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

Hormoz Island

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

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

Hormoz Island

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.

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.

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.

Hormoz Island

Which benign Breast lesions may be encountered with microcalcification?

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

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

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

Hormoz Island

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

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

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

SCLEROSING ADENOSIS Mammogram  microcalcification

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

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

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

Persian Golf

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

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

RADIAL SCAR MAMMOGRAM GROSS APPEARANCE

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)

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

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

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

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

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

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

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

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

Hormoz Island

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

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

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

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

Mild increased risk of subsequent carcinoma: 1. 5-2 Mild increased risk of subsequent carcinoma: 1.5-2.0x relative risk or - 5-7% lifetime risk Risk similar to that for moderate or florid ductal epithelial hyperplasia Surgical consultation for lesions> 10 mm.

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

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.

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

Calcification in ALH

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

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

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

Hormoz Beach

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

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

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

Sunset in Hormoz