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Cystically Dominant Lesions of the Breast

UCSF 32nd AnnualCurrent Issues in Anatomic Pathology and Cytology SANDRA J. SHIN, MDPROFESSOR OF PATHOLOGY AND LABORATORY MEDICINECHIEF OF BREAST PATHOLOGYWEILL CORNELL MEDICINE

Pattern-based diagnosis in breast pathology� Fundamental skill of diagnostic pathologists� Surprisingly, not necessarily the first step when evaluating a new lesion or proliferation. Instead, slide is scanned for key morphologic features diagnostic for specific entities -arriving at the diagnosis faster� Pattern-based evaluation as an initial step� Helps to generate a complete differential diagnosis that includes even uncommon or rare lesions�Most useful in core biopsies since key diagnostic features may not be present or compromised

Top 6 patterns seen in breast pathology� Small glandular proliferation� Spindle cell proliferation� Cystically dominant lesions� Vascular lesions� Fibroepithelial lesions � Papillary lesions

Top 6 patterns seen in breast pathology� Small glandular proliferation� Spindle cell proliferation� Cystically dominant lesions- focus on core biopsies� Vascular lesions� Fibroepithelial lesions � Papillary lesions

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MAMMOCALCS

NEEDLE CORE BIOPSY

DIAGNOSIS

Cystically Dominant Lesions with calcs +/- secretions

� Larger caliber ducts�Cysts in the fibrocystic disease�Duct stasis/ duct ectasia�Cystic hypersecretory lesions�Juvenile Papillomatosis� Lobulocentric / TDLU�Columnar cell lesions and flat epithelial atypia�Pregnancy-like (pseudolactational) change or hyperplasia�Mucocele-like lesions

Secretions and Calcifications� Secretions �May or may not be present within glandular/cystic lumens �Vary in amount, color, consistency�None are pathognomic for an entity� Calcifications �Associated with full spectrum of breast disease�Vary in amount, size, appearance, location�None are pathognomic for an entity

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Cysts of fibrocystic disease

Blue-domed Cyst

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Cysts of fibrocystic disease

Calcium Oxalate Crystals

Thin, translucentlightly eosinophilic or basophilic secretions

Cysts of fibrocystic disease

Cysts of fibrocystic disease on core biopsy

No excisional biopsy if there is pathologic-radiologic concordance

Duct ectasia

Courtesy of Dr. Timothy D’Alfonso

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Duct ectasia

No calcifications

Fluffy translucent lightly eosinophilic secretions

Macrophages

Duct stasis

Translucent pale blue/gray secretions

Duct ectasia on core biopsy

No excisional biopsy if there is pathologic-radiologic concordance

Cystic Hypersecretory Lesions

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Cystic hypersecretory lesions

CAN BE MISTAKEN FOR CYSTS OF FIBROCYSTIC DISEASE AT SCANNING MAGNIFICATION

Cystic hypersecretory hyperplasia

Parallel Cracks“Venetian Blinds”

Retracted Dense Colloid-Like

HistiocytesLymphocytic inflammation

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Atypical cystic hypersecretory hyperplasiaAm J Surg Pathol 2014; 38:45-53

10 patients; female; average age 63 yearsClinical presentation: mass but also calcifications and bloody nipple dischargeMicroscopic extent: 9 mm (2 mm to 2.7 cm)Histology: micropapillary growth pattern; intermediate or high nuclear gradearising in a background of CHH and/or atypical CHHBiomarker profile: ER+ HER2- (80%) ER/PR- HER2- (20%) including one case with microinvasive carcinoma and micrometastasis to one SLN1/10 (10%) lacked investing myoepithelium by p63, SMM, CK5Treatment of 4 patients: EXBX + RT (2 patients); EXBX + RT + Chemo (1 patient); MX + Tamoxifen (1 patient)Clinical follow-up: All NED mean 5.5 years

Cystic hypersecretory (in-situ) carcinoma

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Cystic hypersecretory(in-situ) carcinoma

DIMINISHED SECRETIONS AND HIGH NUCLEAR

GRADEER

Invasive cystic hypersecretory carcinoma

Cystic hypersecretory hyperplasia on core biopsy

Recommend excisional biopsy regardless ofpathologic-radiologic concordance or lack of atypia

Columnar cell lesionsFlat epithelial atypia

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Columnar cell change Flat epithelial atypia(columnar cell change with atypia)

Courtesy of Dr. Stuart Schnitt

FLAT EPITHELIAL ATYPIA(COLUMNAR CELL

CHANGE WITH ATYPIA)

Courtesy of Dr. Stuart Schnitt

FLAT EPITHELIAL ATYPIA

(COLUMNAR CELL HYPERPLASIA WITH

ATYPIA)

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Hallmark FeaturesColumnar Cell Change� Elongated nuclei� Epithelial polarization� No cytologic atypia� Round or irregular shaped lumens� Monolayer or broad papillary tufting growth pattern� No mitoses� Calcifications

Flat Epithelial Atypia� Rounded nuclei� Loss of epithelial polarization “jumbled”� Low grade cytologicatypia-monomorphic� Round shaped lumens� Monolayer or pseudostratified growth pattern� No mitoses� Calcifications

Flat Epithelial AtypiaColumnar Cell Change

Columnar Cell Hyperplasia

Courtesy ofDr. Stuart Schnitt

Yamashita Y, et al. Virchows Arch March 2016Morphometric Analysis 7917 nuclei of 22 FEA cases5010 nuclei of 13 CCC/CCH casesResults/ConclusionsNuclear roundness was more characteristic of FEA than CCC/CCH (statistically significant; p<0.001)Nuclear roundness was more characteristic of FEA with malignancy than FEA without malignancy(statistically significant; p<0.001)

Flat Epithelial AtypiaColumnar Cell Change

Columnar Cell Hyperplasia

Courtesy ofDr. Stuart Schnitt

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FEA

Tubular ca

CCL/FEA

Inv tubular ca

LCIS

Courtesy ofDr. Stuart Schnitt Abdel-Fatah T, et al AJSP 2007;31:417-426

+1q-16q

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p63 Recommend excisional biopsy only if flat epithelial atypia is identified

Juvenile Papillomatosis

Juvenile PapillomatosisRosen PP, et al. Cancer 1985;55:1345-1352

30 yrs or younger (range 12-48; mean 23)Painless and mobile mass – clinically mistaken for fibroadenomaUsually solitary, sometimes bilateral25/180 (14%) recurrent JPFamily history of breast cancer: Majority of secondary relatives (23/39; 59%) were from maternal side

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Courtesy of Dr. Timothy D’Alfonso

Spectrum of benign changes arranged in a localized fashion: Cysts – simple or apocrine; with luminal histiocytesHyperplasia- ductal and apocrine with histologic mergingPapillary epithelial proliferation (papillomasor papillomatosis)Sclerosis/ radial sclerosing changes

Juvenile Papillomatosis

Merging of Ductal and Apocrine Hyperplasia

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Lobular carcinoma in-situ (LCIS)Arising in Juvenile Papillomatosis

� Pts with carcinoma: slightly older at time of JP dx (27 yrs versus 23 yrs) and higher frequency of positive family history (56%) � Management: EXBX with clear margins of JP; clinical follow up of pt and pt’s female relatives

Juvenile Papillomatosis and Carcinoma

Juvenile Papillomatosis on Core Biopsy

Recommend excisional biopsy with clear margins

Pregnancy-like (pseudolactational) change/hyperplasia

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Pregnancy-like (pseudolactational) change

Am J Surg Pathol 2000; 24(12):1670-1674

12 cases of PLH as primary dx (4- NCB; 8-EXBX)5/12 performed for mammo calcs4/12 mass; 1/12 “abnl mammo”; 1/12 galactorrhea5/12 co-existing CHH

3/5 merging and with atypia1/5 separate and PLH with atypia1/5 separate and no atypia

4/5 with co-existing CHH also showed atypiaTake home messages:Do not mistake PLH for ADHRecognize PLH and CHH can co-exist and even merge

Pregnancy-like Change Pregnancy-like Hyperplasia Atypical Pregnancy-like Hyperplasia

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Histologically Combined PLH and CHH Lesions

Am J Surg Pathol 2004; 28:789-793

9 cases of DCIS (plus inv ca in 1) arising from PLH and CHHAll women; age 35-49 years old (average 42)6/9 performed for mammo calcs2/9 mass; 1/9 nipple discharge5/9 merging PLH and CHH (one or both with atypia)DCIS: 2/9 micropapillary type, both from PLH7/9 CHC type; 4 arising from atypical CHH; 1 also had invasive ca – well diff IFDC- 4mm with ITC in 1 SLNTake home messages:If PLH or CHH with atypia or combined PLH-CHH without atypia are identified in NCB; recommend EXBX

Atypical Pregnancy-like Hyperplasia Micropapillary DCIS Calcifications Associated With Pregnancy-like (pseudolactational) Proliferations

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Secretions in Pregnancy-like(pseudolactational) Proliferations

Pregnancy-like change on core biopsy

Recommend excisional biopsy only if atypia or combined PLH-CHH is identified

Mucocele-like lesions

Mucocele-like lesion

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Calcifications Associated With Mucocele-likeLesions

Secretions in Mucocele-like Lesions

Pathologic upgrade rate in EXBX of benign MLL diagnosed in core biopsy

Authors Year N totalexcised

N upgrade

Upgradediagnosis

% upgrade

Ha et al 2015 23 0 - 0

Diorio et al 2015 35 2 DCIS 5.7

Rakha, et al 2013 54 2 DCIS 4

Sutton et al 2012 22 0 - 0Jaffer et al 2011 45 1 DCIS 2.2Carkaci et al 2011 9 0 - 0

Take home messages:Most MLLs today are biopsieddue to their association with calcsEven in studies with an inherent selection bias, the pathologic upgrade rate is lowRecent studies suggest that not all benign MLLs need to be excised

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Mucocele-like lesion in core biopsy

Recommend excisional biopsy only if atypical ductal hyperplasiaor carcinoma is identified

Not all benign MLLs may need to be excised and such cases should be managed in a multidisciplinary setting

MLLs and columnar cell lesions occurring as a morphologic continuum

Fadare O, Mariappan MRJ Med Case Reports 2008; 2:138

Thank You