29 Common Consultation Conundrums in Breast Pathology...

29 Common Consultation Conundrums in Breast Pathology

Sandra Shin MD

2011 Annual Meeting – Las Vegas, NV

AMERICAN SOCIETY FOR CLINICAL PATHOLOGY 33 W. Monroe, Ste. 1600

Chicago, IL 60603

29 Common Consultation Conundrums in Breast Pathology Difficult or problematic breast lesions are commonly submitted to breast pathology consultants for a second opinion because of: 1) unusual, unexpected or ambiguous histological features and/or immunohistochemical staining results; 2) lack of consensus in lesion classification; 3) unclear reporting guidelines; or 4) rarity of the lesion. The purpose of this session is to provide pathologists with a practical approach to such problematic breast lesions that they will be able to apply in their daily practice. Discussion topics will include diagnostic problems with papillary, fibroepithelial, columnar cell and in situ lesions, microinvasion, small glandular proliferations, spindle cell lesions, and vascular lesions. Emphasis will be placed on the application and pitfalls of adjunctive immunohistochemical studies to resolve these differential diagnostic dilemmas.

• Correctly classify and diagnose problematic breast lesions. • Understand the uses and limitations of immunostains in resolving diagnostic dilemmas in breast

pathology. FACULTY: Sandra Shin MD Practicing Pathologists Surgical Pathology Surgical Pathology (Derm, Gyn, Etc.) 2.0 CME/CMLE Credits Accreditation Statement: The American Society for Clinical Pathology (ASCP) is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education (CME) for physicians. This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME). Credit Designation: The ASCP designates this enduring material for a maximum of 2 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. ASCP continuing education activities are accepted by California, Florida, and many other states for relicensure of clinical laboratory personnel. ASCP designates these activities for the indicated number of Continuing Medical Laboratory Education (CMLE) credit hours. ASCP CMLE credit hours are acceptable to meet the continuing education requirements for the ASCP Board of Registry Certification Maintenance Program. All ASCP CMLE programs are conducted at intermediate to advanced levels of learning. Continuing medical education (CME) activities offered by ASCP are acceptable for the American Board of Pathology’s Maintenance of Certification Program.

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COMMON CONSULTATION CONUNDRUMS IN BREAST PATHOLOGY

SANDRA J SHIN

2011 ASCP Annual Meeting

SANDRA J. SHINCHIEF OF BREAST PATHOLOGYASOCIATE PROFESSOR OF PATHOLOGY AND LABORATORY MEDICINENEW YORK PRESBYTERIAN HOSPITAL-WEILL CORNELL MEDICAL COLLEGE

DISCLOSURE

NONE


CONSULTATION CONUNDRUMS

THE VAST MAJORITY OF CONSULTATION CASES REPRESENTS THE PROBLEMATIC AREAS IN BREAST PATHOLOGY COMMON TO ALL


PATHOLOGY COMMON TO ALL PATHOLOGISTS

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UNUSUAL, UNEXPECTED OR AMBIGUOUS HISTOLOGIC FEATURES AND/OR IMMUNOHISTOCHEMICAL RESULTS


RESULTSUNCLEAR REPORTING GUIDELINESLACK OF INTRADEPARTMENTAL CONSENSUS OF DIAGNOSISRARITY OF LESION


UNUSUAL, UNEXPECTED OR AMBIGUOUS HISTOLOGIC FEATURES AND/OR IMMUNOHISTOCHEMICAL RESULTS


RESULTSUNCLEAR REPORTING GUIDELINESLACK OF INTRADEPARTMENTAL CONSENSUS OF DIAGNOSISRARITY OF LESION

CHALLENGING AREAS IN BREAST PATHOLOGY

PAPILLARY LESIONSFIBROEPITHELIAL LESIONSSMALL GLANDULAR PROLIFERATIONSSPINDLE CELL LESIONS (i l d VASCULAR)


SPINDLE CELL LESIONS (includes VASCULAR)LOBULAR CARCINOMA IN-SITU (LCIS)

COLUMNAR CELL LESIONSINVASIVE CARCINOMA

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TOPIC 1 OF 5PAPILLARY LESIONS


NO ONE’S FAVORITE BREAST LESION

COMPLEX AND HETEROGENEOUSDO NOT FOLLOW A STEPWISE PROGRESSION OF INCREASING PROLIFERATIVE CHANGES AND “ATYPIA”


GROSS TUMOR SIZE / CLINCIAL SIGNS/SX NOT HELPFULIMMUNOHISTOCHEMISTRY LESS HELPFUL IN CLASSIFYING THESE LESIONS (i.e. INVASIVE VS. IN-SITU)

HISTOLOGIC COMMONALITY OF PAPILLARY LESIONS

PAPILLARY, ARBORSCENT EPITHELIAL PROLIFERATION SUPPORTED BY FIBROVASCULAR STALKS WITH OR


FIBROVASCULAR STALKS WITH OR WITHOUT AN INTERVENING MYOEPITHELIAL CELL LAYER

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SPECTRUM OF PAPILLARY LESIONSPAPILLOMA WITH/WITHOUT PROLIFERATIVE CHANGESPAPILLOMA WITH ATYPIA

AKA….ATYPICAL PAPILLOMA, PAPILLOMA WITH ADH, ATYPICAL PAPILLARY LESION

PAPILLOMA WITH DCIS


PAPILLOMA WITH DCISPAPILLARY (IN-SITU) CARCINOMA

PAPILLARY DCISENCAPSULATED (INTRACYSTIC) PAPILLARY CARCINOMASOLID PAPILLARY CARCINOMA

INVASIVE PAPILLARY CARCINOMA

PROBLEM AREASPAPILLOMA VS. PAPILLARY DCISPAPILLOMA WITH (FLORID DH VS. ADH VS. DCIS)PAPILLOMA WITH FLORID DH VS. SOLID


PAPILLARY CARCINOMA ENCAPSULATED (INTRACYSTIC) PAPILLARY CAPAPILLARY LESIONS IN NEEDLE CORE BXSIN-SITU VS. INVASIVE PAPILLARY CA




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PAPILLOMA VS. PAPILLARY DCIS

HISTOLOGIC OVERLAPWELL-FORMED PAPILLAE WITH FIBROVASCULAR CORES THROUGHOUT LESION


LOW NUCLEAR GRADEINTRADUCTAL/INTRACYSTIC GROWTH PATTERN WITH POINT OF ATTACHMENTVARIABLE SIZE


PAPILLOMA OR PAPILLARY DCIS?


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EPITHELIAL AND MYOEPITHELIAL

HAPHAZARD

NORMOCHROMATIC

EPITHELIAL

UNIFORM, ┴ TO FVC

HYPERCHROMATIC

CELL TYPE

CELL ORIENTATION

NUCLEI

INTRADUCTAL PAPILLOMA PAPILLARY DCIS


NORMOCHROMATIC

PROMINENT; FIBROSIS

PRESENT

HYPERPLASIA

HYPERCHROMATIC

DELICATE

ABSENT

DCIS

NUCLEI

STROMA OF PAPILLAE

APOCRINE MET

PROLIFERATIONIN ADJ DUCTS

Collins LC and Schnitt SJ, Histopathol 2008


OTHER “SOFT” FINDINGS OF PAPILLOMAS

MYOEPITHELIAL HYPERPLASIAAPOCRINE METAPLASIAINFARCTION


SQUAMOUS METAPLASIA

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DISTRIBUTION OF MYOEPITHELIAL CELLSWITHIN PAPILLAE PERIPHERY

PAPILLOMA PRESENT PRESENT

PAPILLOMA WITHADH/DCIS PRESENT/ABSENT PRESENT


PAPILLARY DCIS ABSENT PRESENT

ENCAPSULATEDPAPILLARY CA ABSENT ABSENT

SOLID PAPILLARYCA ABSENT PRESENT

OR ABSENT


WELL-DIFFERENTIATED IN-SITU PAPILLARY CARCINOMA

SMM

2011 ASCP Annual MeetingSMM-HCPAPILLARY DCIS

NEEDLE CORE BIOPSY


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p63


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SMM


POSSIBLE PITFALLS OF MYOEPITHELIAL CELL MARKERS

MEC MARKERS VARY IN SENSITIVITY AND SPECIFICITY - PANELMISTAKEN FOR MEC

PERICYTES


MYOFIBROBLASTS IN THE STROMANEOPLASTIC CELLS

DISPLACED CARCINOMA CELLS CAN BE NEGATIVE FOR ME MARKERS

SMM


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CALPONIN





FLORID DUCT HYPERPLASIA IN A PAPILLOMA


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SOLIDPAPILLARY


CARCINOMA


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PAPILLOMA WITH FLORID DUCT HYPERPLASIA


SOLID PAPILLARY CARCINOMA


PAPILLOMA PRESENT PRESENT(+/-FDH)



ADH/DCIS PRESENT/ABSENT PRESENT



SOLID PAPILLARYCARCINOMA ABSENT PRESENT

OR ABSENT


NORMALDUCT

2011 ASCP Annual Meetingp63

ATTENUATED &ABSENT STAINING

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OTHER USEFUL IMMUNOSTAINS

PAPILLOMA PAPILLOMA SOLID PAP+ FDH + ADH/DCIS CARCINOMA

HMWCK DIFFUSE OR NEG NEG


(CK5/6; K903) MOSAIC

ER FEW POS NEG/POS POS

NE MARKERS NEG NEG POS(SYNAPTO, CD56)

*

FLORID DUCT HYPERPLASIA

2011 ASCP Annual MeetingRabban J, et al. Human Pathol 2006; 37: 789.

CK 5/6

SOLID PAPILLARY CARCINOMA

2011 ASCP Annual MeetingRabban J, et al. Human Pathol 2006; 37: 789.

CK 5/6

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NEEDLE CORE BIOPSY



CK5/6


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OTHER USEFUL IMMUNOSTAINS

PAPILLOMA PAPILLOMA SOLID PAP+ FDH + ADH/DCIS CARCINOMA

HMWCK DIFFUSE OR NEG NEG


(CK5/6; K903) MOSAIC

ER FEW POS NEG/POS POS

NE MARKERS NEG NEG POS(SYNAPTO, CD56)

*

ER


NEEDLE CORE BIOPSY


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2011 ASCP Annual Meeting SYNAPTOPHYSIN

2011 ASCP Annual MeetingER

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2011 ASCP Annual Meeting EXBX

NEUROENDOCRINE MARKERS

MOST COMMONLY POSITIVE IN SOLID PAPILLARY CARCINOMAALSO POSITIVE IN PAPILLARY DCIS AND ENCAPSULATED PAPILLARY CARCINOMA


ENCAPSULATED PAPILLARY CARCINOMA (LESSER EXTENT)SYNAPTOPHYSIN, CHROMOGRANIN, CD56NEURON SPECIFIC ENOLASE – NOT RECOMMENDED

PROBLEM AREASPAPILLOMA VS. PAPILLARY DCISPAPILLOMA WITH (FLORID DH VS. ADH VS. DCIS)PAPILLOMA WITH FLORID DH VS. SOLID PAPILLARY CARCINOMA


ENCAPSULATED (INTRACYSTIC) PAPILLARY CAPAPILLARY LESIONS IN NEEDLE CORE BXSIN-SITU VS. INVASIVE PAPILLARY CA

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NEEDLE CORE BIOPSY




PAPILLOMA PRESENT PRESENT(+/-FDH)



ADH/DCIS PRESENT/ABSENT PRESENT



SOLID PAPILLARYCARCINOMA ABSENT PRESENT

OR ABSENT


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p63


ER


EXBX


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SMM


ENCAPSULATED (INTRACYSTIC) PAPILLARY CARCINOMA

? IN-SITU OR LG INVASIVE CA MORHOLOGICALLY SIMILAR METASTATIC FOCI

PRECURSOR TO MUCINOUS CARCINOMA BUT ALSO OTHER TYPES OF INVASIVE DUCT CAINDOLENT BEHAVIOR WITHOUT CONCURRENT


INDOLENT BEHAVIOR WITHOUT CONCURRENT INVASIVE COMPONENTEVEN WITH INVASION, PROGNOSIS IS FAVORABLE COMPARED TO INVASIVE DUCT CA OF COMPARABLE SIZE




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DIAGNOSTIC PROBLEMS MAGNIFIED IN NEEDLE CORE BXS

MORPHOLOGIC PITFALLS DUE TO SMALL SAMPLE SIZE

ENTRAPPED GLANDS OF A SCLEROSING PAPILLARY LESION MIMICK INVASIVE DUCT


CARCINOMA

ATYPIA, IF PRESENT, CAN BE FOCALTISSUE FRAGMENTATIONRENDERING A FINAL DX OF A PAPILLARY LESION ON NCB IS VIRTUALLY IMPOSSIBLE

BENIGN

FDHUS/ADH

ALL PAPILLARY LESIONS

2011 ASCP Annual MeetingShah VI, et al. Histopathology 2006; 48: 685.

SUSP DCIS

DCIS/INV CA

PATHOLOGIC UPGRADE ON EXBX = 4%

CALPO

NIN

2011 ASCP Annual Meeting Shah VI, et al. Histopathology 2006; 48: 687.B3a LESION – FDH, PROB BENIGN

CK 5/6

P63

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CALPO

NIN

2011 ASCP Annual Meeting Shah VI, et al. Histopathology 2006; 48: 688.B3b LESION – ADH; after IHC CHANGED TO B5 ‐DCIS

CK 5/6

P63

CONCLUSIONS - SHAH ET AL STUDY

With IHC, accuracy of diagnosis increased for all 4 observers

PPV 78-88%NPV 100%


Accuracy 91-95%IHC most helpful to least experienced observerIHC permitted reclassification of all B3a cases into one of two more clinically useful categories (B2 or B3b/4/5)

Am J Surg Pathol 2009;33(11):1615 1623


Am J Surg Pathol 2009;33(11):1615-1623

82 PAPILLARY LESIONS WITH EPITHELIAL PROLIFERATION BETWEEN FIBROVASCULAR CORES52 CASES-TEST 30 CASES-VALIDATION (ALL WITH EXBX)

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615-

1623

CK5

2011 ASCP Annual Meeting Am J

Sur

g Pa

thol

200

9;33

(11)

:16

ER


ER-high/CK5-low immunoprofile identifies atypical papillary lesions at a sensitivity of 93% and specificity of 100%

ER-low/CK5-high immunoprofile identified non-atypical papillary lesions at a sensitivity of 100% and specificity of 93%




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TOPIC 2 OF 5SMALL GLANDULAR PROLIFERATIONS


HISTORY

59 YEAR-OLD FEMALEBREAST NODULE -RETROAREOLARNO OTHER SIGNIFICANT CLINICAL HX


NEEDLE CORE BIOPSY PERFORMED

2006


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2006


DIFFERENTIAL DIAGNOSIS

INVASIVE WELL-DIFFENTIATED DUCT CARCINOMA

TUBULAR FEATURESSYRINGOMATOUS ADENOMA


LOW-GRADE ADENOSQUAMOUS CARCINOMARADIAL SCLEROSING LESIONCOMPLEX SCLEROSING LESIONSCLEROSING ADENOSISSKIN ADNEXAL CARCINOMA

INVASIVE TUBULAR CARCINOMA


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INVASIVE TUBULARCARCINOMA ?


ADENOSIS ?

RADIALSCLEROSINGLESION?


INVASIVE TUBULARCARCINOMA ?

RADIALSCLEROSING

LESION

INVASIVE TUBULAR CARCINOMAARISING IN RSL

OR

ENTRAPPED/PARTICIPATINGBENIGN GLANDS


LESION

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HOW WE LEARN PATHOLOGYMOST DIDACTIC LECTURES ARE FOCUSED AROUND SPECIFIC ENTITIESPATTERN – BASED LEARNING MAY BE MORE USEFUL, ESP IN CERTAIN SETTINGS SUCH AS CORE NEEDLE BIOPSIES


SUCH AS CORE NEEDLE BIOPSIES PATHOLOGIC FINDINGS ARE FRAGMENTEDDIAGNOSTIC FEATURES ARE MISSING

THE SPECTRUM OF BENIGN, ATYPICAL AND MALIGNANT ENTITIES CAN HAVE THE SAME PATTERN

ARRIVING AT THE CORRECT DX

PATTERN RECOGNITION - DDXALGORITHM WHEN WE GET STUCK….


USE ADJUNCTIVE TOOLS (IHC)CONSULT A COLLEAGUEBOTH

ADJUNCTIVE DIAGNOSTIC TOOLS

IMMUNOHISTOCHEMISTRYSPECIAL STAINSMOLECULAR CHARACTERIZATION


FISHGENE PROFILING

ELECTRON MICROSCOPY

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SMALL GLANDULAR PROLIFERATIONS OF THE BREAST (SGPB)

MALIGNANT-APPEARING BUT BENIGN


BENIGN-APPEARING BUT MALIGNANT

MALIGNANT-APPEARING BUT MALIGNANT OF A DIFFERENT TYPE

CASE 1 continued…


DIAGNOSIS RENDERED

INVASIVE DUCT CARCINOMA, WELL-DIFFERENTIATEDRE-REVIEWED AT INSTITUTION WHERE SURGERY WAS PLANNED


SURGERY WAS PLANNEDNEW DIAGNOSIS: SYRINGOMATOUS ADENOMANO SURGERY PERFORMED

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5 YEARS LATER…2011

BREAST MASS GROWN 5 CM LARGE; NEEDS MASTECTOMY IF MALIGNANT




2011


2011


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p63


SMM-HC


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SMM-HC


LOW-GRADE ADENOSQUAMOUS CARCINOMA


29 CASES OF LGASCMYOEPITHELIAL MARKERS (p63, SMM, CD10, CALPONIN, SMA)


)CYTOKERATINS (CKAE1/3, CK7, Cam 5.2, CK5/6, K903)GLANDULAR EPITHELIUM AND ADJACENT STROMA STUDIED

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RESULTS- MYOEPITHELIAL MARKERSGLANDULAR EPITHELIUM

CIRCUMFERENTIAL STAINING IN MOST (>80%) CASES WITH EITHER COMPLETE (~75%) OR WEAK, DISCONTINUOUS (~35%) STAINING USING ANY ONE STAIN. OCCASIONALLY GLANDS ARE NEGATIVE


STAIN. OCCASIONALLY GLANDS ARE NEGATIVE

ADJACENT STROMALAMELLAR STAINING ~45% OF CASES USING ANY ONE STAINDIFFUSE STROMAL POSITIVITY IN >50% (CALPONIN, CD10, SMA); ~12.5% (SMM); 0 (p63)

p63

VARIABLY POSITIVE IN BASALLY LOCATED CELLS


LUMINAL CELLSTAINING

SMOOTH MUSCLE MYOSIN

VARIABLY POSITIVE IN BASALLY LOCATED CELLS


“LAMELLAR” STAINING PATTERN

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SMM-HC


RESULTS- CYTOKERATIN MARKERSGLANDULAR EPITHELIUM

POSITIVE FOR ONE OR MORE STAINS IN ALL CASES DIFFUSE WITH EITHER UNIFORM OR VARIABLY INTENSE INTENSITY IN >75% OF CASES

CORE STAINING IN 25% TO 67% USING ANY ONE STAIN


CORE STAINING IN 25% TO 67% USING ANY ONE STAIN

ADJACENT STROMAUNIFORMLY NEGATIVE IN ALMOST ALL CASES

“CORE” STAINING PATTERN


HMW-CKK903

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2011 ASCP Annual MeetingPR

OTHER SGPB TO CONSIDER IN CORE NEEDLE BIOPSIES

INVASIVE DUCT CARCINOMA (WELL-DIFFERENTIATED, TUBULAR TYPE)RADIAL SCLEROSING LESION


ADENOSIS/SCLEROSING ADENOSIS/ADENOSIS TUMORMICROGLANDULAR ADENOSIS

MORPHOLOGIC FEATURESIFDC (TUBULAR) VS LGASC

WELL-FORMED GLANDSHAPHAZARD , INFILTRATIVE ARRANGEMENTROUND , OVAL, OR TEAR DROP-SHAPED GLANDS

WELL-FORMED GLANDSHAPHAZARD, INFILTRATIVE ARRANGEMENTANGULATED GLANDS +/-SQUAMOUS


DROP-SHAPED GLANDSLOW NUCLEAR GRADEELASTOTIC STROMA

SQUAMOUS DIFFERENTIATIONLOW NUCLEAR GRADEPERI-GLANDULAR SPINDLE CELL METAPLASIA IN STROMALYMPHOCYTIC AGGREGATES

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IMMUNOHISTOCHEMICAL FEATURESIFDC VS LGASC

NEGATIVE FOR MYOEPITHELIAL MARKERS (P63, SMM, CALPONIN)POSITIVE FOR ER/PR (STRONG, DIFFUSE)STROMA - NEGATIVE

CIRCUMERFERENTIAL LY POSITIVE (VARIABLE) FOR MYOEPITHELIAL MARKERS; OCCASIONAL NEGATIVE GLAND(S)“LAMELLAR” POSITIVITY FOR MYOEPITHELIAL MARKERS (SMM) IN SPINDLE CELL


(SMM) IN SPINDLE CELL STROMA P63 ALSO POSITIVE IN EPITHELIUM WITH SQUAMOUS DIFFERENTIATIONPOSITIVE (DIFFUSE, VARIABLE INTENSITIES) FOR MOST CYTOKERATINS CORE STAINING FOR SOME CYTOKERATINS (HMWCK)ER/PR NEGATIVE

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p63


SMM


MORPHOLOGIC FEATURESIFDC (TUBULAR) VS RSL

WELL-FORMED GLANDSHAPHAZARD ARRANGEMENTROUND , OVAL, OR

WELL-FORMED GLANDSCENTRIFUGAL ARRANGEMENTANGULATED OR SLIT-


TEAR-DROP SHAPED GLANDSLOW NUCLEAR GRADECO-EXISTING CCL, ADH,LOBULAR LESIONSELASTOTIC STROMA

LIKE GLANDSLOW NUCLEAR GRADEOTHER FCC ELEMENTS PARTICIPATINGELASTOTIC STROMA+/- HEAVY SCLEROSIS IN NIDUS

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WELL-FORMED GLANDSHAPHAZARD ARRANGEMENTROUND , OVAL, OR TEAR-DROP SHAPED GLANDS

WELL-FORMED GLANDSLOBULOCENTRIC BUT MAY NOT BE APPARENT ON CNBPSEUDOINFILTRATIVE GROWTH PATTERN WITH

MORPHOLOGIC FEATURESIFDC (TUBULAR) VS SA


GLANDSELASTOTIC STROMA

GROWTH PATTERN WITH INCREASING SCLEROSISCAN BE SECONDARILY INVOLVED BY ALH, LCIS, ADH, DCISASSOCIATED CALCS; MASS FORMING IF ADENOSIS TUMOR


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CALPONIN



p63


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SMM


IS THIS TUBULAR CARCINOMA ARISING IN A RADIAL SCLEROSING


ARISING IN A RADIAL SCLEROSING LESION?

IMMUNOHISTOCHEMICAL FEATURESIFDC VS RSL/SA

NEGATIVE FOR MYOEPITHELIAL MARKERS (P63, SMM, CALPONIN)POSITIVE FOR ER/PR

POSITIVE FOR MYOEPITHELIAL MARKERS (P63, SMM, CALPONIN)BUT CAN BE VERY


POSITIVE FOR ER/PR (STRONG, DIFFUSE)

BUT CAN BE VERY ATTENUATED OR ABSENT IN AREAS OF MARKED SCLEROSISER/PR POSITIVE BUT NOT DIFFUSELY

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NOT ALL MYOEPITHELIAL MARKERS ARE CREATED EQUAL

DIFFER IN SENSITIVITIES AND SPECIFICITIESSOME ALSO STAIN MYOFIBROBLASTS (i.e. SMOOTH MUSCLE ACTIN, CD10)

SOME ARE LESS ROBUST IN AREAS OF HEAVY


SOME ARE LESS ROBUST IN AREAS OF HEAVY SCLEROSIS; FALSE NEGATIVITYRECOMMEND USING A PANEL OF MYOEPITHELIAL MARKERSP63, SMOOTH MUSCLE MYOSIN, CALPONIN

SMM-HC


SMOOTH MUSCLE ACTIN


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CALPONIN




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2011 ASCP Annual Meeting E-CAD

INVASIVE CARCINOMA WITH TUBULAR AND LOBULAR FEATURES

BIOMARKER STAINS PENDING


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2011 ASCP Annual MeetingER

2011 ASCP Annual Meeting PR

MICROGLANDULAR ADENOSIS GIVING RISE TO INVASIVE CARCINOMA


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INFILTRATIVE WELL-FORMED GLANDSROUND, OVAL OR TEAR-DROP SHAPED GLANDS

INFILTRATIVE WELL-FORMED GLANDSROUND GLANDSLOW NUCLEAR GRADEBRIGHT EOSINOPHILIC

MORPHOLOGIC FEATURESIFDC (TUBULAR) VS MGA


LOW NUCLEAR GRADEELASTOTIC STROMAIN-SITU COMPONENT IS ABSENT OR ADH/LG DCISCO-EXISTING CCL AND/OR LOBULAR LESIONS

BRIGHT EOSINOPHILIC LUMINAL SECRETIONSSTROMA IS UNALTEREDNO IN-SITU COMPONENT UNLESS ATYPICAL

2011 ASCP Annual Meeting S-100

2011 ASCP Annual Meeting RETICULIN

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2011 ASCP Annual Meeting RETICULIN

NEGATIVE FOR MYOEPITHELIAL MARKERS (P63, SMM, CALPONIN)POSITIVE FOR ER/PR

NEGATIVE FOR MYOEPITHELIAL MARKERS (P63, SMM, CALPONIN)NEGATIVE FOR ER/PR

IMMUNOHISTOCHEMICAL FEATURESIFDC VS MGA


POSITIVE FOR ER/PR (STRONG, DIFFUSE)

NEGATIVE FOR ER/PR POSITIVE FOR BASEMENT MEMBRANE MARKERS (RETICULIN, LAMININ, COLLAGEN TYPE IV)POSITIVE FOR S-100 PROTEIN


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CK AE1/3


INVASIVE LOBULAR CARCINOMA FOCALLY INVOLVING A RADIAL SCLEROSING LESION


INVOLVING A RADIAL SCLEROSING LESION

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RADIAL SCLEROSING LESION (RSL)

OCCURENCE OF INVASIVE OR IN-SITU CARCINOMA INVOLVING RSL OR IN CLOSE PROXIMITY OF RSL IS WELL KNOWN


RATES 0-34%EASILY UNDERDIAGNOSED ON NCB SINCE INVOLVEMENT BY CARCINOMA OF A RSL IS FOCAL OR PERIPHERAL

TOPIC 3 OF 5FIBROEPITHELIAL LESIONS


FIBROEPITHELIAL LESIONS

Fibroadenoma (FA)Variants (cellular, juvenile, complex, giant)

Phyllodes Tumor (PT)G d (b i b d li li t)


Grades (benign, borderline, malignant)

Fibroadenomatoid Mastopathy (Sclerosing Lobular Hyperplasia)

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FIBROADENOMATOID MASTOPATHY


MANAGEMENT

FIBROADENOMASSimple enucleationClinical follow-up if small


PHYLLODES TUMORWide local excision (1cm or more?) for PT (all grades?) compliance by surgeons?Residual PT at margins is a strong predictor of local recurrence; re-excision is recommended

BENGIN PT CALLED FA ON CNB

Clinical F/U only Enucleation (unoriented specimen)

Positive undesignatedmargins in the EXBX

EXBX if clinically worsening


Re‐excision of undesignated margin (s)Potentially more tissue excised

Psychological +/‐ physical morbidity of pt

Potentially higher grade PT in unsampledareas; less favorable cosmetic result if large

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PHYLLODES TUMORS

Rare compared to FA (2-3% of FEL tumors of the breast)Age 35-55 femalesBreast mass +/- rapid growthSize at presentation larger than that of FA but difference is shrinking due to screening


shrinking due to screening1.3cm (PT) vs. 1.0cm (FA) [Komenaka et al. Arch Surg2003]

Clinically and radiologically indistinguishable from FALocal recurrence rates: Benign (8%), BL (29%), HG (36%)Metastatic potential: Benign (0%), BL (<4%), HG (<22%)

MORPHOLOGIC FEATURES

Leaf-like growth patternStroma (cellularity, atypia, overgrowth)Interfield variability of gland to stroma ratio Tumor border (invasive)


Tumor border (invasive)Stromal mitotic figuresPseudoangiomatous stromal hyperplasiaExcessive epithelial hyperplasia (micropapillary)

PseudopapillaryGrowth Patternin Phyllodes Tumor


Fibroadenoma‐intracanalicular type

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2011 ASCP Annual MeetingLEAF-LIKE PATTERN IN PT

2011 ASCP Annual MeetingELONGATED, SLIT-LIKE GLANDS IN PT

Stromal Cellularity/Atypia/PASH


FIBROADENOMA(CELLULAR)

BENIGN PHYLLODES TUMOR

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BENGIN PHYLLODES TUMORMYXOID STROMA


FIBROADENOMA WITHMYXOID STROMA


Stromal Mitoses


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INFILTRATIVE TUMOR BORDER


TUMOR BORDER

MICROPAPILLARY DUCT HYPERPLASIAIN PHYLLODES TUMOR


FA or Fibroadenomatous areas in PT?


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Final Pathology Report

No. of PhyllodesCore Biopsy Result Patients Fibroadenoma Tumor

Favor fibroadenoma 25 23 2Favor phyllodes tumor 23 4 19

Initial and Final Diagnoses


Favor phyllodes tumor 23 4 19Equivocal 9 5 4

Total 57 32 25

NPV 93%PPV 83%

Komenaka IK, et al. Arch Surg 2003; 138: 987-990.

Jacobs, et al. AJCP 2005;124:342-354

29 pts with NCB containing FEL with cellular stroma who had subsequent EXBX“cellular stroma” = 2x normal perilobular stroma


stromaSurgical outcome:

16 (55%) were FA12 (41%) were PT (5-benign,6-LGM,1-HG)

10 HISTOLOGIC FEATURES

Stromal cellularityStromal nuclear atypiaStromal mitotic count

Enhancement of stromal cellularityadjacent to epitheliumInfiltrative tumor border


Stromal proportion to epitheliumStromal overgrowth

borderEpithelial hyperplasiaOverall growth patternMultinucleated giant cells

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10 HISTOLOGIC FEATURES

Stromal cellularityStromal nuclear atypiaStromal mitotic count

Enhancement of stromal cellularityadjacent to epitheliumInfiltrative tumor border


Stromal proportion to epitheliumStromal overgrowth

borderEpithelial hyperplasiaOverall growth patternMultinucleated giant cells

Histopathology 2007;51:336‐344


Seven histologic features significantly different b/t FA and PTStromal cellularity >50% of coreMarked stromal pleomorphismStromal overgrowth (x10 field)Edge-infiltrative (only when edge can be adequately


Edge-infiltrative (only when edge can be adequately assessed in ncb)FragmentationAdipose tissue in stroma (invasive tumor border vslipomatous metaplasia)Stromal mitoses

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Seven histologic features significantly different b/t FA and PTStromal cellularity >50% of coreMarked stromal pleomorphismStromal overgrowth (x10 field)Edge-infiltrative (only when edge can be adequately


Edge-infiltrative (only when edge can be adequately assessed in ncb)FragmentationAdipose tissue in stroma (invasive tumor border vslipomatous metaplasia)Stromal mitoses


112 NCB of FEL (21 PT AND 91 FA ; ALL WITH EXBX)

Patient’s Age at Diagnosis


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Percent Stroma


Stromal Mitoses


RECEIVER-OPERATING CHARACTERISTIC (ROC) ANALYSIS

Objective method for determining optimal cut-off values in frequency distributions for 2 datasets with one variable (tumor type).

CUT OFF VALUES FOR PT OVER FA


CUT OFF VALUES FOR PT OVER FAAGE (50-55) PERCENT STROMA (85-90)MITOSES (≥ 1 PER 2.2 MM2)

CONFIRMED FINDINGS OF LEE, et al.

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261 NCB OF FEL98 (37%) FEL CANNOT EXCLUDE PT

57/98 (58%) UNDERWENT EXBX

MORPHOLOGIC FEATURESEXCLUSIVE FEATURES OF PT

MARKED STROMAL CELLULARITYMARKED STROMAL ATYPIAMITOSES ≥ 2 / 10 HPFILL-DEFINED LESIONAL BORDER


HIGH CORRELATION WITH PT ON EXBXMODERATE STROMAL CELLULARITYSTROMAL OVERGROWTHMODERATE STROMAL ATYPIAPASH

SUMMARY OF STUDIES

MORPHOLOGIC FEATURES OF PTSTROMAL CELLULARITY (MODERATE TO MARKED)STROMAL ATYPIA


STROMAL ATYPIASTROMAL MITOSES (AT LEAST 1)STROMAL OVERGROWTHINFILTRATIVE TUMOR BORDER

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TOPOISOMERASE IIα CD34BE

NIG

NPT

BL

FABEN

IGN

REDUCED≥ 5%, = PT on EXBX

Jara-Lazaro, et al.


MALIGNANT

N PT

BL PT

. Histopathology 2010

BENIGN FIBROEPITHELIAL LESION


TOPIC 4 OF 5SPINDLE CELL LESIONS


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SPINDLE CELL LESIONS

SIMILAR TO SMALL GLANDULAR PROLIFERATIONS, SPINDLE CELL LESIONS CONSISTS OF A SPECTRUM OF BENIGN TO MALIGNANT ENTITIES WHICH SHARE AN


MALIGNANT ENTITIES WHICH SHARE AN OVERALL SIMILAR MORPHOLOGIC APPEARANCEFORMULATING AN ACCURATE DX ON CORE NEEDLE BIOPSIES CAN BE DIFFICULT IF NOT IMPOSSIBLE

CELLS OF ORIGINFIBROBLASTS, MYOFIBROBLASTS

INTRA- AND INTERLOBULAR MAMMARY STROMAPOSITIVE VIMENTIN, BCL-2, CD-99MYOFIBROBLASTS ALSO α-SMOOTH MUSCLE ACTIN DESMIN HORMONE RECEPTORS


ACTIN, DESMIN, HORMONE RECEPTORSEPITHELIALMYOEPITHELIALHISTIOCYTESENDOTHELIAL CELLS

SPINDLE CELL LESIONS

CYTOLOGICALLY BLAND-APPEARING LESIONS

BENIGNMALIGNANT


MALIGNANT

CYTOLOGICALLY ATYPICAL LESIONSMALIGNANT

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CYTOLOGICALLY BLAND SPINDLE CELL LESIONSDIFFERENTIAL DIAGNOSIS

PASH FASICULARTUMOROUS

MYOFIBROBLASTOMABENIGN PHYLLODES TUMOR

SARCOMALOW-GRADE (including well-differentiated angiosarcoma)

METAPLASTIC SPINDLE CELL CARCINOMA

LOW GRADE


(STROMA ONLY)SCARREACTIVE SPINDLE CELL NODULEADENOMYOEPITHELIOMASPINDLE CELL LIPOMANEUROFIBROMALEIOMYOMADERM (DFSP, DF)

LOW-GRADE FIBROMATOSIS-LIKE

CYTOLOGICALLY ATYPICAL SPINDLE CELL LESIONS: DIFFERENTIAL DIAGNOSIS

NODULAR FASCIITISPHYLLODES TUMOR (STROMA ONLY)

BORDERLINE, HIGH GRADEMETASTASES


METASTASESMELANOMA

SARCOMAPRIMARY (HIGH-GRADE ANGIOSARCOMA)METASTATIC

OTHER CO-EXISTING CELLSRED BLOOD CELLS - ANGIOSARCOMAMIXED INFLAMMATORY INFILTRATE & RED BLOOD CELLS – NODULAR FASCIITISLYMPHOCYTES

PERIPHERAL AGGREGATES FIBROMATOSIS


PERIPHERAL AGGREGATES – FIBROMATOSISDISPERSED IN BACKGROUND – SPINDLE CELL METAPLASTIC CARCINOMA, REACTIVE SPINDLE CELL NODULE

UNINVOLVED BREAST TISSUE OR ADIPOSE TISSUE PRESENT?

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CLINICAL AND RADIOLOGIC CORRELATION PAST CLINICAL HISTORY

RECENT HISTORY OF TRAUMA/NEEDLE BX (SPINDLE CELL NODULE)BREAST CARCINOMA AND STATUS POST RADIATION THERAPY (POST-RADIATION ANGIOSARCOMA)


THERAPY (POST-RADIATION ANGIOSARCOMA)OTHER MALIGNANCIES (I.E. MELANOMA)FAMILILAR ADENOMATOUS POLYPOSIS OR GARDNER’S SYNDROMES (FIBROMATOSIS)“BRUISE” ON BREAST SKIN (ANGIOSARCOMA)

CLINICAL AND RADIOLOGIC CORRELATIONTUMOR CHARACTERISTICS

SOLITARY (PHYLLODES TUMOR, MYOFIBROBLASTOMA, MYOEPITHELIOMA, TUMOROUS PASH)WELL-CIRCUMSCRIBED (MYOFIBROBLASTOMA, ADENOMYOEPITHELIOMA)


INFILTRATIVE BORDERS (FIBROMATOSIS, SOME PHYLLODES TUMORS)SMALL SIZE (NODULAR FASCITIS, REACTIVE SPINDLE CELL NODULE)SUPERFICIAL LOCATION (SPINDLE CELL LIPOMA, DFSP, DF)NIPPLE LOCATION (LEIOMYOMA)


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CD 34


MYOFIBROBLASTOMACircumscribed +/- lipomatous differentiationShort fascicles of uniform spindle-shaped cells with round to oval nuclei; mitoses very rareHyalinized collagen bandsMast cells, myxoid change, chondroid or smooth muscle

t l i


metaplasiaVariants exist…most impt, epithelioid confuse with infiltrating carcinomaCD 34 POSITIVE +/- SMOOTH MUSCLE ACTIN, DESMIN; S-100 NEG (unlike spindle cell lipoma)ER, PR, BCL-2, VIMENTIN

MYFIBROBLASTOMA-EPITHELIOID VARIANT


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EXBX


FIBROMATOSISPainless, slowly growing massStroma vary from keloidal to myxoid/fasciitis likeSMA positive; +/ desmin S 100


SMA positive; +/-desmin, S-100High rate of local recurrenceDifficult or impossible to distinguish between fibromatosis and scar in re-excision

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BETA-CATENIN



100% FIBROMATOSIS

BUT ALSO… 23% METAPLASTIC CARCINOMA94% BENIGN PT 57% MALIGNANT PT

EXAMPLE A


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Cam 5.2


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CKAE1/3


CK 7


EXAMPLE B


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CKAE1/3


Cam 5.2


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K903


p63


EXAMPLE C


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CKAE1/3


CK 7


SPINDLE CELL METAPLASTIC CARCINOMA

CKAE1/3 CK7 CAM5.2 K903 P63CASE 1 + + - + +CASE 2 + + + + +CASE 3 + - - + +


*p63 IS DIFFUSELY POSITIVE IF ONE CK IS ALSO

*ALWAYS PERFORM A PANEL OF CK MARKERS TO RULE IN/OUT THIS ENTITY

*A NEGATIVE IMMUNOPANEL ON A CNB DOES NOT EXCLUDE THIS DX

*POSITIVE STAINING CAN BE VERY FOCAL

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SPINDLE CELL METAPLASTIC CARCINOMA

MORPHOLOGIC CLUES BEFORE IHCADMIXED INVASIVE DUCT CARCINOMA, NOSPRESENCE OF DCIS


SPINDLE CELLS THAT AGGREGATE AND CONTAIN MORE CYTOPLASM/LARGER NUCLEI (“EPITHELIOID”)AREAS OF SQUAMOUS DIFFERENTIATIONSCATTERED CHRONIC INFLAMMATION IN THE BACKGROUND (“DIRTY BACKGROUND”)



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p63


LOW-GRADE FIBROMATOSIS-LIKE SCMC

COMPOSED OF BLAND SPINDLE CELLS SIMILAR TO THOSE SEEN IN FIBROMATOSISCAN SEE AREAS THAT ARE MORE


CAN SEE AREAS THAT ARE MORE EPITHELIOID +/- SQUAMOUS DIFFERENTIATIONHIGH RATE OF LOCAL RECURRENCEMETASTASIS IS RARE

What do the findings in the next slides have i ?


in common?

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THEY REPRESENT DIFFERENT AREAS OF THE SAME CASE


OF THE SAME CASE

CD 31


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KI-67


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TOPIC 5 OF 5LOBULAR CARCINOMA IN-SITU

COLUMNAR CELL LESIONSINVASIVE CARCINOMA


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Classical LCIS

Type A Type B




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Loss of E-cadherin Expression

LOH at 16q22 (site of E-cad gene)Mutations Transcriptional silencing by epigenetic


Transcriptional silencing by epigenetic mechanisms (e.g. promoter methylation)

Adjunctive Immunostains To Discern LCIS (particularly variants of) from DCIS

E-cadherinP120 catenin


High molecular weight cytokeratin

DCISE-cadherin Positive


Low grade High grade

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LCIS: Loss of E-cadherin Expression



E-Cadherin Staining in LCIS

Myoepithelial cells (weak, fragmented)R id l d t l ith li l ll


Residual ductal epithelial cellsLCIS cells (weak, fragmented)

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Rosen’s Breast Pathology, 2009

Rat MammaryLobule






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Aberrant E-cadherin “positivity” (incomplete membrane, cytoplasmic or Golgi staining) seen in 4 of 25 ILC despite presence of genetic

Am J Surg Pathol 2008


in 4 of 25 ILC, despite presence of genetic alterations commonly seen in ILC (16q loss, 1q gain)Evidence to suggest that E-cadherin protein in these cases was dysfunctionalPresence and pattern of E-cadherin expression may be related to molecular mechanism of E-cadherin inactivation

P120 Catenin

Present at junction of cell membrane and cytoplasmInvolved in linking E-cadherin to actin

t k l t


cytoskeletonNormal cells/ductal lesions:

membrane distribution

Lobular lesions:cytoplasmic distribution

Dabbs, AJSP, 2007

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P120 cateninDuctal lesions: membranous

LCIS: cytoplasmic


E-cadherin and P120 Catenin in DCIS and LCIS

DCIS LCIS

E-cadherin positive negative


P120 catenin membranous cytoplasmic

Adjunctive Immunostains To Discern LCIS (particularly variants of) from DCIS

E-cadherinP120 catenin


P120 cateninHigh molecular weight cytokeratin

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LCIS


DCIS


LCIS

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Heterogeneity of LCIS

Like DCIS, the term “LCIS” encompasses a heterogeneous group of lesions that differ in morphology, immunophenotype, genetic


alterations and, possibly, clinical behaviorHeterogeneity of LCIS has until recently been largely under-appreciated

VARIANTS OF LCIS

Common feature – E cadherin negativeClinico-pathologic characteristics


Clinico-pathologic characteristicsBiomarker expression by IHCMolecular signature – high res aCGH

FLORID LCIS


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FLORID LCIS


PLEOMORPHIC LCIS


E-CADHERIN IMMUNOSTAIN


CLCIS FLCIS PLCIS

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1q gain 16q loss

Differences Between CLCIS and FLCIS/PLCIS

Classical LCIS FLCIS/PLCIS

Age Younger (premenopausal)

Older (postmenopausal)

Presentation Incidental MammographicER Pos Pos


HER2 Neg Neg or Pos

Ki67 Low High

Genomic changes (aCGH)

Fewer More numerous

Histologic Distinction Between LCIS Variants and DCIS

Feature LCIS Variants DCIS

Loss of cohesion Yes NoIntracytoplasmic vacuoles

More common Less common


vacuolesPagetoid ductalinvolvement


Associated classicalLCIS


Microacini Absent PresentPolarization of cells at periphery

Absent Present

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21 FLORID LCIS (FLCIS); 5 LOW-GRADE SOLID DCISAGE 42-81 (MEAN 61.5)17 LUMINAL NECROSIS

USCAP 2002


17 LUMINAL NECROSIS15 CALCIFICATIONS12/21 CONCURRENT INVASIVE CARCINOMA

10/12 LOBULAR TYPE21/21 E-CADHERIN NEGATIVE15/16 STUDIED SHOWED LOH OF MS MARKER NEAR E-CADHERIN GENE

LCIS VARIANTS (FLCIS, PLCIS)CLINICAL IMPORTANCE

Problem for Pathologist Problem for Clinician


Distinction from DCIS Manage like classical LCIS or like DCIS?

FLCIS / PLCIS

E-cadherin negConcurrent inv ca

+/-Nuclear pleomorphismComedo necrosis


More like DCIS than LCIS

LCIS variant

Treat like LCIS

Comedo necrosisDirect ductal extension“Bad” biomarker profile

Treat like DCIS

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What Does “Treat Like DCIS” Really Mean?

Excision to negative margins?R di ti th ?


Radiation therapy?In the absence of data, is it better to over-treat or under-treat?

Florid and Pleomorphic LCISClinical Significance

No clinical follow-up studies akin to those available for classical LCIS and DCISN t l hi t /bi l i

DATA


Natural history/biologic behavior unknownAppropriate management uncertain


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DOWNS-KELLY E, ET AL ARCH PATHOL LAB MED 2011;135:737-743

26 PTS WITH PLCIS AT OR CLOSE TO SURGICAL MARGIN

16 RECEIVED CHEMOPREVENTION AND/OR RADIATION


RADIATION10 RECEIVED NO ADJUVANT TREATMENT

1/26 (3.8%) HAD RECURRENT PLCIS 18 MO LATER (F/U RANGE 1-104 MO; MEAN 46 MO )

AT MARGIN WITH NO TRUNCATION

COLUMNAR CELL LESIONS(IN THE CONTEXT OF LCIS)


LOBULARCARCINOMA

LOW-GRADEDCIS

HIGH-GRADEDCIS


INVASIVE CARCINOMAWELL-DIFFERENTIATED

+1q, -16q

INVASIVE CARCINOMAPOORLY-

DIFFERENTIATED

+17q

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CCL/FEA

Inv tubular ca

LCIS


FEA

Tubular ca

l AJS

P 20

07;3

1:41

7-42

6


Abd

el-F

atah

T, e

t al

NOMENCLATURE

COLUMNAR CELL CHANGECOLUMNAR CELL CHANGE WITH ATYPIA (FLAT EPITHELIAL ATYPIA)COLUMNAR CELL HYPERPLASIA


COLUMNAR CELL HYPERPLASIA WITH ATYPIA (FLAT EPITHELIAL ATYPIA)ATYPICAL COLUMNAR CELL HYPERPLASIA = ATYPICAL DUCT HYPERPLASIA

Simpson PT, Gale T, Reis-Filho JS, et al. Am J Surg Pathol 2005;29(6):734-46

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Flat Epithelial AtypiaColumnar Cell Change

Columnar Cell Hyperplasia

Irregular contours Irregular contoursSmooth contours


FLAT EPITHELIAL ATYPIA COLUMNARCELL HYPERPLASIA


Flat Epithelial AtypiaColumnar Cell Change

Columnar Cell Hyperplasia


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INVASIVE CARCINOMA (IN THE CONTEXT OF LCIS)


Histologic Type of Cancer Following CLCISMost (up to 75%) are invasive

ductal carcinomas


Frequency of Invasive Lobular Carcinoma Following CLCIS

Study % Invasive Lobular Ca

Chuba (SEER) 23.1%

INVASIVE LOBULAR CARCINOMA – 10-15% OF ALL INV BC


Wheeler 25.0%Haagensen 25.5%Rosen 36.0%Ottesen 37.0%Page 70.0%

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Tumor Recurrence (TR) in cases of CLCIS treated by Local Excision

180 pts exbx only for LCIS12 year follow-up26 (14.4%) ipsilat TR; 14 (7.8%) contralat TR


Cases with slides for review: 8/9 (89%) ipsilat TR and 6/8 (75%) contralat TR – IFLC type96% ipsilat and 100% contralat TRs occurred within the same site as the index LCIS

Fisher ER, Land SR, Fisher B, et al. Cancer 2004; 100:238-44

CLCIS AND MICRO-INVASIVE LOBULAR CARCINOMA, CLASSICAL TYPE


ROSS DS AND HODA SAAM J SURG PATHOL 2011; 35(5):750-756

16/75,250 (0.02%) BREAST CASESAVG AGE 52 YRSPRESENTATION

RADIOGRAPHIC ABNORMALITY 13/16


PALPABLE 3/16U/L R=LALL WITH ASSOCIATED CLCIS=11, FLCIS=4, PLCIS=1NEG SLN 16/16SYNCHRONOUS IFDC =2, DCIS =2

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CLCIS ON NEEDLE CORE BIOPSY

CLASSICAL LCIS IS RARELY THE TARGET OF SCREEN DETECTED NEEDLE CORE BIOPSY

RARELY ASSOCIATED WITH CALCIFICATIONS


CALCIFICATIONSNOT A MASS FORMING LESIONNO SPECIFIC MRI FEATURES

AS A RESULT, MOST CLCIS FOUND IN THIS TYPE OF SURGICAL SPECIMEN IS INCIDENTAL IN NATURE

LCIS/ALH in NCB Literature Review of 27 StudiesCangiarella, 2008

Worse lesion found on excision in 112 of 700 cases (16%)61/307 (20%) with LCIS (range, 0-50%)51/393 (13%) with ALH (range, 0-67%)


CaveatsStudies differ with regard to details of needle biopsy procedure, extent of lesion removalNot all patients with LCIS/ALH underwent excisionSome cases were associated with mass lesions or consisted of non-classical forms of LCIS

OUTCOMES OF PROSPECTIVE EXCISION FOR CLASSIC LCIS AND ALH ON PERCUTANEOUS BREAST CORE BIOPSY (ABSTRACT) LUEDTKE C, ET AL MSKCC, NY

PROSPECTIVE STUDY 2004-200969 PTS / 71 NCBSAGE RANGE 31-73 YEARSCLINICAL PRESENTATION

CALCIFICATIONS 47/71 (66%)


CALCIFICATIONS 47/71 (66%)MASS 7/71 (10%)MRI ENHANCEMENT 17/71 (24%)

RESULTS: 2/71 (3%) PATHOLOGIC UPGRADE ON EXBX

ONE HAD 2.3 MM TUBULAR CARCINOMA AND 2 MM DCIS; OTHER HAD 2 MM DCIS

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MANAGEMENT OF LCIS ON NCB

Excision probably not necessary if CLCIS/ALH is completely incidental finding and there is radiologic-pathologic concordanceExcision recommended if:

another lesion present which by itself would


another lesion present which by itself would be an indication for excision (e.g., ADH)histologic features raise question of LCIS vs DCIS or non-classical LCIS (e.g., PLCIS)radiologic-pathologic discordance

Excision recommended if FLCIS or PLCIS

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29 Common Consultation Conundrums in Breast Pathology...

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