Critical Reviews in Oncology/Hematology 48 (2003) 251–261
Microinvasive squamous cell cervical carcinoma Francesco Raspagliesi a,∗ , Antonino Ditto a , Eugenio Solima a , Pasquale Quattrone b , Rosanna Fontanelli a , Flavia Zanaboni a , Francesco Hanozet a , Gianbattista Spatti a , Enrico Calabrese a , Maria L. Carcangiu b a
Department of Gynecologic Oncology, Istituto per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy b Department of Pathology, Istituto per lo Studio e la Cura dei Tumori, Milan, Italy Accepted 23 September 2002
Contents 1.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
252
2.
Prognostic factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Depth of stromal invasion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Lymph vascular space invasion (LVSI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Morphological criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4. Tumor volume . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5. Confluence of invasive foci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6. Grading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
252 252 253 254 254 254 254
3.
Our experience. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Histology evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Statistical analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5. Histopathological analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
254 254 255 255 255 256
4.
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
257
5.
Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
257
6.
Reviewers (MA 421) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
259
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
259
Biography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
261
Abstract Several histologic tumor-related features are the key factors for further treatment planning in microinvasive cervical cancer (MIC) after conization. To better define the indications for conservative treatment of MIC we conducted a literature review for prognostic factors for MIC and we carried out a prospective observational study evaluating most important pathologic factors and the relationships between tumor and edges of the cone and incidence of recurrences. In our experience seven recurrences were observed. Two distinct groups of patients were identified with a clearance lower or higher of 10 and 8 mm for apical and lateral margin respectively. Depth of infiltration and even lymph-vascular involvement have been confirmed as the most important histologic parameters to be evaluated. Apical and lateral clearance of the tumor are significantly correlated with the recurrence rate. If an adequate lateral border of healthy tissue is present on the specimen, conization may be considered as definitive treatment of MIC. © 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Microinvasive carcinoma of the cervix; Conization; Pathologic features; Disease free survival; Overall survival ∗
Corresponding author. Tel.: +39-02-2390-2719; fax: +39-02-2390-2349. E-mail address:
[email protected] (F. Raspagliesi).
1040-8428/$ – see front matter © 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S1040-8428(03)00130-6
252
F. Raspagliesi et al. / Critical Reviews in Oncology/Hematology 48 (2003) 251–261
1. Introduction Carcinoma of the cervix is currently the fourth most common neoplasm in women. Approximately 10–15% of women with stage I cervical cancer have microinvasive lesions (stage IA) [1,2]. While the rate of cervical invasive carcinoma is relatively constant among women under 40 years of age, the rate of microinvasive cervical cancer (MIC) appears to increase steadily in this young age group. The definition of MIC is not universally established and numerous definitions have been proposed. Since the concept of “microinvasive carcinoma of the cervix”, introduced in 1947 by Mestwerdt [3], there has been disagreement concerning the pathologic definition and the clinical implications about treatment of these patients. Originally, the definition of MIC included all cervical neoplastic lesions whose depth of invasion (DI) was less than 5 mm, measured from the basement membrane [4]. Since then, various histopathologic criteria, other than DI, have been considered in the definition of MIC, including horizontal tumor spread [5], tumor volume [6], lymph-vascular space involvement (LVSI) [7,8], invasive growth pattern [9]. However, the pathologic and prognostic identification of early-invasive squamous cell carcinoma of the cervix remained controversial until 1985, when the International Federation of Gynecology and Obstetrics (FIGO) redefined the early-stage disease as “pre clinical invasive carcinoma diagnosed microscopically only”, further subdividing it into Stage Ia1 or “microscopic stromal invasion” and Stage Ia2 or “tumor with DI of 5 mm or less and 7 mm or less in horizontal spread” [10]. This definition is certainly more specific than prior ones, but raises doubts as to its clinical applications. Taking into account that a classification must be a guide for the evaluation of prognosis and treatment, two major prognostic factors can be identified in the literature: the DI and the presence of LVSI. Two kinds of MIC can be distinguished: those with invasion
