- Email: [email protected]
Pure mucinous carcinoma of the breast
The American Journal of Surgery 187 (2004) 528 –532
Scientific paper
Pure mucinous carcinoma of the breast Ian K. Komenaka, M.D., Mahmoud B. El-Tamer, M.D., F.A.C.S.*, Andrea Troxel, Sc.D., Diane Hamele-Bena, M.D., Kathie-Ann Joseph, M.D., M.P.H., Elizabeth Horowitz, R-P.A.C., Beth-Ann Ditkoff, M.D., F.A.C.S., Freya R. Schnabel, M.D., F.A.C.S. Columbia–Presbyterian Medical Center, Columbia University Breast Center, Atchley Pavilion, 10th Floor, 161 Fort Washington Avenue, New York, NY 10032, USA Manuscript received May 2, 2003; revised manuscript October 17, 2003
Abstract Background: The lack of a standard definition of “pure” mucinous carcinoma of the breast has made it difficult to compare data from different studies. This study used the most stringent criteria to define parameters for truly pure lesions. Methods: Sixty-five patients were identified. The database was used to evaluate patients’ demographics, tumor characteristics, and outcomes. Survival curves and predictors of survival were analyzed. Results: The mean age of presentation was 67 years. The majority (96%) of patients presented with early-stage disease. The 5- and 10-year overall survival rates were 93.6% and 72.8%, respectively. The number of involved axillary lymph nodes was the only significant predictor of death (P ⫽ 0.02). Conclusions: Pure mucinous carcinoma of the breast has a favorable prognosis. Tumor size does not appear to impact survival, perhaps because the volume of mucin overestimates tumor burden. The number of involved axillary lymph nodes was the only significant predictor of death from disease. © 2004 Excerpta Medica, Inc. All rights reserved. Keywords: Breast cancer; Mucinous carcinoma; Pure
Although it was first described in 1826, mucinous carcinoma of the breast has remained one of the uncommon pathologic findings [1]. The reported incidence of mucinous carcinoma has varied between 1% and 6% of all breast malignancies [2]. Initially, any breast malignancy containing a mucinous component was classified as mucinous carcinoma. Early reviews of the subtype demonstrated differing prognoses: some studies showed a remarkably good prognosis, whereas others showed survival lasting only a few years after diagnosis [3,4]. Following these descriptions, Lee et al. [5] recognized that mucinous malignancies could be separated into two subtypes. They found that the prognosis for “pure” lesions, with a predominant mucinous component, was much better than for the “mixed” histology, which displayed a more prominent invasive epithelial component. Silverberg et al. [4] were the first to quantify the cellularity of the lesions as a method of classifying the two groups. Mucinous carcinoma was defined as having a mu-
* Corresponding author. Tel.: ⫹1-212-305-0728; fax: ⫹1-212-305-0727. E-mail address: [email protected]
cinous component of at least 50%. Since the segregation was made, a standard threshold for clear distinction has never been defined for pure mucinous carcinoma. Some classifications have used that terminology when only 25% of the invasive disease displayed the mucinous component, whereas others required a near-100% mucinous component [6 –9]. Furthermore, because a large percentage of patients with mixed mucinous carcinoma have high-grade nuclei and poorly differentiated cells, some classifications place mixed lesions in the same group with infiltrating ductal carcinoma not otherwise specified [6,10]. The lack of a standard definition of pure mucinous carcinoma has made it difficult to compare and combine data from different studies. We present an 18-year review of 65 cases from a single institution. We kept the most stringent criteria for inclusion in our study by requiring a mucinous component an at least 90%. In addition, the tumors in which the nonmucinous invasive component displayed a high cytologic nuclear grade were excluded [11]. Our strict parameters were used in the hope of defining parameters for truly pure lesions.
0002-9610/04/$ – see front matter © 2004 Excerpta Medica, Inc. All rights reserved. doi:10.1016/j.amjsurg.2003.12.039
I.K. Komenaka et al. / The American Journal of Surgery 187 (2004) 528 –532
Methods The patients reviewed were from the Columbia University–Presbyterian Medical Center tumor registry database. The database was queried for patients spanning the period from 1980 to 1998. A total of 128 patients with the diagnosis of “mucinous carcinoma” of the breast were identified. The slides of the patients were then pulled and reviewed by one of the breast pathologists (D.H.B.). Only patients with tumors composed of at least 90% mucin were included in the study population. Furthermore, according to the criteria defined by Rosen [11], lesions could not display high-grade histologic features to be considered a pure mucinous carcinoma. Based on this definition, 65 of the 128 patients were determined to have pathology consistent with pure mucinous carcinoma of the breast. The database was used to evaluate a large set of data fields including patients’ demographics, tumor characteristics (biologic markers, tumor size, grade, stage, and nodal status), and follow-up information including status of vital signs and cause of death. Statistical analysis Tests for association among discrete variables used chisquare or Fisher’s Exact tests as appropriate. Continuous variables were compared using the Student t test. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test; predictors of survival were evaluated using the Cox proportional hazards model. Logistic regression was used to determine the predictors of overall survival and disease-specific survival at 5 and 10 years.
529
had breast-preservation surgery, 25 had radiation therapy. The 11 patients who did not undergo radiation were part of the 15 patients who also did not undergo axillary node dissection as previously described. Ten did not have radiation therapy because of advanced age, significant comorbidities, or both. The one remaining patient who did not undergo radiation therapy after lumpectomy was the 39year-old patient described previously who also did not have an axillary dissection. This patient was lost to follow-up. The majority of patients (96%) presented with earlystage disease. Sixty-two percent presented at stage I (40 of 65), and 33% presented at stage II (22 of 65). Very few patients had advanced disease at diagnosis; one patient presented at stage III and one at stage IV (Fig. 1). Regarding adjuvant therapy, 8 of 65 had chemotherapy, and 28 of 65 had hormonal therapy. Estrogen and progesterone receptors were positive in 91% and 79% of tumors, respectively. Median follow-up was 54 months (range 1 to 195). The 5- and 10-year disease-free survival rates were 81% and 54%, respectively (Fig. 2). Of the 65 patients, 48 patients survived, eight died, and nine were lost to follow-up. The 5and 10-year overall survival rates were 93.6% and 72.8%, respectively (Fig. 3). Of the eight patients who died, mortality was related to breast cancer in four (50%), to other cancers in one (12%), and to other non– cancer-related causes in three patients (38%). The 5- and 10-year diseasespecific survival rates were 95.3% and 79.4%, respectively (Fig. 4). Cox proportional hazards method determined that the number of involved axillary lymph nodes was the only significant predictor of death from disease (P ⫽ 0.02).
Comments Results From 1980 to 1998, a total of 7,676 patients were identified in the database. Of these, 65 were considered to have pure mucinous carcinomas when the diagnosis was limited to ⬎90% mucinous component. This represented 0.8% of breast cancer cases. All of the patients were women, of which 85% (55 of 65) were postmenopausal at the time of diagnosis. The mean age at presentation was 67 years (range 31 to 93). The laterality of the lesions was 52% (34 of 65) right-sided and 48% (31 of 65) left-sided. The median pathologic size was 1.8 cm in diameter (range 0.3 to 12). Microcalcifications were present in 18% (12 of 65) of the specimens. Mastectomy was performed on 29 patients (45%), and the remaining patients underwent breast-conservation operations (55%). Fifty patients (77%) underwent axillary node dissection. Of these, 14% had positive nodes (7 of 50). Of the 15 patients who did not have an axillary dissection, 13 did not have the procedure because of advanced age, significant comorbidities, or both. The remaining two patients who did not undergo axillary dissections were age 39 and 59 years and had well-differentiated lesions of 1.8 cm and 0.5 cm, respectively. Of the 36 patients who
The incidence of pure mucinous carcinoma of the breast at our institution was 0.8% (65 of 7,676), which falls just below the range of 1% to 6% commonly reported in the literature [2]. The low incidence at our center is not surprising considering our rigid inclusion criteria. If we had used less-stringent criteria, the incidence would have been 1.7% (128 of 7,676). The majority of patients (96%) presented at stage I or II. This finding supports previous hypotheses that the lesion displays indolent behavior [3]. Of the 65 patients, the physical examination findings were known in 42 patients. Of these, 29 (69%) were reported to have had palpable lesions at presentation. The median size of the palpable lesions was 2 cm, whereas the median size of all 65 tumors was 1.8 cm. Therefore, more of these lesions were likely palpable. This is likely a higher percentage than found in most other breast malignancy subgroups. Occasionally very large lesions, up to 19 cm, have been described [12]. Presumably one of the reasons may be that its mucinous content does not feel solid or firm on examination. According to the statistical analysis, however, the size of the lesion was not a significant prognostic factor in our patients. This finding should not be surprising because
530
I.K. Komenaka et al. / The American Journal of Surgery 187 (2004) 528 –532
Fig. 1. Stage at presentation.
mucin comprised a majority of the tumor volume. Subsequently, the size can become very large and potentially not impact survival. The tumor size in the traditional TNM staging criteria may therefore not be as significant a factor as for other histologic subgroups. The mean age of diagnosis in our study was 67 years. This is in agreement with
previous reviews of mucinous carcinoma but older than mean age for the overall breast cancer population. The majority of patients presented with palpable disease, perhaps a reflection of delayed presentation. Another reason for the possible presentation as palpable disease may arise in the interpretation of the imaging of these lesions. Only
Fig. 2. Kaplan-Meier disease-free survival rate for the 65 patients.
I.K. Komenaka et al. / The American Journal of Surgery 187 (2004) 528 –532
531
Fig. 3. Kaplan-Meier overall survival curve for the 65 patients.
one third of the mucinous lesions in a recent series had microcalcifications [2]. Our series showed a similarly low percentage with only 18% showing microcalcifications. The large quantity of mucin may preclude detection of suspicious mammographic findings such as microcalcifications. The reason for this finding is unclear. It is possible that the development of microcalcifications in these lesions is an infrequent or late phenomenon. Another possibility is that mucin production disperses the microcalcifications, thus causing them to appear less clustered than in solid lesions. Furthermore, many of the series reported were published before the 1980s, a time when screening mammography was not as widely used by the general public. The most common mammographic appearance, on retrospective review, is a lesion with well-circumscribed margins [13]. This finding may mislead physicians to a benign impression. The combination of a relatively unsuspicious mammography film and soft findings on physical examination may increase the incidence of delayed diagnosis.
These tumors also had a high proportion of expression of hormone receptors; estrogen receptors and progesterone receptors were positive in 91% and 79% of tumors, respectively. The high rate of hormone receptor expression suggested a good prognosis and was likely related to advanced age at presentation as well as our rigid definition of pure mucinous carcinoma of the breast. Modified radical mastectomy was the surgical operation used in 45% of patients. The majority of these operations, however, were performed earlier in the reviewed period when mastectomy was still the preferred surgical option. There was a trend toward breast conservation in more recent patients. Just as size of the tumor was not a significant prognostic factor, the extent of surgery also did not influence survival. Adjuvant therapy was given sporadically. For this reason it was difficult to assess its contribution to the management of these patients. The numbers were too small to derive any statistically significant conclusions, and there did not appear to be any trends toward increased survival.
Fig. 4. Kaplan-Meier disease-specific survival rate for the 65 patients.
532
I.K. Komenaka et al. / The American Journal of Surgery 187 (2004) 528 –532
Positive lymph nodes were found in 7 of 50 patients (14%). Using the Cox proportional hazards method, the number of involved lymph nodes was the only predictor of disease-specific survival in our series. This finding has been supported by those of other series [2,6]. The overall survival and disease-specific survival rates at five and 10 years were very favorable. These findings seem to indicate an optimistic prognosis. One study, however, suggested that recurrences tend to occur after 10 years [8]. This review of 53 patients showed an eight-year median time to develop distant metastasis. The median survival of those who died from their carcinoma was 11.3 years. The fact that the tumor displays the ability for late recurrence indicates that despite its indolent local behavior, it may become systemic before surgical intervention is undertaken. The systemic microscopic disease may also display indolent behavior, which is reflective of the local behavior of the primary lesion. As a result, it appears to require longer time periods to proliferate and manifest clinically. This could explain its propensity for late recurrences. Median follow-up for our patients was 54 months, and only a fraction had presented ⬎10 years ago. The disease-free survival curve (Fig. 2) seemed to show a trend downward around the 10-year mark. This finding supports the hypothesis that pure mucinous cancers are indolent tumors, which take longer to recur than other invasive cancers of the breast. For this reason we may have not yet seen a number of the late recurrences. As these patients pass beyond the 10-year follow-up point, their findings will likely contribute further to our understanding of the management and natural history of this uncommon malignancy. Conclusion Pure mucinous carcinoma of the breast has a favorable prognosis. Tumor size does not appear to significantly im-
pact survival, perhaps because the large volume of mucin may lead to overestimation of tumor burden. The number of involved axillary lymph nodes was the only significant predictor of death from disease.
References [1] Geschickter CF. Gelatinous mammary cancer. Ann Surg 1938;108: 321– 46. [2] Andre S, Cunha F, Bernardo M, et al. Mucinous carcinoma of the breast: a pathologic study of 82 cases. J Surg Oncol 1995;58(3): 162–7. [3] Cheatle GL, Cutler M. Gelatinous carcinoma of the breast. Arch Surg 1930;20:569 –90. [4] Silverberg SG, Kay S, Chitale AR, et al. Colloid carcinoma of the breast. Am J Clin Pathol 1971;55(3):355– 63. [5] Lee BJ, Hauser H, Pack GT. Gelatinous carcinoma of the breast. Surg Gynecol Obstet 1934;59:841–57. [6] Rasmussen BB. Human mucinous breast carcinomas and their lymph node metastases. A histological review of 247 cases. Pathol Res Pract 1985;180(4):377– 82. [7] Capella C, Eusebi V, Mann B, et al. Endocrine differentiation in mucoid carcinoma of the breast. Histopathology 1980;4(6):613–30. [8] Clayton F. Pure mucinous carcinomas of breast: morphologic features and prognostic correlates. Hum Pathol 1986;17(1):34 – 8. [9] Norris HJ, Taylor HB. Prognosis of mucinous (gelatinous) carcinoma of the breast. Cancer 1965;18:879 – 85. [10] Fisher ER, Gregorio RM, Fisher B, et al. The pathology of invasive breast cancer. A syllabus derived from findings of the National Surgical Adjuvant Breast Project (protocol no. 4). Cancer 1975;36(1): 1– 85. [11] Rosen PP. Mucinous carcinoma. In: Rosen PP, editor. Rosen’s Breast Pathology. 2nd ed. Philadelphia, PA: Lippincott, 2001, p 463– 81. [12] Koenig C, Tavassoli FA. Mucinous cystadenocarcinoma of the breast. Am J Surg Pathol 1998;22(6):698 –703. [13] Wilson TE, Helvie MA, Oberman HA, et al. Pure and mixed mucinous carcinoma of the breast: pathologic basis for differences in mammographic appearance. Am J Roentgenol 1995;165(2):285–9.
Scientific paper
Pure mucinous carcinoma of the breast Ian K. Komenaka, M.D., Mahmoud B. El-Tamer, M.D., F.A.C.S.*, Andrea Troxel, Sc.D., Diane Hamele-Bena, M.D., Kathie-Ann Joseph, M.D., M.P.H., Elizabeth Horowitz, R-P.A.C., Beth-Ann Ditkoff, M.D., F.A.C.S., Freya R. Schnabel, M.D., F.A.C.S. Columbia–Presbyterian Medical Center, Columbia University Breast Center, Atchley Pavilion, 10th Floor, 161 Fort Washington Avenue, New York, NY 10032, USA Manuscript received May 2, 2003; revised manuscript October 17, 2003
Abstract Background: The lack of a standard definition of “pure” mucinous carcinoma of the breast has made it difficult to compare data from different studies. This study used the most stringent criteria to define parameters for truly pure lesions. Methods: Sixty-five patients were identified. The database was used to evaluate patients’ demographics, tumor characteristics, and outcomes. Survival curves and predictors of survival were analyzed. Results: The mean age of presentation was 67 years. The majority (96%) of patients presented with early-stage disease. The 5- and 10-year overall survival rates were 93.6% and 72.8%, respectively. The number of involved axillary lymph nodes was the only significant predictor of death (P ⫽ 0.02). Conclusions: Pure mucinous carcinoma of the breast has a favorable prognosis. Tumor size does not appear to impact survival, perhaps because the volume of mucin overestimates tumor burden. The number of involved axillary lymph nodes was the only significant predictor of death from disease. © 2004 Excerpta Medica, Inc. All rights reserved. Keywords: Breast cancer; Mucinous carcinoma; Pure
Although it was first described in 1826, mucinous carcinoma of the breast has remained one of the uncommon pathologic findings [1]. The reported incidence of mucinous carcinoma has varied between 1% and 6% of all breast malignancies [2]. Initially, any breast malignancy containing a mucinous component was classified as mucinous carcinoma. Early reviews of the subtype demonstrated differing prognoses: some studies showed a remarkably good prognosis, whereas others showed survival lasting only a few years after diagnosis [3,4]. Following these descriptions, Lee et al. [5] recognized that mucinous malignancies could be separated into two subtypes. They found that the prognosis for “pure” lesions, with a predominant mucinous component, was much better than for the “mixed” histology, which displayed a more prominent invasive epithelial component. Silverberg et al. [4] were the first to quantify the cellularity of the lesions as a method of classifying the two groups. Mucinous carcinoma was defined as having a mu-
* Corresponding author. Tel.: ⫹1-212-305-0728; fax: ⫹1-212-305-0727. E-mail address: [email protected]
cinous component of at least 50%. Since the segregation was made, a standard threshold for clear distinction has never been defined for pure mucinous carcinoma. Some classifications have used that terminology when only 25% of the invasive disease displayed the mucinous component, whereas others required a near-100% mucinous component [6 –9]. Furthermore, because a large percentage of patients with mixed mucinous carcinoma have high-grade nuclei and poorly differentiated cells, some classifications place mixed lesions in the same group with infiltrating ductal carcinoma not otherwise specified [6,10]. The lack of a standard definition of pure mucinous carcinoma has made it difficult to compare and combine data from different studies. We present an 18-year review of 65 cases from a single institution. We kept the most stringent criteria for inclusion in our study by requiring a mucinous component an at least 90%. In addition, the tumors in which the nonmucinous invasive component displayed a high cytologic nuclear grade were excluded [11]. Our strict parameters were used in the hope of defining parameters for truly pure lesions.
0002-9610/04/$ – see front matter © 2004 Excerpta Medica, Inc. All rights reserved. doi:10.1016/j.amjsurg.2003.12.039
I.K. Komenaka et al. / The American Journal of Surgery 187 (2004) 528 –532
Methods The patients reviewed were from the Columbia University–Presbyterian Medical Center tumor registry database. The database was queried for patients spanning the period from 1980 to 1998. A total of 128 patients with the diagnosis of “mucinous carcinoma” of the breast were identified. The slides of the patients were then pulled and reviewed by one of the breast pathologists (D.H.B.). Only patients with tumors composed of at least 90% mucin were included in the study population. Furthermore, according to the criteria defined by Rosen [11], lesions could not display high-grade histologic features to be considered a pure mucinous carcinoma. Based on this definition, 65 of the 128 patients were determined to have pathology consistent with pure mucinous carcinoma of the breast. The database was used to evaluate a large set of data fields including patients’ demographics, tumor characteristics (biologic markers, tumor size, grade, stage, and nodal status), and follow-up information including status of vital signs and cause of death. Statistical analysis Tests for association among discrete variables used chisquare or Fisher’s Exact tests as appropriate. Continuous variables were compared using the Student t test. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test; predictors of survival were evaluated using the Cox proportional hazards model. Logistic regression was used to determine the predictors of overall survival and disease-specific survival at 5 and 10 years.
529
had breast-preservation surgery, 25 had radiation therapy. The 11 patients who did not undergo radiation were part of the 15 patients who also did not undergo axillary node dissection as previously described. Ten did not have radiation therapy because of advanced age, significant comorbidities, or both. The one remaining patient who did not undergo radiation therapy after lumpectomy was the 39year-old patient described previously who also did not have an axillary dissection. This patient was lost to follow-up. The majority of patients (96%) presented with earlystage disease. Sixty-two percent presented at stage I (40 of 65), and 33% presented at stage II (22 of 65). Very few patients had advanced disease at diagnosis; one patient presented at stage III and one at stage IV (Fig. 1). Regarding adjuvant therapy, 8 of 65 had chemotherapy, and 28 of 65 had hormonal therapy. Estrogen and progesterone receptors were positive in 91% and 79% of tumors, respectively. Median follow-up was 54 months (range 1 to 195). The 5- and 10-year disease-free survival rates were 81% and 54%, respectively (Fig. 2). Of the 65 patients, 48 patients survived, eight died, and nine were lost to follow-up. The 5and 10-year overall survival rates were 93.6% and 72.8%, respectively (Fig. 3). Of the eight patients who died, mortality was related to breast cancer in four (50%), to other cancers in one (12%), and to other non– cancer-related causes in three patients (38%). The 5- and 10-year diseasespecific survival rates were 95.3% and 79.4%, respectively (Fig. 4). Cox proportional hazards method determined that the number of involved axillary lymph nodes was the only significant predictor of death from disease (P ⫽ 0.02).
Comments Results From 1980 to 1998, a total of 7,676 patients were identified in the database. Of these, 65 were considered to have pure mucinous carcinomas when the diagnosis was limited to ⬎90% mucinous component. This represented 0.8% of breast cancer cases. All of the patients were women, of which 85% (55 of 65) were postmenopausal at the time of diagnosis. The mean age at presentation was 67 years (range 31 to 93). The laterality of the lesions was 52% (34 of 65) right-sided and 48% (31 of 65) left-sided. The median pathologic size was 1.8 cm in diameter (range 0.3 to 12). Microcalcifications were present in 18% (12 of 65) of the specimens. Mastectomy was performed on 29 patients (45%), and the remaining patients underwent breast-conservation operations (55%). Fifty patients (77%) underwent axillary node dissection. Of these, 14% had positive nodes (7 of 50). Of the 15 patients who did not have an axillary dissection, 13 did not have the procedure because of advanced age, significant comorbidities, or both. The remaining two patients who did not undergo axillary dissections were age 39 and 59 years and had well-differentiated lesions of 1.8 cm and 0.5 cm, respectively. Of the 36 patients who
The incidence of pure mucinous carcinoma of the breast at our institution was 0.8% (65 of 7,676), which falls just below the range of 1% to 6% commonly reported in the literature [2]. The low incidence at our center is not surprising considering our rigid inclusion criteria. If we had used less-stringent criteria, the incidence would have been 1.7% (128 of 7,676). The majority of patients (96%) presented at stage I or II. This finding supports previous hypotheses that the lesion displays indolent behavior [3]. Of the 65 patients, the physical examination findings were known in 42 patients. Of these, 29 (69%) were reported to have had palpable lesions at presentation. The median size of the palpable lesions was 2 cm, whereas the median size of all 65 tumors was 1.8 cm. Therefore, more of these lesions were likely palpable. This is likely a higher percentage than found in most other breast malignancy subgroups. Occasionally very large lesions, up to 19 cm, have been described [12]. Presumably one of the reasons may be that its mucinous content does not feel solid or firm on examination. According to the statistical analysis, however, the size of the lesion was not a significant prognostic factor in our patients. This finding should not be surprising because
530
I.K. Komenaka et al. / The American Journal of Surgery 187 (2004) 528 –532
Fig. 1. Stage at presentation.
mucin comprised a majority of the tumor volume. Subsequently, the size can become very large and potentially not impact survival. The tumor size in the traditional TNM staging criteria may therefore not be as significant a factor as for other histologic subgroups. The mean age of diagnosis in our study was 67 years. This is in agreement with
previous reviews of mucinous carcinoma but older than mean age for the overall breast cancer population. The majority of patients presented with palpable disease, perhaps a reflection of delayed presentation. Another reason for the possible presentation as palpable disease may arise in the interpretation of the imaging of these lesions. Only
Fig. 2. Kaplan-Meier disease-free survival rate for the 65 patients.
I.K. Komenaka et al. / The American Journal of Surgery 187 (2004) 528 –532
531
Fig. 3. Kaplan-Meier overall survival curve for the 65 patients.
one third of the mucinous lesions in a recent series had microcalcifications [2]. Our series showed a similarly low percentage with only 18% showing microcalcifications. The large quantity of mucin may preclude detection of suspicious mammographic findings such as microcalcifications. The reason for this finding is unclear. It is possible that the development of microcalcifications in these lesions is an infrequent or late phenomenon. Another possibility is that mucin production disperses the microcalcifications, thus causing them to appear less clustered than in solid lesions. Furthermore, many of the series reported were published before the 1980s, a time when screening mammography was not as widely used by the general public. The most common mammographic appearance, on retrospective review, is a lesion with well-circumscribed margins [13]. This finding may mislead physicians to a benign impression. The combination of a relatively unsuspicious mammography film and soft findings on physical examination may increase the incidence of delayed diagnosis.
These tumors also had a high proportion of expression of hormone receptors; estrogen receptors and progesterone receptors were positive in 91% and 79% of tumors, respectively. The high rate of hormone receptor expression suggested a good prognosis and was likely related to advanced age at presentation as well as our rigid definition of pure mucinous carcinoma of the breast. Modified radical mastectomy was the surgical operation used in 45% of patients. The majority of these operations, however, were performed earlier in the reviewed period when mastectomy was still the preferred surgical option. There was a trend toward breast conservation in more recent patients. Just as size of the tumor was not a significant prognostic factor, the extent of surgery also did not influence survival. Adjuvant therapy was given sporadically. For this reason it was difficult to assess its contribution to the management of these patients. The numbers were too small to derive any statistically significant conclusions, and there did not appear to be any trends toward increased survival.
Fig. 4. Kaplan-Meier disease-specific survival rate for the 65 patients.
532
I.K. Komenaka et al. / The American Journal of Surgery 187 (2004) 528 –532
Positive lymph nodes were found in 7 of 50 patients (14%). Using the Cox proportional hazards method, the number of involved lymph nodes was the only predictor of disease-specific survival in our series. This finding has been supported by those of other series [2,6]. The overall survival and disease-specific survival rates at five and 10 years were very favorable. These findings seem to indicate an optimistic prognosis. One study, however, suggested that recurrences tend to occur after 10 years [8]. This review of 53 patients showed an eight-year median time to develop distant metastasis. The median survival of those who died from their carcinoma was 11.3 years. The fact that the tumor displays the ability for late recurrence indicates that despite its indolent local behavior, it may become systemic before surgical intervention is undertaken. The systemic microscopic disease may also display indolent behavior, which is reflective of the local behavior of the primary lesion. As a result, it appears to require longer time periods to proliferate and manifest clinically. This could explain its propensity for late recurrences. Median follow-up for our patients was 54 months, and only a fraction had presented ⬎10 years ago. The disease-free survival curve (Fig. 2) seemed to show a trend downward around the 10-year mark. This finding supports the hypothesis that pure mucinous cancers are indolent tumors, which take longer to recur than other invasive cancers of the breast. For this reason we may have not yet seen a number of the late recurrences. As these patients pass beyond the 10-year follow-up point, their findings will likely contribute further to our understanding of the management and natural history of this uncommon malignancy. Conclusion Pure mucinous carcinoma of the breast has a favorable prognosis. Tumor size does not appear to significantly im-
pact survival, perhaps because the large volume of mucin may lead to overestimation of tumor burden. The number of involved axillary lymph nodes was the only significant predictor of death from disease.
References [1] Geschickter CF. Gelatinous mammary cancer. Ann Surg 1938;108: 321– 46. [2] Andre S, Cunha F, Bernardo M, et al. Mucinous carcinoma of the breast: a pathologic study of 82 cases. J Surg Oncol 1995;58(3): 162–7. [3] Cheatle GL, Cutler M. Gelatinous carcinoma of the breast. Arch Surg 1930;20:569 –90. [4] Silverberg SG, Kay S, Chitale AR, et al. Colloid carcinoma of the breast. Am J Clin Pathol 1971;55(3):355– 63. [5] Lee BJ, Hauser H, Pack GT. Gelatinous carcinoma of the breast. Surg Gynecol Obstet 1934;59:841–57. [6] Rasmussen BB. Human mucinous breast carcinomas and their lymph node metastases. A histological review of 247 cases. Pathol Res Pract 1985;180(4):377– 82. [7] Capella C, Eusebi V, Mann B, et al. Endocrine differentiation in mucoid carcinoma of the breast. Histopathology 1980;4(6):613–30. [8] Clayton F. Pure mucinous carcinomas of breast: morphologic features and prognostic correlates. Hum Pathol 1986;17(1):34 – 8. [9] Norris HJ, Taylor HB. Prognosis of mucinous (gelatinous) carcinoma of the breast. Cancer 1965;18:879 – 85. [10] Fisher ER, Gregorio RM, Fisher B, et al. The pathology of invasive breast cancer. A syllabus derived from findings of the National Surgical Adjuvant Breast Project (protocol no. 4). Cancer 1975;36(1): 1– 85. [11] Rosen PP. Mucinous carcinoma. In: Rosen PP, editor. Rosen’s Breast Pathology. 2nd ed. Philadelphia, PA: Lippincott, 2001, p 463– 81. [12] Koenig C, Tavassoli FA. Mucinous cystadenocarcinoma of the breast. Am J Surg Pathol 1998;22(6):698 –703. [13] Wilson TE, Helvie MA, Oberman HA, et al. Pure and mixed mucinous carcinoma of the breast: pathologic basis for differences in mammographic appearance. Am J Roentgenol 1995;165(2):285–9.