Primary breast lymphoma (PBL) is a type of blood cancer related to myeloma, leukemia, and myeloproliferative neoplasms. In lymphoma, cancer cells originate from lymphocytes, a type of white blood cell. PBL is an extranodal lymphoma — meaning that it occurs outside of lymph nodes or other lymphatic organs — that originates in the breast. PBL does not include lymphomas that have spread to the breast from nearby lymph nodes or other parts of the body, which are called secondary breast lymphomas.

Lymphomas are categorized as either Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). There are five types of Hodgkin lymphoma and more than 60 types of non-Hodgkin lymphoma. PBL is usually aggressive (fast-growing) and usually a type of NHL. Like most NHLs, PBL is usually a type of B-cell lymphoma. B cells are white blood cells that make antibodies.

PBL affects women with a median age of 66 years and almost always occurs in women who are age 50 or older. PBL usually affects the right breast, though sometimes it is bilateral (affects both breasts).

Types of Primary Breast Lymphoma

Primary breast lymphomas are usually B-cell non-Hodgkin lymphomas, but they can be almost any type of lymphoma, including Hodgkin lymphoma. The most commonly seen types of primary breast lymphoma are:

• Diffuse large B-cell lymphoma (or DLBCL), the most common type of PBL
• Follicular lymphoma
• Mucosa-associated lymphoid tissue lymphoma
• Burkitt lymphoma
• Marginal zone lymphoma
• Anaplastic large cell lymphoma (ALCL), including breast implant-associated ALCL (BIA-ALCL)
• Small lymphocytic lymphoma

Symptoms of Primary Breast Lymphoma

PBL can have a variety of symptoms, but the most common include:

• A painless breast lump
• Swollen lymph nodes (lymphadenopathy), usually the lymph nodes in the armpit on the same side as the tumor
• Pain in the breast

Other symptoms sometimes seen in PBL and other types of NHL include:

• B symptoms (unexplained fever, unexplained weight loss, and drenching night sweats)
• Chest pain or difficulty breathing
• Abdominal pain, swelling, or bloating
• Loss of appetite, nausea, and vomiting
• Itchy skin, sometimes with a rash
• Fatigue
• Problems with blood clotting

Diagnosis of Primary Breast Lymphoma

Most cases of PBL present as a lump in the breast and are diagnosed the same way as breast cancer: with a physical exam, medical history, imaging, biopsy, and immunophenotyping of cancer cells. Immunophenotyping entails using advanced laboratory tests to determine what kind of cells are causing a particular cancer.

Imaging

Imaging for breast tumors can involve several tests, which may include:

• X-ray mammography (mammogram)
• Breast ultrasound
• CT scan
• Positron emission tomography scan
• MRI scan

These tests find the location of potential cancer cells in the breast and other parts of the body.

Biopsy

A biopsy is performed to collect a sample of potential cancer cells for analysis. Breast biopsies usually involve an ultrasound-guided core needle biopsy or fine needle aspiration biopsy. Sometimes an excisional (surgical) biopsy is performed to remove a lump (in a procedure called a lumpectomy) for diagnosis.

Immunophenotyping

Immunophenotyping identifies types of cancer cells based on surface antigens (proteins on the cell surface). Flow cytometry or immunohistochemistry are used to see if specific antibodies will bind to surface antigens. Other techniques, such as in situ hybridization, are used to look for specific genetic mutations in the cancer cells. Pinpointing surface antigens and genetic mutations are important for identifying the type of cancer and for determining which treatments will work best.

Stages of Primary Breast Lymphoma

Lymphomas are staged using the Lugano staging system (based on the older Ann Arbor system). The location of the primary tumor and the cancer’s spread to other parts of the body are used to determine the stage and whether or not the cancer involves extranodal sites (sites outside of lymph nodes or other lymphatic organs). PBL is by definition an extranodal NHL.

There are four stages. Stage 1 and stage 2 are considered early or limited stages. They involve lymph nodes and one organ outside the lymphatic system on the same side of the diaphragm. Stage 3 and stage 4 are late or advanced stages in which the lymphoma has spread to both sides of the diaphragm and may include organs outside of the lymphatic system

The International Prognostic Index (IPI) is also used to assess the outlook of lymphomas. The IPI is based on five factors:

• Age
• Lymphoma stage
• Extranodal involvement
• Performance status (ability to perform activities of daily living)
• Blood levels of lactate dehydrogenase (LDH)

Negative prognostic factors that predict higher risk include age over 60 years, advanced-stage disease, involvement of more than one extranodal site, trouble performing daily activities, and high LDH levels.

What Causes Primary Breast Lymphoma?

The cause of PBL and other NHLs is not understood. There are many risk factors for different types of lymphoma, including infection with certain viruses such as Epstein-Barr virus and cytomegalovirus. Having a compromised immune system, such as from HIV, is also associated with lymphoma. BIA-ALCL occurs in people with breast implants, but how breast implants may cause lymphoma is unknown.

Treatment of Primary Breast Lymphoma

Treatment for PBL depends on the type and stage of lymphoma. Generally, PBL is treated like other NHLs with a combination of localized radiation, systemic treatment with chemotherapy, and targeted drug therapy. Surgery such as a mastectomy is sometimes used to remove PBL tumors, but this approach is becoming less common. BIA-ALCL is treated by removing the breast implant and surrounding scar tissue, including the tumor. Removal is sometimes followed by radiation or chemotherapy.

Radiation Therapy

Local radiation is used to treat some types of PBL using focused-beam or external-beam radiation. Radiation can decrease the size of a tumor or kill off cancer cells that remain after surgery.

Chemotherapy

Different types and subtypes of lymphoma respond to different chemotherapy regimens. Some of the most common regimens used for different types of PBL include:

• R-CHOP — Rituxan (rituximab) with cyclophosphamide (sold as Cytoxan), doxorubicin (also known as hydroxydaunorubicin and sold as Adriamycin), vincristine (formerly sold as Oncovin), and prednisone (a corticosteroid)
• CHOEP — Cyclophosphamide, doxorubicin, vincristine, VP-16 (etoposide), and prednisone
• ABVD — Doxorubicin, bleomycin (sold as Blenoxane), vinblastine, and dacarbazine (sold as DTIC-Dome)
• CODOX — Cyclophosphamide, vincristine sulfate, and doxorubicin
• R-EPOCH — Rituximab with etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin

Targeted Therapy

Targeted therapy with rituximab is used for lymphomas that express the CD20 surface antigen. Rituximab is a monoclonal antibody that binds to CD20 and marks cells for destruction by healthy T cells. Other monoclonal antibody drugs target other cell surface proteins. Targeted therapy can be used alone or in combination with other therapies.

Is Primary Breast Lymphoma a Type of Breast Cancer?

This question is not easy to answer. Perhaps the best way to describe PBL is to say that it is a lymphoma of the breast or a lymphoma in the breast, but not breast cancer. The term “breast cancer” is usually reserved for describing breast carcinomas and sarcomas, so calling a lymphoma in the breast “breast cancer” is not accurate.

People usually use the term “breast cancer” to describe cancers such as invasive ductal carcinoma, which come from cells that are specifically part of breast tissue. But PBL does not come from breast tissue — it comes from lymphocytes that happen to be in breast tissue. Breast implant-associated ALCL, for example, is a lymphoma that, by definition, originates in the breast, but not from breast tissue itself. PBL should not be described as breast cancer, as the term does not best represent the nature of the disease.

Primary Breast Lymphoma Outlook

The outlook for specific cases of PBL depends on the type of lymphoma and what stage it is when it is diagnosed. Limited-stage PBL (stage 1 or 2) has a higher five-year survival rate compared to other limited-stage systemic lymphomas. Overall, the outlook for all types of PBL combined is very good, with a five-year relative survival rate for PBL of 90 percent compared to 76 percent for systemic lymphomas.

PBL survival rates are best for stage 1 disease (greater than 90 percent) and stage 2 disease (greater than 75 percent), but worsen significantly with stage 4 disease, which has a survival rate of less than 45 percent.

The different lymphoma subtypes of PBL can have very different outlooks. The five-year relative survival rate of stage 1 and 2 PBL is as high as 100 percent for follicular lymphoma, 95 percent for marginal zone lymphoma, 78 percent for diffuse large B-cell lymphoma, and 74 percent for anaplastic large cell lymphoma.

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