Strong Correlation Between Angiogenesis and Macrophage Counts in Waldenstrom’s Macroglobulinemia: Implications into the Biology of the Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5108-5108
Author(s):  
Evangelos Terpos ◽  
Anna Tasidou ◽  
Efstathios Kastritis ◽  
Evangelos Eleutherakis-Papaiakovou ◽  
Dimitrios Christoulas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Strong Correlation ◽  
Hot Spots ◽  
Immunohistochemical Staining ◽  
High Grade ◽  
Microvessel Count ◽  
Santa Cruz ◽  
Bone Marrow Biopsies ◽  
Double Immunohistochemical Staining ◽  
Microvessel Counts

Abstract Angiogenesis represents an essential step of disease progression in several hematological malignancies. A Mayo Clinic study reported that microvessel density (MVD) was increased (intermediate- or high- grade angiogenesis) in 30% of patients with Waldenstrom s Macroglobulinemia (WM), showed only weak correlation with marrow infiltration and had no impact on patients’ survival [Rajkumar et al, Semin Oncol2003;30:262-4]. Macrophage inflammatory protein-1 alpha (MIP-1alpha) is a potent chemoattractant for macrophages, which contributes to increased angiogenesis in malignant diseases, including multiple myeloma. Our group has reported that serum levels of MIP-1alpha are elevated in WM. To further elucidate the role of angiogenesis in WM, we investigated the association between MVD, MIP-1alpha expression and the macrophage numbers in trephine biopsies of 34 patients with newly-diagnosed WM (3 with asymptomatic disease) and 3 with IgM-Monoclonal Gammopathy of Undetermined Significance (MGUS). Bone marrow biopsies were studied using double immunohistochemical staining for CD34 (endothelial cells) and CD68 (macrophages/mast cells) using antibodies from Becton Dickinson, San Jose, CA, USA & Santa Cruz Biotechnology Inc., Santa Cruz, CA, USA, respectively. We have also used double immunohistochemical staining for CD20/MIP-1alpha and for CD138/MIP-1alpha using an anti-MIP-1alpha antibody from Santa Cruz Biotechnology Inc. (Santa Cruz, CA, USA) to evaluate the MIP-1alpha expression by WM cells. Thirteen patients (35%) showed intermediate-grade and 4 (10%) high-grade angiogenesis. All patients with IgM-MGUS and asymptomatic WM had a very low microvessel count (median: 1, range: 1–2), while the median microvessel count for symptomatic WM was 4 (range: 1–8, p<0.01). There was a strong correlation between the grade of angiogenesis (as assessed by the microvessel counts) and the number of macrophages into the “hot-spots” (r=0.823, p<0.0001). Furthermore, statistically significant correlations were observed between the percentage of lymphoplasmacytoid cell infiltration of the bone marrow with microvessel counts (r=0.554, p=0.002) and macrophage numbers into the “hot spots” (r=0.457, p=0.011). WM patients with intermediate or high grade angiogenesis had increased IgM levels (p=0.007), lower hemoglobin levels (p=0.024), and reduced platelet counts (p=0.043), while patients with high-grade angiogenesis had a tendency to higher incidence of lymphadenopathy compared with all others (3/4, 75% vs. 9/33, 27%; p=0.054). There was no correlation between angiogenesis and survival. We have also observed that WM cells of all patients produced MIP-1alpha. CD138 positive WM cells had higher expression of MIP-1alpha compared to CD20 positive WM cells (p=0.001). Patients with increased numbers of CD68 positive macrophages had increased expression of MIP-1alpha by their WM cells (r=0.732, p<0.001). The results of our on going study suggest that WM cells produce MIP-1alpha to attract macrophages in their bone marrow microenvironment. These macrophages seem to play a significant role in the angiogenesis process and are possibly implicated into the biology of WM.

Overall Survival in Acute Erythroleukemia According to Pathologic Features.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2597-2597
Author(s):  
Xiaohui Zhang ◽  
Alan F List ◽  
Rami Komrokji ◽  
Jeffrey E Lancet ◽  
Lynn Moscinski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myeloid Leukemia ◽  
Median Overall Survival ◽  
De Novo ◽  
High Grade ◽  
Bone Marrow Biopsies ◽  
Pathologic Features ◽  
Marrow Cellularity ◽  
Acute Myeloid

Abstract Abstract 2597 Background: Acute erythroleukemia (AEL) is a rare subtype of acute myeloid leukemia (AML), comprising less than 5% of all AML, with a historically poor prognosis. According to the 2008 World Health Organization (WHO) classification, it is characterized by the presence of more than 50% erythroid precursors in the entire cellularity and more than 20% myeloblasts in the non-erythroid cell population. The clinical and pathologic features of this subtype have not been clearly defined, and due to the lack of sufficient clinical data, there are concerns that the current categorization might not truly reflect the differences among the cases and the distinction from myelodysplastic syndromes (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC). We reviewed ten years of AEL cases from the Moffitt Cancer Center (MCC), as well as high grade MDS and AML-MRC with erythroid predominance (>50% of marrow cells), and compared outcome of these cases according to disease subcategory. Methods: Cases from the MCC data base from 2001 to 2011 were reviewed, identifying 77 cases with a bone marrow aspirate fulfilling the WHO criteria for AEL, and 23 cases of high grade MDS with erythroid predominance of more than 50% of cellularity. Pure erythroid leukemia cases were excluded. Upon further review, of the 77 AEL cases, 22 cases (28.5%) were de novo AEL, 27 cases (35%) evolved from antecedent MDS (MDS-AEL), and 28 cases (36.4%) were re-categorized into AML-MRC as shown by subsequent bone marrow biopsies. Pathological data of serial bone marrow biopsies and clinical data were collected. Patient survival was analyzed with Kaplan-Meier method from the date of diagnosis until death from any cause or last follow up visit. Survival curves were compared by the logrank test. Results: The median overall survival of 22 cases of de novo AEL is 25 months, while the median overall survival of 27 cases of MDS-AEL and 28 cases of AML-MRC are both 14 months. Patients with de novo AEL had better prognosis than those with AML-MRC (p=0.03). There were no significant statistical differences in overall survival between de novo AEL and MDS-AEL, or between MDS-AEL and AML-MRC (p=0.49 and 0.2, respectively). The 23 cases of high grade MDS with erythroid predominance have a median survival of 51 months, compared to 26 months for all the analyzed cases of AML with myelodysplastic features, including MDS-AEL and AML-MRC, when the survival durations were calculated from the date of initial MDS diagnosis. When comparing this group of high grade MDS with MDS-AEL or AML-MRC, the differences were not statistically different (p=0.34). We next analyzed survival of the AEL patients according to blast percentage. In this study, an arbitrary myeloblast count threshold of 10% of the overall marrow cellularity was used. Although myeloblast count did not significantly impact survival, when the cases were subcategorized based on the blast counts of serial bone marrow biopsies including those that did not meet the criteria for AEL, survival was significantly better in the patients with blast counts consistently lower than 10% of all bone marrow cellularity (p=0.03). In addition, patients with normal karyotype had significantly better survival than those with complex karyotypes (p=0.0017). Conclusion: Our findings suggest that there are overlapping features among high grade MDS, AEL and AML-MRC. Serial bone marrow biopsies are more critical in establishing a diagnosis and predicting prognosis than blast percentage calculations on a single marrow. Indicators such as complex cytogenetic changes and appropriate blast percentage threshold are necessary to further refine the classification. Disclosures: No relevant conflicts of interest to declare.

Prognostic value of angiogenesis in solitary bone plasmacytoma

Blood ◽  
2003 ◽  
Vol 101 (5) ◽  
pp. 1715-1717 ◽  
Author(s):  
Shaji Kumar ◽  
Rafael Fonseca ◽  
Angela Dispenzieri ◽  
Martha Q. Lacy ◽  
John A. Lust ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progression Free Survival ◽  
Low Grade ◽  
Solitary Plasmacytoma ◽  
High Grade ◽  
Bone Marrow Biopsies ◽  
Free Survival ◽  
Number Of Patients ◽  
Solitary Bone Plasmacytoma ◽  
Prognostic Importance

Angiogenesis plays an important role in the biology of multiple myeloma (MM) and has prognostic importance in this disease. Solitary plasmacytoma is a localized plasma cell malignancy that progresses to MM in a significant number of patients. We examined if angiogenesis is increased in solitary plasmacytoma and if it can help identify patients likely to progress to myeloma. We studied angiogenesis in plasmacytoma biopsy samples and bone marrow biopsies from 25 patients. High-grade angiogenesis was present in 64% of plasmacytomas. In contrast, bone marrow angiogenesis was low in all patients. Patients with high-grade angiogenesis in the plasmacytoma sample were more likely to progress to myeloma and had a shorter progression-free survival compared with patients with low-grade angiogenesis (P = .02). Angiogenesis is increased in solitary plasmacytoma and is a significant predictor of progression to myeloma and provides further evidence of its importance in the pathogenesis of myeloma.

Patterns of Expression of SHP-1 and JAK-2p in Myelodysplastic Syndromes: A Potential New Prognostic Factor.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3430-3430
Author(s):  
Armando V. Mena-Duran ◽  
Lyudmila A. Bazhenova ◽  
Summanuna Togo ◽  
Jose Cervera-Zamora ◽  
Kelly J. Bethel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Statistical Significance ◽  
Previous History ◽  
Specific Gene ◽  
Santa Cruz ◽  
Bone Marrow Biopsies ◽  
Qualitative Variable ◽  
History Of ◽  
Lower Expression

Abstract The protein-tyrosine-phosphatase (PTPase) SHP-1 is expressed almost exclusively in hematopoetic cells. Most growth factor receptors rely on the Jak/Stat pathway for intracellular transduction, to drive specific gene expression which are involved in cell proliferation and differentiation. Abnormal signaling in some of these pathways has been linked to hematopoietic malignancies, like the ALL tel-Jak2 gene fusion. In some other cases activation is mediated by kinases not normally associated with Stats, like abl. Recently several authors have linked dysregulation of PTPases, especially SHP-1, to non-Hodgkin lymphoma, familial polycythemia, chronic neutropenia and AML. There are no reports on expression of SHP-1 in myelodysplastic syndromes. Here we hypothesize that SHP-1 downregulation may play a role in the leukemic transformation of myelodysplastic syndromes and may impact survival. Retrospectively, from January 1990 to January 2004, we studied 45 patients (29 men, 16 women; median age 70 yrs) with myelodysplastic syndromes (5 RA, 3 RAS, 3 RCMD, 9 RAEB-I, 11 RAEB-II, 2 5q-, 2 Unclass, 3 AML, 6 SMDS). Bone marrow biopsies were examined from each patient. 5 μm sections were dewaxed, heated for antigen retrieval in sodium citrate buffer, and immunostained by routine methods. Antibodies against SHP-1 and Jak-2p were purchased from Santa Cruz Biotechnology (Santa Cruz, CA) and Cell Signaling (Beverly, MA) respectively. SHP-1 and Jak-2p expression were evaluated on bone marrow samples as a percentage of positive cells. A percentage between 33 and 66 was considered normal for SHP-1 expression. Jak-2p positivity was defined as normal, if less or equal to 50 % of cells stained positively. Ranges of normal values were derived from healthy controls. With a median follow-up of 65 months, 13 (28%) showed disease progression, 9 of them towards AML. Median OS and EFS were 15 and 12 months respectively. 25 patients have died, mostly of disease related complications. The U-Mann-Whitney test comparing means between patients that progressed and those that did not was only significant (p<0.05) for hemoglobin and erythropoietin levels at diagnosis. A χ2 test failed to detect any qualitative variable at diagnosis associated with progression: only number of platelets and erythroid dysplasia approached statistical significance. Kaplan-Meier analysis showed that TTP was significantly shorter among those with less cytopenias (p=0.023) and previous history of radiation and/or chemotherapy (p=0.034). Overall survival was also worse among those with previous history of radiation and/or chemotherapy (p=0.009), high risk cytogenetics according to IPSS (p<0.001), lower expression of SHP-1 (p=0.03) or a combination of higher expression of Jak-2p plus lower expression of SHP-1 (p=0.0517). Interestingly none of the commonly accepted prognostic methods for MDS (IPSS, FAB or WHO) showed statistical significance in OS in this analysis. In conclusion, immunostaining of SHP-1 of bone marrow biopsies at diagnosis may be a new prognostic marker for MDS patients.

scholarly journals CD34 immunohistochemical staining of bone marrow biopsies in myelodysplastic syndromes

1995 ◽  
Vol 36 (1) ◽  
pp. 1 ◽  
Author(s):  
Yoo Hong Min ◽  
Seung Tae Lee ◽  
Dong Won Min ◽  
Tai Seung Kim ◽  
Chan Hee Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndromes ◽  
Immunohistochemical Staining ◽  
Bone Marrow Biopsies

Visibility Of Bone Lesions In Relapsed Multiple Myeloma Can Be Improved By FDG-PET Scanning

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5323-5323
Author(s):  
Esther G.M. De Waal ◽  
Riemer H.J.A. Slart ◽  
Marnix J. Leene ◽  
Philip M. Kluin ◽  
Edo Vellenga
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Fdg Pet ◽  
Immunohistochemical Staining ◽  
Conflicts Of Interest ◽  
Whole Body ◽  
Bone Lesions ◽  
Bone Marrow Biopsies ◽  
X Ray

Abstract Osseous involvement is one the predominant features of patients with multiple myeloma (MM). Whole body X-ray (WBX) is the standard method for detecting skeleton abnormalities but has limited value in relapsing disease since it cannot make a distinction between old and new active skeleton lesions. Therefore changes in metabolic activity might be a more useful method to detect new skeleton lesions in MM. This can be assessed by [F-18] fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. Consequently WBX and FDG-PET was studied in relapsing MM prior to treatment. In addition immunohistochemical staining on bone marrow biopsies was performed for glucose transport protein (GLUT) 3 expression, micro vessel density (MVD), and vascular endothelial growth factor (VEGF) to demonstrate whether these parameters might be predictive for the in vivo scanning results. This study included 44 patients (median age 62 yr (range 48-78)) with a median of 3.5 (range 2-12) relapses. Thus far 86% of the patients were treated with autologous stem cell transplantation in combination with bortezomib (78%) or lenalidomide (65%). New lesions on FDG-PET were more frequently demonstrated than new lesions on WBX (p=0.00001). In 78% of the patients FDG-PET demonstrated a median of 4 lesions (range 0-22) per patient with a median standard uptake value (SUV) max of 5.7 (range 0-24). In 42% of the patients new X-ray lesions (median 0 (range 0-7)) were demonstrated and these were concordant with the results of FDG-PET. In 5 % of the patients new X-ray lesions were observed without FDG-PET lesions. For the relapsing patients treatment consisted of dexamethasone in combination with bortezomib (65%) or lenalidomide (50%). CR was obtained in 27% of the patients, PR in 39% and progressive disease in 22%. Average time to next treatment (TTNT) was 11.7 months (2-43). However FDG-PET positivity was not predictive for PFS (p =0.55) and OS (p=0.40) neither if PET positivity was defined as more than 3 lesions nor if the cut off value of SUV max > 4.2 was applied. Immunohistochemical staining on bone marrow biopsies (n=20) with CD34 demonstrated a significant increased MVD of 39 ± 54 (mean ± SD, normal bone marrow MVD 3.5 ± 2.9), in particular when clusters of plasma cells were present. These enhanced MVD was associated with a significant increased expression of VEGF and GLUT-3. However MVD (p = 0.16), VEGF (p = 0.70) or GLUT-3 (p =0.70) expression were not predictive for having a positive or negative FDG-PET. In summary, our results demonstrate that FDG-PET is more informative than WBX for detecting skeleton lesions in relapsing MM patients. However, and in contrast to what was previously shown in patients with newly diagnosed MM, FDG-PET it is not predictive for treatment outcome. This might be due to heterogeneity in studied patients and treatments. Disclosures: No relevant conflicts of interest to declare.

Immunohistochemical staining of bone marrow biopsies for detection of occult metastasis in breast cancer

1990 ◽  
Vol 15 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Marie-Christine Mathieu ◽  
Sam Friedman ◽  
Jacques Bosq ◽  
Bernard Caillou ◽  
Marc Spielmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Marrow ◽  
Immunohistochemical Staining ◽  
Occult Metastasis ◽  
Bone Marrow Biopsies

scholarly journals ANGIOTENSIN II TYPE-1 RECEPTOR (AT1R) DISTRIBUTION IN BPH, HIGH GRADE PIN AND ADENOCARCINOMA OF THE PROSTATE

1970 ◽  
Vol 17 (2) ◽  
Author(s):  
Isdianto Septiadi ◽  
Suwandi Sugandi ◽  
Bambang S Noegroho ◽  
Tjahjodjati Tjahjodjati ◽  
Ferry Safriadi ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Immunohistochemical Staining ◽  
Kidney Tissue ◽  
High Grade ◽  
Santa Cruz ◽  
Adenocarcinoma Of The Prostate ◽  
Poorly Differentiated ◽  
A Prospective Study ◽  
Anatomical Pathology

Objective: The aim of the study was to detect the differences in number and the distribution of angiotensin II type-1 receptor (AT1R) in BPH, high grade PIN, and adenocarcinoma of the prostate. Material & method: A prospective study was performed in RSHS, in collaboration with the Department of Anatomical Pathology. Prostate samples were taken by TUR of the prostate, and then divided into 5 groups. They were BPH, high grade PIN, adenocarcinoma of the prostate in 3 difference grades (well, moderate, and poorly differentiated). Kidney tissue for control. Immunohistochemical staining was done to determine the angiotensin II type-1 (AT1R) receptor distribution as primary antibody used was mouse monoclonal antibody AT1 (TONI-1): sc-57036, Santa Cruz Biotechnology Inc., CA. Results: Angiotensin II type-1 receptor was found in material of BPH, high grade PIN and adenocarcinoma of the prostate. The number and distribution of the receptors were not different. Conclusion: There are no significant differences in number and distribution of angiotensin II type-1 receptor on BPH, high grade PIN, and adenocarcinoma of the prostate.

A Challenging Case of A Myeloid Sarcoma Misdiagnosed as High Grade B-Cell Lymphoma

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S97-S97
Author(s):  
A Herrmann ◽  
B Mai ◽  
S Elzamly ◽  
A Wahed ◽  
A Nguyen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Myeloid Sarcoma ◽  
Proliferation Index ◽  
High Grade ◽  
Cell Markers ◽  
Thoracolumbar Region ◽  
The Right

Abstract Introduction/Objective A 46-year-old female presented with severe back pain associated with progressive bilateral lower extremity weakness and paresthesia, urinary retention, and constipation. Computed tomography revealed a retroperitoneal mass encasing the right psoas muscle, obstructing the right kidney, and extending to the thoracolumbar region resulting in severe spinal compression. An epidural tumor resection was subsequently performed at an outside hospital. Methods Histological sections showed sheets of blastoid neoplastic cells with intermediate to large nuclei, irregular membranes, fine chromatin, and prominent nucleoli. Immunohistochemical stains showed that these cells were positive for CD43, CD79a (weak, focal), BCL2, C-MYC, and PAX5 (weak, focal) and negative for CD10, CD20, CD30, ALK1, BCL6, MUM1, and Tdt. The Ki-67 proliferation index was 75-80%. With this immunophenotype, this patient was diagnosed with a high grade B-cell lymphoma and transferred to our institution for further work-up. On review of the slides, further immunohistochemical testing was requested which revealed positivity for CD117 and myeloperoxidase (MPO). Results The overall morphological and immunophenotypical features are most compatible with myeloid sarcoma (MS) with aberrant expression of B-cell markers and this patient’s diagnosis was amended. Interestingly, the patient’s bone marrow examination only showed 2% myeloblasts with left shifted granulocytosis and concurrent fluorescence in situ hybridization (FISH) studies were negative. Conclusion A literature review showed that 40-50% of MS are misdiagnosed as lymphoma. MS can frequently stain with B-cell or T-cell markers, as seen in this case, which makes it challenging for an accurate diagnosis and sub- classification. In addition, our case is interesting in that there was only extramedullary presentation without bone marrow involvement. Typically, MS develops after the diagnosis of acute myeloid leukemia (AML) with an incidence of 3–5% after AML. It can also manifest de novo in healthy patients, who then go on to develop AML months to years later. Therefore, this patient will require close follow-up.

Spironolactone-Induced Agranulocytosis

1997 ◽  
Vol 31 (5) ◽  
pp. 582-585 ◽  
Author(s):  
Anna M Whitling ◽  
Pablo E Pérgola ◽  
John Lee Sang ◽  
Robert L Talbert
Keyword(s):  
Risk Factors ◽  
Adverse Effect ◽  
Bone Marrow ◽  
Leukocyte Count ◽  
Laboratory Data ◽  
University Hospital ◽  
Drug Induced ◽  
Bone Marrow Biopsies ◽  
Case Summary ◽  
Before And After

OBJECTIVE: TO report a case of agranulocytosis secondary to spironolactone in a patient with cryptogenic liver disease. CASE SUMMARY: A 58-year-old Hispanic woman with cryptogenic cirrhosis was admitted to University Hospital on October 31, 1995. Laboratory data revealed a leukocyte count of 1.0 × 103/mm3 and an absolute neutrophil count (ANC) of 10 cells/mm3. Prior to treatment with spironolactone, the leukocyte count was 10.2 × 103/mm3 and ANC 8400 cells/mm3. Agranulocytosis resolved 5 days following the discontinuation of spironolactone. Results from the bone marrow biopsies before and after treatment with spironolactone suggested that agranulocytosis was caused by the drug's toxic effect on the bone marrow. DISCUSSION: Drug-induced agranulocytosis is a serious adverse effect, occurring at a rate of approximately 6.2 cases per million persons each year. In addition to the case reported here, three other reports of agranulocytosis secondary to spironolactone have been published in the literature. Several factors have been identified that may increase a patient's risk for developing agranulocytosis, including increased age, hepatic or renal impairment, drag dosage and duration, and concurrent medications. CONCLUSIONS: Agranulocytosis secondary to spironolactone is a serious potential adverse effect. Patients with risk factors for developing this adverse effect should be closely monitored since early detection and discontinuation of spironolactone can improve prognosis.

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