Intraductal proliferations of mammary epithelium of the breast form a spectrum that begins with intraductal hyperplasia without atypia (also known as conventional ductal hyperplasia), continues with atypical intraductal hyperplasia, and ends with ductal carcinoma in situ.
Accordingly, atypical intraductal hyperplasia represents a middle point between the benign and malignant poles of aforementioned proliferative continuum. Defining proper pathohistological criteria for atypical intraductal hyperplasia is pivotal in order to separate it from ordinary intraductal hyperplasia and certain forms of ductal carcinoma in situ.
Pathology and Clinical Presentation
Intraductal proliferative lesions of the breast are restricted to the duct-lobular system and stem from the terminal duct-lobular unit with diverse architectural and cytological patterns of proliferation. They also show increased number of cells that are perpendicular to the basement membrane, resulting in distension and total alteration of the normal unit structure of the breast.
If intraductal hyperplasia is traced in serial sections, it is possible to observe multifocal and discontinuous nature of the condition along the course of a single duct. Furthermore, the enlargement of the affected glandular structure is also a common finding – both in terms of greater length and increased diameter.
Intraductal hyperplasia can be found in women of virtually any age, and there are no clinical features that are specifically associated with intraductal hyperplasia. The changes caused by epithelial proliferation in individual ducts (but also in multiple branches of a ductal system) are microscopic in dimension, hence usually not palpable.
An important consequence of such absence of clinical indicators is an inability to determine the duration of these lesions. Consequently, this is considered a source of bias when assessing the precancerous significance of proliferative lesions in individual patients.
In instances when it is clinically evident, intraductal hyperplasia most often occurs in a vague palpable area, usually described as breast thickening. The non-specific mammographic indicators of such changes include parenchymal distortion, altered duct patterns, non-palpable mass lesions, calcification, and breast asymmetry.
In 1999, Tavassoli proposed a classification to encompass all intraductal proliferative lesions into a single category termed DIN (ductal intraepithelial neoplasia). In this system, intraductal hyperplasia was classified as DIN1a, which means the risk of developing an invasive cancer is 1.5 to 2 times higher in comparison to the general population.
Alongside putting intraductal hyperplasia on the map, this system has a myriad of advantages. First and foremost, it diminishes the classical dichotomy of either “cancer” or “no cancer”. In fact, it completely eliminates the term “cancer” in order to diminish the associated emotional stress and anxiety. Moreover, the differences between lesions are quantitative, not qualitative.
Management of the Disease
One of the key steps for the management of this disease is the proper distinction between intraductal hyperplasia and intraductal carcinoma. The major concern is the potential risk of developing carcinoma, which is greater when atypia is present than when hyperplasia is in the ordinary category.
Patients with intraductal hyperplasia are encouraged to regularly participate in a follow-up program that includes self-examination, physician examination, and mammography. Examinations are usually scheduled more frequently for women with atypia and certain risk factors (such as a family history of breast carcinoma).
Tamoxifen, a drug that successfully blocks the effects of the estrogen in the human body, was also used to lower the potential risk of cancer development. In one randomized study that compared women with receiving tamoxifen with women that were given a placebo, a 86% reduction in subsequent invasive carcinoma development in the treated women with atypical intraductal hyperplasia was observed.
Reviewed by Susha Cheriyedath, MSc