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Fibrocystic disease of the breast
Fibrocystic CORRELATION
Disease
OF MORPHOLOGIC
FEATURES
of the Breast WITH
THE
CLINICAL
COURSE
PETER M. MARCUSE, M.D., Houston, Texas From tbe Department of Patbology, St. Joseph’s Hospital and Baylor University College of Medicine, Houston, Texas.
period for 108 patients whose records indicated onIy one excision for fibrocystic disease. Eighteen of these, subsequentIy, had another operation because of the same disease bringing to 142 the number of patients that required more than one excision (I 7.9 per cent of the entire group). In the remaining ninety patients the foIIow-up material indicated that the patient had neither undergone additiona surgery nor had shown any cIinica1 evidence of fibrocystic disease after five years. The pathoIogic observations pertaining to these ninety patients were compared to those of ninety unseIected patients who had had more than one operation for Iibrocystic disease. A patient was not incIuded in either group in whom fibrocystic disease was either preceded by or coexistent with carcinoma of the breast. A separate group was estabIished that comprised thirty-six patients having carcinoma as we11 as fibrocystic disease.
LITERATURE pertaining to Iibrocystic disease of the female mammary gland deals mainIy with the treatment of this condition or with its possibIe reIation to the deveIopment of carcinoma. Few data are available that provide a correlation of the histoIogic features with the tendency toward recurrence or progression. The observations reIated here represent an attempt to categorize fibrocystic disease according to the presence of certain cardina1 pathoIogic features and, further, to correIate this morphoIogic cIassification with the clinical course.
T
HE
MATERIAL AND
METHODS
The cIinica1 records and the tissue sections were avaiIabIe from 794 patients with fibrocystic disease of the breast observed from 1933 to rgsg. The series was comprised of 670 women who had undergone onIy one surgica1 procedure for fibrocystic disease at St. Joseph’s HospitaI and of 124 women each of whom had two or more excisions performed at this institution. FoIIow-up data were avaiIabIe over a five year
HISTOLOGICCLASSIFICATION AI1 sIides were reviewed from every patient in both groups. The sections represented an average of Iive bIocks taken from each of the origina surgical specimens. Five categories were established, each characterized by the of a specific histoIogic feature. presence (TabIe I.) The individua1 patients were assigned to the highest category indicated by the analysis of their pathoIogic data. For exampIe, the presence of microcysts aIone was characteristic of Category I, whereas, gross cysts impIied Category II, regardIess of whether or not they occurred aIone or in combination with microcysts. Increase and condensation of the interstitia1 fibrous tissue were noted in a11specimens regardIess of their cIass&cation. EpitheIiaI hyperplasia was minima1 in Category I and increased in degree through Categories II through v.
TABLE I MORPHOLOGIC EACH
Category
1
II III IV V
FEATURES PATHOLOGIC
CHARACTERIZING CATEGORY
Characteristic
Feature
Microcysts (diameter z mm. or less) Gross cysts Adenosis IntraductaI epithelia1 pIugs Intraductal papiIIary projections
American Journal of Surgery, Volume103, April 1963
428
Fibrocystic TABLE PATIENTS’ AND
AGE
AT THE
AVERAGE
SPECIMEN
OBSERVED
’
i
38
h 5
i
33 5
7
I
2
I
‘3
I
5
9
29
Number of Patients Characterized by Single Excision
Pathologic Category
2.5
WITH
CARCINOMA
logic
in Whom ! Fibrocystic Disease Was Cocxistent
($:;.-
j
patho_
’
Number of Patients in Whom Fibrocystic Disease FoIlowed ,C arcinoma
Number c,I ’ Patients in Whon Fibrocyst ic Disease Precedec i Carcinoma
,FC cTnom;r
Same Side
Same Side
4
III
6
L\ \
Opposite Side
I 3
I
I
7 I
I” 5019:
i
2
j
4
1
The data in Table III Evaluation of Results. indicate a definite predominance of Category I in the group of patients who required only one excision over a five year period. This category is characterized by microcysts associated with interstitial fibrosis and without any appreciable degree of epitheIia1 hyperpIasia. Patients belonging in this category exhibited the Ieast progression of the hbrocystic changes. OnIy six instances of Category I were found in the group of patients who underwent two or more excisions. The Iack of appreciable epithelial hyper-
Opposite Side
2 ~
1Fourth
COMMENTS
---
II
Second, Third
the fourth decade (284 patients), as calculated from each patient’s age at the time of the first excision. Table II lists the age distribution for each of the separate groups of ninety patients. This table further includes the average pathoIogic category per specimen determined by the criteria that are outlined in Table I. TabIe III indicates the frequency with which the individual pathologic categories were encountered in the two separate groups of patients. This tabIe aIso reflects the tendency of the pathologic features to remain in the same cIassification when repeated excisions are required. By actual count, in fifty-nine of the ninety patients, the specimens from the first and second operations belonged to identica1 pathologic categories. Table IV represents the frequency distribution of the different morphoIogic categories in patients in whom hbrocystic disease is combined with carcinoma.
Iv DISEASE
6 48
29 12
The right breast was originally implicated in 329 instances and the Ieft in 400 patients, while initial bilatera1 involvement was recorded sixty-five times. In the 142 patients requiring two excisions or more, the disease was bilateral in thirteen patients at the time of the first surgery. Those having unilateral changes the first time showed eventual invoIvement of the opposite breast in sixty-nine instances (53 per cent). The highest age incidence for the entire series \vas in the hfth decade (298 patients) and in TABLE
Sequence of Operations I-
42
2
I
i
FIBROCYSTIC
GROUPS
Number of Patients Characterized by Multiple Excisions
First
;,
OF
IN
MULTIPLE
T
RESULTS
ASSOCIATIOY
AND
2.5 )
*
-I
SINGLE
2.4
37
5
BY
CATEGORIES
EXCISIONS
! Category
37
I
2
CHARACTERIZED
PER
III
PATHOLOGIC
Excisions
Number
5
OF
DECADE
T Multiple
1.5
4
EACH
Category
INCIDENCE
FLRST EXCISION
CATEGORY
IN
One Excision
I”
Breast TABLE
OF THE
I
3
of the
II
TIME
PATHOLOGIC
Number
Disease
-
429
Marcuse pIasia in multipIe sections, therefore, suggests a reIativeIy inactive course of the disease. Categories 111, IV and v represent variants marked by pronounced epitheIia1 proliferation. The Iesions beIonging to any of these cIasses were almost twice as frequent in patients requiring multipIe excisions than in those who needed only one operation. The tendency toward progression or recurrence may thus be roughly judged by the degree of epitheIia1 hyperplasia. The predominance of the higher categories in the group with muItipIe excisions couId conceivabIy be because of differences in the age distribution. However, as shown in Table II, the average category, as caIcuIated for each decade, is also higher in the group characterized by muItipIe excisions. The association between the degree of epitheIia1 hyperplasia and the tendency toward continued activity is, therefore, independent of the patient’s age. One hundred forty-two of 792 patients required repeated excisions. This incidence (I 7.9 per cent) may be considered the rate of although strictly speaking, the recurrence, second and third episodes were usuaIIy because of new Iesions at sites remote from the first. Evidence of recurrence was found in 12.4 per cent of 484 patients by Hendrick [I] and in 17.6 per cent of 153 patients by Lewison [2]. Davis and Simons [3] reported the resuIts of 201 IocaI excisions for cystic disease. They state that no further surgery was needed in 83 per cent of the patients with unilateral involvement and in 75 per cent of those with bilateral Iesions. Thus, the rate of recurrence lies usuaIly between IO and 20 per cent if based on patients requiring at least two operations within a five year period (“surgica1 recurrence’?). However, the clinical incidence of recurrence is undoubtedIy higher if based on repeated physica examinations over an extended. time span. Haagensen [4] foIIowed up 147 patients for ten or more years and found that 32 per cent deveIoped new grossIy visibIe Iesions after the first cysts had been excised. The same breast was invoIved, alone, in I 1.6 per cent, the opposite breast, alone, in 10.2 per cent and both breasts in 10.2 per cent. TabIe IV faiIs to revea1 any category to be predominantry associated with carcinoma. This negative evidence conforms with the observations by Foote and Stewart [T]. These authors specifically indicate certain histoIogic features
as proliferative Iesions [6]. IncIuded under this designation are hyperpIasia of duct epitheIium, duct papiIlomatosis, apocrine epithelium and adenosis. In Foote and Stewart’s [5] series these changes had a tendency to occur in cyst-containing breasts irrespective of the presence of carcinoma. The data under discussion had no bearing on the controversy over a possible connection between fibrocystic disease and carcinoma. They mereIy failed to indicate any increased tendency toward the development of carcinoma in the presence of marked epitheIia1 prohferation. Conclusions. Fibrocystic disease of the breast is a cIinica1 entity with a variabIe pathologic background. Category I is characterized by the absence of any appreciabIe epithelial proIiferation. Patients in this category may have minima1 cIinica1 invoIvement and their indications for surgery may be equivocal. This category, nevertheless, comprises many surgical specimens in a genera1 hospital because of the understandable inabiIity of the examining physician to ruIe out carcinoma. Lesions in the remaining cIasses, particuIarIy those in Categories III, IV or v, show a notable tendency to recur or to appear in new Iocations, invoIving either breast or both breasts, simuItaneousIy. The new Iesions often foIIow the same pathologic pattern that characterized the origina specimen, EpitheIiaI prohferation may Iead to the formation of masses that often are clinically indistinguishable from malignant tumors. Repeated surgery may, therefore, become necessary for patients in Categories III through v; even though, carcinoma shows no preferential association with any particular variant of fibrocystic disease. The importance of dividing the fibrocystic disease compIex into different morphotogic entities Iies mainly in the anticipation of the probahIe future manifestations of the process. SUMMARY
In 794 patients with hbrocystic disease of the breast, 142 (17.9 per cent) required more than one excision over a five year period. Two groups were estabIished, one representing cIinica1 quiescence, the other comprising patients that had two or more operations. These groups were anaIyzed according to morphoIogic criteria, based on the degree of epitheIia1 hyperpIasia.
Fibrocystic
Disease
of the
Breast
2. LE~ISON, E. F. Breast Cancer, 1st ed. Baltimore, 1955. WiIIiams & Wilkins Company. 3. DAVIS, H. H. and SIMONS, M. Cystic disease of the
Lesions without appreciable epithelial proliferation predominated in the patients who had undergone only one operation. HyperpIasia, moderate to extreme in degree, was present in the majority of those patients who required more than one excision. No increased incidence of carcinoma was noted in the presence of epitheIia1 proliferation.
breast. Arch. Surg., 70: 414. 1955. 4. HAACENSEK, C. D. Diseases of the Breast,
1st. ed. PhiIadeIphia, 1956. W. B. Saunders Company. 5. FOOTE, F. W. and STEWART, F. W. Comparative studies of cancerous versus noncancerous breasts. 11. RoIc of so-caIIed chronic cystic mastitis in mammary carcinogenesis. Influence of certain hormones on human breast structure. Ann. Surg., 121: 197, 1945. 6. FOOTE. F. W. and STEWART. F. W. Comoarative studies of cancerous versus noncancerous breasts. 1. Basic morphoIogic characteristics. Ann. Surg., 121: 6, 1945.
REFERENCES I. HENDRICK, J. W. Results of treatment of cystic disease of the breast. Five to eighteen year survey. Surgery, 44: 457, 1958.
43’
Disease
OF MORPHOLOGIC
FEATURES
of the Breast WITH
THE
CLINICAL
COURSE
PETER M. MARCUSE, M.D., Houston, Texas From tbe Department of Patbology, St. Joseph’s Hospital and Baylor University College of Medicine, Houston, Texas.
period for 108 patients whose records indicated onIy one excision for fibrocystic disease. Eighteen of these, subsequentIy, had another operation because of the same disease bringing to 142 the number of patients that required more than one excision (I 7.9 per cent of the entire group). In the remaining ninety patients the foIIow-up material indicated that the patient had neither undergone additiona surgery nor had shown any cIinica1 evidence of fibrocystic disease after five years. The pathoIogic observations pertaining to these ninety patients were compared to those of ninety unseIected patients who had had more than one operation for Iibrocystic disease. A patient was not incIuded in either group in whom fibrocystic disease was either preceded by or coexistent with carcinoma of the breast. A separate group was estabIished that comprised thirty-six patients having carcinoma as we11 as fibrocystic disease.
LITERATURE pertaining to Iibrocystic disease of the female mammary gland deals mainIy with the treatment of this condition or with its possibIe reIation to the deveIopment of carcinoma. Few data are available that provide a correlation of the histoIogic features with the tendency toward recurrence or progression. The observations reIated here represent an attempt to categorize fibrocystic disease according to the presence of certain cardina1 pathoIogic features and, further, to correIate this morphoIogic cIassification with the clinical course.
T
HE
MATERIAL AND
METHODS
The cIinica1 records and the tissue sections were avaiIabIe from 794 patients with fibrocystic disease of the breast observed from 1933 to rgsg. The series was comprised of 670 women who had undergone onIy one surgica1 procedure for fibrocystic disease at St. Joseph’s HospitaI and of 124 women each of whom had two or more excisions performed at this institution. FoIIow-up data were avaiIabIe over a five year
HISTOLOGICCLASSIFICATION AI1 sIides were reviewed from every patient in both groups. The sections represented an average of Iive bIocks taken from each of the origina surgical specimens. Five categories were established, each characterized by the of a specific histoIogic feature. presence (TabIe I.) The individua1 patients were assigned to the highest category indicated by the analysis of their pathoIogic data. For exampIe, the presence of microcysts aIone was characteristic of Category I, whereas, gross cysts impIied Category II, regardIess of whether or not they occurred aIone or in combination with microcysts. Increase and condensation of the interstitia1 fibrous tissue were noted in a11specimens regardIess of their cIass&cation. EpitheIiaI hyperplasia was minima1 in Category I and increased in degree through Categories II through v.
TABLE I MORPHOLOGIC EACH
Category
1
II III IV V
FEATURES PATHOLOGIC
CHARACTERIZING CATEGORY
Characteristic
Feature
Microcysts (diameter z mm. or less) Gross cysts Adenosis IntraductaI epithelia1 pIugs Intraductal papiIIary projections
American Journal of Surgery, Volume103, April 1963
428
Fibrocystic TABLE PATIENTS’ AND
AGE
AT THE
AVERAGE
SPECIMEN
OBSERVED
’
i
38
h 5
i
33 5
7
I
2
I
‘3
I
5
9
29
Number of Patients Characterized by Single Excision
Pathologic Category
2.5
WITH
CARCINOMA
logic
in Whom ! Fibrocystic Disease Was Cocxistent
($:;.-
j
patho_
’
Number of Patients in Whom Fibrocystic Disease FoIlowed ,C arcinoma
Number c,I ’ Patients in Whon Fibrocyst ic Disease Precedec i Carcinoma
,FC cTnom;r
Same Side
Same Side
4
III
6
L\ \
Opposite Side
I 3
I
I
7 I
I” 5019:
i
2
j
4
1
The data in Table III Evaluation of Results. indicate a definite predominance of Category I in the group of patients who required only one excision over a five year period. This category is characterized by microcysts associated with interstitial fibrosis and without any appreciable degree of epitheIia1 hyperpIasia. Patients belonging in this category exhibited the Ieast progression of the hbrocystic changes. OnIy six instances of Category I were found in the group of patients who underwent two or more excisions. The Iack of appreciable epithelial hyper-
Opposite Side
2 ~
1Fourth
COMMENTS
---
II
Second, Third
the fourth decade (284 patients), as calculated from each patient’s age at the time of the first excision. Table II lists the age distribution for each of the separate groups of ninety patients. This table further includes the average pathoIogic category per specimen determined by the criteria that are outlined in Table I. TabIe III indicates the frequency with which the individual pathologic categories were encountered in the two separate groups of patients. This tabIe aIso reflects the tendency of the pathologic features to remain in the same cIassification when repeated excisions are required. By actual count, in fifty-nine of the ninety patients, the specimens from the first and second operations belonged to identica1 pathologic categories. Table IV represents the frequency distribution of the different morphoIogic categories in patients in whom hbrocystic disease is combined with carcinoma.
Iv DISEASE
6 48
29 12
The right breast was originally implicated in 329 instances and the Ieft in 400 patients, while initial bilatera1 involvement was recorded sixty-five times. In the 142 patients requiring two excisions or more, the disease was bilateral in thirteen patients at the time of the first surgery. Those having unilateral changes the first time showed eventual invoIvement of the opposite breast in sixty-nine instances (53 per cent). The highest age incidence for the entire series \vas in the hfth decade (298 patients) and in TABLE
Sequence of Operations I-
42
2
I
i
FIBROCYSTIC
GROUPS
Number of Patients Characterized by Multiple Excisions
First
;,
OF
IN
MULTIPLE
T
RESULTS
ASSOCIATIOY
AND
2.5 )
*
-I
SINGLE
2.4
37
5
BY
CATEGORIES
EXCISIONS
! Category
37
I
2
CHARACTERIZED
PER
III
PATHOLOGIC
Excisions
Number
5
OF
DECADE
T Multiple
1.5
4
EACH
Category
INCIDENCE
FLRST EXCISION
CATEGORY
IN
One Excision
I”
Breast TABLE
OF THE
I
3
of the
II
TIME
PATHOLOGIC
Number
Disease
-
429
Marcuse pIasia in multipIe sections, therefore, suggests a reIativeIy inactive course of the disease. Categories 111, IV and v represent variants marked by pronounced epitheIia1 proliferation. The Iesions beIonging to any of these cIasses were almost twice as frequent in patients requiring multipIe excisions than in those who needed only one operation. The tendency toward progression or recurrence may thus be roughly judged by the degree of epitheIia1 hyperplasia. The predominance of the higher categories in the group with muItipIe excisions couId conceivabIy be because of differences in the age distribution. However, as shown in Table II, the average category, as caIcuIated for each decade, is also higher in the group characterized by muItipIe excisions. The association between the degree of epitheIia1 hyperplasia and the tendency toward continued activity is, therefore, independent of the patient’s age. One hundred forty-two of 792 patients required repeated excisions. This incidence (I 7.9 per cent) may be considered the rate of although strictly speaking, the recurrence, second and third episodes were usuaIIy because of new Iesions at sites remote from the first. Evidence of recurrence was found in 12.4 per cent of 484 patients by Hendrick [I] and in 17.6 per cent of 153 patients by Lewison [2]. Davis and Simons [3] reported the resuIts of 201 IocaI excisions for cystic disease. They state that no further surgery was needed in 83 per cent of the patients with unilateral involvement and in 75 per cent of those with bilateral Iesions. Thus, the rate of recurrence lies usuaIly between IO and 20 per cent if based on patients requiring at least two operations within a five year period (“surgica1 recurrence’?). However, the clinical incidence of recurrence is undoubtedIy higher if based on repeated physica examinations over an extended. time span. Haagensen [4] foIIowed up 147 patients for ten or more years and found that 32 per cent deveIoped new grossIy visibIe Iesions after the first cysts had been excised. The same breast was invoIved, alone, in I 1.6 per cent, the opposite breast, alone, in 10.2 per cent and both breasts in 10.2 per cent. TabIe IV faiIs to revea1 any category to be predominantry associated with carcinoma. This negative evidence conforms with the observations by Foote and Stewart [T]. These authors specifically indicate certain histoIogic features
as proliferative Iesions [6]. IncIuded under this designation are hyperpIasia of duct epitheIium, duct papiIlomatosis, apocrine epithelium and adenosis. In Foote and Stewart’s [5] series these changes had a tendency to occur in cyst-containing breasts irrespective of the presence of carcinoma. The data under discussion had no bearing on the controversy over a possible connection between fibrocystic disease and carcinoma. They mereIy failed to indicate any increased tendency toward the development of carcinoma in the presence of marked epitheIia1 prohferation. Conclusions. Fibrocystic disease of the breast is a cIinica1 entity with a variabIe pathologic background. Category I is characterized by the absence of any appreciabIe epithelial proIiferation. Patients in this category may have minima1 cIinica1 invoIvement and their indications for surgery may be equivocal. This category, nevertheless, comprises many surgical specimens in a genera1 hospital because of the understandable inabiIity of the examining physician to ruIe out carcinoma. Lesions in the remaining cIasses, particuIarIy those in Categories III, IV or v, show a notable tendency to recur or to appear in new Iocations, invoIving either breast or both breasts, simuItaneousIy. The new Iesions often foIIow the same pathologic pattern that characterized the origina specimen, EpitheIiaI prohferation may Iead to the formation of masses that often are clinically indistinguishable from malignant tumors. Repeated surgery may, therefore, become necessary for patients in Categories III through v; even though, carcinoma shows no preferential association with any particular variant of fibrocystic disease. The importance of dividing the fibrocystic disease compIex into different morphotogic entities Iies mainly in the anticipation of the probahIe future manifestations of the process. SUMMARY
In 794 patients with hbrocystic disease of the breast, 142 (17.9 per cent) required more than one excision over a five year period. Two groups were estabIished, one representing cIinica1 quiescence, the other comprising patients that had two or more operations. These groups were anaIyzed according to morphoIogic criteria, based on the degree of epitheIia1 hyperpIasia.
Fibrocystic
Disease
of the
Breast
2. LE~ISON, E. F. Breast Cancer, 1st ed. Baltimore, 1955. WiIIiams & Wilkins Company. 3. DAVIS, H. H. and SIMONS, M. Cystic disease of the
Lesions without appreciable epithelial proliferation predominated in the patients who had undergone only one operation. HyperpIasia, moderate to extreme in degree, was present in the majority of those patients who required more than one excision. No increased incidence of carcinoma was noted in the presence of epitheIia1 proliferation.
breast. Arch. Surg., 70: 414. 1955. 4. HAACENSEK, C. D. Diseases of the Breast,
1st. ed. PhiIadeIphia, 1956. W. B. Saunders Company. 5. FOOTE, F. W. and STEWART, F. W. Comparative studies of cancerous versus noncancerous breasts. 11. RoIc of so-caIIed chronic cystic mastitis in mammary carcinogenesis. Influence of certain hormones on human breast structure. Ann. Surg., 121: 197, 1945. 6. FOOTE. F. W. and STEWART. F. W. Comoarative studies of cancerous versus noncancerous breasts. 1. Basic morphoIogic characteristics. Ann. Surg., 121: 6, 1945.
REFERENCES I. HENDRICK, J. W. Results of treatment of cystic disease of the breast. Five to eighteen year survey. Surgery, 44: 457, 1958.
43’