Breast Lymphoma: Rare Mimicker of Breast Cancer
Year: 2025
Type: article
Abstract: Dear Editor, Lymphomas involving the breast are uncommon and usually caused by the proliferation of neoplastic B or T cells. The rarity of breast lymphoma is likely due to the relatively low amount of lymphoid tissue within the breast. Breast lymphoma typically presents as a palpable breast mass, alterations in subcutaneous tissue or skin, or lymph node enlargement on clinical and radiological examination. In this report, we present two cases and delve into the clinical manifestations, histological and immunohistochemical profiles of breast lymphoma. This report underscores the significance of prompt and precise diagnosis in guiding tailored treatment approaches. Case 1 A 52-year-old hypertensive man presented with asymptomatic red raised lesions on the right breast, right arm, and abdomen for the past two years. These were associated with recurrent itchy vesiculopustular lesions on both palms. Cutaneous examination revealed multiple firm erythematous nodules with retraction of the right nipple. Bilateral axillary and inguinal lymphadenopathy was detected. A similar subcutaneous nodule was also present on the right arm [Figure 1a]. Both the palms were hyperkeratotic and there were vesico-pustular lesions with crusting [Figure 1b]. Laboratory investigations revealed anemia (hemoglobin: 11.4 g/dl) with markedly raised total leukocyte count (84,510/cmm) and peripheral eosinophilia (eosinophil count of 31.7%). Peripheral blood smear revealed a raised total leukocyte count with 55% atypical lymphocytes.Figure 1: (a) Case 1: Cutaneous examination shows multiple firm erythematous nodules with retraction of the right nipple and subcutaneous nodule on the right arm. (b) Hyperkeratosis of skin on both palms with vesiculopustular lesions and crustingSono-mammography revealed the presence of ill-defined irregular solid hyperechoic mass lesions, the largest one measuring 8 cm × 7 cm in both the breasts with internal vascularity suggestive of neoplastic origin. Fine needle aspiration cytology showed lymphoid-rich aspirate suggestive of low-grade lymphoma. Histopathology from the nodular lesion on the right breast and right arm revealed sheets of atypical small lymphoid cells with plasmacytoid morphology and histiocytes in the dermis [Figure 2a-c]. Immunohistochemistry was positive for CD3, CD4, and CD8 (CD4 > CD8) and showed partial loss of CD7 while negative for CD138, Epstein–Barr virus latent membrane protein 1 (EBV-LMP1), inducible T-cell costimulatory (ICOS, also known as CD278), and programmed cell death protein 1 (PD1). It also showed CD30 positivity in a few scattered cells. MIB-1 labeling index was 30–40% in highest proliferating areas. Positron emission tomography-computed tomography (PET-CT) showed multiple cervical, axillary, retroperitoneal, pelvic, inguinal lymph nodes, multiple intermuscular nodes and subcutaneous deposits, bilateral breast lesions, and subcutaneous deposits in both thighs. This led to a final diagnosis of T-cell non-Hodgkin lymphoma. The patient was referred to an oncology center for further management where he was treated with tablet methotrexate 15 mg per week. With this, he had improvement in skin lesions and hematological parameters at eight-month follow-up [Figure 3a and b].Figure 2: (a) Histopathology from case 1 (hematoxylin and eosin [H and E] stain, 100×), sheets of lymphoid cells within the superficial and deep dermis, (b) H and E stain, 100×, diffuse infiltration of the deep dermis with atypical small lymphoid cells, (c) H and E stain, 400×, atypical small lymphoid cells with plasmacytoid morphologyFigure 3: (a) Improvement in the breast lesions, (b) complete resolution of palmar lesions after five months of treatmentCase 2 A 74-year-old man presented with multiple painless red raised lesions with overlying raw areas on both breasts for two years without any systemic symptoms or comorbidities. Examination revealed multiple ill-defined, erythematous ulcerated nodules on both breasts with lymphadenopathy in both axillae [Figure 4]. Sono-mammography revealed presence of multiple well and ill-defined hypoechoic and isoechoic nodules in both breasts with some lesions showing hyperechoic margins and internal vascularity.Figure 4: Cutaneous examination of case 2 shows multiple ill-defined, erythematous, ulcerated nodules on both breastsPET-CT showed hypermetabolic uptake in both breasts and axillae without the involvement of any other lymph nodes and organs. Histopathology showed a monotonous population of dispersed lymphoid cells in the dermis [Figure 5a]. These atypical lymphoid cells showed a discohesive pattern, high nuclear/cytoplasmic ratio, and clumped chromatin suggestive of lymphoreticular malignancy [Figure 5b-d]. Tumor cells showed positive staining with LCA (CD45) and CD20 and negative staining with CD3, pancytokeratin, and EMA on immunohistochemistry. A final diagnosis of primary diffuse large B-cell lymphoma was considered. The patient was referred to an oncology center but was lost to follow-up.Figure 5: Histopathological images of Case 2. (a) Hematoxylin and eosin (H and E), 40×, showing diffuse infiltration of the dermis with lymphocytes. (b) H and E stain, 100×, showing a monotonous population of dispersed lymphoid cells with a discohesive pattern. (c and d) H and E stain, 400×, atypical lymphoid cells with high nuclear/cytoplasmic ratio and clumped chromatinLymphomas are among the rare neoplasms affecting the breast, accounting for <0.5% of all breast malignancies due to relative paucity of lymphoid tissue in the breast. The exact prevalence of breast lymphoma is difficult to estimate, but it is reported to vary from 0.15% to 1.6%.[1,2] Breast lymphomas can be roughly categorized into primary or secondary types, depending on the presence of lymphoma lesions elsewhere in the body, though clear definitions are still lacking. Differentiating features of primary and secondary breast lymphoma (SBL) are tabulated in Table 1.[3,4]Table 1: Differentiating features of primary and secondary breast lymphomaMost breast lymphomas are of the non-Hodgkin’s B-cell type, with diffuse large B-cell lymphoma (DLBCL) constituting the most prevalent subtype.[10] Among the diverse pathological subtypes of non-Hodgkin’s lymphoma, non-germinal center DLBCL emerges as the dominant subtype in primary breast lymphoma (PBL).[11] Clinically, it presents as erythematous to violaceous small solitary or multiple papules, nodules, and rarely plaques.[12] T-cell lymphomas represent less than 15% of all non-Hodgkin’s lymphoma, with breast T-cell lymphomas being exceptionally rare (prevalence of 3.4% to 15%).[13] Anaplastic large cell lymphoma (ALCL) is one of the common PBLs of T-cell origin with both anaplastic lymphoma kinase (ALK)-positive and ALK-negative phenotypes. Clinical, histopathological, and immunohistochemistry features of T- and B-cell lymphoma affecting breast are summarized in Table 2.[14]Table 2: Clinical, histopathological, and immunohistochemistry features of B- and T-cell lymphoma affecting breastClinical outcomes vary among patients, with some exhibiting aggressive courses and others responding well to therapeutic interventions. Differential diagnoses for cutaneous lymphomas include inflammatory breast carcinoma, allergic contact dermatitis, atopic dermatitis, parapsoriasis, lichen planus, and psoriasis. Diagnostic imaging in lymphoma evaluation is very important in the early detection and subsequent diagnosis and staging of the disease. Ultrasound, mammography, magnetic resonance image (MRI), and PET-CT scan help to characterize the disease, inform locoregional extension, guide biopsies, and facilitate follow-up evaluations. Breast lymphomas can have nonspecific imaging features. Hence, a multimodal diagnostic approach, with confirmation on histopathology and immunohistochemistry is required. Details of imaging modalities used in the diagnosis of lymphoma are discussed in Table 3.Table 3: Imaging modalities in breast lymphoma[2 , 14]Treatment includes chemotherapy and/or radiotherapy.[13,14] Treatment strategies for PBL have evolved over recent decades. While surgical intervention was previously a primary therapeutic option, studies focusing on primary breast DLBCL have revealed inferior survival outcomes with mastectomy and better results with chemotherapy or a combination of both. Surgical treatment can be a preferred treatment option in patients with breast implant-associated ALCL with malignancy localized to the capsule. Full bilateral capsulectomy with implant removal (en bloc resection) is considered.[14,15] Breast lymphomas in males are one of the rare presentations. Our first case had SBL, while the second case had PBL. Clinicians should be aware of this rare occurrence as early diagnosis and treatment can improve the survival of these patients. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Institution: Brihanmumbai Municipal Corporation
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4417523975