Cytomorphological and molecular genetic findings in pediatric thyroid fine‐needle aspiration

BACKGROUND:

The Bethesda System for Reporting Thyroid Cytopathology is largely based on data from adult studies. Although thyroid nodules in children are rare, the rate of malignancy is high. The authors' aim was to analyze the cytomorphology and mutational profiles in pediatric thyroid fine‐needle aspirations (FNAs).

METHODS:

Thyroid FNAs from patients 21 years old or younger were identified from the authors' pathology archive, categorized using the Bethesda System for Reporting Thyroid Cytopathology, and correlated with histological and molecular follow‐up.

RESULTS:

A total of 179 samples from 142 patients were identified, including 96 cases (54%) with histological follow‐up and 66 cases (37%) with molecular data. The diagnoses included 21 (12%) unsatisfactory, 82 (46%) negative, 43 (24%) atypia or follicular lesion of undetermined significance, 19 (11%) suspicious for follicular neoplasm, 6 (3%) suspicious for malignancy, and 8 (4%) positive for malignancy. The rate of malignancy in each category was 0%, 7%, 28%, 58%, 100%, and 100%, respectively. Of the 66 FNAs with molecular data, there were 11 (17%) positive for mutations. All mutation‐positive FNAs were papillary thyroid carcinomas (PTCs) on resection. The overall sensitivity and specificity in this population were 80% and 100%, respectively.

CONCLUSIONS:

This study demonstrates that thyroid FNA in children is a sensitive and highly specific tool. There was a 17% positivity rate for a genetic mutation, which correlated with malignancy in all cases. In comparison to adults, there was a higher prevalence of RET/PTC mutations and lower prevalence of BRAF mutations, which may in part explain the less aggressive nature of PTCs reported in children. Cancer (Cancer Cytopathol) 2012. © 2012 American Cancer Society.     

Two sites of head and neck squamous cell carcinoma: utility of loss of heterozygosity

OBJECTIVES: The prevalence of distant metastasis and second primary tumors is increasing with improved locoregional control in patients with head and neck squamous cell carcinoma. Traditionally, clinicopathologic evidence has been the gold standard used to distinguish distant metastasis from second primary tumors. We report a case in which loss of heterozygosity testing was used to clarify the clonal relationship between the 2 sites of head and neck squamous cell carcinoma. METHODS: A patient with squamous cell carcinoma in the larynx and mandible underwent loss of heterozygosity testing. RESULTS: The loss of heterozygosity testing confirmed that the mandibular cancer was a metastatic presentation of the laryngeal squamous cell carcinoma. CONCLUSIONS: We conclude that loss of heterozygosity testing can be useful in differentiating distant metastasis from second primary cancers in patients with 2 sites of head and neck squamous cell carcinoma, consequently providing important prognostic and staging information.     

Lipid peroxidation in the kidneys of rats with nephritis caused by nephrotoxic serum and with proteinuria induced by albumin loading

Research Institute of Urology, Ministry of Health of the RSFSR. I. I. Mechnikov Research Institute of Vaccines and Sera, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Lopatkin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 9, pp. 237–240, September, 1991.     

Opisthorchiasis at left Dnieper watersheds

Present state of opisthorchosis infestation in the Dnieper watershed (rivers Vorskla, Psyol, Khorol, Sula, Seym, Snov, Desna water basins), situated in the Sumy, Chernigov, and Poltava regions of the Ukraine, is assessed. 7909 humans from 37 villages, 94 cats, 1134 carp fishes, 20013 mollusca and 30 soil samples were screened for the presence of Opisthorchis eggs. Opisthorchosis foci with an over 36% infection rate of population remain in the watersheds of the Dnieper left confluents (rivers Desna, Seym, Vorskla and Khorol). Infestation rate varies between various rivers as well as along one and the same river which is due to several ecological and social factors. Opisthorchis circulation is established at all the rivers but in most areas it didn't involve human population. Distribution pattern of human opisthorchosis in evidently focal and patchy which should be taken into account in the planning and implementation of opisthorchosis control measures.     

Solid variant of papillary thyroid carcinoma: incidence, clinical-pathologic characteristics, molecular analysis, and biologic behavior.

Solid variant is a rare and poorly characterized variant of papillary thyroid carcinoma. In this study we analyzed 20 primary cases of the solid variant of papillary carcinoma found in a series of 756 papillary carcinomas operated at the Mayo Clinic between 1962 and 1989. The criteria for classification included predominantly (>70%) solid growth pattern of primary tumor, retention of cytologic features typical of papillary carcinoma, and absence of tumor necrosis. For each case of the solid variant, a control case of classical papillary carcinoma matched by age, sex, tumor size, and length of follow-up was selected. The follow-up ranged from 6 to 32 years. Two patients with the solid variant of papillary carcinoma (10%) died from disease 7 and 10 years after initial surgery, while another two patients (10%) are alive with lung metastases. In contrast, the control group had no cases with distant metastases or death from disease. Molecular analyses showed a similar prevalence of RET /PTC rearrangements in both groups. In conclusion, the solid variant of papillary carcinoma is associated with a slightly higher frequency of distant metastases and less favorable prognosis than classical papillary carcinoma. However, it should be distinguished from poorly differentiated thyroid carcinoma, which has a reported lower survival rate compared with the solid variant of papillary carcinoma.     

Frequent loss of heterozygosity at chromosome 3p14.2–3p21 in human pancreatic islet cell tumours

OBJECTIVE: Pancreatic islet betacell tumours occur either sporadically or as part of inherited neoplastic syndromes, most commonly multiple endocrine neoplasia (MEN) type 1. Recently, a transgenic mouse model has been established in which the expression of the SV40 large T antigen was targeted to betacells by the rat insulin promoter, leading to the development of multiple pancreatic betacell tumours. In the advanced stages of tumour evolution, these tumours exhibited a high prevalence of loss of heterozygosity (LOH) on mouse chromosomes 9 and 16, at regions syntenic with regions 3q, 3p21, 6q12, 15q24 and 22q of the human genome. DESIGN: Loss of heterozygosity in human islet cell tumours was analysed in a PCR based approach at regions of the human genome syntenic with the mouse loci linked to pancreatic betacell tumours as well as the MEN1 gene on chromosome 11q13. These included 35 microsatellite markers in the human chromosomal regions 3q, 3p21, 6q12, 11q13, 15q24 and 22q. PATIENTS: 21 patients diagnosed with insulinoma were analysed. Histologically, 16 tumours were benign, while 5 were malignant insulinomas. RESULTS: Thirteen of 21 (62%) tumours were found to have loss of genetic material on chromosome 3. The shortest region of overlap implicated a deletion at 3p14.2-3p21 region, corresponding to the marker D3S1295. We did not detect a substantial frequency of LOH in the other syntenic regions, except for the region of MEN 1 gene on 11q13 found to be deleted in 6 (29%) cases, including 3 of 4 tumours from MEN 1 families. Deletions of 3p14. 2-3p21 were observed in 8 of 15 (53%) benign tumours, and in 5 of 6 (83%) malignant neoplasms. CONCLUSIONS: These results indicate the high frequency of 3p14.2-3p21 deletions in human pancreatic betacell neoplasms. These finding suggest the presence of a tumour suppressor gene in this region, that may be important in the microevolution of these tumours towards malignancy.     

BRAF mutation detection in indeterminate thyroid cytology specimens

BACKGROUND:

BRAF mutations are highly specific for papillary thyroid carcinoma (PTC) and many cytology specimens with BRAF mutations are expected to demonstrate cytologic features typical of PTC. However, indeterminate thyroid cytology cases are inevitable and understanding the significance of the BRAF mutation within the context of the Bethesda System for Reporting Thyroid Cytopathology would be valuable.

METHODS:

Thyroid cytology cases submitted for conventional cytomorphologic evaluation and BRAF mutational analyses were selected from the authors' cytopathology files from April 2007 to October 2011. From this group, the diagnostic usefulness of BRAF mutations in indeterminate and malignant cases was assessed and analyses of cytologic and histopathologic features associated with the mutations in this gene were performed.

RESULTS:

A total of 131 cases with a BRAF mutation were identified. Of these, 119 underwent surgical pathology resection follow‐up and demonstrated PTC. Approximately 75% of the cases were cytologically diagnosed as being positive for malignancy and these cases were associated with both the classic and tall cell variants of PTC at the time of resection, a greater likelihood of extrathyroidal extension, and the V600E type of BRAF mutation. In contrast, BRAF‐mutated cases with diagnoses of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm/suspicious for follicular neoplasm were found to be more strongly associated with the follicular variant of PTC, a K601E BRAF mutation, and a lower likelihood of extrathyroidal extension. However, a subset of AUS/FLUS cases with the V600E BRAF mutation appeared to represent sampling variability of the classic or tall cell variants of PTC.

CONCLUSIONS:

Bethesda thyroid diagnoses in the setting of a BRAF mutation reflect differences in PTC subtypes, the nature of cytology specimens, and molecular characteristics. Cancer (Cancer Cytopathol) 2013;121:197–205. © 2012 American Cancer Society.     

The Value of Rapid Antigen Tests for Identifying Carriers of Viable SARS-CoV-2

The search for effective methods to detect patients who excrete a viable virus is one of the urgent tasks of modern biomedicine. In the present study, we examined the diagnostic value of two antigen tests, BIOCREDIT COVID-19 Ag (RapiGEN Inc., Anyang, Korea) and SGTI-flex COVID-19 Ag (Sugentech Inc., Cheongju, Korea), for their diagnostic value in identifying patients who excrete viable SARS-CoV-2. As part of the study, we examined samples from 106 patients who had just been admitted to the hospital and who had undergone quantitative RT-PCR and assessment of viability of SARS-CoV-2 using cell culture. Assessment of the tests’ value for detecting samples containing viable virus showed high sensitivity for both tests. Sensitivity was 78.6% (95% CI, from 49.2% to 95.3%) for SGTI-flex COVID-19 Ag and 100% (95% CI, from 76.8% to 100%) for Biocredit COVID-19 Ag. The specificity of rapid tests was significantly higher than that of RT-PCR and was 66.3% (95% CI, from 55.7% to 75.8%) and 67.4% (95% CI, from 56.8% to 76.8%) for SGTI-flex COVID-19 Ag and Biocredit COVID-19 Ag versus 30.4% (95% CI, from 21.3% to 40.9%) obtained for PCR. Thus, for tasks of identifying viable SARS-CoV-2 during screening of conditionally healthy people, as well as monitoring those quarantined, rapid tests show significantly better results.     

MicroRNA expression profiling of thyroid tumors: biological significance and diagnostic utility

OBJECTIVE: MicroRNA (miRNA) expression is deregulated in many types of human cancers. We sought to investigate the expression patterns of miRNA in all major types of thyroid tumors, including tumors carrying distinct oncogenic mutations, and to explore the utility of miRNA profiling for the preoperative diagnosis of thyroid nodules. DESIGN: miRNA expression levels were detected in 60 surgically removed thyroid neoplastic and nonneoplastic samples and in 62 fine-needle aspiration (FNA) samples by RT-PCR using TaqMan MicroRNA Panel or individual miRNA sequence-specific primers. miRNA expression levels were calculated relative to normal thyroid tissue. All tumors were genotyped for most common mutations. RESULTS: Various histopathological types of thyroid tumors, including those deriving from the same cell type, showed significantly different profiles of miRNA expression. Oncocytic tumors, conventional follicular tumors, papillary carcinomas, and medullary carcinomas formed distinct clusters on the unsupervised hierarchical clustering analysis. Significant correlation between miRNA expression patterns and somatic mutations was observed in papillary carcinomas. A set of seven miRNAs (miR-187, miR-221, miR-222, miR-146b, miR-155, miR-224, and miR-197) that were most differentially overexpressed in thyroid tumors vs. hyperplastic nodules in the surgical samples was validated in the FNA samples, showing high accuracy of thyroid cancer detection. CONCLUSIONS: In this study, we demonstrate that various histopathological types of thyroid tumors have distinct miRNA profiles, which further differ within the same tumor type, reflecting specific oncogenic mutations. A limited set of miRNAs can be used diagnostically with high accuracy to detect thyroid cancer in the surgical and preoperative FNA samples.