As breast disease screening and screening are widely carried out, more and more breast lesions are diagnosed by surgical biopsy, minimally invasive biopsy and hollow needle aspiration, and more and more pre-cancerous breast lesions are detected, but because the concept, disease name and classification of benign hyperplastic diseases, pre-cancerous lesions and carcinoma in situ of the breast have not been fully unified and standardized, the reference standard and diagnostic level of pathological diagnostic names are not consistent among hospitals. As a result, there are various pathological reports with different diagnostic names in clinical practice, which has troubled clinicians and confused patients. The author has sorted out this problem to help patients have a preliminary knowledge of pathology report of breast diseases.
I. Basic Understanding – Tumorigenesis
The process of normal cells developing into tumors is called tumorigenesis. From the cellular level, the occurrence of cancer is an extremely fortuitous event. Genetically, cancer cells all develop from a normal cell, from a cell that has lost its proliferation control. The human body has millions of trillions of cells, and billions of cells divide every day. Theoretically, almost any cell could become cancerous by a change in genetic composition, but this is not actually the case. The malignant transformation of a cell requires multiple genetic changes under the action of multiple external factors, i.e., multiple genetic mutations in one cell. Thus tumorigenesis is a progressive process involving multiple levels of response and accumulation of mutations.
Definition of cancer: Malignant epithelial cell tumor, in medical terms, refers specifically to malignant tumors of epithelial tissue origin. Breast cancer occurs primarily from the ductal epithelium of the breast. The mesenchymal connective tissue origin of the breast is often called sarcoma (including fibroepithelial tumors) and is not part of this discussion.
In the past, it has been considered that the development from normal cells to tumor cells goes through a process or classification, taking the ductal glandular epithelial cells of the breast as an example, namely: normal cells; proliferating cells (normal type UDH); atypical proliferating cells (ADH also called atypical proliferation); carcinoma in situ (low grade, intermediate grade, high grade; difficult to distinguish from some highly atypical proliferations); and invasive carcinoma, while atypical proliferation Atypical hyperplasia is the intermediate stage from benign to malignant changes and is the key point from quantitative to qualitative changes, therefore, atypical hyperplasia is called “precancerous lesion”. It is worth noting that the occurrence of breast cancer has its own pattern, and the above linear progression theory is too simple. The relationship between intraductal hyperplasia and invasive breast cancer is far more complex and does not necessarily follow the above pathway. Atypical hyperplasia is a morphologic change of precancerous lesions. The proliferating epithelial cells appear somewhat heterogeneous in morphology and structure, but are not sufficient for the diagnosis of cancer. However, it must be pointed out that not all precancerous lesions are necessarily transformed into cancer, and not all cancers can be seen in clear precancerous stages.
Second, the commonly used domestic diagnostic classification (In the past, intraductal proliferative lesions were often classified into the following three categories. Although the nomenclature is a little different from the 2003 version of WHO classification standards, many medical institutions still habitually use certain names and classification methods, which still have certain guiding significance for clinical work).
1. General hyperplasia (ductal epithelium of the breast)
(1) general mild hyperplasia: ductal dilatation, lobular hyperplasia, macrosomia, etc.
(2) Cyst-based hyperplasia: simple cysts, lipid cysts, sweat gland cysts, etc.
(3) Adenopathy-based hyperplasia: ductal adenopathy, sclerosing adenopathy, fibrosclerosis, blind ductal adenopathy, nodular adenopathy, etc.
(4) Fibroadenoma-like predominant hyperplasia: fibroadenoma-like hyperplasia, fibroadenoma.
(5) Highly hyperplastic
2, ductal atypical hyperplasia (see later for details)
(1) morphology: sieve-shaped, papillary, solid, glandular duct-like.
(2) Grading: mild, moderate, severe.
(3) Ductal carcinoma in situ (DCIS includes an extremely diverse group of lesions that differ in their mode of presentation, pathological patterns, biological markers, genetic and molecular biological alterations, and risk of progression to invasive carcinoma).
The fourth edition of WHO Histologic Classification of Breast Tumors 2012 (now it has gradually entered the mainstream pathologic diagnostic names, and many large medical institutions have started to adopt the relevant diagnostic names and classification methods) (here mainly enter the pathologic diagnostic names related to the content of this article)
1.Epithelial tumor
(1) Microinvasive carcinoma (omitted)
(2) Invasive breast cancer (omitted)
(3) Epithelial-myoepithelial tumor (omitted)
(4) Antecedent lesions.
①Ductal carcinoma in situ
(2) lobular tumors: lobular carcinoma in situ (classic, pleomorphic); atypical lobular hyperplasia
(5) Intraductal proliferative lesions.
(1) common ductal hyperplasia (UDH)
(2) columnar cell lesions (including flat epithelial atypical hyperplasia)
(3) atypical ductal hyperplasia (ADH)
(6) Papillary lesions
①Intraductal papillary tumor
②Intraductal papillary carcinoma
(3) Intraperitoneal papillary carcinoma
④Solid papillary carcinoma (in situ, infiltrative)
(7) Benign epithelial hyperplasia
①Sclerosing adenopathy
(ii) sweat adenoma
(3) Microglandular adenopathy
④Radiation scar/composite sclerosing lesion
⑤ Adenoma: ductal adenoma, lacteal adenoma, sweat adenoma, ductal adenoma
2.mesenchymal tumor (omitted)
3.Fibroepithelial tumors
(1) Fibroadenoma
(2) Lobular tumors: benign, junctional, malignant, periductal mesenchymal tumors
(3) Malformation tumor
4.Papillary tumors
(1) Papillary adenoma
(2) Sweat duct-like tumor
(3) Papillary Paget’s disease
5.Malignant lymphoma (omitted)
6.Metastatic tumor (omitted)
7.Male breast tumor（略）
8.Clinical pattern (omitted): inflammatory carcinoma, bilateral breast cancer.
IV. Atypical hyperplasia
1.Definition of atypical hyperplasia is a term of pathology, which mainly refers to the abnormal hyperplasia of epithelial cells, manifested as proliferating cells of different sizes, diverse morphology, large and densely stained nuclei, increased nucleoplasm ratio, nuclear division can increase but mostly show normal nuclear division image. The cells are arranged in a disorganized manner, with increased cellular hierarchy and loss of polarity. But generally do not see pathological nuclear division; can occur in the skin or mucosal surface of the covered epithelium, can also occur in the glandular epithelium.
2.Treatment of atypical hyperplasia The treatment of atypical hyperplasia depends on the extent of the lesion. Some research data show that intraductal hyperplasia is associated with the risk of developing invasive breast cancer, and the risk varies among different types, with UDH being roughly 1.5 times higher than normal, ADH 3-5 times higher, and DCIS 8-10 times higher. However, this does not mean that atypical hyperplasia will necessarily develop into cancer. If atypical hyperplasia is treated and monitored aggressively, many of them will stop developing and may also reverse and return to normal. Therefore, adequate attention should be paid to this important pathological stage of atypical breast hyperplasia.
For mild lesions, treatment is usually not required, but regular follow-up should be performed. However, for moderate and severe lesions, appropriate treatment is required because they are difficult to be removed by autologous clearance. Clinically, surgery is the main treatment.
V. Several points of consensus 95% of clinically diagnosed lobular hyperplasia are simple lobular hyperplasia (common type UDH) and breast cancer are not closely related.
However, highly hyperplastic and atypical hyperplasia (ADH) may become cancerous and is one of the risk factors for the development of breast cancer.
Therefore, the majority of lobular hyperplasia is not precancerous, but atypical hyperplasia and breast cancer have a close relationship. Timely detection and treatment of these atypical hyperplasia can prevent the occurrence of the corresponding cancer.