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LITERATURE - 2016, Journal of Hungarian Obstetricians and Gynaecologists

Histological types of ovarian cancer in Arad county: a fifteen years retrospective analysis

Furău Cristian

Authors: Furău Gheorghe MD1, Furău Cristian MD1, Daşcău Voicu MD1, Dimitriu Mihai MD2, Păiuşan Lucian MD1
1”Vasile Goldiş” Western University of Arad, Romania,
2“Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania

 

Objectives: The purpose of this study is to examine the histological types of ovarian cancer in Arad County during 1998–2012. Materials and methods: The data were collected from the Histopathology Exams (HPE) registers and were retrospectively analyzed and compared with international database using GraphPad Software and Epi Info 7.

Results: Ovarian cancer was discovered in 118 cases, representing 6.73% of all genital cancers (1754 cases). There were 112 cases of primary cancer (94.92%) and five cases of ovarian metastatic cancer (4.24%), one patient having a combination of the two (0.85%). Different histological types of carcinoma were detected in 105 cases of the 113 primary cancer cases, who had 118 histological types (88.98% of the histological types), yolk sac tumors, tumors of the granulosa, immature teratoma, and disgerminoma in three cases each (2.54% each), and Sertoli–Leydig tumors in one case (0.85%). Five (2.56%) had an association of two cancer types (yolk sac tumor with embryonal carcinoma, immature teratoma with neuroepithelial carcinoma, endometrioid+secretory adenocarcinoma, mucinous+coloid adenocarcinoma, papillary serous adenocarcinoma+ clear cell carcinoma) (4.24% of all patients, 4.42% of all patients with primary ovarian cancer). All six metastases were represented by carcinomas: one intestinal, one sigmoidian, two with unknown origin and two with several possible primary sites. The mean ages of the patients were 51.66±14.22 years.

Conclusion: The results of our study are similar to those in previous researches regarding the frequency of different histological types and the median age. Ovarian cancer still remains a serious public health issue, thus demanding a well organized screening program.

Keywords: ovarian cancer, ovarian carcinoma, yolk sac tumor, granulosa tumor, disgerminoma, immature teratoma, Sertoli–Leydig tumor, ovarian metastasis, histology, mean age

Introduction

Ovarian cancer has one of the most complex classifications. For a better understanding of our analysis we decided to present the main characteristics of these from the specialty literature.

1. Common epithelial tumors

The current classification of ovarian cancers is published by the WHO [1].

Approximately 90% of ovarian cancers are derived from cells of the coelomic epithelium or modified mesothelium [2] and approximately 75% to 80% of epithelial cancers are of the serous histological type. Less common types are mucinous (10%), endometrioid (10%), clear cell, Brenner, and undifferentiated carcinomas, each of the latter three representing less than 1% of epithelial lesions [3].

Each tumor type has a histological pattern that reproduces the epithelial features of a section of the lower genital tract [4–7].

Nonepithelial malignancies of the ovary account for approximately 10% of all ovarian cancers [8, 9].

2. Sex cord and stromal tumors

Granulosa and stromal cell tumor

Sex-cord-stromal tumors of the ovary account for approximately 5% to 8% of all ovarian malignancies [8–11, 17–21]. This group of ovarian neoplasm is derived from the sex cords and the ovarian stroma or mesenchyme. Granulosastromal- cell tumors include granulosa cell tumors, thecomas and fibromas; granulosa cell tumor is a low-grade malignancy [20–23].

Germ cell tumors

Germ cell tumors are derived from the primordial germ cells of the ovary [8, 9]. Although 20% to 25% of all benign and malignant ovarian neoplasm is of germ cell origin, only some 3% of these tumors are malignant [8]. Teratoma, the most common benign germ cell tumor, accounts for more than 90% of the tumors in this group. Primary malignant germ cell tumors are also uncommon and include dysgerminoma, embryonic carcinoma, yolk sac tumor, and choriocarcinoma. Except for dysgerminoma, all other primary germ cell tumors are high-grade malignancies and are not graded.

The dysgerminoma is the most common malignant germ cell tumor, accounting for approximately 30% to 40% of all ovarian cancers of germ cell origin [9, 12]. The tumors represent only 1% to 3% of all ovarian cancers [8, 11, 13]. The pure immature teratoma accounts for less than 1% of all ovarian cancers, but it is the second most common germ cell malignancy [8].

Endodermal sinus tumors (ESTs) have also been referred to as yolk sac carcinomas because they are derived from the primitive yolk sac [8].

Embryonic carcinoma of the ovary is an extremely rare tumor [14].

Pure nongestational choriocarcinoma of the ovary is an extremely rare tumor [16].

Polyembryoma of the ovary is another extremely rare tumor, which is composed of “embryonic bodies” [8, 12].

Mixed germ cell malignancies of the ovary contain two or more elements of the lesions described above. In one series [15], the most common component of a mixed malig nancy was dysgerminoma. The most frequent combination was a dysgerminoma and an EST.

Sertoli–Leydig tumors

Sertoli-Leydig tumors account for less than 0.2-1% of ovarian cancers [8].

Lipoid cell tumors are thought to arise in adrenal cortical rests that reside in the vicinity of the ovary. More than 100 cases have been reported, and bilateralism has been noted in only a few [8].

Malignant mixed mesodermal sarcomas of the ovary are extremely rare [24–30]. Most lesions are heterologous.

Metastases

Approximately 5% to 6% of ovarian tumors are metastatic from other organs, most frequently from the female genital tract, the breast, or the gastrointestinal tract [31–45]. The Krukenberg tumor, which can account for 30% to 40% of metastatic cancers to the ovaries, arises in the ovarian stroma and has characteristic mucin-filled, signet-ring cells [38, 39].

Rare cases of malignant melanoma metastatic to the ovaries have been reported [46].

Metastatic carcinoid tumors are rare, representing fewer than 2% of metastatic lesions to the ovaries [47].

Lymphomas and leukemia can involve the ovary.

The aim of our study is to assess the frequency of different histological types of ovarian cancers in our hospital over a fifteen year period and to compare the data with the one in literature.

Materials and methods

Our retrospective study concerning the histological types of ovarian cancer covers the 1998–2012 time-span, the data being collected from the Histopathology Exams (HPE) registers. During this time-frame there were 1754 gynecological cancers discovered, out of the total of 22841 histopathological examinations performed, ovarian malignancy being found in 118 cases. The data obtained was compared with similar studies from literature.

Results

During the fifteen year period, a number of 1754 gynecological cancers were diagnosed in our hospital by the anatomopathology department: 1020 cervical cancers (58.15%), 556 uterine cancers (31.70%), 118 ovarian cancers (6.73%), 51 vulvar cancers (2.91%), and 9 vaginal cancers (0.51%). There were 112 cases of primary ovarian cancers (94.92%), five metastases with different origins (4.24%) and a combination thereof (0.85%); in total, 113 patients had primary ovarian cancers (95.76%) and six had metastases (5.08%).

 

Figure 1. Ovarian cancer age groups
Figure 1. Ovarian cancer age groups

 

Figure 1 shows the age distribution of the cases; the mean age was 51.66±14.22 years (age range 18–77 years). Table 1 shows the histological types of all the 118 cases of ovarian cancer (metastases are in bold), while table 2 shows the histological types of the 113 cases of primary ovarian cancer (non-carcinoma types in bold), the tumor grading of the primary ovarian cancers and the histological types of the 104 cases of ovarian carcinoma, with adenocarcinoma being present in 84 cases (80.76%); different papillary adenocarcinoma types represented 54 cases of all adenocarcinomas (64.29% of adenocarcinomas, 51.92% of all carcinomas).

 

Table 1. Ovarian cancer cases
Cancer type No. %
Papillary serous adenocarcinoma 29 25.42
Papillary mucinous adenocarcinoma 18 15.25
Endometrioid adenocarcinoma 10 8.47
Clear cell carcinoma 9 7.63
Serous adenocarcinoma 5 4.24
Anaplasic carcinoma/Papillary endometrioid adenocarcinoma 4 3.39
Clear cell adenocarcinoma/Papillary secretory adenocarcinoma/Granulosa cell tumor/Mucinous adenocarcinoma/Disgerminoma 3 2.54
Anaplasic small cell carcinoma/Yolk sac tumor/Papillary adenocarcinoma/Secretory adenocarcinoma/Metastatic carcinoma, unknown origin 2 1.69
Papillary serous adenocarcinoma+ clear cell carcinoma/Endometrioid+secretory adenocarcinoma/Mucinous+coloid adenocarcinoma/Sertoli–Leydig tumor/ Nondiff erentiated carcinoma/Serous carcinoma/Yolk sac tumor+embrional carcinoma/ Immature teratoma with neuroepithelial carcinoma/Immature teratoma/Mature teratoma with squamous epidermoid carcinoma/Immature teratoma with mucinous adenocarcinoma of intestinal metastatic origin/Papillary mucinous adenocarcinoma of sigmoidian metastatic origin/Metastatic carcinoma, unknown origin (gastric, breast, colon)/Metastatic diff use type carcinoma (gastric or breast) +lobular carcinoma 1 0.85

 

Different histological types of carcinoma were detected in 104 cases of the 113 primary cancer cases, who had 118 histological entities (88.16% of the histological types), yolk sac tumors, tumors of the granulosa, immature teratoma, and disgerminoma in three cases each (2.54% each), and Sertoli–Leydig tumors in one case (0.85%). Five (2,56%) had an association of two cancer types (yolk sac tumor with embryonal carcinoma, immature teratoma with neuroepithelial carcinoma, endometrioid+secretory adenocarcinoma, mucinous+coloid adenocarcinoma, papillary serous adenocarcinoma+ clear cell carcinoma) (4.24% of all patients, 4.42% of all patients with primary ovarian cancer). One patient had a simultaneous uterine cancer (0.85%) (Table 2).

 

Table 2. Ovarian cancer histological types and grading
Primary ovarian cancer type No. % of types (118) % of patients (113) % of primary carcinomas G1 G2 G3 N/A
          No. % No. % No. % No. %
Papillary serous cystadenocarcinoma 28 23.73 24.78 26.92 14 50 11 39.29 3 10.71 0 0
Papillary mucinous cystadenocarcinoma 18 15.25 15.93 17.31 8 44.4 9 50 1 5.56 0 0
Clear cell carcinoma 9 7.63 7.96 8.65 1 11.1 4 44.45 3 33.33 1 11.11
Endometrioid adenocarcinoma 7 5.93 6.19 6.73 2 28.57 4 57.14 1 14.29 0 0
Papillary endometrioid adenocarcinoma 5 4.24 4.42 4.81 0 0 5 100 0 0 0 0
Clear cell adenocarcinoma 4 3.39 3.54 3.85 0 0 2 50 1 25 1 25
Anaplasic carcinoma 4 2.54 2.65 2.88 0 0 0 0 3 75 1 25
Mucinous cystadenocarcinoma 3 2.54 2.65 2.88 3 100 0 0 0 0 0 0
Endometrioid cystadenocarcinoma 3 2.54 2.65 2.88 2 66.67 0 0 1 33.33 0 0
Serous cyst-adenocarcinoma 3 2.54 2.65 2.88 1 33.33 0 0 2 66.67 0 0
Papillary secretory cystadenocarcinoma 3 2.54 2.65 2.88 2 66.7 1 33.3 0 0 0 0
Secretory cyst-adenocarcinoma 3 2.54 2.65 2.88 0 0 0 0 3 100 0 0
Serous adenocarcinoma 2 1.69 1.77 1.92 0 0 0 0 1 50 1 50
Papillary serous adenocarcinoma 2 1.69 1.77 1.92 1 50 1 50 0 0 0 0
Anaplasic small cell carcinoma 2 1.69 1.77 1.92 0 0 0 0 0 0 3 100
Papillary cystadenocarcinoma 2 1.69 1.77 1.92 1 50 1 50 0 0 0 0
Undifferentiated carcinoma 1 0.85 0.88 0.96 0 0 0 0 1 100 0 0
Serous carcinoma 1 0.85 0.88 0.96 0 0 1 100 0 0 0 0
Squamous epidermoid carcinoma 1 0.85 0.88 0.96 0 0 0 0 0 0 1 100
Mucinous adenocarcinoma 1 0.85 0.88 0.96 0 0 0 0 0 0 1 100
Neuroepithelial carcinoma 1 0.85 0.88 0.96 0 0 1 100 0 0 0 0
Colloid adenocarcinoma 1 0.85 0.88 0.96 0 0 0 0 0 0 1 100
Yolk sac tumor 3 0.85 0.88 0.96 0 0 0 0 0 0 3 100
Granulosa cell tumor 3 2.54 2.65 - 0 0 0 0 0 0 3 100
Disgerminoma 3 2.54 2.65 - 0 0 0 0 0 0 3 100
Immature teratoma 3 2.54 2.65 - 0 0 0 0 0 0 3 100
Sertoli–Leydig tumor 1 2.54 2.65 - 0 0 0 0 0 0 1 100
Embryonal carcinoma 1 0.85 0.88 - 0 0 0 0 0 0 1 100

 

The SEER database (48) shows the following distribution of the histological types (Table 3).

Metastases represented 5.08% versus 5-6% in literature [31–45].

Several ovarian cancer histological types in our study are similar or close to those in literature, the differences being partially explained by the relatively small number of cases in our study.

 

Table 3. Comparison between our studies results and SEER database
Histology (48) All Races Present study Other (2), (8), (11), (13)
  Count Percent    
Carcinoma 22,533 92.1% 88.16% 90%
Epidermoid carcinoma 177 0.7% 0.85%  
Adenocarcinoma 20,671 84.5% 72.03%  
Adenocarcinoma 3,223 13,2%    
Papillary adenocarcinoma 531 2.2% 1.69%  
Clear cell adenocarcinoma 1,263 5.2% 3.39%  
Endometrioid carcinoma 2,479 10.1% 12.71%  
Cystadenocarcinoma 143 0.6%    
Serous cystadenocarcinoma 3,490 14.3% 2.54%  
Papillary serous cystadenocarcinoma 6,840 28.0% 23.73%  
Mucinous cystadenocarcinoma 519 2.1% 2.54%  
Mucinous adenocarcinoma 880 3.6% 0.85%  
Mucin-producing adenocarcinoma 75 0.3%    
Other adenocarcinoma 1,228 5.0%    
Anaplasic carcinoma     5.08% 5%
Other specific carcinomas 544 2.2% 2.54%  
Stromal cell tumor 327 1.3% 2.54%  
Other 217 0.9%    
Sertoli–Leydig tumor     2.54% 0.2-1%
Dysgerminoma     2.54% 1-3%
Unspecified, Carcinoma 1,141 4.7%    
Sarcoma and other soft tissue tumors 87 0.4%    
Other specific types 1,629 6.7%    
Mullerian mixed tumor 697 2.9%    
Teratoma, malignant 358 1.5% 2.54%  
Other 574 2.3%    
Unspecified 206 0.8%    
Total 24,455 100%    

Conclusions

Ovarian cancer, although less frequent than other gynecological cancers, is usually diagnosed in advanced stages due to the non-specific signs and symptoms, which lead to many errors in interpreting them and to undesired delays in diagnosis and treatment, and to the lack of an organized and well conducted screening program. Due to the cost of biochemical screening, as FIGO also suggest, we find inappropriate a national screening program using CA 125, but including a transvaginal ultrasound examination in a yearly based control program can help identifying high risk patients. The use of ROMA score could be assessed in comparison to the use of only CA 125, increasing both sensitivity and specificity in high risk patients. CT scan and MRI should be used in suspicious ultrasound results.

Arad County has the second highest cancer incidence in Romania after Bucharest. The age of discovering ovarian cancer (51.6 year) can be considered significantly lower than the international mean (~60 year), although the rates of different ovarian histological types of cancer is very similar to the international databases (SEER). This particularity can be a point of further research in the Euro region.

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