Br. J. Surg. Vol. 66 (1979) 209-211
Cytological study of fluid from breast cysts P . N . C O W E N A N D E. A. B E N S O N * SUMMARY
A series of 215 patients with breast cysts has provided 348 specimens of cyst fluid for cytological diagnosis. Only one of these specimens was reported positive for malignant cells and this patient had a carcinoma. Nine specimens were reported as suspicious, but none of these patients had or subsequently developed carcinoma. In 338 specimens cytology was negative. A total of 178 patients (294 specimens) was available for follow-up. Of these 2proved to have carcinomas on immediate followup, i.e. a lump persisted after aspiration, rind a further 2 patients developed cancers in the same breast, one 4 and the other 7 years after aspiration. We therefore conclude that the routine submission of’ breast cyst fluid for cyfology is wasteful of time and resources.
WE do not propose to discuss the merit of needle aspiration in the management of breast cysts. Controversy has existed in the past as to whether excision biopsy is a safer procedure (Atkins, 1952; Keynes, 1966). We believe, however, that aspiration is now a generally acceptable procedure, and are supported in this view by Patey and Nurick (1953), Schnug and Cavanagh (1966), Forrest (1974),Rimsten et al. (1975) and Rosemond et al. (1977). We propose to confine ourselves to investigating the value of the routine cytological examination of fluid removed from breast cysts, since it appears that there is a difference of opinion as to its value. Patey and Nurick (1953) appear to have been the first to suggest the importance of cytology in reducing the risk of missing a breast carcinoma (although these authors also stated, somewhat paradoxically, that there was no clear relationship between fibrocystic disease and breast cancer). Their view is supported by Forrest (1974) and Rimsten et al. (1975). Equally, Schnug and Cavanagh (1966) and Rosemond et al. (1977) are of the opinion that cytological examination of cyst fluid is unnecessary. It appears that the type of carcinoma which may be present can have a bearing on the usefulness of cytological examination and there are two situations to consider. First, in the case of true intracyst carcinoma (Fig. l a ) , cyst fluid cytology could conceivably be valuable; however, the incidence of this particular type of growth is extremely low. Gatchell et al. (1958) quote an incidence of only 0.5 per cent, Kalisher (1977) states that it is ‘a rare entity’ and Rosemond et al. (1977) quote an incidence of 0.1 per cent. This conclusion has been borne out by our experience in this teaching hospital pathology department, where carcinomas are rarely seen in association with cysts and where intracystic carcinoma is virtually non-existent. If, therefore, we aim to avoid missing these extremely rare tumours by using cytological examination, we shall be assessing a large number of samples totally unnecessarily. If we consider the second situation, the coincidental occurrence of a carcinoma side by side with cysts in the same breast (again, in our experience, an uncommon, though perhaps not rare, situation) (Fig. l b ) , routine examination of cyst fluid is not likely to help in this case as the growth is at some
a
b
Fig. 1. ( a ) A true cystic carcinoma; (6) carcinoma coincidental with a breast cyst.
Fig. 2. Needle aspiration of a breast cyst.
distance from the cyst and cannot be expected to exfoliate cells into the cyst fluid. It should be noted, however, that decompression of the cyst may well make the carcinoma easier to feel clinically. Having analysed the problem in this way it appeared to us, on theoretical grounds at least, that it was highly improbable that routine cytology of aspirates from breast cysts was likely to be of any significant value whatsoever as regards detecting an occult carcinoma, and we felt impelled to re-examine the logic of this exercise. We were influenced in this by a retrospective study by one of us (P. N. C.), who had reviewed 106 specimens from 83 patients with breast cysts collected between 1964 and 1970. NOmalignant cells were found in any of these specimens and of the 67 patients who could be followed up, none subsequently developed breast cancer.
* General Infirmary, Leeds. Correspondence to: E. A. Benson.
210
P. N. Cowen and E. A. Benson
a
h
Fig. 3. Nan-malignant cells seen i n cyst asoirates: ( a ) probably epithelial; (0)foamy macrophages with polyniorphs. (HI:. >: 390.)
Table I: SUMMARY OF NUMBERS OF PATIENTS AND SPECIMENS IN THE SURVEY TOGETHER WITH THEIR CYTOLOGY REPORTS AND THE RESULTS OF FOLLOW-UP Report No. of No of patients specimens +ve Suspect -ve Totals 215 348 1 9 338 Cases lost to 31 54 0 I 53 follow-up Cases 178 294 I* 8t 285$ followed up Result of follow-up: * Positive confirmed. I’None had or developed a new growth. t Four had o r developed breast cancer.
Fig. 4. Large, bizarre cells from squamous carcinoma with pus cells. (HE. x 390.)
Patients and methods A prospective study was undertaken from November 1970 to December 1976. Patients were attending the surgical outpatients’ clinic a t the General Infirmary at Leeds and the majority were attending one unit, i.e. the Combined Breast Clinic. Patients whose lesions were diagnosed as breast cysts wer? treated by needle aspiration, without local anaesthetic (F;g. 2). Each cyst was aspirated as completely as possible and the fluid sent in a clean, dry, sterile bottle to the pathology department where it was received within 2 h. T he fluid was then centrifuged for 5 min at 1500 revimin (MSE Super Minor Centrifuge), the supernatant was pipetted off and the sediment then smeared on t o a slide which was fixed in S O / S O ether alcohol or pure absolute alcohol. The slide (which was never allowed to become dry) was then stained with haematoxylin and eosin and the sniear mounted with a cover slip as for conventional histology. Typical smears of breast cyst contents are seen in Fig. 3.
Results In general, a few cells were found in the cyst smears. Most were recognized as epithelial cells or histiocytes and occasionally numerous pus cells were present. The results are shown in Table I . Three hundred and forty-eight specimens were obtained from 215 patients (some being repeat aspirations in the same patient) and in 1 case positive cytology was obtained (Fig. 4), though there were 9 ‘suspicious’ reports. Three hundred and thirty-eight specimens contained either
benign or no cells. The single patient with positive cytology did indeed have a breast carcinoma, though this was not intracystic but a squamous carcinoma that had become necrotic centrally. Although we had failed to detect cancer at initial presentation in the vast majority of these women it was just conceivable that a neoplastic lesion might have been missed, and for this reason as many of these patients as possible were followed up. Thirtyseven patients were lost to follow-up, leaving a total of 178 for study over a period of up to 7 years. Eight of the 9 suspicious cases were followed and none developed a carcinoma, 5 of these also have negative biopsies. The 1 suspicious case was lost to follow-up but we have no reason to believe (because of referral patterns in Leeds) that this patient developed a carcinoma. Four patients with negative cytology, however, were subsequently proved to have breast carcinoma. In 2 of these cases, on immediate follow-up a lump persisted after aspiration and in both cases a carcinoma was found at the site of the lump, i.e. their carcinomas had been clinically unmasked by decompression of coexisting breast cysts. In the other 2 cases the patients developed a carcinoma in the same breast as the cyst, one at 4 and the other at 7 years after aspiration. In our opinion these cases could hardly be considered false negatives. Discussion Once a cytology service is established surgeons will tend to send samples to it without necessarily critically examining its usefulness. However, Forrest et al.
Cytological study of fluid from breast cysts (1975), are of the opinion that breast cyst cytology is useful, since out of 149 cysts aspirated by them, abnormal findings in 36 patients led to excision of the cyst, revealing carcinoma in 4 cases. This yield was significantly higher than ours. Others have also reported a higher incidence of cancer associated with cysts than we experienced; Patey and Nurick (1953) found 8 carcinomas associated with 76 cysts and Rosemond et al. (1955) reported 2 carcinomas associated with 140 cysts. As we have indicated previously, intracystic carcinoma is in itself extremely rare and it seems a futile exercise to hope to recognize such growths by routine cytology. Furthermore, since there is no definite relationship between fibrocystic disease and breast cancer, needle aspiration of cysts in fibrocystic disease is not likely to be particularly rewarding. Gaspar (1961) reviewed 15 surveys of breast cyst aspiration studies, including his own, and his conclusion was that ‘As Papanicolaou examination of breast cyst fluid is unrewarding, this procedure has been abandoned.’ His review included a total of 1364 patients with breast cysts, 12 of whom had cancers. In 4 cases these carcinomas were associated with cysts, in a further 4 patients these occurred in the same breast but not in the cyst and in the remaining 4 they occurred in the contralateral breast. Small surveys are reported by Roth et al. (1977) and Van Bogaert and Mazy (1977) in which 72 cysts were aspirated and all were negative cytologically. A recent large survey is that of Rosemond et al. (1977), who had only 3 cancers in 3000 cyst aspirates and therefore concluded that cytology is unnecessary. From our own experience, we have confirmed that needle aspiration of breast cysts is a safe and reliable method of treatment. We conclude that there is nothing to be gained by routinely submitting breast cyst fluid for cytology, since the risk of missing a carcinoma is very small, particularly if the following clinical protocol is obeyed : Recommend biopsy if (a) aspiration fails, i.e. the lump may be solid, or (b) the lump recurs after re-examination at I month, if mammograms indicate the necessity. Routine cytology is therefore not only unnecessary but wasteful of time and resources. In this series we were interested to note that 4 of the 178 patients with negative cytology either had (2 cases) or subsequently developed (2 cases) a carcinoma. This does not appear to indicate an
211
appreciable risk for patients with fibrocystic disease and we believe that this is generally the experience of others. Finally, we would reiterate the general clinical rules for follow-up in patients in whom cysts are aspirated. It is most important after aspiration of a cyst that careful re-examination of the breast at the time and again 4 weeks later is carried out. Should a lump persist or recur we believe that mammography is indicated and a decision is then taken as to whether repeat aspiration or excision biopsy should be undertaken. References ATKlNs H. (1952) Pain in the breast. Laricer 1, 271-274. FORREST A. P. M. (1974) Primary cancer of the breast: indication for therapy. In: ATKINS H. (ed.) The Treatnient of’ Breast
Cancer. Lancaster, MTP, p. 32.
and ROBERTS M. M. (1975) Needle aspiration of breast cysts. B. Meti. J. 3, 30-31. GASPAR M. R. (1961) Aspiration of breast cysts. Calif. Med. 95, 227-231. GATCHELL F. c., DOCKERTY M. B. and CLAGETT 0. T. (1958) Intracystic carcinoma of the breast. Siirg. Gynecol. Obstet. 106, 347-352. KALISHER L. (1977) Intracystic carcinoma of the breast. Breast 3 , 32-33. KEYNES hi. (1966) Lumps in the breast. (Letter to the Editor.) Br. Med. J. 2, 235. PATEY D. H. and NURICK A. W. (1953) Natural history of cystic disease of the breast treated conservatively. Br. Med. J. 1, 15-17. RIMSTEN A., STENKVIST B., JOHANSON H. et al. (1975) The diagnostic accuracy of palpation and fine-needle biopsy and an evaluation of their combined use in the diagnosis of breast lesions. Ann. Surg. 182, 1-8. ROSEMOND G. P., BURNETT w. E., CASWELL H. T. et al. (195s) Aspiration of breast cysts as a diagnostic and therapeutic measure. Arch. Surg. 71,223-229. ROSEMOND G. P., MAIER w. P. and BROBYN T. J. (1977) Needle aspiration of breast cysts. J. Family Prnctice 4, 11571160. ROTH J. A,, FEINBERG M. and MCAVOY J. M. (1977) Carcinoma arising in the wall of a breast cyst during pregnancy. Ann. Surg. 185, 247-250. SCHNUG E. 0. and CAVANAGH c. R. (1966) Aspiration in the management of recurrent cysts of the breast. Surg. Gynecol. Obstet. 122, 355-357. V A N BOCAERT L. G. and MAZY G. (1977) Reliability of the cytoradio-clinical triplet in breast pathology diagnosis. Acra Cytol. 21, 60-62. FORREST A. P. M., KIRKPATRICK 3. R.
Paper accepted 17 July 1978.
Cytological study of fluid from breast cysts P . N . C O W E N A N D E. A. B E N S O N * SUMMARY
A series of 215 patients with breast cysts has provided 348 specimens of cyst fluid for cytological diagnosis. Only one of these specimens was reported positive for malignant cells and this patient had a carcinoma. Nine specimens were reported as suspicious, but none of these patients had or subsequently developed carcinoma. In 338 specimens cytology was negative. A total of 178 patients (294 specimens) was available for follow-up. Of these 2proved to have carcinomas on immediate followup, i.e. a lump persisted after aspiration, rind a further 2 patients developed cancers in the same breast, one 4 and the other 7 years after aspiration. We therefore conclude that the routine submission of’ breast cyst fluid for cyfology is wasteful of time and resources.
WE do not propose to discuss the merit of needle aspiration in the management of breast cysts. Controversy has existed in the past as to whether excision biopsy is a safer procedure (Atkins, 1952; Keynes, 1966). We believe, however, that aspiration is now a generally acceptable procedure, and are supported in this view by Patey and Nurick (1953), Schnug and Cavanagh (1966), Forrest (1974),Rimsten et al. (1975) and Rosemond et al. (1977). We propose to confine ourselves to investigating the value of the routine cytological examination of fluid removed from breast cysts, since it appears that there is a difference of opinion as to its value. Patey and Nurick (1953) appear to have been the first to suggest the importance of cytology in reducing the risk of missing a breast carcinoma (although these authors also stated, somewhat paradoxically, that there was no clear relationship between fibrocystic disease and breast cancer). Their view is supported by Forrest (1974) and Rimsten et al. (1975). Equally, Schnug and Cavanagh (1966) and Rosemond et al. (1977) are of the opinion that cytological examination of cyst fluid is unnecessary. It appears that the type of carcinoma which may be present can have a bearing on the usefulness of cytological examination and there are two situations to consider. First, in the case of true intracyst carcinoma (Fig. l a ) , cyst fluid cytology could conceivably be valuable; however, the incidence of this particular type of growth is extremely low. Gatchell et al. (1958) quote an incidence of only 0.5 per cent, Kalisher (1977) states that it is ‘a rare entity’ and Rosemond et al. (1977) quote an incidence of 0.1 per cent. This conclusion has been borne out by our experience in this teaching hospital pathology department, where carcinomas are rarely seen in association with cysts and where intracystic carcinoma is virtually non-existent. If, therefore, we aim to avoid missing these extremely rare tumours by using cytological examination, we shall be assessing a large number of samples totally unnecessarily. If we consider the second situation, the coincidental occurrence of a carcinoma side by side with cysts in the same breast (again, in our experience, an uncommon, though perhaps not rare, situation) (Fig. l b ) , routine examination of cyst fluid is not likely to help in this case as the growth is at some
a
b
Fig. 1. ( a ) A true cystic carcinoma; (6) carcinoma coincidental with a breast cyst.
Fig. 2. Needle aspiration of a breast cyst.
distance from the cyst and cannot be expected to exfoliate cells into the cyst fluid. It should be noted, however, that decompression of the cyst may well make the carcinoma easier to feel clinically. Having analysed the problem in this way it appeared to us, on theoretical grounds at least, that it was highly improbable that routine cytology of aspirates from breast cysts was likely to be of any significant value whatsoever as regards detecting an occult carcinoma, and we felt impelled to re-examine the logic of this exercise. We were influenced in this by a retrospective study by one of us (P. N. C.), who had reviewed 106 specimens from 83 patients with breast cysts collected between 1964 and 1970. NOmalignant cells were found in any of these specimens and of the 67 patients who could be followed up, none subsequently developed breast cancer.
* General Infirmary, Leeds. Correspondence to: E. A. Benson.
210
P. N. Cowen and E. A. Benson
a
h
Fig. 3. Nan-malignant cells seen i n cyst asoirates: ( a ) probably epithelial; (0)foamy macrophages with polyniorphs. (HI:. >: 390.)
Table I: SUMMARY OF NUMBERS OF PATIENTS AND SPECIMENS IN THE SURVEY TOGETHER WITH THEIR CYTOLOGY REPORTS AND THE RESULTS OF FOLLOW-UP Report No. of No of patients specimens +ve Suspect -ve Totals 215 348 1 9 338 Cases lost to 31 54 0 I 53 follow-up Cases 178 294 I* 8t 285$ followed up Result of follow-up: * Positive confirmed. I’None had or developed a new growth. t Four had o r developed breast cancer.
Fig. 4. Large, bizarre cells from squamous carcinoma with pus cells. (HE. x 390.)
Patients and methods A prospective study was undertaken from November 1970 to December 1976. Patients were attending the surgical outpatients’ clinic a t the General Infirmary at Leeds and the majority were attending one unit, i.e. the Combined Breast Clinic. Patients whose lesions were diagnosed as breast cysts wer? treated by needle aspiration, without local anaesthetic (F;g. 2). Each cyst was aspirated as completely as possible and the fluid sent in a clean, dry, sterile bottle to the pathology department where it was received within 2 h. T he fluid was then centrifuged for 5 min at 1500 revimin (MSE Super Minor Centrifuge), the supernatant was pipetted off and the sediment then smeared on t o a slide which was fixed in S O / S O ether alcohol or pure absolute alcohol. The slide (which was never allowed to become dry) was then stained with haematoxylin and eosin and the sniear mounted with a cover slip as for conventional histology. Typical smears of breast cyst contents are seen in Fig. 3.
Results In general, a few cells were found in the cyst smears. Most were recognized as epithelial cells or histiocytes and occasionally numerous pus cells were present. The results are shown in Table I . Three hundred and forty-eight specimens were obtained from 215 patients (some being repeat aspirations in the same patient) and in 1 case positive cytology was obtained (Fig. 4), though there were 9 ‘suspicious’ reports. Three hundred and thirty-eight specimens contained either
benign or no cells. The single patient with positive cytology did indeed have a breast carcinoma, though this was not intracystic but a squamous carcinoma that had become necrotic centrally. Although we had failed to detect cancer at initial presentation in the vast majority of these women it was just conceivable that a neoplastic lesion might have been missed, and for this reason as many of these patients as possible were followed up. Thirtyseven patients were lost to follow-up, leaving a total of 178 for study over a period of up to 7 years. Eight of the 9 suspicious cases were followed and none developed a carcinoma, 5 of these also have negative biopsies. The 1 suspicious case was lost to follow-up but we have no reason to believe (because of referral patterns in Leeds) that this patient developed a carcinoma. Four patients with negative cytology, however, were subsequently proved to have breast carcinoma. In 2 of these cases, on immediate follow-up a lump persisted after aspiration and in both cases a carcinoma was found at the site of the lump, i.e. their carcinomas had been clinically unmasked by decompression of coexisting breast cysts. In the other 2 cases the patients developed a carcinoma in the same breast as the cyst, one at 4 and the other at 7 years after aspiration. In our opinion these cases could hardly be considered false negatives. Discussion Once a cytology service is established surgeons will tend to send samples to it without necessarily critically examining its usefulness. However, Forrest et al.
Cytological study of fluid from breast cysts (1975), are of the opinion that breast cyst cytology is useful, since out of 149 cysts aspirated by them, abnormal findings in 36 patients led to excision of the cyst, revealing carcinoma in 4 cases. This yield was significantly higher than ours. Others have also reported a higher incidence of cancer associated with cysts than we experienced; Patey and Nurick (1953) found 8 carcinomas associated with 76 cysts and Rosemond et al. (1955) reported 2 carcinomas associated with 140 cysts. As we have indicated previously, intracystic carcinoma is in itself extremely rare and it seems a futile exercise to hope to recognize such growths by routine cytology. Furthermore, since there is no definite relationship between fibrocystic disease and breast cancer, needle aspiration of cysts in fibrocystic disease is not likely to be particularly rewarding. Gaspar (1961) reviewed 15 surveys of breast cyst aspiration studies, including his own, and his conclusion was that ‘As Papanicolaou examination of breast cyst fluid is unrewarding, this procedure has been abandoned.’ His review included a total of 1364 patients with breast cysts, 12 of whom had cancers. In 4 cases these carcinomas were associated with cysts, in a further 4 patients these occurred in the same breast but not in the cyst and in the remaining 4 they occurred in the contralateral breast. Small surveys are reported by Roth et al. (1977) and Van Bogaert and Mazy (1977) in which 72 cysts were aspirated and all were negative cytologically. A recent large survey is that of Rosemond et al. (1977), who had only 3 cancers in 3000 cyst aspirates and therefore concluded that cytology is unnecessary. From our own experience, we have confirmed that needle aspiration of breast cysts is a safe and reliable method of treatment. We conclude that there is nothing to be gained by routinely submitting breast cyst fluid for cytology, since the risk of missing a carcinoma is very small, particularly if the following clinical protocol is obeyed : Recommend biopsy if (a) aspiration fails, i.e. the lump may be solid, or (b) the lump recurs after re-examination at I month, if mammograms indicate the necessity. Routine cytology is therefore not only unnecessary but wasteful of time and resources. In this series we were interested to note that 4 of the 178 patients with negative cytology either had (2 cases) or subsequently developed (2 cases) a carcinoma. This does not appear to indicate an
211
appreciable risk for patients with fibrocystic disease and we believe that this is generally the experience of others. Finally, we would reiterate the general clinical rules for follow-up in patients in whom cysts are aspirated. It is most important after aspiration of a cyst that careful re-examination of the breast at the time and again 4 weeks later is carried out. Should a lump persist or recur we believe that mammography is indicated and a decision is then taken as to whether repeat aspiration or excision biopsy should be undertaken. References ATKlNs H. (1952) Pain in the breast. Laricer 1, 271-274. FORREST A. P. M. (1974) Primary cancer of the breast: indication for therapy. In: ATKINS H. (ed.) The Treatnient of’ Breast
Cancer. Lancaster, MTP, p. 32.
and ROBERTS M. M. (1975) Needle aspiration of breast cysts. B. Meti. J. 3, 30-31. GASPAR M. R. (1961) Aspiration of breast cysts. Calif. Med. 95, 227-231. GATCHELL F. c., DOCKERTY M. B. and CLAGETT 0. T. (1958) Intracystic carcinoma of the breast. Siirg. Gynecol. Obstet. 106, 347-352. KALISHER L. (1977) Intracystic carcinoma of the breast. Breast 3 , 32-33. KEYNES hi. (1966) Lumps in the breast. (Letter to the Editor.) Br. Med. J. 2, 235. PATEY D. H. and NURICK A. W. (1953) Natural history of cystic disease of the breast treated conservatively. Br. Med. J. 1, 15-17. RIMSTEN A., STENKVIST B., JOHANSON H. et al. (1975) The diagnostic accuracy of palpation and fine-needle biopsy and an evaluation of their combined use in the diagnosis of breast lesions. Ann. Surg. 182, 1-8. ROSEMOND G. P., BURNETT w. E., CASWELL H. T. et al. (195s) Aspiration of breast cysts as a diagnostic and therapeutic measure. Arch. Surg. 71,223-229. ROSEMOND G. P., MAIER w. P. and BROBYN T. J. (1977) Needle aspiration of breast cysts. J. Family Prnctice 4, 11571160. ROTH J. A,, FEINBERG M. and MCAVOY J. M. (1977) Carcinoma arising in the wall of a breast cyst during pregnancy. Ann. Surg. 185, 247-250. SCHNUG E. 0. and CAVANAGH c. R. (1966) Aspiration in the management of recurrent cysts of the breast. Surg. Gynecol. Obstet. 122, 355-357. V A N BOCAERT L. G. and MAZY G. (1977) Reliability of the cytoradio-clinical triplet in breast pathology diagnosis. Acra Cytol. 21, 60-62. FORREST A. P. M., KIRKPATRICK 3. R.
Paper accepted 17 July 1978.
