Diagnostic Accuracy and Scope of Intraoperative Transoral Ultrasound and Transoral Ultrasound-Guided Fine-Needle Aspiration of Retropharyngeal Masses.

The use of transoral sonography-guided fine-needle aspiration for intraoperative localization of retropharyngeal masses has been described by Fornage et al. The purpose of this study was to assess the accuracy of this technique. We reviewed the images and medical records of 26 patients with a retropharyngeal lesion suspicious for a metastatic lymph node of Rouviere identified on CT and/or PET/CT. There were 14 patients with a history of thyroid cancer, 7 with mucosal squamous cell carcinoma, 1 with renal cell carcinoma, 1 with parotid acinic cell cancer, 1 with metastatic colon adenocarcinoma, and 2 with no history of cancer. Intraoperative transoral sonography was performed using a commercially available endovaginal transducer. A transoral sonography-guided fine-needle aspiration was performed with a 25-cm-long 20-ga Chiba needle through a needle guide attached to the transducer shaft. Cytopathologic results were categorized as malignant, benign, or nondiagnostic. Transoral sonography and transoral sonography-guided fine-needle aspiration were performed in all patients. A diagnostic specimen was obtained in 25 of 26 (96%) patients with a 100% overall accuracy. Twelve patients underwent subsequent transoral resection of the retropharyngeal mass. In each patient, surgical pathology confirmed the fine-needle aspiration biopsy result. In 4 patients, transoral sonography-guided injection of methylene blue was used to facilitate intraoperative localization of the metastatic retropharyngeal mass. Transoral sonography and transoral sonography-guided fine-needle aspiration of suspicious masses in the retropharyngeal space are highly accurate procedures for identification and cytologic evaluation of benign and metastatic lymph nodes of Rouviere and for presurgical localization.

Telesonography: virtual 3D image processing of remotely acquired abdominal, vascular, and fetal sonograms.

PURPOSE: To design and test a new telesonography technique using remote volume acquisition by untrained operators in locations without access to trained sonographers, postprocessing, and interpretation done at expert centers. MATERIALS AND METHODS: The technique was tested with 84 sonograms of organs acquired in pregnant women (n = 8) and patients with various abdominal pathologic conditions (n = 11) located in French Guyana (France), Ceuta (Spain), and Murighiol (Romania). An operator inexperienced in sonography (US) placed the transducer over the predetermined acoustic window for each organ, then swept it from a -45° to a +45° position to scan the targeted organ. The acquired volume dataset was sent to an expert center via the Internet and reconstructed using a proprietary software, which allowed a trained sonographer to navigate through the appropriately reconstructed sonograms. RESULTS: After three-dimensional processing at the expert center, the organs scanned in the obstetrical cases were adequately visualized by the expert in seven of eight (88%) examinations of the fetal head, femur, and umbilical cord and eight of eight (100%) examinations of the fetal abdomen and placenta, whereas in the general abdominal cases, the liver, gallbladder, portal vein, and right kidney were correctly visualized in 10 of 11 (91%) examinations. CONCLUSIONS: Telesonography allowed untrained operators to scan and transfer the US volume datasets over the Internet to an expert center where an expert sonographer could navigate through the reconstructed US volume and visualize sonograms of diagnostic quality.

Adverse prognostic significance of infraclavicular lymph nodes detected by ultrasonography in patients with locally advanced breast cancer.

BACKGROUND: Ultrasonography is increasingly used to evaluate the nodal status of breast cancer patients and specialized positioning permits assessment of the infraclavicular fossa. However, the incidence and significance of infraclavicular (level III) adenopathy detected sonographically in locally advanced breast cancer (LABC) has not been defined. METHODS: The study population consisted of 146 LABC patients registered in a prospective trial of induction chemotherapy between 1991 and 1996. All patients underwent ultrasound imaging before and after chemotherapy. Median follow-up was 32 months. RESULTS: Forty-two of 146 patients (29%) had suspicious infraclavicular adenopathy; all 42 had additional positive axillary lymph nodes by ultrasound. Disease-free and overall survival for the patients with suspicious infraclavicular adenopathy was significantly worse compared with patients without this feature; disease-free survival 50% versus 68% (P = 0.112); overall survival 58% versus 83% (P = 0.026). CONCLUSIONS: Nearly one third of LABC patients will have infraclavicular lymph node involvement by ultrasound imaging; this finding is a significant adverse prognostic feature, and we recommend that infraclavicular nodal evaluation become a routine component of the sonographic workup of breast cancer patients, particularly if lower axillary lymph nodes appear involved.

Radiofrequency ablation of solid tumors.

Radiofrequency ablation of solid tumors is produced by frictional heating caused when ions in the tissue attempt to follow the changing directions of a high-frequency alternating current. The radiofrequency probe is typically placed under ultrasound guidance, and the ablation is performed with real-time ultrasound monitoring. Radiofrequency ablation has been demonstrated to be effective in the treatment of unresectable hepatic tumors, and promising results have also been obtained in tumors of the lung, bone, brain, kidney, prostate gland, and pancreas. Most recently, radiofrequency ablation has been tested in the treatment of invasive breast tumors. A preliminary study reported that intraoperative radiofrequency ablation causes invasive breast cancer cell death in patients with locally advanced breast cancer. An ongoing study is investigating the use of radiofrequency ablation for the treatment of breast tumors 2 cm or less in diameter.

Diffuse large B-cell non-Hodgkin's lymphoma presenting as a vaginal mass in a patient with a history of intestinal mucosa-associated lymphoid tissue (MALT) lymphoma.

Vaginal involvement in non-Hodgkin's lymphoma is uncommon and is often secondary to disseminated disease. Primary disease at this site is quite rare. We present here an unusual case of a patient who developed a diffuse large B-cell lymphoma presenting as a vaginal mass after having been treated for primary intestinal mucosa-associated lymphoid tissue (MALT) lymphoma 4 years earlier. Combined chemotherapy and radiation therapy for the intestinal MALT lymphoma produced complete remission that lasted for 2 years. Chemotherapy given for the diffuse large B-cell lymphoma with secondary vaginal involvement produced a second complete remission. The second remission was consolidated with high-dose chemotherapy and autologous bone marrow transplantation. Although the patient died from complications related to the transplant procedure, the disease was in complete remission at the time of her death. Given the rarity of primary intestinal MALT lymphoma and primary vaginal lymphoma, no standard treatment has been established. Treatment options have included chemotherapy, radiation therapy, or surgery, given alone or in combination.

Novel translational model for breast cancer chemoprevention study: accrual to a presurgical intervention with tamoxifen and N-[4-hydroxyphenyl] retinamide.

Surrogate end point biomarkers for risk assessment and efficacy of potential chemopreventive agents are needed to improve the efficiency and reduce the cost of chemoprevention trials. It is imperative to develop the best clinical breast model for translational surrogate end point biomarker studies, especially with respect to accrual feasibility. We have initiated a prospective study to develop biomarkers for tamoxifen and N-[4-hydroxyphenyl] retinamide by administering either a placebo or both drugs for 2-4 weeks to women with ductal carcinoma in situ or early invasive cancers in the interval between the initial diagnostic core biopsy and definitive surgery. The principle end point is pretreatment versus posttreatment tumor levels of Ki-67; a number of other exploratory markers will also be examined. The planned target sample size is 100 patients. Between February 1997 and February 2000, 4514 women who had either an abnormal mammogram or a diagnosed breast cancer were screened for the study. Of these 4514 screened patients, 52 (1%) were registered on the study. Major factors of nonparticipation in the remaining 4462 women were as follows: (a) no evidence of malignancy (2081 patients; 46%); (b) ineligible per protocol criteria (575 patients; 13%); (c) preoperative chemotherapy/tamoxifen (520 patients; 11%); (d) surgery scheduling conflict (360 patients; 8%); (e) outside needle biopsy (221 patients; 5%); (f) no residual disease after excisional biopsy (345 patients; 8%); and (g) second opinion only (123 patients; 3%). Other nonparticipation factors included fine needle aspiration only, refusal, tumor size > 2 cm, and estrogen replacement therapy (35 patients each; 2% each). The protocol was amended in midstudy to allow outside needle biopsy, tumor > 2 cm, and estrogen replacement therapy. Accrual to biomarker (nontherapeutic) protocols with delay in definitive cancer surgery is challenging but feasible. Although some accrual problems remain, we have nonetheless succeeded in recruiting 50% of our target sample size in a 3-year period.

The correlation of axillary ultrasonography with histologic breast cancer downstaging after induction chemotherapy.

BACKGROUND: The goal of this study was to examine the role of ultrasonography in detecting axillary lymph node metastases in stage II breast cancer patients after induction chemotherapy (IC). METHODS: Of 172 consecutive patients with T1-3, N0-1, M0 breast cancer registered in a prospective IC trial, a subset of 130 evaluable patients were chosen, with (1) both physical and ultrasonographic examinations of the axilla before and after IC; (2) exactly four cycles of IC; (3) no presurgical radiation therapy; and (4) an axillary lymph node dissection. RESULTS: Before IC, 32 patients (25%) were negative for axillary involvement by both physical and ultrasonographic examinations. After IC, this number increased to 64 (49%). Of these, 31 (48%) were positive by pathology examination. In most cases, however, the residual tumor was minimal. CONCLUSIONS: Stage II breast cancer patients who were or became node negative by both ultrasonographic and physical examinations after IC had a 48% incidence of nodal metastases. Because the residual tumor was minimal, irradiation may be sufficient for adequate local control of the axilla.

Recent advances in breast sonography.

Breast sonography has come to maturity during the past decade. Recent and ongoing technological developments include higher-frequency wideband transducers, 2-D array phased-array technology, extended-field-of-view imaging, three-dimensional sonography, higher-sensitivity color and power Doppler imaging, contrast agents, and harmonic imaging. Applications of breast sonography have thus expanded, with more reliable tissue characterization and differentiation between benign and malignant diseases and improved staging of cancer patients. Sonography has become the guidance technique of choice not only for percutaneous needle biopsy but also for many other interventional procedures involving nonpalpable breast masses. In selected cases, sonography can even be used to biopsy or localize calcifications that can be clearly identified on sonography. A growing field of research is ultrasound-guided percutaneous ablation of breast lesions using cryotherapy or radiofrequency.

Sonography of palpable breast cancer.

PURPOSE: Because of the increasing use of sonography to rule out cancer in women with palpable breast abnormalities, this study was performed to determine the rate of sonographically occult malignancy in this clinical setting. METHODS: Women who were recommended for biopsy based on mammographic and/or clinical findings underwent breast sonography. This study retrospectively analyzed the subset of patients with palpable malignant lesions. Lesions were classified as visible or occult on mammography and sonography. Patients without a tissue diagnosis of tumor were excluded. RESULTS: Of 1,346 masses that underwent biopsy or aspiration, 616 lesions were palpable, and of these, 293 were malignant. Sonography detected all 293 palpable malignant lesions (95% confidence interval for sensitivity, 99-100%). Eighteen lesions were mammographically occult. The median lesion size as determined by sonography was 1.8 cm; for the lesions that were mammographically occult, the median size was 1.6 cm. The most common histopathologic diagnosis for both groups of lesions was infiltrating ductal carcinoma. CONCLUSIONS: All palpable malignant breast lesions were visible by sonography in patients in whom a biopsy was recommended. However, we caution that until the false-negative rate of sonography for equivocal palpable abnormalities is determined prospectively, sonography cannot be accurately applied to rule out malignancy in this setting.

US with extended field of view: phantom-tested accuracy of distance measurements.

To evaluate the accuracy of distance measurements obtained with the extended-field-of-view (FOV) software of a commercially available ultrasonographic scanner, two custom-designed phantoms that allowed scanning of flat and curved surfaces were used. Five hundred forty measurements of various known distances in the phantoms were made by three examiners using various transducers. Although minor differences were observed between operators and transducers, 99.4% (537 of 540) of the distance measurements were accurate within plus or minus 4%. This extended-FOV technology provides accurate measurements of large objects in vitro.

Tubular carcinoma of the breast: mammographic and sonographic features.

OBJECTIVE: The purpose of this study was to define specific mammographic and sonographic features of tubular carcinoma of the breast. MATERIALS AND METHODS: Seventeen pathologically confirmed cases of tubular carcinoma were characterized retrospectively by two radiologists. Mammograms and sonograms were available for all patients. RESULTS: Fifteen of the 17 tubular carcinomas appeared as irregularly shaped masses with spiculated margins on mammography. Sixteen of the 17 masses had central densities. Spicules longer than the diameter of the central lesion were noted in eight (53%) of 15 tubular carcinomas. Eight tubular carcinomas had associated calcifications, with calcifications suspected of being malignant in four cases. On sonography, 15 hypoechoic masses were seen. The margins of the masses on sonography were described as ill-defined in 14 (93%) of the 15 cases. Posterior acoustic shadowing was present in 14 of the 15 cases. CONCLUSION: Tubular carcinomas are usually seen on mammography as irregularly shaped masses with central densities and spiculated margins, and most tubular carcinomas can be identified on sonography as hypoechoic masses with ill-defined margins and posterior acoustic shadowing. Although the mammographic and sonographic features of tubular carcinoma are not sufficiently specific to differentiate tubular carcinomas from radial scars, sonography can be useful for guiding biopsies and evaluating for multifocal and multicentric disease.

The case for ultrasound of muscles and tendons.

Ultrasound is a highly sensitive technique that can be conveniently employed in the evaluation of muscle lesions of many types, ranging from neuromuscular diseases seen by neurologists to mass lesions and injuries seen by orthopedists. The technique is perhaps underutilized given its utility in these applications compared with other cross-sectional imaging techniques. Particularly when recent developments, such as extended field of view and color Doppler techniques, are integrated, ultrasound becomes highly attractive in the imaging evaluation of various lesions. This article reviews characteristic ultrasound appearances of various muscle and tendon lesions and discusses various newer techniques and interventional applications.

US-guided implantation of metallic markers for permanent localization of the tumor bed in patients with breast cancer who undergo preoperative chemotherapy.

Metallic markers were implanted with ultrasonographic guidance in 51 malignant breast tumors in 49 patients to tag the tumor bed in anticipation of complete or almost complete response to preoperative neoadjuvant induction chemotherapy before breast-conservation surgery. The markers were the only remaining evidence of the original tumor site in 47% (23 of 49) of the patients preoperatively. This technique effectively addresses the problem of preoperative localization of the tumor bed in complete or nearly complete response of breast cancer to neoadjuvant chemotherapy.

Sonographically guided needle biopsy of nonpalpable breast lesions.

This article describes the techniques of sonographically guided fine-needle aspiration (FNA) and core-needle biopsy (CNB) of nonpalpable breast lesions. Virtually any nonpalpable breast lesion that is clearly demonstrated on sonograms can be sampled with a needle under ultrasound guidance. Advantages of ultrasound-guided FNA include its pinpoint accuracy, the excellent tolerance by patients, and the ability to aspirate or inject fluid or air. Advantages of ultrasound-guided CNB include a near 100% tissue recovery rate even in fibrous masses, the ability to assess the invasiveness of a cancer, and the fact that tissue cores are readily interpreted by any pathologist. In institutions in which an expert cytopathologist is available, FNA is often used as a first-line biopsy technique, with CNB being reserved for situations in which FNA cannot provide a definitive answer to the question asked. In most institutions, however, CNB has become the standard for percutaneous needle biopsy of breast masses, and sonography has replaced stereotaxy as the standard guidance technique for nonpalpable masses.

Ultrasound-guided fine-needle aspiration (FNA) of nonpalpable breast lesions: a review of 1885 FNA cases using the National Cancer Institute-supported recommendations on the uniform approach to breast FNA.

BACKGROUND: A probabilistic approach to the classification of fine-needle aspirates (FNAs) of the breast recently was recommended and received endorsement from the National Cancer Institute (NCI). In this system, FNAs are classified as benign, indeterminate/atypical, suspicious/probably malignant, and malignant, but to the authors' knowledge the use of these diagnostic categories has not been evaluated on a large scale. Furthermore, this classification scheme has not been applied to FNAs of nonpalpable lesions of the breast obtained under imaging guidance. Thus, the current study focused on whether the diagnostic categories could be applied usefully to ultrasound-guided FNAs (US-FNAs) of nonpalpable breast lesions. METHODS: Between 1988-1996, 1885 US-FNAs were performed on 1639 patients. The original FNA diagnoses were reclassified into the NCI-supported recommendations for diagnostic categories of breast FNAs. The cytologic findings were correlated with the tissue specimens, which were available in 851 cases, or with clinical follow-up of a minimum of 2 years in 127 of the 274 patients with benign solid lesions. RESULTS: The 1885 cases were categorized as follows: 1057 (56.1%) as benign, 86 (4.6%) as atypical, 79 (4.2%) as probably malignant, 502 (26.6%) as malignant, and 161 (8.5%) as unsatisfactory (defined as < 6 epithelial cell groups on all slides). The benign US-FNAs included 480 (45.4%) cysts and 577 (54.6%) solid lesions. Combined clinical and surgical follow-up showed that the frequency of malignancy was 3.7% in US-FNAs classified as benign, 52.9% in those designated as atypical, 75.8% in those designated as suspicious, and 98.9% in those classified as malignant. Based on combined histologic and clinical follow-up, a sensitivity of 97.1% and specificity of 99.1% were found for US-FNAs when definitive benign and malignant diagnoses were considered. A false-negative rate of 3.7% was attributed to sampling error. A false-positive rate of 0.68% was secondary to interpretative error of proliferative lesions. CONCLUSIONS: Application of the NCI-supported diagnostic categories to US-FNA of nonpalpable breast lesions is useful in stratifying aspirates based on the likelihood of underlying malignancy. The subcategories of US-FNAs diagnosed as atypical have similar probabilities of malignancy; this justifies their being grouped as a single category wherein tissue biopsy would be required to exclude carcinoma. Benign and inadequate FNA diagnoses must be correlated with the clinical and imaging findings and in noncorrelative cases the patient should undergo biopsy. US-FNA is a sensitive and specific means with which to diagnose nonpalpable breast lesions.

Role of axillary lymph node dissection after tumor downstaging with induction chemotherapy for locally advanced breast cancer.

BACKGROUND: Induction chemotherapy has become the standard of care for patients with locally advanced breast cancer (LABC) and currently is being evaluated in prospective clinical trials in patients with earlier-stage disease. To better gauge the role of axillary lymph node dissection in patients with LABC this study was performed to assess initial axillary status on physical and ultrasound examination, axillary tumor downstaging following induction chemotherapy, and the accuracy of physical examination compared with axillary sonography in predicting which patients will have axillary lymph node metastases found on pathologic examination. METHODS: Between 1992 and 1996, 147 consecutive patients with LABC were registered in a prospective trial of induction chemotherapy using 5-fluorouracil, doxorubicin, and cyclophosphamide. Physical and ultrasound examinations of the axilla were performed at diagnosis and after induction chemotherapy. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed, followed by postoperative chemotherapy and irradiation of the breast or chest wall and regional lymphatics. RESULTS: Following induction chemotherapy, 43 (32%) of the 133 patients with clinically positive lymph nodes on initial examination had axillary tumor downstaging as assessed by physical and ultrasound examination. The sensitivity of axillary sonography in identifying axillary metastases was significantly higher than that of physical examination (62% vs. 45%, P=.012). The specificity of physical examination (84%) was higher than that of sonography (70%), but the difference did not reach statistical significance. Among the 55 patients in whom the findings of both physical and ultrasound examination of the axilla were negative following induction chemotherapy, 29 patients (53%) were found to have axillary lymph node metastases on pathologic examination of the axillary contents. However, 28 (97%) of these patients had either 1 to 3 positive lymph nodes or only micrometastases 2 to 5 mm in diameter. CONCLUSIONS: Preoperative clinical assessment of the axilla by physical examination combined with ultrasound examination is not completely accurate in predicting metastases in patients with LABC following tumor downstaging. However, patients with negative findings on both physical and ultrasound examinations of the axilla may be potential candidates for omission of axillary dissection if the axilla will be irradiated because minimal axillary disease remains. Patients who have positive findings on preoperative physical or ultrasound examinations should receive axillary dissection to ensure local control. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following induction chemotherapy is currently underway.

Can we detect or predict the presence of occult nodal metastases in patients with squamous carcinoma of the oral tongue?

BACKGROUND: When to do a neck dissection as part of the surgical treatment for a patient with squamous carcinoma of the oral tongue is controversial, particularly when the primary can be resected without entering the neck. If the patient who is at high risk for having occult nodal disease in the neck can be identified, node dissection with the glossectomy could be justified. To better identify patients for this procedure, we correlated various tumor and patient factors along with preoperative diagnostic studies with the presence or absence of pathologically positive nodes in a group of patients who underwent node dissection. METHODS: Ninety-one previously untreated patients with biopsy-proved squamous carcinoma of the oral tongue were prospectively studied. All patients had a glossectomy and neck dissection as their initial treatment. The pathology findings (ie, lymph nodes with squamous cancer) were correlated with many preoperative and intraoperative factors, and a statistical analysis was made. RESULTS: The use of computed tomography and ultrasound was not better than the clinical examination in determining the presence or absence of nodal metastases. The best predictors were depth of muscle invasion, double DNA aneuploidy, and histologic differentiation of the tumor. CONCLUSIONS: All patients with stage T2-T4 squamous cancers of the oral tongue should have an elective dissection of the neck. Patients with T1N0 cancer who have a double DNA-aneuploid tumor, depth of muscle invasion > 4 mm, or have a poorly differentiated cancer should definitely undergo elective neck dissection. Ultrasound and computed tomography are of little value in predicting which patients have positive nodes.

In search of specimen adequacy in fine-needle aspirates of nonpalpable breast lesions.

Pathology-related medical malpractice claims frequently concern fine-needle aspirations (FNAs) of breast lesions, and diagnostic errors have been attributed in part to the inadequacy of the specimens. Cytologic criteria for adequate FNA specimens, specifically in cases without malignancy, have not been clearly defined. From January 1988, to August 1995, 669 ultrasonographic-guided FNAs of nonpalpable, solid breast lesions with subsequent histologic examination were performed at our institution. From these, 54 cases with cytologic diagnoses of insufficient or nonspecific benign findings were identified. All aspirates were reviewed, and the number and size of the epithelial cell groups were quantitated in each case. By using criteria for adequate aspirates of palpable breast lesions (six or more epithelial cell groups per case with a minimum of 5-10 cells per group), 23 of the 54 aspirates were deemed inadequate and 31 adequate. Eleven (48%) of the inadequate aspirates and 17 (55%) of the adequate aspirates were from histologically confirmed carcinomas (ductal carcinoma in situ, 6; invasive carcinoma, 22, of which 12 were ductal, 7, lobular, and 3, mixed ductal and lobular). For the mammographic diagnoses "probably benign," "indeterminate," and "suggestive of malignancy or malignant," the probability of malignancy in aspirates of adequate cellularity (eg, > 6 epithelial groups) was 9%, 40%, and 93%, respectively. These findings indicate that a significant proportion of breast aspirates still may yield false-negative results despite adequate to high cellularity. Although a definition of adequacy based on cellularity is useful in reducing false-negative results, cellularity alone cannot be relied on in the management of nonpalpable lesions. For mammographic findings that are indeterminate or suggestive of malignancy or malignant, nonspecific FNA findings should be followed by core or excisional biopsy to exclude carcinoma.