H. Bharucha

An automated machine vision system for the histological grading of cervical intraepithelial neoplasia (CIN)

The histological grading of cervical intraepithelial neoplasia (CIN) remains subjective, resulting in inter‐ and intra‐observer variation and poor reproducibility in the grading of cervical lesions. This study has attempted to develop an objective grading system using automated machine vision. The architectural features of cervical squamous epithelium are quantitatively analysed using a combination of computerized digital image processing and Delaunay triangulation analysis; 230 images digitally captured from cases previously classified by a gynaecological pathologist included normal cervical squamous epithelium (n=30), koilocytosis (n=46), CIN 1 (n=52), CIN 2 (n=56), and CIN 3 (n=46). Intra‐ and inter‐observer variation had kappa values of 0.502 and 0.415, respectively. A machine vision system was developed in KS400 macro programming language to segment and mark the centres of all nuclei within the epithelium. By object‐oriented analysis of image components, the positional information of nuclei was used to construct a Delaunay triangulation mesh. Each mesh was analysed to compute triangle dimensions including the mean triangle area, the mean triangle edge length, and the number of triangles per unit area, giving an individual quantitative profile of measurements for each case. Discriminant analysis of the geometric data revealed the significant discriminatory variables from which a classification score was derived. The scoring system distinguished between normal and CIN 3 in 98.7% of cases and between koilocytosis and CIN 1 in 76.5% of cases, but only 62.3% of the CIN cases were classified into the correct group, with the CIN 2 group showing the highest rate of misclassification. Graphical plots of triangulation data demonstrated the continuum of morphological change from normal squamous epithelium to the highest grade of CIN, with overlapping of the groups originally defined by the pathologists. This study shows that automated location of nuclei in cervical biopsies using computerized image analysis is possible. Analysis of positional information enables quantitative evaluation of architectural features in CIN using Delaunay triangulation meshes, which is effective in the objective classification of CIN. This demonstrates the future potential of automated machine vision systems in diagnostic histopathology. Copyright

Computerized diagnostic decision support system for the classification of preinvasive cervical squamous lesions

Previous studies have revealed considerable interobserver and intraobserver variation in the histological classification of preinvasive cervical squamous lesions. The aim of the present study was to develop a decision support system (DSS) for the histological interpretation of these lesions. Knowledge and uncertainty were represented in the form of a Bayesian belief network that permitted the storage of diagnostic knowledge and, for a given case, the collection of evidence in a cumulative manner that provided a final probability for the possible diagnostic outcomes. The network comprised 8 diagnostic histological features (evidence nodes) that were each independently linked to the diagnosis (decision node) by a conditional probability matrix. Diagnostic outcomes comprised normal; koilocytosis; and cervical intraepithelial neoplasia (CIN) I, CIN II, and CIN III. For each evidence feature, a set of images was recorded that represented the full spectrum of change for that feature. The system was designed to be interactive in that the histopathologist was prompted to enter evidence into the network via a specifically designed graphical user interface (i-Path Diagnostics, Belfast, Northern Ireland). Membership functions were used to derive the relative likelihoods for the alternative feature outcomes, the likelihood vector was entered into the network, and the updated diagnostic belief was computed for the diagnostic outcomes and displayed. A cumulative probability graph was generated throughout the diagnostic process and presented on screen. The network was tested on 50 cervical colposcopic biopsy specimens, comprising 10 cases each of normal, koilocytosis, CIN I, CIN II, and CIN III. These had been preselected by a consultant gynecological pathologist. Using conventional morphological assessment, the cases were classified on 2 separate occasions by 2 consultant and 2 junior pathologists. The cases were also then classified using the DSS on 2 occasions by the 4 pathologists and by 2 medical students with no experience in cervical histology. Interobserver and intraobserver agreement using morphology and using the DSS was calculated with kappa statistics. Intraobserver reproducibility using conventional unaided diagnosis was reasonably good (kappa range, 0.688 to 0.861), but interobserver agreement was poor (kappa range, 0.347 to 0.747). Using the DSS improved overall reproducibility between individuals. Using the DSS, however, did not enhance the diagnostic performance of junior pathologists when comparing their DSS-based diagnosis against an experienced consultant. However, the generation of a cumulative probability graph also allowed a comparison of individual performance, how individual features were assessed in the same case, and how this contributed to diagnostic disagreement between individuals. Diagnostic features such as nuclear pleomorphism were shown to be particularly problematic and poorly reproducible. DSSs such as this therefore not only have a role to play in enhancing decision making but also in the study of diagnostic protocol, education, self-assessment, and quality control.

Endometrial stromal sarcoma arising in pelvic endometriosis in a patient receiving unopposed oestrogen therapy

A 39 year old woman, presented with menorrhagia in 1972. An ultrasound scan revealed a cystic lesion within the right ovary. Total abdominal hysterectomy and right ovarian cystectomy was performed with conservation of both ovaries. Pathological examination (the histology of which has subsequently been reviewed) showed a simple serous cystadenoma within the right ovary. There was no significant pathology within the uterus. In 1990 she had been prescribed transdermal oestradiol hormone replacement therapy (HRT) because of menopausal symptoms. She continued this until June 1995 when she developed vaginal bleeding, and oestrogen therapy was discontinued. Examination under anaesthesia revealed a soft friable mass involving the vaginal vault and rectovaginal septum, extending laterally to the left pelvic side wall. Histological examination of a biopsy from the mass at the vaginal vault showed intact surface vaginal squamous epithelium. Endometrial glands and surrounding stroma were present beneath the mucosa, in keeping with endometriosis (Fig. 1). At review the mass had not reduced in size, despite withdrawal of exogenous oestrogens. A computerised tomography scan of the pelvis confirmed an irregular soft tissue mass in the rectovaginal septum. Laparoscopy confirmed that the mass lay retroperitoneally in the rectovaginal septum. A repeat biopsy showed histological features similar to the original. At the next review two months later the mass had apparently increased in size. Laparotomy was performed and a 5 cm irregular diffuse tumour-like mass was identified in the upper third of the rectovaginal septum. The mass extended to involve the left ovary and was adherent to the rectum and sigmoid colon. Several tumour nodules were also present within the

Uterine leiomyosarcoma in patient receiving tamoxifen therapy

Tamoxifen is a non‐steroidal triphenylethyl compound which is widely used as adjuvant therapy in the treatment of breast cancer because of its anti‐estrogen properties. This antiestrogen effect is felt to be mediated by its competitive binding to the estrogen receptor (1). Tamoxifen has been perceived as a safe and effective drug with negligible side effects. However, in addition to its antiestrogen properties, tamoxifen may have a weak estrogenic effect (2) and, in recent years, several studies have described the effects of tamoxifen on the human endometrium (3‐7). A general consensus has emerged that tamoxifen may be implicated in the development of endometrial proliferative lesions including polyps, hyperplasia and carcinoma. The development of uterine sarcoma in association with tamoxifen therapy has been less well documented. In 1994 Silva et al. (8) reviewed 72 patients who developed malignant neoplasms of the uterine corpus after being treated for breast carcinoma with either tamoxifen or other therapeutic regimens. Twelve leiomyosarcomas were included in this group. We report an additional case of uterine leiomyosarcoma arising in a postmenopausal woman on long‐term tamoxifen therapy for breast carcinoma. Immunohistochemistry for estrogen and progesterone receptors was performed in order to ascertain whether the tumor was hormone responsive. The literature on uterine mesenchymal lesions arising in association with tamoxifen therapy is discussed.