Imprint cytology of the sentinel lymph node in the assessment of axillary node status in breast carcinoma

doi:10.1016/j.ejso.2003.11.005

European Journal of Surgical Oncology (EJSO)

Volume 30, Issue 3, April 2004, Pages 238-242

https://doi.org/10.1016/j.ejso.2003.11.005 Get rights and content

Abstract

Background. Intra-operative assessment of the sentinel lymph node (SLN) status may allow the surgeon to complete the breast cancer surgery in most patients in one sitting. We have studied the role of imprint cytology in the assessment of SLN status.

Patients and methods. Imprint cytology of the SLN in 132 patients with invasive breast carcinoma was correlated with the histopathological assessment of the SLN and overall axillary nodal status. In 26 patients, the cytology was reported intra-operatively.

Results. Imprint cytology reflected the status of the parent node well (sensitivity 86%, specificity 97%, positive predictive value (PPV) 92%, negative predictive value (NPV) 93%). Its ability to reflect the axillary status was also good (sensitivity 70%, specificity 97%, PPV 95% and NPV 83%) but somewhat diminished by the relatively high number of false-negative SLN in the study. Intra-operative assessment (sensitivity 86%, specificity 100%, PPV 100% and NPV 95%) did not reduce the accuracy of imprint cytology in predicting the SLN status and took a mean of 24.5 min.

Conclusions. Imprint cytology is an accurate and relatively simple method for the assessment of the SLN and can be a useful intra-operative tool.

Introduction

Sentinel lymph node (SLN) biopsy is now well established in breast cancer surgery. A SLN free of tumour could eliminate the need for lymph node clearance in suitable patients, avoiding an unnecessary procedure with its associated morbidity.¹ Routine assessment of paraffin-wax sections of SLN takes many hours to complete and as a result patients with metastatic tumour in the SLN will have to be recalled for an axillary clearance. Intra-operative assessment of the SLN status would allow concurrent axillary clearance to be performed in the node-positive patients and also helps to inform the patients of their axillary nodal status immediately after the surgery.

Any method used in such assessment should be quick, so as not to waste theatre time, and reliable, to avoid unacceptable levels of false-positive or false-negative results. A false-negative result (missed metastatic tumour in the SLN) will result in the patient being recalled for further surgery after earlier reassurance that this would probably not be necessary. A false-positive result (metastatic tumour diagnosed where in fact there was no tumour) will result in a normal axilla being cleared of lymph nodes. At present only two methods appear to have a role in the intra-operative identification of the SLN status: frozen section histology and imprint cytology.

The role of frozen section histology has been assessed in a number of studies but the problem with most studies had been a lack of sensitivity due to high false-negative rates, as high as 48%.2., 3. One way to reduce this problem might be to examine the entire sentinel node by taking multiple sections, as reported by Veronesi's group from Milan.⁴ Having reported a false-negative rate of 36% with routine frozen sections previously⁵ they eliminated this problem by examining 60 frozen sections per node and by using both haematoxylin and eosin (H & E) stained sections and immunohistochemistry. Most would agree that this is neither practical in the intra-operative setting nor cost effective for most pathology laboratories. Frozen section examination also results in the loss of a large amount of lymph node tissue and in freeze-thaw artefact in the remaining tissue, both compromising the subsequent paraffin-wax section assessment.

Imprint cytology, on the other hand, is simple, relatively quick and inexpensive and does not result in any loss of nodal tissue. A number of recent studies have suggested that imprint cytology allows most patients who require an axillary clearance to be identified intra-operatively.6., 7., 8., 9., 10. Here we have studied the role of imprint cytology in the assessment of SLN status.

Section snippets

Patients and methods

Female patients with both screen-detected and symptomatic breast carcinoma underwent SLN biopsy as part of their definitive surgical treatment at the breast unit of the Norfolk and Norwich University Hospital over a 20-month period. The SLN was identified either by using only the Patent blue V dye (Guerbet Laboratories Ltd, Milton Keynes, UK) or a combination of dye and isotope (Nanocoll, Nycomed Amersham, Bucks, UK). Isotope and the dye were injected subdermally over the tumour (in case of

Results

During the study period SLN biopsy was attempted in 139 patients with invasive breast carcinoma. Blue dye alone was used in 119 patients and dye and isotope in 20 patients. The SLN was identified in 133 patients (96%) and these patients constitute the study population. The mean age of these patients was 60.4 years (range 28–87). Twenty-seven patients had impalpable tumours. The mean size of the tumours preoperatively was 18.6 mm. The mean time for SLN biopsy was 9 min (range 2–24). Fifty-one

Discussion

Intra-operative assessment of the SLN status may enable the surgeon to complete the breast cancer surgery in one sitting in most patients, avoiding the risks and cost as well as patient anxiety associated with a second operation. This work suggests that imprint cytology accurately reflects the lymph node from which it was taken. The commonest reason for false-negative imprint results was the presence of small metastases away from the bisected surface of the node. This is recognised¹¹ but was

Acknowledgements

We would like to thank Mr S.D. Scott for contributing patients to the study and Dr Skrypniuk for scintigrams. We acknowledge the assistance of Professor Ell and Mr Keshtgar from the Department of Nuclear Medicine and Surgery, University College Hospital, in establishing the sentinel lymph node technique in Norwich.

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Cited by (16)

Intra-operative imprint cytology for assessing the sentinel node in breast cancer - Results of its routine use over 8 years
2009, European Journal of Surgical Oncology
Citation Excerpt :
None of the false negatives were due to cells from lobular carcinoma being mistaken for lymphoid cells as has been described previously.11, 12 The reported sensitivity of IIC using lymph node bisection (the technique used in this study) in previous research studies ranges from 41% to 86%4,9,13–17 (Table 2). However, time and economic and other pressures may vary significantly between normal clinical practice and a research setting.
Intra-operative imprint cytology (IIC) for analysing sentinel lymph node/s (SLN) in breast cancer allows definitive axillary surgery as a one-step procedure. Most reported studies are research oriented. This study reports long-term results of IIC done as routine clinical practice.
Eight hundred ninety-six female, operable breast cancer patients underwent SLN biopsy over an 8-year period (January 1999–December 2006). Data were extracted retrospectively from medical records. SLNs were sent intra-operatively to the laboratory where they were bisected, touch imprinted and stained with Hematoxylin & Eosin. Patients with positive IIC had axillary clearance. Formal histological analyses of SLNs were compared with IIC findings. The impact of routine pre-operative axillary ultrasound (introduced in 2003) on IIC sensitivity and specificity was also assessed.
Median age was 61 years (26–89) and median tumour size was 18 mm (2–100). A total of 244/896 patients had SLN metastases on final paraffin histology of which 177 were correctly detected by IIC (67 false negatives). 39/67 false negatives could be attributed to sampling error. The overall sensitivity and specificity of IIC for the identification of SLN metastases was 73% and 100%, respectively. The sensitivity of IIC after introduction of pre-operative axillary ultrasound decreased from 75% to 71%.
Routine use of IIC for analysis of the SLN in breast cancer allows complete axillary surgery during a single anaesthetic for a majority of patients undergoing SLN biopsy. Almost two thirds of positive axillae were spared a second operation. False negative results are frequent and patients should be warned about the potential need for further axillary surgery.
Patients' view on intraoperative diagnosis of sentinel nodes in breast cancer: Is it an automatic choice?
2007, International Journal of Surgery
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This emphasizes the need to ensure that patients understand the potential for a false negative result and have realistic expectations of what can be achieved at their treating hospital. False positive diagnoses have been reported for both frozen section and touch imprint cytology, which could lead to unnecessary extensive surgery (ALND).6–8 There were no false positive diagnoses in this study.
Intraoperative detection of sentinel node metastases in breast cancer enables immediate axillary lymph node dissection. This approach, however, introduces uncertainty for patients as to the extent of surgery. Waking to find a surgical drain implies more extensive surgery and worse prognosis disease. False negative diagnoses may cause disappointment.
To evaluate patients' views and preferences on intraoperative diagnosis of sentinel nodes in breast cancer.
Questionnaire based survey of 100 patients who had previously undergone sentinel node biopsy with intraoperative diagnosis using touch imprint cytology (TIC). Patients were encouraged to add free text comments.
Sixty-four patients responded to the questionnaire. Patients rated the information provided and their understanding of the procedure highly. Fifty-nine percent of respondents overestimated the sensitivity of TIC. Ninety-five percent of patients would choose to undergo intraoperative diagnosis in future if required. Five percent of patients would choose not to undergo intraoperative diagnosis, citing the resultant uncertainty, disappointment on waking and needing time to come in terms with the diagnosis of metastases as reasons.
Given the choice, most patients would choose intraoperative diagnosis, though a minority would explicitly not, due to the adverse psychological effect thereof. Despite a good understanding of the procedure, the majority of patients overestimate the sensitivity of intraoperative diagnosis of sentinel nodes, which may heighten disappointment when a false negative diagnosis occurs. Intraoperative diagnosis should not be the automatic choice and patients should be actively involved in this decision making process.
Accuracy of intraoperative imprint cytology of sentinel lymph nodes in breast cancer
2006, American Journal of Surgery
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Intraoperative IC allowed 49 (55%) of the N1 or greater patients to benefit from synchronous ALND. Previous series examining the accuracy of intraoperative IC have reported sensitivities ranging from as low as 34% to as high as 96% [3,14–21]. Table 2 shows a summary of our review of the English literature.
In breast cancer treatment, immediate completion of axillary lymph node dissection (ALND) can be performed if the intraoperative sentinel lymph node (SLN) examination is positive. This study evaluates the accuracy of intraoperative imprint cytology (IC) for detecting SLN metastases.
Pathology reports from 385 SLN biopsy examinations were reviewed retrospectively. The SLNs were serially sectioned perpendicular to the long axis and IC was performed intraoperatively. The SLNs then were formalin-fixed for permanent sections. Final pathology was compared with the intraoperative IC results.
The sensitivities for IC detection of N0(i+) (n = 36), N1mi (n = 24), and N1a-3a (n = 65) metastases were 0%, 4%, and 74%, respectively. The specificity was 100%.
Final pathology identified 89 (23%) patients with N1 or greater disease. IC allowed 49 (55%) of these patients to undergo synchronous completion of ALND. No unnecessary completion ALNDs were performed. The sensitivity of IC decreased with decreasing size of the metastasis.
Lymphatic mapping in management of patients with primary cutaneous melanoma
2005, Lancet Oncology
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Intraoperative frozen-section examination of sentinel nodes in patients with melanoma has been abandoned in most centres because of high rates of false-negatives.75 However, other methods of rapid intraoperative sentinel-node assessment, such as examination of fine-needle aspirates by use of magnetic resonance spectroscopy, are being investigated,76 as is the accuracy of imprint cytology in patients having sentinel-node biopsy for breast cancer.77,78 Interim results of the first Multicenter Selective Lymphadenectomy Trial,3,68,79 suggest that sentinel-node biopsy, with immediate completion regional-node dissection if micrometastatic disease is found in a sentinel node, improves survival for patients who are node-positive.
In patients with primary cutaneous melanoma, knowledge of regional lymph-node status provides important information on outlook. Evidence suggests that early removal of nodes that contain metastatic disease improves survival outcome. Lymphatic drainage occurs first to sentinel nodes, which are therefore the nodes most likely to contain metastatic disease. Lymphatic mapping with lymphoscintigraphy is important to identify reliably sentinel nodes for removal and thus establish the status of regional nodes. Mapping studies in patients with melanoma have provided new insights into lymphatic anatomy and have shown previously unsuspected drainage pathways, which have important implications for accurate identification and removal of sentinel nodes. Because it is impossible to predict the site or sites of sentinel nodes clinically in individual patients, routine preoperative lymphoscintigraphy is a prerequisite if reliable results are to be obtained from sentinel-node biopsy.
Intraoperative evaluation of sentinel lymph nodes for breast cancer
2005, Breast Diseases
Clinical significance of MSKCC nomogram on guiding the application of touch imprint cytology and frozen section in intraoperative assessment of breast sentinel lymph nodes
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Imprint cytology of the sentinel lymph node in the assessment of axillary node status in breast carcinoma

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Acknowledgements

Lancet

J Am Coll Surg

Proceedings of the consensus conference on the role of sentinel lymph node biopsy in carcinoma of the breast, April 19–22, 2001, Philadelphia, Pennsylvania

Cancer

Intraoperative sentinel lymph node examination by imprint cytology and frozen sectioning during breast surgery

Br J Surg

Accuracy of intraoperative frozen section analysis of axillary nodes

Br J Surg

Intraoperative examination of axillary sentinel lymph nodes in breast carcinoma patients

Cancer

Intraoperative assessment of sentinel lymph nodes in patients with breast carcinoma. Accuracy of rapid imprint cytology compared with definitive histologic workup

Cancer (Cancer Cytopathol)

Intraoperative touch imprint of sentinel lymph nodes in breast carcinoma patients

Cancer (Cancer Cytopathol)

Intraoperative sentinel lymph node examination by imprint cytology during breast surgery

Curr Med Res Opin