Multiple Cervical Biopsies Research Articles

The role of random cervical biopsies in addition to colposcopy-directed biopsies in detection of CIN2+

The aim of this study was to determine the additional values of multiple cervical biopsies when any colposcopy was performed. We developed a cross-sectional study of 92 women, who had been referred for a colposcopy because of their abnormal cervical cytology. Colposcopy-directed biopsies were taken from lesions and random non-directed biopsies were added, if their directed biopsies were fewer than four in number. The biopsy sites were ranked according to the impression of the clinicians. Among the 92 women, the first biopsy was normal in 29.4%, revealing CIN1 in 28.3% and CIN2+ in 42.3%. In the second and third biopsies, the CIN2+ was found to have increased to 35.8% and 36.8%, respectively. The accumulative sensitivity for detecting CIN2+ was 84.8%, for a single biopsy. This increased to 97.0%, after two biopsies and then to 100%, after three and four biopsies. To conclude, although the taking of the additional biopsies increased the CIN2+ detection, collecting three cervical biopsies might be sufficient.Impact StatementWhat is already known on this subject? The colposcopy is considered to be the standard procedure in the detection of precancerous lesions of the cervix. However, nowadays, colposcopic biopsy practices do not have any single, acceptable guideline for the number of biopsies performed, and whilst a single biopsy is the most commonly adopted practice, some centres have used a biopsy protocol with multiple biopsies.What the results of this study add? This study determined the rate of the detection of CIN2+ by using multiple biopsy protocols during colposcopy for women who were referred with their abnormal cervical cytology. We explored the benefit of collecting additional lesion-directed biopsies and additional biopsies of a normal-appearing cervix in addition to a single biopsy. We found that two or three biopsies from a colposcopy should be enough for increasing the detection of CIN2+. Also, multiple biopsies increased the sensitivity of CIN2+ detection, especially in colposcopic impression for the low grade lesions.What the implications are of these findings for clinical practice and/or further research? We suggest that colposcopy-directed biopsies should be supplied by one or two random biopsies from other quadrants of the cervix.

Does the use of multiple cervical biopsies during colposcopy significantly improve diagnostic yield?

EVIDENCE-BASED ANSWER Yes. In women referred to colposcopy for abnormal cervical cytology, the yield for detection of CIN2 or higher increases by 9% to 17% with 2 versus 1 biopsy. The sensitivity for detecting CIN2 or higher with 1 biopsy ranges from 61% to 78%, and increases up to 96% with 3 biopsies (SOR: C, diagnostic studies, disease-oriented evidence).

CADM1 and MAL methylation status in cervical scrapes is representative of the most severe underlying lesion in women with multiple cervical biopsies.

Recent studies have shown that CADM1/MAL methylation levels in cervical scrapes increase with severity and duration of the underlying cervical intraepithelial neoplasia (CIN) lesion. Multiple lesions of different histological grades and duration are frequently present on the cervix. To gain more insight into the possible epigenetic heterogeneity and its consequences for the methylation status in cervical scrapes, we performed an exploratory study of CADM1/MAL methylation in different grades of CIN lesions present in women with multiple cervical biopsies. CADM1-M18 and MAL-M1 methylation was assessed using a standardised, multiplex, quantitative methylation specific PCR on 178 biopsies with various grades of CIN in 65 women, and in their corresponding cervical scrapes. CADM1/MAL methylation positivity increased with disease severity, from 5.5% in normal biopsies to 63.3% and 100% in biopsies with CIN3 and cervical cancer, respectively. In the majority (8/9) of women where besides a CIN2/3 lesion a biopsy from normal cervical tissue was present, the CIN2/3 biopsy was CADM1/MAL methylation positive and the normal biopsy was CADM1/MAL methylation negative. A good concordance (78%) was found between CADM1/MAL methylation results on the scrapes and the biopsy with the worst diagnosis, particularly between samples of women with CIN3 and cervical cancer (92% and 100% concordance, respectively). Thus, in women with multiple cervical biopsies, CADM1/MAL methylation increases with severity of the lesion and is lesion-specific. CADM1/MAL methylation status in cervical scrapes appears to be representative of the worst underlying lesion, particularly for CIN3 and cervical cancer.

Unusual form of superficial spreading squamous cell carcinoma of cervix involving the endometrium, bilateral tubes and ovaries: a case report with literature review

Although the majority of metastatic ovarian tumors arise within the female genital tract, squamous cell carcinoma of the cervix is a rare form of metastases to the bilateral ovaries by endometrial and transtubal spreading. A 53-year-old woman was referred to the oncology clinic with postmenopausal bleeding. On vaginal examination, a 3 cm tumor arising from the cervix was inspected. Multiple cervical biopsies and endocervical curettage revealed large cell, non-keratinized squamous cell cervix carcinoma. Radical hysterectomy and bilateral salpingo-oophorectomy were performed. Bilateral pelvic and para-aortic lymph nodes were also removed. The final pathology report revealed endometrial, focal myometrial, bilateral tubal mucosal, fimbrial and bilateral ovarian squamous cell carcinoma involvement. Pelvic and para-aortic nodes were free from metastases. Although the incidence of ovarian metastases of adenocarcinoma of the cervix is significantly higher, squamous cell carcinoma may also metastasize to the ovaries by endometrial and transtubal spreading in the absence of lymph node involvement. Especially in young patients for whom preservation of the ovaries is supposed, gross intraoperative inspection of the radical hysterectomy specimen and endometrium should be done and ovaries should be evaluated carefully.

Cervical tuberculosis detection in Papanicolaou‐stained smear: Case report with review of literature

Genital tract tuberculosis is usually secondary to an extragenital tubercular focus. Cervical tuberculosis, however, is rare accounting for up to 3% of all genital tract diseases. The diagnosis of tuberculosis is usually established on multiple cervical biopsies followed by bacteriological confirmation. There are only a handful of reports on the diagnosis of tubercular cervicitis in cervical smears. We hereby report a case of cervical tuberculosis which was diagnosed on cervical smear. We also carried out a brief literature review of the cases diagnosed previously on cervical smear.

Comparison of three management strategies for patients with atypical squamous cells of undetermined significance, after six months delay: A three‐year experience in an Iranian university hospital

A Pap test result of atypical squamous cells of undetermined significance (ASCUS) presents a clinical challenge. Only 5-10% of women with ASCUS harbour serious cervical disease. We screened 3619 women, who attended to Mirza Koochak Khan Hospital at Tehran University of Medical Sciences with Pap smears, of whom 100 returned with ASCUS. After six months, each subject underwent a standard cytology (conventional Pap smear), human papillomavirus (HPV) DNA testing (identifying high-risk HPV types with polymerase chain reaction) and colposcopy with multiple cervical biopsies. Mean age was 44.09 +/- 8.6 years. The estimated prevalence of cervical intraepithelial neoplasia (CIN) II or higher was 4%. When histologically verified high-grade lesions (> or = CIN II) were observed, the relative sensitivity of HPV DNA testing was 100% compared with conventional Pap smear, which performed 75% versus 100% relative sensitivity, respectively, using cytological diagnosis high-grade squamous intraepithelial lesion, or low-grade squamous intraepithelial lesion (LSIL) as the cut-off. Negative and positive predictive values (NPV and PPV) of Pap test were 98.9% and 100%. The NPV and PPV of HPV DNA testing were 100%. Although less complicated than colposcopy, the repeat Pap smear triage algorithm for ASCUS may underdiagnose some women with high-grade CIN, when compared with colposcopy. Considering the high sensitivity of HPV testing, it may be useful as an alternative to the current policy of six-month repeat cytology for women with ASCUS results.

Clinical observation of cervial intraepithellal neoplasla managed by loop electrosurgical excision procedure

Objective To evaluate the clinical value of cervical intraepithelial neoplasia treated by loop elec-trosurgical excision procedure. Methods A retrospective analysis was performed in 192 patients with CIN which were diagnosed after LCT, oolpoccopy and multiple cervical biopsies. Results The satisfactory rate was 99. 5% (191/192) ,the LCT and digital colposcopy were all negative after operation 4 -6 months, 12 months, 18 months and 24 months. Conclusion LEEP is an effective treatment for CIN, with the advantages of easy, safe and quick procedure, minimal damage and blood loss. LEEP helps to avoid misdiagnosis of earlier cervical cancer. Key words: Cervical intraepithelial neoplasia; Conization; Electrocoagulation

Postmenopausal uterine bleeding

The incidence of uterine or adnexal malignancies in the 211 patients with postmenopausal uterine bleeding was 27.5 per cent (58 patients). It is low because our current practice of hospitalizing most patients with postmenopausal uterine bleeding has increased the total number of patients to a greater extent than it has the number of patients with cancer.Benign lesions were the cause of, or were involved in the production of the bleeding in 72 (34.1 per cent) of the 211 patients.The cause of the bleeding could not be demonstrated in 81 (38.4 per cent) of the 211 patients. This is a greater incidence than recorded in most reports because we exclude as causes such pathologic findings as chronic cervicitis (diagnosed histologically), adenomyosis, atrophic endometrium, and some fibroids.A single episode of spotting for 2 days, 2 or 3 months before the patient is examined, may indicate the presence of cancer. Postmenopausal patients with cancer may have no bleeding at all for 3 to 6 months between episodes or after a single episode of uterine bleeding. This occurred in 9 of the 58 patients with cancer reported here. The longest period without flow was 6 months. This happened in 2 of the 9 patients. The conclusion drawn is that even though the bleeding occurs several months prior to the time the patient reports to her physician, it must be considered to be indicative of cancer until it is proved otherwise.The quantity, duration, or character of the bleeding neither indicates accurately the extent of the cancer nor provides a means of distinguishing malignant from benign lesions.Curettage is not infallible although it is so considered by many clinicians. In 3 of the 52 patients with uterine cancer curettage failed to provide the diagnosis and caused a delay of 6, 14, and 17 months, respectively, in the recognition of the endometrial carcinomas.In the management of postmenopausal uterine bleeding curettage should always be performed. It is considered adequate therapy in many instances. In our study 97 (63.4 per cent) of the 153 patients in whom the bleeding was from nonmalignant cause were so treated. This procedure should always be accompanied by curettage of the endocervix and multiple cervical biopsies. It is important that such patients have follow-up examinations, since postmenopausal patients with uterine cancer may have no bleeding for periods of 3 to 6 months, and since curettage and cytosmears are not completely reliable.Definitive procedures (hysterectomy or radiation) are carried out at the time of the curettage whenever feasible. This is desired because the incidence of cancer is high in patients with postmenopausal bleeding, and because it is known that the diagnostic procedures are subject to error. Of the 153 patients with bleeding from benign causes, 56 (36.6 per cent) were treated definitively. Fifty of these were so treated at the time of the curettage. Often there are coexisting lesions that require surgical management, such as vaginal relaxation, which provides the opportunity to extend the procedure to include removal of the pelvic organs. In other instances, bleeding alone is an adequate indication for consummation of definitive measures. Of these 56 patients, definitive treatment was carried out in 12 for the indication of bleeding only.We prefer surgical procedures to radiation in the treatment of patients with postmenopausal uterine bleeding from nonmalignant causes. Radiation is reserved for the treatment of malignancies. It is used in benign conditions only when there are contraindications to surgical procedures. Our preference of surgical procedures is vaginal hysterectomy but in the past we have not always removed the tubes and ovaries if they were atrophic and free of tumor and if the procedure was unusually difficult. We are now convinced that they must be removed when a hysterectomy is performed in a patient with postmenopausal uterine bleeding. If this cannot be accomplished readily vaginally, either a combined vaginal and abdominal procedure should be performed or the abdominal approach should be selected initially.If bleeding continues or recurs after a diagnostic curettage is performed, a second curettement is indicated. At the same time, if the bleeding is determined to be from a benign cause, definitive treatment is given. This is done unless there is some contraindication.Curettage, repeated at intervals, does not constitute the best management of continued or recurrent postmenopausal uterine bleeding.

Exfoliative dyskaryotic cells associated with atypical cervical lesions

1.1. Cytologic study of vaginal smears has proved to be of definite value in the detection of early cervical carcinoma and carcinoma in situ.2.2. Cervical dyskaryotic cells are atypical and characterized by large, hyperchromatic nuclei, often with a distinct perinuclear vacuole. The cells may be mono- or multinucleated. Some show marked cornification and are acidophilic.3.3. The significance of the dyskaryotic smear is discussed. Of 2,000 consecutive cases studied by vaginal smears, 12 showed a predominance of dyskaryotic cells, an incidence of 0.06 per cent. Biopsy study of the cervix in these cases revealed the presence of “atypism” in all instances. The histologic picture included a varying degree of epithelial proliferation, anaplasia, and cell atypism with and without mitosis. The basement membrane was found always to be intact.4.4. During a follow-up of 9 months to 4 years, one woman developed a squamous-cell carcinoma of the cervix, 2 years after the initial smear and biopsy. In 2 instances there was a regression to normal. The remaining 9 cases were persistently unchanged.5.5. Of 556 consecutive cervical biopsies taken 4 to 10 years ago, 13 showed atypism as described above. Investigation of the present status of these patients indicated that 3 had died of unrelated causes, 9 had remained well, and one had developed a squamous-cell carcinoma of the cervix, 6 years after the initial biopsy.6.6. Whether a relationship exists between the finding of a dyskaryotic smear and an atypical biopsy, and the future development of a true malignancy is speculative. The finding of an 8 per cent incidence, 2 and 6 years after the initial biopsy, is suggestive. Repeated vaginal smears and multiple cervical biopsies are most certainly indicated.