Intraoperative evaluation of axillary sentinel lymph nodes using touch imprint cytology and immunohistochemistry. Part II. Results

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Abstract

Aim

In order to operate selectively on positive axillae during the initial operative session for early breast cancer, an accurate and rapid intraoperative method to examine an axillary node sample (ANS) or a sentinel node biopsy (SNB) is required. The aim of this study was to determine the feasibility and accuracy of Immunohistochemistry (IHC)-stained touch imprints in detecting metastatic axillary nodes intraoperatively.

Material and methods

Four hundred and thirty-two axillary nodes from 52 patients (23 axillary node clearance (ANC), 15 ANS and 14 SNB) were bisected, imprinted and stained with anti-cytokeratin 19 IHC. Results were compared with those of routine haematoxylin and eosin (H&E)-stained sections.

Results

IHC imprints detected 32 positive nodes from 12 patients. H&E sections detected 31 positive nodes from 11 patients. IHC imprints missed metastases in three nodes and missed the diagnosis of positive axillae in two patients. H&E missed metastases in four nodes and missed the diagnosis of positive axillae in 3 patients. On a node-basis, sensitivities were 91.4 and 88.5%, negative predictive values (NPV) were 99.2 and 99.0% and overall accuracies were 99.3 and 99.1% for IHC imprints and H&E sections, respectively. On a patient-basis, sensitivities were 85.7 and 78.5%, NPVs were 95.2 and 93.1% and overall accuracies were 96.1 and 94.2% for IHC imprints and H&E sections respectively. There were no false positives. Interpretation of the results by a non-histopathologist was concordant with that of a histopathologist. Results might be obtained within 30–45 min depending on the number of examined nodes.

Conclusion

Intraoperative IHC staining of touch imprints of axillary sentinel nodes is feasible and is a reliable method for evaluating axillary nodes. Slides can be reliably interpreted by a trained non-histopathologist.

Introduction

There is a need for selective axillary surgery to avoid the complications of ANC in patients with early breast cancer. SNB is considered an accurate method for detecting axillary lymph node status in patients with early breast cancer.1, 2 However, there is no universal agreement on the optimal method for the intraoperative examination of the sentinel nodes.3, 4, 5, 6 The use of IHC might increase the sensitivity of imprint cytology and make its interpretation by a non-cytopathologist easier. We have previously described a protocol for the intraoperative immunostaining of axillary node touch imprints.7 We report here the final results of this study, whose preliminary results were reported earlier on.8

Section snippets

Material and methods

Fifty-two patients (23 ANC, 15 ANS and 14 SNB) who attended the University Hospital of Wales for treatment of early breast cancer (stages I and II) gave informed consent and took part in this study, which was approved by the Local Research Ethics Committee prior to its start. Some of the patients were among the ALMANAC (axillary lymphatic mapping against nodal axillary clearance) trial. The SNB procedure was done according to the standard protocol of the ALMANAC trial.

Four hundred and

Results

Four hundred and thirty-two nodes from the 52 patients in the study were examined by both IHC imprints and routine H&E pathology.

On IHC imprints, 12 patients had positive axillary nodes, with a total of 32 positive nodes. On H&E sections, only 11 patients had positive axillary nodes, with a total of 31 positive nodes. IHC imprints missed metastases in three nodes and missed the diagnosis of a positive axilla in two patients. Routine H&E pathology missed metastases in four nodes and missed the

Discussion

Results of IHC imprints in this study were concordant with results of other imprint cytology methods published by Motomura et al.,5 Ratanawichtrasin et al.,12 Rubio et al.4 and Anastasiadis et al.13

In a recent publication, Lambah et al.14 reported their results of using anti-cytokeratin immunostaining of imprint cytology as an intraoperative diagnostic tool for the assessment of axillary lymph nodes. They studied 238 nodes from 53 patients with early breast cancer. Imprints were stained with

Conclusion

Immunostained imprint cytology is a reliable method for intraoperative detection of metastatic axillary nodes. Combined with sentinel node biopsy, it can spare patients with positive axillae a second axillary procedure, and patients with negative axillae complications of unnecessary routine axillary clearance. Immunostaining of touch imprints is also an easy technique that aids the interpretation of the slides by non-cytologists and can be widely used.

References (15)

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    Touch imprint cytology of axillary sentinel nodes has also been used with similar sensitivities to frozen section. Depending on local expertise some centres found it to be feasible and a reliable method for evaluating axillary nodes.55 More recently intraoperative molecular analysis using RT-PCR has been reported, and many centres in the UK are using it.

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    Detection of metastasis was easier using immunohistochemistry in combination with Papanicolaou staining, and the false-negative rate was decreased significantly. Salem and colleagues reported that by using immunostaining with an anti-cytokeratin antibody, a non-pathologist was able to diagnose SLN metastasis with the same accuracy as a histopathologist.13 However, even though the sensitivity of intraoperative detection of SLN metastasis could be increased by combining Papanicolaou staining and immunohistochemistry, there were four false-negative cases in the present study, including two cases of micrometastasis.

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