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Atypical Hyperplasia

Atypical hyperplasia carries a 4 fold increase in the risk of carcinoma over average. If there is a history of breast cancer in a parent or sibling, the risk is ten-fold over average. The most common form of atypical hyperplasia is atypical ductal hyperplasia (ADH), comprising 75-85% of all atypical epithelial hyperplasias diagnosed. The term ductal indicates the morphology of the hyperplasia, not its origin. Virtually all lesions of ADH occur in the terminal duct lobular unit. ADH is a clonal proliferation. Investigators have shown that ADH has some of the mutations and DNA methylation changes found in low grade ductal carcinoma. ADH is defined as a lesion that is identical to low grade ductal carcinoma in situ but is smaller than two millimeters OR a larger lesion that has most but not all morphologic features of low grade ductal carcinoma in situ. Below is an example of ADH having all the features of low grade DCIS but is less than 2 mm in largest dimension. Atypical ductal hyperplasia frequently presents on imaging associated with florid hyperplasia or enlarged lobular units that have foci of suspicious calcifications.

This example of ADH shows a cribriform architecture with identical cells.

Most lesions of atypical ductal hyperplasia will be 100% estrogen receptor positive, similar to low grade Ductal Carcinoma In-Situ.

In contrast, florid ductal hyperplasia will show a ""salt and pepper"" pattern of estrogen receptor activity with scattered strongly positive nuclei mixed with negative nuclei.

Atypical hyperplasia can also be classified by nuclear features. This example shows nuclear enlargement with focal loss of polarity, moderate atypia. Lesions with moderate and focal severe nuclear atypia may be difficult to separate from lesions of florid hyperplasia.

The image below shows a small lesion , under 1 mm, with severe cytologic atypia, apocrine features and no necrosis. Because the architecture is disorganized, lesions such as these may not even classified as atypical hyperplasia.

Atypical lobular hyperplasia or lobular neoplasia is the second most common form of atypical hyperplasia, comprising about 20% of all atypical hyperplasias. It rarely presents as an imaging lesion and is usually discovered as an incidental finding on biopsies and excision. Rarely, it may develop calcifications that warrant biopsy.  The finding of lobular neoplasia in a breast increases a patient's risk of invasive carcinoma. The degree of risk is dependent on the volume of the lesion. Very small lesions have the same risk as florid ductal hyperplasia, about 1.5-2 times increased risk above average. Larger lesions that fill lobular units and enlarge them 3 to 5 time normal volume have the same risk as atypical ductal hyperplasia. Lesions of lobular neoplasia that involve large ducts have 7 to 8 fold elevated risk of invasive breast cancer. Very large lesions of lobular neoplasia are called lobular carcinoma in-situ and carry the same risk of invasive carcinoma as ductal carcinoma in situ.

Lesions of lobular neoplasia have many of the same gene abnormalities that are found in low grade invasive carcinoma of the breast.  Most invasive carcinomas that arise in association with lobular neoplasia are low grade ductal carcinomas, but a greater minority are invasive lobular carcinomas. Also low grade ductal carcinoma in-situ may give rise to invasive lobular carcinoma, but at a lower rate than lobular neoplasia.

The cells of atypical lobular hyperplasia or lobular neoplasia resemble the cells that normally populate the acini of the terminal duct lobular unit. The cells of ALH differ from cells of atypical ductal hyperplasia by lacking e-cadherin, a cell-cell adhesion molecule.

Lobular neoplasia stained for estrogen receptor activity. Only very rarely are lesions of lobular neoplasia estrogen receptor negative.

An enlarged lobular unit containing lobular neoplasia on the left and cystically dilated acini lined by columnar epithelium and containing calcium phosphate. The cells of lobular neoplasia are almost completely replacing the normal epithelial elements in the portion of the lobular unit affected. This is an example of a small lesion of atypical lobular hyperplasia or Lobular neoplasia, grade 2.

One form of lobular neoplasia, called pleomorphic lobular neoplasia, has a higher risk of development of invasive carcinoma. The cells in this lesion are highly variable, with nuclear pleomorphism , intracytoplasmic lumens, mitotic figures and tumoral necrosis.
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