Pathology of carcinoma breast

Pathology of carcinoma breast

1. Staging and Pathology of carcinoma breast -Dr Deepika Malik JR – II, Dept. of Radiotherapy

2. Staging The AJCC ( American Joint Committee On Cancer) staging is the most widely used staging systems for carcinoma breast.

3. Staging.. Major changes in 7 th edition of AJCC manual – Identified specific imaging modalities that can be used to estimate clinical tumor size,including mammography, USG, MRI Maintained that the term , “inflammatory carcinoma” be restricted to cases with typical skin changes involving a third or more of skin of breast.

4. Staging.. 3. classification of isolated tumor clusters and single cells is more stringent. Smallclusters of cells less than 0.2 mm or non confluent clusters of cells( <200 cells in a single histological lymph node are classified as isolated tumor cells. 4. stage I has been divided into IA and IB IB includes small tumors with exclusive micrometastasis in lymph nodes.

5. Staging.. 5. created new M0 ( i +) category, --presence of either disseminated tumor cells or found incidently in other tissues (such as ovaries removed prophylactically ) if not exceeding 0.2 mm.

6. Primary Tumor (T) Classification of primary tumor are same for clinical and pathological classification TX - Primary tumor cannot be assessed T0 - No evidence of primary tumor Tis - Carcinoma in situ Tis (DCIS) Ductal carcinoma in situ Tis (LCIS) Lobular carcinoma in situ Tis (Paget’s) Paget’s disease of the nipple NOT associated with invasive carcinoma and/or carcinoma in situ (DCIS and/or LCIS) in the underlying breast Note- Paget’s disease associated with a tumor are categorized based on the size

7. T1 - Tumor ≤ 2 cm in greatest dimension T1mi - Tumor ≤ 1 mm in greatest dimension T1a - Tumor > 0.1 cm but ≤ 0.5 cm in greatest dimension T1b- Tumor > 0.5 cm but ≤ 1 cm in greatest dimension T1c- Tumor > 1 cm but ≤ 2 cm in greatest dimension

8. T2 - Tumor > 2 cm but ≤ 5 cm in greatest dimension T3- Tumor > 5 cm in greatest dimension

9. T4 - Tumor of any size with direct extension to the chest wall and/or to the skin (ulceration or skin nodules) Note: Invasion of the dermis alone does not qualify as T4 T4a- Extension to the chest wall, not including pectoralis muscle adherence/invasion T4b- Ulceration and/or ipsilateral satellite nodules and/or edema (including peau d’orange ) of the skin, which do not meet the criteria for inflammatory carcinoma T4c- Both T4a and T4b T4d- Inflammatory carcinoma

10. AJCC definition of inflammatory carcinoma Staging as T4d requires these clinical features to be present: -diffuse erythema and edema involving a third or more of the skin of the breast. -Microscopically, dermal lymphatic invasion is typically seen in this setting, however dermal lymphatic invasion alone is NOT sufficient (nor necessary) to diagnose inflammatory carcinoma or stage pT4d. The clinical features must be present; if they are present but involve less than a third of the breast, AJCC states this should be staged as pT4b, not pT4d. Carcinoma that ulcerates the skin is staged as pT4b. If the clinical features are present but dermal lymphatic invasion is not, the patient may still be classified as inflammatory carcinoma and asT4d

11. Regional Lymph Nodes ( N) CLINICAL STAGING NX- Regional lymph nodes cannot be assessed (for example, previously removed) N0- No regional lymph node metastases N1- Metastases to movable ipsilateral level I, II axillary lymph node(s)

12. N2a- Metastases in ipsilateral level I, II axillary lymph nodes fixed to one another (matted) or to other structures N2b- Metastases only in clinically detected* ipsilateral internal mammary nodes and in the absence of clinically evident level I, II axillary lymph node metastases

13. N3a- Metastases in ipsilateral infraclavicular lymph node(s) N3b- Metastases in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) N3c- Metastases in ipsilateral supraclavicular lymph node

14. PATHOLOGICAL STAGING ( pN ) pNX - Regional lymph nodes cannot be assessed (for example, previously removed, or not removed for pathologic study) pN0- No regional lymph node metastasis identified histologically

15. pN0( i −) - No regional lymph node metastases histologically , negative IHC pN0( i +)- Malignant cells in regional lymph node(s) no greater than 0.2 mm (detected by H&E or IHC) pN0(mol−)- No regional lymph node metastases histologically , negative molecular findings (RT-PCR) pN0(mol+) - Positive molecular findings (RT-PCR)**, but no regional lymph node metastases detected by histology or IHC

16. pN1mi- Micrometastases (greater than 0.2 mm and/or more than 200 cells, but none greater than 2.0 mm) pN1a - Metastases in 1–3 axillary lymph nodes, at least one metastasis greater than 2.0 mm pN1b- Metastases in internal mammary nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected*** pN1c- Metastases in 1–3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected

17. pN2- pN2a- Metastases in 4–9 axillary lymph nodes (at least one tumor deposit greater than 2.0 mm) pN2b- Metastases in clinically detected internal mammary lymph nodes in the absence of axillary lymph node

18. pN3a -Metastases in >=10 axillary lymph nodes (at least one tumor deposit greater than 2.0 mm); or metastases to the infraclavicular (level III axillary lymph) nodes pN3b- Metastases in clinically detected ipsilateral internal mammary lymph nodes in the presence of one or more positive axillary lymph nodes; or >3 axillary lymph nodes and in internal mammary lymph nodes with micrometastases or macrometastases detected by sentinel lymph node biopsy but not clinically detected*** pN3c Metastases in ipsilateral supraclavicular lymph nodes

19. Distant Metastases (M) M0- No clinical or radiographic evidence of distant metastases cM0( i +) No clinical or radiographic evidence of distant metastases, but deposits of molecularly or microscopically detected tumor cells in circulating blood, bone marrow, or other nonregional nodal tissue that are < 0.2 mm in a patient without symptoms or signs of metastases M1- Distant detectable metastases as determined by classic clinical and radiographic means and/or histologically proven larger than 0.2 mm

20. Group staging

21. Pathological classification of carcinoma breast WHO classification AJCC histopathological classification of breast tumors

22. AJCC on Cancer histopathological classification of breast tumors In situ carcinomas    NOS     Intraductal ( in situ )    Paget's disease and intraductal Invasive carcinomas    NOS     Ductal    Inflammatory     Medullary , NOS     Medullary with lymphoid stroma     Mucinous    Papillary (predominantly micropapillary pattern)    Tubular    Lobular    Paget's disease    Undifferentiated     Squamous cell    Adenoid cystic     Secretory     Cribriform NOS, not otherwise specified

23. Microinvasive carcinoma Definition- extension of cancer cells beyond the basement membrane into the adjacent tissues with no focus more than 0.1 cm in greatest dimension. Staged as T1mic, a subset of T1 breast cancer. Note- when there are multiple foci of microinvasion , - the size of only the largest focus is used to classify the microinvasion - the sizes of the individual foci should not be added together.

24. Carcinoma in situ Neoplastic population of cells limited to ducts and lobules by basement membrane. Does not invade into lymphatics , blood vessels and cannot metastasize.

25. Ductal carcinoma in situ malignant population of cells limited to ducts and lobules by basement membrane. Is a clonal proliferation and usually involves only a single ductal system. However cells can spread through ducts and lobules--- acini get distorted and give appearance of small ducts.

26. Majority of DCIS cannot be detected on visual inspection or palpation. Sometimes when associated with periductal fibrosis --- thickening of tissue. Many cases of DCIS progress to invasive carcinoma.

27. Paget’s disease and intraducat carcinoma IS Rare, 1-2 % of breast cancer Malignant cells called as paget cells extend from DCIS to nipple skin without crossing basement membrane. Tumor cells disrupt the normal epithelial barrier and this allows extracellular fluid to seep out on nipple surface

28. Invasive (infiltrating) carcinoma Neoplastic population of cells invade beyond the basement membrane into stroma . May also invade vasculature, reach regional lymph nodes and also metastasize

29. Invasive (infiltrating) ductal carcinoma (IDC) most common type of breast cancer comprising more than 50% of all cases. appears as solid cords or groups of ductal tumor cells varying in size and cytoplasmic content and degree of differentiation

30. Invasive (infiltrating) ductal carcinoma of the breast

31. Inflammatory carcinoma Clinical presentation of carcinoma involving extensively dermal lymphatics resulting in large erythematous breast Typically does not form a discrete palpable mass This results in confusion with inflammatory breast conditions and delay in diagnosis. Staged as T4d.

32. Medullary carcinomas Composed of cords and masses of large cells with reticular pleomorphic nuclei with prominent nucleoli Scant fibrous stroma , prominent lymphoid infiltrate. Microscopically and grossly well circumscribed. Prognosis in general is better than other types. More common in young females.

33. Medullary carcinoma breast

34. Mucinous (colloid) carcinoma Exremely soft tumor Tumor cells seen as clusters and small islands of cells within large flakes of mucin . Slow growing Rare lymphatic invasion Overall prognosis is better than with IDC

35. Invasive Papillary carcinoma Growth of tumor cell clusters in prominent clear spaces resembling dilated angiolymphatic vessels. Rare, <1 % of invasive breast carcinomas.

36. Invasive papillary carcinoma breast

37. Tubular carcinoma breast Composed of tubular structures lined by a single layer of well differentiated epithelium Axillary metastasis is rare Exelllent prognosis.

38. Tubular carcinoma

39. Lobular invasive carcinoma Cells appear singly or in small clusters Aggressive , multicenric Prone for distant metastasis.

40. Metaplastic carcinoma breast Relatively rare Wide variety of rare types of breast cancer including adenocarcinoma , SCC,and carcinomas with prominent spindle component , difficult to distinguish from sarcomas.

41. Adenoid cystic carcinoma Rare in breast Prognosis is good.

42. Cystosarcoma phylloides Usually benign Large tumors Usually encapsulated Frequently develop from preexisting fibromas and have a long initial period of slow growth followed by sudden , rapid increase in size.

43. Primary breast lymphomas Rare, 0.4-0.5% Lymphoepithelial lesions in ducts and lobules, Frequent vascular invasion

44. Histological grading of breast tumors The grade of a breast cancer is representative of the "aggressive potential" of the tumor "low grade" cancers tend to be less aggressive than "high grade" cancers. Determining the grade is thus very important, and the clinicians use this information to help guide the treatment options for patients.

45. Nottingham Histologic Score system (the Elston -Ellis modification of Scarff -Bloom-Richardson grading system) In this scoring system, there are three factors that the pathologists take into consideration: -the amount of gland formation ("differentiation" or how well the tumor cells try to recreate normal glands) -the nuclear features (" pleomorphism “ ) -the mitotic activity (how much the tumor cells are dividing) Each of these features is scored from 1-3, and then each score is added to give a final total score ranging from 3-9. 

46. Glandular ( Acinar )/Tubular Differentiation Score 1 : >75% of tumor area forming glandular/tubular structures Score 2 : 10% to 75% of tumor area forming glandular/tubular structures Score 3 : <10% of tumor area forming glandular/tubular structures

47. Nuclear Pleomorphism Score 1 : Nuclei small with little increase in size in comparison with normal breast epithelial cells, regular outlines, uniform nuclear chromatin, little variation in size Score 2 : Cells larger than normal with open vesicular nuclei, visible nucleoli, and moderate variability in both size and shape Score 3 : Vesicular nuclei, often with prominent nucleoli, exhibiting marked variation in size and shape, occasionally with very large and bizarre forms

48. Mitotic Count The pathologist will count how many mitotic figures are seen in 10 high power fields. Using a high power field diameter of 0.50 mm, the criteria are as follows: Score 1 : less than or equal to 7 mitoses per 10 high power fields Score 2 : 8-14 mitoses per 10 high power fields Score 3 : equal to or greater than 15 mitoses per 10 high power fields

49. Grade 1( well diff) tumors - score of 3-5 Grade 2 (mod diff) -score of 6-7 Grade 3 (poorly diff) - score of 8-9

50. Hormone regulation The degree of exposure to estrogen is a well-established risk factor for developing ER-positive breast cancer. Estrogen is a steroid hormone that has a profound proliferative effect on normal human mammary epithelium through its activation of ER ER is overexpressed in as many as 70% of breast cancers. Carcinoma breast patients with hormonal receptors have a significantly higher survival rate.

51. Molecular subtypes

52. Model histopathological report ( WHO guidelines, 2006) For invasive carcinoma Laterality of breast and procedure Histological type Histological grade Margins of resection- - state if tumor is at the margin -if not at margin , distance from margin to be specified.

53. Lymph node status number of nodes removed number of nodes positive perinodal extension into fat +/- Lymphovascular invasion Size of tumor- maximum diameter ER/PR/Her2Neu status

54. For DCIS Laterality of breast and procedure Grade Necrosis- +/- Architectural type- cribriform , micropapillary,solid , comedo , papillary, mixed Margins Size

55. Model histopathology report ( TMH, 2009) • Tumour size (all 3 dimensions) • Tumour type • Tumour grade (Modified Richardson Bloom Score) • Presence of extensive intraductal carcinoma (EIC) • Lymphovascular embolisation • Cut Margin status (gross positive/ focal positive/ negative) in case of lumpectomy or wide excision • No. of positive/total axillary lymph node dissected Receptor status: ER and PgR (by IHC )

56. Thankyou