Primary MALT lymphoma of the breast: pathological and radiological characteristics.

PURPOSE: Primary Mucosa-associated lymphoid tissue (MALT) lymphoma is a rare diagnosis in the breast, and clinical diagnosis based on radiological features is often challenging. This study aimed to evaluate the clinicopathological, and radiological characteristics of the patients diagnosed with primary breast MALT lymphoma. METHODS: This study examined 18 cases of primary MALT lymphoma of the breast diagnosed at a single tertiary center between January 2002 to December 2020. Medical charts, radiological imaging and original pathology slides were reviewed for each case. RESULTS: All cases were female (gender assigned at birth) and presented with a palpable mass or an incidental imaging finding. Imaging presentation ranged from mammographic asymmetries, circumscribed masses, and ultrasound masses lacking suspicious features. Seventeen cases were biopsied under ultrasound; one received a diagnostic excision biopsy. Microscopic examination of the breast specimens demonstrated atypical small lymphocyte infiltration with plasmacytoid differentiation and rare lymphoepithelial lesions. Immunohistochemistry was performed in all cases and established the diagnosis. Most patients were treated with radiotherapy, and only three were treated with chemotherapy. The median follow-up period was 4 years and 7.5 months, and all patients were alive at the last follow-up. CONCLUSION: Primary MALT breast lymphomas are usually indolent and non-systemic, and local radiotherapy may effectively alleviate local symptoms. Radiological findings show overlap with benign morphological features, which can delay the diagnosis of this unusual etiology. Although further studies involving a larger cohort could help establish the clinical and radiological characteristics of primary breast MALT lymphomas, pathology remains the primary method of diagnosis. TRIAL REGISTRATION NUMBER: University Health Network Ethics Committee (CAPCR/UHN REB number 19-5844), retrospectively registered.

Primary breast diffuse large B-cell lymphoma characterized by CNS relapse and successful hematopoietic stem cell transplantation salvage therapy.

BACKGROUND: Primary breast diffuse large B-cell lymphoma (PB-DLBCL) is rare, with a high incidence of central nervous system (CNS) relapse. This study aims to investigate clinical characteristics, prognostic factors, and outcomes in Taiwanese PB-DLBCL patients and review the literature on PB-DLBCL. METHODS: Thirty-one PB-DLBCL patients diagnosed between 2000 and 2021 were retrospectively enrolled for analysis. RESULTS: The median age was 49 (range 26-79) years. The complete remission (CR) rate was 90.3%. Nine (90%) of the ten patients who experienced relapse had CNS involvement at the time of relapse. The one-year, two-year, and five-year progression-free survival (PFS) rates were 86.6% (95% confidence interval [CI] 75.2-99.8), 75.8% (95% CI 61.6-93.2), and 45.1% (95% CI 29.5-68.9), respectively. The five-year overall survival (OS) rate was 64.1% (95 % CI 48.4-85.0). A stage-modified International Prognostic Index (mIPI) less than two (five-year PFS rate 52.5% vs. 17.1%, P = 0.02) and the achievement of CR after first-line treatment (two-year PFS rate 80.3% vs. 33.3%, P < 0.001) were significant favorable prognostic factors for PFS. Hematopoietic stem cell transplantation (HSCT) after the first relapse was associated with significantly improved post-relapse OS (five-year OS rate 85.7% vs. 20.0%, P = 0.02) and PFS (five-year PFS rate 85.7% vs. 20.0%, P = 0.02). CONCLUSION: Patients with low-risk mIPI scores, CR after first-line treatment, and those who underwent HSCT after the first relapse had significantly better survival. Intrathecal chemotherapy conferred no benefit in preventing CNS relapse. Further research is needed to assess frontline HSCT's effectiveness in improving outcomes and preventing CNS relapses in PB-DLBCL patients.

Clinicopathological characteristics, local treatment, and prognostic factors in IE/IIE primary breast lymphoma: a retrospective study of 67 patients.

INTRODUCTION: Primary breast lymphoma (PBL) is a rare disease, treatment of which excerpts does not reach a consensus. This retrospective study was conducted to analyze clinical features and survival outcomes of different therapeutic methods. MATERIALS AND METHODS: Records of 67 patients with stage IE/IIE primary breast lymphoma were reviewed from the medical record system. Survival information was gathered by searching the outpatient system. Clinicopathological characteristics were compared by chi-squared or Fisher's exact tests. A comparison of survival curves was performed by log-rank tests. The Cox proportional hazard model was applied for multivariate analysis. RESULTS: At the median follow-up time of 65.23 months (range, 9-150 months), there were 27 (40.3%) relapses, 28 (41.8%) distant metastases, and 21 (31.3%) deaths. The 5-year progression-free survival (PFS) and overall survival (OS) were 52.1% and 72.4%. Pathological types (DLBCL vs. non-DLBCL, p = 0.001) and rituximab use (p < 0.001) were statistically associated with longer PFS in patients with PBL. Nodal sites involved and radiotherapy administration were significant predictors for 5-year OS. Multivariate analysis suggested that nodal sites involved (p = 0.005) and radiotherapy administration (p < 0.003) were independent prognostic factors for OS in patients with PBL (p < 0.05). Radical surgery was not an independent factor for patients with PBL. CONCLUSIONS: Radiotherapy improved the survival of patients with PBL. Radical mastectomy offered no additional benefit in the treatment of PBL.

The prognostic value of IPI in patients with primary breast lymphoma, a multicenter retrospective study.

BACKGROUND: Due to the rarity of PBL and the lack of large-scale studies, the prognostic value of IPI in PBL was controversial. Especially in the rituximab era, the ability of IPI to stratify prognosis in patients receiving immunochemotherapy was severely reduced. Then revised IPI (R-IPI) and National Comprehensive Cancer Network IPI (NCCN-IPI) were introduced. The present study aimed to evaluate the prognostic value of IPI and the other IPIs in patients with PBL in a Chinese population. METHODS: We performed a multicenter retrospective study of 71 patients with PBL from 3 institutions in China. The Kaplan-Meier method and log-rank tests were used for the survival analysis. Cox regression analysis was performed to evaluate the prognostic factors. Subgroup analysis was performed to assess the prognostic significance of IPI scores, R-IPI scores, and NCCN-IPI scores. RESULTS: The median follow-up was 4.7 years (0.7-21.8 years). The 5-year progression-free survival (PFS) and overall survival (OS) rates were 90.2% and 96.3%. In the multivariate analysis, only IPI scores and radiotherapy were significantly associated with OS and PFS (P < 0.05). Applying the R-IPI in our patient cohort indicates a significant difference in PFS between the two groups of R-IPI (P = 0.034) but not for OS (P = 0.072). And the NCCN-IPI was prognostic for OS (P = 0.025) but not for PFS (P = 0.066). Subgroup analyses of IPI showed that survival analysis of IPI scores for the PFS and OS of patients using rituximab were not significantly different (P > 0.05). CONCLUSIONS: Our study confirms the prognostic value of IPI in patients with PBL, but the predictive value of IPI proved to be relatively low with the addition of the rituximab. The R-IPI and NCCN-IPI can accurately assess the high and low-risk groups of PBL patients but were insufficient to evaluate the intermediate risk group.

Single organ microenvironment and the common features of tumors of leukemia, lymphoma, and myeloma cells growing there: A literature review.

OBJECTIVE: To explore whether the growth and treatment resistance of lymphoma and myeloma tumors is similar to that previously observed in leukemic and solid tumors growing in the same organ microenvironment. METHODS: All published cases of 3 primary hematologic malignancies in breast, without systemic involvement, were identified, with follow-ups solicited from authors. Treatment approaches were analyzed to highlight the most effective. RESULTS: Similar histologic features and biology among primary tumors of leukemia, lymphoma, plasmacytoma, and solid breast cancer was revealed. Review of treatments: tumor-directed, chemotherapy, or combination showed the benefit of tumor removal, and use of systemic agents in adjunct, not primary, treatment. Optimal assessment is limited by few cases of PET/CT verifying limited tumor extent. The common biology observed and cases of long survival after tumor/stroma eradication point to the complicity of organ microenvironment in the chemoresistance and treatment failure commonly observed in patients. CONCLUSIONS: The interaction of an organ microenvironment, particularly its adipocytes, with malignant cells, results in similar histologic changes, metastatic potential, and chemoresistance in 3 hematologic malignancies and solid cancers. Improved survival in hematologic malignancies could result from adopting PET/CT to find tumor and its extent, eradicating tumor, and elucidating common therapeutic targets.

Primary Breast Lymphoma Mimicking Metastatic Breast Cancer on 18F-FDG PET-CT.

18F-Fluorodeoxyglucose (FDG) PET-CT is an excellent imaging modality for the evaluation of non-Hodgkin lymphoma (NHL). We report a case of a 45-year-old woman presented with a large right breast mass and suspicious right axillary lymph nodes referred for 18F-FDG PET-CT for staging. 18F-FDG PET-CT images show large hypermetabolic right breast mass infiltrating the skin, multiple hypermetabolic right axillary and subpectoral lymph nodes, along with multiple hypermetabolic bone lesions at axial and appendicular skeleton. Findings are mimicking primary breast cancer with nodal and bone metastases. Biopsy revealed diffuse large B cell lymphoma. 18F-FDG PETCT is helpful in evaluation of disease extent and response evaluation of primary breast lymphoma.

[Spontaneous remission of primary breast diffuse large B-cell lymphoma].

A 71-year-old woman became aware of a 25-mm mass in her right breast as identified by her previous doctor. Needle biopsy findings suggested malignant lymphoma, and she was referred to our hospital for further evaluation. She was diagnosed with diffuse large B-cell lymphoma (DLBCL) at our hospital. Positron emission tomography-computed tomography (PET-CT) revealed an elevated SUVmax (maximum standardized uptake value; 10.3), with the mass localized in the right breast, but magnetic resonance imaging findings revealed that the mass had shrunk to 10 mm. Needle biopsy was repeated in our hospital, and lymphoma cells were absent. Two months later, CT scan revealed complete disappearance of the mass, and, since then, the patient has been free of recurrence. Although there are reports of spontaneous remission of nonHodgkin's lymphoma, it is rare in the case of high-grade B-cell lymphoma. The mechanism of spontaneous remission is unclear; however, advancing age, localized stage, activated B-cell (ABC) or nongerminal center B-cell (GCB) type, and a history of infection are the associated factors. The findings from this case suggest that DLBCL can be cured without therapeutic intervention; however, careful followup may be needed.

Primary breast double-hit lymphoma management and outcomes: a real-world multicentre experience.

BACKGROUND: Primary breast double-hit lymphoma (PB-DHL) is a rare, highly aggressive malignancy that poses challenges regarding accurate diagnosis and selecting optimal treatment regimens. METHODS: We retrospectively reviewed 48 cases of patients diagnosed with PB-DHL in six academic centres between June 2014 and June 2020 in China. Study-specific data were recorded, including treatment options, therapeutic evaluation, prognostic factors and relapse patterns, and the overall survival (OS) and progression-free survival (PFS) were evaluated. RESULTS: In total, 48 patients were enrolled, with 14 patients treated with DA-EPOCH-R/MA (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, alternating with high-dose methotrexate and cytarabine), 18 patients treated with DA-EPOCH-R (rituximab, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin), and 16 patients treated with R-HyperCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with cytarabine plus methotrexate). The overall 5-year OS and PFS rates were 41.7% (95% confidence interval [CI], 27.6-56.8%) and 37.5% (95% CI, 24.0-52.6%), respectively. Of the three treatment regimens, the 5-year OS was higher in DA-EPOCH-R/MA group than in the DA-EPOCH-R or R-HyperCVAD subgroups (57.1% vs. 38.9% vs. 31.3%; P = 0.016), as was the 5-year PFS (50.0% vs. 38.9% vs. 25.0%; P = 0.035). Autologous stem cell transplantation (ASCT) prolonged the OS and PFS compared with non-ASCT patients (5-year OS: 72.2% vs. 23.3%; P < 0.001; 5-year PFS: 72.2% vs. 16.7 %, P < 0.001). Multivariate analysis identified tumour size, risk stratification, treatment with DA-EPOCH-R/MA, breast irradiation, and ASCT as significant prognostic factors. CONCLUSIONS: DA-EPOCH-R/MA is a promising regimen for PB-DHL, and breast irradiation yields complementary benefits for prognosis. ASCT significantly decreased disease relapse, providing a potential curative PB-DHL intervention and justifying ASCT as first-line therapy for young patients. More effective treatment strategies for PB-DHL patients remain encouraging.

Primary breast lymphoma of childhood: a case report and review of literature.

BACKGROUND: Primary breast lymphoma (PBL) is an extremely rare neoplasm in children; by definition, it manifests in the breast without evidence of lymphoma elsewhere, except ipsilateral axillary nodes. CASE PRESENTATION: We report a case of a 15-year-old girl diagnosed with diffuse large B-cell lymphoma (DLBCL) of the right breast: the patient received chemotherapy and rituximab, achieving complete remission. A literature review revealed other 11 cases of pediatric PBL; it mainly affects female adolescents and can involve right and left breast equally. Different histologic subtypes have been described, arising from both B-cell and T-cell. Therapeutic approaches were very different, from chemotherapy to local treatment with surgery and/or radiotherapy. CONCLUSIONS: Our case is the first in which rituximab was administered, suggesting to be a promising therapy in B-cell PBL, as already demonstrated in pediatric B-cell lymphoma from other sites. Further investigations are needed to identify prognostic factors and establish the most effective treatment.

[Primary breast diffuse large B-cell lymphoma in an elderly man maintaining long-term complete response].

Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare non-Hodgkin's lymphoma that mostly affects women. Here, we report a case of primary breast DLBCL that affected an older man without any autoimmune disease or drug-related female hormones. The patient was a 65-year-old man whose chief complaints were gradually-increasing lump in the right chest and swelling of the right axillary lymph nodes. He was diagnosed with malignant lymphoma through a needle biopsy on suspicion of right breast cancer with right axillary lymph node metastasis. Since the histological type could not be confirmed, right breast mass resection was performed. The patient was referred to our department for treatment because of the diagnoses of primary breast DLBCL, germinal center B-cell type (Hans classification), and clinical stage IIA. In addition to the six courses of R-CHOP therapy, intrathecal injections were used in combination to prevent CNS infiltration. He has been in complete remission for 5 years. Although rare, breast lymphoma can also occur in men; therefore, early histological diagnosis and response to CNS recurrence prevention are important.

Combination of baseline total metabolic tumor volume measured on FDG-PET/CT and ß2-microglobulin have a robust predictive value in patients with primary breast lymphoma.

The aim was to build a prognostic model to stratify patients at diagnosis into different risk categories. We investigated the prognostic value of functional PET parameters and clinical features in 64 primary breast lymphoma (PBL) patients. With a median follow-up of 60 months, 5-year progression-free survival (PFS) and overall survival (OS) was 62.5% and 73.4%. In multivariate analysis, baseline total metabolic tumor volume (TMTV0) and ß2-microglobulin remained more reliable predictors of survival than other prognostic factors. The optimal TMTV0 cut-off value was 90 cm3 . Among 29 patients with high TMTV0, 5-year PFS and OS were 44.8% and 62.1%, respectively, while 5-year PFS and OS of 35 patients with low TMTV0 were 74.3% and 85.7%, respectively. TMTV0 combined with ß2-microglobulin identified three groups with very different prognosis, including low-risk group with low TMTV0 and ß2-microglobulin≤normal (n = 30), intermediate-risk group with high TMTV0 or ß2-microglobulin>normal (n = 20), and high-risk group with high TMTV0 and ß2-microglobulin>normal (n = 14). In the three groups, 5-year PFS rates were 80%, 55% and 28.6% (P = .003), and 5-year OS rates were 90%, 65%, and 50% (P = .023) respectively. We established a new prognostic model through TMTV0 and ß2-microglobulin, and can divide PBL at diagnosis into different risk categories.

[Primary diffuse large B-cell lymphoma of the breast in a male patient with Sjögren's syndrome].

When a 74-year-old male patient visited our hospital for the treatment of herpes zoster, his computed tomography (CT) revealed a mass in his right breast, axillary lymph node enlargement, and multiple lung nodules. A histological examination of the breast and lymph node biopsies revealed diffuse large B-cell lymphoma (DLBCL) while the bronchial and salivary gland biopsies showed secondary amyloidosis and Sjögren's syndrome (SjS). According to the Ann Arbor staging, the clinical stage of the lymphoma was evaluated as IIE. The patient achieved a complete remission after six cycles of rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (R-THP-COP) combined with intrathecal chemotherapy to prevent meningeal infiltration and irradiation after chemotherapy. Primary breast lymphoma was diagnosed within 2% of the breast tumor. Only sixteen male cases of breast lymphoma have been previously reported. In those reports, gynecomastia and hormonal therapy accounted for nine cases, but none of the cases coexisted with SjS. The present case is suggestive of the need to investigate possible autoimmune involvement in the development of lymphoma.

PRIMARY HODGKIN'S LYMPHOMA OF THE BREAST INITIALLY TREATED BY SURGICAL EXCISION AND AXILLARY DISSECTION.

Primary breast lymphoma accounts for 0.04%-0.5% of all breast malignancies. Primary non-Hodgkin's lymphomas of the breast are extremely rare and represent approximately 0.38%-0.7% of all cases. Epstein-Barr virus (EBV) has been postulated to play an important role in the pathogenesis of Hodgkin's lymphoma. We present a case of EBV-positive primary Hodgkin's lymphoma of the breast. Although there is no sufficient data on this challenging diagnosis, it is known that it could be misdiagnosed with inflammatory breast carcinoma. A crucial part of the proper histopathologic diagnosis is immunohistochemistry. Different modalities of treatment include operative procedure, chemotherapy and radiotherapy. Recent studies suggest chemotherapy and radiotherapy to be initial treatment for patients with primary breast lymphomas.

Management and outcomes of women diagnosed with primary breast lymphoma: a multi-institution experience.

PURPOSE: Primary breast lymphoma (PBL) comprises < 1% of breast malignancies, leading to a paucity of data to guide management. We evaluated PBL recurrence patterns across two academic hospitals in the era of modern systemic-therapy and radiotherapy. METHODS: Patients diagnosed with PBL between October 1994 and June 2016 were identified. Demographic/clinical variables were assessed via primary chart review. Local control (LC) was estimated using the cumulative incidence function and overall survival (OS) using the Kaplan-Meier method. RESULTS: Thirty-five patients were identified. Median follow-up 5.8 years (range 0.3-17.8 years). Median age at diagnosis 66 years (range 35-86 years). Indolent versus aggressive lymphoma represented 57% (n = 20) and 43% (n = 15) of the cohort, respectively. All patients with aggressive lymphoma received systemic therapy. Thirty patients (86%) received radiotherapy (RT). Breast-only RT was used in 57% (n = 20); 23% (n = 7) received regional nodal irradiation (RNI), and 6% (n = 2) received limited-field RT. Local recurrences were observed in 3% (n = 1), contralateral breast 9% (n = 3), CNS 6% (n = 2), distant non-CNS 30% (n = 10), both local and distant 3% (n = 1). There were no regional nodal recurrences. The 6-year LC rate was 95% for indolent and 81% for aggressive subtypes. The 6-year OS rate was 87% for indolent and 70% for aggressive subtypes. CONCLUSIONS: The majority of patients in this PBL cohort received breast-only RT with no nodal relapses, suggesting that prophylactic RNI may be unnecessary. Given the prevalence of contralateral breast involvement at diagnosis and at recurrence, vigilant surveillance of bilateral breasts may be warranted. The role of CNS prophylaxis requires further investigation.

Hematolymphoid lesions of the breast.

Hematolymphoid malignancies of the breast are most commonly neoplasms of mature B-lymphocytes, and may arise as a primary disease or by secondary involvement of a systemic disease. Primary breast lymphomas (PBL) account for 0.04-0.5% of breast malignancies, less than 1% of all non-Hodgkin's lymphomas (NHL), and less than 5% of extranodal lymphomas (Lakhani et al., 2012; Swerdlow et al., 2008; Joks et al., 2011; Barista et al., 2000; Giardini et al., 1992; Brogi and Harris, 1999; Topalovski et al., 1999).1-7 Secondary breast lymphomas (SBL) are also rare, with an estimated annual incidence of 0.07% (Domchek et al., 2002; Talwalkar et al., 2008).8,9 Recognition of breast lesions as hematolymphoid is critical to distinguish them from other entities that can occur in the breast.

Primary breast diffuse large B-cell lymphoma in a male.

A 74-year-old male with a mass in the right breast visited the Department of Breast and Endocrine Surgery in November 20XX. Core needle biopsy was performed. Pathological diagnosis was diffuse large B-cell lymphoma. The Ann Arbor clinical stage was IIA, and international prognostic index was low-intermediate. Six courses of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone and four courses of intrathecal chemotherapy were administered, and the patient achieved complete remission.

[Primary breast diffuse large B-cell lymphoma developing subsequent to estramustine therapy for prostate cancer].

An 85-year-old male presented with 1-year history of a right breast mass. Needle biopsy of the mass revealed diffuse proliferation of large lymphoid cells that were positive for CD20, BCL2, BCL6, and MUM1 and negative for CD5, CD10, MYC, and EBER. The patient was diagnosed as having diffuse large B-cell lymphoma, a type of primary breast lymphoma (PBL). Sex hormone imbalance, which causes conditions such as gynecomastia, is associated with PBL development in males. Estramustine is a nitrogen mustard moiety linked to estradiol. For 5 years, the patient underwent estramustine therapy for treating prostate cancer. Our case suggests an important role of estrogen in PBL development.

Primary breast lymphoma: A rare case report.

INTRODUCTION AND IMPORTANCE: Primary breast lymphoma (PBL) is an extremely rare neoplasm, accounting for less than 1 % of breast malignancies and less than 2 % of extranodal non-Hodgkin lymphomas (NHLs). CASE PRESENTATION: This case report discusses a 60-year-old female patient presenting with a primary breast lymphoma, specifically diffuse large B-cell lymphoma. The patient had no personal history of breast cancer but exhibited a painless, palpable mass in the left breast with axillary lymphadenopathy. CLINICAL DISCUSSION: Diagnostic challenges in distinguishing PBL from primary breast carcinoma are addressed, emphasizing the importance of considering PBL in cases of rapidly enlarging breast masses. Radiological examinations, including mammography and ultrasound, play a crucial role in diagnosis, and excisional biopsy with immunohistochemical staining is essential for accurate histopathological subcategorization. CONCLUSION: The presented case underscores the rarity of PBL in the Middle East and highlights the diagnostic and classification challenges, emphasizing the central role of accurate techniques in guiding treatment decisions.

A rare case of primary breast lymphoma presenting as calcifications on screening mammography.

Extranodal marginal zone lymphoma (EMZL) is a low-grade subtype of B-cell non-Hodgkin lymphoma that can affect any mucosal tissue, most commonly the GI tract. Primary involvement of the breast, known as primary breast lymphoma (PBL), is a very rare manifestation. We report an unusual case of a 65-year-old woman with primary breast EMZL presenting as calcifications discovered during screening mammography. This represents an exceedingly atypical appearance of primary breast lymphoma that is rarely described in the literature.