Beyond the Usual: An Uncommon Cause of Breast Mass

INTRODUCTION

The primary breast lymphoma (PBL) is an incredibly rare condition that makes up 0.04-0.5% of all breast malignancies and 0.38-0.7% of all lymphomas. Breast cancer is the most common malignant tumour in women. It typically originates from the epithelial or stromal components of the breast tissue. Additionally, B-cell subtype non-Hodgkin lymphomas account for the majority of PBL cases. In contrast, extranodal presentation of marginal zone mucosa-associated lymphoid tissue (MALT) lymphoma of the breast is very rare.^[1,2] With or without ipsilateral axillary lymphadenopathy, PBL typically manifests as a quickly expanding, painless, palpable, solitary tumour that is relatively movable and resembles breast cancer. It mostly affects women in their fifth or sixth decade of life.^[3] One uncommon type of breast cancer is breast MALT lymphoma. It frequently manifests clinically as a painless breast lump that might be confused with breast cancer. There are currently no established treatment and follow-up protocols for breast MALT lymphoma, and research has mostly concentrated on the pathophysiology and management of gastric MALT lymphoma.^[4] Here, we describe the diagnosis of extranodal marginal zone lymphoma of the breast in a 44-year-old South Indian female.

CASE REPORT

A 44-year-old female who is a homemaker came with complaints of a lump in the left breast for 2 years and palpable left axillary lymph nodes. History was unremarkable. Not a k/c/o Type 2 DM/IHD/Systemic HTN/TB/Asthma. Family history and personal history are not significant. Patient is moderately built and nourished. Vitals are within normal limits. The patient had pallor and palpable lymph nodes in the left axilla and inguinal region. Haematological investigations are Hb - 9.8 G/dL, TC - 5950 cells/mm³, Platelet count- 360000 cells/mm³, ESR- 20 mm at the end of 1hour.

A local examination of the left breast revealed a lump, measuring 5 × 6 cm, located in the left lower outer quadrant, which was non-tender. The axillary lymph node was palpable, measuring 4 × 5 cm, and was non-tender and mobile. The right breast appears to be normal.

USG scan of the left breast showed multiple solid, cystic lesions noted in the lower outer quadrant of the left breast with multiple hypoechoic enlarged axillary lymph nodes with BIRADS IV/V.

PET CT scan showed hypermetabolic homogeneously enhancing deposits in the left breast. Hypermetabolic multiple mediastinal lymph nodes and left pleural deposits. Hypermetabolic soft tissue deposit in the pelvis, probably an ovarian deposit. Also noted were enlarged abdominal, pelvic, and inguinal lymph nodes.

FNAC of the left breast and lymph node revealed a highly cellular background with a monotonous population of atypical lymphoid cells, comprising small to intermediate-sized lymphoid cells with a high N: C ratio, indented nuclei, coarse chromatin, prominent nucleoli, nuclear moulding, and scant cytoplasm. The background showed lymphoglandular bodies [Figures 1a and b]. Cytological features were suggestive of non-Hodgkin’s lymphoma of the left breast and axillary lymph node.

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Figure 1: Fine needle aspiration cytology of the left breast and lymph node, revealing a highly cellular smear with a monotonous population of atypical lymphoid cells using (a) MGG, 40x, (b) MGG, 100x. MGG: May-Grünwald Giemsa stain.

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Histopathological examination of a USG-guided biopsy of a left breast lump on microscopy showed sheets of atypical lymphoid cells. These cells are small to intermediate in size, with a high N: C ratio and a cleaved nucleus. The tumour cells had clear to vacuolated cytoplasm. Tumour cells are invading adjacent adipose tissue [Figures 2a and b]. No residual breast tissue identified. Features are those of a non-Hodgkin lymphoma biopsy from the left breast. Hence, advised an IHC examination for definitive tumour typing. IHC revealed that CD20 and BCL2 were positive, as shown in Figures 3a and b. CD3, as shown in Figure 3c, CD10, BCL6, C-Myc, Cyclin D1, and MUM1 were negative, while Ki-67 showed around 20% positivity, as shown in Figure 3d. Hence, the final diagnosis of left breast lump- B-cell non-Hodgkin lymphoma, favouring extranodal marginal zone lymphoma. The R-CHOP regimen was recommended as treatment. The patient has tolerated the 6 cycles of chemotherapy well.

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Figure 2: Histopathology showing sheets of atypical lymphoid cells. The cells are small to intermediate in size, with a high N:C ratio and a cleaved nucleus . N:C ratio stands for nucleus-to-cytoplasm ratio. (a) H&E, 40x, (b) H&E, 40x. H&E: Haematoxylin and eosin stain.

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Figure 3: Immunohistochemistry showing immunoexpression of (a) CD20 (IHC, 100x), (b) BCL-2 (IHC,100x), (c) CD3 negative (IHC, 100X), (d) Ki67 (IHC, 100x). IHC: Immunohistochemistry.

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DISCUSSION

Extranodal marginal zone lymphoma of MALT is a low-grade primary extranodal B-cell lymphoma composed of small lymphoid cells. It can be localised as a single lesion in the breast parenchyma or, rarely, multiple or bilateral lesions. The mass lesion can be detected on physical examination or on radiology. Constitutional symptoms are absent.

The incidence of PBLs has grown over the past 40 years, particularly in young women, according to Thomas et al.’s biggest dataset on primary breast lymphomas in the United States.^[2] This may be the result of more radiological screening for breast lesions and more sensitive diagnosis methods. Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of primary breast lymphomas, accounting for almost 50% of all PBLs. Other indolent histopathological subtypes, such as marginal zone lymphoma, are incredibly uncommon.^[1,4]

Mucosa-associated lymphoid tissue (MALT) lymphomas account for approximately 7-8% of all B-cell lymphomas, with only about 2% originating in the breast. Among primary breast lymphomas, MALT lymphoma represents the second most frequent histologic subtype. It predominantly affects middle-aged to older women, most commonly presenting in the sixth to seventh decades of life. Although the majority of cases arise sporadically, rare associations with autoimmune disorders or immunodeficiency states have been reported. Grossly, these tumours appear as solid, fleshy masses of varied sizes. In histology, they demonstrate nodular or diffuse growth patterns with infiltrative borders. The tumour cell population shows small- to medium-sized lymphoid cells exhibiting mildly irregular nuclei and variable amounts of pale cytoplasm. Reactive lymphoid follicles are frequently present, and features such as follicular colonisation and lymphoepithelial infiltration of adjacent epithelial structures may also be observed.^[2-6]

Immunohistochemical markers used to evaluate the lesion include CD20, CD79a, and Bcl2. The negative markers are CD5, CD10, CD23, BCL6, Cyclin D1 and SOX11.The differential diagnosis of the lesion is Mantle cell lymphoma, Follicular lymphoma, Small lymphocytic lymphoma/CLL, Chronic inflammatory conditions, and Diabetic mastopathy.^[5-7]

Mantle cell lymphoma is characterised by small lymphoid cells with irregular nuclei and CD5 and cyclin D1 positivity. In contrast, follicular lymphoma exhibits a follicular growth pattern, marked by CD10, BCL6, and BCL2 expression. Small lymphocytic lymphoma/CLL consists of small round lymphocytes with poorly defined proliferation centres, whereas marginal zone lymphomas and hairy cell leukaemia rarely involve the breast and are CD5-/CD10-. Reactive conditions, such as diabetic or lymphocytic mastopathy, mimic lymphoma but feature less dense infiltrates, germinal centres, fibrosis, fewer B cells, and more IgG+ plasma cells. Diagnosis requires breast parenchyma involvement, atypical B-cell infiltrates with clonality and exclusion of other B-cell lymphomas, with desirable features including lymphoepithelial lesions and monotypic plasmacytic differentiation.^[4-8]

Accurate histopathological characterisation and appropriate immunophenotyping are essential for differentiating primary breast lymphoma from other lymphoproliferative lesions, as management strategies differ significantly.^[6-8] Age at diagnosis, clinical presentation, and survival outcomes vary considerably between primary and secondary breast lymphomas, underscoring the importance of accurate classification and comprehensive diagnostic evaluation.^[7] Increased clinical awareness of this unusual presentation will facilitate timely diagnosis and intervention, ultimately improving prognosis for affected patients.^[8] Treatment varied across patients, with approaches including radiotherapy, chemoimmunotherapy, or active surveillance, and outcomes demonstrated relatively favourable overall survival, though relapse rates were substantial, particularly within certain subgroups.^[9] MALT Lymphoma of the breast has a better prognosis than DLBCL and follicular lymphoma of the breast. A subset of patients develops extranodal relapses involving the ipsilateral or contralateral breast, subcutaneous tissue, larynx, chest wall, orbit, and lymph node.

CONCLUSION

Primary breast lymphoma is an unusual extranodal entity with unique clinical characteristics. The scarcity of cases has limited clarity on standardised treatment, yet available data indicate that integrated therapeutic regimens achieve the best outcomes.