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Original Article |
1 Mastology Department, Hospital Sírio Libanês, Rua Adma Jafet, 91, Bela Vista, São Paulo, SP, Brazil 01308-000
2 Nuclear Medicine Department, Hospital Sírio Libanês, São Paulo, Brazil
3 Radiology Department, Hospital Sírio Libanês, São Paulo, Brazil
4 Laborato' rio Diagno' stika, São Paulo, Brazil
Correspondence: Address correspondence and reprint requests to: Alfredo C. S. D. Barros, MD, E-mail: clinab{at}terra.com.br
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ABSTRACT |
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Methods: A total of 115 nonpalpable lesions were studied: 101 with high suspicion of malignancy from which frozen sections had been produced, and 14 carcinomas diagnosed by mammotomy. On the day before surgery, 0.2 mL of solution of dextran labeled with 15 MBq of 99mTc was injected into the center of the lesions under imaging guidance. All patients underwent lymphoscintigraphy and open-surgery biopsy guided by gamma probe, followed by radiographic verification of the specimen. If malignancy was detected, in cases of infiltrating or ductal carcinoma-in-situ with comedonecrosis or high nuclear grade, breast-conserving surgery and SLN biopsy were performed during the same operation.
Results: The combination of ROLL and SLN biopsy was feasible and practical. The rate of simultaneous SLN mapping by lymphoscintigraphy was 97.4% (112 of 115), and the confirmation rate for breast lesion removal by specimen radiography was 100%. It was known that 57 cases were malignant at the time of surgery. After segmental breast resection, SLN immediately underwent biopsy in 50 cases (34 infiltrating carcinomas and 16 ductal carcinoma-in-situ) with probe monitoring. Three were cytologically positive for metastasis and required full axillary dissection.
Conclusions: ROLL and SLN biopsy are emerging procedures that can be used simultaneously. They permit exact breast lesion excision, immediate local breast surgery, and intraoperative SLN biopsy in a single procedure. The combination of radioguided non-palpable lesion localization and SLN biopsy is a suitable alternative to working up subclinical imaging-detected breast carcinomas.
Key Words: Nonpalpable breast lesions • Radioguided localization • Lymphoscintigraphy • Sentinel lymph node biopsy
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INTRODUCTION |
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In breast cancer cases diagnosed by ROLL, radioguided SLN biopsy remains a useful approach for staging the axilla to select patients for complete axillary lymph node dissection. In the present study, we report on our experience with a novel strategy for nonpalpable breast cancer diagnosis and treatment that combines both procedures. In this combined routine, ROLL and scintigraphic SLN mapping were followed by breast-conserving surgery and immediate SLN biopsy, and the whole procedure was performed after a single injection of 99mTc-labeled dextran.
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METHODS |
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The patients presented with circumscribed unifocal nonpalpable breast lesions with a maximum mammographic or sonographic diameter of 2 cm, with no clinical evidence of axillary lymph node involvement. There was a high suspicion of malignancy in 101 cases (71 classified as BI-RADS 4; 20 as BI-RADS 5; and 10 as BI-RADS 3 in high-risk women). There were another 14 malignant cases (12.1%) with clips placed after vacuum-assisted biopsy.
The day before surgery, a 20-gauge needle was inserted into the center of the lesion under stereotaxic guidance by mammography or ultrasound guidance. After needle placement, 0.2 mL of a solution containing dextran particles (particle size, 2 to 4 nm) labeled with approximately 15 MBq of 99mTc was injected through the needle. A small volume (0.1 mL) of saline solution was immediately injected to avoid radiotracer reflux that might interfere with readings during surgery.
After removal of the needle, planar scintigraphic images of the breast (in anterior and lateral views) were obtained with a gamma camera at 30 minutes and 3 hours after tracer administration to confirm that the tracer had marked the lesion and the SLN (Fig. 1
). Lymphoscintigraphy was performed with the patient in the supine position, with the arms completely abducted. Exposure time was 180 seconds per image with a high-resolution collimator; the acquisition matrix was 128 x 128 pixels.
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After performing a small (3 to 4 cm) incision over the area of maximum count detection, the surgeon was able to perform the biopsy under radioguidance by inserting the probe into the wound at different angles to check the position of the lesion. The resection margins were considered adequate when the count in the surgical bed, after tissue excision, dropped to 10% of the counts in the hot spot.
A 1-cm margin around the suspected lesion is recommended. The surgical specimens were placed in a special Plexiglas device with a grid of small holes and radiographed to document the removal of the mammographic lesion and to guide the pathologist in the evaluation of the specimen.
In the cases in which frozen sections had been produced, the specimen was sectioned into 3- to 4-mm slices, and these were examined with a magnifying glass (x10) to identify suspected areas. Cytological imprints were collected, and cases with macroscopically or cytologically suspicious areas >5 mm underwent cryostatic sectioning for histopathological analysis. For lesions measuring <5 mm, no frozen sections were produced, so that damage to the tissue would be avoided, thereby preserving the tissue for definitive examination of the paraffin-embedded tissue.
If malignancy was detected (by frozen section or definitive examination after mammotomy), adequate local resection with intraoperative evaluation of surgical margins was performed in accordance with a standard protocol.7 Cases of infiltrating carcinoma and ductal carcinoma-in-situ (DCIS) with high nuclear grade or comedonecrosis immediately underwent SLN biopsy with gamma probe monitoring. Regardless of the different tumor locations in the breast, SLN collection was always performed through the same incision used for segmental breast resection by means of appropriately illuminated valves, long scissors, and calipers.
SLNs were freshly cut at 1-mm intervals for intraoperative imprint cytological testing, and depending on the result, complete axillary dissections would or would not be performed.
Definitive SLN analysis was performed later, when the nodes were sectioned at 50-µm intervals (slices 4 µm thick) and stained with hematoxylin and eosin for examination under the microscope.
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RESULTS |
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In 103 cases (89.5%), radiography of the specimen revealed the presence of the target lesion or clip within the first tissue sample removed. All the other lesions were excised after subsequent enlarged biopsies. The exact lesion excision was always confirmed by specimen radiography, and thus the final lesion removal rate has so far been 100%.
Fourteen malignant cases had previously been diagnosed by mammotomy, and 43 cases of carcinoma were detected by frozen section. Among the 101 cases examined by frozen section (69 clusters of microcalcifications, 27 solid masses, and 5 architectural distortions), the analysis revealed 30 infiltrating carcinomas (29.7%), 13 DCIS (12.8%), 10 atypical hyperplasias (9.9%), 42 fibrocystic changes (41.5%), and 6 inconclusive diagnoses (5.9%) that needed further examination.
Excluding the inconclusive results, concordance was obtained between the benign and malignant results in frozen sections and in definitive analysis in 92 (96.8%) of 95 cases. There were no false-positive results from the frozen sections, but three false-negative results (2.9%) were found: two cases of atypical hyperplasia and one case of fibrocystic changes, which were subsequently diagnosed as DCIS.
At the time of the surgery, malignancy was known to be present in 57 cases: 36 infiltrating carcinomas (30 diagnosed by frozen section and 6 by mammotomy) and 21 DCISs (13 diagnosed by frozen section and 8 by mammotomy). In all of these 57 cases, the tumor was no more than 3 cm at its maximum diameter, and these patients underwent breast-conserving surgery.
The SLN immediately underwent biopsy in 50 cases: 16 DCIS and 34 early infiltrating carcinomas. The SLN was always negative in DCIS cases, either from the intraoperative imprint cytological test or from subsequent paraffin-section histopathological examination. SLN biopsies were not performed in 2 of the 36 infiltrating carcinoma cases: one with an extensive in situ component, and another presenting multicentricity. Among the 34 SLN biopsy samples in infiltrating tumors, the imprint cytological test was negative in 30 cases and positive in 4. In the positive SLN cases, immediate full axillary lymph node dissection was carried out, and in all of these, the SLN was the only lymph node involved. All the negative results from intraoperative cytological test were subsequently confirmed by definitive analysis of these cases.
In five cases of infiltrating carcinoma, the SLN was located in the internal mammary chain (exclusively in two cases and coinciding with another chain in the axilla in three cases). Among these cases, three women underwent intercostal probe-guided biopsies, and it was found that their internal mammary SLNs were free of involvement. In the other two cases, the SLN in the mammary chain did not undergo biopsy, and these patients received postoperative radiotherapy of the lymphatic chain.
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DISCUSSION |
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Needle-hookwire localization was a remarkable advance introduced in 1980.9 Nevertheless, this method presents some disadvantages such as local discomfort, displacement, migration, accidental transection, and continuing presence of hook fragments as foreign bodies left inside the breast. Moreover, when a hookwire is used, the surgeon follows the path of the wire, which is not always the shortest or most practical route for reaching the lesion. The ability to constantly verify the location of the target with the gamma probe makes the operation quicker and more certain than when needle localization techniques are used.5 The possibility of verifying the area of localized radioactivity subsequent to radioisotopic targeting of nonpalpable breast lesions provides information on their exact location, so that the surgical access that is most appropriate from the practical and esthetic points of view can be selected.
Radioguided excision has proved to be reliable and effective in localizing occult lesions, reducing excision volumes and better centering the lesions within the surgical specimen.10 ROLL also facilitates complete surgical removal of the suspicious lesions at the center of the specimen, plus sufficient margin of tissue presumed to be normal.11,12 However, radiographic imaging of the specimen is recommended to confirm lesion removal and to guide the pathologist.
The feasibility of frozen section analysis of non-palpable breast lesions is highly controversial and was not the focus of the present study. Nevertheless, the concerns that have sometimes been expressed regarding the efficacy of this technique were not shown to be a problem in the present series. There are few published studies addressing this question, but similar good results have been found by Dorel-Le Theo et al.13 and Ferreiro et al.14
Traditionally, it has been considered that ROLL and SLN biopsy cannot be used simultaneously because problems might arise from interaction between the two procedures, caused by colloid migration from the injection site to the lymphatic vessels, thereby adversely affecting radioguided tumor excision.15 Therefore, ROLL and SLN biopsy have almost always been undertaken separately, and when they have been used together in the same intervention, two different radiopharmaceuticals have usually been used: one for breast lesion marking, and the other for SLN identification.
In 2002, Feggi et al.16 demonstrated that it is possible to perform ROLL and SLN mapping with a single injection of a nanocolloid with a particle size of <80 nm labeled with 99mTc. They successfully used this technique in 73 patients with cytologically diagnosed nonpalpable breast cancer. Likewise, Tanis et al.17 also found that both SLN investigation and probe-guided lesion excision were feasible with the aid of intralesional administration of a single tracer.
In the first publications about ROLL, only macroaggregates of serum albumin were used as the radiotracer. However, dextran is also useful for SLN mapping in breast carcinoma cases, thereby enabling SLN identification rates equivalent to those observed with other colloids, and also equivalent biopsy accuracy for predicting axillary node status.18 Dextran is made up of particles ranging 2 to 4 nm in size and is much less expensive than human albumin. Our experience has demonstrated that dextran labeled with 99mTc provides ROLL and SLN mapping with a single tracer injection.
Another radioisotopic method for localization of nonpalpable breast lesions on the basis of the insertion of titanium seeds containing iodine-125 has been proposed. After experience with 100 cases, Gray et al.19 stated that they highly favored radioactive seed over needle wire for the localization of subclinical breast lesions.
Assuming that radioguided SLN biopsy is a safe procedure for screening axillary nodes for metastasis among women with small-sized breast carcinoma20 and that ROLL is a valid option for dealing with nonpalpable breast carcinomas,11 it is reasonable to combine the two procedures, and we strongly recommend this. The combination of ROLL and SLN biopsy is a suitable alternative to working up subclinical imaging-detected breast carcinomas. It is practical and well tolerated, and it often requires only a 1-day stay in the hospital.
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