Sonographic Evaluation of Intrathyroid Metastases.

OBJECTIVES: Intrathyroid metastases from extrathyroid primary tumors are rare. Clinical findings may be subtle, but detection of intrathyroid metastases has improved with sonography. The objective of this study was to evaluate the sonographic appearance of intrathyroid metastases. METHODS: Patients with thyroid masses with cytopathologic features matching those of an extrathyroid primary tumor were retrospectively identified. The appearances of intrathyroid metastases on sonography were reviewed for the following features: size, margin regularity, echogenicity, echotexture, vascularity on power or color Doppler ultrasonography, and the presence or absence of any associated cervical adenopathy. RESULTS: The study included 52 patients. The most frequent primary tumor sites were lung, head and neck, and breast. Intrathyroid metastases presented as a discrete nodule in 34 patients and as diffuse infiltration of the gland in 18 patients. The discrete nodules ranged in size from 1.1 to 5.6 cm (mean ± SD, 2.5 ± 1.2 cm). Thirty-three lesions (63%) had irregular margins, and 19 (37%) had well-defined margins. Most of the lesions were heterogeneously hypoechoic (n = 50, 96%). Vascularity was present in 32 of 50 measured lesions (64%) that were evaluated with Doppler sonography. Cervical adenopathy was present in 37 patients (71%). CONCLUSIONS: Intrathyroid metastases have sonographic characteristics similar to those described for both benign and malignant thyroid diseases. In patients with a previous or current extrathyroid malignancy, thyroid nodules or diffuse infiltration of the thyroid gland on sonography should be viewed as a potential intrathyroid metastasis and evaluated via ultrasound-guided fine-needle aspiration regardless of the site of the primary tumor.

Ultrasonography should not guide the timing of thyroidectomy in pediatric patients diagnosed with multiple endocrine neoplasia syndrome 2A through genetic screening.

BACKGROUND: American Thyroid Association (ATA) guidelines suggest that thyroidectomy can be delayed in some children with multiple endocrine neoplasia syndrome 2A (MEN2A) if serum calcitonin (Ct) and neck ultrasonography (US) are normal. We hypothesized that normal US would not exclude a final pathology diagnosis of medullary thyroid cancer (MTC). METHODS: We retrospectively queried a MEN2A database for patients aged<18 years, diagnosed through genetic screening, who underwent preoperative US and thyroidectomy at our institution, comparing preoperative US and Ct results with pathologic findings. RESULTS: 35 eligible patients underwent surgery at median age of 6.3 (range 3.0-13.8) years. Mean MTC size was 2.9 (range 0.5-6.0) mm. The sensitivity of a US lesion≥5 mm in predicting MTC was 13% [95% confidence interval (CI) 2%, 40%], and the specificity was 95% [95% CI 75%, 100%]. Elevated Ct predicted MTC in 13/15 patients (sensitivity 87% [95% CI 60%, 98%], specificity 35% [95% CI 15%, 59%]). The area under the receiver operating characteristic curve (AUC) for using US lesion of any size to predict MTC was 0.50 [95% CI 0.33, 0.66], suggesting that US size has poor ability to discriminate MTC from non-MTC cases. The AUC for Ct level at 0.65 [95% CI 0.46, 0.85] was better than that of US but not age [AUC 0.62, 95% CI 0.42, 0.82]. CONCLUSIONS: In asymptomatic children with MEN2A diagnosed by genetic screening, preoperative thyroid US was not sensitive in identifying MTC of any size and, when determining the age for surgery, should not be used to predict microscopic MTC.

Common locations of parathyroid adenomas.

BACKGROUND: We have developed a nomenclature system that succinctly specifies the locations of parathyroid adenomas in the neck. We report our experience using the system in a large, contemporary cohort of patients. METHODS: A prospective, endocrine surgery database at a single, tertiary care center was retrospectively analyzed. We reviewed the records of 271 patients operated on for sporadic primary hyperparathyroidism between January 2006 and May 2008 and analyzed the effect of adenoma location at operative intervention and outcome. RESULTS: Adenomatous gland locations were classified intraoperatively as: A (adherent to posterior thyroid capsule) in 12.5% of cases; B (tracheoesophageal groove) in 17.3%; C TE groove but (close to clavicle) in 13.7%; D (directly over the recurrent laryngeal nerve) in 12.2%; E (easy to identify, inferior thyroid pole) in 25.8%; F (fallen into thymus) in 7.4%; and G gauge (within thyroid gland) in 0.4%. More than one enlarged gland was present in 10.7% of patients and usually involved coexistence of enlarged types A and E glands. Type F glands were associated with a longer mean operative time (p = 0.0487) and type E glands with a higher rate of outpatient surgery (p = 0.0195). At 6 months from the surgery, 94.5% of the patients were normocalcemic. CONCLUSIONS: Our nomenclature system provides a simple way to describe the locations of parathyroid adenomas. Type E adenomas were associated with a higher rate of outpatient surgery and type F adenomas with a longer operative time. Biochemical cure rates were comparable for all locations of single adenomas.

18F-PET/CT imaging of metastasis to the thyroid gland: Imaging findings and effect on patient management.

PURPOSE: While metastasis to the thyroid from a primary cancer remote to the thyroid is uncommon, current imaging techniques have improved detection of these intrathyroid metastases. The purpose of this study was to evaluate the 18F-PET/CT appearance of intrathyroid metastases and assess the impact of detection on patient management. METHODS: The 18F-PET/CT appearance of intrathyroid metastasis, including standardized uptake value (SUV), disease extent, and the effect on patient management following diagnosis were retrospectively reviewed. Inclusion criteria included 18F-PET/CT imaging and diagnosis of the intrathyroid metastasis matching the remote primary tumor. RESULTS: Intrathyroid metastasis were detected in 24 patients. The intrathyroid metastases presented on 18F-PET/CT as focal nodular uptake (n = 21), multiple nodular uptake (n = 2), or diffuse uptake/infiltration of the thyroid gland (n = 1). The SUV ranged between 3.9 and 42 (median 12.5 ± 7.5); in 2 patients, the FDG-avidity was minimal. On 18F-PET/CT, distant metastases were present outside the neck (n = 18), or limited to the neck (n = 6). In 2 of these 6 patients, the thyroid was the only site of metastatic disease. Due to the metastatic disease, the therapy was changed in 23 of 24 patients; 1 patient was lost to follow-up. CONCLUSION: In any patient with a previous or current history of an extrathyroid malignancy, an 18FDG-avid thyroid mass or diffuse infiltration of the thyroid on 18F-PET/CT should be considered a potential intrathyoid metastasis until proven otherwise. Knowledge of an intrathyroid metastasis may impact patient management, especially if the thyroid or neck are the only sites of metastatic disease.

Pre-operative ultrasound identification of thyroiditis helps predict the need for thyroid hormone replacement after thyroid lobectomy.

OBJECTIVE: To evaluate whether pre-operative thyroiditis identified by ultrasound (US) could help predict the need for thyroid hormone replacement (THR) following thyroid lobectomy. METHODS: Data from patients who underwent thyroid lobectomy in 2006-2011, were not taking THR pre-operatively, and had ≥1 month of follow-up were reviewed retrospectively. THR was prescribed for relatively elevated thyroid-stimulating hormone (TSH) and hypothyroid symptoms. The Kaplan-Meier method was used to estimate the percentage of patients who required THR at 6, 12, 18, and 24 months postoperatively, and Cox proportional hazards regression models were used to evaluate prognostic factors for requiring post-thyroid lobectomy THR. RESULTS: During follow-up, 45 of 98 patients required THR. Median follow-up among patients not requiring THR was 11.6 months (range, 1.2 to 51.3 months). Six months after thyroid lobectomy, 22% of patients were taking THR (95% confidence interval [CI], 15-32%); the proportion increased to 46% at 12 months (95% CI, 36-57%) and 55% at 18 months (95% CI, 43-67%). On univariate analysis, significant prognostic factors for postoperative THR included a pre-operative TSH level >2.5 µ international units [IU]/mL (hazard ratio [HR], 2.8; 95% CI, 1.4-5.5; P = .004) and pathology-identified thyroiditis (HR, 2.4; 95% CI, 1.3-4.3; P = .005). Patients with both pre-operative TSH >2.5 µIU/mL and US-identified thyroiditis had a 5.8-fold increased risk of requiring postoperative THR (95% CI, 2.4-13.9; P<.0001). CONCLUSION: A pre-operative TSH level >2.5 µIU/mL significantly increases the risk of requiring THR after thyroid lobectomy. Thyroiditis can add to that prediction and guide pre-operative patient counseling and surgical decision making. US-identified thyroiditis should be reported and post-thyroid lobectomy patients followed long-term (≥18 months).

In papillary thyroid cancer, preoperative central neck ultrasound detects only macroscopic surgical disease, but negative findings predict excellent long-term regional control and survival.

BACKGROUND: Ultrasound (US) of the central neck compartment (CNC) is considered of limited sensitivity for nodal spread in papillary thyroid cancer (PTC); elective neck dissection is commonly advocated even in the absence of sonographic abnormalities. We hypothesized that US is an accurate predictor for long-term disease-free survival, regardless of the use of elective central neck dissection in patients with PTC. METHODS: A retrospective chart review of 331 consecutive PTC patients treated with total thyroidectomy at M.D. Anderson Cancer Center between 1996 and 2003 was performed. Information retrieved included preoperative sonographic status of the CNC, surgical treatment of the neck, demographics, cancer staging, histopathological variables and use of adjuvant treatment. The endpoints for the study were nodal recurrence and survival. RESULTS: There were 112 males and 219 females with a median age of 44 years (range 11-87). The median follow-up time for the series was 71.5 months (range 12.7-148.7). There were 151 (45.6%) patients with a T1, 58 (17.5%) with a T2, 70 (21.1%) with a T3, and 52 (15.7%) with a T4. Preoperative sonographic abnormalities were present in the CNC in 79 (23.9%) patients. During the surveillance period, 11 (3.2%) patients recurred in the central neck, with an average time for recurrence of 22.8 months. Advanced T stage (T3/T4) and abnormal US were independent prognostic factors for recurrence in the central neck (p=0.013 and p=0.005 respectively). There were 119 (35%) patients with a sonographically negative central compartment who underwent elective central neck dissection; 85 of them (71.4%) were found to be histopathologically N(+) while 34 (28.6%) were pN0. There were no differences in overall survival (p=0.32), disease specific survival (DSS; p=0.49), and recurrence-free survival (p=0.32) between these two groups. Preoperative US of the CNC was an age-independent predictor for overall survival (p<0.001), DSS (p=0.0097), and disease-free survival (p=0.0005) on bivariate Cox regression. CONCLUSIONS: US of the central compartment is an age-independent predictor for survival and CNC recurrence-free survival in PTC. Prophylactic neck dissection of the central compartment does not improve long-term disease control, regardless of the histopathological status of the lymph nodes retrieved. Our findings emphasize the ability of US to clinically detect relevant nodal disease and support conservative management of the CNC in the absence of abnormal findings.

Preoperative lateral neck ultrasonography as a long-term outcome predictor in papillary thyroid cancer.

OBJECTIVE: To evaluate the long-term outcomes and prognostic value of our sonographically based surgical approach to the lateral neck for recurrences in papillary thyroid cancer (PTC). DESIGN: Retrospective medical chart review. SETTING: Tertiary cancer institution. PATIENTS: The study population comprised 331 consecutive patients primarily treated for papillary thyroid carcinoma (PTC) at a tertiary cancer institution between 1996 and 2003. The lateral neck compartments were surgically addressed only in the presence of abnormalities on ultrasonography (US). MAIN OUTCOME MEASURES: Recurrence-free interval and overall, disease-specific, and recurrence-free survival. RESULTS: There were 112 male and 219 female patients, with a median age of 44.7 years (range, 11-87 years). The median follow-up time for the series was 77.9 months (range, 12.7-148.7 months). Preoperative US abnormalities were found in the right neck in 13.3%, in the left neck in 12.3%, and bilaterally in 11.2%; all of these patients underwent a lateral neck dissection at the time of the thyroidectomy. There were 11 recurrences in the series (0.3%), with a median time to presentation of 22.8 months (range, 6.0-55.3 months). Predictors of lateral neck disease-free interval were T stage and distant disease at presentation (P = .01 and P < .001, respectively) and the sonographic status of the ipsilateral and central neck (P = .001 and P < .001). The number of abnormal neck compartments in US correlated with the risk of regional failure (P = .01). The presence of US abnormalities in the lateral neck decreased the 10-year disease-specific survival from 98.3% to 66.9% (P < .001). CONCLUSIONS: Preoperative US is an excellent outcome predictor for lateral neck disease-free interval and for disease-specific survival in PTC. Sonographically based surgical approach provides excellent long-term regional control and validates current treatment guidelines.

Cystic lymph nodes in the lateral neck as indicators of metastatic papillary thyroid cancer.

OBJECTIVE: To determine whether radiographic findings portend to metastatic disease in patients with papillary thyroid carcinoma (PTC) and whether cystic lymph node metastasis can be recognized by preoperative, ultrasound-guided fine-needle aspiration (FNA). METHODS: We performed a retrospective review of patients with cystic lymph nodes in the lateral neck identified on preoperative ultrasonography between March 1996 and December 2009. Factors examined included demographic information; stage; cytologic and final pathologic findings; and imaging characteristics including location, size, and presence of vascularity and calcifications. Time of cystic node identification in relationship to initial diagnosis was also recorded. RESULTS: Thirty patients had cystic lymph nodes in the lateral neck on cervical ultrasonography during the study period. Among this group, 28 (93%) had PTC, 1 (3%) had papillary serous carcinoma of the ovary, and 1 (3%) had poorly differentiated thyroid cancer. Median age at initial cancer diagnosis was 41 years (range, 16-64 years). Twenty-one patients (70%) were women, and median lymph node size was 1.8 cm (range, 0.6-4.8 cm). Twenty-three patients (77%) had a solitary cystic lymph node, and the remainder had more than 1 cystic lymph node. Cystic lymph nodes were identified at initial presentation in 11 patients (37%), while cystic lymph nodes were discovered in 19 patients (63%) after the initial operation. FNA was performed on the cystic lymph nodes of 23 patients (77%). Cytologic findings were positive for metastatic disease in 18 of 23 patients (78%). Among the 5 of 23 patients with negative cytologic findings, thyroglobulin aspirate was obtained in 1 patient, confirming metastatic PTC. Final pathologic review after surgical resection of cystic lymph nodes with negative cytologic findings from FNA was consistent with metastatic disease in 4 of 5 patients (80%). CONCLUSIONS: In patients with PTC, the presence of a cystic lymph node by ultrasonographic examination is highly suggestive of locally metastatic disease. Confirmation of metastatic PTC may sometimes be achieved with thyroglobulin aspirate from cystic lymph nodes when cytologic findings are negative. Clinicians should strongly consider surgical lymph node resection of cystic lymph nodes regardless of the preoperative cytologic findings by FNA.

Efficacy of 4D-CT preoperative localization in 2 patients with MEN 2A.

Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant syndrome that is associated with hyperparathyroidism in 20% to 30% of adult gene carriers. The appropriate surgical management of these patients remains in question. Approaches to this disease range from selective gland resection to a subtotal parathyroidectomy with or without autotransplantation. Despite surgical intervention, disease recurrence is problematic. Surgical management of patients found to have recurrence relies on localizing the anatomic location of the hyperfunctional gland(s). The primary imaging modality for localization of hyperfunctioning parathyroid glands is technetium 99m sestamibi single photon emission computed tomography (SPECT). Although sestamibi imaging has a sensitivity of 60% to 90%, specific anatomic detail is not always present by this imaging modality. Four-dimensional computed tomography (4D-CT) scans allow localization of ectopic parathyroid glands and autotransplanted parathyroid tissue, and they provide the anatomic detail necessary for decisions about appropriate surgical management. Another benefit of the 4D-CT scan is that enhancement characteristics, which are determined by contrast opacification of the hyperfunctional parathyroid tissue over 4 phases of the scan, correlate with metabolic activity. We recommend the use of 4D-CT scanning because of its capacity to identify hyperfunctional parathyroid glands and to provide anatomic information important in preoperative planning.

Metastases to intramammary lymph nodes in patients with breast cancer: sonographic findings.

PURPOSE: To describe the sonographic characteristics of intramammary lymph node metastasis (ILNM) in patients with breast cancer and to assess the value of sonography and sonographically guided fine needle aspiration biopsy (FNAB) in their diagnosis. METHODS: We retrospectively reviewed the charts and films of 19 women with biopsy-documented ILNM who were seen in our breast diagnostic center between December 1999 and July 2003. The sonographic appearance of the nodes was analyzed and correlated with clinical and mammographic findings and with biopsy results. RESULTS: The ILNMs were clinically and mammographically occult in 7 (37%) of the 19 women. The diameter of the ILNMs was less than 1 cm in 15 (79%) cases. The volume of the central echogenic hilum was less than 50% of the total volume of the node in each of the patients. There was marked decrease in cortical echogenicity of the ILN in all cases. Metastatic involvement was established via sonographically guided FNAB in each of the 19 suspicious intramammary lymph nodes. CONCLUSION: Sonography and sonographically guided FNAB are valuable methods of assessment for ILNM in patients with known or suspected breast cancer. The most consistent sonographic features associated with ILNM were reduction in the volume of the central echogenic hilum and marked hypoechogenicity of the node's cortex.

Impact of clinicopathological factors on sensitivity of axillary ultrasonography in the detection of axillary nodal metastases in patients with breast cancer.

BACKGROUND: Ultrasonography and fine-needle aspiration (FNA) are used to evaluate the breast and regional nodes in breast cancer patients. We sought to identify factors influencing the sensitivity of ultrasonography for detection of nodal metastasis. METHODS: Patients with a clinically negative axilla who underwent axillary ultrasonography and sentinel lymph node biopsy were included. RESULTS: Of 208 patients, axillary ultrasonography was negative in 180 (86%) and suspicious or indeterminate in 28 (14%). FNA was performed in 22 patients whose findings were indeterminate or suspicious, and 3 were positive for malignancy. Final pathological examinations revealed positive nodes in 53 patients: 39 (22%) of 180 with negative ultrasonographic findings and 14 (50%) of 28 with indeterminate or suspicious ultrasonographic findings (P =.001). Excisional biopsy was more common for patients with indeterminate or suspicious findings on preoperative ultrasonography (P =.038). There were no significant differences in tumor size, histological features, size of nodal metastasis, or number of positive nodes between patients whose ultrasonography findings were negative and those whose findings were indeterminate or suspicious. CONCLUSIONS: Ultrasonographically suggested nodal metastasis is associated with the finding of nodal disease on final pathological examination. No significant clinicopathologic criteria were found to impact sensitivity of ultrasonography; however, excisional biopsy for diagnosis may be a confounding variable in subsequent axillary ultrasonography.