Localized Breast Amyloidosis Associated with Sjörgren Syndrome.

1. Introduction

Sjörgren syndrome is an uncommon systemic autoimmune disease characterized by dry eyes (keratoconjunctivitis sicca) and dry month (xerostomia) [ 1 ]. The disease results from an autoimmune process of unknown etiology that is directed against lacrimal and salivary glands. A recent review of the literature found Sjörgren syndrome associated with amyloidosis in 57 cases [ 2 ]. Amyloid deposits were localized in the majority of cases, mainly to the skin and lung. They were systemic in only 3 cases, and only 2 patients had amyloid deposits in the breast [ 2 ]. Sjörgren syndrome is associated with B-cell hyperactivity, and patients have an increased risk of hematolymphoid disorders, specifically marginal zone B-cell lymphomas [ 2 , 3 ].

Amyloidosis is a heterogeneous group of diseases defined by deposits of abnormal extracellular fibrillary proteins that cause tissue damage. The most common types are AL and AA amyloidosis. In AL amyloidosis, deposits are composed of immunoglobulin light chains secreted in hematolymphoid disorders such as plasma cell dyscrasia or multiple myeloma. In AA amyloidosis, deposits are derived from serum amyloid A- (SAA-) associated protein. SAA protein production by the liver is increased in chronic inflammatory conditions, including autoimmune disorders such as rheumatoid arthritis, and in chronic infections. Amyloidosis of the breast was first described in 1973 [ 4 ]. It is a rare diagnosis and can occur as localized disease without extramammary involvement or as part of systemic amyloidosis. Five series of 3 or more breast amyloidosis cases have been published in the past 40 years and comprise a mixture of cases with either localized breast or systemic involvement [ 5 – 9 ]. The association of Sjörgren syndrome with localized breast amyloidosis is rare. It appears to be an emerging association, with 6 cases reported to date. The current case is the seventh case reported in which breast amyloidosis is associated with Sjörgren syndrome.

2. Case Presentation

A 61-year-old female presented with calcifications of the left breast on mammography and underwent stereotactic vacuum-assisted core biopsy. The patient had a history of Sjörgren syndrome, chronic renal failure, hypertension, anemia, lymphadenopathy, arthritis, rash, restrictive pulmonary disease, and gastrointestinal symptoms. Clinical workup with a bone marrow biopsy, lymph node biopsy, and splenectomy did not show evidence of a hematolymphoid neoplasm or systemic amyloidosis, and a small bowel biopsy was unremarkable. Her chronic renal failure was attributed to hypertensive renal disease. Six years after her breast biopsy, she developed end-stage kidney disease and entered hospice care.

H&E-stained sections of the 9-gauge vacuum-assisted breast core biopsy showed benign breast parenchyma with amyloid deposits in various stages (Figures 1(a) and 1(b) ). Multiple breast lobules had marked thickening of periductular basement membranes by eosinophilic deposits ( Figure 1(b) ). Ductules surrounded by heavy deposits appeared atrophic or partially replaced by amyloid ( Figure 1(b) ). Deposits were also present in the periductal and perivascular interstitial areas and in the walls of arteries and veins (Figures 1(c) and 1(d) ). The Congo red stain highlighted more subtle amyloid deposits in periductular basement membranes ( Figure 1(e) ). Congophilic deposits demonstrated apple green birefringence under polarized light, while areas of collagenous stroma had gray-white birefringence (Figures 1(d) and 1(f) ). No epithelial atypia, neoplasm, or hematolymphoid lesion was present. Given the negative clinical workup, the amyloid deposits in the breast were considered localized and not associated with systemic amyloidosis.

3. Discussion

This report describes only the seventh case of Sjörgren syndrome associated with breast amyloidosis. Amyloid deposits were localized to the breast. This is the fourth case reported in 2019 and 2020, suggesting that this may be an emerging association. A recent comprehensive review of Sjörgren syndrome associated with amyloidosis reported 57 cases, and the vast majority of patients had localized deposits, most often in the skin and lung [ 2 ]. Sjörgren syndrome patients rarely have systemic amyloidosis, and only 3 of 57 cases had systemic deposits. Only two patients in this review had amyloid deposits in the breast, including one with a primary breast marginal zone lymphoma ( Table 1 ) [ 2 ]. Sjörgren syndrome is uncommon, with an estimated incidence of 3-11 per 100,000 [ 1 ]. Although it is associated with an increased risk of lymphoma [ 1 ], only one of the reported cases with breast amyloidosis had a documented hematolymphoid malignancy, a marginal B-cell lymphoma that was also located in the breast ( Table 1 ) [ 10 ].

Breast amyloidosis is a rare diagnosis. Only 5 case series with a total of 63 cases have been published in the past 40 years ( Table 2 ) [ 5 – 9 ]. Only 2 of these 63 patients also had Sjörgren syndrome ( Table 2 ). Five cases with this association have been published since 2002 ( Table 1 ). Three of these 5 cases were reported in 2019 and 2020, and the association between these 2 diseases may be increasingly recognized.

Of the 57 cases summarized by Hernandez-Molina et al., most had AL-type deposits, and only 7 (12%) patients had an associated lymphoma [ 2 ]. This is in contrast to rheumatoid arthritis and ankylosing spondylitis, where most deposits are of the AA type [ 2 ]. These authors suggest that amyloid deposits in Sjörgren syndrome may be secondary to hypergammaglobulinemia related to B-cell hyperactivity rather than secretion of monoclonal light chains by a hematolymphoid neoplasm [ 2 ].

As surgical pathologists examine breast biopsies, unexpected abnormalities such as amyloid deposits are rarely encountered. Breast amyloidosis has been associated with other autoimmune disorders that include systemic lupus erythematosus, rheumatoid arthritis, and polymyalgia rheumatica [ 7 ]. Their clinical significance lies in the possible association with systemic amyloidosis, plasma cell neoplasms, lymphomas, and systemic inflammatory diseases and should trigger an appropriate clinical workup.

Data Availability

No other data or other supporting materials were collected or used for this report.

Conflicts of Interest

The author has no conflict of interest.

References

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Associated Data

Data Availability Statement

No other data or other supporting materials were collected or used for this report.