scholarly journals Solid Thyroid Follicular Nodules With Longitudinal Nuclear Grooves: Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 18 Cases

2021 ◽  
Author(s):  
David Suster ◽  
A. Craig Mackinnon ◽  
Vania Nosé ◽  
Saul Suster
Keyword(s):  
Growth Pattern ◽  
Thyroid Nodules ◽  
Molecular Genetic ◽  
Follicular Adenoma ◽  
Cytokeratin 19 ◽  
Low Grade ◽  
Single Nucleotide Variants ◽  
Molecular Genetic Study ◽  
Clinicopathologic Characteristics ◽  
Atypical Features

Context.— Follicular thyroid nodules can be a source of diagnostic difficulties, particularly when they display atypical features commonly associated with malignancy, such as nuclear grooves. Objective.— To differentiate lesions with atypical features from similar-appearing benign and malignant lesions. Design.— Eighteen cases of atypical follicular thyroid nodules characterized by a solid growth pattern and prominent longitudinal nuclear grooves were studied and examined for clinicopathologic characteristics. Results.— The lesions occurred in 16 women and 2 men aged 36 to 88 years and measured from 0.2 to 1.5 cm. The tumors were well circumscribed and noninvasive, and histologically characterized by a predominantly solid growth pattern with rare scattered follicles or a combination of solid growth pattern with minor follicular areas. A striking feature seen in all cases was the occurrence of longitudinal nuclear grooves. Immunohistochemical stains showed negativity for cytokeratin 19 (CK19) and HBME-1 in 8 cases; in the other 10, there was focal positivity for HBME-1 in 4 cases and diffuse positivity in 6. All cases were negative for galectin-3 and for CK19, with the exception of 1 case, which was CK19+/HBME-1−. Next-generation sequencing of 16 cases with a 161-gene panel detected 14 single nucleotide variants in 12 cases, predominantly NRAS and HRAS mutations. Clinical follow-up ranging from 18 to 72 months (median, 43.7 months) did not disclose any evidence of recurrence or metastases. Conclusions.— We interpret these lesions as low-grade, indolent follicular proliferations that need to be distinguished from papillary thyroid carcinoma, follicular adenoma, and noninvasive follicular thyroid neoplasms with papillary-like nuclear features.

scholarly journals Clinicopathological investigation of secretory carcinoma cases including a successful treatment outcome using entrectinib for high-grade transformation: a case report

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Kensuke Suzuki ◽  
Hiroshi Harada ◽  
Masayuki Takeda ◽  
Chisato Ohe ◽  
Yoshiko Uemura ◽  
...  
Keyword(s):  
Head And Neck ◽  
Genetic Study ◽  
Locoregional Recurrence ◽  
Molecular Genetic ◽  
Labeling Index ◽  
Low Grade ◽  
High Grade ◽  
Secretory Carcinoma ◽  
Molecular Genetic Study ◽  
Ki 67

Abstract Background Secretory carcinoma (SC) of the salivary gland is a recently described malignant tumor harboring characteristic ETV6-NTRK3 gene fusion. SC generally has a favorable clinical course, and is currently regarded as a low-grade carcinoma. However, a small subset of SCs demonstrates aggressive clinical features with histologically high-grade transformed morphology, the molecular pathogenesis of which has not yet been elucidated. In this study, we performed a clinicopathological and molecular genetic study of patients with SC of the head and neck displaying various clinical characteristics to investigate the differences of pathological and molecular genetics between low-grade and high-grade components of SC. Case presentation Three cases with SC of the head and neck, including a conventional low-grade SC and two high-grade transformed SCs are described. High-grade transformed SCs with histological features such as nuclear polymorphism, distinctive nucleoli and increased mitotic activity developed locoregional recurrence and distant metastasis. Immunohistochemical analysis revealed that low- and high-grade components showed different expression patterns for S-100 protein and mammaglobin, whereas all examined components were positive for p-STAT5. p53-positive cell population was markedly higher in one case with high-grade transformed SC. The proliferative activity of high-grade components was markedly increased, with the Ki-67 labeling index ranging up to 30–32%. A fluorescence in situ hybridization study with an ETV6 (12p13) break apart probe revealed split signals in the nuclei in all 3 cases. A targeted next-generation sequencing-based fusion assay demonstrated that all 6 clinical samples from the 3 patients showed the presence of the ETV6-NTRK3 fusion transcripts. One patient with high-grade transformed SC showed a dramatic clinical response to the pan-TRK inhibitor, entrectinib, for the treatment of locoregional recurrence and pulmonary metastasis. Conclusions High-grade transformed SC showed aggressive clinical and pathological features with increased Ki-67 labeling index. Molecular genetic study of gene rearrangement appears to be beneficial treatment as the presence of ETV6-NTRK3 translocation may represent a therapeutic target in SC, particularly the high-grade transformed type.

Molecular genetic markers for thyroid FNAB

2015 ◽  
Vol 54 (03) ◽  
pp. 94-100 ◽  
Author(s):  
P. B. Musholt ◽  
T. J. Musholt
Keyword(s):  
Genetic Markers ◽  
Thyroid Nodules ◽  
Molecular Genetic ◽  
Genetic Alterations ◽  
Diagnostic Tools ◽  
Ultrasound Screening ◽  
Thyroid Malignancy ◽  
Thyroid Carcinomas ◽  
Molecular Genetic Markers ◽  
The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

Challenges in the differential diagnosis of multiple endocrine neoplasia syndrome type 1 with isolated family hyperparathyroidism

2020 ◽  
Vol 98 (3) ◽  
pp. 218-225
Author(s):  
J. A. Krupinova ◽  
N. G. Mokrysheva ◽  
N. Y. Kalinchenko ◽  
A. K. Eremkina ◽  
A. N. Polyakov ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Molecular Genetic ◽  
Pancreatic Neuroendocrine Tumor ◽  
Family Type ◽  
Dynamic Monitoring ◽  
Heterozygous Mutation ◽  
Molecular Genetic Study ◽  
Men 1 ◽  
Endocrine Neoplasia

Multiple endocrine neoplasia type 1 (MEN-1) is the most common cause of the hereditary type of primary hyperparathyroidism (PHPT). If a family type of PHPT is suspected, a dynamic monitoring of patients and their close relatives should be carried out throughout their lives. We present a clinical case of a family in which four members of a pedigree were diagnosed with familial isolated hyperparathyroidism (FIHP). The diagnosis was changed to MEN-1, because it appeared that one of the patients had pancreatic neuroendocrine tumor. Molecular genetic study of MEN1 by direct by means of Sanger sequencing revealed that six family members had a new heterozygous mutation in exon 9: s. 1252 G> T p. D418Y.

scholarly journals Prospects for the Personalized Multimodal Therapy Approach to Pain Management via Action on NO and NOS

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2431
Author(s):  
Natalia A. Shnayder ◽  
Marina M. Petrova ◽  
Tatiana E. Popova ◽  
Tatiana K. Davidova ◽  
Olga P. Bobrova ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Molecular Genetic ◽  
Pain Syndrome ◽  
Medical Problem ◽  
Single Nucleotide Variants ◽  
Genetic Studies ◽  
Pain Syndromes ◽  
Nos Inhibitors ◽  
Peripheral Pain

Chronic pain syndromes are an important medical problem generated by various molecular, genetic, and pathophysiologic mechanisms. Back pain, neuropathic pain, and posttraumatic pain are the most important pathological processes associated with chronic pain in adults. Standard approaches to the treatment of them do not solve the problem of pain chronicity. This is the reason for the search for new personalized strategies for the prevention and treatment of chronic pain. The nitric oxide (NO) system can play one of the key roles in the development of peripheral pain and its chronicity. The purpose of the study is to review publications devoted to changes in the NO system in patients with peripheral chronical pain syndromes. We have carried out a search for the articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar databases. The search was carried out using keywords and their combinations. The role of NO and NO synthases (NOS) isoforms in peripheral pain development and chronicity was demonstrated primarily from animal models to humans. The most studied is the neuronal NOS (nNOS). The role of inducible NOS (iNOS) and endothelial NOS (eNOS) is still under investigation. Associative genetic studies have shown that single nucleotide variants (SNVs) of NOS1, NOS2, and NOS3 genes encoding nNOS, iNOS, and eNOS may be associated with acute and chronic peripheral pain. Prospects for the use of NOS inhibitors to modulate the effect of drugs used to treat peripheral pain syndrome are discussed. Associative genetic studies of SNVs NOS1, NOS2, and NOS3 genes are important for understanding genetic predictors of peripheral pain chronicity and development of new personalized pharmacotherapy strategies.

scholarly journals Low-grade serous epithelial ovarian cancer: a comprehensive review and update for radiologists

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sofia Amante ◽  
Filipa Santos ◽  
Teresa Margarida Cunha
Keyword(s):  
Ovarian Cancer ◽  
Serous Carcinoma ◽  
Low Grade ◽  
Resonance Imaging ◽  
Clinicopathologic Characteristics ◽  
Borderline Tumour ◽  
Molecular Features ◽  
Serous Epithelial Ovarian Cancer ◽  
The Difference

AbstractLow-grade serous carcinoma (LGSC) is an infrequent subtype of ovarian cancer, corresponding to 5% of epithelial neoplasms. This subtype of ovarian carcinoma characteristically has molecular features, pathogenesis, clinical behaviour, sensitivity to chemotherapy, and prognosis distinct to high-grade serous carcinoma (HGSC). Knowing the difference between LGSC and other ovarian serous tumours is vital to guide clinical management, which currently is only possible histologically. However, imaging can provide several clues that allow differentiating LGSC from other tumours and enable precise staging and follow-up of ovarian cancer treatment. Characteristically, LGSC appears as mixed lesions with variable papillary projections and solid components, usually in different proportions from those detected in serous borderline tumour and HGSC. Calcified extracellular bodies, known as psammoma bodies, are also a common feature of LGSC, frequently detectable within lymphadenopathies and metastases associated with this type of tumour. In addition, the characterisation of magnetic resonance imaging enhancement also plays an essential role in calculating the probability of malignancy of these lesions. As such, in this review, we discuss and update the distinct radiological modalities features and the clinicopathologic characteristics of LGSC to allow radiologists to be familiarised with them and to narrow the differential diagnosis when facing this type of tumour.

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