Is it important to evaluate the demographic characteristics and radiological findings of patients who have micro calcific lesions in the breast with biopsy results in the decision of excision?

doi:10.21203/rs.3.rs-1705371/v1

Introduction

The B3 lesions of the breast with unknown malignant potential are common in practice (3–21%). Although these lesions have a low malignant potential (0.2-5%), they are evaluated with biopsy due to the risk of invasive carcinoma.

Material-Methods

The compliance of mammography, ultrasonography, and pathological data of 109 patients who had micro calcifications between January 2018 and March 2021 were analyzed retrospectively; and micro calcification sizes and histological types were recorded.

Results

The mean age of the patients was found to be 46.86 ± 9.65, and the mean overall size of the micro calcification was 13.78 ± 6.51 mm. When the compliance of B3 lesions of the breast with malignancy was evaluated, it was found that 74% were compatible, but 25.9% were incompatible. A total of 11.1% of these lesions were up-grade. Malignant potential was more in Atypical Ductal Hyperplasia (ADH) in postmenopausal patients who were older than 47 years (p = 0.002).

Conclusion

Although micro calcifications require excisional biopsy in advanced-age and postmenopausal patients because of the up-grade risk, other benign lesions can be followed with imaging methods and fine needle biopsies.

B3 – micro calcifications

breast imaging

risk factors

Atypical ductal hyperplasia, flat epithelial atypia, ductal carcinoma in situ, papilloma, sclerosing adenosis, apocrine metaplasia, radial scar etc. are heterogeneous lesions of the breast that have uncertain malignant potentials. [1] According to the international guidelines, B3 lesions can be excised surgically or followed-up clinically and radiologically. In our present day, biopsy or percutaneous vacuum excision is preferred over open surgical procedures. The risk of carcinoma is 2-35.1% in these lesions [1] .

The purpose of the present study was to examine the correlation of the mammographic images of suspected malignant lesions of the breast with needle biopsy and excisional tissue pathology, and to investigate whether there is a relation with patient demographics.

The clinical, radiological, and pathological data of 109 patients who underwent biopsy and excision because of microcalcification between January 2018 and March 2021 were recorded; and 14 G-thick needle and excisional tissue biopsies were reviewed retrospectively. The maximum diameters of B3 lesions were measured mammographically and ultrasonographically based on the long axis. The core biopsy was performed with ultrasound, and the areas that had suspicious or insufficient tissue biopsy were excised totally.

The Breast Imaging and Reporting Data System (BI-RADS) was used to classify the lesions in mammography. These lesions were visualized as microcalcifications, masses or structural distortions. Since BI-RADS 4 lesions had suspected malignant potentials, ultrasound guided fine needle biopsy was performed. BI-RADS resulted as 4A low suspicious, 4B moderate, and 4C high-grade malignant risk. [2] Stereotactic wire-marked excisional biopsy was performed to patients who were not diagnosed with invasive carcinoma.

Statistics

When the findings obtained in the study were evaluated, the SPSS 22.0 Statistics package program was used for statistical analysis. The characteristics of the contents were examined descriptively. The Pearson Chi-Square Test and Fisher’s Exact Test were used with cross tables for the comparisons of qualitative data. The results of the comparisons were evaluated between 95% and 99% Confidence Interval at p < 0.05 at p < 0.01 significance level.

The mean overall size of microcalcification that was measured with mammography or ultrasonography of B3 lesions was found to be 13.78 ± 6.51 mm, respectively according to subtypes; BEP (Benign Epithelial Proliferation) was 14.31 ± 5.85 mm, papillary lesions were 11.61 ± 5.18 mm, ADH (Atypical Ductal Hyperplasia) was 12.50 ± 4.51 mm, and malignant lesions were 14.45 ± 9.43 mm. The BIRADS distribution rates of the patients were recorded as 61.47% 4A, 28.44% 4B, and 10.09% 4C (Table 1).

Table 1

Distribution of B3 lesions by age and size of microcalcification
		N	Mean		Min.	Max.			Frequency	Rates (%)
Age	BEP	64	45.98	9.14	31.00	73.00	BIRADS
	PAPİLLARY	19	47.37	8.83	32.00	71.00
	ADH	6	39.67	8.82	25.00	47.00
	MALİGNANCY (DCIS + IC)	20	51.35	10.84	25.00	68.00		4A	67	61.47
	Total	109	46.86	9.65	25.00	73.00		4B	31	28.44
Microcalcification (mm)	BEP	62	14.31	5.85	4.00	35.00		4C	11	10.09
	PAPİLLARY	18	11.61	5.18	4.00	23.00		Total	109	100.00
	ADH	6	12.50	4.51	7.00	20.00
	MALİGNANCY (DCIS + IC)	20	14.45	9.43	5.00	38.00
	Total	106	13.78	6.51	4.00	38.00

Table 2

Relationship of B3 lesions with demographic features of patients
		BEP N = 64	PAPİLLARY N = 19	ADH N = 6	MALİGNANCY N = 20	Chi-square	p
Age	< 47	44(68.75%)	10(52.63%)	6(100.0%)	6(30.00%)	13.668	0.002**
Age	> 47	20(31.25%)	9(47.37%)	0	14(70.00%)	13.668	0.002**
Smoking	No	40(76.92%)	8(66.67%)	3(100.0%)	12(92.31%)	2.804	0.373
Smoking	Yes	12(23.08%)	4(33.33%)	0	1(7.69%)	2.804	0.373
Menopause	Pre	41(77.36%)	11(91.67%)	3(100.0%)	4(30.77%)	13.014	0.002**
Menopause	Post	12(22.64%)	1(8.33%)	0	9(69.23%)	13.014	0.002**
BMI	< 30	49(75.56%)	12(63.16%)	5(83.33%)	16(80.00%)	1.892	0.627
BMI	> 30	15(23.44%)	7(36.84%)	1(16.67%)	4(20.00%)	1.892	0.627
Lactation Period(month)	< 25	29(56.86%)	8(72.73%)	1(50.00%)	5(50.00%)	1.579	0.723
Lactation Period(month)	> 25	22(43.14%)	3(27.27%)	1(50.00%)	5(50.00%)	1.579	0.723
Menarche Age(year)	< 13	30(56.60%)	8(66.67%)	2(66.67%)	7(53.85%)	0.733	0.928
Menarche Age(year)	> 13	23(43.40%)	4(33.33%)	1(33.33%)	6(46.15%)	0.733	0.928
First Gestational Age(year)	< 20	13(24.53%)	3(25.00%)	2(66.67%)	9(69.23%)	10.608	0.009**
First Gestational Age(year)	> 20	40(75.47%)	9(75.00%)	1(33.33%)	4(30.77%)	10.608	0.009**
Number of Births	0	2(33.33%)	0(0.0%)	1(16.67%)	3(50.0%)	17.726	0.045*
	1	6(75.00%)	2(25.00%)	0	0(0.0%)
	2	28(71.79%)	7(17.95%)	0	4(10.26%)
	3	17(66.67%)	3(11.11%)	0(0.0%)	4(22.22%)
	4+	5(50.00%)	1(10.00%)	2(20.00%)	2(20.00%)
*p < 0.01;p < 0.05

The mean age of the patients was found to be 46.86 ± 9.65 years. The mean ages of B3 lesions were Benign Epithelial Proliferation (BEP) 45.98 ± 9.14, papillary lesions 47.37 ± 8.83, atypical ductal hyperplasia (ADH) 39.67 ± 8.82, and ductal carcinoma in situ (DCIS), and malignancies 51.35 ± 10.35 years (Table 1).

When the compliance of B3 lesions of the breast and the malignity was evaluated, 74% were found to be compatible, but 25.9% were incompatible. A total of 11.1% of these lesions were up-grade (Table 3). The mean up-grade rate of the B3 lesions in the literature was reported as 9.9–35.1% .[3, 4] Up-grade was detected by 3–45% [3, 5] in ADH, 4.72-9% in papillary lesions [1, 3], and 11.4% in BEP [6].

Table 3

Discordance and concordance rates of benign lesions
Variability	Discordance Concordance Total	Frequency 21 60 81	Percent (%) 25.9 74.0 100
Benign epitelial proliferation (BEP)	Papilloma Atipical ductal hiperplasia Cancer	6 1 1	28.57 4.76 4.76
Papilloma	BEP Atipical ductal hiperplasia Cancer	5 1 3	23.8 4.76 14.29
Atipical ductal hiperplasia	BEP Cancer	1 3	4.76 14.29
Total		21	100

BEP, papillary, ADH, and malignancy were more common in B3 lesions in our cases when the microcalcification size was more than 50% of the lesion and if the mean size was below 13 mm (Fig. 1, p = 0.334). The rate of breast cancer in ADH cases was higher than in other B3 lesions (20%) .[7] In microcalcifications between 10–20 mm, invasive cancer rates were 18% for ADH [7], 0–12% for benign papillary lesions, and 21–72% for atypical papillary lesions [8].

The Mammography findings of the benign lesions of the breast might be mass, asymmetry, distortion, microcalcification, or a combination of these [2]. When the microcalcifications and distortions seen on mammography are excised, they may be up-grade with DCIS or cancer findings. In the literature, the malignancy rate was reported to be 35% if the microcalcification area was < 10 mm, 23% if it was between 11–20 mm, and no malignancy was detected if it was > 20 mm. [9] In the present study, the mean microcalcification size was 13.78 ± 6.51 mm in B3 lesions, and covered more than 50% of the lesion (Fig. 1). However, there were no relations between size and malignancy (p = 0.334).

Atypical ductal hyperplasia and carcinoma were detected with excision in 9 (8.64%) of 109 patients who had suspicious lesions which were not diagnosed as pre-malignant/malignant in the first biopsy in our follow-ups. In the remaining cases, 20 patients (18.3%) who had DCIS had similar cytology at excision and the others (73.0%) were those who needed to be followed up with mere fine needle biopsy. The compliance between fine needle biopsy and stereotactic excisional biopsy was found to be 74.07% in the cases.

Smoking causes angiogenesis, desmoplasia, and abnormal ductal epithelial-stromal proliferation [10]. No relations were detected between smoking and the B3 lesion incidence (p = 0.373). Can high body fat cause carcinogenesis by inducing growth hormone as well as prepare the ground for pre-malignant lesions? [11]. Pre-malignant lesions were not associated with BMI > 30 in our cases (p = 0.627). The inflammation in mammarian glands after lactation causes disruption in the stromal structure of the glands[12]. Pre-malignant lesions did not have any relations with lactation period < 25 months and age at first menstruation (p = 0.723, p = 0.928). It was also not found to be significant with lactation duration in the Mariscotti et al.’s study [1] ; and 40/109 (75%) BEP was found to be significant in those who were older than 20 years of age at first birth (p = 0.009). The incidence of BEP was significant in those who had 2 deliveries when compared to those with less than two or more deliveries (28/109, 71%, p = 0.045, Table 2).

A significant relation was detected between pathological lesions and menopause. Although BEP, papillary, and ADH lesions were found to be common in premenopausal patients, the rate of malignancy was found to be higher in postmenopausal patients who were older than 47 years of age (Table 2, p = 0.002). Contrary to their radiological image, microcalcifications may be up-grade in these patients [1]. If the calcific BI-RADS 4b-c lesion is greater than 10 mm especially in older postmenopausal women, it is likely to up-grade to malignancy [1, 9].

In the present study, 9 cases that were up-grade with excisional biopsy were detected among 81 cases (11.11%), and 20 cases had DCIS and both biopsies were similar.

Pre-malignant/malignant potential was detected in only 8.64% of our cases when excisional removal was applied. Excision may not be required in lesions without atypia findings in fine needle biopsy if there is no microcalcification residue left behind. Mammography and ultrasound follow-up are sufficient in lesions without atypia findings in fine needle biopsy, and additional surgical excision will be an aggressive approach and a costly procedure. In the present study, 74% compliance was detected between fine needle and excisional biopsy. The number of the patients was less than the cases in the literature because of the difficulty of reaching the demographic characteristics of the patients retrospectively. However, the study can provide an insight on the approach to benign lesions and patient profiles.

Detecting atypical ductal hyperplasia in needle biopsies performed on suspected malignant lesions that are greater than 10 mm in mammography increases the probability of up-grade for advanced-age and postmenopausal women. Excisional biopsy is recommended in these cases regarding the possibility of DCIS or invasive carcinoma. Other lesions can be followed with non-invasive methods such as ultrasonography and mammography.

Ethical Declarations

Ethical Approval and consent to participate

Included patients from our institute provided signed informed consent and the study was approved by the Ethical Committee of Kanuni Sultan Suleyman Research Hospital (ID : KAEK /2020.07.164 ). Written informed consent was obtained from all individual participants included in the study. All methods were carried out in accordance with relevant guidelines and regulations.

Ethical Statement

The study was conducted according to the guidelines of the Nuremberg Code and Declaration of Helsinki and approved by the Ethics Committee of Kanuni Sultan Suleyman Hospital

Consent for publication

No applicable

Data availability Statement

The data set used during the current study are available from the corresponding author upon request.

Conflict of interest

The authors declare no conflict of interest

Funding

We did not receive financial support for this project.

Acknowledgements

This study’s data was procured from general Surgery and Oncology Department of Kanuni SS Hospital

Author Contribution

Article topic found and written by N.B. S.D. collected and recorded data and S.S. performed radiological imaging and biopsy procedures. The authors read and approved the final manuscript.

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No competing interests reported.

Is it important to evaluate the demographic characteristics and radiological findings of patients who have micro calcific lesions in the breast with biopsy results in the decision of excision?

Status:

Version 1

Abstract

Introduction

Material-Methods

Results

Conclusion

Figures

Introduction

Method

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1