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Next-Generation Sequencing and the Management of Patients With Clinically Advanced Breast Cancer

Introduction Cancer develops due to an accumulation of mutations in DNA. For many years, it has been widely accepted that the development and progression of cancer is associated with alterations in the DNA sequence of the cancer cell genome, such as base substitutions, short insertions and deletions, homozygous deletions, and amplifications and fusions (translocations) of genetic material. Improved understanding of the genetic mechanisms that initiate or…

Metastatic Tumors in the Breast

Introduction The most common metastatic tumors in the breast are from contralateral breast primaries, but these are excluded in most series and are not discussed here. Breast metastases from extramammary malignant neoplasms are uncommon and account for up to 3% of all breast malignancies, although their incidence at autopsy is greater than 6%. The rarity of metastatic disease from an extramammary location is due to the…

Hematolymphoid Tumors of the Breast

Introduction Breast hematological malignancies are rare. Breast lymphoma represents less than 1% of all malignant breast tumors and accounts for only 1% to 2% of extranodal lymphomas. The vast majority of primary breast lymphomas (PBLs) are non-Hodgkin’s lymphomas (NHLs). A recent study which queried the Surveillance, Epidemiology, and End Results (SEER) database identified an increase from 0.66 to 2.96 in the incidence of PBLs in the…

Breast Tumors in Children and Adolescents

Introduction Breast enlargement in children and adolescents (<20 years of age) can be due to normal or abnormal physiological causes, reactive changes, or neoplastic proliferations. The patient’s age, gender, hormonal status, and other clinical findings need to be considered in concert with the histological findings. The vast majority of breast masses arising in the first 3 decades of life are benign and the approach to managing…

Neoplasia of the Male Breast

Introduction The male breast is different in many respects from the female breast, in terms of both composition and pathology. Malignant conditions may occur, albeit far less commonly than seen in females, with advanced molecular studies suggesting that these conditions are different from female breast cancers (FBCs). The resulting implications for patient management are being increasingly recognized, with recent clinical studies specifically designed for understanding and…

Mesenchymal Tumors of the Breast

This chapter discusses the more common benign and malignant mesenchymal tumors that occur in the breast. Most of these lesions are uncommonly encountered in routine practice and offer specific challenges to the pathologist. Spindle cell proliferations in particular can have overlapping clinicopathological, morphological, and immunophenotypic features and generate a broad differential diagnosis that can range from benign to malignant. The most frequently encountered spindle cell neoplasm…

Rare Breast Carcinomas: Adenoid Cystic Carcinoma, Neuroendocrine Carcinoma, Secretory Carcinoma, Carcinoma With Osteoclast-like Giant Cells, Lipid-Rich Carcinoma, and Glycogen-Rich Clear Cell Carcinoma

Introduction This chapter details a group of breast carcinomas that occur rarely and have unique clinical and pathological features. The study of these unusual variants of carcinoma contributes to the knowledge of the pathogenesis of breast carcinomas. Adenoid Cystic Carcinoma Adenoid cystic carcinoma (AdCC) of the breast is a rare special histological type of breast cancer, accounting for approximately 0.1% to 1% of all breast cancers.…

Special Types of Invasive Breast Carcinoma: Tubular Carcinoma, Cribriform Carcinoma, Mucinous Carcinoma, Micropapillary Carcinoma

Introduction Distinguishing a “special type” of breast carcinoma from invasive carcinoma of no special type (IC-NST) is based on characteristic morphology. It is important to correctly identify these entities because each type has a fairly predictable biological behavior. Tubular Carcinoma Tubular carcinoma (TC) is a special type of invasive carcinoma characterized by a distinct morphology and an excellent clinical outcome. The overall incidence of TC is…

Pathology of Neoadjuvant Therapeutic Response of Breast Carcinoma

Introduction Administration of chemotherapy or endocrine therapy before definitive surgery (neoadjuvant systemic therapy [NST]) is a standard treatment for inflammatory and inoperable locally advanced breast cancer. With advances in breast imaging and improvements in tumor characterization and staging, patients who are eligible for adjuvant chemotherapy or endocrine therapy for operable early stage breast cancer are now being offered NST. Clinical trials have shown no difference in…

Paget’s Disease of the Breast

Paget’s disease (PD) of the nipple is an uncommon malignancy, accounting for 1% to 3% of all breast tumors, characterized by eczematous eruption and ulceration. Velpeau described the eczematous lesions of the nipple-areola in 1856, but it was Sir James Paget who first described the association of these lesions with underlying breast cancer in 1874. In his paper, Paget described 15 women between the ages of…

Apocrine Carcinoma of the Breast

Introduction The word apocrine in medical literature is used in general to denote a gland or cell exhibiting a distinct type of glandular secretion in which the free end of the secreting cell is cast off along with the secretory products accumulated therein, resembling apocrine sweat glands. Apocrine morphology in breast pathology refers to distinct cytological features in mammary epithelial cells including eosinophilic and granular to…

Metaplastic Breast Carcinoma

Metaplastic breast carcinomas are a heterogeneous group that can display adenocarcinoma, squamous, spindle cell, and/or heterologous mesenchymal growth patterns, often in various combinations. These combinations have suggested monikers such as matrix-producing carcinoma , carcinosarcoma , spindle cell carcinoma , and carcinoma with pseudosarcomatous metaplasia . The carcinomatous component may be minimal, be hard to find, or present only as carcinoma in situ. Metaplastic carcinomas as defined…

Triple-Negative and Basal-like Carcinoma

Introduction Triple-negative breast cancer (TNBC) lacks expression of the estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor 2 (HER2) and accounts for approximately 15% of invasive breast cancers (IBCs) among screened individuals and up to 20% to 40% among unscreened populations. TNBC is a heterogeneous category of carcinoma subtypes whose diversity is seen at all levels: histological, immunophenotypic, transcriptomic, genomic, and prognostic. The…

Invasive Ductal Carcinoma of No Special Type and Histological Grade

IDC, or ductal carcinoma of no special type (ductal NST), is a heterogeneous group of tumors that fail to exhibit sufficient characteristics to achieve classification as a specific histological type, such as lobular, mucinous, or tubular carcinoma ( Fig. 23.1 ). Therefore, ductal NST should not be considered a distinct type of breast carcinoma, but is in essence the default category left when a tumor is…

Ductal Carcinoma In Situ

Ductal carcinoma in situ (DCIS) is a heterogeneous group of lesions defined as a proliferation of neoplastic epithelial cells within the mammary duct lobular system. Major diagnostic criteria that differentiate DCIS from invasive cancer are the presence of intact basement membrane and a peripheral myoepithelial cell layer at the epithelial stroma interface. DCIS is a nonobligate precursor for invasive breast cancer (IBC). Ductal Carcinoma In Situ…

Lobular Neoplasia and Invasive Lobular Carcinoma

Despite the earlier descriptions by Ewing, the term lobular carcinoma is largely credited to Foote and Stewart, who, in 1941, published their seminal paper describing a detailed morphological analysis of a distinctive subgroup of in situ carcinomas of the breast, which was not well recognized by pathologists at that time. As opposed to usual intraductal carcinomas, this subset of lesions was preferentially located in the lobules…

Molecular Classification of Breast Carcinoma

Introduction Historically, breast cancers have been classified broadly based on morphology into ductal and lobular types and characterized by tumor grading. A smaller percentage of tumors are classified as “special subtype carcinomas.” This classification system has provided useful prognostic information. Long-term follow-up studies have shown an excellent prognosis for Nottingham grade I tumors and a poor survival rate for Nottingham grade III tumors. Although extremely useful,…

Columnar Cell Change, Flat Epithelial Atypia, and Atypical Ductal Epithelial Hyperplasia

Introduction: Screening and Detection As the imaging modalities used for breast cancer screening and diagnosis have improved, the types of specimens evaluated by pathologists for risk-associated lesions have changed. In contemporary practice, atypical ductal hyperplasia (ADH) and atypical lobular hyperplasia (ALH) are much more likely to be diagnosed in image-guided core needle biopsy (CNB) specimens versus excisional biopsies. The adoption of digital mammography has resulted in…

Fibrocystic Change and Usual Epithelial Hyperplasia of Ductal Type Fibrocystic Change

Fibrocystic change (FCC) refers to a complex of lesions including gross and/or microscopic cysts, apocrine metaplasia, fibrosis, and blunt duct adenosis (BDA), and minor degrees of sclerosing adenosis and usual epithelial hyperplasia. It is important to realize that cystic change is an alteration of lobules. Three-dimensional studies of sections with FCC have established that the cysts gradually develop first by dilatation and then by coalescence of…