Ovarian Neoplasms: Clinicopathological Spectrum in Tribal Rajasthan, India

1. Associate Professor, Department of Pathology, Geetanjali Medical College, Udaipur, Rajasthan, India. 2. Associate Professor, Department of Obstetrics and Gynaecology, Geetanjali Medical College, Udaipur, Rajasthan, India. 3. Third Year Resident, Department of Obstetrics and Gynaecology, Geetanjali Medical College, Udaipur, Rajasthan, India.

Abstract

Introduction: Ovarian neoplasms have increased in incidence in leading sites of cancer in five old population based cancer registries on comparing first ten and last ten years data. All three germ layers are afflicted in process of ovarian neoplasm-ceolomic epithelium, germ cell and sex chord/stromal cells. Due to this, ovarian masses are spread widely over all age groups. However, a correct pathological diagnosis goes a long way in management of the disease and consequent benefit to patient.

Aim: To assess the histopathological pattern, age, laterality and distribution of ovarian tumours in a tertiary care centre of tribal part of Rajasthan.

Materials and Methods: Retrospective hospital based study wherein 157 ovarian specimens received in Department of Pathology of Geetanjali Medical College and Hospital, Udaipur, Rajasthan over a period of three years were studied after obtaining permission from ethical committee. Details such as age, signs and symptoms, laterality were retrieved from patient file. Only benign, borderline or malignant ovarian neoplasm specimens removed surgically were included. Physiological cysts were excluded. Descriptive statistics were used and results were expressed as percentages.

Results: Out of 157 ovarian neoplasms, 42 (26.75%) were from hysterectomy specimen, 44 (28.03%) from planned cystectomy for mass, 71 (45.22%) from cytoreductive surgery or tissue obtained from Exploratory Laparotomy. A 63.06%, 33.76% and 3.18% of neoplasms were benign, malignant and borderline, respectively. Extremes of age lied between 14 to 84 years. Mean age for benign, malignant and borderline tumours respectively was 38.60 years (SD=15.21), 47.79 years (SD=14.53) and 38.4 years (SD=14.04), respectively. Unilateral tumours were clearly in abundance with 85.35%. Right-sided tumours were more (49.04%). Surface Epithelial Tumours (SET’s), Germ Cell Tumour (GCT’s) and Sex Chord Stromal Tumours (SCSCT’s) were 59.24%, 34.39% and 6.37%, respectively. Out of 10 cases, 60% were malignant (Granulosa cell tumour). No metastatic tumour was seen during the study period.

Conclusion: To effectively reverse the trend in a developing country like India each and every gynaecologist should be aware and well versed with histo-morphological pattern of ovarian neoplasms specific to a region.

Age, Benign, Borderline, Germ cell tumour, Malignant, Mass ovary, Sex chord stromal tumour

Ovarian neoplasms have increased in incidence in leading sites of cancer in five old population based cancer registries viz., Barshi rural (1988-2016), Bangalore (1982-2014), Bhopal (1988-2015), Chennai (1982-2016) and Mumbai (1982-2015) on comparing first ten and last ten years data (1). All three germ layers are afflicted in process of ovarian neoplasm-ceolomic epithelium, germ cell and sex chord/stromal cells. Also, ovarian masses are spread widely over all age groups. By the year 2040, the mortality rate of ovarian cancer will rise significantly (2).

Vague symptoms, being an internal organ, lack of screening protocols make timely diagnosis of ovarian masses an enigma. Early diagnosis being an issue, lack of access to specialised treatment, high incidence of recurrence and poor compliance to therapy are factors which result in increased morbidity associated with neoplastic ovarian masses (3). However, a correct pathological diagnosis goes a long way in management of the disease and consequent benefit to patient. Borderline tumours further complicates already complex scenario of diagnosis that is there.

Epidemiological diversity of different pathogenic types is due to differing factors prevalent in a particular geographic area. The purpose of this study was to assess the histopathological pattern, age, laterality distribution of ovarian tumours in a tertiary care centre of tribal part of Rajasthan, India. To the best of knowledge, single study has been done on this topic in this region (4).

Material and Methods

This was a retrospective hospital-based study wherein 157 ovarian specimens received in Department of Pathology of Geetanjali Medical College and Hospital, Udaipur, Rajasthan, India over a period of three years (July 2017 to June 2020) and the data was studied from mid-June to mid-December (2^nd June to 2^nd December 2020). The Institutional Ethical committee approval was obtained prior to the study (IEC-948).

Inclusion criteria: All histologically proven cases of ovarian tumours whose surgery was done in institute were included.

Exclusion criteria: Physiological cysts and biopsies from surgery done outside the institute were excluded.

Consecutive sampling was done. Details such as age, signs and symptoms, laterality were retrieved from patient file. Only benign, borderline or malignant ovarian neoplasm specimens were taken. The World Health Organisation (WHO) classification of ovarian tumours was used (5). Routine paraffin techniques used for processing of the paraffin blocks and sections stained with haematoxylin and eosin stain were examined microscopically in detail.
Statistical Analysis

Descriptive statistics were used and results were expressed as percentages.

Results

Among the specimens received, 157 ovarian tumours were investigated. Out of 157 ovarian neoplasms, 42 (26.75%) were from hysterectomy specimen, 44 (28.03%) from planned cystectomy for mass, 71 (45.22%) from cytoreductive surgery or tissue obtained from Exploratory Laparotomy.

Dyspepsia appeared as the most encountered symptom in 90 patients (57.32%) closely followed by pain 67 (42.68%). Mass abdomen in 24 (15.28%), menstrual irregularities in 24 (15.29%), bloating, nausea, headache in 13 (8.28%). Mass on imaging guided 56 (35.66%) to diagnose and get themselves operated. This is shown in (Table/Fig 1).

Benign, malignant and borderline ovarian neoplasms detected were 99/157 (63.06%), 53/157 (33.76%) and 5/157 (3.18%), respectively. Surface Epithelial Tumours (SET’s) were most common comprising of 93 cases (59.24%), followed by Germ Cell Tumour (GCT’s) and Sex Chord Stromal Tumours (SCSCT’s) having 54/157 (34.39%), 10/157 (6.37%) each as shown in (Table/Fig 2).

Equal number of benign and malignant variety were found in SET’s with 44/93 (47.31%) each while borderline tumours were 5/93 (5.37%). SCST’s had 6/10 malignant and 4 benign tumours. GCT’s had 51/54 (94.44%) benign and 3/54 (5.55%) malignant tumours. Neither any metastatic tumour nor any borderline tumours of GCT’s or SCST’s origin was found in study duration. Nature of three distinct hisopathological types are shown in (Table/Fig 3).

Serous cystadenoma 31 cases (33.33%) was most frequent SET closely followed by serous adenocarcinoma with 29 cases (31.18%). An important finding unearthed was that the SET’s benign and malignant cases both were equal having 44 cases (47.31%) each. A single case of undifferentiated carcinoma was present. As in WHO classification (5), it is kept under SET’s. Brenner’s tumour had three benign, one borderline and one malignant histopathological type. One collision repored tumour Brenner tumour in one ovary with mucinous cystadenoma.

As an individual tumour, mature teratoma was most common neoplasm of total 51/157 (32.48%) and 94.44% of GCT’s. It was the most prevailing of all benign neoplasm in current search. Dysgerminoma being second most frequent GCT with 3 cases (5.56% of GCT’s). Out of 10 cases of SCST’s, 60% were Granulosa cell tumour i.e., malignant. Two cases of fibrothecoma and one each of thecoma and steroid (lipid) cell tumours were observed. Current survey did not observe any case of immature teratoma or metastatic neoplasm. These findings are shown in (Table/Fig 4).

Age distribution is shown in (Table/Fig 5). Mean age for benign, malignant and borderline tumours were 38.60 years (SD=15.21), 47.79 years (SD=14.53) and 38.4 years (SD=14.04) respectively. Extremes of age lied between 14 years to 84 years. Majority of benign lesions presented in age group 20-49 years, 50/99 cases (50.50%). Maximum malignant lesions 29/53 (54.72%) were found in 4^th and 5^th decade. Reproductive age i.e., 20-49 years 78.43% (40/51) tumours were mature teratoma. In age group 14-19 years; total 6 cases, out of which four were benign and two malignant. Age 70 years and above had five benign and three malignant cases with eight cases in total.

Unilateral tumours were in majority of cases 134/157 (85.35%). Among the 23 bilateral tumours, one was undifferentiated malignancy, three of mucinous malignancy and 14 of serous malignancy. A meager three out of 23 bilateral tumours were benign. All bilateral tumours were surface-epithelial type. Two tumours were of borderline serous variety. Right sided tumours were more 77/157 (49.04%). Laterality of tumour types as in (Table/Fig 6).

Discussion

Ovarian neoplasms are a cataclysm which spares none i.e., pre-pubertal, pubertal, reproductive age group, postmenopausal, even women with hysterectomy done. Ovarian neoplasms raise concerns regarding fertility, hormonal irregularities, marital relationships, cardiac and bone health related issues in general population. Analysis of histopathological pattern in a region specific is important as it unearths changing trends, most frequent, clinical course of tumours to empower primary as well as specialist physicians alike to provide speciality patient care.

As depicted in (Table/Fig 7) (6),(7),(8),(9),(10),(11),(12),(13),(14),(15),(16),(17), a significant contrast study done in region of Valsad, Gujarat which showed 49.40% malignant tumours and 10.50% borderline tumours (13).

Present study done in tribal Rajasthan had benign, borderline and malignant tumours 63.06%, 3.18% and 33.76%, respectively. Overall, these findings are in accordance with studies done in Pune, Varanasi, Jaipur and Rawalpindi; Pakistan (6),(9),(13),(15). SETs were most common (59.24%) in analysis, followed by GCTs (34.39%) and then SCST’s (6.37%) cell tumours and one was found to be poorly differentiated which is placed in SETs group as per WHO classification (4).

This paper confirms SET’s to be most frequent histopathological class. The findings are in line with previous work done by Cheema MK et al., and Kaur A et al., (13),(15). They differ with Singh M et al., only, who reported GCT’s to be the predominant tumour (12). Comparing with other studies, contrastingly GCT’s in current probe had higher incidence (5),(7),(9),(12),(13),(16), as shown in (Table/Fig 8) (6),(8),(9),(10),(11),(12),(13),(14),(15),(17).

Most common benign tumour revealed to be mature cystic teratoma which contrasts with various studies (5),(6),(7),(9),(10),(12),(13),(14),(16),(17). Similar pattern found only in studies done by Singh M et al., and Karki LRC et al., (12),(19). Serous cystadenocarcinoma was the most common malignant tumour. Patel AS et al., Mondal SK et al., Kant RH et al., were the only ones differed with this (14),(16),(18) while many others showed similar results (5),(6),(7),(8),(9),(10),(11),(12),(13). These are shown in (Table/Fig 9) (6),(7),(8),(9),(10),(11),(12),(13),(14),(18),(20).

According to the classification of WHO tumours, borderline tumours are an interesting class (5). Peculiar feature being that they are benign with low malignant potential. So, surgery is the definitive treatment. In present study, incidence of borderline tumours was 3.18%. Brenner’s tumour presented as benign, malignant as well as borderline. Hashmi AA et al., found mucinous borderline tumours of higher frequency while serous borderline was more frequent in this probe (20). Collision tumour (Brenner tumour in one ovary and mucinous cystadenoma in other) was unearthed in one case. Ten cases were reported by Wang Y et al., (21). They speculated Brenner is an intermediate step in formation of mucinous tumours; a clonal relationship. Similar, 2 cases were reported by Modepalli N and Venugopal SB, (22).

In age group 14-19 years, six patients were found. Benign cystadenoma was present in three girls and in one benign cystic teratoma. Malignancy found in two patients - one of germ cell origin (dysgerminoma) and other a mucinous adenocarcinoma. In extreme of age, 70 years and above among total 8 cases 37.5% were malignant. Out of 5 benign; three belonged to SET’s and one each to GCT’s and SCST’s. Puri S et al., reported 24.4% of cases to be in age group of 50-59 years followed by 24.0% in 40-49 years age group (23). Extremes of age noticed in probe was similar to Agrawal P et al., i.e., 12-80 years while Singh M et al., Kaur A et al., Itha MB and Veeragandham S, Kant RH et al., had 13-72 years, 15-70 years, 9 months -72 years and 15-65 years, respectively (6),(12),(15),(17),(18). Gupta N et al., observed a six-day-old child having GCT (9). Malignant tumours were reported to be more common in 5^th decade of life by Cheema MK et al., as well as Mondal SK et al., (13),(16). Mean age of more than 50 years was reported by Agarwal D et al., and Prasad AE et al., (10),(24). Mean age among all histopathological types was 33.9 years in work by Kant RH et al., and 41 years by Garg R et al., (18),(25). Present study reported no case of borderline tumour in age less than 21 years. Similar findings were reported by Xu M et al., (26).

Sharadha S et al., reported age of malignancy as 41 years (7). Mean age for of benign tumours was 39 years. Rathore R et al., in 25-year study in adolescent and childhood found 112 cases below 20 years age. A 34.8% were malignant and 65.2% benign. Mature cystic teratoma was most frequent in their study and 71.1% of all malignancies were GCT (27). Bilateral tumours in current study were 14.01%. Similar findings were observed in work of Patel AS et al., and Kant RH et al., (14),(18) whereas, Itha MB and Veeragandham S, and Garg R et al., depicted double the frequency of bilateral tumours in their work (17),(25).

Left sided lesion was predominant in studies by Patel AS et al., and Kant RH et al., while Itha MB and Veeragandham S, and Rathore R et al., observed right sided frequency more (14),(18),(17),(27). Mature cystic teratoma, the most frequent tumour in present study was 100% unilateral with right sided predeliction. While in studies by Rathore R et al., it was 8.9% bilateral (27).

Granulosa cell tumour reported benign with malignant potential (26) or borderline (16) or benign (11) is termed as malignant by WHO latest classification (28). Granulosa cell tumour in this study was reported in 2^nd decade, 3^rd decade, 4^th decade, 6^th decade and even after that. So, for granulosa cell tumour no age preferences were found. Dridi M et al., stated that GCT’s are notorious for relapsing even years after curative treatment (29).

Brenner tumour can be benign, borderline or malignant. Current analysis reports three benign, one malignant and one borderline Brenner tumour. No case of Endometroid tumour, Yolk sac tumour or metastatic tumour was found in study.

Studies done on the basis of WHO classification were easier to search within. WHO classification of tumours of reproductive organ 2014 has attempted to integrate the histologic diagnosis with molecular diagnosis. 2-tier system of grading of serous carcinoma is used and epithelial borderline tumour is also called as atypical proliferative tumour in it (30). WHO has been tirelessly working on modification of it and WHO Classification of Tumours of Reproductive organs has been updated in 2020. It emphasises on unique synthesis of histopathological diagnosis with digital and molecular pathology (28). Hence, the importance of such studies so that evidence-based medicine can be employed for future of patient.

Limitation(s)

The main limitation of this study is it is a single center experience and thus referrals may be a bias. Also, tumour markers, immune-phenotype is not correlated in current enquiry. Future studies could elaborate incidence of ovarian neoplasms formation after removal of fallopian tubes during hysterectomy or due to any other reason.

Conclusion

In female reproductive organs, there is a premalignant lesion for all organs (vagina, vulva, cervix, uterus and ovary) but not for ovary. Ovary is one organ where all benign neoplasms with malignant potential or frank malignant tumours are sighted. To effectively reverse the trend in a developing country like India each and every gynaecologist should be aware and well versed with histomorphological pattern of ovarian neoplasms specific to a region.

DOI and Others

10.7860/JCDR/2021/47999.15111

Date of Submission: Dec 30, 2020
Date of Peer Review: Jan 06, 2020
Date of Acceptance: May 27, 2021
Date of Publishing: Jul 01, 2021

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? NA
• For any images presented appropriate consent has been obtained from the subjects. NA

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