Radiation-Induced Well-Differentiated Thyroid Cancer: Disease Characteristics and Survival.

BACKGROUND: Radiation exposure is a well-known risk factor for well-differentiated thyroid cancer (WDTC). However, disease characteristics, optimal treatment, time from exposure to disease appearance, and the effect of age at initial exposure on the outcome have yet to be determined. OBJECTIVES: To identify the characteristics of radiation-induced thyroid carcinoma. METHODS: We retrieved the charts of all patients previously exposed to radiation who were diagnosed with WDTC between the years 1985 and 2013 in a tertiary referral center. RESULTS: Forty-four patients were reviewed. Median time from radiation exposure to diagnosis was 23 years. These patients had higher rates of aerodigestive symptoms and distant metastases on presentation than seen in non-radiated patients. Patients who were exposed to radiation before age 15 years tended to develop the disease at a younger age but had a longer latency period (34.7 ± 15.3 vs. 16.3 ± 10 years, P < 0.001) and none had significantly higher rates of vocal cord palsy, hoarseness on presentation, or aggressive variants on histology compared to patients exposed to radiation at an older age. Disease-specific survival (DSS) was the same for both groups and were similar to that seen in the general population (95% 20 year DSS). CONCLUSIONS: Radiation-induced thyroid cancer has a more aggressive presentation and the age at exposure affects the presentation of disease. Nonetheless, appropriate treatment leads to a favorable prognosis.

Pediatric Thyroid Cancer: Postoperative Classifications and Response to Initial Therapy as Prognostic Factors.

CONTEXT: Prognostic factors for pediatric differentiated thyroid cancer (DTC) are not well established. OBJECTIVE: The objective of the study was to retrospectively compare the postoperative risk-stratification systems: American Thyroid Association (ATA) risk categories, Schneider Children's Medical Center of Israel (SCMCI) score, and the response to initial therapy as predictors for disease outcome. PATIENTS AND METHODS: Fifty-four DTC patients, median age at diagnosis 13.9 years (range 1.9-17 y), followed up for a median of 8.8 years (range 2.6-20.5 y) were stratified into prepubertal (n = 9), pubertal (n = 25), and postpubertal (n = 20) groups. All patients underwent total/near-total thyroidectomy; 48 received radioiodine therapy. The extent of DTC was evaluated by applying the ATA risk categories and the novel SCMCI score. Postoperative risk stratifications (low/intermediate/high) were determined using histopathological, laboratory, and imaging findings. Response to initial therapy (complete/acceptable/incomplete) was based on stimulated thyroglobulin and imaging results during the first 2 years of follow-up. RESULTS: The risk for recurrent/persistent disease, as assessed by the postoperative ATA risk-stratification system and the SCMCI score and by the response to initial therapy, was higher in the prepubertal group (P < .001, P = .002, and P = .02, respectively). Outcome prediction by the risk-stratification systems was applicable: ATA risk categories, P = .014, R(2) = 0.247, predictive ability 80.4%; SCMCI score, P < .001, R(2) = 0.435, predictive ability 86.3%; and response to initial therapy stratification, P < .001, R(2) = 0.789, predictive ability 96.1%. The proportion of variance explained by the ATA risk categories (0.25), SCMCI score (0.44), and response to initial therapy (0.79) indicated that the latter was the most precise predictor and that the SCMCI score reflected the disease outcome better than ATA risk categories. CONCLUSIONS: Our data confirm that the postoperative pediatric ATA stratification system and the novel SCMCI score are suitable for predicting the risk of recurrent/persistent disease in this population. The response to initial therapy classification performed 1-2 years after the initial therapy may be more appropriate for guiding surveillance recommendations.

Size discrepancy between sonographic and pathological evaluation of solitary papillary thyroid carcinoma.

BACKGROUND: Sonographic size of suspicious thyroid lesions is an essential parameter in the evaluation of thyroid nodules, determining the need for needle biopsy and has impact on the extent of surgery. Limited data is available on the correlation between the size of the thyroid nodule on sonography and the actual size measured during histological examination. The aim of the present study was to compare these two modalities and to discuss the potential clinical implications of the findings in the study population. METHODS: The database of Rabin Medical Center was reviewed for all patients with histologically proven papillary carcinoma of the thyroid treated by thyroid surgery between 2005 and 2010. RESULTS: 292 patients with papillary thyroid carcinoma were included. The mean sonographic size of the nodule was 2.19 ± 1.15 cm. The mean pathological diameter was 1.69 ± 1.09 cm. Discrepancies between tumor histological diameter and the sonographically measurement were more prominent in tumors larger than 1.5 cm. Nonetheless, 18.8% of thyroid nodules that were measured by US as larger than 1cm, were found to be smaller than 1cm on final pathology. Similarly, 7.2% of nodules evaluated by sonography were determined as being larger than 4 cm, while their definitive size was smaller than 4 cm. CONCLUSIONS: We noted a significant discrepancy between the preoperative sonographic and the pathologic size measurements for papillary thyroid carcinoma. The sonographic evaluation misclassifies both patients with small and large thyroid tumors, and consequently exposes them to unnecessary workup and more extensive operation. This discrepancy between the ultrasound findings and actual tumor size should be taken into account in clinical practice and help guide the evaluation and treatment of patients with thyroid nodules.

Thyroid gland involvement in advanced laryngeal cancer: association with clinical and pathologic characteristics.

BACKGROUND: Indications for thyroidectomy during laryngectomy are controversial. We examined whether clinicopathologic features can predict thyroid gland involvement, and the prognostic effect of thyroid gland involvement in patients undergoing total laryngectomy. METHODS: The study set out to review preoperative assessment, operation findings, pathologic findings, and follow-up data. RESULTS: Thyroid gland involvement was found in 11 of 53 patients (21%) undergoing total laryngectomy and thyroidectomy. Preoperative work-up failed to predict thyroid gland involvement. Thyroid gland involvement was associated with salvage procedures (p = .025), paratracheal metastases (p = .003), and poor overall survival (hazard ratio = 2.74, p = .008). CONCLUSIONS: Thyroid gland involvement in patients undergoing total laryngectomy is frequent and is associated with poor prognosis. Preoperative assessment failed to predict thyroid gland involvement. We believe that thyroidectomy should be considered in cases with paratracheal lymphatic spread irrespective of tumor location within the larynx.

Early death from papillary thyroid carcinoma.

PURPOSE: The natural history of papillary thyroid carcinoma (PTC) is characterized by a slow growth rate and an excellent prognosis at 20 and 30 years. However, there is a small subset of patients with poorer outcome. METHODS: Twenty patients who died of PTC within 10 years of diagnosis were studied to identify prognostic indicators and biological markers of early death. Findings were statistically compared with a previous review of all patients with PTC treated in the same institute and studies in the literature. RESULTS: The study group included 6 men and 14 women with a mean age of 65 years at diagnosis. Average tumor size was 3.6 cm; 16 patients had extracapsular extension. All tumor samples studied histologically stained poorly for p53, Ki67, and CD34. Regional metastases were present in half the patients, and distal metastases in all. All patients had an advanced disease stage (Tumor, Node, Metastases classification), and only 4 had a low score on the Metastases, Age, Completeness of resection, local Invasion, tumor Size risk stratification. Analysis of the findings against data in the literature for the whole population of patients with PTC, who had a considerably better survival (<8% mortality within 8-15 years vs 100% within 10 years in our sample), yielded significant differences for rates of extrathyroidal extension (P = .0001), regional metastases (P = .016), and distant metastases (P = .0001). CONCLUSION: Extrathyroid extension, late regional metastases, and distant metastases may be risk factors for early death from PTC.

Immunocompetency in children with recurrent respiratory papillomatosis: prospective study.

OBJECTIVES: We sought to investigate the immunologic status of children with recurrent respiratory papillomatosis and to evaluate possible correlations between the patients' immunocompetency and the clinical course of the disease. METHODS: Twenty children with recurrent respiratory papillomatosis underwent immunologic evaluation every 6 months for determination of complete blood count, serum immunoglobulin levels, lymphocyte subpopulations, lymphocyte response to mitogen stimulation, and natural killer cell function. The patients were observed prospectively (42 to 56 months), and their clinical course was recorded. The findings were compared with those in healthy age-matched controls. RESULTS: The CD4/CD8 ratio and the lymphocyte response to mitogen stimulation were significantly reduced in the study children compared to normal controls. A reduction in lymphocyte response to mitogen stimulation was significantly correlated to a high number of papilloma sites and more frequent recurrences. Abnormal natural killer cell function was significantly correlated to more frequent recurrences. CONCLUSIONS: A compromised cell-mediated immune response may be associated with repeated or persistent human papillomavirus infections, leading to the development of recurrent respiratory papillomatosis. Patients with an aggressive clinical course may have underlying cell-mediated immunodeficiency. Long-term prospective investigations are needed to establish the role of the host immune system in the pathogenesis of recurrent respiratory papillomatosis in children.

Endoscopic adenoidectomy in children with submucosal cleft palate.

OBJECTIVE: To determine the safety and effectiveness of endoscopic partial adenoidectomy for the treatment of nasal obstruction in children with submucosal cleft palate. METHODS: The medical files of children with symptoms of nasal obstruction and submucosal cleft palate who underwent partial transnasal endoscopic adenoidectomy from January 1993 to December 2003 were reviewed. Operative complications, relief of nasal obstruction, presence of postoperative velopharyngeal insufficiency were recorded. RESULTS: There were no operative complications. All the children had relief of nasal obstruction. Velopharyngeal insufficiency was not observed during the postoperative follow-up. CONCLUSIONS: Endoscopic partial adenoidectomy is a safe and effective procedure for the treatment of nasal obstruction in children with submucosal cleft palate.

Invasive well-differentiated thyroid carcinoma: effect of treatment modalities on outcome.

OBJECTIVE: Well-differentiated thyroid carcinoma is considered an indolent malignant disease. Although rare, extrathyroidal invasion is associated with a worse prognosis and increased risk of morbidity. Management remains controversial, with some authors advocating conservative treatment with preservation of midline structures and others, aggressive extensive en bloc resection. The aim of this study was to report our 40-year experience with invasive thyroid carcinoma, with emphasis on the clinical characteristics and the effect of different treatment modalities on survival. STUDY DESIGN AND SETTING: A retrospective study including a file review of 1,200 patients with a diagnosis of well-differentiated thyroid carcinoma of whom 49 (5%) showed involvement of an adjacent structure (larynx, trachea and esophagus) (study group). Type of surgery, radiation treatment, radioiodine treatment, and patient demographics were evaluated. RESULTS: Compared to the rest of the patients, the study group was characterized by a higher rate of male patients (39% vs 25%), and older average age (58 vs 45 years). Average size of the primary tumor was 3.7 cm. Sixteen patients underwent radical surgery and 33 conservative surgery followed by radioiodine treatment. Five-year survival and recurrence rates for the whole group were 78% and 52%, respectively. The only statistically significant factor for survival was large tumor size. Distant metastases developed in 46% of patients, all in the lungs. Ten of 14 deaths were due to distant metastases. External radiation, used in 52% of the patients, was associated with worse prognosis. CONCLUSION: Conservative procedures followed by radioiodine treatment are associated with similar survival rates as aggressive techniques, with less perioperative mortality and lower overall morbidity. SIGNIFICANCE: This study provides further evidence that in cases of invasive thyroid tumors the extent of the primary surgery seems to have no influence on survival. EBM RATING: C-4.

Minimally invasive procedure for resection of a parathyroid adenoma: the role of preoperative high-resolution ultrasonography.

PURPOSE: Solitary adenoma of the parathyroid is the major cause of primary hyperparathyroidism. Many centers advocate a minimally invasive surgical approach, wherein the surgeon explores only a localized area of the neck according to the preoperative imaging evaluation, and the adenoma is resected without histological sampling from the other parathyroid glands. The aim of this study was to evaluate the ability of high-resolution ultrasonography (US) to localize adenomas preoperatively and thereby aid in patient selection for minimal procedures. METHODS: We reviewed the medical records of 77 consecutive patients who underwent resection of a parathyroid adenoma following ultrasonographic imaging between 2001 and 2002, and we assessed the accuracy of the preoperative localization of the adenomas as well as the efficacy of the minimally invasive procedure. RESULTS: US correctly localized the adenoma to a specific quadrant of the neck in 87% of the cases and to a specific side of the neck in 94%. Overall, US sensitivity was 89%, with a positive predictive value of 98%. Its sensitivity was not reduced by the presence of nodular disease of the thyroid gland. Success rate for the minimal procedure was 98% (50/51 patients). CONCLUSIONS: US performed by a skilled operator is a reliable tool for adenoma localization prior to minimally invasive parathyroidectomy. If the US findings are inconclusive, a Tc-sestamibi scan should be used. If there is a high clinical suspicion of adenoma in the presence of negative imaging studies, bilateral neck exploration should be performed.

Sentinel node guided surgery for melanoma in the head and neck region.

Sentinel lymph node biopsy may be more technically challenging for melanoma of the head and neck compared with other locations because of the complex lymphatic drainage patterns. This study demonstrates the value of sentinel node biopsy for head and neck melanoma, and highlights the associated difficulties. Thirty consecutive patients with primary cutaneous melanoma of the head and neck (n=26) or draining to the neck (n=4) underwent preoperative lymphoscintigraphy. This was followed by intraoperative lymphatic mapping using blue dye alone (n=8) or in combination with a hand-held gamma probe (n=22) and sentinel lymphadenectomy. Modified neck dissection was performed in all patients with positive sentinel nodes. The study population had a male predominance (73%). Most lesions were nodular and were not ulcerated. In two patients (6.2%) preoperative lymphoscintigraphy failed to demonstrate the draining nodes, which were retrieved by surgery, and in two patients (6.2%) the sentinel node was not found at surgery despite preoperative visualization. Overall, the sentinel node was identified 93% of the time: in seven out of eight cases (88%) using blue dye alone, and in 21 out of 22 cases (96%) using a combination of blue dye and gamma probe. Four out of 28 basins were deemed positive for metastases. Twenty-three of the 24 patients with negative sentinel nodes were free of disease at a median of 31 months (range 9-91 months). There was one false-negative case salvaged by surgery. The sentinel node technique is technically demanding but advantageous for most patients with head and neck melanoma. Identification rates seem to be better when preoperative lymphoscintigraphy is combined with intraoperative blue dye mapping and a hand-held gamma probe. The relative contribution of each component could not be determined.

Immunohistochemical profile and treatment of uncommon types of thyroid carcinomas.

The distinction of uncommon types of thyroid carcinomas is important, because their treatment and prognosis differ. The aim of this study was to describe retrospectively the immunohistochemical profile of uncommon types of thyroid carcinomas and mode of treatment. Of the 1194 patients with thyroid carcinomas treated in Rabin Medical Center from 1954 to 2001, 153 were uncommon types (not papillary or follicular carcinomas). Specimens from archival tissue obtained from thyroidectomies in all these cases were revised and immunohistochemically examined. Anaplastic carcinomas (n=59) were positive for high molecular weight cytokeratin (CK HMW), low molecular molecular weight cytokeratin (CK LMW), cytokeratin (CK) 7, CK 8 and 18, thymoglobulin, EMA and vimentin; medullary carcinomas (n=39) were positive for CK LMW, CK 19, CK 8 and 18, CK 10, CK 7, carcinoembryonic antigen (CEA) and calcitonin; Hurthle cell carcinomas (n=30) for CK LMW, CK 19, CK 8 and 18, thyroglobulin, epithelial membrane antigen (EMA) and CEA; squamous cell carcinomas (SCC) (n=12) for CK HMW and cytokeratin total (CKs); lymphomas (n=7) for leukocyte common antigen (LCA) and B-cells (CD 20), and clear cell carcinomas (n=6) for CK LMW, CEA and thyroglobulin. Use of an immunohistochemical panel has diagnostic value in the differentiation of uncommon types of thyroid carcinoma, which help to plan the best mode of treatment.