What is your diagnosis? Mammary mass in a male dog

A 13-year-old male neutered German Shepherd Dog mix presented to the University of Florida small animal hospital to evaluate a mass associated with the left cranial abdominal mammary gland. The mass was first noticed 1 year before presentation and had grown significantly over the previous 4 months. It was firm, multilobulated, measuring 6.3 × 3.4 × 2.4 cm, and heavily mineralized on radiographs. No pulmonary metastases were detected on thoracic radiographs, and regional lymph nodes palpated normally. Fine-needle aspirate cytology of the mammary mass was submitted for evaluation (Figures 1 and 2). Cytologic interpretation: Epithelial neoplasia with evidence of bone formation and extramedullary hematopoiesis; compatible with mixed mammary tumor. The slides (Figure 3) had moderate cellularity distributed on a pink, stippled proteinaceous background with numerous erythrocytes. Moderate numbers of epithelial cells were arranged in tightly to loosely cohesive sheets, frond-like formations, clusters, and, less commonly, individually. The epithelial cells were cuboidal, polygonal, round, crescent, or spindled in shape with scant to abundant deep blue cytoplasm and distinct cell borders. The cytoplasm sometimes contained many small vacuoles or was markedly distended by one to two large, ballooning vacuoles, which displaced the nucleus peripherally. The nucleus was round, oval, or reniform and measured ~1.5–3×, occasionally up to 5–6×, the diameter of an erythrocyte with coarse chromatin and one to multiple, frequently prominent, large and/or angular nucleoli. Anisocytosis and anisokaryosis were marked with a variable N:C ratio. Occasional binucleated cells and nuclear molding were observed. Other cell populations included frequent non-degenerate neutrophils and erythroid precursors, occasional osteoblasts, few macrophages, and rare megakaryocytes and osteoclasts. The mammary mass was surgically excised and submitted for histologic evaluation (Figure 4), revealing a moderately cellular, poorly demarcated, multinodular, infiltrative, and unencapsulated neoplasm. The neoplasm was composed of both epithelial and mesenchymal elements. The epithelial population formed tubules and papillae of numerous layers of cells, supported by a moderately thick fibrovascular stroma, and comprised only 10% of the neoplasm. These cells had medium to large nuclei with vesicular to stippled chromatin and four mitotic figures per 2.37 mm2. The second population (presumed myoepithelial cells) were polygonal to fusiform with variably distinct cell borders embedded in a prominent fibro-collagenous stroma. Approximately 80% of the neoplasm was replaced by coalescing islands of well-differentiated trabecular bone, which occasionally contained clusters of hematopoietic precursors within intertrabecular spaces and cartilage. Areas of necrosis comprised less than 10% of the neoplasm. Neoplastic cells did not extend to the tissue edges. The final morphologic diagnosis was a mixed mammary carcinoma, Grade II. Additional treatment was deemed unnecessary due to the resolution of local disease and the absence of distant metastasis. The referring veterinarian assumed responsibility for subsequent monitoring, and the dog was lost to follow-up. Mammary tumors are among the most common neoplasms in female dogs, especially when intact or allowed to undergo one or more estrus cycles before spaying; however, they are rare in male dogs.1, 2 When they do occur in males, the majority of mammary tumors are benign, and only a few malignant tumors have been reported.1 Epidemiologic factors appear similar to female dogs, with older and small breed dogs overrepresented, though no association with neuter status has been reported.3, 4 Estrogen and progesterone receptor expression has been found in male mammary tumors. However, the role these hormones play in tumorigenesis is unclear as concurrent conditions that cause hormonal derangements, such as testicular tumors, are only rarely reported.1, 4 Mammary tumors can be diagnostically challenging on cytology owing to the diversity of tumor types and the variability that can be present within a single tumor. This often complicates cytologic evaluation of malignancy as well-differentiated, benign-appearing epithelial cells and pleomorphic, atypical epithelial cells can be seen in the same aspirate.5 Furthermore, histologic evaluation of malignancy often relies on the detection of infiltration, which cannot be evaluated cytologically.2 In this case, there was a concern for malignancy based on the degree of atypia seen in the epithelial population (Figure 1A). However, this was interpreted cautiously for the aforementioned reasons, presuming that they apply equally to male dogs, and because benign mammary tumors are more common in males.1, 3 Epithelial neoplasms are the most common mammary tumor type, which can be further characterized as simple—having only an epithelial neoplastic component, complex—having both epithelial and myoepithelial neoplastic components, or mixed—having the features of a complex tumor plus production of osteoid and/or chondroid matrices.2 Furthermore, in mixed tumors, the osteoid/chondroid matrix may be produced by the myoepithelial neoplastic population, osteoblasts, or chondroblasts.2 When osteoblasts/chondroblasts are recognized cytologically, evaluation of criteria of malignancy should be performed irrespective of the epithelial population because malignant mixed mammary tumors (carcinosarcoma), primary osteosarcoma, and primary chondrosarcoma are all possible.2 The osteoblasts were well-differentiated in this case (Figures 2 and 3), so a benign mesenchymal component was favored. The presence of hematopoietic precursors (Figure 3) further supported a mixed mammary tumor, as this feature has been reported previously, albeit uncommonly.5 This case exemplifies an uncommon presentation of a common tumor and highlights the wide variety of cell populations that can be recognized within these tumors. Understanding different mammary tumor types and their correlation to certain cytologic features was critical to correctly interpreting this complex (or, rather, mixed) tumor in this case. The authors declare that they have no conflict of interest.