Japanese Journal of Clinical Oncology 30:263-266 (2000)
© 2000 Foundation for Promotion of Cancer Research
Blue Nodes Left Behind After Vital Blue Dye-guided Axillary Sentinel Node Biopsy in Breast Cancer Patients
Departments of 1Surgical Pathology and 2Nuclear Medicine and Surgery, Bács-Kiskun County Teaching Hospital affiliated to the Albert Szent-Györgyi Medical University, Kecskemét, Hungary
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentREFERENCES |
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Background: Vital dye-guided sentinel node biopsy is affordable in most hospitals, but may be of limited accuracy in identifying all sentinel nodes. Leaving sentinel nodes in the axilla may result in a false nodal staging of breast carcinomas.
Methods: From a series of 112 successful sentinel lymph node biopsies with Patent Blue dye followed by axillary dissection, 10 cases were identified where 1–3 blue nodes were found in the axillary dissection specimens. These 10 cases were compared with those which had all blue nodes identified during surgery. Five of the 10 patients with missed blue nodes also underwent lymphoscintigraphy with 99m-Tc-labeled colloidal human albumin and all of their nodes were subjected to external gamma well counting postoperatively.
Results: There were six false-negative sentinel lymph node biopsies overall, but none in patients with missed blue nodes. Patients with primarily unidentified blue nodes had more sentinel nodes and a higher rate of multiple sentinel nodes than the others.
Conclusion: Blue nodes missed during surgery may be either true sentinel nodes or second echelon nodes labeled by dye overflow. This type of error may occur in <8% of patients and may lead to false-negative sentinel node-based staging in an even smaller proportion of cases (none in this series).
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentREFERENCES |
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A number of studies have documented that the histological assessment of sentinel lymph nodes (SLNs) is highly predictive of the overall axillary nodal status in breast cancer patients and the use of step sectioning and/or immunohistochemistry may allow a more accurate staging (1–4). It seems that SLN biopsy may become the standard of care for a significant subset of breast cancer patients and may allow the obviation of axillary dissection in SLN-negative cases which are considered axillary node-negative also.
Intraoperative gamma probe and vital dye-guided SLN biopsy techniques have been described (5,6). Without listing all their advantages and disadvantages, it is essential to point out that gamma probe guidance allows an easy identification of multiple SLNs, but may lead to the identification of more nodes than necessary, because SLNs are defined as those which are more radioactive than the background or the other nodes. How much more is not easy to define and may depend on many still unstandardized factors, such as the overall radioactivity dose, the particle size and type of the colloid used, the injection technique, etc. On the other hand, the vital dye technique allows an accurate definition of the SLNs as stained nodes or nodes at the end of stained lymphatic vessels. However, this technique makes the identification of multiple SLNs more difficult and some SLNs may be left behind.
The present analysis was undertaken to assess the frequency of blue nodes missed during surgery, since such failures may lead to the establishment of a false nodal status, with untreated metastatic deposits being left in the axilla.
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentREFERENCES |
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A retrospective analysis was carried out on all primary operable breast cancer patients with successful lymphatic mapping operated on at our institution between August 1997 and August 1999. The method of lymphatic mapping was previously described in connection with the first half of the present series (7). Briefly, 5–10 min following peritumoral injections of 2–4 ml of Patent Blue dye (Patentblau V2.5%, Byk Gulden, Konstanz, Germany), stained lymphatics were searched for from an anterior axillary incision and SLNs (as defined in the Introduction) were removed separately. A mapping procedure was categorized as successful whenever at least one SLN was identified during surgery. The SLN biopsy was always completed by a formal level I and II axillary dissection. Most of the SLNs and axillary dissection specimens were received fresh at the pathology department and cut up immediately. Formalin-fixed and paraffin-embedded SLNs were accessed by serial sectioning and immunohistochemistry for epithelial markers (cytokeratins and epithelial membrane antigen). All blue nodes were considered as SLNs in this context, irrespective of their intraoperative or postoperative identification. Non-SLNs were processed conventionally. Although intraoperative reporting of sentinel nodal status is of paramount importance in the biopsy setting, we introduced SLN imprint cytology only at the end of this series and cannot address the issues of reliability at the moment, owing to the lack of an adequate number of cases. No frozen sections were performed on sentinel nodes because of the fear of missing micrometastases by the minimal tissue loss associated with this technique and because of the suboptimal quality of our frozen specimens.
Thirty patients underwent lymphoscintigraphy prior to vital blue dye-guided SLN biopsy. This was performed 30 min and 2 h after the peritumoral injection of 0.5 ml of 99m-Tc-labeled colloidal human albumin (50–60 MBq; mean particle size <80 nm for some cases, >200 nm for the others) on the day before surgery. In these cases, all recovered nodes were assessed with an external gamma well counter postoperatively. Nodes with high counts (at least 10 times higher than the rest of the nodes) were marked and the overlap between nodes identified by this means and blue-stained SLNs was evaluated.
Cases with blue nodes identified in the axillary dissection specimens by the pathologist were chosen for this analysis (Group A). These were compared with cases with all SLNs identified during surgery (Group B). The two groups were compared statistically via Student’s t-test for parametric data and via the chi squared test for categorical data.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentREFERENCES |
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From a total of 130 mapping procedures, 113 (87%) were successful, with most of the failures occurring at the beginning of the period in question (7). One of the tumors was a fibroadenoma that had been misdiagnosed on fine needle aspiration; this tumor was excluded from further analysis. The mean age of the patients was 57.9 years (median 57 years; range 34–85 years). The average size of successfully mapped tumors was 2.4 cm (median 2.3 cm; range 0.1–6 cm). A total of 76 (68%) cases were axillary node-positive; 106 (95%) SLN biopsies proved to be predictive of the nodal status. The six false-negative cases resulted in an 8% false-negative rate (defined as the number of false-negative cases divided by the number of all metastatic cases expressed as a percentage). None of the cases in Group A were false-negative.
Table 1 compares categorical (clinical or histopathological) variables of Groups A and B, and Table 2 compares the two groups on the basis of parametric data relating to tumors and lymph nodes. There were no significant differences between the groups in terms of type of operation, pT or pN categories of the TNM system, histological type and grade of the tumors, incidence of (lymph) vascular invasion, tumor size, lymph nodes recovered or SLNs identified during surgery. However, patients with missed blue nodes had more SLNs that could be identified with the blue dye method.
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The metastatic status of primarily identified and missed blue nodes is listed in Table 3. The patient identified as No. 54 had the missed blue node in the breast quadrantectomy specimen and not the axillary dissection specimen (intramammary sentinel node). The axillary localization of the other blue nodes unidentified during the operation is unknown, because levels I and II were dissected together without identification of the boundary between them. Although no false-negative case was found in Group A, six of the 13 missed nodes were involved and in two cases missed metastatic nodes were seen in connection with non-metastatic and metastatic SLNs. The nodes identified by higher gamma counts displayed a considerable overlap with the blue-stained SLNs, but the gamma counter identified more nodes as potential SLNs than did the blue dye (data not shown).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentREFERENCES |
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The SLN theory proposes that lymphogenic metastases of certain tumors, including breast cancer, follow an orderly pathway and the tumor draining pathway can be identified with peritumorally injected substances that are transported in the lymphatics and remain trapped within the first lymph node they enter. To date, most of the published work relates to either vital blue dye-guided methods (7–12) or 99m-Tc-labeled colloids and gamma probe-guided identification of SLNs (13–16). A combination of the two techniques has been found to be the best and recommended for optimal performance (17); hence, several studies have employed the combined technique (18–25). The reported institutional studies have led to the initiation of multicenter clinical trials to test the apparently well-founded hypothesis that patients with negative SLNs need no further primary axillary treatment (26).
Vital dye-guided SLN identification may be the only choice in several settings. The relatively high price of gamma probes does not allow the widespread use of these tools in countries with low health budgets. The availability of appropriate colloids authorized for human diagnostics may also be a limiting factor influencing the choice of the method. One point in favor of vital dye-guided SLN biopsy is that some series documented high (9,27,28) or even 100% predictive value for the overall axillary nodal status (8,29). Although we experienced an 8% false-negative rate in our series, most of the false-negative cases occurred early in the study and we have pointed out earlier that a better patient selection may lead to better results (7). For example, extensive peritumoral vascular invasion seems to be a factor predisposing to the labeling of an inappropriate node as SLN (30). Thus, not all false-negative SLN patients would be spared an axillary dissection. The ease and low costs of the vital dye method make it an acceptable alternative to the gamma probe-guided or the combined method in some medical settings, as it can also obviate axillary surgery in a subset of patients. This is why it is essential to know how effective this method is in identifying all SLNs.
In this feasibility study with the histological assessment of non-SLNs too, we have identified a 7.7% failure rate in cases of successful lymphatic mapping. The fact that none of the 10 cases with blue nodes left in the axilla were false-negative can be interpreted in several ways. If these are really first echelon nodes, missing them may lead to a false SLN staging. The fact that this did not occur is probably due to chance only. Alternatively, some or all of the blue nodes left in the axilla may be second echelon nodes stained blue because of dye overflow. There is no way to establish which of the two explanations may be true in a given case. The fact that some of the primarily unidentified blue nodes were also labeled by 99m-Tc may be due to either overflow of the colloid or real first draining nodes left in situ. This latter possibility is favored in cases 87, 94 and 132 assessed with the dual method, because larger colloidal particles were used and these tend to label fewer nodes and are therefore more accurate for labeling only the first echelon nodes (31).
It is interesting that the patients in Group A had a higher proportion with more that one SLN identified than those in Group B. Accordingly, the first group is perhaps predisposed to have missed blue nodes not only because these patients have significantly more blue nodes than other patients, but also because the surgeon has identified more nodes and this may make him or her less likely to search for further nodes.
Overall, we conclude that the proportion of SLNs left in situ after a vital dye tracer-guided SLN biopsy is <8%. Further, this type of failure probably causes a false SLN-based nodal staging in an even smaller proportion of patients (0/10 in this series), because patients with this type of error may be node-negative (one case in our series), or have more SLNs removed during surgery, allowing a better chance for staging; and the error may be due to dye overflow in some cases. The tumors in our series were not especially large (except for three pT3 category tumors) for a non-screened population, but in patients with smaller, screen-detected tumors the chances of missing metastatic blue nodes during successful SLN biopsies thought to be complete may be even lower.
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Acknowledgment |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentREFERENCES |
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This work was supported by a János Bolyai Research Fellowship of the Hungarian Academy of Sciences.
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FOOTNOTES |
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+ For reprints and all correspondence: Gábor Cserni, Department of Surgical Pathology, Bács-Kiskun County Teaching Hospital affiliated to the Albert Szent-Györgyi Medical University, Nyíri út 38, H-6000 Kecskemét, Hungary. E-mail: cserni@freemail.c3.hu
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONAcknowledgmentREFERENCES |
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1 Giuliano AE, Dale PS, Turner RR, Morton DL, Evans SW, Krasne DL. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 1995;180:700–4.
2 Jannink I, Fan M, Nagy S, Rayudu G, Dowlatshahi K. Serial sectioning of sentinel nodes in patients with breast cancer: a pilot study. Ann Surg Oncol 1998;5:310–4.[Web of Science][Medline]
3 Czerniecki BJ, Scheff AM, Callans LS, Spitz FR, Bedrosian I, Conant EF, et al. Immunohistochemistry with pancytokeratins improves the sensitivity of sentinel lymph node biopsy in patients with breast carcinoma. Cancer 1999;85:1098–103.[Web of Science][Medline]
4 Cserni G. Metastases in axillary sentinel lymph nodes in breast cancer as detected by intensive histopatological work-up. J Clin Pathol 1999;52:922–4.[Abstract]
5 Krag DN, Weaver DL, Alex JC, Fairbank JT. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol 1993;2:335–40.[Web of Science][Medline]
6 Giuliano AE, Kirgan DM, Guenther JM, Morton DL. Lymphatic mapping and sentinel lymphadenectomy for breast cancer. Ann Surg 1994;220:391–8.[Web of Science][Medline]
7 Cserni G, Boross G, Baltás B. The value of axillary sentinel nodal status in breast cancer. World J Surg 2000;24:341–4.[Web of Science][Medline]
8 Giuliano AE, Jones RC, Brennan M, Statman R. Sentinel lymphadenectomy in breast cancer. J Clin Oncol 1997;15:2345–50.
9 Guenther JM, Krishnamoorthy M, Tan LR. Sentinel lymphadenectomy for breast cancer in a community managed care setting. Cancer J Sci Am 1997;3:336–40.[Web of Science][Medline]
10 Koller M, Barsuk D, Zippel D, Engelberg S, Ben-Ari G, Papa MZ. Sentinel lymph node involvement – a predictor for axillary node status with breast cancer – has the time come? Eur J Surg Oncol 1998;24:166–8.[Web of Science][Medline]
11 Flett MM, Going JJ, Stanton FD, Cooke TG. Sentinel node localization in patients with breast cancer. Br J Surg 1998;85:991–3.[Web of Science][Medline]
12 Rodier JF, Routiot T, Mignotte H, Janser JC, Bremond A, Barlier C, et al. Individualisation du ganglion axillaire sentinelle par colorant lymphotrope dans les cancers du sein. Étude de faisabilité a propos de 128 cas. Chirurgie 1998;123:239–46.[Medline]
13 Roumen RM, Valkenburg JG, Geuskens LM. Lymphoscintigraphy and feasibility of sentinel node biopsy in 83 patients with primary breast cancer. Eur J Surg Oncol 1997;23:495–502.[Web of Science][Medline]
14 Borgstein PJ, Pijpers R, Comans EF, Diest PJ van, Boom RP, Meijer S. Sentinel lymph node biopsy in breast cancer: guidelines and pitfalls of lymphoscintigraphy and gamma probe detection. J Am Coll Surg 1998;186:275–83.[Web of Science][Medline]
15 Veronesi U, Paganelli G, Viale G, Galimberti V, Luini A, Zurrida S, et al. Sentinel lymph node biopsy and axillary dissection in breast cancer: results in a large series. J Natl Cancer Inst 1999;91:368–73.
16 Krag DN, Ashikaga T, Harlow SP, Weaver DL. Development of sentinel node targeting technique in breast cancer patients. Breast J 1998;4:67–74.
17 Albertini JJ, Lyman GH, Cox C, Yeatman T, Balducci L, Ku N, et al. Lymphatic mapping and sentinel node biopsy in the patient with breast cancer. J Am Med Assoc 1996;276:1818–22.
18 Bass SS, Cox CE, Ku NN, Berman RJ, Reintgen DS. The role of sentinel lymph node biopsy in breast cancer. J Am Coll Surg 1999;189:183–94.[Web of Science][Medline]
19 O’Hea BJ, Hill AD, El-Shirbiny AM, Yeh SD, Rosen PP, Coit DG, et al. Sentinel lymph node biopsy in breast cancer: initial experience at Memorial Sloan-Kettering Cancer Center. J Am Coll Surg 1998;186:423–7.[Web of Science][Medline]
20 Barnwell JM, Arredondo MA, Kollmorgen D, Gibbs JF, Lamonica D, Carson W, et al. Sentinel node biopsy in breast cancer. Ann Surg Oncol 1998;5:126–30.[Web of Science][Medline]
21 Cavanese G, Gipponi M, Catturich A, Di Somma C, Vecchio C, Rosato F, et al. Sentinel lymph node mapping opens a new perspective in the surgical management of early-stage breast cancer: a combined approach with vital blue dye lymphatic mapping and radioguided surgery. Semin Surg Oncol 1998;15:272–7.[Web of Science][Medline]
22 van der Ent FWC, Kengen RAM, van der Pol HAG, Hoofwijk AGM. Sentinel node biopsy in 70 unselected patients with breast cancer: increased feasibility by using 10 mCi radiocolloid in combination with a blue dye tracer. Eur J Surg Oncol 1999;25:24–9.[Web of Science][Medline]
23 Schneebaum S, Stadler J, Cohen M, Yaniv D, Baron J, Skornick Y. Gamma probe-guided sentinel node biopsy – optimal timing for injection. Eur J Surg Oncol 1999;24:515–9.
24 Linehan DC, Hill AD, Akhurst T, Yeung H, Yeh SD, Tran KN, et al. Intradermal radiocolloid and intraparenchymal blue dye injection optimize sentinel node identification in breast cancer patients. Ann Surg Oncol 1999;6:450–4.[Web of Science][Medline]
25 Jaderborg JM, Harrison PB, Kiser JL, Maynard SL. The feasibility and accuracy of the sentinel lymph node biopsy for breast carcinoma. Am Surg 1999;65:699–703.[Web of Science][Medline]
26 McNeil C. Sentinel node biopsy: studies should bring needed data. J Natl Cancer Inst 1998;90:728–30.
27 Imoto S, Hasebe T. Initial experience with sentinel node biopsy in breast cancer at the National Cancer Center Hospital East. Jpn J Clin Oncol 1999;29:11–5.
28 Noguchi M, Bando E, Tsugawa K, Miwa K, Kunihiko Y, Nakajima K, et al. Staging efficacy of breast cancer with sentinel lymphadenectomy. Breast Cancer Res Treat 1999;57:221–9.[Web of Science][Medline]
29 Dale PS, Williams JT. Axillary staging utilizing selective sentinel lymphadenectomy for patients with invasive breast carcinoma. Am Surg 1998;64:28–32.[Web of Science][Medline]
30 Veronesi U, Zurrida S, Galimberti V. Consequences of sentinel node in clinical decision making in breast cancer and prospects for future studies. Eur J Surg Oncol 1998;24:93–5.[Web of Science][Medline]
31 Paganelli G. Sentinel node biopsy: role of nuclear medicine in conservative surgery of breast cancer. Eur J Nucl Med 1998;25:99–100.[Web of Science][Medline]
Received 28 February 2000; accepted April 5, 2000.
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