Int. J. Life. Sci. Scienti. Res., 3(6): 1467-1470, November 2017
Significance of Thrombocytosis in Epithelial Ovarian Tumors
Shwetha Ramu1*, Ruchi Sinha2
1Assistant Professor, Department of Pathology, Basaveshwara Medical College and Hospital, Chitradurga, India
2Associate Professor, Department of Pathology, Kasturba Medical College, Mangalore, India
*Address for Correspondence: Dr. Shwetha Ramu,Assistant Professor, Department of Pathology, Basaveshwara Medical College and Hospital, Chitradurga, India
ABSTRACT- Thrombocytosis has been reported in association with ovarian tumors and is often a poor prognostic factor. The present study aims to study the incidence of pre-operative thrombocytosis in epithelial ovarian tumors and to correlate it with anemia, serum CA-125 levels, presence or ascites, FIGO staging and tumor histology. Total 160 cases of resected specimens of surface epithelial ovarian tumors (SEOT) received in department of Pathology, Kasturba Medical College Mangalore were studied. The preoperative platelet count, haemoglobin levels and serum CA-125 levels were collected. The presence and degree of ascites was assessed. International Federation of Obstetrics and Gynaecology (FIGO) staging was done. The incidence of thrombocytosis and its correlation with the presence of anaemia, elevated CA-125 levels, FIGO stage and presence and degree of ascites among malignant cases were statistically analysed. The incidence of pre-operative thrombocytosis was noted more in malignant SEOTs 80% (40/160). The mean pre-operative platelet count in the present study was 321X109 /L. It was more prevalent in serous epithelial ovarian tumors (83.3%) and these findings were statistically significant (p=0.0001). There was a statistically significant association of pre-operative thrombocytosis with the presence and degree of ascites and advanced FIGO staging (p=0.0001). Pre-operative thrombocytosis is a frequent finding in malignant SEOTs and is associated with other prognostic markers. This implies that thrombocytosis is probably a marker of tumor aggressiveness, and that platelet may have a role in cancer growth and progression. Thus, presence of pre-operative thrombocytosis has significance as a poor prognosticator in epithelial ovarian tumors.
Key-words- Thrombocytosis, Surface Epithelial Ovarian Tumors (SEOT), CA 125, FIGO staging
INTRODUCTION- Thrombocytosis refers to platelet count above the normal value (>400x109/L). Thrombocytosis can be primary or secondary. Malignancy is one of the most important causes of secondary thrombocytosis. [1-2] The association between thrombocytosis and malignancies is known.  Thrombocytosis has been reported in variety of neoplastic diseases including Hodgkin lymphoma, sarcoma and several solid tumors such as lung, renal, gastric, breast, pancreatic, colonic and gynecological malignancies.[4-8]
In ovarian cancer thrombocytosis is a poor prognostic factor in locally advanced disease. [9-10] Chalas et al.  found thrombocytosis in 56% of the reviewed cases of epithelial ovarian malignancies.
The etiology of neoplastic megakaryopoiesis remains unclear, it might be related to increased platelet production are due to certain cytokines (IL-6, IL-1) and growth factors released by malignant cells. Platelet aggregates with tumor cells and prevents immune mediated tumor cell clearance. Thrombospondin-1 helps in adhesion of circulating tumor cells to endothelium, extravasation of tumor cells and metastasis. 
In an attempt for better understanding the importance of thrombocytosis in epithelial ovarian tumors we studied the association of thrombocytosis with CA 125 and other prognostic markers.
MATERIALS AND METHODS- In the present study, 160 cases of epithelial ovarian tumors were studied prospectively between the periods of October 2010 to June 2012 in the Department of Pathology, Kasturba Medical College Mangalore, India. The data were collected regularly during the study period from the case records and laboratory reports at Kasturba Medical College Hospital. The clinical details, histopathological reports, haematological and biochemical parameters were collected pro forma. Patients with any history of myeloproliferative disorders, acute inflammatory conditions, secondary overt malignancies and splenectomy were excluded in the present study. The data collected in the present study were pre-operative platelet counts, haemoglobin and serum CA-125 levels. All patients underwent staging laparotomy. Tumor stage (FIGO staging), tumor histology and presence and degree of ascites in patients were noted. Tissue was fixed in 10% buffered formalin, and processed .The routine H & E stained slides of all the cases were reviewed thoroughly and the histopathological findings were recorded. The patients with thrombocytosis were correlated with the presence of anaemia, elevated CA-125 levels.
Statistical Analysis - FIGO stage and presence and degree of ascites among malignant cases were statistically analysed by Chi-square test and Fisher’s exact test. In the present study, a ‘p value’ < 0.05 was considered significant for the performed tests. All tabulations or statistical analysis was done using the XLSTAT software.
RESULTS- In the present study, 160 cases of surface epithelial ovarian tumors were studied. Majority of the cases i.e. 28.1% (45/160) were in the fourth decade and least number of cases i.e. 3.1% (5/160) were in the first and the eight decade. Age of the patients ranged from 17 to 80 years with a mean age of 43.64 years. The mean ages of patients for benign, borderline and malignant cases were 38.85, 46.0 and 53.18 years respectively. The most common symptom was pain abdomen 68.8%. Majority of the cases were benign (64.4%), followed by malignant (50%) and borderline cases (4.4%). Serous ovarian tumors (70.6%) were the most common histologic type, followed by mucinous (27.5%) tumors. Other tumors include two cases of endometrioid carcinoma and one case of mixed ovarian tumor composed of endometrioid and clear cell carcinoma components.
Fig. 1: Distribution of SEOTs as benign, borderline and malignant cases
Fig. 2: Distribution of SEOTs according to differentiation
Fig. 3: Correlation of thrombocytosis in SEOTs with malignancy
Fig. 4: Correlation of thrombocytosis in SEOTs with CA 125 levels
The platelet count ranged from 172x109/L to 641x109 /L and mean of the value was 321x109 /L.
DISCUSSION- In our study, thrombocytosis was seen in 49 (30.6%) cases of SEOTs. 80% of malignant cases had pre-operative thrombocytosis. Forty seven cases of malignant ovarian tumors had thrombocytosis, and majority of the cases 42 (84%) were of serous type. The presence of pre-operative thrombocytosis was more prevalent in serous and mucinous cystadenocarcinomas (83.30%).
The mean platelet count for malignant epithelial ovarian tumors was 435X109 /L, for borderline tumors was 371X109 /L and for benign tumors was 262X109 /L. Forty (80%) out of fifty cases of malignant surface epithelial ovarian tumors had pre-operative thrombocytosis. Levin and Conley  reported in 1964 that nearly 40% of the patients with inoperable cancer had platelet counts greater than 400X109 /L. A similar study done by Chalas et al.  on 241 patients presenting with pelvic mass demonstrated that thrombocytosis was noted in 56% of malignant cases.
Ziemet et al.  in their study on 130 patients with epithelial ovarian cancer showed that forty-nine (38%) of ovarian cancer patients had thrombocytosis. Kerpsack and Finan  reported that out of 87 patients who had a malignant pelvic mass, 54.2% of malignant epithelial ovarian tumors had thrombocytosis as compared to 22.6% of benign epithelial tumors.
Li et al.  found that 41 (22.4%) out of 183 women with epithelial ovarian carcinomas had thrombocytosis at presentation with a mean platelet count was 542X109 /L which was higher than in the present study.
Forty six cases of malignant ovarian tumors had elevated serum CA-125 level, and majority of the cases (87%) were of serous type. Thirty eight (95%) cases of malignant ovarian tumors had elevated serum CA-125 levels. In our study, serum CA-125 levels more than 35 U/ml was considered abnormal. The mean serum CA-125 level in this study was 508 U/ml (range 1.06 U/ml-12750 U/ml). The mean values of serum CA-125 for malignant, borderline and benign epithelial ovarian tumors were 1579 U/ml (range 21.36 U/ml-12750 U/ml), 112 U/ml (range 23 U/ml-376 U/ml) and 15.17 U/ml (range 1.06 U/ml-78 U/ml), respectively.
Higher CA-125 level was seen in malignant (92%) and borderline epithelial ovarian tumors (71.40%) when compared with benign (8%) tumors.
Similar to our study, Schilthuis et al.  had elevated pre-operative serum CA-125 levels in 44 of 46 (96%) patients with epithelial ovarian cancer, which is lower in our study. Their serum CA-125 levels ranged from 36 U/ml to 8670 U/ml. They also found that there was a high prevalence of elevated serum CA-125 levels among serous cystadenocarcinoma followed by mucinous cystadenocarcinoma. Correlation of serum CA-125 and tumor stage was found.
Majority of surface epithelial ovarian carcinomas were in stage III (72%) followed by stage IV (14%). Thirty nine out of forty cases of malignant ovarian tumors with thrombocytosis were in advanced stage of disease (stage III /stage IV) and one (2.5%) case which was in stage II disease. Thirty two (80%) cases were in stage III and seven (17.5%) cases were in stage IV.
Pre-operative thrombocytosis is associated with many malignancies including ovarian neoplasia. Similar to the present study by Chalas et al.  on 241 patients with pelvic masses found that majority of the cases were in stage III (39 cases) and stage IV (22 cases) followed by stage I (11 cases) and stage II (2 cases). Li et al.  in their study on 183 ovarian cancer patients found that one hundred forty-four cases (78.7%) were diagnosed with stage III or stage IV disease, and 39 cases (21.3%) were diagnosed with stage I or stage II disease, which was similar to our study.
In present study, the pre-operative thrombocytosis in malignant ovarian tumors were associated with elevated serum CA-125 levels (95%), advanced FIGO stages III (80%) and IV (17.5%), and histologic type. Lund et al.  in their study on ovarian cancer patients found a significant linear association between pre-operative platelet count and stage, which was similar to the current study. Thrombocytosis was associated with higher serum CA-125 levels compared with normal platelet count (p<0.001).
The prevalence of thrombocytosis was 24% and 27% in patients with FIGO stages I and II, respectively and increased to 39% and 69% in patients with stages III and IV, respectively. They noted no significant differences in the occurrence of thrombocytosis and histologic type. Li et al.  in their study on epithelial ovarian cancer patients, showed that patients with thrombocytosis were found to have statistically greater elevations of pre-operative serum CA-125 levels (p=0.026), which was not similar to the present study (P=0.174). Also thrombocytosis was statistically associated with advanced stage disease (p=0.016). These findings were similar to the current study. Similar to our study, Bozkurt et al.  reported that 16 out of 37 patients had thrombocytosis with stage III and 1 out of 37 patients with stage IV epithelial ovarian malignancies.
CONCLUSIONS- We studied 160 cases of surface epithelial ovarian tumors comprising of 103 benign, 7 borderline and 50 malignant cases. Majority of the malignant ovarian tumors had statistically significant pre-operative thrombocytosis when compared to borderline and benign tumors. Pre-operative thrombocytosis and concomitant raised CA 125 levels was more prevalent in serous cystadenocarcinoma. Pre-operative thrombocytosis and raised CA 125 levels also correlated with advanced FIGO stage. This implies that pre-operative thrombocytosis is useful as a marker of tumor aggressiveness along with CA 125 levels, implying that platelet may have a role in cancer growth and progression. Further the role of platelets in evolution of metastasis of ovarian tumors needs to be studied.
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