Retrospective cohort links core biopsy to rare breast blood cancers

In a retrospective cohort of 24 patients treated at a Spanish tertiary referral hospital, hematologic malignancies involving the breast were diagnosed by image-guided core needle biopsy, and 22 of the 24 patients were managed without surgical removal of the breast. The study at University Hospital Reina Sofía in Córdoba covered diagnoses made from January 2008 through June 2023. Diffuse large B-cell lymphoma was the most frequent subtype, and most deaths in the cohort were not attributed to progression of the hematologic malignancy. The findings describe the clinicopathological features, treatment patterns and long-term outcomes of this rare and histologically heterogeneous group, but they do not establish a general treatment standard.

Breast involvement by hematologic malignancies is uncommon and can closely resemble primary breast carcinoma. The malignancies in this study included lymphomas and leukemic disease involving the breast, whether classified as primary breast involvement or secondary involvement by previously known systemic disease. Patients could present with a palpable mass, a mammographic density or an incidental imaging finding, while imaging features on ultrasound or magnetic resonance imaging generally did not permit reliable distinction from epithelial breast cancer. Histologically, diffuse large B-cell lymphoma and small B-cell lymphomas with a single-file infiltrative pattern can resemble invasive lobular carcinoma, particularly when the initial immunohistochemical panel does not include hematolymphoid markers. Because most such malignancies do not require mastectomy or axillary dissection, accurate lineage classification before surgery is a central diagnostic issue.

The investigators searched institutional pathology and oncology databases and selected patients with histopathologically confirmed hematologic malignancy involving the breast, complete clinical, imaging and pathology records, and available follow-up. Cases with insufficient tissue for immunohistochemical analysis or incomplete records were excluded, leaving 24 participants. The group included 23 women, or 95.8%, and one man. Mean age at diagnosis was 60.3 years, the median was 60.5 years, and ages ranged from 17 to 93. Primary breast involvement was assigned retrospectively under the Wiseman–Liao framework using the available presentation and staging information: 21 cases, or 87.5%, were classified as primary and three, or 12.5%, as secondary. A previous hematologic malignancy and retrospective classification as primary or secondary involvement were analyzed as separate variables.

Pathological reassessment under the fifth edition of the World Health Organization classification of hematolymphoid tumors, with reference to the 2022 International Consensus Classification, identified seven entities and reclassified two cases relative to their original diagnoses. Diffuse large B-cell lymphoma accounted for eight cases, or 33.3%, followed by MALT lymphoma with five cases, or 20.8%. Follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma each accounted for three cases, or 12.5%. The cohort also included two nodal marginal zone lymphomas, two B-lymphoblastic lymphomas/leukemias and one Burkitt lymphoma. No myeloid malignancy, T-cell lymphoma, plasma-cell neoplasm or breast implant-associated anaplastic large cell lymphoma was identified, and no patient had breast implants. The authors cautioned that the small, single-center sample and the institution’s referral pattern mean these absences cannot be generalized to the full spectrum of hematologic breast malignancies.

Twelve patients, or 50.0%, had disease confined to the breast parenchyma, while the other 12 had concurrent ipsilateral axillary lymph-node involvement. Anatomical extent and Ann Arbor stage were reported separately rather than treated as interchangeable: 11 cases, or 45.8%, were stage IE and 13, or 54.2%, were stage IIE. One stage IIE patient had regional non-axillary nodal disease without axillary involvement. Mean tumor size was 2.5 centimeters, with a standard deviation of 1.8, among the 21 patients for whom an imaging measurement was available; the range was 0.9 to 8.0 centimeters. Only two patients, or 8.3%, had B symptoms, defined as fever, night sweats or unintentional weight loss. Eleven cases were detected by mammography, eight presented as a palpable mass and five were identified incidentally or during follow-up imaging, but inconsistently recorded imaging descriptors prevented the investigators from assigning a distinctive radiologic pattern.

Immunohistochemical evaluation was central to reassessing the tumors and assigning their lineage. The pathology work included hematoxylin and eosin staining and markers selected according to morphology and diagnostic context, such as CD20, CD3, CD10, BCL2, BCL6, MUM1 and Ki-67, with cyclin D1, TdT, CD5, CD23, CD138 and CD56 applied selectively. No positive estrogen-receptor or progesterone-receptor result was found among cases with available documentation, although the testing denominator and original testing indications could not be reconstructed reliably. The authors said this observation may support a hematologic lineage assignment within a broader marker panel but cannot independently distinguish these malignancies from breast carcinoma, including triple-negative or metaplastic carcinoma, and hormone-receptor expression has also been reported in lymphoma. By contrast, molecular and genomic data—including MYC, BCL2 and BCL6 rearrangement status, cell-of-origin classification and sequencing profiles—were not systematically available and therefore were not central to the cohort’s lineage analysis or linked to outcomes.

Treatment varied with histological subtype, disease extent, patient characteristics and changes in clinical practice over the 15.5-year accrual period. Systemic treatment was given to 19 patients, or 79.2%; breast-directed radiotherapy to nine, or 37.5%; and mastectomy to two, or 8.3%. Diffuse large B-cell lymphoma was treated principally with R-CHOP, comprising rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma received rituximab-based treatment, while those with MALT lymphoma received rituximab monotherapy or rituximab-bendamustine according to disease extent and clinical context. Both patients with B-lymphoblastic lymphoma/leukemia and the patient with Burkitt lymphoma received intensive HyperCVAD-based induction chemotherapy. Radiotherapy was used mainly as consolidation in diffuse large B-cell lymphoma or as definitive local treatment in selected patients with localized disease.

Both mastectomies were undertaken at the patients’ request after disclosure of the hematologic diagnosis and multidisciplinary discussion, rather than because of a formal oncological indication. The remaining 22 patients, or 91.7%, were managed without breast resection, while the authors described breast surgery as reserved for exceptional circumstances rather than a standard approach. The cohort cannot establish the comparative effectiveness of particular chemotherapy regimens or radiotherapy strategies. Radiation doses, treatment fields and techniques, numbers of systemic-treatment cycles, formal response assessments and rituximab maintenance were not consistently recorded. No patient was documented as receiving prophylactic central nervous system-directed treatment, but CNS-IPI components and laterality were not consistently available, preventing assessment of the appropriateness or potential benefit of such prophylaxis.

Outcomes differed sharply when survival from any cause was separated from survival attributed to the hematologic malignancy. During a median observed duration of 86.9 months, with a range of 7.9 to 217.6 months, 11 patients, or 45.8%, experienced progression or relapse and 13 died. Only three of those 13 deaths were attributed to progression of the hematologic malignancy; six were unrelated, two were associated with a second neoplasm, one followed treatment toxicity and one was unrecorded. Median overall survival was 115.7 months, with a 95% confidence interval of 54.9 months to not reached. Estimated overall survival was 70.8% at five years, 46.5% at 10 years and 31.9% at 15 years. Median disease-specific survival was not reached, with an estimated 86.8% at five, 10 and 15 years. The reverse Kaplan–Meier potential-follow-up estimate was 159.7 months. These descriptive estimates have wide uncertainty because of the small sample and few events and should not be treated as generalizable benchmarks.

Subgroup outcomes also varied by disease type and cause of death. Among eight patients with diffuse large B-cell lymphoma, six died, but only one death was attributed to lymphoma progression; median overall survival in that subgroup was 102.1 months. Both patients with B-lymphoblastic lymphoma/leukemia died of progressive disease, at 7.9 and 50.3 months. Both deaths in the chronic lymphocytic leukemia/small lymphocytic lymphoma group and the single death among patients with MALT lymphoma were attributed to unrelated causes, and no progression event was documented in the former subgroup. The median time to progression was 43.7 months among the 10 patients with a dated progression event; one additional patient had a progression event without a reliable date and was included in the overall count but excluded from that calculation. The retrospective single-center design, small and heterogeneous cohort and changing diagnostic and treatment practices prevented multivariable analysis or reliable subgroup comparisons, while incomplete prognostic indices, staging modalities, molecular data and independent cause-of-death adjudication further limited interpretation. The study therefore characterizes one institution’s experience and supports larger multicenter cohorts with systematic staging, molecular characterization and standardized outcome assessment.

Subject of Research: Clinicopathological features, management and long-term outcomes of hematologic malignancies involving the breast

Article Title: Hematologic breast malignancies: a single-institution cohort study of 24 patients diagnosed between January 2008 and June 2023, with clinicopathological and outcome analysis

Article References: Navarro, L., de la Haba, M., Flores-Paco, P., Atance, V., Jiménez Nájar, F. J., Haro-Yuste, S., Leiva-Cepas, F., Herrera Arroyo, C., Morales-Estevez, C., Aranda, E., & de la Haba-Rodríguez, J. (2026). Hematologic breast malignancies: a single-institution cohort study of 24 patients diagnosed between January 2008 and June 2023, with clinicopathological and outcome analysis. Frontiers in Oncology, 16, Article 1925669. https://doi.org/10.3389/fonc.2026.1925669

Image Credits: AI Generated

DOI: 10.3389/fonc.2026.1925669

Keywords: breast lymphoma, hematologic malignancies, core needle biopsy, diffuse large B-cell lymphoma, MALT lymphoma, immunohistochemistry, breast surgery, survival outcomes, retrospective cohort, Hematologic, breast, malignancies