acid-phosphatase and Lymphoma--B-Cell

Annexin-1 and T-bet are recently described immunohistochemical stains that reportedly assist in the diagnosis of hairy cell leukemia (HCL). Our objective was to assess the sensitivity and specificity of a panel of immunohistochemical stains in distinguishing HCL from other B-cell neoplasms, particularly splenic and extranodal marginal zone lymphomas (SMZL and ENMZL, respectively). The study included 234 bone marrow biopsy specimens: 101 HCL, 13 SMZL, and 10 ENMZL cases were assessed with CD20, tartrate-resistant acid phosphatase (TRAP), DBA.44, a-1, T-bet, and cyclin D1, and 110 control cases were assessed with annexin-1 and T-bet. Our study showed that annexin-1 is a specific and sensitive marker for HCL; however, interpretation is limited by positivity within myeloid precursors. T-bet, DBA.44, and TRAP immunohistochemical stains lack sufficient sensitivity and specificity to differentiate HCL from either form of marginal zone lymphoma. However, our data suggest that the addition cyclin D1 to the immunostaining panel will increase the sensitivity and specificity of HCL diagnosis.

Topics: Acid Phosphatase; Annexins; Antigens, CD20; Bone Marrow; Cyclin D1; Diagnosis, Differential; Humans; Immunohistochemistry; Isoenzymes; Leukemia, Hairy Cell; Lymphoma, B-Cell; Sensitivity and Specificity; T-Box Domain Proteins; Tartrate-Resistant Acid Phosphatase

The differential diagnosis of hairy cell leukemia (HCL) includes HC variant (HC-V) and marginal zone lymphoma (MZL). There is a high sensitivity of combined DBA.44/TRAP-positivity (+) in confirming HCL. A previous study of mucosa-associated lymphoid tissue lymphoma showed DBA.44+ in 10%, TRAP+ in 29%, and DBA.44+/TRAP+ in 5%.. We now study nodal MZL (NMZL) and HC-V.. Two HCL, 2 HC-V, 3 MZL of bone marrow (BM), 2 MZL versus B-cell lymphoma, not otherwise specified (BCL, NOS) of BM, and 4 NMZL and 5 extranodal MZL (EMZL) were stained with DBA.44 and TRAP and reviewed for staining pattern/intensity.. DBA.44 intensely stained all cells in 2/2 HCL, 1/2 HC-V, and 1 EMZL; intensely stained >20% of neoplastic cells (NCs) in 7 MZLs (1 BM, 3 NMZL, and 3 EMZL); and was negative/stained <10% of NCs in 1/2 HC-V, the remaining MZLs (2 BM, 1 NMZL, and 1 EMZL), and 2/2 MZL versus BCL, NOS-BM. TRAP intensely stained all cells in 2/2 HCL, the DBA.44+ HC-V, and 1 MZL versus BCL, NOS-BM; intensely stained >20% of NCs in 1 MZL versus BCL, NOS-BM, 1 MZL-BM, and 1 EMZL; and was negative in the remainder (1 HC-V, 2 MZL-BM, 1 MZL vs. BCL, NOS-BM, the 4 NMZL, 3 EMZL) in which it was able to be performed. There was combined DBA.44+/TRAP+ in 2/2 HCL, 1/2 HCV, 1/3 MZL-BM, and 1/5 EMZL. Only 1 case (MZL vs. BCL, NOS-BM) was TRAP+/DBA.44-.. Although combined intense, diffuse TRAP+/DBA.44+ is highly sensitive for HCL, it is not entirely specific, and may be observed in HC-V and EMZL, further supporting a histogenetic relationship between these entities.

Topics: Acid Phosphatase; Biomarkers, Tumor; Diagnosis, Differential; Humans; Isoenzymes; Leukemia, Hairy Cell; Lymphoma, B-Cell; Ribosomal Proteins; Tartrate-Resistant Acid Phosphatase

Osteolysis and hypercalcemia are observed in 5-15%, and 10%, respectively, of malignant lymphoma patients during their clinical course. However, both osteolysis and hypercalcemia are uncommon at onset of the disease. We encountered a 24-year-old male non-Hodgkin's lymphoma patient who had multiple osteolytic lesion from the onset of the disease and repeated episodes of hypercalcemia during the clinical course. The patient died with refractory disease. We studied the expression of chemokines which might affect bone resorption using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Increased expressions of MIP-1alpha, MIP-1beta and RANKL, which are osteoclast-activating factors, were observed in the RNA derived from the patient's lymphoma cells. The secretion of osteoclast-activating factors such as MIP-1alpha by the tumor cells (and/or bone marrow stromal cells) might be involved in the etiology of osteolysis and hypercalcemia in some malignant lymphoma cases.

Topics: Acid Phosphatase; Adult; Biopsy; Bone Marrow Cells; Bone Resorption; Carrier Proteins; Chemokine CCL3; Chemokine CCL4; Chemokines; Fatal Outcome; Humans; Hypercalcemia; Immunophenotyping; Isoenzymes; Low Back Pain; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Macrophage Inflammatory Proteins; Magnetic Resonance Imaging; Male; Membrane Glycoproteins; Osteoclasts; Osteolysis; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Reverse Transcriptase Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase

Intravascular large B-cell lymphoma (IVL) has been treated as fever of unknown origin (FUO), and many patients have been treated inadequately based on incorrect diagnoses. We previously cares for a patient with IVL who tested positive for prostatic acid phosphatase (PAP), a marker of prostate cancer. Since then, we have regularly examined this mather when IVL was suspected to investigate the usefulness of PAP as a diagnostic marker for IVL. We retrospectively evaluated the usefulness of PAP as diagnostic marker of IVL.. We reviewed the clinical courses of 5 patients with IVL (3 males, 2 females) in comparison with 23 controls with hematologic malignancies other than IVL.. Serum levels of PAP were elevated in all 5 patients with IVL and 2 of the 23 controls. The difference was statistically significant using a chi-squared test (p=0.0002). The sensitivity and specificity of PAP were 100% and 91%, respectively, in the diagnosis of IVL. Its serum levels were closely associated with disease status.. This study suggests that PAP might be a useful marker for the screening and assessment of disease activity and responses to the treatment of IVL.

Topics: Acid Phosphatase; Aged; Biomarkers, Tumor; Case-Control Studies; Clinical Enzyme Tests; Female; Humans; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Protein Tyrosine Phosphatases; Retrospective Studies; Vascular Neoplasms

Intravascular large B-cell lymphoma (LBCL) is a rare and aggressive subtype of diffuse LBCL characterized by disseminated intravascular proliferation of neoplastic lymphocytes. Obstruction of blood flow by tumor cells in a variety of organs can cause an array of clinical changes, including alteration of the neural and spinal system and the respiratory system, as well as skin lesions. It is usually very difficult to diagnose intravascular LBCL in a patient simply from clinical symptoms or laboratory examinations. We here document our findings that serum prostatic acid phosphatase levels in both males and a female (2.2-24.0 microg/L) reflect the presence of intravascular LBCL, changing synchronously in response to chemotherapy. To determine whether prostatic acid phosphatase (PAP) might be a useful tumor marker for early diagnosis, we reviewed five intravascular LBCLs. Immunohistochemically, tumor cells in all cases were positive for anti-PAP antibody. The results were further confirmed in one case by Western-blot analysis and in another by the detection of amplified messenger RNA for PAP in microdissected tumor cells, respectively. PAP has not been detected in 17 lymphomas (diffuse LBCL, 8 cases; follicular lymphoma, 3 cases; T-cell lymphoma, 3 cases; Hodgkin lymphoma, 3 cases) by Western blot analyses. We conclude that serum PAP is a useful tumor marker for intravascular LBCL and that it deserves further investigation in this context.

Topics: Acid Phosphatase; Biomarkers, Tumor; Blotting, Western; Dissection; Female; Humans; Immunohistochemistry; Laser Therapy; Leukocyte Common Antigens; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Protein Tyrosine Phosphatases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vascular Neoplasms

The demonstration of tartrate-resistant acid phosphatase (TRAP) activity has long been a cornerstone in the diagnosis of hairy cell leukemia (HCL). Recently a monoclonal antibody to this enzyme has been developed that can be used in an immunoperoxidase method on paraffin-embedded tissues. By using a peroxidase-labeled streptavidin biotin method, paraffin sections of B5 and formalin-fixed tissue from 86 cases of HCL (41 bone marrow, 36 spleen, 9 liver) were stained with the antibody to TRAP and compared against staining for CD20 (L26) and DBA.44 (DAKO, Carpinteria, Calif). In addition, 193 specimens (127 bone marrow, 42 lymph node, 19 spleen, 5 other) from a variety of neoplastic and nonneoplastic hematologic conditions were stained using the monoclonal antibody to TRAP. For comparison, these cases were also stained with DBA.44. In the cases of HCL, 80 of 86 specimens were immunoreactive for TRAP. While the antibody to TRAP generally stained less than 50% of the hairy cells, CD20 and DBA.44 stained 90% and 50% to 60% of hairy cells, respectively. Two of three cases of marginal zone lymphoma showed weak immunoreactivity to the TRAP antibody. Two specimens from a patient with Gaucher's disease and 8 of 13 cases of mastocytosis also showed positivity to the TRAP antibody in the macrophages and mast cells, respectively. In contrast, staining for DBA.44 was positive in 3 of 9 cases of B-cell large cell lymphoma, 1 of 4 cases of mantle cell lymphoma, and in the paraimmunoblasts of 1 of 7 cases of small lymphocytic lymphoma. Only HCL was TRAP and DBA.44 positive. This antibody to TRAP is a useful addition to the diagnosis of HCL but should be used in conjunction with CD20 and DBA.44. The use of this antibody to determine minimal residual disease after chemotherapy was not addressed.

Topics: Acid Phosphatase; Antibodies, Monoclonal; Biomarkers, Tumor; Bone Marrow; Bone Marrow Neoplasms; Diagnosis, Differential; Gaucher Disease; Humans; Immunohistochemistry; Isoenzymes; Leukemia, Hairy Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Liver; Liver Neoplasms; Lymph Nodes; Lymphoma, B-Cell; Lymphoproliferative Disorders; Macrophages; Mast Cells; Paraffin Embedding; Pathology, Clinical; Spleen; Splenic Neoplasms; Tartrate-Resistant Acid Phosphatase

A new B-cell line (VL51) with cytoplasmic villi was established from a female patient with splenic lymphoma with circulating villous lymphocytes (SLVL). The patient exhibited a clinical picture characteristic of SLVL, including massive enlargement of the spleen. Tartrate-resistant acid phosphatase (TRAP)-negative villous lymphocytes were seen in the peripheral blood, bone marrow (BM) and both red and white pulps of the spleen. Monoclonality of the VL51 cell line was confirmed by clonal genotype abnormalities in the immunoglobulin heavy chain (IgH) gene and the T-cell receptor beta (TCR beta) gene. Evidence for commitment of phenotype of the VL51 cell line to the B lineage was also shown by the immunophenotype, including expression of CD10, CD19, CD20 and surface immunoglobins. The VL51 cells were positive for Epstein-Barr virus nuclear antigen (EBNA). The VL51 cell line is the first SLVL cell line to be established, and it is expected to be useful in clarifying the leukemogenesis of SLVL.

Topics: Acid Phosphatase; Aged; B-Lymphocytes; Female; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; Histocytochemistry; Humans; Immunophenotyping; Isoenzymes; Karyotyping; Lymphoma, B-Cell; Microscopy, Electron; Microscopy, Electron, Scanning; Microvilli; Splenic Neoplasms; Tartrate-Resistant Acid Phosphatase; Tumor Cells, Cultured

A well-demarcated solitary splenic mass (20 x 20 x 15 cm in size) containing hemorrhagic and necrotic foci was observed in a 4-year-old Thoroughbred stallion. Histologically, the mass consisted of lymphoma cells of the diffuse large non-cleaved type, with a high mitotic index and scattered macrophages that formed a starry sky pattern. The lymphoma cells revealed diffuse positivity for acid phosphatase and alpha naphthyl butyrate esterase, and were also positive for intracytoplasmic IgM on occasion, and mostly for proliferating cell nuclear antigen. Ultrastructural examination revealed moderately-developed rough endoplasmic reticulum sometimes with dilated cisternae. Thus, the diagnosis was a primary splenic lymphoma of B cell origin, but the exact reason for the absence of invasive growth or metastasis despite the high proliferative activity of this neoplasm was unclear.

Topics: Acid Phosphatase; Animals; Carboxylic Ester Hydrolases; Horse Diseases; Horses; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Microscopy, Electron; Mitotic Index; Splenic Neoplasms

Bryostatin 1 (Bryo1), a macrocyclic lactone and a protein kinase C activator, is extracted and purified from the marine bryozoan Bugula neritina. In this study we describe its effect on morphology, surface immunophenotype, acid phosphatase (AcP), tartrate-resistant acid phosphatase (TRAP), proliferation and cell cycle of non-Hodgkin's B-lymphoma cell lines representing four differentiation stages. Except for the WSU-BL, a high-grade SCNCL, all other cell lines showed obvious changes in their morphology when treated with 200 nM Bryo1. Phenotypically, a dramatic decrease of CD10 and induction of CD11c and BL7 on some cell lines consistent with further B-cell differentiation was seen. The lines in control cultures showed variable expression of AcP and TRAP. Following treatment with Bryo1, there was a general increase in AcP expression except in WSU-BL line. WSU-FSCCL and WSU-DLCL were TRAP-negative but became TRAP-positive when treated with Bryo1. Cell growth and cycle analysis during treatment of different cell lines revealed evidence of strong, moderate, or no growth inhibition by Bryo1 compared with control cultures. Our results indicate that Bryo1 shows differentiation effects on low-grade FSCCL, intermediate-grade FLCL and high-grade DLCL, and stimulatory or no effect on high-grade SCNCL. Since Bryo1 does not have tumor-promoting activity, it has a potential therapeutic role as a B-cell differentiating agent.

Topics: Acid Phosphatase; Antigens, CD; Antineoplastic Agents; Bryostatins; Cell Cycle; Cell Differentiation; Cell Division; Humans; Lactones; Lymphoma, B-Cell; Macrolides; Phenotype; Tartrates; Tumor Cells, Cultured

Conventional light and electron microscopic studies, together with cytochemical and immunocytochemical staining procedures, were carried out to ascertain whether the lymphomata of four elderly female patients living within 10 kilometers of each other, who presented within a short space of time with massive splenomegaly and varying cytopenia, belonged to any particular subgroup of lymphoma. In each case the lymphoma had a diffuse pattern and mature B cell phenotype. The malignant cells were of uniform cell type, slightly larger than admixed polymorphonuclear leucocytes, and showed minimal nuclear irregularity and positivity for tartrate resistant acid phosphatase (TRAP) staining. Their clinical and morphological features were compared with those of other lymphoproliferative disorders, but while sharing some features in common with each condition, this small group of patients seemed to have a unique combination of findings. The cytopenias of all four responded well after removal of the spleen and their disease has not been aggressive. It is concluded that these patients have a distinct subgroup of lymphoma, which it is important to recognise so that inappropriate use of aggressive cytotoxic drugs can be avoided.

Topics: Acid Phosphatase; Aged; Female; Humans; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Middle Aged; Space-Time Clustering; Splenic Neoplasms; Staining and Labeling; Tartrates