Ultrasonographically-guided fine-needle aspiration of axillary lymph nodes: role in breast cancer management

The knowledge of the status of axillary lymph nodes (LN) of patients with breast cancer is a fundamental prerequisite in the therapeutic decision. In the present work, we evaluated the impact of fine-needle aspiration cytology (FNAC) of ultrasonographically (US) selected axillary LN in the diagnosis of LN metastases and subsequently in the treatment of patients with breast cancer. Axillary US was performed in 298 patients with diagnosed breast cancer (267 invasive carcinomas and 31 ductal carcinoma in situ DCIS), and in 95 patients it was followed by FNAC of US suspicious LN. Smears were examined by routine cytological staining. Cases of uncertain diagnosis were stained in immunocytochemistry (ICC) with a combination of anticytokeratin and anti-HMFG2 antibodies. Eighty-five FNAC were informative (49 LN were positive for metastases, 36 were negative). In 49 of 267 patients with invasive breast carcinoma (18%), a preoperative diagnosis of metastatic LN in the axilla could be confirmed. These patients could proceed directly to axillary dissection. In addition, US-guided FNAC presurgically scored 49 out of 88 (55%) metastatic LN. Of all others, with nonsuspicious LN on US (203 cases including 31 DCIS), in which no FNAC examination was performed, 28 invasive carcinomas (16%) turned out to be LN positive on histological examination. Based on these data, US examination should be performed in all patients with breast cancer adding ICC-supported FNAC only on US-suspect LN. This presurgical protocol is reliable for screening patients with LN metastases that should proceed directly to axillary dissection or adjuvant chemotherapy, thus avoiding sentinel lymph node biopsy.     

The impact of axillary lymph nodes removed in staging of node-positive breast carcinoma

PURPOSE: Number of positive lymph nodes in the axilla and pathologic lymph node status (pN) have a great impact on staging according to the current American Joint Committee on Cancer staging system of breast carcinoma. Our aim was to define whether the total number of removed axillary lymph nodes influences the pN and thus the staging. METHODS AND MATERIALS: The records of 798 consecutive invasive breast cancer patients with T1-3 tumors and positive axillary lymph nodes who underwent modified radical mastectomy between 1999 and 2005 in our hospital were reviewed. The total number of removed nodes were grouped, and compared with the patient and tumor characteristics and the influence of the number of nodes removed on the staging was analyzed. RESULTS: The proportion of patients with > or =4 positive nodes (59%), and pN3 status (51%) were the highest in the group with 21-25 nodes removed. Compared with patients with 1-20 nodes removed, the proportion of patients with > or =4 positive nodes (52%), and pN3 status (46%) were significantly higher in those with more than 20 nodes removed. Although the proportion of Stage IIA and IIB decreased, the proportion of Stage IIIA and IIIC increased in patients with >20 nodes removed compared with those with 1-20 nodes removed. CONCLUSIONS: In patients with axillary node-positive breast carcinoma, staging is highly influenced by total number of removed nodes. Levels I-III axillary dissection with more than 20 axillary lymph nodes removed could lead to more effective adjuvant chemotherapy and increases substantially the proportion of patients to receive radiotherapy.     

The evolving role of axillary lymph node fine-needle aspiration in the management of carcinoma of the breast

BACKGROUND:

Image‐guided fine‐needle aspiration (FNA) studies of axillary lymph nodes (LN) to evaluate breast carcinoma have shown high specificity but variable sensitivity. The purposes of this study were to evaluate the performance of axillary LN FNA depending on clinicoradiologic findings and to document how treatment varied according to FNA results.

METHODS:

The study cohort consisted of consecutive axillary LN FNA cases over a 4‐year period, in which subsequent treatment was known. Clinicoradiologic assessment was classified as “low suspicion” or “high suspicion” and cytopathologic findings as “positive,” “negative,” or “indeterminate”. The test performance for each, using surgical pathology outcome as the “gold standard,” was calculated. The impact of axillary LN FNA on subsequent management decisions was analyzed.

RESULTS:

Of the 163 cases, axillary FNA was positive in 94 of 163 (58%), negative in 55 of 163 (34%), and atypical/nondiagnostic in 14 of 163 (8%). A clinicoradiologic assessment of “high suspicion” had a positive predictive value (PPV) of 88%, whereas a “low suspicion” assessment had a negative predictive value (NPV) of only 68%. In contrast, the PPV and NPV of axillary LN FNA were 98.7% and 81.8%, respectively. Whereas all of the FNA‐nonpositive cases were managed surgically, surgery was deferred in 26 of 94 of the FNA‐positive cases, including 11 cases of neoadjuvant treatment. Most of the remaining (65 of 68) FNA‐positive patients were spared sentinel lymph node biopsy.

CONCLUSIONS:

Image‐guided LN FNA is highly sensitive and specific for lymph node involvement by breast carcinoma and plays a role both in sparing sentinel lymph node biopsy and in triaging cases for systemic therapy. Cancer (Cancer Cytopathol) 2011. © 2011 American Cancer Society.     

腋窝微小淋巴结在乳腺癌分期中的作用

目的探讨乳腺癌腋窝微小淋巴结对乳腺癌分期的影响。方法127例乳腺癌不同根治性手术清除的腋窝组织经专人按常规方法寻找淋巴结后，把腋窝脂肪组织切1cm厚浸泡于溶脂液（Carnoy＇s solution）6～12h，取出腋窝脂肪组织置于玻璃板上寻找微小淋巴结，检出的淋巴结行常规病理检查。结果依靠常规方法检出淋巴结2483枚（平均每例19．55±7．95枚）；腋窝组织经溶脂液浸泡后检出1—6mm的淋巴结878枚（平均每例6．9±5．31枚），其中3mm以下的淋巴结781枚。使平均腋窝淋巴结检出数量增加到26，47±9．69枚。7例患者的pN改变，其中4例pN0升为pN1，2例pN1升为pN2，1例pN2升为pN3。结论该溶脂法能简捷地检出腋窝微小淋巴结，有助于乳腺癌的精确分期。     

Ultrasound-guided fine needle aspiration cytology of axillary lymph nodes in breast cancer patients. A preoperative staging procedure

Currently, axillary lymph node dissection is increasingly being replaced by the sentinel node procedure. This method is time-consuming and the full immunohistochemical evaluation is usually only first known postoperatively. This study was designed to evaluate the accuracy of preoperative ultrasound-guided fine needle aspirations (FNAs) for the detection of non-palpable lymph node metastases in primary breast cancer patients. We evaluated the material of 183 ultrasound-guided FNAs of non-palpable axillary lymph nodes of primary breast cancer patients. The cytological results were compared with the final histological diagnosis. Ultrasound-guided FNA detected metastases in 44% (37/85) of histologically node-positive patients, in 20% of the total patient population studied. These pecentages are likely to be higher when women with palpable nodes are included. Cytologically false-negative and false-positive nodes were seen in 28 (15%) and three cases (1.6%), respectively. Interestingly 25% (n=7) of the false-negative nodes, revealed micrometastases on postoperative histology. The sensitivity was 57%, the specificity 96%. We conclude that ultrasound-guided FNA of the axillary lymph nodes is an effective procedure that should be included in the preoperative staging of all primary breast cancer patients. Whether lymph nodes are palpable or not, it will save considerable operating time by selecting those who need a complete axillary lymph node dissection at primary surgery and would save a significant number of sentinel lymph node dissections (SLNDs).     

Role of axillary ultrasound,magnetic resonance imaging,and ultrasound-guided fine-needle aspiration biopsy in the preoperative triage of breast cancer patients

Purpose

Roughly two-thirds of early breast cancer cases are associated with negative axillary nodes and do not benefit from axillary surgery at all. Accordingly, there is an ongoing search for non-surgical staging procedures to avoid lymph-node dissection or sentinel node biopsy (SNB). Non-invasive imaging techniques with very high sensitivity (Se) and negative predictive value (NPV) could eventually replace SNB. We aimed to establish the role of axillary US and MRI, alone or in combination, associated with ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the prediction of axillary node involvement.

Methods/patients

Between January 2003 and September 2015, we included 1505 of the 1538 breast cancer patients attending our centres. All patients had been referred from a single geographical area. Axillary US, magnetic resonance imaging and ultrasound-guided fine-needle aspiration biopsy (US-FNAB) were performed if required.

Results

1533 axillary US examinations and 1351 axillary MRI studies were analyzed. For axillary US, Se, Specificity (Sp), Positive Predictive Value (PPV), and NPV were 47.5, 93.6, 82.5, and 73.8%, respectively. For axillary MRI, corresponding values were 29.8, 96.6, 84.9, and 68.4%. When both tests were combined, Sp and PPV slightly improved over individual tests alone. US-FNAB showed a 100% Sp and PPV, with a Se of 80%.

Conclusion

We may confidently state that axillary US and US-FNAB have to be included in the preoperative work-up of breast cancer patients.

     

Histopathologic examination of axillary sentinel lymph nodes in breast carcinoma patients

The axillary sentinel lymph node biopsy (SLNB) has gained increasing popularity as a novel surgical approach for staging patients with breast carcinoma and for guiding the choice of adjuvant therapy with minimal morbidity. Patients with negative SLNB represent a subset of breast carcinoma patients with definitely better prognosis, because their pN0 status is based on a very thorough examination of the sentinel lymph nodes (SLNs), with a very low risk of missing even small micrometastatic deposits, as compared with routine examination of the 20 or 30 lymph nodes obtained by the traditional axillary clearing. The histopathologic examination of the SLNs may be performed after fixation and embedding in paraffin, or intraoperatively on frozen sections. Whatever is the preferred tracing technique and surgical procedure, the histopathologic examination of each SLN must be particularly accurate, to avoid a false-negative diagnosis. Unfortunately, because of the lack of standardised guidelines or protocols for SLN examination, different institutions still adopt their own working protocols, which differ substantially in the number of sections cut and examined, in the cutting intervals (ranging from 50 to more than 250 microm), and in the more or less extensive use of immunohistochemical assays for the detection of micrometastatic disease. Herein, a very stringent protocol for the examination of the axillary SLN is reported, which is applied either to frozen SLN for the intraoperative diagnosis, and to fixed and embedded SLN as well.     

Ultrasound-guided fine-needle aspiration of suspicious nodes in breast cancer patients; selecting patients with extensive nodal involvement

The aim of this study was to evaluate the value of Ultrasonography (US) guided fine-needle aspiration (FNA) of the axilla to identify breast cancer patients with extensive nodal involvement. A prospective database of breast cancer patients who underwent US-guided FNA of suspicious nodes, diagnosed between 2000 and 2007 was analyzed. Patients with a negative axillary US or C2 (benign) FNA result underwent SLNB. Patients with C5 (malignant) FNA result underwent axillary lymph node dissection (ALND). All SLNB positive patients underwent completion ALND. The number of positive nodes after ALND was documented and analyzed. A total of 1,448 patients were included. US sensitivity was 34.2 %, specificity was 96.2 % and the accuracy was 71.7 %. For US-guided FNA this was 89, 100 and 90.4 %, respectively. In 234/1,448 patients (16.2 %) US-guided FNA was performed. A total of 19/41 C2 patients (46.3 %) had a positive SLNB. A median of 1 (range 1–6) positive node was found. A median of 4 (range 1–30) positive nodes were found in 158 C5 patients. In 376/1,214 patients with a negative US, SLNB was positive. A median of 2 (range 1–38) positive nodes were found. There was a significant difference in nodal involvement between C5 and SLNB positive patients (p = 0.043 and p < 0.0001, respectively). Ultrasound-guided FNA is a highly specific technique for detecting axillary metastases in breast cancer patients. Patients with US-guided FNA-diagnosed axillary metastases have significantly more involved nodes compared to SLNB positive patients.     

Accuracy of fine-needle aspiration cytology of axillary lymph nodes in breast cancer patients: a study of 115 cases with cytologic-histologic correlation

BACKGROUND: Fine-needle aspiration (FNA) cytology of axillary lymph nodes is a simple, minimally invasive technique that can be used to improve preoperative determination of the status of the axillary lymph nodes in patients with breast cancer, thereby serving as a tool with which to triage patients for sentinel versus full lymph node dissection procedures. The aim of the current study was to determine the sensitivity and specificity of FNA cytology to detect metastatic breast carcinoma in axillary lymph nodes. METHODS: A total of 115 FNAs of axillary lymph nodes of breast cancer patients with histologic follow-up (subsequent sentinel or full lymph node dissection) were included in the current study. The specificity and sensitivity, as well as the positive and negative predictive values, were calculated. RESULTS: The positive and negative predictive values of FNA cytology of axillary lymph nodes for metastatic breast carcinoma were 1.00 and 0.60, respectively. The overall sensitivity of axillary lymph node FNA in all the cases studied was 65% and the specificity was 100%. The sensitivity of FNA was lower in the sentinel lymph node group than in the full lymph node dissection group (16% vs 88%, respectively), which was believed to be attributable to the small size of the metastatic foci in the sentinel lymph node group (median, 0.25 cm). All false-negative FNAs, with the exception of 1 case, were believed to be the result of sampling error. There was no 'true' false-positive FNA case in the current study. CONCLUSIONS: FNA of axillary lymph nodes is a sensitive and very specific method with which to detect metastasis in breast cancer patients. Because of its excellent positive predictive value, full axillary lymph node dissection can be planned safely instead of a sentinel lymph node dissection when a preoperative positive FNA result is rendered. .     

Accuracy of fine needle aspiration cytology (FNAC) of axillary lymph nodes as a triage test in breast cancer staging

Introduction Axillary node fine needle aspiration cytology (FNAC) has the potential to triage women with operable breast cancer to initial nodal surgical procedure. Because of variability in the reported accuracy of this test its role and clinical utility in pre-operative staging remains controversial. Methods We retrospectively evaluated the accuracy of ultrasound-guided axillary FNAC in all consecutive clinically T1–2 N0–1 breast cancers that had undergone this test (491 biopsies). We included subjects with clinically or sonographically indeterminate or suspicious nodes. Pathological node status was used as the reference standard (based on axillary dissection or sentinel node biopsy). Results Sensitivity of node FNAC was 72.6% (67.3–77.9) and specificity was 95.7% (92.5–98.8) for all cases, sensitivity was lower at 64.6% (59.3–70.0) if inadequate cytology was included as a negative result. FNAC sensitivity was highest in women with clinically suspicious nodes [92.5% (88.2–96.7)] and lowest in women with sonographically abnormal and clinically negative nodes [50.0% (41.3–58.7)]. Specificity was high in both groups, 81.2% (54.5–96.0) and 97.2% (94.6–99.9), respectively. The false-negative rate was 15.3% (12.1–18.5), the false-positive rate was 1.4% (0.4–2.5), and the inadequacy rate was 10.8% (8.0–13.5). The likelihood of node FNAC being positive was significantly associated with tumour grade and stage, and the number of nodes involved with metastases. Discussion Our data show that axillary FNAC has moderate sensitivity (which varies according to selection criteria for the test) and consistently high specificity, is associated with low inadequacy and very few false positives. We estimate that its use would have improved triage to initial nodal procedure in about one quarter of our cases. If one accepts the premise that initial surgical staging of the axilla should be based on all information available through pre-operative diagnosis, then axillary FNAC should be adopted routinely into clinical practice.     

Intraoperative examination of axillary sentinel lymph nodes in breast carcinoma patients.

BACKGROUND: Routine histologic examination of axillary sentinel lymph nodes predicts axillary lymph node status and may spare patients with breast carcinoma axillary lymph node dissection. To avoid the need for two separate surgical sessions, the results of sentinel lymph node examination should be available intraoperatively. However, routine frozen-section examination of sentinel lymph nodes is liable to yield false-negative results. This study was conducted to ascertain whether extensive intraoperative examination of sentinel lymph nodes by frozen section examination would attain a sensitivity comparable to that obtained by routine histologic examination without intraoperative frozen section examination. METHODS: In a consecutive series of 155 clinically lymph node negative breast carcinoma patients, the axillary sentinel lymph nodes were examined intraoperatively, before complete axillary lymph node dissection. The frozen sentinel lymph nodes were sectioned subserially at 50-microm intervals. For each level, one section was stained with hematoxylin and eosin and the other section immunostained for cytokeratins using a rapid immunocytochemical assay. RESULTS: Sentinel lymph node metastases were detected in 70 of the 155 patients (45%). In 37 cases the sentinel lymph nodes were the only axillary lymph nodes with metastases. Immunocytochemistry did not increase the sensitivity of the examination. Five patients had metastases in the nonsentinel axillary lymph nodes despite having negative sentinel lymph nodes. The general concordance between sentinel and axillary lymph node status was 96.7%; the negative predictive value of intraoperative sentinel lymph node examination was 94.1%. CONCLUSIONS: The intraoperative examination of axillary sentinel lymph nodes is effective in predicting the axillary lymph node status of breast carcinoma patients and may be instrumental in deciding whether to spare patients axillary lymph node dissection.     

Gamma probe and ultrasonographically-guided fine-needle aspiration biopsy of sentinel lymph nodes in breast cancer patients.

AIM: The purpose of the present study was to evaluate the usefulness of gamma probe and ultrasonographically-guided fine-needle aspiration biopsy (FNAB) in the pre-operative detection of sentinel node (SN) metastasis in breast cancer patients. METHODS: Sentinel node biopsy (SNB) was performed in patients with stage I or II breast cancer with clinically negative nodes using dye and radio-isotope. Axillas of 60 patients in whom a hot spot was detected by gamma probe were examined by ultrasonography. Pre-operative diagnosis of SN metastasis by gamma probe and ultrasonographically-guided FNAB was compared with the histological results of SN. RESULTS: The sensitivity, specificity and overall accuracy of ultrasonography in the diagnosis of SN metastasis were 50.0%, 92.1% and 76.7%, respectively. SNs were visualized by ultrasonography in 29 of 60 patients. Of 14 patients with positive results by ultrasonography, four had positive and two had negative cytology. The combination of ultrasonography and ultrasonographically-guided FNAB for visualized nodes had a sensitivity of 78.5%, specificity of 93.3% and overall accuracy of 86.2%. Blind FNAB in the hot spot was not useful in the detection of SN metastasis in patients whose SNs failed to be detected by ultrasonography. CONCLUSIONS: Gamma probe and ultrasonographically-guided FNAB is a potentially useful method for pre-operative detection of SN metastasis. In patients with positive SNs, SNB is not indicated and complete axillary lymph-node dissection can be performed as a primary procedure. Copyright Harcourt Publishers Limited.     

Radiological imaging features of invasive micropapillary carcinoma of the breast and axillary lymph nodes

Invasive micropapillary carcinoma of the breast is of growing clinical significance. The purpose of this study was to identify the radiological imaging features for this type of breast carcinoma and the axillary lymph nodes. The study population consisted of 30 breast cancer patients (8 invasive micropapillary carcinomas and 22 other types of invasive ductal carcinoma). The breast lesions were evaluated with mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) prior to neoadjuvant chemotherapy. The pathological outcome of the axillary lymph nodes in 27 patients was correlated with the sonographic findings. Only contrast-enhanced MRI showed characteristic findings for invasive micropapillary carcinoma. Although invasive micropapillary carcinoma is commonly irregular in shape (7/8) compared with other types of invasive carcinoma (6/22) (p=0.012, chi(2) test), a careful interpretation of radiological imaging to identify lesion borders helped the complete clearance of cancer cells from 6/8 patients with invasive micropapillary carcinoma in one-time breast conservative surgery. The positive and negative predictive values of sonography in diagnosing axillary lymph node metastases in cases of invasive micropapillary carcinoma were 100 and 50%, respectively. In conclusion, contrast-enhanced MRI reveals the irregular shape of invasive micropapillary carcinoma and helps conservative breast surgery to be performed safely. The pathological analysis of axillary nodes in cases of invasive micropapillary carcinoma may prove to be indispensable due to the relatively low negative predictive value of sonography.     

Minimal risk of macrometastases in the non-sentinel axillary lymph nodes in breast cancer patients with micrometastatic sentinel lymph nodes and preoperatively ultrasonically uninvolved axillary lymph nodes

Micrometastases in the sentinel lymph node (SLN) carry a considerable risk of macrometastases in the non-sentinel lymph nodes (NSLN), resulting in axillary lymph node dissection (ALND). Preoperative ultrasound (US) examination of the axillary lymph nodes combined with a fine-needle aspiration biopsy (FNAB) has been proved to discover metastases in the axillary lymph nodes. The aim of our study was to assess the risk of macrometastases in NSLN in patients with micrometastatic SLN after a preoperative US examination of the axillary lymph nodes. The study included 36 patients in whom, after preoperative axillary US, micrometastases in the SLN were revealed and ALND was subsequently performed. At final histopathology, no macrometastases were discovered in the NSLN. In four patients, additional micrometastases were discovered in the NSLN. In conclusion, the risk of macrometastases in the NSLN in patients with preoperatively ultrasonically uninvolved axillary lymph nodes is minimal.     

Ultrasound and ultrasound-guided fine needle aspiration biopsy of supraclavicular lymph nodes in patients with esophageal carcinoma

The use of ultrasound combined with ultrasound-guided fine-needle aspiration biopsy (UGFAB) of supraclavicular lymph nodes in the pretreatment staging of 37 patients with squamous cell carcinoma of the esophagus is described. All patients underwent computed tomography (CT) scans of the chest and the abdomen and ultrasound of the abdomen and supraclavicular regions. Supraclavicular lymph node metastases (Stage IV disease according to the tumor nodes metastasis [TNM] classification) were cytologically diagnosed in seven (18.9%) of the 37 patients. In two of these patients, no other metastases were found. In the other five patients, UGFAB replaced more invasive diagnostic procedures. Due to their superficial location, ultrasound and UGFAB of the supraclavicular lymph nodes was relatively simple to perform, and contributed to an improved staging of squamous cell carcinoma of the esophagus.     

Endoscopic ultrasound-guided fine-needle aspiration in the diagnosis and staging of lung cancer and its impact on surgical staging.

PURPOSE: The diagnosis and staging of lung cancer critically depends on surgical procedures. Endoscopic ultrasound (EUS) -guided fine-needle aspiration (FNA) is an accurate, safe, and minimally invasive technique for the analysis of mediastinal lymph nodes (LNs) and can additionally detect tumor invasion (T4) in patients with centrally located tumors. The goal of this study was to assess to what extent EUS-FNA could prevent surgical interventions. PATIENTS AND METHODS: Two hundred forty two consecutive patients with suspected (n = 142) or proven (n = 100) lung cancer and enlarged (> 1 cm) mediastinal LNs at chest computed tomography were scheduled for mediastinoscopy/tomy (94%) or exploratory thoracotomy (6%). Before surgery, all patients underwent EUS-FNA. If EUS-FNA established LN metastases, tumor invasion, or small-cell lung cancer (SCLC), scheduled surgical interventions were cancelled. Surgical-pathologic verification occurred when EUS-FNA did not demonstrate advanced disease. Cancelled surgical interventions because of EUS findings was the primary end point. RESULTS: EUS-FNA prevented 70% of scheduled surgical procedures because of the demonstration of LN metastases in non-small-cell lung cancer (52%), tumor invasion (T4) (4%), tumor invasion and LN metastases (5%), SCLC (8%), or benign diagnoses (1%). Sensitivity, specificity, and accuracy for EUS in mediastinal analysis were 91%, 100% and 93%, respectively. No complications were recorded. CONCLUSION: EUS-FNA qualifies as the initial staging procedure of choice for patients with (suspected) lung cancer and enlarged mediastinal LNs. Implementation of EUS-FNA in staging algorithms for lung cancer might reduce the number of surgical staging procedures considerably.