (n=5), glioblastoma (n=7), PCNSL (n=6), and normal brain (n=3) were studied (total of 21 samples) using cDNA array technology. The hierarchical clustering algorithm was used to obtain a phylogenetic tree, and it revealed a striking feature: PCNSL was clearly separated. The genes encoding laminin receptor 2, thioredoxin peroxidase, and elongation factor-1 were selected as specific genes in PCNSL by principal component analysis (PCA). When Mann-Whitney tests were performed to identify genes responsible for the differences between responders and non-responders to the treatment schedule for PCNSL, 76 known genes were found to show significantly different expression patterns between the two groups at the P<0.01 level. The two groups were clearly separated by the re-clustering method using the selected genes related to response to chemo-radiotherapy. This is the first report describing the gene expression profiles of PCNSL. In conclusion, accumulation of data with respect to the expression profiles of PCNSL specimens, clinicopathological data, susceptibility to treatment, and outcome will provide information for identifying optimal therapeutic modalities for individual patients and novel therapeutic targets.

Primary extranodal non-Hodgkin’s lymphoma (NHL): the impact of alternative definitions tested in the Comprehensive Cancer Centre West population-based NHL registry

The definition of primary extranodal non-Hodgkin's lymphoma (NHL) is a controversial issue, especially in patients where both nodal and extranodal sites are involved. The impact of different definitions of primary extranodal NHL on incidence and prognosis is explored using data from a population-based NHL registry. Using liberal criteria, 389 (34%) cases were classified as primary extranodal NHL. Overall survival (OS) rates of nodal and extranodal NHL patients defined this way were comparable; however, extranodal NHL patients had a better disease-free survival (DFS). When strict criteria were applied, 231 cases (20%) were classified as primary extranodal NHL. OS and DFS rates of extranodal NHL patients defined this way were superior to nodal NHL patients; however, the difference in OS was reversed after correction for differences in International Prognostic Index and malignancy grade. This study illustrates the selection bias that is introduced when a strict definition of primary extranodal NHL, that excludes cases with disseminated disease, is used. Patients with primary extranodal NHL were found to have a superior DFS, irrespective of which definition of primary extranodal NHL was used.

Non-Hodgkin's lymphomas and organic solvents.

Organic solvents have been suggested as a possible risk factor for non-Hodgkin's lymphomas (NHL). We studied 109 NHL incident cases and 276 controls with other cancers (1990/1996) in the city of Salvador, Brazil. Occupational exposure to organic solvents was evaluated through standardized questionnaires and defined by industrial hygienists, taking into account individuals' lifetime history. An association between occupational exposure to organic solvents and NHL was observed, OR = 1.67 (95% CI, 0.97 to 2.87), especially among individuals less than 64 years, OR = 1.91 (95% CI, 0.99 to 3.67), and among those who used domestic insecticides, OR = 2.24 (95% CI, 1.01 to 3.97). Odds ratios were similar for nodal and diffuse NHL. These results suggest that organic solvents may contribute to the causation of NHL, especially among young individuals, and that synergism may play a role in the process of lymphomagenesis.

Expression of cyclin B1 and cdc2 in nodal non-Hodgkin's lymphoma and its prognostic implications.

To investigate the role of cyclin B1 and cdc2 in the pathogenesis and progression of malignant lymphoma, 68 cases of nodal non-Hodgkin's lymphoma were examined about the expression of cyclin B1 and cdc2 along with p53 and Ki-67 by immunohistochemical method. The correlation of their expression with various clinicopathologic findings was also analyzed. Cyclin B1 and cdc2 were diffusely expressed in 39 cases (57.4%) and 54 cases (79.4%) out of 68 cases studied, respectively. The mean labeling indices of cyclin B1 and cdc2 in malignant lymphoma were 31.9% and 68.0%, respectively. In normal lymphoid tissues, cyclin B1 and cdc2 were expressed predominantly in the germinal center with mean labeling indices of 13.9% and 28.3%, respectively. The correlation between the expression of cyclin B1 and cdc2 was noted (p=0.013). The expression of Ki-67 was correlated with that of cyclin B1 (p=0.023) and marginally correlated with that of cdc2 (p=0.056). The expression of cdc2 and p53 in complete remission group to chemotherapy was lower than that of progressive disease group (p=0.047, p=0.049). In multivariate analysis, the clinical stage alone showed significance on overall survival (p=0.049). In conclusion, cyclin B1 and cdc2 appeared to be involved in the genesis or progression of malignant lymphoma and cdc2 can be a useful marker for response to chemotherapy.

Clinical presentation, therapy and prognosis of non-Hodgkin lymphomas of the major salivary glands

About 5 - 10 % of all Non-Hodgkin-Lymphomas (NHL) present within the major salivary glands. Two etio-pathologically different groups, the (extranodal)-parenchymal NHL and NHL of intra- or periglandular lymphnodes (nodal lymphomas) have to be distinguished. It was the aim of this study to evaluate the clinical presentation, therapy and biological behaviour of these etiopathologically different lymphoma-groups. In a retrospective study, therapy and course of disease of 26 patients with a NHL of the major salivary glands were examined (diagnosis and treatment between 1988 and 1996). Staging results in the group of parenchymal lymphoma always showed the disease limited to the effected gland, whereas nodal NHL presented with a stadium II to IV (Ann-Arbor) at time of diagnosis. Local recurrencies were five times higher in nodal NHL compared to parenchymal NHL. In only one case (7.7 %) of the patients with parenchymal NHL, dissemination was observed. In the group of nodal NHL, a dissemination was observed in 6 patients (46.2 %). 7 of 13 patients (53.8 %) with a nodal NHL died due to lymphoma dissemination, compared to one patient (7.7 %) with a parenchymal NHL. Based on the presented data, the histopathological diagnosis, under special recognition of the particular lymphoma-pathogenesis, constitutes an important prognostic factor in patients with NHL of the major salivary glands.

A trial of fludarabine and cyclophosphamide combination chemotherapy in the treatment of advanced refractory primary cutaneous T-cell lymphoma

The combination of fludarabine and cyclophosphamide shows synergistic toxicity in vitro and has been used to treat nodal non-Hodgkin's lymphoma and relapsed chronic lymphocytic leukaemia. To test the efficacy of this combination in 12 patients with cutaneous T-cell lymphoma (CTCL). Nine patients with erythrodermic CTCL were identified for the study, eight of whom met the criteria for Sézary syndrome (SS), and three with tumour-stage mycosis fungoides (MF). Patients received intravenous fludarabine and cyclophosphamide 3 days monthly for 3-6 months. Six patients tolerated at least three cycles. Five with SS had a response (one had a complete clinical response and four a partial response) and one patient with MF had stable disease. The mean duration of the response was 10 months. Six patients had treatment withdrawn, five due to bone marrow suppression and one due to progressive disease. No difference in pretrial parameters were found in those who had treatment withdrawn and those who tolerated at least three courses. Survival since the trial was similar in both groups at 11 months. These data indicate that the combination of fludarabine with cyclophosphamide may be of clinical benefit in patients with SS but does not affect patient survival. As with other multiagent chemotherapy regimens, bone marrow toxicity is a common and severe side-effect. These data suggest that this regimen should be considered palliative and should be reserved for patients with refractory disease without bone marrow suppression.

Splenic Lymphoproliferative Disorders in Human T Lymphotropic Virus Type-I Endemic Area of Japan: Clinicopathological, Immunohistochemical and Genetic Analysis of 27 Cases

Primary splenic involvement in lymphoid neoplasms is rare and the clinicopathologic features of splenic lymphoma are not well described compared to nodal non-Hodgkin's lymphoma (NHL). Here we characterized splenic lymphomas in an human T lymphotropic virus type-I (HTLV-I) endemic area of Japan. To assess the pattern of splenic involvement and evaluate prognosis, we reviewed 27 specimens consisting of 26 splenectomies and one necropsy, which were classified using REAL classification. Cases were divided into primary splenic lymphoma in 11 patients and secondary in 16 patients. The incidence of primary splenic lymphoma was 0.3% (11 of approximately 4,000 malignant lymphomas). Primary splenic lymphomas included 7 diffuse large B cell lymphoma (DLBL), 2 follicular lymphomas (FL), and 1 each of splenic marginal zone lymphoma (SMZL) and anaplastic large cell lymphoma (ALCL). Secondary splenic lymphomas included 6 DLBL, 4 mantle cell lymphoma (MCL), 2 FL, 2 Hodgkin's disease (HD), 1 each of hairy cell leukemia and ALCL. Gross examination showed two patterns of splenic involvement; solid type (formation of large nodular mass, n = 16) and disseminated type (multiple nodules with diffuse infiltration but no large nodular formation, n = 10). The type could not be determined in one case. Most solid types were DLBL or FL, while MCL was of the disseminated type. Immunohistochemistry showed all but each 2 cases of ALCL and HD were of B lineage. Follow-up of 26 patients indicated that all but one patient with primary lymphoma were still alive (range, 1–89 months) and 8 of 15 patients with secondary lymphomas died due to the progression of malignant lymphoma; the survival rate at 2 years was 50% in these patients. No elevation of anti-HTLV-I antibody was found. In situ hybridization for Epstein-Barr virus (EBV) showed no reactivity of lymphoma cells, although a few small lymphocytes were positive for EBV. Hepatitis C virus was observed in 6 of 20 (30%) patients examined and 4 of 11 (36%) cases of primary splenic lymphoma. Our findings indicate that patients with primary splenic lymphoma have a favorable prognosis after splenectomy.