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The relationship of cervical dysplasia to in situ and invasive carcinoma of the cervix
The relationship of cervical dysplasia to in situ and invasive carcinoma of the cervix ALEXANDER Los
Angeles,
VARGA,
M.D.
California
P A P A N I c o L A o u smears taken routinely on all women have increased the detection rate of nonmalignant squamous cell atypias of the cervix. The terms dysplasia, dyskeratosis, and atypical hyperplasia have been used to identify this atypism. The author prefers the term dysplasia, and will apply it in reference to premalignant squamous cell lesions. Earlier retrospective studies attempted to relate invasive carcinoma to previous biopsy evidence of dysplasia, and thus suggested the possible relationship of dysplasia to malignancy. Recently, investigatorsl, ? indicate that dysplasia can be regarded as a stage in the progression to cancer of the cervix. This report represents a prospective study of patients in whom the diagnosis of cervical dysplasia was determined by punch biopsy. Subsequent evaluation by repeat punch biopsy, cervical conization, and hysterectomy, separately or in combination, was performed in order to determine the significance of this diagnosis and to establish an acceptable uniform approach to the management of this lesion. Materials
and
tained by punch biopsy of the cervix, either as random samplings or selectively from Schiller-positive areas. The racial origins of the patients were predominantly Negro or Mexican. The lesions were most prevalent in the 20 and 30 year age groups. Cervical dysplasia was diagnosed histologically in 151 patients. Follow-up evaluation was obtained in only 78 patients. The remaining 73 patients who did not return characterize a transient or uneducated population which seeks sporadic medical care, and uses alias names without traceable addresses. Subsequent evaluation of the 78 patients were made as follows: ( 1) repeated punch biopsies without other evaluation, in 25 cases, (2) cervical conization followed by hysterectomy in 38 cases, and (3) hysterectomy without preceding conization, but on occasion preceded by repeat punch biopsy, in 15 cases. Results
Follow-up of the 78 cases of cervical dysplasia initially diagnosed by punch biopsy revealed that in 28 cases the lesion remained less than in situ carcinoma, in 39 cases carcinoma in situ was diagnosed, and in 11 cases the lesion proved to be invasive carcinoma. Therefore, 50 of 78 cases (64 per cent) of dysplasia were associated with or developed into in situ or fankly invasive carcinoma. The correlation of final diagnosis to method of obtaining the tissue specimens is outlined in Table I. For the 28 cases in which the lesion remained less than in situ the tissue specimens were obtained by re-
methods
The patients in this project were derived from the gynecology clinic at the Los Angeles County General Hospital, during the interval from June, 1954, through December, 1960. The initial tissue specimens were obFrom the Departments of Gynecology and Pathology, University of Southern California School of Medicine, and the Department of Pathology, Los Angeles County General Hospital.
759
760 Varga
Table I. Follow-up of 78 cases of cervical dysplasia, demonstrating 11 cases, in situ carcinoma in 39 cases, and less than in situ in 28 cases
Method
i j
of follow-up
Punch biopsy alone, repeated Cervical conization, with additional or hysterectomy Punch biopsy plus hysterectomy Hysterectomy alone
biopsy
Fig. 1. Squamous
3. Punch
cefl
i ’ I
(39
cases)
i
in
(11
cases)
and/
peated punch biopsy in 9 cases, by cervical conization in 8 instances, by punch biopsy followed by hysterectomy in 3 cases, and by hysterectomy alone in 8 cases. The hysterectomies in these cases were performed because of other significant pathology such as symptomatic leiomyomas. The diagnosis of in situ carcinoma in 39 cases was established by punch biopsy in 6 instances, cervical conization followed by hysterectomy in 29 cases, and by hysterectomy alone in 4 cases. The 11 invasive lesions were diagnosed by repeated punch biopsy in 10 cases, and by cervical conization in the remaining one case. It is important to note that repeat punch biopsy in this series was highly accurate in detecting invasive carcinoma.
Figs. 1 through
Lesion Less than in Jitu (28 ca.re.s)
invasion
biopsy
dyspIasia.
Comment In the presence of a significantly atypical Papanicolaou smear the question arises as to the soundness for punch biopsy in preference to cervical conization as the primary diagnostic procedure. Basically, the simplest procedure required to establish the presence of invasive squamous cell carcinoma is the one that is preferred. The complications of infection, hemorrhage, and possible dissemination of invasive disease are formidable with conization, whereas they are virtually nonexistent with biopsy. Ideally, conization and hysterectomy should be utilized to further evaluate punch biopsy lesions which are histologically less than invasive. Difficulty is encountered on attempting to
of cervix,
(x125.)
different
quadrants.
Volume 95 Number
Cervical
6
Fig.
2. In situ
carcinoma
with
relate dysplasia as diagnosed by punch biopsy to the subsequent discovery of in situ or invasive cancer. It cannot be stated with certainty that the two lesions did not coexist at the initial punch biopsy. Pahl and associate? circumvent this dilemma by using a temporal relationship. They presumed if in situ carcinoma was diagnosed within a year the lesions coexisted; if diagnosed beyond one year, the lesion had progressed. In this series, no attempt will be made to establish an individual time relationship for the subsequent development in in situ or invasive carcinoma. Nor is there intent to resolve the argument as to whether lesions coexist or subsequently develop from the dysplasia. Figs. 1 through 3 demonstrate impressively the coexistence of various degrees of atypia in different cervical quadrants. On the other hand some patients were under observation for several years before the carcinoma was discovered by repeated cervical biopsy. The 64 per cent incidence of dysplasia related to in situ and invasive carcinoma appears to be dramatically high. Pahl reported 29.6 per cent for a similar relationship. An explanation for the disparity in results may be that in this series many cases belong in the era prior to routine use of
gland
duct
Fig.
dysplasia
involvement.
3. Invasive
and
carcinoma
of cervix
761
(x40.)
carcinoma.
(x55.)
Papanicolaou smears, and represents patients with gynecologic complaints such as metrorrhagia or leukorrhea which prompted cervical biopsy. On the other hand, Pahl describes normal appearing cervices biopsied because of atypical Papanicolaou smears. However, further scrutiny of his figures re-
762
Varga
\reals that when the dysplasia involvrd less than 50 per cent of the epithelial thickness, the associated in situ incidence was only 18 per cent: while in those cases in which the dysplasia involved more than ‘75 per cent of the epithelium the associated in situ incidence was 52 per cent. The latter figure approximates that reported in this paper and also more accurately represents the tissue specimens which predominated in this series. Summary
A prospective whom the initial
study of 78 patients cervical punch biopsy
in re-
REFERENCES
1. 2.
Pahl, I. R., Stein, A. A., Rome, D., and E. J.: Obst. & Gynec. 25: 201, 1965. Stern, Elizabeth, and Neely, Peter M.: cytol. 7: 357, 1963. 375 Huntington San Ma&o,
Drive California
91108
Plotz: Acta
vealed dysplasia is prr5entctl. Siihsecluel~t r\zaluation established a diagnosis ot irl situ carcinoma in 39 cases and in\2si\xx cardnoma in an additional 1 1 cases. ‘I’tlcx association of severe dysplasia to malignant disease in 64 per cent of thesr cases indicates the importance of this diagnosis and cmphasizes the necessity for its thorough investigation. If childbearing function is no longer desirable, and the cervical cone biopsy contains severe dysplasia, particularly if the lesions approximates the edge of the COW, removal of the uterus as a rneans of definitive therapy should be considered.
Angeles,
VARGA,
M.D.
California
P A P A N I c o L A o u smears taken routinely on all women have increased the detection rate of nonmalignant squamous cell atypias of the cervix. The terms dysplasia, dyskeratosis, and atypical hyperplasia have been used to identify this atypism. The author prefers the term dysplasia, and will apply it in reference to premalignant squamous cell lesions. Earlier retrospective studies attempted to relate invasive carcinoma to previous biopsy evidence of dysplasia, and thus suggested the possible relationship of dysplasia to malignancy. Recently, investigatorsl, ? indicate that dysplasia can be regarded as a stage in the progression to cancer of the cervix. This report represents a prospective study of patients in whom the diagnosis of cervical dysplasia was determined by punch biopsy. Subsequent evaluation by repeat punch biopsy, cervical conization, and hysterectomy, separately or in combination, was performed in order to determine the significance of this diagnosis and to establish an acceptable uniform approach to the management of this lesion. Materials
and
tained by punch biopsy of the cervix, either as random samplings or selectively from Schiller-positive areas. The racial origins of the patients were predominantly Negro or Mexican. The lesions were most prevalent in the 20 and 30 year age groups. Cervical dysplasia was diagnosed histologically in 151 patients. Follow-up evaluation was obtained in only 78 patients. The remaining 73 patients who did not return characterize a transient or uneducated population which seeks sporadic medical care, and uses alias names without traceable addresses. Subsequent evaluation of the 78 patients were made as follows: ( 1) repeated punch biopsies without other evaluation, in 25 cases, (2) cervical conization followed by hysterectomy in 38 cases, and (3) hysterectomy without preceding conization, but on occasion preceded by repeat punch biopsy, in 15 cases. Results
Follow-up of the 78 cases of cervical dysplasia initially diagnosed by punch biopsy revealed that in 28 cases the lesion remained less than in situ carcinoma, in 39 cases carcinoma in situ was diagnosed, and in 11 cases the lesion proved to be invasive carcinoma. Therefore, 50 of 78 cases (64 per cent) of dysplasia were associated with or developed into in situ or fankly invasive carcinoma. The correlation of final diagnosis to method of obtaining the tissue specimens is outlined in Table I. For the 28 cases in which the lesion remained less than in situ the tissue specimens were obtained by re-
methods
The patients in this project were derived from the gynecology clinic at the Los Angeles County General Hospital, during the interval from June, 1954, through December, 1960. The initial tissue specimens were obFrom the Departments of Gynecology and Pathology, University of Southern California School of Medicine, and the Department of Pathology, Los Angeles County General Hospital.
759
760 Varga
Table I. Follow-up of 78 cases of cervical dysplasia, demonstrating 11 cases, in situ carcinoma in 39 cases, and less than in situ in 28 cases
Method
i j
of follow-up
Punch biopsy alone, repeated Cervical conization, with additional or hysterectomy Punch biopsy plus hysterectomy Hysterectomy alone
biopsy
Fig. 1. Squamous
3. Punch
cefl
i ’ I
(39
cases)
i
in
(11
cases)
and/
peated punch biopsy in 9 cases, by cervical conization in 8 instances, by punch biopsy followed by hysterectomy in 3 cases, and by hysterectomy alone in 8 cases. The hysterectomies in these cases were performed because of other significant pathology such as symptomatic leiomyomas. The diagnosis of in situ carcinoma in 39 cases was established by punch biopsy in 6 instances, cervical conization followed by hysterectomy in 29 cases, and by hysterectomy alone in 4 cases. The 11 invasive lesions were diagnosed by repeated punch biopsy in 10 cases, and by cervical conization in the remaining one case. It is important to note that repeat punch biopsy in this series was highly accurate in detecting invasive carcinoma.
Figs. 1 through
Lesion Less than in Jitu (28 ca.re.s)
invasion
biopsy
dyspIasia.
Comment In the presence of a significantly atypical Papanicolaou smear the question arises as to the soundness for punch biopsy in preference to cervical conization as the primary diagnostic procedure. Basically, the simplest procedure required to establish the presence of invasive squamous cell carcinoma is the one that is preferred. The complications of infection, hemorrhage, and possible dissemination of invasive disease are formidable with conization, whereas they are virtually nonexistent with biopsy. Ideally, conization and hysterectomy should be utilized to further evaluate punch biopsy lesions which are histologically less than invasive. Difficulty is encountered on attempting to
of cervix,
(x125.)
different
quadrants.
Volume 95 Number
Cervical
6
Fig.
2. In situ
carcinoma
with
relate dysplasia as diagnosed by punch biopsy to the subsequent discovery of in situ or invasive cancer. It cannot be stated with certainty that the two lesions did not coexist at the initial punch biopsy. Pahl and associate? circumvent this dilemma by using a temporal relationship. They presumed if in situ carcinoma was diagnosed within a year the lesions coexisted; if diagnosed beyond one year, the lesion had progressed. In this series, no attempt will be made to establish an individual time relationship for the subsequent development in in situ or invasive carcinoma. Nor is there intent to resolve the argument as to whether lesions coexist or subsequently develop from the dysplasia. Figs. 1 through 3 demonstrate impressively the coexistence of various degrees of atypia in different cervical quadrants. On the other hand some patients were under observation for several years before the carcinoma was discovered by repeated cervical biopsy. The 64 per cent incidence of dysplasia related to in situ and invasive carcinoma appears to be dramatically high. Pahl reported 29.6 per cent for a similar relationship. An explanation for the disparity in results may be that in this series many cases belong in the era prior to routine use of
gland
duct
Fig.
dysplasia
involvement.
3. Invasive
and
carcinoma
of cervix
761
(x40.)
carcinoma.
(x55.)
Papanicolaou smears, and represents patients with gynecologic complaints such as metrorrhagia or leukorrhea which prompted cervical biopsy. On the other hand, Pahl describes normal appearing cervices biopsied because of atypical Papanicolaou smears. However, further scrutiny of his figures re-
762
Varga
\reals that when the dysplasia involvrd less than 50 per cent of the epithelial thickness, the associated in situ incidence was only 18 per cent: while in those cases in which the dysplasia involved more than ‘75 per cent of the epithelium the associated in situ incidence was 52 per cent. The latter figure approximates that reported in this paper and also more accurately represents the tissue specimens which predominated in this series. Summary
A prospective whom the initial
study of 78 patients cervical punch biopsy
in re-
REFERENCES
1. 2.
Pahl, I. R., Stein, A. A., Rome, D., and E. J.: Obst. & Gynec. 25: 201, 1965. Stern, Elizabeth, and Neely, Peter M.: cytol. 7: 357, 1963. 375 Huntington San Ma&o,
Drive California
91108
Plotz: Acta
vealed dysplasia is prr5entctl. Siihsecluel~t r\zaluation established a diagnosis ot irl situ carcinoma in 39 cases and in\2si\xx cardnoma in an additional 1 1 cases. ‘I’tlcx association of severe dysplasia to malignant disease in 64 per cent of thesr cases indicates the importance of this diagnosis and cmphasizes the necessity for its thorough investigation. If childbearing function is no longer desirable, and the cervical cone biopsy contains severe dysplasia, particularly if the lesions approximates the edge of the COW, removal of the uterus as a rneans of definitive therapy should be considered.