British Journal of Obstetrics and Gynaecology January 1977. Vol 84. pp 67-70
MICROINVASIVE SQUAMOUS CARCINOMA OF CERVIX IN THE TAYSIDE REGION OF SCOTLAND BY
I. D. DUNCAN,Lecturer AND
J. WALKER, Professor The University, Dundee, Department of Obstetrics and Gynaecology
Summary A total of 117 patients with microinvasive squamous carcinoma of the cervix encountered between 1960 and 1972 is reviewed. No lymph node metastases were found in the 42 patients who had pelvic lymphadenectomy and only one died from her disease. The proposal is made that when the depth of invasion is 3 mm or less, microinvasive carcinoma can be treated in the same way as carcinoma in situ.
NO single definition of microinvasive carcinoma of the cervix is accepted. Govan et a1 (1966 and 1969) regarded microcarcinoma as minimal stromal invasion stemming from carcinoma in situ. Various terms have been used for microinvasive carcinoma and include carcinoma in situ with minimal or superficial invasion, early invasive carcinoma, incipient carcinoma and preclinical carcinoma. The International Federation of Gynaecology and Obstetrics (FIGO) defined Stage Ia carcinoma of the cervix as carcinoma which was not detectable by clinical examination and recommended subdivision of Stage Ia lesions into (1) those showing early stromal invasion and (2) occult invasive carcinoma. In this study we look retrospectively at our results for the treatment of Stage Ia (1) carcinoma of the cervix.
cases has also been kept. Patients are followed for at least ten years being traced through General Practitioners, Executive Councils, other hospitals and registrars of death. The records of all patients with squamous carcinoma of the cervix were studied. Between 1960 and 1972, there were 285 cases of Stage I squamous carcinoma of the cervix. These included 187 cases of Stage la disease and 98 cases of Stage Ib disease. In 117 of the Stage Ia cases, the reporting pathologist employed one of the following terms : microinvasive, superficially invasive, early invasive, very early invasive, or minimally invasive carcinoma. These 117 patients are considered as FIGO Stage la (1) and are the subject of this report. RESULTS Clinical features The age of the 117 patients ranged from 21 years to 93 years with a median of 44 years. The median age of Stage Ia (2) occult invasive lesions was 46 years and of Stage Ib lesions 49 years. The mean parity of the Stage Ia (I) patients was 3. 7 compared with 3 . 3 in both the Stage la
METHODS In 1974, with slight alterations of its boundaries, the Eastern Region of Scotland became Tayside Region. All cases of malignant disease have been registered since 1951 and a clinical register of all gynaecological cancer 67
68
DUNCAN AND WALKER
(2) and the Stage Ib patients. Only two patients were nulliparous. The initial diagnosis was made by histological examination of tissue obtained by cone biopsy (86 patients), punch biopsy (13 patients), hysterectomy (16 patients) or amputation of the cervix at pelvic floor repair (2 patients).
carcinoma of breast in her sixth year after treatment for microinvasive carcinoma of cervix ; another from vaginal carcinoma which developed TABLE I1 Survival after microinvasive squamous carcinoma of cervix, Tayside Region 1960 to 1972
Treatment The treatment is summarized in Table I. TABLEI Summary of treatment of 117 patients Treatment
Number Eligible
~~~
No. of patients
Number free of disease Number when lost alive to follow-up
Corrected survival (per cent)
~
3-year follow-up
117
3
98
5
114
100
~~
Radical n = 43
Nonradical n = 74
Wertheim’s hysterectomy Wertheim hysterectomy followed by vault radium Wertheim hysterectomy after intracavitary radium Total abdominal hysterectomy and BSO followed by vault radium and external irradiation
39
Total abdominal hysterectomy Total abdominal hysterectomy followed by vault radium Vaginal hysterectomy Cone biopsy alone Amputation of cervix alone Radium alone
51
1
2 1
4 5 11 2 1
In none of the 42 patients who had a pelvic lymphadenectomy were the lymph nodes involved by carcinoma. Of the 86 cone biopsies yielding the diagnosis, 76 were followed by hysterectomy : residual microinvasive carcinoma was found in 25 specimens, residual carcinoma in situ in 13 specimens and residual dysplasia in 5 specimens: no residual disease was found in 33 specimens but two of the patients had had preoperative radium. There were two patients who developed (and were cured of) urinary fistulae (one ureterovaginal and one vesicovaginal) after a Wertheim’s hysterectomy : the former fistula was treated by reimplantation of the ureter and the latter by surgical closure. Results of treatment (Table 11) Two patients are known to have died: one from cerebral metastases from an untreated
5-year follow-up -
93*
100
~~
* includes
1 patient with recurrent disease dying less than 1 year later.
2 years after radical hysterectomy and was treated by vaginectomy and external irradiation with death of the patient after a further threeyear interval. Five patients were lost to follow-up but two of them were free of recurrence at more than three years after treatment. There were 89 patients without evidence of disease at least five years after treatment and 19 patients who were free of disease at three to five years after treatment. One patient had persistently abnormal smears after radical hysterectomy and pelvic lymphadenectomy. Vaginal biopsies at first showed carcinoma in situ of the vaginal vault and microinvasive carcinoma five years after operation; this patient was successfully treated with intravaginal radium and was free from disease five years later. One patient developed a positive smear five years after a cone biopsy, having had a successful pregnancy in the interim ; abdominal hysterectomy showed a cervical carcinoma in situ.
DISCUSSION Our study has shown that microinvasive carcinoma of the cervix should be treated like intraepithelial carcinoma of the cervix. Radical hysterectomy and lymphadenectomy or radiotherapy have been recommended on the basis of multiple foci of microinvasion with a confluent pattern (Boyes et al, 1970), a depth of invasion
MICROINVASIVE CARCINOMA OF CERVIX
of 3 to 5 mm (Mussey et al, 1969; Ng and Reagan, 1969), lymphatic channels containing tumour cells (Mussey et al, 1969; Tweeddale et al, 1969), and anaplasia of the tumour (Ng and Reagan, 1969; Tweeddale et al, 1969; Christopherson and Parker, 1964). Mussey et a1 (1969) reported 91 patients with carcinoma of the cervix with stromal invasion of 5 mm or less. Only 2 of the 76 patients with invasion to less than 3 mm showed vascular channel involvement, whereas vascular channel involvement was apparent in 8 of the 15 patients who had stromal invasion in the 3 to 5 mm depth. Only 2 of the 91 patients had metastatic disease, both with vascular channel involvement. Roche and Norris (1975) reported 30 patients with carcinoma of the cervix invading to a depth of 2 to 5 mm. Exhaustive serial sections revealed lymphatic space invasion in 57 per cent of their patients but no patient had metastatic disease. Creasman and Parker (1973), in a study of 98 patients with microinvasive carcinoma of cervix, found only one case of lymph node involvement in the 19 patients treated by Wertheim’s hysterectomy: they had no deaths due to cancer in their series which suggested that this was the only patient with metastases. Kolstad (1969) concluded that risk of potential spread in microinvasive cervical cancer is 1 per cent or less. No metastases were reported by Way (1964) in 54 patients, by Ullery et a1 (1965) in 28 patients nor by Brudenell et a1 (1973) in 24 patients. On the other hand, Deiker (1956) reported a case of lymph node involvement as did Friedell and Graham (1959); and Lock (1961) noted one positive node in five patients with microinvasive carcinoma. Between 1955 and 1962, Donald and Walker (1 970) reported 327 cases of squamous carcinoma of cervix in Tayside Region giving an average of 41 patients per year. Between 1960 and 1972, there were 553 patients (an average of 43 per year). In the former period the average annual number of Stage I lesions was 11, and only 8 cases of subclinical invasive carcinoma and two cases of microinvasive were noted altogether. We found an average of 22 Stage I lesions per year, 5 were clinical and 17 were subclinical of which 9 were microinvasive. This may be because cytological screening of the cervix became established in Tayside in 1964.
69
If the cervical smear contains differentiated tumour cells suggestive of invasive carcinoma (Ng and Reagan, 1969) and there is no clinical suspicion of invasive carcinoma, cone biopsy of the cervix will provide the pathologist with adequate tissue for a diagnosis. Provided that the pathologist and clinician are satisfied that the lesion fits the concept of microinvasion, simple hysterectomy, either by the abdominal or vaginal route, with conservation of the ovaries should be perfectly adequate treatment. Indeed, in only 1 of our I 1 patients treated by cone biopsy did a recurrence occur. Taking a cuff of vagina or performing lymphadenectomy in some patients has not influenced the prognosis. We would urge that pathologists should routinely report maximal depths of stromal invasion from the base of the overlying epithelium. If Roche and Norris (1975) found 57 per cent of their patients had lymphatic space invasion, then this phenomenon can be assumed in at least some of our patients. Pending an exhaustive re-examination of the histology along the lines of Roche and Norris (1975), the only criterion which we would use to distinguish those patients requiring more radical treatment would be stromal invasion to a depth of more than 3 mm. The importance of continued cytological surveillance need hardly be emphasized.
ACKNOWLEDGEMENTS We are grateful to Professor W. W. Park and Dr Helen L. D. Duguid of the Department of Pathology for their helpful comments. REFERENCES Boyes, D. A., Worth, A. J., and Fidler, H. K. (1970): Journal of Obstetrics and Gynaecology of fhe British Commonwealth, 77, 769. Brudenell, M.,Cox, B. S., and Taylor, C. W. (1973): Journal of Obstetrics and Gynaecology of the British Commonwealth, 80, 673. Christopherson, W., and Parker, J. E. (1964): Cancer, 17, 1123. Creasman, W. T., and Parker, R. T. (1973): Clinical Obstetrics and Gynecology, 16, 261. Deicker, W. H. (1956): American Journal of Obstetrics and Gynecology, 72, 1 1 16. Donald, J., and Walker, J. (1970): Journal of Obstetrics and Gynaecology of the British Commonwealth, 77, 435.
70
DUNCAN AND WALKER
Friedell, G. H., and Graham, J. B. (1959): Surgery, Gynecology and Obstetrics, 108, 51 3. Govan, A. D. T., Haines, R. M., Langley, F. A,, Taylor, C. W., and Woodcock, A. S. (1966): Journal of Obstetrics and Gynaecology of the British Commonwealth, 73, 883. Govan, A. D. T., Haines, R. M., Langley, F. A,, Taylor, C. W., and Woodcock, A. S. (1969): Journal of Clinical Pathology, 22, 383. Kolstad, P. (1969): American Journal of Obstetrics and Gynecology, 104, 1015. Lock, R. F. (1961): In Latour, J. P. A. American Journal of Obstetrics and Gynecology, 81, 51 1, Discussion p 517.
Mussey, E., Soule, E. H., and Welch, J. S. (1969): American Journal of Obstetrics and Gynecology, 104, 738. Ng, A. B. P., and Reagan, J. W. (1969): American Journal of Clinical Pathology, 52, 5 1 1. Roche, W. D., and Norris, H. J. (1975): Cancer, 36, 180. Tweeddale, D. N., Langenbach, S. R., Roddick, J. W., and Holt, M. L. (1969): Acta cytologica, 13, 447. Ullery, J. C., Boutselis, J. G., and Botschner, A. C . (1965): Obstetrics and Gynecology, 26, 866. Way, S. (1964): Acta cytologica, 8, 14.
MICROINVASIVE SQUAMOUS CARCINOMA OF CERVIX IN THE TAYSIDE REGION OF SCOTLAND BY
I. D. DUNCAN,Lecturer AND
J. WALKER, Professor The University, Dundee, Department of Obstetrics and Gynaecology
Summary A total of 117 patients with microinvasive squamous carcinoma of the cervix encountered between 1960 and 1972 is reviewed. No lymph node metastases were found in the 42 patients who had pelvic lymphadenectomy and only one died from her disease. The proposal is made that when the depth of invasion is 3 mm or less, microinvasive carcinoma can be treated in the same way as carcinoma in situ.
NO single definition of microinvasive carcinoma of the cervix is accepted. Govan et a1 (1966 and 1969) regarded microcarcinoma as minimal stromal invasion stemming from carcinoma in situ. Various terms have been used for microinvasive carcinoma and include carcinoma in situ with minimal or superficial invasion, early invasive carcinoma, incipient carcinoma and preclinical carcinoma. The International Federation of Gynaecology and Obstetrics (FIGO) defined Stage Ia carcinoma of the cervix as carcinoma which was not detectable by clinical examination and recommended subdivision of Stage Ia lesions into (1) those showing early stromal invasion and (2) occult invasive carcinoma. In this study we look retrospectively at our results for the treatment of Stage Ia (1) carcinoma of the cervix.
cases has also been kept. Patients are followed for at least ten years being traced through General Practitioners, Executive Councils, other hospitals and registrars of death. The records of all patients with squamous carcinoma of the cervix were studied. Between 1960 and 1972, there were 285 cases of Stage I squamous carcinoma of the cervix. These included 187 cases of Stage la disease and 98 cases of Stage Ib disease. In 117 of the Stage Ia cases, the reporting pathologist employed one of the following terms : microinvasive, superficially invasive, early invasive, very early invasive, or minimally invasive carcinoma. These 117 patients are considered as FIGO Stage la (1) and are the subject of this report. RESULTS Clinical features The age of the 117 patients ranged from 21 years to 93 years with a median of 44 years. The median age of Stage Ia (2) occult invasive lesions was 46 years and of Stage Ib lesions 49 years. The mean parity of the Stage Ia (I) patients was 3. 7 compared with 3 . 3 in both the Stage la
METHODS In 1974, with slight alterations of its boundaries, the Eastern Region of Scotland became Tayside Region. All cases of malignant disease have been registered since 1951 and a clinical register of all gynaecological cancer 67
68
DUNCAN AND WALKER
(2) and the Stage Ib patients. Only two patients were nulliparous. The initial diagnosis was made by histological examination of tissue obtained by cone biopsy (86 patients), punch biopsy (13 patients), hysterectomy (16 patients) or amputation of the cervix at pelvic floor repair (2 patients).
carcinoma of breast in her sixth year after treatment for microinvasive carcinoma of cervix ; another from vaginal carcinoma which developed TABLE I1 Survival after microinvasive squamous carcinoma of cervix, Tayside Region 1960 to 1972
Treatment The treatment is summarized in Table I. TABLEI Summary of treatment of 117 patients Treatment
Number Eligible
~~~
No. of patients
Number free of disease Number when lost alive to follow-up
Corrected survival (per cent)
~
3-year follow-up
117
3
98
5
114
100
~~
Radical n = 43
Nonradical n = 74
Wertheim’s hysterectomy Wertheim hysterectomy followed by vault radium Wertheim hysterectomy after intracavitary radium Total abdominal hysterectomy and BSO followed by vault radium and external irradiation
39
Total abdominal hysterectomy Total abdominal hysterectomy followed by vault radium Vaginal hysterectomy Cone biopsy alone Amputation of cervix alone Radium alone
51
1
2 1
4 5 11 2 1
In none of the 42 patients who had a pelvic lymphadenectomy were the lymph nodes involved by carcinoma. Of the 86 cone biopsies yielding the diagnosis, 76 were followed by hysterectomy : residual microinvasive carcinoma was found in 25 specimens, residual carcinoma in situ in 13 specimens and residual dysplasia in 5 specimens: no residual disease was found in 33 specimens but two of the patients had had preoperative radium. There were two patients who developed (and were cured of) urinary fistulae (one ureterovaginal and one vesicovaginal) after a Wertheim’s hysterectomy : the former fistula was treated by reimplantation of the ureter and the latter by surgical closure. Results of treatment (Table 11) Two patients are known to have died: one from cerebral metastases from an untreated
5-year follow-up -
93*
100
~~
* includes
1 patient with recurrent disease dying less than 1 year later.
2 years after radical hysterectomy and was treated by vaginectomy and external irradiation with death of the patient after a further threeyear interval. Five patients were lost to follow-up but two of them were free of recurrence at more than three years after treatment. There were 89 patients without evidence of disease at least five years after treatment and 19 patients who were free of disease at three to five years after treatment. One patient had persistently abnormal smears after radical hysterectomy and pelvic lymphadenectomy. Vaginal biopsies at first showed carcinoma in situ of the vaginal vault and microinvasive carcinoma five years after operation; this patient was successfully treated with intravaginal radium and was free from disease five years later. One patient developed a positive smear five years after a cone biopsy, having had a successful pregnancy in the interim ; abdominal hysterectomy showed a cervical carcinoma in situ.
DISCUSSION Our study has shown that microinvasive carcinoma of the cervix should be treated like intraepithelial carcinoma of the cervix. Radical hysterectomy and lymphadenectomy or radiotherapy have been recommended on the basis of multiple foci of microinvasion with a confluent pattern (Boyes et al, 1970), a depth of invasion
MICROINVASIVE CARCINOMA OF CERVIX
of 3 to 5 mm (Mussey et al, 1969; Ng and Reagan, 1969), lymphatic channels containing tumour cells (Mussey et al, 1969; Tweeddale et al, 1969), and anaplasia of the tumour (Ng and Reagan, 1969; Tweeddale et al, 1969; Christopherson and Parker, 1964). Mussey et a1 (1969) reported 91 patients with carcinoma of the cervix with stromal invasion of 5 mm or less. Only 2 of the 76 patients with invasion to less than 3 mm showed vascular channel involvement, whereas vascular channel involvement was apparent in 8 of the 15 patients who had stromal invasion in the 3 to 5 mm depth. Only 2 of the 91 patients had metastatic disease, both with vascular channel involvement. Roche and Norris (1975) reported 30 patients with carcinoma of the cervix invading to a depth of 2 to 5 mm. Exhaustive serial sections revealed lymphatic space invasion in 57 per cent of their patients but no patient had metastatic disease. Creasman and Parker (1973), in a study of 98 patients with microinvasive carcinoma of cervix, found only one case of lymph node involvement in the 19 patients treated by Wertheim’s hysterectomy: they had no deaths due to cancer in their series which suggested that this was the only patient with metastases. Kolstad (1969) concluded that risk of potential spread in microinvasive cervical cancer is 1 per cent or less. No metastases were reported by Way (1964) in 54 patients, by Ullery et a1 (1965) in 28 patients nor by Brudenell et a1 (1973) in 24 patients. On the other hand, Deiker (1956) reported a case of lymph node involvement as did Friedell and Graham (1959); and Lock (1961) noted one positive node in five patients with microinvasive carcinoma. Between 1955 and 1962, Donald and Walker (1 970) reported 327 cases of squamous carcinoma of cervix in Tayside Region giving an average of 41 patients per year. Between 1960 and 1972, there were 553 patients (an average of 43 per year). In the former period the average annual number of Stage I lesions was 11, and only 8 cases of subclinical invasive carcinoma and two cases of microinvasive were noted altogether. We found an average of 22 Stage I lesions per year, 5 were clinical and 17 were subclinical of which 9 were microinvasive. This may be because cytological screening of the cervix became established in Tayside in 1964.
69
If the cervical smear contains differentiated tumour cells suggestive of invasive carcinoma (Ng and Reagan, 1969) and there is no clinical suspicion of invasive carcinoma, cone biopsy of the cervix will provide the pathologist with adequate tissue for a diagnosis. Provided that the pathologist and clinician are satisfied that the lesion fits the concept of microinvasion, simple hysterectomy, either by the abdominal or vaginal route, with conservation of the ovaries should be perfectly adequate treatment. Indeed, in only 1 of our I 1 patients treated by cone biopsy did a recurrence occur. Taking a cuff of vagina or performing lymphadenectomy in some patients has not influenced the prognosis. We would urge that pathologists should routinely report maximal depths of stromal invasion from the base of the overlying epithelium. If Roche and Norris (1975) found 57 per cent of their patients had lymphatic space invasion, then this phenomenon can be assumed in at least some of our patients. Pending an exhaustive re-examination of the histology along the lines of Roche and Norris (1975), the only criterion which we would use to distinguish those patients requiring more radical treatment would be stromal invasion to a depth of more than 3 mm. The importance of continued cytological surveillance need hardly be emphasized.
ACKNOWLEDGEMENTS We are grateful to Professor W. W. Park and Dr Helen L. D. Duguid of the Department of Pathology for their helpful comments. REFERENCES Boyes, D. A., Worth, A. J., and Fidler, H. K. (1970): Journal of Obstetrics and Gynaecology of fhe British Commonwealth, 77, 769. Brudenell, M.,Cox, B. S., and Taylor, C. W. (1973): Journal of Obstetrics and Gynaecology of the British Commonwealth, 80, 673. Christopherson, W., and Parker, J. E. (1964): Cancer, 17, 1123. Creasman, W. T., and Parker, R. T. (1973): Clinical Obstetrics and Gynecology, 16, 261. Deicker, W. H. (1956): American Journal of Obstetrics and Gynecology, 72, 1 1 16. Donald, J., and Walker, J. (1970): Journal of Obstetrics and Gynaecology of the British Commonwealth, 77, 435.
70
DUNCAN AND WALKER
Friedell, G. H., and Graham, J. B. (1959): Surgery, Gynecology and Obstetrics, 108, 51 3. Govan, A. D. T., Haines, R. M., Langley, F. A,, Taylor, C. W., and Woodcock, A. S. (1966): Journal of Obstetrics and Gynaecology of the British Commonwealth, 73, 883. Govan, A. D. T., Haines, R. M., Langley, F. A,, Taylor, C. W., and Woodcock, A. S. (1969): Journal of Clinical Pathology, 22, 383. Kolstad, P. (1969): American Journal of Obstetrics and Gynecology, 104, 1015. Lock, R. F. (1961): In Latour, J. P. A. American Journal of Obstetrics and Gynecology, 81, 51 1, Discussion p 517.
Mussey, E., Soule, E. H., and Welch, J. S. (1969): American Journal of Obstetrics and Gynecology, 104, 738. Ng, A. B. P., and Reagan, J. W. (1969): American Journal of Clinical Pathology, 52, 5 1 1. Roche, W. D., and Norris, H. J. (1975): Cancer, 36, 180. Tweeddale, D. N., Langenbach, S. R., Roddick, J. W., and Holt, M. L. (1969): Acta cytologica, 13, 447. Ullery, J. C., Boutselis, J. G., and Botschner, A. C . (1965): Obstetrics and Gynecology, 26, 866. Way, S. (1964): Acta cytologica, 8, 14.
