Clinical and imaging characteristics of breast ductal carcinoma in situ with microinvasion

Background: We analyzed the clinical and imaging characteristics of patients with breast ductal carcinoma in situ with microinvasion (DCISM) and breast ductal carcinoma in situ (DCIS). Methods: We analyzed the records of 40 patients diagnosed with DCISM and 61 patients with DCIS who were hospitalized at Shengjing Hospital (Shenyang, China) from January 2009 to June 2016. The size, hardness, and degree of calci ﬁ cation of tumors were determined by mammography and ultrasonography. Results: In all, 37 DCISM patients and 45 DCIS patients showed clinical palpable masses (92.5% vs 73.77%, P = 0.018). Mammography showed that the mean size of tumor was larger in DCISM patients than that of DCIS patients (3.13 ± 1.51 vs 2.68 ± 1.77, P = 0.030). Ultrasound examination revealed calci ﬁ cation shadows in the solid tumor mass in 17 DCISM cases and 11 DCIS patients (42.5 vs 18.03%, P = 0.007). Furthermore, estrogen receptor positivity and progesterone receptor positivity were more common in DCIS patients (32.5% vs 54.10%, P = 0.033; 22.5% vs 45.90%, P = 0.017), and the percentage of menopausal patients were higher in DCISM patients than that of DCIS patients (70.00% vs 47.54%, P = 0.026). Conclusion: Clinically palpable and calci ﬁ ed tumor masses on sonography are more commonly encountered in DCISM lesions.


| INTRODUCTION
The incidence of breast cancer has been on the increase in recent decades. Breast ductal carcinoma in situ with microinvasion (DCISM) is defined as ductal carcinoma in situ (DCIS) with tumor cells infiltrating the basal membrane and the infiltration less than 1 mm in diameter. 1 DCISM is also referred as T1mic by American Joint Committee on Cancer (AJCC). Compared with DCIS, DCISM has a higher risk of distant metastasis. [2][3][4] More DCIS cases are diagnosed in clinical practice while DCISM is not common and its incidence is <1% of breast cancer. [5][6][7] Previous studies mainly focused on the pathological features of DCISM. Meanwhile, the clinical and radiological characteristics of DCISM have not been clearly reported. 3,5,8 Mammography and ultrasound have been used for diagnosing breast diseases. However, whether mammography and ultrasound could benefit the diagnosis of DCISM and DCIS is unknown. 9

2.B | Radiological and ultrasound examinations
The size of breast neoplasm and its calcification degree were detected with mammography, and the distort and disorder of tumor structure was detected with ultrasound. If the lesion was unclear under mammography, ultrasound was used to measure the size of the lesion. The maximal diameter of neoplasm or calcification lesion was determined with ultrasound. Ultrasonograms and mammograms were reviewed retrospectively by two breast imaging radiologists with more than 5 yr of experience in breast ultrasonography who were blind to the pathologic data of the patients. Difference between the two radiologists was resolved by involving a third radiologist to reach a consensus.
Sonographic examinations were performed using an Aplio400 (Toshiba Medical Systems, Japan). The probe frequency was 4-15 MHz. The SMI had color mode (cSMII) or monochrome mode (mSMI) and CDFI was used for observing blood flow in the tumor.
Two vertical images of each tumor were obtained. Ultrasonograms were reviewed retrospectively by two breast imaging radiologists with more than 5 yr of experience in breast ultrasonography who were blind to the pathologic data of the patients. Difference between the two radiologists was resolved by involving a third radiologist to reach a consensus. The sonographic findings including shape, orientation, margin, echo pattern, and posterior features were described using the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) lexicon. 13 Mammography was done using FDR MS-3500 with two standard imaging planes (mediolateral oblique and craniocaudal) and imaging analysis was done by two experienced breast imaging radiologists and types of lesions including mass and calcification, asymmetry, density, and microcalcification and their distribution were analyzed using the BI-RADS.

2.C | Statistical analysis
Continuous variables were expressed as mean±standard deviation.
Normally distributed data were analyzed with Student's t test and with non-normally distributed data were analyzed with Wilcoxon two sample tests. Categorical data were expressed as frequency (%) and were analyzed using Chi-square test or the Fisher exact test.

3.A | Clinical characteristics
The mean age of the DCISM patients was 51.45 ± 11.64 yr, 28 (70%) of them were menopausal and 2 did not bear children. One   Table 2). Ultrasound showed solid mass with calcification in 11 patients, pure solid mass shadow in 28 patients, pure calcification in 5 patients, irregular structure with calcification in 3 patients, and irregular structure in 4 patients (Fig. 2). Solid mass with calcification on ultrasound was more common in DCISM (P = 0.007) while F I G .

| DISCUSSION
DCIS has been uncommon until breast mammography has been widely applied in clinical practice. The percentage of newly diagnosed breast DCIS has been on the rise recently, but DCISM is still rare. 10,14,15 It was reported that <1% of breast cancer was confirmed as DCISM, which is similar to the percentage observed in our patient cohort. DCISM is defined as infiltration of breast tumor cells into the basal membrane and surrounding tissues in a diameter less than 1 mm by AJCC. If there are more than one microinvasion lesions, the maximal diameter of the lesion is used for classification rather than the sum of diameters of all the lesions. 1 We hypothesized that DCISM was a transition from DCIS to early infiltrative tumor.
Besides, as the tumor grows fast, once the tumor cells infiltrate the basal membrane, the infiltration lesion will exceed 1 mm, which may be the main reason why DCISM is rare.
At present, DCISM of the breast is considered T1mic. There is still a controversy on whether the pathology of DCISM is different from that of DCIS, indicating that making an accurate pathological diagnosis is of vital importance. DCISM has a risk of metastasis, and it is estimated that the incidence of lymph node metastasis in DCISM is 0-14%. 1

| CONCLUSION
In this study, we demonstrated that clinically palpable mass and calcified mass on ultrasound are commonly encountered in DCISM lesions.

AUTHORS' CONTRIBUTI ON
GH, SH, and FQ contributed to the study design. All authors collected the data and performed the data analysis. All authors prepared the manuscript. GH, SH, FQ, and YH amended the manuscript critically.

CONFLI CT OF INTEREST
All the authors declare that they have no conflict of interest.

Ethical approval was given by the Ethics Committee of Shengjing
Hospital of China Medical University. All patients gave their written information consent.

DATA AVAILABILITY STATEMENT
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.