MALIGNANT TUMOURS OF THE BREAST BY DR. HOSAM ELSROGY

1. MALIGNANT TUMOURSOF THE BREASTBYDR. HOSAM ELSROGY

2. SARCOMA Incidence Pathology Clinical Picture • General incidence: rare (0.5-1% of malignant tumors of the breast). • Age incidence: the commonest age ranges between 30 & 40 years. • It may develop de novo or o top of soft fibroadenoma. • It includes fibrosarcoma, liposarcoma, rhabdomyosarcoma & angiosarcoma. • M.P: Spindle cell sarcoma (the commonest type), round cell sarcoma, or mixed cell sarcoma. • The tumor forms a fleshy massive swelling, which infiltrates the breast, does not fix (usually) to the underlying structures but fungates through the skin & disseminates to lungs & viscera. • The swelling is highly vascular with variable consistency. The skin becomes stretched & shows dilated veins. • Lymph nodes are characteristicallynotnecessarily enlarged.

3. Differential Diagnosis: 1.Breast Abscess Severe throbbing pain Fired red skin Firing edema Temperature 39-40°C Leucocytosis Pus on aspiration Sarcoma Mild pain.Dusky red skin Non-pitting edema Temperature 37-3 8°C No leucocytosisNo pus on aspiration 2.Encephaloid carcinoma (areas of cystic degeneration are usually suggestive of sarcoma). 3.Cystosarcoma phylloides Treatment: A multimodality treatment: Simple mastectomy + Radiotherapy + Chemotherapy. Prognosis: Prognosis is usually very poor.

4. CARCINOMA INCIDENCE : General Incidence Age Sex Race Site ETIOLOGY / RISK FACTORS Reproductive Experience Ovarian Activity Hormonal Factors Age Sex Race Genetic predisposition Multiple 1ry cancers Diet & Obesity Precancerous conditions& carcinogens

5. INCIDENCE: General Incidence: It is the commonest malignant tumor in women (= 25% of all female cancers). Age: Any age after puberty can be affected with a maximum incidence at 40-50Y (till menopause). There may be two peaks of incidence; at 45 & 65 years of age. Sex (Gender): Female to male ratio is 99:1. Race: It affects white races > black races. It is more common in USA & Europe than in Japan. Site: The upper outer quadrant (containing the axillary tail) is the commonest site & the lower inner quadrant is the least affected, tubular carcinomahas special characteristics; multicentricity& bilaterality

6. PATHOLOGY Gross appearance Histological types 1-Foot & stewart classification . Paget`s disease . carcinoma of duct origin . carcinoma of lobular origin 2-Ackermann classification . neoplasms of mamary tissue . malignant mesenchymal neoplasm . malignant neoplasm of skin & skin adnexa . metastatic neoplasms

7. Gross appearance • A hard, poorly defined, grayish white mass with areas of hemorrhage and necrosis ± calcification. • Ramifying processes are seen extending from the tumor to the surrounding tissue. • Extension of the tumor through the fascia and muscles leads to its fixation. • The skin may be involved leading to ulceration or nodule formation. • Lymph nodes may be involved. They become enlarged, hard and may be matted.A cut section shows grayish yellow areas due to metastatic deposits. Histological types

8. I. Foote & Stewart Classification • Paget's disease of Nipple • 2. Carcinoma of Duct Origin • A. Non-infiltrating (in-situ, intraductal) • B. Infiltrating: • Scirrhous (carcinoma simplex). • Medullary. • Colloid. • Comedo. • Papillary. • Tubular. • 3. Carcinoma of Lobular Origin • A. Non-infiltrating (in-situ). • B. Infiltrating:

9. 2-Ackermann classificationneoplasmes of mammary tissue; A..neoplasmes of lobular epithelial origin:1.lobular carcinoma in situ2.lobular carcinoma invasive B neoplasmes of ductal epithelial origin1.non infiltrating carcinomaa. intraductal carcinoma, non invasiveb. intracystic papillary carcinoma, non invasive2.infiltrating ductal carcinoma:a)carcinoma simplex = non-otherwise specifiedb) special types.scirrhous.medullary.colloid (mucoid, mucinous).comedo.papillary.cribriform.secretoryC. unusual presintations:1. inflamatory carcinoma2. pagets disease of the nipple& areola

10. MALIGNANT NEOPLASMES OF MESENCHYMAL ORIGIN;1. SARCOMA2.LYMPHOMAMALIGNANT NEOPLASMES OF SKIN& SKIN ADNEXA:skin neoplasmes: squamous cell carcinoma, basal cell carcinoma.Skin adnexa neoplasmes; carcinoma of sweat or sebaceous glandsMETASTATIC NEOPLASMES:1. FEMALES;adults: from melanoma,other breast, endocrinal tumors children: from hemopoitic tumors rabdomyosarcoma2. MALES: from prostatic carcinoma

13. Lobular Carcinoma • Carcinoma originating in the terminal ductules of the lobules. It is often bilateral & family history may be positive. It is either non-invasive (m-situ) or invasive. • M.P: Terminal lobules are packed with small, hyperplastic, uniform cells, often arranged in rows or beads with mitoses, hyperchromatism & nuclear anaplasia.

14. B. Ductal Carcinoma • 1. Non-infiltrating (Ductal Carcinoma in-situ = DCIS): • The cells have the microscopic characteristics of malignancy but do not invade the basement membrane of the ductal epithelium. Multicentricity within the same (ipsilateral) breast is common. • 2. Infiltrating Duct Carcinoma (IDC): • a) Scirrhous Carcinoma (simplex = IDC with productive fibrosis): • It is the commonest variety constituting about 75-80% of invasive carcinomas. • It is so called because of its hard consistency & occurs typically in middle-aged females.NEA: • The tumour is rather small in size and may be fixed firmly within the breast substance, and liesmost often in the upper outer quadrant (UOQ). When sectioned with a knife, the cut surface: • Gives a gritty sensation (due to small spiules of calcification). • Becomes concave due to its retraction. • Has a gray color with yellow specks of necrotic tissue. • Has an infiltrating edge without any form of capsule.

15. M.P: Irregular groups and columns of spheroidal cells in a dense fibrous tissue stroma. There is a great variation in cellularity; in some cases the malignant cells are relativelyscanty, presenting finger-like processes in the copious stroma; in others there are solidmasses of tumor cells with relatively little connective tissue. Mitotic figures are present only in small numbers, because the tumor grows slowly & celldivision is infrequent. • b) Medullary (Encephaloid) Carcinoma: • It occurs typically in well-developed breasts of young women, in the form of a rapidlygrowing large fleshy mass which infiltrates widely & disseminates early • NEA: brain-like cut surface (encephaloid) with areas of hemorrhages & necrosis. • M.P: • Masses of highly malignant cells with marked lymphocytic infiltration supported in adelicate vascular stroma.

16. c) Mucoid Carcinoma (Colloid or Mucinous Adenocaricnoma): • A rare type (1%) in the form of a bulky soft well-demarcated though non-capsulated mass with areas of mucoid degeneration & necrosis. It may reach an enormous size, but grows slowly & disseminates late so that the prognosis after operation is favorable. • MP: • the mucoid material distends the cells to form signet-ring shaped cells & may be set free in the intercellular stroma. d) Comedo Carcinoma: It has characteristic plugs of pasty material expressible from the surface of the neoplasm. NEA: Well-circumscribed, firm, grayish mass. M.P: Cores of highly cellular epithelial tissue with focal calcifications occluding the ducts.

17. e) Papillary Carcinoma: It has the lowest frequency of axillary nodal involvement with the best 5-year survival. It typically appears in younger age groups (35-40 y). Nipple discharge (bloody) is common. NEA: Bulky mass, centrally located. M.P: Large sheets of cells with papillary formation. Cells show numerous mitoses, hyperchromatism, and loss of polarity f) Tubular Carcinoma: A rare (1%) well-differentiated ductal lesion that forms tubules. It has a relatively good prognosis.

18. C. Carcinomas with Unusual Presentation • 1. Acute Inflammatory Carcinoma (Mastitis Carcinomatosa): • It is the most malignant form, but represents <3% of all cases. It is called inflammatory or lactational carcinoma as it usually occurs in the lactating hypertrophied breast. • The breast becomes diffusely swollen, painful, tender & hot on palpation, with dilated veins on the overlying skin so that the condition is often mistaken for acute mastitis. However, there is no pyrexia, no leucocytosis, no responseto antibiotics, no tender lymph nodes (though enlarged), besides it is a rapidly growing & spreading tumor. • M.P: Very rapid proliferation of anaplastic cells with very little fibrous reaction so that the turnpr may resemble a sarcoma. The inflammatory changes are caused by carcinomatous invasion of the dermal lymphatics resulting in edema & hyperemia.

21. 2. Paget's Disease: It is a rare disease (1%), of middle aged & elderly women. It begins as a malignant eczema (due to intradermal lymphatic obstruction, epitheliosis & invasion of dermis by Paget's cells. It erodes the nipple & spreads peripherally for about 2 years by which time a scirrhous carcinoma appears within the breast. It is believed to arise in the terminal ducts as an intraductal cancer, which spreads both, out\vards to affect the nipple & skin, and inwards to produce the underlying carcinoma. M.P: by hyperplasia of all layers of epidermis withthe presence of large vacuolated cells withsmall deeply stained nuclei in the deeperlayers of the epidermis (Paget's cells) +epidermoid hypertrophy + subdermal roundcell infiltration. N.B. Paget's disease may be extra-mammary affecting the axilla, groin, umbilicus, and perianal region.

24. • It should be differentiated from: eczema

25. According to cellular growth pattern, breast cancer may be classified into 4 types as follows:

26. SPREAD OF BREAST CANCER; • 1. Direct (Local) Spread: • From the site of origin, malignant cells invade the surrounding "corpus mammae" & adjacent soft tissue & then spread to involve the overlying skin in various ways (dimpling, peau d'orange, nodules ...etc). • In late cases, the tumor invades also deeply to involve the deep fascia & chest wall. • 2. Lymphatic Spread: • The main drainage from the breast is towards the axilla. Usually the first L.Ns to be affected are those in the pectoral group, later the central & finally the apical group. In 5-10% of unselected cases, the internal mammary L.Ns. are involved before the axillary L.Ns. • Once the tumor invades the lymph vessels, it spreads by permeation & embolization to the L.Ns, which become full with malignant cells & enlarge significantly. By permeation & embolization, malignant cells reach the subareolar & fascial pectoral plexuses, and then along other pathways: • Laterally —> axillary L.Ns (pectoral, central & apical) & then —> supraclaviculai L.Ns. • Medially -> internal mammary & mediastinal L.Ns. then -» opposite breast & axilla. • Upwards —> supraclavicular L.Ns directly. • Downwards -> rectus sheath, falciform ligament, liver & peritoneum. • Deeply —> infraclavicular L.Ns & then —> Apical axillary L.Ns by piercing the fascia. • • Virchow 's L.Ns (left supraclavicular) are involved (=Trousier sign) via mediastinal L.Ns & thoracic duct.

27. 3. Blood Spread: • Blood bome emboli are carried to the lungs first, and then through the pulmonary capillary bed to other sites (bones, brain, liver). • Bone metastases may occur without lung metastasis via vertebral veins where emboli pass via the intercostal veins to the vertebral system. The most common sites affected are the ribs, spine, skull, pelvis, and upper ends of femur & humerus. Bone metastases are almost always osteolytic wherever they occur;however, they may be osteosclerotic if the 1™ was of the scirrhous type. • Voluntary muscles are practically never involved (due to their metabolic property or because by contracting they expel the malignant cells before having time to engraft). • The spleen also, is rarely affected (it is not properly understood why?) • 4. Transcelomic Spread: • Spread reaches the peritoneum first, then the liver, pelvic organs & Douglas pouch (Plummer's shelf or Sheraton's shelf). • Recently, involvement of theovary (Krukenburg tumor) is believed to be bybloodspread& not transcelomic because the outer surface of the ovary is almost always free

28. CLINICAL FEATURES; • I. (Complaints) Symptoms • Main Complaints: • Lump in the breast. • Pain (usually in late stages, except in mastitis carcinomatosa). • Discharge (blood-stained). It may be the first symptom as in duct carcinoma. • Symptoms due to Spread: • Direct: skin, nipple & areola manifestations. • Lymphatic: Lump in the axilla (Lymph node enlargement). • Blood: Respiratory distress & hemoptysis (lungs), bone ache, pathological fractures (bones), malignant ascites or metastatic lumps (nodules) anywhere in the body.

29. II. Signs (Clinical Examination) • General Examination: • Chest: Pleural effusion, pulmonary deposits & enlarged mediastinal L.Ns. • Abdomen: Hepatomegaly, malignant ascites & peritoneal deposits. • Pelvis: PV & PR examination to detect secondaries in the ovaries (Krukenburg's disease). • Bones: Tenderness, weakness, deformity & pathological fractures. Local & Regional Examination: 1. Lump in the Breast: A malignant tumor can be differentiated from a B.T. by the following characteristics: It is felt by the flat of the hand than by fingertips. It is not tender. It is stony hard, irregular better in shape, with ill-defined borders & flat deep surface. It may be anchored in its bed. Fixation to skin or chest wall occurs late. • 2.Nipple Changes: • Depression, Destruction, Discharge, • Displacement, Deviation, and Discoloration • Recent Retraction It results from neoplastic fibrosis & lactiferous duct invasion. It should be differentiated from other causes of nipple retraction i.e. congenital & chronic inflammation. • Erosion (Destruction): It results from malignant eczema or Paget's disease.

30. Discharge: Usually there is no nipple discharge, but in duct carcinoma a bloody discharge is present, and in scirrhous carcinoma, a crystal clear discharge is rarely observed. • 3. Breast Changes: (Fibrosis causes the following): • It becomes puckered & displaced. • It is pulled upward on raising arms above the head • It does not protrude freely when the patient leans forwards. • 4.Skin Changes: • Dimpling: It is the earliest manifestation & results from contraction or pull of the ligament of Cooper.It is more evident on raising the arm or leaning forwards. • Puckering: It is due to tumor attachment to the skin & fibrosis with enfolding of the skin. • Dilated veins: Due to increased vascularity of the breast & block of the venous return.

31. Peau d'orange: Edema of the skin due to dermal & subdermal lymphatic obstruction. Sites of hair follicles appear as pits on the edematous skin as they are more attached to the subcutaneous tissueThey may also occur with chronic breast abscess or FCD. • Skin lymphedema: Due to obstruction of the lateral lymphatic trunk (drains the breast skin). • Fixation of the skin to the tumor: Due to growth of the tumor beneath the skin. • Cancerous nodules & satellites: Due to retrograde tumor spread to the skin. • Malignant ulceration or fungation due to extensive skin invasion. • Cancer-en-Cuirasse (late): Indurated thickening of the skin due to diffuse infiltration of the dermis (skin) by malignant cells in addition to lymphedema (obstruction of the deep lymphatics).It extends as a semirigid case around the chest and may involve the neck, arm & trunk. • Inflammatory Signs: In case of acute cancer of pregnancy & lactation. • Nipple & areola changes

32. 5. Opposite Breast: • Metastases may be detected on careful palpation, but when seen early, it seems more probable that it should be regarded as independent 1ry growth. • Since the two breasts are identical in structure, in function, and in their response to hormonal influence it is not surprising that the liability to cancer is also shared. • It seems that in such cases both breasts have been the site of FCD especially such types as lobular carcinoma in-situ which gives multifocal nodules of true invasive cancer. • Lymph Nodes (L.Ns): • Axillary & supraclavicular L.Ns on both sides should be examined for enlargement, consistency, tenderness & mobility. They become enlarged, hard, not tender, mobile but fixed later. • 7. The Arms: • The arms are palpated for swelling, skin nodules or other abnormalities. In late cases of cancer, the arm may be swollen due to lyrnphedema or venous thrombosis

33. III. Special Clinical Situations of Breast Cancer • Inflammatory Carcinoma: • Clinically, there is a rapidly growing mass, sometimes painful. The overlying skin is erythematous, edematous & warm. Often there is no distinct mass when the tumors infiltrate the breast diffusely, • It should be differentiated from acute breast abscess. Diagnosis should be put in mind if redness involves >l/3 of the skin over the breast & if there is no response to antibiotics within 1-2 weeks. • Paget's Disease: • C/O: Burning sensation with itching & tenderness, and occasionally, bleeding per nipple. • The surface of the nipple & areola is encrusted, scaly, hyperemic & may be eroded & destroyed. • A palpable subareolar mass may be felt.It should be differentiated from eczema.

34. C. Breast Cancer During Pregnancy & Lactation: • About 1-2% of breast cancer occurs during pregnancy & lactation. • The problems encountered by the physician are the following: • The tumor is in adverse circumstances: • (1) Delayed diagnosis due to enlargement of the breastwhich may mask the tumor, • (2) increased hormone levels, lymphatics & hyperemia, • (3) Reduced immunity, and • (4) most tumors (70%) are estrogen receptor negative. • Weapons are lacking: radiotherapy, chemotherapy & hormonal therapy are all contraindicated. • Surgery may induce abortion in the 1SI trimester or premature labor in the last trimester. • D. Bilateral Breast Cancer: • Breast cancer may occur simultaneously in both breasts in about 1% of cases, and later on (metachronous) in 5-8% of cases. • Bilaterality is more common in women below 50 years of age, lobular or comedo carcinoma, and positive family history. • E. Breast Cancer in Children & Adolescents: • Breast Cancer, whether carcinoma, sarcoma, or metastases from other areas, is rare in childhood & adolescence. At most, 3-4 cases of Iry breast cancer/ year occur in women below 20 years, in USA. • • Any unusual appearance of a breast lesion at children is an indication for biopsy.

35. INVESTIGATIONS: • I. Laboratory Investigations • General Tests:Complete blood picture, bleeding time, coagulation time, Hb%, glucose level...etc. • Liver Functions Tests (LFT):Alkaline phosphatase, bilirubin, liver enzymes (AST, ALT). • Renal Function Tests: Serum urea & creatinine. • Cytological Examination of Nipple Discharge: As a rule, mammography or biopsy is required when nipple discharge (or cyst fluid) is bloody. • Biochemical Tumor Markers: • Urinary hydroxyproline (HYPRO):Massive spread, especially to the bone causes breakdown of collagen, which results in t excretion in urine as hydroxyproline (Normal level = 35 mg/dl). • Alkaline phosphatase(t in bone & liver metastases). • Hypercalcemia (Occurs in advanced breast cancer - Plasma Calcitonin (useful in staging). • Blood count (anemia or pancytopenia occurs with bone marrow involvement). • Others: ESR (may t in disseminated cancer), Serum ferretin, Alpha-feto protein (AFP), Carcino-embryonic antigen (CEA), Human chorionic gonadotrophin (HCG), and iC-cassein.

36. II. Radiological Investigations (Breast Imaging Techniques) • 1. Soft Tissue Mammography: • It is the only reliable means of detecting breast cancer before a mass can be palpated in the breast. Although false positive & false negative results occasionally occur, mammograms are correctly interpreted in over 90% of cases. • Mammography is never a substitute for biopsy because it may not reveal clinical cancer in a dense breast as in young women with mammary dysplasia. Also, it often fails to reveal medullary carcinoma. • Mammographic features suspicious of malignancy ARE: • Punctate calcifications (similar to salt) in 30% of cases (i.e.clustered, irregular • microcalcifications). • The lump shows a dense shadow with very irregular outlines against the softer shadow of the breast. • 2RY breast changes (asymmtery, architectural distortion) & nipple retraction.

37. Mammographic features OF Benign Tumor • Course calcification • (fibroadenoma) in 30% of cases. • The lump appears as a homogenous dense smooth lesion. • A surrounding halo of a thin radiolucent layer of fat. • Ultrasonography (US): • It can differentiate between solid & cystic lesions. • It cannot diagnose early cancer because it can neither detect lesion <0.05 cm nor rmcrocalcifications, Computerized Tomography: Can be used for diagnosis of breast cancer but uses large doses of radiation Magnetic Resonance Imaging (MRI): Cannot detect microcalcifications & is still under evaluation

39. 2. Xerography: • mammography made on a selenium plate producing positive It is a method of impression with accentuation of density differences. • Although xerography is very sensitive, yet ordinary film of mammography (film screen) ispreferred because it is accomplished with a lower dose of irradiation. • 3. Galactography: • The secreting duct is cannulated & sterile water-soluble contrast material is injected until the patient feels discomfort & then 2 projections of mammography are taken. • It is particularly valuable in cases of nipple discharge as it can show the nature, site and size of the underlying lesion especially when clinical examination & mammography are negative. • 4. Thermography (Heat Map of the Breast): • General Rule: It is not essential for diagnosis (C/E & mammography are enough in 98% of cases). • Indications: {never for detection}, • Coupled with mammography in high-risk patients, it yields better surveillance of the other breast, • Follow-up of irradiated breast (persistent hyperthermic zone after irradiation is a bad sign) • Prognostic: The pattern of thermal changes varies according to the severity of the disease. • • Appearance Malignant Breast Lesions: Hyper-vascularization, hot spot > 3°C, diffuse t intemperature (> 2°C), edge sign (loss of convex margin of breast), and L.N secondaries (hotter if cancer is on the same side) especially supra & infraclavicular L.Ns.

40. III. Imaging Techniques for Metastases • Plain X-ray (PXR) of the chest & suspected bones. • Computerized Tomography (CT) of the liver & brain (when metastases are suspected). • Bone Scanning using ""Tc-labeled phophates is more sensitive than PXR in detecting bone metastases. • Lymphsintigraphy: For detection of axillary L.Ns before being detected clini

41. IV. Breast Biopsy • 1. Open Biopsy:• • It provides enough tissue material of the tumor for:Histologic Diagnosis (type & grade of the tumor). • Hormone Receptor Estimation (estorgen & progesterone receptors): Receptor-positive tumorsrespond more to hormonal therapy & have a better prognosis than receptor-negative tumors. • Flow Cytometry to determine if the tumor is diploid or aneuploid, and to determine the S-Phase Fraction. Aneuploid tumors with a large S-Phase Fraction have poor prognosis. • •Methods: • /. Paraffin-Section Biopsy: • •Excisional Biopsy: It is the best method & could be done in the operating room undergeneral anesthesia, or in the outpatient clinic under local anesthesia. • •Incisional Biopsy: It is more appropriate in patients with large or deeply seated carcinomas.

42. 2. Frozen-Section Biopsy: • A glance at the cut section intra-operatively often indicates the nature of the tumor, which should be confirmed by immediate histological examination by the frozen-section technique. If the tumor proves malignant, all instruments & towels are changed & the radical procedure is carried out. • Limitations of frozen-section: • (1) It needs an expert pathologist, • (2) Few sections areusually done because of short time, • (3) Freezing causes nuclear changes & may interfere with diagnosis.

43. 3. Needle Biopsy: • If results are negative, it should be followed by an open biopsy because false negative results are obtained in about 15-20% of cases. • Methods. • a) Fine Needle Aspiration Cytology (FNAC): • Advantages: • (1) No need for local anesthesia, and (2) it does not cause dissemination. • b) Core Biopsy: • Under local anesthesia, through a small 2 mm incision a special needle is inserted ( Tru-cut needle).

44. DIAGNOSIS OF BREAST CANCER: • A. Diagnosis of the Lump: • 1.Clinical Assessment: • History Taking: Special notes should be made for breast cancer risk factors, relation of the mass to the menstrual cycle, previous breast problems, and any systemic complaint. • Examination: It should be performed with the patient sitting (arms at sides & then upwards overhead) and then when lying down. The upper outer quadrant is most commonly affected because it contains the largest volume of breast tissue. The smaller the size of the lump, the lesser the chance of lymph node metastases. • Biopsy: for confirmation of diagnosis of cancer & histological grading. • Breast Imaging Techniques (Mammography is the best). • Cytological Examination of nipple discharge. • B. Diagnosis of Spread by Lymph Nodes: • Clinical Picture: Palpable lymph nodes (axillary, supraclavicular & internal mammary). • Chest X-ray (CXR): may show enlarged mediastinal lymph nodes. • Biopsy: Histological examination of L.Ns removed at surgery may show a 25% clinical error • Radioactive Isotope Scanning using "c Tm (Lymphsintigraphy). • C. Diagnosis of Systemic Spread:

47. C. Diagnosis of Systemic Spread: • 1. Clinical Criteria: • Tumor size, skin affection & chest wall fixation. • Axillary & supraclavicular lymph node enlargement. • Distant metastases. • 2. Investigations: • Radiological: • PXR (chest & bones), Isotope scanning (liver, bone and brain), US, CT, MRI. • Biochemical: • Anemia/pancytopenia (bone marrow), Urinary HYPRO (bone), AP (liver & bone), Hypercalcemia (bone), Serum ferretin, AFP, CEA, HCG.

48. STAGING OF BREAST CANCER: 1. Clinical Staging A. International Classification (Manchester); 188

49. B. TNM Staging N (Lymph Nodes) T (Tumor) M (Metastases) • Mo = No known distant • metastases. Ml = Positiye distant • metastases. To = No demonstrable tumor. T1 = Tumor < 2 cm: T1a: No deep fixation. T1b: With deep fixation. T2 = Tumor 2-5 cm: T2a: No deep fixation. T2b: With deep fixation. T3 = Tumor 5-10 cm: T3a: No deep fixation. T3b: With deep fixation. T4 = Tumor of any size: T4a: Direct chest extension. T4b: Skin involvement. T4c: T4a + T4b. No = Not palpable (axillary L.Ns). Nl = Palpable (axillary L.Ns). Nla: clinically not malignant. NIb: clinically malignant. N2 = Palpable axillary L.Ns (clinically malignant & fixed). N3= Palpable homolateral supra- orinfra- clavicular L.Ns (malignant & fixed).

50. To T1 T2 T3 T4