The document discusses knowledge and education. It provides three key points: 1) Knowledge is only truly valuable if it brings joy and freedom, rather than making one feel wise or burdened. 2) Education must go beyond learning subjects to developing one's character and using knowledge to benefit others. 3) For education to be meaningful, it must equip people to live happily and see all of humanity, not just teach facts.

1. Knowledge is a burden, If it robs you of innocence, If it makes you feel you are special, If it gives you an idea you are wise, If it is not integrated into life, If it does not bring you joy, If it does not set you free. Sri Sri Ravi Shankar, humanitarian and founder of the Art of Living Foundation, Bangalore, India. (quote from Clinical Pathology 2005;58:785; doi:10.1136/jcp.2005.030247)

6. “ Strength does not come from winning, Struggles & Hardship develop strength….! Arnold Schwarzenegger Bodybuilder, Actor & now Leader..! We gain knowledge by studying not by passing exam….!

7. Pathology of Breast Dr. Venkatesh M. Shashidhar Associate Prof. & Head of Pathology

9. Anatomy:

10. Breast Physiology:

11. Normal Breast

12. Normal Breast – glands & stroma Dense stroma Loose stroma Acinus

13. Breast - Acini

16. Differentials in a Breast clinic:

17. Lump in Breast: Diagnosis & Features Nipple adenoma Nipple adenoma Paget's disease Paget's disease Nipple adenoma Nipple adenoma Nipple ulceration, eczema In situ carcinoma In situ carcinoma Duct papilloma Duct papilloma Uncommon Uncommon Bloody Duct ectasia Duct ectasia Uncommon Uncommon Clear Nipple discharge Fat necrosis Carcinoma Carcinoma Carcinoma* Uncommon Firm lump ± tethering (fixed) Sclerosing adenosis Uncommon Fibrocystic change Fibrocystic change Uncommon Ill-defined lump/s or lumpy areas Phyllodes tumour Fibroadenoma Phyllodes tumour Fibroadenoma Fibroadenoma Mobile lump (single) >55 years 35-55 years 25-35 years <25 years Clinical presentation

22. Duct Ectasia: Cheesy discharge

24. Fibrocystic Disease: A. Simple Fibrocystic change. B. Lobular hyperplaisa without atypica (adenosis) C,D - Ductal hyperplasia without atypia (E. with atypia - cribriform) F. Lobular hyperplasia.

26. Cysts & Fibrosis Apocrine Metaplasia Rubin Essentials of Pathology Apocrine Metaplasia

27. Fibrocystic Disease

28. Fibrocystic Disease Fibrosis Cyst

29. Fibrocystic Disease-Blue dome cyst

30. Fibrocystic Disease: Cysts & fibrosis

31. Fibrocystic Disease: Cysts & fibrosis adenosis (1), papilloma formation (2), epithelial hyperplasia (3) and small cysts (4).

32. Fibrocystic Change

33. Sclerosing Adenosis:

34. Sclerosing Adenosis

35. Fibrocystic Disease

36. Ductal Hyperplasia

37. DCIS- High grade

38. Education must instill the fundamental human values; it must broaden the vision to include the entire world and all mankind. Education must equip man to live happily . … Am I educated ?

40. Fibroadenoma Note well demarcated, mobile, capsulated, nodular tumour

41. Fibroadenoma Note well demarcated, capsulated, nodular tumour

42. Mammogram - Benign

43. Fibroadenoma Slit like glands Gross: Well demarcated, capsulated, nodular tumour Micro: Compressed slit like glands in cellular stroma. Fibrous stroma

44. Fibroadenoma

45. P P P In In Fibroadenoma C = capsule; In = intracanicular pattern; P = pericanicular pattern

46. Fibroadenoma

47. Fibroadenoma

48. Breast Fibroadenoma Elongated duct like structures surrounded by loose connective tissue

50. Phylloides Tumor: Giant Fibroadenoma

51. Cystosarcoma Phyllodes:

52. Benign Cystosarcoma Phyllodes

53. Fibroadenoma – Giant Fibroadenoma Flat slit like glands, loose fibrous stroma Branching leaf like glands, Cellular stroma

56. Intraductal papilloma Fibrovascular core

57. Education has two important characteristics. One is learning of a subject. The other is the personality to apply this knowledge to the benefit of community. Skill & Attitude One without the other …. ???

60. Genetic - BRCA Hormone - Estrogens. Environment- Diet, Obesity… Less Well-Established Influences Exogenous estrogens, Oral contraceptives, Obesity, High-fat diet, Alcohol consumption Cigarette smoking. 6.9-12.0 Lobular carcinoma in situ >2.0 Proliferative disease with atypical hyperplasia 1.6 Proliferative disease without atypia Benign breast disease 3.0 Nulliparous 2.0-3.0 First live birth after age 35yr 1.9 First live birth after age 30yr 1.5 First live birth from ages 25 to 29yr Pregnancy 1.5-2.0 Age at menopause >55yr 1.3 Age at menarche <12yr Menstrual history 4.0-5.4 Postmenopausal and bilateral 1.5 Postmenopausal 8.5-9.0 Premenopausal and bilateral 3.1 Premenopausal 1.2-3.0 First-degree relative with breast cancer Family history Increases after age 30yr Age Varies in different areas Geographic factors Well-Established Influences Relative Risk Breast Cancer Risk Factors

61. Pathogenesis of Breast Cancer. Hyperplasia  Dysplasia  DCIS  Carcinoma Duct Ca. in-Situ DCIS

63. Histological Types Histologic Type Freq. (UK) Infiltrating Duct Ca 63.6 (75) Lobular Carcinoma 5.9 (10) Infiltrating Ductal & Lobular Ca 1.6 Medullary Carcinoma 2.8 (3) Mucinous (colloid) Carcinoma 2.1 (3) Comedocarcinoma 1.4 Carcinoma-In-Situ 5%

64. Breast Ca

65. Breast Ca

66. Mammogram - Ca

67. Mammogram - Ca

68. Breast Carcinoma

73. Infiltrating Duct Carcinoma: small hard

74. Breast Carcinoma

75. Infiltrating Duct Carcinoma: Advanced

76. Ca Breast – fat removal

77. ADH is recognised by its histologic resemblance to ductal carcinoma in situ (DCIS), including a monomorphic cell population, regular cell placement, and round lumina. However, the lesions are characteristically limited in extent, and the cells are not completely monomorphic in type or they fail to completely fill the ductal spaces. Atypical Ductal Hyperplasia

78. Ductal Carcinoma in Situ, DCIS Solid & Cribriform pattern

79. Intraductal in-situ Carcinoma

80. Intraduct Carcinoma-in-situ

81. Intraduct Carcinoma

82. Solid DCIS completely fills the involved spaces. Ductal Carcinoma in Situ (Solid type)

83. Intraduct Carcinoma (DCIS)

84. Intraduct Carcinoma (DCIS)

86. Duct Ca In Situ - DCIS Intact ME cells DCIS

87. Intraduct Carcinoma (DCIS) Intact ME cells DCIS Necrosis/comedo

88. Breast Carcinoma - Schirrous Nipple

89. Infiltrating Duct Carcinoma: small hard

90. Medullary Carcinoma: Large soft

91. Infiltrating Duct Carcinoma Fibrosis Glands

92. Infiltrating Duct Carcinoma

93. Infiltrating Duct Carcinoma: Fibrosis India file arrangement with duct formation

94. Medullary Carcinoma: Inflammation.

95. Inflammatory Carcinoma

96. Tumours shows tubules lined by minimally atypical cells within dense fibrotic stroma giving the tumour a hard consistency on palpitation. (difficult to distinguish from benign sclerosing lesions.). Typical Invasive Ductal Carcinoma / Duct Ca (NOS)

97. Lobular carcinoma in situ (LCIS) consists of small cells that have round or oval nuclei with small nucleoli that loosely adhere to one another. LCIS rarely distorts the underlying architecture, and the involved acini remain recognisable as lobules. Lobular Carcinoma in situ (LCIS)

98. The histologic hallmark of lobular carcinoma is the pattern of single infiltrating tumour cells, often only one cell in width (in the form of single file; often described as ‘ Indian files ’)) or in loose clusters or sheets. The cells have the same cytologic features as LCIS and lack cohesion, without the formation of tubules or papillae. Tumour cells are frequently arranged in concentric rings surrounding ducts (not illustrated here). Invasive Lobular Carcinoma

99. The arrow points to an Indian file arrangement of tumour cells. Invasive Lobular Carcinoma

100. Immunoperoxidase stain demonstrating Estrogen receptor (ER) in nuclei – +ve -ve

101. Infiltrating Lobular Carcinoma

102. Lobular Carcinoma Lobular Ca In-Situ Lobular Ca. Infiltration

103. Lobular Carcinoma - India file arrangement

104. Breast Ca. Lymphatic spread Pathogenesis of Peu-de Orange appearance. Tumor in lymph Vessel Arrows: Tumour emboli within lymphatic vessels

105. Breast Ca – Peau d’orange ? Pathogenesis

106. Spread of Breast Carcinoma:

107. Pagets Disease

108. Pagets Disease

109. Pagets Disease (Epidermal invasion)

111. Tumor Markers in Breast Ca. ER: Estrogen Receptors. PR: Progesterone Receptors. HER2/neu: Human Epidermal growth factor Receptor 2 E-Cadherin: Cell adhesion protein. BRCA: Breast Carcinoma Antigen.

112. Estrogen receptor (ER) in nuclei

113. Immunoperoxidase stain: Neg 1+ 2+ 3+

117. Progression of Breast Ca: (new)

119. Common Ca. Breast: NST Stellate Lesion on Mammogram Hard irregular - Schirrhous tubules in dense fibrous stroma. Infiltrating duct Carcinoma.

120. Breast Cytology - FNAB Benign Malignant

121. Breast Cytology - FNAB Benign Malignant

133. Q: A 35-year-old nulliparous woman complains that her breasts are swollen and nodular upon palpation. A mammogram discloses foci of calcification in both breasts. A breast biopsy (shown) reveals cystic duct dilation and ductal epithelial hyperplasia without atypia. What is the appropriate diagnosis?

135. Q: A 53-year-old woman discovers a lump in her breast and physical examination confirms a mass in the lower, outer quadrant of the left breast. Mammography demonstrates an ill-defined, stellate density measuring 1 cm with microcalcification. Following Needle aspiration, A modified radical mastectomy is performed. The surgical specimen is shown. Which of the following cellular markers would be the most useful to evaluate before considering therapeutic options for this patient?

144. Q: A 20-year-old woman asks for your advice regarding her risk of developing breast cancer. Her mother, maternal aunt, and maternal grandmother all developed breast cancer. She would like to know if she has a genetic predisposition. Laboratory tests for mutations in which of the following genes would be most likely to answer your patient's question?

147. Q: A 26-year-old woman presents with a breast mass that was detected on self-examination one week earlier. Mammography reveals a round, sharply demarcated 1-cm nodule in the right breast (shown). Biopsy of the breast mass shows neoplastic epithelial ductal structures situated within a fibromyxoid stroma. The patient refuses further treatment and informs you that she wishes to become pregnant. Which of the following is the most likely effect of pregnancy on this breast lesion?

149. Q: A 35 year old woman consults her family physician because of painful swelling of her breats. Particularly as she approaches the end of her menstrual cycle. On self-examination she recently felt a tender nodule in the right breast. Physical examination reveals an irregular nodularity of both breasts with diffuse tenderness. Examination of the acilla is negative. A mammogram demonstrates irregular areas of density in the lower outer quadrants of both breasts. Which of the following histopathologic features is considered to be a risk factor for the development of carcinoma in this patient?

151. Q: A 30y old woman presentas with white nipple discharge of 3 weeks duration. The patient has not menstruated for the past 4 months, and she is not pregnant. The breasts are firm and nontender. A cytologic smear of the discharge shows no evidence of acute of acute or chronic inflammatory cells. Which of the following is the most likely cause of galactorrhea in this patient?

157. The power of Words: Words have the power to both destroy and heal. When words are both true and kind , they can change our world. Buddha

159. Mammogram - Benign

160. Mammogram - Ca

161. Mammogram – Ca

164. Possibly due to metastatic breast carcinoma or associated with hypercalcaemia BONE PAIN OR FRACTURE Often due to metastatic breast carcinoma AXILLARY NODES ++ Dystrophic calcification associated with benign changes, e.g. cysts, sclerosing adenosis, or in situ or invasive carcinoma MICROCALCIFICATION (ON MAMMOGRAPHY) Inflammatory lesion (e.g. mastitis) • ON PALPATION Benign breast changes • CYCLICAL BREAST PAIN Paget's disease of nipple (cancer) or eczema • ERYTHEMA AND SCALING Tethering by invasive carcinoma • RETRACTION Bloody-duct papilloma or carcinoma (rare) White/green-duct ectasia Milky-pregnancy or prolactinoma • DISCHARGE NIPPLE Increased blood flow due to inflammation or tumour • ERYTHEMA Invasion of skin by carcinoma • PUCKERING AND TETHERING Impaired lymphatic drainage due to carcinoma • OEDEMA (PEAU D'ORANGE) SKIN FEATURES Invasive neoplasm (carcinoma) • TETHERED Benign neoplasm (usually fibroadenoma) • MOBILE Neoplasm or solitary cyst • DISCRETE Fibrosis, epithelial hyperplasia and cysts in fibrocystic change • DIFFUSE LUMP Pathological basis Sign or symptom

165. Both lesions were described by Sir James Paget (1814-1899). There is no other relationship between these lesions. Paget's disease of the nipple & of bone The term medullary refers only to the soft consistency (resembling the medulla of the brain). There is no other relationship between these lesions. Medullary carcinoma of the breast & of the thyroid Radial scars and complex sclerosing lesions differ only in size: the latter are >10 mm diameter. Both mimic carcinomas radiologically and histologically, but they are benign non-neoplastic lesions. Radial scar & complex sclerosing lesion Ductal epithelial hyperplasia is a benign proliferation of duct epithelium, whereas ductal carcinoma in situ has undergone neoplastic transformation, although it is not yet invasive. These lesions can have morphological similarities. A proportion share genetic alterations. Ductal epithelial hyperplasia & ductalcarcinoma in situ both comprise neoplastic epithelial and fibrous tissue components. However, in phyllodes tumours the fibrous tissue component is more cellular and abundant, and the lesion has less well defined margins; borderline and malignant variants occur. Fibroadenoma & phyllodes tumour Fibroadenoma is a localized circumscribed benign neoplasm comprising epithelial cells and specialised fibrous tissue. Fibroadenosis is an obsolete name for fibrocystic change, a diffuse hyperplastic lesion. Fibroadenoma & Fibroadenosis Distinction and explanation Confusion

168. Mammogram – Benign

169. Fibroadenoma Types Solitary Few (< 5 / breast ) Multiple (> 5 / breast ) Giant (> 4 / 5 cms) & Juvenile Natural history Majority remain small & static 50% involute spontaneously No future risk of malignancy

173. Management algorithm for cysts

174. Management protocol for musculo skeletal pain

177. Management of nipple retraction

178. Breast Ca - DNA flowcytometry

180. Fibrocystic Disease – Radial scar

181. Mammogram – Ca

182. Stage Definition 5-year Surv (%) 7-year Surv (%) I Tumor 2 cm or less without spread 96 92 II Tumor 2-5cm with regional lymph node involvement but without distant metastases, OR > 5 cm in diameter without spread 81 71 III Any size with skin/chest wall fixation, & axillary or internal mammary nodal involvement, without distant metastases 52 39 IV Tumor of any size with or without regional spread but with evidence of distant metastases 18 11