We report an extraordinary case of a collision tumor consisting of invasive ductal carcinoma with adjacent malignant lymphoma presenting as a single mass in the breast. A 79-year-old woman presented with a breast mass. A core biopsy performed at an outside hospital was interpreted as medullary carcinoma. On review of the breast core biopsy, a diagnosis of a synchronous malignant lymphoma and invasive ductal carcinoma was rendered. The patient underwent lumpectomy and axillary dissection. The excised specimen revealed a 2.1-cm, moderately differentiated invasive ductal carcinoma, partially surrounded by malignant lymphoma with areas where both tumors were intermixed. All 27 axillary lymph nodes were extensively involved by lymphoma, and 1 lymph node demonstrated metastatic carcinoma. The morphology and results of immunohistochemistry, flow cytometry, and cytogenetic analysis were consistent with extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.

The occurrence of synchronous adenocarcinoma and malignant lymphoma has been reported previously in different organs, such as stomach, lung, or colon.1–5 Coexistent metastatic carcinoma and lymphoma have been reported previously in axillary lymph nodes, but to our knowledge not in breast.6 We found only one previous reference to such a collision tumor occurring in breast.7 In this report, we describe a rare case of synchronous invasive ductal carcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma in the breast.

A 79-year-old woman presented with a single mass in her left breast that had an irregular, stellate appearance by mammography. The core biopsy, performed at an outside institution, showed carcinoma with a background of monomorphous lymphoid cells and was interpreted by the outside pathologist as invasive carcinoma consistent with medullary carcinoma (Figure 1). A metastatic survey was performed, including a bone scan that revealed uptake in the left distal femur. Magnetic resonance imaging showed replacement of the bone marrow spaces, but no bone involvement. A percutaneous needle biopsy of the femoral lesion performed in the outside hospital demonstrated bone marrow spaces with clusters of small lymphocytes that were positive for CD20. The exact classification of lymphoma in this scant bone biopsy could not be evaluated further. The patient sought a second opinion on management at our institution. Review of the breast core biopsy showed invasive ductal carcinoma intermixed with MALT lymphoma.

Figure 1.

Core biopsy of breast mass. The arrow points to the carcinoma. The lymphoid infiltrate is on the right (hematoxylin-eosin, original magnification ×4). Figure 2. Excised lumpectomy (inset, entire specimen with a ruler). The white arrow points to the poorly defined mass formed by carcinoma. The lymphoid infiltrate (black arrow) appears as the adjacent gelatinous tan tissue. Figure 3. Section through the transition zone of the excised specimen. The arrow points to the moderately differentiated carcinoma in the top half of the section. The monomorphic lymphoid infiltrate is located in the bottom half (hematoxylin-eosin, original magnification ×4).  Figure 4. Monomorphous lymphoid infiltrate composed of small regular lymphocytes with monocytoid features (hematoxylin-eosin, original magnification ×20). Figure 5. Lymphoid infiltrate is composed of a B-cell population, as shown by immunohistochemical CD20 stain (original magnification ×20). Figure 6. Metastatic carcinoma in a lymph node infiltrated by malignant lymphoma. The arrow points to carcinoma (hematoxylin-eosin, original magnification ×10)

Figure 1.

Core biopsy of breast mass. The arrow points to the carcinoma. The lymphoid infiltrate is on the right (hematoxylin-eosin, original magnification ×4). Figure 2. Excised lumpectomy (inset, entire specimen with a ruler). The white arrow points to the poorly defined mass formed by carcinoma. The lymphoid infiltrate (black arrow) appears as the adjacent gelatinous tan tissue. Figure 3. Section through the transition zone of the excised specimen. The arrow points to the moderately differentiated carcinoma in the top half of the section. The monomorphic lymphoid infiltrate is located in the bottom half (hematoxylin-eosin, original magnification ×4).  Figure 4. Monomorphous lymphoid infiltrate composed of small regular lymphocytes with monocytoid features (hematoxylin-eosin, original magnification ×20). Figure 5. Lymphoid infiltrate is composed of a B-cell population, as shown by immunohistochemical CD20 stain (original magnification ×20). Figure 6. Metastatic carcinoma in a lymph node infiltrated by malignant lymphoma. The arrow points to carcinoma (hematoxylin-eosin, original magnification ×10)

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The patient underwent conservative surgical management for the breast cancer, consisting of left breast lumpectomy and axillary dissection. Twenty-seven lymph nodes were identified in the specimen, all demonstrating lymphoma; 1 lymph node showed metastatic breast cancer. Staging bone marrow biopsy showed involvement by B-cell lymphoma with no evidence of carcinoma. The patient recovered well from surgery, but developed right chest pain and an associated effusion 1 week later. A computed tomographic scan demonstrated a pulmonary embolism, and anticoagulation therapy was initiated. She recovered uneventfully. Additional computed tomographic scans of the chest, abdomen, and pelvis showed no evidence of tumor. Treatment consisting of breast irradiation and an aromatase inhibitor was undertaken for the breast cancer, and rituximab was prescribed for therapy of the lymphoma.

The gross specimen consisted of a lumpectomy with axillary dissection. The excision specimen measured 8.0 × 7.5 × 4.0 cm. Serial sections showed a white-tan, stellate, hard mass measuring approximately 2.5 cm. The edges of the mass were not well defined. The mass was partially surrounded by firm and fleshy tan tissue, measuring 2.0 cm in largest diameter (Figure 2). The contents of the axillary dissection contained 27 lymph nodes, most of which were firm and enlarged.

Microscopic sections of the stellate lesion showed invasive ductal carcinoma, which we classified as grade 2 according to the modified Bloom-Richardson grading system. The invasive carcinoma measured 2.1 cm in greatest diameter on microscopic slides and was completely excised with negative margins. The carcinoma had a solid architectural pattern with an intermediate nuclear grade and a low mitotic rate. Lymphovascular invasion was not identified. The carcinoma was positive for estrogen receptor and negative for both progesterone receptor and HER-2 immunohistochemical stains (Dako Corporation, Carpinteria, Calif). At the edge where the 2 tumors collided, nests of invasive carcinoma were intermixed with sheets of lymphoma cells (Figure 3).

The lymphocytic infiltrate was predominantly composed of marginal zone (centrocyte-like) B cells with small to medium-sized, slightly irregular nuclei; dispersed chromatin; and relatively abundant, pale cytoplasm (Figure 4). Scattered large transformed lymphocytes and plasma cells were present. There were foci of lymphoepithelial lesions.

Immunophenotyping by flow cytometry and immunohistochemistry revealed that the neoplastic lymphocytes expressed monoclonal κ light chain, CD20 (Figure 5), and CD19, but not CD5, CD10, Bcl-1, or Bcl-6. All antibodies were obtained from Dako, except Bcl-1, which was obtained from Novocastra Laboratories Ltd (Newcastle upon Tyne, United Kingdom). Conventional cytogenetic study identified no metaphase cells for analysis. Thus, interphase fluorescence in situ hybridization for t(14;18) was performed, and no translocation was found. These findings were diagnostic of extranodal marginal zone B-cell MALT-type lymphoma. Also, the lymphoma involved all of the axillary lymph nodes. A single lymph node contained a metastatic focus of invasive ductal carcinoma measuring 6.0 mm (Figure 6). Bone marrow biopsy showed peritrabecular aggregates of CD20-positive, small lymphoid cells.

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, approximately 1.7% to 2.2% of all extranodal lymphomas, and 0.38% to 0.7% of all non-Hodgkin lymphomas.8–10 Most are B-cell lymphomas, the majority of which are diffuse large B-cell lymphomas.9–12 

Extranodal marginal zone B-cell MALT-type lymphoma is a distinct subgroup of primary lymphoma of the breast with a reported incidence varying from 0% to 44% of breast lymphomas and is characterized by indolent behavior and good prognosis.10,11 A lymphocytic mastopathy characterized by a lymphocytic infiltrate within the breast epithelium has been described in association with breast lymphoma, but its relevance as a precursor lesion of MALT-type lymphoma of the breast is uncertain.11,13 The mechanism for the simultaneous occurrence of extranodal marginal zone B-cell lymphoma and carcinoma in this particular case remains uncertain. This patient had no known autoimmune disorders, a recognized risk factor for MALT lymphoma. It is possible that the antigenic stimulation of the adjacent carcinoma may have driven the lymphomagenesis as an analog to that of stomach MALT lymphoma. The latter is believed to be driven by continuous antigenic stimulation from Helicobacter pylori infection. It is also possible that both neoplasms had a common etiologic stimulus. It has been shown that breast carcinoma and non-Hodgkin lymphoma are diagnosed in some patients more frequently than is expected, with no evidence that the second tumor was therapy induced.14 

This case also emphasizes the importance of careful review of cases considered to be medullary carcinoma of breast for the possibility of synchronous lymphoma (particularly MALT lymphoma) and carcinoma. Careful morphologic evaluation with adequate immunohistochemical stains should be applied without hesitation in ambiguous cases.

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Author notes

Reprints: Barbara Susnik, MD, PhD, Department of Pathology, Medical College of Wisconsin, 9200 W Wisconsin Ave, Milwaukee, WI 53226 ([email protected])