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
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CONSULTATION CONUNDRUMS
THE VAST MAJORITY OF CONSULTATION CASES REPRESENTS THE PROBLEMATIC AREAS IN BREAST PATHOLOGY COMMON TO ALL
2011 ASCP Annual Meeting
PATHOLOGY COMMON TO ALL PATHOLOGISTS
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CONSULTATION CONUNDRUMS
UNUSUAL, UNEXPECTED OR AMBIGUOUS HISTOLOGIC FEATURES AND/OR IMMUNOHISTOCHEMICAL RESULTS
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RESULTSUNCLEAR REPORTING GUIDELINESLACK OF INTRADEPARTMENTAL CONSENSUS OF DIAGNOSISRARITY OF LESION
CONSULTATION CONUNDRUMS
UNUSUAL, UNEXPECTED OR AMBIGUOUS HISTOLOGIC FEATURES AND/OR IMMUNOHISTOCHEMICAL RESULTS
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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)
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SPINDLE CELL LESIONS (includes VASCULAR)LOBULAR CARCINOMA IN-SITU (LCIS)
COLUMNAR CELL LESIONSINVASIVE CARCINOMA
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TOPIC 1 OF 5PAPILLARY LESIONS
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NO ONE’S FAVORITE BREAST LESION
COMPLEX AND HETEROGENEOUSDO NOT FOLLOW A STEPWISE PROGRESSION OF INCREASING PROLIFERATIVE CHANGES AND “ATYPIA”
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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
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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
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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
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PAPILLARY CARCINOMA ENCAPSULATED (INTRACYSTIC) PAPILLARY CAPAPILLARY LESIONS IN NEEDLE CORE BXSIN-SITU VS. INVASIVE PAPILLARY CA
PROBLEM AREASPAPILLOMA VS. PAPILLARY DCISPAPILLOMA WITH (FLORID DH VS. ADH VS. DCIS)PAPILLOMA WITH FLORID DH VS. SOLID
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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
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LOW NUCLEAR GRADEINTRADUCTAL/INTRACYSTIC GROWTH PATTERN WITH POINT OF ATTACHMENTVARIABLE SIZE
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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
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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
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OTHER “SOFT” FINDINGS OF PAPILLOMAS
MYOEPITHELIAL HYPERPLASIAAPOCRINE METAPLASIAINFARCTION
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SQUAMOUS METAPLASIA
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DISTRIBUTION OF MYOEPITHELIAL CELLSWITHIN PAPILLAE PERIPHERY
PAPILLOMA PRESENT PRESENT
PAPILLOMA WITHADH/DCIS PRESENT/ABSENT PRESENT
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PAPILLARY DCIS ABSENT PRESENT
ENCAPSULATEDPAPILLARY CA ABSENT ABSENT
SOLID PAPILLARYCA ABSENT PRESENT
OR ABSENT
Collins LC and Schnitt SJ, Histopathol 2008
WELL-DIFFERENTIATED IN-SITU PAPILLARY CARCINOMA
SMM
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NEEDLE CORE BIOPSY
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p63
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SMM
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POSSIBLE PITFALLS OF MYOEPITHELIAL CELL MARKERS
MEC MARKERS VARY IN SENSITIVITY AND SPECIFICITY - PANELMISTAKEN FOR MEC
PERICYTES
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MYOFIBROBLASTS IN THE STROMANEOPLASTIC CELLS
DISPLACED CARCINOMA CELLS CAN BE NEGATIVE FOR ME MARKERS
SMM
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CALPONIN
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PROBLEM AREASPAPILLOMA VS. PAPILLARY DCISPAPILLOMA WITH (FLORID DH VS. ADH VS. DCIS)PAPILLOMA WITH FLORID DH VS. SOLID
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PAPILLARY CARCINOMA ENCAPSULATED (INTRACYSTIC) PAPILLARY CAPAPILLARY LESIONS IN NEEDLE CORE BXSIN-SITU VS. INVASIVE PAPILLARY CA
FLORID DUCT HYPERPLASIA IN A PAPILLOMA
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SOLIDPAPILLARY
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CARCINOMA
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PAPILLOMA WITH FLORID DUCT HYPERPLASIA
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SOLID PAPILLARY CARCINOMA
DISTRIBUTION OF MYOEPITHELIAL CELLSWITHIN PAPILLAE PERIPHERY
PAPILLOMA PRESENT PRESENT(+/-FDH)
PAPILLOMA WITHADH/DCIS PRESENT/ABSENT PRESENT
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ADH/DCIS PRESENT/ABSENT PRESENT
PAPILLARY DCIS ABSENT PRESENT
ENCAPSULATEDPAPILLARY CA ABSENT ABSENT
SOLID PAPILLARYCARCINOMA ABSENT PRESENT
OR ABSENT
Collins LC and Schnitt SJ, Histopathol 2008
NORMALDUCT
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ATTENUATED &ABSENT STAINING
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OTHER USEFUL IMMUNOSTAINS
PAPILLOMA PAPILLOMA SOLID PAP+ FDH + ADH/DCIS CARCINOMA
HMWCK DIFFUSE OR NEG NEG
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(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
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CK5/6
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OTHER USEFUL IMMUNOSTAINS
PAPILLOMA PAPILLOMA SOLID PAP+ FDH + ADH/DCIS CARCINOMA
HMWCK DIFFUSE OR NEG NEG
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(CK5/6; K903) MOSAIC
ER FEW POS NEG/POS POS
NE MARKERS NEG NEG POS(SYNAPTO, CD56)
*
ER
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NEEDLE CORE BIOPSY
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NEUROENDOCRINE MARKERS
MOST COMMONLY POSITIVE IN SOLID PAPILLARY CARCINOMAALSO POSITIVE IN PAPILLARY DCIS AND ENCAPSULATED PAPILLARY CARCINOMA
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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
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ENCAPSULATED (INTRACYSTIC) PAPILLARY CAPAPILLARY LESIONS IN NEEDLE CORE BXSIN-SITU VS. INVASIVE PAPILLARY CA
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NEEDLE CORE BIOPSY
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DISTRIBUTION OF MYOEPITHELIAL CELLSWITHIN PAPILLAE PERIPHERY
PAPILLOMA PRESENT PRESENT(+/-FDH)
PAPILLOMA WITHADH/DCIS PRESENT/ABSENT PRESENT
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ADH/DCIS PRESENT/ABSENT PRESENT
PAPILLARY DCIS ABSENT PRESENT
ENCAPSULATEDPAPILLARY CA ABSENT ABSENT
SOLID PAPILLARYCARCINOMA ABSENT PRESENT
OR ABSENT
Collins LC and Schnitt SJ, Histopathol 2008
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p63
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ER
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EXBX
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SMM
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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
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INDOLENT BEHAVIOR WITHOUT CONCURRENT INVASIVE COMPONENTEVEN WITH INVASION, PROGNOSIS IS FAVORABLE COMPARED TO INVASIVE DUCT CA OF COMPARABLE SIZE
PROBLEM AREASPAPILLOMA VS. PAPILLARY DCISPAPILLOMA WITH (FLORID DH VS. ADH VS. DCIS)PAPILLOMA WITH FLORID DH VS. SOLID PAPILLARY CARCINOMA
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ENCAPSULATED (INTRACYSTIC) PAPILLARY CAPAPILLARY LESIONS IN NEEDLE CORE BXSIN-SITU VS. INVASIVE PAPILLARY CA
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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
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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%
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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
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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
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Sur
g Pa
thol
200
9;33
(11)
:16
ER
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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%
PROBLEM AREASPAPILLOMA VS. PAPILLARY DCISPAPILLOMA WITH (FLORID DH VS. ADH VS. DCIS)PAPILLOMA WITH FLORID DH VS. SOLID PAPILLARY CARCINOMA
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ENCAPSULATED (INTRACYSTIC) PAPILLARY CAPAPILLARY LESIONS IN NEEDLE CORE BXSIN-SITU VS. INVASIVE PAPILLARY CA
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TOPIC 2 OF 5SMALL GLANDULAR PROLIFERATIONS
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HISTORY
59 YEAR-OLD FEMALEBREAST NODULE -RETROAREOLARNO OTHER SIGNIFICANT CLINICAL HX
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NEEDLE CORE BIOPSY PERFORMED
2006
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2006
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DIFFERENTIAL DIAGNOSIS
INVASIVE WELL-DIFFENTIATED DUCT CARCINOMA
TUBULAR FEATURESSYRINGOMATOUS ADENOMA
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LOW-GRADE ADENOSQUAMOUS CARCINOMARADIAL SCLEROSING LESIONCOMPLEX SCLEROSING LESIONSCLEROSING ADENOSISSKIN ADNEXAL CARCINOMA
INVASIVE TUBULAR CARCINOMA
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INVASIVE TUBULARCARCINOMA ?
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ADENOSIS ?
RADIALSCLEROSINGLESION?
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INVASIVE TUBULARCARCINOMA ?
RADIALSCLEROSING
LESION
INVASIVE TUBULAR CARCINOMAARISING IN RSL
OR
ENTRAPPED/PARTICIPATINGBENIGN GLANDS
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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
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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….
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USE ADJUNCTIVE TOOLS (IHC)CONSULT A COLLEAGUEBOTH
ADJUNCTIVE DIAGNOSTIC TOOLS
IMMUNOHISTOCHEMISTRYSPECIAL STAINSMOLECULAR CHARACTERIZATION
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FISHGENE PROFILING
ELECTRON MICROSCOPY
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SMALL GLANDULAR PROLIFERATIONS OF THE BREAST (SGPB)
MALIGNANT-APPEARING BUT BENIGN
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BENIGN-APPEARING BUT MALIGNANT
MALIGNANT-APPEARING BUT MALIGNANT OF A DIFFERENT TYPE
CASE 1 continued…
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DIAGNOSIS RENDERED
INVASIVE DUCT CARCINOMA, WELL-DIFFERENTIATEDRE-REVIEWED AT INSTITUTION WHERE SURGERY WAS PLANNED
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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
NEEDLE CORE BIOPSY PERFORMED
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NEEDLE CORE BIOPSY PERFORMED
2011
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p63
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SMM-HC
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SMM-HC
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LOW-GRADE ADENOSQUAMOUS CARCINOMA
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29 CASES OF LGASCMYOEPITHELIAL MARKERS (p63, SMM, CD10, CALPONIN, SMA)
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)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
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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
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LUMINAL CELLSTAINING
SMOOTH MUSCLE MYOSIN
VARIABLY POSITIVE IN BASALLY LOCATED CELLS
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“LAMELLAR” STAINING PATTERN
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SMM-HC
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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
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CORE STAINING IN 25% TO 67% USING ANY ONE STAIN
ADJACENT STROMAUNIFORMLY NEGATIVE IN ALMOST ALL CASES
“CORE” STAINING PATTERN
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HMW-CKK903
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OTHER SGPB TO CONSIDER IN CORE NEEDLE BIOPSIES
INVASIVE DUCT CARCINOMA (WELL-DIFFERENTIATED, TUBULAR TYPE)RADIAL SCLEROSING LESION
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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
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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
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(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
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SMM
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MORPHOLOGIC FEATURESIFDC (TUBULAR) VS RSL
WELL-FORMED GLANDSHAPHAZARD ARRANGEMENTROUND , OVAL, OR
WELL-FORMED GLANDSCENTRIFUGAL ARRANGEMENTANGULATED OR SLIT-
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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
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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
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p63
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SMM
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IS THIS TUBULAR CARCINOMA ARISING IN A RADIAL SCLEROSING
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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
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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
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SOME ARE LESS ROBUST IN AREAS OF HEAVY SCLEROSIS; FALSE NEGATIVITYRECOMMEND USING A PANEL OF MYOEPITHELIAL MARKERSP63, SMOOTH MUSCLE MYOSIN, CALPONIN
SMM-HC
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SMOOTH MUSCLE ACTIN
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CALPONIN
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INVASIVE CARCINOMA WITH TUBULAR AND LOBULAR FEATURES
BIOMARKER STAINS PENDING
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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
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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
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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
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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
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INVASIVE LOBULAR CARCINOMA FOCALLY INVOLVING A RADIAL SCLEROSING LESION
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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
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RATES 0-34%EASILY UNDERDIAGNOSED ON NCB SINCE INVOLVEMENT BY CARCINOMA OF A RSL IS FOCAL OR PERIPHERAL
TOPIC 3 OF 5FIBROEPITHELIAL LESIONS
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FIBROEPITHELIAL LESIONS
Fibroadenoma (FA)Variants (cellular, juvenile, complex, giant)
Phyllodes Tumor (PT)G d (b i b d li li t)
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Grades (benign, borderline, malignant)
Fibroadenomatoid Mastopathy (Sclerosing Lobular Hyperplasia)
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FIBROADENOMATOID MASTOPATHY
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MANAGEMENT
FIBROADENOMASSimple enucleationClinical follow-up if small
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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
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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
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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)
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Tumor border (invasive)Stromal mitotic figuresPseudoangiomatous stromal hyperplasiaExcessive epithelial hyperplasia (micropapillary)
PseudopapillaryGrowth Patternin Phyllodes Tumor
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Fibroadenoma‐intracanalicular type
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Stromal Cellularity/Atypia/PASH
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FIBROADENOMA(CELLULAR)
BENIGN PHYLLODES TUMOR
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BENGIN PHYLLODES TUMORMYXOID STROMA
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FIBROADENOMA WITHMYXOID STROMA
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Stromal Mitoses
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INFILTRATIVE TUMOR BORDER
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TUMOR BORDER
MICROPAPILLARY DUCT HYPERPLASIAIN PHYLLODES TUMOR
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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
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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
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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
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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
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Stromal proportion to epitheliumStromal overgrowth
borderEpithelial hyperplasiaOverall growth patternMultinucleated giant cells
Histopathology 2007;51:336‐344
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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
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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
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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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112 NCB of FEL (21 PT AND 91 FA ; ALL WITH EXBX)
Patient’s Age at Diagnosis
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Percent Stroma
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Stromal Mitoses
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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
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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
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HIGH CORRELATION WITH PT ON EXBXMODERATE STROMAL CELLULARITYSTROMAL OVERGROWTHMODERATE STROMAL ATYPIAPASH
SUMMARY OF STUDIES
MORPHOLOGIC FEATURES OF PTSTROMAL CELLULARITY (MODERATE TO MARKED)STROMAL ATYPIA
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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.
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MALIGNANT
N PT
BL PT
. Histopathology 2010
BENIGN FIBROEPITHELIAL LESION
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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
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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
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ACTIN, DESMIN, HORMONE RECEPTORSEPITHELIALMYOEPITHELIALHISTIOCYTESENDOTHELIAL CELLS
SPINDLE CELL LESIONS
CYTOLOGICALLY BLAND-APPEARING LESIONS
BENIGNMALIGNANT
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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
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(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
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METASTASESMELANOMA
SARCOMAPRIMARY (HIGH-GRADE ANGIOSARCOMA)METASTATIC
OTHER CO-EXISTING CELLSRED BLOOD CELLS - ANGIOSARCOMAMIXED INFLAMMATORY INFILTRATE & RED BLOOD CELLS – NODULAR FASCIITISLYMPHOCYTES
PERIPHERAL AGGREGATES FIBROMATOSIS
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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)
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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)
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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
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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
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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
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FIBROMATOSISPainless, slowly growing massStroma vary from keloidal to myxoid/fasciitis likeSMA positive; +/ desmin S 100
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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
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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
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CK 7
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EXAMPLE B
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CKAE1/3
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Cam 5.2
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K903
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p63
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EXAMPLE C
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CKAE1/3
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CK 7
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SPINDLE CELL METAPLASTIC CARCINOMA
CKAE1/3 CK7 CAM5.2 K903 P63CASE 1 + + - + +CASE 2 + + + + +CASE 3 + - - + +
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*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
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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
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LOW-GRADE FIBROMATOSIS-LIKE SCMC
COMPOSED OF BLAND SPINDLE CELLS SIMILAR TO THOSE SEEN IN FIBROMATOSISCAN SEE AREAS THAT ARE MORE
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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 ?
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in common?
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THEY REPRESENT DIFFERENT AREAS OF THE SAME CASE
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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
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Transcriptional silencing by epigenetic mechanisms (e.g. promoter methylation)
Adjunctive Immunostains To Discern LCIS (particularly variants of) from DCIS
E-cadherinP120 catenin
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High molecular weight cytokeratin
DCISE-cadherin Positive
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Low grade High grade
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LCIS: Loss of E-cadherin Expression
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E-Cadherin Staining in LCIS
Myoepithelial cells (weak, fragmented)R id l d t l ith li l ll
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Residual ductal epithelial cellsLCIS cells (weak, fragmented)
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Rosen’s Breast Pathology, 2009
Rat MammaryLobule
E-Cadherin Staining in LCIS
Myoepithelial cells (weak, fragmented)R id l d t l ith li l ll
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Residual ductal epithelial cellsLCIS cells (weak, fragmented)
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E-Cadherin Staining in LCIS
Myoepithelial cells (weak, fragmented)R id l d t l ith li l ll
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Residual ductal epithelial cellsLCIS cells (weak, fragmented)
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
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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
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cytoskeletonNormal cells/ductal lesions:
membrane distribution
Lobular lesions:cytoplasmic distribution
Dabbs, AJSP, 2007
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P120 cateninDuctal lesions: membranous
LCIS: cytoplasmic
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E-cadherin and P120 Catenin in DCIS and LCIS
DCIS LCIS
E-cadherin positive negative
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P120 catenin membranous cytoplasmic
Adjunctive Immunostains To Discern LCIS (particularly variants of) from DCIS
E-cadherinP120 catenin
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P120 cateninHigh molecular weight cytokeratin
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LCIS
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DCIS
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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
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alterations and, possibly, clinical behaviorHeterogeneity of LCIS has until recently been largely under-appreciated
VARIANTS OF LCIS
Common feature – E cadherin negativeClinico-pathologic characteristics
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Clinico-pathologic characteristicsBiomarker expression by IHCMolecular signature – high res aCGH
FLORID LCIS
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FLORID LCIS
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PLEOMORPHIC LCIS
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E-CADHERIN IMMUNOSTAIN
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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
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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
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vacuolesPagetoid ductalinvolvement
More common Less common
Associated classicalLCIS
More common Less common
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
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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
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Distinction from DCIS Manage like classical LCIS or like DCIS?
FLCIS / PLCIS
E-cadherin negConcurrent inv ca
+/-Nuclear pleomorphismComedo necrosis
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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 ?
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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
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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
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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)
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LOBULARCARCINOMA
LOW-GRADEDCIS
HIGH-GRADEDCIS
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INVASIVE CARCINOMAWELL-DIFFERENTIATED
+1q, -16q
INVASIVE CARCINOMAPOORLY-
DIFFERENTIATED
+17q
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CCL/FEA
Inv tubular ca
LCIS
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FEA
Tubular ca
l AJS
P 20
07;3
1:41
7-42
6
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Abd
el-F
atah
T, e
t al
NOMENCLATURE
COLUMNAR CELL CHANGECOLUMNAR CELL CHANGE WITH ATYPIA (FLAT EPITHELIAL ATYPIA)COLUMNAR CELL HYPERPLASIA
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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
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FLAT EPITHELIAL ATYPIA COLUMNARCELL HYPERPLASIA
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Flat Epithelial AtypiaColumnar Cell Change
Columnar Cell Hyperplasia
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INVASIVE CARCINOMA (IN THE CONTEXT OF LCIS)
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Histologic Type of Cancer Following CLCISMost (up to 75%) are invasive
ductal carcinomas
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Frequency of Invasive Lobular Carcinoma Following CLCIS
Study % Invasive Lobular Ca
Chuba (SEER) 23.1%
INVASIVE LOBULAR CARCINOMA – 10-15% OF ALL INV BC
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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
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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
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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
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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
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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%)
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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%)
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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
10/8/2011
98
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
2011 ASCP Annual Meeting
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
THANK YOU!
2011 ASCP Annual Meeting
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