Incidental Finding of Metastatic Papillary Thyroid Carcinoma in a Patient with Primary Hyperparathyroidism

ObjectiveTo report on the management of a patient with the rare concurrence of primary hyperparathyroidism and incidentally found metastatic papillary thyroid carcinoma in an adjacent lymph node.MethodsWe present a case report, including scintigraphic and histologic documentation, and a summary of the related literature.ResultsPrimary hyperparathyroidism with concomitant occurrence of nonmedullary thyroid carcinoma is rare, occurring in less than 4% of patients. We report a case of a 53-year-old woman with no prior history of endocrine disease with primary hyperparathyroidism and an incidental finding of a concurrent thyroid carcinoma. In this patient, technetium 99m scintigraphy revealed a parathyroid adenoma beneath the inferior pole of the left thyroid bed. Parathyroidectomy was performed successfully with no complications. The final pathology examination showed a large parathyroid adenoma with an incidental finding of a small adjacent lymph node containing metastatic papillary thyroid carcinoma. The patient subsequently underwent total thyroidectomy, and the pathology evaluation revealed papillary thyroid carcinoma, follicular variant.ConclusionTo our knowledge, this case of concomitant primary hyperparathyroidism and papillary thyroid cancer is unique in the way in which the diagnosis of metastatic papillary thyroid cancer was made. The presence of parathyroid adenoma should not exclude the diagnosis of thyroid carcinoma; therefore, careful thyroid evaluation should be considered for all patients with primary hyperparathyroidism. (Endocr Pract. 2007;13:380-383)     

Metastatic Renal Cell Carcinoma to the Thyroid Gland

ObjectiveTo examine the presentation, diagnosis, and appropriate management of renal clear cell carcinoma metastasis to the thyroid gland.MethodsWe describe a clinical case of solitary thyroid metastasis from renal clear cell carcinoma and present a comprehensive review of the related English-language literature. Common patterns of presentation and generalized overall management recommendations are evaluated and summarized.ResultsEight years after nephrectomy for renal carcinoma at age 61 years, a man presented with a thyroid mass. Cytology and histopathologic surgical findings were consistent with a solitary metastasis most compatible with metastatic clear cell carcinoma from his previous renal carcinoma. After left thyroid lobectomy and isthmusectomy, the patient remains disease-free 5 years later. Although uncommon, nearly 150 cases of clinically recognized metastatic renal cell carcinoma to the thyroid have been reported in the English-language literature. Metastatic disease from the kidney to the thyroid gland can occur more than 20 years after nephrectomy with the average time interval being 7.5 years. Obtaining a full clinical history in any patient who presents with a thyroid nodule is essential to allow consideration of possible metastatic disease from previous primary tumor. Metastatic disease to the thyroid gland can be correctly diagnosed preoperatively. If metastatic renal cancer is limited to the thyroid gland only, prompt, appropriate surgical intervention can be curative.ConclusionMetastatic renal carcinoma to the thyroid should be considered in any patient presenting with a thyroid mass and a medical history of renal cell carcinoma. (Endocr Pract. 2008;14:1040-1046)     

Macrophage-rich reaction in lymph nodes as a mimic of metastatic renal cell carcinoma on fine needle aspiration. A case report

BACKGROUND: Renal cell carcinomas have a high metastatic potential. Many of them are occult at initial presentation and mimic a primary neoplasm of the metastatic site. However, not all lymph node enlargements in a patient with a history of renal cell carcinoma are due to metastasis. Foamy macrophages can mimic metastatic renal cell carcinoma cells. CASE: A 60-year-old male with a known diagnosis of renal cell carcinoma of clear cell type developed enlarged neck nodes 44 months after the diagnosis. These were aspirated to yield cystic fluid that, on smears, showed numerous clear cells with low nuclear grade. Immunohistochemical stains revealed these cells to be foamy macrophages (CD68 immunoreactive) and not metastatic renal cell carcinoma, as had been suspected on initial examination of Diff-Quik and Papanicolaou-stained smears. CONCLUSION: Immunohistochemistry is a valuable adjunct in avoiding a false diagnosis of metastatic carcinoma in macrophage-rich nodal reactions in patients with a history of renal cell carcinoma.     

Intraoperative imprint cytology of the thyroid gland with computer-assisted morphometric analysis of cell clusters

Imprint preparations were used in addition to frozen sections in the intraoperative diagnosis of 37 cases of benign and malignant lesions of the thyroid gland, including adenomatous goiter, follicular adenoma, follicular carcinoma and papillary carcinoma. In the imprints, the cytologic features specific for carcinoma, as compared with benign lesions, were (1) the folding of the nuclear contour, (2) the increased density of the cytoplasmic matrix and (3) the frequent appearance of cell clusters of larger size. The size and frequency of cell clusters were morphometrically analyzed by a computer image analyzer. There was an increasing number of large clusters, plus the appearance of clusters of more than 300 micron in diameter, in both follicular and papillary carcinoma. In benign lesions, on the contrary, the majority of cells were isolated or in small clusters, the diameter of which never exceeded 300 micron in diameter. These results demonstrate that (1) the imprint cytology of the thyroid gland is useful in making a rapid intraoperative diagnosis and (2) the introduction of computer-assisted quantitative analysis is of practical value in the diagnosis of malignancy.     

Be Aware of the Patient With Benign Follicular Thyroid Lesion Histology and Rising Thyroglobulin Level

Objective: The accurate diagnosis of thyroid follicular/Hürthle cell tumors is challenging and a matter of controversy. We present a series of patients in whom a misclassification of follicular/Hürthle cell thyroid lesions as benign has led to devastating clinical outcomes.Methods: The Thyroid Cancer Registry of Rabin Medical Center was screened for patients with metastatic differentiated thyroid carcinoma (DTC) who had been initially diagnosed with benign follicular lesion between 1974 and 2015 and treated with hemithyroidectomy. Clinical, pathologic, and outcome data were collected from the medical files. Adequate pathology specimens, when available, were re-evaluated.Results: Seven patients met the inclusion criteria. The original pathologic diagnosis was follicular adenoma in 4 patients and Hürthle cell adenoma in 3 patients. Five patients had bone metastases, of whom one also had lung metastases and one, liver metastases. One patient had both cervical and lung metastases, and 1 patient had only meta-static neck lymph nodes. Six patients had a final diagnosis of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), and 1 patient was diagnosed as having follicular thyroid cancer metastasis by bone biopsy. In 3 of the patients, capsular invasion was detected retrospectively; only 1 patient had evidence of vascular invasion. All 7 patients had high levels of thyroglobulin at diagnosis of metastatic DTC.Conclusion: Misclassification of follicular thyroid lesions as benign may lead to progressive disseminated DTC. To minimize the clinical risk of misdiagnosis, especially if a thorough evaluation of the specimens by an experienced pathologist is unfeasible, we suggest long-term follow-up of serum thyroglobulin levels.Abbreviations: DTC = differentiated thyroid carcinoma; EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FVPTC = follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid carcinoma     

Signet-ring follicular adenoma of the thyroid diagnosed by fine needle aspiration. Report of a case with cytologic description

BACKGROUND: Follicular cells of the thyroid may undergo squamous, oncocytic or clear cell metaplastic changes. Of these, the clear cell change with signet-ring formation is the most unusual, and follicular adenoma of the thyroid with signet-ring formation is extremely rare. We describe for the first time the cytologic features of a clear cell adenoma of the thyroid obtained by fine needle aspiration (FNA). CASE: A 48-year-old woman in a euthyroid state presented with a 2-cm, right-sided thyroid nodule. Smears obtained by FNA of the nodule revealed clusters of large signet-ring cells in a bloody background. The signet-ring cells were round to oval, with large cytoplasmic vacuoles and hyperchromatic, eccentric nuclei. Colloid in the background was very scanty. Histologic examination of the right hemithyroidectomy specimen revealed a signet-ring follicular adenoma. CONCLUSION: Lack of familiarity with signet-ring cell adenoma of the thyroid could lead to an erroneous diagnosis of metastatic signet-ring cell carcinoma.     

Basement membrane-like substance in cytologic diagnosis in clear cell adenocarcinoma of the minor salivary gland of the palate. A case report

BACKGROUND: Clear cell adenocarcinoma (CCA) of the minor salivary gland accounts for < 1% of all tumors of the salivary gland. CASE: A 32-year-old woman with a history of papillary carcinoma of the thyroid 1 year earlier complained of pain on the left side of the neck. After a detailed examination, the patient underwent the resection of a tumor located at the palate. Imprint cytology of the tumor revealed cohesive tumor cells of uniform size containing an abundant clear cytoplasm and round nuclei with extra but fine granular chromatin and conspicuous nucleoli. A basement membrane-like substance (BMS) was stained in light green with Papanicolaou staining and was positive for laminin with immunohistochemical staining. Histopathologic analysis confirmed the trabecular or nest-like arrangement of the cells with the clear cytoplasm and BMS substance surrounded by tumor cells, which were positive for laminin and AE1 immunohistochemically. CONCLUSION: Although CCA of the palate is extremely rare, an accurate cytologic diagnosis can be made if the characteristic findings of CCA, including BMS, are imaged.     

Expression of FAS/APO 1/CD 95 in thyroid tumors

Using immunohistochemistry, Fas/Apo-1 protein expression was investigated in thyroid cancers of 67 patients. Thyroid biopsies from twenty eight patients with benign thyroid diseases were also examined. The patients with thyroid cancer manifested a variable histology of the cancer, including 14 patients with follicular carcinoma, 48 with papillary carcinoma, 5 patients with medullary carcinoma. The benign thyroid disease involved nodular goitre in 11 patients and follicular adenoma in other 17 patients. The study aimed at examining immunohistochemical expression of Fas protein in order to determine whether the level of its expression correlated with histological diagnosis. In individual patients Fas expression was more prevalent in thyroid carcinomas as compared to benign tumors (p=0.001). A marked increase in Fas expression was found in papillary carcinoma, as compared to follicular and medullary carcinomas (p=0.02). In conclusion, Fas was significantly more frequently overexpressed in thyroid cancer, indicating its role in thyroid tumorigenesis.     

Follicular adenoma of the thyroid with intranuclear vacuoles and clear nuclei. A case report

Although the presence of intranuclear vacuoles in fine needle aspiration biopsy specimens and clear nuclei in histologic specimens is considered characteristic of papillary carcinoma of the thyroid, these findings are not pathognomonic of this disease. This paper reports a case of follicular adenoma of the thyroid with such features and emphasizes the importance of not relying solely on these criteria for the diagnosis of papillary carcinoma.     

Intranuclear cytoplasmic inclusions in aspirates of follicular neoplasms of the thyroid. A report of two cases

Two cases are reviewed in which the presence of intranuclear cytoplasmic inclusions in fine needle aspiration biopsy specimens of the thyroid suggested a diagnosis of papillary carcinoma. Subsequent surgical specimens were consistent with diagnoses of microfollicular adenoma and follicular carcinoma. These cases suggest that the presence of intranuclear inclusions in epithelial thyroid cells is not limited to papillary and medullary carcinoma, as some authors have suggested.     

Fine needle aspiration cytology of a thyroid metastasis of metaplastic breast carcinoma: a case report

BACKGROUND: Metaplastic breast carcinoma is defined as mesenchymal and/or squamous cell components associated with ductal carcinoma. Because of the heterogeneous nature of this tumor, cytologic interpretation on fine needle aspirates can be quite challenging. This is especially true of metastatic lesions of this rare tumor type. Metastasis to the thyroid has not been previously reported. CASE: A 57-year-old woman with a history of metaplastic breast carcinoma for which she underwent mastectomy, chemotherapy and radiation therapy 2 years earlier presented with a fast-growing left thyroid mass with progressive hoarseness and dysphasia. Clinical presentation and findings from a neck computed tomographic scan were strongly suggestive of a primary thyroid malignancy. The aspirate specimen was composed of scant, highly atypical epithelial cells in a background of an abundant chondromyxoid matrix and scattered, benign follicular cells. A literature review confirmed the novelty of this case. CONCLUSION: This case emphasizes the value of clinical information and the importance of generous sampling in achieving a correct diagnosis of metastatic metaplastic carcinoma.     

Cytopathology of Follicular Tumours of the Thyroid With Clear Cell Change

A retrospective cytological study of nine follicular tumours of the thyroid with clear cell change was undertaken. In five clear cell adenomas and one moderately differentiated clear cell follicular carcinoma the epithelial cells occurred singly or in sheets and clusters; they sometimes assumed a trabecular or follicular pattern. The cells usually had pale diffusely vacuolated cytoplasm with ill-defined boundaries, a variable degree of anisonucleosis, nucleolar enlargement, and nuclear overlapping. Smears from a signet-ring cell adenoma contained in addition a few cells with large cytoplasmic vacuoles and compressed eccentric nuclei. In these cases a cytological diagnosis of 'follicular lesion' (or follicular neoplasia), clear cell type or signet-ring cell type, was given. A cytodiagnosis of 'carcinoma' was made only in the poorly differentiated follicular carcinoma-clear cell variant studied which showed unequivocal features of malignancy. Features suggestive of thyroid cyst, nodular goitre, Hashimoto's thyroiditis, and cell hyperactivity (marginal vacuoles, 'fire flare') were also found in the aspirated specimens of these cases of clear cell tumour of the thyroid.     

Serum levels of IGF-I, HGF, TGFbeta1, bFGF and VEGF in thyroid gland tumors

IGF-I, HGF, TGFbeta1, bFGF and VEGF are involved in the pathogenesis of thyroid gland tumors and their growth. We decided to find whether changes in the production of these cytokines by thyroid tumor cells are reflected by changes of their peripheral blood. Using ELISA kits, we measured the concentrations of growth factors in the peripheral blood serum in 28 patients with thyroid gland tumors (14 adenomas, 14 papillary carcinomas) and compared these concentrations with those in healthy people. We found significantly lower serum levels of IGF-I in patients with thyroid adenoma compared to the healthy population. Serum levels of HGF and bFGF were significantly higher in patients with thyroid adenoma and papillary carcinoma compared with those in healthy subjects. Serum concentrations of TGFbeta1 and VEGF were not significantly different in any groups of investigated subjects. Changes in the production of these cytokines by thyroid gland tumor cells are reflected in their peripheral blood levels, but these levels also depend on a number of other physiological and pathological processes in the organism. However, significant differences of HGF and bFGF serum levels can be explained by their very high production by thyroid tumor cells and by their strong effect on the follicular and endothelial cell proliferation.     

Use of immunohistochemistry in fine needle aspiration of thyroid nodules in patients with a history of malignancy. A report of two cases

BACKGROUND: A history of a nonthyroid malignancy may present a diagnostic dilemma in the assessment of fine needle aspiration (FNA) of thyroid nodules. One reported series, on patients with prior malignancies and a thyroid nodule, indicated that in 17% of patients, the thyroid nodule represented metastatic malignancy, 6% were classified as primary thyroid cancers, and the remainder were benign or inconclusive lesions. The resolution of this problem is essential to patient management. CASES: We report two cases in which patients with a history of renal cell carcinoma presented with a thyroid nodule. The first patient was an 80-year-old female whose Papanicolaou-stained FNA demonstrated clusters of round to polygonal cells with round to ovoid, hyperchromatic nuclei and abundant, wispy cytoplasm. The second patient was a 55-year-old female with clusters and single cells with round to oval, eccentric nuclei and copious, granular, gray cytoplasm noted on Papanicolaou-stained material. In each case, the diagnosis was inconclusive on initial review of Papanicolaou-stained slides, and immunohistochemical staining was ordered to better characterize the lesions. Tumor cells from case 1 were positive for cytokeratin cocktail and vimentin and negative for thyroglobulin, epithelial membrane antigen and calcitonin, suggestive of metastatic renal cell carcinoma. In contrast, the tumor cells from case 2 expressed cytokeratin, thyroglobulin and vimentin, consistent with a primary thyroid neoplasm. In each case, the cytologic diagnoses were confirmed in the resected specimens. CONCLUSION: Immunohistochemistry is a helpful adjunct in the evaluation of thyroid nodules in patients with a past history of malignancy.     

Fibroblast Growth Factor Receptor-2 Expression in Thyroid Tumor Progression: Potential Diagnostic Application

Fibroblast growth factor receptor-2 (FGFR-2) plays an important role in tumorigenesis. In thyroid cancer it has been observed a FGFR-2 down-modulation, but the role of this receptor has not been yet clarified. Therefore, we decided to examine the expression of both FGFR-2 isoform, FGFR-2-IIIb and FGFR-2-IIIc, in different histological thyroid variants such as hyperplasia, follicular adenoma and papillary carcinoma. Immunohistochemistry and quantitative Real-Time PCR analyses were performed on samples of hyperplasia, follicular adenoma and papillary carcinoma, compared with normal thyroid tissue. Thyroid hyperplasia did not show statistically significant reduction in FGFR-2 protein and mRNA levels. Interestingly, in both follicular adenoma and papillary carcinoma samples we observed a strongly reduced expression of both FGFR-2 isoforms. We speculate that FGFR-2 down-modulation might be an early event in thyroid carcinogenesis. Furthermore, we suggest the potential use of FGFR-2 as an early marker for thyroid cancer diagnosis.     

Multiparameter analysis of AgNOR in thyroid lesions: comparison with PCNA expression

The aim of the study was to examine numerous features of argyrophilic proteins related to nucleolar organizer regions (AgNORs) in thyroid tumors, relate them to PCNA expression and evaluate which of these features might be useful in the diagnosis of thyroid lesions. Paraffin sections of 100 thyroid tumors were silver-stained and divided into 9 groups: nodular goiter (NG), simple adenoma (SA), microfollicular adenoma (MFA), follicular carcinoma (FC), follicular variant of papillary carcinoma (PC-F), classical variant of papillary carcinoma (PC-C), Hürthle cell adenoma (HA), Hürthle cell carcinoma (HC), and anaplastic carcinoma (AC). The slides were analyzed with the computerized system for image analysis. A weak correlation was found between PCNA expression and AgNOR size. AC differed significantly from all other examined groups in many features of AgNOR dots. Hürthle cell neoplasms were characterized by the presence of a usually single and relatively large dot. With respect to diagnosing follicular lesions, we found that the evaluation of the total area of dots in the nucleus seemed to be the most useful for discrimination: the assumption of 4.9 micro m2, as a cut-off value, allowed a correct classification of 77% of FC cases. Computer-aided morphometric analysis of AgNORs may be useful in the diagnostics of thyroid lesions.     

Clear cell carcinoma arising from pleomorphic adenoma of a minor salivary gland: Report of a case with fine needle aspiration, histologic and immunohistochemical findings

BACKGROUND: Malignant changes in pleomorphic adenoma (PA) of the salivary gland (carcinoma ex pleomorphic adenoma) are not common. Clear cell carcinoma is a rare form of salivary gland tumor and involves mostly minor salivary glands, especially those of the palate. Only 3 cases of clear cell carcinoma arising in PA have been reported, 2 in submandibular glands and 1 in a minor salivary gland of the palate. CASE : A 53-year-old man presented with an enlarged mass on the left side of the palate. He had a history of palate mass about 30 years earlier; it was excised and reported as PA. Since then the tumor had recurred twice in the same place; it had been excised and was diagnosed as PA again. A few years later the mass showed rapid growth over a few months. Fine needle aspiration of the mass showed epithelial clusters with bland nuclear features and myxohyaline material typical of PA. Also noted were large and small papillary, trabecular and well-circumscribed clusters of neoplastic cells with a moderate amount offoamy, vacuolated cytoplasm with distinct borders. Glandlike and acinar structures with hyaline globule material resembling cannonballs were also noted. The cytology was suspicious for malignancy. Incisional biopsy was reported as PA. Due to the suspicion of malignancy, the whole mass was excised up to the floor of the orbit. The final diagnosis was clear cell carcinoma expleomorphic adenoma. CONCLUSION: Due to nonspecific cytologic findings in clear cell carcinoma and a mixture of elements of PA in this case, we did not consider clear cell carcinoma as the malignant component.     

Fine-needle aspiration of mucin-producing thyroid tumors

Objective: Mucin-producing thyroid tumors are extremely rare. Nonetheless, we have encountered three such cases in fine-needle aspiration. We report the cytologic and histologic findings and review the literature. Study Design: Cytologic features were studied on direct smears using Romanovsky stain to detect background substance and Papanicolaou stain to analyze nuclear and cytoplasmic features. The cytologic features were correlated with histology. Mucin was demonstrated by mucicarmine, Alcian Blue/PAS, and Alcian Blue (pH 2.5). Results: The cytologic features related to mucin include: (1) thick luminal mucin globules and signet ring cells aspirated from an 83-year-old woman with a 3-cm signet ring cell follicular adenoma, (2) abundant fluffy mucin containing signet ring cells in cohesive fragments aspirated from a 75-year-old man with the bilateral signet ring cell follicular variant of papillary carcinoma, which is the first case in the English literature, and (3) abundant thin mucoid mucin aspirated from the lymph node of an 86-year-old woman with a 5-cm mucinous poorly differentiated thyroid carcinoma. Conclusion: The occurrence of mucin in thyroid fine-needle aspiration does not necessarily indicate metastasis, and the presence of mucin in cervical lymph nodes does not exclude the thyroid gland as a possible primary.     

Fine needle aspiration biopsy of the thyroid. Differential diagnosis by videoplan image analysis

Fine needle aspiration biopsy of cold thyroid nodules has become increasingly popular in determining neoplastic versus nonneoplastic conditions. The differential diagnosis between follicular adenoma and low-grade follicular carcinoma has not been consistently attainable, however; adenomatous goiter also may present problems in diagnosis, while papillary carcinoma seldom proves to be a difficult diagnosis. Image analysis, utilizing the Videoplan image analysis system, was performed on fine needle aspiration biopsy smears from these four types of nodules. The nuclear area, maximum diameter, minimal diameter and approximation to a circle were determined for 25 randomly selected cells with intact nuclei in each smear. These values were calculated with a range and standard deviation and were graphed for each parameter by case category. Cytoplasmic measurements could not be performed due to the absence of definite cytoplasmic boundaries. There was no significant difference in mean nuclear area between follicular adenoma, follicular carcinoma and adenomatous goiter. Papillary carcinoma was the only lesion to show any difference with this single parameter. The mean of maximum and minimum diameter and approximation to a circle were similar for all the types of thyroid masses examined in this study. The Videoplan image analysis system provided an efficient and accurate means of obtaining the nuclear measurements and calculating the statistics. These data illustrate that a differential diagnosis between follicular adenoma, follicular carcinoma and adenomatous goiter, while difficult by light microscopy, is not aided by image analysis of individual cell nuclei.     

Diagnosis of metastatic renal cell and thyroid carcinomas by intermediate filament typing and cytology of tumor cells in fine needle aspirates

Coexpression of keratin and vimentin was found in carcinoma cells of 13 fine needle aspirates of metastatic lesions that showed some cytologic features considered to be consistent with a renal or thyroid origin, but in which a large number of other possible primary sites would have to be taken into account on the basis of the morphologic evidence alone. Immunochemistry thus narrowed the cytologic differential diagnosis to thyroid, renal, endometrial and ovarian carcinomas, which are known to show true coexpression of keratin and vimentin. In most cases, clinical data available at the time of the fine needle aspiration supported the thyroid or renal origin of the carcinoma cells found in the aspirates. In two cases, which lacked significant clinical information, the diagnosis of metastatic renal cell carcinoma was provided on the basis of the combined morphologic and immunocytochemical evidence. In these two cases, computed tomography or ultrasonography revealed kidney tumors, which were removed and confirmed histologically to be clear cell carcinomas.