Metachronous isolated breast metastasis from pulmonary adenocarcinoma with micropapillary component causing diagnostic challenges
© Jeong et al.; licensee BioMed Central Ltd. 2014
Received: 15 July 2014
Accepted: 26 September 2014
Published: 1 October 2014
Breast metastasis from extramammary malignancy is uncommon and often presents diagnostic challenges. Herein, we report a case of a patient with metachronous isolated breast metastasis from pulmonary adenocarcinoma with micropapillary component.
A 47-year-old woman presented with left breast nodule detected on a screening breast ultrasonography. She had surgery for pulmonary adenocarcinoma 3 years ago, and was disease-free state in the follow up studies. The patient was diagnosed with invasive micropapillary carcinoma of the breast by core needle biopsy. She underwent left breast lumpectomy and sentinel lymph node biopsy, and the histologic findings revealed micropapillary carcinoma. Based on the immunohistochemical study, the final diagnosis was solitary breast metastasis from pulmonary adenocarcinoma with micropapillary component.
The diagnosis of metastasis to the breast from extramammary malignancies is difficult but important for proper management and prediction of prognosis. A careful clinical history with a thorough clinical examination is needed to make the correct diagnosis.
KeywordsBreast metastasis Pulmonary adenocarcinoma Micropapillary component Lung cancer
Metastases to the breast from extramammary malignancy are relatively rare though breast cancer is the most common malignancy in women . Most malignancies seen in the breast are primary carcinomas  and the incidence of metastatic disease to the breast is 0.2-6.6% of all malignant breast tumors [3–8]. The primary malignancies most commonly metastasizing to the breast are leukemia, lymphoma, malignant melanoma and carcinomas from the lung, genitourinary or gastrointestinal tract [9–11]. These metastatic tumors can morphologically simulate breast cancer and lead to misclassification , which causes clinical problems because the treatment and prognosis of each tumor differs significantly.
Although lung cancer is one of most common cancer worldwide, there have been only a few published cases of pulmonary carcinoma metastasizing to the breast, particularly with micropapillary component [12–14]. Invasive micropapillary carcinomas have been described in several organs including urinary bladder, lung, major salivary glands, ovary and breast . Adenocarcinoma with micropapillary component is a morphologic variant of carcinoma and usually recognized as a poor prognostic predictors . We report a case of metachronous isolated breast metastasis from pulmonary adenocarcinoma with micropapillary component which was initially favored to be primary breast cancer. The institutional review board at Daegu Catholic University Hospital granted an exemption from requiring ethics approval for this study.
We reviewed the histopathologic findings of the lung cancer removed 3 years ago and compared them with the findings of the breast tumor. H&E-stained paraffin sections of the lung cancer revealed diffuse infiltration of malignant epithelioid cells showing solid and micropapillary patterns, which resemble the findings of the breast tumor. Also, the lung cancer had the same immunoprofiles as the breast tumor.
From the above results, the patient was diagnosed solitary breast metastasis from pulmonary adenocarcinoma with micropapillary component. Since the mutation test for EGFR was positive, the patient has been taking Gefitinib, being disease-free at 23 month after the diagnosis of the breast metastasis.
The breast is an unusual site for metastasis from extramammary tumors and metastatic cancer is an unexpected diagnosis in a woman presenting with a breast mass [16, 17]. The distinction between breast metastasis from extramammary malignancy and primary breast cancer is important for patient management . Some authors have described clinical and histological characteristics of breast metastasis from extramammary malignancies [5, 8, 11, 18]. The most common symptoms are solitary discrete lesions in the breast [5, 11], while in one study, most patients presented with a history of loco-regional and wide spread metastases of extramammary neoplasms . The most common mammographic appearance is of a round mass with well-defined or slightly irregular margins [11, 18]. In our patient, mammography revealed only a focal asymmetry in left upper and ultrasonography revealed two irregular shaped and microlobulated hypoechoic small masses in left upper breast categorized according to BI-RADS 4C. Histological features of metastases to the breast include atypical histologic features for a primary breast carcinoma, a well-circumscribed tumor with multiple satellite foci, the absence of an intraductal component, and the presence of many lymphatic emboli . However, pathologic diagnosis of breast metastases is difficult, because many extramammary malignancies lack specific histological features and sometimes the features are similar to those of primary breast cancer, particularly with extensive micropapillary patterns [12, 13].
Clinical history, radiologic findings and histologic features are helpful in the evaluation of metastatic lesions in the breast. In a review of the ultrasonographic appearances of breast metastases from extramammary malignancies, there are several typical features of breast metastases . Typical ultrasound features of hematogenous metastases include single or multiple, round to oval shaped, well-circumscribed hypoechoic masses without spiculations, calcifications, or architectural distortion . However, lesions show variable radiologic features in some cases and a possibility of a metastasis should be suspected for a breast tumor in a patient with a history of cancer, even if clinically or radiologically benign . Most of primary breast carcinomas originate in the ducts or lobules of the breast and the presence of an in situ (intraductal) component is the only absolute proof of the primary breast carcinoma . After all, whenever a well-circumscribed tumor is identified in the breast showing lack of in situ components, the possibility of metastatic cancer should be considered and excluded , especially in high grade tumors without an in situ component. Also, ER and PR are highly specific markers for breast cancer  and ER/PR negative breast tumor without an in situ component is the most common clue for suspicion of metastatic tumor in the breast.
Immunohistochemical studies are necessary for pathologic diagnosis if no primary tumor was known and the clues are subtle to show specific histological features [4, 11]. An immunohistochemical analysis using a panel of antibodies may be useful to discriminate a primary mammary tumor from an extramammary malignancy because specificity or sensitivity of specific markers is not always 100% . The combination CK7 and CK20 is useful in categorizing carcinomas [11, 22]. The most of breast carcinomas are CK7+ and CK20-, and a CK20+ or CK7- pattern would make breast origin less likely . GCDFP-15 is also highly specific marker for breast cancer . TTF-1 is a very useful marker in distinguishing pulmonary adenocarcinomas from other primary carcinomas. TTF-1 is expressed in about 75% of pulmonary adenocarcinomas , and no breast carcinomas have been reported to be positive for TTF-1 except rare small cell carcinomas of the breast [23, 24]. Napsin A is a new marker for pulmonary adenocarcinoma and is known to be more sensitive and specific than TTF-1 in the differential diagnosis of primary pulmonary carcinoma . In our case, the tumor cells showed negative immunoreactivity for ER, PR, HER2/neu and GCDFP-15, and positive for TTF-1, CK-7 and Napsin A.
Clinical features of case reports of breast metastasis from pulmonary adenocarcinoma with micropapillary components
Method of detection for breast tumor
Breast tumor size
Initial stage of lung cancer
Ko K, et al., 2012 
Chest pain with dyspnea
Palpable mass on P/Ex.
1 cm in diameter
Cisplatin/Irinotecan followed by erotinib
Maounis N, et al., 2010 
Dyspnea with dry cough
Palpable mass on P/Ex
Sanguinetti A, et al., 2013 
Dyspnea with dry cough
Palpable mass on P/Ex
Simple mastectomy + Chemotherapy
Breast nodule on screening exam
1.3 cm ×1 cm
Lumpectomy + Chemotherapy
It has been documented that breast metastasis from extramammary malignancy has a poor prognosis because most patients have been reported as widely disseminated disease and die within a year of diagnosis [10, 11]. Specifically, synchronously-presenting lung cancer metastasizing to the breast, namely stage IV lung cancer has carried a very poor prognosis . For patients presenting synchronous lung cancer with breast metastasis, removal of the breast lesion offers no patient benefit . However, removal of the breast lesion could be a useful treatment option for patients with metachronously-presenting lung cancer metastasizing to the breast only, although it has not been established yet whether surgical treatment will affect the prognosis or not. In our case, the patient had only metastasis to the breast and was treated with surgery and anti-EGFR (Gefitinib) treatment. She has been survived with disease free for 23 months following the diagnosis of the breast metastasis.
Micropapillary component is generally thought to have prognostic significance and is associated with a manifestation of aggressive behavior such as lymph node metastases and distant metastases [27, 28]. In 3 previous reports [12–14] of synchronously-presenting breast metastasis from pulmonary adenocarcinoma with a micropapillary component, 2 patients died 6 months and 8 months following diagnosis, respectively [13, 14], and a patient were alive 8 months after the initial diagnosis of lung cancer , although all patients have received systemic chemotherapy. Our patient is currently alive without additional metastasis 23 months after the diagnosis of the breast metastasis, but long-term follow-up is needed.
Here, we report a rare case of metachronous isolated metastasis to the breast from a pulmonary adenocarcinoma with micropapillary component. The distinction between breast metastasis from pulnomary adenocarcinoma with micropapillary component and primary breast micropapillary carcinoma may cause diagnostic challenges. An immunohistochemical analysis is useful for accurate diagnosis. Furthermore, although it is rare, the possibility of metastatic disease to the breast should be considered before making the diagnosis of primary breast cancer, particularly with micropapillary component.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor of this journal.
The authors wish to thank Sung-Hee Mun (Department of Radiology, Catholic University of Daegu School of Medicine) for her technical support and interpretation of data.
- National Cancer Institute: Probability of Breast Cancer in American Women. [http://www.cancer.gov/cancertopics/factsheet/detection/probability-breast-cancer]
- Rosen PP: The pathological classification of human mammary carcinoma: past, present and future. Ann Clin Lab Sci. 1979, 9: 144-156.PubMedGoogle Scholar
- Canda AE, Sevinc AI, Kocdor MA, Canda T, Balci P, Saydam S, Harmancioglu O: Metastatic tumors in the breast: a report of 5 cases and review of the literature. Clin Breast Cancer. 2007, 7: 638-643. 10.3816/CBC.2007.n.023.View ArticlePubMedGoogle Scholar
- Vergier B, Trojani M, de Mascarel I, Coindre JM, Le Treut A: Metastases to the breast: differential diagnosis from primary breast carcinoma. J Surg Oncol. 1991, 48: 112-116.View ArticlePubMedGoogle Scholar
- Toombs BD, Kalisher L: Metastatic disease to the breast: clinical, pathologic, and radiographic features. Am J Roentgenol. 1977, 129: 673-676. 10.2214/ajr.129.4.673.View ArticleGoogle Scholar
- Vaughan A, Dietz JR, Moley JF, DeBenedetti MK, Aft RL, Gillanders WE, Eberlein TJ, Ritter J, Margenthaler JA: Metastatic disease to the breast: the Washington University experience. World J Surg Oncol. 2007, 5: 74-10.1186/1477-7819-5-74.View ArticlePubMedPubMed CentralGoogle Scholar
- Hajdu SI, Urban JA: Cancers metastatic to the breast. Cancer. 1972, 29: 1691-1696. 10.1002/1097-0142(197206)29:6<1691::AID-CNCR2820290637>3.0.CO;2-4.View ArticlePubMedGoogle Scholar
- McCrea ES, Johnston C, Haney PJ: Metastases to the breast. Am J Roentgenol. 1983, 141: 685-690. 10.2214/ajr.141.4.685.View ArticleGoogle Scholar
- Klingen TA, Klaasen H, Aas H, Chen Y, Akslen LA: Secondary breast cancer: a 5-year population-based study with review of the literature. APMIS. 2009, 117: 762-767. 10.1111/j.1600-0463.2009.02529.x.View ArticlePubMedGoogle Scholar
- Williams SA, Ehlers RA, Hunt KK, Yi M, Kuerer HM, Singletary SE, Ross MI, Feig BW, Symmans WF, Meric-Bernstam F: Metastases to the breast from nonbreast solid neoplasms: presentation and determinants of survival. Cancer. 2007, 110: 731-737. 10.1002/cncr.22835.View ArticlePubMedGoogle Scholar
- Lee AH: The histological diagnosis of metastases to the breast from extramammary malignancies. J Clin Pathol. 2007, 60: 1333-1341.View ArticlePubMedPubMed CentralGoogle Scholar
- Ko K, Ro JY, Hong EK, Lee S: Micropapillary lung cancer with breast metastasis simulating primary breast cancer due to architectural distortion on images. Korean J Radiol. 2012, 13: 249-253. 10.3348/kjr.2012.13.2.249.View ArticlePubMedPubMed CentralGoogle Scholar
- Maounis N, Chorti M, Legaki S, Ellina E, Emmanouilidou A, Demonakou M, Tsiafaki X: Metastasis to the breast from an adenocarcinoma of the lung with extensive micropapillary component: a case report and review of the literature. Diagn Pathol. 2010, 5: 82-10.1186/1746-1596-5-82.View ArticlePubMedPubMed CentralGoogle Scholar
- Sanguinetti A, Puma F, Lucchini R, Santoprete S, Cirocchi R, Corsi A, Triola R, Avenia N: Breast metastasis from a pulmonary adenocarcinoma: case report and review of the literature. Oncol lett. 2013, 5: 328-332.PubMedGoogle Scholar
- Nassar H: Carcinomas with micropapillary morphology: clinical significance and current concepts. Adv Anat Pathol. 2004, 11: 297-303. 10.1097/01.pap.0000138142.26882.fe.View ArticlePubMedGoogle Scholar
- Yeh CN, Lin CH, Chen MF: Clinical and ultrasonographic characteristics of breast metastases from extramammary malignancies. Am Surg. 2004, 70: 287-290.PubMedGoogle Scholar
- Babu KS, Roberts F, Bryden F, McCafferty A, Downer P, Hansell DT, Richard J, Robert M: Metastases to breast from primary lung cancer. J Thorac Oncol. 2009, 4: 540-542. 10.1097/JTO.0b013e31819c8556.View ArticlePubMedGoogle Scholar
- Lee SK, Kim WW, Kim SH, Hur SM, Kim S, Choi JH, Cho EY, Han SY, Hahn BK, Choe JH, Kim JH, Kim JS, Lee JE, Nam SJ, Yang JH: Characteristics of metastasis in the breast from extrammary malignancies. J Surg Oncol. 2010, 101: 137-140. 10.1002/jso.21453.View ArticlePubMedGoogle Scholar
- Mun SH, Ko EY, Han BK, Shin JH, Kim SJ, Cho EY: Breast metastases from extramammary malignancies: typical and atypical ultrasound features. Korean J Radiol. 2014, 15: 20-28. 10.3348/kjr.2014.15.1.20.View ArticlePubMedPubMed CentralGoogle Scholar
- Alexander HR, Turnbull AD, Rosen PP: Isolated breast metastases from gastrointestinal carcinomas: report of two cases. J Surg Oncol. 1989, 42: 264-266. 10.1002/jso.2930420412.View ArticlePubMedGoogle Scholar
- Moinfar F: Special Types of Breast Carcinomas. Essentials of Diagnostic Breast Pathology: A Practical Approach. 2007, Heidelberg: Springer, 223-239.Google Scholar
- Tot T: Cytokeratin 20 and 7 as biomarkers: usefulness in discriminating primary from metastatic adenomcarcinoma. Eur J Cancer. 2002, 38: 758-763. 10.1016/S0959-8049(02)00008-4.View ArticlePubMedGoogle Scholar
- Christie M, Chin-Lenn L, Watts MM, Tsui AE, Buchanan MR: Primary small cell carcinoma of the breast with TTF-1 and neuroendocrine marker expressing carcinoma in situ. Int J Clin Exp Pathol. 2010, 3: 629-633.PubMedPubMed CentralGoogle Scholar
- Klingen TA, Chen Y, Gundersen MD, Aas H, Westre B, Sauer T: Thyroid transcription factor-1 positive primary breast cancer: a case report with review of the literature. Diagn Pathol. 2010, 5: 37-10.1186/1746-1596-5-37.View ArticlePubMedPubMed CentralGoogle Scholar
- Turner BM, Cagle PT, Sainz IM, Fukuoka J, Shen SS, Jagirdar J: Napsin A, a new marker for lung adenocarcinoma, is complementary and more sensitive and specific than thyroid transcription factor 1 in the differential diagnosis of primary pulmonary carcinoma: evaluation of 1674 cases by tissue microarray. Arch Pathol Lab Med. 2012, 136: 163-171. 10.5858/arpa.2011-0320-OA.View ArticlePubMedGoogle Scholar
- Mirrielees JA, Kapur JH, Szalkucki LM, Harter JM, Salkowski LR, Strigel RM, Traynor AM, Wilke LG: Metastasis of primary lung carcinoma to the breast: a systematic review of the literature. J Surg Res. 2014, 188: 419-431. 10.1016/j.jss.2014.01.024.View ArticlePubMedGoogle Scholar
- Amin MB, Tamboli P, Merchant SH, Ordóñez NG, Ro J, Ayala AG, Ro JY: Micropapillary component in lung adenocarcinoma: a distinctive histologic feature with possible prognostic significance. Am J Surg Pathol. 2002, 26: 358-364. 10.1097/00000478-200203000-00010.View ArticlePubMedGoogle Scholar
- Maeda R, Isowa N, Onuma H, Miura H, Harada T, Touge H, Tokuyasu H, Kawasaki Y: Lung adenocarcinomas with micorpapillary components. Gen Thorac Cardiovasc Surg. 2009, 57: 534-539. 10.1007/s11748-009-0436-y.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/736/prepub
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