Long-Term Treatment Results for Ovarian Tumors with Malignant Effusion in Seven Dogs
Surgery and platinum-based chemotherapy are highly efficacious for treating advanced ovarian cancers in humans, but their efficacy is less known in dogs. We evaluated the long-term treatment outcomes of seven dogs with malignant ovarian tumors with malignant abdominal effusion. Ovariohysterectomies (OVHs) were performed on all dogs; four had ovarian adenocarcinoma (AC) with gross dissemination in the peritoneum (two with pleural effusion), and three had a granulosa cell tumor (GCT) with no gross dissemination in the peritoneal cavity, although one showed pleural effusion. Effusion resolved after the OVH in all dogs. Six dogs (three ACs, three GCTs) received postoperative IV carboplatin therapy. Two dogs with GCT had no postoperative recurrence or metastasis, and one dog with GCT had recurrence 1811 days postoperatively. All dogs with AC developed recurrent effusion 171–584 days postoperatively, which resolved after intracavitary administration of cisplatin or carboplatin, with a subsequent disease-free interval of 155–368 days. Overall survival was longer for dogs with GCTs (822–1840 days) than for those with ACs (617–841 days). These results suggest that dogs with ovarian tumors with malignant effusion can survive relatively long after platinum-based chemotherapy in addition to OVH, with a more favorable prognosis for GCT than AC.
Introduction
Ovarian tumors account for 0.5–1.4% of all canine tumors1 but are common in sexually intact bitches. Studies have found ovarian tumors in 6.3% of necropsies of intact bitches2 and in 6.6% of healthy bitches undergoing an ovariohysterectomy (OVH).3 Ovarian tumors have been classified into epithelial, sex-cord, germ-cell, and mesenchymal tumors1; epithelial tumors account for 36–44%,2,4–6 and granulosa cell tumors (GCTs), included in sex-cord tumors, account for 17–52%.2,4–6
The malignancy rate among ovarian epithelial tumors varies among reports; adenocarcinomas (ACs) accounted for 64% in one study6 and 9–20% in other studies.2,4,5 Most GCTs are benign, and malignant behavior was identified in only 11% of cases (8/70). 2,4–6 Malignant ovarian tumors tend to metastasize as peritoneal dissemination regardless of tumor type.2,4–6 Abdominal effusions associated with ovarian tumor rupture or dissemination, which represents an advanced stage,7,8 may be observed at the time that ovarian ACs9–14 or GCTs10,15 are clinically detected. These metastatic cases are intuitively considered as having a poor prognosis,1 but there is little information on this subject.
In women with advanced ovarian cancers, cytoreductive surgery and chemotherapy including IV or intracavitary (IC) platinum administration can be highly effective8,16,17 and are recommended as standard therapy in clinical guidelines.18 Similar treatments for ovarian ACs or GCTs with malignant effusion have been sporadically reported in dogs.9,11,13,14,19 This study aimed to describe the long-term course of seven dogs with malignant ovarian tumors with malignant effusions and to evaluate the differences in outcomes between ACs and GCTs.
Materials and Methods
We retrospectively reviewed the medical records of 18 dogs with histologically diagnosed ovarian tumors, who were treated at Aoba Animal Hospital between 2005 and 2015. The inclusion criteria were dogs with cytologically diagnosed malignant abdominal effusion at the time of presentation, full documentation of treatment, and complete follow-up. We collected information on signalment, diagnostic imaging, fluid cytology, surgical procedures, intraoperative findings, tumor size, histological findings, postoperative treatment, and prognosis. Details of the first case (case 1) were previously reported.20
Initial Evaluation of Malignant Effusion
Abdominal and pleural effusions were detected via radiography and ultrasonography, and malignant effusion (i.e., tumor cells in the effusion) was cytologically diagnosed by one of the authors, a board-certified pathologist (K.U.). The volume of the abdominal effusion was calculated from the volume aspirated or estimated from the difference in body weight before and after surgery and was classified as mild (<5%), moderate (5–10%), or severe (>10%) based on the abdominal effusion to body weight ratio.
Clinical Staging
Diagnostics performed included evaluation of the effusion, radiographs, intraoperative exploratory, and histologic assessment of the lesions. A modification of a human ovarian cancer system (the International Federation of Gynecology and Obstetrics, 20137) was used for staging (Table 1). Briefly, stages 1–4 were classified according to the human system7 except for changing the definition of stage 2 from “tumor extension to pelvic intraperitoneal tissues or organs (uterus, fallopian tubes)” to “tumor extension to the surrounding tissues or organs.” Subclassifications of stages 1C1–3 and 3A–C in humans7 were unified into stages 1C and 3, respectively.
Surgery
All dogs with suspected malignant ovarian tumors underwent laparotomies. The abdominal effusion was completely aspirated and removed, and routine OVHs were performed. Because intraperitoneal disseminated lesions were extensive and small (<1 cm), histological sampling was performed, but complete debulking surgery was not.
Chemotherapy
All dogs but one (case 1) underwent carboplatina-IV every 3 wk as postoperative adjuvant therapy. The dosage started at 150–180 mg/m2 and was increased by 10–30 mg/m2 unless adverse events occurred. The adverse events were evaluated according to grades of the Veterinary Cooperative Oncology Group Common Terminology Criteria for Adverse Events (VCOG-CTCAE).21
If pleural or abdominal effusions recurred, cisplatinb-IC (50 mg/m2) or carboplatin-IC (180–250 mg/m2) was administered every 3 wk according to previous reports.22 Systemic doses were diluted with 0.9% NaCl (1 L/m2 for intraperitoneal IC and 250 mL/m2 for intrathoracic IC) and administered through a 16–22 gauge catheter canula after aspirating the malignant effusion. When administered to both the thoracic and abdominal cavities, half the dose was administered to each cavity. The dogs were hydrated with 0.9% NaCl before (IV, 105 mL/m2/hr, for 14 hr) and after (IV, 105 mL/m2/hr, for 6 hr) cisplatin-IC. Immediately before IC, as much pleural effusion was removed as possible via thoracentesis. Metoclopramidec (0.5 mg/kg, IV) and furosemided (4 mg/kg, IV) were given immediately before cisplatin-IC. The diuresis, medication administration, and pleural fluid aspiration performed after cisplatin-IC were not performed with the carboplatin-IC.
Evaluation of Outcomes
The postoperative disease-free interval (PO-DFI) was defined from the time of OVH to confirmation of recurrent pleural or abdominal effusion or to death without recurrence/metastasis. The post-recurrent disease-free interval (PR-DFI) was defined as the time of the diagnosis of recurrence until the next recurrence. Overall survival time (OST) was from the time of OVH to death.
Results
Eleven dogs with histologically diagnosed ovarian tumors were excluded because they did not have effusion. Seven dogs with effusion, four with ACs, and three with GCTs were included in this study.
Signalments and Clinicopathological Tumor Features
All dogs were medium to older aged (7–14 yr, median 10 yr), and four (57%) were shih tzus (Table 2). Clinical signs included sex hormone-related signs (n = 3), abdominal distention (n = 2), mild dyspnea (n = 1), pain during defecation (n = 1), and anorexia (n = 1). Only one dog (case 7) was asymptomatic, and the tumor was found incidentally during an examination for dermatitis.
Abdominal effusion was severe in two AC cases, moderate in four cases (two ACs, two GCTs), and mild in one GCT case and was accompanied by pleural effusion in three cases (two ACs, one GCT). Cytologically, the AC effusions contained large numbers of cell clusters, with a papillary form (Figure 1A). In contrast, the GCT effusions contained monolayer sheets of cells that were morphologically distinct from mesothelial cells (Figure 1B). From these findings, the cell clusters were considered as tumor cells, leading to the diagnosis of malignant effusion.
Citation: Journal of the American Animal Hospital Association 57, 3; 10.5326/JAAHA-MS-7117
Ultrasonographic examination revealed ovarian masses in all dogs. Metastatic mass lesions or enlarged lymph nodes were not identified on imaging tests, including radiographs, or by intraoperative exploration.
All ovarian masses were ruptured upon inspection during laparotomy. All four ACs were bilateral, and the three GCTs were unilateral. The maximum tumor diameter was greater in the GCTs (10.2–14.4 cm, median 11.1 cm) than in the ACs (4.1–7.2 cm, median 4.7 cm). All AC cases were found to have small (<1 cm) intraperitoneal disseminated lesions. Histologically, typical papillary growth of tumor cells was seen in three AC cases (cases 1–3), and typical solid plus microfollicular patterns without papillary or adenomatous lesions were seen in three GCT cases. Both papillary and solid growth area were seen in case 4, and AC was diagnosed based on negative immunostaining for the specific marker of GCT, inhibin-α.23 Macroscopic disseminated lesions in AC cases were histologically confirmed as metastasis with papillary growth fashion. Cases were classified as stage 1C (cases 5 and 7), stage 3 (cases 2 and 3) or stage 4 (cases 1, 4, and 6) according to the modified staging system for human ovarian cancer7 (Table 1).
Early Clinical Course After Surgery
Findings are summarized in Table 3. No dogs had reaccumulation of abdominal effusion between the OVH and the start of chemotherapy at 10–31 days (median 16 days) postoperatively. The pleural effusion in three cases had disappeared by the start of chemotherapy on 30, 11, and 10 days postoperatively, in cases 1, 4, and 6, respectively. Because the first dog with AC (case 1) treated with piroxicame alone after the OVH developed malignant effusion 308 days postoperatively, carboplatin-IV adjuvant therapy was performed after the OVH in the other six dogs (cases 2–7). Carboplatin-IV was administered 2–8 times (median 5.5 times) in these six dogs. The median dosages of carboplatin used in each case were 150–200 mg/m2 (median 180 mg/m2) with the highest dosages used being 150–250 mg/m2 (median 180 mg/m2). Figure 2 shows the clinical courses of all dogs.
Citation: Journal of the American Animal Hospital Association 57, 3; 10.5326/JAAHA-MS-7117
Clinical Courses After Chemotherapy in AC Cases
Carboplatin-IV was started 10–20 days postoperatively in three dogs (cases 2–4). These dogs showed VCOG-CTCAE grade 1 (cases 2 and 4) or grade 3 thrombocytopenia (case 3) or grade 2 neutropenia (case 4), 2 wk after administering the highest doses used. The highest tolerated doses were administrated thereafter. These three dogs underwent a total of 4–8 treatments (median 6 treatments) with the highest doses being 180–250 mg/m2 (median 200 mg/m2).
All four dogs with ACs developed pleural effusion after PO-DFIs of 171–380 days (median 333 days) with simultaneous abdominal effusion in three cases (cases 1, 3, and 4). In one dog (case 1), exploratory laparotomy and thoracotomy was performed. No mass lesion was noticed, but biopsies of the peritoneum and pleura revealed thin layers of the tumor cells covering the surface of the serosa, with vascular invasion of the cells immunohistochemically positive for cytokeratin. In the other three dogs (cases 2–4), no mass lesion was identified on either the radiography or ultrasonography, but cytology of the effusions revealed large numbers of cell clusters, similar to those observed in the effusion before the OVH. From these findings, all four cases were diagnosed as having metastases (stage 4A).
One dog (case 1) received two doses of cisplatin-IC (50 mg/m2) after histological diagnosis of metastasis; both pleural and abdominal effusions disappeared by 20 days after the first treatment. Further therapy was not performed because of an increase in plasma creatinine level (before 0.8 mg/dL, after 1.3 mg/dL). The pleural effusion recurred 155 days after first cisplatin-IC, and palliative treatments including piroxicam, periodical thoracocentesis, and intrapleural chemotherapy using low-dose cisplatin (10 mg/m2), carboplatin (100 mg/m2), and bleomycinf (10 mg/m2)13 were continued. No favorable response to these treatments was observed; the dog died of uncontrolled pleural effusion 704 days after the first surgery.
The other three dogs (cases 2–4) received carboplatin-IC with or without carboplatin-IV at the highest dose previously tolerated in the postoperative adjuvant setting. Case 2 received two doses of IC followed by three doses of IV (200 mg/m2), case 3 received one dose of IC (250 mg/m2), and case 4 received one dose of IC followed by three doses of IV (180 mg/m2). The disappearance of the effusions was confirmed by 8–21 days (median 19 days) after the first treatment in these cases. Two dogs (cases 2 and 3) were treated with chemotherapy and thoracentesis after the next recurrence but died of uncontrolled pleural effusion. One dog (case 4) was reported to have had dyspnea similar to that observed at recurrence on postoperative day 748 and died immediately before visiting the hospital. Death from the tumor was suspected, but no necropsy was performed in these four cases. PR-DFIs in these four AC cases after the first recurrences/metastasis were 155–368 days (median 176 days). Regarding adverse events after platinum-IC, case 1 had VCOG-CTCAE grade 1 vomiting 4–5 hr after cisplatin-IC, and case 4 had grade 1 thrombocytopenia 2 wk after carboplatin-IV.
Clinical Courses After Chemotherapy in GCT Cases
Carboplatin-IV treatment was started 10–16 days in all three dogs with GCT. Two dogs (cases 6 and 7) showed VCOG-CTCAE grade 1 anorexia and grade 2 lethargy 1–2 wk after the first two treatments, and the dogs continued with the doses at that time (180 mg/m2 in case 6, 150 mg/m2 in case 7). After five to six treatments, no recurrence or metastasis occurred, and these two dogs died of tumor-unrelated causes.
Another dog with GCT (case 5) showed VCOG-CTCAE grade 1 thrombocytopenia 2 wk after the second carboplatin-IV (180 mg/m2) and did not return to the hospital until it later relapsed. On postoperative day 1811, the dog presented with abdominal distension because of abdominal effusion and a large recurrent mass at the primary site. The dog underwent resection of the lesion, and a large mass (24 × 15 cm) fixed to the left kidney and ureter that extended into the bladder level was isolated and resected. The postoperative course was uneventful, and the resected mass was histologically diagnosed as a recurrence of the GCT. Carboplatin-IV (180 mg/m2) was performed 19 days postoperatively based on the results of blood examination just before surgery (blood urea nitrogen 10 mg/dL, creatinine 1.1 mg/dL, urinalysis was not performed), but 9 days later, the dog died of acute renal failure (blood urea nitrogen >200 mg/dL, plasma creatinine 9.3 mg/dL, potassium 7.3 mEq/L). Necropsy could not be performed.
Outcomes
The PO-DFI and OST for all dogs were 171–1811 days (median 584 days) and 617–1840 days (median 822 days), respectively. Both the PO-DFI and OST were longer in dogs with GCTs (median: 1410 and 1410 days, respectively) than in dogs with ACs (median: 333 and 726 days, respectively). Survival time after recurrence in the four dogs with ACs was 257–446 days, which corresponded to 31–72% (median 54%) of the OSTs in each case.
Discussion
The present study suggests that dogs with malignant ovarian tumors with malignant effusion can expect relatively long survival times after undergoing an OVH and platinum-based chemotherapy. Previous studies also reported long-term survival (623–1154 days) with similar treatment in four dogs with malignant effuion.9,11,15,19
Malignant ovarian tumors are reported to occur in dogs of middle to older age.6,10 In addition to abdominal distention due to effusion, clinical signs associated with sex hormones such as vaginal enlargement, vaginal hemorrhages, and mammary gland enlargement have often been observed.10,11,14,19 Among the reported cases with malignant effusion, 7/10 ovarian ACs were bilateral,2,4,9–14,24 and 3/3 GCTs were unilateral.10,15,24 The tumor diameters described in these cases were 15 cm in a GCT15 and ≤7.5 cm in ACs.9,12,13,24 These findings are consistent with those in our study and may support the clinical diagnosis of malignant ovarian tumors with abdominal effusion. Four of the seven dogs (57%) were shih tzus, which is higher than the percentage of this breed among the total dog population (5.1%, 230/4550 dogs) admitted to our hospital during the study period, suggesting a possible higher risk for this breed.
Interestingly, both abdominal and pleural effusion disappeared after the OVH in all dogs in this study. A similar resolution of abdominal effusion after an OVH alone for 7 mo24 and at least 8 mo12 was previously reported. Several mechanisms are considered to cause abdominal effusion development due to ovarian tumors in dogs: secretion from the primary or metastatic site,10,12,13,15 lymphatic obstruction10,12,13,15 or stimulation of the serosal surface10 by disseminated cells, and lymphatic compression of the primary tumor.10 OVH, thereby removing the primary lesions and source for intracavitary cellular spread, may decrease or cure the effusion. Nishida et al.24 postulated similarities to Meigs’ syndrome due to benign ovarian tumors including GCT25 or pseudo-Meigs’ syndrome due to other ovarian tumors including ovarian carcinoma26 in women. These syndromes are characterized by massive abdominal and pleural effusions that resolve after ovarian tumor resection.25 Edema of the stromal tumor, increased vascular permeability due to inflammatory cytokines, and/or growth factor release associated with ovarian lesions are thought to cause the nonmalignant abdominal effusion in these conditions, and translocation of the abdominal effusion via diaphragmatic pores directly causes the pleural effusion, but the exact pathogenesis remains unknown.25 A similar phenomenon may have caused the improvement after the OVHs in the present cases.
Human ovarian cancer prognoses are worsened by clinical stage progression.7 For this staging, differentiation from nonmalignant effusion is made via cytology,25 but it was suggested that differentiating between mesothelial cells and ovarian tumor cells in the abdominal effusion via cytology can be difficult.24,27 The effusion cytology of canine AC is typically characterized by papillary cell clusters consisting of cells with mild to moderate pleomorphism, with a background of blood,27,28 which was observed in our AC cases. When these findings are combined with other information including ovarian masses or disseminated lesions, diagnosis of AC (i.e., malignant effusion) has been suggested to be possible.27 The histologic growth patterns of GCTs are variable, and the characteristics of the cells in the abdominal effusion have not been studied, but loosely cohesive, monolayer cell clusters, with mild to moderate cellar atypia, have been observed in samples taken directly from GCTs.28
In the present study, malignant effusion was diagnosed in three dogs with GCTs because of a large, ruptured tumor and many large cell clusters in the abdominal effusion with the cytological features described above.28 Postoperative carboplatin-IV was given at lower than standard doses or less frequently in these GCT cases, but their PO-DFIs were considerably longer than expected. In humans, GCTs are rare and typically indolent, and even for high-risk GCTs (i.e., >10–15 cm, rupture, and tumor cells in the abdominal effusion), postoperative recommendations include platinum-based therapy or observation alone.18 A mass that recurred 60 mo postoperatively in one dog with a GCT (case 5) suggested a slowly progressive indolent nature. Other studies have reported similar late GCT recurrences 38 mo after an OVH without chemotherapy24 and no recurrence of abdominal effusion due to a disseminated GCT for 24 mo after an OVH and immunotherapy.15 Therefore, postoperative carboplatin-IV in our GCT cases may not have been necessary.
In human ovarian ACs, patients’ prognoses do not differ between stages 1A and 1C, likely owing to platinum-based adjuvant therapy being used to treat stage 1C patients.7,8 A PO-DFI of >31 mo after cisplatin-IC was reported in a dog with stage 1C of ovarian AC.11 The four dogs with stages 3–4 ACs in the present study experienced 171–584 day (median 333 day) PO-DFIs after undergoing OVHs with or without carboplatin-IV. This is consistent with PODFIs reported in canine ovarian ACs: 120 days (stage 3) after oral chlorambucil/cyclophosphamide/lomustine,13 180 and 473 days (stage 3) after cisplatin-IC,9,14 and 330 days (stage 4B) after carboplatin/paclitaxel-IV.19
Because of our clients’ desires to minimize side effects, we elected to reduce the starting dosage of carboplatin with client consent. Adverse events, even those of a low grade, limited the dose escalation with the clients’ concerns in this study, but standard, reported doses should be used from the beginning to potentially enhance therapeutic efficacy. Five dogs initially received 5–8 doses of carboplatin-IV, which is similar to six cycles of carboplatin-based adjuvant therapy as recommended in humans.18 Considering the effects of OVH, the efficacy of carboplatin-IV remains uncertain in this retrospective study. One dog (case 5) died of acute renal failure after one dose of postrecurrent carboplatin-IV, but the dosage used was relatively low, and the dog had undergone major surgery that severely invaded the kidney and ureter. Therefore, we speculated that surgical invasion or repair reactions, rather than the effects of the drug, contributed to the crisis of acute renal insufficiency.
Disappearances of recurrent malignant effusions after cisplatin-IC or carboplatin-IC (cases 1–4) suggest that canine ovarian ACs are highly sensitive to platinum, as reported in humans.16,17 In experimental rat models, platinum drug levels on tumor surfaces were higher after IC than after IV administration, but the drug penetrated only a few millimeters of the surface.29 Thus, cytoreductive surgery can be used to enhance the efficacy of platinum-IC.16,17 Carboplatin was cleared from the body cavity more slowly than was cisplatin, but less carboplatin than cisplatin penetrated the tumor surface.29 We speculate that carboplatin-IC was effective because the metastatic lesions mainly existed on the pleural and peritoneal surfaces as histologically confirmed in case 1. Differences in doses of platinum-IC (1–2 doses) occurred because of the nature of the retrospective study and differences in case management. Two dogs (case 2 and 4) underwent three doses of carboplatin-IV after carboplatin-IC because IV administration was technically simple. PR-DFIs in four AC cases (stage 4A) were 155–368 days (median 176 days) after the initiation of cisplatin-IC or carboplatin-IC. However, a longer PRDFI (607 days) was reported in a dog with recurrent AC (stage 4A) who received three doses of cisplatin-IC.9 Whether this difference was due to differences in the drug used or the number of IC doses should be further investigated.
A recent randomized controlled trial of human ovarian carcinomas showed a significantly lower progression rate at 9 mo postoperatively for the carboplatin-IC–based regimen compared with that for carboplatin-IV–based regimen (23 versus 42%).30 Comparing the effects of IC and IV administration of platinum drugs was not feasible in the present study. However, one dog (case 3) developed pleural effusion 76 days after completing the initial carboplatin-IV cycles and experienced a 195-day PR-DFI after one carboplatin-IC dose. In another dog (case 4), both pleural and abdominal effusions appeared 140 days after completing the initial carboplatin-IV cycles, whereas no recurrence was observed for 267 days after completing four cycles that included carboplatin-IC. These differences in DFI lengths in the same cases may suggest that IC administration is possibly more effective than IV administration of carboplatin for stage 4A patients, but prospective, randomized controlled trials are needed to clarify this.
Dogs with GCTs experienced longer PO-DFIs and OSTs than dogs with ACs in this study, likely owing to differences in tumor characteristics. Smaller ACs than GCTs at the time of detection, with gross disseminated lesions, may represent the more aggressive nature of AC. Given the slow progressive nature of GCT and low dose intensity of carboplatin used, dogs with GCT may achieve long-term remission by OVH alone, whereas dogs with AC may develop malignant pleural effusions as in the cases of the present and other reports.9,13,24 The need for postoperative chemotherapy or the appropriate protocol for these patients should be evaluated in further studies. The overall clinical course suggests that treatment can prolong survival even after malignant effusions recur. Although tumor cells appear to develop drug resistance over time as previously reported,9,19 repeated thoracentesis may still be a useful palliative treatment in some cases without gross metastasis.24
The limitations of this study include the small number of cases and the retrospective nature. Cases with large disseminated lesions, as opposed to the small disseminated lesions in our study, may behave differently. Given the effect of OVHs on PO-DFIs, results from a small number of patients cannot determine a benefit of postoperative carboplatin-IV. The efficacy of platinum-IC for the recurrent effusions was confirmed, but the optimal protocol cannot be evaluated. To evaluate the benefit of carboplatin-IV after OVH and platinum-IC after recurrence, prospective, randomized studies would need to be performed, first only in naive cases, followed by separate evaluation of cases with progressive disease. Variability in the long-term treatment courses limits comparing OSTs between dogs. In addition, although 6/7 cases in our study were classified as AC or GCT based on typical histologic features, a more objective classification based on immunohistochemistry23 would be desirable. Even considering these limitations, the results of the present study and other reports9,11,13,14,19,24 suggest that malignant ovarian tumors with malignant effusions are highly responsive to therapy.
Conclusion
Malignant ovarian tumors with abdominal effusion generally represent advanced disease stages in dogs, but OVHs and chemotherapy may enable relatively long survival times. OVHs can help transiently improve malignant effusions, and chemotherapy containing platinum-IC effectively treats recurrent malignant effusions. DFIs and OSTs were longer in dogs with GCTs than in those with ACs, likely owing to the slowly progressive nature of GCT. Even if the malignant pleural effusions recur, thoracentesis and chemotherapy including platinum-IC may enable prolonged survival. Further prospective, randomized studies are needed to determine the optimal chemotherapy protocol for these malignancies.
Cytological features of cell clusters in abdominal effusion in dogs with ovarian papillary adenocarcinoma (A) and granulosa cell tumor (B). Diff quick stain, original magnification ×400. (A) Papillary clusters of epithelial cells are present (case 2). The cells are tightly cohesive, with moderate nuclear pleomorphism. (B) A cluster of monolayer cells, with moderate cellular and nuclear pleomorphism, is present (case 6). The cells with abundant cytoplasm are loosely cohesive, which are morphologically distinct from reactive mesothelial cells.
Clinical processes after ovariohysterectomies in seven dogs with malignant ovarian tumors. *Others-IC, described in Table 3, is performed.
Contributor Notes
From Aoba Animal Hospital, Miyazaki, Japan (T.I., A.K.); Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan (K.U., J.C.); and Division of Animal Medical Research, Hassen-kai, Miyazaki, Japan (T.I., A.K., H.S.).
