Sentinel Lymph Node Biopsy Specimens Research Articles

The prognostic value of tumor mitotic rate in children and adolescents with cutaneous melanoma: A retrospective cohort study

Mitotic rate is a strong predictor of outcome in adult patients with primary cutaneous melanoma, but for children and adolescent patients this is unknown. We sought to assess the prognostic value of primary tumor mitotic rate in children and adolescents with primary melanoma. This was a cohort study of 156 patients who were <20years of age and who had clinically localized cutaneous melanoma. Patients <12years of age were classified as children and those 12 to 19years of age as adolescents. Clinicopathologic and outcome data were collected. Recurrence-free and melanoma-specific survival were calculated. Univariable and multivariable analyses were performed using Cox proportional hazard models. Thirteen of 156 patients (8%) were children. The mitotic rate was ≥1/mm2 in 104 patients (67%) and correlated with increasing Breslow thickness. A positive sentinel node was found in 23 of 61 patients (38%) in whom a sentinel lymph node biopsy specimen was obtained. The median follow-up was 61months. Five-year melanoma-specific and recurrence-free survival rates were 91% and 84%, respectively. Mitotic rate was a stronger predictor of outcome than tumor thickness and was the only factor independently associated with recurrence-free survival. This research was conducted at a single institution and the sample size was small. Mitotic rate is an independent predictor of recurrence-free survival in children and adolescents with clinically localized melanoma.

488 - Outcomes of penile cancer patients with micro-metastases in dynamic sentinel lymph node biopsy specimens: An eUROGEN collaboration

INTRODUCTION AND OBJECTIVES:Prognosis of penile squamous cell carcinoma is determined by TNM staging. Inguinal nodal involvement can be associated with poor survival; therefore investigation of bot...

Clinical features and prognosis of Asian patients with acral lentiginous melanoma who have nodal nevi in their sentinel lymph node biopsy specimen

Nodal melanocytic nevi (NNs) encountered during sentinel lymph node biopsy (SLB) for malignant melanoma are usually difficult to distinguish from metastatic melanoma. However, NNs have not been well studied in acral lentiginous melanoma (ALM) in Asian populations. To investigate the clinical characteristics and significance of NNs in SLB specimens from patients with ALM. We retrospectively analyzed 84 patients with ALM who underwent SLB between June 2010 and July 2017. Of the 84 patients with ALM, 9 (10.7%) had NNs in their SLB specimens. NNs were significantly more common in SLB specimens than in specimens not obtained by SLB. The presence of pre-existing melanocytic lesions was found to be associated with NNs (P<.001). The 5-year overall survival was significantly higher in patients with ALM with NNs than in patients with a positive SLB result (P=.047). Distant recurrence in patients with ALM with NNs was significantly lower than in patients a positive SLB result (P=.03). The small sample size, single-center study design, and retrospective nature of the study were the limitations. In Asian populations, the prevalence of NNs in ALM is similar to that reported in Europe andthe United States. The rates of distant recurrence and overall survival in patients with ALM who have NNs are similar to those of patients who do not have metastatic melanoma.

Sentinel Lymph Node Biopsy for Cutaneous Squamous Cell Carcinoma on the Head and Neck

Metastasis of cutaneous squamous cell carcinoma (SCC) to the nodal basin is associated with a poor prognosis. The role of sentinel lymph node biopsy (SLNB) for regional staging in patients diagnosed with SCC is unclear. To evaluate a single institution's experience with use of SLNB for regional staging of SCC on the head and neck. A retrospective review of 53 patients who were diagnosed with SCC on the head and neck, at high risk for nodal metastasis based on National Comprehensive Cancer Network (NCCN) risk factors, and treated with wide local excision (WLE) and SLNB from December 1, 2010, through January 30, 2015, in a single academic referral center was performed. The follow-up period ended November 5, 2015. Sentinel lymph node biopsy paraffin blocks were retrieved and processed retrospectively with serial sectioning and immunohistochemical analysis (IHC) in cases with nodal recurrence following a negative SLNB. Sentinel node (SN) identification rate, SLNB positivity rate, local recurrence, regional nodal recurrence, and distant recurrence. In 53 patients with 54 tumors the SN identification rate was 94%. The SLNB positivity rate was 11.3%. On more thorough tissue processing and IHC, metastatic SCC was identified in 2 of 5 (40%) cases previously deemed negative. After reclassification of these cases, the adjusted SLNB positivity rate was 15.1%. The adjusted rate of false omission was 7.1% (95% CI, 2%-19%). Nodal disease developed in 20.8% overall. Angiolymphatic invasion (Cohen d, 3.52; 95% CI, 1.83-5.21), perineural invasion (Cohen d, 0.81; 95% CI, 0.09-1.52), and clinical size (Cohen d, 0.83; 95% CI, 0.05-1.63) were associated with the presence of nodal disease. Rigorous study of SLNB for cutaneous SCC incorporating prospectively-collected comprehensive data sets based on standardized treatment algorithms is justified with potential to modify clinical practice. Our study demonstrates the critical importance of serial sectioning and IHC of the SLNB specimen for accurate diagnosis. Use of the NCCN guidelines may facilitate identification of patients with SCC at high risk for nodal metastasis.

Sentinel lymph node biopsy in T1/T2 squamous cell carcinomas of the tongue: A prospective study.

Commonly used staging procedures often cannot predict the absence of cervical metastases (CM) in squamous cell carcinomas (SCCs) of the oral cavity. Due to the high incidence of occult CM in numerous N0 cases in the clinic, an elective neck dissection (ND) is performed. The sentinel lymph node biopsy (SNB) is a common concept in the modern surgical therapy of malignancies. The present study evaluates the applicability of this concept for T1/T2-SCC of the tongue. In a prospective clinical study, 10 consecutive patients with T1/T2-SCC of the tongue and cN0 necks, were enrolled. Following sentinel lymph node (SLN) scintigraphy, all patients underwent SNB with a γ-probe and a subsequent ND. SNB specimens were compared with histopathological assessments of surgical specimens from the ND. A total of 5 female and 5 male patients (mean age, 52 years; women, 62 years; men, 42 years), with a median follow-up time of 33.5 months (range, 10–40 months), were treated. All patients presented with detectable SLNs. In 7 cases, the SLN(s) and the residual ND were negative for CM. In 3 cases, the SLN(s) were positive without further CM in the other neck nodes. Furthermore, 1 patient showed additional CMs after 10 months in the contralateral neck and lung metastasis after 18 months, but none at the time of the initial treatment. The concept of an SNB appears to be applicable to the management of the cN0 neck in small SCC of the tongue. The role of SNB in the management of SCC requires further investigation by prospective trials with larger patient numbers.

Thin Serial Step Sectioning of Sentinel Lymph Node Biopsy Specimen May Not Be Necessary to Accurately Stage the Neck in Oral Squamous Cell Carcinoma

The purpose of this study was to assess the predictability of sentinel lymph node biopsy (SNB) for oral squamous cell carcinoma (OSCC) when pathologic processing is performed without serial step sectioning. We prospectively enrolled 36 patients with T1 or T2 cN0 OSCC into this institutional review board-approved prospective cohort study, and they underwent gamma probe-guided SNB in addition to selective neck dissection. The rate of patients with negative SNB results whose neck dissection was also negative for metastasis (negative predictive value) was the primary endpoint. Of the 28 patients whose sentinel lymph nodes were found to be pathologically and clinically node negative by routine hematoxylin-eosin stain and immunohistochemistry, 27 were found to have no other pathologically positive nodes, corresponding to a negative predictive value of 96%. The results of this study suggest that SNB performed without the use of thin serial step sectioning may accurately predict neck stage in OSCC.

Intraoperative frozen section analysis of margins in breast conserving surgery significantly decreases reoperative rates: one-year experience at an ambulatory surgical center.

Intraoperative frozen section (FS) margin evaluation is not common practice for patients undergoing breast conservation therapy (BCT), but offers a significant reduction in reoperation. In this study, a technique to allow for more effective freezing of breast tissue was developed to perform FS evaluation of lumpectomy margins (FSM) for all patients undergoing BCT at an ambulatory surgery center. FS evaluation of sentinel lymph node biopsy specimens was performed concurrently. One hundred eighty-one study and 188 control patients, with and without FS evaluation, were compared. Reexcision was reduced 34% (from 48.9% to 14.9%) and reoperation was reduced 36% (from 55.3% to 19.3%) with FS evaluation. Most of the decrease in reoperative rate was because of a decrease in the need for margin reexcision. The number of patients requiring 1, 2, or 3 operations to complete therapy was 84, 92, and 12, respectively, in the control group, and 146, 33, and 2, respectively, in the study group. Lobular subtype, multifocal disease, and larger tumor size (≥2 cm) were significantly associated with failure of FSM to prevent reoperation, but reoperation rates were still significantly decreased in this subgroup of patients (from 75.5% to 43.8%) with FSM. This study highlights an innovative yet simple and adaptable FS approach that resulted in a nearly 3-fold reduction in reoperation for patients undergoing BCT.

Diagnostic utility of IMP3 in segregating metastatic melanoma from benign nevi in lymph nodes

Depending on the Breslow depth of the primary melanoma, sentinel lymph node biopsy is considered as standard of care for the staging of cutaneous melanoma, and is one of the most important prognostic factors. The histologic analysis of these specimens becomes difficult to interpret when benign intranodal nevic cells mimic metastases. Insulin-like growth factor-II messenger RNA (mRNA)-binding protein-3 (IMP3), also known as K homology domain-containing protein overexpressed in cancer or L523S, is a member of the insulin-like growth factor-II mRNA-binding protein family and has been shown to have diagnostic utility in distinguishing cutaneous melanoma from benign nevi. In this study, 43 sentinel lymph node biopsy specimens, including 13 with benign intranodal nevi and 30 with metastatic melanoma (two cases containing both benign nevi and metastatic melanoma), from 41 patients were immunohistochemically analyzed with a monoclonal antibody against IMP3. None of the benign intranodal nevi expressed IMP3, whereas 21 out of 30 (70%) of the lymph nodes containing metastatic melanoma did. It seems that IMP3 is helpful in distinguishing benign intranodal nevi from metastatic melanoma in sentinel lymph node biopsy specimens, and could be a valuable diagnostic adjunct in sentinel lymph node biopsy assessment in which questions arise as to the malignancy of the melanocytes present.

5120 Predicting the likelihood of non-sentinel lymph node metastases in breast cancer patients by three nomograms suitable for different institutions

Sentinel lymph node biopsy (SLNB) is the standard procedure performed to stage the axillae, and axillary node clearance (ANC) or radiotherapy is the treatment for nodal involvement. The aims of this study were to assess (1) the role of preoperative axillary ultrasonography (US), (2) the number of positive lymph nodes on ANC after either positive SLNB results or preoperative ultrasonographically guided nodal biopsy, and (3) the role of ANC in patients with node-positive breast cancer.All patients with invasive breast cancer and axillary node involvement (but clinically negative nodes on presentation) who underwent ANC between January 2008 and December 2009 were identified, and information regarding clinicopathologic parameters and the nodal yield was collected. ANC was performed for 3 groups: patients with micrometastasis seen in SLNB specimens, macrometastasis seen in SLNB specimens, and positive axillary nodes detected on US biopsy.ANC was performed 141 times over the 2-year period. Forty-two percent of axillary node involvement was diagnosed by biopsy or preoperative US, and 40% of these patients received neoadjuvant chemotherapy. The remainder of cases were diagnosed by SLNB: 30% had micrometastases and 70% had macrometastases. Fifty percent of cancers with an ultrasonographic diagnosis of lymph node involvement were high grade and 56% had 4 or more positive nodes on ANC; this was significantly higher than in patients with positive SLNB results (P = .0001). Only 20% of patients with macrometastases on SLNB had 4 or more positive nodes in comparison with 56% with positive axillary lymph nodes by US (P < .0001).The routine use of preoperative axillary US and biopsy of abnormal nodes helps in identifying high-risk patients and thus aids in planning treatment.

Utility of frozen-section analysis of sentinel lymph node biopsy specimens for melanoma in surgical decision making

Utility of frozen-section analysis of sentinel lymph node biopsy specimens for melanoma in surgical decision making

Utility of frozen-section analysis of sentinel lymph node biopsy specimens for melanoma in surgical decision making

Background Debate exists whether frozen-section analysis of sentinel lymph nodes (SLNs) for melanoma is an accurate method to detect disease that has metastasized to the lymph nodes. The purpose of this study was to evaluate the utility of intraoperative frozen section for SLNs in melanoma. Methods We reviewed 133 patients (271 nodes) who underwent SLN biopsy with frozen section for melanoma between April 2003 and September 2007. Frozen-section diagnosis was compared with final diagnosis to determine concordance between intraoperative and postsurgical diagnosis. Results A total of 11 nodes (8% of patients) were found to have metastatic disease. All patients underwent lymph node dissections at the time of SLN biopsy. No false-positive SLNs were found on frozen section. The false-negative rate for SLN biopsy frozen section was 8% (1 of 133 patients). Conclusions Intraoperative frozen section can be an accurate and reliable tool in the right setting for analysis of sentinel nodes in cutaneous melanoma and deserves further study.

Correlation of the use of axillary ultrasound and lymph node needle biopsy with surgical lymph node pathology in patients with invasive breast cancer

Background Results vary regarding the utility of perioperative axillary ultrasound (AUS) and biopsy for detecting axillary metastases. Methods Patients diagnosed with invasive breast cancer from 2004 through 2005 who underwent preoperative AUS with or without biopsy, and their surgical pathologic findings were reviewed. Results Of 152 patients who underwent preoperative AUS, 38% had abnormal AUS findings. Sixty-two percent of biopsy specimens were positive. The sensitivity of AUS both with and without biopsy was 54%, and specificity was 96%. The positive predictive value was 91%, and the negative predictive value was 71%. Conclusions Our results correlate favorably with published reports of preoperative AUS. Standardization of AUS report descriptors is needed. Preoperative AUS should be included in the preoperative workup of clinically node-negative patients. A positive biopsy specimen decreases the need for a sentinel lymph node biopsy specimen; however, a negative AUS result or biopsy specimen does not replace the need to obtain a sentinel lymph node biopsy specimen.

2076 POSTER In early breast cancer, obesity is no contraindication for sentinel lymph node biopsy under local anaesthesia without sedation

Sentinel lymph node biopsy (SLNB) is the standard procedure performed to stage the axillae, and axillary node clearance (ANC) or radiotherapy is the treatment for nodal involvement. The aims of this study were to assess (1) the role of preoperative axillary ultrasonography (US), (2) the number of positive lymph nodes on ANC after either positive SLNB results or preoperative ultrasonographically guided nodal biopsy, and (3) the role of ANC in patients with node-positive breast cancer.All patients with invasive breast cancer and axillary node involvement (but clinically negative nodes on presentation) who underwent ANC between January 2008 and December 2009 were identified, and information regarding clinicopathologic parameters and the nodal yield was collected. ANC was performed for 3 groups: patients with micrometastasis seen in SLNB specimens, macrometastasis seen in SLNB specimens, and positive axillary nodes detected on US biopsy.ANC was performed 141 times over the 2-year period. Forty-two percent of axillary node involvement was diagnosed by biopsy or preoperative US, and 40% of these patients received neoadjuvant chemotherapy. The remainder of cases were diagnosed by SLNB: 30% had micrometastases and 70% had macrometastases. Fifty percent of cancers with an ultrasonographic diagnosis of lymph node involvement were high grade and 56% had 4 or more positive nodes on ANC; this was significantly higher than in patients with positive SLNB results (P = .0001). Only 20% of patients with macrometastases on SLNB had 4 or more positive nodes in comparison with 56% with positive axillary lymph nodes by US (P < .0001).The routine use of preoperative axillary US and biopsy of abnormal nodes helps in identifying high-risk patients and thus aids in planning treatment.

Sentinel Lymph Node Biopsy for Atypical Melanocytic Lesions with Spitzoid Features

Sentinel lymph node biopsy (SLNB) is routinely used as a staging procedure for melanomas, however may also assist in understanding the biology of atypical and controversial spitzoid melanocytic skin lesions. Five hundred and forty-nine sentinal lymph node excisions were performed over a 5-year period. Fourteen patients with controversial melanocytic lesions were identified and of these ten underwent SLNB. The histology of the primary skin lesion and corresponding sentinal lymph nodes were evaluated and correlated with outcome. Thickness of the primary melanocytic lesion ranged from 1.22 to 4 mm. Fifty percent of patients were less than 17 years of age. Ten patients underwent SLNB and three cases (30%) displayed metastatic disease in the SLNB specimen. All three patients were under 17 years of age and all underwent completion axillary dissection. One completion axillary dissection had an additional node with metastasis on routine H&E and immunohistochemical staining. No capsular invasion was seen. All three cases with metastatic disease received adjuvant systemic therapy and remain disease free at 29, 49 and 57 months follow-up. All patients with a negative SLNB remain disease free at mean follow-up of 28.1 months (range: 13-40 months). Our results confirm that some of these spitzoid lesions metastasize to regional lymph nodes and SLNB is a valuable adjunct tool in staging these lesions. However, molecular studies and a prolonged follow-up are needed to determine whether these lesions, especially those occurring in children are comparable to stage matched overt melanoma in adults.

Diagnosis and Treatment of Malignant Melanoma of the Foot

Patients diagnosed with melanoma of the foot have been reported to have a poor prognosis. We reviewed our experience at a tertiary-care medical clinic to determine the disease course in patients diagnosed with melanoma of the foot. A retrospective review was performed of 38 patients with a diagnosis of primary or locally recurrent melanoma of the foot treated between January, 1988, and July, 2004. The main outcome measures included methods of diagnosis, clinical and histopathologic features, and patterns of recurrence. The mean age at diagnosis was 61 years; most were women (58%) and Caucasian (95%). The average time to diagnosis was 17 months. Initial clinical diagnosis had been considered benign in 12 (32%). The median Breslow thickness was 1.75 mm, T1 lesions were the most common, and acral lentiginous melanoma accounted for 42%. Thirteen patients (34%) had ulcerated lesions. Sentinel lymph node biopsy specimens of 25 patients identified four (16%) with metastatic disease. Surgical complications occurred in 12 patients, usually after skin graft or soft-tissue flap reconstruction. Systemic recurrence developed in six patients, four of whom also had regional recurrence. Most patients were elderly Caucasian women and most presented with early-stage disease, but diagnosis can be difficult and a subgroup presented with thick melanomas. Reconstructive surgical procedures had a high rate of complications; however, overall functional outcomes were good. Stage of cancer at diagnosis was associated with systemic metastases.

Breast conserving therapy (BCT) for stage I-II breast cancer in elderly. Analysis of 927 cases

Sentinel lymph node biopsy (SLNB) is a minimally invasive technique to stage the axillary lymph node status. The burden of nodal metastasis is of great concern, as the clinical relevance and therapeutic implications of pN1mi and pN0(i+) in the sentinel lymph node (SLN) remain a matter of debate.We examined the pathological features of 901 patients above the age of 65 presenting with clinical T1–T2 N0M0 breast tumours (<3 cm), detecting tumours related to llary non-sentinel node (NSN) metastases when the SLN was minimally involved.A total of 270 patients underwent complete axillary lymph node dissection (cALND) after their SLNB specimen tested positive for macrometastasis, micrometastasis and isolated tumour cells (ITCs). Seventy-six patients were diagnosed with micrometastatic disease pN1mi (27.5%), whilst ITCs (pN0i+) were detected in seven patients (2.5%). NSNs were found to be involved in two patients (2.6%) with micrometastases at the SLN. No further metastatic disease was detected in NSNs when the SLN contained ITCs. At a median follow-up period of 5.8 years, no axillary recurrence was observed among pN1mi and pN0(i+) patients. Lobular histotype, multicentricity and lymphovascular invasion were found to be associated with NSN involvement.The results from our case series are supported by IBCSG 23-01 level 1 evidence, which demonstrated a local recurrence rate of 1% in ‘minimally involved not-surgical treated axilla’.Based on current evidence, we spare well-informed and consenting patients from further axillary surgery when the SLN is minimally involved in early breast cancer within an agreed protocol, whilst scheduling adjuvant treatment based on the patients' primary tumour characteristics.

Vulvar melanoma in a 10-year-old girl in association with lichen sclerosus

Vulvar melanoma in a 10-year-old girl in association with lichen sclerosus

Inefficacy of F‐18 fluorodeoxy‐D‐glucose‐positron emission tomography scans for initial evaluation in early‐stage cutaneous melanoma

The purpose of the current study was to determine the sensitivity and specificity of initial F-18 fluorodeoxy-D-glucose-positron emission tomography (FDG-PET) scanning for detection of occult lymph node and distant metastases in patients with early-stage cutaneous melanoma. The authors conducted a prospective nonrandomized clinical trial. Inclusion criteria were patients with cutaneous melanoma tumors > 1.0 mm Breslow thickness, local disease recurrence, or solitary intransit metastases without regional lymph or distant metastases by standard clinical evaluation. All patients underwent whole-body FDG-PET scanning before surgical therapy. Abnormal PET findings were studied by targeted conventional imaging and/or biopsy. FDG-PET scans were interpreted in a blinded fashion. Regional lymph node basins were staged by sentinel lymph node biopsy (SLNB). PET scan findings in regional lymph nodes were compared with histology of SLNB specimens. Abnormal distant PET scan findings were studied with repeat conventional scan imaging at 3-6 months and were correlated with the first site(s) of clinical disease recurrence. Blinded PET scan findings were correlated with all information to determine sensitivity and specificity. There were 144 assessable patients with a mean tumor depth of 2.8 mm. The median follow-up for these patients was 41.4 months. Blinded interpretations of FDG-PET scan images showed that 31 patients (21%) had signs of metastatic disease, 13 patients had probable regional lymph node metastases, and 18 patients had 23 sites of possible distant metastases. SLNB and/or follow-up demonstrated regional lymph node metastases in 43 of 184 lymph node basins in 40 patients (27.8%). Compared with all clinical information, FDG-PET scan sensitivity for detection of regional lymph node metastases was 0.21 (95% confidence [CI], 0.10-0.36) and specificity was 0.97 (95% CI, 0.93-0.99). No distant sites were confirmed to be true positive by targeted conventional imaging/biopsy at the time of presentation. Thirty-four patients (23.6%) presented with 54 foci of metastatic disease at initial disease recurrence. FDG-PET scan sensitivity for prediction of the first site(s) of clinical disease recurrence was 0.11 (95% CI, 0.04-0.23). Excluding patients with brain metastases, FDG-PET scan sensitivity for detection of occult Stage IV disease in patients was 0.04 (95% CI, 0.001-0.20) and specificity was 0.86 (95% CI, 0.79-0.92). FDG-PET scanning did not impact the care of patients with early-stage melanoma already staged by standard techniques. Routine FDG-PET scanning was not recommended for the initial staging evaluation in this population.

Breast Cancer Pseudometastasis in a Sentinel Lymph Node with Cytokeratin-Positive Debris

We report extensive pseudometastasis detected by immunohistochemical (IHC) staining within a sentinel lymph node. An 83-year-old woman underwent simple mastectomy and sentinel lymph node biopsy (SLNB) for infiltrating ductal carcinoma. Intraoperative frozen section of the SLNB specimen appeared histologically negative for metastasis. IHC staining for cytokeratin in permanent sections, however, showed what was reported as micrometastasis in the subcapsular sinus. Since these cells did not resemble the primary tumor cells morphologically, and had actually been called histiocytes in the frozen section, further IHC staining was done. The subcapsular cells were negative for epithelial membrane antigen (EMA) staining, but they were positive for CD68, a macrophage marker. Thus the cytokeratin-positive cells were not metastatic breast tumor cells, but rather were histiocytes with phagocytized cytokeratin debris. This case report illustrates that IHC staining for cytokeratin in SLNB specimens for breast cancer must be supported by morphologic assessment and further appropriate staining before it can become the basis for treatment decisions.

Is completion lymphadenectomy after a positive sentinel lymph node biopsy for cutaneous melanoma always necessary?

Completion lymph node dissection (CLND) has usually been recommended after metastatic disease is identified in the sentinel lymph node (SLN) biopsy to eradicate further metastases in nonsentinel nodes. We hypothesized that patients with negative lymph nodes included in the initial SLN specimen have low risk of metastases in the residual draining basin and may not require CLND. Chart review. University-affiliated tertiary care referral center. Between January 1, 1997, and May 31, 2003, 506 consecutive patients underwent SLN biopsy for staging of primary cutaneous melanoma. The SLN biopsy identified 87 patients (17.2%) with metastatic melanoma, of whom 80 underwent CLND. In 28 patients, all SLNs were found to contain metastatic melanoma. Seven (25%) of these patients had additional metastases identified in the CLND specimen. In 52 patients, 1 or more SLNs did not contain metastatic melanoma. Five (10%) of these patients had additional metastases in the CLND specimen (P =.02). Although no evidence of metastatic melanoma was found on CLND in most patients in whom negative nodes had been removed with positive SLNs at the initial biopsy, 10% of these patients did have further metastases. This subgroup of patients (positive SLNs and negative nodes in the SLN biopsy specimen) is at significantly lower risk for further metastasis, but CLND cannot be safely omitted even for these patients.