Surgical Treatment of Hurthle Cell Tumors of the Thyroid

Hurthle cell tumors are relatively rare thyroid tumors and their management and prognosis is controversial. We retrospectively review 135 Hurthle cell adenomas and 28 Hurthle cell carcinomas of the thyroid surgically treated at our institute. No significant difference was found between the adenoma and carcinoma groups in patient age, gender, and tumor size. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of fine-needle aspiration cytology (FNAC) in detecting malignancy were 87.5%, 19.3%, 31.2%, 18.6%, and 88.0%. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of frozen section in detecting malignancy of the thyroid gland were 40.0%, 100.0%, 92.9%, 100.0%, and 92.0%. Most of the adenomas were treated with procedures no less invasive than lobectomy/isthmusectomy. Meanwhile, most of the carcinoma patients underwent total thyroidectomy. Operative morbidity occurred in six patients (3.8%), including transient recurrent laryngeal nerve palsy in three patients, damage to the external branch of the superior laryngeal nerve in two patients, and transient hypocalcemia in one patient. No recurrence of Hurthle cell adenomas was noted. Five adenoma patients died of causes unrelated to their Hurthle cell tumors, but no carcinoma patients died during the follow-up period. In conclusion, clinical factors and FNAC are not helpful in the differentiation between adenoma and carcinoma. Unilateral Hurthle cell adenoma can be treated by lobectomy/isthmusectomy, and Hurthle cell carcinoma can be treated by total thyroidectomy with minimal operative morbidity.     

手术治疗单侧喉返神经麻痹的甲状腺肿瘤

目的分析术前单侧喉返神经麻痹的甲状腺肿瘤患者的临床、病理特点,探讨合理处理受侵喉返神经的方法。方法回顾分析2004年5月～2008年12月收治的2174例甲状腺肿瘤患者的临床资料,其中19例术前诊断单侧喉返神经麻痹,包括结节性甲状腺肿2例,甲状腺恶性肿瘤17例。13例行根治性切除手术,包括双侧甲状腺切除＋颈淋巴结清除术12例,双侧甲状腺切除＋全喉切除术1例,其中6例保留喉返神经,1例切除受侵段神经后予以吻合,另6例切除病变神经;4例行姑息性切除,患侧喉返神经均切除;2例结节性甲状腺肿患者行双侧甲状腺全切除术,喉返神经保护。结果19例患者均无围手术期死亡病例。淋巴结转移者10例。19例均获随访,时间平均64（37～91）月。2例结节性甲状腺肿和6例甲状腺癌术中保留喉返神经者,术后声音改善明显,另1例健侧代偿。6例切除神经者和4例姑息性手术切除喉返神经者术后声音无改善。结论术中探明喉返神经受肿瘤侵犯程度,尽可能保留神经,可以改善患者生活质量,取得较满意治疗效果。     

Molecular Phenotyping of Thyroid Tumors Identifies a Marker Panel for Differentiated Thyroid Cancer Diagnosis

Background  Currently, a large proportion of individuals undergo thyroidectomy as a diagnostic procedure for cancer. The objective of this work was to evaluate the molecular phenotype of differentiated thyroid cancer (DTC) and benign thyroid lesions to identify molecular markers that allow for accurate thyroid cancer diagnosis. Methods  Tissue microarrays consisting of 100 benign and 105 malignant thyroid lesions, plus 24 lymph node samples, were stained for a panel of 57 molecular markers. Significant associations between marker staining and tumor pathology (DTC versus benign) were determined using contingency table and Mann-Whitney U (MU) tests. A Random Forests classifier algorithm was also used to identify useful/important molecular classifiers. Results  Of the 57 diagnostic markers evaluated 35 (61%) were significantly associated with a DTC diagnosis after multiple testing correction. Of these, in DTC compared with benign thyroid tumors, 8 markers were downregulated and 27 upregulated. The most significant markers for DTC diagnosis were: Galectin-3, Cytokeratin 19, Vascular Endothelial Growth Factor, Androgen Receptor, p16, Aurora-A, and HBME-1. Using the entire molecular marker panel, a Random Forests algorithm was able to classify tumors as DTC or benign with an estimated sensitivity of 87.9%, specificity of 94.0%, and an accuracy of 91.0%. Conclusion  Evaluation of the DTC and benign thyroid tumor molecular phenotype has allowed for identification of a marker panel, composed of both established and novel markers, useful for thyroid cancer diagnosis. These results suggest that further study of the molecular profile of thyroid tumors is warranted, and a diagnostic molecular marker panel may potentially improve patient selection for thyroid surgery.     

Growth Regulation of Thyroid and Thyroid Tumors in Humans

In a study of growth regulation of the human thyroid gland and thyroid tumors we investigated the impact of iodine and that of the thyroid-specific growth-stimulating hormone TSH. Further studies included locally active growth factors such as the epidermal growth factor, insulin-like growth factor, and tissue transforming growth factors alpha and beta. In addition to studies of growth regulation by the various growth factors in mostly normal thyrocytes, the impact of tumor-specific mutations in oncogenes and tumor-suppressor genes was investigated. The results demonstrated distinct changes in tissue specificity and sensitivity to external stimuli. This rather complex view on thyrocyte growth regulation may be confusing, but it describes the biologic reality more precisely. Increased knowledge of the regulatory processes may lead to the development of new tumor- and patient-specific therapeutic approaches, especially for preventing benign goiter recurrence and for treating follicular and papillary thyroid cancers.     

Role of Fine-Needle Aspiration Biopsy and Frozen Section Analysis in the Surgical Management of Thyroid Tumors

Introduction:The role of fine-needle aspiration (FNA) and frozen section (FS) in the management of thyroid neoplasms continues to generate considerable controversy. We reviewed our recent experience to determine the clinical utility of FNA and FS in our surgical management and intraoperative decision-making.Methods:All patients who had operations for thyroid disease between January 1996 and June 1999 were identified in our prospective database. Completion and incidental thyroidectomies were excluded. Data obtained from the pathology files included FNA, FS, and the final histologic diagnosis.Results:Five hundred sixty-four patients, including 409 women (73%), with a median age of 50 years (range, 6–94) were identified, of whom 293 (52%) had cancer diagnosed on permanent sections. Three hundred twenty-nine patients (58%) had evaluable FNA, of which 91 (28%) were benign, 94 were malignant (28%), and 144 (44%) were suspicious (46% of these were malignant on final). Frozen section was performed in 397 (70%) patients; of these samples, 170 (43%) were found to be benign, 106 (27%) were malignant, and 121 (30%) were deferred (46% malignant on final). Fine-needle aspiration positively identified 51% of confirmed malignancies; 13% of patients with malignancy had a benign FNA result. Total thyroidectomy was performed in 64% of malignant tumors and 29% of benign thyroid disease (P < .001). Logistic regression revealed no association of extent of surgery with FNA results. A frozen section positive for malignancy was associated with total thyroidectomy (P < .001, RR 6 [CI 3–10]), and a negative frozen section report was associated with lobectomy (P < .05, RR 0.5 [CI 0.3–0.96]). Frozen sections results altered the preoperative plan in only 29 patients (5%).Conclusion:Results of preoperative FNA had no direct impact on the selection of the surgical procedure in this selected cohort. Intraoperative FS added very little to surgical management. The majority of thyroid operations at this institution are planned and performed based on known prognostic factors and intraoperative findings.Presented at the 53rd annual meeting of the Society of Surgical Oncology, New Orleans, Louisiana, March 16–19, 2000     

Immunohistochemical Diagnosis of Thyroid Tumors

Recent insight into the molecular mechanisms of thyroid carcinogenesis has led to studies involving newly directed antibodies. With the introduction of new molecular targeted therapies, these antibodies may represent useful predictors of therapeutic response in tumors unresponsive to radioiodine or insensitive to conventional antitumor therapies. These markers complement the development of markers that are able to discern benign from malignant entities, including hyalinizing trabecular tumors, oncocytic neoplasms, and follicular variant of papillary thyroid carcinoma. The use of antibodies directed to proteins generated by mutated genes may represent a cost-effective method for diagnosing and managing patients affected by thyroid tumors.     

Familial Papillary Thyroid Carcinoma: Genetics, Criteria for Diagnosis, Clinical Features, and Surgical Treatment

Hereditable predisposition to papillary thyroid carcinoma (PTC) and multinodular goiter (MNG) without evidence of an association with other malignancies as a distinct entity was recognized only recently. A meta-review of the literature on familial PTC (FPTC) was undertaken, and characteristics of families with frequent occurrence of PTC or MNG (or both) were summarized. A database on thyroid cancer patients maintained in our institution was searched for potential FPTC families. Clinical examinations were performed in 6 of 12 Hannover kindreds identified, and blood samples of all family members were collected for genetic analyses. Clinical presentations and histopathologic features of the FPTC cases were compiled. Based on the FPTC meta-review and own experience, predictive criteria to identify families at risk were developed: Exclusion criteria were previous radiation exposure and coincidence with neoplasia syndromes. Primary criteria for susceptibility to FPTC are (1) PTC in two or more first-degree relatives and (2) MNG in at least three first- or second-degree relatives of a PTC patient. Secondary criteria are diagnosis in a patient younger than 33 years, multifocal or bilateral PTC, organ-exceeding tumor growth (T4), metastasis (N1, M1), and familial accumulation of adolescent-onset thyroid disease. A hereditary predisposition to PTC is considered if both primary criteria or one primary criterion plus three secondary criteria are present. Family history-taking is recommended for all PTC patients to identify FPTC kindreds at risk. Blood relatives of FPTC index patients who harbor MNG should undergo thorough and regular clinical screening. Suspicious lesions should prompt early surgical intervention.     

腔镜下甲状腺手术方法的技术探讨

目的探讨腔镜下甲状腺手术的技巧及临床应用价值。方法回顾性总结40例腔镜下甲状腺手术,其中甲状腺腺瘤23例,结节性甲状腺肿16例,甲状腺癌1例。结果 38例腔镜手术获得成功,有2例分别因肿瘤直径达4.0 cm和快速切片为甲状腺乳头状癌而中转开放手术。术后1例发生轻度声嘶1,月后恢复;3例颈前皮肤淤斑7,d后自愈;2例发生伤口脂肪液化;未发生永久声嘶及饮水呛咳,无四肢麻木、抽搐等并发症。结论腔镜下甲状腺瘤切除术具有创伤小、恢复快、美容效果好的优点。     

The Impact of Molecular Testing on the Surgical Management of Patients with Thyroid Nodules

Background

The use of molecular tests as an adjunct to FNA diagnosis of thyroid nodules has been increasing. However, the true impact of these tests on surgical practice has not been demonstrated. This study examines the usefulness of molecular testing on surgical management decisions in patients referred for thyroid surgery at a tertiary care center.

Methods

Clinical information was collected from patients who presented to Johns Hopkins Hospital for surgical consultation regarding a thyroid nodule and who underwent molecular testing between August 2009 and March 2013. Tests included an RNA-based gene expression classifier, a DNA-based somatic mutation panel, BRAF, NRAS, and/or RET/PTC translocation. A surgical management algorithm was created by consensus of four thyroid surgeons. Postsurgical pathology analysis in each case was then used to judge the appropriateness of the surgical decision-making and the usefulness of preoperative molecular testing, in guiding surgical planning.

Results

Of 114 patients assessed by preoperative molecular testing, 87 (72 %) underwent surgery. Surgical management was altered in nine (10 %) patients on the basis of molecular testing. Of these, surgical management change was appropriate, relative to the postoperative pathology analysis, for three patients and inappropriate for six patients.

Conclusions

In this study, molecular testing of thyroid nodule did not alter the surgical management of the majority of patients with thyroid nodules. These results indicate that molecular testing may be overused in patients for whom the results would not change surgical management. Furthermore, our data question the usefulness of the molecular tests examined in guiding preoperative surgical decision-making.     

Surgical Decision-making in Immediate Breast Reconstruction

Background

Immediate breast reconstruction has been accepted as safe and practical after mastectomy for breast cancer; factors limiting its use are patient comorbidities and potential complications caused by adjuvant therapies (particularly radiotherapy). The aim of this study was to identify factors considered by surgeons when deciding whether to offer immediate breast reconstruction, to determine the surgeon’s accuracy when predicting postmastectomy radiotherapy, and to assess the impact of premastectomy investigations on decision-making.

Methods

Four oncoplastic breast surgeons completed a survey for every mastectomy performed over an 11-month period. On the survey form they indicated reason for mastectomy, investigations available premastectomy, if they offered immediate reconstruction, and if not offered, why they did not offer it. Data on adjuvant therapies employed was also collected.

Results

A total of 157 women underwent mastectomy during the study period. Seventy-six (48.4%) were offered immediate reconstruction and 36 (22.9%) accepted. The most common reason for not offering immediate reconstruction was the predicted need for postmastectomy radiotherapy (56.8%). Of the 76 patients offered immediate reconstruction, 9 went onto be offered postmastectomy radiotherapy (11.8%). Decision-making was no more accurate in those women who had MRI, axillary staging, or excisional pathology available premastectomy.

Conclusions

The most common reason for not offering immediate breast reconstruction is the need for postmastectomy radiotherapy and surgeons are able to predict this accurately. The addition of invasive and expensive staging investigations premastectomy does not appear to assist this decision-making process. Despite careful patient selection, a high rate of immediate reconstruction may be maintained.     

甲状腺结节手术适应证和术式选择

甲状腺结节的手术适应证和术式选择是临床外科治疗中的常见问题.随着体检的普及和检查手段(超声和细针穿刺细胞学)的不断完善与提高,在各级医院甲状腺结节的检出率和手术量不断攀升,近年来与手术相关的医疗纠纷呈逐年增长趋势,应引起临床外科医生足够重视.     

Integrating Morphology and Genetics in the Diagnosis of Cartilage Tumors

Cartilage-forming tumors of bone are a heterogeneous group of tumors with different molecular mechanisms involved. Enchondromas are benign hyaline cartilage–forming tumors of medullary bone caused by mutations in IDH1 or IDH2. Osteochondromas are benign cartilage-capped bony projections at the surface of bone. IDH mutations are also found in dedifferentiated and periosteal chondrosarcoma. A recurrent HEY1-NCOA2 fusion characterizes mesenchymal chondrosarcoma. Molecular changes are increasingly used to improve diagnostic accuracy in chondrosarcomas. Detection of IDH mutations or HEY1-NCOA2 fusions has already proved their immense value, especially on small biopsy specimens or in case of unusual presentation.     

Surgical Management of Carotid Body Tumors

Background  Carotid body tumors (CBT) should be considered when evaluating every lateral neck mass. Methods  A retrospective study was conducted of 52 patients with 57 CBT. The surgical approach and complications were reviewed. All patients were operated on without preoperative embolization. Results  Multifocal paraganglioma (PG) were detected in six cases. A succinate dehydrogenase subunit D (SDHD) mutation was discovered in four patients. Vascular peroperative complication occurred in one case. Vascular reconstruction was decided peroperatively in five cases (8.8%). Vascular reconstruction was 0% for Shamblin 1 or 2 tumors, but 28.5% for Shamblin 3. A postoperative nerve paresis was reported in 24 patients (42.1%) and vagal nerve paralysis persisted in four cases (7.01%). The rate of serious complications, e.g., permanent nerve palsy, preoperative and postoperative complications, was 14.03%; it was 2.3% for Shamblin 1 or 2 tumors and 35.7% for Shamblin 3. One patient had malignant PG with node metastasis and was not referred for radiotherapy. No recurrence or metastasis was reported after 6-year follow-up. Conclusion  Early surgical treatment is recommended in almost all patients after preoperative evaluation and detection of multifocal tumors. Surgical excision of small tumors was safe and without complication, but resection of Shamblin 3 tumors can be challenging. Routine preoperative embolization of carotid body paragangliomas is not required.     

胃间质瘤的手术治疗

目的探讨胃间质瘤的手术治疗方法及临床病理特点。方法回顾性分析经手术治疗的78例胃间质瘤患者的临床和病理资料,其中男34例,女44例。手术完全切除76例,其中胃楔形切除39例,远端胃大部切除术17例,近端胃大部切除术20例;姑息性切除2例。结果肿瘤平均直径5.5cm,其中<5cm者39例,5~10cm者27例,>10cm者12例。病变位于胃窦部12例,胃体部30例,胃底部36例。胃周淋巴结转移2例(2.6%)。免疫组化结果:CD117阳性74例(94.9%),CD34阳性61例(78.2%),SMA阳性29例(37.2%),Desmin阳性8例(10.3%),S-100阳性8例(10.3%)。72例(92.3%)获随访,平均56.1(3~168)个月,术后5年生存率为70.3%,术后复发转移11例(15.3%),术后复发转移者再次手术治疗6例,再次手术切除可延长患者生命。结论胃间质瘤的治疗以手术为主,术中应注意完整切除和防止肿瘤破裂。