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PubMed2002

Association of expression of CD44v6 with systemic anaplastic large cell lymphoma: comparison with primary cutaneous anaplastic large cell lymphoma.

CD44 is a ubiquitous multifunctional cell surface adhesion molecule family. High expression of the standard form, CD44s (CD44), and its variant form, CD44v6, has been reported to be associated with tumor dissemination in non-Hodgkin lymphoma. To evaluate the potential role of CD44 and/or CD44v6 in different entities of anaplastic large cell lymphoma (ALCL), 30 cases of systemic ALCL (sALCL; 20 cases) and primary cutaneous ALCL (cALCL; 10 cases) were compared for expression of CD44 and CD44v6 by immunohistochemical staining. Expression of CD44v6 also was analyzed with respect to expression of anaplastic lymphoma kinase (ALK) in sALCL. No difference of CD44 expression was noted between sALCL and cALCL In contrast, expression of CD44v6 was found in 18 (90%) of sALCL cases and in 5 (50%) of cALCL cases. There was no correlation between expression of CD44v6 and expression of ALK in sALCL. These results indicate that expression of CD44v6 rather than CD44 correlates with sALCL. Furthermore, these results suggest that CD44v6 and ALK may be independent predictors of risk for the systemic phenotype of ALCL.

Adolescent↗
PubMed2005

Anaplastic lymphoma kinase and its signalling molecules as novel targets in lymphoma therapy.

A crucial issue in the development of molecularly-targeted anticancer therapies is the identification of appropriate molecules whose targeting would result in tumour regression with a minimal level of systemic toxicity. Anaplastic lymphoma kinase (ALK) is a transmembrane receptor tyrosine kinase, normally expressed at low levels in the nervous system. As a consequence of chromosomal translocations involving the alk gene (2p23), ALK is also aberrantly expressed and constitutively activated in approximately 60% of CD30+ anaplastic large cell lymphomas (ALCLs). Due to the selective overexpression of ALK in tumour cells, its direct involvement in the process of malignant transformation and its frequent expression in ALCL patients, the authors recognise ALK as a suitable candidate for the development of molecularly targeted strategies for the therapeutic treatment of ALK-positive lymphomas. Strategies targeting ALK directly or indirectly via the inhibition of the protein networks responsible for ALK oncogenic signalling are discussed.

Anaplastic Lymphoma Kinase↗
PubMedDate not supplied

Intracytoplasmic immunoglobulins in the differential diagnosis of lymphocytic lymphomas of the B-CLL type and immunocytic lymphomas.

One hundred and thirty-three consecutive cases originally classified either as a lymphocytic lymphoma of the B-CLL type or as an immunocytic (IC) lymphoma could be reclassified morphologically and analyzed for the presence of cytoplasmic immunoglobulins (cIg) with the PAP-technique. The morphologic reclassification confirmed the initial diagnosis in most cases, whereas after staining for cIg, the diagnosis was changed in a large number of cases, i.e. from B-CLL to IC, or the reverse, or from IC of the polymorphic subtype (ICp) to 'high-grade' non-Hodgkin lymphoma (NHL). Cases classified as IC were often localized (stage I+II: 22/43) with a long disease-free survival after local radiation therapy, while B-CLL were usually generalized. For patients in stage IV, the prognosis of B-CLL was significantly superior to that of IC, which in turn was superior to the prognosis of cases referred to as 'high-grade' NHL. The difficulties in the morphologic distinction between B-CLL and IC on one hand and between ICp and some 'high-grade' NHL on the other hand, as well as the clinical significance of these distinctions, are discussed.

Adult↗
PubMed1986

Childhood non-Hodgkin's lymphoma and "leukemia-lymphoma syndrome": long-term results with the modified LSA2-L2 protocol.

From June 1976 to December 1984, 48 previously untreated children with non-Hodgkin's lymphoma (NHL) were treated according to the LSA2-L2 protocol, modified by inclusion of cranial irradiation for patients in stage III and stage IV disease. According to the staging system proposed by Wollner, 4 patients were in stage I, 8 in stage II, 11 in stage III, 8 in stage IVA (less than or equal to 25% blasts in the bone marrow), 15 in stage IVB (greater than 25% blasts in the bone marrow), and 2 in stage IV central nervous system disease. The complete remission rate was 95.8%. The relapse-free survival (RFS) rate of 46 complete responders was 76% after a median observation time of 47+ months. Only 1 of 35 high-risk responder patients developed CNS relapse after prophylactic treatment. Clinical stages were related to the RFS: 100% in stage I-II vs. 69% in stage III-IV. All 8 patients in stage IV were alive without evidence of disease with a median observation time of 59+ months. Fifteen patients in stage IVB who had leukemia-lymphoma syndrome attained 59% RFS with a median observation time of 39+ months. After a median observation time of 38+ months, 29 of 37 patients are off therapy. The results emphasize the value of both the histologic and immunologic features and the stage of disease in predicting the outcome of NHL in children. The LSA2-L2 regimen appears to be a very effective protocol for children with lymphoblastic lymphoma, although it may be less efficacious for patients with large bone marrow involvement.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Lymphoma-associated pancreatitis as a presenting manifestation of immunoblastic lymphoma.

A 55 year old man presented with clinical signs and symptoms of subacute pancreatitis of unknown aetiology. Two weeks later, inguinal lymphadenopathy developed and a lymph node biopsy revealed a B cell immunoblastic lymphoma. Computerized tomography showed enlargement of the pancreas and imaging features consistent with pancreatitis. Administration of VACOP-B combination chemotherapy achieved complete resolution of the pancreatic mass and the enlarged lymph nodes. We consider this patient to have had lymphoma associated pancreatitis. This case represents a rare clinical presentation of lymphoma suggesting an alternative aetiology of subacute pancreatitis in some cases.

Acute Disease↗
PubMed2000

Transformation of monocytoid B-cell lymphoma to large cell lymphoma associated with crystal-storing histiocytes.

We report a case of crystal-storing histiocytosis associated with large cell lymphoma in a patient with a history of monocytoid B-cell lymphoma 10 years previously. The cervical lymph node biopsy showed a diffuse proliferation of large lymphocytes with vesicular nuclear chromatin and distinct nucleoli. These lymphocytes were associated with numerous immunoglobulin lambda light-chain crystal-storing histiocytes, which morphologically resembled rhabdomyoblasts. Occasional lymphoid cells also showed large immunoglobulin crystals. This case establishes the association of crystal-storing histiocytes with lymphomas of mucosa-associated lymphoid tissue and emphasizes the need for immunophenotyping to distinguish these unusual cases from other tumors, particularly adult rhabdomyomas.

Aged↗
PubMed1999

[Primary gastrointestinal lymphoma in patients infected with HIV: study of 15 cases in a series of 76 patients with non-Hodgkin's lymphoma and HIV infection].

BACKGROUND: To analyze the main clinical and biological data and the response to therapy in 15 patients with primary gastrointestinal lymphoma (PGIL) from a series of 76 patients with HIV related non-Hodgkin's lymphoma (NHL) diagnosed in a single institution in a 13 years period. PATIENTS AND METHODS: The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the REAL classification. Clinical stage was determined by the Ann Arbor system modified by Rohatiner et al. Response to therapy as well as overall survival (OS) were studied. Results were compared with non-PGIL HIV-related NHL patients. RESULTS: Mean age of the series was 38 years. Thirteen patients were male, and 8 intravenous drug abusers. Then had bad performance status (ECOG 2-4) and 11 B symptoms. All patients had a high grade malignant PGIL and the localization was gastric in 10 cases. The most frequent symptoms were abdominal pain (11 cases), gastrointestinal bleeding (4) and dysphagia (3). Ten patients had advanced stages (IIE2-IV). The median CD4 cell count was lower in PGIL patients (92 x 10(6)/l vs 148 x 10(6)/l; p < 0.05). Thirteen patients received intensive chemotherapy with CHOP regimen (in 5 surgical procedures were previously made). Complete response (CR) was obtained in 4 patients (31%) and 1 of them relapsed. Median OS was 10 months vs 16 months non-PGIL HIV-related lymphoma patients (p < 0.05). CONCLUSIONS: PGIL in HIV patients often presented advanced stages and high grade of malignancy. The most common localization is the stomach, and these patients usually have bad performance status and a low CD4 lymphocyte count. Response to therapy is poor. In our series OS was worse in PGIL patients than in the rest of HIV-related NHL, possibly due to the high degree of immunosuppression in the formers.

Adult↗
PubMed1999

Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL) is an aggressive lymphoma that is frequently associated with the t(2;5)(p23;q35), resulting in expression of a fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which can be detected by either monoclonal or polyclonal antibodies to the ALK protein. The clinical features of adults with ALCL are incompletely described, and the prognostic factors that are useful for predicting survival remain unclear. This report describes the clinical and laboratory findings in 70 adults with systemic ALCL who were treated with curative intent. We attempted to identify the clinical and pathological factors of prognostic importance, including the International Prognostic Index (IPI), immunophenotype, and expression of the ALK protein. The median age of the patients was 49 years (range, 15 to 75). There were 26 women and 44 men with a median follow-up of 50 months for living patients. Advanced stage was present in 56% and B symptoms were noted in 70% of the patients. Immunostains showed that 46% of the cases had a T-cell phenotype, 36% a null phenotype, and 18% a B-cell phenotype. The expression of ALK protein was found in 51% of the cases. The IPI factors were evenly distributed between the ALK+ and ALK- groups, except that the ALK+ patients were younger (median age, 30 v 61 years; P <.002). The ALK+ cohort included cases with null (44%), T-cell (42%), and B-cell (14%) phenotypes. All 10 cases with cytogenetic or molecular evidence of a t(2;5) were ALK+. The 5-year overall survival (OS) of the entire cohort was 65%. The 5-year OS of the ALK+ and ALK- cases was 79% and 46%, respectively (P <.0003). Analysis of only the T-cell/null cases (n = 57) showed a 5-year OS of 93% for the ALK+ cases and only 37% for the ALK- cases (P <.00001). Univariate analysis of the clinical features showed that age </=60 years (P <.007), a normal serum lactate dehydrogenase (LDH) (P <.00001), a good performance status (Eastern Cooperative Oncology Group [ECOG] <2) (P <.03), </=1 extranodal site of disease (P <.012), and an IPI score </=3 (P <.00001) were associated with improved OS. Although a younger age correlated with ALK positivity, multivariate analysis showed that only a normal serum LDH (P <. 00001), an IPI score of </=3 (P <.0005), and ALK protein expression (P <.005) predicted independently for an improved OS. We conclude that ALCL is a heterogeneous disorder. However, ALK protein expression is an independent predictor of survival and serves as a useful biologic marker of a specific disease entity within the spectrum of ALCL.

Adolescent↗
PubMedDate not supplied

[Differential diagnosis of B-cell lymphoma rich in T cells and peripheral T-cell lymphomas].

Clinicomorphological analysis of T-cell-rich B-cell lymphoma in a 50-year-old female and literature data revealed objective difficulties in morphological diagnosis using cytological and histological methods. Large number of epithelioid histiocytes and tumor cells polymorphism resembled Lennert's lymphoma (peripheral T-cell lymphoma). Immunohistochemical study confirmed B-cell origin of tumor cells and large number of reactive T-cells. It is suggested that it would be more correctly to use the term "Lennert-like areas" in such cases with subsequent immunohistochemical study.

Diagnosis, Differential↗
PubMedDate not supplied

Lymphomas: Hodgkin and non-Hodgkin lymphomas.

Results on lymphomas trend analysis carried out in the database of the Italian Network of Cancer Registries (pool AIRT) in the period 1986-1997 are presented. Hodgkin lymphoma (2,959 cases and 911 deaths included in the analysis) shows a decreasing incidence trend, statistically significant among males. Standardised mortality rates decrease significantly in both sexes, on an average of 7-9%/year. As regards non-Hodgkin lymphomas (16, 470 incident cases and 7,193 deaths), there is a significant increasing trend, in both sexes, both for incidence (more than 3 %/years) and mortality (about 2%/year).

Adolescent↗
PubMed2005

[Angioimmunoblastic T-cell lymphoma occurring four months after autologous peripheral blood stem cell transplantation with high-dose chemotherapy for follicular lymphoma].

A 62-year-old Japanese woman was diagnosed as having follicular lymphoma (FL, grade 3, CS IIIA, IPI high-intermediate risk) in May 1998. After eight courses of CHOP therapy, she achieved a complete remission (CR). In November 1998, her FL relapsed, and she achieved a second CR after two courses of MINE therapy. High-dose etoposide was used for autologous peripheral stem cell mobilization. In May 1999, she underwent high-dose chemotherapy with autologous peripheral blood stem cell transplantation (auto-PBSCT). Four months after the auto-PBSCT, bilateral cervical lymphadenopathy developed. Histopathological findings from a biopsied cervical lymph node showed angioimmunoblastic T-cell lymphoma (AILT). The patient was treated with modified CVP therapy, and she is alive with no evidence of lymphoma five years after auto-PBSCT. Clinical and histopathological findings showed that the FL and AILT in this case were not concomitant. It is thought that in this case, the AILT developed as a post-transplant lymphoproliferative disorder after auto-PBSCT for the FL.

Antineoplastic Agents, Phytogenic↗
PubMed1991

[Clinical significance of immunophenotype in diffuse non-Hodgkin's lymphoma: with special emphasis on the clinical characteristics of T-cell lymphoma].

The clinical significance of immunophenotyping of the non-Hodgkin's lymphomas (NHL) is still controversial. Therefore, we evaluated the prognostic significance of T- and B-cell phenotype in 102 patients having diffuse non-Hodgkin's lymphoma who had been treated in a majority with Adriamycin-containing regimens. The significant differences in pretreatment clinical variables between the two patient groups were the higher frequency of markedly elevated LDH (greater than or equal to X 2 normal) and the lower frequency of decreased cholesterol level in B-NHL (p less than 0.05). Patients with B-NHL had a higher complete remission (CR) rate (77% vs 59%: p = NS), a significantly better overall survival (62% vs 34% at 3-years: p less than 0.05) and longer duration of remission for all patients (50% vs 27% at 3-years: p less than 0.05). Among forty-five patients with stages III and IV disease of nodal origin (excluding those with diffuse small cleaved histology), the B-cell group was associated with a better prognosis; a higher CR rate (68% vs 41%: p = NS) and a longer duration of remission for all patients (44% vs 12% at 2-years: p less than 0.05). Furthermore, for patients with T-cell phenotype, the primary site was the only prognostic factor; the patients whose disease originated from Waldeyer's ring, nasal cavity, and paranasal sinuses, achieved a better CR rate (92% vs 40%: p less than 0.05) and a longer duration of remission for all patients (48% vs 15% at 2-years: p less than 0.05). We conclude that advanced T-cell lymphoma of nodal origin is a subgroup of patients with very poor prognosis if treated with less intensive chemotherapeutic regimens.

Adolescent↗
PubMed1989

Flow cytometric analysis of lymphoma and lymphoma-like disorders.

The use of flow cytometry (FC) represents the most recent advance in the phenotypic analysis of lymphocyte subsets, and has emerged as a valuable adjunct in the diagnosis of malignant non-Hodgkin's lymphoma (NHL). In a review of over 200 cases of nodal and extranodal suspected lymphomas studied in the Immunophenotyping Laboratory at the University of New Mexico, the diagnostic utility of FC was assessed. Among cases of NHL, FC was able to confirm a morphologic diagnosis of lymphoma and determine B or T cell lineage in greater than 85% of the samples submitted. Difficulty in lineage determination in the remaining cases of morphologic NHL was multifactorial. Among cases of reactive lymph nodes and Hodgkin's disease, FC showed no characteristic patterns, although several cases exhibited phenotypic profiles suggestive of B or T cell clonality. When combined with routine morphologic review and accompanied by other specialized diagnostic techniques when necessary, the use of FC represents a precise and reproducible method for rapidly and easily studying lymphoproliferative disorders in solid tissue.

Flow Cytometry↗
PubMed1988

[Analysis of non-Hodgkin's lymphomas of 210 patients with nodular and favorable histologies--report of the Japanese Lymphoma Radiation Therapy Study Group].

Between 1972 and 1985, 210 patients with nodular poorly differentiated lymphocytic (NPDL), nodular mixed lymphocytic and histiocytic (NM), nodular histiocytic (NH), or diffuse well differentiated lymphocytic (DWDL) lymphoma according to Rappaport classification were treated among the 7 hospitals belonging to JLRTG (Japanese Lymphoma Radiation Therapy Study Group). Age greater than 50 years adversely affected overall survival. But no obvious survival differences were seen by sex and the primary site. Patients with NH had a significantly poorer survival (P less than 0.01), while there were no differences among the other histologic groups. Aggressive combination chemotherapy is advisable for patients with stages II, II and IV NH. But radiotherapy along may be treatment choice for patients with stage I NH. Because among stage I, over all survival and relapse-free survival of patients with NH were similar to those with the other histologic types. Five-year and 10-year relapse-free survival of stage I patients with the other 3 histologic types by radiotherapy alone were 85% and 67%, respectively. Those of stage II patients were both 58%. These data suggest cure of more than 50% of stages I and II patients with favorable lymphoma by radiotherapy alone.

Adolescent↗
PubMed1986

Alpha interferon treatment of low-grade B-cell non-Hodgkin's lymphomas, cutaneous T-cell lymphomas, and chronic lymphocytic leukemia.

The interferons represent an important first member of a family of biologic response modifiers used in treating human malignancies. Activities associated with the interferons include inhibition of viral replication, influence on cellular protein production, direct antiproliferative effects, and a variety of modulatory effects on the immune response. These regulatory functions of interferon underlie the interest in its use as an anticancer agent. Interferon alpha is the most extensively studied interferon species. Although antitumor activity has been seen both in vivo and in vitro in some solid malignancies, the most impressive responses have occurred in the hematologic malignancies. For the low-grade non-Hodgkin's lymphomas, response rates of 50%, with 10% to 15% complete responses, have been reported. A response rate of 15% has been reported for chronic lymphocytic leukemia in studies outside of the National Cancer Institute (NCI); in our phase II trials at the NCI, only two (11%) of 18 patients had brief partial responses to recombinant interferon alpha. For patients with cutaneous T-cell lymphomas (mycosis fungoides and the Sézary syndrome), a response rate of 45%, with 10% complete responses, was seen in patients treated with recombinant interferon alpha. Based on such findings, interferon appears to be one of the most effective single agents for cutaneous T-cell lymphomas. Further phase II trials are being conducted to determine whether lower doses of interferon alpha are as effective as the high doses used in the previously reported studies. Phase III trials will involve the use of interferons in combination with chemotherapeutic agents as well as in the adjuvant setting.

Humans↗
PubMed1979

Histiocytic lymphoma in a patient with Lennert's lymphoma. Report of a case with unusual cytoplasmic inclusions.

The transformation of Lennert's lymphoma into histiocytic lymphoma appears to be part of the natural history of the disorder rather than therapeutically induced. Unusual paranuclear nonmembrane-bound filamentous inclusions were found in many of the neoplastic cells in the histiocytic lymphoma. We report evidence for the immunoglobulin nature of this material, indicating a B cell origin of the neoplasm.

Abdominal Neoplasms↗
PubMed1997

Somatic mutations of the translocated bcl-2 gene are associated with morphologic transformation of follicular lymphoma to diffuse large-cell lymphoma.

BACKGROUND: Ninety percent of low-grade follicular lymphomas (FLs) carry the t(14;18) translocation. This event juxtaposes the bcl-2 oncogene to the immunoglobulin (Ig) heavy-chain gene and leads to bcl-2 gene overexpression. Morphologic transformation of FL to high-grade lymphoma is associated with multiple secondary chromosomal abnormalities of the neoplastic cells. DESIGN: To analyze whether additional structural alterations of the translocated bcl-2 gene are associated with morphologic transformation of FL, we PCR-amplified, cloned, and sequenced the major breakpoint region (MBR) and the open reading frames (ORF) of the translocated bcl-2 oncogene in six paired samples of FL and subsequent diffuse large-cell lymphoma (DLL). RESULTS: In five cases, FL and DLL cells were clonally related, as suggested by the identical MBR sequences, but in one case they were different. PCR single-strand conformation polymorphism (SSCP) and sequence analyses were performed for identification of structural alterations of the bcl-2 gene in the OFR region corresponding to the 239 amino acid p26-bcl-2a protein. In three of the six patients, a total of 11 point mutations of the ORF were detected in the DLL cells. Four of them, at positions 29, 46, 59, and 106, yielded amino acid replacements. CONCLUSIONS: These findings demonstrate that FL and DLL cells may be clonally related or unrelated. They also show that transformation of FL cells can be associated with somatic point mutations of the bcl-2 oncogene ORF sequence resulting in alteration of the p26-bcl-2a gene product.

Base Sequence↗