The term invasive breast carcinoma refers to a heterogeneous group of epithelial malignancies that originate in breast tissue and are characterized by their ability to invade adjacent normal tissue, and metastasize to body sites distant to the breast. The vast majority of these tumors are adenocarcinomas, and they are thought to arise from mammary epithelial cells in the terminal ductulo lobular unit (TDLU) of the breast.
The traditional histologic classification of invasive breast carcinoma provides prognostic and predictive information about the biological behavior of a particular tumor that supplements the other major prognostic indicators such as lymph node status, histologic tumor grade, tumor size, and lymphovascular invasion. In the future, it is likely that new technologies that allow for the rapid genetic and expression profiling of specific tumors will provide information that will aid and refine the existing traditional morphologic classification of tumors. The World Health Organization (WHO) classification of breast tumors is probably the most widely used morphologic classification schema today, and will be used throughout this chapter.1
The grade of invasive carcinoma is a reflection of the degree of differentiation of the carcinoma. It is generally recognized that histologic grading provides prognostically important information and should be routinely performed for all types of invasive carcinomas of the breast.
The most widely used grading system for invasive breast carcinoma was developed in Nottingham, United Kingdom2 and is commonly referred to as the Nottingham Combined Histologic Grade.3 This grading system is a modification of the Bloom and Richardson grading system. There are 3 components of the histologic grade for invasive breast carcinoma:
Degree of tubule (gland) formation
Degree of nuclear pleomorphism (atypia)
Each component is given a numerical score of 1 to 3, with a score of 1 reflecting prominent gland formation, little nuclear atypia, and little mitotic activity, and 3 reflecting little or no gland formation, prominent nuclear atypia, and prominent mitotic activity. To obtain the overall grade, the score in each category is added to give a total out of 9 (6409118, 20-2, and 20-3):
- Total 3 to 5: grade I
- Total 6 or 7: grade II
- Total 8 or 9: grade III
Invasive duct carcinoma, Nottingham histologic grade I/III (H&E stain, 400×). This invasive carcinoma demonstrates some tubule formation (2/3), mild nuclear atypia (1/3), and no mitotic activity (1/3). The cumulative score is 4/9.
Invasive duct carcinoma, Nottingham histologic grade II/III (H&E stain, 400×). This invasive carcinoma demonstrates no tubule formation (3/3), moderate nuclear atypia (2/3), and occasional mitoses (1/3). The cumulative score is 6/9.