Non-resectable bilateral malignant granulosa cell tumor with metastasis in a dog: a case report

Article information

Korean J Vet Res. 2025;65.e7

Publication date (electronic) : 2025 March 31

doi : https://doi.org/10.14405/kjvr.20240066

Young-Tak Cho^1,†, Chang-Hyeon Choi^1,2,†, Keon Kim^1,2, Chang-Yun Je¹, Jae-Beom Joo¹, Seung-Ju Kang¹, Sang-Ik Park^2,3, Woong-Bin Ro^1,, Chang-Min Lee^1,2,

¹Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea

²BK21 FOUR Program, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea

³Department of Veterinary Pathology, College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Korea

^*Corresponding author: Woong-Bin Ro Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Korea Tel: +82-62-530-2872 E-mail: woongbinro@jnu.ac.kr

^*Chang-Min Lee Department of Veterinary Internal Medicine, College of Veterinary Medicine, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 61186, Korea Tel: +82-62-530-2871 E-mail: cmlee1122@jnu.ac.kr

†These authors contributed equally to this work.

Received 2024 November 5; Revised 2025 January 29; Accepted 2025 March 12.

Ovarian tumors account for 0.5% to 1.2% of all neoplasm cases in dogs [1–4]. This low incidence is probably because most dogs are neutered at an early age [2,3]. Breed predilections are hard to discern; however, the Boxer, Poodle, German Shepherd, and Yorkshire Terrier dog breeds seem to be most commonly affected [4]. In dogs, granulosa cell tumors (GCTs) are sex-cord tumors arising from the ovarian gonadal stroma and account for about half the cases of ovarian neoplasms [2,5]. GCTs are usually unilateral, and the left ovary is commonly affected [6,7]. Malignant GCTs are uncommon and have a metastatic rate of less than 20% [3,6]. Histologically, the granulosa cells in this tumor appear normal and are usually arranged as normal graafian follicles and as sheets in poorly differentiated GCTs. The Call-Exner body consists of a radial aggregate of neoplastic cells around an eosinophilic body at the center, which is a good marker for the microscopic diagnosis of GCT [1]. GCTs can be definitively diagnosed through physical examination, histopathologic assessment, ultrasonography, and radiography [6]. The main therapy for ovarian tumors is ovariohysterectomy (OHE) or oophorectomy. The presence of metastasis at surgery determines the prognosis and indication for chemotherapy [5]. This report describes a bilateral malignant GCT, which could not be surgically removed because of metastasis, in a dog with severe abdominal distention and labored respiration.

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.

Fig. 1.

Computed tomography (CT) findings of the abdomen (A, D) and thoracic cavity (B, C). CT revealed cranial deviation of the abdominal organs due to the tumor (white arrows). A and D were obtained in transverse and dorsal planes, respectively. In the thoracic cavity, the image was also obtained in the transverse plane. CT showed enlarged sternal (B, white arrowheads) and tracheobronchial (C, yellow arrowheads) lymph nodes, implying tumor metastasis to the pleural cavity.

Fig. 2.

Postmortem findings of ovary. Postmortem evaluation showed irregular masses in bilateral ovaries.

Fig. 3.

Histopathological examination of the lymph node (A) and right ovary (B). Neoplastic cells invaded the lymphatic and blood vessels (black arrowhead) (A). Tumor metastasized to other organs. Proliferated malignant granulosa cells with tubules and the Call-Exner body were found (yellow arrows) (B). Hematoxylin and eosin stain, scale bars: (A) 50 μm and (B) 10 μm.

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.