PATHOLOGY OF THE BREAST

Transcription

1 UROGENITAL SYSTEM MBBS 2 nd Yr. Lecture Dr. U.S. Khoo October 3, :45 AM Underground Lecture Theatre 1 New Clinical Building, QMH PATHOLOGY OF THE BREAST Learning Objectives 1. To understand the normal structure, physiological development, and function of the normal breast, in order to better appreciate related pathology. 2. To know of the various benign conditions affecting the breast that may mimic breast cancer. 3. To understand the importance of pathological assessment that contributes toward the diagnosis, management and treatment of breast malignancies. 4. To acquire an awareness of the risk factors, the significance of mammography and other methods of screening that are aimed at reducing the mortality of breast cancer. Structure and function of normal breast The breast is a modified sweat gland that develops into a complete functional structure in the female, but remains rudimentary in the male. The three major components consist of the skin the subcutaneous adipose tissue the functional glandular tissue. The breast is divided into lobes, each based on a branching duct system leading to the terminal duct-lobular unit which is the functional site of milk production. Each lobe is made up of lobules. It responds to various physiological stimuli and goes through stages of alteration through life; development and puberty maturation and differentiation lactation involution and senile atrophy. Fig. 1.1 Schematic cross-section of mature female breast to show the main anatomical structures. It is this sensitivity for ovarian hormones, hormones of pregnancy and other growth factors in the female breast that predispose this organ to a number of pathological conditions. Clinical presentations of breast diseases include pain, presence of a dominant lump, or abnormal nipple discharge. Benign breast conditions are of interest because they may mimic breast cancer. 1

2 I. INFLAMMATORY LESIONS ACUTE MASTITIS AND BREAST ABSCESS are uncommon except during lactation may be the result of infection via the nipple due to abrasion or crack, acquired from the mouth of the baby MAMMARY DUCT ECTASIA Its aetiology is uncertain - presents clinically as dilated ducts filled with cheesy material in the area adjacent to the aerola. Ulceration of the ducts allows liberation of lipids into the connective tissue stroma that leads to a chronic granulomatous inflammatory reaction. Fibrosis can lead to nipple retraction and clinically mimic carcinoma. FAT NECROSIS Most commonly seen in women with obese, pendulous breasts and is due to trauma. There is a localised firm or even hard mass which can on occasions be adherent to the skin and thus be easily mistaken for carcinoma. Traumatic rupture of fat cells results in a foreign-body granulomatous reaction and subsequent fibrosis. OTHER GRANULOMATOUS LESIONS In the past foreign material such as paraffin wax or silicone fluid were injected as means of increasing breast size. These could give rise to florid foreign body type granulomatous reaction. Tuberculosis is an uncommon complication of pulmonary tuberculosis. Idiopathic granulomatous mastitis may have an autoimmune base. II. FIBROCYSTIC DISEASE Cyclical hormonal influences do not affect all parts of the breast equally in each cycle. Hormonal imbalances such as excess of oestrogens, a deficiency of progestrone as well as abnormal end-organ metabolism of hormones are all thought to contribute to the pathogenesis of this multi-patterned disease. Most common around 30 years of age, it is rare after the menopause. It tends to be generalised but frequently a localised area draws attention to the disease. The breast tissue is firmer and more nodular than usual - but not hard and fixed to surrounding tissues as in carcinoma. Cysts 2-10 mm in diameter may be seen and they frequently occur in clusters. Large cysts occur. Characterized by: 1. CYSTIC FORMATION & FIBROSIS - increase in fibrous stroma and formation of cysts of various sizes which can be microscopic or larger. 2. APOCRINE METAPLASIA - the ductal epithelium changes to pink cells with budding of the luminal aspect. 3. EPITHELIAL HYPERPLASIA - proliferation of ductal lining epithelium, which can be associated with increased chance of malignancy, the more severe and atypical the degree of hyperplasia. 2

3 SCLEROSING ADENOSIS - a poorly circumscribed lobulated mass during childbearing and peri-menopausal years. Fibrous alteration of the lobular stroma, causes distortion, compression and elongation of tubules which may simulate malignancy. RADIAL SCARS and COMPLEX SCLEROSING LESIONS can also mimic carcinoma both clinically and radiologically. III. TUMOURS OF THE BREAST (a) BENIGN TUMOURS FIBROADENOMA It is the commonest cause of a palpable lump up to the age of 30. Clinically it is a well-circumscribed firm, mobile and painless lump. Microscopically, it is composed of benign epithelium and proliferation of connective tissue that may compress ducts into slit-like spaces (intracanalicular pattern) or grow circumferentially around them (pericanalicular pattern). DUCT PAPILLOMA Occurs any age and usually within 4 cm of the nipple, it is the commonest cause of a bloody nipple discharge, carcinoma being the next most common cause. Microscopically it consists of a complex papillary structure covered by duct epithelium with a fine fibrovascular core. (b) PHYLLOIDES TUMOUR It resembles a fibroadenoma, but demonstrates variable clinical behaviour, ranging from benign to malignant. Simple enucleation of the tumour will result in a high frequency of recurrence. While the majority of phylloides tumours behave in a benign fashion, 3-12% metastasize. It is differentiated from a fibroadenoma by a cellular stroma and a fond-like arrangement of the fibroepithelial element. The peak age is 45 years. Features for distinguishing the malignant form are: (i) mitoses > 5/10 HPF, (ii) cellular atypia, (iii) invasive edge, (iv) stromal overgrowth. The usual treatment for the benign phyllodes tumour is wide excision and for the malignant ones is mastectomy. (c) CARCINOMA One of the commonest malignancies in women, it is the leading cause of cancer death amongst Caucasian women. One in every 11 women will develop breast cancer in the US. Although at a lower incidence of 40.8 per 100,000 in Hong Kong, it is still the most common cancer in females. A local female has a 1 in 27 chance of developing breast cancer in her lifetime. The incidence of breast cancer rises with age. Past the menopause, a lump in the breast has a higher chance of being a carcinoma. 3

4 RISK FACTORS: The strongest known epidemiologic risk factor for breast cancer is a positive family history. The contribution of hereditary breast cancer however, accounts for only about 10% of all breast cancers. There are other many non-genetic factors that contribute to disease etiology. a. Genetic predisposition BRCA-1 and BRCA-2 are the two major breast and ovarian cancer susceptibility genes, thought to account for the majority of hereditary breast and ovarian cancers. They are autosomal dominant genes, transmitted by Mendelian inheritance. Families with 3 or more related individuals with breast and/or ovarian cancer are at highest risk of carrying mutations in either of these genes. BRCA mutation carriers are predisposed to early onset breast cancer, bilateral breast cancer, ovarian cancer and other associated cancers. Genetic testing aims at identifying the mutation that predisposes the individual or the family to cancer. In families where germ-line mutations in BRCA1 and BRCA2 have been identified, estimates for breast cancer risk can be made with greater accuracy. The lifetime risk of cancer in BRCA mutation carriers ranges from 56% to 84%. Both BRCA genes are very large with absence of mutational hot-spots, which presents difficulties in genetic testing for germ-line mutations in high risk families. Testing is usually performed on affected individuals. Only if a mutation is identified, can other unaffected members of the family be tested to find out if they have inherited this mutation. A negative result from families where no mutation has been identified cannot exclude the possibility that other genes, as yet unknown, may be involved in that family. Ethical issues such as problems of health insurance and disclosure of information and controversies in options for management of women found to have mutations remain. The potential benefit of knowing one has not inherited a predisposition must be weighed against the possible harm that may result from finding one is at risk. The benefits and limitations of such testing together with the potential complexities of genetic counselling should be explained clearly to families beforehand. b. Hormonal imbalance This is thought to play a significant role in the development of carcinoma of breast. The long duration of reproductive life such as early menache (<12 years) and late menopause (>54 years), nulliparity, and late age at first child - all imply increased exposure to oestrogen peaks during the menstrual cycle. Functioning ovarian tumours that elaborate oestrogens are associated with breast carcinoma in postmenopausal women. The risk associated with use of oral contraceptives and hormonal replacement therapy, are controversial. c. Environmental influences Dietary fats and obesity seem to be related to breast carcinoma, particularly after 50 years of age, because they are associated with endogenous hormonal modifications. Ionising radiation may have a limited role, as illustrated by the high incidence among patients who received multiple chest Xrays in the course of treatment of pulmonary tuberculosis. 4

5 CLASSIFICATION OF BREAST CARCINOMA: A. Noninvasive 1. Ductal carcinoma-in-situ (DCIS) 2. Lobular carcinoma in-situ (LCIS) B. Invasive 1. Invasive ductal carcinoma - not otherwise specified (NOS) 2. Invasive lobular carcinoma 3. Tubular and cribiform carcinoma 4. Mucinous carcinoma 5. Medullary carcinoma NON-INVASIVE CARCINOMA DUCTAL CARCINOMA-IN-SITU (DCIS) The tumour is still confined within the ductal basement membranes. The presence of microcalcification allows for these tumors to be detectable by mammography at an early stage. About 50% are centrally situated and may form a palpable mass. High grade comedo DCIS has large pleomorphic cells and central comedo necrosis. About 50% evolve into invasive carcinoma within 5 years. In contrast, for microscopic non-comedo low grade DCIS, only 30% will develop invasive carcinoma within the next years. Subsequent invasive carcinoma is usually in the same area as the initial DCIS. LOBULAR CARCINOMA-IN-SITU Tend to occur in perimenopausal women becoming quite uncommon with advancing age. It has no distinguishing clinical features and may be missed by mammography. It is often multicentric (70%) and bilateral (20-35%), usually concentrated within 5 cm of the nipple in the outer and the upper inner quadrants. The likelihood of developing invasive carcinoma is about 10 times greater than that of the general population, with an absolute risk of 20-25% in 15 years. The site of later invasive carcinoma is equally divided between either breast. The subsequently developed carcinoma can be ductal or lobular. INVASIVE CARCINOMA INVASIVE DUCTAL CARCINOMA (NOS) The carcinomas that lack special features are termed NOS (not otherwise specified). They comprise about 70% of invasive breast cancers and are characterized by a poorly defined hard, yellow-grey mass with radiating fibrous trabeculae. The tumor cuts with a gritty sensation and chalky streaks. The term cancer (crab-like) came from here. INVASIVE LOBULAR CARCINOMA It accounts for approximately 5% of all breast tumours. Frequently multifocal and bilateral, presenting as a poorly circumscribed mass. Microscopically, it is characterized by single cell infiltration, often in single file (Indian filing) or arranged as concentric rings around a duct (target-like lesion) of small to medium-sized tumour cells. 5

6 TUBULAR CARCINOMA AND MUCINOUS (COLLOID) CARCINOMA These are special types of low-grade invasive ductal carcinoma with excellent prognosis in the pure form. Distant metatastasis are most unlikely to occur and they and rarely kill. The mucinous carcinoma tends to occur in older women, and presents as a slowly growing circumscribed mass that produces bulky, soft, gelatinous material. Islands of tumour cells are seen floating in large lakes of mucin. MEDULLARY CARCINOMA Another special type of invasive ductal carcinoma, characterized by syncytial-like sheets of large pleomorphic cells surrounded by heavy lympho-plasmacytic infiltrate and well-circumscribed margins. Traditionally known to have a better prognosis than the usual infiltrative ductal carcinoma. UNUSUAL PRESENTATION OF BREAST CARCINOMA PAGET'S DISEASE OF THE NIPPLE Usually presents with erosion of the nipple and areola, which are red and weeping but occasionally dry, scaly and psoriatic. There is always an underlying intraductal or invasive carcinoma. It is characterized microscopically by the invasion of the epidermis by Paget's cells, which are large, round to oval with pale cytoplasm and contain mucin. SPREAD OF BREAST CARCINOMA Lymphatic spread is influenced by the location of the carcinoma. Lateral tumours will tend to spread to axillary nodes. Medial and deep carcinomas will go to the internal mammary chain. Haematogenous spread of carcinoma will result in metastases to skeleton, lung, liver, ovaries and adrenal glands. PROGNOSIS The dominant characteristic of breast cancer is its heterogeneity. There are many different types of breast cancer that differ in their threat to life. Many options of treatment are also becoming available which include local excision, partial mastectomy and combinations of radiotherapy and chemotherapy. Selection of the appropriate treatment option involves careful characterisation of a patient's cancer. These prognostic and predictive marker of breast carcinoma include:- (i) size (ii) histologic type and grade (iii) lympho-vascular permeation (iv) lymph node metastases (v) proliferation rate (vi) clearance from resection margins (vii) steroid hormone receptor status (viii) oncogene expression Clinico-pathological prognostic assessment is important for appropriate clinical decision making and to predict survival at least of the first five years. The role of the pathologist is not merely to give a diagnosis of breast carcinoma but has a crucial part to play in characterizing the prognostic and predictive profile of each patient. 6

7 BREAST CANCER SCREENING Emphasis is now being placed on early detection and treatment. Earlier detected carcinomas generally have better prognostic features that are more amenable to treatment and control. Countries that offer mammographic breast cancer screening have claimed a reduction of mortality. Mammography aims at detecting impalpable cancers. It can also be used to further characterise palpable lesions and to check for bilaterality. It must be remembered however that 10-20% of carcinomas may still be undetectable by mammography. Fine needle aspiration cytology (FNAC) is now routinely used to arrive at a preoperative diagnosis. This can be used for both clinically palpable as well as screen detected non-palpable lesions which will need image-guidance to perform. The multidisciplinary triple approach is now the recommended way of managing breast lesions. the surgeon, radiologist and pathologist work closely as a team to determine the diagnosis, management, treatment and follow up of patients. IV. GYNAECOMASTIA AND MALE BREAST CANCER The most common disease of the male breast is gynaecomastia which is the enlargement of the male breast. The most common cause is cirrhosis of the liver with failure of oestrogen breakdown. It is also seen in Klinefelter's syndrome, some testicular tumours and as a drug effect. Carcinoma occurs in the male breast with an incidence of one-hundredth that seen in females. Its natural history closely resembles that of the disease in women. REFERENCES: Oxford Textbook of Pathology Vol. 2a, Chapter 22. Pgs Pathologic Basis of Disease. Robbins, Cotran and Kurmar. 6 th Edition. Chapter 25: The Breast. Pgs