Bilateral primary breast Burkitt’s lymphoma in pregnancy

Abstract

Pregnancy-associated cancer is defined as malignancy diagnosed during gestation or up to 1 year post partum. Treatment of cancer during pregnancy is complicated by the risk of harm to the fetus and limitations in safety data. Postpartum patients receiving chemotherapy, tyrosine-kinase inhibitors or hormonal agents should avoid breast feeding to avoid drug excretion in breast milk. Patients who will receive cytotoxic chemotherapy should be advised of the potential impact on their future fertility and offered fertility-preservation options. Breast cancer is the most common pregnancy-associated malignancy and is most frequently either invasive ductal or lobular carcinoma. Breast lymphoma is an exceedingly rare diagnosis that typically presents with unilateral disease in the seventh decade of life. Here, we present the case of a woman who presented with bilateral breast masses during the second trimester of pregnancy and was ultimately diagnosed with primary breast Burkitt’s lymphoma.

Background

Pregnancy-associated cancer (PAC) is diagnosed when malignancy occurs during gestation, lactation or up to 1 year post partum.¹ The incidence of PAC is about 1 in 1000 pregnancies and is increasing with higher rates of advanced maternal age.² Breast cancer is the most common PAC, followed by cervical cancer, lymphoma and ovarian cancer.³ More than 90% of patients diagnosed with pregnancy-associated breast cancer (PABC) present with a unilateral palpable mass, whereas bilateral malignant breast masses are exceedingly rare.⁴

Case presentation

The patient was a female in her 30s who presented with rapidly enlarging, painless bilateral breast masses during the second trimester of her third pregnancy. The patient had no pertinent medical history or family history of cancer. She denied fever, night sweats or unintentional weight loss. Physical examination was notable for large, irregular breast masses. No cervical, axillary or inguinal lymphadenopathy was appreciated. CT scan and breast ultrasound showed irregular masses in both breasts, the largest of which was on the left side and measured 8.1×6.6×9.9 cm; the largest mass in the right breast measured 4.2×3.5×4.0 cm (figures 1–4). The patient was counselled on the importance of prompt diagnostic workup given the high suspicion for malignancy. Specifically, ultrasound-guided diagnostic biopsy was recommended. However, the patient decided to defer all diagnostic workup until after delivery.

Figure 1.

Axial CT image with contrast demonstrating an irregular mass in the left breast (arrow) with associated calcification (arrowhead).

Figure 2.

Grayscale ultrasound image demonstrating percutaneous needle biopsy of mass (arrow).

Figure 3.

Colour Doppler image demonstrating increased vascularity in the mixed solid and cystic mass (arrow).

Figure 4.

Grayscale ultrasound image demonstrating a mixed echogenicity mass with solid (arrow) and cystic components (arrowhead).

Investigations

Bilateral core needle biopsies of the breast masses were taken shortly after term spontaneous vaginal delivery of a healthy female infant at 38 weeks’ gestation. Histological examination showed diffuse infiltrate of medium-sized atypical lymphocytes with round-to-oval nuclei, fine chromatin and scant cytoplasm. Immunohistochemical staining revealed strong expression of Pax5, CD79a, CD10, c-Myc and weak expression of CD20. There was no expression of CD5, CD23, BCL2, BCL6, TDT, CD34, cyclin D1, CD138, pancytokeratin or synaptophysin. The atypical Pax5-positive B cells were nearly 100% positive for Ki-67 and c-Myc. Fluorescence in situ hybridisation showed variant MYC gene rearrangement without evidence of BCL2 or BCL6 rearrangement, MYC gene amplification or IGH-MYC translocation. MRI of the brain, CT scans of the chest, abdomen and pelvis, bone marrow biopsy and lumbar puncture with cerebrospinal fluid analysis were all negative for evidence of lymphoma outside of the breasts.

Differential diagnosis

Gigantomastia is an uncommon complication of pregnancies, with an incidence of 1 per 28 000–100 000 pregnancies and a broad differential including both benign and malignant conditions.⁵ Common benign tumours include fibroadenomas and intraductal papillomas. During pregnancy and lactation, lactating adenomas and galactoceles are also commonly found. The most prevalent malignant breast tumours are invasive ductal carcinomas and invasive lobular carcinomas. Bilateral breast masses may represent synchronous primary cancers or a unilateral cancer and a contralateral benign breast mass. Breast implant-associated lymphoma may involve both breasts and is nearly always large cell anaplastic lymphoma. Common benign processes that may present with breast enlargement include mastitis, abscesses and fibrocystic breast disease. Bilateral breast enlargement without masses is a normal physiological expected finding during pregnancy and post partum.

Treatment

The patient was treated with six cycles of rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (R-EPOCH) with intrathecal methotrexate.

Outcome and follow-up

A positron emission tomography (PET) scan performed after completion of treatment revealed near-complete resolution of uptake in both breasts. Surveillance PET scans 3 months and 6 months after completing treatment showed mild residual uptake in the bilateral breasts without evidence of disease recurrence. The patient is now doing well 9 months after completing treatment without any residual symptoms from her cancer or cancer treatment.

Discussion

PABC can be challenging to diagnose as breast enlargement is a physiological change during pregnancy. Ultrasonography is the preferred initial modality of diagnostic evaluation for pregnant patients with breast masses; mammography with abdominal shielding is also an option when necessary.⁵ MRI is contraindicated in light of the required gadolinium contrast and prone positioning.^{3 4} Most breast masses in pregnancy are benign and therefore biopsy should be reserved for patients with BIRADS 4 or 5 breast imaging.⁵

Our patient had breast lymphoma, which accounts for 0.04%–0.70% of breast neoplasms.^{6 7} Primary breast lymphoma (PBL) is diagnosed only when there is no lymphomatous involvement beyond the axillary lymph nodes.⁸ The average age of PBL diagnosis is in the seventh decade of life, with clinical presentation and imaging findings similar to breast carcinomas.⁷ Most PBLs are diffuse large B-cell lymphoma (DLBCL) or MALT lymphoma.^8–10

Less commonly but with rising incidence is breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), which is a T-cell lymphoma that typically presents as an effusion around a textured implant.¹¹ It is thought that the incidence of BIA-ALCL is 1–2 per 1000 patients who receive implants, with an associated OR of 18.^{1 12} Of note, there is now a Food and Drug Administration box warning stating the association between breast implants and BIA-ALCL. Unlike other lymphomas, surgical resection is paramount to long-term survival.¹¹ For localised disease, surgical resection alone is recommended.^{12 13} For advanced disease, surgery is recommended with adjuvant chemotherapy.^{13 14} Our patient did not have breast implants and was diagnosed with an even rarer case of lymphoma.

Breast Burkitt’s lymphoma (BBL) is much less common than DLBCL, MALT lymphoma and BIA-ALCL, and has only ever been documented in case reports.^{15 16} In most of these rare reported cases, BBL presented as bilateral breast masses during pregnancy, as was the case for our patient. There have been 15 case reports of patients diagnosed with primary BBL.^{16 17} In all but one of these, however, widespread systemic lymphoma was present.¹⁷ The only case of BBL confined to breast tissue was included as part of a case series in 1967 of women in Uganda; the patient was in her 30s and was lactating upon presentation with bilateral breast masses.¹⁸ Unfortunately, she received no treatment and died 3 months later. We present just the second case of primary Burkitt’s lymphoma of the breasts without systemic disease involvement.

Burkitt’s lymphoma is an aggressive cancer that is often rapidly responsive to multiagent chemotherapy. Our patient was treated after delivery with R-EPOCH with intrathecal methotrexate and is now in clinical remission. This case serves to remind clinicians of two distinct points. First, while most breast changes during pregnancy and the postpartum period are benign, a cancer diagnosis should remain a possibility among the differential diagnoses. Second, although the majority of malignant breast masses are carcinomas, breast lymphomas are an alternative possibility to consider.

Learning points.

• Breast cancer should be considered in pregnant women presenting with a breast mass.

• Most pregnancy-associated breast cancers are carcinomas; rarely, breast lymphoma may also be found.

• Primary breast Burkitt’s lymphoma is an exceedingly rare clinical entity reported only in case reports.

Ethics statements

Patient consent for publication

Obtained.