Journal List > J Breast Cancer > v.12(3) > 1036144

Sung, Kim, Kang, Lee, Hwang, and Bae: The Usefulness and Limitations of Intraoperative Frozen Section Analysis of Sentinel Lymph Nodes in Patients with Breast Cancer

Abstract

Purpose

Intraoperative frozen sectioning (FS) of sentinel lymph nodes (SLNs) is widely used to determine whether total axillary lymph node dissection should be performed in patients with breast cancer. We evaluated the usefulness and limitations of the FS protocol, which has been used in our institution for the intraoperative SLN examination.

Methods

We analyzed the FS results of SLNs in 807 invasive breast carcinoma patients who underwent intraoperative SLN biopsy between January 2005 and December 2007. Lymph nodes larger than 5 mm were sliced at 2 mm intervals and all the slices were submitted for FS. The remaining tissue of the SLN was formalin-fixed and paraffin-embedded for permanent sectioning (PS). If the FS result was negative for tumor cells, then immunohistochemical stain for pancytokeratin was performed. The metastatic SLNs were graded according to the AJCC cancer staging manual (6th edition). The results of FS and PS were compared with regard to the pathologic diagnosis.

Results

The average number of SLNs was 2.9 per patients. A total of 204 (25.3%) patients were reported to have a metastatic SLN(s) on the FS. Among the 603 patients with negative FS results, 34 (5.6%) patients showed metastasis on the PS. Another 10 (1.7%) patients who had negative results on FS showed isolated tumor cells on the PS or on the cytokeratin immunohistochemistry. Twenty-nine of the 34 (85.3%) false negative cases showed micrometastasis on the PS. Ten (29.4%) false negative results were caused by interpretation errors and 24 (70.6%) were caused by technical problems.

Conclusion

The false negative rate of our protocol for FS of a SLN was low. The failure of FS was largely caused by the failure to detect micrometastasis. FS is a reliable method for an intraoperative SLN examination if a very stringent protocol is used.

Figures and Tables

Figure 1
Procedures for making frozen (A-C) and permanent section slides (D-F). (A) Sentinel lymph node (SLN) smaller than 5 mm was bisected and SLN larger than 5 mm was sliced in 2 mm interval. (B) All slices from one SLN were embedded in one block. (C) H&E stain was done on the frozen section. (D) After the frozen sections were prepared, the rest of the frozen tissue form B melted on the room temperature. (E) Then the tissue was fixed in formalin and embedded in paraffin. (F) One to three sections were cut and stained with H&E.
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Figure 2
Flow chart of the patients who received sentinel lymph node biopsy.
SLN=sentinel lymph node; FS=frozen section; PS=permanent section; ITC=isolated tumor cell.
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Figure 3
False negative cases. (A) Permanent section slide does not show metastatic tumor cells. (B) However, cytokeratin immunostain highlights isolated tumor cells in the same case. (C) This case was misinterpreted as negative on the frozen section. Black arrows represent tumor glands located in the subcapsular area. (D) Permanent section slide shows the same metastatic deposits. (E) In another false negative case, frozen section slide does not show any metastatic tumor cell. (F) Permanent section slide of the same lymph node shows definite tumor deposit (A, B, D, ×100; C,×200; E, F, ×40, H&E stain except for B). (G) Folded frozen section slide masked metastatic tumor cells which were present on the permanent (H) and resulted in false negativity (G, ×100; H, ×40, H&E stain).
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Table 1
Clinicopathologic characteristics of 807 patients
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Table 2
The results of frozen and permanent sections of sentinel lymph nodes
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NTM=no tumor metastasis; ITC=isolated tumor cells.

*p<0.001 by Fisher's exact test.

Table 3
Sensitivity and accuracy of frozen section analysis according to the T stage and histological type
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Table 4
Causes of the false negative results
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FS=frozen section; PS=permanent section.

Table 5
Comparison of intraoperative frozen section results of sentinel lymph nodes with previous studies
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FS=frozen section; PS=permanent section; H&E=hematoxylin and eosin; LS=level section; IHC=immunohistochemistry for cytokeratin.

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