Bilateral Primary Marginal Zone Lymphoma of the Breast – A Rare Breast Malignancy

Discussion

Primary breast lymphoma, which comprises less than 1% of all non-Hodgkin's lymphomas, is a rare type of breast malignancy. The most common histological subtype of primary breast lymphoma is diffuse large B-cell lymphoma. The second most common is low-grade marginal zone B-cell lymphoma (MZL) (1), accounting for 9% of primary breast lymphoma cases (2). Marginal zone lymphoma has three subtypes: Splenic, extranodal, and nodal. EMZL arise from mucosal sites, with the most frequent being the stomach, lung, thyroid, skin, and salivary and lacrimal glands (2). Primary breast EMZL has been increasing in incidence in the past decade for unclear reasons, even in women younger than 50 years of age (3). To date, there have been no prospective studies on this rare type of cancer.

The etiology of primary breast EMZL is unclear. Exogenous hormone therapy has not shown any strong association with primary breast EMZL (4). Anaplastic large-cell histological type of primary breast lymphoma is reported more frequently in individuals with breast implants, but no such association is significant with EMZL (1). Several infectious agents are known to act as inflammatory triggers for EMZL at other sites, such as Helicobacter pylori in gastric MZL (3). An association between autoimmune diseases and EMZL at other sites has also been established such as Hashimoto's thyroiditis and Sjogren's syndrome in thyroid and salivary EMZL, respectively (5). No such infectious agents, autoimmune diseases, or genetic abnormalities have been consistently associated with primary breast EMZL.

Most cases of breast lymphoma present as a palpable breast mass and some are detected incidentally on screening mammography (1), with a median age at diagnosis of 61-65 years (range=23-88 years) (1, 2). Around 85% of breast EMZL was diagnosed in postmenopausal women (2). Bilateral involvement was seen in a few cases (1).

The initial steps in diagnosis are usually diagnostic mammography or ultrasound followed by core needle biopsy or surgical biopsy to establish a histological diagnosis (2). Breast lymphoma frequently appears as a noncalcified oval or round mass which either has circumscribed or indistinct margins on mammogram (6, 7).

Primary breast EMZL is less aggressive than other forms of breast lymphoma and overall has good outcomes. It shows a good response to initial radiotherapy, and the majority of cases do not require extensive surgery (2, 4). Ludmir et al. reported a good response rate with ultra-low dose radiotherapy of 4 Gy with results comparable to the standard dose of 30 Gy. Breast EMZL also responds very well to single-agent rituximab therapy (4). In the series of Ludmir et al., two out of 11 cases with advanced-stage disease were observed clinically like our case (4).

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Figure 2.

Core biopsy of fibro-adipose tissue showing nodular collection of small lymphoid aggregates on the left [hematoxylin and eosin (HE) staining; original magnification, ×100] and small atypical lymphocytes with perinuclear clear cytoplasm on the right (HE staining, original magnification, ×400).

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Figure 3.

Immunohistochemistry slides showing lymphocytes positive for CD20 (A) and BCL2 apoptosis regulator (B), and negative for BCL6 transcription repressor (C). Original magnification, ×400.

Tumor size or Ann arbor staging did not show any prognostic value for breast EMZL (4). Progression-free survival was 56-60% at 5 years and 34% at 10 years (2), (4). Overall survival was 100% at 3 years, and 92% at 5 years (2). Disease relapse is seen in up to 37% of patients with breast EMZL within 1 year. Relapse is seen mostly at distant sites and 8% in the contralateral breast and also responds very well to treatment (2).