Changes in bone marrow cellularity may involve all or individual cell lines. Changes in the erythroid or myeloid cell lines may shift the M:E ratio relative to controls. Normal M:E ratios of rats and mice are reported between 0.80 and 2.79, with an average of 1.5, and are dependent on strain and age, stressing the importance of comparing treated animals with concurrent controls. Histologic sections allow for a rough estimate of the M:E ratio to aid in the evaluation of cellularity, while cytologic preparations are needed for a more precise determination of the M:E ratio and evaluation of subtle changes in synchrony of maturation.
Hypercellularity of the bone marrow is recorded in treated animals when there is an increase in hematopoietic cells relative to adipocytes compared with concurrent controls (Figure 2, Figure 4, and Figure 5). Hypercellularity may occur as a nonspecific or direct (e.g., with cytokine administration) response to compound administration but more commonly is due to a regenerative response as a consequence of decreases in peripheral blood cells, recovery from a xenobiotic-induced bone marrow injury, or inflammation. For example, hypercellularity may be secondary to sepsis or a result of blood loss, hemolytic anemia or platelet consumption/destruction. Stimulation to produce more of one cell line can cause increased production of other cell lines, causing an overall increase in bone marrow cellularity. With marked hypercellularity, hematopoietic cells may fill the entire marrow space, even extending through the nutrient foramina.
Clinical, interpretative, or diagnostic terms (e.g., “hyperplasia”) should not be used when recording changes in bone marrow cellularity but rather the descriptive term “hypercellularity” as discussed herein. When changes in cellularity warrant further explanation or are treatment related, they should be described and interpreted in the pathology narrative, where interpretive terms or diagnoses, such as erythroid hyperplasia, can be used in context with other histologic findings, available hematologic data, in-life findings, and bone marrow cytologic (e.g., M:E ratio) or flow cytometric findings.
Cline MJ, Maronpot RR. 1985. Variations in the histological distributions of rat bone marrow cells with respect to age and anatomic site. Toxicol Pathol 13:349-355.Abstract: http://www.ncbi.nlm.nih.gov/pubmed/2422724
Evans GO. 2009. Animal Hematotoxicology: A Practical Guide for Toxicologists and Biomedical Researchers. Taylor and Francis, Boca Raton, FL, 23-42.Abstract: http://www.crcpress.com/product/isbn/9781420080094
MacKenzie WF, Eustis SL. 1990. Bone marrow. In: Pathology of the Fischer Rat: Reference and Atlas (Boorman GA, Eustis SL, Elwell MR, Montgomery CA, Mackenzie WF, eds). Academic Press, San Diego, 315-337.Abstract: http://www.ncbi.nlm.nih.gov/nlmcatalog/9002563
Martin RA, Brott DA, Zandee JC, McKeel MJ. 1992. Differential analysis of animal bone marrow by flow cytometry. Cytometry 13:638-643.Abstract: http://www.ncbi.nlm.nih.gov/pubmed/1451595
Provencher-Bolliger A. 2004. Cytological evaluation of bone marrow in rats: Indications, methods and normal morphology. Vet Clin Pathol 33:58-67.Abstract: http://www.ncbi.nlm.nih.gov/pubmed/15195264
Provencher-Bolliger A, Everds NE, Zimmerman KL, Moore DM, Smith SA, Barnhart KF. 2010. Hematology of laboratory animals. In: Schalm’s Veterinary Hematology, 5th ed (Weiss DJ, Wardrop KJ, eds). Wiley-Blackwell, Ames, IA, 852-887.Abstract: http://vet.sagepub.com/content/40/2/223.1
Regan WJ, Irizarry-Rovira A, Poitout-Belissent F, Bollinger AP, Ramaiah SK, Travlos G, Walker D, Bounous D, Walter G. 2011. Best practices for evaluation of bone marrow in nonclinical toxicity studies. Toxicol Pathol 39:435-448.Abstract: http://www.ncbi.nlm.nih.gov/pubmed/21300792
Saad A, Palm M, Widell S, Reiland S. 2000. Differential analysis of rat bone marrow by flow cytometry. Comp Haemat Int 10:97-101.Abstract: http://link.springer.com/article/10.1007%2Fs005800070016
Travlos GS. 2006. Histopathology of the bone marrow. Toxicol Pathol 34:566-598.Abstract: http://tpx.sagepub.com/content/34/5/566.abstract
Weiss DJ. 2010. Drug-induced blood cell disorders. In: Schalm’s Veterinary Hematology, 5th ed (Weiss DJ, Wardrop KJ, eds). Wiley-Blackwell, Ames, IA, 98-105.Abstract: http://vet.sagepub.com/content/40/2/223.1