1. MICROCALCIFICATION IN BENIGN BREAST DISEASE
Dr Azar Naimi MD.ACP
Poursina research Lab

2. Hormoz Island

3. Type I: calcium oxalate dihydrate crystals (Weddelite) are birefringent, predominantly in benign lesions. In ducts.

4. Type II: calcium phosphates largely in the form of hydroxyapatite are not birefringent: in benign and malignant lesions. In ducts and stroma.

5. Hormoz Island

6. What should we do if we receive a kind of specimen, excised for non palpable lesion with microcalcification?
For first step, radiography of the intact specimen is an essential part of the processing of these specimens. This is to ensure that the lesion is contained the calcification.
A specimen X-ray should be sent to the pathologist along with the specimen.

8. If the mammographic abnormality reveals microcalcification, the pathologist should make every effort to identify them in histologic sections.
If X-ray of the sliced tissue specimen is available, all abnormal areas seen should be submitted and labelled on the radiograph.

9. If these are not identified in the sections the following steps should be followed:
The microcalcification may represent calcium oxalate crystals. These requires polarization lenses to visualize.
X-ray of the paraffin blocks and any remaining wet tissue, if any. Multiple level sections can be made of the blocks containing the calcification.
Calcification can be leached out by acidic fixatives or shattered out by the microtome blade. The PH of the fixative should be checked regularly.

10. Hormoz Island

11. Which benign Breast lesions may be encountered with microcalcification?

12. If radiology is looking for a calcs, then report a specific pathologic identity that would be compatible with calcs.

13. Sclerosing adenosis
Radial scar
Columnar cell change
Intraductal papilloma
ALH
Mucocele like lesions
Apocrine metaplasia
Old fibroadenoma
Old fat necrosis
Calcification associated with lactational change
Ductectasia

14. Which of these Breast Lesions do they need excision after Core Biopsy?

15. Hormoz Island

16. Sclerosing adenosis
Microcalcifications are present in > 50% of cases and may be prominent
Calcs usually numerous, fine textured and located within sclerosed acinar lumens

17. Hormone imbalance and dysregulation of ER may play a role in development of SA
Most common in peri menopausal women

18. Most common presentation: Finding during screening mammography
Less commonly presents as a palpable mass
Classified as proliferative disease without atypia

19. SCLEROSING ADENOSIS
Mammogram 
microcalcification

20. Lobulocentric proliferation of acini around a central duct with stromal sclerosis and compression of lumens
Arises within terminal duct lobular unit
Must be at least 2x larger than average lobule
2 cell layers may be best appreciated at periphery
May be difficult to see if center of lesion is sampled in a core needle biopsy

21. Most common benign lesion mistaken for invasive carcinoma
More difficult to diagnose on core needle biopsy when borders and lobulocentric pattern may not be evaluable
1.5-2x increased relative risk for development of invasive carcinoma or 5-7% actual lifetime risk

22. Consider surgical consultation about excisional biopsy: No, unless radiographically discordant

23. Persian Golf

24. Radial scar
Typically, these lesions are identified as 'distortions of architecture'/'stellate lesions' on mammograms
If calcs are seen, which is not uncommon, they are an added extra rather than the main imaging diagnostic feature

25. RADIAL SCAR
Calcs are normally luminal, fine textured and associated with the various pathological processes seen as part of these lesions e.g.
 sclerosing adenosis within the lesion
columnar cell change
usual type epithelial hyperplasia

26. RADIAL SCAR
MAMMOGRAM
GROSS APPEARANCE

27. Complex sclerosing lesion (CSL) is less specific term
Complex sclerosing lesion (CSL) is less specific term. Sometimes defined as a RSL > 1 cm in size
Most RSLs are microscopic findings
Larger RSLs may present as mammographic density or even palpable mass
Both in situ and invasive carcinomas have been reported in association with RSL(>2 cm)

28. RADIAL SCAR Central nidus, varying degrees of fibrosis and
fibroelastosis in stellate or radial configuration
o Associated proliferative epithelial component
o Varying degrees of proliferative epithelial changes
o Smaller ducts can become entrapped in dense fibrous stroma within central fibrotic region

29. RSL is histologic risk factor for subsequent development of breast carcinoma
Presence of epithelial atypia, increased size, and multiple lesions are likely associated with increased risk for development of malignancy
Studies to identify myoepithelial cells may be helpful in difficult case.
However, results of myoepithelial cell studies to rule out malignancy must be interpreted with caution

30. Few small-series studies have shown that 40% of patients with radial scar on CNB had carcinoma (DCIS or invasive) at excision; and 22% reported ADH on follow-up excision
Should be excised

32. Columnar Cell Change Frequently accompanied by microcalcification
Calcs often fine - may be luminal, intra-epithelial or in adjacent stroma
Oxalate calcs uncommon

33. Cells line dilated terminal ductal lobular units (TDLUs)
Cystic spaces frequently contain luminal secretions and flocculent material
Molecular studies show genetic changes similar to those found in low-grade DCIS and invasive cancer
Morphologic spectrum based on presence and degree of epithelial atypia

34. Columnar cell change with periductal calcs
Columnar cell change with intra-epithelial calc
Columnar cell change with periductal calcs

37. FEA What does this mean? Flat epithelial atypia
“older term” clinging carcinoma
FEA(Flat Epithelial Atypia) represents columnar cell lesion with varying degrees of cytologic atypia
Intraductal alteration of the epithelial cells of 1-5 layers of “low grade” nuclei
Frequently coexists with lobular neoplasia and/or tubular carcinoma
If FEA is encountered on excision:
Perform multiple levels to look for architectural changes of ADH or low-grade DCIS
Submit all tissue for microscopic examination

38. FEA found on needle core biopsy:
• Surgical excision is recommended
• Diagnosis is upgraded to more serious lesion in 20-30% of cases CCC found on needle core biopsy (without atypia)
• Most likely incidental finding as result of microcalcifications
• Can be followed as long as there are no other worrisome clinical or mammographic findings

39. Hormoz Island

40. Intraductal papilloma
Benign epithelial proliferative lesions characterized by
papillary ingrowths into major ducts (LDP) or smaller
ducts (SDP)

41. Presentation of LDP:
Nipple discharge present in 80% of cases: unilateral and spontaneous
• Sanguinous or serosanguinous: 70%
• Bloody (less common): May be due to papilloma twisting on stalk and infarction
Palpable subareolar mass
Presentation of SDP
Finding on screening mammography
Incidental finding in a biopsy for another lesion
Usually does not cause discharge or a palpable mass

42. Arborizing fronds of tissue with well-developed central fibrovascular core
Lined by epithelial cells, myoepithelial cell layer
Presence of myoepithelial cells and their distribution in lesion is helpful diagnostic feature
May require use of myoepithelial markers to aid in the diagnostic evaluation in problematic cases

43. Intra ductal papilloma
Calcification common
Fine luminal calcs and/or coarser calcs seen at periphery associated with sclerosis in and around the papilloma

44. Mild increased risk of subsequent carcinoma: 1. 5-2
Mild increased risk of subsequent carcinoma: x relative risk or - 5-7% lifetime risk
Risk similar to that for moderate or florid ductal epithelial hyperplasia
Surgical consultation for lesions> 10 mm.

45. In core needle biopsies:
Management of lesions diagnosed as benign papillomas on core needle biopsy is controversial
Risk of carcinoma on excision of benign papillomas is very low
When cases are carefully selected and there is good radiologic/pathologic correlation, carcinomas on excision are absent or rare « 5%)
However, distinction between benign papillomas and atypical papillomas can be difficult, and some authorities recommend excision of all papillary lesions on core needle biopsy
Papillomas with atypia should be excised as 20-60% of cases will reveal carcinoma on excision

47. Atypical Lobular Hyperplasia
ALH is composed of a monomorphic proliferation of
discohesive polygonal or cuboidal cells that are small and
round. In lobules, these cells begin to fill acinar spaces,
but few are widely distendedrciJ.

48. ALH is an incidental finding in breast biopsies performed for other indications
Calcifications often present in areas adjacent to ALH
The hallmark feature of ALH, LCIS, and invasive lobular carcinoma is loss of E-cadherin expression
ALH is cytologically identical to lobular carcinoma in situ (LClS) but is more limited in extent

49. Calcification in ALH

50. ALH is associated with a 4-5x increased relative risk or a 13-17% lifetime risk of developing invasive carcinoma
In some studies, a strong family history of breast cancer doubles risk of invasive carcinoma to 8x
Ductal involvement by ALH (pagetoid extension) is associated with 8x risk or a 26% lifetime risk
• LClS has a l0x increased relative risk or a lifetime riskof - 30%
• Carcinomas that occur in women after a diagnosis of LN average> 10 years to diagnosis

51. ALH may be found as an incidental finding in a core needle biopsy
• If there is no other reason for excision, the value of excision based solely on presence of ALH is unclear
Likelihood of cancer on excision is higher in the following settings:
• Radiologic lesion is a mass or highly suspicious calcifications (linear &/or branching)
• ALH shows atypical features, such as higher nuclear grade, or is associated with calcifications

52. What is the recommendation?
Surgical consultation
Up to 20% upgraded at lumpectomy

53. Hormoz Beach

54. Mucocele like lesions
Uncommon breast lesion, composed of mucin containing
cysts that may rupture

55. MLL is usually asymptomatic
Screening mammograms may show mass or calcifications
Range from benign to ADH or DCIS to mucinous carcinoma
30% of mucocele-like lesions were identified as mucinous carcinoma on surgical excision

56. Data are limited, and excision is recommended whenever an atypical mucocele-like lesion or acellular stromal mucin identified on CNB

57. Sunset in Hormoz