Breast Pathology PDF 2024

Breast pathology Objective ▪ Breast diseases,congenital anomalies. ▪ Fibrocystic diseases. ▪ benign neoplasms. ▪ Pre-operative diagnosis. ▪ Molecular classification and grading of breast tumors. ▪ Histological types of breast cancer. ▪ Delineate the variables that influence the prognosis of breast...

Breast pathology Objective ▪ Breast diseases,congenital anomalies. ▪ Fibrocystic diseases. ▪ benign neoplasms. ▪ Pre-operative diagnosis. ▪ Molecular classification and grading of breast tumors. ▪ Histological types of breast cancer. ▪ Delineate the variables that influence the prognosis of breast cancer. ▪ Genes involved in breast cancer and mutation screening. ▪ gynecomastia. Origin of different breast lesion Pathological Classification of Breast Diseases: Congenital Anomalies: Ectopia: nipple, axilla, axillary lymph nodes, chest wall,vulva. Accessory Axillary Breast Tissue Congenital Nipple Inversion of Breast Diseases Congenital inversion of the nipple is of significance because similar changes may be produced by an underlying cancer Inflammatory & Related Lesions: Acute Mastitis & Breast Abscess: Localized or generalized inflammation of the breast Precipitated by trauma, lactation. Usually caused by Staph. aureus , less commonly Strept. Pyogenes May leads to cellulites. Chronic Infections & Granulomatous Inflammation: (1) Tuberculosis (2) Sarcoidosis (3) Fungal Infection (4) Granulomatous Mastitis Non- Infective Inflammatory Lesions: 1. Mammary Duct Ectasia: Affect perimenapausal women Patients are often multiparus and have lactated. It begins with dilation of terminal collecting duct beneath the nipple & areola were they become distended with cellular debris & lipid containing material, (plasma cell mastitis). The pathology described above results in firm mass with skin dimpling & nipple retraction. 2. Fat Necrosis. 3. Galactocele.  Fibrocystic Changes or Cystic Mastopathy: In females between puberty and menopause, and regards the commonest cause for breast lump. It is important because: 1. Some variants may clinically mistaken as carcinoma. 2. They may coexist with carcinoma. 3. They may predispose to the development of carcinoma. A. Non- Proliferative change (cyst & Fibrosis): Is the most common type characterized by increased fibrous stroma associated with dilation of the ducts and formation of cysts The cysts vary from smaller than 1cm to 5cm in diameter , they are brown to blue (Blue dome cysts), filled with serous turbid fluid. Histologically: In smaller cyst the epithelium is more cuboidal to columnar, in larger cyst it may be flattened or atrophic. Apocrine metaplasia, is frequent  B. Proliferative Change: I. Epithelial Hyperplasia (Epitheliosis): Hyperplasia affect the mammary duct or ductules It is the histologic variant that increase the risk subsequent development of malignancy, especially if it is associated with atypia Microscopically proliferation causes increase in the layers of the ductal epithelium, sometimes encroaching to completely fills the lumen obliterating it. Atypical duct or lobular hyperplasia may show various degree of cellular or architectural atypia. II. Adenosis and Sclerosing adenosis: Adenosis: Is enlagement of lobules and or formation of new lobules. Physiologic process which occurs during pregnancy and reproductive life. Fibrocystic changes. Sclerosing Adenosis: This variant is characterized histologically by intralobular fibrosis and proliferation of small ductules or acini which yield small glandular masses or cellular cords within a fibrous stroma. Sclerosing Adenosis:  Tumors of the Breast: Benign Tumors Fibroadenoma Tubular adenoma Lactating adenoma Intraductal papilloma Phyloiides tumor Malignant tumors Benign Tumors: Fibroadenoma: Is the most common benign tumor of the female breast. The increase of estrogen activity is thought to be a cause in it's development. This tumor is more commonly seen in young women below 30 years of age. Clinically it appears as freely mobile, discrete, usually solitary mass. Grossly it is firm, uniform, well circumscribed, 1-10cm in diameter, they may exceed 10cm (giant fibroadenoma), Histology: loose fibrous stroma containing duct like epithelium lined spaces of various sizes Rarely insitu lobular or ductal carcinoma arise in fibroadenoma (0.1%).  Phylloides Tumor: Much less common than fibroadenoma Arise from intralobular stroma and not from preexisting fibroadenoma. Clinically median age is 45 years. They are large tumors. Grossly they are well circumscribed, some become lobulated and cystic, leaf-like with clefts and slits. Cystosarcoma phylloides is unfortunate name. Histology: Stromal hypercellularity and benign glandular elements. Features of malignancy in phylloides tumor: 1) Nuclear atypia. 2) Numerous mitosis. 3) Overgrowth of the glands by the sarcomatous stroma. 4) Necrosis.  Malignant Tumors of the Breast (Breast Cancer): Is the most common type of malignancy among Iraqi women accounting for about 30% of the registered female cancers.  General Features ----Epidemiology and Risk Factors 1) Age The large majority of breast cancers are detected during the reproductive years. The incidence curve starts rising at puberty, increases steeply up to menopausal age, and levels off afterwards 2) Incidence more than 1 000 000 cases occurring worldwide annually. 3) Risk factors 1.Country of birth. The incidence is high in North America and Europe. 2. Family history. Women who have a first-degree relative with breast carcinoma have a risk 2or3 times that of the general population, a risk further increased if the relative was affected at an early age and/or had bilateral disease. 3. Menstrual and reproductive history. Increased risk is correlated with early menarche, nulliparity, late age at first birth, and late menopause. Breast carcinoma is rare in women who had oophorectomy before 35 years of age reduces the risk 4. Relationship between breast cancer with fibrocystic change and epithelial hyperplasia: 5. Prolonged exposure to exogenous estrogen: 6. Contraceptive agents. 7. Ionizing Radiation. 8. Breast augmentation. 9. Other less well established factors: Obesity, alcohol consumption, high fat diet. A peculiar association between breast carcinoma and meningioma has been repeatedly noted. Patients with ataxia–telangiectasia syndrome and with Cowden syndrome have an excess risk of breast cancer. Paget disease. The presence or absence of Paget disease in invasive ductal carcinoma is of no prognostic relevance. (Is the name given for crusted lesion of the nipple caused by breast carcinoma. The histological landmark is the involvement of the epidermis by (Paget's cells) )  Pathogenesis Factors that contribute directly to the development of breast cancer can be grouped into genetic, hormonal, and environmental categories.  Genetic. Driver mutations in cancer genes that contribute to breast carcinogenesis can be divided into those that are inherited and those that are acquired. The major germ line mutations conferring susceptibility to breast cancer affect ✓ genes that regulate genomic stability or that are involved in ✓ progrowth signaling pathways. ❖ BRCA1 and BRCA2 are classic tumor suppressor genes, cancer arises only when both alleles are inactivated or defective.BRCA1 and BRCA2 encode proteins that are required for repair of certain kinds of DNA damage. Somatic mutations in BRCA1 and BRCA2 are rare in sporadic cancers. up to 10% of BRCA are related to specific inherited mutations. Women are more likely to carry a BRCA susceptibility gene if they have:- a. BRCA before menopause. b. Bilateral cancer. c. Other associated cancers (e.g., ovarian cancer). d. A significant family history (i.e., multiple relatives affected before menopause). ❖ A common clinically important driver mutation in breast cancer is amplification of the HER2 gene. HER2 is a receptor tyrosine kinase that promotes cell proliferation and opposes apoptosis by stimulating the RAS- signaling pathways. Cancers that overexpress HER2 are pathogenically distinct and highly proliferative.  Hormonal Influences. ❖Estrogens stimulate the production of growth factors, such as transforming growth factor-α, platelet-derived growth factor, fibroblast growth factor, and others, which may promote tumor development through paracrine and autocrine mechanisms. ❖ER (estrogen receptor ) regulates dozens of other genes in an estrogen dependent fashion, some of which are important for tumor development or growth.  Environmental Factors. Environmental influences are suggested by the variable incidence of breast cancer in genetically homogeneous groups (e.g., Japanese women living in Japan and the United States)  Molecular Classification of Breast Cancer There are 5 main intrinsic or molecular subtypes of breast cancer that are based on the genes a cancer expresses: Luminal A breast cancer is hormone-receptor positive (estrogen-receptor and/or progesterone-receptor positive), HER2 negative. Luminal A cancers are low-grade, tend to grow slowly and have the best prognosis. Luminal B (Tripple +ve) breast cancer is hormone-receptor positive (estrogen- receptor and/or progesterone-receptor positive), and either HER2 positive or HER2 negative. Luminal B cancers generally grow slightly faster than luminal A cancers and their prognosis is slightly worse. Triple-negative/basal-like breast cancer is hormone-receptor negative (estrogen-receptor and progesterone-receptor negative) and HER2 negative. This type of cancer is more common in women with BRCA1 gene mutations. This type has aggressive coarse. HER2-enriched breast cancer is hormone-receptor negative (estrogen- receptor and progesterone-receptor negative) and HER2 positive. HER2- enriched cancers tend to grow faster than luminal cancers and can have a worse prognosis, but they are often successfully treated with targeted therapies aimed at the HER2 protein, such as Herceptin (chemical name: trastuzumab). Normal-like breast cancer is similar to luminal A disease: hormone- receptor positive (estrogen-receptor and/or progesterone-receptor positive), HER2 negative. While normal-like breast cancer has a good prognosis, its prognosis is slightly worse than luminal A cancer’s prognosis. Pathologic classification of breast Carcinoma: A. Non invasive: 1. Ductal carcinoma insitu DCIS( intraductal carcinoma). 2. Lobular carcinoma insitu (LCIS) B. Invasive (infiltrating): 1. Invasive ductal carcinoma. 2. Invasive lobular carcinoma. 3. Medullary carcinoma. 4. Colloid carcinoma ( mucinous carcinoma). 5. Tubular carcinoma. 6. Other types. Non- invasive (insitu) carcinoma: ❑Not invade the limiting basement membrane. Ductal carcinoma insitu: Solid Cribriform Papillary Comedocarcinoma In comedo carcinoma there is toothpaste-like necrotic tissue that can be extruded from transected ducts with gentle pressure, calcification is frequent. It may reach large size, and become clinically palpable Comedocarcinoma Paget disease of the nipple is caused by the extension of DCIS up to the lactiferous ducts and into the contiguous skin of the nipple. The clinical appearance is usually of a unilateral crusting exudate over the nipple and areolar skin. In about half of cases, an underlying invasive carcinoma will also be present. Prognosis is based on the underlying carcinoma and is not worsened by the presence of Paget disease.  Eczematous hyperemic and eroded clinical appearance of Paget disease. Insitu lobular carcinoma: unlike DCIS has a uniform appearance, and the cells are monomorphic with bland , round nuclei and occur in discohesive clusters in ducts and lobules. LCIS is a marker of increasing risk for breast cancer in the other breast. Invasive lobular carcinoma: This type tends to be bilateral. Histologically the classical type is characterized by small uniform strands of infiltrating tumor cells dispersed in fibrous matrix (Indian file). Because of considerable amount of fibrosis & uniform tumor cells, fine needle aspiration may reveals few monomorphic cells resulting in false negative cytology report. Indian file pattern of growth of invasive lobular carcinoma. Invasive ductal carcinoma: This is the most common type. exhibiting dense fibrous stroma (scirrhrous). Microscopic appearance is quite heterogeneous. The tumor margins are usually irregular. It may be associated with DCIS. Medullary Carcinoma: This is a relatively rare. Usually appears under age of 50 years Clinically & grossly mistaken for fibroadenoma. The prognosis is better than ordinary ductal carcinoma Colloid (Mucinous) Carcinoma: Usually in postmenopausal women. It has soft consistency. Grossly it has well- circumscribed borders with gelatinous cut section. Tubular Carcinoma: Average age is 50 years. It is small with a mean diameter of 1cm, It has hard consistency, poor circumscription, & high rate of multiplicity. Prognosis is excellent. Inflammatory Carcinoma: Defined by clinical presentation of enlarged, swollen, erythematous breast, usually without a palpable mass. The underlying carcinoma is of no specific type, true inflammation is minimal or absent. Most of these tumors have distant metastasis and extremely poor prognosis. Diagnosis of breast mass : In general the definitive diagnosis of breast mass can be made by: 1.Open biopsy 2.Tissue core needle (True- cut) biopsy 3.Cytology (Fine needle aspiration biopsy and Nipple discharge). Histopathological Grading of Breast Carcinoma: It comprises the description of three characters: 1. The degree of tubular differentiation. 2. The nuclear pleomorphism. 3. The mitotic activity. Accordingly mammary carcinoma could be classified into Grade I……..carry favorable prognosis. Grade II……..moderate prognosis. Grade III…….bad prognosis. Prognostic Factors in Breast Cancer: Prognosis: The prediction of the duration, course and outcome of the disease in a patient, is an essential part of medical practice. 1. Age: Higher mortality rate due to breast cancer are recorded before 35 years of age. 2. Pregnancy: There is a general agreement that breast cancer manifesting during pregnancy and lactation is associated with poor prognosis. 3. Tumor Stage: Depends on: i. The size of the tumor: ii. Lymph Node Involvement: 4.Early diagnosis: is a good prognosis. 5. Histologic Grade: Grade I…….. favorable prognosis. Grade II……..moderate prognosis. Grade III…….bad prognosis 6. Histologic Type: Favorable prognosis are( tubular, cribriform, medullary, pure mucinous, ). 7. Other microscopic findings: i. Type of tumor margins: ii. Stromal Reaction:. iii. Presence or absence of invasion: Skin invasion. Breast carcinomas in which invasion of the overlying skin has occurred are associated with a decreased survival.)bad prognosis). Lymphovascular invasion 8.Distant metastases. 9. The proliferative rate and presence of aneuploidy: The fraction of cells scattered outside the model peaks of DNA histogram correlate with poor behaver. Euploid mammary carcinoma have a significantly better prognosis than aneuploid carcinomas. 10. The presence or absence of hormone receptors: The number of estrogen and progesterone receptors in breast cancer is found proportional to the degree of cell proliferation. Hormone receptor positive tumors carry a better prognosis. 11. Presence of Growth factors or Amplified Oncogenes: BRCA: Early studies suggested that breast carcinomas developing in BRCA1 mutation were associated with worse overall survival. HER2/neu. HER2 :Overexpression of HER2/neu is associated with a poor prognosis. MALE BREAST Gynecomastia refers to enlargement of the male breast, which may occur in response to absolute or relative estrogen excesses. The most important cause of such hyperestrinism in the male is cirrhosis of the liver, with consequent inability of the liver to metabolize estrogens. Other causes include Klinefelter syndrome, estrogen-secreting tumors, estrogen therapy, and digitalis therapy. Grossly, a button-like, subareolar swelling develops, usually in both breasts but occasionally in only one. Carcinoma is a rare, with a frequency ratio to breast cancer in the female of 1: 125. It occurs in advanced age. Because of the scant amount of breast substance in the male, the tumor rapidly infiltrates the overlying skin and underlying thoracic wall. Both morphologically and biologically, these tumors resemble invasive carcinomas in the female.