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ORIGINAL RESEARCH |
From the Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Biology, and the Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts; the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, and the Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Address reprint requests to: John O. Schorge, MD Department of Obstetrics, Gynecology, and Reproductive Biology Brigham and Women’s Hospital 75 Francis Street Boston, MA 02115 E-mail: joschorge{at}bics.bwh.harvard.edu
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Abstract |
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 Abstract Materials and MethodsResultsDiscussionReferences |
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Methods: Two hundred women were diagnosed with early-stage cervical adenocarcinoma from 1982 to 1996. Histopathologic sections were reviewed by a gynecologic pathologist. Medical records were reviewed, and patients included in this study had microscopically identifiable lesions, up to 3 mm invasive depth, up to 7 mm tumor width, and negative margins if cone biopsy was performed.
Results: Twenty-one patients with microinvasive adenocarcinoma met criteria for FIGO stage IA1 carcinoma of the cervix. The median (range) follow-up was 76 (30–172) months and median (range) patient age was 38 (24–75) years. Definitive treatment included type II or III radical hysterectomy in 16 cases, simple abdominal or vaginal hysterectomy in four cases, and loop electrosurgical excision procedure in one case; one patient received adjuvant pelvic radiation. The histologic subtypes were endocervical adenocarcinoma in 18 cases, adenosquamous carcinoma in two cases, and clear-cell adenocarcinoma in one case. There was no evidence of parametrial invasion or lymph node metastases in any patient who had radical surgery, and there were no disease recurrences.
Conclusion: Patients with microinvasive adenocarcinoma who met criteria for FIGO stage IA1 cervical carcinoma had disease limited to the cervix, and conservative surgery, such as cone biopsy or simple hysterectomy, might offer them definitive treatment.
Cervical adenocarcinoma behaves differently from squamous cell carcinoma, yet the influence of cell type on prognosis remains controversial in early-stage disease.1,2 A cancer registrar study involving 703 hospitals found no significant effect of histologic cell type on survival in stage I disease.3 Adenocarcinoma cell type was a poor prognostic factor in a prospective, randomized trial and a large retrospective study of early-stage cervical carcinoma.4,5
The survival of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA1 squamous cell carcinoma of the cervix approaches 99% when managed conservatively with either cone biopsy or simple hysterectomy.6–9 Women with microinvasive cervical adenocarcinoma have excellent prognoses, but a definition has not been established for a lesion that might be managed definitively with conservative therapy.2,6,10–12
The purpose of this study was to propose a definition for stage IA1 cervical adenocarcinoma, based on the FIGO staging system, and to determine if patients meeting the criteria might be candidates for conservative surgery.
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Materials and Methods |
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AbstractMaterials and MethodsResultsDiscussionReferences |
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Hematoxylin and eosin–stained slides were reviewed by gynecologic pathologists at the Brigham and Women’s Hospital (KRL) and Massachusetts General Hospital (CEF). Histopathologic sections were available for all microinvasive cases. Microinvasion was defined as small buds of malignant glandular cells protruding into the stroma from glands with adenocarcinoma in situ (Figure 1
), if the otherwise smooth peripheral contour of adenocarcinoma in situ was absent, or if malignant glands extended below the level of adjacent benign glands or adenocarcinoma in situ. Depth of invasion was measured from the surface of the tumor or overlying benign epithelium to the deepest point, using a calibrated 40x magnification field. Tumor length was measured as the maximal horizontal spread on any one slide. On the basis of the FIGO staging system for stage IA1 carcinoma of the cervix, patients included in this study had microscopically identifiable lesions, up to 3 mm invasive depth, up to 7 mm tumor width, and negative margins if cone biopsy was performed.6 Tumor volume (mm3) was estimated by the method of Burghardt13 to be 1.5 times the largest measured depth or width.
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Results |
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The type of definitive therapy is shown in Table 1. Fourteen patients were treated initially with conization, followed by hysterectomy. One patient with coexisting adenocarcinoma in situ and negative margins was treated with loop electrosurgical excision procedure alone and has had no evidence of persistent or recurrent disease after 45 months. One patient undergoing simple hysterectomy received adjuvant pelvic radiation.
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In 16 patients undergoing type II or III radical hysterectomy, pelvic lymph node dissection was performed, and the median number of submitted nodes was 12 (range 2–30); two patients underwent para-aortic lymph node dissection. No patient undergoing radical surgery had evidence of lymph node metastases or parametrial extension.
Fourteen of 16 patients with coexisting adenocarcinoma in situ were treated initially with conization. Five patients had adenocarcinoma in situ involving the cone margin, and one of those had residual adenocarcinoma in situ in the hysterectomy specimen. Nine had negative adenocarcinoma in situ margins, and one of these had residual adenocarcinoma in situ in the hysterectomy specimen. Six of eight patients with coexisting squamous cell carcinoma in situ (CIS) were treated initially with conization. One of the two patients with CIS involving the cone margin had residual CIS in the hysterectomy specimen. Four patients with negative CIS margins had no residual disease.
There were no disease recurrences or disease-related deaths during the study. One patient had a postoperative pulmonary embolus requiring extended hospital stay; otherwise, there was no major treatment-related morbidity.
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Discussion |
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Lymph-vascular space invasion and grade 3 carcinomas have been reported in less than 10% of patients with microinvasive adenocarcinoma, yet both are independent risk factors for recurrence in squamous cell cervical carcinoma.10,11,16 None of the patients in our study had these histopathologic findings. We were not able to stratify the data to evaluate specifically the importance of multifocal disease or invasion beyond 2 mm, as a result of the small number of patients in this preliminary study. Further investigation of microinvasive adenocarcinoma should address these issues, ideally by means of a prospective clinical trial.
Two-thirds of the patients in our study were younger than 40 years old and might have wanted fertility preserved. Topographic studies suggest that the vast majority of microinvasive and adenocarcinoma in situ lesions are located at the transformation zone, with contiguous involvement of the endocervical canal for a variable distance.17,18 We found that invasive lesions arose predominantly from the endocervical surface, at or within 5 mm of the squamocolumnar junction, regardless of whether lesions were unifocal or multifocal. One patient in our study who wanted fertility preservation was treated with the loop electrosurgical excision procedure alone, and has had no evidence of persistent or recurrent disease after 45 months. We propose that conization or loop electrosurgical excision procedure might be management options for carefully selected microinvasive adenocarcinoma patients who meet criteria for FIGO stage IA1 cervical carcinoma, if preservation of fertility is desired, and the patient is willing to be monitored closely with long-term cytologic and colposcopic follow-up.
Conization or loop electrosurgical excision procedure margins must be free of invasive tumor and adenocarcinoma in situ for a patient to be a candidate for fertility-sparing surgery. Obtaining negative margins for adenocarcinoma in situ decreases, but may not eliminate, the risk of residual adenocarcinoma in situ, or subsequent development of invasive adenocarcinoma.19–21 One of the nine patients in our study with co-existing adenocarcinoma in situ and negative margins had residual adenocarcinoma in situ in her hysterectomy specimen. However, patients with adenocarcinoma in situ alone who want fertility preservation might be managed with conization or loop electrosurgical excision procedure with a relatively low risk of persistent disease.19,21 Patients with microinvasive adenocarcinoma who meet criteria for FIGO stage IA1 cervical carcinoma and have negative margins appear to be at no greater risk for persistent or recurrent disease than patients with adenocarcinoma in situ alone.
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Footnotes |
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Received June 11, 1998. Received in revised form July 27, 1998. Accepted August 6, 1998.
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References |
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2. Berek JS, Hacker NF, Fu YS, Sokale JR, Leuchter RC, Lagasse LD. Adenocarcinoma of the uterine cervix: Histologic variables associated with lymph node metastasis and survival. Obstet Gynecol 1985;65:46–51.
3. Shingleton HM, Bell MC, Fremgen A, Chmiel JS, Russell AH, Jones WB, et al. Is there really a difference in survival of women with squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma of the cervix? Cancer 1995;76:1948–55.[Medline]
4. Landoni F, Maneo A, Colombo A, Placa F, Milani R, Perego P, et al. Randomized study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet 1997;350:535–40.[Medline]
5. Eifel PJ, Burke TW, Morris M, Smith TL. Adenocarcinoma as an independent risk factor for disease recurrence in patients with stage IB cervical carcinoma. Gynecol Oncol 1995;59:38–44.[Medline]
6. Creasman WT. Modification in the staging for stage I vulvar and stage I cervical cancer. Int J Gynaecol Obstet 1995;50:215–6.[Medline]
7. DiSaia PJ, Creasman WT, eds. Clinical gynecologic oncology. 5th ed. St. Louis, Missouri: Mosby-Year Book, Inc., 1997.
8. van Nagell JR Jr, Greenwell N, Powell DF, Donaldson ES, Hanson MB, Gay EC. Microinvasive carcinoma of the cervix. Am J Obstet Gynecol 1983;145:981–91.[Medline]
9. Morris M, Mitchell MF, Silva EG, Copeland LJ, Gershenson DM. Cervical conization as definitive therapy for early invasive squamous carcinoma of the cervix. Gynecol Oncol 1993;51:193–6.[Medline]
10. Kaku T, Kamura T, Sakai K, Amada S, Kobayashi H, Shigematsu T, et al. Early adenocarcinoma of the uterine cervix. Gynecol Oncol 1997;65:281–5.[Medline]
11. Ostor A, Rome R, Quinn M. Microinvasive adenocarcinoma of the cervix: A clinicopathologic study of 77 women. Obstet Gynecol 1997;89:88–93.[Abstract]
12. American College of Obstetricians and Gynecologists. ACOG clinical review, vol. 2, issue 6: NIH consensus statement on cervical cancer, part 2. Washington, DC: American College of Obstetricians and Gynecologists, 1998.
13. Burghardt E. Microinvasive carcinoma in gynaecological pathology. Clin Obstet Gynecol 1984;11:239–57.
14. Piver MS, Rutledge F, Smith JP. Five classes of extended hysterectomy for women with cervical cancer. Obstet Gynecol 1974;44:265–72.
15. Kaspar HG, Dinh TV, Doherty MG, Hannigan EV, Kumar D. Clinical implications of tumor volume measurement in stage I adenocarcinoma of the cervix. Obstet Gynecol 1993;81:296–300.
16. Delgado G, Bundy B, Zaino R, Sevin BU, Creasman WT, Major F. Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: A gynecologic oncology group study. Gynecol Oncol 1990;38:352–7.[Medline]
17. Bertrand M, Lickrish GM, Colgan TJ. The anatomic distribution of cervical adenocarcinoma in situ: Implications for treatment Am J Obstet Gynecol 1987;157:21–5.[Medline]
18. Nicklin JL, Wright RG, Bell JR, Samaratunga H, Cox NC, Ward BG. A clinicopathological study of adenocarcinoma in situ of the cervix. The influence of cervical HPV infection and other factors, and the role of conservative surgery. Aust N Z J Obstet Gynaecol 1991;31:179–83.[Medline]
19. Muntz HG, Bell DA, Lage JM, Goff BA, Feldman S, Rice LW. Adenocarcinoma in situ of the uterine cervix. Obstet Gynecol 1992;80:935–9.
20. Wolf JK, Levenback C, Malpica A, Morris M, Burke T, Mitchell MF. Adenocarcinoma in situ of the cervix: Significance of cone biopsy margins. Obstet Gynecol 1996;88:82–6.[Abstract]
21. Kennedy AW, elTabbakh GH, Biscotti CV, Wirth S. Invasive adenocarcinoma of the cervix following LLETZ (large loop excision of the transformation zone) for adenocarcinoma in situ. Gynecol Oncol 1995;58:274–7.[Medline]
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