The presence of retraction clefts correlates with lymphovascular invasion and lymph node metastasis and predicts poor outcome: Analysis of 2497 breast cancer patients

Invasive micropapillary carcinoma (IMPC) is a rare special histologic subtype of breast cancer, accounting for approximately 3 % to 8 % of all breast cancers [1], [2]. It consists of small, hollow, or morule-like clusters of cancer cells surrounded by clear stromal space [3]. The cells exhibit reversed polarity with the glandular epithelial cells located on the outer surface of the cell nests, revealed by immunohistochemical stain for epithelial membrane antigen (EMA). IMPC is associated with higher incidence of lymphovascular invasion (LVI), lymph node metastasis and poor prognosis [4], [5].

Some invasive breast cancers have tumor cell clusters surrounded by clear stromal space similar to IMPC, but lack the morphological and immunohistochemical characteristics of IMPC. On formalin-fixed paraffin-embedded tissue sections, there are often clear spaces separating tumor cell clusters from adjacent stroma, which can be difficult to distinguish from LVI [6], [7]. Previous studies have shown that the presence of these so-called retraction clefts (RC), may be important for the histologic diagnosis and overall survival of prostate cancer and oral squamous carcinoma [8], [9], [10], in general, RCs are considered artifactual, which may be due to inadequate tissue fixation and tissue contraction. However, characteristic retraction clefts around the tumor cell nests may be found even on frozen section of invasive breast carcinoma [6], and this phenomenon may have special significance, rather than artificial products [11].

In this prospective study, we assessed whether the presence of retraction clefts in tumors without the characteristic histological features of IMPC, is associated with lymphovascular invasion, lymph node metastasis and outcomes in a large consecutive series of invasive breast cancers.

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