Measurements of Heterogeneity of Bone Marrow Cellularity

Introduction: Quantifying cellularity is an integral component of bone marrow examinations. Estimates of marrow cellularity may influence the diagnostic interpretation of bone marrow samples. The accuracy of cellularity estimates may be influenced by the variable distribution of cellular elements within the marrow space. To better understand the degree of heterogeneity of bone marrow cellularity, we undertook a study to quantify the variable distribution of bone marrow cells in bone marrow core biopsies.

Method: 8 gauge bone marrow core biopsies of 20 patients were retrospectively reviewed by 2 hematopathologists (SI,CL). The specimens were recovered from the posterior superior iliac crest using standard technique with 8G Snarecoil biopsy needles by 3 operators (KH, PK, GD). The percent cellularity was determined in sequential 0.2 X 0.4 cm portions of the core biopsies by each of the hematopathologists. Cellularities were recorded in 10% increments.

Results: The mean age of the patients was 73.2 ± 1.8 years. There were 12 males and 8 females. 5 patients had monoclonal gammopathies. Anemia, multiple myeloma and thrombocytopenia were each diagnosed in three patients. 2 patients demonstrated myelodysplasia and 1 patient each had acute leukemia, leukocytosis, non-Hodgkin’s lymphoma and thrombocytosis. The mean white blood cell count, hemoglobin and platelet count were 8.7 (range 3.8–42.8), 12.2 (range 10.1–15.3), and 233 (range 91–226), respectively. The mean length of the core biopsies was 1.78 ± 0.09 cm (range 1.4–3.3) and the median number of 0.2 × 0.4 cm portions examined per core biopsy was 8 (range 5–12). In total, 165 portions were examined by each hematopathologist independently. The cellularity of 12 and 11 portions could not be determined by each of the hematopathologists, respectively, as a result of biopsy artifacts. No core biopsy showed a consistent cellularity within the examined portions, each core demonstrating a range of cellularities. Only 2/20 and 1/20 of the core biopsies, as examined by each hematopathologist, respectively, demonstrated 2 consistent cellularities. A median of 4 different cellularities were identified in each core. The mean range of cellularities of each core’s portions was 43 ± 4.6 %, and 46.5 ± 4.9 %, as determined by the 2 hematopathologists, respectively, which was statistically equivalent (paired t-test p=0.349).

Conclusions:

1. Bone marrow cellularity is heterogeneous.

2. Cellularities of different portions of core biopsies vary significantly.

3. Average differences between minimal and maximal portional cellularities may be as high as 46%.

4. The accuracy of bone marrow cellularity measurements is related to the size of the biopsy specimen.