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PubMed2005

Clinicopathologic, immunophenotypic, and molecular cytogenetic fluorescence in situ hybridization analysis of primary and secondary cutaneous follicular lymphomas.

Although primary cutaneous follicular lymphoma (FL) is considered a distinct variant of FL in the World Health Organization classification ("cutaneous follicle center lymphoma"), its biologic relationship to nodal FL remains controversial. The clinical, morphologic, immunophenotypic, and molecular cytogenetic features of 17 patients with primary cutaneous FL were studied and compared with 16 patients with secondary cutaneous FL. The head and neck region was the most frequent site at initial skin presentation in both the primary and secondary cases. Among the primary cases, 29% of the 31 biopsies were grade 1, 48% grade 2, 13% grade 3, and 10% grade 3 with diffuse large B-cell (DLBCL) areas. Among the secondary cases, 38% of the 29 skin biopsies were grade 1, 45% grade 2, 3% grade 3, and 7% grade 3 with DLBCL areas with two not evaluable. A floral-like pattern was observed in 32% of primary FL but only 5% of secondary cases. Histologic progression was found in 21% of patients. CD10 expression was demonstrated in 90% (27 of 30) of primary cases and 96% (22 of 23) of secondary cases. Bcl-6 was expressed in all cases tested. Bcl-2 expression was detected in 57% (17 of 30) of the primary cases (100% of grade 1, 43% of grade 2, 40% of grade 3), whereas all secondary cases were bcl-2 positive (P=0.0002). The t(14;18) translocation was identified by interphase fluorescence in situ hybridization (FISH) in biopsies from 31% (4 of 13) of the patients with primary FL compared with 77% (10 of 13) of those with secondary lymphoma (P <0.05). Seven of the 17 (41%) patients with primary disease had cutaneous relapse, including 1 who also developed nodal disease. Bcl-2 positivity was seen in 4 of these 7 patients. Eight of the 16 (50%) patients with secondary FL had cutaneous relapse. Primary and secondary cutaneous FL share many clinical and phenotypic features, but primary cases may have some distinctive morphologic features, more frequently lack bcl-2 protein, and often lack the t(14;18) translocation. These findings suggest that primary cutaneous FL are distinctive and often but not always have a pathogenesis different from most of nodal and secondary cutaneous FL.

Adult↗
PubMed1996

Neural network analysis of flow cytometry immunophenotype data.

Acute leukemia is one of the leading malignancies in the United States with a mortality rate strongly influenced by the phenotype. This phenotype is based on detection of cell associated antigens normally expressed during leucopoietic differentiation. In this regard, leukemia classified as lymphoid or myeloid by phenotype is also classified as a candidate for the corresponding chemotherapy protocol. Additionally, the subtype of leukemia based on the degree of differentiation and cell maturity influence prognosis, response to treatment, and median survival times. In this paper, we analyze immunophenotype flow cytometry data toward categorization of leukemia into subcategories based on lineage and differentiation antigen expression. Twenty-eight inputs (derived from the mean fluorescence intensity of up to 27 antibodies, and an additional binary input denoting the past diagnosis of leukemia) are used as input to a neural classifier to categorize a total of 170 cases into the lineage and differentiation categories of leukemia. The neural classifier consisted of a feed forward network trained using back propagation. A complexity regulation term (weight decay) was used to improve the generalization performance of the neural classifier. A training error of 0.0% and a generalization error of 10.3% was obtained for categorization based on lineage, while a training error of 0.0% and a generalization error of 10.0% was obtained for categorization based on differentiation. These results indicate that objective classification of multifaceted phenotypes in leukemia can be achieved for analyzing multiparameter data in flow cytometry and further categorization into the prognostic subtypes.

Adult↗
PubMed1992

CD8+ cutaneous anaplastic large-cell lymphoma: report of two cases with immunophenotyping, T-cell-receptor gene rearrangement and electron microscopic studies.

Two cases are reported of cutaneous anaplastic large-cell lymphoma with the suppressor/cytotoxic (CD8) phenotype. In both cases there was a solitary skin tumour in which there was a dense infiltrate with large irregularly shaped cells which on immunophenotyping expressed CD8. DNA hybridization analysis showed rearrangements of the T-cell-receptor gene in both cases.

Aged↗
PubMed1995

Malignancy-associated multicentric reticulohistiocytosis: a clinical, histological and immunophenotypic study.

The clinical, histopathological, and immunophenotypic characteristics of four cases of malignancy-associated multicentric reticulohistiocytosis (MMR) and one case each of diffuse cutaneous reticulohistiocytosis (DCR) and isolated reticulohistiocytoma (IR), are reviewed. In all four cases of MMR the cutaneous lesions and joint manifestations were judged to be concurrent with the diagnosis of malignancy. Malignancies observed included one case each of pancreatic adenocarcinoma, squamous cell carcinoma of the lung, metastatic melanoma and intraperitoneal grade 4 mucinous adenocarcinoma of uncertain origin. Histologically, all six cases demonstrated the typical changes of a diffuse histiocytic and multinucleated giant cell infiltrate with ground-glass cytoplasm, predominantly in the upper dermis. Immunohistochemical investigation revealed strong cytoplasmic staining with KP-1 (CD68) in all six cases. Prominent membrane staining was noted with leucocyte common antigen (CD45) in four cases (three MMR and one IR), and CD3 in four cases (three MMR and one IR). Weak membrane staining with Leu 22 (CD43) was noted in two MMR cases. UCHL-1 (CD45RO), L26 (CD20), S-100 and BerH2 stains were all uniformly negative. A prominent number of perilesional factor XIIIa-positive dermal dendrocytes were noted in the single case of IR, in contrast with the other five cases. We conclude that MMR, DCR and IR are histopathologically and immunohistochemically similar. The pattern of immunoreactivity observed is consistent with a monocyte-macrophage origin of the infiltrating tumour cells. We emphasize the paraneoplastic association of multicentric reticulohistiocytosis, which we have observed in four of 13 such cases (31%) evaluated at our institution.

Adult↗
PubMed2004

Immunophenotyping of inflammatory cells in lesional skin of the extrinsic and intrinsic types of atopic dermatitis.

BACKGROUND: There is a subgroup of atopic dermatitis (AD) patients with normal total and specific IgE levels and negative skin tests towards common allergens. This form of the disease has been referred to as the 'intrinsic' form of AD. Although previous studies have demonstrated differences in the cytokine profile between the extrinsic and intrinsic subtypes, the pathogenesis of both subtypes of AD remains unclear. OBJECTIVES: To compare the inflammatory micromilieu in both forms of AD. METHODS: Immunophenotyping of the inflammatory cells was performed in lesional and nonlesional skin from 18 patients with extrinsic and 17 with intrinsic AD. RESULTS: Immunohistochemical analysis revealed a high proportion of CD4+ T cells in the dermis, with a similar CD4/CD8 ratio in the two groups. The expression levels of other T-cell markers and epidermal Langerhans cells were increased in both forms of AD. Although the T-cell repertoires in the two subtypes were similar, dermal infiltration of eosinophils and eosinophil granular proteins was more prominent in the extrinsic type than in the intrinsic type. Eotaxin immunoreactivity was also significantly higher in the extrinsic subtype. CONCLUSIONS: The data suggest that although the overall inflammatory microenvironment in the two subtypes appears to be similar, differences in T-cell cytokine production might contribute to the differential tissue eosinophilia in these subtypes.

Adolescent↗
PubMed2004

Syringotropic cutaneous T-cell lymphoma: an immunophenotypic and genotypic study of five cases.

There is uncertainty about the exact nosological relationship between mycosis fungoides, follicular mucinosis, syringolymphoid hyperplasia with alopecia (SLHA) and syringotropic cutaneous T-cell lymphoma (CTCL). We report the clinical, histological, immunophenotypic and genotypic characteristics of a series of five patients (three men and two women) with syringotropic CTCL. We also review the 15 cases of SLHA previously reported in the literature. We conclude that syringotropic CTCL is a distinct clinicopathological variant of mycosis fungoides which may present on its own with characteristic punctate erythema or more commonly in association with folliculotropic lesions. Syringotropic CTCL is characterized histologically by infiltration of sweat glands by atypical lymphocytes in association with syringolymphoid hyperplasia. Cases of SLHA represent a syringotropic form of CTCL in association with follicular involvement, and such cases need to be investigated using T-cell receptor gene analysis of both skin and blood. Only limited conclusions on prognosis can be derived from our preliminary data. However, a review of the literature suggests that the prognosis does not differ significantly from other types of mycosis fungoides of equivalent stage.

Adult↗
PubMed1990

Prognostic importance of immunophenotyping in adults with acute myelocytic leukaemia: the significance of the stem-cell glycoprotein CD34 (My10)

A series of 23 monoclonal antibodies reactive with normal lymphoid and myeloid cells at various stages of differentiation were used to characterize 96 adult patients with acute myelocytic leukaemia (AML), concentrating on the possible role the expression of these antigens may have in predicting response to intensive chemotherapy. Only the expression of CD34 (P = 0.008) and HLA-DR (P = 0.035) was significant in predicting response to therapy; patients with leukaemic cells expressing CD34 (My10) had a complete remission (CR) rate of 59% compared to 87% for those with blasts not expressing the antigen. In a multivariate analysis predicting for CR, the expression of CD34, the disease category (de novo AML versus secondary AML [SAML] or a history of antecedent haematological disorder [AHD]), and WBC were significant covariates. Adjusting for disease category and WBC, patients with CD34-positive AML were one-third as likely to enter CR as with those with disease not expressing the antigen (P = 0.066). Comparison of clinical characteristics between the 58 patients whose leukaemia expressed CD34 and the 33 which were CD34-negative found that patients with CD34-positive AML had a higher incidence of SAML and AHD, a lower WBC at diagnosis, and a more frequent incidence of chromosomal abnormalities involving chromosomes 5 and/or 7. Twenty-eight of these patients also had immunophenotyping performed at relapse. Patients who presented with CD34-positive AML, and entered remission, and then relapsed all recurred with CD34-positive leukaemia; there was no case of CD34-positive AML at diagnosis relapsing with CD34-negative disease. In addition, there were patients presenting with CD34-negative AML and then relapsing with CD34-positive AML. These results suggest that intensive cytoreductive therapy is ineffective against CD34-positive AML. Patients who present with CD34-positive AML may require different therapeutic approaches to completely eradicate their disease.

Adult↗
PubMed1992

Quality assessment of immunological marker analysis and the immunological diagnosis in leukaemia and lymphoma: a multi-centre study. Dutch Cooperative Study Group on Immunophenotyping of Leukaemias and Lymphomas (SIHON).

In order to standardize and assess the quality of immunophenotyping of leukaemias and lymphomas for diagnostic purposes, a cooperative study group in the Netherlands, SIHON, has formulated guidelines for the composition of antibody panels to be applied and guidelines for the interpretation of the marker analysis. To assess the value of these guidelines frozen cell samples of three patients with different haematological malignancies were sent to the 26 participating laboratories twice a year. Here we present the results with respect to the marker analysis and to the immunological diagnosis on 387 samples from 18 patients. A large inter-laboratory variation was seen in the percentage of positive cells for each marker, which influenced the valuation of a marker to be discordant positive in up to 23% and discordant negative in up to 40%. No single major factor could be traced to explain the large variation in the results. However, probably due to the balanced composition of the antibody panel and to the application of the guidelines for interpretation, this variation did not much influence the agreement in immunological diagnosis. In only 13/387 samples (3.3%) differences in the percentage of positive cells caused disagreement in the final diagnosis. In 23 samples (5.9%) the disagreement was due to an incorrect application of the guidelines. Quantitative data of single observations obtained from different laboratories, in which the materials and methods are not standardized, cannot be compared; but standardization of guidelines for marker sets and for interpretation contributes to a high grade of agreement in immunological diagnosis.

Antibodies, Monoclonal↗
PubMed1992

The immunophenotype in infant acute lymphoblastic leukaemia: correlation with clinical outcome. An Italian multicentre study (AIEOP).

A detailed analysis of immunophenotype of 112 infants aged less than 18 months with acute lymphoblastic leukaemia (ALL) was performed. Patients were divided into three groups on the basis of age at presentation (under 6 months: group 1: 6-12 months: group 2; 13-18 months: group 3). There were three cases of T-ALL (2.6%). The proportion of other subtypes was: common ALL in 59 patients (52.68%), pre-B ALL in 15 patients (13.3%), pre-pre-B ALL in 27 (24.1%) and acute undifferentiated leukaemia (AUL) in eight patients (7.14%). In non-T ALL, positivity to CD10 (corresponding to C-ALL and pre-B ALL) was distributed in the three age groups as follows: 38.88% (group I) 65.38% (group II) and 86.36% (group III). Conversely, immature phenotypes (pre-pre-B and AUL) were found more often in the younger patients of groups I and II, as well as anomalous phenotypes, such as the presence of myeloid antigens (MyAg) and of CD7. Prognostic significance was evaluated as event-free survival (EFS) by statistical analysis. A better outcome in CD10-positive ALL than in CD10-negative ones (48% v. 25% of long-term survivors) was demonstrated in all infants. Similarly, EFS was significantly better in MyAg-negative than in MyAg-positive cases. These results were confirmed also when adjusting for white blood cell count. This allowed the identification of CD10-negative, MyAg-positive ALL, which were relatively more frequent in infants and had a poorer clinical outcome with the current therapies. This study stresses the prognostic relevance of the immunological study in infant leukaemias and its utility in choosing different therapeutic modalities for poor risk phenotypes.

Antigens, CD↗
PubMed1993

Immunophenotypic characterization of myelomonocytic cells in patients with myelodysplastic syndrome.

Infections, an important determining factor in the clinical course of myelodysplastic syndromes (MDS), result in activation of myelomonocytic cells. In this study we demonstrate activation-associated immunophenotypic changes of cell surface antigens on monocytes and granulocytes observed in two groups of MDS patients, one with low and another one with high clinical risk, and compared them to healthy individuals. Significantly changed expression of the complement receptors 1 (CD35) and 3 (CD11b), the Fc gamma receptor I (CD64), the leucocyte-homing receptor (CD44) and the activation associated membrane proteins CD67 and M5 were found on monocytes and/or granulocytes of MDS patients. In low-risk MDS patients we observed activation-associated phenotypic changes only in monocytes, whereas in high-risk MDS patients, both monocytes and granulocytes showed such changes. Additionally, we performed respiratory burst experiments and observed an impaired response of monocytes and granulocytes derived from MDS patients. Despite the fact that all patients were free of infection by clinical criteria, cell surface phenotyping as well as the reduced respiratory burst capacity of myelomonocytic cells suggests in vivo preactivation of these cells.

Antigens, CD↗
PubMed1995

Immunophenotype of c-kit cells in normal human bone marrow: implications for the detection of minimal residual disease in AML.

In the present study, seven normal human bone marrow samples from healthy volunteers have been analysed in order to investigate the immunophenotypic characteristics of the normal CD117+ cells and their utility for the detection of minimal residual disease in 71 acute myeloid leukaemia patients. Our results show that most of normal BM CD117+ cells coexpress the HLADR and the myeloid associated CD33 antigen. In addition, almost half of CD117+ cells are CD34+, these cells displaying a different FSC/SSC distribution when compared to the CD117+/CD34- cells. No CD117+/CD15+ and CD117+/CD10+ cells were detected and very few CD117+ cells (< 1 x 10(-3) expressing the HLADR-/CD34-, CD33+/HLADR- and CD34+/HLADR- phenotypes were found to be present in normal BM. In contrast, from the 71 AML patients analysed, 34 had CD117+/CD15+ blast cells and eight had the CD117+ phenotypes detected at low frequencies (< 1 x 10(-3)) in normal BM. In summary, the present study shows that the use of the CD117 antigen in different monoclonal antibodies combinations may be of great help for the detection of minimal residual disease in a high proportion of AML cases, especially in those patients displaying the CD117+/CD15+ phenotype, because cells coexpressing both antigens in normal BM, if present, are at very low frequencies.

Acute Disease↗
PubMed1995

Trisomy 11: an association with stem/progenitor cell immunophenotype.

The clinicopathological features and the prognostic significance of acute myeloid leukaemia (AML) with trisomy 11 are currently unknown. In this study we describe 15 adult AML cases with trisomy 11. Trisomy 11 was the sole chromosomal anomaly in eight cases; the remaining seven cases were characterized by +11 in association with other karyotypic aberrations. Patients ages ranged from 34 to 79 years. 12 patients were male; three were female. Although there was no correlation of trisomy 11 with any specific FAB subgroup [M2 (n = 7), M1 (n = 5), M4/5 (n = 2), M3 (n = 1)] less mature forms predominated. Immunologically, the leukaemic blasts showed a strikingly consistent stem cell phenotype with expression of HLA-DR, CD34 and the myeloid antigens (CD15, CD33 and/or CD13). In addition, two cases expressed the B-cell associated antigen CD19. The presence of trilineage dysplasia, suggesting the presence of an underlying myelodysplasia (MDS), was observed at presentation in five cases; in another case MDS was evident at relapse only. Unexpectedly, MLL gene rearrangements were observed in two of four cases characterized by trisomy 11 as the sole karyotypic abnormality; however, MLL aberrations were not identified in three cases with trisomy 11 accompanied by other karyotypic anomalies. The majority of patients in each subgroup (i.e. those with and without additional cytogenetic abnormalities) achieved a short first complete remission (CR) (mean 8 months) and failed to obtain a second CR. Only one patient in each trisomy 11 subgroup is in a continuous CR for > 34 months. These findings suggest that trisomy 11 leukaemia is characterized by a stem/progenitor cell immunophenotype with poor response to standard chemotherapeutic regimens and an unfavourable prognosis.

Acute Disease↗
PubMed1995

Expression of interleukin-5 receptors on acute myeloid leukaemia cells: association with immunophenotype and karyotype.

Eosinophilia sometimes occurs in acute myeloid leukaemia (AML) and several laboratories have reported that cells with the t(8;21) or structural abnormalities of chromosome 16 can proliferate and differentiate to eosinophils in the presence of IL-5 in vitro. However, cases without these chromosomal abnormalities can also have eosinophilia. We investigated the association between the expression of IL-5 receptor (IL-5R) gene, karyotype and phenotype in 35 patients with AML. All cases expressed the IL-3R but the IL-5R gene was expressed predominantly in leukaemic cells with either t(8;21) or CD4-positive immunophenotype and was associated with the presence of eosinophilia.

Acute Disease↗
PubMed1995

Combined immunophenotyping and in situ hybridization (FICTION): a rapid method to study cell lineage involvement in myelodysplastic syndromes.

We present a study in which we used a recently described method combining fluorescence in situ hybridization (FISH) and immunophenotyping, i.e. FICTION, to assess the involvement of different cell lineages in myelodysplastic syndrome (MDS) with monosomy 7 (-7), trisomy 8 (+8) or loss of Y chromosome (-Y). Blood or marrow smears or cytocentrifuge preparations were stained both by antibodies to granulocytes (CD15), monocytes (CD14), T lymphocytes (CD3), B lymphocytes (CD20) and by probes specific for chromosomes 7, 8 or Y. Of nine cases of MDS with -7, four with +8 and two with -Y studied, none showed lymphocytic involvement by the chromosome abnormality. In contrast, -7, +8 and -Y were found in granulocytes and monocytes in all patients studied, but they involved a variable proportion of those cells. The partial involvement by -7 and +8 seen in some cases suggests that myelopoïesis was only partially clonal in those cases, or that the chromosome abnormality was a secondary event in the MDS process. FICTION therefore appears to be a simple and easily reproducible method that can be used for the assessment of lineage involvement in MDS and other haematological malignancies.

Adolescent↗
PubMed1999

Diversity of leukaemic cell morphology in ATL correlates with prognostic factors, aberrant immunophenotype and defective HTLV-1 genotype.

To investigate the diversity of morphology in adult T-cell leukaemia/lymphoma (ATL) and its possible association with the pathophysiology of ATL, we selected 36 acute cases and 14 chronic cases phenotypically confirmed to have >90% ATL cells in peripheral blood mononuclear cells. Prototype ATL cells were observed in all cases, although the percentage of all lymphoid cells varied considerably (48.9 +/- 23.8 in acute type, 29.6 +/- 18.9 in chronic type; P = 0.015). Chronic lymphocytic leukaemia (CLL)-like morphology with round nuclei was more frequent in chronic type than in acute type (52.0 +/- 24.9% v 16.6 +/- 13.1%; P < 0.0001). Unusual morphology (UM; lymphoblastic, vacuolated, granular pleomorphic or large cells) was more frequent in acute type than in chronic type (20.1 +/- 18.7% v 2.7 +/- 3.2%; P < 0.0001). Furthermore, there were significant negative and positive correlations of % CLL-like cells and % UM cells respectively, with serum LDH level, hypercalcaemia, performance status, and total number of involved lesions. Cases with aberrant immunophenotype (n = 6) or defective HTLV-1 integration (n = 22) showed lower % CLL-like cells and higher % UM cells than other cases, respectively. Cases with >50% CLL-like cells (n = 7; all chronic type) were younger (53.1 +/- 12.2 v 66.9 +/- 10.6 years; P = 0.038) and showed longer acute-crisis free survival (mean: 16.7 v 3. 0 years; P = 0.012) than chronic cases with <50% CLL-like cells. These results suggest that diversity in genotype, phenotype, morphology and behaviour of ATL are closely associated, and that CLL-like morphology is a good prognostic factor for chronic type.

Adult↗
PubMed1995

Nasal T-cell lymphoma: a clinicopathological and immunophenotypic analysis of 13 cases.

Thirteen cases of nasal lymphomas with T-cell or natural killer (NK)-cell phenotype were studied, with attention to clinical presentation and follow-up, the presence of Epstein-Barr virus (EBV) using in situ hybridization (EBER), the immunophenotype, and the presence of cytotoxic granules. All but two patients presented with stage I disease. In three cases local progression resulted in involvement of the central nervous system. When dissemination occurred, this was predominantly to extranodal localizations, in two cases to the skin. Response to therapy was highly variable, but patients treated with radiotherapy with or without additional chemotherapy had a better prognosis than patients treated with initial chemotherapy alone. All lymphomas were associated with EBV, and most cases showed cytotoxic features, ten of which were CD56 positive. In eight cases a T-cell origin was proven, but in five cases a possible NK-cell origin could not be excluded. No clinical differences were seen between true T-cell lymphomas and possible NK-cell neoplasms. Nasal T-cell lymphomas should be considered as a distinct clinicopathological entity, strongly associated with EBV, and with cytotoxic features in most cases. No prognostic parameters were detected to predict dissemination and response to therapy.

Adult↗
PubMed1995

Assessment of cell proliferation in normal and pathological bone marrow biopsies: a study using double sequential immunophenotyping on paraffin sections.

The proliferative activity of the haematopoietic and plasma cells in bone marrow was evaluated under normal and neoplastic conditions, by means of a sequential double immunostaining technique, using monoclonal antibody MIB-1 recognizing the cell proliferation-associated nuclear antigen Ki-67, and antibodies against glycophorin-C, myeloperoxidase, factor VIII-related antigen, and immunoglobulin light chains. Fifty-eight B5 fixed, paraffin-embedded bone marrow biopsies were analysed, including 11 normal controls. 10 cases of myelodysplasia, 14 cases of chronic myeloproliferative disorder, eight cases of acute non-lymphoid leukaemia, and 15 cases of myeloma. In normal marrows, the highest proliferative activity was noticed in the erythroid cells (75% to 95%; mean 90%), in comparison with myeloid precursors (15% to 80%; mean 38%), and megakaryocytes (10% to 20%; mean 14%): no Ki-67 positive plasma cells were found. In all investigated haematological disorders, the expression of MIB-1 by erythroid cells was similar to that observed in controls. Similarly, the percentage of MIB-1 + myeloid precursors in chronic myeloproliferative disorders and myelodysplasia largely overlapped the values observed in normals, and comparable values were also found in the blast cells from acute non-lymphoid leukaemia type M1 and M2. These findings suggest that the evaluation of either erythroid or myeloid proliferative activity is of little value in the differential diagnosis between these myeloproliferative disorders. By contrast, the obvious increase of Ki-67 expression of megakaryocytes in chronic myeloproliferative disorders, with labelling also of micro-megakaryocytes, might sustain the diagnosis in controversial cases. Since cases of mature myeloma showed less than 2% of Ki-67 positive cells, evaluation of proliferative activity is of no value in the differential diagnosis with reactive plasmacytosis. The sequential double immunophenotyping for Ki-67 antigen and for haematopoietic cell lineage-associated markers can be applied in a consistent manner to routine bone marrow biopsies to evaluate proliferating cells in normal and neoplastic conditions.

Adolescent↗
PubMed2003

Variability in immunophenotype in diffuse large B-cell lymphoma and its clinical relevance.

Diffuse large B-cell lymphoma (DLBCL), the single largest category of lymphoma, is a clinically and biologically heterogeneous disease entity. Clinically, patients differ in their mode of presentation and respond variably to therapy. A combination of clinical parameters can be used to predict the patient's response to therapy and survival. The pathological variability of DLBCL is expressed in morphology, immunophenotype, cytogenetic and molecular genetic features. Numerous markers detectable by immunohistochemistry and linked to different aspects of tumour biology have been studied in DLBCL, including lineage-associated and immune markers, proliferation and apoptosis markers, cell adhesion molecules, and more recently stage-specific markers of B-cell differentiation. This review summarizes these studies in regard to their clinical significance and in the light of recent advances in our understanding of the molecular pathology and histogenesis of DLBCL.

Apoptosis↗