A Unique Late Presentation of Primary Breast Lymphoma: A Case Report

Abstract

Background: Primary breast lymphoma is a rare entity in that it accounts for less than 1% of breast cancer and 2.2% of extranodal lymphoma. The most common histological type is diffuse B-cell lymphoma. Early stages of the disease have relatively good prognosis. Case Presentation: In this case, we are reporting on a forty-four-year-old lady presenting a large fungating right breast mass that turned out to be a primary breast lymphoma and whose outcome was unfortunate due to late presentation. Conclusions: Despite significant evolvement on treatment of lymphoma, negligence and social stigmatization still have a role in patients’ demise. Efforts toward awareness and anti-stigmatization are of paramount importance.

1. Background

Primary breast lymphoma (PBL) is defined as a cancer of the breast lymphatic system localized to one or both breasts, with or without regional lymph nodes, with no antecedent diagnosis of lymphoma. It is a rare extranodal lymphoma subtype, accounting for 1.7–2.2% of extranodal lymphomas. Although breast cancer is a common misfortune experienced by women across the globe, breast lymphoma is a very unusual form of breast malignancy, accounting for 0.5% of all breast malignancies [1,2]. Its pathophysiology is still unknown, but it is thought that it may derive from mucosa-associated lymphoid tissue or lymphoid tissue adjacent to breast ducts and lobes [3]. Of all PBLs, 95% are B-cell lymphomas and only 5% are T-cell lymphomas. Diffuse large B-cell lymphoma (DLBCL) is the most common variant. Other less common variants are follicular lymphoma, Burkitt’s lymphoma, Burkitt-like lymphoma, small lymphocytic lymphoma, marginal zone lymphoma and breast implant–associated anaplastic large cell lymphoma [4]. Moreover, in practice, it is difficult to distinguish between primary breast lymphoma and secondary breast involvement in the late stages. However, the detailed history of the patient and radiological evaluation of the location of the largest disease burden can indicate the origin in most cases.

In our case, this patient presented a fungating breast mass with unusual metastasis over a short course of time, which was a very unusual presentation of primary breast lymphoma. In addition, lack of awareness, social barriers and negligence ended the life of this patient prematurely.

2. Case Presentation

A forty-four-year-old lady from a rural area arrived at our institute emergency department with a fungating breast mass of the right breast. The breast lump was first noticed nine months ago, but she did not seek any medical care due to family and social stigma in her village. The mass had dramatically increased in size over this period of time, and this was accompanied by the worsening of her medical condition. By the time she presented it to us, she was bedbound and not communicating. Her daughter reported that her mother lost weight and had developed a persistent cough. She did not have any significant previous medical or surgical history. Her family history was not significant for cancer.

The examination of her breast revealed multiple ulcerative lesions of 7 × 4 cm, 3 × 2 cm in size with watery, greenish discharge secondary to traditional heat-marking treatment. The breast was engorged with a peau d’orange appearance and the areola and nipple looked normal. There were multiple small red non-tender lesions over her chest. Her vitals were within normal limits. Systemic examination revealed yellowish discoloration of the sclera and chest auscultation exhibited reduced air entry in the right lower zone.

Her laboratory investigation showed high alkaline phosphatase (ALP) of 400 IU/L (the normal range being of 44 to 147 IU/L), high calcium of 3.5 mmol/L (the normal range being of 2.2 to 2.7 mmol/L), high total bilirubin of 37 mmol/L (the normal range being of 3 to 17 mmol/L), high alanine aminotransferase (ALT) of 104 IU/L (the normal range being of 7 to 56 U/L) and high C reactive protein (CRP) of 63.6 mg/L (the normal range being of 8 to 10 mg/L). Her complete blood count (CBC) showed white blood cells (WBCs) of 10.64 × 10⁹/L (the normal range being of 4.5 to 11.0 × 10⁹/L), neutrophils of 7.5 × 10⁹/L (the normal range being of 3 to 7 × 10⁹/L), lymphocyte of 2.1 × 10⁹/L (the normal range being of 1 to 4.8 × 10⁹/L), low hemoglobin of 8.1 gm/dL (the normal range being of 12.3 to 15.3 gm/dL), a platelet count of 336 × 10⁹/L (the normal range being of 150 to 400 × 10⁹/L), U/E: urea of 7.7 mmol/L (the normal range being of 1.8 to 7.1 mmol/L), creatinine of 79 µmol/L (the normal range being of 53 to 97.2 µmol/L), Na of 134 mmol/L (the normal range being of 135 to 145 mmol/L), K 4.6 mmol/L (the normal range being of 3.5 to 5.2 mmol/L), and Cl of 102 mmol/L (the normal range being of 96 to 106 mmol/L). Her coagulation profile was as follows: international normalized ratio (INR) of 1.05, prothrombin time (PT) of 12.1 sec (the normal range being of 11 to 13.5 s) and an activated partial thromboplastin time (APTT) of 33.6 sec (the normal range being of 30 to 40 s). Her right breast ultrasonography (US) showed an irregular hypoechoic mass at the nine o’clock position 12 cm from the nipple, measuring 34 × 37 mm (AP × TS), with no increased vascularity, which was highly suspicious for malignancy. The right axillary US showed a large well-defined mass seen in the right axillary tail, measuring 59 × 59 × 67 mm (TS × AP × CC), with no increased vascularity, suggestive of an enlarged metastatic lymph node (Figure 1). Moreover, there were multiple ill-defined areas of altered echo-texture with hyper-echogenicity representing infiltrated and inflamed fat lobules with increased vascularity, which are associated with skin thickening across the right breast. The left breast parenchyma was normal.

The patient was admitted for further workup and management. An intravenous (IV) enhanced computed topography (CT) scan of the chest, abdomen and pelvis was obtained. It showed a large lobulated right breast with skin thickening and soft tissue cellulitis. There were multiple enhancing soft tissue density masses seen in the posterior abdominal and pelvic wall. There was a right side moderate pleural effusion with pleural thickening extending along the right lateral chest wall. There was a diffuse ground glass-like appearance in both lungs, with multiple sub-centimetric mediastinal, peritoneal and retroperitoneal lymph nodes; the liver was mildly enlarged and hypodense, representing fatty infiltration, minimal free fluid was seen in the pelvis and a well-defined 43 × 35 mm size cyst was seen in the right ovary (Figure 2). Surprisingly, it did not show any bone lesions. The brain CT was normal.

The differential diagnosis was advanced ductal/lobular adenocarcinoma, inflammatory breast cancer, primary/secondary breast lymphoma, breast sarcoma and idiopathy granulomatous mastitis.

Later, an incisional biopsy was taken for histopathological examination. On the next day, the ulcerated lesions started to bleed significantly, which subsequently led to the patient becoming hemodynamically unstable. The bleeding was controlled with hemostatic sutures and she was resuscitated with boluses of IV fluids. A meeting was conducted with the patient’s relatives to discuss her management plan. It was agreed to palliate her only with analgesia and to provide her with full medical support without any surgical intervention. Unfortunately, two days later, the patient passed away.

The histopathology report of the biopsy resulted after one week of high-grade lymphoma. The immunomorphology was consistent with diffuse large B-cell lymphoma, activated B-cell type (non-germinal center B-cell type), pathology category B5b. The immunohistochemistry of the neoplastic cell was positive for LCA, CD20, BCL-2, BCL 6 and MUM-1 and negative for AE1, AE3, CD10, CD3, CD34 and myeloperoxidase (Figure 3). The Ki67 was very high, at more than 90%.

3. Discussion

Primary breast lymphoma diagnostic criteria was initially proposed in 1972 by Wiseman and Liao, which included having an adequate sample with histopathological conformation of lymphomatous infiltrate in a tissue within the breast anatomical location in the absence of prior diagnosis of extramammary lymphoma and the evidence of concurrent widespread disease, except for with ipsilateral axillary lymph nodes [3]. The incidence is higher in woman aged 50 years and older. In addition, the most common histology of PBL is diffuse large B-cell lymphoma (DLBCL), which accounts for around 60% to 85% of PBLs [4,5]. PBL patients usually present a painless mobile solitary breast mass; however, it can have multiple or diffuse lesions. Moreover, nipple manifestation, such as nipple retraction and discharge, are rare [6]. One-third of patients will have lymph node involvement at the time of diagnosis [7].

Mammography of a breast lymphoma usually demonstrates a hyperdense non-calcified lesion with non-specific margins and a speculated abscess. Furthermore, in ultrasonography, the lesion is usually hypoechoic, with hypervascularity. Those features help to distinguish breast lymphoma from adenocarcinoma; however, no radiology features are truly diagnostic and biopsy remains mandatory. Moreover, positron emission tomography/computed topography (PET/CT) scans are important with determining the stage of the disease and can help with the discovery of additional sites of nodal or extranodal disease. However, imaging cannot differentiate primary from secondary breast lymphoma in the presence of widespread disease. Therefore, the clinical context is of significant importance [8].

Although evidence is lacking in describing the etiology of primary breast lymphoma. Lymphoma arising from the breast occurs almost exclusively in women, leading some to propose an estrogen-related mechanism. A recent large study found a 29% increased risk of developing all types of non-Hodgkin lymphoma (NHL) for women treated with unopposed estrogen hormone replacement therapy, compared to women never exposed to it. Autoimmune disease is another associated disease found more commonly in NHL patients, which is non-specific to PBL [9].

Although primary breast lymphoma was initially considered to have a poor prognosis, it is now thought to be like any other lymphoma of the same histological type. This understanding has developed with the shift in care from surgical to non-surgical management over the past four decades [5]. Current recommended treatments from published large cohort studies are R-CHOP (rituximab–cyclophosphamide, doxorubicin, vincristine, prednisolone) immunotherapy and chemotherapy (the standard regimen for nodal DLBCL), plus radiotherapy for consolidation. This treatment regimen for PBL offers a 5-year overall survival of 80–76% and a progression free survival of 77–73%. A special consideration should be made for the rare group of patients with the Hodgkin’s lymphoma variant of PBL to be treated with a ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen. This surgery is usually reserved for patients with breast implant-associated anaplastic large cell lymphoma, where removal of the causative agent and capsulectomy plays a role in disease control [4,9]. Current studies are looking into the clinical development of new small molecule inhibitors for NF-kB activity to improve clinical outcome [9].

In our case the diagnosis made was based on two facts; first, the history provided by the patient’s relatives was consistent with the primary breast origin, and second, the radiological imaging illustrated a high disease burden over the right breast only with direct extension to the chest and with no significant involvement of other sites in comparison. Unfortunately, the patient’s delayed advanced presentation did not warrant complete radiological and histopathological assessment, nor the initiation of mainstay treatment.

4. Conclusions

A primary breast lymphoma diagnosis is reached after the triple assessment of a breast complaint. Advance imaging, such as PET-CT, may help to differentiate primary from secondary involvement, but the clinical context is usually more important. Non-surgical management is usually the mainstay treatment depending on the histopathological variant, and only one variant may benefit from disease control by surgery. Although advances in treatment have changed patient outcomes, we strongly believe that increasing public awareness and fighting local stigma can alter patients’ outcomes dramatically and save lives.