Sentinel lymph nodes and breast carcinoma: which micrometastases are clinically significant?

Sentinel lymph node biopsy is changing surgical management of breast cancer and pathologic evaluation of lymph nodes. Although it has long been known that lymph nodes contain occult metastases, pathologists have not generally pursued their identification. Compared with level I-II axillary dissection, the reduced number of sentinel lymph nodes has made additional evaluation more attractive; however, the consequences of increased detection of micrometastases has not been fully explored or appreciated. National data suggest that the composition of traditional TNM stage groupings is changing, with a recent increase in node-positive, stage II breast cancer, most likely the result of increased pathologic scrutiny. Clinical management of this new group of stage II patients is complicated by the lack of a historic prognostic comparison group because many of these patients would have been classified as stage I, node-negative in the past. Early outcome data in sentinel lymph node biopsy suggest no adverse outcome for patients with metastases no larger than 2.0 mm, a finding aligned with the current definition of micrometastasis. When sentinel lymph nodes are sliced at 2.0-mm intervals and totally embedded, the probability of identifying all metastases >2.0 mm is high. Using reasonable sampling strategies, minute metastases have a nearly equal chance of being missed or detected. New staging guidelines have established a lower limit for micrometastases and defined metastases no larger than 0.2 mm as isolated tumor cells or tumor cell clusters; nodes with isolated tumor cells will be classified as node negative (pN0) for stage grouping. Rigorous strategies designed to reliably detect single cells or small cell clusters in sentinel nodes remain time-intensive and cost prohibitive.     

How many cases are enough for accreditation in sentinel lymph node biopsy in breast cancer?

BACKGROUND: There is considerable argument concerning the number of sentinel node biopsy cases with axillary dissection that surgeons should perform before they are eligible on abandoning axillary dissection in negative sentinel node patients. DATA SOURCES: Papers that (1) address directly or indirectly the subject of credentialing or of learning curve, (2) report on a surgeon's performance, (3) are reported as feasibility or learning curve studies, or both, (4) discuss the learning curve issue, and (5) express an expert's opinion on the learning curve. CONCLUSIONS: The number of procedures of the learning curve can not be fixed for all surgeons. Only surgeons in specialized breast cancer centers can succeed in meeting current recommendations with 20 to 30 cases. Surgeons from affiliated community hospitals will need more than 30 cases, whereas broad-based surgeons might need as many as 60 cases with their current caseload. Not all surgeons will be able to offer the procedure to their patients by the current recommendations.     

Sentinel lymph node biopsies in melanoma: how many nodes do we really need?

BACKGROUND: Sentinel lymph nodes (SLN) biopsy is a widely used method to detect lymphatic spread in patients with cutaneous melanoma. Several methods are used to detect SLNs. Recent reports attempted to identify the adequate number of SLNs to reliably detect malignant spread in regional lymph nodes. METHODS: The radiotracer counts and the pathologic reports of all patients undergoing SLN biopsies were collected prospectively, to determine which of the nodes harboring radiotracer needed to be removed for examination by histopathology between 1998 and 2005. All patients with positive SLN biopsies were investigated in the study. Lymph nodes were ranked according their radiotracer counts and numbered as hottest nodes, second hottest nodes, third hottest nodes, etc. The relationship between radioactivity and the risk of harboring malignancy was determined. RESULTS: Nodal metastases were detected in 55 basins from 53 patients (10.5%). There was a correlation between the radiotracer uptake and risk of harboring malignancy. Excising the 3 hottest nodes and all blue nodes detected 100% of patients with lymphatic malignancy in our series. Most (98%) of positive lymph nodes had radiotracer counts greater than 30% of the hottest node. Only 1 patient (2%) had radioactive count less than 30%, but had visible blue dye. CONCLUSIONS: Removing only the hottest node is inadequate to detect lymphatic spread. On the other hand, removing the 3 hottest nodes and all visible blue nodes is sufficient to detect regional lymphatic spread in patients with cutaneous melanoma. Removing nodes with a radiotracer uptake less than 30% of the hottest nodes may be unnecessary.     

Can axillary lymph node dissection be omitted in patients with breast cancer and positive sentinel nodes?

Sentinel lymph node biopsy has evolved as the surgical procedure of choice for women with clinically negative axillae, as part of an effort to move toward the less invasive surgical management of breast cancer. Axillary lymph node dissection remains the standard of care for patients with a positive axillary node and was previously performed on all patients with breast cancer prior to the implementation of the sentinel lymph node biopsy. There is, however, controversy regarding whether or not all patients with a positive sentinel lymph node need to undergo completion axillary dissection for either prognostic or therapeutic purposes. This article reviews the literature related to this controversial and evolving topic.     

Intramammary lymph nodes and breast cancer: a marker for disease severity, or just another lymph node?

BACKGROUND: Axillary lymph node status is still considered the most significant prognostic factor for breast cancer outcome, and treatment decisions are based on the presence or absence of nodal disease. Intramammary lymph nodes (IMLNs) can be a site of regional spread. Is this a marker for more aggressive disease? METHODS: We reviewed the cancer center pathology database from 1991 to 2005 for all cases of breast cancer with IMLNs. RESULTS: IMLNs were identified in 64 breast cancer patients, with metastatic spread in 20 patients, and benign IMLNs described in 44 patients. Positive IMLNs were associated with more aggressive disease, including higher rates of invasive versus noninvasive cancers (5% ductal carcinoma-in-situ [DCIS] with positive IMLNs vs. 23% with negative IMLNs), lymphovascular invasion (55% vs. 11%), and a higher rate of axillary lymph node involvement (72% vs. 18%). Patients with positive IMLNs were also more likely to undergo mastectomy (75% vs. 54%). CONCLUSIONS: IMLN metastases are a marker for disease severity; recognition of this may influence choice of adjuvant therapy. The presence of metastatic disease in an IMLN is associated with a high rate of axillary nodal involvement, and should mandate axillary dissection. Preoperative lymphoscintigraphy may help identify these extra-axillary metastases.     

How many lymph nodes are enough during sentinel lymphadenectomy for primary melanoma?

BACKGROUND: Sentinel lymph node (SLN) biopsy has been shown to reliably identify nodal metastases and the subsequent need for further surgical and adjuvant therapy in patients with cutaneous melanoma. Although SLN identification rates have improved with the addition of radioactive colloid to the blue dye technique, it remains unclear how many lymph nodes should be removed to accurately determine the histologic status of the nodal basin. The objective of this study was to determine the optimal extent of SLN biopsy in these patients. METHODS: The records of 633 consecutive patients with melanoma (765 nodal basins) whose primary treatment included SLN biopsy with the use of a combination of blue dye and technetium Tc 99 labeled sulfur colloid were reviewed. SLN biopsy consisted of the removal of all of the blue-stained nodes and all nodes with radiotracer uptake activity of at least twice background. RESULTS: SLN biopsy was successful in 765 of 772 basins (99%). A mean of 1.9 SLNs (median, 2 SLNs) per basin were excised. At least 3 SLNs were removed in 176 basins (23%). The overall histologic status of a basin was always established by the first or second SLN harvested (ie, in no patient was the third or subsequent SLN positive when 1 of the first 2 was not). Of the 124 basins containing lymphatic metastases, the SLN that contained the maximal radiotracer uptake (hottest) and/or stained blue was pathologically positive in 118 basins (95%). In only 6 of the 124 positive basins (5%) was the sole evidence of occult nodal metastases identified in an SLN that was neither blue-stained nor the hottest. All but 1 of these SLNs had counts that were at least 66% of the hottest node in the basin. CONCLUSIONS: With a combined modality approach to SLN biopsy, removal of more than 2 SLNs did not provide information that upstaged any patient with primary melanoma. Removal of additional nonblue SLN(s) that contained radioactive counts of at least twice background but lower than two thirds of the SLNs with maximal radiotracer uptake affected patient management in less than 0.2% of all cases. These findings may be helpful in minimizing the extent of surgery and perhaps in reducing the costs and resource use associated with operating room time and pathologic examination.     

Sentinel lymph node biopsy or detection of micrometastasis in bone marrow: which might be an alternative to axillary lymph node dissection in breast cancer patients?

Axillary lymph node status has limited prognostic significance in breast cancer patients and much improvement can be made. Sentinel lymph node biopsy is emerging as an alternative to axillary lymph node dissection for staging, but its prognostic relevance is still uncertain. Detection of micrometastases in sentinel nodes and bone marrow may provide more information, but the clinical significance still needs to be confirmed by ongoing large trials. In this review, we focus on the possibility of sentinel lymph node biopsy or detection of bone marrow micrometastasis replacing traditional axillary lymph node dissection.     

Axillary lymph node dissection in breast cancer: an evolving question?

Axillary lymph node dissection (ALND) is performed for staging purposes. Sentinel lymph node biopsy may decrease the cost and morbidity of ALND. Are there patients that the procedure is not indicated avoiding cost and morbidity? We retrospectively studied the incidence of lymph node metastasis in 423 patients with T1 breast cancer. Thirty-one T1a, 146 T1b, and 246 T1c tumors were seen. The mean age was 61 years. Ten per cent were premenopausal, and 84 per cent were postmenopausal. Tumor size averaged 1.29 cm. Eighty-one per cent of the tumors were node negative and 19 per cent were node positive. One T1a patient (3 per cent) had an axillary metastasis, 19 T1b patients (13%), and 61 T1c patients (25%) were node positive, respectively. Seventy-three per cent were ER positive. Thirty-three patients (8%) died from cancer. Eighty-seven per cent received surgery with axillary lymph node dissection (ALND), and three per cent had surgery without ALND. Younger age, increased tumor size, premenopausal status, and ER negativity affected node positivity rates (P < 0.05). Death from breast cancer was more common among node-positive patients (P < 0.05). No difference was found regarding the performance of ALND and survival (P > 0.05). We feel that ALND can be safely omitted in T1a to reduce the morbidity and the expense of breast cancer treatment. In T1b and T1c tumors, the use of ALND is necessary, but morbidity and cost can be reduced by the use of sentinel lymph node biopsy.     

Do cytokeratin-positive-only sentinel lymph nodes warrant complete axillary lymph node dissection in patients with invasive breast cancer?

The small number of nodes harvested with lymphatic mapping and sentinel lymph node (SLN) biopsy has allowed a more detailed pathologic examination of those nodes. Immunohistochemical stains for cytokeratin (CK-IHC) have been used in an attempt to minimize the false negative rate for SLN mapping. This study examines the value of CK-IHC positivity in predicting further lymph node involvement in the axillary basin. From April 1998 through May 1999, 519 lymphatic mappings and SLN biopsies were performed for invasive breast cancer. SLNs were examined by imprint cytology, hematoxylin and eosin (H&E), and CK-IHC. Patients with evidence of metastatic disease by any of the above techniques were eligible for complete axillary node dissection (CAND). The frequency with which these modalities predicted further lymph node involvement in the axillary basin was compared. Of the 519 lymphatic mappings, 39 patients (7.5%) had a CK-IHC-positive-only SLN. Five (12.8%) of these 39 patients had at least 2 SLNs positive by CK-IHC. Twenty-six of the CK-IHC-positive-only patients underwent CAND. Three of these 26 patients (11.5%) had additional metastases identified after CAND. The sensitivity levels with which each modality detected further axillary lymph node involvement were as follows: CK-IHC, 98 per cent; H&E, 94 per cent; and imprint cytology, 87 per cent. A logistic regression to compare the prognostic value of the three modalities was performed. All were significant, with odds ratios of 19.1 for CK-IHC (P = 0.015), 5.3 for H&E (P = 0.033), and 3.86 for imprint cytology (P = 0.0059). These data validate the enhanced detection of CK-IHC for the evaluation of SLNs. Detection of CK-IHC-positive SLNs appears to warrant CAND in patients with invasive breast cancer. However, the therapeutic value of CAND or adjuvant therapies based on CK-IHC-positive SLNs would be best answered by prospective randomized trials.     

Number of lymph nodes after neoadjuvant therapy for rectal cancer: How many are needed?

Neoadjuvant chemoradiation is the standard treatment for advanced rectal tumor,providing better local control of disease and potentially increasing sphincter preservation surgery.Neoadjuvant radiation may affect the number of lymph nodes harvested after resection or alter their prognostic value.Over the past 10 years,standards for lymph node harvests in colorectal cancer have been proposed.Several studies have recommend examination of at least 12 lymph nodes(LNs) in the specimen and this number is now used as a reflection of surgical quality.Nevertheless,recent reports have identified significantly decreased LN harvests in patients treated with neoadjuvant radiation.And preoperative chemoradiation has a significant effect on the number of nodes harvested in rectal specimens and this should be considered in staging of the tumor.In the near future,the total number of nodes will be less important than specific biologic markers in detecting high-risk patients and improving their prognosis with adjuvant therapy tailored.     

Sentinel lymph node biopsy for gastric cancer: Where do we stand?

Development of sentinel node navigation surgery (SNNS) and advances in minimally invasive surgical techniques have greatly shaped the modern day approach to gastric cancer surgery.An extensive body of knowledge now exists on this type of clinical application but is principally composed of single institute studies.Certain dye tracers,such as isosulfan blue or patent blue violet,have been widely utilized with a notable amount of success;however,indocyanine green is gaining popularity.The double tracer method,a synchronized use of dye and radio-isotope tracers,appears to be superior to any of the dyes alone.In the meantime,the concepts of infrared ray electronic endoscopy,florescence imaging,nanoparticles and near-infrared technology are emerging as particularly promising alternative techniques.Hematoxylin and eosin staining remains the main method for the detection of sentinel lymph node (SLN) metastases.Several specialized centers have begun to employ immunohistochemical staining for this type of clinical analysis but the equipment costs involving the associated ultra-rapid processing systems is limiting its widespread application.Laparoscopic function-preserving resection of primary tumor from the stomach in conjunction with lymphatic basin dissection navigated by SLN identification represents the current paramount of SNNS for early gastric cancer.Patients with cT3 stage or higher still require standard D 2 dissection.     

Prostate biopsy: how many cores are enough?

Systematic prostate biopsy has revolutionized our ability to detect prostate cancer. Sextant biopsies were the mainstay of cancer detection since their inception in 1989. Over the past several years more extensive systematic prostate sampling has been introduced and has demonstrated an improved ability to detect prostate cancer. The optimal prostate biopsy scheme should be easy to perform, be able to be done in the clinic without intravenous sedation or general anesthetic, provide a high sensitivity for cancer detection, and have a low complication rate. We review several studies evaluating various biopsy schemes for both initial and repeat biopsy patients and propose an optimal biopsy scheme.