Pathological Evaluation of Sentinel Lymph Node Biopsy in Breast Cancer

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