Clinicopathologic study of malignant ovarian tumors: A study of fifty cases
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/MJDRDYPU.MJDRDYPU_41_17
Keywords: Malignant, ovary, surface epithelium, tumors
Ovarian malignancy is the second most common cancer of the female reproductive system and the leading cause of death from gynecologic malignancy.[1],[2],[3],[4] Incidence and prevalence of ovarian cancer vary in different geographical areas of the country. Indian trend analysis reveals a steady increase in the age-standardized incidence rate of ovarian cancer ranging from 0.26% to 2.44% per year in different area registries.[5] It has worst prognosis among all gynecological malignancies and highest case fatality rate. The overall 5-year survival is 45% primarily because of the late stage at diagnosis of the disease.[6] However, the clinical behavior of this malignancy varies widely, from an excellent prognosis and high likelihood of cure to rapid progression and poor prognosis, most probably reflecting variation in the tumor, biological properties. The survival rate of patients with early stage disease approaches 90%, but most cases are diagnosed late when the symptoms such as abdominal distension caused by ascites or large tumor masses become apparent.[7] Histomorphological features with immunohistochemical (IHC) profile and radiological, clinical, and other ancillary investigations including tumor markers hold keys for early diagnosis. The purpose of this study is to study the histopathological spectrum of malignant tumors of the ovary and to find out the frequency of various malignant ovarian tumors with respect to age and clinical features.
The prospective cohort study was carried out. Inclusion criteria All cases of primary and metastatic malignant ovarian tumors which were diagnosed on clinical, radiological findings and confirmed by histopathological findings were included in the study. Exclusion criteria All benign neoplasms of ovary were excluded from the study. The total fifty cases were included in the study. The detailed clinical findings such as clinical history, signs, symptoms and radiological findings were noted including important laboratory investigations such as CA-125. The tumors received for histopathological examination were grossed, and multiple sections were taken for histopathological examination. Tissue sections were formalin fixed and paraffin processed. Two to three microns sections were cut and stained with hematoxylin and eosin. Detailed histomorphological features were studied. Histochemical and IHC staining was done to support histological diagnosis. Histomorphological features were correlated with clinical findings.
Of fifty cases, maximum (n = 13) were seen in 51–60 years of age group, followed by 11 cases in 21–30 years of age group. [Table 1] shows detailed age distribution of fifty malignant ovarian tumors. The lump in the abdomen (n = 16) was the most common presenting symptom, followed by pain and lump in abdomen (n = 9) and pain in abdomen (n = 8). The least common symptom was per-rectal bleeding; gastrointestinal complaints with ascites and anorexia and weight loss one each. [Table 2] shows detailed clinical presentation of fifty cases. Right ovary (n = 24) was slightly more involved than left ovary (n = 22), and in four cases, both the ovaries were involved. Of fifty cases, majority (n = 47) were primary malignant tumors while remaining (n = 3) were metastatic.
Of fifty tumors, 27 were more than 10 cm while 23 were <10 cm. Grossly, 22 malignant ovarian tumors were solid/cystic in nature. While 21 were solid, seven were purely cystic in nature. CA-125 blood levels were done in all fifty cases, of which 27 cases showed elevated levels (>35 U/ml). Maximum cases of surface epithelial tumors showed elevated CA-125 levels. Ultrasound and color Doppler examination were done in all cases. The diagnosis of malignancy on ultrasound examination was supported by clinical features such as pain and abdominal distension, ascites, and elevated CA-125 levels and ultrasound findings such as irregular solid tumor, ascites, papillary structures, large multilocular solid tumor, and high Doppler content on color Doppler. MRI was carried out in eight cases. The diagnosis of malignancy was based on following features, namely, solid/cystic mass, presence of papillary projections, and thick septa in cystic lesion. Maximum number of cases (n = 31) were surface epithelial tumors, followed by germ cell tumors (n = 9) and sex cord-stromal tumors (n = 7). Remaining three cases were metastatic tumors. On histological examination, maximum (n = 15) were serous cystadenocarcinoma followed by mucinous cystadenocarcinoma (n = 7). [Table 3] shows detailed frequency of various histology diagnoses of fifty malignant tumors.
Ovarian tumors lead to considerable morbidity and mortality, especially during active period of life. These tumors manifest a wide spectrum of clinical, morphological, and histological features. They occur at any age in children, adolescence, and old age. In our study, the most common age group for malignant ovarian tumors was 51–60 (26%) years followed by 21–30 (22%). The youngest case in our present study was an 8-year-old female child. In contrast, 41–60 years was the most common age group in other studies.[8],[9] Few studies found ovarian cancers rarely before the age of 40 years.[10],[11],[12] In contrast, a significant proportion of ovarian malignancies was found in women younger than 40 years.[8],[9] Okugawa et al. found that mean age of malignant tumor was 51.9 years.[13] In our study, mean age was younger, 45.4 years. The possible variation in age group of various studies will depend on types of carcinomas in the study and stage at which patients presented. Pain and lump in the abdomen (n = 36) was the most common presenting symptom in the present study. Similar observations were made by Goff et al.,[14] Bhuvanesh and Logambal,[15] Kuladeepa et al.,[16] Kanthikar et al.,[17] and Mankar and Jain [9] found ascites in 10% of malignant cases. However, in our study, it was found in only 2% of cases. Variation in the symptoms can be due to type of carcinoma and stage of the disease. We did not find any predilection of ovarian cancer either in the right ovary or in the left ovary. In our study, majority of cases were unilateral (92%). Our findings were in accordance with other studies.[18],[19] The 94% of cases in our study were primary and 6% were secondary. Our results were in accordance with other studies.[20],[21],[22],[23] In contrast, in studies conducted by Mankar and Jain [9] and Jha and Karki,[8] metastatic tumors were 20% and 15.38%, respectively. [Table 4] shows detailed comparison of histomorphological types of malignant ovarian tumors in various studies. In our study, the mean diameter of tumor was 10.73 ± 4.2 cm. Okugawa et al.[13] in their study found the mean diameter of 13.6 ± 6.5 cm. Maximum (44%) malignant tumors were solid/cystic in nature in our study. Similar observations were made in other studies.[17],[18],[21]
In our study, maximum (62%) cases were of surface epithelial tumors. Similar observations were made by many authors [Table 4].[8],[9],[20],[21] The serous cystadenocarcinoma was the most common tumor in the present study. Similar observations were made in other studies.[24],[25],[26],[27] Grossly, the tumor was solid/cystic [Figure 1]a. Histopathological examination revealed that ovarian stroma was infiltrated by tumor, exhibiting papillary and glandular architecture. Neoplastic cells showed cellular and nuclear features of pleomorphism [Figure 1]b. Psammoma bodies were seen in 40% of tumors [Figure 1]c. Of 15 cases, five were well-differentiated, four were moderately differentiated, and six were poorly differentiated. Tumor tissue showed immunoreactivity with CK-7 and epithelial membrane antigen (EMA) [Figure 1]d and was nonreactive with CK-20 and carcinoembryonic antigen (CEA).
The 16% (n = 8) of tumors were of mucinous cystadenocarcinoma. Similar incidence has been reported by many authors.[24],[25],[26],[27] Grossly, the tumors were solid/cystic [Figure 2]a. Out of eight cases, five were of intestinal type and three were of Mullerian type. Intestinal type was characterized by an epithelial lining with a “picket fence” appearance, goblet cells. Second and less common type endocervical or Mullerian type was characterized by papillary architecture, lining of tall nonciliated cells with basally located nuclei and abundant intracellular mucin [Figure 2]b. Neoplastic cells showed cellular and nuclear features of pleomorphism. The five tumors were well-differentiated, two were moderately differentiated, and one was poorly differentiated. IHC staining was positive for CEA and EMA [Figure 2]c.
Histopathological examination of endometrioid carcinoma showed tumor cells arranged in tubules, cords, papillae, and solid sheets. Capsule was invaded by tumor tissue. Neoplastic cells showed cellular and nuclear features of pleomorphism [Figure 3]a and [Figure 3]b. Endometrioid carcinomas may or may not show papillary formation.[28] In the present study, in both cases, papillary formation was present and both cases were moderately differentiated.
The only case of malignant Brenner tumor showed solid sheets of epithelial cells resembling transitional epithelium surrounded by fibroblastic stroma. Nuclei of tumor cells showed small but distinct nucleoli. Nuclear pleomorphism was seen [Figure 3]c and [Figure 3]d. There was stromal invasion. Tumor showed areas of necrosis and hemorrhage. The four cases were diagnosed as transitional cell carcinoma in our study. Grossly, external surface was lobulated and cut-section was solid/cystic [Figure 4]a. Microscopy showed elongated bands of neoplastic epithelial cells separated by necrotic material and fibrovascular tissue. Papillae are shown in [Figure 4]b. Many tumor cells showed nucleoli. Mitotic activity is shown in [Figure 4]c. A Brenner-like component was absent. IHC staining showed negative staining of CK-7 and CK-20 and positive staining with Wilms tumor protein (WT 1) [Figure 4]c and [Figure 4]d.
The only case of malignant mixed Mullerian tumor in our study showed solid/cystic tumor, and histopathological examination showed carcinomatous and sarcomatous elements [Figure 5]a and [Figure 5]b. The tumor was moderately differentiated.
Out of nine cases of germ cell tumors, three were dysgerminoma, one was yolk sac tumor, four cases were immature malignant teratoma, and one case was of mixed germ cell tumor. Malignant germ cell tumors constitute about 18% of all ovarian cancers [29] and are usually seen in children and young adults.[29],[30] Usually, younger the patient, more likely germ cell tumor will be malignant.[30],[31] Similar observations were made in our study. The eight cases were seen in children and young adults, while only one case was seen in a 65-year-old woman. Dysgerminoma constitutes about 5% of malignant ovarian tumors.[32] Grossly, all cases showed encapsulated tumor with bosselated surface. Cut surface was solid and gray [Figure 6]a. Usually, dysgerminoma is more common on the right side. However, in our study, only two cases of dysgerminoma were in the left ovary. Histopathological examination showed well-defined nests of tumor cells separated by fibrous septa which were infiltrated by lymphocytes. Tumor cells were monomorphic and had large nuclei, prominent 1–2 nucleoli, and abundant finely granular cytoplasm containing glycogen [Figure 6]b and [Figure 6]c. IHC staining showed CD-117 and PLAP positive [Figure 6]d and CD-30 negative.
The only case of yolk sac tumor was in a 30-year-old woman. Usually, yolk sac tumor is a neoplasm of children and young adults though it also occurs in elderly.[33] In the series of Kurman and Norris, 23% of patients were prepubertal at the time of diagnosis.[34] Histopathological examination showed microcystic areas formed by cuboidal cells. Schiller–Duval bodies were seen [Figure 7]a and [Figure 7]b. Intracytoplasmic and extracellular PAS-positive hyaline droplets are nearly always present [Figure 7]c.[35] Similar observations were made in our study. Tumor tissue was nonimmunoreactive with WT1.
The 8% of cases were (n = 4) diagnosed as immature (malignant) teratoma. They may be solid, solid-cystic, or predominantly cystic.[36] All four cases in our study were solid-cystic [Figure 8]a. Histopathological examination showed mixture of mature and immature tissue. Immature element was mostly in the form of neuroepithelial tissue [[Figure 8]b; arrow].
Grading system of immature teratoma correlates with various types of karyotypic abnormalities.[37] It is graded into three grades as Grade I: abundance of mature tissue, intermixed with loose mesenchymal tissue with occasional mitoses, immature cartilage, and tooth anlage; Grade II: fewer mature tissues, rare foci of neuroepithelium with mitoses not exceeding three per low-magnification fields in any one slide; and Grade III: few or no mature tissues, numerous neuroepithelial elements, merging with a cellular stroma occupying four or more low-magnification fields. In our study, one case each was of Grade I and Grade II and two cases were of Grade III. In mixed germ cell tumors, the most common combination is dysgerminoma and yolk sac tumor though other combinations can occur.[38] The only case in our study was a combination of carcinoid and yolk sac tumor elements and it was moderately differentiated. The 14% (n = 7) tumors were diagnosed as sex cord-stromal tumors. Six cases were granulosa cell tumors and one case was Sertoli cell tumor. The two distinct types of granulosa cell tumors exist. One is adult type, which is more common, and other is juvenile type, which is less common.[39] In the present study, all six cases were adult type. Of six cases, two cases were solid, three cases were solid-cystic [Figure 9]a, and one case was cystic. Histopathological examination showed tumor cells arranged in solid sheets. Call–Exner bodies, mitotic figures, and nuclear grooves were seen [Figure 9]b,[Figure 9]c,[Figure 9]d. Usually, patterns of growth include microfollicular (with Call–Exner bodies), macrofollicular, trabecular, insular, watered-silk, solid, pseudopapillary, and diffuse (sarcomatoid).[40],[41],[42] Nuclei showed grooves resulting in coffee-bean appearance. IHC staining with EMA was negative and tumor cells were estrogen receptor and progesterone receptor positive.
Only case of Sertoli cell tumor was yellowish and cut-section was solid. Histopathological examination showed tumor cells arranged in cords and sheets. At places, tumor cells appeared as aggregates of Sertoli-like cells which were separated by spindle-shaped stromal cells [Figure 10]a and [Figure 10]b. Foci of Leydig cells were recognized. Diagnosis of Meyer type II Sertoli cell tumor was made. Neoplastic cells showed cellular and nuclear features of pleomorphism.
Three cases were diagnosed as metastatic ovarian tumors [Table 2]. One case showed signet ring cells [Figure 10]c. Although half of metastatic tumors are bilateral, all three cases in our study were unilateral. Most of the ovarian cancers are diagnosed late when symptoms such as abdominal distension caused by ascites or large tumor mass become apparent. Even after surgical debulking and chemotherapy, the prognosis of late stage ovarian cancer is dismal. The introduction of paclitaxel in 1990 improved the initial rates complete response (51% vs. 31%), progression-free survival (18 months vs. 13 months), and overall survival (38 months vs. 24 months).[43],[44]
Ovarian malignancy is the second most common cancer of the female reproductive system. Although the most common age group for malignant ovarian tumors is 51–60 years, significant number of tumors occurs between 21 and 30 years of age. The most common clinical presentation is pain and lump in the abdomen Malignant surface epithelial tumors are the most common tumors among the other histomorphological types of malignant ovarian tumors. Serous cystadenocarcinoma is the most common malignant tumor, followed by mucinous cystadenocarcinoma and granulosa cell tumors. Clinical symptoms, radiological findings, and other ancillary investigations such as CA-125 are the keys in establishing the preoperative diagnosis of ovarian carcinoma. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]
[Table 1], [Table 2], [Table 3], [Table 4]
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