Benign-Malign Differentiation of Axillary Lymph Nodes: The Role Of Superb Microvascular Imaging
Condition: Diagnosis; Axilla; Breast
Study type: Interventional

Summary: 
      102 patients who have suspicious ALNs were included in our prospective study, which was
      approved by a tertiary health care facility ethics committee. Each suspicious lymph nodes
      (LNs) were examined with PDUS and SMI in terms of distribution, appearance and number of
      vascular structures and the still images were stored. Subsequently, imaging findings were
      re-evaluated after histopathological or follow-up results and were compared between benign
      and malign groups. In addition, we revealed the diagnostic perfomance of using the each
      possible combination of these features in PDUS and SMI. Finally, two radiologists with 22
      years and 4 years of experience analyzed the images and interobserver agreement was assessed
    

Detailed description: 
      MATERIAL AND METHOD Patient The hospital's ethics committee approved this single-center
      prospective study (E-93471371-514.10). 139 female patients, ages 18 to 74, who had suspicious
      lymph nodes in the axilla during a breast ultrasound examination at our clinic between April
      2021 and April 2022 were included in the study. 20 patients did not come back for follow-ups,
      4 patients' ultrasonographic images were not sufficient diagnostic quality, and 13 patients
      were excluded from the study because the biopsy result was not diagnostic and the patient did
      not undergo re-biopsy. As a result, 108 lymph nodes from 102 patients were included in the
      study, and 37 patients were excluded.

      Patients who were male, under the age of 18, underwent axillary lymph node dissection, had
      active infection in the axillary region, were diagnosed with histopathologically confirmed
      axillary lymph node metastasis, had received known chemotherapy or radiotherapy to the
      axillary region, or did not sign the informed consent form were excluded from the study.
      Patients who had their pathology results unavailable or who later decided not to participate
      in the study were also excluded.

      Ultrasonographic Evaluation Suspicious axillary lymph nodes in the patients included in the
      study were evaluated with Toshiba Aplio a (Toshiba Medical Systems Corporation, Tokyo, Japan)
      ultrasound (US) device and 14-18 MHz high frequency linear probe. Gray scale US, PDUS and SMI
      images of the lymph nodes were stored. PRF and gain settings were adjusted to prevent from
      artifacts and to obtain the highest amount of signal while images were taken. In both Doppler
      methods, these parameters remained unchanged. The routine examination time for each patient
      extended 1-2 minutes by the SMI evaluation. At the end of the evaluation, a histological
      assessment using a 21G fine needle aspiration (FNA) biopsy or core biopsy (16-18G) from the
      relevant lymph nodes, or follow-up with US was performed, depending on the clinical
      suspicion. Any lymph nodes that regressed or disappeared throughout the US follow-up period
      of 1-3 months were considered benign. The lymph nodes that remained stable or progressed were
      evaluated through histopathological sampling. In case of non-diagnostic biopsy, patients were
      recalled and FNA/core biopsy was repeated. Cytology and pathology specimens were evaluated by
      a pathologist with at least 10 years of experience. Before the histopathological diagnosis,
      all patients were prospectively evaluated with ultrasonography by a radiologist blinded to
      the patient's clinic and history, and images were taken. After the pathology results, PDUS
      and SMI images were re-evaluated and the findings were compared with each other and pathology
      results. Finally, two radiologists with 22 years and 4 years of experience evaluated the
      images in terms of separately determined features without knowing the patient's clinical
      information and pathology result. The results were compared with each other in order to
      assess interobserver agreement.

      Both PDUS and SMI assessed vascular patterns based on the number of internal vessels, the
      distribution (avascular/central/peripheral/mixed) and appearance (normal, dysplasic,
      avascular) of internal vessels. On SMI, both monochrome (mSMI) and color (cSMI) images were
      assessed. If there was diffuse cortical thickening of the lymph node, the entire cortex was
      included the images. Likewise if there was an asymmetric cortical thickening, images focused
      on that part.

      Cortical flow signals were taken into account while internal vascularity was quantified. The
      lymph nodes with no vascular signals in the cortex were classified as avascular, the nodes
      with peripheral vascular signals as peripheral, the nodes with vascular signals extending
      from the hilus to the cortex as central, and the nodes with vascular signals in both the
      periphery and the central as mixed. To evaluate the morphology of the vessels, the signals
      with smooth, symmetrical hilar extension were considered as normal, the eccentric signals
      were identified as diplasic, and the lymph nodes without a signal were regarded as avascular.

      Statistical Analysis In the study, mean and standard deviation were used for continuous
      variables, while frequency and percentage values were used when specifying categorical
      variables. The Kolmogorov-Smirnov and Shapiro Wilk test was used to evaluate the homogeneity
      of the patient distribution. Student t-test and Mann Whitney U test were used for continuous
      variables. Chi-square test or Fisher's exact chi-square test was used to evaluate categorical
      features In order to evaluate the diagnostic performance of each investigated feature of
      Doppler methods in the differentiation of benign and malignant lymph nodes, the area under
      the curve (AUC) was calculated separately by receiver operating characteristic (ROC)
      analysis, depending on whether they were used individually or together. Logistic regression
      analysis was used to determine the significance value when the features were used together.
      In addition, sensitivity, specificity, positive predictive value(PPV), negative predictive
      value (NPV) and accuracy of each method were evaluated.

      The Kohen Kappa test was used for categorical features in both SMI and PDUS to assess
      interobserver agreement. Intragroup correlation coefficient test was used to compare vascular
      numbers. Chi-square test or Fisher's exact chi-square test was used to evaluate vascular
      properties between benign and malignant categories after consensus.

      All statistical analyses was performed with SPSS version 25.0 (IBM Corp. Armonk, NY: USA.
      Released 2017). P value <0.05 was considered statistically significant.
    

Intervention name(s): Ultrasound and biyopsy
Intervention type(s): Diagnostic Test
Intervention description(s): Each participant has undergone to ultrasound and biopsy procedure if they have suspicious lymph node in axillar region
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Diagnostic
Keywords: Axilla; Lymph node; Ultrasound; Doppler; Malignancy; SMI; PDUS