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Superficially invasive carcinoma and carcinoma in situ of the uterine cervix
Superficially
invasive carcinoma and carcinoma
in situ of the uterine cervix E.
EARLE
GORDON Shreveport,
DILWORTH, E.
M.D.
MAXWELL,
M.D.
Louisiana
T H E definition, diagnosis, and therapy of carcinoma in situ of the uterine cervix are gradually becoming clarified, disseminated, and effectively used by the medical profession; however, the true boundaries of carcinoma in situ are still obscure. Much work is being done on differentiating the anaplasias and hyperplasias from carcinoma in situ; more work is needed to clarify the distinction between the advanced variants of carcinoma in situ and true Stage I invasive carcinoma. The importance of this distinction is one of therapy. Early Stage I carcinoma, treated with adequate irradiation, should have a five year survival rate of over 90 per cent. Carcinoma in situ, treated with hysterectomy plus wide-cuff excision, should have a cure rate approaching 100 per cent; but if treated inadvertently as Stage I results in the demonstrably higher morbidity of irradiation. A Stage I lesion treated with a simple hysterectomy will probably recur. The classification of the lesion which presents as predominantly carcinoma in situ but which has microscopic strands or cords of tumor cells reaching into the cervical stroma is not adequate. TeLindel states that at Johns Hopkins they use “Stage 0 to indicate cases of in situ carcinoma or very early microscopic invasion.” Latour* of McGill University basically agrees with TeLinde, stating that the microscopically in-
vasive carcinoma is related to carcinoma in situ in origin, response to therapy, and prognosis, and that it does not meet the clinical criteria for Stage I carcinoma. Friedell, Hertig, and Younge3 reviewed the cases at the Free Hospital for Women, and Fenne1P 5 reviewed the cases at the Massachusetts General Hospital and they found that patients with superficially invasive carcinoma treated as carcinoma in situ have not had recurrences or metastases. Fiedler and BoyesG have reviewed the literature and found superficial invasion present in from 5 to 63 per cent of all cases treated as carcinoma in situ. They discuss and beautifully illustrate the microscopic features of early invasion. Figs. 1 and 2 demonstrate the microscopic features of carcinoma in situ and superficially invasive carcinoma. Our definition of superficial invasive carcinoma (Fig. 2) is a tumor involving the epithelium, but one in which the basement membrane and superficial stroma are shallowly penetrated by narrow strands or cords of malignant cells. This lesion has been referred to as early invasion, minimal invasion, microscopic invasion, and superficial invasion, by different writers in this field. If these cords of tumor cells extend into lymphat.ics, vessels, or coalesce into tumor nodules, it is considered to be definite stromal invasion. Materials
From the Department Gynecology, Confederate Medical Center.
of Obstetrics Memorial
and
methods
In our effort to evaluate treatment and results, and to give uniformity to our classification, we have reviewed all cases with a
and
83
84
Dilworth
and
July 1, 1962 Am. J. Obst. & Gynec.
Maxwell
Fig. 1. Carcinoma in situ. Hyperchromatism, polarity in all layers of epithelium. (x100;
pleomorphism, reduced ‘/.)
loss of stratification,
and
Fie.
loss of
2.
Suuerficiallv incarcinoma. ’ Cell formation similar to carcinoma in situ, but with multiple cords of tumor cells shallowly penetrating the basement layers. (x100; reduced g.) V&e
;
recorded diagnosis of carcinoma in situ or superficially invasive carcinoma of the cervix from Jan. 1, 1947, through Dec. 31, 1956. This review yielded 150 cases; 108 of carcinoma in situ and 42 of superficial invasion. As will be noted in the appropriate tables, no case was excluded because of lack of treatment or follow-up.
Carcinoma in situ. Of these 108 patients with carcinoma in situ, 103 had one or more punch biopsies. The diagnosis of carcinoma in situ was made on 92, and was considered questionable on 3. Eight biopsies showed benign tissue. Of the 95 women with definite or questionable carcinoma in situ, 66 had knife conization of the cervix. Eighteen
voiume a4 Number
Superficially
1
showed no residual carcinoma, and 48, including the 3 formerly doubtful cases, showed carcinoma in situ. On 13 or 12 per cent of these women hysterectomy was performed without the diagnosis of carcinoma in situ being made. Eight had punch biopsies prior to operation, with 7 diagnoses reported as cervicitis and one as anaplasia. These 8 false negatives out of 103 biopsies demonstrate the inadequacy of the punch biopsy in evaluating cervical epithelium. This defect is now partly circumvented by vaginal cytology. In the other 5, no biopsy was taken. Eleven of these patients had hysterectomy for fibroids, one for ovarian cyst, and one for uterine prolapse. It is immediately apparent that vaginal cytology must be a routine procedure and should not be denied any patient because of age. Twenty-one per cent of our cases of carcinoma in situ (Fig. 3) occurred in patients 20 to 29 years old. The treatment of carcinoma in situ at Confederate Memorial Medical Center is hysterectomy, either abdominal or vaginal, including a wide excision of the vaginal cuff. Eighty-five of the patients had this operation; one had amputation of the cervix. Of these 86 surgical specimens, 33 showed residual carcinoma in situ, while in 53, no residual carcinoma was found. Eight pa-
Table
I. Deaths
Patient
Age at diagnosis
E. R.
47
E. D.
67
H. S.
64
R. C.
72
N. S.
47
B. H. C. R. D. C.
61
H.H. w. L.
40 33
48 65
Cause
of
Adenocarcinoma of cervix cinema in situ) Coronary thrombosis
invasive
carcinoma
85
tients were treated only with conization; 3 of these had benign cone specimens; 2 have had subsequent negative biopsies; 2 have been lost to follow-up; and one with a positive post-cone biopsy is reported to be well, 7 years later. Four were treated by irradiation, 3 because of associated uterine malignancy, and 1 because of breakdown in communication. This patient had a biopsy reported as epidermoid carcinoma confined to the glands. Ten had no treatment at this hospital after biopsy. Five were too sick from other causes to be treated, and will be discussed under deaths; 5 refused treatment and either were treated elsewhere or have had no treatment. One is reported by her private physician to be well, 7 years later; the others we have been unable to contact. Of the total group of 108 patients, with or without treatment, 10 have died (Table 1). Of the 71 followed over 5 years, 70 are living without evidence of carcinoma; one, treated with irradiation because of concurrent carcinoma in situ and adenocarcinoma of cervix, died 68 months later with metastatic adenocarcinoma of the cervix. Of the 7 patients followed 3 to 5 years, 5 are living without evidence of carcinoma; one died 56 months after treatment of coronary occlusion, and one died elsewhere
death
(concurrent
Interval
with
car-
Unknown (no evidence of carcinoma 6 months prior to death) Arteriosclerotic heart disease with coronary thrombosis Transitional cell carcinoma of bladder Leiomyosarcoma of uterus Metastatic carcinoma of stomach Arteriosclerotic heart disease, congestive heart failure Hypertensive vascular disease, uremia Acute abdominal crisis (complications of old gunshot wound) .
Therapy carcinoma
68 months
Irradiation
56 months
Abdominal tomy Abdominal tomy None
38 months 13 months 13 months
for in situ
hysterechysterec-
8 months 2 weeks 1 week
Hysterectomy, cystectomy Irradiation None None
1 week 1 week
None None
86
Dilworth
and
July 1, 1962 Am. J. Obat. & Gynec.
Maxwell
25
Fig. 3. Age
at diagnosis
of carcinoma
in situ.
38 months after therapy with a clinical diagnosis of carcinoma of the spine. She had been examined here 6 months prior to death and found to have osteoarthritis with no evidence of carcinoma, so it is doubtful if her death at the age of 67 was due to recurrent cervical carcinoma. Twelve were followed 1 to 3 years. Ten had no evidence of carcinoma at their last examination; one died 13 months after treatment with a myocardial infarction, and one, who had concurrent carcinoma in situ and transitional cell carcinoma of the bladder, died 13 months after an anterior Brunschwig procedure from carcinoma of the bladder. Eighteen were followed less than 1 year: this includes 5 who refused treatment, 5 who died with the carcinoma in situ untreated, and 8 who had no evidence of carcinoma at the last examination. One death due to leiomyosarcoma occurred 8 months after irradiation therapy for concurrent leiomyosarcoma of the uterus and carcinoma in situ. One died from metastatic adenocarcinoma of the stomach. Two died from congestive heart failure and one died while being prepared for operation for an acute abdominal crisis. Four of the 5 who refused treatment have had no follow-up examinations; one is reported by her pri-
vate physician to have evidence of carcinoma 7 years later. None of the patients who were treated for carcinoma in situ have evidence of residual disease or have died from epidermoid carcinoma of the cervix. There is a wide spectrum of associated gynecologic disease in the patients treated for carcinoma in situ (Table II). Because the diagnosis of carcinoma in situ in pregnancy is difficult, the diagnosis and management in our 6 patients with associated pregnancy is of interest. Three patients had a preoperative diagnosis of carcinoma in situ with fibroids, and pregnancy was not suspected. Two were known to have recently had abortions and conization with curettement was performed which revealed placental fragments plus carcinoma in situ. The sixth patient had an abortion 2 months after the biopsy diagnosis of carcinoma in situ; the biopsy was still positive 1 month later,, but she refused treatment. Complications of therapy were minimal. There was no primary operative mortality; 7 had significant postoperative morbidity. There were 2 wound dehiscences with secondary closure, and 1 incisional hematoma. Late complications included 2 laparotomies for Iysis of adhesions; one patient had bilateral salpingo-oophorectomy for benign ovarian cysts; and one was hospitalized for irradiation proctitis. Superficially invasive carcinoma. Fig. 4 illustrates the ages at diagnosis by decades
Fig. 4. Age carcinoma.
at diagnosis
of superficially
invasive
Volume Number
Table
81 1
Superficially
II.
carcinoma
Other in situ
diseases
associated
with
No. of cases Associated gynecologic disease Fibromyomas Pregnancy Ovarian tumors Dermoid Thecoma Papillary cystadenocarcinoma Endometriosis Fibroma Adenocarcinoma of cervix Sarcoma of uterus Prolapse of uterus Associated diseases of other systems Cardiovascular disease Carcinoma of bladder Carcinoma of stomach
27 6 6 2 1 1 1 1 2 1 1 5 1 1
of patients with superficially invasive carcinoma. Again, note that 10 per cent are in their twenties. All 42 women had initial cervical biopsies. Thirty-three were reported as superficially invasive carcinoma and 9 as carcinoma in situ. Twenty-two then had conization of the cervix. Fourteen of the conization specimens, including the 9 previously diagnosed as carcinoma in situ, showed superficiallv invasive carcinoma; 5 cone specimens showed only carcinoma in situ, and 3 showed no carcinoma. Secondary or complicating disorders were frequently present. Ten had fibroids, 3 had ovarian tumors, 2 were pregnant, and 4 had serious cardiovascular disease. Until relatively recently we have regarded superficially invasive carcinoma as a type of Stage I carcinoma and have treated it with irradiation, followed by Wertheim hysterectomy with bilateral pelvic lymphadenectomy, if the patient is a good surgical risk. Eighteen of these patients had irradiation alone; 9 had irradiation plus Wertheim hysterectomy. Twelve patients were treated primarily with hysterectomy. One patient with a benign cone specimen following a biopsy diagnosis had no further treatment and is free of disease, 5 years later. Two have refused treatment or further examina-
invasive
carcinoma
87
tion but are reported by letter to be well 3 and 8 years later. Four of these 42 women are dead; 2 from congestive heart failure, 1 from a stroke, and 1 from metastatic gastric carcinoma. Thirty-six of the 38 survivors have been followed over 5 years with no evidence of recurrent disease. In this series of 39 patients treated with a major procedure, all types of therapy have produced the same apparent cure rate, 100 per cent; but a rather marked difference in morbidity and complications must be noted. Of the 12 treated with abdominal hysterectomy, one had wound dehiscence with secondary closure. Of the 18 treated with irradiation, one underwent laparotomy for recovery of a radium needle; 2 were hospitalized for irradiation proctitis; one developed a rectovaginal fistula requiring a permanent colostomy; and one was hospitalized for a vaginal slough. In the 9 patients treated with irradiation followed by the Wertheim procedure, 5 had major complications. One developed a rectovagina1 fistula which required a colostomy. One developed a ureterovaginal fistula; she underwent an unsuccessful attempt at repair and then a nephrectomy. Two had prolonged febrile courses; one of these had a nonfunctioning right kidney; she developed a wound dehiscence requiring second degree closure, and the other had acute pyelonephritis with bilateral hydroureter and hydronephrosis. One patient required 2 laparotomies for lysis of adhesions. In brief, surgery alone had a complication rate of 1 in 12; irradiation, 5 in 18; and irradiation plus surgery, 5 in 9. Summary
and
conclusion
1. Our experience with carcinoma in situ and superficially invasive carcinoma has been reviewed for a 10 year period. Ninetyeight cases of carcinoma in situ were treated with no mortality from therapy or from recurrent epidermoid cervical carcinoma. 2. In 39 patients with carcinoma in situ treated with major procedures, all types of
88
Dilworth
and
July 1, 1962 Am. J. Obst. & Gynec.
Maxwell
therapy produced this same apparent cure rate, 100 per cent; but a markedly lower incidence of complication was incurred with the surgical approach only, rather than with irradiation, with or without subsequent surgery. 3. There is evidence to show that very early invasion of the cervical stroma by cords of malignant cells behaves like carcinoma in situ and can be treated definitively with hysterectomy plus excision of a wide vaginal cuff.
4. These patients should experience the low morbidity and high cure rate of patients with carcinoma in situ, and be spared the trauma of irradiation or radical surgery. 5. In order to classify this large group of patients with marginal lesions accurately, adequate cone biopsy material must be obtained and the pathologist must express his findings clearly. It is absolutely essential that the pathologist and the clinician have the same understanding of the term “superficial invasion.”
REFERENCES
1. 2. 3.
TeLinde, R.: AM. J. OBST. & GYNEC. 74: 792, 1957. Latour, J. P. A.: ARI. J. OBST. & GYNEC. 74: 354, 1957. Friedell, G. H., Hertig, A. T., and Younge, P. A.: A. M. A. Arch. Path. 66: 494, 1958.
4. 5. 6.
Fennell, R. H.: Cancer 8: 302, 1955. Fennell, R. H.: Cancer 9: 374, 1956. Fidler, H. K., and Boyes, D. A.: Cancer 673, 1959. 1541 Kings Shreveport,
Highway Louisiana
12:
invasive carcinoma and carcinoma
in situ of the uterine cervix E.
EARLE
GORDON Shreveport,
DILWORTH, E.
M.D.
MAXWELL,
M.D.
Louisiana
T H E definition, diagnosis, and therapy of carcinoma in situ of the uterine cervix are gradually becoming clarified, disseminated, and effectively used by the medical profession; however, the true boundaries of carcinoma in situ are still obscure. Much work is being done on differentiating the anaplasias and hyperplasias from carcinoma in situ; more work is needed to clarify the distinction between the advanced variants of carcinoma in situ and true Stage I invasive carcinoma. The importance of this distinction is one of therapy. Early Stage I carcinoma, treated with adequate irradiation, should have a five year survival rate of over 90 per cent. Carcinoma in situ, treated with hysterectomy plus wide-cuff excision, should have a cure rate approaching 100 per cent; but if treated inadvertently as Stage I results in the demonstrably higher morbidity of irradiation. A Stage I lesion treated with a simple hysterectomy will probably recur. The classification of the lesion which presents as predominantly carcinoma in situ but which has microscopic strands or cords of tumor cells reaching into the cervical stroma is not adequate. TeLindel states that at Johns Hopkins they use “Stage 0 to indicate cases of in situ carcinoma or very early microscopic invasion.” Latour* of McGill University basically agrees with TeLinde, stating that the microscopically in-
vasive carcinoma is related to carcinoma in situ in origin, response to therapy, and prognosis, and that it does not meet the clinical criteria for Stage I carcinoma. Friedell, Hertig, and Younge3 reviewed the cases at the Free Hospital for Women, and Fenne1P 5 reviewed the cases at the Massachusetts General Hospital and they found that patients with superficially invasive carcinoma treated as carcinoma in situ have not had recurrences or metastases. Fiedler and BoyesG have reviewed the literature and found superficial invasion present in from 5 to 63 per cent of all cases treated as carcinoma in situ. They discuss and beautifully illustrate the microscopic features of early invasion. Figs. 1 and 2 demonstrate the microscopic features of carcinoma in situ and superficially invasive carcinoma. Our definition of superficial invasive carcinoma (Fig. 2) is a tumor involving the epithelium, but one in which the basement membrane and superficial stroma are shallowly penetrated by narrow strands or cords of malignant cells. This lesion has been referred to as early invasion, minimal invasion, microscopic invasion, and superficial invasion, by different writers in this field. If these cords of tumor cells extend into lymphat.ics, vessels, or coalesce into tumor nodules, it is considered to be definite stromal invasion. Materials
From the Department Gynecology, Confederate Medical Center.
of Obstetrics Memorial
and
methods
In our effort to evaluate treatment and results, and to give uniformity to our classification, we have reviewed all cases with a
and
83
84
Dilworth
and
July 1, 1962 Am. J. Obst. & Gynec.
Maxwell
Fig. 1. Carcinoma in situ. Hyperchromatism, polarity in all layers of epithelium. (x100;
pleomorphism, reduced ‘/.)
loss of stratification,
and
Fie.
loss of
2.
Suuerficiallv incarcinoma. ’ Cell formation similar to carcinoma in situ, but with multiple cords of tumor cells shallowly penetrating the basement layers. (x100; reduced g.) V&e
;
recorded diagnosis of carcinoma in situ or superficially invasive carcinoma of the cervix from Jan. 1, 1947, through Dec. 31, 1956. This review yielded 150 cases; 108 of carcinoma in situ and 42 of superficial invasion. As will be noted in the appropriate tables, no case was excluded because of lack of treatment or follow-up.
Carcinoma in situ. Of these 108 patients with carcinoma in situ, 103 had one or more punch biopsies. The diagnosis of carcinoma in situ was made on 92, and was considered questionable on 3. Eight biopsies showed benign tissue. Of the 95 women with definite or questionable carcinoma in situ, 66 had knife conization of the cervix. Eighteen
voiume a4 Number
Superficially
1
showed no residual carcinoma, and 48, including the 3 formerly doubtful cases, showed carcinoma in situ. On 13 or 12 per cent of these women hysterectomy was performed without the diagnosis of carcinoma in situ being made. Eight had punch biopsies prior to operation, with 7 diagnoses reported as cervicitis and one as anaplasia. These 8 false negatives out of 103 biopsies demonstrate the inadequacy of the punch biopsy in evaluating cervical epithelium. This defect is now partly circumvented by vaginal cytology. In the other 5, no biopsy was taken. Eleven of these patients had hysterectomy for fibroids, one for ovarian cyst, and one for uterine prolapse. It is immediately apparent that vaginal cytology must be a routine procedure and should not be denied any patient because of age. Twenty-one per cent of our cases of carcinoma in situ (Fig. 3) occurred in patients 20 to 29 years old. The treatment of carcinoma in situ at Confederate Memorial Medical Center is hysterectomy, either abdominal or vaginal, including a wide excision of the vaginal cuff. Eighty-five of the patients had this operation; one had amputation of the cervix. Of these 86 surgical specimens, 33 showed residual carcinoma in situ, while in 53, no residual carcinoma was found. Eight pa-
Table
I. Deaths
Patient
Age at diagnosis
E. R.
47
E. D.
67
H. S.
64
R. C.
72
N. S.
47
B. H. C. R. D. C.
61
H.H. w. L.
40 33
48 65
Cause
of
Adenocarcinoma of cervix cinema in situ) Coronary thrombosis
invasive
carcinoma
85
tients were treated only with conization; 3 of these had benign cone specimens; 2 have had subsequent negative biopsies; 2 have been lost to follow-up; and one with a positive post-cone biopsy is reported to be well, 7 years later. Four were treated by irradiation, 3 because of associated uterine malignancy, and 1 because of breakdown in communication. This patient had a biopsy reported as epidermoid carcinoma confined to the glands. Ten had no treatment at this hospital after biopsy. Five were too sick from other causes to be treated, and will be discussed under deaths; 5 refused treatment and either were treated elsewhere or have had no treatment. One is reported by her private physician to be well, 7 years later; the others we have been unable to contact. Of the total group of 108 patients, with or without treatment, 10 have died (Table 1). Of the 71 followed over 5 years, 70 are living without evidence of carcinoma; one, treated with irradiation because of concurrent carcinoma in situ and adenocarcinoma of cervix, died 68 months later with metastatic adenocarcinoma of the cervix. Of the 7 patients followed 3 to 5 years, 5 are living without evidence of carcinoma; one died 56 months after treatment of coronary occlusion, and one died elsewhere
death
(concurrent
Interval
with
car-
Unknown (no evidence of carcinoma 6 months prior to death) Arteriosclerotic heart disease with coronary thrombosis Transitional cell carcinoma of bladder Leiomyosarcoma of uterus Metastatic carcinoma of stomach Arteriosclerotic heart disease, congestive heart failure Hypertensive vascular disease, uremia Acute abdominal crisis (complications of old gunshot wound) .
Therapy carcinoma
68 months
Irradiation
56 months
Abdominal tomy Abdominal tomy None
38 months 13 months 13 months
for in situ
hysterechysterec-
8 months 2 weeks 1 week
Hysterectomy, cystectomy Irradiation None None
1 week 1 week
None None
86
Dilworth
and
July 1, 1962 Am. J. Obat. & Gynec.
Maxwell
25
Fig. 3. Age
at diagnosis
of carcinoma
in situ.
38 months after therapy with a clinical diagnosis of carcinoma of the spine. She had been examined here 6 months prior to death and found to have osteoarthritis with no evidence of carcinoma, so it is doubtful if her death at the age of 67 was due to recurrent cervical carcinoma. Twelve were followed 1 to 3 years. Ten had no evidence of carcinoma at their last examination; one died 13 months after treatment with a myocardial infarction, and one, who had concurrent carcinoma in situ and transitional cell carcinoma of the bladder, died 13 months after an anterior Brunschwig procedure from carcinoma of the bladder. Eighteen were followed less than 1 year: this includes 5 who refused treatment, 5 who died with the carcinoma in situ untreated, and 8 who had no evidence of carcinoma at the last examination. One death due to leiomyosarcoma occurred 8 months after irradiation therapy for concurrent leiomyosarcoma of the uterus and carcinoma in situ. One died from metastatic adenocarcinoma of the stomach. Two died from congestive heart failure and one died while being prepared for operation for an acute abdominal crisis. Four of the 5 who refused treatment have had no follow-up examinations; one is reported by her pri-
vate physician to have evidence of carcinoma 7 years later. None of the patients who were treated for carcinoma in situ have evidence of residual disease or have died from epidermoid carcinoma of the cervix. There is a wide spectrum of associated gynecologic disease in the patients treated for carcinoma in situ (Table II). Because the diagnosis of carcinoma in situ in pregnancy is difficult, the diagnosis and management in our 6 patients with associated pregnancy is of interest. Three patients had a preoperative diagnosis of carcinoma in situ with fibroids, and pregnancy was not suspected. Two were known to have recently had abortions and conization with curettement was performed which revealed placental fragments plus carcinoma in situ. The sixth patient had an abortion 2 months after the biopsy diagnosis of carcinoma in situ; the biopsy was still positive 1 month later,, but she refused treatment. Complications of therapy were minimal. There was no primary operative mortality; 7 had significant postoperative morbidity. There were 2 wound dehiscences with secondary closure, and 1 incisional hematoma. Late complications included 2 laparotomies for Iysis of adhesions; one patient had bilateral salpingo-oophorectomy for benign ovarian cysts; and one was hospitalized for irradiation proctitis. Superficially invasive carcinoma. Fig. 4 illustrates the ages at diagnosis by decades
Fig. 4. Age carcinoma.
at diagnosis
of superficially
invasive
Volume Number
Table
81 1
Superficially
II.
carcinoma
Other in situ
diseases
associated
with
No. of cases Associated gynecologic disease Fibromyomas Pregnancy Ovarian tumors Dermoid Thecoma Papillary cystadenocarcinoma Endometriosis Fibroma Adenocarcinoma of cervix Sarcoma of uterus Prolapse of uterus Associated diseases of other systems Cardiovascular disease Carcinoma of bladder Carcinoma of stomach
27 6 6 2 1 1 1 1 2 1 1 5 1 1
of patients with superficially invasive carcinoma. Again, note that 10 per cent are in their twenties. All 42 women had initial cervical biopsies. Thirty-three were reported as superficially invasive carcinoma and 9 as carcinoma in situ. Twenty-two then had conization of the cervix. Fourteen of the conization specimens, including the 9 previously diagnosed as carcinoma in situ, showed superficiallv invasive carcinoma; 5 cone specimens showed only carcinoma in situ, and 3 showed no carcinoma. Secondary or complicating disorders were frequently present. Ten had fibroids, 3 had ovarian tumors, 2 were pregnant, and 4 had serious cardiovascular disease. Until relatively recently we have regarded superficially invasive carcinoma as a type of Stage I carcinoma and have treated it with irradiation, followed by Wertheim hysterectomy with bilateral pelvic lymphadenectomy, if the patient is a good surgical risk. Eighteen of these patients had irradiation alone; 9 had irradiation plus Wertheim hysterectomy. Twelve patients were treated primarily with hysterectomy. One patient with a benign cone specimen following a biopsy diagnosis had no further treatment and is free of disease, 5 years later. Two have refused treatment or further examina-
invasive
carcinoma
87
tion but are reported by letter to be well 3 and 8 years later. Four of these 42 women are dead; 2 from congestive heart failure, 1 from a stroke, and 1 from metastatic gastric carcinoma. Thirty-six of the 38 survivors have been followed over 5 years with no evidence of recurrent disease. In this series of 39 patients treated with a major procedure, all types of therapy have produced the same apparent cure rate, 100 per cent; but a rather marked difference in morbidity and complications must be noted. Of the 12 treated with abdominal hysterectomy, one had wound dehiscence with secondary closure. Of the 18 treated with irradiation, one underwent laparotomy for recovery of a radium needle; 2 were hospitalized for irradiation proctitis; one developed a rectovaginal fistula requiring a permanent colostomy; and one was hospitalized for a vaginal slough. In the 9 patients treated with irradiation followed by the Wertheim procedure, 5 had major complications. One developed a rectovagina1 fistula which required a colostomy. One developed a ureterovaginal fistula; she underwent an unsuccessful attempt at repair and then a nephrectomy. Two had prolonged febrile courses; one of these had a nonfunctioning right kidney; she developed a wound dehiscence requiring second degree closure, and the other had acute pyelonephritis with bilateral hydroureter and hydronephrosis. One patient required 2 laparotomies for lysis of adhesions. In brief, surgery alone had a complication rate of 1 in 12; irradiation, 5 in 18; and irradiation plus surgery, 5 in 9. Summary
and
conclusion
1. Our experience with carcinoma in situ and superficially invasive carcinoma has been reviewed for a 10 year period. Ninetyeight cases of carcinoma in situ were treated with no mortality from therapy or from recurrent epidermoid cervical carcinoma. 2. In 39 patients with carcinoma in situ treated with major procedures, all types of
88
Dilworth
and
July 1, 1962 Am. J. Obst. & Gynec.
Maxwell
therapy produced this same apparent cure rate, 100 per cent; but a markedly lower incidence of complication was incurred with the surgical approach only, rather than with irradiation, with or without subsequent surgery. 3. There is evidence to show that very early invasion of the cervical stroma by cords of malignant cells behaves like carcinoma in situ and can be treated definitively with hysterectomy plus excision of a wide vaginal cuff.
4. These patients should experience the low morbidity and high cure rate of patients with carcinoma in situ, and be spared the trauma of irradiation or radical surgery. 5. In order to classify this large group of patients with marginal lesions accurately, adequate cone biopsy material must be obtained and the pathologist must express his findings clearly. It is absolutely essential that the pathologist and the clinician have the same understanding of the term “superficial invasion.”
REFERENCES
1. 2. 3.
TeLinde, R.: AM. J. OBST. & GYNEC. 74: 792, 1957. Latour, J. P. A.: ARI. J. OBST. & GYNEC. 74: 354, 1957. Friedell, G. H., Hertig, A. T., and Younge, P. A.: A. M. A. Arch. Path. 66: 494, 1958.
4. 5. 6.
Fennell, R. H.: Cancer 8: 302, 1955. Fennell, R. H.: Cancer 9: 374, 1956. Fidler, H. K., and Boyes, D. A.: Cancer 673, 1959. 1541 Kings Shreveport,
Highway Louisiana
12: