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PubMed2006

A variant chronic B-cell lymphoma characterized by villous cells with novel immunophenotypic and cytogenetic profiles.

The less common chronic B-cell lymphomas include hairy cell leukemia, hairy cell leukemia variant and splenic lymphoma with villous lymphocytes. These disease entities can sometimes cause a diagnostic dilemma; however, immunophenotypic markers have been identified as disease specific and scoring systems have been proposed to assist the process. This study reports a case of a chronic B-cell lymphoma with long cytoplasmic projections which does not fit into any of the published disease categories based upon a combination of clinical and morphological features and immunophenotyping. Furthermore, this case featured a combination of cytogenetic abnormalities not previously described in the published literature in association with a B-cell lymphoproliferative disorder.

Cell Surface Extensions↗

PubMedDate not supplied

A web-based database for diagnosis of haematologic neoplasms using immunophenotyping by flow cytometry.

The interpretation of immunophenotyping results by flow cytometry involves pattern recognition of different haematologic neoplasms that may have similar immunologic marker patterns. The numerous markers available in the flow cytometry laboratory make these patterns difficult to remember, especially for those of uncommon neoplasms. We describe the design and implementation of a Web-based database for diagnosis of haematologic neoplasms using results of immunophenotyping by flow cytometry. This database aims to assist pathology and haematology residents in interpreting flow cytometry data, and is designed to reach a wide base of users who use a variety of browsers on different computer platforms. Five modules are developed in this comprehensive program: (a) differential diagnosis: to generate a list of differential diagnoses that closely match the marker results in a given case; (b) display of disorders: typical results of markers for each disorder; (c) display of markers: relevant information of each immunologic marker; (d) display of archived cases for a disorder: marker results of cases previously diagnosed for a disorder; and (e) display of summary for archived cases: summary of marker results of all the archived cases for each disorder. Our experience with this Web-based database in teaching pathology residents has been very encouraging. Since the World Wide Web is increasingly more accessible to computer users, it has become an ideal medium for distribution of clinical decision-support software.

Antigens, CD↗

PubMed2004

Immunophenotypic and molecular studies in the diagnosis and classification of malignant lymphoma.

Immunophenotypic and molecular studies play an increasingly important role in the diagnosis and classification of lymphoid neoplasms. These studies are not yet a substitute for expert histopathologic evaluation, but are a valuable adjunct to the examination of the hematoxylin and eosin-stained slide. Major applications include determination of lineage, determination of B and T cell monoclonality, detection of oncoprotein expression, and detection of oncogene rearrangements and chromosomal translocations. The recognition of the lymphomas as distinct biologic entities with specific immunophenotypic and genotypic features, as embodied in the Revised European-American Lymphoma (REAL) and World Health Organization (WHO) classifications, is a key to the future development and application of targeted biologic and molecular therapies. In the future, application of gene expression array analysis to the lymphoid neoplasms will permit classification of the lymphomas at a molecular level.

B-Lymphocytes↗

PubMed2002

Distribution and immunophenotype of DC-SIGN-expressing cells in SIV-infected and uninfected macaques.

DC-SIGN (dendritic cell-specific ICAM-3 grabbing nonintegrin), an external C-type lectin expressed on dendritic cells (DCs), has been proposed to play a pivotal role in trafficking HIV/SIV from mucosal surfaces to lymphoid tissues. Although the location of DC-SIGN expression has been established in a limited number of human tissues, its distribution in the rhesus macaque has not yet been determined. This study characterized the distribution and immunophenotype of DC-SIGN-expressing cells in SIV-infected and uninfected macaque tissues by immunohistochemistry (IHC) and confocal microscopy. IHC, using monoclonal and polyclonal antibodies against DC-SIGN, was performed on a variety of tissues. To further define the immunophenotype of DC-SIGN(+) cells, double-labeling with antibodies to CD68, fascin, and HLA-DR was done. In both infected and uninfected macaques, DC-SIGN(+) cells were located within the submucosa and lamina propria of tongue, vagina, rectum, and tonsil; however, no positive cells were present within the epithelium of any tissue. Antibodies to DC-SIGN also labeled Kupffer cells within the liver and scattered perivascular cells in the brain. Within lymph nodes, numerous positive cells were present within sinusoids in addition to cells consistent with interdigitating reticular cells in the paracortex and scattered follicular dendritic cells within germinal centers. In spleen of uninfected macaques, there was a similar distribution of DC-SIGN(+) cells with sinusoidal, marginal zone, and interdigitating dendritic cells staining; however, there was a marked paucity of staining in the spleens of SIV-infected macaques. DC-SIGN(+) cells were consistently CD68(+), but fascin(-) and HLA-DR(-). The absence of intraepithelial DC-SIGN-positive cells in mucosal tissues suggests that DC-SIGN does not play a significant role in transmucosal passage of HIV/SIV.

Animals↗

PubMed2002

Acute promyelocytic leukemia M3: cytomorphologic, immunophenotypic, cytogenetic, and molecular variants.

Acute promyelocytic leukemia (APL) M3 is an acute myeloid leukemia (AML) subtype characterized by proliferation of malignant promyelocytes with mature myeloid immunophenotype and the translocation t(15;17)(q22;q11), which results in the fusion of retinoic acid receptor-alpha (RARalpha) gene on chromosome 17 and the gene PML on chromosome 15. There are three M3 morphologic variants: the typical hypergranular form and the microgranular and basophilic variants. Although most leukemic cells in M3 patients express t(15;17), other cytogenetic abnormalities have also been reported. Also, there are three molecular variants of the PML/RARalpha transcript (bcr1, bcr2, bcr3). Blasts had typical hypergranular appearance (13 patients) with a mature myeloid immunophenotype (HLA-DR(-),CD13(+), and/or CD33(+)) (10 patients) in the majority of patients with M3 followed in this study. The typical translocation [t(15;17)(q22;q11)] was detected by cytogenetic analysis in 5 M3 patients, but PML/RARalpha was positive in 13 out of 15 patients, as assessed by RT-PCR (8 patients with bcr1 and 5 with bcr3 subtype). Cytogenetic diversity was found in three patients (1 with t(17;17), 1 with +8, and 1 with add (7)(q22); -7; +8). According to many studies, leukemic cell heterogeneity in APL influences the clinical outcome of disease. The analysis of certain leukemic cell characteristics on the clinical outcome in our study revealed that patients with bcr3 had shorter medians of first remission and survival in comparison to patients with the bcr1 isoform of PML/RARalpha. Also, the clinical relapse of disease in 4 APL patients with reverted PML/RAR alpha positivity is consistent with the view that detection of PML/RARalpha by RT-RCR in patients in remission implies a poor prognosis. On the contrary, lack of detection of PML/RARalpha by RT-PCR at least three times is a sign of long remission and survival.

Adult↗

PubMed1993

Simultaneous genotypic and immunophenotypic analysis of interphase cells for the detection of contaminating maternal cells in cord blood and their respective CFU-GM and BFU-E.

Contamination of cord blood (CB) specimens by maternal blood provides a source of cells that may be capable of graft-versus-host reactivity. To confirm the genetic purity of collected CB samples (six samples, volume 110 +/- 21 ml, total nucleated cells 1.22 +/- 0.36 x 10(9)) the HLA-DR beta exon 2 for the noninherited material allele was examined by polymerase chain reaction amplification. No maternal cell contamination was detected in samples of 1 x 10(5) cells. In the case where the mother was homozygous for DR and DQ, the purity of the sample could not be tested by PCR and therefore in situ hybridization on interphase cells with a fluorescein labeled Y- and X-probe in male CB specimens was performed. This sensitive method also revealed no contamination of the CB by maternal white cells. In addition, picked CB-CFU-GM and BFU-E colonies (cultured in hu-SLF, GM-CSF, and Epo) were analyzed by simultaneous genotypic (for Y and X) and immunophenotypic analysis (monoclonal antibodies [MAbs] CD13, CD14, CD2, CD8, CD4, and glycophorin A). This approach permits simultaneous visualization of both the immunophenotype (MAbs, APAAP, red fluorescence) and the genotype (chromosomes, fluorescein isothiocyanate, green fluorescence) within the same cell. In contrast to PCR and restriction fragment length polymorphism, this method has the advantage that the donor-recipient origin of each lymphohematopoietic lineage (i.e., BFU-E, CFU-GM, T cells, B cells) can be determined in sex-mismatched transplantations. Thus confocal scanning laser microscopy is most suitable not only for the detection of contaminating maternal cells, but also for the detection of mixed hematopoietic chimerism after transplantation.

Adult↗

PubMed1993

Diffuse low-grade B-cell lymphomas. Four clinically distinct subtypes defined by a combination of morphologic and immunophenotypic features.

The authors studied 56 cases of diffuse low-grade B-cell lymphoma using frozen tissue sections and a large panel of monoclonal antibodies that distinguish subsets of normal B cells. They compared the immunophenotypes with the histologic subtypes defined by the Rappaport classification, Working Formulation, and Kiel classification to correlate antigen expression with the morphologic subtypes defined in these classification schemes and to define the contribution of immunophenotype to clinically relevant subclassification. All categories in all classifications showed some heterogeneity of antigen expression; however, antigen expression correlated better with four major subgroups defined by the Kiel classification: (1) CD5+ CD10- CD23+ CD43+: chronic lymphocytic leukemia (CLL); (2) CD5+ CD10-/+CD23- CD43+: centrocytic (mantle cell) lymphoma; (3) CD5- CD10+/- CD23-/+ CD43-: centroblastic/centrocytic (CB/CC) lymphoma; and (4) CD5- CD10- CD23-/+CD43-/+: immunocytoma, mucosa-associated lymphoid tissue (MALT)-type, and monocytoid B-cell lymphoma. These subgroups had distinctive clinical features. Patients with centrocytic lymphoma were predominantly male (5.5:1) and had a significantly worse probability of survival than those with either CLL or MALT-type lymphoma (P = 0.001). The group with CB/CC lymphoma had an equal male-female ratio and an intermediate prognosis. Most patients with MALT-type and nodal monocytoid B-cell lymphomas were female (2:1); the disease-free survival for patients with extranodal MALT-type lymphoma was significantly better than that for all patients with other lymphoma subtypes except CB/CC (P < 0.01). The group with non-MALT immunocytoma had a slight male predominance, a high frequency of monoclonal gammopathy, and an intermediate prognosis. In differential diagnosis, CD23 was useful in distinguishing B-cell CLL from centrocytic lymphoma (P < 0.0001); CD5 (P < 0.0001), CD6 (P < 0.005), and CD43 (P < 0.0001) distinguish centrocytic lymphoma from CB/CC lymphoma; and CD10 (P < 0.005), CD43 (P = 0.06), Leu-8 (P = 0.08), and Ig heavy chain (P = 0.01) may help distinguish CB/CC lymphoma from immunocytoma, monocytoid B-cell lymphoma, and MALT-type lymphoma. Differences in antigen expression and clinical features among these Kiel classification subgroups suggest that they represent distinct biologic entities. The Working Formulation categories do not delineate these diseases clearly.

Adult↗

PubMed1994

Molecular genetic, cytogenetic, and immunophenotypic analyses in Castleman's disease of the plasma cell type.

Systemic Castleman's disease shows characteristic morphologic features in the lymph node and laboratory findings, but patients with this disease have variable clinical courses. The disease may constitute a spectrum of benign to malignant diseases. Thus, the clonal nature of the proliferating lymphoid cells was determined to obtain further insight into the malignant process of the disease. Two cases of systemic Castleman's disease were evaluated immunophenotypically, immunogenotypically, and cytogenetically. Both patients had a chronic relapsing clinical course. One patient had a clonal rearrangement of the immunoglobulin (Ig) lambda chain gene, but no restriction of the light chain expression was detected. This patient showed germ-line configurations of the Ig heavy-chain and T-cell receptor (TCR) beta chain genes; no detectable abnormal metaphases in the lymph node were noted. Another patient had predominance of lambda chain-positive plasma cells in the lymph node with a clonal chromosome change, but had germ-line Ig and TCR beta chain genes. The authors identified clonal changes in two cases of systemic Castleman's disease; one had a clonal immunogenotypic change and the other had a clonal cytogenetic change with an Ig light chain deviation. In both cases, however, a discordance of immunogenotypic and immunophenotypic changes was evident. Thus, the alteration may represent a type of lymphoproliferative disorder that lies between benign and malignant diseases.

Castleman Disease↗

PubMed1994

Histiocytic sarcomas and monoblastic leukemias. A clinical, histologic, and immunophenotypical study.

Eight histiocytic sarcomas, identified by examination of more than 2000 malignant lymphomas, are described. For comparison, tumor infiltrates from five monoblastic leukemias were also analyzed. The histiocytic sarcomas were all high-grade malignancies consisting of markedly pleomorphic large cells with many mitotic figures. At presentation, six of the patients had systemic symptoms (fever, fatigue, loss of weight), skin infiltrates, and lymphadenopathy. Despite aggressive chemotherapy, clinical remissions were short, and six patients died of disease .5-48 months (mean, 6.5 months) after diagnosis. The remaining two patients are alive and in partial or complete remission 7 and 12 months after diagnosis. Immunotypic examination showed that all the histiocytic sarcomas were positive for macrophage-related antigens and negative for antigens on B cells, T cells, myeloid cells, epithelial cells, and melanocytes. T-cell receptor and immunoglobulin genes were studied in three cases and were present in a germline configuration. One of the histiocytic sarcomas resembled Langerhans' cells in phenotype and morphology; it was classified as a Langerhans' cell sarcoma. The remaining histiocytic sarcomas did not express accessory cell-associated antigens, but more closely resembled "ordinary" tissue macrophages; they were positive for lysozyme and/or CD68, followed in frequency by CD11c, CD4, CD11b, CDw32, peanut agglutinin receptor, and CD13. Similar features were seen in the monoblastic leukemias. These conditions could only be distinguished from histiocytic sarcoma by clinical and morphologic, rather than immunophenotypic, criteria. Expression of oncoprotein p53 was studied in nine cases and was positive in six of six histiocytic sarcomas and one of three monoblastic leukemias. Rare malignancies show features consistent with the derivation from macrophages. Two entities may be distinguished: those that resemble antigen-presenting accessory cells and those that more closely resemble ordinary tissue macrophages. Recognition of these tumors is important clinically and requires assessment of clinical, morphologic, and immunophenotypic features, supplemented by analysis of T-cell receptor and immunoglobulin genes. Whether (or how) p53 gene mutations are implicated in their pathogenesis will be an important topic for future investigation.

Adolescent↗

PubMed1994

Hematogones in the bone marrow of adults. Immunophenotypic features, clinical settings, and differential diagnosis.

Hematogones (HGs) comprise a B-lineage lymphoid precursor cell population in the bone marrow (BM) that may simulate acute lymphoblastic leukemia or lymphoma. Increased numbers of HGs have been noted in children, but few reports describe their occurrence in adults. We identified 13 adult patients with significant numbers of BM lymphoid cells with the morphologic and immunophenotypic features of HGs. Common features in these patients included (1) presence of small numbers of lymphoid cells in the BM aspirate with morphologic features of HGs; (2) absence of cytologic atypia or abnormal localization of lymphoid cells in the BM biopsy; (3) absence of abnormal morphology or CD10 (common acute lymphoblastic leukemia antigen) expression in circulating lymphocytes; (4) normal BM karyotype; (5) persistence of cytopenia(s) without apparent cause, often for a prolonged period of time; and (6) no evidence of neoplastic marrow involvement, confirmed by clinical follow-up. Flow cytometry demonstrated surface expression of CD10, CD19, a lower percentage of CD20, minimal expression of CD22, and limited but polyclonal immunoglobulin light chain. Nine patients had received previous immunosuppressive therapy or BM transplantation or both, seven for hematolymphoid neoplasia. However, four patients with cytopenias of unknown etiology had no antecedent history of malignancy or marrow suppressive therapy. These findings demonstrate the clinical, morphologic, and immunophenotypic features of HGs in adults, and emphasize the difficulty in distinguishing these cells from residual marrow blasts after chemotherapy.

Adult↗

PubMed1996

Splenic marginal zone cell lymphoma. An immunophenotypic and molecular study of five cases.

Splenic marginal zone cell lymphoma (SMZCL) is a recently described clinicopathologic entity, that is reported to overlap with splenic B-cell lymphoma with villous lymphocytes. The authors describe the clinicopathologic, immunophenotypic, and molecular findings in five cases of SMZCL. There were two males and three females, with a mean age of 68.4 years, who presented with peripheral blood cytopenias and splenomegaly. One patient had an absolute lymphocytosis with many villous lymphocytes. With clinical follow-up of 9 to 37 months, two patients are alive and three patients died of unrelated causes. Splenectomy was done in each patient and the spleens were large, 970-2,400 g. Histologically, the SMZCLs preferentially replaced the marginal and mantle zones with partial or complete replacement of germinal centers in the white pump. The neoplastic cells were predominantly small to medium in size with oval or slightly irregular nuclei and relatively abundant pale or eosinophilic cytoplasm. Immunophenotypic studies demonstrated that the neoplastic cells expressed monotypic immunoglobulin, IgD in four tumors, pan-B-cell antigens, and bcl-2. The tumor cells were negative for the CD2, CD3, CD5, CD10, CD11c, CD25, CD35, CD38, CD45RO, and CD68 antigens, and tartrate-resistant acid phosphatase. Southern blot hybridization revealed immunoglobulin gene rearrangements in all tumors. The major breakpoint region of the bcl-2 gene and the T-cell receptor beta chain gene were in the germline configuration. Polymerase chain reaction studies did not identify the t(14;18) or t(11;14). All cases were negative for p53 protein and single-stranded conformational polymorphism analysis for p53 gene mutations was negative. Our results support the concept that SMZCL is a clinically indolent, low grade B-cell lymphoma that probably arises from splenic marginal zone lymphocytes.

Aged↗

PubMed1997

Association of immunophenotype with cerebrospinal fluid involvement in childhood B-lineage acute lymphoblastic leukemia.

The records of 71 pediatric patients who had B-lineage acute lymphoblastic leukemia (ALL) were studied retrospectively to document the correlation between antigenic phenotype of leukemic blasts in bone marrow (BM) and cerebrospinal fluid (CSF) involvement. Immunofluorescence assay for terminal deoxynucleotidyl transferase (TdT-IF) was used to examine specimens of CSF for the presence (CSF+) or absence (CSF-) of leukemic blasts at diagnosis and at various times after the induction of chemotherapy. The results of immunophenotyping of the leukemic blasts in the BM of the CSF+ and CSF patient groups were then compared, and the relative risk ratio and positive predictive value were calculated for each marker. In addition, other possible prognostic factors, such as gender, race and ethnicity, age, and initial leukocyte count were compared between the two groups. Thirty-eight percent of all patients, including those who had cytologically confirmed cases of CNS leukemia, had TdT+ cells in the CSF at diagnosis or during the course of the disease. No differences were observed between the CSF+ and CSF- groups with respect to clinical and demographic factors. However, the cases of CSF+ leukemia had the almost exclusive expression of cytoplasmic immunoglobulin heavy chain (c mu) or surface CD22 (Leu-14), CD23 (B6), and/or IgM markers, which normally characterize the most developmentally mature members of the B-cell series in BM. The expression of any of these antigenic markers at diagnosis appears to identify at least 88% of cases of B-lineage ALL that have or ultimately may have TdT+ cells in CSE The results of this study therefore may have both basic and clinical implications: The former concerns the mechanisms by which these phenotypically defined forms of ALL invade and persist in the CNS; the latter concerns the utility of routine immunophenotyping of BM blasts at diagnosis to assess the biologic predisposition to CNS involvement in individual cases of ALL.

Adolescent↗

PubMed2000

Recurrences in nodal T-cell lymphoma. Changes in histologic appearance and immunophenotype over the course of disease.

We examined the patterns of relapse or persistence in 37 cases of nodal peripheral T-cell lymphoma (PTCL) to address the morphologic and immunophenotypic findings. Relapses were documented in lymph node (25 cases) and/or a variety of extranodal sites at a mean of 21 months after presentation; several cases recurred as late as 13 years. Persistent bone marrow involvement was a feature of angioimmunoblastic lymphoma (AIL) and histiocyte-rich and small-cell tumors. Relapses in anaplastic tumors often involved unusual extranodal sites. The majority of relapsed PTCLs retained a similar histologic appearance, pattern of nodal involvement, and immunophenotype. Histologic progression, as assessed by increased numbers of large cells, was seen in 3 cases of AIL, in 1 case with an initial small cell morphologic appearance, and in 2 cases of PTCL with an initial mixed small and large cell appearance. Immunostains for T-cell activation markers showed increased immunoreactive cells in 5 of the 6 cases, whereas increased numbers of p53-positive tumor cells were noted in 3 of the 6 cases. The discrete large cell transformation occasionally seen in B-cell lymphoma and extranodal T-cell lymphoma was not observed in these cases.

Adolescent↗

PubMed1991

Immunophenotyping of non-Hodgkin's lymphomas in paraffin-embedded tissue sections. A comparison with genotypic analysis.

Several monoclonal antibodies (MoAbs) are now available for immunophenotyping non-Hodgkin's lymphomas (NHLs) in paraffin-embedded tissue sections. To determine the reliability of these reagents in predicting the genotype, 44 cases of NHL were studied with the alkaline phosphatase-anti-alkaline phosphatase technique with the use of the following MoAbs: leukocyte common antigen (CD45), Mac 387, L26, 4KB5, MB1, MB2, LN2, UCHL1, MT1, and MT2. The lineage of the neoplastic cells was determined in all cases by gene rearrangement studies for immunoglobulin heavy chain and for the T-cell receptor beta-chain. Genotypic results showed B-cell lineage in 33 cases (75%), T-cell lineage in 6 cases (14%), and mixed or undetermined lineage in 5 cases (11%). A concordance of lineage assignment by paraffin section immunophenotyping with gene rearrangement studies was observed in 37 of 39 (95%) lymphomas with an unequivocally defined genotype. MoAb L26 was the most sensitive in detecting B-cell genotype; MoAbs MT1 and UCHL1 were the most sensitive and specific, respectively, in detecting T-cell genotype. The authors conclude that lineage assignment of NHLs in paraffin sections is reflective of the corresponding genotype when an appropriate panel of MoAbs is used.

Antibodies, Monoclonal↗

PubMed1991

Leukemia and lymphoma immunophenotyping in cell smears with immunogold-silver staining.

The potential of the immunogold-silver staining (IGSS) technique for immunophenotyping leukemia and lymphoma cells in cell smears was examined. Peripheral blood, bone marrow aspirates, lymph node biopsy specimens, fine-needle aspirates, and biologic fluids of 83 patients with acute or chronic leukemias, non-Hodgkin's lymphomas, or Hodgkin's disease were labeled. Cell smears, cytocentrifuge preparations, or imprints were fixed, incubated with the reagents, and counterstained with May-Grünwald-Giemsa. Stable immunostaining and good morphologic characteristics allowed accurate cell identification and rapid enumeration of the positive cells. The immunophenotypes obtained with the use of 35 monoclonal antibodies with different specificities were similar to those determined by flow cytometry or immunohistochemical studies on the same samples. This IGSS method was especially useful for the examination of poor samples or complex cell suspensions with rare malignant cells. It could be an alternative to the immunoenzyme methods that generally are used for this purpose.

Antibodies, Monoclonal↗

PubMed1992

The "CD43 only" phenotype. An aberrant, nonspecific immunophenotype requiring comprehensive analysis for lineage resolution.

Paraffin section immunohistology of leukocytic proliferations is a routine method of immunophenotyping in many clinical laboratories. Furthermore, a relatively standard antibody screening panel that includes L26 (CD20), Leu22 (CD43), and UCHL1 (CD45RO) appears to be widely used. Although paraffin section immunophenotyping in general, and this panel in particular, have been shown to be very reliable in defining B-cell lineage, characterization of T-cell lineage is less definitive. This is related primarily to the relatively poor specificity of the commercially available T-cell-associated reagents. CD43 (Leu22) in particular has a broad immunoreactivity profile that has not been stressed adequately in some reports. Seventeen cases with a "CD43 only" phenotype were identified during the last several years while using the relatively standard screening panel mentioned above. These cases were quite heterogeneous with respect to cellular differentiation and most were not T-cell proliferations. Specifically, eight cases were extramedullary leukemic infiltrates (five myeloid, two monocytic, one mixed lineage), four cases were T-cell lymphomas, three cases were B-cell lymphomas and two cases were plasmacytomas. Although CD43 has demonstrable utility in a leukocyte screening panel, this report stresses the aberrancy and lack of specificity of the "CD43 only" phenotype. Caution is recommended in assigning a specific lineage to such cellular proliferations without additional immunologic or genotypic analysis. Recommendations for comprehensive diagnostic evaluation of these proliferations are provided.

Antigens, CD↗

PubMed2003

Age- and sex-specific incidence of childhood leukemia by immunophenotype in the Nordic countries.

BACKGROUND: Studies from various countries have found an increasing incidence of childhood leukemia in recent decades. To characterize time trends in the age- and sex-specific incidence of childhood acute leukemia during the last 20 years in the Nordic countries, we analyzed a large set of population-based data from the Nordic Society of Paediatric Haematology and Oncology (NOPHO) in their acute leukemia database covering a population of approximately 5 million children aged 0-14 years. METHODS: Temporal trends in acute myeloid leukemia and acute lymphoblastic leukemia incidence rates overall and for acute lymphoblastic leukemia immunophenotypes and for specific age groups were analyzed by Poisson regression adjusting for age, sex, and country. All statistical tests were two-sided. RESULTS: We identified 1595 girls and 1859 boys diagnosed with acute lymphoblastic leukemia between January 1, 1982, and December 31, 2001, and 260 girls and 224 boys diagnosed with de novo acute myeloid leukemia between January 1, 1985, and December 31, 2001. No statistically significant change was seen in the overall incidence rate for acute lymphoblastic leukemia during the 20-year study (annual change = 0.22%, 95% confidence interval [CI] = -0.36% to 0.80%). The incidence rate of B-precursor acute lymphoblastic leukemia remained unchanged (annual change = 0.30%, 95% CI = -0.57% to 1.18%) from January 1, 1986, through December 31, 2001. A somewhat lower incidence in the first years of the study period indicated an early increasing incidence of B-precursor acute lymphoblastic leukemia that corresponded to a simultaneous decreasing incidence of unclassified acute lymphoblastic leukemia. Incidences of T-cell acute lymphoblastic leukemia (annual change = 1.55%, 95% CI = -1.14% to 4.31%) and acute myeloid leukemia (annual change = 0.58%, 95% CI = -1.24% to 2.44%) were stable during the study period. CONCLUSION: Incidences of acute myeloid leukemia overall, acute lymphoblastic leukemia overall, and specific acute lymphoblastic leukemia immunophenotypes have been stable in the Nordic countries over the past two decades.

Adolescent↗

PubMed2000

Extranodal marginal zone B-cell lymphoma of the skin: a morphologic and immunophenotypic study of 11 cases.

Extranodal marginal zone B-cell lymphoma (MZBL) is a recently recognized low-grade lymphoma that has been well described in other organs such as the stomach and salivary gland. It has only recently been described in skin, where it may be difficult to distinguish from reactive processes and other types of B-cell lymphoma such as follicle center lymphoma. These cases may have been classified as pseudolymphomas in the past. Extranodal MZBL was referred to as mucosa-associated lymphoid tissue (MALT) lymphoma before the Revised European-American Classification of Lymphoid Neoplasms was published in 1994. Important histologic features that aid in the diagnosis of MALT lymphoma are atypical lymphocytes (centrocyte-like and monocytoid B cells) often admixed with plasmacytoid lymphocytes, a prominent plasma cell component, lymphoepithelial lesions, intranuclear inclusions (Dutcher bodies), and reactive germinal centers that may be colonized by neoplastic cells. Immunophenotypic studies demonstrating a B-cell phenotype, light chain restriction, coexpression of CD43, and staining of atypical lymphocytes with bcl-2 support a diagnosis of MALT lymphoma. We studied 11 cases of extranodal MZBL of the skin from the Armed Forces Institute of Pathology files. There were six women and five men ranging in age from 30 to 69 years (median, 54 years). The anatomical sites included the trunk, head and neck areas, and upper extremities. There were no other sites of disease besides the skin in any of the cases. The follow-up period ranged from 5 months to 8 years (median, 24 months). Histologic results included an atypical lymphoid infiltrate with B-cell phenotype, reactive germinal centers, and a variable plasma cell component in all cases. No Dutcher bodies or lymphoepithelial lesions were noted. Extranodal MZBL of skin is a diagnostic challenge because of a heterogeneous cellular infiltrate that may be interpreted as a reactive process. The most significant neoplasm with which it is confused is follicular lymphoma. It is important to recognize the characteristic histologic and immunophenotypic features of extranodal MZBL so that the appropriate therapeutic approach may be applied.

Adult↗