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Journal of Cancer Research and Therapeutics, Vol. 7, No. 4, October-December, 2011, pp. 433-437 Original Article Histologic pattern, bilaterality and clinical evaluation of 957 ovarian neoplasms: A 10-year study in a tertiary hospital of eastern India Santosh Kumar Mondal1, Ranjana Banyopadhyay2, Dipanwita Roy Nag1, Suprio Roychowdhury1, Palash Kumar Mondal1, Swapan Kumar Sinha1 1 Department of Pathology, Medical College, Kolkata, India Code Number: cr11116 DOI: 10.4103/0973-1482.92011 Abstract Objective: The aim was to study the distribution of morphological pattern of benign and malignant ovarian neoplasms in different age groups in eastern India and to determine the likelihood of bilateral involvement in different morphologic subtypes. Keywords: Bilaterality, clinical evaluation, histology, ovarian neoplasm Introduction Ovarian malignancy is the second most common cancer of the female reproductive system and the leading cause of death from gynecologic malignancy. [1] The total number of ovarian cancer cases worldwide has been estimated to be 1,92,000 per year in 2000, representing 4% of all cancers in women and the sixth leading site of malignancy. [2] Histology of ovarian tumors exhibits wide spectrum of variation. Distribution of the different ovarian neoplasms has been widely studied in western countries. However, no such study is available on this from eastern India. Indian Cancer Registry data project ovary as an important site of cancer in women, comprising up to 8.7% of cancers in different parts of the country. [3] In this background, we have studied the clinical presentation, histological spectrum and follow-up of patients with ovarian tumors in a tertiary care hospital in eastern India. Materials and Methods The study included 957 cases of ovarian tumors studied over a period of 10 years (from January 2001 to December 2010). This study was undertaken to ascertain the pattern and incidence of neoplastic lesions of the ovary in this part of the country. Detailed clinical information and radiologic findings were recorded from the case sheets. These included age and sex of the patients, signs and symptoms, fine needle aspiration cytology (FNAC) findings of the available cases, complete blood count, ultrasonography (USG)/computed tomography (CT) findings and biochemical investigations including serum tumor markers like CA125, α fetoprotein and β human chorionic gonadotrophin (β HCG). Oophorectomy specimens as well as hysterectomy with unilateral or bilateral salphingoophorectomy specimens were included in this study. Formalin-fixed, paraffin-embedded tissue sections were stained with Hematoxylin and Eosin and other special stains as and when required. Immunohistochemistry was performed in selected cases. The patients were divided into six age groups to study the proportion of benign and malignant tumors in these age groups and the predominant histologic type in each of these groups. The proportion of malignant cases was noted in the four major histological subtypes of ovarian neoplasms. All histopathology slides were reviewed individually by three different pathologists. Patients were followed up for a period of 6 months to 5 years (median 3 years) and were evaluated clinically, radiologically and with repeated serum tumor marker estimation to identify recurrences. Results Among the 957 cases of ovarian tumor, the median age at presentation was 35 years. Most of the benign tumors occurred between 20 and 40 years of age, while the malignant lesions presented commonly between 41 and 50 years [Table - 1]. Germ cell tumors were encountered in younger age group (median age 19 years). The presentation of surface epithelial tumors varied widely involving all age groups. The most common histological types were serous cystadenoma (29.9%), followed by mature teratoma (15.9%) and mucinous cystadenoma (11.1%). Major proportion of malignant ovarian tumors was contributed by surface epithelial tumors (60.9%) [Table - 2]. Serous cystadenocarcinoma predominated the malignant group (11.3%), followed by mucinous carcinomas (3.3%). Only 12 cases of endometrioid carcinoma (1.2%) and 15 cases of clear cell carcinoma (1.5%) were identified in the present series. Dysgerminoma predominated the malignant germ cell group (2.6% of all ovarian tumors), followed by yolk sac tumor (1.2%) [Table - 3]. Serous tumor was the commonest borderline epithelial tumor comprising 10.4% of all serous tumors and 5.3% of all ovarian neoplasms. Of the 54 cases of stromal tumors, 11 cases of malignancy were diagnosed which comprised 6 granulosa cell tumor and 5 Sertoli-Leydig cell tumor. For granulosa cell tumor, cases showing increased mitosis (4 per 10 hpf) and having intraabdominal spread were classified as malignant. For Sertoli-Leydig cell tumors, poorly differentiated morphology and presence of extraovarian spread were considered to be the markers of poor prognosis. Studying the bilaterality of different ovarian tumors, metastatic tumors were found to involve the bilateral ovaries in 72%, while malignant serous tumor was found to be the predominant primary ovarian neoplasm showing bilateral involvement (49.5%). Borderline serous tumors showed bilateral involvement more commonly (27.4%) than borderline mucinous tumors (15.7%). Immunohistochemistry for CK7 and CK20 was performed to differentiate from metastatic colorectal adenocarcinoma. Most of the malignant tumors presented as stage III (60%) or stage II (20%) disease. Complete resection of the tumor was attempted in all the cases, but optimal debulking (residual diseases <2 cm) could be achieved only in few of the advanced cases. Neo-adjuvant (cytoreductive) chemotherapy was tried in stages III and IV diseases with unresectable tumors. Postoperative chemotherapy was advised in all cases of ovarian carcinoma except in stage IA or IB disease with grade 1 or 2 tumor. Chemotherapy was not offered to patients with stage IV disease, having multiple metastases with poor performance score. Five-year follow-up was available for 192 of 284 malignant and 40 of the 70 borderline tumors. All the patients with benign neoplasms were followed up for 1 year. During this period, three patients with borderline serous tumor developed recurrence and one patient with borderline mucinous tumor developed peritoneal implant. The overall survival rate was 85% for stage I tumors, 65% for stage II, 30% for stage III and 15.5% for stage IV tumors. Discussion Diagnosis of ovarian tumors can be difficult due to a variety of pathologic conditions that can affect the ovaries and present with similar clinical and radiologic manifestations. Knowledge of morphology and age-specific characteristics can help refine the diagnosis. [4] In the present study, the median age of presentation of all ovarian tumors was 35 years while the median age of presentation of all malignant lesions was 48 years. Benign tumors were diagnosed mostly in patients between 20 and 40 years of age. Similar studies by other investigators have highlighted that most ovarian tumors (47.2%) are seen between 21 and 40 years, whereas most malignant tumors have been noted (73.1%) above 40 years. [5] In another study from Iran, the median age for malignant lesions was reported to be 49 years. A higher median age of 60-65 years for malignant lesions has been reported from the western countries and from southern and western part of India. [3],[6],[7] With the increase in absolute numbers of older women, the effect of ovarian cancer for this age group is expected to be amplified. [6] Malignant epithelial and sex cord stromal tumors have been found to be more common after 50 years, while germ cell tumors are more prevalent before the age of 20. [8] In the present study, malignant epithelial tumors were found predominantly in 41-60 year age group. However, a significant number of malignant surface epithelial tumors were also found in the 30-40 year group. Benign and borderline tumors dominated the picture in 20-30 and 31-40 year age groups. The indication toward an earlier presentation of malignant lesions in our study compared to western countries warrants prompt and thorough investigation of any vague abdominal complaint in women of this age group. In these women, symptoms are commonly attributable to a variety of conditions, and thus important symptoms may be neglected or ascribed to other problems. [6] The major fraction of ovarian neoplasm in the present study comprises benign tumors (63.1%), followed by malignant (29.6%) and borderline tumors (7.3%). In a similar study, Gupta et al. reported 72.9% benign, 4.1% borderline and 22.9% malignant tumors. [9] A higher proportion (nearly 20%) of borderline cases has been reported in other studies. [10] Ovarian tumors display histological heterogeneity. [11],[12],[13] The histological classification of ovarian tumors by the World Health Organization (WHO) is based on the histogenesis of the normal ovary. [14] Histologically, surface epithelial tumors are the commonest. These tumors comprise 48.8% and 63.5% of all ovarian tumors in different studies. [9],[15] The major burden of malignant tumors is also contributed by this group (93%). [6] Similarly, in the present study, surface epithelial tumors comprised 67.9% of all tumors and 60.9% of the malignant group. Endometrioid ovarian carcinoma comprises 10-25% of all primary ovarian carcinomas in literature. [16],[17] Most of these reports are from the western part of the world. In a study from eastern India, the endometrioid tumors were found to be only 5% of all malignant tumors. [18] Similarly, in our study; endometrioid tumors comprised 4.2% of all malignant ovarian tumors. This may be a reflection of geographic variation of diseases. Germ cell tumor was the second major group of tumors in the present study (23.1%). The proportion of germ cell tumors varied in other studies from 23.9 to 42.2%. [5],[9] Significantly higher number of germ cell tumors has been reported from South Africa. [19] Mature teratoma was the commonest benign germ cell tumor in our study, comprising 15.9% of all ovarian tumors. The proportion was even higher than mucinous cystadenoma. Mature teratoma has been found to be the most common benign tumor in one study. [15] Pregnancy has been an association of mature teratoma in 3% of patients and malignant changes are observed in 5% cases. [20] In a study of 41 patients with malignant ovarian germ cell tumors, 23 (56%) had dysgerminomas, 8 (19.5%) had mixed germ cell tumors, 3 (7.3%) had yolk sac tumors, 3 (7.3%) had immature teratomas, 2 (4.8%) had squamous cell carcinoma arising from a mature teratoma, 1 (2.4%) had embryonal carcinoma and 1 had choriocarcinoma. [21] In the present study, we encountered 69 malignant germ cell tumors with predominance of dysgerminoma (36.2% of malignant germ cell tumors, 2.6% of all ovarian tumors). In contrast to the above study, a higher number of yolk sac tumors were noted in our study (17.4% of malignant germ cell tumors and 1.2% of all ovarian tumors). The distribution of sex cord stromal tumors and metastatic tumors in the present study was similar to that reported in other studies. [5],[9] Ovarian tumors are well known for bilateral involvement. The likelihood of bilateral involvement by primary ovarian tumors varies with histologic subtype. In one study, using data collected by the Surveillance Epidemiology and End Results (SEER) program including 22,328 women diagnosed with a borderline or malignant epithelial ovarian tumor, malignant serous tumors were found to be bilateral in 57.5% of cases. Corresponding figures for mucinous, clear cell, endometrioid and other epithelial tumors were 21.3%, 13.3%, 26.8%, and 35.6%, respectively. Borderline serous tumors were bilateral in 29.8% of the cases compared to only 7.0% of mucinous tumors. [22] Bilaterality in borderline serous tumor has been reported to be as high as 40%, whereas over 90% of the mucinous borderline tumors are unilateral. This is an important statistic because bilaterality of a mucinous tumor should always suggest the possibility of a metastatic tumor to the ovaries from the appendix or other gastrointestinal sites, the pancreas or the endocervix, rather than a primary ovarian neoplasm. [23] In the present study, the most common ovarian tumor with bilateral involvement was malignant serous tumor (49.5% bilateral). This was followed by 28.1% of malignant mucinous tumors. Higher number of borderline serous tumors were found to be bilateral in our study (27.4%) compared to mucinous borderline tumors (15.7%). Prognosis is strongly associated with the stage at diagnosis, but the histologic grade also plays a prognostic role, particularly in predicting recurrence. [24] Of women diagnosed with stage I disease, 74% are under 65 years of age. [6] Up to 70% of patients with epithelial ovarian cancer present at stage III or IV. [25] Epithelial ovarian cancer is histologically determined to be of low malignant potential in 15% of patients, is often diagnosed at stage I, and has a 95-99% 10-year survival rate. [26] Older women are more likely to be initially diagnosed with advanced disease. Therefore, they experience the worse prognoses. For the oldest women, those aged 85 years and older, there is a very high percentage of unknown stage disease (18%). This category most likely includes advanced stage disease. A mere 11% of women of 85 years and older are initially diagnosed with stage I disease, as compared to 47% of women under 45 years. [27] In the present study, we encountered 60% stage III and 10% stage IV disease. A lower number of stage III diseases may be due to an earlier age at presentation of malignant tumors in our study (most of our malignant cases were in the 41-50 year age group in contrast to >50 years in the western countries). In this study, we noted an earlier age at presentation of malignant tumors. The proportion of mature teratoma was higher in this study, being the second most common benign tumor (after serous cystadenoma). We also noted a lower percentage of endometrioid tumors which was comparable to that reported in a similar study from eastern India. This may be important as endometrioid tumors are said to have a better prognosis compared to serous or mucinous carcinomas. Lower number of stage IV tumors was noted, with a significant number of malignant ovarian tumors presenting at an earlier age. References
Copyright 2011 - Journal of Cancer Research and Therapeutics The following images related to this document are available:Photo images[cr11116t2.jpg] [cr11116t1.jpg] [cr11116t3.jpg] |
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