Skin Tumours Diagnosed at Department of Pathology, Sir Salimullah Medical College, Dhaka During Two Years Study Period


Skin Tumours Diagnosed at Department of  Pathology, Sir Salimullah Medical College, Dhaka During Two Years Study Period

*Hossain MD,1 Islam MN,2  Kabir E ,3  Begum S 4

Abstract

During the past century, cancer has emerged as the most challenging problems for public health systems in medium and low income countries. With a cancer load of more than one million, Bangladesh is not an exception. In this study we found that  squamous cell carcinoma was the most common malignant tumour and lipoma was the most common benign tumour of skin adnexa. The lower income generating group was the more vulnerable group for both benign and malignant tumours. It also showed that both benign and malignant tumours were more common in patients with risk behaviours as well as in patients with no risk behaviours. Tumours of the skin adnexa were the most common benign tumour found in our study

[Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):47-50]

 Key words: Skin, Tumour

  1. *Dr. Md. Delwar Hossain, Lecturer, Department of Pathology, Sir Salimullah Medical College, Dhaka. mehruddelwar@gmail.com
  2. Professor Dr. Md. Nasimul Islam, Professor and Head, Department of Pathology, Sir Salimullah Medical College, Dhaka
  3. Professor Dr. Enamul Kabir, Professor, Department of Pathology, Sir Salimullah Medical College, Dhaka
  4. Shahnaj Begum, Assistant Professor, Department of Pathology, Sir Salimullah Medical College, Dhaka

 

*For correspondence

Introduction

Cancer burden causes serious health problems both in developed and developing countries.1 Cancer has devastating effect on individual, family and society of Bangladesh. Cancer is one of the major causes of morbidity and mortality among the non-communicable diseases in our population. Appropriate prevention of cancer deserves urgent attention since the disease is expected to double in the next 20 to 25 years in most of the  countries.1 Cancer in Bangladesh is one of the major killer diseases like many other countries particularly because of ubiquitous exposure to environmental carcinogens, oncogenic viruses and microorganisms, coupled with lack of screening, awareness and poor health seeking behaviors associated with poverty, malnutrition and illiteracy. The magnitude of the problem from cancer is often unrecognized by health and general policy makers alike to other  overwhelming and more visible competitive   health problems and natural calamities.

According to Bangladesh Bureau of Statistics cancer is the sixth leading cause of death in Bangladesh.2 The number of people developing cancer is expected to increase in number mainly because of increase in life expectancy and life style factors. Each year more than 200,000 people develop cancer and 150,000 die of the disease. International Agency for Research on Cancer (IARC) has estimated death from cancer in Bangladesh was 7.5 % in 2005 and will be increased up to 13 %  in 2030.3  

IARC has projected death from 10 leading cancers in females of Bangladesh (2002) are: (1) mouth and oropharyngeal, (2) cervical, (3) breast, (4) oesophageal, (5) ovarian, (6) Lung, (7) lymphoma, (8) stomach, (9) liver and (10) colorectal cancer.3

IARC has projected death from 10 leading cancers in males of Bangladesh (2002) are: (1) mouth and oropharyngeal, (2) lung, (3) oesophagus, (4) lymphoma, (5) stomach, (6) bladder, (7) liver, (8) leukaemia, (9) colorectal and (10) prostate cancer.3

During the 2 years study period 2908 histopathological cases and 5187 cytopathological cases were diagnosed at the department of Pathology and 70 haematological malignant tumours were handled at the department of Haematology, Sir Salimullah Medical College (SSMC) and Mitford Hospital, Dhaka.4 This study was done to find out patterns of skin tumours in these cases.

Methods

This study was partial presentation of a two years tumour registry study done at the Department of Pathology, SSMC, Dhaka from 1 July, 2013 to 30 June, 2015. It was a cross-sectional observational study done on all patients diagnosed as cases of both benign and malignant tumors by cytopathology, histopathology and haematology.

 Data collection procedure

A predesigned questionnaire both in Bangla and English was developed according to MacLennan method and software was generated with the technical assistance by the University of Chicago Research Bangladesh by the cooperation of department of Pathology, Bangabandhu Seikh Mujib Medical University (BSMMU), Dhaka. Prior to the commencement of this study, approval was taken from the Ethical Review Committee of SSMC. Each patient was interviewed and relevant information was recorded systematically in a prescribed format. A written consent also attached with the questionnaire and was explained before the patient/patient’s guardian. The first part of the questionnaire was designed to record the demographic details of patients. The second part of the questionnaire was to record the pathological diagnosis of tumour with its ICD 0-3 and ICD-10 codes.  The information collected was entered into the database by software Microsoft Access 2003 and Visual Basic 6.

Recording of Data

The data were recorded according to database software. All the patients were supplied 1st part of the questionnaire (topography portion) during access to the department for submission of the specimen or for FNAC or other procedures. The data were entered case after case from the filled up questionnaire received from the patients during collection of their reports following a self-made registrar which recorded 10 items for each case likely  (1) case serial number, (2) specimen type –histopathological, cytopathological or haematological specimen (3) referred by, (4) yearly serial number i.e., accession number (5) diagnosis, (6) sites of specimen, (7) date of diagnosis and (8) Reported by.

Data were entered into the computer database software accordingly.

 Analysis of the data

Statistical analyses of the results were obtained by using Microsoft access and Window based computer software devised with Statistical Packages for Social Sciences (SPSS-15). The information was partially coded according to ICD-10 (International Classification of Diseases version-10) and ICD-3 (International Classification of Diseases – Oncology version 3).

 Results

Out of total 767 benign tumours of skin and skin adnexa lipoma was found in highest number in 91.13%, ganglioneuroma in 4.05%, nevus in 0.92%, benign fibrous histiocytoma in 0.65% and all were found more in female patients than males in both age group. On the other hand neurofibroma in 1.69% and benign mesenchymal lesion in 0.65% found more in male than female patients in both age groups (Table I)

Out of 49 malignant tumours of skin squamous cell carcinoma was found in highest number in 55.10% and 99.63% in male patients and none in female of adult age group but found only in one female of paediatric age group which was the only malignant tumour of skin of this age group. Basal cell carcinoma 22.45% and malignant melanoma 6.12% were found more in female than male and deratofibrosarcoma 10.21% and verrucous carcinoma 6.12% were found more in male than female  patients only in adult age group  (Table II).

Table I: Diagnostic distribution of benign tumours of skin / skin adnexa according to age and sex

 

Diagnosis Paediatric Adult Total (%)
Male Female Male Female
Lipoma 15 29 302 353 699 91.13
Neurilemoma/Ganglioneuroma 2 4 12 13 31 4.05
Neurofibroma 5 1 5 2 13 1.69
Nevus 0 1 1 5 7 0.92
Epithelioid mesothelioma benign 1 0 3 1 5 0.65
Benign fibrous histiocytoma 1 0 1 3 5 0.65
Fibromatosis 1 0 0 1 2 0.26
Squamous papilloma 1 0 1 0 2 0.26
Pilomatricoma 0 0 1 1 2 0.26
Cylindroma 0 0 0 1 1 0.13
Total 26 35 326 380 767 100.00

 

Table II: Diagnostic distribution of malignant tumours of skin according to age and sex:

 

Diagnosis Paediatric Adult Total (%)
Male Female Male Female
Squamous cell carcinoma 0 1 26 0 27 55.10
Basal cell carcinoma 0 0 5 6 11 22.45
Dermatofibrosarcoma 0 0 4 1 5 10.21
Verrucous carcinoma 0 0 2 1 3 6.12
Malignant melanoma 0 0 1 2 3 6.12
Total 0 1 38 10 49 100.00

 Discussion

A total of 767 benign and 49 malignant tumours of skin and skin adnexa those were diagnosed in this study found more in females than males both in paediatric and adult age group patients. Highest benign tumour of skin and skin adnexa found in this study was lipoma followed by ganglioneuroma, neurofibroma, nevus, benign mesenchymal lesion, benign fibrous histiocytoma, fibromatosis, sqamous papilloma, pilomatricoma and cylindroma. Squamous cell carcinoma was the highest malignant tumour of skin found in this study only in adult males but in no females of adult age group. Squamous cell carcinoma was found only in one female child of the paediatric age group. No other malignant tumour was found in paediatric age group either in male or female. The next malignant tumour of skin was basal cell carcinoma which was found more in adult females than in adult males. Both dermatofibrosarcoma and verrucous carcinoma were found more in male than in female. The NICRH also showed that about 60% of the male cancer patients were smokers and among them more than half (53%) had squamous cell carcinoma.5 Farhad et al. also found lipoma was the top one (35.70%) benign tumour of skin adnexa.6 Lipoma, ganglioneuroma and nevus in both age group were found more in female than in male. Neurofibroma and benign mesenchymal lesion found in both age groups were more in male than in female.

 Most of the patients were from low income generating groups and they were house wives, students, unemployed, garments or industrial workers and hawkers. The patients were mainly illiterate and a few number of the study patients were mostly up to SSC level educated. Most of the study patients were Muslim and a small number were Hindu. Most of the patients hailed from Dhaka city followed by Munshigonj, Shariatpur, Madaripur, Comilla, Manikgonj, Narayangonj, Bhola, Kishoregonj, Patuakhali, Gazipur and Narsingdi and also from other districts of Bangladesh. Out of total 64 districts of Bangladesh patients from only 7 districts were unavailable.

Conclusion

Cancer registries play a major role in providing the data to justify the establishment, implementation and monitoring of a national cancer control programme, therefore, stability in cancer registration is of pivotal importance.

This is the partial study of the two years study done (from July 1st, 2013 to June 30th, 2015) on “Establishment of Pathology Based Tumour Registry at SSMC, Dhaka.” The whole study like this one along with other institutions of the country may pave the path of a nationwide population based cancer registry in future.

 

References

  1. Iqbal S. Cancer: A Bangladesh perspective

(http://ds.cc.yamaguchi-u.ac.jp/~applied/initiative/18-internship-houkokusyo/kiseitai/Iqbal-Mohd.Shamim.htm)

  1. Bangladesh Bureau of Statistics, 2008: Faiz et al, 2008.
  2. Wagner G (1991). History of cancer registration. In Jensen OM, Parkin DM, MacLennan R, Muir CS, and R.G. Skeet RG, editors. Cancer Registration: Principles and Methods. IARC Scientific Publications No. 95. Lyon, France. IARC.2002. p.22-28.
  3. Delwar et al. Establishment of Pathology Based Tumour Registry at Sir Salimullah Medical College, Dhaka, Bangladesh. December, 2015. P. 19 (Thesis).
  4. National Institute of Cancer Research and Hospital (NICRH), Dhaka December, 2009. Zaman MM and BakiMO (eds) (2009). 2005-2007:1-19.
  5. Farhad et al. Pathology Based Tumour Registry at BSMMU Shahbagh, Dhaka. 2013. p.57.

 

A Study on Uterine Leiomyoma with Clinicopathological Spectrum


A Study on Uterine Leiomyoma with Clinicopathological Spectrum

 *Raza AM,1 Tazri SA,2 Ahmed M,3 Nahar S,4 Afroz D,5 Barua D6

 Abstract

Leiomyoma is the commonest benign neoplasm affecting uterus of females in the reproductive age group. They are noted clinically in 20-30% of women over 30 years of age and have a tendency to regress after the menopause. Their gross appearances are often altered by various secondary changes. Subtypes of leiomyoma are chiefly of interest as they may mimic malignancy in some cases. This study was conducted to analyze the clinicopathologic spectrum of uterine leiomyoma with regards to their clinical presentation, associated changes and variants and to compare these findings with similar studies from different parts of the world. All the hysterectomy and myomectomy specimens which were received in the department of pathology, Jahurul Islam Medical College, Kishoreganj over a period of two years with leiomyomas were included in the study. The specimens were properly labeled, fixed in formalin, examined grossly, processed, stained and examined microscopically. Age range of the patients with leiomyoma was 18-62 years. Majority of the patients were between 41-50 years (46.84% cases). Menorrhagia was the commonest symptom constituting 37.97% cases and fibroid uterus was the most common clinical diagnosis (44%). Most common location of leiomyoma was intramural (57.43%) followed by subserosal (30.69%). 56.96% leiomyoma were single and 43.04% were multiple. Degenerative changes were observed in 16.46% cases, amongst which hyaline change was the most common (6.33%). Nine types of leiomyoma variants were seen and cellular leiomyoma (6.33%) was the commonest. Adenomyosis was associated with leiomyoma in 19.23% cases.

[Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):41-46]

 Keywords: Leiomyoma, Myometrium, Hysterectomy, Myomectomy.

  1. *Dr. AKM Maruf Raza, Assistant Professor, Department of Pathology, Jahurul Islam Medical College, Kishoreganj, Bangladesh. drmarufraza@gmail.com
  2. Sumia Ahmed Tazri, Assistant Professor, Department of Gynaecology and Obstetrics, Jahurul Islam Medical College and Hospital, Kishoreganj, Bangladesh.
  3. Monira Ahmed, Professor, Department of Gynaecology and Obstetrics, Jahurul Islam Medical College and Hospital, Kishoreganj, Bangladesh.
  4. Shamsun Nahar, Assistant Professor, Department of Gynaecology and Obstetrics, Jahurul Islam Medical College and Hospital, Kishoreganj, Bangladesh.
  5. Dil Afroz, Assistant Professor (Current Charge), Department of Gynaecology and Obstetrics, Jahurul Islam Medical College and Hospital, Kishoreganj, Bangladesh.
  6. Dipi Barua, Associate Professor, Department of Gynae and Obs, Holy Family Red Crescent Medical College and Hospital, Dhaka

 *For correspondence

 Introduction

Myometrium is the thick smooth muscle coat of the uterus which encases the endometrium and is lined by the peritoneum derived serosa.1 Myometrial lesions form a diverse group of lesion in which leiomyoma (benign smooth muscle tumor) is the commonest. Leiomyoma is the commonest visceral neoplasm affecting females in reproductive age group.2 They are noted clinically in 20-30% of women over 30 years of age and are found in as many as 75% of uterus.3 They are rare prior to the menarche, common in reproductive  life, have a tendency to regress after the menopause and are associated with endometrial hyperplasia, all of which suggest their estrogen dependency.4

The importance of leiomyoma lies as they cause pain, abnormal uterine bleeding and a sensation of pressure. Large tumors produce diffuse uterine enlargement or an irregular uterine contour, which may be associated with infertility.4

 

Grossly, they are well-circumscribed, firm, gray-white bulging masses (varying in size from barely visible nodules to large tumors that fill the pelvis) and have a whorled appearance on cut surface with cells arranged in fascicles on microscopy. The gross appearances are often altered by secondary or degenerative changes, which are commonly seen.5,6 Hyaline degeneration/necrosis is present in more than 60% cases, particularly in postmenopausal women, and cystic degeneration, myxoid change, fatty degeneration and calcification each occur in about 4% cases. After menopause or delivery leiomyomas can undergo atrophy with significant shrinkage and fibrosis. Red degeneration is associated with pregnancy and contraceptive use and is due to thrombosis in tumour.5

Most subtypes of leiomyoma are chiefly of interest in that they mimic malignancy in one or more respects. These subtypes are mitotically active leiomyoma, cellular leiomyoma, haemorrhagic cellular leiomyoma, leiomyoma with bizarre  nuclei, epithelioid  leiomyoma, and myxoid leiomyoma.7-9

 In the histopathology laboratory of Department of Pathology, Jahurul Islam Medical College we examined a good number of specimen of leiomyoma. This study was conducted to analyze the clinicopathologic spectrum of uterine leiomyoma with regards to their clinical presentation, associated changes and variants and to compare these findings with similar studies from different parts of the world.

 Methods

The study included all the hysterectomy and myomectomy specimens received in the department of Pathology, Jahurul Islam Medical College, Bajitpur, Kishoreganj over a period of two years from September 2015 to July 2017.  A total of 79 cases diagnosed with leiomyoma were included in the study. The clinical information and the relevant investigations of the patients were obtained from the histopathological requisition forms and clinical record files. The specimens received in the department of pathology were properly labeled, numbered and fixed in 10% buffered formalin. After a detailed gross examination of the specimens, multiple sections were taken from representative sites, processed and paraffin blocks were made. The blocks were sectioned and stained routinely with haematoxylin and eosin. Special stains were used wherever required.

 Results

Age of the patients with leiomyoma ranged from 18 to 62 years. Majority of the patients were between 41-50 years accounting for 46.84% cases (Table I).

 Table I: Age wise distribution of patients with leiomyoma (n=79)

 

Age range (in years) No. of cases Percentage(%)
Below 20 01 1.27%
21-30 40 5.06%
31-40 16 20.25%
41-50 37 46.84%
51-60 19 24.05%
Above 60 02 2.53%
Total 79 100%

Menorrhagia was the commonest symptom constituting 37.97% cases, followed by pain in abdomen in 18.99% cases and dysmenorrhea in 17.72 cases (Table II).

 Table II: Chief complaints of patients with uterine leiomyoma (n=79)

 

Chief complaint No. of cases Percentage(%)
Menorrhagia 30 37.97%
Pain in abdomen 15 18.99%
Dysmenorrhea 14 17.72%
Mass per vaginum 13 16.46%
Post-menopausal bleeding 04 5.06%
Leucorrhoea 02 2.53%
Infertility 01 1.27%
Total 79 100%

Clinical diagnoses  were fibroid uterus in 44% cases, utero-vaginal prolapse in 20% cases, dysfunctional uterine bleeding in 19% cases and pelvic inflammatory disease in 17% cases. Most common site of leiomyomas was intramural (57.43%) followed by subserosal (30.69%), submucosal 8.91% cases while broad ligament leiomyomas constituted 2.97% cases.

In the present study, out of 79 cases of leiomyomas, 45(56.96%) were single and 34 (43.04%) were multiple. Number of leiomyomas observed in the present study varied from 1 to 10. Sub-serosal leiomyomas varied from few mm to 6 x 5 x 4 cm in size. Intramural leiomyomas varied from few mm to 12 x 10 x 8 mm in diameter. Sub-mucosal leiomyomas varied from few mm to 3.5 cm in diameter.

In this study, majority of leiomyomas were diagnosed in multiparous women. Out of 79 patients with leiomyomas, 78 (98.73%) were parous, which includes 10 cases of uniparous patients and only 1 was nulliparous (1.28%). We observed 42 cases of typical leiomyomas (53.16%), followed by leiomyoma variants in 24 cases (30.38%) and degenerative changes in 13 cases (16.46%) (Figure 1).

Figure 1. Various pathological changes seen in uterine leiomyomas (n=79)

 

Degenerative changes were observed in 13 leiomyomas (16.46%). Among these, 5 leiomyomas (6.33%) showed hyaline change which constituted the most common degenerative change observed in this study, 3 leiomyomas (3.8%) showed myxoid change, 3 cases (3.8%) showed calcification, 3 cases (3.8%) showed cystic and 2 cases (2.53%) demonstrated carneous (red) degeneration. We observed 9 types of variants of leiomyoma in the present study among the total 79 leiomyomas (Figure 2), which included cellular leiomyoma (6.33%), diffuse leiomyomatosis (5.05%), apoplectic leiomyoma (3.8%), cotyledonoid leiomyoma (3.8%), palisaded leiomyoma (2.53%), vascular leiomyoma (3.8%), intravascular leiomyoma (2.53%), mitotically active leiomyoma (1.27%) and atypical leiomyoma (1.27%). Adenomyosis was found associated with leiomyoma in 15 cases (19.23%).

Figure 2. Variants of uterine leiomyoma observed in the present study (n=79)

 Discussion

Leiomyomas continue to be a major cause of morbidity in perimenopausal women. Limited data is available from our community regarding clinicopathologic patterns of uterine leiomyomas. This study was conducted to analyze the clinicopathologic spectrum of uterine leiomyomas with regards to their presentation, location, associated changes and variants and to compare our findings with those of other similar studies from different parts of the world.

The ages of the patients ranged from 18-62 years. The average age of patients was 45.82 years. Highest numbers of patients included in this study were between 41-50 years (46.82%). These findings were similar to that observed by Gupta et al (51.40%), Rather et al (47.27%), Vaidya et al (45.63%) and Rizvi et al (44.56%).10-13 In this study, menorrhagia was the commonest presenting symptom seen in 37.97% cases, followed by dysmenorrhea in 18.99% cases. Menorrhagia was also the presenting complaint in studies by Sarfraz (68%), Karthikeyan (62.5%), Rather (35.43%), Gowri (49.03%) and Manjula K (35.4%).11, 14-17

The most common preoperative diagnosis was fibroid uterus in 44% cases followed by utero-vaginal prolapse in 20 % cases, dysfunctional uterine bleeding in 19% cases and pelvic inflammatory disease in 17 % cases. These findings are consistent with the data reported by Vaidya et al (42.96% and 18.95%), Siwatch et al (39% and 22.6%), utero-vaginal prolapse was the commonest indication in a study by Jha et al (37.1%), Gupta et al (40.0%).10,12,18,19 In the present study, out of 79 cases of leiomyomas, 45 (56.96%) were single and 34 (43.04%) were multiple. In a study by Sarfraz et al (2010) multiple leiomyomas were seen in 60.87% cases.16

The most common site of leiomyomas in our study was intramural (57.43%) followed by subserosal leiomyomas (30.69%), submucosal leiomyomas (8.91%) and broad ligament leiomyomas (2.97%). Jung et al observed intramural fibroids in 55.7% cases, subserous fibroids in 16.3% cases, 15.6%, and submucosal fibroids in 12.4% cases respectively.20 Intramural leiomyomas were also the commonest types in studies by Gowri et al (48%) and Rosario et al (52%).15,21

In the present study, degenerative changes were observed in 13 leiomyomas (16.46%). Among these, 6.33% showed hyaline change which constituted the most common degenerative change observed in this study, 6.33% showed myxoid change, 3.8% showed calcification, 3.8% showed cystic and 2.53% demonstrated red (carneous) degeneration. Jung at al found secondary (degenerative) changes in 9.2% cases and the most common change was hyaline degeneration (5.7%).20 Abraham and Saldanha observed secondary changes in 22.2% cases; among these 49% showed hyaline change, 4.9% showed myxoid change, 4.9% showed calcification, 3.35 showed red degeneration and 4.9% showed hydropic change.21

In the present study, 9 variants of leiomyoma were seen in 24 cases out (30.38%) of the total 79 leiomyomas, which included following types of variants-cellular leiomyoma (6.33%), apoplectic leiomyoma (3.8%), diffuse leiomyomatosis (5.05%), cotyledonoid leiomyoma (3.8%), palisaded leiomyoma (2.53%), vascular leiomyoma (3.8%), intravascular leiomyoma (2.53%), mitotically active leiomyoma (1.27%) and atypical leiomyoma (1.27%). Abraham and Saldanha in their study encountered leiomyoma variants in 7.5% cases, of which 78% were cellular leiomyomas, 9.5% were lipoleiomyoma and 4.7% were bizarre (symplastic) leiomyomas and 2.3% were epithelioid leiomyomas.21

 Conclusion

From our study we can conclude that leiomyoma is the most common benign tumor of the uterus in our community. They are commonly seen in perimenopausal females and present with menorrhagia, pain in abdomen or dysmenorrhea. Intramural site was the most common location, hyaline change was the most common degeneration and cellular variant was the most common subtype seen. The pathologist needs to be cautious while diagnosing cases of atypical, mitotically active or bizarre leiomyoma due to their morphologic homogeneity with leiomyosarcoma.

 References

  1. Christopher PC. The female genital tract in: Kumar, Abbas, Fauster eds. Robbins and Cottron Pathologic Basis of Disease. 8th Ed. India Elsevier; 2010:1036-8.
  2. Silverberg SG, Tabbara SO. The uterine corpus. In: Silverberg SG, Delellis RA, Frable WJ, Eds. Principles and Practice of Surgical Pathology and Cytopathology. Vol 3 (3rd edition). New York: Churchill Livingstone; 1997:2459-516.
  3. Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol, 1990; 94:435-8.
  4. Zaloudek CJ, Hendrickson MR, Soslow RA. Mesenchymal tumors of uterus. In: Blaustein Pathology of the female genital tract. 6th ed; 2011:459-466.
  5. Persaud V, Arjoon PD. Uterine leiomyoma: incidence of degenerative change and a correlation of associated symptoms. Obstetrics and Gynaecology, 1970; 35(3):329-492.
  6. Samaila Modupeola OA, Adesiyun AG, Agunbiade OA, Mohammed D. A clinicopathological assessment of hysterectomies in Zaria. Eur J Gen Med, 2009; 6(3):150-3.
  7. Ojeda VJ. The pathology of hysterectomy specimens. NZ Med J, 1979; 89(631):169-71.
  8. Adelusola KA, Ogunniyi SO. Hysterectomies in Nigerians: histopathological analysis of cases seen in Ile-Ife. Niger Postgrad Med Journal, 2001; 8:37-40.
  9. Smooth JS, Zaloudek C. Myometrial and stromal lesions of the uterus Gynaecologic pathology. Clinics in Lab Medicine, 1995; 15(3):545-73.
  10. Gupta G, Kotasthane D, Kotasthane V. Hysterectomy: a clinico-pathological correlation of 500 cases. The Internet Journal of Gynecology and Obstetrics, 2009; 14(1):1-5.
  11. Rather GM, Gupta Y, Bardhwaj S. Patterns of lesions in hysterectomy specimens: a prospective study. JK Science, 2013; 15(2):35-8.
  12. Vaidya S, Vaidya SA. Patterns of lesions in hysterectomy specimens in a tertiary care hospital. J Nepal Med Assoc, 2015; 53(197):18-23.
  13. Rizvi G, Pandey H, Pant H, Chufal SS, Pant P. Histopathological correlation of adenomyosis and leiomyoma in hysterectomy specimens as the cause of abnormal uterine bleeding in women in different age groups in the Kumaon region: a retro prospective study. J Midlife Health, 2013; 4(1):27-30.
  14. Karthikeyan TM, Veenaa NN, Ajeeth Kumar CR, Thomas E. Clinico-pathological study of hysterectomy among rural patients in a tertiary care center. IOSR Journal of Dental and Medical Sciences. 2015; 14(5):25-7.
  15. Gowri M, Mala G, Murthy S, Nayak V. Clinicopathological study of uterine leiomyomas in hysterectomy specimens. Journal of Evolution of Medical and Dental Sciences, 2013; 2(46):9002-9.
  16. Sarfraz R, Sarfraz MA, Kamal F, Afsar A. Pattern of benign morphological myometrial lesions in total abdominal hysterectomy specimens. Biomedica, 2010; 26:140-3.
  17. Manjula K, Rao KS, Chandrasekhar HR. Variants of Leiomyoma: histomorphological study of tumors of myometrium. Journal of South Asian Federation of Obstetrics and Gynecology, 2011; 3(2):89-92.
  18. Siwatch S, Kundu R, Mohan H, Huria A. Histopathologic audit of hysterectomy specimens in a tertiary care hospital. Sri Lanka J Obstet Gynaecol, 2012; 34(4):155-8.
  19. Jha R, Pant AD, Jha A, Adhikari RC, Sayami G. Histopathological analysis of hysterectomy specimens. J Nep Med Assoc, 2006; 45:283-90.
  20. Jung JK, Koi MS, Jung BW, Lee HH, Choi HJ, Shin SK. A clinical analysis of uterine myoma. Korean J Obstet Gynecol, 1998; 41(1):210-9.
  21. Abraham J, Saldanha P. Morphological variants and secondary changes in uterine leiomyomas. Is it important to recognize them? Int J of Biomed Research, 2013; 4(12):254-64.

Histopathological Pattern of Endometrial Hyperplasia in Peri- and Postmenopausal Women


Histopathological Pattern of Endometrial Hyperplasia in Peri- and Postmenopausal Women

*Fardousi F,1 Sultana SS,2 Kaizer N,3 Dewan RK,4 Jinnah MS,5 Jeba R,6 Hoque MN,7 Hussain M8

Abstract

Endometrial hyperplasia is one of the major gynaecological problem in peri- and post-menopausal women worldwide. It deserves special attention because of its relationship with endometrial carcinoma. The histopathological pattern of endometrial hyperplasia in peri- and post-menopausal women and their relationship with clinicopathological features are imperative to reach a diagnosis as well as early management. To find out the histopathological patterns of endometrial hyperplasia in peri- and post-menopausal women this descriptive cross-sectional study was carried out at the Department of Pathology, Dhaka Medical College, Dhaka during the period from January 2013 to December 2014. A total of seventy histopathologically diagnosed cases of endometrial hyperplasia were included in this study according to inclusion and exclusion criteria. Among the 70 cases, endometrial curettage biopsy specimens were 45 and hysterectomy specimens were 25. Routine Haematoxylin & Eosin staining was done on all cases. Out of all endometrial hyperplasia cases, 53 cases were simple endometrial hyperplasia without atypia, 8 cases were simple endometrial hyperplasia with atypia, 6 cases were complex endometrial hyperplasia without atypia and 3 cases were complex endometrial hyperplasia with atypia. Majority of the patients 35 (50%) were between 41-50 years of age. The study revealed that most common histopathological pattern of endometrial hyperplasia was simple endometrial hyperplasia without atypia, followed by simple endometrial hyperplasia with atypia. The importance of knowledge about the histological pattern of endometrium in abnormal uterine bleeding in different age group is useful in managing the cases with accuracy.

[Journal of Histopathology and Cytopathology, 2018 Jan; 2 (1):30-40]

 Key words: Endometrial hyperplasia, gynecological problem, peri- and postmenopausal women, histopathological pattern.

  1. *Dr. Farzana Fardousi, Lecturer, Department of Cytopathology, National Institute of Cancer Research and Hospital (NICRH), Mohakhali, Dhaka. farzanafardousi@yahoo.com
  2. SK Salowa Sultana, Assistant Professor, Department of Pathology, Ad Din Women’s Medical College.Dhaka
  3. Nahid Kaizer, Associate Professor (CC), Department of Pathology, Shahabuddin Medical College. Dhaka
  4. Professor Dr. Rezaul Karim Dewan, Head of the Department of Pathology, Dhaka Medical College.
  5. Mohammed Shahed Ali Jinnah, Associate Professor, Department of Pathology, Dhaka Medical College.
  6. Ruksana Jeba, Associate Professor Department of Pathology, Dhaka Medical College.
  7. Md. Nazmul Hoque, Ex Associate Professor, Department of Pathology, Dhaka Medical College
  8. Professor Dr. Maleeha Hussain , Ex Head of the Department of Pathology, Dhaka Medical College.

*For correspondence

Introduction

Endometrial hyperplasia is defined as an increased proliferation of the endometrial glands relative to the stroma, resulting in an increased gland-to-stroma ratio when compared with normal proliferative endometrium. Endometrial hyperplasia deserves special attention because of its relationship with endometrial carcinoma in peri and postmenopausal women.1 Worldwide, endometrial cancer is the most common invasive cancer of female genital tract.

In 50% cases of endometrial adenocarcinoma, endometrial hyperplasia particularly atypical hyperplasia is found as a premalignant lesion.2 Endometrial hyperplasia usually develops in the presence of continuous estrogen stimulation unopposed by progesterone. In the years before menopause, women may have numerous cycles without ovulation (anovulatory) during which there is continuous unopposed estrogen activity. Similarly, hormone replacement therapy consisting of estrogen without progesterone may lead to endometrial hyperplasia.3 The endometrium becomes atrophic after menopause as a result of ovarian failure. The postmenopausal endometrium which despite being atrophic, retain a weak proliferative pattern for many years probably as a response to continuous low level of estrogenic stimulation. These are at a higher risk of progression to endometrial hyperplasia and subsequently to endometrial malignancy.3 Many classifications of endometrial hyperplasia have been proposed over the years. The one that is currently preferred and which has been recognized by the World Health Organization (WHO) was originally proposed.4 It takes into account both the architectural and cytologic features, for reasons of dividing the hyperplasias into simple and complex based on architecture and subdividing each into typical and atypical on the basis of their cytological pattern.5 The type I endometrial cancers which is endometrioid variant is associated with unopposed estrogen exposure and is often preceded by atypical endometrial hyperplasia. However, type II endometrial cancers where a non-endometrioid histology (usually papillary, serous or clear cell) has an aggressive clinical course, is not preceded by any type of endometrial hyperplasia.6 According to WHO, endometrial hyperplasia is divided into four major categories: Simple hyperplasia without atypia, Simple hyperplasia with atypia, Complex hyperplasia without atypia and Complex hyperplasia with atypia. The confirmed diagnosis of endometrial hyperplasia can be made by histopathological examination.7 Endometrial hyperplasia is associated with prolonged estrogen stimulation of the endometrium, which can be due to anovulation, increased estrogen production from endogenous sources or exogenous estrogen. The factors associated with endometrial hyperplasia include obesity, menopause, polycystic ovarian diseases, functioning granulosa cell tumors of the ovary, excessive cortical function and prolonged administration of estrogenic substances.1 The primary presenting symptom of endometrial hyperplasia is abnormal uterine bleeding, which typically prompts an endometrial biopsy to rule out carcinoma.8 Approximately, 70% of women with abnormal uterine bleeding are diagnosed with benign findings and 15% are diagnosed with carcinoma. The remaining 15% receive a diagnosis of endometrial hyperplasia, which includes a broad range of lesions, from mild, reversible proliferations to the immediate precursors of carcinoma. Abnormal uterine bleeding is the chief complaints of endometrial hyperplasia and can be categorized into dysfunctional uterine bleeding or postmenopausal bleeding. Long reproductive life has risk for development of endometrial hyperplasia. Different studies have shown that, women who have achieved early menarche or late menopause have more risk for development of endometrial hyperplasia and endometrial carcinoma, as estrogen exposure especially unopposed by progesterone is a known risk factor for the development of endometrial carcinoma. Parity causes estrogen-hormonal environment throughout the fertile years of a woman, which may increase risk for the development of endometrial carcinoma.9 Obesity is a known risk factor for endometrial hyperplasia and this excess risk is associated with the endocrine and inflammatory effects of adipose tissue. Adipocytes express aromatase that converts ovarian androgens into estrogens, which induce endometrial proliferation.10 It was observed in different studies that, endometrial hyperplasia was found in diabetic and hypertensive patient, but whether this association is statistically significant or not or whether it carries a risk of endometrial carcinoma for diabetic and hypertensive women need to be ascertained with further studies in a larger series of population. It was observed in many studies that endometrial hyperplasia is associated with family history of endometrial cancer. Because a common genetic alteration found in a significant number of endometrial hyperplasias and related endometrial carcinomas i.e. inactivation of the PTEN tumour suppressor gene.11 The study was aimed to find out the histopathological patterns of endometrial hyperplasia in peri- and post-menopausal women.

Methods

Place and period of study

This is a descriptive cross-sectional study which was carried out at the Department of Pathology, Dhaka Medical College, Dhaka, during the period of January 2013 to December 2014.

Sample Size

For this study, 110 peri- and postmenopausal women with dysfunctional uterine bleeding or postmenopausal bleeding who underwent D&C or hysterectomy were screened. A total of seventy histopathologically diagnosed cases of endometrial hyperplasia who met the enrollment criteria (inclusion & exclusion criteria) were included in this study. Among 70 cases, endometrial curettage biopsy specimens were 45 and hysterectomy specimens were 25. Routine Haematoxylin & Eosin staining was done on all cases.

Collection of Sample

Ethical clearance was taken for this study from institutional ethical committee of Dhaka Medical College, Dhaka. Each patient was interviewed before collection of the specimen and relevant information was recorded in a prescribed clinical proforma. Detail history with particular attention to age, clinical features, age at menarche, parity, obesity, history of contraceptives, history of hormone replacement therapy, history of diabetes, history of hypertension, history of estrogen producing ovarian tumor, age at menopause were taken.

 Histopathological Examination

All specimens obtained either by endometrial curettage biopsy or hysterectomy were immersed in 10% formalin. The specimens were examined in the department of pathology, Dhaka Medical College with a particular emphasis on number, size, shape, color and consistency. This part was done by experienced pathologist in the department of Pathology of Dhaka Medical College. Tissue processing and staining: Routine tissue processing and Haematoxylin & Eosin staining were done at the Department of Pathology, Dhaka Medical College.

Microscopic Analysis

Following histopathological diagnoses were made according to WHO classification of endometrial hyperplasia: Simple endometrial hyperplasia without atypia, Simple endometrial hyperplasia with atypia, Complex endometrial hyperplasia without atypia, Complex endometrial hyperplasia with atypia.5

Statistical Analysis

Statistical analyses of the results were obtained by using window based computer software devised with Statistical Packages for Social Sciences (SPSS-16). Percentages were calculated to find out the proportion of the findings. The results were presented in Tables and Figures.

Results

Out of 70 histopathologically diagnosed endometrial hyperplasia cases, 53 cases were simple endometrial hyperplasia without atypia, 8 cases were simple endometrial hyperplasia with atypia, 6 cases were complex endometrial hyperplasia without atypia and 3 cases were complex endometrial hyperplasia with atypia. Majority of the patients 35(50%) were between 41-50 years of age (Table I).

Table I: Distribution of the study patients by Age (n=70)

 

Age (Years) SEH without atypia

(n=53)

SEH with atypia

(n=8)

CEH without atypia

(n=6)

CEH with atypia

(n=3)

Total

(n=70)

n %
35-40 12 1 4 1 18 25.7
41-50 30 5 0 0 35 50.0
51-60 11 2 1 2 16 22.9
61-70 0 0 0 0 0 0.0
>70 0 0 1 0 1 1.4
Total 53 8 6 3 70 100

 

(SEH without atypia- Simple endometrial hyperplasia without atypia, SEH with atypia- Simple endometrial hyperplasia with atypia, CEH without atypia – Complex endometrial hyperplasia without atypia and CEH with atypia- Complex endometrial hyperplasia with atypia)

Table II: Distribution of the study patients by menstrual history (n=70)

 

Menstrual history SEH without atypia

(n=53)

SEH with atypia

(n=8)

CEH without atypia

(n=6)

CEH with atypia

(n=3)

Total

(n=70)

n %
Irregular menstrual bleeding 42 8 4 1 55 78.6
Post-menopausal bleeding 11 0 2 2 15 21.4

Majority of the patients (56 cases) achieved their menarche at 12-13 years of age in simple endometrial hyperplasia without atypia and no patient achieved early menarche (before 10 years) (Table III)

Table III: Distribution of the study patients by age of menarche (n=70)

 

Age of menarche (years) SEH without atypia

(n=53)

SEH with atypia

(n=8)

CEH without atypia

(n=6)

CEH with atypia

(n=3)

Total

(n=70)

n %
12-13 47 3 4 2 56 80.0
14-15 6 5 2 1 14 20.0
Mean±SD 13.7±0.7 13.8±1.3 13.3±1.0 12.7±0.6 13.6 ±0.9
Range (Min-max) 12-15 12-15 12-15 12-13 12-15

 

Out of 70 cases, 45(57.14%) were multipara. Among 45 cases, 36(51.4%) cases had 3 children, 6(8.6%) cases had 4 children and 3(4.3%) cases had 5 children (Table V).

By Basal Metabolic Index, obesity (BMI more than 30) was found in 34(48.6%) cases, among them 27 cases in simple endometrial hyperplasia without atypia, 5 cases in simple endometrial hyperplasia with atypia and 2 cases in complex endometrial hyperplasia with atypia (Table VI).

 

Table IV: Distribution of the study patients by age of menopause (n=70)

 

Age of menopause SEH without atypia

(n=53)

SEH with atypia

(n=8)

CEH without atypia

(n=6)

CEH with atypia

(n=3)

Total

(n=70)

n %
50 3 0 1 0 4 26.6
51 4 0 0 1 5 33.3
52 4 0 1 1 6 40.0
Mean±SD 51.09±0.8 0±0 51.0±0 51.5±0.7 51.1 ±0.8
Range (Min-max) 50-52 51-51 50-52 51-52 50-52

 

Table V: Distribution of the study patients by parity (n=70)

 

Para SEH without atypia

(n=53)

SEH with atypia

(n=8)

CEH without atypia

(n=6)

CEH with atypia

(n=3)

Total

(n=70)

n %
2 18 4 2 1 25 35.7
3 29 4 2 1 36 51.4
4 4 0 1 1 6 8.6
5 2 0 1 0 3 4.3
Mean±SD 2.8±0.8 2.5±0.5 3.2±1.2 3.0±1.0 2.8±0.8
Range (Min-max) 2-5 2-3 2-5 2-4 2-5

 

 

Table VI: Distribution of the study patients by obesity by calculating Basal Metabolic Index (BMI) (n=70)

 

Obesity by BMI (kg/m2) SEH without atypia

(n=53)

SEH with atypia

(n=8)

CEH without atypia

(n=6)

CEH with atypia

(n=3)

Total

(n=70)

n %
Present 27 5 0 2 34 48.6
Absent 26 3 6 1 36 51.4

 

Out of the total study cases, diabetes was found in 11 cases, hypertension was found in 24 cases, and history of associated estrogen producing tumor of ovary was found in 1 case (Table VII).

 

Table VII: Distribution of the study patients by diabetes, hypertension and history of associated estrogen producing tumour of ovary (n=70)

 

Diseases SEH without atypia

(n=53)

SEH with atypia

(n=8)

CEH without atypia

(n=6)

CEH with atypia

(n=3)

Total

(n=70)

n %
Diabetes 4 5 1 1 11 15.7
Hypertension 20 2 1 1 24 34.3
History of associated estrogen producing tumour of ovary 0 0 0 1 1 1.4

 

History of oral contraceptive pill was found in 15(21.4%) cases and history of hormone replacement therapy was found in 12(17.15%) cases (Table VIII).

 

Table VIII: Distribution of the study patients by history of Oral contraceptive pill (OCP) and history of Hormone replacement therapy (HRT) (n=70)

 

History SEH without atypia

(n=53)

SEH with atypia

(n=8)

CEH without atypia

(n=6)

CEH with atypia

(n=3)

Total

(n=70)

n %
H/O OCP 7 4 3 1 15 21.4
H/O HRT 10 0 0 2 12 17.15

 

 

 

 

 

 

Figure 1. Photomicrograph showing simple endometrial hyperplasia without atypia (H & E stain, x10)

 

 

 

 

 

Figure 2. Photomicrograph showing simple endometrial hyperplasia with atypia (H & E stain, x40)

 

 

 

 

 

Figure 3. Photomicrograph showing complex endometrial hyperplasia without atypia(H & E stain, x40)

 

 

 

 

 

 

Figure 4. Photomicrograph showing complex endometrial hyperplasia with atypia(H & E stain, x40)

Microscopic pictures of different types of endometrial hyperplasia are shown in figures 1, 2,3 and 4. Pie chart showing the commonest diagnosis in 70 patients was SEH without atypia (75.7%) followed by SEH with atypia (11.4%; Fig-5).

 

 

 

 

Figure 5. Pie chart showing distribution of the patients by diagnosis (n=70)

 

 

 

 

 

Figure 6.  Bar diagram showing distribution of the patients according to mean age with diagnosis (n=70)

Discussion

Endometrial hyperplasia has a significant place in gynecological morbidity in women of reproductive age (10% to 18%).12 It is associated with menstrual irregularities and anaemia in women and poses a high risk for malignant transformation into endometrial cancer.13 Worldwide endometrial cancer is the most common gynecological cancer in peri and postmenopausal women.14,15 The incidence of endometrial adenocarcinoma not only has remained high but in recent years has tended to significantly increase in many countries, including Bangladesh.12,16

 

The diagnosis and classification of endometrial hyperplasia can be made by histopathological examination. The present cross-sectional study was carried out with an aim to observe the histopathological pattern of endometrial hyperplasia in peri and post-menopausal women. In the present study, the commonest diagnosed lesion was simple endometrial hyperplasia without atypia which was 53(75.7%), followed by simple endometrial hyperplasia with atypia 8(11.4%), complex endometrial hyperplasia without atypia 6(8.6%) and then complex endometrial hyperplasia with atypia 3(4.3%).

In this study it was observed that, the mean age was 43.7±7.9 years in simple endometrial hyperplasia without atypia, 44.3±5.9 years in simple endometrial hyperplasia with atypia, 48.5±15.5 years in complex endometrial hyperplasia without atypia and 50.0±13.2 years in complex endometrial hyperplasia with atypia. In our study, the age ranged from 35 to 75 years with a mean age of 45 years. The highest number of cases 35(50%) were in the fourth decade. These findings are almost similar to the studies carried out.17,13 In their study, they also found maximum cases in the fourth decade. However, the present study differed from the study conducted by Trimble et al.2 who reported the mean age as 58 years and the age range between 25 to 89 years. Probably this discrepancy is due to small number of cases in our study. The present study also differed from the study conducted.18 They observed that, the incidence of simple and complex hyperplasia without atypia were highest in women aged 50 to 54 years, whereas the rate of atypical hyperplasia was highest in women aged 60 to 64 years. This variation may be due to high expectancy of life in developed countries.

We observed, 55 cases were in their reproductive age and on menstrual history, all of them had irregular menstrual bleeding. Among 55 cases, majority (42) were diagnosed as simple endometrial hyperplasia without atypical, followed by (8) as simple endometrial hyperplasia with atypia. In this study it was observed that, 15 cases achieved menopause and postmenopausal bleeding. Out of 15 cases, on histopathological examination, 11 were diagnosed as simple endometrial hyperplasia without atypia, 2 as complex endometrial hyperplasia without atypia and 2 as complex endometrial hyperplasia with atypia. This finding is in concordance with that found in the study of Farquhar et al.19 Thus, it can be concluded that, postmenopausal bleeding does not always indicate a risk for development of endometrial carcinoma as simple endometrial hyperplasia without atypia has only 1 to 3% risk for development of endometrial carcinoma.1

In the present study, postmenopausal patients were 15 in number. The mean age at which they achieved menopause was 51.09±0.8 years in simple endometrial hyperplasia without atypia, 51.0±0 years in complex endometrial hyperplasia without atypia and 51.5±0.7 years in complex endometrial hyperplasia with atypia. In this study it was observed that, most patients achieved menopause at the age of 52 years. This result is in concordance with the study done by Jetley et al.20 However, the number of menopausal patient is inadequate to come to any definite comment.

All the patients of this study were parous women. Parity causes estrogen-hormonal environment throughout the fertile years of a woman.9 In the present study it was found that, range of parity varied from 2 to 5 in all types of endometrial hyperplasia. This result is in concordance with the study done by Topcu et al.21,22

They also observed range of parity from 2 to 5 among the patients with endometrial hyperplasia. However, this finding has a pitfall of not having nullipara patient in the present study.

Obesity is a known risk factor for endometrial cancer. This excess risk is associated with the endocrine and inflammatory effects of adipose tissue. Adipocytes express aromatase that converts ovarian androgens into estrogens, which induce endometrial proliferation.10 In the present study, it was observed that by Body Mass Index (BMI), obesity (BMI more than 30) was found in 34 cases (48.6%). Among them, majority (27) cases were simple endometrial hyperplasia without atypia. This result is in concordance with the study done by Epplein et al. 23,21,17 they also found 48.89% cases of endometrial hyperplasia in obese women.

In this study. it was observed that diabetes was found in 11 cases (15.7%). Similar study was done by Bera et al.17 They also found association of diabetes mellitus in 18 cases (15%) of endometrial hyperplasia.

In present study it was observed that, hypertension was found in 24 cases (34.3%). This result is in concordance with the study done by Bera et al.17 They also found 36 cases (35%) of endometrial hyperplasia in hypertensive patients. It is observed that, in the present study and other comparable studies, endometrial hyperplasia is found in diabetic and hypertensive patient, but whether this association is statistically significant or not or whether it carries a risk of endometrial carcinoma for diabetic and hypertensive women need to be ascertained with a large series of study population.

The history of associated estrogen producing tumor of ovary was found in 1 case and it was a case of complex endometrial hyperplasia with atypia. Though this number is very insignificant in our study, Gregory et al.24 have shown in their study that, women with ovarian tumor and polycystic ovarian syndrome (PCOS) have a higher risk of development of estrogen-induced endometrial hyperplasia and cancer.

We observed that history of OCP in 15 cases. Out of 15 cases, 7 cases were simple endometrial hyperplasia without atypia, 4 cases were simple endometrial hyperplasia with atypia, 3 cases were complex endometrial hyperplasia without atypia and 1 case was complex endometrial hyperplasia with atypia. Epplein et al.23 also the found association of OCP in 18 cases of endometrial hyperplasia in the women of reproductive age.

History of hormone replacement therapy (HRT) was found in 12 cases and majority (10) were simple endometrial hyperplasia without atypia. Epplein et al.23 have found similar association with HRT which is composed of estrogen only.

In the present study, no patient gave family history of endometrial hyperplasia or endometrial carcinoma. This may be due to unawareness of the study patients about their family history. Other studies also found no association with the family history of endometrial hyperplasia or endometrial carcinoma, though they were aware about their family history.17, 23

Limitation of the Study

Our study included few numbers of postmenopausal women. It was a cross-sectional study. To evaluate the risk factors for endometrial hyperplasia and the risk of endometrial hyperplasia to progress to endometrial carcinoma, ideally a cohort or follow-up study should be done.

 Conclusion

We found that most of the patients were in the fourth decade and all the patients had chief complaints of either irregular menstrual bleeding or postmenopausal bleeding. On USG, all of them had bulky uterus and all the patients were parous women. We found no significant association with obesity, diabetes mellitus, hypertension, oral contraceptive pill or estrogen producing ovarian tumour but significant association was found with HRT in postmenopausal women. None of the patient had family history of endometrial hyperplasia or endometrial carcinoma.

Recommendations

A large follow–up study is recommended for patients of endometrial hyperplasia selected for conservative treatment with progestogen and GnRH-agonists. Monitoring should be done by observing the Ki-67 expression in these patients. If the Ki-67 expression increases, they should be treated by surgical intervention.

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