Proliferative, Borderline and In-situ Proliferations

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Proliferative, Borderline and In-situ Proliferations Marilin Rosa, MD Department of Anatomic Pathology Moffitt Cancer Center and Research Institute University of South Florida Weekends of Pathology- March 2018

Transcript of Proliferative, Borderline and In-situ Proliferations

Page 1: Proliferative, Borderline and In-situ Proliferations

Proliferative, Borderline and

In-situ Proliferations

Marilin Rosa, MD

Department of Anatomic Pathology

Moffitt Cancer Center

and Research Institute

University of South Florida

Weekends of Pathology- March 2018

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No conflict of interest

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Objectives

o To provide an overview of proliferative, borderline and in-situ lesions diagnosed on core needle biopsy (CNB)

o To discuss the importance of the identification of patients with these lesions

o To briefly discuss follow-up options

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Background

o Each year, approx. 1.6 million breast biopsies are performed in the United States

o Approximately 20% of these biopsies carry a diagnosis of malignancy

o The majority of breast biopsies are classified within the spectrum of benign, atypical and borderline breast disease

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Background Modified classification (from Dupont and Page 1985)

o Non-proliferative breast

changes

Cysts Mild hyperplasia Simple fibroadenoma Papillary apocrine change Epithelial-related calcifications Ductal ectasia Non-sclerosing adenosis Periductal fibrosis

o Proliferative breast changes

without atypia

Complex fibroadenoma Moderate-florid hyperplasia Sclerosing adenosis Intraductal papillomas Radial scar

o Proliferative breast changes

with atypia

Atypical ductal hyperplasia Atypical lobular hyperplasia (Any of the above with atypia)

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Non-proliferative

changes

No elevation in breast cancer risk Proliferative breast

changes without atypia

Relative breast cancer risk: 1.3–1.9

Proliferative breast

changes with atypia

Relative breast cancer risk:3.9–13

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Core needle biopsy diagnosis • Requires multidisciplinary approach • Availability of only limited material • Sampling error • Loss of calcifications during processing • Association with a more significant lesion at excision • Inaccurate tumor grading • Lack of uniform diagnostic criteria and terminology • Diagnostic difficulties with certain lesions • Lack of consensus on managing

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Core needle biopsy diagnosis Multidisciplinary approach

• To confirm that the targeted lesion was biopsied • To confirm that there is pathological/radiological

correlation • To confirm that there is clinical/pathological

correlation • To evaluate management options

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Core needle biopsy Sampling error

Pathologic

Diagnosis

Incidence of malignancy

after excision

Ductal carcinoma in situ Up to 20%

Atypical ductal hyperplasia 33 - 87%

Lobular neoplasia 13 – 28%

Radial sclerosing lesion 0 – 40%

Papillary lesions 14 – 25% Corben AD, Edelweiss M, Brogi E. Challenges in the interpretation of breast core biopsies. Breast J. 2010 Sep-Oct;16 Suppl 1:S5-9.

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Core needle biopsy Sampling error/Processing

• Small biopsy size • Distortion and fragmentation of the tissue

samples • Differences regarding tissue processing • Available laboratory technology/ resources

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Core needle biopsy Lack of uniform diagnostic criteria and terminology

• Variable histologic diagnostic criteria • Variable terminology • Confusing or inadequate terminology • Interobserver variability • Lack of adequate clinical history and

radiologic findings

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Core needle biopsy Diagnostic difficulties

• Papillary lesions

• Mucinous lesions • Radial sclerosing lesions • Columnar cell changes

• Atypical proliferative lesions vs. low grade in-situ carcinoma (Borderline lesions)

• Adenosis

• Fibroepithelial lesions with cellular stroma • Spindle cell lesions • Residual or recurrent carcinoma after radiation • Specific tumor types

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Papillary lesions

Papillomas: Central vs. Peripheral Central (large duct papilloma): o Close to nipple within principal

lactiferous ducts o 90% solitary o 70% associated with nipple

discharge o No increased risk of

subsequent malignancy

Peripheral: o Multiple o Clinically occult, discovered by

mammographic calcifications o Increased risk of subsequent

malignancy, particularly if

ADH/ALH is present

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Papillary lesions in CNB

Most commonly used terminology: • Intraductal papilloma/ papillary lesion

without atypia • Papilloma with atypia/ atypical papilloma • DCIS, papillary type • In-situ papillary carcinoma • DCIS with features of solid papillary

carcinoma DCIS: Ductal carcinoma in situ

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Papillary lesions in CNB When to use the terms “atypical papilloma”, “DCIS, papillary type” and “in-situ papillary carcinoma”? Papilloma with atypia: Basic lesion is a papilloma Morphologic features of atypia/low nuclear grade DCIS Atypia in <33% of the papilloma Atypia in 33-90% of the papilloma = Carcinoma arising in papilloma ADH focus involving <3 mm/Atypical papilloma Atypical focus involving >3 mm = DCIS arising within a papilloma DCIS, papillary type: Usually admixed with other morphologic types of DCIS Retain a myoepithelial cell layer In situ papillary carcinoma: Fragmented biopsy Doubtful regarding invasion or type of papillary lesion

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p63 p63

CK5/6 ER

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Columnar cell changes • Often associated with microcalcifications detected on

mammogram • Classified as columnar cell change (CCC) and

columnar cell hyperplasia • Each of these categories can have associated atypia • Atypical columnar cell lesions are also known as flat

epithelial atypia Because CCC has been referred to by several different names in the literature, data on its significance as a risk marker for development of invasive cancer or the risk of finding adjacent associated malignancy are limited

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Columnar cell changes • Columnar cell lesions should be examined at intermediate or high magnification

because atypia may be unapparent at low power

CCC-atypia (low-

moderate)

Two layers

CCC atypia (flat epithelial

atypia)

More than 2 layers

No or minimal architectural

changes

Columnar cell hyperplasia with atypia

Complex architectural

changes

ADH

CCC-high grade atypia

Flat high-grade DCIS

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Proliferative changes without atypia Usual ductal hyperplasia

Architectural features

• Irregular fenestrations • Peripheral fenestrations • Stretched or twisted bridges • Streaming • Overlapped nuclei

Cellular features • Multiple cell types (epithelial,

myoepithelial, apocrine) • Variation in appearance of

epithelial cells • Indistinct cell margins • Variation in nuclear

appearance

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Ductal proliferations Ductal hyperplasia of usual type,

florid

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Borderline breast disease Atypical ductal hyperplasia

• A neoplastic proliferation of evenly distributed, monomorphic cells similar to those of low-grade DCIS

• The cells do not fill or distend the entire acini within a lobule

• Architectural atypia does not involve the entire duct

• Lesion is less than 2 mm or 2 contiguous ducts

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Ductal proliferations Atypical ductal hyperplasia

• Size • Duct involvement

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Core needle biopsy Adenosis

• Adenosis can cause diagnostic problems

especially in CNB • Microglandular adenosis is the only benign

lesion with an infiltrative growth pattern and absence of myoepithelial cells

• Use myoepithelial cell markers in difficult cases and be conservative in small biopsies

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Core needle biopsy Adenosis

Sclerosing adenosis • A benign lobulocentric

lesion with significant sclerotic stromal changes

• SA can be associated with perineural and perivascular invasion

• Relative risk for development of invasive carcinoma is approx. 1.7

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Core needle biopsy Adenosis

Microglandular adenosis The glands contain

deep eosinophilic colloid-like intraluminal secretion

The glands are round and not angulated as seen in tubular carcinoma

ER, PR negative S-100 positive

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Core needle biopsy To excise or NOT to excise?

• There is current consensus that lesions diagnosed as “atypical” on minimally invasive procedures should be excised

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Core needle biopsy Excise or NOT excise, that is the

question! What to do with some proliferative lesions

without atypia diagnosed on CNB?

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Core needle biopsy Diagnostic difficulties

To excise or NOT to excise?

Problems with current studies • Selection criteria • Terminology, grading, interobserver variability • Present of other premalignant/ atypical lesions in

the same biopsy • The extent of core needle biopsy sampling • The way biopsies are processed

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Core needle biopsy To excise or NOT to excise?

• There is radiologic–pathologic disagreement • Sampling technique:

– Needle gauge – Number of cores – Use of vacuum-assisted techniques

• Size of the lesion • Patient’s age and personal or family history of

breast cancer

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Core needle biopsy diagnosis

Summary

o Pathologists carry a major responsibility in patient diagnosis, risk stratification and management

o Despite attempts to refine and improve the diagnostic accuracy of atypia in CNB, there are still substantial differences in the interpretation and management of “borderline” lesions

o In some cases, excisional biopsy is the only reliable method for establishing the presence of prognostically significant lesions

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References: 1. Jensen RA, Dupont WD, Page DL.

Diagnostic criteria and cancer risk of proliferative breast lesions. J Cell Biochem Suppl. 1993;17G:59-64.

2. Guray M, Sahin AA. Benign breast diseases: classification, diagnosis, and management. Oncologist. 2006 May;11(5):435-49.

3. Masood S, Rosa M. Borderline breast lesions: diagnostic challenges and clinical implications. Adv Anat Pathol. 2011 May;18(3):190-8.

4. Collins LC, Schnitt SJ. Papillary lesions of the breast: selected diagnostic and management issues.Histopathology. 2008 Jan;52(1):20-9.

5. Saremian J, Rosa M. Solid papillary carcinoma of the breast: a pathologically and clinically distinct breast tumor. Arch Pathol Lab Med. 2012 Oct;136(10):1308-11.

6. Khazai L, Rosa M. Use of Immunohistochemical Stains in Epithelial Lesions of the Breast. Cancer Control. 2015 Apr;22(2):220-5