NEODUCTGENESIS AS A PROGNOSTIC MARKER IN “DUCTAL” CARCINOMA IN SITU OF THE BREAST

Objective. Ductal carcinoma in situ (DCIS) of the breast is becoming more and more frequent in women after the introduction of breast screening programmes. Once the diagnosis is confirmed on the surgical specimen, its prognosis is excellent, but still some tumours recur as in situ or even invasive neoplasms in the same or contralateral breast. Neoductgenesis (NGD), defined by László Tabár and Tibor Tot as the presence of “casting type” calcifications on mammography, an abnormal number of ducts, periductal desmoplastic reaction and lymphocytic infiltrate, has been proposed as a marker of aggressiveness in “early” breast carcinoma (1 2). We analysed this phenomenon in pure DCIS by correlating its presence with clinical and instrumental findings, morphological and immunohistochemical features, and with patients’ prognosis. Materials and Methods. We selected 199 cases of breast DCIS undergone surgery between 2004 and 2016, available at the Unit of Pathology of the Academic Hospital of Trieste, and performed a re-evaluation of the histological slides in order to define the presence or absence of NDG, based on the morphological features previously described2. Furthermore, a subgroup of 64 cases underwent radiological review by two expert radiologists (AF, MT) in order to re-classify the mammographic findings according to specific types of calcifications1. The correlation between morphological NDG, casting type calcifications and prognostic markers of breast DCIS, such as extension, grade and expression of hormonal receptors and HER2-neu, as well as with disease recurrence, was evaluated through Chi-Square independence test or Fisher test as appropriate. Results. NDG was identified in 33 cases (16.6%) and was found to be positively associated with the larger size of lesions on mammography (p=0.008), histological high grade (p<0.001), presence of necrosis (p<0.001), low expression of hormonal receptors (p<0.001), HER2-neu overexpression (p=0.005) and high proliferative index (p<0.001). Casting type calcifications were present in 54% of DCIS with NDG and 44% of DCIS without NDG (p=0.70). They were also found in 63% of DCIS with comedo type necrosis versus 35% of DCIS without comedo necrosis (p=0.07). Nine patients (4.64%) developed disease recurrences during the follow-up and among them 5 had tumours with the morphological features of NDG. Conclusions. Consistent with literature, the morphological features of NDG were able to identify lesions with an “aggressive” biological phenotype. Interestingly, NDG was found to positively correlate with disease recurrences in patients with pure DCIS.