Post on 17-Jan-2016
description
Pathological Evaluation of Sentinel Lymph Node Biopsy in
Breast Cancer
N. Krishnani
Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow
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Sentinel Lymph Node
First node to which lymph drainage and metastasis from breast cancer occurs
•Central group of level I (most common)•Level II or III•Intramammary•Interpectoral or internal mammary node
Proceedings of the Consensus Conference on Role of SLNB, 2001 Philadelphia
Sentinel Lymph Node
•Represent the entire nodal basin•Most likely to contain tumor if metastasis has occurred•If sentinel nodes are patholgically benign, all of the other axillary nodes can be considered tumor free
SLNB is suitable replacement for axillary dissection as a staging and diagnostic procedure in T1 andT2 breast cancers
Sentinel Lymph Node
Approximately 40% of operable breast cancer have axillary disease according to conventional histological methods
Stage Positive SLN•T1a 4.3%•T1b 19.5%•T1c 23.8%•T2 48.9%•T3 66.7%
Inclusion and Exclusion Criteria
•Stage T1 or T2 disease without palpable nodal metastases
•Palpable axillary node metastases•Multifocal breast cancer•Pregnancy or currently breast feeding•Prior major breast or axillary operations•Allergies to blue dye or radiocolloid
Proceedings of the Consensus Conference on Role of SLNB, 2001 Philadelphia
Sentinel Node Biopsy in Ductal Carcinoma In-situ
• Not indicated in mammographically detected DCIS or
incidental finding.
Indications:• Palpable mass • Large areas of calcification• large lumpectomy• High grade with or without comedo necrosis
(microinvasion may be overlooked because of the
area of disease is so large)
Handling of Specimen• Measured and cut along its longitudinal axis into 2 mm-
thick sections• Gross examination to detect focal lesions• Each 2 mm thick sections be cut at three levels• Imprint cytology smears are prepared• Remaining lymph node sections are then submitted for
paraffin section histology• Each paraffin block should be sectioned at 3 levels• Report include individual cell / colonies / large size and
location of malignant cellsProceedings of the Consensus Conference on Role of SLNB, 2001 Philadelphia
Am J Surg Pathol 2003;27(3):385-389
2-3 mm2 mm
Am J Surg Pathol 2003; 27(3):385-389
Metastases
Macrometastases: Any tumor deposit > 2mm
Micrometastases: Cohesive cluster of malignant cells, 0.2 mm and upto and including 2.0 mm in diameter. Indicate residual disease in approx. 10% of patients
Sub-micrometastases: Clusters of malignant cells measuring less than 0.2 mm. Seen by IHCNo clinical significance and highly unlikely to be associated with significant residual metastasis and predict an adverse outcome
Frozen SectionAdvantages
Interpretation of nodal architecture availableMore specific diagnosis possibleSize of metastatic focus measurableCan be complemented by rapid IHCHistologists are more familiar with the method
DisadvantagesRelatively time-consumingMore expensiveFreezing artifactsSome tissue is lostMore expensive
Imprint CytologyAdvantages
Simple / cheap / rapidInterpretation of cytological / nuclear details availableAvoid tissue lossCan be complemented by IHC
DisadvantagesSize and area of metastatic focus not detectableMore indeterminate / deferred diagnosesNeed special training to interpretCan not differentiate between micro and macrometastases
Authors H&E sections
N Accuracy Sensitivity Specificity False-negative
Canavese et al 3 96 96 86 100 14
Schneebaum et al
Not described
47 98 91 100 9
Koller et al 3 consequti. 107 83 64 100 36
Imot et al Not described
52 96 89 100 11
Noguchi et al 2 38 79 60 100 40
Noguchi et al .>3 45 93 85 100 15
Noguchi et al 2 mm interval
26 100 100 100 0
Motomura et al
1 101 88 52 100 48
Intraoperative Frozen-section Diagnosis
Authors N Study design Std. Methods
Upgraded by alternative methods
Turner et al 52 2 HE at 40 mm interval Vs 2 HE at 160 mm interval
19 5
Nahrig et al 40 1 HE vs 4 additional HE at 150 mm intervals
45 18
Torrenga et al 250 1HE vs additional 4 HE at 250 mm interval
28 4
Multiple Levels of H&E Sections
Authors No. of Sections
N Accuracy Sensitivity Specificity False-Negative rate
Moriya et al 1 286 99 95 100 5
Rubio et al 1 124 99 96 100 5
Ratan- et al 2 55 98 93 100 7
Motomura et al 2 mm interval
101 96 91 99 9
Henry et al >1 479 99 94 100 6
Karamlou et al 1 446 - 75 100 5
Intraoperative Imprint Cytology
Intraoperative Cytology
•Diagnostic accuracy did not exceed that of frozen section
•Occasional false positive case
•Concordance rate is approx. 90%
•When both method employed, diagnostic accuracy improve
Takeshi Nagashima et al, Acta Cytol 2003;47:1028-1032
Immunohistochemical Technique• More accurate and used as adjunct to routine stain• Antibody to cytokeratin used to detect small focus
of malignant cells (Micrometastases or isolated
tumor cells)
False positiveBenign transport of breast epitheliumDegenerating cells in transitDendritic cellsMacrophagesEpidermal squamous cells
Authors N Study design Std Method
Upgrade by IHC
Czemiecki et al 41 1HE Vs 4 levels of IHC
29 7
Noguchi et al 62 1HE vs IHC 39 2
Pendas et al 478 1HE vs IHC 19 9
Kowolik et al 33 2HE vs IHC 24 12
Mann et al 51 1HE vs IHC 20 20
Wong et al 973 1HE vs 2 levels of IHC
11 6
Torrenga et al 250 1HE vs IHC 28 2
Torrenga et al 250 1 HE vs 4levels of IHC
28 7
Immunohitochemical Staining
Probability of non-SLN metastasis will be less
than 0.1% if SLN negativity is confirmed by
both H&E and immunohistochemistry
Turner et al: Am J Surg Pathol 1999;23:263-267
H&E and Immunohistochemistry
• What is the significance of occult metastases in terms of prognosis
• What is the significance of occult metastases in terms of predicting further nodal involvement (approx. 12%)
• Do these patient stand to benefit from completion axillary lymph node dissection and / or systemic chemotherapy
Implications of Micrometastases Seen Only on Immunohistochemistry
Implications of Micrometastasies Seen Only on Immunohistochemistry
•Data are inconclusive at this time•Additional studies are needed in order to establish the role of IHC detected lymph node metastases
Recommendations
•Ignore the presence of isolated tumor cells•Either refrain from examining SLN by IHC or address on case by case basis
Allweis et al, Breast 2003;12:163-167 and European Consensus group for Breast Screening Pathology
Recommendations
•Standard practice and, the pathology report should state only whether metastasis are found on H&E stained slide •IHC may be performed when the H&E stained slides have suspicious cells that are equivocal•Cytokeratin positive malignant cells be quantified
Proceedings of the Consensus Conference on Role of SLNB, 2001 Philadelphia
Recommendations
Adjuvant therapy, either chemotherapy or hormonal treatment (or for completion axillary dissection or axillary radiation) should not be made solely on the basis of information obtained by IHC of sentinel lymph node
Proceedings of the Consensus Conference on Role of SLNB, 2001 Philadelphia
Molecular Analysis
•Assesment by reverse transcription-polymerase chain reaction (RT-PCR)
•More sensitive than immunohistochemistry•Specific markers are lacking, and false negative tests•Relevance is even more debatable than occult metastasis detected by immunohistochemistry
•Results are highly variable and high rate of upstaging (14-50%)
•Experimental assessment•Not feasible in all pathology lab
Summary of Consensus•Intraoperative assessment of SNs is strongly recommended•Careful handling specimen and cut node into 2 mm section
and examine for any focal lesion•Step sectioning or multiple level assessment should be
used, although the optimal distance between these step is
controversial•Choice of method should be institutional depending on the
resources•Imprint cytology should be done in conjunction with frozen
section
Summary of Consensus
•Immunohistochemistry is optional in routine patient management
•Molecular analysis be restricted to research purposes as controversies over the interpretation and the lack of specific markers