Glandular abnormalities on cervical smear: a study to compare the accuracy of cytological diagnosis with underlying pathology.

The interpretation of glandular abnormalities detected by cervical smear provides a diagnostic dilemma. This study aims to compare the accuracy of cytological diagnosis with underlying pathology so that guidelines for the investigation and management of abnormal glandular smears may be formulated. A retrospective review of 150 women with glandular abnormalities reported on cervical smear collected over 12 months from 1996 in a University hospital was performed. Smears were graded by the initial report into 3 groups, dependent on the severity of abnormality. Investigation, treatment and subsequent 3-year follow-up were recorded. The accuracy of prediction for a significant neoplastic or preneoplastic glandular pathology only was 0% with mild, 9% (3/35) with moderate, and 24% (9/38) with severe abnormalities. When squamous lesions were included, the chance of finding any dysplastic squamous or glandular abnormality was 16% (12/77), 51% (18/35) and 82% (31/38), respectively, following a smear showing a suspected glandular abnormality only. Our results highlight the poor specificity of predicting glandular neoplasia or preneoplasia from cervical smears, with a final diagnosis of high grade CIN in 35% (17/49) of patients with dyskaryotic glandular cytological changes only and 83% (20/24) where concomitant squamous dyskaryosis was reported. The reporting of reactive or minor changes in endocervical cells was of no diagnostic value. Management protocols for moderate and severe glandular abnormalities should include visualisation and biopsy of the uterine cavity to exclude endometrial neoplasia.

Interval cervical cancer following treatment for cervical intraepithelial neoplasia.

The objective of this study was to determine whether those women who developed cervical cancer following treatment for preinvasive disease had common features in their history which could identify those at increased risk of progression and therefore be used to modify management protocols. A retrospective case note review from clinical and histopathologic records was undertaken at a teaching hospital in Wessex, Southern England. The review included 33 women diagnosed with cervical carcinoma between 1985 and 1996 who had previously undergone treatment for cervical intraepithelial neoplasia (CIN) or cervical glandular intraepithelial neoplasia (CGIN). The diagnosis prior to treatment was CIN 3 in 19 cases, CGIN 3 in 2 cases, CIN 2 in 9 cases (97% high grade CIN/CGIN) and CIN 1 in 1 case. At primary treatment, among those treated by knife cone biopsy or Large Loop Excision of the Transformation Zone (LLETZ), and for whom the margins of the treatment specimen were reported, 14 out of 15 had incomplete margins. Local ablation (in which completeness of excision could not be histologically assessed) was performed in 12 cases. In 58% (19/33) of cases, the patient was 40 years or older at the time of initial treatment. Fifteen women had one or more negative smears after treatment, of which only 6 had transformation zone sampling. The interval between treatment of CIN/CGIN and diagnosis of invasion ranged from 8 to 216 months. (mean 40.4 months), with 67% of cases of invasive cancer occurring within 5 years of treatment for CIN/CGIN and 94% within 10 years. Screen detection was achieved in 91% (30/33) of cases with 53% diagnosed while stage 1A. In conclusion, most treatment screen detection of invasive disease at an early (and often microinvasive) stage was achieved for most patients, although a third of patients were diagnosed more than 5 years after initial treatment. The data suggest the need to follow up longer than 5 years when there are risk factors such as incomplete excision of high grade CIN/CGIN and in women over 40 years of age at the time of initial diagnosis.

Expression of integrin adhesion molecules in normal ovary and epithelial ovarian tumors.

The metastatic potential of a solid tumor is dependent upon its ability to interact with the extracellular matrix. The integrin superfamily is a group of proteins that are fundamental in such interactions and play a major role in cell-cell and cell-matrix adhesion. Localization of the integrin proteins was performed in normal ovary, primary epithelial ovarian tumors and metastatic tumor cells in ascitic samples. Expression of alpha1, alpha3, alpha6 and beta4 was observed on normal ovarian epithelium with variable expression of alpha5. Loss of alpha1 expression by malignant cells in the primary tumors was noted. beta4, a component of the laminin receptor which was strongly expressed by both normal ovary and solid tumor, was absent from the ascitic tumor cells in the majority of cases. There was an associated loss of alpha6 expression, indicating a deficiency of hemidesmosomes in the ascitic tumor cells. This alteration of integrin expression by metastatic malignant epithelial ovarian tumor cells may therefore represent one important mechanism by which metastatic disease occurs.

Second look laparotomy in the management of epithelial cell carcinoma of the ovary.

Case histories from 20 patients undergoing postchemotherapy "second look" laparotomy for metastatic epithelial cell carcinoma of the ovary were reviewed in an attempt to evaluate the usefulness of this procedure and its likely impact on patient survival. The patient population comprised 18 patients treated with a combination of cisplatin, adriamycin and cyclophosphamide (PACe) and 2 patients treated with chlorambucil. The findings at second look were often predictable, and related to the adequacy of initial surgery. Complete tumour regression identified a group of patients with a relatively good prognosis. However in most patients residual tumour was found which rarely proved resectable. Second line chemotherapy was poorly tolerated, and appeared to have little impact on the disease particularly after combination chemotherapy had been used initially. There was little evidence that second look surgery itself positively contributed to survival. This procedure and its timing should be regarded as experimental and a suitable subject for randomised clinical trials.