Concurrent Invasive Ductal Carcinoma of the Breast and Malignant Follicular Lymphoma, Initially Suspected to Be Metastatic Breast Cancer: A Case Report
A 40-year-old woman presented with a large palpable lump in the right breast. Mammography revealed a large mass involving the entire breast with nipple retraction and multiple bilateral axillary lymphadenopathies (). Ultrasonography (US) images showed an 8×6×3 cm irregular hypoechoic mass in the right breast without any suspicious lesion in the left breast. US of the regional lymph nodes showed multiple enlarged lymph nodes in the axillae on both sides and in the left supraclavicular area (). US-guided core needle biopsy (CNB) of the right breast mass indicated invasive ductal carcinoma. Immunohistochemical (IHC) staining showed that the biopsy specimen was positive for estrogen receptor (ER) and progesterone receptor (PR) (4+, 4+, respectively), and fluorescence in situ hybridization (FISH) revealed that the specimen was negative for human epidermal growth factor receptor 2 (HER2) expression. ER and PR expressions were quantified using the Allred score, a semiquantitative system based on the proportion of positive cells (scored from 0 to 5) and staining intensity (scored from 0 to 3) []. The proportion and intensity scores were added to yield a total score of 0 to 8. An Allred score >2 was considered positive for ER or PR. HER2 IHC staining was quantified using the HercepTest scoring system (0 and 1+, negative; 2+, equivocal; and 3+, positive). Specimens with an IHC staining score 2+ results were subjected to a second test and were tested with FISH. A HER2-positive tumor was defined as one with an intensity score of 3+ on IHC staining or as a HER2/CEP17 (centromeric probe for chromosome 17) ratio of more than 2.2 on double-probe FISH assays [].\nOn contrast-enhanced magnetic resonance imaging (CE-MRI), the right breast mass appeared as an irregular mass with initial rapid and late washout enhancement and diffusion restriction. Multiple enlarged lymph nodes were observed in the axillae on both sides, without any suspicious lesion in the left breast. Positron emission tomography/computed tomography (PET/CT) with 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) revealed multiple lymphadenopathies with increased FDG uptake in the axillae on both sides, in the neck, and in the left external iliac and inguinal areas ().\nWe initially considered disseminated metastatic disease from breast cancer, but other pathologies with multiple lymph node involvement such as lymphoproliferative disease and metastasis from another primary malignancy could not be ruled out. US-guided fine needle aspiration (FNA) of an enlarged cervical lymph node and CNB of a left axillary lymph node revealed reactive hyperplasia.\nClinically, metastatic breast cancer was strongly suggested (clinical stage IV, T3N3M1), and therefore initial hormone therapy with zoladex (3.6 mg) and tamoxifen (20 mg) was administered according to the current guidelines for metastatic ER+ breast cancer in a premenopausal woman. One month later, the patient visited another hospital for a second opinion. During the following 8 months, she was enrolled in a clinical trial at another hospital and underwent 8 cycles of maintenance chemotherapy. The regimen comprised 175 mg/m2 paclitaxel, administered intravenously on day 1 and every 21 days thereafter, and 1,250 mg/m2 gemcitabine administered as a 30-minute intravenous infusion on days 1 and 8 and every 21 days thereafter. Postchemotherapy response evaluation showed stable disease, but she refused further chemotherapy because of a poor performance status. Eight months after the discontinuation of chemotherapy, a PET/CT scan at our hospital showed that the primary breast malignancy was stable but that the multiple lymphadenopathies were aggravated, and a new bone metastasis was detected in one thoracic vertebral body (). Therefore, hormone therapy with tamoxifen was initiated. After 1 year of hormone therapy, bilateral neck and right leg swelling developed. A PET/CT scan showed aggravated lymphadenopathies throughout the torso and splenomegaly (), strongly suggesting a lymphoproliferative disease such as lymphoma. Excisional biopsy of a left neck lymph node revealed malignant follicular lymphoma ().\nThe lymphoma was diagnosed as clinical stage IV and the patient was administered chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisolone. Four months after chemotherapy, the clinical symptoms had improved and a PET/CT scan showed complete remission of the lymphoma.\nPalliative surgery for the breast cancer was planned and mammography, US and MRI were performed. During the evaluation, a new suspicious lesion was found in the upper outer region of the left breast. This lesion showed a 3.5×1.5 cm heterogeneous hypoechoic area on US () and a 4 cm focal area with initial rapid and late plateau enhancement on CE-MRI. US-guided CNB revealed invasive ductal carcinoma. Radical mastectomy with axillary lymph node dissection and a pedicled transverse rectus abdominis muscle flap for chest wall reconstruction was performed for the right-sided breast cancer, and a simple total mastectomy with ipsilateral lymph node sampling was performed for the left-sided breast cancer. Pathology results demonstrated invasive ductal carcinoma (both, modified Bloom and Richardson grade II: tubule and gland formation 3, nuclear grade of pleomorphism 2, mitotic count 1) in both breasts and axillary lymph nodes. On IHC staining, both breast carcinomas was positive for ER and PR (right: 7+ and 7+, respectively; left: 8+ and 5+, respectively) and Ki-67 (right: 2%; left: 5%), and negative for HER2 and epidermal growth factor receptor. Pathologically, the left breast cancer was suspected to have arisen due to metastasis from the right-sided breast cancer ( and ). The postsurgical pathological staging was stage IV (T3N3M1). Maintenance chemotherapy including rituximab for lymphoma was scheduled for 2 years and hormone therapy and palliative radiotherapy were considered for breast cancer.