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New issues in the interpretation of breast biopsies

New issues in the interpretation of breast biopsies. Sami Shousha, MD, FRCPath Charing Cross Hospital & Imperial College, London. July 2008. Discussion Topics. 1. How to differentiate between: Florid usual type ductal hyperplasia Atypical ductal hyperplasia Low grade DCIS

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New issues in the interpretation of breast biopsies

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  1. New issues in the interpretation of breast biopsies Sami Shousha, MD, FRCPath Charing Cross Hospital & Imperial College, London July 2008

  2. Discussion Topics 1. How to differentiate between: • Florid usual type ductal hyperplasia • Atypical ductal hyperplasia • Low grade DCIS 2. Intraductal/ intracystic papillary lesions 3. Examination of specimens removed after neo-adjuvant chemotherapy

  3. I. How to differentiate between: • Florid usual type ductal hyperplasia • Atypical ductal hyperplasia • Low grade DCIS

  4. Florid Usual Type Ductal Hyperplasia • The proliferating cells are similar to the normal cells lining the ducts • The cells are haphazardly arranged, may overlap or have a streaming arrangement • When spaces are present, they are irregular and mostly peripheral • An occasional mitotic figure may be present

  5. ADH

  6. Evenly spaced uniform cells With uniform oval or rounded nuclei Abundant pale cytoplasm And distinct cell borders Forming the entire population of cells of at least 2 ducts Low Grade DCIS Distinguishing florid hyperplasia from low grade DCIS is not always easy

  7. Florid Regular Hyperplasia vs. Low grade DCISIf still in doubt: Stain for cytokeratin 5/6

  8. CK 5/6 • In (benign) florid usual type hyperplasia: Most of the proliferating cells are cytokeratin 5/6 positive

  9. CK 5/6 • Malignant (& atypical) cells are CK 5/6negative

  10. CK5/6 ER Diagnosis: Florid usual type ductal hyperplasia

  11. F20, Right breast lump CK5/6 Diagnosis: Complex Sclerosing Lesion with Florid Usual Type Ductal Hyperplasia

  12. CK5/6 Diagnosis: DCIS

  13. But remember:Cytokeratin 5/6 is positive in basal cell type carcinomas Metaplastic (spindle cell) carcinoma Basal cell type Carcinoma

  14. Atypical ductal hyperplasia/ Low grade DCIS (depending on extent)

  15. II. Papillary Lesions

  16. Papillary lesions I. Benign • Benign intraduct papilloma • Multiple intraduct papillomas • Intraduct papilloma with focal usual type hyperplasia II. Atypical • Intraduct papilloma with focal atypical hyperplasia (atypical intraduct papilloma) • Intraduct papilloma with focal DCIS III. Malignant • Papillary DCIS • Intracystic (encapsulated) papillary carcinoma • Solid papillary carcinoma* *Collins LC, Schnitt SJ. Histopathology 2008, 52,20-29

  17. Papillary lesions I. Benign • Benign intraduct papilloma • Multiple intraduct papillomas • Intraduct papilloma with focal usual type hyperplasia II. Atypical • Intraduct papilloma with focal atypical hyperplasia (atypical intraduct papilloma) • Intraduct papilloma with focal DCIS III. Malignant • Papillary DCIS • Intracystic (encapsulated) papillary carcinoma • Solid papillary carcinoma* *Collins LC, Schnitt SJ. Histopathology 2008, 52,20-29

  18. 1. Benign Intraduct Papilloma

  19. Benign Intraduct Papilloma • Fronds covered by 2 layers of cells: luminal and myoepithelial • Myoepithelial cells surround the dilated duct

  20. Benign Intraduct Papilloma SMA

  21. 2. Multiple Benign intraduct papillomas* *5 or more

  22. Multiple intraduct papillomas SMA CK 5/6 p63

  23. 3. Intraduct papilloma with focal usual type hyperplasia • The fronds are covered by more than 2 layers of epithelial cells • With no atypia *Page DL et al. Cancer 1996,78: 258-266

  24. Intraduct papilloma with focal usual type hyperplasia • CK 5/6 (& ER) will show 2 populations of cells: negative and positive CK 5/6

  25. Papillary lesions I. Benign • Benign intraduct papilloma • Multiple intraduct papillomas • Intraduct papilloma with focal usual type hyperplasia II. Atypical • Intraduct papilloma with focal atypical hyperplasia (atypical intraduct papilloma) • Intraduct papilloma with focal DCIS III. Malignant • Papillary DCIS • Intracystic (encapsulated) papillary carcinoma • Solid papillary carcinoma* *Collins LC, Schnitt SJ. Histopathology 2008, 52,20-29

  26. 4. Intraduct papilloma with focal atypical hyperplasia • atypical cells occupy an area less than 3mm • Atypical cells are relatively large with abundant cytoplasm and large uniform nuclei • Cells are CK 5/6 negative, ER positive

  27. Criteria used for diagnosing atypia in intraduct papillomas* • Presence of hyperchromatic nuclei or marked nuclear atypia • Cribriform pattern • Absence of supporting stroma • Monotonous cell population with no admixed myoepithelial cells (which can be confirmed by staining for cytokeratin 5/6 or smooth muscle antigen) * Kraus F, Neubecker R. Cancer 1962; 15: 444-455

  28. 5. Intraduct papilloma with focal DCIS • Atypical cells occupy an area larger than 3mm

  29. Incidence of papillomas* • 5% of all benign breast lesions • 78% single with no atypia (risk of developing carcinoma: 2) • 11% single with atypia (risk: 5) • 8% multiple with no atypia (risk: 3) • 2% multiple with atypia (risk: 7) • *From a study of 480 cases by: Lewis JT et al. Am J Surg Pathol 2006; 30: 665-672

  30. Benign papillary Lesions on Core Biopsies To Excise? or not to excise?

  31. Benign papillary Lesions on Core Biopsies (I)* • 43 cases • 7 Follow up • 36 Excised: • 10 no residual lesion • 14 benign intraduct papilloma • 2 multiple intraduct papillomas • 8 benign intraduct papilloma + adjacent ADH (22%) • 2 papillary carcinoma (6%) • The authors strongly recommend excision of all papillomas *C L Mercado et al. Radiology 2006;238: 801-808 (New York, USA)

  32. Benign papillary Lesions on Core Biopsies (II)* • 16 cases (B2:1, B3:15) were excised • 1 adenoma • 9 benign intraduct papilloma • 4 benign intraduct papilloma with ADH (25%) (3 had Florid Usual type hyperplasia in cores) • 1 multiple intraduct papillomas • 1 complex sclerosing lesion • No cancers • Authors conclusion: excision of benign papillomas may not always be necessary *P J Carder. Histopathology 2005; 46: 320-327 (Leeds, UK)

  33. Benign papillary Lesions on Core Biopsies (III)* • 38 cases were excised • 18 benign papillomas with no or minimal atypia: Excision: all benign • 7 papillomas with ADH: Excision: Carcinoma in 2 (29%) • 13 papillomas with severe atypia suspicious of malignancy (?B4): Excision: Carcinoma in 12 (92%). • Authors conclusion: Lesions diagnosed on cores as papillomas with no or minimal atypia do not need excision *A A Ranshaw et al. Am J Clin Pathol 2004;122: 217-221P (Miami, USA)

  34. Benign papillary Lesions on Core Biopsies (IV)* • 36 cases were excised • 11 benign papillomas with no atypia: Excision: all benign • 25 papillomas with ADH: Excision: Carcinoma in 12 (48%) • Authors conclusion: Lesions diagnosed on cores as papillomas with no atypia do not need excision; but patients have to be followed up *Agoff SN, Lawton TJ. Am J Clin Pathol 2004; 122: 440-443 (Seattle, USA)

  35. Benign papillary Lesions on Core Biopsies (V)* • 14 cases were excised • 6 benign papillomas with no atypia: Excision: all benign • 8 papillomas with atypia: Excision: Carcinoma in 6 (75%) • Authors conclusion: Lesions diagnosed on cores as papillomas with no atypia do not need excision; but patients have to be followed up *Ivan D et al. Modern Pathol 2004; 17: 165-171 (Houston, USA)

  36. Benign papillary Lesions on Core Biopsies/ Conclusions • Papillary lesions well sampled by core biopsy • that do not show evidence of atypia or malignancy, • are unlikely to harbour more advanced changes • and excision may not be needed* • (but follow up is advised) *Ibarra JA. The Breast J. 2006;12: 237-251

  37. Papillary lesions I. Benign • Benign intraduct papilloma • Multiple intraduct papillomas • Intraduct papilloma with focal usual type hyperplasia II. Atypical • Intraduct papilloma with focal atypical hyperplasia (atypical intraduct papilloma) • Intraduct papilloma with focal DCIS III. Malignant • Papillary DCIS • Intracystic (encapsulated) papillary carcinoma • Solid papillary carcinoma* *Collins LC, Schnitt SJ. Histopathology 2008, 52,20-29

  38. 6. Papillary DCIS CK5/6

  39. Case No. 152: F 64y, Left Breast, Cystic Lump7. Intracystic (encapsulated) papillary carcinoma • These are well-defined lesions consisting entirely of malignant cells covering papillary fronds, with no underlying myoepithelial cells, • developing in an apparently dilated , usually subareolar, duct , • surrounded by a thick fibrous capsule

  40. Intracystic (encapsulated) papillary carcinoma • But, in contrast to papillary DCIS, there may be no myoepithethelial cells around the lesion • Thus, the lesion may be in fact a form of low grade invasive carcinoma with an expansile growth pattern • Or part of progression from in situ to invasive carcinoma

  41. Intracystic (encapsulated) papillary carcinoma • But, in contrast to papillary DCIS, there are no myoepithethelial cells around the lesion • Thus, the lesion may be in fact a form of low grade invasive carcinoma with an expansile growth pattern • Or part of progression from in situ to invasive carcinoma

  42. Case No. 152: F 64y, Left Breast, Cystic LumpIntracystic (encapsulated) papillary carcinoma • This is supported by the presence of axillary node metastases in rare cases* • However, they have excellent prognosis, and it might be prudent, for the time being, to continue treating them as in situ lesions** *Mulligan AM, O’Malley FP. Int J Surg Pathol 2007,15: 143-147 **Collins & Schnitt 2008 (Histopathology)

  43. Case No. 152:F 64y, Left Breast, Cystic LumpIntracystic (encapsulated) papillary carcinoma/ IH

  44. Intracystic (encapsulated) papillary carcinoma • The lesion may be associated with foci of DCIS or frankly invasive carcinoma • In the latter case, Collins & Schnitt recommend considering only the size of the frankly invasive component for staging purposes

  45. 8. Solid Papillary carcinoma • Circumscribed solid nodule • May be associated with adjacent foci of in situ or invasive carcinoma

  46. Solid Papillary carcinoma • Discrete papillae are not present, • but the underlying papillary structure is represented by a network of fibrovascular cores among the solid epithelial proliferation

  47. Solid Papillary carcinoma • There are no myoepithelial cells within the lesion • And myoepithelial cells may be also lacking around the lesion in some cases, • raising the possibility, as in intracystic encapsulated lesions, that at least some of these cases also represent low grade expansile invasive cancers CK 5/6

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