Practical Considerations in Breast Papillary Lesions: A Review of the Literature

In this review, we highlight adaptations in the WHO 2012 classification of papillary and neuroendocrine breast lesions as compared with the previous 2003 version. Consensus criteria for distinguishing atypical ductal hyperplasia from ductal carcinoma in situ within an intraductal papilloma are proposed. The absence of myoepithelial cells around the wall of an encapsulated papillary carcinoma, although raising consideration of an indolent tumour with minimal invasion, is currently regarded as in-situ disease for staging purposes. The majority of solid papillary carcinomas are classified as in-situ tumours, but lesions with irregular tumour islands within desmoplastic stroma may be considered to be invasive. The diagnosis of solid papillary carcinoma without further qualification as either in-situ or invasive disease is discouraged. When invasive papillary carcinoma is seen in the breast, metastatic papillary carcinoma from other organ sites needs to be excluded. WHO 2012 classifies neuroendocrine breast tumours as well-differentiated neuroendocrine tumour, small-cell carcinoma, and invasive breast carcinoma with neuroendocrine differentiation. There is currently no clinical impact of identifying neuroendocrine differentiation in conventional invasive breast carcinomas, apart from acknowledging its frequent occurrence in subtypes such as the hypercellular variant of mucinous carcinoma and solid papillary carcinoma.

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.

Papillary carcinoma (PC) of the breast, which accounts for 0.5% to 1% of breast cancer, is a distinct histologic subtype that is characterized by malignant epithelial proliferation supported by fibrovascular stalks. However, the classification of PC (whether they are in situ or invasive), its behavior, and management remain a matter of debate. In this study, we reviewed 302 PCs including 247 pure PCs without coexisting conventional non-PCs collected from 3 institutions. This included 208 (84%) intracystic PCs (IPC), 30 (12%) solid PCs (SPC), and 9 (4%) papillary ductal carcinoma in situ (DCISs). In addition, previous studies of PC were reviewed. This included 339 pure PCs of a total of 521 PC patients. Clinical and outcome analyses were carried out to assess nature and behavior of these lesions and to determine their optimal outcome-based management. SPC is more frequently associated with coexisting conventional invasive carcinoma than IPC (P<0.05). Although the majority of papillary DCIS and some cases of IPC and SPC (both called encapsulated PC) that are surrounded by an intact layer of myoepithelial cells are considered to be true in situ lesions, PC lacking a peripheral layer of myoepithelial cells can be regarded as a special type of invasive carcinoma associated with low incidence of stromal/skeletal muscle invasion, low frequency of lymph node metastasis (3%), and infrequent development of local or distant recurrence. These lesions are therefore characterized by indolent behavior and extremely favorable prognosis. Encapsulated PC can be treated with adequate local therapy. Routine use of adjuvant therapy, particularly chemotherapy, is clearly not appropriate in view of the very low risk of subsequent events. However, hormonal therapy may be indicated in certain cases such as recurrent PC.