Lymphomas of the breast: pathology and clinical behavior.

Semin Oncol 1999 Jun;26(3):357-64
Brogi E, Harris NL.

Massachusetts General Hospital, and the Department of Pathology, Harvard Medical School, Boston 02114, USA.

Lymphomas of the breast are uncommon, and a broad variety of histologic types have been reported. The majority are B-cell lymphomas, and the most common type is diffuse large B-cell lymphoma (40% to 70%). MALT-type lymphoma is a distinct subgroup of primary lymphoma of the breast with a reported incidence between 0% and 44% and is characterized by indolent behavior and good prognosis. Burkitt's or Burkitt-like lymphoma can bilaterally involve the breast of a young pregnant or lactating woman and typically behaves aggressively. Primary breast lymphomas behave similarly to lymphomas of similar histologic types and stages presenting at other sites. Treatment of primary breast lymphomas does not include surgery, but is typically based on local radiotherapy, often combined with systemic chemotherapy.

Lymphoma of the breast. A clinicopathologic study of primary and secondary cases.

Topalovski M, Crisan D, Mattson JC.
Arch Pathol Lab Med 1999 Dec;123(12):1208-18
Pathology and Laboratory Medicine Service, Department of Veterans' Affairs Medical Center, Kansas City, MO, USA.

Primary lymphomas of the breast are rare, accounting for 1.7% to 2.2% of extranodal lymphomas and 0.38% to 0.7% of all non-Hodgkin lymphomas. Although secondary breast lymphomas are also rare, they represent the largest group of metastatic tumors of the breast. OBJECTIVES:  We conducted a retrospective review of 22 cases of breast lymphoma diagnosed at William Beaumont Hospital, Royal Oak, Mich, during a 30-year period (1963-1994). Eleven of the 22 cases fulfilled the criteria for primary breast lymphoma; these cases represented 0.6% of all non-Hodgkin lymphomas seen in our hospital. Of the 11 cases, 5 were diffuse large B-cell lymphomas, 2 were follicle center lymphomas, 2 were marginal zone B-cell lymphomas (mucosa-associated lymphoid tissue type), 1 was a lymphoplasmacytoid lymphoma, and 1 was a peripheral B-cell neoplasm, unclassified. Using a panel of immunohistochemical stains (CD45RO, CD45RA, CD43, CD3, CD20, CD30, CD68, and HLA-DR), 8 cases demonstrated unequivocal B-cell phenotype and 3 cases had equivocal or weak staining patterns for B-cell markers. We identified no cases of T-cell lymphoma. Of 7 cases that had bone marrow biopsies for staging, 3 were positive morphologically for bone marrow involvement. Molecular analysis of B- and T-cell gene rearrangement was used to exclude bone marrow involvement in one case with bone marrow lymphoid aggregates and to confirm negativity in a case that was morphologically negative. Of the 11 secondary breast lymphomas, 5 were diffuse large B-cell lymphomas; 1 was diffuse large B-cell, primary mediastinal subtype; and 5 were follicle center lymphomas. CONCLUSIONS: Breast lymphomas represented 1.2% of all non-Hodgkin lymphomas in this study; the frequency of primary and secondary cases was equal. In both groups, right breast lesions were predominant, and the most frequent morphologic type was diffuse large B-cell lymphoma. Gene rearrangement analysis is helpful in selected cases to rule out bone marrow involvement, especially in older patients, in whom lymphoid aggregates are common.

Lymphomas of the breast. A clinicopathologic and immunohistochemical study of primary and secondary cases.

Cancer 1991 Mar 1;67(5):1359-69
Cohen PL, Brooks JJ.

Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical School, Philadelphia.

Primary mammary lymphoma is rare, and little is known about the immunophenotype of such cases. The authors studied both primary and secondary breast lymphomas with a broad panel of T- and B-cell markers using paraffin-embedded tissue and the avidin-biotin immunoperoxidase method. Cases of primary B-cell lymphoma were further tested to determine light and heavy chain type. Thirty-five cases were analyzed, including 16 primary lymphomas. Diffuse large cell lymphoma was present in ten of 16 primary and 14 of 18 secondary cases. Lymphoepithelial lesions in ducts and lobules and frequent vascular involvement were found in both primary and secondary cases. Immunohistochemistry studies on 13 tumors revealed all of the primary tumors to be B-cell in origin, except for one case of primary T-cell lymphoma; to the authors' knowledge, this represents the first description of this entity. Fifteen of 17 secondary tumors exhibited B-cell markers and one of 17 exhibited T-cell markers; in only one case could lineage not be determined. Among primary B-cell cases, IgM was found to be the most frequent heavy chain type; IgA reactivity was found in only one case. Survival was related to stage and histologic characteristics; patients with Stage II disease and higher grade histologic lesions had a worse prognosis. Half of the patients with primary lymphoma have had recurrent disease. Although local recurrences were observed, the authors also saw a tendency for recurrence in other extranodal sites. The authors conclude that, although primary lymphoma of the breast is compatible with long-term survival, a significant number of patients eventually die of their disease. As with other extranodal lymphomas, survival rate appears most related to stage of disease. Also, the vast majority of primary tumors are B-cell in origin, express IgM heavy chain, and can be considered tumors of mucosa-associated lymphoid tissue.

Breast lymphoma. A B-cell spectrum including the low grade B-cell lymphoma of mucosa associated lymphoid tissue.

Am J Surg Pathol 1993 Jun;17(6):574-87
Mattia AR, Ferry JA, Harris NL.

James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston 02114.

We studied the morphologic, immunologic, and clinical features of 31 cases of malignant lymphoma involving the breast. Primary breast lymphoma occurred in nine women with a median age of 69 years (range, 51-87 years); median follow-up was 31 months (range, 9-67 months). Eight cases were low grade, one was high grade, and all expressed B-lineage antigens. Four cases had features of lymphoma of mucosa-associated lymphoid tissue (MALT); three were free of disease after excision alone at 10, 12, and 48 months, whereas the fourth relapsed with transition to immunoblastic lymphoma and died at 25 months. Four patients had follicular lymphomas, three of which relapsed, causing death from active disease at a median of 55 months (range, 25-67 months). One case of small noncleaved cell lymphoma relapsed, causing death at 31 months. Lymphoma secondarily involved the breast in 22 patients (21 women, one man) with a median age of 60 years (range, 39-83 years) at breast relapse; these patients were followed for a median of 88 months (range, 2-271 months) from primary diagnosis and 4 months (range, 0-116 months) from breast relapse. Nineteen patients had prior documented lymphomas (10 nodal or splenic, nine extranodal), and breast involvement most commonly occurred as part of widespread, predominantly nodal disease. Three patients had breast involvement by lymphomas that were generalized at diagnosis or staging. Thirteen cases were low grade (nine follicular), seven intermediate grade, and one high grade; 19 of 20 cases expressed B-lineage antigens, and one expressed T-lineage antigens. Four cases had features of MALT-type lymphoma; in these patients, isolated breast relapses were interspersed with other extranodal relapses, with interim resolution of disease after local or systemic therapy; two were free of disease and two were alive with localized disease on treatment at median follow-up of 60 months (range, 9-91 months). In contrast, 15 of 18 nonMALT lymphomas had widespread disease at breast relapse (median, 29 months; range, 0-259 months); 16 of 18 received systemic therapy, 10 died with active disease, and five of eight had disseminated active disease at last follow-up. Primary breast lymphomas were commonly low grade. The follicular lymphomas had clinical behavior similar to nodal follicular lymphoma. Primary MALT-type lymphomas were a distinct subset with a potential for disease-free survival after local therapy. Secondary breast lymphomas were heterogeneous and more commonly higher grade, although follicular lymphoma was the most common subtype

Primary breast lymphoma: a report of 20 cases.

Ribrag V, Bibeau F, El Weshi A, Frayfer J, Fadel C, Cebotaru C, Laribi K, Fenaux P.
Br J Haematol 2001 Nov;115(2):253-6
Departement de Medecine, Institut, Gustave-Roussy, Villejuif, France. ribrag@igr.fr

Limited data are available concerning treatment and outcome of primary lymphoma of the breast (PLB), especially after CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, prednisone) chemotherapy. We retrospectively reviewed 20 consecutive cases of localized PLB seen at our institution over a 20 year period. All PLB were of B-cell origin: treatment was CHOP or a CHOP-like regimen in all patients. Sixteen of the 20 patients achieved complete remission (CR) and two achieved partial remission (> 75% tumour regression). Two patients had progressive disease on therapy. With a median follow-up of 54 months, six patients relapsed after 8-66 months. Two of the relapses involved the central nervous system (CNS) (isolated in one case, associated with other sites of relapse in the other). The two patients who achieved partial remission also had progression in the CNS, 4 and 8 months after the end of CHOP chemotherapy. All four patients have died as a result of their disease 3, 6, 10 and 13 months after CNS relapse. Of the 16 centroblastic diffuse large B-cell lymphoma (DLCL), three had CNS disease at relapse. We also observed three (15%) controlateral breast relapses. Thirteen of the initial 20 patients are alive in CR, six patients have died as a result of their lymphoma and one of unrelated disease. In conclusion, we observed a high incidence of CNS relapse in this group of localized extranodal lymphoma, strongly suggesting that CNS prophylaxis should be associated with systemic chemotherapy in localized PLB

Malignant lymphoma of the breast. A study of 53 patients.

Ann Surg 1987 Feb;205(2):144-50
Brustein S, Filippa DA, Kimmel M, Lieberman PH, Rosen PP.

Fifty-three patients with non-Hodgkin's lymphoma of the breast were reviewed and classified using four current classifications of lymphoma. All patients were female with a mean age of 57 years. The majority of patients had histiocytic or large-cell lesions and presented as clinical Stage I. The tumors were described clinically as primary in the breast, and mammary parenchyma was found in 79% of the diagnostic biopsy specimens. The other specimens showed lymphoma in mammary adipose tissue. Survival was not influenced by the presence or absence of breast parenchyma in the biopsy. Statistically significant survival differences were found to be related to stage at presentation as well as to tumor grade, using Kiel and Working Formulation categories. Patients with Stage I disease and those with low-grade lesions had a more favorable prognosis. No discernible factors, including stage or histologic findings, appeared to affect the recurrence rate.

Primary lymphoma of the breast.

Clin Radiol 1986 Nov;37(6):567-70
Liu FF, Clark RM.

Primary lymphoma of the breast is a rare entity. This paper adds a further 16 cases to the world literature. Axillary nodal status appears to be an important prognostic factor for survival. Stage IE patients should be treated with an excisional biopsy followed by radiation to the breast and to the regional nodes. Combined treatment with systemic chemotherapy with local irradiation should be considered for patients with Stage IIE disease (breast and axillary nodes).

Non-Hodgkin's lymphoma involving the breast.

Am J Surg Pathol 1994 Mar;18(3):288-95
Arber DA, Simpson JF, Weiss LM, Rappaport H.

Division of Pathology, City of Hope National Medical Center, Duarte, California.

Breast involvement by non-Hodgkin's lymphoma is rare. Differences between primary and secondary breast lymphoma have been reported, and a relationship between primary breast lymphoma and lymphomas of mucosa-associated lymphoid tissue has been suggested. We reviewed 61 cases of breast lymphoma (41 primary, 13 secondary, and 7 unclear) that included 28 right-sided masses at presentation, 17 left-sided, 12 bilateral, and 4 in which the side was not known. A subgroup of bilateral breast lymphomas was identified that occurred in young women, four of which were pregnant or postpartum. A high incidence of intermediate- and high-grade lymphomas were present in both cases of primary and secondary lymphomas as was a high frequency of B-cell phenotype. Additional immunohistochemical studies failed to demonstrate evidence of marginal or mantle cell differentiation in seven of eight cases studied. Lymphoepithelial lesions were identified in a majority of cases, including 67% of primary and 64% of secondary lymphomas. This study failed to demonstrate a morphologic difference between primary or secondary lymphomas of the breast and suggests that breast lymphomas differ from other extranodal lymphomas in that the latter are frequently low grade.

Primary non-Hodgkin lymphoma of the breast. Is it possible to avoid mastectomy?

J Exp Clin Cancer Res 2000 Jun;19(2):149-54
Babovic N, Jelic S, Jovanovic V.

Institute of Oncology and Radiology of Serbia, Belgrade, Yugoslavia.

Primary lymphoma of the breast is a rare disease that has been estimated to represent from 0.05% to 0.53% of all malignant breast tumors and approximately 2.2% of all extranodal lymphomas. The aim of this study is to review all cases of primary lymphoma of the breast at the Institute of Oncology and Radiology of Serbia from 1984 to 1996 in order to determine the incidence, patterns of clinical presentation, radiological features, histopathology, mode of therapy and outcome of the disease. The criteria for inclusion in this retrospective study corresponded to a revision of the original criteria suggested by Wiseman and Liao. The clinical histories of ten patients with breast lymphomas were reviewed. Clinical follow-up was obtained through a review of the patients hospital chart or by direct contact with the patients. Ten cases of primary lymphoma of the breast have been identified during the 12-yr period, presenting 0.05% of all patients with malignant breast disease. All patients were female, median age at diagnosis 58 years (range 49-69), all presented with breast lumps (3 right, 7 left) of median size 5 cm (range 3.5-8 cm). Mammography and breast echography were unable to bring a suspicion of lymphoma. Histologically, 6 cases were diffuse large cell, 3 of which with features consistent with immunoblastic lymphoma; 2 were diffuse mixed cells and 2 had small lymphocytic morphology. In 4 out of 5 patients, in the clinical stage corresponding to the "operable breast cancer" category, the ex tempore histological analysis could not differentiate lymphoma from cancer, so that all of them had mastectomy with axillary dissection. Those corresponding to the "locally advanced breast cancer" category, escaped mastectomy and a classical biopsy was performed, anticipating eventual neoadjuvant procedures. Thus, four patients underwent radical mastectomy, 1 wide local excision and 5 diagnostic biopsies. Further treatment included chemotherapy for 8 patients. The projected probability of a 10-years survival was 0,60. The rarity of this disease, and uneven treatment modalities make prognosis of breast lymphoma difficult. It seems that cooperation between the surgeon and the pathologist is necessary in order to reach the correct diagnosis during ex tempore analysis. With the limitations of available diagnostic procedures, it appears that most patients with breast lymphoma, in the stage corresponding to the "operable breast cancer" category, will unnecessarily undergo mastectomy and axillary dissection as primary treatment approach.