Screen-detected ductal carcinoma in situ found on stereotactic vacuum-assisted biopsy of suspicious microcalcifications without mass: radiological-histological correlation

Nation-wide and population-based breast cancer screening program is targeting women aged 50–69, with exclusion of females undergoing treatment or being followed-up due to breast cancer. Two-view mammography (cranio-caudal and oblique) is used as a standard screening test. High-quality analogue (screen-film) or full field digital mammography (FFDM) are both allowed in screening program in Poland. Routine round length of the program is two years. All women with radiological findings categorised as suspicious of malignancy (BIRADS 4) or highly suggested for cancer (BIRADS 5) are referred to further assessment and invasive investigations. In patients with masses ultrasound-guided core-needle or vacuum-assisted biopsy is carried out, whereas in patients with other lesions, not well seen in ultrasound, a stereotactic biopsy under digital mammography guidance is performed.

A cohort of 127 consecutive non-symptomatic patients with screen-detected DCIS diagnosed in years 2009–2014 was enrolled. All of them fulfilled the study entering criteria: BIRADS category 4 or 5 microcalcifications without mass or architectural distortion, pure DCIS found on histological examination, lack of invasion or microinvasion (≤ 1 mm in the longest diameter), absence of any other breast malignancy or border-line lesion. Median (mean, range) patient age was 60 years (59.6, 50–69). All the patients underwent the same type of minimal-invasive biopsy under the stereotactic guidance. Study was approved by the Independent Ethics Committee (UMED KB-376) and the Institutional Board (NDOK/668). Patients signed the informed consent.

In each case an informed consent to undergo biopsy was obtained. All the procedures were performed by one breast-dedicated radiologist (PK), in the same breast care unit, according to the same standardised protocol to assure quality control. Five specimens was the minimal number of tissue cores. Each biopsy was done under the local anaesthesia using 10 cm³ of 1% lidocaine in two-step approach: 5 cm³ superficially and 5 cm³ deeply. Biopsies were completed under digital mammography guidance using a designated prone table unit (Mammotest Plus / S, Fisher Imaging, Denver, USA) with 10G needle (EnCore Breast Biopsy System, SenoRx Inc., Irvine, CA or EnCore Enspire Breast Biopsy System, C.R. Bard Inc., Tempe, AZ).

All hematoxylin and eosin stained slides of formalin-fixed and paraffin-embedded tissue blocks were assessed by board-certified pathologists experienced in breast cancer. In all the cases pathological examination reported pure DCIS without invasive or microinvasive component. In cases with any doubt about the origin E-cadherin immunochemistry was used to exclude a pleomorphic type of lobular carcinoma in situ. Evaluation of DCIS histology was performed according to the well-defined and widely accepted criteria.

Comedonecrosis was determined as present if the central areas of necrosis with ghost outlines of cells and cellular debris were found. Grading system was expressed by the assessment of nuclear grade (NG) categorising DCIS as low, intermediate, and high grade, based on the recommendations of the College of American Pathologists.⁹,¹⁰ Finally, all the slides were reviewed and re-evaluated by study supervising pathologist (AH) to confirm the original diagnosis of DCIS and its histological features as well as the absence of invasion or microinvasion.

Data were collected in a prospective manner and entered a computer database. Statistical analysis was performed by professional statistician (PB). Following features were investigated: patient age, DCIS nuclear grade and the presence of comedonecrosis (as described above) as well as distribution pattern and morphology of microcalcifications. With regard to distribution pattern microcalcifications were classified as clustered (< 1 cm), grouped (1–2 cm), and regional (> 2 cm). Morphological type was categorised according to Tabar classification (Figure 1–3) as powdery (cotton ball-like: indistinct, amorphous), crushed stone-like (pleomorphic), and casting-type (linear, branching).¹¹ Mammographic appearance was assessed before biopsy (without knowledge of the histopathological diagnosis) by two board-certified radiologists with special expertise in breast imaging (double reading) and then reviewed and re-evaluated by study supervising radiologist (PK) using analogue microfocus magnification techniques in orthogonal planes or, in cases of FFDM, on-screen magnification. Baseline characteristics are presented in Table 1. Association between investigated variables was analysed using Pearson’s chi-square test. P values less than 0.05 were considered statistically significant.

84% (n = 16) of powdery microcalcifications were clustered, 16% (3) were grouped, while none had regional distribution. Considering crushed stone-like and casting-type morphology 75% (61) and 30% (8) of microcalcifications were clustered, 20% (16) and 44% (12) were grouped, 5% (4) and 26% (7) had regional pattern, respectively. With regard to clustered and grouped microcalcifications 19% (16) and 10% (3) were powdery, 72% (61) and 51% (16) were crushed stone-like, while 9% (8) and 39% (12) were casting-type, respectively. None of regional microcalcifications had powdery morphology, 36% (4) were crushed stone-like, and 64% (7) were casting-type. To sum up, powdery microcalcifications were most often clustered, never regional. Similarly, just one-fourth of crushed stone-like microcalcifications were grouped or regional. Clustered microcalcifications were most rarely of casting-type while regional were most commonly. The association between morphology and distribution of microcalcifications was of very high statistical significance (t1 X-squared = 25.281, df = 4, P = 4.416e-05) (Table 2).

All over 74% (14) of powdery microcalcifications revealed DCIS with low NG, 16% (3) intermediate, and 10% (2) high NG. Crushed stone-like microcalcifications were related to low NG in 58% (47), intermediate in 33% (27), and high in 9% (7). In contrast, 33% (9) of casting-type microcalcifications had high NG DCIS, 30% (8) intermediate, while 37% (10) had low NG DCIS. 50% (9) of high NG DCIS were presenting as casting-type microcalcifications, 39% (7) as crushed stone-like, and 11% (2) as powdery. 21% (8) of DCIS with intermediate NG was found in casting-type microcalcifications, 71% (27) in crushed stone-like, and 8% (3) in powdery. With regard to low NG DCIS, 14% (10) was detected in casting-type microcalcifications, while 66% (47) and 20% (14) in crushed stone-like and powdery, respectively. In summary, high NG DCIS was most commonly related to casting-type microcalcifications while low NG DCIS most rarely. DCIS with intermediate NG was most often found in crushed stone-like microcalcifications. Just one-fourth of powdery microcalcifications revealed DCIS with NG other than low. The association between morphology of microcalcifications and NG of DCIS was statistically significant (t1 X-squared = 13.363, df = 4, P = 0.009632) (Table 3).

Comedonecrosis was found in 47% (9) of powdery microcalcifications, 57% (46) of crushed stone-like, and in 52% (14) of casting-type. DCIS with comedonecrosis was presenting as powdery in 13% (10), crushed stone-like in 67% (46), and casting-type microcalcifications in 20% (14) of cases. Considering DCIS without comedonecrosis, powdery microcalcifications were detected in 17% (10) of patients while crushed stone-like and casting-type in 60% (35) and 23% (13), respectively.

58% (11) of patients with powdery microcalcifications were 50-60 years old, whereas 54% (44) and 44% (12) of those with crushed stone-like and casting-type, respectively (Table 4). Patients aged 50–60 years had powdery microcalcifications in 16% (11), crushed stone-like in 66% (44), and casting-type in 18% (12). Among older patients (61–69) powdery microcalcifications were present in 13% (8), crushed stone-like in 62% (37), and casting-type in 25% (15) of cases. Neither patient age nor the presence of comedonecrosis was significantly related to morphology of microcalcifications (t1 X-squared = 1.0293, df = 2, P = 0.5977; t1 X-squared = 0.63551, df = 2, P = 0.7278; respectively).

In 64% (54) of clustered microcalcifications low NG DCIS was found, whereas intermediate and high NG DCIS in 27% (23) and 9% (8), respectively. Grouped microcalcifications revealed low, intermediate and high NG DCIS in 45% (14), 39% (12), and 16% (5) of cases while regional microcalcifications in 27% (3), 27% (3), and 46% (5), respectively. 76% (54) and 60% (23) of DCIS with low and intermediate NG were presenting as clustered micro-calcifications, 20% (14) and 32% (12) as grouped, and 4% (3) and 8% (3) as regional, respectively. Among patients with high NG DCIS 44% (8) had clustered, while 28% (5) each had grouped and regional microcalcifications. Summarising, low NG DCIS was the most common in clustered microcalcifications and very rare in regional, where high NG DCIS was the most often, being found in nearly half of cases. The association between distribution of microcalcifications and NG of DCIS was statisnificantly related to the distribution of microcalcifications (t1 X-squared = 3.2839, df = 2, P = 0.1936).

In 94% (17) of high NG DCIS the comedonecrosis was present, whereas in 47% (18) and 48% (34) of intermediate and low NG, respectively. Among patients without comedonecrosis 2% (1) had high NG, while 34% (20) and 64% (37) had intermediate and low NG DCIS, respectively. In the group with comedonecrosis high, intermediate, and low NG DCIS were diagnosed in 25% (17), 26% (18), and 49% (34) of cases, respectively. In summary, almost all the patients with high NG DCIS had comedonecrosis while just less than half of others. In almost all the patients without comedonecrosis DCIS of low or intemediate NG was found. The association between NG and the presence of comedonecrosis was statistically significant (t1 X-squared = 13.604, df = 2, P = 0.001112) (Table 5).

Younger patients (50–60) had low, intermediate, and high NG DCIS in 57% (38), 28% (19), and 15% (10), while older women (61–69) in 55% (33), 32% (19), and 13% (8), respectively. In cases of high, intermediate, and low NG DCIS 56% (10), 50% (19), and 54% (38) of patients were in younger age. Patient age was not significantly related to NG of DCIS (t1 X-squared = 0.18908, df = 2, P = 0.9098).

Comedonecrosis was present in 54% (36) of younger patients and in 55% (33) of those aged 61–69 years. When comedonecrosis was absent 53% (31) of patients were 50–60 years old. Similarly, among patients with comedonecrosis 52% (36) was in younger group. The association was not significant (t1 X-squared = 0, df = 1, P = 1).

Significance level of correlation between investigated variables is presented in Table 6.