Primary Plasmacytoma of the Breast

Extramedullary myeloma (plasmacytoma) is a malignant tumor composed entirely of plasma cells in the absence of bone involvement. These tumors can occur anywhere in the soft tissue, especially in the upper respiratory tract and oral cavity. Isolated cases are reported in the breast, mostly as a secondary involvement during the evolution of a multiple myeloma1,2 or as a plurifocal plasmacytoma.3,4 Very few cases have presented as primary tumors mimicking primitive breast carcinomas.5–10 

We describe a case of solitary extramedullary plasmacytoma of the breast that was not associated with bone marrow or other sites of involvement during a 15-month follow-up period. Differential diagnosis with other breast lesions must be established to ensure the correct histologic examination and proper therapy, especially when evaluating the lesion on frozen sections.

A 37-year-old woman was admitted to our hospital because of a lump in her right breast of 2 months' duration. She was affected by β-thalassemia minor. The patient had a family history of breast cancer.

Mammography showed a well-defined mass measuring about 3 cm in diameter in the inferior outer quadrant of the right breast (Figure 1). Preoperative workup for metastatic breast disease, including radiographs of the thorax, liver ultrasound, bone scintiscans, and blood markers were all negative.

The fine-needle aspiration cytology, performed elsewhere, showed few plasma cells, few lymphocytes, and some naked nuclei and was judged inconclusive by the referring cytopathologist. A surgical biopsy of the mass was obtained and was sent for frozen section.

Macroscopically, the surgical specimen consisted of a well-circumscribed, 2.6 × 1.6-cm, brownish, fleshy mass surrounded by wide normal breast tissue. The frozen section showed an undifferentiated tumor composed of noncohesive, roundish, small cells, sometimes arranged in a linear fashion, focally surrounding but not infiltrating normal lobules. The cytoplasm was not evident. The overall impression suggested a lobular carcinoma, but the macroscopic appearance was closer to a lymphoproliferative disease. The frozen section diagnosis was a possible lymphoproliferative disorder, and we decided to delay the final histologic diagnosis, waiting for the paraffin-embedded blocks.

In the formalin-fixed tissue, the cells clearly appeared as plasma cells with a large amount of basophilic cytoplasm and eccentric nuclei with clockwise arrangement of the chromatin (Figure 2). Most cells were mature and had occasional binucleate forms, Russell bodies, and mitoses.

Immunohistochemically, the cells were focally positive for vimentin; diffusely and strongly positive for immunoglobulin (Ig) A (Figure 3, A) and κ light chains (Figure 3, B); and negative for IgG, IgM, λ light chains, leukocyte common antigen, CD20, cytokeratin, S100, HMB45, and smooth muscle antigen. The histologic diagnosis of plasmacytoma was made.

Consequently, an extensive search for a multiple myeloma was performed. Serum immunoelectrophoresis did not reveal hyperproteinemia or paraproteinemia. A skeletal survey failed to show any bone lesions. A bone marrow biopsy disclosed that less than 5% of plasma cells were present. Southern blot analysis performed on the bone marrow sample using J_H probe after digestion with 3 different restriction enzymes (BglII, HindIII, and EcoRI) failed to show any clonal rearrangement. On the basis of these results, a definitive diagnosis of solitary breast plasmacytoma was made.

Because the tumor had been completely resected with wide normal margins, no therapy was instituted and the patient was discharged with close monitoring. She is still asymptomatic and free of disease after 15 months.

Extramedullary plasmacytomas are known to occur in many different organs, such as skin, lung, gastrointestinal tract, and bladder, but especially in the head and neck region. Occasional cases of extramedullary plasmacytomas are reported in the breast. They usually represent secondary involvement by a systemic process1,2 or develop after an extramedullary plasmacytoma has been discovered elsewhere in the body.3,4 In these cases, the correct diagnosis could be clinically suspected by the anamnestic information. In a few cases, they appear as primary solitary breast lesions,6,7,9,10 occasionally as the initial manifestation of multiple myeloma8 or before other extramedullary localized lesions are discovered clinically.5 In such cases clinical history is usually not helpful, and the patient is referred for surgery because of suspected breast carcinoma. It is noteworthy that even the histologic diagnosis in cases of extramedullary plasmacytoma is sometimes incorrect, causing an unnecessary radical mastectomy.2,6 Therefore, careful judgement is required, especially when the specimen is evaluated on frozen sections. In our case, the frozen section of the tumor closely resembled a lobular carcinoma similar to the one misdiagnosed as “poorly differentiated malignant tumor” in a previously reported case,2 but the macroscopic, well-circumscribed, fleshy appearance was not the feature we are accustomed to seeing in a carcinoma. It was worth waiting for the formalin-fixed sections, since they allowed us to make the correct diagnosis and avoid an unnecessary radical surgery.

The histologic differential diagnosis of a plasmacytoma in the breast includes some reactive and malignant processes. The first of these processes is plasma cell mastitis, which consists of a mixed chronic inflammatory infiltrate with many plasma cells present, especially around the ducts. The lumen is often filled with histiocytes and debris, and acute inflammatory cells may be present within the epithelial lining. Plasma cells do not show any light-chain restriction. Pseudolymphoma is a rare, probably reactive entity composed of mixed inflammatory cells, mainly lymphocytes, and reactive germinal centers. Of the malignant neoplasms, plasmacytoma can be misdiagnosed for malignant epithelioid melanoma because of the eccentric location of the nucleus and the abundant cytoplasm. However, the melanocytic cells are larger and pleomorphic with pseudonuclear inclusions, melanotic pigment, and frequent mitotic figures. Moreover, they are immunohistochemically positive for S100 and HMB-45. Non-Hodgkin lymphoma with plasmacytic features usually represents a dissemination of nodal disease. The nuclear feature is closer to a lymphocyte, and the cells show lymphoid antigens, such as leukocyte common antigen, CD20, and CD79.

Careful follow-up is recommended for patients with this type of neoplasia because of the development of multiple myeloma even after many years of remission.

The authors thank F. Frigeri, MD, and A. A. Mastro, MD, for providing clinical information and R. Marano and A. Barbato for their technical assistance.