Breast: DE: Ductal Carcinoma In Situ

Introduction

Definition: Ductal carcinoma in-situ (DCIS) is a neoplastic proliferation of luminal type ductal epithelial cells. Clinical Significance: Ductal carcinoma in-situ comes to clinical attention because of the presence of calcifications on a mammogram or linear enhancement on MRI. In the uncommon situation in which it produces a pronounced stromal reaction, it can present as a mass. DCIS represents the precursor to invasive ductal carcinoma and usually leads to treatment of the entire involved breast (mastectomy or excision and irradiation). Oncologists usually also recommend hormonal therapy to reduce the risk of developing carcinoma in the contralateral breast. When a core biopsy reveals ductal carcinoma in-situ, a surgeon will typically carry out an excision of the targeted area and marginal tissue. If the radiological or the pathological findings indicate extensive involvement of the breast and in certain other circumstances, the surgeon will recommend a mastectomy and sentinel node excision rather than an excision. Current thinking based on morphological, clinical, and genetic studies asserts that the low-grade and high-grade forms of ductal carcinoma in-situ represent distinct biological entities whose morphological precursors and genetic aberrations do not overlap. Gross Findings: Low-grade DCIS does not usually exhibit macroscopic findings. Transected ducts of high-grade DCIS may exude yellow-white, granular or pasty material (comedonecrosis), corresponding to necrotic carcinoma cells in the duct lumen. Calcifications associated with DCIS may impart a granular texture. Microscopic Findings: Expansive proliferation of polarized, atypical, slightly dishesive epithelial cells characterizes DCIS. Differential Diagnosis: Usual ductal hyperplasia (highly cohesive, nonpolarized cells), atypical ductal hyperplasia (typically low-grade, less expansive), lobular carcinoma in-situ (dishesive, nonpolarized cells) Discussion: Although the cellular features of ductal carcinoma in-situ vary from case to case and can differ somewhat within cases, four alterations represent consistent findings: cellular polarization, cellular enlargement, cytological atypia, and architectural atypia.

Ductal carcinoma in-situ (top) gives rise to invasive ductal carcinoma (bottom).

Cellular Polarization

The cells of DCIS display the phenomenon of cellular polarization, a fundamental characteristic of normal epithelial cells. We recognize polarization by the location of the nucleus at one end of the cell (referred to as the basal pole) and the accumulation of cytoplasm at the opposite end (referred to as the apical cytoplasmic compartment). Normal ductal epithelial cells rely on signals associated with the basement membrane to establish the orientation needed to achieve polarity. The ability of ductal carcinoma cells to establish polarity far from the basement membrane differentiates these malignant cells from normal mammary cells and from neoplastic lobular cells.

Low-grade DCIS	Intermediate-grade DCIS

Polarized ductal cells typically display a columnar shape, an eccentric nucleus, and an apical cytoplasmic compartment. Polarization is usually obvious in the cells of low-grade DCIS (above left) and in some cases of intermediate-grade DCIS (above right); however, it may be difficult to appreciate the polarized state in other cases of intermediate-grade DCIS (below left) or in high-grade DCIS (below right). The diagnosis of these later examples of DCIS hinges on recognizing the cells' large size and pronounced cytologic atypia.

Intermediate-grade DCIS	High-grade DCIS

Cellular Enlargement

Besides displaying polarization, the cells of DCIS demonstrate enlargement of the nucleus and increase in the amount of the cytoplasm; thus, the size of the cell increases. Contrasting the malignant cells with nearby benign cells highlights these alterations. In the focus to the right we can easily compare the size of the cells in an entrapped benign gland (center) to the size of the surrounding DCIS cells.

Cytologic Atypia

The cytological atypia that characterizes DCIS varies according to the grade of the carcinoma. Features of low-grade atypia include: uniformity of the nuclei, round or oval nuclear shapes, smooth nuclear contours, and inconspicuous nucleoli.

The chromatin of low-grade atypia can appear dark and dispersed (below left) or somewhat pale and finely granular (below middle). When it is pale and finely granular, you can usually see small nucleoli (below right).

Chromatin: dark and dispersed	Chromatin: pale and finely granular	Small nucleoli

The cytoplasm of low-grade atypia usually appears pale, delicate, and faintly eosinophilic to amphophilic (below left), but certain examples consist of cells with clear (below middle) or densely eosinophilic (below right) cytoplasm.

Cytoplasm: faintly eosinophilic to amphophilic	Cytoplasm: clear	Cytoplasm: densely eosinophilic

In low-grade atypia, the cell borders often appear distinct, as they do in the picture to the right and the pictures above.

In high-grade DCIS, cells appear greatly enlarged and they demonstrate obvious nuclear enlargement, variation in the size and shape of the nuclei, and variation in the number, size, and shape of the nucleoli. Mitotic figures abound, and the cells often undergo necrosis.

Cases of intermediate-grade DCIS typically exhibit enlargement of the cells and their nuclei, but otherwise do not have a consistent set of cellular alterations. As in the case to the right, their nuclei and nucleoli appear more variable in size and shape than those of low-grade ductal carcinoma in-situ but less so than those of high-grade ductal carcinoma in-situ.

The chromatin of intermediate-grade DCIS varies from dark and smudgy (left) to pale and coarsely granular (right).

Chromatin: dark and smudgy	Chromatin: pale and coarsely granular