Pathological prognostic factors in breast cancer.

Background Although numerous studies have shown that the status of the sentinel node is an accurate predictor of the status of the axillary nodes in breast cancer, the efficacy and safety of sentinel-node biopsy require validation. Methods From March 1998 to December 1999, we randomly assigned 516 patients with primary breast cancer in whom the tumor was less than or equal to 2 cm in diameter either to sentinel-node biopsy and total axillary dissection (the axillary-dissection group) or to sentinel-node biopsy followed by axillary dissection only if the sentinel node contained metastases (the sentinel-node group). Results The number of sentinel nodes found was the same in the two groups. A sentinel node was positive in 83 of the 257 patients in the axillary-dissection group (32.3 percent), and in 92 of the 259 patients in the sentinel-node group (35.5 percent). In the axillary-dissection group, the overall accuracy of the sentinel-node status was 96.9 percent, the sensitivity 91.2 percent, and the specifi...

A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(97)01004-0.pdf

Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes.

A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer

Purpose To develop a guideline for the use of sentinel node biopsy (SNB) in early stage breast cancer.

/pdf/american-society-of-clinical-oncology-guideline-4gxe1ksq70.pdf

American Society of Clinical Oncology Guideline Recommendations for Sentinel Lymph Node Biopsy in Early-Stage Breast Cancer

Objective. —To identify the sentinel lymph node(s) (SLN[s]) (the first node[s] draining the primary tumor in the regional lymphatic basin) in patients with invasive breast cancer and to test the hypothesis that the histologic characteristics of the SLN predict the histologic characteristics of the remaining lymph nodes in the axilla. Design. —A prospective trial. Participants. —Sixty-two patients with newly diagnosed invasive breast cancers. Intervention. —Patients underwent intraoperative lymphatic mapping using a combination of a vital blue dye and filtered technetium-labeled sulfur colloid. The SLN was identified and removed, followed by a definitive cancer operation, including a complete axillary node dissection. Main Outcome Measure. —The metastatic distribution in the axilla was determined in patients with occult nodal disease. Results. —The SLN was successfully identified in 57 (92%) of 62 patients using the 2 lymphatic mapping procedures. After localization, 18 patients (32%) were found to have metastatic disease, and the SLN tested positive in all 18 patients. There were no "skip" metastases, defined as an SLN that tested negative with higher nodes that tested positive. In 12 (67%) of 18 patients with metastatic disease, the SLN was the only site of disease. The metastatic distribution significantly favored SLN involvement. Among subjects with discordant nodal involvement, the probability of observing the distribution of SLN involvement by chance is very small (P Conclusions. —This study confirms that lymphatic mapping is technically possible in the patient with breast cancer and that the histologic characteristics of the SLN probably reflect the histologic characteristics of the rest of the axillary lymph nodes. The procedure also allows the pathologist to focus the histologic examination on 1 or 2 nodes, potentially increasing the yield of positive dissections and the accuracy of staging.

Lymphatic mapping and sentinel node biopsy in the patient with breast cancer

Background: Sentinel lymph node (SLN) mapping is an effective and accurate method of evaluating the regional lymph nodes in breast cancer patients. The SLN is the first node that receives lymphatic drainage from the primary tumor. Patients with micrometastatic disease, previously undetected by routine hematoxylin and eosin (H&E) stains, are now being detected with the new technology of SLN biopsy, followed by a more detailed examination of the SLN that includes serial sectioning and cytokeratin immunohistochemical (CK IHC) staining of the nodes. Methods: At Moffitt Cancer Center, 87 patients with newly diagnosed pure ductal carcinoma in situ (DCIS) lesions were evaluated by using CK IHC staining of the SLN. Patients with any focus of microinvasive disease, detected on diagnostic breast biopsy by routine H&E, were excluded from this study. DCIS patients, with biopsy-proven in situ tumor by routine H&E stains, underwent intraoperative lymphatic mapping, using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised SLNs were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. All SLNs that had only CK-positive cells were subsequently confirmed malignant by a more detailed histological examination of the nodes. Results: CK IHC staining was performed on 177 SLNs in 87 DCIS breast cancer patients. Five of the 87 DCIS patients (6%) had positive SLNs. Three of these patients were only CK positive and two were both H&E and CK positive. Therefore, routine H&E staining missed microinvasive disease in three of five DCIS patients with positive SLNs. In addition, DCIS patients with occult micrometastatic disease to the SLN underwent a complete axillary lymph node dissection, and the SLNs were the only nodes found to have metastatic disease. Of interest, four of the five nodepositive patients had comedo carcinoma associated with the DCIS lesion, and one patient had a large 9.5-cm low grade cribriform and micropapillary type of DCIS. Conclusions: This study confirms that lymphatic mapping in breast cancer patients with DCIS lesions is a technically feasible and a highly accurate method of staging patients with undetected micrometastatic disease to the regional lymphatic basin. This procedure can be performed with minimal morbidity, because only one or two SLNs, which are at highest risk for containing metastatic disease, are removed. This allows the pathologist to examine the one or two lymph nodes with greater detail by using serial sectioning and CK IHC staining of the SLNs. Because most patients with DCIS lesions detected by routine H&E stains do not have regional lymph node metastases, these patients can safely avoid the complications associated with a complete axillary lymph node dissection and systemic chemotherapy. However, DCIS patients with occult micrometastases of the regional lymphatic basin can be staged with higher accuracy and treated in a more selective fashion.

Sentinel node biopsy in ductal carcinoma in situ patients.

Sentinel lymphadenectomy is gaining increasing popularity in the staging and treatment of patients with melanoma at risk for metastases. As a result, pathologists are encountering these specimens more frequently in their daily practice. The pathologic status of the sentinel lymph node is pivotal to the patient's care because it provides staging information that dictates the need for further therapy, and therefore detailed pathologic assessment is warranted. A standard pathology protocol to handle these nodes has been developed at our institution and involves complete submission of all tissue with routine use of immunohistochemical staining for S-100 protein. By using this protocol, 838 sentinel lymph nodes from 357 patients have been examined, and metastases were found in 16% of patients. Although the metastasis was clearly seen on sections stained with hematoxylin and eosin in 55% of the positive patients, the immunostain showed metastatic disease not appreciable on initial hematoxylin and eosin screening in an additional 28 lymph nodes (45% of node-positive patients). Intraoperative touch preparation cytology may be used as an adjunct technique in sentinel lymph nodes grossly suspicious for metastatic disease. This technique has been performed on 23 sentinel lymph nodes, with no false positives and an overall sensitivity of 62%. The thorough pathologic evaluation of sentinel lymph nodes in patients with malignant melanoma requires complete submission of all tissue, routine use of immunohistochemistry, and touch preparation cytology in selected cases.

Pathologic examination of the sentinel lymph node in malignant melanoma.

Residual microscopic disease after lumpectomy may cause significant local recurrence. This study evaluated the use of touch preparation cytology to assess lumpectomy margins. For 90 specimens, the findings on Diff-Quik-stained touch preparations (rendered intraoperatively within 15 minutes after the lumpectomy) were correlated with the gross findings, frozen-section results and, later, the findings in the permanent histologic sections. Three specimens were cytologically unsatisfactory, 68 yielded benign findings, and 19 were suspicious or diagnostic for malignancy. The margins showed tumor involvement in 5 lumpectomy samples by gross examination, in 13 by frozen-section evaluation and in 17 by the study of permanent sections. Touch preparation cytology was putatively falsely positive in two cases while frozen-section evaluation was falsely negative in four cases. Cytology had a sensitivity of 100%, a specificity of 97.1% and a diagnostic accuracy of 97.7%. These results demonstrate that touch preparation cytology rapidly and reliably evaluates lumpectomy margins and can overcome some sampling errors and artifacts related to frozen-section analysis. Touch preparation cytology is now being used to complement frozen-section evaluation of lumpectomy margins as part of a protocol aimed at reducing the local recurrence rate.

Cytology of lumpectomy specimens.

The surgical evolution of breast cancer treatment over the past century from Halsted through Haagensen and Urban has demonstrated the utility of radical and ultra-radical surgery. Patey, Meyer, and subsequently Fisher’s studies have initiated the movement toward surgical breast conservation. The continued progress toward lesser surgery has brought the value of axillary lymph node dissection (ALND) under close scrutiny (Frazier et al. 1977; Silverstein et al. 1987; Balch et al. 1993).

N. N. K. Ku

Papers

Lymphatic mapping and sentinel node biopsy in the patient with breast cancer

Sentinel node biopsy in ductal carcinoma in situ patients.

Pathologic examination of the sentinel lymph node in malignant melanoma.

Cytology of lumpectomy specimens.

Sentinel lymphadenectomy: a safe answer to less axillary surgery?