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Spectrum of Extramammary Malignant Neoplasms in the Breast With Radiologic-Pathologic Correlation
Current Problems in Diagnostic Radiology ] (2015) ]]]–]]]
Current Problems in Diagnostic Radiology journal homepage: www.cpdrjournal.com
Spectrum of Extramammary Malignant Neoplasms in the Breast With Radiologic-Pathologic Correlation Sirishma Kalli, MDa,n, Michael Lanfranchi, MDa, Andrew Alexander, MDb, Shital Makim, MDa, Phoebe E. Freer, MDc a
Department of Radiology, Tufts Medical Center, Boston, MA Department of Pathology, Tufts Medical Center, Boston, MA c Avon Comprehensive Breast Center, Massachusetts General Hospital, Boston, MA b
Although primary breast cancer is the most common malignancy identified by breast imaging, extramammary malignancies may also rarely be encountered. These uncommon lesions may reflect primary neoplasms of nonmammary origin as well as secondary metastatic lesions, and include lymphoma, melanoma, neuroendocrine tumors, gastrointestinal tract malignancies, and angiosarcoma among other entities. Malignant extramammary breast lesions may be encountered during routine mammographic screening, identified during the diagnostic evaluation of a palpable breast abnormality, or may be detected incidentally during imaging of other organs of interest. As such, the radiologist should have familiarity with the appearance of these lesions. This article focuses on a review of several of the most common extramammary metastases to the breast, as well as a few lesions that may develop as either primary or secondary lesions. & 2015 Mosby, Inc. All rights reserved.
Introduction
carcinoma metastasis may also contain calcifications that may appear similar to malignant ductal microcalcifications.5
The incidence of extramammary metastatic lesions to the breast ranges from 0.5%-6.6%.1-3 The most common lesions in order of descending frequency include lymphoma, melanoma, rhabdomyosarcoma, and lung and ovarian carcinoma.1,2 Metastases may arise from either hematogenous or lymphangitic spread, each generally manifesting with different imaging features. Hematogenous spread often leads to a discrete circumscribed mass or masses without spiculations or microcalcifications.4,5 On the other hand, lymphangitic spread often leads to more diffuse findings such as edema, increased trabeculation, and skin thickening.4,5 Both types of dissemination may mimic benign entities, with hematogenously spread lesions mimicking benign cysts or fibroadenomas, and lymphangitic spread mimicking mastitis. Both types of dissemination may also mimic other malignant entities, with hematogenously spread lesions mimicking less ominous appearing subtypes of primary breast malignancy such as medullary, mucinous, or papillary carcinoma, whereas lymphangitic spread may appear identical to inflammatory breast carcinoma. Though microcalcifications are not frequently present in metastatic lesions, if present, they most commonly indicate an ovarian carcinoma, due to the presence of psammoma bodies (Fig 1).2,5,6 Additionally, hepatocellular carcinoma, medullary thyroid carcinoma, or gastric
n Reprint requests: Sirishma Kalli, MD, Department of Radiology, Tufts Medical Center, 800 Washington St Box 299, Boston, MA 02111. E-mail address: [email protected] (S. Kalli).
http://dx.doi.org/10.1067/j.cpradiol.2015.07.012 0363-0188/& 2015 Mosby, Inc. All rights reserved.
Fig. 1. (A) A female patient with a history of ovarian carcinoma presented for diagnostic mammogram for 2 palpable lesions in the right axilla. Magnified RMLO view demonstrates punctate microcalcifications within a partially imaged axillary node (arrows), which upon further workup revealed metastatic ovarian carcinoma. RMLO, right mediolateral oblique.
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Fig. 2. (A) Diagnostic mammogram with spot compression views in a 38-year-old woman with a palpable lump within the right breast did not reveal a mammographic abnormality (not shown). Ultrasound imaging in the same patient reveals an oval, complex solid and cystic mass with microlobulated margins and mild internal vascularity. FNA revealed dense lymphoid infiltrate (not shown). (B) Subsequent Whole body FDG-PET/CT (select fused axial image shown) reveals a solitary area of abnormal FDG uptake within the right breast corresponding with the ultrasound abnormality (arrow). No additional areas of abnormal FDG localization were identified throughout the body. (C) Photomicrograph (hematoxylin and eosin stain, 20) from a subsequent core biopsy specimen reveals a diffuse infiltrate of large, atypical lymphocytes with vesicular chromatin, and irregular nuclear contours, which were positive for CD20, CD10, BCL2, and BLC6 (not shown). Findings are consistent with diffuse large B-cell lymphoma. FNA, fine-needle aspiration; FDG, fluorodeoxyglucose; PET, positron emission tomography; CT, computed tomography. (Color version of figure is available online.)
Specific Subtypes of Extramammary Metastases Breast Lymphoma Breast lymphoma most often presents as secondary involvement due to disseminated disease. Lymphoma less commonly presents as a primary breast lymphoma, occurring in less than 0.5% of instances.7 Clinically, both primary and secondary breast lymphomas frequently present as a palpable, painful mass within the upper outer quadrant, with axillary lymphadenopathy present
in 30%-50% of cases.7 The most common subtypes of breast lymphoma include diffuse large B-cell lymphoma, marginal-zone lymphoma (mucosa-associated lymphoid tissue lymphoma), and follicular lymphoma, all of which are of B-cell origin. Whereas diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma occur in both primary and secondary settings, follicular lymphoma occurs solely in the setting of disseminated disease.8,9 T-cell lymphomas are much rarer, occurring in less than 10% of all cases.8 At mammography breast lymphoma often appears as an indistinct mass or masses, and an irregular,
Fig. 3. (A) Axial CT in a 52-year-old male patient with long-standing GERD and epigastric pain depicts nodular masses within the gastric wall (arrows). Subsequent endoscopic biopsy revealed Burkitt's lymphoma. The patient underwent systemic chemotherapy with initial remission. (B) FDG-PET/CT for restaging 19 months later reveals area of abnormal FDG localization within the retroareolar right breast (arrow) (select axial fused PET/CT image shown). An additional area of abnormal FDG localization was noted within the left sacrum (not shown). (C) Targeted retroareolar ultrasound of the right breast reveals a correlating oval, parallel, and heterogeneous mass with indistinct margins and internal vascularity. (D) Photomicrograph (hematoxylin and eosin stain, 40) from the subsequent right core needle biopsy of the mass reveals atypical, dense lymphoid infiltrate which was immunohistochemically positive for CD20, CD10, Pax5, and Ki67 within greater than 95% of cells. Findings are consistent with a high-grade B-cell lymphoma. GERD, gastroesophageal reflux; FDG, fluorodeoxyglucose; PET, positron emission tomography; CT, computed tomography. (Color version of figure is available online.)
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Fig. 4. (A) A 59-year-old woman with a history of a left chest wall marginal-zone lymphoma is noted to have an incidental right breast mass on follow-up CT (arrow) (axial image shown). (B and C) RMLO (B) and RCC views (C) from a diagnostic mammogram reveal an irregular, ill-defined mass within the lower inner quadrant (circles). (D) Ultrasound of the right breast confirms a suspicious round, heterogeneous mass with indistinct margins. (E) Photomicrograph (hematoxylin and eosin stain, 20) from biopsy of the same patient revealed atypical, dense lymphoid infiltrate, which was positive for CD20 and negative for CD10. Findings are consistent with a marginal-zone lymphoma of mucosa-associated lymphoid tissue (MALT) type. RMLO, right mediolateral oblique; RCC, right craniocaudal. (Color version of figure is available online.)
heterogeneous, hypervascular mass or masses at ultrasound, which may be hyperechoic (Figs 2-4).7As noted previously, due to lymphangitic spread of disease, overlying skin changes may be present at both mammography and ultrasound. 7 On magnetic resonance (MR) imaging, breast lymphoma often appears as an irregular mass or masses with mild, heterogeneous internal enhancement.10 Biopsy specimens reveal atypical lymphocytes staining positive for immunohistochemical stains such as CD10, CD20, and CD30. An extremely rare subtype of lymphoma, breast implant associated anaplastic large cell lymphoma, was first described in 1997 and reflects a subtype of T-cell lymphoma that frequently presents as a pericapsular effusion, less commonly a mass.8,11 Though the direct cause of this entity is yet to be proven, nearly no cases have occurred in breasts lacking implants, suggesting a very strong association.8
Plasmacytoma Breast plasmacytoma may develop in the setting of multiple myeloma, or less commonly present as a primary lesion. In the primary setting, periodic surveillance is necessary even long after remission, as these patients may subsequently develop multiple myeloma. 15 Similar to other extramammary malignant lesions, breast plasmacytoma often presents as a circumscribed mass or masses without spiculations or microcalcifications (Fig 7).3 At ultrasound, these lesions appear as a round, hypoechoic mass or masses, which may demonstrate posterior shadowing.3 As these lesions are exceedingly rare, their appearance on MR imaging is not well reported in the literature.
Neuroendocrine Tumors Melanoma Similar to lymphoma, breast melanoma may represent either primary or metastatic disease. Patients possessing BRCA2 mutations, and possibly BRCA1, are at an increased risk for melanoma.12,13 Melanoma often appears as a circumscribed mass or masses without spiculations or microcalcifications at mammography and may have a variety of imaging appearances at ultrasound (Figs 5 and 6).14 On MR imaging, melanoma can demonstrate T1 hyperintensity, not only due to the presence of melanin, but also due to the presence of hemorrhage in these lesions, which have a high tendency to bleed.5 Histologically, melanoma specimens reveal nuclear pleomorphism and stain positive for MART-1.
Breast neuroendocrine tumors may be categorized into 3 subtypes: ductal carcinoma with neuroendocrine differentiation, primary neuroendocrine tumors of the breast, or metastatic disease. Histologically, primary breast neuroendocrine tumors can be differentiated from secondary lesions, as primary lesions often stain positive for GCDFP-15 and mammaglobin, whereas metastases generally do not.16 Frequently these lesions appear as a noncalcified, nonspiculated mass at mammography, and an irregular, hypoechoic, hypervascular mass without posterior enhancement at ultrasound (Figs 8-10).17 Dynamic contrast-enhanced MR imaging usually reveals an irregular mass demonstrating washout kinetics.17
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Fig. 5. (A and B) LMLO (A) and LCC views (B) from a screening mammogram demonstrate 2 adjacent hyperdense masses in the lateral left breast (arrows). (C and D) In retrospect, the masses are seen to have progressed from an LMLO (C) and LCC views (D) from a screening mammogram obtained 2 years prior (arrows), (white circles visualized are mole marker stickers placed by the technologist at the time of imaging on benign skin lesions). Specimen radiograph following needle localization with bracketing of the lesions again revealed hyperdense, circumscribed masses without microcalcifications (not shown), which were biopsy-proven malignant melanoma. LMLO, left mediolateral oblique; LCC, left craniocaudal.
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Fig. 6. (A and B) A 59-year-old woman presented with a palpable abnormality in the left breast. LCC (A) and LMLO views (B) from a diagnostic mammogram reveal 3 discrete, irregular masses (arrows) within the lower inner quadrant. (C) Diagnostic ultrasound of one of the masses reveals an irregular, hypoechoic lesion with microlobulated margins, which corresponded to the palpable abnormality and mammographic findings. Although the sonographic findings alone could be mistaken for a complicated cyst, the patient had a history of lymph node negative localized malignant melanoma excised from her back 2 years prior. The patient therefore underwent restaging with FDGPET/CT revealing a large area of abnormal FDG localization within the medial left breast corresponding to the mammographic, ultrasound, and palpable abnormalities (not shown). (D) Photomicrograph (hematoxylin and eosin stain, 20) of a partial mastectomy specimen reveals sheets of discohesive cells with marked nuclear pleomorphism. These cells were immunohistochemically positive for MART-1 consistent with metastatic melanoma. LCC, left craniocaudal; LMLO, left mediolateral oblique; FDG, fluorodeoxyglucose; PET, positron emission tomography; CT, computed tomography. (Color version of figure is available online.)
Gastric Carcinoma Metastatic gastric adenocarcinoma of the breast may both clinically and mammographically mimic inflammatory breast
cancer with erythematous, edematous skin, often without evidence of a mass or microcalcifications (Fig 11).18 As a visible underlying mass is often absent, these lesions may also be occult on ultrasonography, and subsequently, a skin punch biopsy may be
Fig. 7. (A) LCC view in a 68-year-old woman with a history of multiple myeloma who presented with a palpable abnormality within the left breast reveals an oval, partially obscured mass (arrow). (B) Ultrasound of the 12-o'clock region demonstrates a hypoechoic lesion with internal septation and increased vascularity. Pathology revealed cells positive for CD45, CD138, and CD56, as well as 70% Ki67 (not shown). Findings were consistent with plasmablastic plasmacytoma. LCC, left craniocaudal. (Color version of figure is available online.)
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Fig. 8. (A) Axial contrast-enhanced MRI in a 52-year-old woman with a 3-month history of odynophagia and voice change reveals a left supraglottic mass (arrow), which was a biopsy-proven atypical carcinoid. (B) After 2 years, the patient presented with a palpable breast mass which was biopsied without image guidance. Fused axial PET/CT image in the same patient reveals an area of abnormal FDG localization (arrow) in the left medial breast, which was a metastatic atypical carcinoid from the patient's prior supraglottic mass. MRI, MR imaging; PET, positron emission tomography; CT, computed tomography; FDG, fluorodeoxyglucose. (Color version of figure is available online.)
necessary for diagnosis. Biopsy often reveals atypical cells invading dermal lymphatics, which demonstrate positivity for CK7, CK20, and CDX2, and remain negative for estrogen, progesterone, and mammaglobin stains. Due to the rarity of this entity, the MR findings of metastatic gastric carcinoma to the breast are not well reported in the literature.
Osteosarcoma Breast osteosarcoma is one of the few extramammary lesions that do contain calcifications, although the calcifications appear large and coarse at mammography and ultrasound, not microscopic, and may mimic an involuting fibroadenoma (Fig 12).14,19,20
Fig. 9. (A) A woman with a history of carcinoid tumor a few years prior was found to have an incidental lesion in the superior right breast on chest CT (not shown). RCC magnification view from a needle localization procedure demonstrates an irregular, spiculated mass which was a biopsy-proven metastatic lesion from the patient's original carcinoid tumor. (B) LMLO view from a mammogram 6 years later reveals a round mass at the level of the nipple, which also resulted in a metastatic neuroendocrine tumor. CT, computed tomography; RCC, right craniocaudal; LMLO, left mediolateral oblique.
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Fig. 10. (A) Fused axial PET/CT in a 72-year-old woman with a palpable, enlarged left supraclavicular node depicts asymmetric FDG localization (arrow) within the retroareolar right breast. (B) Right retroareolar ultrasound in the same patient reveals a smaller, microlobulated hypoechoic mass, and a larger, indistinct hypoechoic mass, corresponding to the area of abnormal FDG uptake. (C) Photomicrograph (hematoxylin and eosin stain, 20) reveals a primary breast neuroendocrine carcinoma with 4 50% neuroendocrine differentiation. PET, positron emission tomography; CT, computed tomography; FDG, fluorodeoxyglucose. (Color version of figure is available online.)
Although the MR appearance of breast osteosarcoma is not well reported in the literature, one would expect the large, coarse calcifications to demonstrate hypointensity on gradient echo imaging.21 Clinically, breast osteosarcoma often presents as a rapidly enlarging mass or masses occasionally with nipple discharge, and may metastasize to the lungs, where the lesions also demonstrate coarse calcifications.19 This entity most often develops in patients with a history of prior breast irradiation, and should be considered in this patient population when lesions with coarse calcifications arise.14,22
Thyroid Carcinoma Metastatic thyroid carcinoma in the breast is extremely rare, with only a few cases reported.23 The Hurthle cell subtype has the highest incidence of metastases among differentiated thyroid carcinomas.24 On mammography, metastatic differentiated thyroid carcinomas may contain calcifications, whereas the appearance of these lesions at ultrasound and MR imaging is not well reported in the literature (Fig 13).23 Treatment of metastatic thyroid carcinoma to the breast often includes resection with or without I-131 therapy.23
Fig. 11. (A) Axial CT image in a 49-year-old woman with history of metastatic gastric adenocarcinoma demonstrates diffuse gastric wall thickening (arrow) and peritoneal carcinomatosis (not shown). (B) Diffuse increased density and skin thickening were noted in the left breast (arrow). The differential for the breast findings included infectious mastitis, lymphatic obstruction due to metastases, or inflammatory breast cancer. (C) Subsequent mammogram LCC view confirmed diffuse increased breast density and skin and trabecular thickening. (D) Skin punch biopsy of the breast (hematoxylin and eosin stain, 20) reveals a dermal lymphatic channel containing atypical cells (circled) with hyperchromatic nuclei and cytoplasmic vacuoles, which were positive for CK7, CK20, and CDX2 and negative for estrogen receptor, progesterone receptor, and mammaglobin. Findings were consistent with lymphangitic spread of gastric adenocarcinoma. CT, computed tomography. (Color version of figure is available online.)
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Fig. 12. (A) LMLO implant displaced view in a 56-year-old woman with a palpable left breast mass demonstrates a calcified mass adjacent to the implant (arrow). (B) Ultrasound image during core biopsy reveals coarse calcifications within an oval, circumscribed, hypoechoic mass. Pathology revealed an extraskeletal osteosarcoma. LMLO, left mediolateral oblique.
Rhabdomyosarcoma Metastatic breast rhabdomyosarcoma is the most prevalent breast metastasis within adolescent females, and should be considered strongly in young patients with an appropriate clinical history.1 In the breast, rhabdomyosarcoma may mimic invasive lobular carcinoma, appearing as a mammographic focal asymmetry and an ill‐ defined, hypoechoic, shadowing lesion at ultrasound, while the MR appearance is not well described.14 Similar to rhabdomyosarcoma, infiltrative leukemia is another entity that may have similar findings that resemble invasive lobular carcinoma.14 Angiosarcoma Patients who have received breast conservation therapy may develop radiation-induced angiosarcoma in as many as 2% of
cases.25 This malignancy emerges as multiple cutaneous masses often following an extensive latency period of up to 10 years on average.25 These skin lesions can be difficult to differentiate from tumor recurrence, as they often manifest as skin thickening with or without an associated parenchymal mass at mammography and ultrasound, but should be included in the differential in the postradiated breast.25,26 Much rarer, breast angiosarcoma may develop as a primary lesion, comprising less than 0.4% of all breast neoplasms.25 At mammography this entity may appear as an ill-defined, noncalcified mass or focal asymmetry, and as an ill-defined, highly vascular mass at ultrasound. 26 Both primary and secondary breast angiosarcomas often reveal a predominantly T1 hypointense, T2 hyperintense, heterogeneous mass demonstrating plateau or washout kinetics at MR imaging, with secondary cases also demonstrating focal areas of skin thickening and enhancement.25,26
Fig. 13. (A) A 52-year-old patient with a history of a left invasive ductal carcinoma, status post partial mastectomy, radiation, and chemotherapy, as well as a Hurthle cell carcinoma, status post thyroidectomy and high-dose I-131 therapy, presented with a palpable right breast abnormality. RCC view reveals an isodense, circumscribed mass within the medial right breast. (B) This mass appeared new when compared to a negative screening mammogram obtained 2 months earlier. (C) Ultrasound of the palpable abnormality reveals an oval, circumscribed, and heterogeneous mass, which was biopsy-proven metastatic Hurthle cell carcinoma.
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Fig. 14. (A and B) A screening mammogram in a female with a history of a right invasive ductal carcinoma demonstrated expected breast conservation findings of scar and architectural distortion at the lumpectomy site in the lateral right breast (not shown). RCC (A) and LCC views (B) 3 years later demonstrate new bilateral round, isodense masses consistent with diffuse bilateral breast cancer metastases. On further workup, the patient had pathology-proven breast cancer visceral, osseous, and skin metastasis (not shown). RCC, right craniocaudal; LCC, left craniocaudal.
Mammary Metastases The most common metastases to the breast are from a primary breast malignancy of the contralateral breast (Fig 14).5 In cases of mammary metastases, triple negative cancers pose a high risk of recurrence and metastases.27 Though contralateral disease typically spreads through lymphatic drainage of the internal mammary chain, development of contralateral axillary metastases may also rarely occur in 3.6%-6% of cases, some of which may not reveal visible breast disease (Fig 15).28,29 Damage to the normal lymphatic pattern of drainage may occur due to obstruction from the
primary ipsilateral malignancy, or as a result of surgical or radiation therapy.28,29 Subsequently, alternate routes of drainage via the chest wall and dermal lymphatics may develop, providing pathways for contralateral spread of disease.28,29
Conclusion Although rare, extramammary malignant neoplasms should be considered in the differential diagnosis for breast lesions in the appropriate clinical setting. Hematogenously spread metastases
Fig. 15. (A) LMLO view in a patient with a history of right invasive ductal carcinoma, status post breast conservation therapy and recurrence status post right mastectomy, demonstrates contralateral axillary adenopathy, without any visible breast disease. (B) Axial contrast-enhanced MR image in the same patient demonstrates bulky contralateral axillary adenopathy (arrows), the pathology of which revealed metastases from the patient's original primary tumor. LMLO, left mediolateral oblique.
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Table Summary of imaging findings of malignant extramammary malignant neoplasms within the breast
Lymphoma
Melanoma Plasmacytoma Neuroendocrine tumor Gastric carcinoma
Osteosarcoma
Mammography
Ultrasound
MRI
Indistinct mass(es) often with axillary lymphadenopathy, may have skin thickening Circumscribed mass(es) without spiculation or microcalcifications Circumscribed mass(es) without spiculation or microcalcifications Circumscribed mass(es) without spiculation or microcalcifications Skin thickening, increased trabeculation indicating edema, may contain macrocalcifications Mass(es) containing large, coarse macrocalcifications
Irregular, heterogeneous, hypervascular mass(es), may be hyperechoic, may have skin thickening Variable appearance
Irregular mass(es) with mild, heterogeneous internal enhancement
Thyroid carcinoma
May contain microcalcifications in cases of medullary thyroid carcinoma
Rhabdomyosarcoma
Focal asymmetry
Primary angiosarcoma
Ill-defined noncalcified mass or focal asymmetry Skin thickening and postsurgical or radiation changes 7 ill-defined asymmetric parenchymal mass
Secondary angiosarcoma
Round, hypoechoic mass(es) Irregular, hypoechoic, hypervascular mass(es) May be occult
Circumscribed hypoechoic mass(es) with multiple large, echogenic foci with shadowing indicating calcifications Findings not well reported in the literature; may appear as an oval, heterogeneous mass (Fig 13C) Ill-defined, hypoechoic, shadowing lesion(s) Ill-defined, highly vascular mass Skin lesions may be occult, heterogeneous parenchymal mass may be present
Often T1 hyperintense mass(es) due to melanin or hemorrhage Findings not well reported in the literature Irregular mass(es) demonstrating washout kinetics Findings not well reported in the literature
Areas of susceptibility corresponding to macrocalcifications
Findings not well reported in the literature
Findings not well reported in the literature Heterogeneous mass, T1 hypointense, T2 hyperintense demonstrating plateau or washout kinetics for both types; skin thickening and enhancement in secondary cases
MRI, MR imaging.
often develop as a circumscribed mass or masses without spiculations or microcalcifications, whereas lymphangitic spread of disease often presents as diffuse breast edema and skin thickening. The imaging findings of several subtypes of extramammary malignant neoplasms are summarized in the Table. Awareness of these possibilities may aid patient diagnosis and lead to quicker, more appropriate management strategies.
Acknowledgments Breast osteosarcoma case courtesy of Matthew C. Oliff, MD and Troy Maetani, MD, Brigham and Women's Hospital, Boston, MA. References 1. Bartella L, Kaye J, Perry NM, et al. Metastases to the breast revisited: Radiological-histopathological correlation. Clin Radiol 2003;58(7):524–31. 2. Alvarado Cabrero I, Carrera Alvarez M, Perez Montiel D, et al. Metastases to the breast. Eur J Surg Oncol 2003;29(10):854–5. 3. Karan B, Pourbagher A, Bolat FA. Unusual malignant breast lesions: Imagingpathological correlations. Diagn Interv Radiol 2012;18(3):270–6. 4. Mun SH, Ko EY, Han BK, et al. Breast metastases from extramammary malignancies: Typical and atypical ultrasound features. Korean J Radiol 2014;15(1):20–8. 5. Surov A, Fiedler E, Holzhausen HJ, et al. Metastases to the breast from nonmammary malignancies: Primary tumors, prevalence, clinical signs, and radiological features. Acad Radiol 2011;18(5):565–74. 6. Klein RL, Brown AR, Gomez-Castro CM, et al. Ovarian cancer metastatic to the breast presenting as inflammatory breast cancer: A case report and literature review. J Cancer 2010;2(1):27–31. 7. Yang WT, Lane DL, Le-Petross HT, et al. Breast lymphoma: Imaging findings of 32 tumors in 27 patients. Radiology 2007;245(3):692–702. 8. Miranda RN, Aladily TN, Prince HM, et al. Breast implant-associated anaplastic large-cell lymphoma: Long-term follow-up of 60 patients. J Clin Oncol 2014;32 (2):114–20. 9. Talwalkar SS, Miranda RN, Valbuena JR, et al. Lymphomas involving the breast: A study of 106 cases comparing localized and disseminated neoplasms. Am J Surg Pathol 2008;32(9):1299–309. 10. Liu K1, Xie P, Peng W, et al. The features of breast lymphoma on MRI. Br J Radiol 2013;86(1031):20130220.
11. Keech JA, Creech BJ. Anaplastic T-cell lymphoma in proximity to a saline-filled breast implant. Plast Reconstr Surg 1997;100:554–5. 12. Mersch J, Jackson MA, Park M, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer 2015;121(2):269–75. 13. Breast Cancer Linkage Consortium. Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 1999;91(15):1310–6. 14. Harvey JA. Unusual breast cancers: Useful clues to expanding the differential diagnosis. Radiology 2007;242(3):683–94. 15. De Chiara A, Losito S, Terracciano L, et al. Primary plasmacytoma of the breast. Arch Pathol Lab Med 2001;125(8):1078–80. 16. Richter-Ehrenstein C, Arndt J, Buckendahl AC, et al. Solid neuroendocrine carcinomas of the breast: Metastases or primary tumors. Breast Cancer Res Treat 2010;124:413–7. 17. Park YM, Wu Y, Wei W, et al. Primary neuroendocrine carcinoma of the breast: Clinical, imaging, and histologic features. Am J Roentgenol 2014;203(2): W221–W230. 18. Kwak JY, Kim EK, Oh KK. Radiologic findings of metastatic signet ring cell carcinoma to the breast from stomach. Yonsei Med J 2000;41(5):669–72. 19. Thomas KA, Roy N, Troxel M, et al. Osteosarcoma of the breast. Breast J 2014;20 (2):204–6. 20. Sabaté JM, Gómez A, Torrubia S, et al. Osteosarcoma of the breast. Am J Roentgenol 2002;179(1):277–8. 21. Fatemi-Ardekani A, Boylan C, Noseworthy MD. Identification of breast calcification using magnetic resonance imaging. Med Phys 2009;36(12):5429–36. 22. Lagrange JL, Ramaioli A, Chateau MC, et al. Sarcoma after radiation therapy: Retrospective multiinstitutional study of 80 histologically confirmed cases. Radiation Therapist and Pathologist Groups of the Fédération Nationale des Centres de Lutte Contre le Cancer. Radiology 2000;216(1):197–205. 23. Song HJ, Xue YL, Qiu ZL, et al. Uncommon metastases from differentiated thyroid carcinoma. Hell J Nucl Med 2012;15(3):233–40. 24. Al-abed Y, Gray E, Wolfe K, et al. Metastatic Hurthle cell carcinoma of the thyroid presenting as a breast lump: A case report. Int Semin Surg Oncol 2008;5:14. 25. Kalli S, Freer PE, Rafferty EA. Lesions of the skin and superficial tissue at breast MR imaging. Radiographics 2010;30(7):1891–913. 26. Glazebrook KN, Magut MJ, Reynolds C. Angiosarcoma of the breast. Am J Roentgenol 2008;190(2):533–8. 27. Ahmad A. Pathways to breast cancer recurrence. ISRN Oncol 2013;2013: 290568. 28. Lanitis S, Behranwala KA, Al-Mufti R, et al. Axillary metastatic disease as presentation of occult or contralateral breast cancer. Breast 2009;18(4): 225–7. 29. Huston TL, Pressman PI, Moore A, et al. The presentation of contralateral axillary lymph node metastases from breast carcinoma: A clinical management dilemma. Breast J 2007;13(2):158–64.
Current Problems in Diagnostic Radiology journal homepage: www.cpdrjournal.com
Spectrum of Extramammary Malignant Neoplasms in the Breast With Radiologic-Pathologic Correlation Sirishma Kalli, MDa,n, Michael Lanfranchi, MDa, Andrew Alexander, MDb, Shital Makim, MDa, Phoebe E. Freer, MDc a
Department of Radiology, Tufts Medical Center, Boston, MA Department of Pathology, Tufts Medical Center, Boston, MA c Avon Comprehensive Breast Center, Massachusetts General Hospital, Boston, MA b
Although primary breast cancer is the most common malignancy identified by breast imaging, extramammary malignancies may also rarely be encountered. These uncommon lesions may reflect primary neoplasms of nonmammary origin as well as secondary metastatic lesions, and include lymphoma, melanoma, neuroendocrine tumors, gastrointestinal tract malignancies, and angiosarcoma among other entities. Malignant extramammary breast lesions may be encountered during routine mammographic screening, identified during the diagnostic evaluation of a palpable breast abnormality, or may be detected incidentally during imaging of other organs of interest. As such, the radiologist should have familiarity with the appearance of these lesions. This article focuses on a review of several of the most common extramammary metastases to the breast, as well as a few lesions that may develop as either primary or secondary lesions. & 2015 Mosby, Inc. All rights reserved.
Introduction
carcinoma metastasis may also contain calcifications that may appear similar to malignant ductal microcalcifications.5
The incidence of extramammary metastatic lesions to the breast ranges from 0.5%-6.6%.1-3 The most common lesions in order of descending frequency include lymphoma, melanoma, rhabdomyosarcoma, and lung and ovarian carcinoma.1,2 Metastases may arise from either hematogenous or lymphangitic spread, each generally manifesting with different imaging features. Hematogenous spread often leads to a discrete circumscribed mass or masses without spiculations or microcalcifications.4,5 On the other hand, lymphangitic spread often leads to more diffuse findings such as edema, increased trabeculation, and skin thickening.4,5 Both types of dissemination may mimic benign entities, with hematogenously spread lesions mimicking benign cysts or fibroadenomas, and lymphangitic spread mimicking mastitis. Both types of dissemination may also mimic other malignant entities, with hematogenously spread lesions mimicking less ominous appearing subtypes of primary breast malignancy such as medullary, mucinous, or papillary carcinoma, whereas lymphangitic spread may appear identical to inflammatory breast carcinoma. Though microcalcifications are not frequently present in metastatic lesions, if present, they most commonly indicate an ovarian carcinoma, due to the presence of psammoma bodies (Fig 1).2,5,6 Additionally, hepatocellular carcinoma, medullary thyroid carcinoma, or gastric
n Reprint requests: Sirishma Kalli, MD, Department of Radiology, Tufts Medical Center, 800 Washington St Box 299, Boston, MA 02111. E-mail address: [email protected] (S. Kalli).
http://dx.doi.org/10.1067/j.cpradiol.2015.07.012 0363-0188/& 2015 Mosby, Inc. All rights reserved.
Fig. 1. (A) A female patient with a history of ovarian carcinoma presented for diagnostic mammogram for 2 palpable lesions in the right axilla. Magnified RMLO view demonstrates punctate microcalcifications within a partially imaged axillary node (arrows), which upon further workup revealed metastatic ovarian carcinoma. RMLO, right mediolateral oblique.
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Fig. 2. (A) Diagnostic mammogram with spot compression views in a 38-year-old woman with a palpable lump within the right breast did not reveal a mammographic abnormality (not shown). Ultrasound imaging in the same patient reveals an oval, complex solid and cystic mass with microlobulated margins and mild internal vascularity. FNA revealed dense lymphoid infiltrate (not shown). (B) Subsequent Whole body FDG-PET/CT (select fused axial image shown) reveals a solitary area of abnormal FDG uptake within the right breast corresponding with the ultrasound abnormality (arrow). No additional areas of abnormal FDG localization were identified throughout the body. (C) Photomicrograph (hematoxylin and eosin stain, 20) from a subsequent core biopsy specimen reveals a diffuse infiltrate of large, atypical lymphocytes with vesicular chromatin, and irregular nuclear contours, which were positive for CD20, CD10, BCL2, and BLC6 (not shown). Findings are consistent with diffuse large B-cell lymphoma. FNA, fine-needle aspiration; FDG, fluorodeoxyglucose; PET, positron emission tomography; CT, computed tomography. (Color version of figure is available online.)
Specific Subtypes of Extramammary Metastases Breast Lymphoma Breast lymphoma most often presents as secondary involvement due to disseminated disease. Lymphoma less commonly presents as a primary breast lymphoma, occurring in less than 0.5% of instances.7 Clinically, both primary and secondary breast lymphomas frequently present as a palpable, painful mass within the upper outer quadrant, with axillary lymphadenopathy present
in 30%-50% of cases.7 The most common subtypes of breast lymphoma include diffuse large B-cell lymphoma, marginal-zone lymphoma (mucosa-associated lymphoid tissue lymphoma), and follicular lymphoma, all of which are of B-cell origin. Whereas diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma occur in both primary and secondary settings, follicular lymphoma occurs solely in the setting of disseminated disease.8,9 T-cell lymphomas are much rarer, occurring in less than 10% of all cases.8 At mammography breast lymphoma often appears as an indistinct mass or masses, and an irregular,
Fig. 3. (A) Axial CT in a 52-year-old male patient with long-standing GERD and epigastric pain depicts nodular masses within the gastric wall (arrows). Subsequent endoscopic biopsy revealed Burkitt's lymphoma. The patient underwent systemic chemotherapy with initial remission. (B) FDG-PET/CT for restaging 19 months later reveals area of abnormal FDG localization within the retroareolar right breast (arrow) (select axial fused PET/CT image shown). An additional area of abnormal FDG localization was noted within the left sacrum (not shown). (C) Targeted retroareolar ultrasound of the right breast reveals a correlating oval, parallel, and heterogeneous mass with indistinct margins and internal vascularity. (D) Photomicrograph (hematoxylin and eosin stain, 40) from the subsequent right core needle biopsy of the mass reveals atypical, dense lymphoid infiltrate which was immunohistochemically positive for CD20, CD10, Pax5, and Ki67 within greater than 95% of cells. Findings are consistent with a high-grade B-cell lymphoma. GERD, gastroesophageal reflux; FDG, fluorodeoxyglucose; PET, positron emission tomography; CT, computed tomography. (Color version of figure is available online.)
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Fig. 4. (A) A 59-year-old woman with a history of a left chest wall marginal-zone lymphoma is noted to have an incidental right breast mass on follow-up CT (arrow) (axial image shown). (B and C) RMLO (B) and RCC views (C) from a diagnostic mammogram reveal an irregular, ill-defined mass within the lower inner quadrant (circles). (D) Ultrasound of the right breast confirms a suspicious round, heterogeneous mass with indistinct margins. (E) Photomicrograph (hematoxylin and eosin stain, 20) from biopsy of the same patient revealed atypical, dense lymphoid infiltrate, which was positive for CD20 and negative for CD10. Findings are consistent with a marginal-zone lymphoma of mucosa-associated lymphoid tissue (MALT) type. RMLO, right mediolateral oblique; RCC, right craniocaudal. (Color version of figure is available online.)
heterogeneous, hypervascular mass or masses at ultrasound, which may be hyperechoic (Figs 2-4).7As noted previously, due to lymphangitic spread of disease, overlying skin changes may be present at both mammography and ultrasound. 7 On magnetic resonance (MR) imaging, breast lymphoma often appears as an irregular mass or masses with mild, heterogeneous internal enhancement.10 Biopsy specimens reveal atypical lymphocytes staining positive for immunohistochemical stains such as CD10, CD20, and CD30. An extremely rare subtype of lymphoma, breast implant associated anaplastic large cell lymphoma, was first described in 1997 and reflects a subtype of T-cell lymphoma that frequently presents as a pericapsular effusion, less commonly a mass.8,11 Though the direct cause of this entity is yet to be proven, nearly no cases have occurred in breasts lacking implants, suggesting a very strong association.8
Plasmacytoma Breast plasmacytoma may develop in the setting of multiple myeloma, or less commonly present as a primary lesion. In the primary setting, periodic surveillance is necessary even long after remission, as these patients may subsequently develop multiple myeloma. 15 Similar to other extramammary malignant lesions, breast plasmacytoma often presents as a circumscribed mass or masses without spiculations or microcalcifications (Fig 7).3 At ultrasound, these lesions appear as a round, hypoechoic mass or masses, which may demonstrate posterior shadowing.3 As these lesions are exceedingly rare, their appearance on MR imaging is not well reported in the literature.
Neuroendocrine Tumors Melanoma Similar to lymphoma, breast melanoma may represent either primary or metastatic disease. Patients possessing BRCA2 mutations, and possibly BRCA1, are at an increased risk for melanoma.12,13 Melanoma often appears as a circumscribed mass or masses without spiculations or microcalcifications at mammography and may have a variety of imaging appearances at ultrasound (Figs 5 and 6).14 On MR imaging, melanoma can demonstrate T1 hyperintensity, not only due to the presence of melanin, but also due to the presence of hemorrhage in these lesions, which have a high tendency to bleed.5 Histologically, melanoma specimens reveal nuclear pleomorphism and stain positive for MART-1.
Breast neuroendocrine tumors may be categorized into 3 subtypes: ductal carcinoma with neuroendocrine differentiation, primary neuroendocrine tumors of the breast, or metastatic disease. Histologically, primary breast neuroendocrine tumors can be differentiated from secondary lesions, as primary lesions often stain positive for GCDFP-15 and mammaglobin, whereas metastases generally do not.16 Frequently these lesions appear as a noncalcified, nonspiculated mass at mammography, and an irregular, hypoechoic, hypervascular mass without posterior enhancement at ultrasound (Figs 8-10).17 Dynamic contrast-enhanced MR imaging usually reveals an irregular mass demonstrating washout kinetics.17
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Fig. 5. (A and B) LMLO (A) and LCC views (B) from a screening mammogram demonstrate 2 adjacent hyperdense masses in the lateral left breast (arrows). (C and D) In retrospect, the masses are seen to have progressed from an LMLO (C) and LCC views (D) from a screening mammogram obtained 2 years prior (arrows), (white circles visualized are mole marker stickers placed by the technologist at the time of imaging on benign skin lesions). Specimen radiograph following needle localization with bracketing of the lesions again revealed hyperdense, circumscribed masses without microcalcifications (not shown), which were biopsy-proven malignant melanoma. LMLO, left mediolateral oblique; LCC, left craniocaudal.
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Fig. 6. (A and B) A 59-year-old woman presented with a palpable abnormality in the left breast. LCC (A) and LMLO views (B) from a diagnostic mammogram reveal 3 discrete, irregular masses (arrows) within the lower inner quadrant. (C) Diagnostic ultrasound of one of the masses reveals an irregular, hypoechoic lesion with microlobulated margins, which corresponded to the palpable abnormality and mammographic findings. Although the sonographic findings alone could be mistaken for a complicated cyst, the patient had a history of lymph node negative localized malignant melanoma excised from her back 2 years prior. The patient therefore underwent restaging with FDGPET/CT revealing a large area of abnormal FDG localization within the medial left breast corresponding to the mammographic, ultrasound, and palpable abnormalities (not shown). (D) Photomicrograph (hematoxylin and eosin stain, 20) of a partial mastectomy specimen reveals sheets of discohesive cells with marked nuclear pleomorphism. These cells were immunohistochemically positive for MART-1 consistent with metastatic melanoma. LCC, left craniocaudal; LMLO, left mediolateral oblique; FDG, fluorodeoxyglucose; PET, positron emission tomography; CT, computed tomography. (Color version of figure is available online.)
Gastric Carcinoma Metastatic gastric adenocarcinoma of the breast may both clinically and mammographically mimic inflammatory breast
cancer with erythematous, edematous skin, often without evidence of a mass or microcalcifications (Fig 11).18 As a visible underlying mass is often absent, these lesions may also be occult on ultrasonography, and subsequently, a skin punch biopsy may be
Fig. 7. (A) LCC view in a 68-year-old woman with a history of multiple myeloma who presented with a palpable abnormality within the left breast reveals an oval, partially obscured mass (arrow). (B) Ultrasound of the 12-o'clock region demonstrates a hypoechoic lesion with internal septation and increased vascularity. Pathology revealed cells positive for CD45, CD138, and CD56, as well as 70% Ki67 (not shown). Findings were consistent with plasmablastic plasmacytoma. LCC, left craniocaudal. (Color version of figure is available online.)
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Fig. 8. (A) Axial contrast-enhanced MRI in a 52-year-old woman with a 3-month history of odynophagia and voice change reveals a left supraglottic mass (arrow), which was a biopsy-proven atypical carcinoid. (B) After 2 years, the patient presented with a palpable breast mass which was biopsied without image guidance. Fused axial PET/CT image in the same patient reveals an area of abnormal FDG localization (arrow) in the left medial breast, which was a metastatic atypical carcinoid from the patient's prior supraglottic mass. MRI, MR imaging; PET, positron emission tomography; CT, computed tomography; FDG, fluorodeoxyglucose. (Color version of figure is available online.)
necessary for diagnosis. Biopsy often reveals atypical cells invading dermal lymphatics, which demonstrate positivity for CK7, CK20, and CDX2, and remain negative for estrogen, progesterone, and mammaglobin stains. Due to the rarity of this entity, the MR findings of metastatic gastric carcinoma to the breast are not well reported in the literature.
Osteosarcoma Breast osteosarcoma is one of the few extramammary lesions that do contain calcifications, although the calcifications appear large and coarse at mammography and ultrasound, not microscopic, and may mimic an involuting fibroadenoma (Fig 12).14,19,20
Fig. 9. (A) A woman with a history of carcinoid tumor a few years prior was found to have an incidental lesion in the superior right breast on chest CT (not shown). RCC magnification view from a needle localization procedure demonstrates an irregular, spiculated mass which was a biopsy-proven metastatic lesion from the patient's original carcinoid tumor. (B) LMLO view from a mammogram 6 years later reveals a round mass at the level of the nipple, which also resulted in a metastatic neuroendocrine tumor. CT, computed tomography; RCC, right craniocaudal; LMLO, left mediolateral oblique.
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Fig. 10. (A) Fused axial PET/CT in a 72-year-old woman with a palpable, enlarged left supraclavicular node depicts asymmetric FDG localization (arrow) within the retroareolar right breast. (B) Right retroareolar ultrasound in the same patient reveals a smaller, microlobulated hypoechoic mass, and a larger, indistinct hypoechoic mass, corresponding to the area of abnormal FDG uptake. (C) Photomicrograph (hematoxylin and eosin stain, 20) reveals a primary breast neuroendocrine carcinoma with 4 50% neuroendocrine differentiation. PET, positron emission tomography; CT, computed tomography; FDG, fluorodeoxyglucose. (Color version of figure is available online.)
Although the MR appearance of breast osteosarcoma is not well reported in the literature, one would expect the large, coarse calcifications to demonstrate hypointensity on gradient echo imaging.21 Clinically, breast osteosarcoma often presents as a rapidly enlarging mass or masses occasionally with nipple discharge, and may metastasize to the lungs, where the lesions also demonstrate coarse calcifications.19 This entity most often develops in patients with a history of prior breast irradiation, and should be considered in this patient population when lesions with coarse calcifications arise.14,22
Thyroid Carcinoma Metastatic thyroid carcinoma in the breast is extremely rare, with only a few cases reported.23 The Hurthle cell subtype has the highest incidence of metastases among differentiated thyroid carcinomas.24 On mammography, metastatic differentiated thyroid carcinomas may contain calcifications, whereas the appearance of these lesions at ultrasound and MR imaging is not well reported in the literature (Fig 13).23 Treatment of metastatic thyroid carcinoma to the breast often includes resection with or without I-131 therapy.23
Fig. 11. (A) Axial CT image in a 49-year-old woman with history of metastatic gastric adenocarcinoma demonstrates diffuse gastric wall thickening (arrow) and peritoneal carcinomatosis (not shown). (B) Diffuse increased density and skin thickening were noted in the left breast (arrow). The differential for the breast findings included infectious mastitis, lymphatic obstruction due to metastases, or inflammatory breast cancer. (C) Subsequent mammogram LCC view confirmed diffuse increased breast density and skin and trabecular thickening. (D) Skin punch biopsy of the breast (hematoxylin and eosin stain, 20) reveals a dermal lymphatic channel containing atypical cells (circled) with hyperchromatic nuclei and cytoplasmic vacuoles, which were positive for CK7, CK20, and CDX2 and negative for estrogen receptor, progesterone receptor, and mammaglobin. Findings were consistent with lymphangitic spread of gastric adenocarcinoma. CT, computed tomography. (Color version of figure is available online.)
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Fig. 12. (A) LMLO implant displaced view in a 56-year-old woman with a palpable left breast mass demonstrates a calcified mass adjacent to the implant (arrow). (B) Ultrasound image during core biopsy reveals coarse calcifications within an oval, circumscribed, hypoechoic mass. Pathology revealed an extraskeletal osteosarcoma. LMLO, left mediolateral oblique.
Rhabdomyosarcoma Metastatic breast rhabdomyosarcoma is the most prevalent breast metastasis within adolescent females, and should be considered strongly in young patients with an appropriate clinical history.1 In the breast, rhabdomyosarcoma may mimic invasive lobular carcinoma, appearing as a mammographic focal asymmetry and an ill‐ defined, hypoechoic, shadowing lesion at ultrasound, while the MR appearance is not well described.14 Similar to rhabdomyosarcoma, infiltrative leukemia is another entity that may have similar findings that resemble invasive lobular carcinoma.14 Angiosarcoma Patients who have received breast conservation therapy may develop radiation-induced angiosarcoma in as many as 2% of
cases.25 This malignancy emerges as multiple cutaneous masses often following an extensive latency period of up to 10 years on average.25 These skin lesions can be difficult to differentiate from tumor recurrence, as they often manifest as skin thickening with or without an associated parenchymal mass at mammography and ultrasound, but should be included in the differential in the postradiated breast.25,26 Much rarer, breast angiosarcoma may develop as a primary lesion, comprising less than 0.4% of all breast neoplasms.25 At mammography this entity may appear as an ill-defined, noncalcified mass or focal asymmetry, and as an ill-defined, highly vascular mass at ultrasound. 26 Both primary and secondary breast angiosarcomas often reveal a predominantly T1 hypointense, T2 hyperintense, heterogeneous mass demonstrating plateau or washout kinetics at MR imaging, with secondary cases also demonstrating focal areas of skin thickening and enhancement.25,26
Fig. 13. (A) A 52-year-old patient with a history of a left invasive ductal carcinoma, status post partial mastectomy, radiation, and chemotherapy, as well as a Hurthle cell carcinoma, status post thyroidectomy and high-dose I-131 therapy, presented with a palpable right breast abnormality. RCC view reveals an isodense, circumscribed mass within the medial right breast. (B) This mass appeared new when compared to a negative screening mammogram obtained 2 months earlier. (C) Ultrasound of the palpable abnormality reveals an oval, circumscribed, and heterogeneous mass, which was biopsy-proven metastatic Hurthle cell carcinoma.
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Fig. 14. (A and B) A screening mammogram in a female with a history of a right invasive ductal carcinoma demonstrated expected breast conservation findings of scar and architectural distortion at the lumpectomy site in the lateral right breast (not shown). RCC (A) and LCC views (B) 3 years later demonstrate new bilateral round, isodense masses consistent with diffuse bilateral breast cancer metastases. On further workup, the patient had pathology-proven breast cancer visceral, osseous, and skin metastasis (not shown). RCC, right craniocaudal; LCC, left craniocaudal.
Mammary Metastases The most common metastases to the breast are from a primary breast malignancy of the contralateral breast (Fig 14).5 In cases of mammary metastases, triple negative cancers pose a high risk of recurrence and metastases.27 Though contralateral disease typically spreads through lymphatic drainage of the internal mammary chain, development of contralateral axillary metastases may also rarely occur in 3.6%-6% of cases, some of which may not reveal visible breast disease (Fig 15).28,29 Damage to the normal lymphatic pattern of drainage may occur due to obstruction from the
primary ipsilateral malignancy, or as a result of surgical or radiation therapy.28,29 Subsequently, alternate routes of drainage via the chest wall and dermal lymphatics may develop, providing pathways for contralateral spread of disease.28,29
Conclusion Although rare, extramammary malignant neoplasms should be considered in the differential diagnosis for breast lesions in the appropriate clinical setting. Hematogenously spread metastases
Fig. 15. (A) LMLO view in a patient with a history of right invasive ductal carcinoma, status post breast conservation therapy and recurrence status post right mastectomy, demonstrates contralateral axillary adenopathy, without any visible breast disease. (B) Axial contrast-enhanced MR image in the same patient demonstrates bulky contralateral axillary adenopathy (arrows), the pathology of which revealed metastases from the patient's original primary tumor. LMLO, left mediolateral oblique.
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Table Summary of imaging findings of malignant extramammary malignant neoplasms within the breast
Lymphoma
Melanoma Plasmacytoma Neuroendocrine tumor Gastric carcinoma
Osteosarcoma
Mammography
Ultrasound
MRI
Indistinct mass(es) often with axillary lymphadenopathy, may have skin thickening Circumscribed mass(es) without spiculation or microcalcifications Circumscribed mass(es) without spiculation or microcalcifications Circumscribed mass(es) without spiculation or microcalcifications Skin thickening, increased trabeculation indicating edema, may contain macrocalcifications Mass(es) containing large, coarse macrocalcifications
Irregular, heterogeneous, hypervascular mass(es), may be hyperechoic, may have skin thickening Variable appearance
Irregular mass(es) with mild, heterogeneous internal enhancement
Thyroid carcinoma
May contain microcalcifications in cases of medullary thyroid carcinoma
Rhabdomyosarcoma
Focal asymmetry
Primary angiosarcoma
Ill-defined noncalcified mass or focal asymmetry Skin thickening and postsurgical or radiation changes 7 ill-defined asymmetric parenchymal mass
Secondary angiosarcoma
Round, hypoechoic mass(es) Irregular, hypoechoic, hypervascular mass(es) May be occult
Circumscribed hypoechoic mass(es) with multiple large, echogenic foci with shadowing indicating calcifications Findings not well reported in the literature; may appear as an oval, heterogeneous mass (Fig 13C) Ill-defined, hypoechoic, shadowing lesion(s) Ill-defined, highly vascular mass Skin lesions may be occult, heterogeneous parenchymal mass may be present
Often T1 hyperintense mass(es) due to melanin or hemorrhage Findings not well reported in the literature Irregular mass(es) demonstrating washout kinetics Findings not well reported in the literature
Areas of susceptibility corresponding to macrocalcifications
Findings not well reported in the literature
Findings not well reported in the literature Heterogeneous mass, T1 hypointense, T2 hyperintense demonstrating plateau or washout kinetics for both types; skin thickening and enhancement in secondary cases
MRI, MR imaging.
often develop as a circumscribed mass or masses without spiculations or microcalcifications, whereas lymphangitic spread of disease often presents as diffuse breast edema and skin thickening. The imaging findings of several subtypes of extramammary malignant neoplasms are summarized in the Table. Awareness of these possibilities may aid patient diagnosis and lead to quicker, more appropriate management strategies.
Acknowledgments Breast osteosarcoma case courtesy of Matthew C. Oliff, MD and Troy Maetani, MD, Brigham and Women's Hospital, Boston, MA. References 1. Bartella L, Kaye J, Perry NM, et al. Metastases to the breast revisited: Radiological-histopathological correlation. Clin Radiol 2003;58(7):524–31. 2. Alvarado Cabrero I, Carrera Alvarez M, Perez Montiel D, et al. Metastases to the breast. Eur J Surg Oncol 2003;29(10):854–5. 3. Karan B, Pourbagher A, Bolat FA. Unusual malignant breast lesions: Imagingpathological correlations. Diagn Interv Radiol 2012;18(3):270–6. 4. Mun SH, Ko EY, Han BK, et al. Breast metastases from extramammary malignancies: Typical and atypical ultrasound features. Korean J Radiol 2014;15(1):20–8. 5. Surov A, Fiedler E, Holzhausen HJ, et al. Metastases to the breast from nonmammary malignancies: Primary tumors, prevalence, clinical signs, and radiological features. Acad Radiol 2011;18(5):565–74. 6. Klein RL, Brown AR, Gomez-Castro CM, et al. Ovarian cancer metastatic to the breast presenting as inflammatory breast cancer: A case report and literature review. J Cancer 2010;2(1):27–31. 7. Yang WT, Lane DL, Le-Petross HT, et al. Breast lymphoma: Imaging findings of 32 tumors in 27 patients. Radiology 2007;245(3):692–702. 8. Miranda RN, Aladily TN, Prince HM, et al. Breast implant-associated anaplastic large-cell lymphoma: Long-term follow-up of 60 patients. J Clin Oncol 2014;32 (2):114–20. 9. Talwalkar SS, Miranda RN, Valbuena JR, et al. Lymphomas involving the breast: A study of 106 cases comparing localized and disseminated neoplasms. Am J Surg Pathol 2008;32(9):1299–309. 10. Liu K1, Xie P, Peng W, et al. The features of breast lymphoma on MRI. Br J Radiol 2013;86(1031):20130220.
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