Axillary Ultrasound Fine Needle Aspiration Biopsy: Is There a Role in the Post Z-0011 Era?

OBJECTIVES: Axillary ultrasound with fine needle aspiration (AXUSFNA) in early-stage breast cancer has required reappraisal. ACOSOG Z-0011 and after mapping of the axilla: radiotherapy or surgery have shown that women with limited nodal disease at sentinel lymph node biopsy got no survival advantage with completion axillary node dissection. We hypothesize that AXUSFNA may be sufficiently accurate for staging for some patients and sentinel lymph node biopsy need not be performed. We define the false negative rate (FNR) of AXUSFNA in different subsets of patients. MATERIALS AND METHODS: This retrospective cohort study included node positive patients who also underwent AXUSFNA between 1/2006 and 12/2010 followed by axillary surgery. The FNR was calculated for the entire group and for subgroups determined by tumor, nodal, and ultrasound findings. RESULTS: Out of ∼700 AXUSFNA patients, 128 node positive patients were included in the study. The overall AXUSFNA FNR was 35.9% (95% confidence interval, 28.1%-44.6%). There was a significantly higher FNR with smaller tumors and presence of ductal carcinoma in situ on multivariate analysis. On ultrasound, benign-appearing nodes had a higher FNR than indeterminate nodes (78.9% vs. 60.9%, P=0.2) and significantly higher than suspicious nodes (78.9% vs. 2.9%, P<0.0001). CONCLUSIONS: In our cohort, the FNR for AXUSFNA was comparable with the rate of residual disease in the control arms of Z-0011 (27.4%) and after mapping of the axilla: radiotherapy or surgery (33%). However, our analysis suggests that we may be able to identify more appropriate patients for AXUSFNA and halve the FNR. As primary tumor characteristics and genomics drive systemic therapeutic recommendations, there may be an ongoing role for AXUSFNA in axillary staging.

Axillary ultrasound and fine-needle aspiration in the preoperative evaluation of the breast cancer patient: an algorithm based on tumor size and lymph node appearance.

OBJECTIVE: The objective of our study was to evaluate the utility of ultrasound-guided fine-needle aspiration (FNA) of the axillary lymph nodes in breast cancer patients depending on the size of the primary tumor and the appearance of the lymph nodes. SUBJECTS AND METHODS: Data were collected about tumor size, lymph node appearance, and the results of ultrasound-guided FNA and axillary surgery of 224 patients with breast cancer undergoing 226 ultrasound-guided FNA. Lymph nodes were classified as benign if the cortex was even and measured < 3 mm, indeterminate if the cortex was even but measured ≥ 3 mm or measured < 3 mm but was focally thickened, and suspicious if the cortex was focally thickened and measured ≥ 3 mm or the fatty hilum was absent. The results of ultrasound-guided FNAs were analyzed by the sonographic appearance of the axillary lymph nodes and by the size of the primary tumor. The sensitivity and specificity of ultrasound-guided FNA were calculated with axillary surgery as the reference standard. The sensitivity and specificity of axillary ultrasound to predict the ultrasound-guided FNA result were calculated. RESULTS: Of the 224 patients, 51 patients (23%) had a positive ultrasound-guided FNA result, which yields an overall sensitivity of 59% and specificity of 100%. The sensitivity of ultrasound-guided FNA was 29% in patients with primary tumors ≤ 1 cm, 50% in patients with tumors > 1 to ≤ 2 cm, 69% in patients with tumors > 2 to ≤ 5 cm, and 100% in patients with tumors > 5 cm. The sensitivity of ultrasound-guided FNA in patients with normal-appearing lymph nodes was 11%; indeterminate lymph nodes, 44%; and suspicious lymph nodes, 93%. Sonographic characterization of lymph nodes as suspicious or indeterminate was 94% sensitive and 72% specific in predicting positive findings at ultrasound-guided FNA. CONCLUSION: Ultrasound-guided FNA of the axillary lymph nodes is most useful in the preoperative assessment of patients with large tumors (> 2 cm) or lymph nodes that appear abnormal.

Axillary lymph nodes: US-guided fine-needle aspiration for initial staging of breast cancer--correlation with primary tumor size.

PURPOSE: To retrospectively assess the sensitivity and specificity of ultrasonographic (US)-guided fine-needle aspiration (FNA) of axillary lymph nodes for preoperative staging of breast cancer across a range of primary tumor sizes, by using histologic findings as a reference standard. MATERIALS AND METHODS: Institutional review board approval was obtained for this HIPAA-compliant study; informed consent was waived. US-guided FNA results in 74 patients with breast cancer (75 axillae) were compared with final pathologic results. Lymph nodes were classified as benign, indeterminate, or suspicious on the basis of US characteristics at retrospective review. US-guided FNA in the most suspicious node at US, or the largest node if all appeared benign, was performed. Final pathologic results (sentinel lymph node biopsy [SNB] or axillary lymph node dissection [ALND]) were compared with US and preoperative US-guided FNA results. Results were assessed according to tumor size. Sensitivity, specificity, and positive predictive value of US and US-guided FNA were calculated. RESULTS: Primary tumor sizes were 0.3-12 cm (mean, 3 cm). Patient age range was 31-81 years (mean age, 51 years). Sensitivity of US-guided FNA for predicting positive results at ALND or SNB was 71%-75%. Specificity was 100%. Sensitivity of US-guided FNA increased with primary tumor size. CONCLUSION: US-guided FNA of axillary lymph nodes in patients with newly diagnosed breast cancer had a sensitivity that increased with increasing size of the primary tumor.

Ovarian cancer associated with testosterone supplementation in a female-to-male transsexual patient.

Ovarian cancer is the most fatal gynecologic malignancy. Women often present late and though median survival has improved, a majority of women will succumb to their disease. The incidence of ovarian cancer among female-to-male transsexuals is not known. We report only the second case of ovarian cancer in a female-to-male transsexual while on androgen supplementation therapy. Staining of his tumor for androgen receptors showed abundant expression. Androgen supplementation in this population may be associated with an increased risk of both ovarian cancer and of endometrial cancer. Consideration for bilateral salpingo-oophorectomy as part of gender reassignment surgery should be given, especially in this poorly studied group of patients whose overall risk of ovarian cancer remains unknown.

BI-RADS lexicon for US and mammography: interobserver variability and positive predictive value.

PURPOSE: To retrospectively evaluate interobserver variability between breast radiologists by using terminology of the fourth edition of the Breast Imaging Reporting and Data System (BI-RADS) to categorize lesions on mammograms and sonograms and to retrospectively determine the positive predictive value (PPV) of BI-RADS categories 4a, 4b, and 4c. MATERIALS AND METHODS: Institutional review board approval was obtained; informed consent was not required. This study was HIPAA compliant. Ninety-four consecutive lesions in 91 women who underwent image-guided biopsy comprised 59 masses, 32 calcifications, and three masses with calcification. Five radiologists retrospectively reviewed these lesions. Each observer described each lesion with BI-RADS terminology and assigned a final BI-RADS category. Interobserver variability was assessed with the Cohen kappa statistic. A pathologic diagnosis was available for all 94 lesions; 30 (32%) were malignant and 64 (68%) were benign. Pathologic analysis of benign lesions was performed on tissue obtained with image-guided core-needle biopsy. In cases referred for excisional biopsy after needle biopsy because of atypia or discordance, final surgical pathologic analysis was used for correlation with imaging findings. PPV for category 4 or 5 lesions was determined for all readers combined. RESULTS: For ultrasonographic (US) descriptors, substantial agreement was obtained for lesion orientation, shape, and boundary (kappa = 0.61, 0.66, and 0.69, respectively). Moderate agreement was obtained for lesion margin and posterior acoustic features (kappa = 0.40 for both). Fair agreement was obtained for lesion echo pattern (kappa = 0.29). For mammographic descriptors, moderate agreement was obtained for mass shape, mass margin, and calcification distribution (kappa = 0.48, 0.48, and 0.50, respectively). Fair agreement was obtained for calcification description (kappa = 0.32). Slight agreement was obtained for mass density (kappa = 0.18). Fair agreement was obtained for final assessment category (kappa = 0.28). PPVs of BI-RADS category 4 and 5 assignments were as follows: category 4a, six (6%) of 102; category 4b, 17 (15%) of 110; category 4c, 48 (53%) of 91; and category 5, 71 (91%) of 78. CONCLUSION: Interobserver agreement with the new BI-RADS terminology is good and validates the US lexicon. Subcategories 4a, 4b, and 4c are useful in predicting the likelihood of malignancy.

Role of imaging in pretreatment evaluation of early invasive cervical cancer: results of the intergroup study American College of Radiology Imaging Network 6651-Gynecologic Oncology Group 183.

PURPOSE: To compare magnetic resonance imaging (MRI) and computed tomography (CT) with each other and to International Federation of Gynecology and Obstetrics (FIGO) clinical staging in the pretreatment evaluation of early invasive cervical cancer, using surgicopathologic findings as the reference standard. PATIENTS AND METHODS: This prospective multicenter clinical study was conducted by the American College of Radiology Imaging Network and the Gynecologic Oncology Group from March 2000 to November 2002; 25 United States health centers enrolled 208 consecutive patients with biopsy-confirmed cervical cancer of FIGO stage > or = IB who were scheduled for surgery based on clinical assessment. Patients underwent FIGO clinical staging, helical CT, and MRI. Surgicopathologic findings constituted the reference standard for statistical analysis. RESULTS: Complete data were available for 172 patients; surgicopathologic findings were consistent with FIGO stages IA to IIA in 76% and stage > or = IIB in 21%. For the detection of advanced stage (> or = IIB), sensitivity was poor for FIGO clinical staging (29%), CT (42%), and MRI (53%); specificity was 99% for FIGO clinical staging, 82% for CT, and 74% for MRI; and negative predictive value was 84% for FIGO clinical staging, 84% for CT, and 85% for MRI. MRI (area under the receiver operating characteristic curve [AUC], 0.88) was significantly better than CT (AUC, 0.73) for detecting cervical tumors (P = .014). For 85% of patients, FIGO clinical staging forms were submitted after MRI and/or CT was performed. CONCLUSION: CT and MRI performed similarly; both had lower staging accuracy than in prior single-institution studies. Accuracy of FIGO clinical staging was higher than previously reported. The temporal data suggest that FIGO clinical staging was influenced by CT and MRI findings.

Characterization of breast masses with sonography: can biopsy of some solid masses be deferred?

OBJECTIVE: To determine whether sonography can be used to categorize some solid breast masses as probably benign so that biopsy can be deferred. METHODS: We prospectively characterized 844 sonographically visible solid breast masses referred for biopsy. Mammographic and sonographic features of the masses were recorded, and all masses were categorized by American College of Radiology Breast Imaging Reporting and Data System classification before biopsy. Of the 844 masses, 148 were categorized as probably benign (Breast Imaging Reporting and Data System category 3). Sonographically guided biopsy (n = 804) or fine-needle aspiration (n = 40) was performed for pathologic correlation. RESULTS: Of the 148 masses that met the sonographic criteria for probably benign masses, there was 1 malignancy, for a negative predictive value of 99.3%. CONCLUSIONS: Follow-up can be an acceptable alternative to biopsy for sonographically probably benign solid masses.

Mammographic findings in pseudoxanthoma elasticum.

BACKGROUND: There have been isolated case reports of arterial and skin calcification in mammograms of patients with pseudoxanthoma elasticum (PXE), and unpublished anecdotes of many women with PXE undergoing breast biopsy for evaluation of microcalcifications. OBJECTIVE: Our aim was to systematically evaluate mammography and breast pathology in PXE. METHODS: The mammograms of 51 women with confirmed PXE were compared with those of a control sample of 109 women without PXE, noting each of the following characteristics on each mammogram: breast density, skin thickening, skin microcalcifications, vascular calcification, breast microcalcifications and macrocalcifications, and masses. The characteristics of the 2 samples were compared using the 2-tailed t test with a pooled estimate of variance. The indications for mammography and data for each of the mammographic findings were analyzed using the chi(2) test. Available breast biopsy material was reviewed. RESULTS: The PXE and control groups were similar in age and indications for mammography. There was a statistically significant increase in skin thickening, vascular calcification, and breast microcalcifications in the PXE group (P <.001 each). Breast density, masses, macrocalcifications, and skin calcification did not differ statistically in the 2 groups, but no control patient had axillary calcification, or both vascular calcification and microcalcifications (P <.001). Nearly 1 in 7 of the patients with PXE demonstrated at least 3 of the following: microcalcifications, skin calcifications, vascular calcification, and skin thickening; whereas none of the control group did. Histopathologic findings of breast tissue showed calcification of dermal elastic fibers, subcutaneous arteries, and elastic fibers of the deep fascia and interlobular septae of the fat adjacent to breast parenchyma. CONCLUSION: Breast microcalcification and arterial calcification are not rare in the normal population and are not of diagnostic value. The presence of both of these findings, especially with skin thickening or axillary skin calcification, should suggest a diagnosis of PXE. The majority of breast calcifications in PXE are benign.

Axillary staging using ultrasound-guided fine needle aspiration biopsy in locally advanced breast cancer.

BACKGROUND: Axillary lymph node status is important for staging and planning therapy prior to neoadjuvant chemotherapy in patients with locally advanced breast cancers (LABC). The objective of this study was to evaluate the use of axillary ultrasonography coupled with fine needle aspiration biopsy (US-FNAB) to determine lymph node status prior to initiation of neoadjuvant chemotherapy. METHODS: Patients with a LABC, defined as a breast cancer clinically larger than 3.0 cm or a cytology positive axillary lymph node, were evaluated by clinical examination followed by ultrasonographic evaluation. Lymph nodes were categorized as suspicious for malignancy based on size >1.0 cm, decrease in the fatty hilum, or parenchymal echogenicity. US-FNAB was performed on all patients. Most patients received neoadjuvant chemotherapy followed by definitive surgery. Axillary surgery consisted of axillary lymph node dissection. Axillary status by clinical examination and US-FNAB was compared with that obtained by axillary node dissection. RESULTS: From January 1998 to May 2001, 26 patients (27 axillae) presented with LABC to our institution. The median age of these patients was 48 years. The sensitivity and specificity of US-FNAB for evaluating axillary metastatic disease in patients with LABC were 100% and 100%, respectively. CONCLUSIONS: In patients with locally advanced breast cancer, axillary ultrasonography coupled with fine needle aspiration biopsy can accurately stage the axilla. It is particularly useful and should be used more frequently in patients undergoing neoadjuvant chemotherapy. The use of ultrasonography to stage the axilla in patients who present with small breast cancers should be explored.