Original Research Article

A retrospective study of uterine leiomyomas with associated changes in and

Rajashree Ingin1, Siddaganga Mangshetty2, Geetanjali Jeevangi3*

1Professor and HOD, 2Assistant Professor, 3Tutor, Department of Pathology, Gulbarga Institute of Medical Sciences, Kalaburagi. Email: [email protected]

Abstract Background: Leiomyoma is a smooth muscle tumor and is most common of all uterine neoplasms accounting for more than 75% of the benign tumors in women of reproductive age group. They are dependent on steroid hormones for their growth and maintenance. Endometrium also undergoes dynamic reorganization through each in response to the steroid hormones. Studies have shown the presence of estrogen and progesterone receptors in endometrium and . This study deals with changes in endometrium and ovary associated with leiomyoma with special focus on location of leiomyoma in total abdominal hysterectomy with salphingo-oophorectomy specimens. Material and Methods: A retrospective study was conducted in Department of Pathology, Gulbarga Institute of Medical Sciences, Kalaburagi, Karnataka from Jan 2018 to Dec 2018. Among the total abdominal hysterectomy with salphingo- oophorectomy specimens received, only those with leiomyoma were included in the study. The tissue bits were routinely processed, stained and evaluated for histomorphological patterns of leiomyoma, endometrial changes, endometrial gland pathology and lesions in ovary associated with leiomyoma. Results: Of 332 hysterectomies, 106 showed leiomyoma. They commonly occurred in the age group of 41-50 yrs (40.6%). Solitary (86.8%) and intramural fibroid (61.3%) were common presentation. Hyaline change (8.5%) was most frequent secondary change. Proliferative pattern was the most common endometrial change. was seen in 11.3% cases. Follicular cyst (12.3%) followed by simple serous cyst (6.6%) were common lesions in ovary. Conclusion: Cyclic changes in endometrium occurring due to hormonal influence may represent a common cause for both the leiomyoma and endometrial changes. Endometrial changes like thinning, distorted glands and secondary changes in leiomyoma could be explained due to the large size and mechanical effect on the endometrium overlying or opposite, or close to the leiomyoma. Follicular cyst of the ovary explains its association with leiomyoma in hyper estrogenic state. Key Words: Adenomyosis, Endometrial changes, Follicular Cyst Ovary, Leiomyoma.

*Address for Correspondence: Dr. Geetanjali Jeevangi, Tutor, Department of Pathology, Gulbarga Institute of Medical Sciences, Kalaburagi, Karnataka, INDIA. Email:[email protected] Received Date: 27/04/2019 Revised Date: 20/05/2019 Accepted Date: 17/07/2019 DOI: https://doi.org/10.26611/1051124

hysterectomy worldwide2. Depending on location and Access this article online size of tumor, uterine leiomyomas commonly manifest

with menstrual disturbances (menorrhagia, metrorrhagia, Quick Response Code:

Website: and dysmenorrhoea), pressure symptoms (pain, urinary

www.medpulse.in disturbances or constipation), or recurrent pregnancy loss and rarely mass per abdomen3. Leiomyomas can be located anywhere in the myometrium. Intramural leiomyomas are the most Accessed Date: common type. Submucosal leiomyomas compress the 05 August 2019 overlying endometrium and bulge into the endometrial

cavity as they enlarge (Fig 4). Subserosal leiomyomas can become pedunculated and if the pedicle undergoes torsion INTRODUCTION and necrosis, the leiomyoma can lose its connection with Uterine leiomyomas are extremely common tumors the uterus, some of them become parasitic in rare accounting for 75% of the benign tumors in women of instances. The appearance of a leiomyoma is commonly reproductive age group1. It is the most common cause of altered by degenerative changes (Fig 3) such as

How to cite this article: Rajashree Ingin, Siddaganga Mangshetty, Geetanjali Jeevangi. A retrospective study of uterine leiomyomas with associated changes in endometrium and ovary. MedPulse International Journal of Pathology. August 2019; 11(2): 77-80. https://www.medpulse.in/Pathology/ MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 11, Issue 2, August 2019 pp 77-80 hemorrhage, necrosis, edema, myxoid change, oophorectomy cases were received for histopathological hypercellular foci and increase in mitotic activity examination. Only those specimens associated with particularly if they are large or occur in pregnant women leiomyoma were further analyzed. A brief clinical data or in those patients undergoing high-dose progestin was obtained from patients records. The specimen therapy. Cystic degeneration and calcification can also received was examined for size and weight of uterus, occur4. Uterus comprises of the endometrium and the endomyometrial thickness, number and location of myometrium. While endometrium undergoes dynamic leiomyomas, and tubes. The standard grossing reorganization through each menstrual cycle in response protocol was followed. Tissue bits were taken from to the steroid hormone, uterine leiomyomas also representative areas for further histopathological frequently occur and show increase in size during processing. The sections were processed routinely. pregnancy or on intake of oral contraceptive pills. This is Through paraffin blocks 5microns thick sections were due to the fact that both endometrium and myometrium obtained and stained with hematoxylin and eosin. The express higher levels of estrogen and progesterone sections were examined for endometrium- phase, type receptors. The number of receptors has been shown to be and arrangement of glands, epithelial cell changes; higher in leiomyoma tissue when compared to the Myometrium– location, number of leiomyoma and homologous myometrium4. Treatment with gonadotropin secondary changes if any; presence of adenomyosis; and releasing hormone agonist (GnRHa) results in shrinkage ovarian lesions. The collected data were analyzed and of leiomyomas facilitating myomectomy and reduce the results were tabulated. risk of hemorrhage during surgery5.Thus, this explains the importance of sex hormones in the development and RESULTS maintenance of leiomyomas and their association with A total of 332 hysterectomy specimens were received endometrial changes. during the period, Jan 2018 to Dec 2018 out of which 106 showed leiomyoma. Incidence of leiomyoma among the AIMS AND OBJECTIVES hysterectomy specimens is 31.92%.The study samples 1. To study the incidence and distribution of were in the age group which ranged from 25-70 years leiomyomas in uterus. with peak incidence in the 5th decade (44.3%) followed 2. To study the histomorphological patterns of by 4rth decade (40.5%).The most common symptom was leiomyoma. menorrhagia(37.7%) followed by (33%). 3. To study endometrial changes and ovarian Other symptoms were mass per abdomen (9.4%), lesions associated with leiomyoma uterus. metrorrhagia (8.4%), (7.5%) and frequent 4. To correlate the morphology of leiomyoma with urination (2.8%).Of the 106 cases, 92(86.8%) had single endometrial changes and ovarian lesions. leiomyoma among which 16% were submucous in location. Intramural and subserous were 61.3% and 9.4% MATERIAL AND METHODS respectively. Multiple leiomyomas were seen in 15 cases The present study was conducted in Department of (14%) among which submucous + intramural were 1.8%. Pathology, Gulbarga Institute of Medical Sciences, Subserous + intramural were 9.4%. The leiomyomas Kalaburagi, Karnataka from Jan 2018 to Dec 2018. A located in all three sites were 1.8% (Table I). total of 332 total abdominal hysterectomy with salphingo-

Table 1: Leiomyoma Based On Location In Uterus S.No. Location Number(N=106) Percentage(%) 1. SubMucous 17 16% 2. Intra Mural 64 61.32% 3. Sub Serous 10 9.4% 4. SubMucous(+)Intra Mural 3 2.8% 5. Sub Serous (+)Intra Mural 10 9.4% 6. SubMucous(+)Intra Mural(+)Sub Serous 2 1.8% Uterine leiomyomas are of great concern as they can undergo secondary degenerative changes. In our study, 8.5% showed hyaline change, 3.8% showed calcareous degeneration (Fig 3), 2.8% showed myxoid degeneration, 1.9% had focal areas of hemorrhage. No secondary changes were noted in 83% of cases. 11.3% of cases are associated with adenomyosis (Fig 7).Endometrium showed proliferative pattern in 59 cases (55.7%), followed by secretary pattern (24.5%). (8.4%), atrophic endometrium (8.4%), (6.6%) and disordered proliferative pattern (2.8%) were other changes observed. (Table II).

MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 11, Issue 2, August 2019 Page 78 Rajashree Ingin, Siddaganga Mangshetty, Geetanjali Jeevangi

Table 2: Endometrial Changes Associated With Fibroid Uterus S.No. Endometrial pattern/phase Number Percentage(%) 1. Proliferative Phase 59 55.7 2. Secretory Phase 26 24.5 3. Disordered Proliferative Phase 3 2.8 4. Atrophic Endometrium 9 8.4 S.No. Epithelial cell changes Number Percentage(%) 1. Simple Hyperplasia 8 7.55 2. Complex Hyperplasia 1 0.94 Endometrial glands separated 3. 12 11.3 by muscle fibres 4. Polyposis 7 6.6 We have also studied the association of endometrial changes with leiomyoma based on their location. Majority of leiomyomas were intramural and show proliferative pattern as commonest endometrial change (Fig 5). They were also associated with highest number of endometrial hyperplasia, adenomyosis and endometrial polyp (Fig 1). Thinning of endometrium, distorted glands (Fig 6) were seen in submucous and large sized intramural leiomyomas due to mechanical pressure and in postmenopausal women due to decreased level of hormones. (Table III).

Table 3: Endometrial Changes Associated With Leiomyoma Uterus On The Basis Of Location Disordered Endometrial Proliferative Secretory Atrophic Adenomyosi Location of fibroid Proliferative Polyp Total hyperplasia phase phase endometrium s Phase SubMucous 1(5.9% - 8(47%) 4(23.5%) - 5(29.4%) 1(5.9%) 17(16%) ) Intra Mural 3(3.1% 64(61.32 5(7.8%) 39(60.9%) 15(23.4%) 2(3.1%) 3(4.7%) 7(10.9%) ) %) Sub Serous 2(20%) 5(50%) 3(30%) - - 1(10%) 1(10%) 10(9.4%)

SubMucous+ Intra 1(33.3 - 2(66.7%) - 1(33.3%) - - 3(2.8%) Mural %) Intra Mural(+)Sub 2(20%) 5(50%) 3(30%) - 2(10%) 1(10%) 10(9.4%) Serous SubMucous(+)Intr a Mural(+)Sub - - 1(50%) - 1(50%) - - 2(1.8%) Serous Ovarian lesions were seen in 27 cases (25.5%). Follicular cyst of ovary (12.3%) was most common lesion (Fig 8) followed by simple serous cyst (6.6%) and corpus leuteal cyst (2.8%). 3 cases of dermoid cyst (2.8%) and one case of fibroma (0.9%) of ovary were observed in our study. (Table IV).

Table 4: Ovarian Lesions Associated with Leiomyoma Ovarian Lesions Sl.No: No. of cases Percentage (%)

1. Follicular cyst 13 12.3 2. Simple serous cyst 7 6.6 3. Corpus leuteal cyst 3 2.8 4. Dermoid cyst 3 2.8 5. Fibroma 1 0.9

DISCUSSION seen in post menopausal age groups which occur due to Uterine leiomyoma being the most common benign tumor enhanced estrogen stimulation causing uterine of the uterus is the leading indication for hysterectomies leiomyomas explained in theory by Muram et al.7 Solitary (Fig 1,2). This retrospective study included 106 cases of leiomyoma was common (86.8%) and intramural fibroid uterus among which 44.3% were common in 5th leiomyoma (61.3%) was the commonest location. Similar decade of life followed by 40.5% in 4rth decade with results were observed in study by Usha et al.8 and drastic decrease in 6th decade. This indicates their Chhabra et al.9 The secondary changes in leiomyoma like common occurrence in pre and perimenopausal age group hyaline change, hemorrhage, necrosis, edema, myxoid due to hormone imbalance, which is found similar in change, red degeneration, calcification, fatty change and study done by Gull B et al6. Only 5.6% of cases were cystic change occur due to inadequate blood supply or

Copyright © 2019, Medpulse Publishing Corporation, MedPulse International Journal of Pathology, Volume 11, Issue 2 August 2019 MedPulse International Journal of Pathology, Print ISSN: 2550-7605, Online ISSN: 2636-4697, Volume 11, Issue 2, August 2019 pp 77-80 interference in capsular circulation (Fig 3).10 Hyaline large leiomyomas and estrogen stimulation. Presence of change (15%) is the commonest change seen in study follicular cyst in ovary explains its association with done by Persaud et al.11 which is similar to present study leiomyoma in hyper estrogenic state. Hence we conclude (8.5%).Adenomyosis in leiomyoma is an associated that both hormonal and mechanical factors are feature in this study seen in 11.3% cases (Fig 7). responsible for the occurrence of endometrial changes Adenomyosis of the uterus is a condition characterized by and ovarian lesions seen in leiomyoma uterus. a benign invasion of the endometrium in the uterine musculature associated with diffuse overgrowth of uterus REFERENCES (Jeff coat et al) 12. Raju GC et al13 reported 16% and 1. Crum C P. Body of uterus and Endometrium. In: Kumar V, Thomas JS et al14 had noted more frequent association. Abbas A K, Fausto N, Eds. Robbins and ,Cotran Raju GC et al showed that association of adenomyosis in Pathologic Basis of Disease.7th edition. Philadelpia: leiomyoma was most frequently observed in multiparous Saunders, 2004:1089-90. 2. Telinde text book of Surgical 8th Edition; 731- women between 30 and 50 years of age. The present 765. study also had similar observation of their occurrence in 3. Silverberg S G, Tabbara S O. The uterine corpus. In: 40-50 years of age group. In the present study, Silverberg S G, Delellis R A, Frable W J, Eds. Principles proliferative phase (54.7%) was most common and Practice of Surgical Pathology and Cytopathology. endometrial pattern followed by secretary phase similar to Vol 3(3rd edition). New York: Churchill Livingstone, study done by Dayal S et al15. Cases of Endometrial 1997: 2459-516. 4. Charles JZ, Michael RH, Robert AS. Mesenchymal Tumors hyperplasia were found in 8.4% which represent of the Uterus. In: Robert J. Kurman, Lora H E and estrogenic phase as that of proliferative endometrium. Brigitte M. Ronnett,Eds. Blaustein’s Pathology of the Khan JS16 showed that both proliferative phase and Female Genital Tract. 6th Edition, 2011:459-461. endometrial hyperplasia occur due to hyper estrogenic 5. Marsh EE, Bulun SE. Steroid hormones and leiomyomas. state. Endometrial polyps were seen in 6.6% cases in our Obstet Gynecol Clin N Am, 2006:33(1):59–67. study which are also estrogen dependent and may develop 6. Gull B, Karlson B, Milsom I, Gramberg S. Factors associated with endometrial thickness and uterine size in in association with endometrial hyperplasia. Atrophic random samples of postmenopausal women. Am J Obstet endometrium may occur either due to mechanical Gynecol 2001; 185(2): 386-91. pressure effect or due to insufficient hormones in 7. Muram D, Gillieson M, Wallers. JH Myomas of the Uterus postmenopausal state as explained by Dayal S et al. 8.4% AmJ Obstet Gynacol 1980; 138; 16-19. of cases showed endometrial atrophy in our study. 25.5% 8. Usha, Narang BR, Tiwari PV, et al. Clinicopathological of ovarian lesions were found associated with leiomyoma, study of benign tumors of the uterus. Indian Med Gazette. 1992; 12:68-71. in which follicular cyst (12.3%) was found to be most 9. Chhabra S, Ohri N. Leiomyomas of uterus Aclinical study. common ovarian pathology (Fig 8) followed by simple J Obstet and Gynaecol of India 1993; 43(3): 436-39. serous cyst (6.6%). Follicular cyst may be associated with 10. Juan Rosai. Rosai and Ackerman’s Surgical Pathology. endometrial hyperplasia and the cyst fluid contains Mosby. 9th Edition. 2005.2892p. estrogen (Ackerman)10. 3 cases (2.8%) of dermoid cyst of 11. Persuad V, Arjoon PD. Uterine Leiomyoma. Incidence of the ovary were observed in present study. Although both degenerative change and correlation of associated symptoms. Obstet Gynecol. 1970; 35:432-6. leiomyoma and dermoid cyst commonly occur in 12. Jeffcoat text book of Clinical Gynaecology; 260-289. reproductive age group but their synchronous occurrence 13. Raju GC, Narayan singh V, Woo J, Jankey N Aust NZJ is rare. Katke RD17 explained this rare occurrence of obstet Gynacol. 1988, Feb 28(1): 72-3. dermoid cyst of ovary with multiple leiomyomas as twin 14. Thomas JS Jr, Clark JF. Natl Med Assoc. 1989 Sep; pathology in her study. One case of fibroma (0.9%) of 81(9); 969-72 ovary was also noted in our study. 15. Dayal S, Nagrath A. Clinicopathological correlation of endometrial, myometrial and ovarian pathologies with secondary changes in leiomyoma. Journal of Pathology of CONCLUSION Nepal. 2016; 6:937-941. The study showed a higher incidence of leiomyomas in 16. Jargal Sai Khan B, Galtrog L, Erdenetrogt D, reproductive age group. Most of the leiomyomas were Yanjinsuren D. Endometrial epithelial changes associated seen in intramural location. Proliferative phase, with uterine leiomyoma. Mangolian Journal Of Health Sciences 2013; 1:1-7. adenomyosis, endometrial polyp and endometrial 17. Katke RD. Torsion of huge cystic teratoma of ovary with hyperplasia were significant endometrial changes multiple fibroids uterus: a case report and review of observed suggesting estrogenic influence. Secondary literature. Int J Reprod Contracept Obstet Gynecol 2014; changes in leiomyoma occur due to mechanical effect of 3:793-5.

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