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Chapter 11

single carcinomatous focus typically limited to one region or quadrant. The latter condition is commonly referred to as multifocality . One commonly employed criterion for establishing the presence of multifocality depends on the number of histologic sections that show DCIS. For example, Fisher et al. stated that “ductal carcinoma in situ in only one section of two or more obtained from different blocks was considered to be unifocal. Its presence in sections from two or more different blocks was considered multifocal.” On the basis of this definition, 329 (60.8%) of 541 evalu- able specimens of DCIS were classified as multifocal in data from National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B17. 265 Silverstein et al. 269 considered DCIS to be multifocal when “. . . separate foci of DCIS [duct carcinoma in situ ] more than 2 cm from primary site . . .” were found in a mastectomy specimen. On the basis of this criterion, multifocality was present in 41 (41%) of 98 breasts examined after mastectomy. Multicentricity, defined as car- cinoma outside the index quadrant, was present in 15% of these breasts. Multifocality and multicentricity were not significantly related to the histologic category of DCIS when stratified as comedo and noncomedo type. 269 Hardman et al. 273 found multicentric carcinoma in 27% of mastec- tomy specimens from patients with carcinoma of the com- edo type. Multicentricity was reported in 33% 18 and 37% 274 of mastectomies performed for diverse types of DCIS. A proportion of “multifocal” DCIS, albeit a minor one, may be a product of artifact, because of the inherent problem of two-dimensional viewing of a three-dimensional arborizing disease process. In an effort to circumvent these technical issues, some investigators have set anatomic limits on the distribution of carcinoma to somewhat arbitrarily distinguish between unicentric and multicentric diseases. For example, carci- noma has been deemed to be multicentric if it is detected in more than one quadrant or if it is 5 cm from the index lesion. 93,274–276 Silverstein et al. 277 classified as multicentric if two foci were separated by more than 2.0 cm. Schwartz et al. 93,278 studied the frequency of multicentric- ity in the breasts of patients with DCIS who underwent mas- tectomy. Multicentricity was defined as “the presence [of] invasive ductal or lobular carcinoma, microinvasive ductal carcinoma, or DCIS in an area or quadrant outside the bi- opsy site . . . . If the lesion was centrally located, the cancer was considered multicentric only if additional foci of carci- noma were found outside a perimeter of 5 cm from the edge of the nipple and areola.” 93 Multicentricity was found in 18 (36%) of 50 93 and 4 (36%) of 11 278 breasts. Multicentricity was more often present in lesions detected because of nipple discharge (71%) or Paget disease (50%) than in those found by mammography (38%). 93 When classified on the basis of the predominant growth pattern, micropapillary DCIS was more often multicentric (86%) than papillary (33%) or com- edo (42%) DCIS. No multicentricity was encountered in five cribriform and seven solid DCIS. Bellamy et al. 86 also found multicentricity to be present significantly more often in pa- tients with micropapillary DCIS than in those with other patterns of DCIS.

If the sample provided for histologic diagnosis is an ex- cisional biopsy limited to the region of the index lesion, the material is not suitable for determining whether the patient has multicentric carcinoma. According to some definitions, more than a quadrantectomy is necessary to detect multi- centricity. In practice, the distinction between multifocal- ity and multicentricity is difficult to make with certainty in slides prepared by random sampling of breast specimens for diagnostic purposes. Serial sequential sectioning of smaller excisional biopsy specimens facilitates mapping of the extent of disease, and this method should be utilized whenever fea- sible. Advanced techniques such as stereoscopic dissection and subgross microscopic–radiologic correlative studies are more reliable methods for identifying true multicentricity and multifocality, but they are too costly and time consum- ing to be practical procedures for routine diagnostic work. Given the limited resources available in most pathology lab- oratories, it may be unrealistic to expect diagnostic reports on breast biopsies to routinely distinguish multicentricity from multifocality. It is likely that multifocal and multicentric DCIS will be increasingly detected with growing use of MRI. In a study of 285 patients with newly diagnosed DCIS, MRI exami- nation performed for the evaluation of extent of disease showed separate foci of invasive carcinoma “elsewhere” in the breast, that is, either multicentric or contralateral, in 16 (5.6%) patients. 279 A meta-analysis of 19 studies ( n = 2,610) demonstrated that MRI detected additional foci of carci- noma (invasive and/or in situ ) in 16% of invasive and/or in situ carcinoma cases that had not identified by traditional evaluation. 280 In summary, multicentric DCIS refers to its presence in distinctly different regions of the breast, usually in two or more quadrants, whereas multifocal DCIS is confined to one quadrant and is generally regarded as that which is spatially closer, with at least some normal breast tissue separating the neoplastic foci. The adjectives, multicentric and multifocal ought not to be used interchangeably owing to the divergent clinical implications of each term. 281 MICROINVASION Genomic and phenotypic similarities, among other clini- cal and pathologic forms of evidence, support the conclu- sion that DCIS is a nonobligate precursor of invasive ductal carcinoma. Microinvasive carcinoma (abbreviated as T1 mic in the TNM American Joint Committee on Cancer [AJCC]- Union Internationale Contre le Cancer [UICC] staging system) is the earliest manifestation and stage of invasive mammary ductal carcinoma. The upper limit of the extent of invasion for an invasive carcinoma to qualify for this des- ignation is 0.1 cm (i.e., 1 mm). Ultrastructural studies have detected foci of discontinuity in the basement membranes of ducts with DCIS, 282,283 and similar observations have been reported in tissues studied by IHC. 284 Breaks in the basement membrane were more com- mon when DCIS was of high nuclear grade with or without