Non-primary breast malignancies: a single institution’s experience of a diagnostic challenge with important therapeutic consequences—a retrospective study
- Florian E. Buisman†1, 2Email author,
- Linda van Gelder†1,
- Marian B. E. Menke-Pluijmers1,
- Bob H. C. Bisschops3,
- Peter W. Plaisier1 and
- Pieter J. Westenend4
© The Author(s). 2016
Received: 8 September 2015
Accepted: 15 June 2016
Published: 23 June 2016
Breast cancer is a common malignancy, but metastases to the breast of extramammary malignancies are very rare. Treatment and prognosis are different. The aim of the study is to report the incidence of lymphomas and metastases to the breast of extramammary malignancies in our 30-year archive.
The pathology database of a single institute was reviewed for all breast neoplasms which were coded in our system as a metastasis in the period 1985–2014. Metastatic tumors from primary breast carcinoma were excluded.
A total of 47 patients were included (7 men/40 women, mean age 63 years). The majority originated from lymphoma (n = 18) and primary melanoma (n = 11). Other primary tumor sites included the ovary (n = 6), lung (n = 6), colon (n = 3), kidney (n = 1), stomach (n = 1), and chorion (n = 1). In 24/47 patients (51 %), metastasis was the first sign of the specific malignant disease. In seven patients (15 %) surgery was performed, the diagnosis of metastatic disease was adjusted in four patients (9 %) postoperatively.
It is important to distinguish lymphomas and metastases to the breast from common primary breast carcinoma for proper treatment and prognosis. Therefore, we emphasize the need for a histological or cytopathological diagnosis before any treatment is commenced. The pathologist plays a key role in considering the diagnosis of metastasis if the histological features are unusual for a primary breast carcinoma. The pathologist should therefore be properly informed by the clinical physician although lymphomas and metastases to the breast are the first presentation of malignant disease in half the cases.
Metastases from extramammary malignant neoplasms are very rare, since they account for less than 2 % of all breast malignancies . In general, symptoms are similar in those of primary mammary carcinoma, including palpable relatively well-circumscribed and freely movable masses within the breast, pain, tenderness, and inflammation. Non primary breast malignancies are generally well defined and rounded, and calcification is unusual. On mammography, these lesions can be mistaken for benign (fibroadenoma) as well as primary breast malignancies [1, 2].
Metastasis from many extramammary neoplasms have been described, such as lymphomas, malignant melanoma, carcinomas of the lung, ovary, prostate, kidney, stomach, small bowel, large bowel, thyroid, cervix, and soft tissues [1, 3–8].
Distinction of metastases to the breast from extramammary neoplasms from primary breast neoplasms is important for determining the best management. In patients with metastatic disease, a systemic and palliative approach is usually more effective. Moreover, correct diagnosis may prevent unnecessary surgery. The aim of this study is to report the incidence of lymphomas and metastases to the breast of extramammary malignancies in our 30-year archive.
The pathology database of a single institute was used to identify all breast neoplasms which were coded in our system as a metastasis in the period of 30 years (1985–2014). Each case was retrospectively reviewed by an experienced pathologist in order to determine whether or not the malignancy was rightly coded as non primary breast malignancy. We also included secondary metastases from leukemia-lymphomas to the breast. For all patients, histological reports were reviewed to determine the primary site of the tumor. We reviewed the first manifestation of the primary tumor. Patients with metastatic tumors from primary (contralateral) breast carcinoma were excluded. Additional data were obtained from the hospital electronic record system, retrospectively.
Number of patients (%)
Time interval diagnosis: primary neoplasm metastasis (incl. lymphomas)
Known malignant disease (incl. lymphomas)
Number of patients (%)
No history of primary malignant disease
24 (51 %)
History of primary malignant disease
23 (49 %)
Histology of breast metastases
Number of patients (%)
Interval (months): primary-secondary (mean)
18 (38.3 %)
11 (23.4 %)
No primary site
Primary side detected
6 (12.8 %)
No history of ovarian carcinoma
History of ovarian carcinoma
6 (12.8 %)
No history of lung carcinoma
History of lung carcinoma
Adenocarcinoma of the colon
3 (6.4 %)
No history of colon carcinoma
History of colon carcinoma
Renal cell carcinoma
1 (2.1 %)
No history of renal cell carcinoma
History of renal cell carcinoma
Adenocarcinoma of the stomach
1 (2.1 %)
No history of stomach carcinoma
History of stomach carcinoma
1 (2.1 %)
No history of choriocarcinoma
History of choriocarcinoma
47 (100 %)
Type of diagnostics and surgery
Final diagnosis after surgery
- Lymphoma (n = 1)
- Melanoma (n = 1)
- Ovarian carcinoma (n = 1): palliative resectiona
Fine needle aspiration
- Melanoma (n = 2): palliative resectiona
- Colon carcinoma (n = 1)
- Ovarian carcinoma (n = 1)
Breast metastases of extramammary neoplasms are extremely rare. In our laboratory, we found a total of 47 patients with metastases to the breast from non mammary primary in a 30-year period, representing an incidence of approximately 0.5 %. In our study, lymphomas and melanomas were the most prevalent primary neoplasms (38 and 23 %, respectively), which is in accordance with previous reported studies [1, 2, 4, 9]. Lee et al. reported gastric cancers to be the most common metastases to the breast. However, gastric carcinoma is the most common form of cancer in Korea and the incidence of melanoma is much lower .
In our study, patients with breast metastases presented with a mean of 39 months after diagnoses of primary cancer. Patients with primary melanomas presented with the largest time interval between primary presentation and breast metastases with a mean of 66 months, probably reflecting the well-known natural history of melanoma with a subgroup showing late recurrence. Lee et al. reported a mean time interval of 14 months, but this difference in interval might be explained by the larger amount of melanomas included in our study (23 vs 6 %) .
In this study, in four patients (9 %), the diagnosis had to be corrected postoperatively. This percentage seems poor; however, it should be considered that diagnosis of extramammary metastasis to the breast is difficult not only because clinical presentation may be similar to primary breast malignancies but also because it may be the first presentation of unknown metastatic disease. In addition, the diagnosis is hard to make on cytology alone. Obviously, proper clinical information may be helpful and should be provided to the pathologist at all times.
Histological diagnosis is important to distinguish metastases to the breast from common primary breast carcinoma for effective treatment and direct attention to the extramammary primary, and in case of metastases to the breast prevent unnecessary surgery. Lee et al. reviewed histological and immunohistochemical features that are useful in the diagnosis of metastases to the breast. They discovered that about a third of the lesions do not show specific histological features. Elastosis and carcinoma in situ are common histological characteristics in primary mammary cancers. Different types of carcinoma are suggestive for specific origins, such as clear cell carcinoma for renal origin, small cell carcinoma of pulmonary origin, and papillary carcinoma of ovarian serous papillary carcinoma. For malignant melanomas, the appearance of cytoplasmic pigment, intranuclear inclusions, and spindle cells may be useful clues .
Sensitive markers for specific metastases, these markers are negative in breast cancer
Lung small cell carcinoma
Pax-8, WT1, Ca 125
Malignant B cell lymphoma
Renal cell carcinoma
Several authors emphasized the usages of fine-needle cytology [16–19]. Fulciniti et al. emphasized the usage of cytopathological criteria in combination with immunocytochemistry when considering the diagnosis of metastases to the breast . As stated before, diagnosis of metastases to the breast of non primary breast malignancies should be performed by a combination of clinical presentation and evaluation of the pathology and specific antibodies.
It is concluded that although metastases to the breast are rare, it should be considered in the differential diagnosis of breast cancer if the morphology is unusual for primary breast malignancies and if there is a history of a prior (treated) malignancy, in order to avoid unnecessary surgery.
Ca 125, cancer antigen 125; CD56, cluster of differentiation 56; CD79a, cluster of differentiation 79a; CDX2, cluster of differentiation X2; CK20, cytokeratin 20; GCDFP-15, gross cystic disease fluid protein-15; HCG-beta, human chorionic gonadotropin-beta; HMB45, human melanoma black 45; Melan-A, melanoma antigen; Pax-5, paired-box gene 5; Pax-8, paired-box gene 8; RCC, renal cell carcinoma marker; TTF-1, thyroid transcription factor 1; WT1, Wilms tumor 1
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Availability of data and materials
FB drafted and revised the manuscript for content, contributed to the design of the study, analyzed and interpreted the data, acquired the data, and handled the study coordination. LG revised the manuscript for content, contributed to the design of the study, acquired the data, and interpreted the data. MM and BB revised the manuscript for content and interpreted the data. PP and PW revised the manuscript for content, contributed to the design of the study, interpreted the data, and handled the study supervision. All authors gave final approval for publication of this manuscript.
The authors declare that they have no competing interests.
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Ethics approval and consent to participate
The review board waived the consent.
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- Hajdu SI, Urban JA. Cancers metastatic to the breast. Cancer. 1972;29(6):1691–6.View ArticlePubMedGoogle Scholar
- McCrea ES, Johnston C, Haney PJ. Metastases to the breast. AJR Am J Roentgenol. 1983;141(4):685–90.View ArticlePubMedGoogle Scholar
- Alva S, Shetty-Alva N. An update of tumor metastasis to the breast data. Arch Surg. 1999;134(4):450.View ArticlePubMedGoogle Scholar
- Williams SA, Ehlers 2nd RA, Hunt KK, Yi M, Kuerer HM, Singletary SE, et al. Metastases to the breast from nonbreast solid neoplasms: presentation and determinants of survival. Cancer. 2007;110(4):731–7.View ArticlePubMedGoogle Scholar
- van Rossen ME, Westenend PJ, Plaisier PW. Response to “Breast metastases from colorectal carcinoma” by R. Mihai et al. The Breast 2004; 13, 155-8. Breast. 2005;14(1):80–1. author reply 2.PubMedGoogle Scholar
- Wood B, Sterrett G, Frost F, Swarbrick N. Diagnosis of extramammary malignancy metastatic to the breast by fine needle biopsy. Pathology. 2008;40(4):345–51.View ArticlePubMedGoogle Scholar
- DeLair DF, Corben AD, Catalano JP, Vallejo CE, Brogi E, Tan LK. Non-mammary metastases to the breast and axilla: a study of 85 cases. Mod Pathol. 2013;26(3):343–9.View ArticlePubMedGoogle Scholar
- Georgiannos SN, Chin J, Goode AW, Sheaff M. Secondary neoplasms of the breast: a survey of the 20th Century. Cancer. 2001;92(9):2259–66.View ArticlePubMedGoogle Scholar
- Toombs BD, Kalisher L. Metastatic disease to the breast: clinical, pathologic, and radiographic features. AJR Am J Roentgenol. 1977;129(4):673–6.View ArticlePubMedGoogle Scholar
- Lee SK, Kim WW, Kim SH, Hur SM, Kim S, Choi JH, et al. Characteristics of metastasis in the breast from extramammary malignancies. J Surg Oncol. 2010;101(2):137–40.View ArticlePubMedGoogle Scholar
- Lee AH. The histological diagnosis of metastases to the breast from extramammary malignancies. J Clin Pathol. 2007;60(12):1333–41.View ArticlePubMedPubMed CentralGoogle Scholar
- Miettinen M, McCue PA, Sarlomo-Rikala M, Rys J, Czapiewski P, Wazny K, et al. GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol. 2014;38(1):13–22.View ArticlePubMedPubMed CentralGoogle Scholar
- Davis DG, Siddiqui MT, Oprea-Ilies G, Stevens K, Osunkoya AO, Cohen C, et al. GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas. Hum Pathol. 2016;47(1):26–31.View ArticlePubMedGoogle Scholar
- Nonaka D, Chiriboga L, Soslow RA. Expression of pax8 as a useful marker in distinguishing ovarian carcinomas from mammary carcinomas. Am J Surg Pathol. 2008;32(10):1566–71.View ArticlePubMedGoogle Scholar
- Hwang H, Quenneville L, Yaziji H, Gown AM. Wilms tumor gene product: sensitive and contextually specific marker of serous carcinomas of ovarian surface epithelial origin. Appl Immunohistochem Mol Morphol. 2004;12(2):122–6.View ArticlePubMedGoogle Scholar
- Fulciniti F, Losito S, Botti G, Di Mattia D, La Mura A, Pisano C, et al. Metastases to the breast: role of fine needle cytology samples. Our experience with nine cases in 2 years. Annals Oncol Off J Eur Soc Med Oncol / ESMO. 2008;19(4):682–7.View ArticleGoogle Scholar
- Sneige N, Zachariah S, Fanning TV, Dekmezian RH, Ordonez NG. Fine-needle aspiration cytology of metastatic neoplasms in the breast. Am J Clin Pathol. 1989;92(1):27–35.View ArticlePubMedGoogle Scholar
- Shukla R, Pooja B, Radhika S, Nijhawan R, Rajwanshi A. Fine-needle aspiration cytology of extramammary neoplasms metastatic to the breast. Diagn Cytopathol. 2005;32(4):193–7.View ArticlePubMedGoogle Scholar
- David O, Gattuso P, Razan W, Moroz K, Dhurandhar N. Unusual cases of metastases to the breast. A report of 17 cases diagnosed by fine needle aspiration. Acta Cytol. 2002;46(2):377–85.View ArticlePubMedGoogle Scholar