breast carcinoma part various types1.pptx

breast carcinoma

1. Introduction Breast carcinoma is the most common malignant tumor and the second most common cause of carcinoma death in women . Women who live to age 90 have a one in eight chance of developing breast cancer

2. Etiology The etiology of breast cancer in most women is unknown but most likely is due to a combination of genetic, hormonal and environmental factors. Breast carcinomas can, therefore, be divided into S poradic cases - related to hormonal exposure. Hereditary cases- associated with family history or germ-line mutations.

3. Risk Factors Country of origin- High incidence - North America and northern Europe, Intermediate - southern European and Latin American countries, Low - most Asian and African countries. Family history :- >1 first degree relative, young age, multiple cancers – RR >4 First degree relative – RR 2.1 - 4.0

4. Menstrual and reproductive history :- Early menarche(<12 years), Late menopause(>55years). Late age at first birth,(>35 years) Nulliparity, Absence of breast feeding Postmenopausal women with a hyperandrogenic plasma hormone profile.

5. Risk-reducing salpingo-oophorectomy <35 years of age - RR reduced by ½. Younger age at first pregnancy Longer the period of breast feeding Bi lateral oophorectomy:- bre ast carcinoma is rare.

6. Exogenous estrogens . Contraceptive agents . Ionizing radiation .

7. Genetic Predisposition Approximately 5%–10% of all breast cancers are familial. Mutations in BRCA1 and BRCA2 are responsible for 80-90% of single gene familial breast cancers and about 3-6% of all breast cancers.

8. Syndromes associated with hereditary breast cancer Syndrome Gene involved Clinical features Hereditary breast cancer and ovarian cancer syndrome BRCA1 Breast cancer, High risk (50-80%) Ovarian cancer, high risk (40-50%) Hereditary breast cancer and ovarian cancer syndrome BRCA2 Breast cancer, High risk (50-70%) Ovarian cancer, intermediate risk (10%) Prostate cancer, Pancreatic cancer, melanoma Li-Fraumeni 2 syndrome CHECK2 Breast cancer, intermediate risk (about two fold), Sarcomas, brain tumours Familial linitis plastica type gastric cancer and lobular breast carcinoma syndrome CDH1 Gastric cancer, lobular breast cancer

9. Syndrome Gene involved Clinical features (FANC)Fanconi anaemia syndrome PALB2 FANCN, FANCA, FANCE, BRIP1 FANCJ PALB2/FANCN and BRIP1/FANCJ : moderate risk of breast cancer development Other FANC genes: low risk of breast cancer development

10. Syndrome Gene involved Clinical features Louis-Bar syndrome ATM Lymphoma , cerebellar ataxia, immune deficiency, glioma, medulloblastoma, breast cancer Li-Fraumeni syndrome TP53 High penetrance of breast cancer at young age Risk of soft tissue sarcomas and osteosarcomas, brain tumours, leukaemia and adrenocortical carcinoma Cowden Syndrome PTEN Increased risk of developing neoplasms( breast cancer, thyroid carcinoma, endometrial carcinoma and others) Hamartomatous polyps of gastrointestinal tract Mucocutaneous lesions

11. Syndrome Gene involved Clinical features Bannayan -Riley- Ruvalcaba syndrome PTEN Breast cancer, meningioma, follicular cell tumour of the thyroid Peutz - Jeghers syndrome STK11 Melanocytic macules of the lips, buccal mucosa, and digits Multiple gastrointestinal Hamartomatous polyps Increased risk of various neoplasms( breast, testis, pancreas and cervix) Lynch cancer family syndrome II MSH2, MSH3, MSH6, MLH1, PMS1, PMS2 Increased risk of endometrial carcinoma & colorectal carcinoma High risk of multiple primary malignant neoplasms, including breast, ovarian, gastrointestinal, and genitourinary carcinomas, sarcomas, glioblastoma, and leukemia

12. LOCATION Approximately 33% are in the Upper Outer quadrant, 9% in the upper inner quadrant, 6% in the lower outer quadrant, 5% in the lower inner quadrant, 7% in the central region (within 1 cm of the areola),

13. 40% occur in overlapping quadrants 33% 9% 6% 5% 7% UOQ UIQ LIQ LOQ

14. Classification of breast cancer ( Based on WHO 2019 classification of breast tumours)

15. Benign epithelial proliferations and precursors Usual ductal hyperplasia Columnar cell lesions including flat epithelial atypia Atypical ductal hyperplasia Adenosis and benign sclerosing lesions Sclerosing adenosis Apocrine adenoma Microglandular adenosis Radial scar / complex sclerosing lesion

16. Adenomas Tubular adenoma, NOS Lactating adenoma Duct adenoma, NOS Epithelial myoepithelial tumors Pleomorphic adenoma Adenomyoepithelioma , NOS Adenomyoepithelioma with carcinoma Epithelial myoepithelial carcinoma

17. Papillary neoplasms Intraductal papilloma Ductal carcinoma in situ, papillary Encapsulated papillary carcinoma Encapsulated papillary carcinoma with invasion Solid papillary carcinoma in situ Solid papillary carcinoma with invasion Intraductal papillary adenocarcinoma with invasion

18. Noninvasive lobular neoplasia Atypical lobular hyperplasia Lobular carcinoma in situ, NOS Classic lobular carcinoma in situ Florid lobular carcinoma in situ Lobular carcinoma in situ, pleomorphic Ductal carcinoma in situ (DCIS) Ductal carcinoma, noninfiltrating, NOS DCIS of low nuclear grade DCIS of intermediate nuclear grade DCIS of high nuclear grade

19. Invasive breast carcinoma Infiltrating duct carcinoma, NOS Oncocytic carcinoma Lipid rich carcinoma Glycogen rich carcinoma Sebaceous carcinoma Lobular carcinoma, NOS Tubular carcinoma Cribriform carcinoma, NOS Mucinous adenocarcinoma Mucinous cystadenocarcinoma, NOS Invasive micropapillary carcinoma of breast Metaplastic carcinoma, NOS

20. Rare and salivary gland type tumors Secretory carcinoma Acinar cell carcinoma Mucoepidermoid carcinoma Polymorphous adenocarcinoma Adenoid cystic carcinoma Classic adenoid cystic carcinoma Solid basaloid adenoid cystic carcinoma Adenoid cystic carcinoma with high grade transformation Tall cell carcinoma with reversed polarity

21. Neuroendocrine neoplasms Neuroendocrine tumor , NOS Neuroendocrine tumor , grade 1 Neuroendocrine tumor , grade 2 Neuroendocrine carcinoma, NOS Neuroendocrine carcinoma, small cell Neuroendocrine carcinoma, large cell

22. Based on expression of hormonal receptors ER positive/HER2 negative - 50-65% of cancer HER2 positive- ER positive or negative; 10%–20% of cancers Triple negative- ER, PR, and HER2 negative; 10%–20% of cancers

23. Alternative classification (based on gene expression) Luminal A - The majority are low-grade ER-positive and HER2 negative . Luminal B - The majority are high-grade ER-positive that may be HER2 positive HER2-enriched - The majority overexpress HER2 and do not express ER Basal-like - The majority have basally located myoepithelial cells and ER-negative, HER2-negative (TNBC)

24. Breast Carcinoma: Classification Almost all (majority) are adenocarcinoma There are two major types: Ductal (in-situ and invasive) Lobular (in-situ and invasive)

25. Carcinoma in situ This is epithelial proliferation that is still confined to the TDLU, has not invaded the basement membrane . There are two subtypes: Ductal carcinoma in situ (DCIS) or intraductal carcinoma. Lobular carcinoma in situ.

26. Ductal Carcinoma In Situ (DCIS)

27. DCIS is the non-invasive proliferation of malignant cells within the duct system without breaching the underlying basement membrane. Often multifocal —malignant cells can spread widely through the ductal system without breaching the basement membrane.

28. On mammography DCIS frequently shows micro-calcifications . Less frequently they can present as a mammographic density or a vaguely palpable mass or nipple discharge. Mammography is a very sensitive diagnostic procedure for detecting DCIS since majority of DCIS are not palpable.

29. Different patterns/subtypes of DCIS can be seen e.g. C omedo (central necrosis) C ribiform (cells arranged around “punched-out” spaces) Papillary Micropapillary and Solid (cells fill spaces) DCIS can be of different grades i.e. low, intermediate and high grade

30. Comedo DCIS: is characterized by large central zones of necrosis with calcified debris

31. Cribriform DCIS comprises cells forming round, regular (" cookie cutter") spaces. The lumens are often filled with calcifying secretory material.

32. Micropapillary DCIS The micropapillary pattern shows epithelial micropapillations projecting into the ductular lumen; these lack connective tissue support and often show a bulbous expansion at the tip.

33. In the solid form of DCIS , the acini of the TDLU are filled by a proliferation of medium-sized cells, often with low-grade monomorphic nuclei. solid form of DCIS

34. T he cells attempt to polarize, creating a rosette or micro acinar pattern within the solid proliferation( true lumen formation is absent ) ( d/f from LCIS )

35. Clinging pattern DCIS shows one or two layers of neoplastic epithelial cells lining a space often with an empty lumen, though necrosis may be seen. The lining cells are large, highly atypical, and associated with apoptosis.

36. Rare morphologic variations of DCIS include C ases W ith signet ring cells , W ith apocrine cytology , W ith squamous features , W ith evidence of (neuro) endocrine differentiation.

37. DCIS with apocrine features.

38. DCIS With Endocrine Features

39. Low Nuclear Grade DCIS There is neoplastic proliferation of monomorphic epithelial cells growing in solid, cribriform, papillary, or micropapillary patterns. The cells have round, regular nuclei with even chromatin and inconspicuous nucleoli.

40. Mitoses are rare . Punctate or even Comedo necrosis may be seen but is unusual. Microcalcifications are often present. DCIS , low nuclear grade, cribriform pattern

41. Intermediate Nuclear Grade DCIS The cells with slightly more nuclear variability than low nuclear grade DCIS. The cells are larger and less evenly spaced. Polarization is still observed, but is less pronounced. Calcification, mitoses, and necrosis may be present.

42. DCIS, intermediate nuclear grade , cribriform pattern with necrosis. There is greater nuclear variability compared with that seen in low-grade DCIS .

43. High Nuclear Grade DCIS N eoplastic proliferation of highly atypical epithelial cells with large pleomorphic nuclei, coarse clumped chromatin, and prominent nucleoli. The proliferation may be solid, cribriform, or micropapillary in architectural pattern, but the cells are poorly organized and polarization is not usually evident.

44. Mitoses are abundant , and necrosis is a common, though not a required, feature. Comedo necrosis is said to be present when approximately half of the involved space has abundant necrotic material and is surrounded by DCIS cells.

45. DCIS , high nuclear grade, solid pattern with necrosis.

46. Lobular Carcinoma in Situ (LCIS)

47. LCIS alone is always an incidental finding in breast biopsy performed for another reason. LCIS tends to be multicentric in 60-80% and bilateral in 30-40% cases. It does not form a palpable mass so cannot be detected clinically on palpation or on gross pathological examination.

48. Microscopically, T he lobules are distended and completely filled by relatively uniform, round, small-to-medium-sized neoplastic epithelial cells with round and Normochromatic or mildly hyperchromatic nuclei.

49. Pleomorphic LCIS T he tumor cells are of medium-to-large size, with more marked nuclear pleomorphism , often prominent nucleoli, and moderate-to-abundant cytoplasm .

50. Important IHC features of LCIS A n absence of expression with E-cadherin and β -catenin , and C ytoplasmic positivity for p120 catenin . By contrast, DCIS is consistently positive for all three markers, with a membranous pattern of expression.

51. p120 catenin immunostaining. There is cytoplasmic staining in the LCIS cells. Myoepithelial cells and adjacent normal ductal epithelium show a membranous staining pattern. β -Catenin immunostaining. Like E-cadherin, there is absence of staining in the LCIS cells with myoepithelial cells and adjacent normal ductal epithelium showing a membranous staining pattern. E-cadherin immunostaining . There is absence of staining in the LCIS cells. Myoepithelial cells and adjacent normal ductal epithelium show a membranous staining pattern.

52. F lorid LCIS with Comedo necrosis T he involved TDLU is greatly expanded by a proliferation of LCIS cells, accompanied by Comedo necrosis and calcifications.

53. T he histologic triad ( R osen triad ) of T ubular carcinoma (arrows), C olumnar cell lesion (arrowheads) and L obular carcinoma in situ (asterisk).

54. Invasive carcinoma

55. Tumors in which stromal invasion is detectable, whether an in situ component is identifiable or not, and regardless of the relative proportion of the two components . I n other words, it also includes “ microinvasive carcinoma .” ( any breast carcinoma showing stromal invasion not exceeding 1 mm in extent ) M ost invasive tumors can be divided into two major categories:- D uctal type and L obular type

56. Invasive ductal carcinoma Grossly, The lesion is firm and poorly circumscribed, cuts with a resistant gritty sensation, and shows a yellowish–gray cut surface, with trabeculae radiating through the surrounding parenchyma. R esulting in the stellate or crab-like configuration, from which the word “ cancer ” originated.

57. It is common for these neoplasms to exhibit “ chalky streaks ” on the cut surface, a feature caused by duct elastosis. Gross Appearance of Invasive Ductal Carcinoma

58. Microscopically, T umor can grow in diffuse sheets, well-defined nests, cords, or as individual cells. Glandular/tubular differentiation may be well developed or may be not. The tumor cells vary in size and shape, the nuclei are large with varying degrees of pleomorphism, and nucleoli may be prominent. Mitotic figures vary from infrequent to more numerous. Calcification is seen in approximately 60% of cases-as coarse/fine deposits/as psammoma bodies(rarely ) .

59. Irregularly shaped glands infiltrate through the stroma in a haphazard pattern.

60. Invasive Lobular Carcinoma Classic type :- it is characterized by the presence of small and relatively uniform tumor cells growing in single file and in a targetoid fashion around ducts. Gland formation is not a feature of invasive lobular carcinoma. The stroma is usually abundant, of dense fibrous type, with areas of periductal and perivenous elastosis.

61. Invasive Lobular Carcinoma . The tumor cells are small and uniform with round nuclei and grow in single file fashion.

62. Typical target-like growth of tumor cells around an uninvolved duct in invasive lobular carcinoma.

63. Single file pattern of growth of invasive lobular carcinoma.

64. Invasive Carcinoma With Ductal and Lobular Features Carcinomas in which some part having definite features of invasive ductal carcinoma and in other part definite features of invasive lobular carcinoma. M ore commonly seen are tumors with features neither definitively lobular nor definitively ductal.

65. Invasive carcinoma with ductal and lobular features; in some areas there is gland formation, while in others, the tumor cells align in a single file ( lower portion of field) .

66. References ROSAI AND ACKERMAN’S SURGICAL PATHOLOGY Eleventh Edition . Koss’ Diagnostic Cytology AND ITS HISTOPATHOLOGIC BASES. WHO classification of breast tumours 5 th edition.

67. Thank you