Papillary Lesions of the Breast: An Update

Invasive micropapillary carcinoma (IMPCa) of breast is histologically characterized by growth of cohesive tumor cell clusters within prominent clear spaces resembling dilated angiolymphatic vessels. In this study, eighty three breast carcinomas with IMPCa differentiation were identified by review of the invasive carcinoma cases in our institution and correlated retrospectively with standard clinicopathologic parameters and survival status relative to a control series of cases (mean follow up 7 years). IMPCa growth pattern was present in 6% of all breast carcinomas; it was generally a focal component in otherwise typical invasive ductal carcinoma. It comprised more than 80% of the total neoplasm in only 10 cases (12%), 50-80% of the neoplasm in 7 cases (8%), 20-50% of the neoplasm in 22 cases (26%) and less than 20% in 44 cases (53%). The mean tumor size was 4 cm, 22% invaded skin, and 58% were poorly differentiated, but 71% were ER positive. Axillary node metastases were present in 77% of cases, were typically multiple (51% had three or more positive), and usually contained an IMPCa component (81% of the cases). There was no significant difference in node status, ER status, size, tumor grade, or peritumoral angiolymphatic invasion between tumors with predominant (more than 50%) v/s focal IMPCa components. In both groups 46% of the patients died from their disease (mean interval to death = 36m). Skin involvement and nodal status were the only parameters which predicted poor survival (P =.01). The outcome of patients with IMPCa did not differ significantly from infiltrating ductal carcinomas of similar node status. In conclusion, our results suggest that IMPCa growth pattern may be a manifestation of aggressive behavior, as shown by frequent skin invasion and extensive nodal involvement. However, clinicopathologic features and outcome of IMPCa are not strongly dependent on the relative amount of micropapillary component.

The relatively small group of patients with breast tumors other than the ductal, lobular or mixed ducto-lobular types, has reached nonnegligible numbers due to the ongoing increase in the incidence of breast cancer. We investigated stage and grade distribution of uncommon breast tumors using the nation-wide Netherlands Cancer Registry (population 16.5 million) and incidence patterns, treatment and long-term survival (up to 19 years) using the regional Eindhoven Cancer Registry (population 2.4 million). Incidence of all uncommon breast tumors together was 9.2/100,000 person years (age-standardized, ESR). The proportion of stage I tumors was 70% among patients with tubular (n = 3,456) and 40-50% for mucinous (n = 3,482), papillary (n = 1,078), cribriform (n = 503) and neuroendocrine (n = 76) tumors, contrasting to 27, 28 and 36%, respectively among patients with Signet ring cell cancer (n = 75), Paget's disease (n = 818) and the common invasive ductal carcinomas (n = 121,656). A better age-, stage-, and grade-adjusted prognosis was observed for patients with lobular (death risk ratio 0.8, 95%CI: 0.7-0.9), mucinous (0.5, 0.3-0.9), medullary (0.5, 0.3-0.9) and tubular (0.4, 0.2-0.6) carcinoma or phyllodes tumor (0.02, 0.0-0.2), compared with invasive ductal carcinomas. For patients with papillary (0.6, 0.2-1.6) and cribriform (0.1, 0.0-5.1) tumors better prognosis was not statistically significant. In conclusion, histologic type was an essential determinant of survival for about 10% of all newly diagnosed women with invasive breast cancer. Because patients with mucinous, tubular, medullary and phyllodes tumors have such a good prognosis, less aggressive treatment should be considered in some cases whereby specific guidelines are becoming increasingly desirable. Communication to patients with these specific histological types should reflect this.

Breast papillomas may be single or multiple and associated with atypical ductal or lobular hyperplasias (ADH/ALH). The risk of breast carcinoma development in patients with papillomas, particularly those with multiple or atypical lesions, is incompletely defined. Fibrocystic lesions were histopathologically classified in a benign breast disease cohort of 9155 who underwent biopsy from 1967 to 1991, with papilloma assessment in 9108. Individuals with papillomas (N=480) were classified into 4 groups: single papilloma (SP, N=372), single papilloma with ADH or ALH (SP+A, N=54), multiple (>5) papillomas (MP, N=41), and multiple papillomas with ADH or ALH (MP+A, N=13). Those without papillomas were classified as nonproliferative (NP, N=6053), proliferative without atypia (PDWA, N=2308), and ADH/ALH [atypical hyperplasia (AH), N=267]. The relative risk of cancer development within our cohort was compared to that expected in the general population using standardized incidence ratios. The relative risk of breast cancer development associated with SP [2.04, 95% confidence interval (CI) 1.43-2.81] was greater than NP (1.28, 95% CI 1.16-1.42) but similar to PDWA (1.90, 95% CI 1.66-2.16). The risk associated with SP+A (5.11, 95% CI 2.64-8.92) was highly elevated but not substantively different than atypical hyperplasia (4.17, 95% CI 3.10-5.50). Patients with MP are at increased risk compared with PDWA or SP (3.01, 95% CI 1.10-6.55), particularly those with MP+A (7.01, 95% CI 1.91-17.97). There was a marginal increase in breast cancer risk (16%) among patients with proliferative disease if a papilloma was present, but this did not reach statistical significance (P=0.29). The observed frequency of ipsilateral (vs. contralateral) breast cancer development in papilloma subsets was not significantly different than other patient groups. We conclude that SP imparts a cancer risk similar to conventional proliferative fibrocystic change. The presence of papilloma in, or associated with, atypia does not modify the risk connotation of ADH/ALH overall. MP constitutes a proliferative breast disease subset having unique clinical and biologic behavior.