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PubMedDate not supplied

Synchronous appearance of germ cell tumor and papillary carcinoma of the thyroid.

Synchronous appearance of 2 different malignancies in one patient is a rare phenomenon. We describe our experience of 2 patients with synchronous malignancies of the testis and thyroid gland, and of a third patient who developed a thyroid neoplasm unrelated to recent treatment for a germ cell tumor. The medical records of 3 male patients treated for both a germ cell tumor and a thyroid cancer between 1989 and 1994 were reviewed. Two patients with nonseminomatous germ cell tumor received postoperative chemotherapy after orchiectomy and developed a papillary carcinoma of the thyroid during treatment. A third patient, who received radiation therapy for a clinical stage 1 seminoma, recurred with biopsy proven seminoma in the neck in association with a thyroid nodule 2 years later. All 3 patients had their thyroid cancer treated by surgical resection, and one received adjuvant radioactive iodine. Two of the patients are currently alive and disease-free. One patient died of pulmonary complications that stemmed from bleomycin toxicity. Synchronous appearance of germ cell tumor and papillary carcinoma of the thyroid has not been previously described. Genetic predisposition may play a role in the development of such simultaneous neoplasms.

Adult↗
PubMed2004

Renal cell carcinoma metastatic to Hurthle cell adenoma of thyroid.

Metastases to the thyroid gland are a common finding at autopsy in patients who died of malignancy and are often misdiagnosed as primary thyroid neoplasms clinically. We present a patient with a rare, unusual case of renal cell carcinoma (RCC) metastatic to a Hurthle cell adenoma of the thyroid. A 53-year-old woman was admitted to a University of Texas Medical Branch Hospital (Galveston, TX) for a large right thyroid mass that was present for 3 months. A fine needle aspiration of the thyroid mass was performed and interpreted as suggestive of a Hurthle cell neoplasm. A total thyroidectomy revealed Hurthle cell adenoma containing clusters of cytologically atypical cells with clear cytoplasm. Subsequent patient evaluation and computed tomography revealed a renal mass. Left radical nephrectomy was performed at a later date for left renal mass and the microscopic examination confirmed the diagnosis of primary clear cell carcinoma of the kidney. Further studies confirmed that the thyroid mass was metastases from RCC. Although carcinoma of the kidney is responsible in most instances of metastatic disease to the thyroid, metastatic RCC to a thyroid neoplasm is extremely rare, with only two reports found in the English literature. The possibility of metastatic RCC should always be taken under consideration, especially when nests of clear cells are seen infiltrating into the thyroid parenchyma or neoplasm.

Adenoma, Oxyphilic↗
PubMed1989

Renal cell carcinoma metastatic to the thyroid.

Metastatic renal cell carcinoma to the thyroid is an uncommon occurrence that can cause clinical and pathologic problems in diagnosis. The authors report seven cases from the files of The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Each presented clinically as a palpable thyroid nodule months or years after the primary renal cell carcinoma had been resected. Although renal cell carcinoma is more common in men, we found a female predominance of 6:1 in this series. These lesions appear as solitary "cold" nodules on iodine 131 scans and may be misdiagnosed as primary thyroid neoplasms, especially if the renal primary is still unrecognized. A correct diagnosis is important because surgical management can be curative. The diagnosis is facilitated by the use of fat stains, electron microscopic study, and immunoperoxidase stains.

Aged↗
PubMed2026

Afirma genomic sequencing classifier performance in young patients with cytologically indeterminate thyroid nodules.

CONTEXT: The Afirma Genomic Sequencing Classifier (GSC) is validated in patients &#x2265; 21 years with a 96% negative predictive value for malignancy when GSC-(B)enign. Afirma GSC has not been formally studied in patients <21 years of age with indeterminate thyroid nodules (ITNs). OBJECTIVE: To evaluate Afirma GSC in young patients with ITNs. DESIGN: Retrospective analysis of Afirma GSC testing. SETTING: ITNs referred for molecular testing in a real-world setting. PARTICIPANTS: Forty-nine ITNs from 49 patients < 21 years of age who had histopathology or 2 years' clinical follow-up data ascertained. INTERVENTION: None. MAIN OUTCOME MEASURE: Afirma GSC test performance. RESULTS: In 49 ITNs from patients aged 9 to 20 years (median 18.5 [interquartile range, 17.3-19.8]), 30 were GSC-B and 19 GSC-(S)uspicious, among which 14 (73.7%) were malignant (ie, true positive) and 5 (26.3%) were benign (ie, false positive). All 30 Afirma GSC-B cases were either histologically (n = 9) or clinically benign (n = 21) (ie, true negative). All 14 malignancies were GSC-S (sensitivity 100% [95% CI, 77-100]); 30/35 clinically or histologically benign cases were GSC-B (specificity 86% [95% CI, 70-95]). Negative predictive value for an Afirma GSC-B result was 100% [95% CI, 88-100]. Genomic alterations were not detected in the 30 GSC-B samples. Among the 14 malignant samples, there were 9 papillary thyroid carcinomas, 1 oncocytic carcinoma, 1 noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and 3 follicular thyroid carcinomas. CONCLUSION: In young patients with ITNs, the Afirma GSC demonstrated an excellent negative predictive value when defining a thyroid nodule result by histology or clinical follow-up.

Thyroid Nodule↗
PubMedDate not supplied

Follicular carcinoma of the thyroid with aggressive metastatic behavior in a pregnant woman: report of a case and review of the literature.

Distant metastases as initial presentation of follicular carcinoma of the thyroid is rare, especially in young patients. We report the clinical and pathological features of a 33-year old pregnant patient with follicular carcinoma of the thyroid who presented with widespread bone and lung metastases at the time of diagnosis. the resected tumor had a focal insular component that showed extensive vascular invasion spreading beyond the thyroid capsule, and was associated with widespread bone and lung metastases. Despite its aggressive behavior, the tumor had low mitotic activity and Ki-67 nuclear labeling index. tumor cells showed high microvascular density and down-regulation of E-cadherin, a calcium-dependent trans-membrane epithelial protein molecule known to promote intercellular adhesion. We suggest that architectural differentiation of the tumor and cell proliferation rate are not reliable markers of metastatic behavior in this particular thyroid neoplasm. Microvascular density and down-regulation of E-cadherin expression in the tumor should be included among histologic hallmarks of metastatic potential. the role of pregnancy in the aggressive behavior of this tumor is discussed along with a literature review.

Adenocarcinoma, Follicular↗
PubMed1993

Diagnostic approach to thyroid carcinoma in Graves' disease.

Among 545 surgically treated Graves' disease patients, 17 were found to have coexisting thyroid neoplasms. Of these 17 patients, 11 turned out to have thyroid carcinomas. These patients could be divided into 2 groups; Group I with a diffusely enlarged gland with a clinically palpable nodule (n = 6) and Group II without a palpable nodule (n = 5). In Group I, 4 patients were diagnosed by preoperative fine needle aspiration cytology, and the remaining 2 by intraoperative frozen-section examination. In Group II, none of the patients were suspected of any concurrent thyroid carcinoma preoperatively, and only 2 were identified by intraoperative frozen-section examination. Thus, 8 of the 11 patients were diagnosed preoperatively or intraoperatively. These observations suggest that in all patients with Graves' disease and concurrent thyroid nodules, the suspicion of associated malignancy may be raised. And also, fine needle aspiration cytology in every case of Graves' disease with a palpable nodule and intraoperative frozen-section examination of the suspicious lobe in the cases of non-palpable nodules appear worthwhile in detecting a concurrent thyroid carcinoma.

Adult↗
PubMed2002

Phyllodes tumor metastatic to thyroid Hürthle cell adenoma.

We present a case of a malignant phyllodes tumor metastasizing to a Hürthle cell adenoma of the thyroid. A 55-year-old woman underwent mastectomy for a malignant phyllodes tumor. Two years later, she presented with a left thyroid mass, which was a single, circumscribed, soft, deep red-brown nodular lesion with an eccentric area of firmer consistency. Histologically, the thyroid tumor was composed of 2 distinct types of cellular proliferation. Atypical spindle cells were infiltrating between the Hürthle cell cords and follicles in a fibrosarcomatous pattern. A battery of immunohistochemical stains was applied to both the thyroid and breast tumors for comparison. Based on the histologic and immunophenotypic features of the fibrosarcomatous components of both the breast and thyroid tumors, we rendered a diagnosis of cystosarcoma phyllodes metastatic to Hürthle cell adenoma. To the best of our knowledge, this unusual case is a first report of tumor-to-tumor metastasis of a sarcoma to a primary thyroid neoplasm.

Adenoma, Oxyphilic↗
PubMed2002

Expression of p57/Kip2 protein in normal and neoplastic thyroid tissues.

p57 (Kip2) belongs to the Cip/Kip family and is one of the universal negative regulators of the cell cycle. In this study, we investigated the p57 expression of various types of thyroid neoplasm. p57 overexpression was observed in only 4.2% of normal thyroid tissues. In follicular adenoma and minimally invasive follicular carcinoma, p57 was overexpressed in 100% and 91.7% of the cases, respectively. However, its incidence was significantly lower (p<0.0001) in widely invasive follicular carcinoma, of which only 36.4% overexpressed p57. This phenomenon was seen in 63.1% of papillary carcinoma and 13.3% of anaplastic (undifferentiated) carcinoma. Furthermore, poorly differentiated and undifferentiated carcinoma more frequently lacked p57 expression (p<0.0001). These results suggest that the down-regulation of p57 may play a role in the dedifferentiation of thyroid carcinoma and in follicular carcinoma mutating to be more invasive.

Cell Differentiation↗
PubMedDate not supplied

A low-grade follicular thyroid carcinoma in a woman with Down syndrome.

AIMS: Analysis of a thyroid neoplasm in a person with Down syndrome. METHOD: Report of a case and review of the literature. RESULTS: A 34-year-old woman with Down syndrome developed a right thyroid low-grade follicular carcinoma. She is alive 20 years after the discovery of the initial tumor. A review of the literature including epidemiological studies revealed only one unspecified cancer, one papillary carcinoma and one lymphoma. Persons with Down syndrome present an excess of goiter and thyroiditis and often are overweight and have low serum selenium, all these conditions being risk factors for thyroid carcinomas. CONCLUSION: Thyroid malignant neoplasms are very rare in persons with Down syndrome. We suspect that some constitutional, hormonal and genetic factors could protect these subjects against thyroid carcinoma.

Adenocarcinoma, Follicular↗
PubMed1997

Hashimoto's thyroiditis: cytodiagnostic accuracy and pitfalls.

To determine the cytodiagnostic accuracy rate and pitfalls of Hashimoto's thyroiditis (HT), the files and smears prepared from the thyroid needle aspirates of 146 patients with suspected HT and/or clinically and serologically confirmed HT were reviewed. Of those patients, 105 presented with a diffuse and rubbery thyroid enlargement, and 41 with one or two prominent nodules. For the first group (105 patients), the needle aspiration biopsy (NAB) was performed on one or two thyroid lobes during their initial endocrinologic consultation, and for the second group (41 patients), the NAB was performed on and around the predominant nodules that were found either at initial physical examination or during the patients' routine follow-ups. In 134 cases, a cytodiagnosis of HT was made on the first NAB. Among the 41 patients with a prominent thyroid nodule, a thyroid neoplasm was suspected clinically in four because their thyroid nodules increased in size. In the other 12 patients, a cytodiagnosis of follicular neoplasm (FN) was made in five cases, and a Hürthle cell tumor (HCT) was diagnosed or suspected in seven patients. All 16 patients had thyroid surgery, and a HT was histologically confirmed in all cases. In the first four patients, no tumor was found. Among five patients with a cytodiagnosis of FN, one had a hyperplastic follicular cell nodule (HFCN), two had follicular adenomas, and two had papillary carcinomas of follicular variant. For the seven patients with a cytodiagnosis of HCT, HCT was confirmed in three, three were found to have hyperplastic Hürthle cell nodules (HHCN), and one showed a benign colloid nodule with Hürthle cell changes and remote hemorrhagic necrosis. It is concluded that NAB is highly sensitive in diagnosing HT, with a diagnostic accuracy rate of 92% by the first biopsy attempt. The cytologic differential diagnosis between an HFCN and a follicular neoplasm and between an HHCN and an HCT is impossible in some cases.

Adolescent↗
PubMed1990

Hürthle cell neoplasms of the thyroid.

The approach to Hürthle cell neoplasms of the thyroid gland remains controversial because there is no consensus on the criteria used to establish malignancy. Invasion into the thyroid capsule, blood vessels, and contiguous structures in the neck and lymph nodes, or distant metastases establishes malignancy. Benign Hürthle cell lesions should be treated with total lobectomy and isthmusectomy. Total thyroidectomy is the recommended treatment for malignant Hürthle cell lesions.

Age Factors↗
PubMed1998

Two-dimensional electrophoretic analysis of membranous protein from human thyroid tissues and cancer cell lines.

Thyroid neoplasm is the most commonly encountered neoplastic disorder in endocrine clinics. Thyroid scan, ultrasonography, and fine needle aspiration cytology (FNAC) are used as diagnostic tools to differentiate a malignant nodule from a benign lesion. There are certain limitations and pitfalls in FNAC, especially in the diagnosing of follicular tumors. The lack of characteristic findings or a specific tumor marker are the most common problems in the preoperative diagnosis of thyroid follicular carcinoma. Although serum thyroglobulin level has been used as a tumor marker for post-operative, well-differentiated thyroid cancer, the assay cannot be used for preoperative diagnosis of thyroid carcinoma. In this study, various thyroid tissues and cancer cell lines including CGTH W-1, CGTH W-3, RO 82 W-1, SW 579 cell lines were used for the investigation of tumor markers. Specific spots were identified in the area near the 60 kDa molecular mass protein and isoelectric point (pI) 5.9 of the CGTH W-1 cell line. These spots could not be found in the papillary or anaplastic thyroid cancer cell lines. Another spot with a molecular weight of about 9.8 kDa with a low pI of 4.8 was present in the CGTH W-1 and RO 82 W-1 cell lines. This spot appeared to be a tumor marker of follicular cancer cells. This spot could not be found in the papillary and anaplastic cancer cell lines and other benign thyroid tissues. Specific proteins that were identified in this study may be useful as tumor markers for follicular thyroid carcinoma.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1998

Genetic and epigenetic alterations of the cyclin-dependent kinase inhibitors p15INK4b and p16INK4a in human thyroid carcinoma cell lines and primary thyroid carcinomas.

BACKGROUND: D-type cyclins, in association with the cyclin-dependent kinases CDK4 and CDK6, promote progression through the G1 phase of the cell cycle. CDK activity is modulated by inhibitors such as p15INK4b and p16INK4a. Loss of function of p15INK4b and p16INK4a (multiple tumor suppressor-I and CDK4 inhibitor) determines impairment in the control of the cell cycle and contributes to the transformation of several cell types. METHODS: The authors examined 20 thyroid neoplasms (12 papillary carcinomas and 8 follicular adenomas) and 4 human thyroid carcinoma cell lines for gene mutations and epigenetic modifications of the p15INK4b and p16INK4a genes by Southern blot analysis, single strand conformation polymorphism, and a polymerase chain reaction-based methylation assay. RESULTS: Abnormalities of p16 were found in the four cell lines studied. In follicular carcinoma (WRO) cells, both the p15 and p16 genes were homozygously deleted. Undifferentiated carcinoma (FRO) cells had a nonsense point mutation at codon 72 (CGA-TGA, Arg-Stop) of p16, whereas the poorly differentiated papillary carcinoma (NPA) line harbored a point mutation at the exon 1-intron 1 boundary that altered the donor splicing site and caused an aberrantly spliced form of p16INK4a. Furthermore, p16 allelic loss was evident in the DNA of both FRO and NPA cells. Finally, p16 expression was absent in the ARO cell line, likely due to a de novo methylation of exon 1 of p16INK4a. Regarding the primary thyroid tumors, a missense point mutation at codon 91 was found in 1 of 12 papillary thyroid carcinomas (GCC-GTC, Ala-Val). No mutations were found in follicular adenomas. However, in 6 of 20 primary tumors there was hypermethylation at exon 1 of p16. CONCLUSIONS: The high prevalence of p15 and p16 mutations in the cell lines described suggests involvement of these genes in immortalization in vitro. The p16 defects may have preexisted in a small subclone of the primary tumor that were selected for in vitro. Alternatively, p16 mutations may have arisen de novo during cell culture. Mutations of p15INK4b and p16INK4a do not appear to be critical events in the development of follicular adenomas or papillary carcinomas. However, de novo methylation of the 5' CpG island of p16 is common in primary tumors, indicating that the function of this gene may be lost as an epigenetic event during disease progression.

Adenoma↗
PubMed1983

Total thyroidectomy for Hürthle cell neoplasm of the thyroid.

The treatment of Hürthle cell neoplasms of the thyroid is controversial because of a lack of information about their clinical behavior and long-term follow-up. We reevaluated our experience of the past 33 years and compared our early experience with the more aggressive surgical approach used during the past ten years. We treated 62 patients with Hürthle cell neoplasm from 1949 through 1982. Twenty-six patients had benign neoplasms and 35 had malignant neoplasms proven by capsular or vascular invasion or nodal metastasis. Fourteen deaths were directly attributable to recurrent or metastatic disease, three among those with benign lesions. An aggressive surgical approach, involving total thyroidectomy or early-completion total thyroidectomy following lobectomy for all tumors histologically malignant or larger than 2 cm, resulted in a lower recurrence rate (21% v 59%) and fewer operations per patient (1.7 v 2.9) than in patients having other operations.

Adolescent↗
PubMed1996

Prevalence of activating ras mutations in morphologically characterized thyroid nodules.

Ras proteins are signal-transducing proteins that share common properties with membrane-anchored G proteins. Mutations at codon 12/13 or codon 61 alter GTP-binding or GTPase activity, respectively. Such activating mutations are present in nearly 30-50% of various malignancies including colon, breast, and lung carcinomas. There are conflicting data regarding the prevalence of ras mutations in the thyroid and their possible pathogenetic role in the different tumor types. To address this question, we examined 45 morphologically characterized thyroid carcinomas, adenomas, and hyperplastic nodules using a highly sensitive single-stranded conformation polymorphism (SSCP) approach combined with DNA-sequencing. DNA from cell lines with known mutations served as controls. A G to A H13 codon substitution replacing an Asp for a Gly residue was detected in 1 papillary carcinoma. Although no H12 or H61 codon substitutions were identified, 2 discrete alterations were identified in codons H17 and 22. No N12/13 codon substitutions were identified. N61 codon substitutions of A to G resulting in a Gly to Arg substitution were detected in 2 papillary carcinomas; the same mutation was also found in one follicular adenoma. Interestingly, K12/13 and K61 ras mutations were not present in any of the tumors examined. These data establish a low prevalence of mutations in all ras gene family members in human thyroid neoplasms. This difference from neoplasms of other organs may explain the relatively indolent biologic behavior of many thyroid tumors and supports an alternate early genetic mutation that is more characteristic of these neoplasms.

Adult↗
PubMed2004

Clinical evaluation of color Doppler imaging for the differential diagnosis of thyroid follicular lesions.

Ultrasonography (US) of the thyroid gland has recently proved to be a useful clinical diagnostic method, and the newly developed high-resolution US with a color Doppler flow mapping function can reveal fine details of the thyroid gland and the hemodynamic features of a thyroid neoplasm. US can yield a diagnostic accuracy of more than 90% for thyroid carcinoma, especially papillary carcinoma. However, neither conventional B-mode US imaging nor aspiration biopsy cytology has delivered satisfactory results for follicular carcinoma. The aim of this study was to evaluate the clinical usefulness of color Doppler imaging for the differential diagnosis of thyroid follicular lesions. A color Doppler scan was performed in 310 patients with a solitary cold nodule, and a combination of B-mode US and color Doppler findings, including tumor vascularity and results of a fast Fourier transform (FFT) analysis were used to create the following diagnostic grading system for differential diagnosis of follicular lesions: grade 1, benign follicular lesion [no color flow mapping (CFM) inside the nodule]; grade 2, benign peripheral type [CFM only in peripheral area, pulsatility index (PI) < 1.0]; grade 3, suspected follicular carcinoma (penetrating CFM, vascularity moderate); grade 4, follicular carcinoma (high-velocity penetrating CFM, PI = 1.0). All patients were subjected to surgical resection, and histologic examination was used to confirm the diagnosis. The grades of the 177 adenomatous nodules were as follows: grade 1, 46.9%; grade 2, 48.0%; grade 3, 5.1%; grade 4, 0%. The corresponding percentages for the 89 follicular adenomas were 16.9%, 49.4%, 30.3%, and 3.4%; and for the 44 follicular carcinomas they were 0%, 13.6%, 45.5%, and 40.9%. On the assumption that grade 1 and 2 lesions are benign and grade 3 and 4 lesions are malignant, 38 of the 44 follicular carcinomas and 227 of the 266 benign tumors had been accurately diagnosed, yielding a sensitivity of 88.9%, a specificity of 74.2%, and an accuracy of 81.0% for the grading system. Color Doppler imaging of 310 follicular tumors has revealed that high-velocity pulsatile blood flow penetrating the tumor is a characteristic finding of follicular carcinoma and is a new diagnostic criterion for performing color Doppler imaging. The differential diagnostic grading scores for color Doppler examinations and the results of FFT analysis demonstrate that US with the color Doppler function can play an important role in the differential diagnosis of thyroid tumors.

Adenoma↗
PubMedDate not supplied

Ossifying fibromyxoid tumor misdiagnosed as follicular neoplasia. A case report.

BACKGROUND: Fine needle aspiration of an ossifying fibromyxoid tumor (OFMT) at a prethyroidal location is initially misinterpreted as follicular neoplasia. Though the histopathologic criteria have been analyzed in detail, no experience with the cytologic features of OFMT is reported in the literature. CASE: A 50-year-old male presented clinically with a recurrent goiter. Aspiration cytology (Giemsa stained) was characterized by a predominant fine fibrillary, pink matrix and moderate cellularity. The nuclei were eccentrically located, round to oval and slightly plemorphic, with fine chromatin. Focally, mild nuclear crowding and a few rosettelike structures were present. CONCLUSION: The cytologic features were consistent with a soft tissue tumor of probably neurogenic origin, like OFMT. Differential diagnosis in this particular location not only included follicular thyroid neoplasms but also neurofibroma, neuroma, chondroma and, less likely, neuroepithelial tumors. However, since some diagnostic criteria of OFMT, like the nodular growth pattern and mature bone, can be found only histologically, the diagnostic value of aspiration cytology seems to be limited.

Biopsy, Needle↗