Histopathological Findings in Symptomatizing Patients After Supracervical Hysterectomy: A Cross Sectional Study
Summary
Background: Supra-cervical hysterectomy (SCH) is widely common and has many complications either immediate or delayed, including bleeding, infection, and chronic pelvic pain. Clinical studies evaluating histopathological findings in these patients are few.
Objective: To study the underlying pathological changes in the cervical stump after supracervical hysterectomy in symptomatizing patients.
Patients and Methods: This cross-section study was conducted at Tanta University. All patients (n=132) underwent cervical stump biopsy for histopathological examinations. Immunohistochemical expression of P16 was also performed in all patients with cervical pathological abnormalities as a recommended biomarker for cervical lesions.
Results: Vaginal bleeding was the most common presentation of enrolled patients (54/132). Endometriosis was the commonest pathological lesion detected in patients with cervical stump bleeding (27/54). After Hematoxylin and eosin staining was applied; 52 cases showed normal cervical tissue, chronic non-specific cervicitis in 11 cases, endometriosis in 27 cases, squamous metaplasia with no atypia in 6 cases, cervical intraepithelial neoplasia in 32 cases, squamous cell carcinoma in 3 cases and adenocarcinoma in only one case. P16 immuno-staining showed negative expression in chronic cervicitis and squamous metaplasia with no atypia, ambiguous p16 expression was observed in 50%, 63.2% and 80% cases of CIN I, CIN II, and III respectively, while 100% of cervical cancer cases showed block positive expression.
Conclusion: Pathological lesions of cervical stump following SCH could be screened by p16 immuno-staining as a complementary test for early detection of cervical cancer. Ambiguous expression of p16 should not be neglected as the lesion may have a low possibility of harboring high-risk human papilloma
Keywords: Cervical stump; Histopathology; p16 expression; Supracervical hysterectomy
Abbreviations: BMI: Body Mass Index; CIN: Cervical Intraepithelial Neoplasia; H&E: Hematoxylin and Eosin; HSIL: High-grade Squamous Intraepithelial Lesions; HPV: Human Papilloma Virus; IHC: Immunohistochemistry; SCH: Supracervical Hysterectomy.
Introduction
Hysterectomy is the second most common major operation after cesarean section, that met within gynecological and obstetrics clinic. By the age of 65, more than a third of all women are expected to have had this surgery [1].
In subtotal supracervical hysterectomy, only the body of the uterus is removed compared to the total hysterectomy where the cervix along with the uterus are excised. In the last century, it was thought that leaving the cervix in place preserve better bowel, urinary and sexual function as well as avoidance of post- total hysterectomy complications as vaginal cuff abscesses, urethral injury, and incontinence. A meta- analysis of nine randomized studies of women with a history of supracervical or complete hysterectomy for benign gynecologic disorders disapproved this claim. There was no difference in sexual function or incontinence after surgery [2]. However, cervical stump symptoms can cause some sort of distress in certain individuals to require further operation and cervical stump excision [3].
The current studies on risk factors for constant postoperative cervical stump bleeding are inconclusive. Some research found endometriosis to be a risk factor [4], whereas others failed to find such a link [3]. The data on endocervical removal during hysterectomy were inconclusive [5]. The main disadvantage of subtotal hysterectomy is still the risk of developing cervical stump cancer and the need for regular cervical screening following the surgery [6].
Although the screening programs using pap smears are highly successful and being used routinely in some countries, a significant number of cases of cervical cancer have still been missed which can be attributed to false negative test results due to sampling errors, inter and intra observer variability [7].
The diagnostic interpretation of hematoxylin and eosin (H&E)– stained cervical biopsies is subject to substantial variability between readers, leading to potential under-treatment of women with high-grade precancerous lesions (high-grade squamous intraepithelial lesions [HSIL]) or greater, or overtreatment in case of false-positive diagnostic interpretations [8,9].
This makes a bad need for a more sensitive and specific test for improving cervical cancer screening and accurately diagnosing precancerous lesions [10]. Since the lower anogenital terminology (LAST) project performed by the American Society for Colposcopy and cervical pathology(ASCCP) and the college of American pathology(CAP), the published literature recommended the use of biomarkers to improve diagnostic agreement [11]. It has been suggested that p16 staining is a recommended biomarker for cervical lesions [12]. However, even today the use of p16 protein as a prognostic biomarker of cervical cancer remains controversial.
In the view of the current study, symptomatizing patients after SCH was recruited and biopsy was taken to show what are the underlying pathological findings of the cervical stump in those patients, and to aid for putting the comprehensive therapeutic strategy for their treatment. The study also was designed to evaluate the immuno-staining pattern of p16 compared to histopathological diagnosis and its accuracy in diagnosis and interpretation of cervical biopsy results.
Patients and Methods
Study design and settings
This study is a cross section descriptive study conducted at Tanta University Hospital, in both Obstetrics & gynecology and Pathology departments. The study was conducted in the period from December 2017 till January 2021.
Patients
All symptomatic patients following hysterectomy were recruited and eligible patients were included according to inclusion and exclusion criteria. The inclusion criteria were (a) Any age (b) Supracervical hysterectomy, (c) Symptomatic patients. The exclusion criteria were (a) Total hysterectomy, (b) hysterectomies for malignant lesions indications, and (c) Patients refusing to participate.
Sample size calculation
Sample was calculated using Epi-Info 2000 statistical program. The standard normal variate (at 5% type 1 error) was 1.96, the expected prevalence of cervical cancer in stump up to 9% [13], p-value of 0.05, the sample was 110 cases.
Methods
All patients’ demographic data, indication of hysterectomy, duration since operation, postoperative complications, latent period, and their main complaint were recorded.
Interventions
Gynecological interventions: Under general anesthesia, cervical biopsy (4-quadrant punch biopsy) was taken from all patients, put in formalin sterile container, and sent for histopathological examination.
Histopathological examination: All the received cervical specimens were formalin fixed and paraffin embedded. Hematoxylin and eosin (H&E)–stained slides were subjected to routine histopathological examination. The pathological findings were categorized into; endometriosis, non-specific cervicitis, squamous metaplasia, cervical intraepithelial neoplasia (CIN) and cancer cervix. Cervical intraepithelial neoplasia is classified into; CIN I, CIN II, and CIN III according to how much tissue affected by dysplasia; lower one third, lower two thirds or more than two thirds respectively [14].
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