Rosen's Breast Pathology, 4e

333

Ductal Carcinoma In Situ

The increased age-adjusted incidence of in situ breast carcinoma in the United States coincides with a leveling off in the overall age-adjusted incidence of invasive carcinoma and of localized carcinoma, and a decline in the incidence of invasive carcinoma classified as “regional.” 25 These changes in incidence by stage have been accompanied by a signifi- cant decline in age-adjusted breast carcinoma mortality. 25 The beneficial effects of mammography as a diagnostic or screening modality, and of improved systemic therapy, are reflected in these trends. Although the incidence of DCIS has steeply escalated over the last few decades, this rise has not been uniform across various histologic types: low-grade DCIS has accounted for the majority of the recent increase in incidence owing to en- hanced radiologic detection, whereas the incidence of high- grade DCIS has remained stable. 26 Risk Factors Data on epidemiologic risk factors specific to DCIS are lim- ited. 27,28 There appear to be some age-related differences in associations, but overall the risk factors for DCIS and invasive carcinoma appear to be similar. 27 The risk for both lesions increases with age, an association that is stronger for inva- sive carcinoma. Risk factors for incident DCIS include posi- tive family history. 29 BRCA (breast cancer [gene]) mutations were found in 13% of women with DCIS diagnosed before 50 years of age. 30 In the largest analysis of DCIS patients in non–Ashkenazi Jewish women, the prevalence of a BRCA1/2 mutation was 5.9%. 31 The risk was significantly higher among women younger than 50 years with a personal and family his- tory of breast carcinoma than those 50 years or older. Mammography and Calcifications The great majority of currently diagnosed cases of DCIS are nonpalpable and are detected by various radiologic tech- niques. Mammography is a highly sensitive diagnostic pro- cedure for detecting DCIS. 32 In 2002, it was estimated that about 1 in every 1,300 screening mammograms resulted in a diagnosis of DCIS. 33 Until recently, on initial screening, 8% to 43% of mammographically detected carcinomas were intraductal. 34–40 Twenty-five percent to 30% of nonpalpable carcinomas detected by mammography were intraductal lesions. 37,41–43 In a series of nearly 20,000 patients, 30 of 70 carcinomas (43%) found in biopsies performed only for clustered calcifications detected by mammography were DCIS. 38 Mammographically detected calcifications were found in 72% to 98% of DCIS. 44–47 The proportion of DCIS was not substantially higher in subsequent mammography screening, but some investigators have described a greater frequency of small invasive tumors in later examinations. 34,39 The interval between screening examinations can influ- ence the clinical characteristics of DCIS detected by mam- mography. 48 The size of DCIS determined bymammographic measurement was significantly smaller in women examined annually (mean, 1.69 cm; range, 0.3 to 7.7 cm) than in those examined on a biennial (mean, 2.27 cm; range, 0.4 to 10 cm) or triennial (mean, 3.49 cm; range 0.6 to 10 cm) schedule.

Comedo-type (high-grade solid) DCIS was significantly more frequent in the biennial (73.7%) than in the annual (46.8%) screening group. Tumor size and nuclear grade were inversely related to the mean sizes for low-, intermediate-, and high-grade lesions determined to be 1.19, 1.85, and 2.82 cm, respectively. The frequency of microinvasion tended to increase with longer intervals between examina- tions, but the differences were not statistically significant. Approximately 10% to 15% of DCIS are discovered as in- cidental lesions in biopsies performed for other indications, usually a palpable abnormality. 32,43,46 Radiologic findings that lead to the detection of a small proportion of “inciden- tal” DCIS are densities and asymmetric soft tissue changes, sometimes with microcalcifications in the noncarcinoma- tous abnormality. Calcifications alone are more likely to be the mammographic indicator of DCIS in women younger than 50 years, whereas coexistent soft tissue abnormalities are evident more often in women older than 50, a distinc- tion that probably results from variation in overall breast density in these age groups rather than from intrinsic tumor differences. 46 Relatively specific findings of DCIS on mammograms in- clude microcalcifications of certain types and patterns, that is, the calcifications may be pleomorphic, coarse, and fine and are either clustered or linear in distribution. 47 Calcifica- tions associated with DCIS are generally described as linear “casts” or as granular on mammography (Fig. 11.1). Round or oval, well-circumscribed calcifications are less common in DCIS. Predominantly linear, granular, or mixed types of calcifications occur with approximately equal frequency in DCIS. Calcifications may be clustered, dispersed, or dis- persed around clustered foci. Branching calcifications with linear patterns that outline the distribution of one or more ducts may consist of casts or granular particles. The type of calcifications is not related to age at diagnosis or to the size of the area involved mammographically. 46 The level of sus- picion for DCIS is a function of the character and the num- ber of calcifications. The majority of DCIS have five or more calcifications. 46 On mammograms, linear, pleomorphic calcifications are commonly seen in high-grade DCIS, and granular segmen- tal calcifications are typical of lower grade lesions. Ducts afflicted with high-grade DCIS harbor calcifications more often than those with low-grade DCIS. In some cases of low- grade DCIS, the majority of calcifications are in adjacent benign glands. Thus, DCIS may be smaller, larger, or equal to the extent of mammographic calcifications, and calcifica- tions do not always “map-out” DCIS, particularly in lower grade lesions. Despite such nuances, the mammographic distribution of calcifications is commonly used as a guide to the extent of DCIS or the dimensions of the involved area. However, these measurements typically tend to underesti- mate the size of the lesion compared with careful histologic sampling. 49 When the extents of lesions were measured mammographically and pathologically, discrepancies were found more often between the interpretations for cases that were predominantly cribriform or micropapillary than for high-grade, solid DCIS. A discrepancy of more than 20 mm was found in 44% of pure cribriform–micropapillary lesions,