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Am J Case Rep
Am J Case Rep
amjcaserep
The American Journal of Case Reports
1941-5923
International Scientific Literature, Inc.

39285626
10.12659/AJCR.944755
944755
Articles
Amyloidosis Found in the Breast: A Case Report
Nguyen Dinh N. A D E F 1
Qureshi Abid A D E F 1
Salvian Michael A. E F 1
Xiao Philip B C 2
Chen Cynthia A E F 1
1 Department of Surgery, Brooklyn Hospital Center, Brooklyn, NY, USA
2 Department of Pathology, Brooklyn Hospital Center, Icahn School of Medicine at Mount Sinai, New York City, NY, USA
Authors’ Contribution:

A Study Design

B Data Collection

C Statistical Analysis

D Data Interpretation

E Manuscript Preparation

F Literature Search

G Funds Collection

Conflict of interest: None declared

Financial support: None declared

Corresponding Author: Abid Qureshi, e-mail: aqureshi@tbh.org
2024
17 9 2024
25 e944755-1e944755-4
07 4 2024
26 7 2024
05 8 2024
© Am J Case Rep, 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Patient: Female, 60-year-old

Final Diagnosis: Breast amyloidosis

Symptoms: Breast lesion

Clinical Procedure: —

Specialty: Surgery

Objective:

Rare disease

Background:

Amyloidosis results in fibrillar sheets of beta-pleated amorphous congophilic protein deposition in the extra-cellular space. Breast amyloidosis is a rare entity, with the first case reported in 1973 and only 2 major case series published since. These deposits can have local or systemic manifestations and typically present unilaterally, although bilateral involvement has been described. Some reported cases of amyloidosis have been linked to breast cancer.

Case Report:

The patient was a 60-year-old woman who presented to the breast surgery clinic for evaluation after image-guided biopsy of a right breast lesion. Core needle biopsy under stereotactic guidance demonstrated pathology consistent with nodular deposition of amyloid, associated with calcifications. Microscopic examination revealed extracellular deposition of acellular eosinophilic material in fat, stoma, and blood vessels. Congo red special stain was positive. Amyloid with Congo red special stain showed apple green birefringence under polarized light. Surgical excision under needle localization was performed, with the final surgical pathology report confirming amyloid deposits.

Conclusions:

Breast amyloidosis can have calcium affinity, create a foreign body-like reaction with giant cell infiltration, and distribute through periductal, perivascular, or intralobar patterns. Some factors that can contribute to an increased risk or are associated with breast amyloidosis are predisposing clinical conditions, including autoimmune disease, various breast cancers, and B-cell lymphomas. Amyloidosis of the breast should be treated either as primary or secondary, based on etiology. Further studies need to be conducted on whether there are specific genetic markers that predispose populations to the development of amyloidosis of the breast.

Key words:

Amyloidosis
Breast Neoplasms
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pmcIntroduction

Amyloidosis results in fibrillar sheets of beta-pleated amorphous congophilic protein deposition in the extracellular space [1]. Breast amyloidosis is a rare entity, with the first case reported in 1973 and only 2 major case series published since. These deposits can have local or systemic manifestations and typically present unilaterally, although bilateral involvement has been described. Clinically, the patient can present with a breast mass, increased breast density, or thickening of the skin [2]. Mammogram and sonogram findings include patterns similar to those of fibrocystic changes and ductal carcinoma in situ [3]. Due to a close resemblance to cancer on radiographic imaging, a breast biopsy is typically required to make a definitive diagnosis [4]. Amyloidosis of the breast can be classified as primary with immunoglobulin light chain or secondary in the setting of infection or inflammation causing elevation of acute phase protein serum amyloid A, with prognosis for primary amyloidosis more favorable than secondary, due to the association of systemic disease that can be treated [5]. Some reported cases of secondary amyloidosis have been linked to cancer, such as invasive ductal or lobular carcinoma or non-Hodgkin lymphoma. In this report, we highlight a rare case of localized breast amyloidosis to raise awareness of a topic that warrants established management.

Case Report

A 60-year-old woman presented to the breast surgery clinic for evaluation after image-guided biopsy of a right breast lesion. The patient had a medical history significant for hypertension, osteoporosis, hyperlipidemia, and rheumatoid arthritis. She did not have any breast-related symptoms, and physical examination was unremarkable, with no discrete masses, skin changes, or nipple inversion. Recent screening mammogram showed a focal area of indeterminate calcifications in the posterior outer right breast, which persisted on diagnostic imaging (Figure 1). Core needle biopsy under stereotactic guidance demonstrated pathology consistent with “nodular deposition of amyloid associated with calcifications, concerning for primary amyloidosis versus a secondary systemic process” (Figure 2). Microscopic examination revealed extracellular deposition of acellular eosinophilic material in fat, stoma, and blood vessels (Figure 3). Congo red special stain was positive (Figure 4). Amyloid with Congo red special stain showed apple green birefringence under polarized light (Figure 5). A biopsy specimen was sent to a tertiary center for further analysis of amyloid subclassification. Mass spectrometry analysis elicited normal results, flow cytometry was negative, and amyloid protein analysis was inconclusive, with amyloid deposition in an unconventional pattern. It should be noted that liquid chromatography tandem mass spectrometry was not available. Because the biopsy results were discordant with calcifications on mammogram and were benign with amyloidosis, the decision was made to perform an excisional biopsy to rule out cancer. Subsequent surgical excision under needle localization was performed, with the final surgical pathology report confirming amyloid deposits, with no evidence of cancer. However, due to initial negative workup for systemic disease and lack of symptoms, the patient was not treated beyond resection. The patient continued to be followed with serial imaging and examination monitoring for disease recurrence or other breast pathologies bi-annually.

Discussion

Amyloidosis is a rare disorder characterized by abnormal aggregation of misfolded insoluble proteins in tissues, with over 20 precursor proteins identified. The diagnosis requires staining tissue specimens with Congo Red, resulting in qualitative generation of an apple-green birefringence upon polarization [6]. Further analysis and confirmation can be done with liquid chromatography tandem mass spectrometry, which defines chemical and structural properties on the amyloid proteins, providing characterization details. However, it should be noted that this technology is not available at most clinical laboratories [7]. Breast amyloidosis can have calcium affinity, create a foreign body-like reaction with giant cell infiltration, and distribute through periductal, perivascular, or intralobar patterns. It can be classified as primary or secondary. Primary amyloidosis is typically caused by abnormal proliferation of abnormal antibodies, typically known as light chains. Other types of systemic amyloidosis consist of serum amyloid A, transthyretin amyloidosis, and beta-2 microglobulin amyloidosis. While primary breast amyloidosis can affect various organs, the propensity is specifically to affect the breast tissue [8]. Secondary breast amyloidosis is typically associated with chronic inflammatory conditions, such as rheumatoid arthritis and systemic autoimmune disease.

Breast amyloidosis is often asymptomatic and is found incidentally on mammography as spiculated high-density areas with amorphous microcalcifications [8]. Mammograms are commonly used as an initial screening tool for breast abnormalities. Amyloid deposits typically appear as a dense, irregular spiculated mass on mammograms with possible microcalcifications. Breast ultrasound can also be used to help distinguish between solid masses, cysts, and amyloid deposits. On ultrasound, amyloids can appear as hypoechoic masses. In addition to this, magnetic resonance imaging can be useful to evaluate the characteristics and extent of amyloid deposits. A needle core biopsy is the definitive method to diagnose breast amyloidosis, which looks for classical histopathology of apple-green birefringence under polarized light when stained with Congo red.

Primary amyloidosis of the breast is typically treated surgically, including patient preferences for mastectomy. However, there is no strong data to suggest recurrence of amyloid deposits if positive margins exist or to support the use of adjuvant radiation therapy. Postoperative management consists of physical examinations and a baseline mammogram at 6 months. Patients who have undergone mastectomy also have the option of undergoing delayed breast reconstruction, involving both prosthetic and autologous options, with further studies needed for the superior option [9]. On the other hand, secondary amyloidosis of the breast is treated via treating the etiology, dependent on the systemic disease.

Due to its rarity, specific risk factors for the development of breast amyloidosis are not well defined. However, some factors that can contribute to an increased risk or are associated with breast amyloidosis are predisposing clinical conditions, including autoimmune disease, various breast cancers, and B-cell lymphomas [10,11]. Occurrences of breast amyloidosis have also been reported with diabetes mellitus and chronic kidney disease [11,12]. De Crem et al reported a case of secondary breast amyloidosis in relation to systemic lupus erythematosus, in which the patient had metachronous bilateral breast amyloidosis [13]. Sjorgen syndrome was reported in association with breast amyloidosis in a study by Fischer, in which 2 patients were respectively found to have invasive breast cancer and marginal B-cell lymphoma [14].

In relation to rheumatoid arthritis, there have been reports dating back to 1974 of amyloid infiltrates found in the breast [15]. Uncontrolled chronic rheumatoid arthritis can lead to the deposition of amyloid A proteins, most often deposited in the extracellular space. Diagnosis and treatment for amyloidosis of the breast require careful evaluation of the underlying cause for appropriate management of the disease. One limitation of our study was the amyloidosis was not able to be subclassified due to limitations of the clinical laboratory. This is important because, depending on primary versus secondary amyloidosis, management would have been different. Even though the patient had a diagnosis of rheumatoid arthritis, the systemic workup for the disease was negative. This directed management treated our patient as having primary amyloidosis rather than autoimmune disease-related secondary amyloidosis.

Conclusions

Breast amyloidosis can be primary or secondary and has been linked to breast cancer. It presents a diagnostic challenge, as it is found incidentally on mammography as spiculated high-density areas with amorphous microcalcifications. Amyloidosis of the breast should be treated either as primary or secondary based on etiology. Further studies need to be conducted on whether there are specific genetic markers that predispose populations to development of amyloidosis of the breast, as well as for preventative measures.

Figure 1. Right breast diagnostic mammogram exhibiting a focal area of indeterminate calcifications in the posterior outer right breast.

Figure 2. Post-stereotactic right breast biopsy mammogram demonstrating the sampled region of indeterminate calcifications, with a marker clip at the biopsy site in a satisfactory position.

Figure 3. Microscopic examination reveals extracellular deposition of acellular eosinophilic material in fat, stoma, and blood vessels (staining with hematoxylin and eosin, 40× magnification).

Figure 4. Congo red special stain is positive (40× magnification).

Figure 5. Amyloid proteins with Congo red special stain show apple green birefringence under polarized light (40× magnification).

Publisher’s note: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher

Institution Where Work Was Done

The Brooklyn Hospital Center, Brooklyn NY, USA.

Declaration of Figures’ Authenticity

All figures submitted have been created by the authors who confirm that the images are original with no duplication and have not been previously published in whole or in part.
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