Pathology of Breast Disorders

1. Pathology of Breast Disorders 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)

2. CPC 4.4 - 45 Year Woman. <ul><li>Mrs. JM, 45y woman, primary school teacher, living in Weipa. ‘I have noticed a odd change in my left breast when I was showering last week’ </li></ul><ul><li>History: </li></ul><ul><ul><li>Duration. Noticed it 8 days ago ? </li></ul></ul><ul><ul><li>What: ‘My left breast feels a bit thicker – just here’ (points to upper outer breast) </li></ul></ul><ul><ul><li>Pain? No - ? </li></ul></ul><ul><ul><li>Nipple discharge: No - ? </li></ul></ul><ul><ul><li>Trauma to breast: No - ? </li></ul></ul><ul><ul><li>Menstrual cycle: regular - ? </li></ul></ul><ul><ul><li>Mastalgia: not usually ? </li></ul></ul><ul><li>Differential Diagnosis - ??? </li></ul> CPC 4.4 - 45 Year Woman. <ul><li>Mrs. JM, 45y woman, primary school teacher, living in Weipa. ‘I have noticed a odd change in my left breast when I was showering last week’ </li></ul><ul><li>History: </li></ul><ul><ul><li>Duration. Noticed it 8 days ago ? </li></ul></ul><ul><ul><li>What: ‘My left breast feels a bit thicker – just here’ (points to upper outer breast) </li></ul></ul><ul><ul><li>Pain? No - ? </li></ul></ul><ul><ul><li>Nipple discharge: No - ? </li></ul></ul><ul><ul><li>Trauma to breast: No - ? </li></ul></ul><ul><ul><li>Menstrual cycle: regular - ? </li></ul></ul><ul><ul><li>Mastalgia: not usually ? </li></ul></ul><ul><li>Differential Diagnosis - ??? </li></ul>

3. CPC 4.4- 45 Year Woman. <ul><li>LMP : about 4/52 ago; K due ? </li></ul><ul><li>Age of menarche :13 years ? </li></ul><ul><li>Parity : none ? Importance? </li></ul><ul><li>Appetite: : normal ? </li></ul><ul><li>Weight: : stable ? </li></ul><ul><li>All other systems : negative </li></ul><ul><li>Meds : Was on COCP 17yrs – 30 yrs ? </li></ul><ul><li>Imms : up to date </li></ul><ul><li>Cervical smear : up to date; has never had abnormal smear ? </li></ul><ul><li>Differential Diagnosis ??? </li></ul> CPC 4.4- 45 Year Woman. <ul><li>LMP : about 4/52 ago; K due ? </li></ul><ul><li>Age of menarche :13 years ? </li></ul><ul><li>Parity : none ? Importance? </li></ul><ul><li>Appetite: : normal ? </li></ul><ul><li>Weight: : stable ? </li></ul><ul><li>All other systems : negative </li></ul><ul><li>Meds : Was on COCP 17yrs – 30 yrs ? </li></ul><ul><li>Imms : up to date </li></ul><ul><li>Cervical smear : up to date; has never had abnormal smear ? </li></ul><ul><li>Differential Diagnosis ??? </li></ul>

4. CPC 4.4- Examination <ul><li>R breast NAD, L breast firm thickening upper outer axillary tail; no discrete mass; no skin tethering / changes; no nipple inversion; no areola changes, no axillary or supracla. LN. </li></ul><ul><li>What Differentials: </li></ul><ul><li>Benign proliferations & Breast malignancy </li></ul><ul><li>What further investigations? </li></ul><ul><li>Mammogram, FNAB, CT Scan, Bone Scan, Biopsy+immunochemistry. </li></ul> CPC 4.4- Examination <ul><li>R breast NAD, L breast firm thickening upper outer axillary tail; no discrete mass; no skin tethering / changes; no nipple inversion; no areola changes, no axillary or supracla. LN. </li></ul><ul><li>What Differentials: </li></ul><ul><li>Benign proliferations & Breast malignancy </li></ul><ul><li>What further investigations? </li></ul><ul><li>Mammogram, FNAB, CT Scan, Bone Scan, Biopsy+immunochemistry. </li></ul>

5. CPC 4.4- Examination <ul><li>Mammogram – solid infiltrating irregular mass lying at the 10 o’clock position of the L breast. Mass has prominent radiating spicules ; 2 x small calcifications within the mass. Overall mass 1x 1.5x 1cm. </li></ul><ul><li>USS guided FNAB : high grade infiltrating ductal carcinoma </li></ul><ul><li>CT scan : no sign metastasic disease liver or lung </li></ul><ul><li>Bone scan: no sign bony metastases </li></ul><ul><li>Immunochemistry : ER : positive PR : negative HER2 : +++positive </li></ul> CPC 4.4- Examination <ul><li>Mammogram – solid infiltrating irregular mass lying at the 10 o’clock position of the L breast. Mass has prominent radiating spicules ; 2 x small calcifications within the mass. Overall mass 1x 1.5x 1cm. </li></ul><ul><li>USS guided FNAB : high grade infiltrating ductal carcinoma </li></ul><ul><li>CT scan : no sign metastasic disease liver or lung </li></ul><ul><li>Bone scan: no sign bony metastases </li></ul><ul><li>Immunochemistry : ER : positive PR : negative HER2 : +++positive </li></ul>

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

8. Introduction <ul><li>Modified sweat glands. </li></ul><ul><li>Lobes and lobules of gland </li></ul><ul><li>in fat tissue stroma. </li></ul><ul><li>Ducts emerge from acini of glands </li></ul><ul><li>Smaller ducts join to form lactiferous ducts </li></ul><ul><li>Lactiferous ducts merge just beneath the nipple to form a lactiferous sinus. </li></ul><ul><li>Then individually open on nipple </li></ul> Introduction <ul><li>Modified sweat glands. </li></ul><ul><li>Lobes and lobules of gland </li></ul><ul><li>in fat tissue stroma. </li></ul><ul><li>Ducts emerge from acini of glands </li></ul><ul><li>Smaller ducts join to form lactiferous ducts </li></ul><ul><li>Lactiferous ducts merge just beneath the nipple to form a lactiferous sinus. </li></ul><ul><li>Then individually open on nipple </li></ul>

9. Anatomy:

10. . Breast Physiology:

11. . Normal Breast

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

13. . Breast - Acini

14. . Involution @ Menopause <ul><li>Acinar cell loss. </li></ul><ul><li>Connective & Fat tissue increases. </li></ul><ul><li>Loose to dense fibrous connective tissue. </li></ul><ul><li>Thickened basement membranes. </li></ul><ul><li>Fibro - cystic change – common. </li></ul>

15. . Disorders of Breast: <ul><li>Congenital </li></ul><ul><ul><li>Aplasia – turners, Juvenile hypertrophy </li></ul></ul><ul><ul><li>Accessory breasts – along milk line. </li></ul></ul><ul><li>Inflammatory </li></ul><ul><ul><li>Acute/Chronic Mastitis </li></ul></ul><ul><ul><li>Trauma - Fat necrosis </li></ul></ul><ul><ul><li>Duct ectasia - discharge, sinus, Galactocele </li></ul></ul><ul><li>Proliferative Conditions </li></ul><ul><ul><li>Fibrocystic disease – common cause of lumps </li></ul></ul><ul><ul><li>Cysts, Adenosis, Metaplasia & mixed. </li></ul></ul><ul><li>Neoplastic </li></ul><ul><ul><li>Benign - Fibroadenoma </li></ul></ul><ul><ul><li>Malignant – Carcinoma – several types. </li></ul></ul>

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

18. . Diagnosis: History First….! <ul><li>Mammorgraphy </li></ul><ul><li>Fine Needle Aspiration Biopsy </li></ul><ul><li>Core/Needle Biopsy </li></ul><ul><li>Excision Biopsy </li></ul><ul><li>Ultrasound </li></ul><ul><li>Frozen section </li></ul><ul><li>Immunoperoxidase – HER2, Estrogen rec. </li></ul><ul><li>Molecular techniques – Gene detection. </li></ul>Triple Assessment  Clinical, Imaging & pathology.

19. . Gynecomastia: <ul><li>Breast enlargement in men. </li></ul><ul><li>Estrogen excess – Klinefelter’s, Hyperthyroidism, pituitary & adrenal tumors, testicular failure, hormonal. </li></ul><ul><li>Liver failure, cirrhosis </li></ul><ul><li>Lung, Testicular Cancer </li></ul><ul><li>diethylstilbestrol therapy of prostatic carcinoma. </li></ul><ul><li>Drugs (Spironolactone, H2 antagonists, Neuroactive agents). </li></ul><ul><li>Microscopy – only duct & stromal hyperplasia. </li></ul>

20. . Acute Mastitis: <ul><ul><li>Non Lactational (central, rare) </li></ul></ul><ul><ul><li>Lactational (periphery, common) </li></ul></ul><ul><li>First few weeks after delivery. </li></ul><ul><li>Crack in the nipple or keratotic plug at the orifice of a duct. </li></ul><ul><li>Staphylococcus aureus , Strep. pyogenes. </li></ul><ul><li>Localized inflammation, Swelling erythema & pus. </li></ul><ul><li>Complications - Breast abscess, septicemia. </li></ul><ul><li>Rarely other infections. TB, Fungal, etc. </li></ul>WBC in gland

21. . Duct Ectasia: <ul><li>>50y, multiparous. Present with a poorly defined palpable periareolar mass & thick cheesy nipple secretion. </li></ul><ul><li>Duct obstruction, fatty contents, periductal Inflammation. </li></ul><ul><li>Pain/erythma uncommon, may have skin retraction mimics Ca. </li></ul><ul><li>Recurrent abscess / fistula draining pus. </li></ul><ul><li>Usually affect one duct.. Rarely multiple. </li></ul><ul><li>Irregular dilated, duct with periductal inflammation. Foamy macrophages in the lumen. </li></ul><ul><li>Scarring results in nipple inversion is 30% cases – mimics Ca. </li></ul>

22. . Duct Ectasia: Cheesy discharge

23. . Fibrocystic Disease <ul><li>Synonyms: Fibroadenosis, Fibrocystic change </li></ul><ul><li>Hormone induced – Oestrogens. </li></ul><ul><li>Commonest (10-50%) cause of lumps, 20-40y. </li></ul><ul><li>Periodic discomfort – cyclic pain (menstrual) </li></ul><ul><li>Irregular palpable firm lumps – mimic ca. </li></ul><ul><li>Epithelial hyperplasia – premalignant </li></ul><ul><li>Fibrosis & cysts, metaplasia, hyperplasia, dysplasia (atypical). Ca in-situ  Ca. </li></ul>

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.

25. . Fibrocystic Disease <ul><li>Common cause of lumps & surgery. </li></ul><ul><li>20-40 years of age </li></ul><ul><li>hyperplasia of glands & stroma. </li></ul><ul><li>Estrogen excess / estrogen-progesterone imbalance / varying response to them. </li></ul><ul><li>Irregular multiple nodules with cysts. </li></ul><ul><li>Epithelial hyperplasia – risk of cancer. </li></ul><ul><ul><li>Apocrine metaplasia, </li></ul></ul><ul><ul><li>Radial scar </li></ul></ul>

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

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39. . Benign Neoplasms: <ul><li>Fibroadenoma </li></ul><ul><li>Duct Papilloma </li></ul><ul><li>Adenoma </li></ul><ul><li>Connective tissue tumors * rare </li></ul><ul><li>Fibroadenoma – Features. </li></ul><ul><ul><li>Young age 3 rd decade. </li></ul></ul><ul><ul><li>Single*, rounded, mobile, painless lump </li></ul></ul><ul><ul><li>No scarring or calcification. </li></ul></ul><ul><ul><li>Slit like glands in loose fibrous stroma </li></ul></ul><ul><ul><li>“ Mouse in the breast”.. </li></ul></ul>

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

49. . Phyllodes Tumor <ul><li>On gross examination exhibit “leaf-like” clefts and slits - Cystosarcoma phyllodes. </li></ul><ul><li>Resembles fibroadenoma but may grow to large size (10-15 cm in diameter) - giant fibroadenoma. </li></ul><ul><li>Benign to malignant varieties. </li></ul><ul><li>Local recurrence common, metastasis 15% </li></ul><ul><li>Both stroma and epithelium may show malignant change. </li></ul><ul><li>Hypercellurity, anaplasia in malignant. </li></ul>

50. . Phylloides Tumor: Giant Fibroadenoma