Unusual Breast Cancers: What do we know?

Unusual Breast Cancers: What do we know? Poster No.: C-1267 Congress: ECR 2015 Type: Educational Exhibit Authors: D. A. Puentes Bejarano, C. Oliva Fonte, C. Sibaja Castro, J. Pereda Rodríguez, J. Gonzalez Llorente, F. J. Rodríguez Recio, M. Lobo Garcia; Segovia/ES Keywords: Cancer, Biopsy, Ultrasound, MR, Mammography, Oncology, Breast DOI: 10.1594/ecr2015/C-1267 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 23

Learning objectives This poster will provide an overview of a few unusual types of breast cancer. Describe the main features of image, patient demographics, clinical characteristics and some histopathological findings may suggest that the findings are unusual breast cancer. Background Invasive ductal carcinoma not otherwise specified (IDC-NOS) and ductal carcinoma in situ (DCIS) account for about 85% of breast cancers. The remaining 15% of breast cancers are other types of malignant neoplasm. Unusual breast neoplasms may be broadly divided into: Invasive lobular carcinoma (ILC) Tubulolobular carcinoma Well-differentiated subtypes of invasive ductal carcinoma (IDC) Cancers of stromal origin Metastatic neoplasms. Invasive lobular carcinoma infiltrates the breast in thin sheets of cells similar to a spiderweb, typically resulting in thickening at clinical examination, architectural distortion without a central mass at mammography, and areas of shadowing on a US scan. The well-differentiated subtypes of invasive ductal carcinoma (IDC) (mucinous, medullary, tubular, and papillary carcinomas) have a better prognosis than IDC not otherwise specified, because the former are characterized by slow growth (except medullary carcinoma) and a relatively circumscribed appearance at mammography (except tubular carcinoma, which appears spiculated at mammography but is "tubular"). Phyllodes tumor mimics fibroadenoma in appearance but is typically large in size and occurs in middle-aged and older women. Page 2 of 23

Findings and procedure details INVASIVE LOBULAR CARCINOMA (Fig. 1,2) Terminology Invasive cancer characterized by loss of normal cell adhesion; invades as individual cells or single-file cell columns. Clinical Issues Accounts for 6%-9% of breast cancers; 10-15% of all invasive breast cancer Palpable mass or vague palpable area thickening, shrinking breast, skin/nipple retraction. Matched by stage and grade, prognosis is similar to that of IDC NOS. Imaging Overrepresented among missed or delayed diagnoses Mammography (MMG): Spiculated mass (most common), new focal asymmetry, may be one-view only; Architectural distortion, shrinking breast. Calcifications are rare. US: Irregular mass, posterior shadowing, focal shadowing without discrete mass. MR: Irregular, spiculated mass with heterogeneous enhancement or non-mass enhancement. Multifocal, multicentric, bilateral disease > IDC Pathology Infiltrative growth pattern, like a spiderweb. Lacks E-cadherin on immunohistochemistry. E-cadherin: Related to cell-cell adhesion Differential Diagnoses Invasive ductal carcinoma NOS, tubular carcinoma Lobular carcinoma in situ, diabetic mastopathy Page 3 of 23

Fibrosis, postoperative scar, radial scar. TUBULOLOBULAR CARCINOMA (Fig. 3,4) Terminology Morphologically distinct type of mammary carcinoma consisting of minute, well-formed tubules and single dyscohesive cells. Radiologic and clinical point of view, the tumor is more akin to invasive lobular carcinoma Often unrecognized breast cancer variant. Clinical Issues Rare (1-2% invasive carcinomas); range: 32-79 years Presents as palpable mass, less commonly as mass on screening mammogram Intermediate prognosis between pure tubular and invasive lobular carcinoma; 91% 10year survival. Have the same likelihood of nodal metastases when matched by size that invasive moderately differentiated ductal carcinoma Imaging Imaging characteristics are identical to lobular breast cancer, and there is the same tendency to multifocality and multicentricity. Mammography: Irregular mass, focal asymmetry, architectural distortion US: Irregular, hypoechoic mass with microlobulated, angular, spiculated margins and posterior shadowing MR: Irregular, enhancing mass, spiculated margins Pathology Has hybrid histologic characteristics of tubular and invasive lobular carcinoma with the same cells comprising well-formed glands contiguous with single file infiltration of stroma. Immunohistochemical studies imply a ductal phenotype. Page 4 of 23

Tubulolobular pattern in # 75% of tumor Low-grade invasive carcinoma with tubule formation and single cell lobular pattern. Tubular component: Small, uniform, low-grade nuclei & inconspicuous nucleoli; Lobular component: Single cell infiltration & small, round, dyscohesive cells Differential Diagnoses Tubular carcinoma, invasive lobular carcinoma, radial scar. SUBTYPES OF INVASIVE DUCTAL CARCINOMA MUCINOUS MEDULLARY TUBULAR PAPILLARY Have a better prognosis than IDC. Are characterized by slow growth (except medullary carcinoma). Relatively circumscribed appearance at mammography (except tubular carcinoma, which appears spiculated at mammography). MUCINOUS CARCINOMA (Fig. 5,6) Terminology 1-4% breast cancers. Synonyms: Colloid, gelatinous, or mucous carcinoma. Pure type: # 90% of tumor shows mucin production. Tumors with less extensive mucin = mixed type. Clinical Issues Palpable in 50% of patients, predominantly female; slow growing. Page 5 of 23

1% in women # 35 years, 7% in women # 75 years. Pure type more common in postmenopausal women. Mixed type more common in premenopausal women. More favorable prognosis than IDC NOS. 10-year survival for pure form: 90%. Imaging Mammography: Partially circumscribed, round, oval, irregular, dense mass; ~ 20% occult Calcifications more common in mixed type US: Round, oval, or irregular, isoechoic, hypoechoic mass; posterior enhancement in > 50%; partially circumscribed or microlobulated margins. Power Doppler: Vascularity noted in ~ 1/3 of tumors. MR: T2 hyperintensity due to high mucin content; avid, slow rim enhancement Pathology Aggregates of tumor cells surrounded by abundant extracellular mucin. Associated DCIS in 75% of cases Axillary metastases < 12%, less frequent than in IDC Pools of mucin on core biopsy require excision to exclude paucicellular tumor. Differential Diagnoses Fibroadenoma. IDC-NOS. Mucocele-like lesión. Cyst with debris MEDULLARY CARCINOMA (Fig. 7,8) Terminology Atypical medullary carcinoma (MC) = IDC NOS with medullary features. Page 6 of 23

Mimics poorly differentiated carcinoma at histologic examination but also has a good prognosis. Clinical Issues 1-7% of breast cancer, 10% in women < 35 years Enlarging, soft, palpable mass and axillary nodes Survival better than IDC NOS; 5-year survival: 89-95% Rapid growth, median size: 2-3 cm Imaging Mammogram: Oval, round, lobular, noncalcified mass; partially circumscribed, indistinct margins. US: Hypoechoic mass with posterior enhancement # pseudocystic appearance (confused with lymphoma); satellite nodules and axillary adenopathy common MR Findings: T2WI FS: May show cystic component in necrotic areas. T1WI C+ FS: Oval or lobulated enhancing mass with smooth margin, delayed peripheral enhancement; plateau or washout type with rapid initial rise on time-intensity curve. Pathology Locally aggressive; necrosis or hemorrhage, oval or microlobulated; axillary metastases uncommon. Defined by presence of 5 histologic features in # 90% of tumor: Syncytial pattern (>75%), sharply circumscribed pushing borders, marked lymphoplasmacytic infiltrate (diffuse and involves periphery), high nuclear grade and mitotic count, absence of glandular formation. Differential Diagnoses IDC NOS, mucinous, papillary DCIS. Non-Hodgkin lymphoma. Fibroadenoma (women under 35), phyllodes. TUBULAR CARCINOMA (Fig. 9) Page 7 of 23

Terminology Well differentiated, low metastatic potential, excellent prognosis. Pure: Proportion of tubular structures # 90%. Mixed: 50-89% tubular pattern. Clinical Issues 10-30% of screen-detected cancers; presents as nonpalpable MMG-/MR-detected mass (60-70%). 1-4% of breast cancers in unscreened population. Slow growing, 95-98% 5-year survival. Imaging Mammography: Small, irregular, spiculated mass; Ca++ in up to 50%; architectural distortion, asymmetry. US: Irregular, spiculated mass with indistinct margins. MR: Irregular, spiculated, enhancing T1-isointense mass; rapid initial enhancement, washout kinetics. Pathology Associations: Columnar cell change, flat epithelial atypia, low-grade DCIS (90%), lobular neoplasia (15-55%), contralateral cancer (10-15%), multifocality (20%), multicentricity (20-50%). Composed of small glands or tubules haphazardly arranged in stroma with low-grade cells; absent myoepithelial cell layer: Lacks actin or p63 staining. Low incidence of axillary node metastasis (7-15%). Differential Diagnoses Radial scar or radial sclerosing lesion. Postsurgical scar, fat necrosis, granular cell tumor. IDC NOS, invasive lobular carcinoma, DCIS. Page 8 of 23

PAPILLARY CARCINOMA (Fig. 10) Terminology Carcinoma within single circumscribed cystic space. Synonyms: Encapsulated, Intracystic papillary carcinoma. Clinical Issues Palpable, circumscribed mass; nipple discharge (bloody, serosanguineous). 0.5-2% of breast cancers in postmenopausal women (median age: 70 years). Imaging Mammography: Round, oval, or lobulated, circumscribed, dense mass, solitary or multiple; amorphous/pleomorphic Ca++. US: Solid or complex, cystic and solid mass with posterior enhancement, hypervascularity. Galactography: Nipple discharge evaluation; ductal wall irregularity, filling defects, truncation. MR: Enhancing, circumscribed, intracystic mass. Pathology Carcinoma within circumscribed space, may contain hemorrhage or cystic areas; delicate thin papillary fronds with thin fibrovascular core. Lack myoepithelial cells (p63) in capsule or in fronds. ~ 25% show frank invasion, focally at periphery. Rare axillary node metastases. Differential Diagnoses Papillary neoplasm, invasive ductal carcinoma. Page 9 of 23

Complicated cyst, galactocele, abscess, hematoma. Phyllodes tumor, lymphoma, metastases. MALIGNANT NEOPLASMS OF STROMAL ORIGIN PHYLLODES TUMOR A very large, relatively circumscribed breast mass is usually. Mimics fibroadenoma in appearance. Like giant fibroadenoma if the patient is young. ANGIOSARCOMAS AND OSTEOSARCOMAS Occur more frequently after radiation therapy and should be considered with the appearance of a highly vascular mass and large unusual-appearing calcification, respectively. METASTATIC LESIONS NON-HODGKIN LYMPHOMA RHABDOMYOSARCOMA LEUKEMIA May manifest as adenopathy or multiple relatively circumscribed masses. Infiltrative metastasis, may mimic ILC. LYMPHOMA (Fig. 11) Terminology Non-Hodgkin lymphoma (NHL). Clonal population of malignant lymphocytes. Primary lymphoma: Breast ± axillary node(s) only. Page 10 of 23

Secondary lymphoma: Breast ± axillary involvement with concurrent or prior systemic lymphoma. Clinical Issues Secondary lymphoma: Axillary adenopathy (30-50%); multiple, nonpalpable, bilateral breast masses; rapidly enlarging palpable mass; asymptomatic. Age range: 13-90 years; bimodal peaks at 38 and 58 < 0.5% of malignant breast tumors, < 0.7% of all lymphomas; prognosis related to histologic subtype, age, tumor size, bilaterality, axillary nodal disease Treatment: Chemotherapy, radiation therapy (effective local control); surgery not indicated. Imaging Mammography: Noncalcified oval or lobulated mass(es), circumscribed, indistinct margins. US: Markedly hypoechoic to anechoic mass, can be hyperechoic or mixed echogenicity, hypervascular. MR: Circumscribed, rapidly enhancing mass. Pathology Monotonous round cells, variable nuclear pleomorphism and mitotic activity. Majority diffuse large B-cell lymphoma (40-70%). T-cell lymphoma is less common (< 10%). Hodgkin disease of breast is rare. Differential Diagnoses Axillary adenopathy (metastases, granulomatous disease, autoimmune disorders). Circumscribed breast cancer, metastases to breast. Images for this section: Page 11 of 23

Fig. 1: Invasive Lobular Carcinoma. Right Breast. 43 year old woman. Mammographic views (a) Craniocaudal (CC). (b) Mediolateral oblique (MLO). Show an apparent decrease in size of the right breast (arrows). Show focal asymmetry (circled area), with subtle architectural distortion. Page 12 of 23

Fig. 2: Invasive Lobular Carcinoma. Right Breast. US (same patient Fig. 1) (a,c) Shows a small, irregular hypoechoic masses with indistinct margins. (b,d) Irregular, hypoechoic masses with some indistinct margins (red arrows) and subtle posterior shadowing (blue arrows). Page 13 of 23

Fig. 3: Tubulolobular Carcinoma. Right Breast 61 year old woman with a palpable mass. Mammographic views with node marked (a) CC. Subtle focal asymmetry only in this projection (circled area). (b) MLO. US (c,d) Shows a small, irregular hypoechoic masses with indistinct margins (arrows). Page 14 of 23

Fig. 4: Tubulolobular Carcinoma. Right Breast MR Post-contrast (same patient Fig. 3) (a) Axial T1WI C+ FS. (b) Sagittal T1WI C+ FS. (c) Sagittal T1 C+ Subtraction. Shows irregular, enhancing masses (arrows). Page 15 of 23

Fig. 5: Mucinous Carcinoma. Right Breast 40 year old woman with a palpable mass. Mammography (a) CC. (b) MLO. Irregular, isodense mass with indistinct margins (circled area). US (c,d) Shows isoechoic mass with indistinct margins and internal vascularity. Page 16 of 23

Fig. 6: Mucinous Carcinoma. Right Breast. MR (same patient Fig. 5) (a)t1wi (b)t2wi Shows contiguous, oval, T2-hyperintense masses (blue arrow) with adjacent satellite nodule (red arrow). (c,d) Sagittal, Axial T1WI C+ FS Slow rim enhancement. Page 17 of 23

Fig. 7: Medullary Carcinoma. Right Breast 37 year old woman with a palpable nodule. Mammographic views with node marked (a) CC. (b) MLO. Lobular mass, with indistinct margins. US (c,d) Shows hypoechoic mass with microlobulated margins and internal vascularity. Page 18 of 23

Fig. 8: Medullary Carcinoma. Right Breast. MR (same patient Fig. 7) (a) Sagittal T1WI Isointense mass. (b) Sagittal T2WI. (c,d) Sagittal, Axial T1WI C+ FS Lobulated enhancing mass with rapid initial rise. Page 19 of 23

Fig. 9: Tubular Carcinoma. Right Breast. 48 year old woman. Sent from the screnning for architectural distortion in the right breast. Mammographic views. (a) CC. (b) MLO. (c) Magnified. Spiculated mass (arrows). US (d) Irregular, spiculated mass with indistinct margins. vacuum assisted breast biopsy (VABB) was conducted considering radial scar, pathological result of tubular carcinoma. Fig. 10: Papillary Carcinoma. Left Breast. 80 year old woman with a palpable mass. Mammographic views with node marked (a) CC. (b) MLO. Lobulated, circumscribed, dense mass. US (c,d) Complex, cystic and solid mass with posterior enhancement and hypervascularity. Page 20 of 23

Fig. 11: Lymphoma. Right Breast. 45 year old woman lymphoma known mass mammographic finding. Mammographic (a) MLO. Oval mass with indistinct margins (b) MLO 28 months after, treatment disappears mass (circled area). US (c,d) Mixed echogenicity and vascular mass. CT (e) Axial. Oval mass with indistinct margins. (f) Axial. 24 months after, mass decreased in size with treatment (blue arrows). Page 21 of 23

Conclusion Unusual breast neoplasms may be broadly divided into invasive lobular carcinoma, tubulolobular carcinoma, well-differentiated subtypes of invasive ductal carcinoma, cancers of stromal origin, and metastatic neoplasms. The well-differentiated subtypes of IDC have a better prognosis than does IDC not otherwise specified. They are characterized by slow growth (except medullary carcinoma) and a relatively circumscribed appearance at mammography (except for tubular carcinoma, which appears spiculated). Mucinous carcinoma has low density on a mammogram and high signal intensity on T2-weighted MR images due to high mucin content. Medullary carcinoma mimics poorly differentiated carcinoma at histologic examination. Phyllodes tumor mimics fibroadenoma in appearance but is typically large in size and occurs in middle-aged and older women. Personal information dapuentesb@gmail.com References 1. 2. 3. 4. 5. 6. 7. 8. Berg JW, Hutter RV. Breast cancer. Cancer 1995;75:257-269. Deanna L. Lane; Wei Tse Yang. Invasive Lobular Carcinoma. Elsevier's STATdx. 2005-2015. Dillon DA, Guidi AJ, Schnitt SJ. Pathology of invasive breast cancer. In: Diseases of the Breast, 4th, Harris JR, Lippman ME, Morrow M, Osborne CK (Eds), Lippincott, Williams and Wilkins, Philadelphia 2009. Feder MJ, Shaw PE, Hogge PJ, Wilken JJ. Unusual Breast Lesions: Radiologic-Phathologic Correlation. RadioGraphics. Volume 19. October 1999. Harvey.J.A. Unusual Breast Cancers: Useful Clues to Expanding the Differential Diagnosis. Radiology. Vol 242:Number 3,March 2007. Harvey.J.A, Glassman.L.M, Comstock.C.E. Radiologic pathology. Breast Imaging. Unusual Breast Cancers. AIRP. Ira J Bleiweiss, Anees B Chagpar, Don S Dizon. Pathology of breast cancer. 2013. UpToDate. Li CI, Uribe DJ, Daling JR. Clinical characteristics of different histologic types of breast cancer. Br J Cancer. 2005;93(9):1046. Page 22 of 23

9. Orvieto E, Maiorano E, Bottiglieri L, Maisonneuve P, Rotmensz N, Galimberti V, Luini A, Brenelli F, Gatti G, Viale G. Clinicopathologic characteristics of invasive lobular carcinoma of the breast. Cancer. 2008;113(7):1511. 10. Wei Tse Yang. Tubulolobular Carcinoma, Mucinous Carcinoma, Tubular Carcinoma, Medullary Carcinoma, Encapsulated papillary carcinoma, Lymphoma secondary. Elsevier's STATdx. 2005-2015. Page 23 of 23