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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.
[Cell growth and neoplasms of the thyroid gland in horses].
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[Current clinical, diagnostic and therapeutic trends in solitary nodular neoplasms of the thyroid].
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Neoplasm of the thyroid gland.
Although the prevalence of thyroid nodule is approximately 1% to 5% in the general adult population, 6% to 10% of older persons may have solitary nodules. Between 2% and 10% of thyroid nodules are noted to be carcinomatous. Approximately 1200 persons die of thyroid carcinoma each year in the United States alone; the incidence is much higher in women than in men. With early diagnosis and treatment, patients with thyroid cancers are living longer than ever before. In terminally ill older patients with nonresectable tumors and distant metastasis, all attention must be given to adequate pain control and maintenance of quality of life.
Encapsulated papillary neoplasm of the thyroid: retrospective clinicopathological study with long term follow up.
OBJECTIVE: To study the clinical course of patients with the encapsulated variant of papillary thyroid carcinoma, in which there is a well-defined fibrous wall completely separating the tumour cells from the adjacent tissue. DESIGN: Retrospective review. SETTING: University hospital, Spain. SUBJECTS: Of a total of 163 patients whose papillary thyroid carcinomas were treated surgically between 1975 and 1985, there were 25 encapsulated tumours. MAIN OUTCOME MEASURES: Clinicopathological features and survival rate compared with those of non-encapsulated papillary thyroid carcinomas. RESULTS: Mean follow up was 9 years (range 7-17), and 42 were excluded because follow up was incomplete. Encapsulated tumours differed from the earlier age of other types in that they presented earlier (mean age 36 years compared with 45), they were significantly less likely to have symptoms of compression (1/25 compared with 24/96, p = 0.024), or nodal metastases (3/25 compared with 43/96, p = 0.002), or to recur (0/25 compared with 33/96, p = 0.002). No patients died in the encapsulated group compared with 11/96 in the other group. CONCLUSIONS: Encapsulated papillary carcinomas have an excellent prognosis, and can be cured by operation.
[The diagnosis and surgical treatment of nodular neoplasms of the thyroid in childhood and adolescence].
The authors made an analysis of results of surgical treatment of 215 children and adolescents aged 5 to 20 years. Carcinoma of the thyroid gland was diagnosed in 25.6% of the patients. The operations were organ-saving and oncologically adequate. An analysis of long-term results has shown the survival of the absolute majority of the patients and good functional compensation of the thyroid remnant.
Molecular defects in thyroid carcinomas: role of the RET oncogene in thyroid neoplastic transformation.
Tumors are believed to arise as a result of an accumulation of mutations in critical genes involved in the control of cell proliferation. Thyroid neoplasms represent a good model for studying the role of these mutations in epithelial cell multistep carcinogenesis because they comprise a broad spectrum of lesions with different degrees of malignancy. Recent reports have described the involvement of specific genetic alterations in different types of thyroid neoplasms. Papillary carcinomas are characterized by the activation of the receptor tyrosine kinases RET and TRK-A proto-oncogenes. Ras point mutations are frequently observed in tumors with follicular histology and a high prevalence of p53 point mutations have been found in anaplastic carcinomas. A definition of molecular defects characterizing thyroid tumors will be helpful in establishing sensitive and specific detection strategies and, in addition, to define genetic and environmental factors important for their pathogenesis.
Diagnostic approach, genetic screening and prognostic factors of medullary thyroid carcinoma.
Medullary thyroid carcinoma is the least frequent thyroid neoplasm; it originates in thyroid parafollicular cells (calcitonin secreting C cells). In 80% of cases it is sporadic, in the remaining 20% it is familial, associated or not to other endocrinopathies as pheochromocytoma and hyperparathyroidism (MEN 2A, MEN 2B, and isolated familial medullary thyroid carcinoma). Preclinical diagnosis in relatives of affected subjects (preferably at pediatric age) is essential for successful therapy and is performed with genetic and biochemical screening tests. The genetic screening is based on DNA analysis (RET proto-oncogene mutations) of the patient, and if positive of all first degree relatives, to separate sporadic (somatic mutations) from familial (germline mutations) forms. The biochemical screening is based on calcitonin determination and its increase after pentagastrin stimulation, (a peculiar characteristic of medullary thyroid carcinoma, the first biochemical disorder in a subject at risk) and is mainly used in genetically silent familial medullary thyroid carcinoma. The principal negative prognostic factors of medullar thyroid carcinoma and the debate concerning the use of calcitonin determination in the diagnosis of the "cold" thyroid nodule have been analyzed.
Biomarker identification through spatial proteomics for the characterization of indeterminate thyroid nodules.
PURPOSE: The identification of novel molecular biomarkers may assist in the characterization of indeterminate thyroid nodules, which pose significant diagnostic challenges. Here, we aimed to explore the potential of proteomic analyses to support biomarker discovery in challenging thyroid lesions. METHODS: Linear Discriminant Analysis (LDA) was applied to Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) data from 44 thyroid neoplasms to select the most impactful molecular features for the classification of different tumor histologies, as well as for the distinction between NRAS-mutant (mNRAS) and NRAS-wild-type (wtNRAS) tumors. Relevant peaks were subsequently identified through nanoscale liquid chromatography electrospray ionization tandem mass spectrometry (nLC-ESI-MS/MS). RESULTS: The LDA selected nine relevant molecular markers distinguishing noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) from other tumor histologies (balanced accuracy = 73%), as well as 19 relevant markers able to identify mNRAS cases (balanced accuracy = 84%). Nine differentially expressed proteins were putatively identified: among them, ATP-dependent RNA helicase DDX42 showed a similar distribution between NIFTPs and papillary thyroid carcinomas (PTCs) / follicular variant PTCs (FVPTCs), while the distribution of the Histone H4 signal was similar between NIFTPs and follicular adenomas (FAs). In addition, Protein disulfide-isomerase A1 and Complement C4-B were overexpressed in wtNRAS compared to mNRAS cases, regardless of histology. CONCLUSION: The LDA-selected features enable to distinguish NIFTPs from morphologically similar lesions and to discriminate between mNRAS and wtNRAS cases. The identified markers might complement genetic analyses and provide insights into the distinct pathogenic drivers behind the development of mNRAS compared to wtNRAS lesions.
[Value of immunohistocytochemistry in the diagnosis of laterocervical masses in patients with a previous history of thyroid carcinoma].
BACKGROUND: The aim of this study is to evaluate the additional diagnostic significance of immunocytochemical staining of thyreoglobulin (TG) in Fine Needle Aspiration Biopsy (FNAB) of neck lymph-nodes, in patients with a previous history of thyroid carcinoma. METHODS: Twenty-five smears performed by ultrasound-guided FNAB on laterocervical nodes with a 21-23 gauge needle were evaluates. All smears were stained according to Papanicolaou and microscopically examined. RESULTS: Of these 25 smears, 15 were diagnostic and 10 were non diagnostic. Of the 15 diagnostic cases, 10 were positive for metastatic lesions from thyroid neoplasm and the other 4 were classified as reactive lymphoadenitis. One smear for each case was selected for the immunohistochemical stain. All the 10 non-diagnostic cases showed no reaction to thyreoglobulin. Neoplastic cells, from 9 out of 11 cytologically positive smears, expressed thyreoglobulin in the cytoplasm. In one case no reaction was evident and the other one was discarded for technical reasons. In 3 of the 4 cases cytologically classified as lymphoadenitis, immunoreactive thyreoglobulin was not found. In the fourth case, blastic-like cells showed a scanty cytoplasmic rime which was immunoreactive for TG and thus was classified as a metastatic tumour. On this basis, it is suggested that FNAB should be performed routinelly in the diagnostic evaluation of neck masses of unknown origin in patients with a previous history of thyroid neoplasm. CONCLUSIONS: If the FNAB is inconclusive, a second aspiration should be performed while immunoperoxidase stain to evidentiate TG may be an adjuntive diagnostic tool in cytologically negative cases.
Point mutations of ras oncogenes are an early event in thyroid tumorigenesis.
Identifying the nature of the genetic mutations in thyroid neoplasms and their prevalence in the various tumor phenotypes is critical to understanding their pathogenesis. Mutational activation of ras oncogenes in human tumors occurs predominantly through point mutations in two functional regions of the molecules, codons 12, 13 (GTP-binding domain) or codon 61 (GTPase domain). We examined the prevalence of point mutations in codons 12, 13, and 61 of the oncogenes K-ras, N-ras, and H-ras in benign and malignant human thyroid tumors by hybridization of PCR-amplified tumor DNA with synthetic oligodeoxynucleotide probes. None of the eight normal thyroid tissues harbored point mutations. Four of nineteen nodules from multinodular goiters (21%), 6/24 microfollicular adenomas (25%), 3/14 papillary carcinomas (21%), and 0/3 follicular carcinomas contained ras point mutations. The predominant mutation was a valine for glycine substitution in codon 12 of H-ras. None of the multinodular goiter tumors known to be polyclonal (and thus due to hyperplasia) had point mutations, whereas one of the two monoclonal adenomas arising in nodular glands contained in H-ras codon 12 valine substitution, which was confirmed by sequencing the tumor DNA. These data show that ras activation is about equally prevalent in benign and malignant thyroid neoplasms, and thus may be an early event in the tumorigenic process.
Sentinel lymph node biopsy in thyroid tumors: a pilot study.
The purpose of this study was to assess the feasibility of sentinel lymph node (SLN) biopsy in thyroid neoplasms. Ten patients with uninodular thyroid disease and no evidence of lymph node metastases were examined. Lymph node mapping was performed by preoperative lymphoscintigraphy and intraoperative use of a hand-held gammaprobe. Following thyroidectomy, the SLN(s) were selectively excised and worked-up histologically for occult metastases. Overall detection of SLNs was possible in 50% of the cases with lymphoscintigraphy and in 100% with the gammaprobe. All SLNs in the lateral compartment and upper mediastinum were accurately detected with lymphoscintigraphy. One patient with a papillary carcinoma showed a metastasis in the SLN. One patient experienced temporary lesion of the recurrent laryngeal nerve. In conclusion, sentinel lymph node biopsy is technically feasible. The combination of lymphoscintigraphy and gammaprobe accurately reveals SLNs in the central and lateral compartment and in the mediastinum. Search for SLNs in the lower central compartment enhances the risk of injuring the recurrent laryngeal nerve. The clinical relevance of SLN biopsy in papillary thyroid cancer is unclear, and the subgroup of patients benefiting from it has still to be defined.
Morphometric studies on nuclei in smears of fine needle aspirates from oxyphilic tumors of the thyroid.
Morphometry was applied to smears of fine needle aspirates from 26 oxyphilic thyroid neoplasms. Thirteen tumors were considered benign as judged from histologic findings and clinical follow-up for 2 to 20 years after the operation. Thirteen tumors were considered malignant histologically; four of these had proven metastases. In each case the mean and standard deviation of the projected nuclear area were calculated from 200 nuclei in the smear. Our results indicate that morphometric estimation of mean nuclear size and/or degree of anisokaryosis is of no practical value in distinguishing between benign and malignant thyroid neoplasms of the oxyphilic type.
CURRENT STATUS OF ABCC-NIH STUDIES OF CARCINOGENESIS IN HIROSHIMA AND NAGASAKI.
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Simultaneous expression of keratan sulphate epitope (a sulphated poly-N-acetyllactosamine) and blood group ABH antigens in papillary carcinomas of the human thyroid gland.
The monoclonal antibody 5-D-4 recognizes heavily sulphated forms of keratan sulphate epitope. It reacted strongly with the cell surfaces of most thyroid papillary carcinomas from all the individuals examined, independently of the blood group of the patients. Cells of follicular variants of papillary carcinomas were also labelled by 5-D-4. In contrast, no labelling with this antibody was observed in other types of thyroid neoplasms, or in normal tissues. The reactivity of 5-D-4 with papillary carcinomas was markedly reduced or abolished by prior digestion with endo-beta-galactosidase, keratanase II, or N-glycosidase F. Although keratanase digestion had no effect on 5-D-4 labelling, it revealed the binding sites of Griffonia simplicifolia agglutinin II (GSA-II), which recognizes terminal N-acetylglucosamine in a limited number of carcinoma cells from some individuals. Blood group ABH antigens, which are simultaneously expressed together with keratan sulphate epitope in cancer cells, were eliminated by digestion with endo-beta-galactosidase and N-glycosidase F, but were resistant to keratanase and keratanase II treatment. These results indicate that keratan sulphate oligosaccharides are cancer-associated and are probably oncofoetal antigens, as are the blood group antigens in human thyroid glands. The results suggests that poly-N-acetyllactosamine, which is ubiquitously and consistently produced in papillary carcinomas, is modified in two different ways: sulphation on the 6-position of at least some units of either galactose or N-acetylglucosamine or both, and decoration of non-reducing termini with the blood group antigens. Along with the endo-beta-galactosidase-GSA-II labelling procedure, labelling with 5-D-4 may be a useful diagnostic means for distinguishing papillary carcinoma from other types of thyroid neoplasms.
E2F-1 transcription factor is overexpressed in oxyphilic thyroid tumors.
In thyroid tumors, several cell cycle regulators have been found to be altered or overexpressed, but no data exist on E2F transcription factors. Such factors (E2F-1 in particular) act as the final effectors in the retinoblastoma pathway but are also involved in apoptosis. To analyze E2F-1 expression in thyroid neoplasms, we investigated 73 thyroid tumors, including 28 oxyphilic and 45 nonoxyphilic lesions, by immunohistochemistry, in parallel with other cell cycle-related proteins (p27, pRb, p53, and Ki67). p27, Ki-67, pRb, and p53 expression patterns generally overlapped the literature data. E2F-1 was expressed in all thyroid tumor types, both benign and malignant, with no statistical correlation with proliferative status (except for anaplastic carcinoma). A significantly higher percentage of tumor cells expressed E2F-1 in oxyphilic adenomas (71.5%) and oxyphilic carcinomas (66.1%) as compared with that of the corresponding nonoxyphilic lesions (30.8% and 34.5%, respectively; P < .05). These same tumors had a relatively low proliferative index. Therefore, because oxyphilic tumors of the thyroid show peculiar morphological, phenotypic, and ultrastructural features, possibly related to their particular metabolic conditions, it is possible that E2F-1 overexpression is linked to activities other than cell cycle entry in oxyphilic tumors. In conclusion, E2F-1 is expressed in both benign and malignant thyroid tumors, thus suggesting a wide involvement of the retinoblastoma pathway in thyroid tumorigenesis. In addition, in oxyphilic tumors, more than two thirds of tumor cells express E2F-1, an event possibly linked to proapoptotic rather than proliferative signals in such neoplasms.
Associations between lymphocytic thyroiditis, hypothyroidism, and thyroid neoplasia in beagles.
The thyroids were evaluated in 276 control Beagles that were allowed to live out their full life span (mean = 12 years) in a closed breeding colony. Lymphocytic thyroiditis was found in 26.3% of the dogs. This lesion was characterized by lymphoplasmacytic inflammation accompanied by follicular destruction. The thyroiditis was progressive, resulting in severe atrophy of follicular tissue, and 44 dogs (15.9%) were diagnosed as hypothyroid at the time of death. In accordance with the experimental protocol, hypothyroid dogs were not given thyroxine replacement therapy. There was a high degree of heritability for the hypothyroidism. Hypothyroid dogs had an increased risk for thyroid follicular epithelial neoplasia and, in particular, for follicular adenocarcinomas. Twenty-four of the 44 hypothyroid dogs (54.5%) had one or more follicular thyroid neoplasms, whereas only 53 of the 232 (22.8%) clinically euthyroid dogs had similar tumors. Multiple thyroid tumors were present in 14 of the 44 (31.8%) hypothyroid dogs but in only 12 of the 232 (5.2%) euthyroid dogs. One or more follicular adenocarcinomas were present in 15 of the 44 (34.1%) hypothyroid dogs but in only 16 of the 232 (6.9%) euthyroid dogs. There was no difference in prevalence of hypothyroidism or tumors between the sexes. The strong association between progressive lymphocytic thyroiditis, hypothyroidism, and thyroid follicular neoplasia in these Beagles probably relates to promotion of residual follicular epithelium by chronic excess thyrotropin stimulation.