When diagnosing the etiology of pathological nipple overflow related breast diseases, in addition to detailed medical history and physical examination, careful observation of the nature of nipple overflow, single or multiple pore overflow, in addition to relevant ancillary tests should be performed to aid in the diagnosis.
1.Smear examination of overflow
It is used to examine blood, plasma blood, and plasma overflow, with an accuracy rate of about 30%. The smear can see ductal epithelial cells, foamy cells, large juicy adenoid cells, squamous epithelial cells, inflammatory cells and calcified material. Calcified material is commonly seen in cancerous overflow smear and also in certain chronic diseases such as ductal dilatation overflow. The diagnostic positivity rate of papillary overflow cytology is between 30-60%. It has been reported that the sensitivity of ductal aspiration cytology is 75%, the specificity is 86.3%, and the accuracy is up to 85.1%, which is a significant improvement over the previous methods. However, papillary overflow smear examination can only be used as a simple and effective preliminary screening diagnostic method.
2.Cytological examination of milk duct flushing fluid
We need to note that the specificity of TCT examination is high (98.9%), but the sensitivity is low (82.8%), and a negative TCT examination cannot completely exclude the possibility of breast cancer. This has been confirmed by many studies.
3.B-mode ultrasound examination of the breast
Ultrasound diagnosis of intraductal papilloma, the mass is usually located in the areola area, and the sonogram type is mainly cystic solid. However, the detection rate of diagnosing nipple overflow breast cancer is only 11.8% [12]. The detection rate of ultrasound in our study was 16.5%, which may be due to the small degree of infiltration of simple nipple overflow breast cancer lesions or regular morphology, making ultrasound less resolved than mammography for microstructures and calcified foci at the edges of the mass.
4.Mammography with high frequency
High-frequency mammography is currently the imaging technique with a high accuracy rate in diagnosing breast diseases, with a sensitivity of >85%. Due to the application of breast high-frequency X-ray in the screening of healthy women, the early diagnosis rate of breast cancer has increased, which has led to a 30% to 50% decrease in the mortality rate of breast cancer. Breast high-frequency X-ray is also one of the means of screening for pathological nipple overflow, of but in simple nipple overflow breast cancer, the sensitivity of breast high-frequency X-ray is significantly reduced, and the positive rate of breast high-frequency X-ray for simple nipple overflow breast cancer in my study is 32.9%. This is partly due to the large proportion of intraductal carcinoma in simple papillary overflow breast cancer. Studies in the literature have shown that about 50% of breast HF X-rays with papillary overflow as the manifestation of intraductal carcinoma have no malignant features, and the negative rate increases significantly.
5.Selective ductography
Signs of selective ductography for pathological nipple discharge breast-related disease include: duct disruption, duct traction displacement, duct stiffness, duct dilatation, filling defect, duct compression displacement, duct branching reduction, disorganization, and tumor or peritumor interstitial shadowing. It can provide valuable imaging information for breast cancer, intraductal papilloma and ductal dilatation, and is one of the effective means for early diagnosis of nipple discharge breast cancer. Selective ductography can be an important method to clarify the lesion site, nature and extent of the overflow before surgery, and it does not require special equipment and can be carried out in the majority of primary units without ductoscopy. However, selective mammography has the disadvantages of not being able to see the lesion directly, low diagnostic rate, time-consuming, painful for patients, and allergy in some patients cannot be examined.
6.Mammary duct endoscopy
Breast duct endoscopy can directly observe the characteristics of the lesion and perform excisional biopsy of the lesion under direct vision, which plays an important role in the diagnosis of pathological nipple overflow compared to other traditional examinations of the breast. It can be inserted along the course of the milk ducts to the terminal milk ducts to clearly visualize microscopic lesions in the lumen of the milk ducts from the opening to the distal 5-6 cm. The endoscopy of the milk ducts has characteristic images under direct vision, plus a better localization with about 10-fold image magnification, and a high diagnostic rate of 81%-95%.
In my article published in 2011, Logistic regression evaluated the diagnostic value of ductal image features in breast cancer with nipple overflow, and obtained a practical equation for the diagnosis of breast cancer with nipple overflow by ductal image features. For the judgment of breast cancer with nipple overflow, the importance of the value of ductal features is: surface morphology of duct wall > elasticity of duct wall > number of lesions > terminal bleeding > color = surface shape > shape > lesion location, and it is clinically important to master these to improve the diagnosis rate of breast cancer with nipple discharge [19].
I first proposed a breast ductoscopy grading based on the image features and pathological findings of nipple microscopy. Among them, grade 0 is a failure of operation such as no adequate signs or pseudo-tract formation, grade 1, negative, simple dilation of milk ducts, this grade is more frequent in clear water-like, plasma-like, and milk-like overflow; grade 2, typical benign signs, breast ductoscopy shows: dilation of milk ducts, smooth duct walls or a small amount of bleeding spots visible, only a small amount of blood in the lumen, no active bleeding, and no terminal bleeding. This grade is mostly considered clinically as mastitis; grade 3, benign possibility, the ductoscopy meets all benign lesion signs (lesion is spherical, solitary, located in I or II breast duct; smooth duct wall, no terminal bleeding, etc.), this grade has the highest possibility of intraductal papilloma, malignancy rate ≤ 3%, surgical excision biopsy is recommended; grade 4, suspicious malignancy, the ductoscopy finds that it cannot fully meet the benign lesion signs, and Grade 4, suspicious of malignancy, is a breast ductoscopy finding that does not fully comply with the benign lesion signs, but does not meet more than 3 malignant signs, and may have one of the typical features of breast cancer ductoscopy, such as multiple lesions, irregularity or massive bleeding at the end, recommending surgical excisional biopsy; Grade 5 image features include: multiple lesions, located in the breast duct or end below grade 3, irregular, non-tip, longitudinal extension along the duct wall or circular growth along the duct wall, grayish or colorful, rough, thickened, stiff, poorly elastic or with a surface of the duct wall. If the papillary overflow cytology is malignant, the diagnosis is grade 6, and the accuracy of this classification is 96.6%. The clinical management of the lesion is surgical excisional biopsy, regardless of the signs of the lesion under the ductoscope.
In addition to endoscopy, minimally invasive biopsy of the breast duct and cytological examination of the combined ductal irrigation fluid are feasible to further improve the diagnostic rate and provide a basis for the selection of the procedure.
The defects of breast duct endoscopy: the diagnostic value of end duct lesions is limited, and only the surface of the mass can be observed when a mass is protruding and obstructing the breast duct, and the infiltration in and around the breast duct cannot be observed at the same time as imaging, and the success rate of breast ductoscopy with simultaneous biopsy is not high at present, which has certain limitations.
7.Mammary MRI
Many studies have shown that breast MR has a higher specificity and sensitivity compared with mammography and ultrasound in the diagnosis of breast cancer with nipple discharge. Ishikawa et al. concluded that MR dynamic enhancement scans of the breast are more useful for the differentiation of benign and malignant breast diseases and can provide early diagnosis of malignant breast diseases, such as in situ and intraductal carcinoma, and are more sensitive than ductography and ultrasound. The results of our study show that malignant nipple overflow has characteristic manifestations on MRI, with segmental enhancement, internal nodular changes, and type 3 outflow curves being the most characteristic. The superiority of other examinations.
8. Molecular biology of pathological nipple discharge
The determination of CEA in nipple discharge is important for identifying the nature of breast disease and aiding in the diagnosis of breast cancer. The determination of CEA in nipple discharge, especially in patients who have nipple discharge but cannot find a breast lump, is an easy and practical method for identifying the cause of nipple discharge, providing indications for surgical biopsy, and detecting and diagnosing early breast cancer.
Some studies have shown that uPA and PAI-1 expression is significantly higher in nipple discharge breast cancer or precancerous lesions than in benign lesions, and the detection of uPA, PAI-1 and TF may be useful for the early diagnosis of breast cancer. More and more molecular markers are being explored for the diagnosis of nipple discharge, screening of nipple discharge, and differential diagnosis of benign and malignant nipple discharge diseases, but the real application to the clinic still needs more exploration.