Intracystic Papillary Carcinoma of Breast: Interrelationship With in Situ and Invasive Carcinoma and a Proposal of Pathogenesis

Array Comparative Genomic Hybridization Study of 14 Cases

Thaer Khoury; Qiang Hu; Song Liu; Jianmin Wang


Mod Pathol. 2014;27(2):194-203. 

In This Article

Abstract and Introduction


Classifying intracystic papillary carcinoma under invasive or in situ ductal carcinoma is still a matter of debate. The purpose of this study was to explore the genomic relationship of this tumor to its concurrent invasive ductal carcinoma and ductal carcinoma in situ using array comparative genomic hybridization. Intracystic papillary carcinoma cases were classified into three categories: pure, with concurrent ductal carcinoma in situ or with concurrent invasive ductal carcinoma. Each component was dissected using laser capture microdissection. DNA was extracted and array comparative genomic hybridization was performed. The test of difference in copy number changes among the three tumors was carried out using CGHMultiArray. Intracystic papillary carcinoma clustered with four of five concurrent ductal carcinoma in situ cases and with two of two invasive ductal carcinoma cases. Intracystic papillary carcinoma showed the highest proportions of genome copy number aberration, followed by ductal carcinoma in situ, and then by invasive ductal carcinoma (P=0.06). Comparing intracystic papillary carcinoma with invasive ductal carcinoma vs without invasive ductal carcinoma, the former had 11q22.1–23.3 loss (P=0.031) and chr5 gain (P=0.085), and was enriched with matrix metalloproteinase genes. Comparing intracystic papillary carcinoma with ductal carcinoma in situ vs without ductal carcinoma in situ, the former had gain in 5q35.3 (P=0.041), 8q24.3 (P=0.041) and 21q13.2 to 21q13.31 (P=0.011). Comparing intracystic papillary carcinoma with ductal carcinoma in situ, the latter acquired a group of genes involved in cell adhesion and motility, whereas intracystic papillary carcinoma differentially expressed genes that are involved in papillary carcinomas of other organs (thyroid and kidney). We conclude that the overall molecular change in intracystic papillary carcinoma is closer to ductal carcinoma in situ than to invasive ductal carcinoma, which may explain the indolent behavior of this tumor. We offer herein a proposal of intracystic papillary carcinoma pathogenesis through its relation to invasive ductal carcinoma and ductal carcinoma in situ.


Intracystic papillary carcinoma is a distinctive variant of papillary ductal carcinoma, confined to a dilated cystic space and surrounded by a fibrous capsule, and characterized by thin fibrovascular stalks devoid of a myoepithelial cell layer, and a neoplastic cell population with histological features characteristic of low-grade ductal carcinoma in situ. It can be present as an isolated lesion or associated with conventional non-papillary ductal carcinoma in situ and/or invasive ductal carcinoma. When it occurs as an isolated lesion with no concurrent ductal carcinoma in situ or invasive ductal carcinoma, the tumor has favorable prognosis with no reported lymph node metastases or disease-related death. The presence of ductal carcinoma in situ or invasive ductal carcinoma in the surrounding breast tissue is associated with increased risk of local recurrence for the former and local and metastatic rates in the latter.[1]

The classification of intracystic papillary carcinoma as a form of invasive ductal carcinoma or ductal carcinoma in situ is controversial. Although the absence of myoepithelial cell layer would suggest intracystic papillary carcinoma as a form of invasive ductal carcinoma, the presence of collagen IV would suggest that it is a form of ductal carcinoma in situ.[2–5] The WHO Working Group reached a consensus that intracystic papillary carcinoma should be staged and managed like ductal carcinoma in situ.[1]

Genetic alterations in the form of interstitial deletions, loss of heterozygosity at 16q and 1p, and numerical and structural alterations at chromosomes 16q and 1p with fusion of chromosome 16 and 1 (der(1;16)) have been described in intracystic papillary carcinoma.[6–8] Duprez et al[9] studied the genomic characterization of papillary carcinoma including intracystic type and compared it with non-concurrent invasive ductal carcinoma. In addition, many studies have attempted to classify intracystic papillary carcinoma using immunohistochemistry.[2–5]

This is the first study that compared between intracystic papillary carcinoma with concurrent ductal carcinoma in situ and invasive ductal carcinoma on the genomic level. We propose an evolutionary pathway between these three entities.