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    -  Enshaei A
    -  Mohammadi A
    -  Moosavi Toomatari SB
    -  Yekta Z
    -  Moosavi Toomatari SE
    -  Ghasemi-Rad M
    -  Shamspour SZ
    -  Sarabi ZK
    -  Sepehrvand N

 
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ORIGINAL ARTICLE
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Diagnostic value of a power Doppler ultrasound-based malignancy index for differentiating malignant and benign solid breast lesions


1 Department of Surgery, Urmia University of Medical Sciences, Urmia, Iran
2 Department of Radiology, Urmia University of Medical Sciences, Urmia, Iran
3 Department of General Surgery, Zanjan University of Medical Sciences, Zanjan, Iran
4 Department of Community Medicine, Urmia University of Medical Sciences, Urmia, Iran
5 Department of General Surgery, Tabriz University of Medical Sciences, Tabriz, Iran
6 Department of Radiology, Baylor College of Medicine, Houston, TX, USA
7 Department of Neurosurgery, Shiraz University of Medical Sciences, Shiraz, Iran
8 Department of Anesthesiology, Urmia University of Medical Sciences, Urmia, Iran
9 Department of Medicine, University of Alberta, Edmonton, AB, Canada

Correspondence Address:
Seyed Babak Moosavi Toomatari,
Department of General Surgery, Zanjan University of Medical Sciences, Zanjan
Iran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_424_18

  Abstract 


BACKGROUND: Power Doppler ultrasound (PDUS) can provide useful information regarding the vascularity of breast lesions. The aim of this study was to investigate the diagnostic performance of a new PDUS-driven malignancy index in differentiating between malignant and benign causes of solid breast lesions.
MATERIALS AND METHODS: Patients with solid breast lesions were enrolled consecutively and evaluated first by PDUS and subsequently by histopathologic assessment after undergoing surgical biopsy. A custom-made software was used to extract data from images for calculating malignancy index formula.
RESULTS: A total of 87 patients with solid breast lesions were enrolled. Histopathologic evaluation identified 49 patients as benign and 38 patients as malignant. Malignancy index was significantly higher in the malignant group as compared to benign tumors (6.31 vs 0.30, P < 0.001). Area under the receiver operating characteristics (ROC) curve (AUC) was 0.98 (95% confidence interval (CI) 0.95–1.00). According to the ROC curve analysis, the cut-off point of 1.23 for malignancy index had a sensitivity and specificity of 94.7% (95% CI 82.2–99.3) and 94.0% (95% CI 83.1–98.7), respectively.
CONCLUSION: Comparing with the histopathologic evaluation as the gold standard for diagnosing breast lesions, PDUS-driven malignancy index was shown to have a high discriminative performance in identifying malignant lesions with high sensitivity, specificity, and diagnostic accuracy. The noninvasive nature of PDUS is an important advantage that could prevent unnecessary biopsies.


Keywords: Breast, malignancy, power Doppler, ultrasonography



How to cite this URL:
Enshaei A, Mohammadi A, Moosavi Toomatari SB, Yekta Z, Moosavi Toomatari SE, Ghasemi-Rad M, Shamspour SZ, Sarabi ZK, Sepehrvand N. Diagnostic value of a power Doppler ultrasound-based malignancy index for differentiating malignant and benign solid breast lesions. Indian J Cancer [Epub ahead of print] [cited 2020 Jan 17]. Available from: http://www.indianjcancer.com/preprintarticle.asp?id=275392





  Introduction Top


Breast cancer is the most common cancer in women with 2.4 million new cases each year worldwide. It is also the leading cause of cancer death (~0.5 million) and disability-adjusted life-years in that specific population.[1] Early detection and treatment are vital to improve survival. Mammography is the guideline-recommended screening modality for breast lesions that is shown to reduce mortality.[2] Besides mammography, breast ultrasonography has high sensitivity in detecting breast lesions. Sonomorphological features such as shape, margin, orientation, posterior echo, calcification, internal echogenicity, echotexture distribution, and presence or absence of retraction pattern are some of the features that were used in the differential diagnosis between benign and malignant lesions.[3],[4],[5] Irregular shape, nonparallel orientation of the tumor and spiculated, and poorly defined margins are shown to be highly suggestive of malignancy.

Despite having high sensitivities, both mammography and classical ultrasonography have shown low specificity in identifying malignant tumors and 65–90% of biopsied lesions end up with a benign diagnosis.[6],[7]

Power Doppler ultrasound (PDUS) can provide information regarding the vascularity of breast lesions. It has been shown that adding the visualization of blood flow and vascularity in solid lesions to the findings of gray-scale ultrasound (US) imaging has incremental diagnostic value in differentiating benign and malignant masses as compared with gray-scale ultrasonography alone.[8],[9],[10]

In this study, our aim was to investigate the diagnostic performance of a new PDUS-driven malignancy index in differentiating between malignant and benign causes of solid breast lesions.


  Materials and Methods Top


The study was approved by the Institutional Review Board of Urmia University of Medical Sciences (UMSU), Urmia, Iran. Informed consent was obtained from all participants. A total of 87 consecutive patients with solid breast lesions seen in gray-scale B-mode ultrasonography were enrolled in this single-center prospective study (from June 2014 to March 2015). Patients were excluded if they were not willing to undergo surgical removal of breast tumor.

US images were acquired with a Medison Accuvix V20 US system (Medison, South Korea) using a 7–12 MHz broadband width transducer. The examinations were performed by a board-certified radiologist with 20 years of experience in US imaging who was unaware of the results of other clinical investigations.

All lesions were solid and palpable without cystic components in echo. All masses were assessed at baseline with two-dimensional (2-D) PDUS to assess tissue vascularity even in slow and poor flow areas (pulse repetition frequency 0.4–0.6 kHz, depth of Doppler 3 cm, overall gain adjusted to 60 dB, and wall filter was minimal) [Figure 1]. We selected PDUS over color Doppler US to evaluate the vascular pattern of breast lesions as PDUS is shown to have higher sensitivity in small vessels with low flow rates. It is angle-independent and avoids aliasing artifacts.[11] The linear array probe was positioned in a way to maximize the visualized vascularity in the tumor. No compression was used during power Doppler ultrasonography. All lesions were surgically removed and were assessed by a single experienced pathologist.
Figure 1: Identifying tumor boundaries and vascularity in power Doppler ultrasonography of breast masses showing well-defined benign tumors (a and b) with scanty peripheral vascularity, irregular-shaped malignant tumor with peripheral and minimal central vascularity (c), and spiculated malignant mass (d) with peripheral and marked central vascularity

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Computer software

Images were saved in the bitmap (BMP) file format. Each image was assessed with a custom-made Windows-based computer software [Figure 2] and data were collected on parameters such as blood flow velocity (BFV). Only a single image was used per patient. The PDUS image reflecting the longest diameter of the lesion was selected and saved for later assessment and measurements with software. As depicted in [Figure 2], first the boundaries of the solid lesion were identified and then the pixels were assessed by the software. A histogram of the frequency distribution of each pixel was developed [Figure 3]. The X-axis in the histogram reflects the BFV which is shown with colors ranging from 1 to 128 scale, depending on the flow intensity. The Y-axis represents the frequency of each scale, i.e., specific blood flow. The software calculates the mean and standard deviation of BFV as well as the number of colored and total number of pixels in the studied area. The malignancy index was calculated automatically by the software using the following formula which is developed and named by our group:
Figure 2: Flowchart of custom-made software that analyzed PDUS images

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Figure 3: Histogram of BFV in PDUS

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Zahra malignancy index (ZMI) = [Standard deviation/average] × [colored pixels/total pixels] × 100

Statistical analysis

We compared the data obtained from power Doppler ultrasonography between groups with benign and malignant breast lesions using independent t-test or Mann–Whitney U-test, depending on the normality of distribution. The diagnostic performance of the malignancy index was compared with histopathologic assessment as the gold standard using the receiver operating characteristics (ROC) curve, and the optimal cut-off point was identified.


  Results Top


A total of 87 patients with solid breast lesions were enrolled. Histopathologic evaluations identified 49 patients as benign and 38 were identified as malignant. Among those with malignant lesions, 32 (84.2%) and 6 (15.8%) were identified as ductal and lobular carcinoma, respectively. The diagnosis of benign tumors was as follows: fibroadenoma 23 (46.9%), fibrocystic changes 19 (38.8%), inflammatory disease 5 (10.2%), and adenoma in 2 (4.1%) patients.

Malignant and benign tumors were compared in [Table 1]. [Figure 4] depicts the results of the ROC curve analysis. Area under the ROC curve (AUC) was 0.98 [95% confidence interval (CI) 0.95–1.00]. In the ROC curve analysis, the cut-off point of 1.23 for malignancy index had a sensitivity and specificity of 94.7% (95% CI 82.2–99.3) and 94.0% (95% CI 83.1–98.7), respectively [Table 2].
Table 1: Patient characteristics and malignancy index in malignant and benign masses

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Figure 4: ROC curve of malignancy index in identifying malignant breast lesions

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Table 2: Diagnostic performance of PDUS-driven breast malignancy index

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Positive and negative predictive values were 92.3% (95% CI 80.0–97.3) and 95.8% (95% CI 85.6–98.9), respectively, and the diagnostic accuracy was calculated to be 94.2% (95% CI 87.1–98.1).


  Discussion Top


In this study we propose a formula for evaluating solid breast masses using power Doppler US. The malignancy index was able to successfully differentiate the malignant masses from benign ones with a high sensitivity and specificity.

Angiogenesis, i.e., the growth of abnormal new blood vessels from preexisting vessels is shown to be related to tumor growth, invasion, and metastasis.[4],[8],[12],[13] The presence of intratumoral vessels is revealed to be linked to malignancy in both palpable and nonpalpable breast lesions.[14] This phenomenon is a physiologic process to meet the increased metabolic needs of the malignant tissue.[15]

Several studies in the literature have shown that malignant lesions have significantly higher vascular indices than benign ones.[16],[17],[18] Vascularity index (VI) defined as the number of vessel pixels divided by the number of all pixels of the whole tumor in 2-D PDUS image is one of those indices that is shown to be higher in malignant tumors as compared to benign ones.[19],[20] Nevertheless, the tumor vascularity has not been a sufficient criterion until now for classification of breast tumors to malignant versus benign and yet to get integrated into clinical practice.[18],[21] Also there are conflicting results on which vascularity parameter has the highest diagnostic performance and which could be used in routine practice.[20]

In our study, malignant lesions had significantly higher malignancy (i.e., vascularity) index than benign ones. This is consistent with the findings of previous studies showing the higher vascular indices in malignant lesions.[20]

This study showed higher diagnostic accuracy for PDUS-derived malignancy index as compared to other PDUS morphological or vascularization studies.[2],[3],[5],[8],[16],[17],[18],[22],[23] 93.8% unnecessary biopsies that are diagnosed to be benign can be avoided without missing any malignancies, which can reduce the unnecessary fear, anxiety, discomfort, pain, and financial cost to the patients.

The widespread availability of US machines is an advantage for the potential expansion of this diagnostic method. US machines can be found today in most hospitals in the world.[24] It is not expected from an ultrasonographer to calculate this index himself. Hence computer-aided diagnosis [25] can calculate this index and can assist physicians to differentiate the tumor more effectively.[26]

Several limitations are noteworthy. We have used 2-D power Doppler US for this study, since we wanted the diagnostic test to be feasible in almost every setting. However, several studies have shown the advantages of using a 3-D system, as it visualizes the whole tumor instead of using limited transverse and longitudinal planes with 2-D US.[27],[28] In future, this index should be tested in 3-D power Doppler US as well. In this study, instead of using vessel morphology determined by radiologists, we used quantitative measurements including the pixel counts and their related mean and standard deviation on the histogram to differentiate between malignant and benign lesions. It has been shown that none of these are superior to the other one,[29],[30] and quantitative indices have the benefit of being less-subjective and unbiased and the potential to be automatically extracted. Further prospective studies with larger sample size are warranted for external validation of this index.

In conclusion, PDUS-driven malignancy index was shown to have a high discriminative performance in identifying malignant lesions with a high sensitivity, specificity, and diagnostic accuracy. The noninvasive nature of the PDUS is an important advantage that could reduce unnecessary biopsies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

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