Differentiation of soft tissue benign and malignant peripheral nerve sheath tumors with magnetic resonance imaging

PURPOSE: The objective of this study was to differentiate the magnetic resonance (MR) imaging appearance of benign peripheral nerve sheath tumors (PNSTs) from that of malignant PNSTs. MATERIALS AND METHODS: Twenty-six patients who underwent MR imaging and had a histologic diagnosis of benign (schwannoma, n=16; neurofibroma, n=1) or malignant (n=9) PNST were retrospectively reviewed. The size, location, shape, margin, and signal intensities of the tumors on precontrast and gadolinium-enhanced MR imaging were analyzed. In each patient, the presence or absence of split fat, target, and fascicular signs was determined. RESULTS: The mean size of the benign PNSTs (3.4 cm, S.D.=2.5 cm) was significantly smaller than that of the malignant tumors (8.2 cm, S.D.=3.1 cm) (P<.001). Seventeen (65.4%) of the 26 tumors were spindle shaped or ovoid (12 benign and 5 malignant tumors). Contiguity with specific nerves was identified in 15 (88.2%) of the 17 benign PNSTs but in none of the malignant tumors (P<.05). Well-defined margins were noted in all 17 benign PNSTs but in only 3 (33.3%) of the 9 malignant tumors (P<.001). Five (55.6%) of the 9 malignant PNSTs but none of the benign tumors showed signal intensity change in adjacent soft tissue (P<.05). There was no significant difference in signal intensity between the benign and malignant tumors on T(1)-weighted, T(2)-weighted, and contrast-enhanced MR images. The split fat and target signs were present more frequently in the benign PNSTs than in the malignant PNSTs (P<.05).Conclusions: Benign and malignant PNSTs are often spindle shaped. Recognition of contiguity with adjacent nerves, a well-defined margin, and the presence of the split fat sign may suggest benignity. Imaging features suggestive of malignancy can be a larger size and an infiltrative margin.     

ECM1 and TMPRSS4 are diagnostic markers of malignant thyroid neoplasms and improve the accuracy of fine needle aspiration biopsy

OBJECTIVE: The objective of this study was to determine whether genes that regulate cellular invasion and metastasis are differentially expressed and could serve as diagnostic markers of malignant thyroid nodules. SUMMARY AND BACKGROUND DATA: Patients whose thyroid nodules have indeterminate or suspicious cytologic features on fine needle aspiration (FNA) biopsy require thyroidectomy because of a 20% to 30% risk of thyroid cancer. Cell invasion and metastasis is a hallmark of malignant phenotype; therefore, genes that regulate these processes might be differentially expressed and could serve as diagnostic markers of malignancy. METHODS: Differentially expressed genes (2-fold higher or lower) in malignant versus benign thyroid neoplasms were identified by extracellular matrix and adhesion molecule cDNA array analysis and confirmed by real-time quantitative polymerase chain reaction (PCR). The area under the receiver operating characteristic (AUC) curve was calculated to determine diagnostic accuracy of gene expression level cutoffs established by logistic regression analysis. RESULTS: By cDNA array analysis, ADAMTS8, ECM1, MMP8, PLAU, SELP, and TMPRSS4 were upregulated, and by quantitative PCR, ECM1, SELP, and TMPRSS4 mRNA expression was higher in malignant (n = 57) than in benign (n = 38) thyroid neoplasms (P< 0.002). ECM1 and TMPRSS4 mRNA expression levels were independent predictors of a malignant thyroid neoplasm (P < 0.003). The AUC was 0.956 for ECM1 and 0.926 for TMPRSS4. Combining both markers improved their diagnostic use (AUC 0.985; sensitivity, 91.7%; specificity, 89.8%; positive predictive value, 85.7%; negative predictive value, 82.8%). ECM1 and TMPRSS4 expression analysis improved the diagnostic accuracy of FNA biopsy in 35 of 38 indeterminate or suspicious results. The level of ECM1 mRNA expression was higher in TNM stage I differentiated thyroid cancers than in stage II and III tumors (P < or = 0.031). CONCLUSIONS: ECM1 and TMPRSS4 are excellent diagnostic markers of malignant thyroid nodules and may be used to improve the diagnostic accuracy of FNA biopsy. ECM1 is also a marker of the extent of disease in differentiated thyroid cancers.     

Can localization studies be used to direct focused parathyroid operations?

BACKGROUND: There is considerable controversy today concerning the most appropriate surgical approach for patients with primary hyperparathyroidism. The conventional surgical operation involves a bilateral neck exploration through a collar incision with identification of all parathyroid tissue and removal of abnormal parathyroid glands while the patient is under general anesthesia. The success rate of this operation is about 95% or greater in the hands of an experienced endocrine surgeon. Preoperative localization techniques are generally considered to be unnecessary before initial parathyroid operations. The purpose of this investigation was (1) to evaluate the individual and combined accuracy of ultrasonography and technetium 99m sestamibi scans in localizing abnormal parathyroid glands and (2) to determine whether such scans could be used to direct a focused operation. METHODS: We retrospectively studied 338 patients with sporadic primary hyperparathyroidism who had preoperative neck localization studies, ultrasonography and/or technetium 99m sestamibi scans, and parathyroid exploration (238 patients or, reexploration, 60 patients) from January 1996 to April 2000 at the University of California San Francisco/Mount Zion Medical Center. The preoperative localization studies were recorded as true-positive, false-positive, and false-negative and compared with the surgical and pathologic findings and with the outcome of the operation. RESULTS: All of the abnormal parathyroid glands were correctly identified by ultrasonography in 184 of 303 patients (60.7%) and by technetium 99m sestamibi scanning in 183 of 237 patients (77.2%). The sensitivities of ultrasonography and sestamibi were 65% and 80%, respectively. Among the 202 patients who received both ultrasonography and sestamibi scans, a parathyroid tumor was identified at the same site in 105 (52%) of them. When both techniques identified a parathyroid tumor at the same site, the tests were correct in 101 of 105 patients and the sensitivity increased to 96%. CONCLUSIONS: When both the ultrasonography and sestamibi scans identified the same, solitary parathyroid tumor in patients with sporadic primary hyperparathyroidism, this was the only abnormal parathyroid gland in 96% of the patients. A focused parathyroidectomy could therefore be performed in such patients with an acceptable ( approximately 95%) success rate.     

Results of surgical treatment for hyperparathyroidism associated with renal disease

Recently, the role and timing of surgery for treating secondary and tertiary hyperparathyroidism (HPT) have been questioned. In order to delineate the indications for surgery in these patients, a retrospective analysis of 53 consecutive patients treated with parathyroidectomy was conducted. Subtotal thyroidectomy was done in 37 of 45 patients undergoing their initial operations for HPT. Eight additional patients were referred after failed operations. Of 33 patients with preoperative bone pain, 70% improved. Joint pain improved in 87% of 30 patients, pruritus improved in 81% of 27 patients, and preoperative malaise improved in 73% of 33 patients after parathyroidectomy. Abdominal pain and irritated eyes were unlikely to improve. The best predictors of a successful outcome were a markedly elevated preoperative immunoreactive parathyroid hormone (mid-region) level and an elevated alkaline phosphatase level. There were no perioperative deaths. One patient (1.6%) had a recurrent laryngeal nerve injury, and one patient required reoperation for a neck hematoma. No patient had permanent hypoparathyroidism, but transient hypocalcemia (less than 7 mg/dL) occurred in 22%. Postoperative hypocalcemia correlated with elevated preoperative alkaline phosphatase levels (r2 = 0.247).     

Total Thyroidectomy or Thyroid Lobectomy in Patients with Low-risk Differentiated Thyroid Cancer: Surgical Decision Analysis of a Controversy Using a Mathematical Model

There is a general consensus that total or near-total thyroidectomy is the optimal treatment for patients with high risk differentiated thyroid cancer (DTC), but the optimal extent of thyroidectomy in patients with low risk DTC continues to be controversial. To determine the optimal extent of thyroidectomy in patients with low risk DTC, we used decision analysis to compare the trade-offs of total thyroidectomy (TT) to thyroid lobectomy (TL). The decision analysis model included the probabilities of thyroidectomy complications, risk of DTC recurrence, and death from DTC. This information was obtained from the literature and from outcome data for patients with low risk DTC from our institution. In addition, the concept of utilities was used in the analysis. To determine the utility of each health outcome state (thyroidectomy complication, DTC recurrence, and DTC mortality for low risk patients) a survey was conducted. Overall, prospective patients viewed DTC recurrence as less desirable than thyroidectomy complication. The utilities assigned by the survey participants varied over a wide range, with 61.5% of the individuals viewing the occurrence of a thyroidectomy complication as better than DTC recurrence. At baseline utilities and probabilities, TT had a higher expected utility than TL. One-way sensitivity analysis varying the rates of (1) thyroidectomy complication, (2) DTC recurrence, and (3) DTC mortality over the possible range showed that complication from initial thyroidectomy was the most important factor that determined the preferred extent of thyroidectomy. TL was the preferred surgical approach only if a complication rate of > 33:1, TT/TL complication rate ratio, was assumed. When no differences in DTC recurrence between the two approaches was assumed in the model, TL had a higher expected utility using the baseline utilities of thyroidectomy complication and DTC mortality. The analysis indicates that TT in patients with low risk DTC is preferable to TL. However, TL is preferred if (1) no difference in the DTC recurrence rate between the two approaches is assumed, (2) a higher complication rate for TT is used (> 33 times higher), or (3) the utility ratio of thyroidectomy complication to DTC recurrence is < 0.8 TL. We believe this decision analysis model provides an objective approach that others can use to select the optimal extent of thyroidectomy based on patient preference of health outcome states, institution-specific outcome data for DTC recurrence or mortality, and the surgeon-specific complication rate.     

Topical corticosteroids in psoriasis: strategies for improving safety

Corticosteroids are a mainstay of topical therapy for psoriasis. While efficacious and relatively safe when used carefully, the potential for side effects, notably skin atrophy and adrenal suppression, have been associated with excesses in potency, prolonged or widespread use. The International Psoriasis Council Working Group on Topical Therapy has reviewed the efficacy and safety of topical corticosteroids and recommends strategies for safe, long‐term use of these agents.