Japanese Journal of Clinical Oncology 30:33-36 (2000)
© 2000 Foundation for Promotion of Cancer Research
Three Cases of Malignant Lymphoma of the Breast
Departments of 1Surgery and 2Pathology, Tokai University School of Medicine, Isehara, Kanagawa, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONCASE REPORTSDISCUSSIONREFERENCES |
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We report three cases of malignant lymphoma (ML) of the breast and discuss diagnosis and management. The first case is a 35-year-old woman who had a left breast tumor. Fine needle aspiration cytology (FNAC) showed ML. Mastectomy was performed without any adjuvant chemotherapy. Histology revealed diffuse large B-cell lymphoma of REAL classification. Seventy one months after surgery, lesions indicating relapse were detected in nodes of the right axilla, mediastinum and para-aorta.She underwent eight cycles of CHOP regimen, but 1 month after the chemotherapy a brain metastasis was detected. The patient then received a high-dose methotrexate regimen with whole-skull irradiation. The second case is a 47-year-old woman who had anterior neck swelling and bilateral breast tumors. Histology of the tumor revealed diffuse large B-cell lymphoma. The patient underwent eight cycles of CHOP regimen and high-dose chemotherapy (HDC) with peripheral blood stem cell transplantation (PBSCT). Forty eight months after the PBSCT, there is no evidence of disease. The third case is a 38-year-old woman who had a right breast tumor. FNAC of the breast tumor showed ML and a CT scan of the chest revealed lymphadenopathy at the crus of the diaphragm. Histology of the tumor revealed low-grade B-cell lymphoma of MALT type.The patient underwent six cycles of CHOP regimen and HDC supported by PBSCT. Eighteen months after the PBSCT, relapse lesions were detected in nodes of the neck, mediastinum and renal hilum. The patient received nine cycles of a THP–COP regimen.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTSDISCUSSIONREFERENCES |
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We report three cases of malignant lymphoma (ML) of the breast and discuss diagnosis and management.Although there are no data, breast lymphoma has a poor prognosis and the therapeutic management of breast lymphoma is controversial and is not fully established as yet; we think that intensive treatment, including high-dose chemotherapy (HDC) supported by peripheral blood stem cell transplantation (PBSCT), may be an option.
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CASE REPORTS |
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TOPABSTRACTINTRODUCTIONCASE REPORTSDISCUSSIONREFERENCES |
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Case 1
A 35-year-old woman presented with a mass in the lateral part of the left breast in November 1990. The patient had no contributory past or family history. On admission, blood chemistry results, including serum levels of tumor markers CEA, CA15-3 and NCC-ST-439, showed no abnormalities except for anemia (Hgb 8.0 g/dl). Two ill-defined, elastically firm and uneven large tumors, measuring 9 x 8 and 10 x 8 cm, were recognized in the upper and lateral part of the left breast. The tumors were fixed to the chest wall. Neither nipple discharge nor axillary lymphadenopathy was detected. An ultrasonogram of the left breast revealed lobulated hypoechoic and heterogeneous masses (Fig. 1). Results of a FNAC of the tumor revealed ML cells. Since graphical examinations gave no evidence of disease, we diagnosed the tumors as primary ML of the breast, stage IE by Ann Arbor staging, and classified as the low risk group because the international prognostic index (IPI) score (1) was 1. We performed an extended mastectomy, but the patient refused adjuvant chemotherapy. The histology of the tumors revealed diffuse large B-cell lymphoma of REAL classification (Fig. 2). In November 1996, 71 months after surgery, legions indicating relapse were detected in nodes of the right axilla, mediastinum and para-aorta. The patient then received eight cycles of the CHOP regimen (CPA 750 mg/m2, d.i.v. day 1; ADM 50 mg/m2, d.i.v. day1; VCR 1.4 mg/m2, i.v. day 1; and prednisolone 100 mg, p.o. days 1–5). Complete remission was obtained. However, multiple brain metastases were detected in November 1997, so the patient received four cycles of a high-dose MTX regimen (MTX 3 g/m2, d.i.v. day 1; LV 96 mg/body/day, d.i.v. days 1–5) with irradiation (whole skull 30 Gy, partial 50 Gy). To date, the patient is free of disease.
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Case 2
A 47-year-old woman experienced joint pain systemically from November 1993. The patient was referred to our department with anterior neck swelling and bilateral breast masses in December 1993. The patient had no contributory past or family history. Physical examination revealed a marked painless swelling of the thyroid and well-defined, elastically firm, multiple tumors measuring 2–5 cm in both breasts. The serum chemistry values, including levels of the tumor markers CEA, CA15-3 and NCC-ST-439 and thyroid function, were within normal limits, except for anemia (Hgb 9.2 g/dl) and elevated serum levels of lactate dehydrogenase (1387 U/l; normal range, 221–412). Neither nipple discharge nor axillary adenopathy was detected. An ultrasonogram of the thyroid gland revealed a hypoechoic mass with internal high echoic spots (Fig. 3). Mammography showed a homogeneous density with regular borders, but without microcalcificaton or spiculation (Fig. 4a) and an ultrasonogram of the breast showed a mixed pattern hypoechoic mass (Fig. 4b). Other graphical studies were grossly unremarkable. Results of a FNAC of the thyroid tumor and an excisional biopsy of a breast tumor revealed ML cells (Fig. 5a and b). Histology of the tumor revealed diffuse large B-cell lymphoma of REAL classification. Other graphical studies were unremarkable. The patient was diagnosed as stage IIE by Ann Arbor staging and classified into the low intermediate risk group because the IPI score was 2. We administered eight cycles of CHOP regimen (CPA 800 mg/m2, d.i.v. day 1; ADM 50 mg/m2, d.i.v. day 1; VCR 1.4 mg/m2, i.v. day 1; and prednisolone 60 mg, p.o. days 1–5), followed by HDC (MCNU 400 mg/m2, d.i.v. days 8, 3; CBDCA 1200 mg/m2, d.i.v. days 7, 6, 5, 4; VP-16 1500 mg/m2, d.i.v. days 6, 5, 4; CPA 100 mg/kg, d.i.v. days 3, 2) with PBSCT. Forty eight months after the PBSCT, the patient is alive and free of relapse.
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Case 3
A 38-year-old woman came to our institution complaining of a lump that was 2 cm in diameter and located in the upper outer quadrant of the left breast in March 1994. On admission, the lump was well circumscribed and elastically firm, measuring 2.2 x 1.8 cm. She had no past medical history or contributory family history. Laboratory tests were normal. A mammogram revealed a faint tumor shadow without microcalcification or spiculation (Fig. 6a) and an ultrasonogram of the breast showed a clear border hypoechoic mass (Fig. 6b). A chest CT scan showed lymphadenopathy near the crus of the diaphragm. Although FNAC of the tumor showed class II cells, the tumor was diagnosed as ML by excisional biopsy (stage IIIE by Ann Arbor staging), extranodal marginal zone B-cell lymphoma (low-grade B-cell lymphoma of MALT type) of REAL classification (Fig. 7) This case was also classified into the low intermediate risk group because the IPI score was 2. The patient underwent six cycles of CHOP regimen (CPA 670 mg/m2, d.i.v. day 1; ADM 45 mg/m2, d.i.v. day 1; VCR 1.4 mg/m2, i.v. day 1; and prednisolone 50 mg, p.o. days 1–5) followed by HDC (VP-16 1200 mg/m2/day, d.i.v. days 6, 5, 4; CBDCA 1200 mg/m2/day, d.i.v. days 6, 5, 4; and IFO 12 g/m2/day, d.i.v. days 5, 4, 3) with PBSCT. Although complete remission was achieved, 30 months after the PBSCT a relapse was detected in nodes of the neck, para-trachea and left renal hilum in September 1997. The patient was treated with nine cycles of THP–COP regimen (THP 50 mg/m2, d.i.v. day 1; CPA 875 mg/m2, d.i.v. day 1; VCR 1.4 mg/m2, i.v. day 1; and prednisolone 60 mg, d.i.v. day 1) and has had no evidence of relapse since.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONCASE REPORTSDISCUSSIONREFERENCES |
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Malignant lymphoma (ML) is a neoplasm originating from lymph tissue and extranodal ML occurs in the intestinal tract and Waldeyer’s ring. Primary non-Hodgkin’s lymphoma of the breast is a rare disease, representing only 0.12–0.53% of all reported malignant breast tumors (2). It is important to determine whether ML of the breast originated in the breast or systemically. We treated three patients, one with tumors only in the breast, a second with tumors in both breasts and the thyroid and and the third with tumors in the breast and intraperitoneal lymph nodes. Wiseman and Liao (3) reported that a diagnosis of primary malignant lymphoma of the breast must satisfy several criteria: (i) adequate pathological evaluation; (ii) both mammary tissue and lymphomatous infiltrate must be in close association; and (iii) the exclusion of either systemic lymphoma or previous extramammary lymphoma (the presence of ispilateral axillary node involvement was considered acceptable).
On graphical examination, there are no characteristic findings in ML of the breast. A mammogram often shows a homogeneous faint tumor shadow without either microcalcification or spiculation. An ultrasonogram reveals a coarse internal echo, a hypoechoic mass with an irregular border and occasionally a lobulated mass representing a huge tumor (4). At any rate, it is difficult to distinguish ML from breast cancer during its early stages. Because neither an excisional biopsy with frozen sections nor an FNAC is helpful in differentiation, ML is often misdiagnosed as breast cancer (5).
Therapeutic management of ML of the breast is controversial and is not fully established as yet. DeCosse et al. (6) reported that localized tumors within the breast had a good prognosis by surgical intervention alone. However, relapses were reported 10 years after surgery (7) without adjuvant therapy, as happened with our patients. On the other hand, if the ML is determined to be of systemic origin, surgery plus chemotherapy is effective (4,8). In addition, an opinion exists that irradiation alone is effective (9).
Recently, Katsuki et al. reviewed 104 patients concerning therapy for ML of the breast (5); 38 patients (36.5%) were treated by surgery and chemotherapy, 38 (36.5%) by surgery, chemotherapy and irradiation and 20 (19.2%) by surgery and irradiation. Abbondanzo et al. reviewed 31 patients in the recent literature (10); 22 patients (70.9%) were treated by surgery and chemotherapy, four (12.9%) by surgery and irradiation, two (6.4%) by surgery, chemotherapy and irradiation and two (6.4%) by surgery alone.
To date, we have treated advanced and metastatic breast cancer patients with HDC supported by PBSCT (11). Thus, we used HDC with PBSCT for two of our patients. Because the tumors of patients 2 and 3 were not localized in the breast, they were considered to be of systemic origin and first-generation chemotherapy, CHOP, VEPA and BACOP was considered suitable. However, their complete remission (CR) rates were 58% (12), 52% (13) and 46% (14) and the >2-year survival rates were 30% (12), 26% (13) and 35% (14), so the results cannot be considered satisfactory. Treatment of recurrent or relapsed ML by second- and third-generation chemotherapy has a poor prognosis.
Anthony et al. (15) and Giardini et al. (16) reported 17 MALT-type breast lymphoma cases with follow-up data. They described that these patients had a markedly increased potential for prolonged disease-free survival; most (10 of 17) remained free of disease after only local therapy. We treated one case of MALT-type breast lymphoma using HDC supported by PBSCT; particularly in case 3, multiple nodal recurrence was detected after PBSCT. Although there are no data, breast lymphoma has a poor prognosis and the therapeutic management of breast lymphoma is controversial and is not fully established as yet; we think that intensive treatment, including HDC supported by PBSCT, may be an option.
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FOOTNOTES |
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+ For reprints and all correspondence: Yutaka Tokuda, Department of Surgery, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan. E-mail: tokuda@is.icc.u-tokai.ac.jp
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REFERENCES |
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TOPABSTRACTINTRODUCTIONCASE REPORTSDISCUSSIONREFERENCES |
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Received June 15, 1999; accepted October 25, 1999.
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