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A Retrospective Analysis of Mature Cystic Teratomas of the Ovary:A Cross Sectional Study from a Tertiary Care Hospital of Central Region of Nepal

Received: August 28, 2014 Revised: Oct. 29, 2014 Accepted: Nov. 12, 2014 Published online: Dec. 30, 2014 Abstract Background Mature cystic teratoma (MCT), usually known as dermoid cysts derived from primordial germ cells. Comparing with different other types of germ cell tumors like dysgerminomas, and endodermal sinus tumors, they are most commonly observed. The aim of this study was to evaluate the prevalence, clinical and pathological characteristics; and complications of MCT of the ovary in Chitwan district, central region of Nepal.


Background
Mature cystic teratoma of the ovary is commonly known as the dermoid cyst which contains developmentally mature skin-related structures with hair follicles and sweat glands. It is originated from primordial germ cells and histologically composed of three well-differentiated elements, namely ectoderm, mesoderm and endoderm [1][2][3]. Although Germ cell layer derivatives originated mainly from the ectoderm, but there are frequent evidences of mesodermal and endodermal derivatives [4]. It accounts for approximately 15% of all ovarian neoplasms [1,2]. It is not only the most common germ cell tumor [5], also the most common ovarian tumor in patients between 20 to 40 years of age [6]. Majority of the cases, patients admitted in the hospital with a clinical presentation of acute pelvic pain and mass [4]. Relatively fewer occurrences (10-15%) of MCT documented bilaterally [1,2,7]. Torsion, rupture and infection are the most common complains among MCT patients [8,9]. The possibility of the development of a malignancy should be considered in case of tumors with a diameter larger than 10 cm, in women aged over 45 years [10]. Growth rate of MCTs are slow, at an average rate of 1.8 mm each year, which may prompt clinician towards nonsurgical management of relatively smaller (<6-cm) tumors [11]. Although there are several studies of MCT in Asian countries, from Nepal reports are less [12,13]. Bashyal and Lee reported three cases of MCT from Chitwan, but there was no retrospective cross sectional analysis to understand the epidemiological scenario of the disease [14,15]. The prognosis for malignant transformation of MCT is very poor with a five year survival of only 15-30%. So early diagnosis is required [13]. This is the first study to investigate the prevalence, clinical and pathological characteristics; and complications in MCT cases in the Bharatpur district, central region of Nepal.

Study Period
Three years records of MCT (July 2011 to June 2014) was collected for this study from the Department of Pathology in Chitwan Medical College Teaching Hospital, Bharatpur-10 Chitwan, Nepal.

Study design and the collection of data
It was a retrospective, hospital based study conducted in the Department of Pathology. A total number of 151 ovarian neoplasms were analyzed in this study, among them, 74 cases of MCTs in 62 patients (bilaterality in 12 patients). All the histopathologically confirmed cases of MCTs were considered for this study. We included all the cases, specimens were received and processed in the Department of Pathology of this hospital. Sociodemographic details, patient's history, complications, clinical features, diagnosis, types of surgical interventions, were retrieved from the departmental records. Conventional techniques were followed in processing the tissues. Tissues were fixed in 10% buffered solution of formalin, a series of treatments performed and as a routine procedure embedded in paraffin. Sections were cut into 5 micron or even thinner when necessary and stained with routine Hematoxylin and Eosin (H & E) stain using standard procedure. The WHO classification of ovarian tumors was used for categorizing the tumors [16].

Inclusion criteria
All the histopathologically confirmed cases of ovarian MCTs included, for this study irrespective of age or any other factors.

Exclusion criteria
Incomplete sociodemograchic records or clinical history of the patients were excluded to avoid study bias.

Ethical committee approval
The samples used in this study were from routine clinical specimens. This is a retrospective study and not interfering with routine clinical care so written permission was obtained at the beginning of the experiment from the Head of the Department, Pathology, Chitwan Medical College Teaching Hospital.

Outcome variable
Clinical manifestations like abdominal pain, discomfort, pelvic pain, tumor related complications, tumor diameter were set up as outcome variable.

Explanatory variables
The demographic factors were considered as explanatory variables

Data management and statistical analysis
Data were expressed as mean, median, range, number and percentages. Comparison was made and the two-tailed student t-test and Mann Whitney U-test was used as appropriate. Probability level of P<0.05 was considered statistically significant.

Results
Out of a total number of 151 cases of ovarian neoplasms, 74(49%) cases of MCTs of the ovary in 62 patients (including bilaterally in 12 patients) were diagnosed.

Microscopic features
On histopathological examination, a total of 71 (95.94%) cases of MCTs were purely composed of biphasic or triphasic components of germ layer derivatives.   Table 4. Among all cases, only one was associated with infection and showed accompanying neutrophilc abscess formation.

Age distribution and MCT
MCTs were encountered mostly at the average age of 30.8 to 35.4 years [4,12,17]. In this present study, we found average age of the patient was 30.87±12.43 years. The majority of cases were of patients aged 17-45 years and 20-30 years [12,18]. Our findings also corroborates the same, most patients (74.19%) were in reproductive age group of 21-40 years. Early detection of MCT is very important in this context. Conservative ovarian surgery in childhood and adolescence helps in normal puberty also minimize impact on future fertility [19]. In MCT Laparoscopic oophorectomy is the best choice in children and ovarian cystectomy is used in adults [20][21][22]. The reason, MCT are found in reproductive age group may be because of their development, which is from a single primordial germ cell which has completed meiosis I and meiosis II-is suppressed [23]. Anatomic distribution of teratomas throughout the migration pathway of primordial germ cells from the yolk sac to the gonadal ridges also supports this [24]. Comparing with different other types of germ cell tumors like dysgerminomas, and endodermal sinus tumors, they are most commonly observed. [25][26][27]; and also the most common tumor among all ovarian neoplasms accounting for 40.3% to 42.8% of all ovarian tumors [27][28][29]. The incidence of MCTs during pregnancy was 0.2% among ovarian tumors [17] while the incidence was higher in range of 3% to 3.5% in other series Mature cystic teratomas of the ovary: report from Bharatpur, Nepal [12,18] which is comparable with our series. None of these patients had any complications related to the tumors in our study similar to as the case series of Comerci et al. [30].

Clinical manifestations associated with MCTs
MCTs have symptoms related to the size such as pain, urinary and gastrointestinal complaints, and menstrual irregularities [4,30]. The most common symptom of these tumors was abdominal pain, reported in about half of the cases [12,29]. In our series, abdominal pain was found in higher incidence about 64.52%, similar to the incidence rate reported by Papadias et al. MCTs are often discovered as an incidental finding during a routine physical examination or during pelvic surgery for other reasons [12,18,29,30]. Frequency of asymptomatic patients varied in different series ranging from 16.6 to 75.5% [4,12,17,18,29,31]. Of greater interest, an unexpectedly high incidence of asymptomatic patients was reported [17]. In this research, 22.58% of the patients were asymptomatic similar to the study of Ayan et al. Torsion of the pedicle was the most common complication of these tumors with the frequency of 3.5 to 9.2% [12,17,30,32]. In contrast, the most common complication in our study was ascites comprising 6.4% and torsion being the second common complication. The most important prognostic factors for malignant transformation are age and tumor diameter [22,23]. Even though mature cystic teraromas occur frequently during reproductive age group, they do not develop malignancy until after the menopause [31]. Malignant transformation of these tumors is very rare, 0.7 to 1.2% [20,21], most often in the form of a squamous cell carcinoma [12,17,15]. Right-sided mature tumors outnumbered left sided tumors, which is consistent with our study. Bilateral teratomas are uncommon with the reported rate of 8.2 to 16.7% [4,12,18,29,30,32]. We observed slightly higher incidence rate (19.35%) of bilateral tumors. Thus, we suggest that in the presence of a unilateral teratoma, careful gross inspection and adequate sections of the contralateral ovary should be kept for histopathological examination. Majority of the tumors (78%) measured 5 to 10 cm in the greatest diameter and only 6 cases were more than 10 cm [18], and approximately 60% measured 5-10 cm in diameter and around 10% were larger than 15 cm [30]. We found, 85% of tumors were 5 to 10 cm, and a relatively less (5.40%) were larger than 10 cm.

Identification of germ layer derivatives
During the re-evaluation of these tumors classification problems were encountered with the cases of MCTs and epidermoid cysts. The WHO classification of ovarian tumors (2003) separated epidermoid from dermoid cysts [16]. Epidermoid cysts are classified as benign surface epithelialstromal tumors of the ovary and considered to arise from squamous metaplasia of epithelial elements, and are lined by stratified squamous epithelium, without evidence of mesodermal or endodermal tissue. There were two cases of epidermoid cysts among all ovarian neoplasms in our institution during the study period of three years. Germlayer derivatives were ectodermal origin in 98.9%, mesodermal origin in 54.2%, and endodermal origin 29.2% [4]. This is compared to figures of 98.64%, 67.56%, and 36.48% respectively in our series. There were altogether 17 individual derivatives observed in this research work. In our study skin and its appendages were the frequent derivatives, each constituting 98.64%, similar to other studies, whereas it was observed in 100% of the tumors in a case series reported by Ayan et al. [4,27]. The dominant mesodermal structures were bone and/or cartilage either or both were detected in 100% of cases [32].  [4,27].

Conclusion
MCT is the most common germ cell tumor that accounts for 49% of all ovarian neoplasm. They occur primarily during the reproductive years, but may occur in postmenopausal women or in children. We found ascites as the most common complication and the prevalence rates of torsion less than those previously reported by most other series. Larger tumors have more risk of undergoing torsion than smaller tumors. The most common germ-layer derivative is ectodermal in origin with high frequency of skin and its appendages. These histopathological findings and the complications will help early diagnosis of MCTs and create awareness among the physicians of Nepal.

Limitations & future scope of the study
This is a hospital-based study conducted only in a single institution; hence our sample size is less. Thus, it strongly recommended conducting broad spectrum multi-centric studies in future including other districts to explore more information. Apart from this, our study period is relatively less, so prolonged investigations may give more information about MCT.