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ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 3  |  Page : 946-951

Clinicopathological differences between type I and type II endometrial carcinoma


Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt

Date of Submission03-Sep-2015
Date of Acceptance30-Sep-2015
Date of Web Publication15-Nov-2017

Correspondence Address:
Hend A Kasem
Shibin El-Kom, Menoufia, 325111
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.218267

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  Abstract 

Objective
The aim of this study was to investigate the differences between type I and type II endometrial carcinoma (EC) as regards relevant clinicopathological features.
Background
EC is the most frequent gynecological malignancy in the USA accounting for 3% of deaths yearly. However, in Egypt, it accounts for 1.6% of total female cancers, ranking 13th. It is the third most common gynecological cancer after cancer of the ovary and the cervix constituting about 23%.
Methods
Data were collected from the archive of Department of Pathology, Menoufia University, during the period from 2010 to 2014. The slides presented were examined to meet the inclusion criteria. The slides were examined to differentiate between type I and type II EC. If the slides did not fulfill the inclusion criteria, they were excluded. Study quality assessment included adequate information and defined assessment measures. All slides were examined and comparisons were made between type I and type II EC and the results were tabulated.
Results
Forty-nine of 67 (73.1%) cases were of type I EC, whereas 18 (26.9%) cases were of type II EC. High grade (100%), advanced stage (55.6%), high mitotic count (mean ± SD: 6.72 ± 2.49), and low apoptotic count (mean ± SD: 8.28 ± 10.18) were in favor of type II EC.
Conclusion
Type I EC is more frequent compared with type II. Type II EC is more aggressive compared with type I and is manifested by presentation at high grade, advanced stage, high mitoses, and low apoptotic count.

Keywords: endometrial carcinoma, histopathology, types I and II


How to cite this article:
Abd El-Wahed MM, Abdou AG, Al-Sharaky DR, Kasem HA. Clinicopathological differences between type I and type II endometrial carcinoma. Menoufia Med J 2017;30:946-51

How to cite this URL:
Abd El-Wahed MM, Abdou AG, Al-Sharaky DR, Kasem HA. Clinicopathological differences between type I and type II endometrial carcinoma. Menoufia Med J [serial online] 2017 [cited 2019 Nov 21];30:946-51. Available from: http://www.mmj.eg.net/text.asp?2017/30/3/946/218267


  Introduction Top


Endometrial carcinoma (EC) is the most frequent gynecological malignancy in the USA [1]. It ranks fourth among cancers in women, accounting for 3% of deaths yearly. It occurs around or after menopause between 60 and 75 years of age. However, in Egypt, it represents 1.6% of total female cancers, ranking 13th. It is the third most common gynecological cancer after cancer of the ovary and the cervix constituting about 23% [2] with a high mortality rate [3].

Endometrial adenocarcinoma has two basic clinicopathologic forms, type I and type II [4]. Type I EC is generally well-to-moderately differentiated and accounts for 80–85% of all ECs and includes tumors of endometrioid histology [5] and its variants such as villoglandular, secretory, mucinous, ciliated, glassy, adenoacanthoma, and adenosquamous [6]. Type I tumors develop in an estrogenic environment, associated with high levels of hormone receptors and usually respond to hormonal therapy such as progestins. Such tumors generally arise on a background of endometrial hyperplasia and have a good prognosis with a 5-year survival of 80% or better [7]. In contrast, type II represents about 15–20% of cases, is poorly differentiated, generally of a nonendometrioid histological subtype, frequently lack steroid receptors, more likely to recur after treatment, and are not responsive to antiestrogenic therapy; these tumors often arise within atrophic endometrium [7]. These tumors include grade 3 endometrioid and other tumors of nonendometrioid histology such as serous, clear cell, squamous, transitional, and undifferentiated carcinomas [5].

Type I and type II EC tend to have different mutations involved; inactivation of PTEN occurs early in type I ECs that lead to the upregulation of the PI3k/Akt/mTOR pathway, which causes cell growth [8], but the primary genetic defect in type II EC is mutation of the p53 gene, observed in 75–100% of tumors [9].


  Materials and Methods Top


Search strategy

This retrospective study was conducted on 67 Egyptian EC patients. Cases were retrieved from the archival material of Pathology Department, Faculty of Medicine, Menoufia University, spanning the period between 2010 and 2014.

Study selection

All slides were independently assessed for inclusion. They were included if they fulfilled the criteria given below.

Inclusion criteria

Clinical records including clinical data such as age, presentation, type of surgery, and menopausal status were included. Mean ± SD, median, and range were assessed for both age and tumor size. For menopausal status, it was divided into perimenopausal and postmenopausal groups.

Histopathological features: the histological types were assessed according to the 2003 WHO classification [10]. ECs were divided into two types (types I and II) as described by Hedrick Ellenson et al. [11]. Grading was performed according to the International Federation of Gynecology and Obstetrics (FIGO) system [12]. In this current study we considered grade III endometrioid as type II EC as reported by Felix et al. [5]. Staging was based on the 2009 FIGO staging system [13] and the stages were grouped into two for statistical purposes: early stage (including stages I and II) and advanced stage (including stages III and IV). The presence or absence of necrosis was assessed. Evaluation of mitosis and apoptosis was carried out using an Olympus CH2 light microscope with wide angle (field size: 0.274 mm2, field diameter: 0.59 mm2; Olympus, Tokyo, Japan). The mitotic and apoptotic counts were calculated as the total number of figures counted in 10 high-power field of vision [14],[15]. Lymphovascular invasion, myoinvasion, and surrounding stromal reaction were also assessed [16]. Absence of any sarcomatoid differentiation was recorded.

Data extraction

If the slides did not fulfill the above criteria, they were excluded.

Quality assessment

The quality of all slides was assessed. Important factors included study design and specified assessment measures.

Data synthesis

A structured systematic review was performed with the results tabulated.


  Results Top


Clinicopathological characteristics of endometrial carcinoma types

Clinical data

Type I EC constituted 49 cases of the total 67 studied cases, whereas type II EC constituted 18 cases. The age in type I EC ranged from 46 to 79 years, with a mean ± SD of 59.93 ± 6.94 years and a median of 59 years, whereas the range of age in type II EC was from 49 to 71 years with a mean ± SD of 61.88 ± 7.11 years and a median of 64 years. Four of 49 (8.2%) cases of type I EC were perimenopausal, whereas 45 (91.8%) cases were postmenopausal, and 17/18 (94.4%) cases of type II EC were postmenopausal and only one (5.6%) case was perimenopausal. For type I EC tumor size ranged from 1 to 10 cm with a mean ± SD of 4.5 ± 2.05 cm and a median of 4 cm and for type II EC it ranged from 1.5 to 7 cm with a mean ± SD of 4.33 ± 1.62 cm and a median of 4.25 cm [Table 1].
Table 1: Clinical and pathological data of carcinoma cases

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Histopathological data

Histologically type I EC comprised 27 cases of endometrioid adenocarcinoma [Figure 1], six cases of endometrioid carcinoma with squamous differentiation [Figure 2], 15 cases of villoglandular variant of endometrioid carcinoma [Figure 3], and only one case of mucinous adenocarcinoma. Type II EC comprised six cases of papillary serous adenocarcinoma [Figure 4], six cases of clear cell carcinoma [Figure 5], and six cases of grade III endometrioid carcinoma [Figure 6].
Figure 1: Well-differentiated. (grade. I) endometrioid adenocarcinoma showing irregular crowded glands lined by columnar epithelium with pseudostratified nuclei and mild cytologic atypia. H and E, ×100.

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Figure 2: Moderately differentiated (grade II) endometrioid adenocarcinoma with well-formed squamous morules (red arrow) surrounded by the glandular component. H and E, ×200.

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Figure 3: Endometrioid adenocarcinoma grade II villoglandular variant characterized by finger-like projections with delicate fibrovascular cores (red arrow) lined by tall columnar cells with bland nuclei. H and E, ×200.

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Figure 4: Low power of papillary serous adenocarcinoma showing malignant cells arranged in papillae and papillary cluster and surrounded by desmoplastic reaction. H and E, ×100.

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Figure 5: Clear cell carcinoma formed of malignant clear cells or hobnail cells with marked degree of nuclear atypia arranged in solid growth pattern. H and E, ×200.

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Figure 6: Poorly differentiated (grade III) adenocarcinoma with predominant solid sheets of malignant nonsquamous cells (red arrows). H and E, ×100.

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According to FIGO grade, 8/49 (16.3%) cases of type I were of grade I and 41/49 (83.7%) cases were of grade II, and all cases of type II EC were of grade III.

According the 2009 FIGO staging system, 32/49 (65.3%) cases of endometrioid adenocarcinoma were of stage I, 9/49 (18.4%) cases were of stage II, 6/49 (12.2%) were of stage III, and finally 2/49 (4.1%) cases were of stage IV. For type II EC, 7/18 (38.9%) cases were of stage I, 1/18 (5.6%) cases was of stage II, and 10/18 (55.6%) cases were of stage III. A total of 41/49 (83.7%) cases of type I EC presented at early stage, whereas 10/18 (55.6%) cases of type II EC belonged to the advanced stage.

Forty-six of 49 cases of type I EC showed myometrial invasion, whereas only three cases were superficial, lacking myometrial invasion. For type II EC, 16/18 cases displayed myometrial invasion, whereas only two cases were free of invasion. As regards type I EC, 18/46 cases with myometrial invasion displayed invasion of less than half of the myometrium, whereas 28 cases displayed an invasion of more than half of the myometrium. As regards type II EC, 3/16 cases with myometrial invasion displayed invasion of less than half of the myometrium, whereas 13 cases displayed invasion of more than half of the myometrium.

Eight (16.3%) cases of type I EC and only six (33.3%) cases of type II EC were positive for lymphovascular invasion. Ten of 49 cases of type I EC and 7/18 cases of type II EC showed necrosis.

As regards type I EC, 12/49 (24.5%) cases were found to have inflammatory stromal reaction, five (10.2%) cases had desmoplastic stromal reaction, and 32 (65.3%) cases showed both desmoplastic and inflammatory stromal reaction. For type II EC, 3/18 (16.7%) cases were found to have inflammatory stromal reaction, six (33.3%) cases showed desmoplastic stromal reaction, and 9/18 (50%) cases demonstrated both desmoplastic and inflammatory stromal reaction.

The mitotic count in type I EC ranged from 1 to 9 with a mean ± SD of 5.12 ± 1.95 and a median of 5 and for type II EC it ranged from 3 to 13 with a mean ± SD of 6.72 ± 2.49 and a median of 7. The apoptotic count in type I EC ranged from 7 to 56 with a mean ± SD of 29.65 ± 13.88 and a median of 30, and for type II EC it ranged from 3 to 40 with a mean ± SD of 8.28 ± 10.18 and a median of 4 [Table 1].


  Discussion Top


The two main pathological variants of EC were first described by Bockman [4]. Type I tumors are low grade and estrogen-related endometrioid carcinomas that usually develop in perimenopausal women and coexist or are preceded by complex and atypical endometrial hyperplasia. In contrast, type II tumors are nonendometrioid, very aggressive tumors, unrelated to estrogen stimulation, arising occasionally in endometrial polyps or from precancerous lesions, and develop in atrophic endometrium, which mainly occur in older women [4].

This study was carried out on 67 cases of both type I and type II EC. Type I EC included 49 (73.1%) cases and type II included 18 (26.9%) cases. This is in agreement with the findings of Felix et al. [5], who reported that the major types of EC are of endometrioid type.

The mean age of type I EC cases was 59.93 ± 6.94 years, and the mean age for type II EC cases was 61.88 ± 7.11 years. This is in agreement with the findings of Fadare et al. [17], who found that most of the EC cases were diagnosed above 50 years of age. The median age of cases of type II EC was older than that of type I EC cases, which is in agreement with previous reports [5],[18],[19],[20].

In the current study, 91.8% of type I and 94.4% of type II cases presented at postmenopausal period. This result is contradictory to the findings of Bockman [4], who stated that type I EC develops in perimenopausal, whereas type II occurs in older women. This could be attributed to many factors such as ignorance, poverty, and lack of educational programs and screening health programs in our community.

In this study, all cases of type II EC were statistically in favor of grade III. This is in agreement with the findings of Creasman [21], who reported that type II EC is usually presented at high grade and advanced stage.

Forty-one (83.7%) cases of type I EC were initially diagnosed at early stage (stages I and II) and only eight (16.3%) cases were diagnosed at late stages (stages III and IV). This is in agreement with that reported by Salvsen and colleagues [22],[23],[24], who stated that the majority of type I EC are diagnosed at early stage because of early symptoms of vaginal bleeding, but still 30% of all cases are diagnosed at later stages. Moreover, Hill and Dizon [25] demonstrated that EC was commonly confined in the endometrium and most tumors could be removed by means of hysterectomy. However, 55.6% of type II presented at advanced stage; this is in agreement with the findings of Creasman [21], who found type II EC to be of poor histopathological subtype with a propensity for extrauterine spread, even if the myometrium is superficially involved. We also agree with Saksouk and Al-Kadhi [24], who stated that type II EC is aggressive with early extrauterine spread and in some patients with transtubal peritoneal dissemination.

In this study, there was no difference between the two EC subtypes as regards myometrial invasion. This could be attributed to the fact that type II EC has been shown to metastasize without deep myometrial invasion [26].

In this study, high mitotic count and low apoptotic count were in favor of type II EC. This is in agreement with the findings of Judit et al. [27], who found an increased mitotic index with histological grade and all cases of type II EC investigated in our study were formed entirely of grade III. We also agree with Vaskivuo et al. [28], who reported that the decrease in the rate of apoptosis in grade III adenocarcinoma may reflect loss of control of cell homeostasis, decreased differentiation, and increased malignancy.

The decrease in the rate of apoptosis in grade III adenocarcinoma may reflect loss of control of cell homeostasis, decreased differentiation, and increased malignancy.


  Conclusion Top


Type I EC is more frequent compared with type II in Egyptian patients. Type II EC is more aggressive compared with type I manifested by presentation at high grade, advanced stage, high mitotic count, and low apoptotic count.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
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