Clinicopathological Correlation of Adenomyosis with Literature Review – A Retrospective Audit

We retrospectively searched the records of women who have undergone hysterectomies for various indications from April 2019 to April 2020. The records of women who have undergone hysterectomies for various indications in the year of the study were searched to understand the incidence of the condition and the nature of their clinical presentation.

Out of 146 cases in the study period, we had 41.78% of the patients having histopathological evidence of adenomyosis. Adenomyosis on histopathology was found in 7 out of 25 women operated for prolapse uterus, 12 out of 55 women operated for fibroid, and 3 out of 12 women operated for endometrial causes. Only 80% of the women with a preoperative diagnosis of adenomyosis showed the histopathological features of adenomyosis, and 20% had no evidence of the condition. Out of 146 specimens with histopathological elements of adenomyosis, only 21 women had a preoperative diagnosis of the condition.

Most of the time, the definitive diagnosis of adenomyosis is retrospective by histopathological examination of hysterectomy specimens. The presence of adenomyosis – as seen on histopathological examination of the uteri – does not always match the clinical presentation.

Bird defines adenomyosis as a benign invasion of the myometrium, producing a diffusely enlarged uterus with microscopically demonstrable ectopic, nonneoplastic endometrial glands with stroma surrounded by hypertrophic and hyperplastic myometrium.[1] The condition is not as uncommon as it is believed, as it is observed in 54% of uteri at necropsies.[2] Risk factors include age close to menopause, multiparity, previous surgeries such as dilatation and evacuation, dilation and curettage, smoking, and excess of estrogen.[2,3] Even with multiple biopsies, the sensitivity of the test is only 45%, too low to be of clinical value.[3] Most of the time, the diagnosis is retrospective by examination of endometriotic gland islands in the myometrium in hysterectomized uteruses. The criteria for the diagnosis are endometrial glands in more than one high-power field on low-power microscopy about 2.5 mm from the endometrium, but the definition keeps changing in different studies,[2,4,5] and only 10% of the cases may be diagnosed by ultrasonography.[6] Although hormonal therapy is useful in some cases, in the end, surgery is the most sought-after option for treatment in most patients with adenomyosis.[7] The aim of this retrospective study was to find the prevalence of adenomyosis in hysterectomy specimens of women who have undergone surgery for various reasons and to correlate adenomyosis with the clinical presentation of these women.

This retrospective study was conducted in Shri Guru Ram Rai Institute of Medical and Health Sciences, Dehradun, over a period of 1 year from April 2019 to April 2020. The approval of the Institutional Review Board was taken prior to the initiation of the study. We searched the records of women who have undergone hysterectomies for various indications in the year of the study to understand the incidence of the condition and the nature of their clinical presentation. Histopathology of hysterectomized uteri was viewed to assess the occurrence and severity of adenomyosis. Cases included were the women who had undergone hysterectomies for fibroids, abnormal uterine bleeding (AUB), uterovaginal prolapse, postmenopausal bleeding, endometriosis, cervical and uterine malignancies, and other indications. Histopathological criteria for diagnosis were the presence of endometriotic foci about 1–2.5 mm inside the basal layer of the endometrium on histopathology. Their presenting symptoms and the severity were noted. Statistical analysis The data were collected, tabulated, and coded using Microsoft Corporation (2021). Microsoft Excel (Version 2021). Microsoft Corporation, Redmond, WA, USA., and the analysis was done using IBM SPSS Statistics for Windows (Version 21.0). IBM Corporation, Armonk, NY, USA. Descriptive statistics such as frequency and percentages were used. The data were not normally distributed as the variables were categorical.

In this study, of the 146 patients who had undergone hysterectomy, 41.78% patients had adenomyosis on histopathology. Table 1 shows the age-wise distribution of patients. Majority of the women were in the age group of 45–60 years (61.64%). Indication for hysterectomy was fibroid in 55 (37.67%), 25 (17.12%) women were operated for uterovaginal prolapse, 14.38% had a preoperative diagnosis of abnormal uterine bleeding -adenomyosis (AUB-A), while 8.21% had endometrial causes for the surgery abnormal uterine bleeding-endometrial disorders (AUB-E). 17.3% of the patients had both adenomyosis and fibroid uterus and 7% were operated for chronic pelvic inflammatory disease (PID) [Table 2]. Severity of symptoms in women diagnosed with adenomyosis Table 4 shows that the major comorbidity found among these patients was type 2 diabetes mellitus. Other comorbidities included hypertension, hypothyroidism, hyperthyroidism, heart disease, concurrent hypertension, and diabetes. Adenomyosis was found on histopathology in 7 out of 25 patients who had undergone surgery for prolapse uterus, and in 12 out of 55 patients who had undergone hysterectomy for diagnosis of fibroid uterus, and in 3 out of 12 patients who had undergone hysterectomy for endometrial causes. Only 80% of the women with preoperative ultrasound diagnosis of adenomyosis showed the histopathological features of adenomyosis and 20% had no evidence of the condition before surgery [Table 5]. Associated histopathology in hysterectomy specimens

Adenomyosis is not an uncommon entity. This mysterious condition has only been recognized since the 1980s. The exact nature and cause still remains an enigma. The present study was done in 146 women who had undergone hysterectomy for various indications to understand the occurrence of adenomyosis. In our study, we observed that there were 19.17% of women were below the age of 45 years, 39% of women were between the ages of 45 and 50 years, 22.6% were in the age group of 55 and 60 years, 10.96% were between 61 and 65 years, and 8.2% of women were more than 65 years. In our study, we found that out of 146 women who had undergone hysterectomy for various reasons, 55 (37.6%) women had hysterectomy for fibroid uterus, 25 (17.12%) for uterovaginal prolapse, 26 (17.18%) for abnormal uterine bleeding - leiomyoma+adenomyosis (AUB (L + A)), and 21 (14.38) for adenomyosis. Twelve (8.21%) patients were hysterectomized for Abnormal uterine bleeding-endometrial disorders (AUB (E)), seven (4.79%) for chronic pelvic pain and PID, and two women needed hysterectomy for postmenopausal bleeding. A total of 61% of the specimens (of the total of 146) showed the elements of adenomyosis on histopathology, while only 21 women had a preoperative ultrasound diagnosis of adenomyosis. The rest of the women did not have symptoms suggestive of adenomyosis even if they had diagnostic foci of adenomyotic lesions on HPE. This study observed that in the women with adenomyosis, the most predominant symptom was heavy menstrual bleeding, followed by dyspareunia and chronic backache. In a study by Owolabi and Strickler, adenomyosis was present in 161 of 1619 consecutive hysterectomy specimens. Adenomyosis coexisted with other pelvic pathology in 97 women and was the only histologic finding in 64 women. Most patients were 35–50 years of age, parous, white, had not taken steroid hormones, had not had uterine surgery, and complained of AUB and/or pelvic pain. Adenomyosis was most associated with leiomyomata, endometrial hyperplasia and carcinoma, and endometriosis. The clinical signs of uterine enlargement and tenderness were rarely observed. At surgery, adenomyosis was not recognized in 65% of patients.[3] In the present study, we observed other coexistent pathologies such as metaplasia, cervicitis, and endometritis in the hysterectomy specimen. In a similar study of 255 hysterectomy specimens, Taran et al. observed that 85 women had a leiomyoma along with adenomyosis and 170 women had only fibroids.[8] In our observation, there were 19% of women with fibroid and adenomyosis together. Both being estrogen-dependent conditions, they often coexist. Even in the cases of endometrial cancer, there could be an associated adenomyosis, in which case, of course, the prognosis does not change. This finding closely correlates to the study by Kitawaki et al. The incidence of adenomyosis was reported more in women in the age group between 40 and 50 years. In our study, 58.21% of women were in this age group.[6] Curtis et al., in a study of 1300 women with adenomyosis, tried to correlate the surgical disruption of the endomyometrial junction after dilatation and curettage and the occurrence of adenomyosis and found that women with two or more abortions followed by sharp curettage were at a higher risk for developing adenomyosis than women who had cesarean sections.[9] In the present study, we observed that out of 21 women operated for adenomyosis, 17 (80%) women had histopathologic evidence of the condition, and 20% of women had no adenomyotic foci in the uterine specimens, and in the women with a preoperative diagnosis of adenomyosis, there was no history of uterine curettage. On a closer look at histopathology, we found that many conditions coexisted in the hysterectomy specimen and included squamous metaplasia, chronic cervicitis, chronic polypoidal cervicitis, and myohyperplasia. There were 21 (28%) cases of adenomyosis diagnosed preoperatively by ultrasound that underwent hysterectomy in this study. Surgery is still deemed the best resolution to the condition, as was found by Bergeron et al. during their work on finding the pathology of adenomyosis. They observed that even though adenomyosis is hormone sensitive, progesterone treatment is ineffective, and gonadotrophin-releasing hormone analogs and danazol offer only temporary relief, leaving surgery as the best option.[10] Farquhar and Brosens commented that since most of the cases of adenomyosis are diagnosed postoperatively in the hysterectomy specimens, there are no good trials to rely upon for the medical management of the condition.[7] In our observation, we found that 40% of women with adenomyosis had tried hormonal treatment before resorting to the surgery. This study observed conflicting results where majority of women with pathological adenomyotic lesions in their uteri had no symptoms, and 20% of women with prediagnosed adenomyosis had no evidence of the condition on histopathology.

Adenomyosis, an ill-understood uterine disorder in women, in their reproductive age, is not an uncommon entity. Many women who harbor the condition do not have any symptoms, and the condition is diagnosed incidentally. Most of the time, the diagnosis of adenomyosis is retrospective by histopathological examination of hysterectomy specimens. The severity of adenomyosis – as seen on histopathological examination of the uteri – does not always match the clinical presentation. Authors’ contribution AC, PJ, and SN contributed to the concept design, definition of intellectual content, literature search, recruitment of participants, statistical analysis, and manuscript preparation and revision. PJ, SA, and AT contributed to data acquisition, data analysis, and data interpretation. SA and AT also prepared, edited, and substantially revised the manuscript. AC and SN contributed to the critical revision, design of the work, and analysis and interpretation of data. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

1. Bird CC, McElin TW, Manalo-Estrella P. The elusive adenomyosis of the uterus – Revisited. Am J Obstet Gynecol 1972;112:583–93. 2. Weiss G, Maseelall P, Schott LL, Brockwell SE, Schocken M, Johnston JM. Adenomyosis a variant, not a disease? Evidence from hysterectomized menopausal women in the Study of Women's Health Across the Nation (SWAN). Fertil Steril 2009;91:201–6. 5. Sun YL, Wang CB, Lee CY, Wun TH, Lin P, Lin YH, et al. Transvaginal sonographic criteria for the diagnosis of adenomyosis based on histopathologic correlation. Taiwan J Obstet Gynecol 2010;49:40–4. 9. Curtis KM, Hillis SD, Marchbanks PA, Peterson HB. Disruption of the endometrial-myometrial border during pregnancy as a risk factor for adenomyosis. Am J Obstet Gynecol 2002;187:543–4.