In Brief

Article Outline

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The diagnosis of breast cancer has been around since approximately 1600 BC when a roll of papyrus was created by an Egyptian physician named Imhotep, who documented cases of breast tumors. Although crude in nature, the treatment included surgical therapy for removal of these masses. Today, our knowledge of the breast and the types of tumors it can produce has increased tremendously and is now quite vast. Most recently, the World Health Organization produced a list of more than 55 types of benign and malignant breast tumors.

Although molecular advances are still emerging, we still rely heavily on the use of microscopes that were originally developed in the late 1500s, for the pathologic diagnoses of tumors. Invasive ductal carcinoma is still the most common diagnosis (65% to 80% of cases), and invasive lobular carcinoma is second (5% to 15% of cases). Unusual variants manifest on a frequent enough basis that their clinical, morphologic, and biologic traits must be evaluated by experienced pathologists, radiologists, and surgeons. We now know that mixed forms of invasive cancers and unusual cases can often confound the literature and confuse the delivery of appropriate treatments. The pathologic evaluation of breast cancer patients has increasingly become the most critical factor in patients with breast masses or abnormal calcifications, not only for treatment but also for prognosis.

Historically, rare and unusual breast tumors have been reported in the literature since the 1800s. Many of these pathological anomalies have no consensus on their optimal treatment. They comprise only 5% of all primary breast cancers. We are now beginning to get a better sense of these tumors, but there is still a very broad array of pathological distinctions. For this reason we felt it important to have a synopsis of the literature that would focus on pathologic distinctions, clinical diagnosis and radiologic evaluation, treatment, and outcome.

The days of routine radical or even modified radical mastectomy have been replaced in large part by the less morbid lumpectomy and reconstruction. It has been said that routine radiation only benefits 30% of patients, with 60% who would do well without it and 10% who would recur regardless of radiation therapy. Thus, recent trials have focused on determining which patients would be suited for surgical extirpation alone. In that regard, surgical pathology becomes extremely important and even carcinomas of the usual type are cataloged in extreme detail in terms of size, nuclear grade, presence of lymphovascular invasion, size and grade of any in situ component, multifocality versus multicentricity, hormone receptor status, Her-2-neu amplification, width of the margin, and axillary nodal status. Ninety-five percent of breast tumors can be cataloged in this manner. The remaining 5% fall into categories that we do not often encounter and thus our intent is to discuss their unique clinical presentations, pathology, and treatment. We have classified the tumors into unusual carcinomas that represent a distinct differentiation from common mammary carcinomas, malignant mesenchymal or pure stromal tumors, metastatic carcinomas, tumors of lymphoid or hematopoietic origin, myoepithelial tumors, phylloides tumors that contain both epithelial and stromal elements, and benign stromal tumors of the breast. Finally we will discuss some unusual presentations of breast cancer. This manuscript is devised in a way that is similar to the system of classification used by the World Health Organization in 2003.

The unusual breast carcinomas discussed in this compendium include: metaplastic breast carcinoma, low grade adenosquamous carcinoma, invasive micropapillary carcinoma, apocrine breast carcinoma, squamous cell carcinoma of the breast, neuroendocrine carcinoma, oncocytic carcinoma, secretory breast carcinoma, intracystic papillary carcinoma, adenocystic carcinoma, and acinic cell carcinoma. The common thread with these unusual carcinomas is the underlying differentiation of cells from the more common ductal carcinomas. Some of them, such as metaplastic carcinoma and invasive micropapillary carcinoma, can be rather aggressive, have a high grade at presentation, and metastasize to the axillary nodes. Others are more benign types of cancer that only require local resection with very uncommon axillary metastases. These include secretory and intracystic papillary lesions.

Malignant mesenchymal neoplasms include: osteosarcoma of the breast, malignant fibrous histiocytoma and fibrosarcoma, liposarcoma, leiomyosarcoma, rhabdomyosarcoma, myofibroblastoma, malignant schwannoma, and chondrosarcoma of the breast. The underlying distinction with these tumors, aside from being rare, is the fact that many other types of breast carcinoma pathology must be ruled out in the process of their evaluation. Metaplastic carcinoma and phylloides tumors must be disproved, desmin and actin stains may be necessary, and S-100 positivity is common.

A section on metastatic carcinomas of the breast is then presented coupled with a section on tumors of lymphoid or hematopoietic origin, lymphoma and leukemias of the breast, and plasmacytoma of the breast. These require simple excision for diagnostic purposes.

Myoepithelial lesions are then discussed and include descriptions of adenomyoepithelioma, and malignant adenomyoepithelioma and phylloides tumors. Phylloides tumors were initially described in 1838 by Johannes Muller. Since that time, we have learned that they fall into 3 categories, including benign, intermediate, and malignant, each requiring more aggressive therapy ranging from simple excision of the benign to mastectomy for larger malignant phylloides tumors.

Vascular tumors of the breast are well known for their ability to form various vascular anastomotic entities. Angiosarcoma while usually presenting after radiation therapy, is discussed along with its rapidly progressive and poor prognosis. Other vascular tumors include hemangiopericytoma and hemangioma.

The final section of unusual breast tumors comprises benign stromal tumors of the breast. These benign entities are more benign than not; however, their treatment should include excision due to chances of recurrence. Fibromatosis, granular cell tumors, pseudoangiomatous hyperplasia (PASH), syringomatous adenoma, leiomyoma, and neurofibroma are included in this discussion.

The topic of unusual presentations of breast cancer includes discussions of mammary Paget's disease, carcinoma presenting during pregnancy, carcinoma arising in a fibroadenoma, carcinoma arising in axillary breast tissue or supernumerary nipples, and inflammatory breast cancer.

We are now in the dawn of a new age of personalized molecular medicine and yet detailed microscopic analysis and categorization remains critical to treatment and prognostic paradigms. It would behoove us and our esteemed colleagues to continue to document these rare types of breast cancer, catalog them, and develop registries for them at centers of excellence to advance our understanding of their histopathologic behaviors and enable us to find an eventual cure for this multifaceted disease.