Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma

The histopathologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) can be difficult. Recent reports have suggested that this neoplasm may be frequently overdiagnosed by pathologists. We examined the observer variation in the diagnosis of FVPCA in 87 tumors by 10 experienced thyroid pathologists. The criteria that the reviewers considered most helpful for making a diagnosis of FVPCA were also assessed. A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39%. In this series, 24.1% of the patients had metastatic disease (n = 21). In the cases with metastatic disease, a diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 66.7%, and 7 of the reviewers made a diagnosis of FVPCA with a cumulative frequency of 100%. The most important criteria used to diagnose FVPCA included the presence of cytoplasmic invaginations into the nucleus (pseudo-inclusions), abundant nuclear grooves, and ground glass nuclei. These results suggest that although the diagnosis of FVPCA is variable even among experienced thyroid pathologists, most reviewers agreed on this diagnosis for patients with metastatic disease. The use of well-defined histopathologic features should improve the consistency in diagnosing FVPCA. Since most cases with metastatic disease had obvious invasion, caution should be used in making a diagnosis of FVPCA in the absence of the major histopathologic features or clear-cut invasive growth.     

CD10在甲状腺疾病中的表达及意义

目的研究CD10在甲状腺疾病中的表达及意义。方法收集70例甲状腺良、恶性病变组织,其中15例滤泡性腺瘤、15例腺瘤性甲状腺肿、30例乳头状癌和10例滤泡性癌。采用免疫组织化学的方法检测CD10在上述病变中的表达。结果9例滤泡型乳头状癌中,7例表达CD10,CD10阳性率为77％。10例滤泡性癌中,8例表达CD10,阳性率为80％。而在滤泡性腺瘤和腺瘤性甲状腺肿及21例普通型乳头状癌组织中CD10均不表达。CD10在滤泡型乳头状癌和滤泡性癌中的阳性率显著高于滤泡性腺瘤和腺瘤性甲状腺肿中的阳性率（P〈0．01）。结论对CD10表达的检测有助于对甲状腺滤泡性癌和滤泡型乳头状癌的诊断。     

Measurement of cellular DNA content in thyroid tumors by the flow cytometer

Cellular DNA contents measured by flow cytometer were analysed in relation to histopathological classification and clinicopathological findings in 94 patients with thyroid tumors. The DNA determination was carried out on both tumor tissues and surrounding thyroid tissues. As an indicator of tumor growth, proliferative index (PI) and DNA index were calculated from DNA histograms. The PI value (mean +/- SD) was 32.5 in medullary carcinoma, 31.3 +/- 10.2 in follicular carcinoma, 28.2 +/- 6.2 in papillary carcinoma, 21.6 +/- 4.4 in follicular adenoma, and 20.6 +/- 4.4 in adenomatous goiter, respectively, whereas the value in normal thyroid tissues was 4.1 +/- 2.2. PI values in the surrounding thyroid tissues in cases of follicular and papillary carcinomas were significantly (p less than 0.01) lower than those of the corresponding cancer tissues, but they were higher than that of the normal tissues. The DNA index and frequencies of aneuploidy were 1.15 and 50.0% in medullary carcinoma; 1.25 +/- 0.27 and 66.7% in follicular carcinoma; 1.19 +/- 0.25 and 64.2% in papillary carcinoma; 1.01 +/- 0.04 and 9.3% in follicular adenoma; and 1.00 +/- 0.00% in adenomatous goiter. The result implies that PI value and DNA index are relatively correlated with clinicopathological criteria of malignancy of individual thyroid tumors, and they may become a putative tool for determination of the biological malignancy.     

CD10表达在甲状腺滤泡性癌和滤泡型乳头状癌诊断中的作用

目的研究CD10表达在甲状腺滤泡性癌和滤泡型乳头状癌诊断中的作用。方法收集70例甲状腺良、恶性病变组织，其中包括15例滤泡性腺瘤、15例腺瘤性甲状腺肿、30例乳头状癌（包括9例滤泡型乳头状癌）和10例滤泡性癌，采用免疫组织化学方法检测CD10在上述组织中的表达。结果9例滤泡型乳头状癌中，7例表达CD10（77．8％），10例滤泡性癌中8例表达CD10（80．0％）；CD10在非滤泡型乳头状癌、滤泡性腺瘤、腺瘤性甲状腺肿和正常甲状腺组织中均不表达。结论对CD10表达的检测有助于对甲状腺滤泡性癌和滤泡型乳头状癌的诊断。     

Hyperplastic ductal and lobular lesions and carcinomas in situ of the breast: reproducibility of current diagnostic criteria among community- and academic-based pathologists

Due to the increased efforts of early detection and biopsy of breast lesions, the number of cases with hyperplastic and in situ lesions seen in most pathology laboratories has increased significantly. Pathologists are faced with a greater number of biopsies and a wider spectrum of lobular and ductal lesions including papillary lesions. A set of 31 randomly selected glass slides of ductal, lobular and papillary lesions (benign, borderline, and carcinomas in situ) was circulated among five community- and five academic-based pathologists (median 9 years of experience). The pathologists filled out a standard form for each case which included lesion type (ductal, lobular, or papillary) and diagnostic category (ductal, lobular, or papillary; hyperplasia or carcinoma). We compare the participants' diagnoses, their histologic criteria, and the reproducibility of the diagnoses. Kappa statistics were calculated to measure the levels of agreement among community and academic pathologists, overall for all the pathologists, and within a subgroup of eight participants reporting the use of the same diagnostic criteria (Page's). All pathologists agreed with the diagnosis of cancer in 10 cases (33%), kappa overall 0.347 (fair); with the diagnostic category of lesions in 8 cases (27%), kappa overall 0.537 (moderate); and with the lesion type in 16 cases (53%), kappa overall 0.789 (substantial). Community pathologists were more likely to interpret ductal and papillary lesions as hyperplasias than carcinomas in situ. In contrast, academic pathologists interpreted more cases as carcinomas than hyperplasias (60 versus 45). There was little to no improvement in the level of agreement observed when we considered the subgroup of pathologists using the same standardized criteria. This study demonstrates that the overall agreement in the diagnosis of carcinoma in situ of the breast remains low between pathologists using or not using standardized diagnostic criteria. Papillary and ductal lesions pose a significant problem between observers in characterizing them as benign or malignant. Current diagnostic criteria need to be modified, reemphasized, or replaced, either through the literature or with additional training to decrease interobserver variability.     

Thyroid papillary carcinoma. Pathological and philosophical controversies

An encapsulated thyroid tumor with a papillary architecture is statistically much more likely to be a hyperplastic follicular adenoma than a papillary carcinoma, for the latter are uncommonly encapsulated. Hyperfunction of such a tumor is diagnostic of an adenoma. Various histopathologic features are useful in the differential diagnosis, but these are more accurately termed guidelines than criteria. The presence of psammoma bodies, fibrovascular stalks of papillae and pale nuclear changes are probably the most reliable histopathologic features of a carcinoma. The value of needle biopsy as a diagnostic tool for the screening of thyroid nodules is emphasized. Encapsulated variants of papillary carcinoma are discussed, including the rare pure follicular variant and those intermixed with adenomatous components, suggesting the possibility that some papillary carcinomas might arise in a preexisting adenoma. When the histopathologic diagnosis is equivocal, a benign interpretation is favored since encapsulated papillary carcinomas are very low grade, have an unusually favorable prognosis, and need no further resection. The polarization in past years of clinicians into radical and conservative operative fractions is reviewed. This stemmed from different interpretations of the presence of lymph node metastases in a majority of cases and the high frequency of intraglandular microscopic dissemination of neoplasm. It is clear that biological behavior of this unusual cancer is more important than a literal interpretation of the pathologic findings as a determinant for patient management. The surgical pathologist should be mindful that he plays an important role in patient management, not only by providing a diagnosis but also by serving as a consultant to the surgeon in pathologic correlation.     

Fat-containing lesions of the thyroid gland

Thyroid lesions containing adipose tissue are rare; only scattered case reports are recorded. This study of 17 lipomatous thyroid lesions on file at the Armed Forces Institute of Pathology was undertaken to better document the full range of these abnormalities. Patient ages ranged from 11 to 75 years; nine patients were female and eight were male. Fat-containing thyroid neoplasms included seven papillary carcinomas, four adenomatoid nodules, one follicular adenoma, and one minimally invasive follicular carcinoma. Nonneoplastic conditions associated with adipose tissue included four cases of amyloid goiter, two cases of lymphocytic thyroiditis, one case of dyshormonogenetic goiter, and one case of thyroid atrophy. This study documents the presence of adipose tissue in a wider range of benign and malignant thyroid lesions than has previously been reported.     

Expression of Vascular Endothelial Growth Factor and Presence of Angiovascular Cells in Tissues from Different Thyroid Disorders

Background

Vascular endothelial growth factor (VEGF) is involved in tumor angiogenesis and other pathophysiological processes.

Materials and methods

We studied the localization of VEGF in human thyroid tissues to clarify its involvement in proliferative processes in a variety of thyroid disorders. Immunohistochemical analysis using purified rabbit polyclonal anti-human VEGF or anti-human CD34 antibody and a streptavidin–biotin peroxidase complex detection system was performed on 58 tissue specimens from 53 patients with different thyroid disorders and 5 normal thyroid glands.

Results

Vascular endothelial growth factor was not detected in normal thyroid follicular cells. However, some thyroid tumor cells expressed VEGF in the cytoplasm (papillary carcinoma, 10/18; follicular carcinoma, 1/3; medullary carcinoma, 2/2; follicular adenoma, 3/11; adenomatous goiter, 2/4). In benign follicular adenoma and adenomatous goiter, weak expression of VEGF was found in small areas of the tumor, whereas in malignant thyroid tumors, it was strongly expressed in many cells. However, VEGF was not expressed in anaplastic carcinoma, malignant lymphoma, or Graves’ disease. Angiovascular cells stained with CD34 antibody in tissues from different thyroid disorders reflected statistically significant differences in papillary carcinoma, follicular adenoma, and Graves’ disease compared with normal thyroids, and such cells showed a trend toward increases in medullary carcinoma and adenomatous goiter. In contrast, low vascularity was observed in anaplastic carcinoma, malignant lymphoma, and follicular carcinoma.

Conclusions

Because VEGF probably functions as a hypoxia-inducible angiogenic factor, overexpression of this mediator, concomitant with hypervascularity, may be induced more strongly in malignant thyroid tumors, which need more oxygen to proliferate, than in benign follicular tumors. However, neither VEGF nor CD34 was expressed in anaplastic thyroid carcinoma, which is an extremely poorly differentiated malignant tumor. CD34 but not VEGF was expressed in the hyperplastic thyroid tissues of Graves’ disease composed of nontransformed cells. Thus, the expression of VEGF concomitant with CD34 is suggested to reflect both the transformation and differentiation state of malignant tumors.     

Pathohistologic and immunohistochemical characteristics of thyroid carcinoma

Numerous pathohistologic criteria, difficulties and pitfalls in the process of diagnosing of thyroid carcinoma are discussed. Benign hyperplastic papillae may be present in colloidal cystic goiter and hyperplastic goiter. These structures are lined by cells with normochromatic nuclei and do not disturb the thyroid tissue architecture. Papillae in papillary thyroid carcinoma have cells with ground-glass, hypochromatic nuclei. Follicles inspissated in capsula of follicular or even colloidal adenoma may be evaluated as capsular invasion--diagnostic feature of follicular carcinoma. Undifferentiated thyroid carcinoma is sometimes similar to fibrosarcoma and reveal cellular pleomorphism, anaplasia and numerous foci of necrosis. Medullary thyroid carcinoma with scanty stromal amyloid, its papillary variant and carcinoid-like histologic type consist of oval cells with eosinophilic cytoplasm and dark nuclei.     

Differential expression of galectin-3 in papillary projections of malignant and non-malignant hyperplastic thyroid lesions

Galectin-3 is a a beta-galactoside binding protein recently proposed to be a promising presurgical molecular marker for distinguishing benign from malignant thyroid neoplasms. We analyzed galectin-3 expression immunohistochemically in papillary areas of hyperplastic lesions of benign thyroid tissue in comparison with malignant papillary projections of papillary thyroid carcinoma (PTC). A monoclonal antibody to galectin-3 and ABC immunohistochemical technique were used to evaluate galectin-3 expression in 26 cases of benign papillary hyperplasia (8 cases of hyperplastic adenoma, 8 cases of hyperplastic colloid goiter, 10 cases of Graves disease) in comparison with 25 cases of PTC. Immunohistochemical results showed no reactivity for galectin-3 in papillary areas of benign hyperplastic lesions. Strong cytoplasmic galectin-3 immunoreactivity was found in all 25 cases of PTC. These results show that galectin-3 expression is a feature of malignant papillary projections but not of benign papillary hyperplasia. Thus, the immunohistochemical evaluation of galectin-3 might contribute to differential diagnosis between malignant and benign thyroid lesions with papillary projections.     

Encapsulated papillary neoplasms of the thyroid. A study of 14 cases followed for a minimum of 10 years

Fourteen cases of encapsulated papillary thyroid neoplasm in which extracapsular extension was not observed and a minimum of 10 years follow-up was available are herein presented. The cases were divided into three categories: encapsulated papillary carcinomas (five cases), which had cytologic features typical of papillary thyroid carcinoma (vesicular or indented nuclei) and an entirely or predominantly thick capsule with capsular invasion; encapsulated papillary neoplasms of undetermined malignancy (seven cases), in which the cytologic features were also typical of papillary carcinoma but the capsule was predominantly thin (less than 0.1 mm thick) or was thick without capsular invasion; and follicular adenomas with papillae (two cases), which resembled follicular adenomas cytologically (rounded, stippled nuclei and Hürthle cell change) but contained a significant number of papillary structures (both cases had an entirely or predominantly thin capsule). The only evidence of malignant behavior in the entire series was a cervical lymph node metastasis in one case of encapsulated papillary carcinoma; the "encapsulated papillary neoplasms of undetermined malignancy" were so labeled because other authors have reported "encapsulated papillary carcinomas without capsular invasion" and it was therefore thought that the malignant potential of this category is as yet best considered undefined.     

Cytologic evaluation of solitary thyroid nodules

Fine-needle aspiration is a low-cost diagnostic tool with principal value in determining which patients with thyroid nodules should undergo surgery. Team work and close cooperation among endocrinologists, surgeons, and pathologists are essential for success. Cytologic criteria for diagnosis of the most frequent conditions (benign cystic lesions), Hashimoto thyroiditis and malignancies found in thyroid aspirates have been provided. The unsolved problem of the so-called "follicular" or oxyphilic lesion or neoplasia will be investigated by immunocytochemistry.     

结节性甲状腺肿合并甲状腺癌的诊治分析

目的提高结节性甲状腺肿合并甲状腺癌的诊断和治疗水平。方法回顾性分析我院近年收治的158例结节性甲状腺肿患者的临床资料,所有患者均首先采用单侧或双侧甲状腺次全切除术,术中送冰冻病理检查,根据冰冻病理结果或石蜡切片病理结果补充行患侧甲状腺叶全切＋峡部＋对侧甲状腺叶次全切除术。结果158例结节性甲状腺肿患者中,合并甲状腺癌23例,其中乳头状腺癌22例,滤泡状腺癌1例。术后随访5-12个月,1例患者出现颈部淋巴结肿大,再次行功能性颈部淋巴结清扫术。Logistic回归分析显示,判断结节性甲状腺肿合并甲状腺癌的因素中,结节个数较少与结节直径较小是结节性甲状腺肿合并甲状腺癌的危险因素。结论对某些虽然无明确症状,但发现甲状腺有较小的实性结节的结节性甲状腺肿患者应持更积极的治疗态度。     

Cytohistologic correlation of thyroid nodules

BACKGROUND: Fine-needle aspiration (FNA) is widely used as a diagnostic tool to assess thyroid nodules. This study correlates FNA cytology results with surgical pathologic findings. METHODS: All thyroidectomies performed between 1994 and 2004 were reviewed, identifying 242 patients. Data were obtained for FNA diagnosis, demographics, findings on ultrasound, and histologic findings. RESULTS: Among 89 patients with a carcinoma on FNA, 89% of cases were verified on final histopathology. Of 78 patients with "follicular lesion" on FNA, only 36% of cases were verified to be malignant at surgery. Only 13% of the 75 cases diagnosed as benign, mostly colloid nodules, on FNA were found to have a carcinoma on histopathology. CONCLUSION: A cytologic diagnosis of papillary carcinoma has a highly predictive of thyroid cancer. When dealing with follicular lesions the predictive value of FNA drops considerably. However, we found a 13% false positive result to occur in FNA declared benign lesions.     

Hyperthyroidism and concurrent thyroid malignancies

In a 17-year period 1848 patients with hyperthyroidism were operated on. Fourteen (0.76%) had a coexisting thyroid malignancy. Preoperative scintiscan and pathologic diagnoses were compared: 10 malignancies were in cold nodules, two were unidentifiable preoperatively due to small size, and two were in hot areas. Five patients had papillary cancer, four follicular, three anaplastic, and two medullary. Patients with uninodular toxic goiter had a low rate of associated malignancy (0.27%, 3/1108). In contrast, patients with multinodular toxic goiter had an incidence of 1.63% (11/676). No patient with Graves' disease (n = 64) had a carcinoma. Extensive use of fine-needle aspiration biopsy enabled preoperative diagnosis in a majority of the cases (9/14, 64%). We conclude that the incidence of coexisting thyroid malignancy and hyperthyroidism is rare in our endemic iodine-deficiency goiter area.     

结节性甲状腺肿合并甲状腺微小癌72例临床分析

目的总结结节性甲状腺肿合并甲状腺微小癌的临床特点及其诊断和治疗要点。方法回顾分析1993-01—2010-01手术治疗并病理证实的72例结节性申状腺肿合并甲状腺微小癌患者的临床资料。结果该组72例,占同期手术治疗结节性甲状腺肿患者的6.2%。术前彩超检查可疑恶性者占20.8%。术中快速冰冻检查诊断准确率为98.6%。病理类型以乳头状癌为主(93.1%)。手术方式主要是患侧腺叶+峡部切除+对侧腺叶次全/部分切除。结论结节性甲状腺肿合并甲状腺微小癌以乳头状癌为主,淋巴结转移发生率低。术中快速冰冻检查是诊断结节性甲状腺肿合并甲状腺微小癌的关键。对结节性甲状腺肿合并甲状腺微小癌不做预防性淋巴结清扫是安全的。     

Incidental carcinoma in thyroid pathology: our experience and review of the literature

The diagnosis of incidental thyroid carcinoma in patients submitted to thyroidectomy for a benign disease is quite frequent. A retrospective analysis was performed on 240 patients submitted to surgical intervention in order to establish the incidence of the carcinoma. One hundred sixty five patients (68.75%) were affected by benign disease (132 multinodular goiter, 30 uninodular goiter, 2 Plummer and 1 Basedow) and 75 (31.25%) by carcinoma. In 30 of 165 patients (18.2 %), affected by benign disease, occurred a histological diagnosis of thyroid carcinoma, (18 papillary carcinoma, 6 follicular carcinoma, 5 papillary carcinoma follicular variant and 1 oncocytic carcinoma). In this study it's considered incidental thyroid carcinoma the one occurred in patients who never underwent FNA and there were no suspicious features in all exams that may suggest the presence of carcinoma. Fifteen of the 30 incidental carcinoma (50%) were microcarcinomas; in the other 13, dimensions were more than 1 cm, but less than 2 cm in 9 cases. Two patients had a synchronous carcinoma. Actually these patients are still in a follow up program and no recurrency of disease is occasionally observed. This study shows that the only way to put doubts on the real benignity of the disease is the fine needle aspiration; there are no other instruments that could let think about the occurrence of the carcinoma. Moreover in the majority of cases the incidental carcinoma is a microcarcinoma, it doesn't reach significant volume, may be not centered by a FNAB, but in must cases it's not really biologically aggressive.     

Implications of follicular neoplasms, atypia, and lesions suspicious for malignancy diagnosed by fine-needle aspiration of thyroid nodules

OBJECTIVE: To break out subcategories of atypical and suspicious cytologic interpretations of thyroid aspirations and correlate those with final histologic diagnosis. SUMMARY BACKGROUND DATA: Fine-needle aspiration (FNA) of thyroid nodules has become the primary diagnostic tool in the initial evaluation of thyroid nodules. Management of thyroid nodules is based on statistical data correlating a specific cytologic reading with the probability of malignancy. Two particular cytologic readings that frustrate both cytopathologists and surgeons are follicular neoplasms and cells that show atypia. In most reported series, follicular neoplasms and cells showing atypia are included in a broad "suspicious" category, with reported overall malignancy rates generally between 20% and 30%. However, there is interest in determining whether these suspicious lesions can be subcategorized, allowing a more accurate assessment of the risk of malignancy. In addition, there is recent evidence that the incidence of follicular cancer may be declining in this country, possibly decreasing the probability that a "follicular neoplasm" will prove to be a follicular cancer. METHODS: From January 1994 through December 2000, 709 thyroid FNAs were performed at a single institution. Those interpreted as suspicious and the subsequent histologic reports were reviewed. From this set, four specific categories were defined, and the clinical records for patients whose cytology matched these categories form the subject of this study. These four categories are follicular neoplasms without atypia, follicular neoplasms with atypia, atypia, and suspicious for malignancy. In addition, lesions with nondiagnostic cytology were reviewed. Only lesions for which there was histologic follow-up were considered. RESULTS: Ninety-eight aspirates were categorized as follicular neoplasms without atypia, follicular neoplasms with atypia, or atypia alone. Of 74 follicular neoplasms without atypia, only 5 (6.8%) were malignant, and none of these were follicular thyroid cancers. Nine of the lesions were follicular neoplasms with atypia, and four (44.4%) of these were malignant, including two that were invasive follicular cancers. Of 15 lesions showing atypia alone, 3 (20%) were malignant, all of which were papillary thyroid cancers. Twenty-five additional patients had lesions highly suspicious for malignancy. Twenty-one (84%) of these lesions were malignant, the majority being papillary thyroid cancers. Only one was a follicular cancer. Fifty patients with nondiagnostic cytology had subsequent action taken. Thirty-one of these lesions were resected, with five (16.1%) proving to be malignant. CONCLUSIONS: Thyroid nodules whose FNA is diagnosed as highly suspicious for malignancy should be resected unless there are significant contraindications to a surgical procedure. The extremely low rate (2%) of invasive follicular cancers among all follicular neoplasms may reflect changing histologic criteria for follicular carcinoma, a true change in the disease frequency, or both. For thyroid nodules whose cytology shows a follicular neoplasm without atypia, malignancy rates of 8% or less may allow nonsurgical options, including reevaluation in selected populations. Continued efforts to correlate malignancy rates to specific cytologic criteria will allow patients to make more informed decisions regarding their medical care.     

结节性甲状腺肿合并分化型甲状腺癌诊断与治疗

目的：探讨结节性甲状腺肿合并分化型甲状腺癌的临床特点及诊治原则。 方法：回顾性分析2003年10月—2011年10月收治的47例结节性甲状腺肿合并分化型甲状腺癌的临床资料。 结果：患者均表现为颈部包块或颈部增粗,术前B超显示结节伴细沙粒样钙化者19例（40.43%）。47例患者均行手术治疗,术后经病理学检查确诊为分化型甲状腺癌（其中乳头状癌36例,占76.60%;滤泡样癌11例,占23.40%）,手术方式包括：患侧腺叶+峡部全切术+VI区淋巴结清扫;两侧腺叶+峡部全切术+VI区淋巴结清扫;颈部淋巴结肿大、转移者加行改良颈清扫术。术后均给予左旋甲状腺素片治疗。47例患者术后随访6~36个月,平均为（15.6±8.9）个月,3例分别于术后16~33个月复发,再次手术,效果良好。全组无死亡病例。 结论：结节性甲状腺肿合并甲状腺癌术前诊断困难,术前超声检查可提供可考依据,术中快速冷冻切片病理学检查是提高甲状腺癌检出率的关键;个体化、精细规范的手术治疗对结节性甲状腺肿合并分化型甲状腺癌有良好的治疗效果。