U. Stendahl

Classification and Grading of Invasive Squamous Cell Carcinoma of the Uterine Cervix

In 155 patients with invasive squamous carcinoma of the uterine cervix malignancy point grading was based on histologic examination of pretreatment biopsies. The observation time extended over 10 years. All patients received similar radiologic treatment. Tumour cell population and tumour-host relationship were estimated separately using eight parameters graded from 1 to 3. A fairly sharp border is distinguishable at 16 points, but an overlap occurred in both directions. The curable recurrences had 16 points or less. The necessity of deep biopsies for adequate grading was demonstrated.

Invasive Squamous Cell Carcinoma of the Uterine Cervix I. Definition of parameters in a histopathologic malignancy grading system

A histologic malignancy grading system for invasive squamous cell carcinoma of the uterine cervix is presented. The method is based upon evaluation of the tumour cell population in terms cell differentiation, structure, nuclear polymorphism and the frequency of mitotic figures in terms of a 1 to 3 point scale. The tumour-host relationship was also estimated in terms of a 1 to 3 point scale, by the mode of invasion, stage of invasion, vascular invasion and degree of lymphoplasmocytic infiltration. These parameters permitted a grading with 8 to 24 points totally.

Invasive Squamous Cell Carcinoma of the Uterine Cervix II.: Reproducibility of a histopathologic malignancy grading system

A histopathologic malignancy grading system for invasive squamous carcinoma of the uterine cervix has previously been presented. The grading results in a total malignancy point value for every patient (range 8-24). This score has been proven to have a significant prognostic value for the individual patient. The inter-observer reproducibility of this system has been examined by two pathologists, on the pretreatment biopsies of 100 patients and the intra-observer reproducibility on 190 patients (observer one) and on 100 patients (observer two). These biopsies were estimated twice and three times, respectively, without knowledge of former results and at an interval of 2 to 6 months. The inter-observer correlation coefficient was 0.54, the intra-observer correlation coefficients 0.94 and 0.74, respectively.

Prognosis of invasive squamous cell carcinoma of the uterine cervix: a comparative study of the predictive values of clinical staging IB--III and a histopathologic malignancy grading system.

: The prognostic values of clinical staging IB--III and a histopathologic malignancy grading system have been compared in a retrospective study on 338 women with invasive squamous cell carcinoma of the uterine cervix. The superiority of the grading system to staging was significant (p less than 0.01). However, staging had an additional prognostic value. Using both the malignancy grading system and clinical staging together provided a better capacity to predict the clinical outcome in individual patients. Prognostication according to clinical staging alone will result in a considerable loss of information.

Invasive Squamous Cell Carcinoma of the Uterine Cervix III. A malignancy grading system for indication of prognosis after radiation therapy

The predictive value of a malignancy grading system embodied by 8 histopathologic parameters and of staging, age, year of admission and the different treatment modalities were compared in relation to 5- and 8-year survival. The material consisted of 196 patients in stage II according to the FIGO classification. The grading system proved superior with high significance (p less than 0.001) to the other predictors including each histopathologic parameter apart from vascular invasion (p = 0.01). All histopathologic parameters but 2 (differentiation into cell type and mitosis) exhibited significant (p less than 0.01) decrease in survival with higher grade at the 5- and 8-year controls. Patients in stage II could be divided into groups with low, intermediate and high malignancy points. Both groups of extremes showed a marked and highly significant difference in survival rates compared with the intermediate group, and the grading system made it possible to predict 60 per cent of the patients with acceptable specificity. In the group of high malignant tumours the system maintained a continual prognostic value even among patients still alive at the 5-year control.

Bleomycin‐mitomycin C in advanced carcinoma of the cervix: A third look

Thirty‐three patients with advanced cervical cancer (31 squamous cancer, two adenosquamous cancer) previously untreated with cytotoxic drugs, were treated with bleomycin, 5 mg daily, for seven days and mitomycin C, 10 mg, on day 8. This regimen was repeated four times at two‐week intervals. All but one patient had previously been treated with radiotherapy; 36% of the patients had an objective response (five complete remission (CR), median duration 12 months; seven partial remission (PR), median duration six months). Severe myelosuppression occurred in nine patients. One drug‐related death due to thrombocytopenia occurred. Three patients developed pulmonary fibrosis and one of them died of respiratory failure. The bleomycin‐mitomycin C regimen has a definite but clearly limited effect in advanced cancer of the uterine cervix.

Malacoplakia of the cervix and corpus uteri: A light microscopic, electron microscopic, and X-ray microprobe analysis of a case

Malacoplakia in the female genital tract is rare. A case of a 71-year-old woman with malacoplakia of the cervical mucosa and endometrium is described. By light microscopy, von Hansemann cells containing calcified bodies (Michaelis-Gutmann bodies) could be visualized. Similar formations could also be seen extracellularly. Typical Michaelis-Gutmann bodies with electron-dense areas, as well as with pale centers and a dark periphery, could be identified by electron microscopy. Occasional trilaminar bacteria were seen. X-ray microanalysis indicated the presence of silica, sulfur, chloride, calcium, magnesium, and iron. Malacoplakia in this region may cause diagnostic problems for the pathologist, but the presence of a monotonous tumor-like infiltrate of pale histiocytes should lead to a careful search for Michaelis-Gutmann bodies.

Invasive Squamous Cell Carcinoma of the Uterine Cervix IV. Analysis of a histopathologic malignancy grading system and construction of a partial index

A new histopathologic malignancy index has previously proved capable of permitting discrimination of patients with carcinoma of the uterine cervix (stage II) with respect to prognosis. Eight histopathologic items graded from 1 to 3 add up to constitute the malignancy index. By regression analysis the number of items could be reduced to 4. Seemingly without loss in the prediction value a partial index was elaborated by the following 4 items: mitosis, mode of invasion, cellular response, and vascular invasion, the latter attributed double the weight. The predictive value of the partial index seemed to be as good as that of the previous malignancy index on an independent materials as well.

Invasive Squamous Cell Carcinoma of the Uterine Cervix Vii. Influence of Vehicle Osmolarity on Biopsy Quality

A histopathologic grading system for more reliable determination of the prognosis in individual patients with squamous cell carcinoma of the uterine cervix necessitates better sampling and fixation techniques. Fixation in 10 per cent formalin and 0.17 mol phosphate buffer at pH 7.0, with an effective osmolarity of 350 mmol/l, gave optimal stainability, and minimized tissue shrinkage and sectioning artefacts. Vessels remained open, which facilitated the analysis of vascular invasion. A newly designed biopsy forceps yielded large and representative specimens with a minimum of pressure distortion.

Invasive squamous cell carcinoma of the uterine cervix. VI. Prediction value of non-keratinizing, parakeratotic and orthokeratotic cell forms and clinical staging.

In 393 patients with invasive squamous cell carcinoma of the uterine cervix stages I to IV the predictive value of the histopathologic classification of Reagan & Wentz (differentiation into cell type) was analysed in relation to 10-year lethality rate. Patients with large cell horn-pearl forming and orthokeratinizing tumours had the poorest, and those with large cell non-keratinizing the best prognosis. Large cell parakeratotic tumours did not differ significantly in prognosis compared with the non-keratinizing cell form. When clinical staging was included the prediction value of the histopathologic classification disappeared except in stage II. From a clinical point of view this additional prognostic information will have little practical consequences.