Canine mixed mammary tumor with extramedullary hematopoiesis and bone formation

Kristiina Ruotsalo 

Animal Health Laboratory, University of Guelph, Guelph, ON. 

AHL Newsletter 2020;24(2):22. 

Direct smears prepared from a fine needle aspirate of a 1 cm mass associated with the right caudal mammary gland in a 9-year-old intact female, mixed breed dog were submitted for cytological evaluation. The dog was otherwise clinically well. 

The slides contained hemorrhagic backgrounds with limited numbers of epithelial cells present in small cohesive uniform clusters. Limited numbers of plump stromal cells were also present and were occasionally found embedded within lightly eosinophilic extracellular matrix. More intensely-staining eosinophilic matrix associated with low numbers of osteoclasts and osteoblasts, thus suggestive of bone, was also found. Foci of lightly basophilic material consistent with collagen were evident. The most prominent feature of this sample was the presence of numerous hematopoietic precursors. All stages of erythroid and granulocytic precursors were identified, and rare megakaryocytes were noted (Fig.1).  

These cytological features were consistent with a mixed mammary tumor with evidence of extramedullary hematopoiesis and osseous tissue.  

As with all mammary masses, excision and histological evaluation were recommended. Histology confirmed the diagnosis of a mixed mammary tumor containing cartilage, bone, and limited numbers of hematopoietic cells (Fig. 2).  Epithelial cells appeared uniform and exhibited tubular formations with no evidence of invasion into surrounding tissues; thus this tumor was characterized as benign.  

Mixed mammary tumors represent up to 50-65% of canine mammary tumors and contain epithelial, fibroblastic, cartilaginous, osseous and rarely, hematopoietic components.  Mixed mammary carcinomas are rare. Of 384 mixed mammary tumors examined in one study, only 4% exhibited both extramedullary hematopoiesis of all three cell lineages, as noted in this case, as well as the presence of bone. The underlying cause of mammary extramedullary hematopoiesis (EMH) is not known. Several suggested hypotheses include: disruption of the bone marrow (for example related to drug therapy, myelofibrosis, marrow neoplasia) which stimulates circulating stem cells to find a favorable environment and differentiate into hematopoietic cells; and focal tissue insults which might induce the production of growth factors or cytokines that activate stem cells already present in these tumors.  

Cytological evaluation of masses within the mammary chain can be used to rule out inflammation or the presence of other masses of non-mammary origin. However, histological evaluation of all mammary tumors is strongly recommended. Accurate diagnostic cytology of mammary tumors is associated with many challenges. Stromal mammary tumors may exfoliate poorly. The heterogeneous nature of some tumors may result in sampling or exfoliation of only one cell type. Mammary hyperplasia, dysplasia, benign epithelial cell tumors, and well-differentiated carcinomas form a continuum of morphologic appearance, often making cytological differentiation difficult. Inflammation may result in cytological changes which mimic malignancy. Finally, it should be noted that the presence of tissue, lymphatic, or blood vessel invasion by tumor cells, which has been identified as one of the most significant histological criteria of malignancy in canine mammary tumors, cannot be evaluated by cytology.   AHL 

Figure 1. Cytological features of a canine mixed mammary tumor with evidence of hematopoietic cells (open arrow head), extracellular matrix (asterisk) and an osteoclast (arrow). (Photo: R. Egan, AHL).

Figure 2. Histological sections of a benign canine mixed mammary tumor with mammary lobules(arrow, Figure 2A), and marrow amongst trabecular bone (asterisk, Figure 2A). Marrow (open arrow heads, Figure 2B) amongst trabecular bone.  (Photos: R. Egan, AHL; L. Tatiersky, Vetpath Canada).