A 17-year-old, intact female Shih Tzu weighing 9 kg presented with persistent abdominal distension for 1 year and labored respiration for 3 days. Physical examination showed severe abdominal distension, labored respiration, and generalized hyperpigmentation. The submandibular, popliteal, and left prescapular lymph nodes (LNs) were enlarged. Complete blood count (CBC), serum biochemical analysis, thoracic and abdominal radiography, and ultrasonography were performed. CBC showed leukocytosis with a stress leukogram (white blood cell count, 38.42 × 10³/µL; range, 4.0-15.5 × 10³/µL) and thrombocytosis. Serum biochemical analysis showed elevated aspartate aminotransferase (53 U/L; range, 15-43 U/L) and D-dimer (1.0 mg/L; range, 0.1-0.5 mg/L) and reduced alkaline phosphatase (12 U/L; range, 15-127 U/L) and total protein (4.9 g/dL; range, 5.4-8.2 g/dL) levels. Thoracic and abdominal radiography showed pleural effusion, severe ascites, sternal LN enlargement, and complete loss of serosa. Abdominocentesis (twice per liter), thoracocentesis (78 mL) and fluid analyses were performed. Tumor cells were observed in the pleural fluid and ascites. Fluid therapy with oxygen supplementation was performed to stabilize the patient. Clopidogrel (4 mg/kg q24h, Plavix; Sanofi, France), amoxicillin clavulanate (12.5 mg/kg q12h, Clavamox; Zoetis, USA), Liver protectant (0.5 T/dog per day q12h, Zentonil; Vetoquinol, France), and furosemide (1 mg/kg q12h, Lasix; Sanofi) were administered for 3 days. However, the patient developed labored respiration and mouth breathing the day after the discharge. Abdominocentesis (875 mL) and thoracocentesis (400 mL; right, 240 mL; left, 160 mL) were performed. Leukocytosis aggravated (from 32.9 to 57.68 × 10³/µL; range, 4.0-15.5 × 10³/µL), and the D-dimer level worsened (from 1.0 to 1.2 mg/L; range, 0.1-0.5 mg/L). Ultrasonography revealed bilateral masses (irregular margin, mixed parenchyma with cysts) in the ovaries and a positive vascular response. A malignant tumor was suspected, and computed tomography (CT) was performed to detect metastasis. The abdominal organs had deviated cranially because of the mass (Fig. 1A and D). Metastasis in the thoracic cavity was confirmed with sternal and tracheobronchial LN enlargement (Fig. 1B and C) and fluid cytology. Metastatic ovarian adenocarcinoma was tentatively diagnosed. Although OHE is the main therapy for ovarian tumors, because of the severe metastasis, possibility of sudden death during OHE, and poor prognosis, chemotherapy with symptomatic therapy was performed after obtaining informed consent from the owner. The symptomatic therapy consisted of periodic abdominocentesis, thoracocentesis, and administrations of celecoxib (2 mg/kg q12h, Celebrex; Pfizer, USA), clopidogrel bisulfate (4 mg/kg, q24h, Plavix), ranitidine (2 mg/kg q12h, Zantac Tab; Sanofi), furosemide (1 mg/kg q12h, Lasix), liver protectant (0.5 T/dog per day q12h, Zentonil), and amoxicillin clavulanate (12.5 mg/kg q12h, Clavamox). In addition, carboplatin (300 mg/m², intravenous [IV], Zofran Inj.; Novartis, Switzerland) was administered every 3 weeks with premedication, including ondansetron (0.5 mg/kg IV, Zofran; GSK, UK), ranitidine (2 mg/kg, subcutaneous [SC], Zantac Inj.; Sanofi), and chlorpheniramine maleate (0.1 mg/kg SC, Histamin Inj.; Samu Median, South Korea). After chemotherapy, the frequency of draining the fluid from the pleural effusion and ascites were significantly delayed (from 1 to 3 weeks), and the patient's vitality and appetite remained normal for 6 months. Six months after starting the treatment, gastrointestinal symptoms occurred as side effects of the chemotherapy. Therefore, chemotherapy was stopped, and only symptomatic therapy was continued. Subsequently, the frequency of ascites drainage was increased, and the appetite decreased gradually. Approximately 6 months later, euthanasia was performed considering the quality of life (QOL). Postmortem evaluation showed ascites, sternal and mesenteric LN enlargement, masses in the upper abdomen and spleen, and irregular masses in both the ovaries (Fig. 2). Histopathological examination showed no normal structures spared by proliferation of the tumor cells in the right ovary and proliferated malignant granulosa cells with tubules were found. Furthermore, the Call-Exner bodies appeared. In the left ovary, the tumor cells invaded the lymphatic and blood vessels. With the tumor cells in the liver and thoracic LNs, general metastasis was found (Fig. 3). Finally, metastatic malignant bilateral GCT was confirmed.

As ovarian neoplasms are uncommon in dogs, and most reports are necropsy surveys and biopsy submissions, their prevalence is unknown [3,6]. Most GCTs are benign and unilateral [6,7]. About 20% cases of GCTs show metastasis [4,5,8]. Sites of GCT metastasis include the sublumbar LNs, liver, peritoneal carcinomatosis, lung, and pancreas [4,5]. In this case, CT and fluid analysis showed tumor metastasis to the peritoneal and thoracic cavities. In addition, necropsy and histopathological examination revealed GCTs in both the ovaries. The ovarian structure was almost destroyed, except for a few follicles, and there was invasive proliferation. The tumor had considerably advanced; therefore, the follicular pattern, which is seen in normal GCTs, was scarcely observed, and tumor cells formed sheets and strings. Tumor thrombus was found in the blood and lymphatic vessels, which might have spread through blood and lymph. Tumor cells metastasized to abdominal structures, such as the LNs and liver, and proliferated closely. Bleeding and inflammation occurred. Bilateral, malignant, and systemic metastatic GCTs are uncommon. Surgical removal of the affected ovary or OHE together with removal of observable metastatic lesions is the standard treatment of GCTs [6]. If metastatic tumors are non-resectable, a chemotherapeutic regimen may be useful, but standard recommendations are rarely established [6]. In humans, the first-line chemotherapy for ovarian GCTs is commonly a combination of bleomycin, cisplatin, and etoposide. Bleomycin and etoposide are not used in dogs because of adverse effects and toxicities. The use of etoposide is limited in veterinary medicine. If etoposide is intravenously administered, it can cause hypersensitivity reactions [5]. Cisplatin is an active single agent against ovarian neoplasms with a response rate in previously untreated patients of 50% to 65% [9]. Radiation therapy and/or chemotherapy to treat ovarian tumors have not been widely studied in veterinary medicine, so recommendations are difficult [4]. In this case, carboplatin was used for chemotherapy. Compared to cisplatin, it is as active against ovarian carcinoma but less toxic [9]. In a previous case of metastasis found during OHE, chemotherapy was initiated postoperatively. The dog was euthanized after 6 postoperative weeks for inappetence, labored breathing, and the owner’s report of declining QOL [5]. However, since metastasis was detected, surgery was not performed, as recommended. Our patient lived for over a year probably because chemotherapy and symptomatic therapy were performed without OHE.

In this case, severe metastasis indicated poor prognosis for the surgery, so chemotherapy and symptomatic therapy were performed to improve QOL. The patient regained vitality and lived healthy for approximately a year. Therefore, chemotherapy and symptomatic therapy may be performed when surgery is contraindicated for metastatic malignant ovarian tumors.