Image Differential Diagnosis And Underestimation Of Vacuum-assisted Breast Biopsy For Breast Ductal Intraepithelial Neoplasia

BackgroundBreast cancer is one of the most common malignancy in women,0stage breast cancer can almost be cured. The best way to improve the cured rate and life quality of breast cancer is early detection, early diagnosis and early treatment. Ductal intraepithelial neoplasia (DIN) is a group of lesions confined in ductal lobular systems which cell morphology and organizational structure are different. As defined by the World Health Organization (WHO) Working Group on Pathology and Genetics of Tumors of the Breast, DIN is mainly divided into atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). Early diagnosis of DIN (ADH and DCIS) and to deal effectively can help to achieve early detection and treatment of breast cancer.DCIS usually has no clinical symptoms and signs that usually only detected by mammography shows as calcifications. The forms of calcifications related to DCIS are amorphous, fine pleomorphic, and fine linear. The suspicious distributions are linear and segmental. ADH is a proliferative lesion that has part of histological characteristics of DCIS but can not be diagnosed as DCIS. As DCIS, the most common mammographic presentation of ADH is microcalcifications. Sometimes it is difficult for differentiating between ADH and DCIS on the limited volume of tissue obtained from core biopsy. Preoperative imaging assessment can help to decide management of ADH, consider DCIS preoperative imaging but core biopsy diagnosis of ADH cases should be recommended for further surgery to exclude malignancy. Some studies have reported that mammography alone is difficult to differentiate ADH and DCIS. Relative to western female, Chinese women have some characteristics such as mammary glands dense, smaller size, younger of breast cancer and so on. Few studies research the differential image diagnosis between ADH and DCIS.With the launching of the breast cancer screening and the people’s awareness of health, the growing number of clinical nonpalpable breast lesions (NPBL) were detected. Preoperative minimally invasive biopsy of breast lesions for pathological diagnosis not only has better cosmetic effect, but also is good for treatment planning. Vacuum-assisted breast biopsy (VAB) combining cutting and vacuum suction can get more tissue volume compared with other biopsy methods, the diagnostic sensitivity is98.0%, specificity is99.9%, and it is an ideal alternative to open surgical biopsy. According to guiding methods, there are stereotactic vacuum-assisted breast biopsy (SVAB), ultrasound-guided vacuum-assisted biopsy and MRI stereotactic vacuum-assisted biopsy. The broader clinical application are SVAB and ultrasound-guided VAB. The VAB underestimation has key influence on its diagnostic accuracy, and it is the main drawback of the method. However, there have not been many analyses of the VAB underestimation of Chinese women. In western countries, the diagnosis of ADH on VAB often results in surgical excision biobsy, but the surgical excision biopsy for all ADH cases is disputing. There is also no guidelines for the management of ADH cases diagnosed at VAB in China.PurposesIn the first part of this study, we retrospectively analysis the clinical manifestations and imaging features of DIN (ADH and DCIS) to improve its diagnostic level; and to explore the different imaging features between ADH and DCIS in order to improve differential diagnosis between ADH and DCIS. In the second part of this study, we adopt to surgical excision biopsy or imaging follow-up for DIN according to pathological features to prospectively study the histology underestimation rate of VAB, and to explore the value of VAB in the diagnosis of DIN and the managetmient of ADH.Materials and methods1. Study Population108patients with a histologically proven DIN were included in this study. All the pathological diagnosis was obtained in Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University between January2008and December2011,66cases were ADH and42cases were DCIS. All patients were female, with a mean age of42years (range from26to65years).2. Equipments and methodsHigh-resolution breast ultrasound was performed using12-15MHz linear array trans-ducers (Siemens). Imaging was performed for all examinations using an Acuson Sequoia512machine (Siemens). Patients were taken a supine position, fully exposed both breasts and armpits, took the nipple as the center of the continuity of radial scanning, combined with the breast each quadrant to take vertical and horizontal continuous scanning. All examinations included in this study were performed and interpreted by one of breast imaging radiologists with at least2years of experience. All radiologists who performed breast US examinations were fully aware of the American College of Radiology BI-RADS of breast US. The final US categorization was based on ACR BI-RADS.Mammographic examinations were performed by digital mammography X-ray (Lorad Selenia) in our hospital. Standard craniocaudal (CC) and mediolateral oblique (MLO) views were routinely obtained, and additional mammographic views were obtained when needed. Mammograms were assessed by one of radiologists with at least3years of experience. Breast lesions were described and graded according to the American College of Radiology BI-RADS (fourth edition). When there were multiple lesions in unilateral breast, it was classificated according to the highest suspicious of malignancy.3. BiopsyHistological specimes were obtained by open surgical excisional biopsies, open surgical biopsies with wire positioning, stereotactic vacuum-assisted breast biopsies, ultrasound-guided vacuum-assisted breast biopsies and Bard gun biopsies.4. Statistical AnalysesAll analyses were performed using statistical software SPSS13.0. Difference between ADH and DCIS in reasons of imaging examination, ultrasound characteristics, ultrasound results of suspicious malignant calcification were evaluated by the fourfold table χ2test or Fisher’s exact test. Difference in morphology and distribution of calcification between the two groups were estimated by the RxC table χ2test. Difference in diagnosis of DCIS between ultrasound and mammography were compared using paired fourfold table x2test. Statistic significance was defined as P<0.05.Results1. There was no significant difference in reasons of imaging examination between these two groups (15.2%vs23.8%, P=0.259).2. Of108DIN patients, only one patient with ultrasound and mammography was normal. Of66ADH patients,44(66.7%) cases showed masses on ultrasound,28(42.4%) cases showed calcifications on mammography. Of42DCIS patients,34(80.9%) cases showed masses on ultrasound,31(73.8%) cases showed calcifications on mammography.3. There was significant difference in diagnosis of DCIS between mammography and ultrasound (81.0%vs38.1%, P=0.001). 4. A total of78cases of ADH and DCIS patients showed masses on ultrasound, there was significant difference in tumor echo characteristic, shape and margin between the two groups of patients (P=0.020,0.012,0.003respectively), but there was no significant difference in orientation, posterior shadowing and presence of calcifications between the two groups of patients (P=0.519,0.229,0.233respectively);18.2%of the ADH and47.1%of DCIS patients assessed as BI-RADS4or5on ultrasound, there was significant difference between the two groups (P=0.006).5. A total of59patients (ADH and DCIS) showed calcifications on mammography, which of ADH28cases and DCS31cases; morphological characteristics, distribution characteristics and BI-RADS classification on mammography of two groups of patients were not significantly different (P=0.156,0.182and0.337, respectively).6. Of59patients (ADH and DCIS) showed calcifications on mammography,77.4%(24/31cases) DCIS patients showed positive US findings, while only28.6%(8/28cases) ADH patients showed positive US findings, there was significant difference between the two groups (P<0.001). Of the positive ultrasound findings cases,12.5%(1/8cases) of ADH showed hypoechoic masses,79.2%(19/24cases) of DCIS showed hypoechoic masses, there was significant difference between the two groups (P=0.002).ConclusionsUltrasound in conjunction with mammography can effectively detect and distinguish diagnosis of DIN. Of the DIN patients showed masses on ultrasound, the specific characteristics of sonography can help for differential diagnosis; Of the DIN patients showed calcifications on mammography, ultrasound positive findings support DCIS diagnosis. Materials and Methods1. Study PopulationBetween January2008and March2011, SVAB and ultrasound-guided VAB were performed for the microcalcifications and nonpalpable breast nodules in ShenZhen Maternity and Child Healthcare Hospital, Southern Medical University. Of these women, DIN (ADH and DCIS) coexisted with invasive breast cancer were excluded, Of the remaining126women diagnosed as DIN (94ADH and32DCIS) made up our final study subjects with a mean age of42years (range from20to77years).2. Equipments and methodsThe nonpalpable calcifications were biopsied by SVAB which procedures wereperformed with the patient prone on a dedicated biopsy table (Lorad, Hologic, MultiCare Platinum) and used10-gauge vacuum-assisted biopsy system (Bard, Vacora).The nonpalpable breast nodules were performed by7-G or8-G ultrasound-guided VAB (Mammotome and EnCor), and the positioning ultrasound were sue by M5portable color Doppler ultrasound system (Mindray) and Siemens G20black and white ultrasound.According to the organizational structure and the degree of cellular atypia, ADH is divided into mild, moderate and severe. When severe ADH and DCIS was difficult to distinguish, pathology described as "severe ADH suspicious for cancer" and then classified as severe ADH group. Cases of DCIS, were treated by mastectomy or breast conserving surgery. Residual cavity surrounding tissues were routinely pathological assessed. Severe ADH and severe ADH suspicious for cancer cases were received further surgery biopsy, if surgery biopsy found cancer, it was defined as histology underestimation, and if found no cancer, they were ginven close imaging follow-up and endocrine therapy (when ER or PR positive). Mild to moderate ADH cases were recommended for imaging follow-up (every6months ultrasound or mammography once a year, one year after that, ultrasound and mammography performed every year). During follow-up, biopsy again was recommended for the new suspicious lesions. We got the follow-up informations by our hospital diagnosis database and telephoning to patients. During follow-up, the original lesion location found cancer was defined as histological underestimation.3. Statistical AnalyseFisher’s exact test was used to compared the underestimation rate of SVAB and ultrasound-guided VAB, and statistic significance was defined as P<0.05, statistical analysis using SPSS13.0statistical software.ResultsA total of82cases were diagnosed as mild or moderate ADH, of which18cases were diagnosed by SVAB and64patients by ultrasound-guided VAB. During ultrasound or mammography follow-up ofter biopsy, had been not yet found histology underestimation. A total of12severe ADH cases undergo further surgical excision biopsy,3cases confirmed as ductal carcinoma in situ, so the the VAB diagnosis of severe ADH histology underestimation rate was25%(3/12cases).3cases diagnosed by SVAB, one case of them confirmed as DCIS;9patients by ultrasound-guided VAB,2cases of them confirmed as DCIS. In summary, the histology underestimation rate of VAB diagnosis ADH was3.2%(3/94cases). The underestimation rate of SVAB and ultrasound-guided VAB was no statistically significant different (4.8%vs2.7%, P=0.536).The histology underestimation rate of VAB diagnosis DCIS was9.4%(3/32cases), that5.3%(1/19cases) of SVAB and15.4%(2/13cases) of ultrasound-guided VAB, the underestimation rate betweem the two groups was no statistically significant different (P=0.552).ConclusionsVAB is a minimally invasive biopsy, has less effection on breast appearance, and can effectively detecte ADH and DCIS. The histology underestimation of VAB is low and is no significant difference between the two image-guided methods. The diagnosis of ADH in VAB does not all need to receive further surgery, taking mild and moderate ADH to imaging follow-up and taking severe ADH to receive surgical excisional biopsy is feasible in clinical practice.