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Case ReportpISSN 1738-2637 / eISSN 2288-2928J Korean Soc Radiol 2017;76(5):354-357https://doi.org/10.3348/jksr.2017.76.5.354

INTRODUCTION

Amyloidosis refers to the extracellular deposition in tissues of fibrils composed of low molecular weight subunits of a variety of proteins, many of which circulate as constituents of plasma. Am-yloid deposits can occur in any body site such as skin, tongue, gastrointestinal tract, urogenital tract and the respiratory tract. However, the breast is an unusual site for amyloidosis involve-ment (1). Here, we describe a case of breast involvement of amy-loidosis in patient with underlying multiple myeloma, detected on a baseline screening mammogram and subsequent ultraso-nography focusing on imaging finding.

CASE REPORT

A 56-year-old menopausal woman with a history of multiple

myeloma visited our breast center for a screening mammogram. She had a prior history of multiple myeloma which was diag-nosed 6 years previously. Even though the multiple myeloma had been treated with chemotherapy and autologous peripheral blood stem cell transplantation, she was diagnosed 3 years later with plasma cell neoplasm for pleural mass by aspiration biopsy, and she was treated with radiation therapy for this lesion. She had no prior history of breast disease or familial history of breast cancer, and had received hormone replacement therapy for 5 years at the gynecology department due to postmenopausal symptoms.

The screening mammogram revealed a focal asymmetry in the outer central portion of the right breast, in the middle third of the breast (Fig. 1A, B), and there was no combined suspicious microcalcification or architectural distortion in her breast. The focal asymmetry was interpreted as Breast Imaging Reporting

Breast Amyloidosis in a Female Patient with Multiple Myeloma: Ultrasonographic and Mammographic Findings다발성 골수종 환자에서 아밀로이드증의 유방 침범의 예: 초음파와 유방촬영술 소견

Ah Rhm Woo, MD1, Joon Mee Kim, MD2, Se Jin Nam, MD1,3*Departments of 1Radiology, 2Pathology, Inha University Hospital, Incheon, Korea3Department of Radiology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea

Amyloidosis is a rare disease characterized by pathological protein deposits in organs or tissues. Breast involvement by amyloidosis is rare. We report a female patient with amyloidosis in the breast, with underlying multiple myeloma, which presents as a fo-cal asymmetry on a screening mammogram and a low suspicious mass lesion by ul-trasonography.

Index termsBreastAmyloidosisMultiple MyelomaMammographyUltrasonography

Received July 18, 2016Revised August 9, 2016Accepted October 1, 2016*Corresponding author: Se Jin Nam, MDDepartment of Radiology, Hallym University Dongtan Sacred Heart Hospital, 7 Keunjaebong-gil, Hwaseong 18450, Korea.Tel. 82-31-8086-2580 Fax. 82-31-8086-2584E-mail: yalliyalla@gmail.com

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distri-bution, and reproduction in any medium, provided the original work is properly cited.

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and Data System (BI-RADS) category 0. Since this was an in-complete assessment, ultrasonography was recommended for further evaluation.

Ultrasonography revealed the lesion to be an approximately 1.1 cm sized, oval shaped, isoechoic mass with a microlobulated margin in the 9 o’clock direction of the right breast, 5 cm away from the nipple (Fig. 1C). Based on ultrasonography findings, the lesion was considered a BI-RADS category 4a, i.e., low suspi-cion for malignancy, and biopsy was recommended for confir-mation.

Ultrasound-guided core biopsy using a 14-gauge needle was performed four times. Ductal and lobular atrophy due to diffuse amyloid deposits in the stroma was revealed by the pathologic examination of the cores (Fig. 1D). Congo-red staining produced

red-orange coloring, and polarized light microscopy showed ap-ple-green birefringence, both results confirming amyloidosis (Fig. 1E, F). Subsequently a large, irregular, enhancing mass was found by chest computed tomography (CT) (Fig. 2). The patient underwent a follow-up surgery for the pleural mass and the le-sion was diagnosed as a plasma cell myeloma forming amyloid tumor by surgical wedge resection. The patient was treated with adjuvant chemotherapy for uncontrolled multiple myeloma. Follow-up breast ultrasonography and chest CT 1 year after re-ceiving chemotherapy revealed a slight increase in the size of the breast mass and a newly developed pleural lesion, suggesting the progression of the multiple myeloma.

Fig. 1. Amyloidosis of the breast in a 56-year-old woman with multiple myeloma.A, B. Mammograms with craniocaudal (A) and mediolateral oblique (B) views show focal asymmetry (arrows) at the outer central portion of the right breast without microcalcification or masses. C. Ultrasonogram shows oval shaped, isoechoic mass with microlobulated margin and parallel orientation, which is located at the 9 o’clock posi-tion of the right breast and 5 cm away from the nipple (the largest diameter: 1.1 cm).D-F. Microscopic examination of 14-gauge core biopsy specimens of breast amyloidosis (D) shows amyloid deposition (arrow) in the periductal stroma of the breast. (H&E, × 200). Congo red stain (× 100) (E) reveals diffuse orange red coloring (arrow) consistent with a strong positive iden-tification of amyloid. Polarizing microscopy (× 100) (F) reveals the characteristic apple-green birefringence (arrow) of amyloid.

D E F

A B C

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DISCUSSION

Amyloidosis can be divided into two major groups according to the type of accumulated amyloid: 1) amyloid light-chain am-yloidosis (AL; primary) associated with plasma cell dyscrasia such as multiple myeloma, in which a monoclonal immuno-globulin (Ig) is detectable in the serum; and 2) amyloid A (sec-ondary) amyloidosis associated with amyloid complicated by chronic infections or inflammatory diseases such as rheuma-toid arthritis, spondyloarthropathy, inflammatory bowel dis-ease or periodic fever syndromes (2).

Breast amyloidosis lacks specific clinical or radiographic fea-tures, and has rarely been reported (2). It can be part of systemic disease or may be isolated to the breast (2, 3), but it mostly oc-curs as a focal involvement of systemic disease (3). Systemic amyloidosis is associated with clonal B-cell or plasma cell pro-liferation such as in multiple myeloma. The incidence of system-ic amyloidosis is approximately one-tenth that of multiple my-eloma (4). Systemic amyloidosis associated with hematologic malignancy is reported to involve the breast in over half of the cases, and breast involvement is usually found as a late presen-tation and typically associated with AL amyloidosis (2). Amyloid fibril protein produced from free Ig light chains secreted by a monoclonal population of plasma cells (5, 6) might be the cause of AL amyloidosis in this condition (5). In our case, monoclonal

light chain was positive in the serum immune histochemical stain analysis.

Breast amyloidosis typically occurs in women from 43 to 86 years of age. The majority of breast amyloidosis patients have no clinical symptoms, and only a few patients have a painless pal-pable mass or localized skin thickening, edema, or erythema (3, 5). In our case, the patient complained of no symptoms or signs, and the lesion was detected by radiologic screening examination.

The common mammographic finding of breast amyloidosis is described as a variety of multiple solid masses, with or without calcifications (7). In our case, only focal asymmetry without a demonstrable mass or microcalcification was identified as an amyloidosis lesion by mammography. Although there are sever-al reports related to mammographic descriptions of amyloidosis, detailed reports on ultrasonographic findings are rare. Our case presented an oval shaped, isoechoic, microlobulated mass on ul-trasonography. Pathologic examination showed amyloid depos-its around ducts, vessels, and within lobules, leading to atrophy, obliteration of glandular components, and calcification or a for-eign body–like reaction (8). We think that these pathologic fea-tures of periductal infiltration, lobular atrophy and inflammatory reaction may cause the low suspicious ultrasonographic features of breast amyloidosis.

The confirmative diagnosis for breast amyloidosis should be made histologically, as it has been reported that radiologic find-ings can mimic malignancy and several coexisting breast can-cers such as tubular carcinoma, invasive ductal carcinoma, and invasive lobular carcinoma (9). The distinctive amorphous pink or red color obtained with Congo red stain, and the apple-green birefringence seen by polarizing microscopy are the pathogno-monic findings for diagnosis of amyloid deposits.

The prognosis for patients with systemic involvement of am-yloidosis is poor (2, 8), and the prognosis for those with associat-ed hematologic disorders is dependent on the underlying hema-tologic disease (2). In patients with localized amyloidosis without hematologic disease, treatment is unnecessary (2). However, pa-tients with systemic amyloidosis associated with hematologic dis-ease require chemotherapy, with or without radiation therapy. Resorption of amyloid deposits after treatment of the associated disease has been reported, but it is rare (8). Patients with myelo-ma-associated amyloidosis have a poorer prognosis than those with other types of systemic amyloidosis (8). The prognosis for

Fig. 2. Chest CT of same patient. Contrast enhanced CT scan shows an irregular enhancing mass in the left lower lung. The lesion was diag-nosed as plasma cell myeloma forming amyloid tumor by surgical wedge resection.

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patients with localized amyloidosis is much better (2, 8).In conclusion, we report a case of breast involvement by sys-

temic amyloidosis in a 56-year-old woman with underlying mul-tiple myeloma. Despite its rarity, if radiologists recognize radio-graphic breast abnormality in multiple myeloma patients, the possibility of breast amyloidosis should be considered as a dif-ferential diagnosis, and systemic evaluation should also be con-sidered to rule out possible disease progression.

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다발성 골수종 환자에서 아밀로이드증의 유방 침범의 예: 초음파와 유방촬영술 소견

우아름1 · 김준미2 · 남세진1,3*

아밀로이드증은 병적인 아밀로이드 단백질이 여러 기관과 조직에 침착되어 발생하는 드문 질환으로, 특히 아밀로이드증의

유방 침범은 매우 드문 것으로 알려져 있다. 우리는 다발성 골수종 환자에서, 검진 유방촬영술에서 국소비대칭, 유방초음

파검사에서 악성질환이 의심되는 소견으로 발현한 아밀로이드증의 유방 침범의 증례를 보고하는 바이다.

인하대학교병원 1영상의학과, 2병리과, 3한림대학교 동탄성심병원 영상의학과