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PubMed1987

Combined chemotherapy in 76 children with non-Hodgkin's lymphoma excluding Burkitt's lymphoma.

From January 1983 to December 1986 seventy-six previously untreated children with non-Hodgkin's lymphoma (NHL) were treated by combination chemotherapy. Burkitt's lymphoma patients were ineligible. The treatment regimens include intermittent chemotherapy and for non-localized patients, prophylactic central nervous system chemotherapy. Intrathoracic non-Hodgkin's lymphoma patients also had cranial prophylactic radiotherapy. Sixty-six patients (86.8%) achieved complete remission. Two year failure-free survival rate was 82.1% for localized (stage I and II) NHL and 53.3% for non-localized (stage III and IV) NHL patients. Failure-free survival did not differ significantly for the two major histologic diagnoses, but two year survival rate was lower in diffuse poorly differentiated lymphoblastic than undifferentiated non-Burkitt's lymphoma (50% versus 66.8% respectively). Failure-free survival rate was 53.7% in mediastinal disease and, 73.2% in abdominal disease at 24 months. Relapse rate was higher in mediastinal cases (46.1%) than primary abdominal cases (24.3%) at 24 months. Eleven (13.5%) died of treatment related sepsis. Although the overall survival rate was 72.4% at 2 years we need novel or more intensive programmes for mediastinal and non-localized disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Hepatosplenic T cell lymphoma. A review on 45 cases since the first report describing the disease as a distinct lymphoma entity in 1990.

Peripheral T cell lymphomas are a heterogeneous group of post-thymic, mature lymphoid malignancies, accounting for approximately 10-15% of all non-Hodgkin's lymphomas. A rare entity within this group is represented by hepatosplenic gammadelta T cell lymphoma, which is characterized by primary extranodal disease with typical sinusoidal or sinusal infiltration of the liver and the spleen, respectively, by expression of the T cell receptor gammadelta chain, and by a number of other frequent clinicopathological features including aggressive course of disease. In contrast to these common attributes some biologic characteristics such as expression of cytotoxic proteins and cytotoxic activity have been controversial. In this review, clinicopathological, immunophenotypical, molecular biological, cytogenetical and biological findings, and diagnostic and therapeutic difficulties in hepatosplenic gammadelta T cell lymphoma are discussed.

Adolescent↗

PubMed1999

Pseudoepitheliomatous hyperplasia in cutaneous T-cell lymphoma. A clinical, histopathological and immunohistochemical study with particular interest in epithelial growth factor expression. The French Study Group on Cutaneous Lymphoma.

Pseudoepitheliomatous hyperplasia has occasionally been reported in cutaneous T-cell lymphoma (CTCL). This association raises the question of the relationship between epidermal hyperplasia and the lymphomatous infiltrate. Because epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) have been demonstrated to be involved in epidermal proliferation through binding to EGF receptor (EGFr), we tested the hypothesis that these cytokines could be secreted by lymphomatous cells, and induce the overlying pseudoepitheliomatous hyperplasia. The purposes of this study were: (i) to describe the clinical and immunohistological features of pseudoepitheliomatous hyperplasia; (ii) to determine its frequency in a large series of CTCLs; and (iii) to evaluate the expression of EGF, TGF-alpha and EGFr in CTCL with or without pseudoepitheliomatous hyperplasia. Eleven cases of CTCL with pseudoepitheliomatous hyperplasia were collected from a series of 353 cases of cutaneous lymphoma registered from 1990 to 1996. They consisted of eight of 28 (28.5%) CD30+ large T-cell lymphomas and three of 148 (2%) cases of mycosis fungoides. Epidermal expression of EGF, EGFr and TGF-alpha was stronger in CTCL than in control normal human skin. Lymphomatous T cells expressed EGF and TGF-alpha whereas no expression of these cytokines could be detected in cutaneous and nodal B-cell lymphomas, nor in a normal lymph node. In addition, epidermal expression of EGFr was stronger in CTCL with pseudoepitheliomatous hyperplasia than in control cases of CTCL without pseudoepitheliomatous hyperplasia, suggesting that these cytokines, in association with other factors, are probably involved in the epidermal hyperplasia observed in some cases of CTCL.

Epidermal Growth Factor↗

PubMed1996

Occurrence of multiple lymphoepithelioma-like carcinomas and MALT-type lymphoma in the stomach: detection of EBV in carcinomas but not in lymphoma.

A multifocal lymphoepithelioma-like carcinoma and a low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-type) were found simultaneously in the stomach of a 65-year-old patient. Carcinoma and lymphoma were intimately associated forming complexes resembling lymphoepithelial lesions at the primary gastric site and in lymph node metastases. The two tumours had developed on a background of severe chronic-atrophic gastritis of the mucosa of antrum and fundus. Autoantibodies to normal gastric glandular tissue could be demonstrated in the patient's sera. Using non-radioactive in situ hybridization (ISH), Epstein-Barr virus (EBV) sequences were detected in virtually all carcinoma cells but neither in the non-neoplastic mucosa nor in the lymphoma. These findings suggest that a focal EBV infection occurred early in the development of the carcinoma followed by a subsequent clonal expansion of the EBV-containing tumour cells. A neoplastic transformation in MALT-type lymphoma is not EBV-related but might be triggered by altered immune mechanisms.

Aged↗

PubMed1999

Primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma with polypoid appearance. Polypoid gastric MALT lymphoma: A clinicopathologic study of eight cases.

In the current study, we report eight cases with primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma endoscopically characterized by polypoid lesions in order to highlight their clinicopathologic significance. Four patients were male, their ages ranging from 40 to 78 years old. The resected specimens revealed a histology of low-grade MALT lymphoma characterized by dense lymphocytic infiltration predominantly in the submucosa and a relatively monotonous proliferation of centrocyte-like cells with reactive follicles and infrequent lymphoepithelial lesions. The tumor cells were of CD5-, CD10-, CD20+, BCL2+ and cycline D1- phenotype, and showed a monoclonal rearrangement of immunoglobulin heavy chain genes in the five of six cases examined. Interestingly, Helicobacter pylori (H. pylori) was detected in three (37.5%) of the eight patients, which was significantly lower than previous reports. Two of the H. pylori-positive cases initially underwent H. pylori eradication, but showed no change in their lymphomas after the cure of H. pylori infection. The clinicopathologic findings of the present cases appeared to closely resemble those of colorectal MALT lymphoma with a polypoid appearance and few association of H. pylori infection in their pathogenesis. These gastric polypoid cases may merit separate consideration because of the therapeutic problems they pose.

Adult↗

PubMed2000

Granzyme B-positive primary gastric T-cell lymphoma: gastric T-cell lymphoma with the possibility of extrathymic T cell origin.

A case of primary gastric T-cell lymphoma, which was positive for granzyme B, is reported. The patient was a 47-year-old Japanese female who complained of a dull upper abdominal pain. Radiographic and endoscopic examinations revealed an ulcerative infiltrative lesion in her stomach. Following the confirmation of a high-grade malignant lymphoma, a distal gastrectomy with regional lymph nodal dissection was performed. The histology of the gastric lesion revealed a malignant lymphoma of the diffuse pleomorphic type without lymph nodal involvement. Immunohistochemistry revealed that the tumor cells were positive for LCA, CD3, TIA-1 and granzyme B, but were negative for CD4, CD8, CD56, CD30, L-26, EMA, TCR alpha/beta and TCR gamma/delta. Because the tumor cells showed T cell nature with cytotoxic activity proved by TIA-1 and granzyme B, and without evidence of further maturation of T cell, a malignant lymphoma originating from extrathymic-derived T cells was suggested.

Biomarkers, Tumor↗

PubMed2006

Precursor B lymphoblastic lymphoma of the orbit in a child: an unusual presentation of a non-Hodgkin lymphoma.

OBJECTIVE: The majority of ocular adnexal lymphomas are marginal zone lymphomas, which occur rarely in children. This case report describes a 6 years old child with a precursor B lymphoblastic lymphoma presenting in the ocular adnexa. The combination of multi-agent chemotherapy with adjuvant radiotherapy seems to be necessary in order to achieve a complete remission of this subtype of lymphoma's in ocular adnexa. DESIGN: Retrospective case study. METHOD: A review of the clinical, pathological, radiological findings and follow-up in a patient from the files available at our center, which were reviewed between the years 1974 and 2004.

Child↗

PubMed2002

Effectiveness of local radiotherapy in primary extranodal marginal zone B-cell lymphoma of MALT or MALT lymphoma of conjunctiva: study of four cases.

Primary lymphomas of the conjunctiva are extremely infrequent and usually belong to extranodal marginal zone B-cell lymphoma of MALT or MALT lymphoma. Radiotherapy with lens shielding is one of the most employed therapeutic options. Four patients with MALT lymphomas of the conjunctiva with complete and maintained response to radiotherapy are reported. The effectiveness as well as the lack of significant toxicity of radiotherapy are emphasized.

Adolescent↗

PubMed2003

Molecular cytogenetic approach to the diagnosis of splenic lymphoma: a case report of blastoid mantle cell lymphoma.

A 69-year-old woman was admitted to hospital due to abdominal pain. An enlarged spleen was detected and extirpated. Histological examination and FACS analysis could not clearly differentiate between a splenic marginal zone lymphoma and a mantle cell lymphoma. Using molecular cytogenetic techniques, a complex karyotype including a translocation between chromosome 11 and 14 consistent with a triple fusion between heavy chain immunoglobulin locus (IgH) and cyclin D1 (CCND1) was demonstrated. Overexpression of cyclin D1 was detected by immunostaining. Thus the diagnosis of a splenic blastoid mantle cell lymphoma could be established. In this report, various aspects of differential diagnosis of splenic lymphomas are discussed.

Aged↗

PubMed1986

Lymphoma models for B cell activation and tolerance. III. Cell cycle dependence for negative signalling of WEHI-231 B lymphoma cells by anti-mu.

WEHI-231 B lymphoma cells have proven to be a useful model for the regulation of growth of normal B cells by anti-Ig reagents. We previously reported that the growth of these lymphoma cells is inhibited by heterologous or monoclonal anti-mu or anti-kappa reagents. Such cells cease to incorporate thymidine within 24-48 h of exposure to anti-Ig reagents, but are not adversely affected by antibodies directed at either class I or class II histocompatibility antigens. In fact, cell cycle analysis revealed that anti-mu causes a block in the transition of these cells from G1 to S phase. To further study the mechanism of growth inhibition, we have purified lymphoma cells in G1 by centrifugal elutriation, or enriched WEHI-231 cells at the G1/S interface by treatment with hydroxyurea, and followed their progression through the cell cycle in the presence or absence of anti-mu. Our data show that WEHI-231 B lymphoma cells receive a negative signal early in G1, since delayed addition of anti-mu (to late G1 cells) leads to no alteration in cell cycle progression at 24 h, and exposure to anti-mu during S does not alter progress through DNA synthesis and mitosis. Moreover, exposure to anti-mu for only 2 h prevents purified G1 cells from entering their first S phase. The nature of the relevant processes in early G1 is discussed in terms of models of B cell activation and tolerance induction.

Animals↗

PubMed1953

Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. II. Studies on the nature of the active serum constituent: histological mechanism of the regression: tests for effects of guinea pig serum on lymphoma cells in vitro: discussion.

In an extension of the experimental studies recorded in an associated paper; attempts were made to isolate and characterize the constituent of guinea pig serum responsible for inducing regression of transplanted lymphomas in vivo. The active material was precipitated readily from the whole serum, along with some of the globulins, by means of ammonium sulfate in concentrations of 2.0 molar or greater; it withstood heating at 56 degrees C. for 20 or 30 minutes, but was inactivated upon heating at 66 degrees C. for similar periods; it was completely inactivated by chymotrypsin in concentrations of 1 or 2 mg./cc. during 6 hours at 37 degrees C. Furthermore, the inhibitory effects of small amounts of the guinea pig serum in vivo were enhanced upon admixture with immune sera prepared by injecting the lymphosarcoma cells into rabbits. The facts as a whole suggest that the active material is a protein, and that it may be one or another of the components of complement; yet they do not suffice to establish its identity. Microscopic studies showed that the cells of subcutaneous lymphomas rapidly died and were resorbed following injections of relatively large amounts of guinea pig serum intraperitoneally into mice carrying them, while similar changes followed more gradually after repeated injections of smaller amounts of guinea pig serum. No changes referable to the guinea pig serum were seen in the normal tissues or organs of mice receiving it. Mouse lymphoma cells, suspended artificially as individuals in a physiological saline solution, regularly remained viable following incubation in vitro in mixture with guinea pig serum during 6 hours at 37 degrees C. The finding provides strong evidence that the regression of lymphomas that follows injection of guinea pig serum in vivo is brought about through some reaction in which the guinea pig serum and the host both participate. Some of the implications of the findings are discussed.

Animals↗

PubMed1985

Morphologic and immunologic evidence of composite B- and T-cell lymphomas. A report of three cases developing in follicular center cell lymphomas.

Composite lymphoma (CL) may be defined as two lymphomas, differing as to their cell of origin, that occur simultaneously in the same tissue specimen. While CL usually is indicated histopathologically by at least two morphologically distinct lymphomatous proliferations, the proof that these proliferations are separate and distinct neoplasms requires immunologic analysis. Many so-called cases of CL actually represent the well-known phenomenon of lymphoid transformation, in which there is a small cell and a large cell component in the same specimen. Immunologic studies in these cases have shown that the cytologically distinct neoplastic cells represent different stages in the same cell line. While studying a large series of follicular center cell (FCC) lymphomas, the authors recognized three cases in which there was both morphologic and immunologic evidence of a true CL. Following an initial diagnosis of a nodular FCC lymphoma, rebiopsies from 21 to 62 months later showed the coexistence of a nodular FCC (B-cell) component and a diffuse large cell (T-cell) component.

Adult↗

PubMed1988

Relapse of intermediate or high-grade (unfavorable) non-Hodgkin's lymphoma as a low-grade (favorable) Non-Hodgkin's lymphoma. Report of four cases.

The authors present four cases of low-grade (favorable) non-Hodgkin's lymphoma appearing after successful treatment of intermediate or high-grade (unfavorable) non-Hodgkin's lymphoma. In each case, the patient had intermediate or high-grade non-Hodgkin's lymphoma, received multiagent chemotherapy, and entered complete remission lasting one to six years. Each patient had a relapse with low-grade non-Hodgkin's lymphoma. Possible explanations and therapeutic implications are discussed.

Adult↗

PubMed2004

Predictive value of Follicular Lymphoma International Prognostic Index (FLIPI) in patients with follicular lymphoma at first progression.

BACKGROUND: Different prognostic scores have been proposed to predict the outcome of follicular lymphoma (FL) patients at diagnosis. A new prognostic index specifically addressing FL patients, the Follicular Lymphoma International Prognostic Index (FLIPI), has recently been developed, which might also be useful in patients with progression. PATIENTS AND METHODS: One hundred and three patients (55 male, 48 female; median age 59 years) with FL in first relapse/progression after an initial response to therapy (50 complete responders/ 53 partial responders) were included in the study. RESULTS: Five-year survival from progression (SFP) was 55% (95% confidence interval 44%-66%). The distribution according to the FLIPI at relapse was 39% good prognosis, 24% intermediate prognosis and 37% poor prognosis. Five-year SFP for these groups were 85%, 79% and 28%, respectively (P < 0.0001). Other variables at relapse with prognostic significance for SFP were age, presence of B symptoms, performance status, bulky disease, number of involved nodal sites, lactate dehydrogenase level, hemoglobin level, histological transformation, the Italian Lymphoma Intergroup prognostic index for FL and the International Prognostic Index for aggressive lymphomas. In the multivariate analysis bulky disease (P=0.01), presence of B symptoms (P=0.03) and FLIPI at relapse (P=0.0003) were the most important variables for predicting SFP. CONCLUSIONS: In patients with FL at first relapse/progression, the FLIPI, along with the presence of bulky disease and B symptoms, are features that predict SFP and thus could be useful to select candidates for experimental treatments.

Age Factors↗

PubMed2007

The results of consolidation with autologous stem-cell transplantation in patients with peripheral T-cell lymphoma (PTCL) in first complete remission: the Spanish Lymphoma and Autologous Transplantation Group experience.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas associated with poor prognosis with standard chemotherapy. Consolidation with autologous stem-cell transplantation (ASCT) may improve survival. We present 74 patients transplanted in first complete response (CR) from the Spanish Lymphoma and Autologous Transplantation Group cooperative group. PATIENTS AND METHODS: Median age was 46 years. Eighty-eight percent presented advanced (III-IV) Ann Arbor stage; 53% had B symptoms; 52% had high lactate dehydrogenase; 65% had two or three risk factors of the adjusted-International Prognostic Index; 58% presented a high Tumor score and in 14% more than two adverse factors of the Prognostic Index for peripheral T-cell lymphoma (PIT) were observed. RESULTS: With a median follow-up of 67 months from diagnosis, the 5-year overall survival (OS) was 68% and progression-free survival (PFS) reached 63%. The multivariate analysis showed that the only factor associated with a shorter OS and PFS was the presence of more than two risk factors from the PIT risk system. CONCLUSIONS: In a retrospective study with a prolonged follow-up, consolidation with ASCT in CR patients who had presented unfavorable prognostic factors at diagnosis substantially increased the OS and PFS when compared with conventional chemotherapy. The PIT risk system identified 14% of patients without benefit from ASCT consolidation. Thus, other innovative therapies are still necessary in certain cases.

Adolescent↗

PubMed1991

The identification of discrete prognostic groups in low grade non-Hodgkin's lymphoma. The Scotland and Newcastle Lymphoma Group Therapy Working Party.

A prognostic model was developed by examination of the prospectively recorded presentation characteristics of patients presenting with low grade non-Hodgkin's lymphomas (LGL). A geographically distinct group (Edinburgh and Borders) was excluded in order to test the validity of the model based on the rest of the Scotland and Newcastle Lymphoma Group (SNLG) population. Between 1979 and 1987 506 patients presented with low grade lymphoma according to Working Formulation definition within one of each of the three main pathology categories. The median available follow-up was 47 months. In a multivariate analysis performance status, age, stage, gender and haemoglobin all contributed separately. 25% of all patients had relatively good prognosis with a median survival not reached and 84% alive at 5 years. Conversely for the worst prognostic group of 25% of patients the median survival is 18 months with only 26% surviving at 5 years. Finally for the intermediate group of 50% of all patients, median survival is 69 months with 58% alive at 5 years. These striking prognostic separations are shown also to be valid in sub-group analysis. Thus young patients within any pathology subgroup have been identified with bad prognostic lymphoma for whom novel strategies in therapy should be devised.

Aged↗

PubMed1988

Angiocentric T-cell lymphoma of the skin. An aggressive lymphoma distinct from mycosis fungoides.

Among 37 consecutive cases of malignant lymphoma in which the skin was either the only site of disease or one of the prominent sites of initial involvement, 19 cases had a distinctive histological appearance. These cases corresponded to what has been termed "angiocentric lymphoma," and all were found to exhibit a T-cell phenotype either by frozen-section immunohistochemistry or by using monoclonal antibodies reactive in paraffin sections. There were nine men and 10 women; the mean age was 48.2 years. The lesions were nodular and were either ulcerated or had intact skin. One case presented with involvement of one anatomical region of skin, five had involvement of multiple regions of skin, and 13 had concurrent extracutaneous disease. The disease pursued an aggressive course and was not uncommonly resistant to treatment. Histologically, the lymphomatous infiltrate occurred predominantly in the mid to deep dermis with involvement of the subcutaneous layer. The pattern was mainly perivascular and peri-adnexal with or without confluence; the overlying epidermis and papillary dermis were often spared. A prominent feature was invasion of small or large blood vessels by lymphoma cells. Eight cases showed extensive coagulative necrosis of the neoplastic and normal tissues, and 12 cases showed intraneural invasion. The neoplastic lymphoid cells consisted of either a monomorphous population or a variable mixture of small, medium-sized, and large cells with stippled chromatin and distinct nucleoli. Although the nuclei were often irregularly folded, few exhibited a cerebriform configuration. The cytoplasm was pale to clear. These cases exhibit a remarkable histological similarity to the T-cell lymphomas of the nasal/nasopharyngeal region; in addition, there are features that overlap with so-called lymphomatoid granulomatosis of the skin.

Adult↗

PubMed1997

Primary low-grade B-cell lymphoma of the dura: a mucosa associated lymphoid tissue-type lymphoma.

The clinicopathologic findings in five patients with primary low-grade B-cell lymphoma of the intracranial dura are described. All patients were women, 40-62 years of age, who presented with focal neurologic symptoms. Radiologic studies showed a well-localized dural mass in each case, raising a preoperative diagnosis of meningioma. Cytologically these were composed of a diffuse infiltrate of small lymphocytes with plasmacytoid differentiation, with a variable admixture of centrocytelike cells. Lambda light chain restriction was found in three cases, and kappa light chain in one. VJ polymerase chain reaction for immunoglobulin heavy-chain rearrangement was positive in three of four cases, including one case in which immunostaining results were equivocal. Staging procedures did not show involvement at any other site. Therapy consisted of radiation (n = 3), chemotherapy (n = 1), or both (n = 1), with excellent response. There was no evidence of recurrence or subsequent dissemination at follow-up of up to 63 months. Low-grade B-cell lymphomas arising in the intracranial dura are rare but appear to be similar to other low-grade B-cell lymphomas arising in extranodal sites in terms of clinical presentation as stage 1E disease, indolent behavior, and favorable response to treatment, suggesting that they may be part of the mucosa associated lymphoid tissue (MALT) lymphoma spectrum. They appear to arise at dural sites where meningothelial cells are concentrated.

Adult↗