D Chen, M Mittler, M Lefkowitz, M Eisenberg, K Black, R Woldenberg, P Farmer, J Li
brain metastasis, breast carcinoma, metapalstic carcinoma, mucinous carcinoma
D Chen, M Mittler, M Lefkowitz, M Eisenberg, K Black, R Woldenberg, P Farmer, J Li. Breast Carcinoma Metastasizes to Brain-Three Unique Cases. The Internet Journal of Pathology. 2010 Volume 12 Number 1.
Metastatic breast carcinoma to the brain is a relatively common occurrence in patients with breast cancer. Brain metastasis is usually the later sequela for breast cancer patients. Mucinous carcinoma and metaplastic carcinoma are rare subtypes of breast cancers. Mucinous carcinoma has favorable prognosis and rarely develops brain metastasis. It is rare that initial presentation of a patient with neurological manifestation leads to the diagnosis of breast cancer. We report three unique cases of brain metastasis of breast carcinoma. 1) Mucinous carcinoma: A 52-year-old female had mucinous carcinoma in both breasts and been free of disease for 8 years. 2) Metaplastic breast carcinoma with an epithelial component with squamous and neuroendocrine differentiation and a mesenchymal component composed of chondroid differentiation: A 41-year-old female was diagnosed with metaplastic carcinoma eleven months ago. 3) Triple negative (negative for estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2) breast carcinoma metastasis to brain as the initial presentation in a 71-year-old female. For less aggressive subtypes of invasive breast carcinomas such as mucinous carcinoma, brain metastasis can occur after many years of remission. For more aggressive subtypes of invasive breast carcinomas such as metaplastic carcinoma or triple negative invasive ductal carcinoma, brain metastasis can occur in the early phase of disease and rarely before the diagnosis of primary breast cancer.
Approximately 15-40% of patients with known primary malignant neoplasms will present with brain metastasis.1.Of all patients with brain metastasis there can be upwards of 15% of these patients with undiagnosed primary.1 Breast cancer is the second most common metastatic tumor to the brain. Approximately 10-20% of breast cancers develop brain metastasis with increasing trend, which usually represent a late event for the patients.2-6
Mucinous carcinoma (colloid carcinoma) is a rare subtype of breast carcinomas, accounting for approximately 2% of all breast carcinomas. It uncommonly develops nodal metastasis and has a favorable prognosis.7-9 It is extremely rare that breast mucinous carcinoma metastasizes to the brain.
Metaplastic carcinoma is a rare tumor, accounting for less than 1% of invasive mammary carcinomas. It is referred to a heterogeneous group of tumors and is divided into purely epithelial and mixed epithelial-mesenchymal tumors. The latter will be called as carcinosarcomas when the mesenchymal component is malignant.10;11 Chondroid, osteoid, or rhabdoid differentiation is the most common mesenchymal component.
The presence of metastatic breast cancer to the brain as initial presentation of breast cancer is very rare in the medical literature. Search of PubMed database yielded no reports of intra-parenchymal brain metastasis as initial presentation of breast cancer. However, we did find one case report of cavernous sinus syndrome and two reports of bilateral choroidal metastases to the eye as initial presentation of breast cancer.12-14
In this paper, we present three unique cases of brain metastasis of breast carcinoma. 1) Mucinous carcinoma. 2) Metaplastic breast carcinoma with an epithelial component and a mesenchymal component. 3) Triple negative breast carcinoma [negative for estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor-2 (HER2)] metastasis to brain as the initial presentation.
The patient was brought to the operating room for a stereotactic guided right frontal craniotomy and excision of tumor. Frozen section sent at the time of surgery showed metastatic carcinoma. The permanent sections and immunostains showed poorly differentiated non-small cell carcinoma, unclear origin. Carcinoma cells were positive for pan-cytokeratin AE1/AE3 and CK7, but negative for CK20, TTF-1, GCDFP-15, p63, synaptophysin, chromogranin, estrogen receptor, progesterone receptor and HER2/neu (Fig. 4). The patient tolerated surgery well and was discharged 3 days later with improving symptoms. Shortly afterwards, she underwent an endoscopy of upper GI tract, which was negative for any suspicious lesions. Within the next few weeks the patient had a breast ultrasound done followed by a biopsy. The pathology of the breast biopsy returned as moderately differentiated ductal cell carcinoma, which was negative for estrogen receptor, progesterone receptor and HER2/neu. The pathologist at our institution received both specimens and confirmed that breast carcinoma was morphologically identical to the metastatic carcinoma in the brain (Fig 4).
Breast cancer is second after lung cancer as the most common cause of brain metastasis, occurring in 10-16% of patients suffering from breast cancer.15 Invasive ductal carcinoma (IDC) is the most common type of breast carcinoma, constituting approximately 70-85% of all invasive breast carcinoma.16 In over 80% of breast cancer cases, the woman discovers a lump on her breast herself, which is the most common symptom.17 The metastasis of breast cancer to the brain is usually a late event. The median time from diagnosis of breast cancer to metastatic brain disease or leptomeningeal involvement is usually 2-3 years.16;17 In the majority of patients, spread to CNS occurs after other systemic metastases to lung, liver or bone are diagnosed.
Mucinous carcinoma and metaplastic carcinoma are two rare subtypes of breast carcinomas. Mucinous carcinoma has a favorable prognosis with low frequency of axillary lymph node metastasis and advanced metastatic disease.18;19 Our patient of case 1 had large mucinous carcinomas in bilateral breasts with positive axillary lymph nodes. After treatment, she had eight years free of disease before she finally developed brain metastasis without systemic metastatic disease and local recurrence. On the other hand, the metaplastic carcinoma is usually more aggressive than the conventional invasive ductal carcinioma.10;11 Our patient of case 2 had a small metaplastic carcinoma (1.9 cm) with negative axillary lymph nodes. Only after 11 months, she developed brain metastasis and systemic metastatic diseases.
Our patient of case 3 did not recognize any lumps on her breast nor had any signs of other systemic cancer involvement. Her initial complaint to her neurologist and primary care physician was that of blurred vision and confusion. After work up with brain MRI and surgery, a breast biopsy afterwards helped us confirm that the metastatic lesions in the brain were of breast origin. The patient had triple negative invasive ductal carcinoma, which did not express estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor-2 (HER2). Both triple negative invasive ductal carcinoma and metaplastic carcinoma have a worse prognosis.
These less aggressive subtypes of invasive breast carcinomas such as mucinous carcinoma need long-term follow-up. Brain CT or MRI for ruling out possible brain metastasis is warranted if the patient suddenly develops CNS symptom even after many years of remission. For these more aggressive subtypes of invasive breast carcinomas such as metaplastic carcinoma or triple negative invasive ductal carcinoma, early CNS imaging study is prudent. Although it is rare, breast carcinoma can present as a brain metastatic carcinoma with unknown primary before having the definitive diagnosis of breast cancer.