Korean Journal of
Veterinary Service

Canine Mammary Gland Tumor (MGT) stands as the most prevalent type of tumor found in intact female dogs, bearing a malignancy rate within the range of 35% to 50% (Gilbertson et al., 1983). Pluripotent stem-like cells present in the mammary gland facilitate the development of various dysplastic and anaplastic cells within canine MGT (Rybicka and Krol, 2016). The morphological classification of MGT is intricate owing to its carcinogenic properties; nonetheless, simple and complex carcinomas are identified as the primary types of MGT (Goldschmidt et al., 2011). Within the malignant spectrum of MGT, tubulopapillary carcinoma emerges as a less common type of epithelial origin tumor, notable for being less invasive yet more predisposed to metastasize to distant organs (Goldschmidt et al., 2011; Rasotto et al., 2017), underscoring the importance of vigilance for potential recurrence.

Uterine tumors are uncommon occurrences in canines, constituting less than 0.5% of all canine tumors, and predominantly affecting middle-aged to older female dogs that have not undergone spaying (Percival et al., 2018). Among these tumors, leiomyomas are the most prevalent, accounting for approximately 90% of cases, while leiomyosarcomas are exceedingly rare. Leiomyosarcomas exhibit slow growth but have the potential to infiltrate the abdominal cavity (Kazmierczak et al., 2023). Both types of tumors manifest apparent endocrine dependency and are frequently linked to various gynecological conditions, including ovarian follicular cysts, estrogen-secreting tumors, endometrial hyperplasia, mammary hyperplasia, and mammary neoplasia (Pena et al., 2006; Tsioli et al., 2011). Leiomyosarcomas, in particular, can induce abdominal distension, dyspnea, and overall lethargy due to their considerable mass within the abdominal cavity.

Pyometra is characterized by the accumulation of exudate in the uterine lumen and is the most prevalent reproductive disease in canines (Hagman, 2018; Xavier et al., 2023). It usually develops during the luteal phase, with Escherichia coli being the most frequently isolated bacterium (Kassé et al., 2016; Castillo et al., 2018; Rainey et al., 2018; Xavier et al., 2023). Other commonly reported microorganisms include Staphylococcus pseudintermedius and Streptococcus canis (Xavier et al., 2023). Canine pyometra often starts with subtle clinical signs, such as polydipsia, polyuria, and vaginal discharge. Without appropriate treatment, it can progress to peritonitis, sepsis, and multi-organ dysfunction (Hagman, 2022). Overall, it is considered a life-threatening systemic infection (Agostinho et al., 2014; Fieni et al., 2014; Jitpean et al., 2014).

Inguinal hernia involves the protrusion of an organ or tissue through the inguinal canal (Waters et al., 1993). In dogs, inguinal hernias are classified as either congenital or acquired. Congenital hernias have been linked to certain breed predispositions, while acquired hernias are most commonly observed in intact, middle-aged females (Waters et al., 1993). Clinical signs vary depending on the size of the hernia and its contents, ranging from a painless inguinal mass to symptoms associated with incarcerated or nonviable small intestine. When intestinal incarceration is not present, surgical repair is typically considered an elective procedure.

The patient underwent surgical treatment for pyometra, inguinal hernia, and two tumors with cancerous lesions in the mammary gland and uterus. Histopathological examination and morphological classification confirmed the presence of primary malignant tumors arising from two different organs.

A 16-year-old intact female Mixed-breed dog was presented with massive masses in the bilateral 4th and 5th mammary glands. On physical examination, the right mass, measuring 5 cm in diameter, was suspected to be a mammary gland tumor due to its hard consistency and muscle adhesion, while the left mass, measuring 4 cm in diameter, was identified as an inguinal hernia.

Laboratory tests revealed normal biochemistry and electrolyte levels. However, the complete blood count (CBC) showed moderate anemia (RBC 4.67×10⁶/µL [reference range: 5.65∼8.87×10⁶/µL], HCT 26.1% [reference range: 37.3%∼61.7%]) and severe leukocytosis (WBC 24.4×10³/µL [reference range: 5.05∼16.76×10³/µL]), along with severe neutrophilia (NEU 20.24×10³/µL [reference range: 2.95∼11.64×10³/µL]). An increased cCRP level of 55 mg/L (reference range: 10∼20 mg/L) was also identified. Vital signs such as appetite, vigor, and body temperature were normal; however, the blood test results raised concerns about additional infectious diseases.

X-rays identified a right mammary gland tumor, a left inguinal hernia, and what appeared to be a dilated uterus (Fig. 1A). Ultrasound confirmed uterine dilatation and intrauterine exudate, diagnosing pyometra (Fig. 1B). Additionally, considering the medical test results from the previous hospital, along with the clear heart murmur and chest radiographic findings, the patient’s heart disease was classified as ACVIM stage C.

Figure 1. Images of X-ray and Sonography. The masses from the 4th and 5th mammary glands along with inguinal hernia were observed on X-ray (a). Severe dilatation of the uterus was observed through sonography (b).

In this case, the best therapeutic approach was considered to be a right caudal partial mastectomy, repair of the left inguinal hernia, and an exploratory laparotomy, with the possibility of performing an ovariohysterectomy (Fig. 2A). Given the patient’s advanced age, severe heart disease, multiple concurrent disease conditions, and the need for simultaneous surgeries, the challenges associated with anesthesia and surgical procedures were significant. The partial mastectomy and inguinal hernia repair were successfully completed (Fig. 2B). Following this, the exploratory laparotomy was performed and confirmed pyometra and a cervical tumor, and an additional ovariohysterectomy was successfully performed (Fig. 2C). After surgery, the patient experienced complications including pancreatitis, a bloodstream infection, and peritonitis secondary to pyometra, but recovered well after a week of hospitalization.

Figure 2. Tumorectomies for MGT and uterine tumor as well as pyometra and inguinal hernia. All surgical process was done at the same time. Pre-operation (a), exploratory laparotomy (b), and post-operation (c).

Following the surgical intervention, each excised mass underwent histopathological examination (Fig. 3). Upon microscopic inspection, the mammary gland masses exhibited consistent histopathological characteristics, featuring tubular formations of neoplastic cells with papillary structures extending into tubular lumens (Fig. 3A). Notably, the papillae were supported by a delicate fibrovascular connective tissue stroma, indicative of tubulopapillary carcinoma (Fig. 3B). The tumor displayed well-differentiated tubules, moderate pleomorphism of the nuclei, and a low mitotic index, thus classifying it as a Grade II malignancy.

Figure 3. Tumor masses found in the mammary gland (a, b) and uterus (c, d). The lesions are characterized by neoplastic tubuloepithelial cells forming papillae supported by a fine fibrovascular connective tissue stroma (a). There is evidence of well-differentiated tubules, moderate pleomorphism, and a few number of mitotic figures, indicating grade II malignancy (b). The tumor in the uterus consists of interlacing bundles of spindle-shaped or stellate smooth muscle cells with elongated, blunt-ended nuclei (c). Some of the lesions display highly pleomorphic neoplastic cells in a fascicular pattern, often showing bizarre tumor cells with notably large nuclei (arrow), along with numerous mitotic figures (arrowhead) throughout the lesions (d).

The uterine tumor lesions predominantly consisted of spindle-shaped or polygonal cells with abundant cytoplasm and indistinct cell borders (Fig. 3C). The nuclei exhibited significant variability in size and shape, with some appearing cigar-shaped or spindle-shaped, while others were vesicular with indistinct nucleoli (Fig. 3D). Furthermore, scattered throughout the lesions were occasional tumor cells with markedly enlarged nuclei. Immunohistochemical analysis targeting desmin revealed a positive reaction in the neoplastic cells, confirming the diagnosis of leiomyosarcoma (detailed data not provided).

The histopathological examination revealed the coexistence of two distinct malignant tumors in anatomically separate organs: a tubulopapillary carcinoma of the mammary gland and a uterine leiomyosarcoma. As the tumors were found to be unrelated, the case was classified as concurrent primary malignant tumors. However, due to insufficient patient medical history, the specific mechanisms of tumorigenesis could not be elucidated. In the field of clinical oncology, precise classification of a tumor’s origin, stage, and grade is crucial for determining the appropriate therapeutic approach. Distinguishing between primary concurrent tumors and metastatic tumors presents a significant challenge for clinicians, as misclassification may impede effective treatment.

In the present case, the initial treatment plan entailed a partial mastectomy and correction of an inguinal hernia. However, subsequent blood tests and imaging studies revealed the presence of additional uterine tumors and pyometra, necessitating a reevaluation of the treatment approach. Despite the owner’s reluctance to authorize a CT scan, physical examination and ultrasound results indicated an absence of additional lymph node involvement or distant metastasis. Considering the patient’s advanced age and severe systemic condition, characterized by severe heart disease, two malignant tumors, pyometra, and an inguinal hernia, other medical facilities had advised euthanasia due to the substantial risks associated with anesthesia and surgery. It is particularly encouraging to observe the successful recovery of the patient following a series of surgical interventions.

The patient has demonstrated sustained stability, with no evidence of recurrence or distant metastasis for two year, as substantiated by regular physical examinations, radiography, and sonography. Of particular note is the favorable prognosis, considering the 1-year survival rates of 19% for mammary cancer and 75% for leiomyosarcoma (Cohen et al., 2003; Rasotto et al., 2017). This case serves to underscore the clinical significance of employing surgical resection as part of the therapeutic approach for each tumor in cases of concurrent malignancies.

On the basis of these findings, it is believed that this report has contributed substantial insights into the diagnosis and management of concurrent primary malignant tumors. Furthermore, the successful surgical outcome emphasizes the potential benefits of surgical intervention even in advanced-aged canines with concomitant systemic diseases. These results shed light on the possibility of surgical procedures serving as a viable modality for treatment and life extension, providing hope and guidance for clinicians confronted with similar complex cases.

This report was supported by “Regional Innovation Strategy (RIS)” through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (MOE) (2021RIS-002) and Chonnam National University (Grant number: 2023-0874).

No potential conflict of interest relevant to this article was reported.