THE MEGAKARYOCYTIC INDEX:A NEW TOOL FOR THE DIAGNOSIS OF ESSENTIAL THROMBOCYTHEMIA
(Abstract release date: 05/19/16)
EHA Library. Randi M. 06/09/16; 132891; E1342
Prof. Dr. Maria Luigia Randi
Contributions
Contributions
Abstract
Abstract: E1342
Type: Eposter Presentation
Background
The 2008 WHO diagnostic criteria of Essential Thrombocythemia (ET) require the integration of clinical, molecular and histological parameters. Megakaryocytes (Mk) are the mainstay of bone marrow (BM) histological assessment, as they are present at increased numbers and display peculiar cytological features. While the morphology of ET-associated Mk has been widely studied, their objective quantification may prove challenging (e.g. biased count due to variable BM cellularity in patients of different age).
Aims
This study aimed to: (i) identify a quantitative parameter to define the number of Mk, irrespective of BM cellularity; (ii) define a Mk threshold to objectively discriminate between ET from non-neoplastic BM samples.
Methods
The present study considered BM biopsies from: (i) 89 patients with WHO-defined ET; (ii) 6 patients with secondary/reactive thrombocytosis (ST); and (iii) 22 controls with normal platelet counts and no evidence of BM disease. For the aims of this study, each biopsy was assessed for the following histological parameters: (i) BM cellularity; (ii) total number of Mk; (iii) BM biopsy area (as measured by digital imaging techniques). These parameters were used to calculate Mk density (ratio between total number of Mk and BM biopsy area) and its cellularity-normalized value (here referred to as “megakaryocytic index”), calculated as:Total number of Mk/(BM biopsy area) x (BM cellularity)Statistical analysis was performed using one-way ANOVA and ROC curve analysis.
Results
Differences in BM cellularity among ET and control cases were not statistically significant. ET patients had higher values of Mk density and Mk index compared to both ST and normal controls (Table 1) (p<0.01). At ROC curve analysis, Mk density had limited efficacy in distinguishing ET from non-neoplastic BM samples (threshold value: 10.5/mm2; sensitivity: 89.9%; specificity: 90.9%). Better results were obtained with the Mk index (threshold value: 25.5/mm2; sensitivity: 94.4%; specificity: 95.5%).
Conclusion
BM cellularity can greatly vary among patients, mainly as a result of the age-related decrease of hematopoietic elements. This may impair the evaluation of the Mk number (a key feature for the diagnosis of ET and other myeloproliferative neoplasms). Our model allows the quantification of Mk, irrespective of BM cellularity. In particular, a megakaryocytic index ≥25.5/mm2 can sensitively and specifically discriminate between ET and non-neoplastic controls. Poorer results have been obtained by Mk density. In conclusion, the megakaryocytic index may represent a valuable tool for the histological diagnosis of ET.
Session topic: E-poster
Keyword(s): Bone marrow biopsy, Essential Thrombocytemia, Megakaryocyte
Type: Eposter Presentation
Background
The 2008 WHO diagnostic criteria of Essential Thrombocythemia (ET) require the integration of clinical, molecular and histological parameters. Megakaryocytes (Mk) are the mainstay of bone marrow (BM) histological assessment, as they are present at increased numbers and display peculiar cytological features. While the morphology of ET-associated Mk has been widely studied, their objective quantification may prove challenging (e.g. biased count due to variable BM cellularity in patients of different age).
Aims
This study aimed to: (i) identify a quantitative parameter to define the number of Mk, irrespective of BM cellularity; (ii) define a Mk threshold to objectively discriminate between ET from non-neoplastic BM samples.
Methods
The present study considered BM biopsies from: (i) 89 patients with WHO-defined ET; (ii) 6 patients with secondary/reactive thrombocytosis (ST); and (iii) 22 controls with normal platelet counts and no evidence of BM disease. For the aims of this study, each biopsy was assessed for the following histological parameters: (i) BM cellularity; (ii) total number of Mk; (iii) BM biopsy area (as measured by digital imaging techniques). These parameters were used to calculate Mk density (ratio between total number of Mk and BM biopsy area) and its cellularity-normalized value (here referred to as “megakaryocytic index”), calculated as:Total number of Mk/(BM biopsy area) x (BM cellularity)Statistical analysis was performed using one-way ANOVA and ROC curve analysis.
Results
Differences in BM cellularity among ET and control cases were not statistically significant. ET patients had higher values of Mk density and Mk index compared to both ST and normal controls (Table 1) (p<0.01). At ROC curve analysis, Mk density had limited efficacy in distinguishing ET from non-neoplastic BM samples (threshold value: 10.5/mm2; sensitivity: 89.9%; specificity: 90.9%). Better results were obtained with the Mk index (threshold value: 25.5/mm2; sensitivity: 94.4%; specificity: 95.5%).
| Table 1. Histological parameters (mean ± SD) of ET, ST and control marrow biopsy samples | |||
| ET | ST | Controls | |
| Cellularity (%) | 42.6 ± 17.3 | 61.7 ± 13.3 | 34.3 ± 18.8 |
| Mk density (n°/mm2) | 20.7 ± 9.4 | 9.6 ± 3.3 | 6.1 ± 2.9 |
| Mk index | 52.3 ± 24 | 15.3 ± 2.9 | 18.9 ± 5 |
Conclusion
BM cellularity can greatly vary among patients, mainly as a result of the age-related decrease of hematopoietic elements. This may impair the evaluation of the Mk number (a key feature for the diagnosis of ET and other myeloproliferative neoplasms). Our model allows the quantification of Mk, irrespective of BM cellularity. In particular, a megakaryocytic index ≥25.5/mm2 can sensitively and specifically discriminate between ET and non-neoplastic controls. Poorer results have been obtained by Mk density. In conclusion, the megakaryocytic index may represent a valuable tool for the histological diagnosis of ET.
Session topic: E-poster
Keyword(s): Bone marrow biopsy, Essential Thrombocytemia, Megakaryocyte
Abstract: E1342
Type: Eposter Presentation
Background
The 2008 WHO diagnostic criteria of Essential Thrombocythemia (ET) require the integration of clinical, molecular and histological parameters. Megakaryocytes (Mk) are the mainstay of bone marrow (BM) histological assessment, as they are present at increased numbers and display peculiar cytological features. While the morphology of ET-associated Mk has been widely studied, their objective quantification may prove challenging (e.g. biased count due to variable BM cellularity in patients of different age).
Aims
This study aimed to: (i) identify a quantitative parameter to define the number of Mk, irrespective of BM cellularity; (ii) define a Mk threshold to objectively discriminate between ET from non-neoplastic BM samples.
Methods
The present study considered BM biopsies from: (i) 89 patients with WHO-defined ET; (ii) 6 patients with secondary/reactive thrombocytosis (ST); and (iii) 22 controls with normal platelet counts and no evidence of BM disease. For the aims of this study, each biopsy was assessed for the following histological parameters: (i) BM cellularity; (ii) total number of Mk; (iii) BM biopsy area (as measured by digital imaging techniques). These parameters were used to calculate Mk density (ratio between total number of Mk and BM biopsy area) and its cellularity-normalized value (here referred to as “megakaryocytic index”), calculated as:Total number of Mk/(BM biopsy area) x (BM cellularity)Statistical analysis was performed using one-way ANOVA and ROC curve analysis.
Results
Differences in BM cellularity among ET and control cases were not statistically significant. ET patients had higher values of Mk density and Mk index compared to both ST and normal controls (Table 1) (p<0.01). At ROC curve analysis, Mk density had limited efficacy in distinguishing ET from non-neoplastic BM samples (threshold value: 10.5/mm2; sensitivity: 89.9%; specificity: 90.9%). Better results were obtained with the Mk index (threshold value: 25.5/mm2; sensitivity: 94.4%; specificity: 95.5%).
Conclusion
BM cellularity can greatly vary among patients, mainly as a result of the age-related decrease of hematopoietic elements. This may impair the evaluation of the Mk number (a key feature for the diagnosis of ET and other myeloproliferative neoplasms). Our model allows the quantification of Mk, irrespective of BM cellularity. In particular, a megakaryocytic index ≥25.5/mm2 can sensitively and specifically discriminate between ET and non-neoplastic controls. Poorer results have been obtained by Mk density. In conclusion, the megakaryocytic index may represent a valuable tool for the histological diagnosis of ET.
Session topic: E-poster
Keyword(s): Bone marrow biopsy, Essential Thrombocytemia, Megakaryocyte
Type: Eposter Presentation
Background
The 2008 WHO diagnostic criteria of Essential Thrombocythemia (ET) require the integration of clinical, molecular and histological parameters. Megakaryocytes (Mk) are the mainstay of bone marrow (BM) histological assessment, as they are present at increased numbers and display peculiar cytological features. While the morphology of ET-associated Mk has been widely studied, their objective quantification may prove challenging (e.g. biased count due to variable BM cellularity in patients of different age).
Aims
This study aimed to: (i) identify a quantitative parameter to define the number of Mk, irrespective of BM cellularity; (ii) define a Mk threshold to objectively discriminate between ET from non-neoplastic BM samples.
Methods
The present study considered BM biopsies from: (i) 89 patients with WHO-defined ET; (ii) 6 patients with secondary/reactive thrombocytosis (ST); and (iii) 22 controls with normal platelet counts and no evidence of BM disease. For the aims of this study, each biopsy was assessed for the following histological parameters: (i) BM cellularity; (ii) total number of Mk; (iii) BM biopsy area (as measured by digital imaging techniques). These parameters were used to calculate Mk density (ratio between total number of Mk and BM biopsy area) and its cellularity-normalized value (here referred to as “megakaryocytic index”), calculated as:Total number of Mk/(BM biopsy area) x (BM cellularity)Statistical analysis was performed using one-way ANOVA and ROC curve analysis.
Results
Differences in BM cellularity among ET and control cases were not statistically significant. ET patients had higher values of Mk density and Mk index compared to both ST and normal controls (Table 1) (p<0.01). At ROC curve analysis, Mk density had limited efficacy in distinguishing ET from non-neoplastic BM samples (threshold value: 10.5/mm2; sensitivity: 89.9%; specificity: 90.9%). Better results were obtained with the Mk index (threshold value: 25.5/mm2; sensitivity: 94.4%; specificity: 95.5%).
| Table 1. Histological parameters (mean ± SD) of ET, ST and control marrow biopsy samples | |||
| ET | ST | Controls | |
| Cellularity (%) | 42.6 ± 17.3 | 61.7 ± 13.3 | 34.3 ± 18.8 |
| Mk density (n°/mm2) | 20.7 ± 9.4 | 9.6 ± 3.3 | 6.1 ± 2.9 |
| Mk index | 52.3 ± 24 | 15.3 ± 2.9 | 18.9 ± 5 |
Conclusion
BM cellularity can greatly vary among patients, mainly as a result of the age-related decrease of hematopoietic elements. This may impair the evaluation of the Mk number (a key feature for the diagnosis of ET and other myeloproliferative neoplasms). Our model allows the quantification of Mk, irrespective of BM cellularity. In particular, a megakaryocytic index ≥25.5/mm2 can sensitively and specifically discriminate between ET and non-neoplastic controls. Poorer results have been obtained by Mk density. In conclusion, the megakaryocytic index may represent a valuable tool for the histological diagnosis of ET.
Session topic: E-poster
Keyword(s): Bone marrow biopsy, Essential Thrombocytemia, Megakaryocyte
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