Variations in sentinel node isolated tumour cells/micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions

doi:10.1016/j.ejca.2008.06.033

European Journal of Cancer

Volume 44, Issue 15, October 2008, Pages 2185-2191

https://doi.org/10.1016/j.ejca.2008.06.033 Get rights and content

Abstract

Breast cancers with nodal isolated tumour cells (ITC) and micrometastases are categorised as node-negative and node-positive, respectively, in the tumour node metastasis (TNM) classification. Two recently published interpretations of the TNM definitions were applied to cases of low-volume sentinel lymph node (SLN) involvement and their corresponding non-SLNs for reclassification as micrometastasis or ITC. Of the 517 cases reviewed, 82 had ITC and 435 had micrometastasis on the basis of one classification, and the number of ITC increased to 207 with 310 micrometastases on the basis of the other. Approximately 24% of the cases were discordantly categorised. The rates of non-SLN metastases associated with SLN ITCs were 8.5% and 13.5%, respectively. Although the second interpretation of low-volume nodal stage categories has better reproducibility, it may underestimate the rate of non-SLN involvement. The TNM definitions of low-volume nodal metastases need to be better formulated and supplemented with visual information in the form of multiple sample images.

Introduction

The prognostic impact of small-volume nodal metastases in breast cancer is widely debated with several studies and reviews suggesting at least a minor disadvantage in survival, and others questioning this.1, 2 With the introduction and acceptance of sentinel lymph node (SLN) biopsy (SLNB) and the resulting increased histopathological scrutiny of the SLNs, the identification rate of low-volume metastases has significantly increased.³ This has resulted in a stage migration, as many of the former node-negative cases containing occult metastases are now placed into the node-positive micrometastatic group.⁴ Because of the statistical artefacts that such a stage migration may cause and the debated prognostic significance of low-volume metastases, the pathological tumour node metastasis (pTNM) classification of malignant tumours and the American Joint Committee on Cancer (AJCC) staging definitions have split the micrometastasis category into two, one consisting of the micrometastasis category per se (pN1mi; micrometastases not larger than 2 mm, but larger than 0.2 mm) and the isolated tumour cell (ITC) category (pN0(i+) for lesions not larger than 0.2 mm).5, 6

Despite the lack of evidence, the distinction between ITC and micrometastasis seems important, as it influences the treatment decisions. Micrometastases are considered true metastases, and are generally treated as such: i.e. completion axillary dissection is often recommended for such SLN involvement, and systemic treatment decisions also consider patients with SLN micrometastasis as node-positive. On the other hand, ITCs are generally considered node-negative for both staging and treatment decisions 2, 7, 8.

It has been suggested that the distinction between micrometastasis and ITC lacks reproducibility.9, 10 This is partly due to the different wording of the two main staging resources: the International Union Against Cancer (UICC) definitions suggest some qualitative features such as the assessment of metastatic activity and extravasation in addition to size for the distinction between pN1mi and pN0(i+)5, 11, whereas the AJCC definitions⁶ depend only on size.⁹ Another cause of the suboptimal reproducibility is the absence of relevant details from the definitions, giving rise to different interpretations.9, 12, 13

Two different interpretations of the current definitions of ITC and micrometastasis5, 6 were recently reported with the identical aim of improving the consistency of nodal staging of breast carcinomas. The European Working Group for Breast Screening Pathology (EWGBSP) suggested that despite an improvement in reproducibility, the distinction between ITC and micrometastasis was still suboptimal,⁹ whereas a recent study resulted in a more consistent classification.¹² However, the latter study allows nodal involvement with a much higher overall volume of tumour cells to be classified as ITC. Our group sought to analyse the validity of the two different interpretations by obtaining the rates of non-SLN metastases associated with small-volume SLN involvement categorised according to the two different interpretations.

Section snippets

Materials and methods

Members of the EWGBSP were asked to collect SLN cases from their own archives which met the following criteria: (A) SLN involvement falling either in the ITC or in the micrometastasis group on the basis of the original report (no macrometastases were allowed in any of the SLNs); (B) Axillary lymph node dissection with a minimum of 6 non-SLNs removed. Cases which were originally reported as micrometastatic or having ITC in the SLN but were considered to be macrometastatic according to any of the

Results

There were 517 breast cancer cases entered in this study. These were all originally diagnosed as SLNs affected by either micrometastasis (n = 421), ITC (n = 58) or a small metastasis, not otherwise specified (n = 38), as the most significant SLN lesion; 235 (45%) of these were identified by immunohistochemistry (IHC). This original distribution of SLN involvement was only used for case selection, because the definition of ITC and its distinction from micrometastasis in the TNM system dates from 1999¹¹

Discussion

The distinction between the ITC and micrometastasis categories of the pTNM system is also a distinction between node-negative and node-positive status.¹⁶ As such it may impact upon decisions concerning completion axillary dissection and systemic adjuvant treatment.²

The main purposes and probably advantages of introducing the ITC category at the lower end of micrometastasis were 1. to avoid the stage migration arising from more thorough pathological assessment of SLNs; 2. to account for possible

Conflict of interest statement

None declared.

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Variations in sentinel node isolated tumour cells/micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Conflict of interest statement

Eur J Cancer

Breast

Breast

Mod Pathol

Eur J Cancer

Significance and management of micrometastases in patients with breast cancer

Expert Rev Anticancer Ther

The prognostic significance of micrometastasis in breast cancer: a SEER population-based analysis

Ann Surg Oncol

Sentinel lymph nodes and breast carcinoma: which micrometastases are clinically significant?

Am J Surg Pathol

American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer

J Clin Oncol

Improving the reproducibility of diagnosing micrometastases and isolated tumor cells

Cancer