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Paget s carcinoma is not common (about 1% of all breast cancers) It affects the nipple and may or may not be associated with a breast mass The basic lesion is usually a well differentiated infiltrating ductal carcinoma or a ductal carcinoma in situ (DCIS) The ducts of the nipple epithelium are infiltrated, but gross nipple changes are often minimal, and a tumor mass may not be palpable Because the nipple changes appear innocuous, the diagnosis is frequently missed The first symptom is often itching or burning of the nipple, with superficial erosion or ulceration These are often diagnosed and treated as dermatitis or bacterial infection, leading to delay or failure in detection The diagnosis is established by biopsy of the area of erosion When the lesion consists of nipple changes only, the incidence of axillary metastases is less than 5%, and the prognosis is excellent When a breast mass is also present, the incidence of axillary metastases rises, with an associated marked decrease in prospects for cure by surgical or other treatment
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The lesions to be considered most often in the differential diagnosis of breast cancer are the following, in descending order of frequency: fibrocystic condition of the breast, fibroadenoma, intraductal papilloma, lipoma, and fat necrosis
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The American Joint Committee on Cancer and the International Union Against Cancer have agreed on a TNM (tumor, regional lymph nodes, distant metastases) staging system for breast cancer Using the TNM staging system enhances communication between researchers and clinicians Table 16 2 outlines the TNM classification
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2 Inflammatory Carcinoma
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This is the most malignant form of breast cancer and constitutes less than 3% of all cases The clinical findings consist of a rapidly growing, sometimes painful mass that enlarges the breast The overlying skin becomes erythematous, edematous, and warm Often there is no distinct mass, since the tumor infiltrates the involved breast diffusely The diagnosis should be made when the redness involves more than one-third of the skin over the breast and biopsy shows infiltrating carcinoma with invasion of the subdermal lymphatics The inflammatory changes, often mistaken for an infection, are caused by carcinomatous invasion of the subdermal lymphatics, with resulting edema and hyperemia If the practitioner suspects infection but the lesion does not respond rapidly (1 2 weeks) to antibiotics, biopsy should be performed Metastases tend to occur early and widely, and for this reason inflammatory carcinoma is rarely curable Radiation, hormone therapy, and chemotherapy are the measures most likely to be of value rather than operation Mastectomy is indicated when chemotherapy and radiation have resulted in clinical remission with no evidence of distant metastases In these cases, residual disease in the breast may be eradicated
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Numerous pathologic subtypes of breast cancer can be identified histologically (Table 16 3) These types are distinguished by the histologic appearance and growth pattern of the tumor In general, breast cancer arises either from the epithelial lining of the large or intermediate-sized ducts (ductal) or from the epithelium of the terminal ducts of the lobules (lobular) The cancer may be invasive or in situ Most breast cancers arise from the intermediate ducts and are invasive (invasive ductal, infiltrating ductal), and most histologic types are merely subtypes with unusual growth patterns (colloid, medullary, scirrhous, mucinous, etc) Ductal carcinoma that has not invaded the extraductal tissue is intraductal or in situ ductal Lobular carcinoma may be either invasive or in situ In situ lobular carcinoma is primarily a risk factor for the development of invasive ductal cancer Except for the in situ cancers, the histologic subtypes have only a slight bearing on prognosis when outcomes are
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Breast
CMDT 2008
Table 16 2 TNM staging for breast cancer
Primary Tumor (T) Definitions for classifying the primary tumor (T) are the same for clinical and for pathologic classification If the measurement is made by physical examination, the examiner will use the major headings (T1, T2, or T3) If other measurements, such as mammographic or pathologic measurements, are used, the subsets of T1 can be used Tumors should be measured to the nearest 01 cm increment TX T0 Tis Tis (DCIS) Tis (LCIS) Tis (Paget s) Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in situ Ductal carcinoma in situ Lobular carcinoma in situ Paget s disease of the nipple with no tumor N3a N3b N3c pNX pN0 N2a N2b Metastasis in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures Metastasis only in clinically apparent1 ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasis Metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary lymph node involvement, or in clinically apparent1 ipsilateral internal mammary lymph node(s) and in the presence of clinically evident axillary lymph node metastasis; or metastasis in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement Metastasis in ipsilateral infraclavicular lymph node(s) Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) Metastasis in ipsilateral supraclavicular lymph node(s)
Note: Paget s disease associated with a tumor is classified according to the size of the tumor T1 T1mic T1a T1b T1c T2 T3 T4 T4a T4b Tumor 2 cm or less in greatest dimension Microinvasion 01 cm or less in greatest dimension Tumor more than 01 cm but not more than 05 cm in greatest dimension Tumor more than 05 cm but not more than 1 cm in greatest dimension Tumor more than 1 cm but not more than 2 cm in greatest dimension Tumor more than 2 cm but not more than 5 cm in greatest dimension Tumor more than 5 cm in greatest dimension Tumor of any size with direct extension to (a) chest wall or (b) skin, only as described below Extension to chest wall, not including petoralis muscle Edema (including peau d orange) or ulceration of the skin of the breast, or satellite skin nodules confined to the same breast Both T4a and T4b Inflammatory carcinoma Regional lymph nodes (N) Clinical NX N0 N1 N2 Regional lymph nodes cannot be assessed (eg, previously removed) No regional lymph node metastasis Metastasis to movable ipsilateral axillary lymph node(s) Metastases in ipsilateral axillary lymph nodes fixed or matted, or in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis
Pathologic (pN) 2 Regional lymph nodes cannot be assessed (eg, previously removed, or not removed for pathologic study) No regional lymph node metastasis histologically, no additional examination for isolated tumor cells
Note: Isolated tumor cells (ITC) are defined as single tumor cells or small cell clusters not greater than 02 mm, usually detected only by immunohistochemical (IHC) or molecular methods but which may be verified on hematoxylin and eosin stains ITCs do not usually show evidence of malignant activity, eg, proliferation or stromal reaction
pN0(i ) pN0(i+) pN0(mol ) pN0(mol+)
No regional lymph node metastasis histologically, negative IHC No regional lymph node metastasis histologically, positive IHC, no IHC cluster greater than 02 mm No regional lymph node metastasis histologically, negative molecular findings (RT-PCR) No regional lymph node metastasis histologically, positive molecular findings (RT-PCR) Metastasis in one to three axillary lymph nodes, and/or in internal mammary nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent1 Micrometastasis (greater than 02 mm, none greater than 20 mm) Metastasis in one to three axillary lymph nodes Metastasis in internal mammary nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent1 Metastasis in one to three axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent1 (If associated with greater than three positive axillary lymph nodes, the internal mammary nodes are classified as pN3b to reflect increased tumor burden) (continued)
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