scholarly journals Thyroid Carcinoma with NSD3::NUTM1 Fusion: a Case with Thyrocyte Differentiation and Colloid Production

2022 ◽  
Author(s):  
Derek B. Allison ◽  
Justin Rueckert ◽  
Virgilius Cornea ◽  
Cortney Y. Lee ◽  
Julie Dueber ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Squamous Carcinoma ◽  
Exceptional Case ◽  
High Grade ◽  
Squamous Differentiation ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated ◽  
Prognostic Implications ◽  
Nut Carcinoma

AbstractIn this report, we present a high-grade thyroid carcinoma with an NSD3::NUTM1 fusion detected on expanded next-generation sequencing testing. Nuclear protein of the testis (NUT) carcinomas comprise high-grade, aggressive tumors characterized by rearrangements of the NUTM1 gene with various partner genes, most commonly the bromodomain protein genes BRD4 and BRD3. Approximately 10% of NUT carcinomas contain an NSD3::NUTM1 fusion. NUT carcinomas manifest as poorly differentiated or undifferentiated squamous carcinomas, and 33% show areas of mature squamous differentiation. Only exceptionally have NUT carcinomas shown histology discordant from poorly differentiated/undifferentiated squamous carcinoma, and a thyroid NUT carcinoma with histologic thyrocyte differentiation has not been described to date. Our patient’s tumor exhibited mixed cytologic features suggestive of squamoid cells or papillary thyroid carcinoma cells. Overt squamous differentiation was absent, and the tumor produced colloid in poorly formed follicles. Immunophenotypically, the carcinoma was consistent with thyrocyte differentiation with expression of monoclonal PAX8, TTF1, and thyroglobulin (the last predominantly in extracellular colloid). There was zero to < 2% reactivity for proteins typically diffusely expressed in NUT carcinoma: p40, p63, and cytokeratins 5/6. NUT protein expression was equivocal, but fluorescence in situ hybridization confirmed a NUTM1 rearrangement. This exceptional case suggests that NUTM1 fusions may occur in an unknown number of aggressive thyroid carcinomas, possibly with distinctive histologic features but with thyrocyte differentiation. Recognition of this entity potentially has significant prognostic implications. Moreover, thyroid carcinomas with NUTM1 fusions may be amenable to treatment with NUT carcinoma-targeted therapy such as a bromodomain and extraterminal domain protein small molecular inhibitor (BETi).

scholarly journals Challenging Diagnosis in NUT Carcinoma

2021 ◽  
pp. 106689692110195
Author(s):  
Grosse Claudia ◽  
Grosse Alexandra
Keyword(s):  
Nuclear Protein ◽  
Hematological Malignancy ◽  
Undifferentiated Carcinoma ◽  
Squamous Differentiation ◽  
Poorly Differentiated Carcinoma ◽  
Poorly Differentiated ◽  
Nut Carcinoma ◽  
Disseminated Disease ◽  
Generation Sequencing

Nuclear protein in testis (NUT) carcinoma represents a highly aggressive, poorly differentiated carcinoma that is genetically defined by rearrangement of NUT gene. The histomorphological appearance ranges from entirely undifferentiated carcinoma to carcinoma with prominent squamous differentiation. NUT carcinoma can display neuroendocrine features. Although it is typically distributed along the midline axis, it may manifest in nonmidline locations. The majority of patients develop rapidly disseminated disease. We illustrate 2 cases of NUT carcinoma, one located in the lung, which closely resembled a neuroendocrine carcinoma, and the other one with assumed lung origin demonstrating metastatic dissemination with diffuse bone involvement, which was clinically first suspected to be a hematological malignancy. Due to its undifferentiated nature, NUT carcinoma may be confused with many entities. NUT immunohistochemistry is considered to be sufficient for the diagnosis. Fluorescence in-situ hybridization analysis and next-generation sequencing are currently used to confirm the diagnosis.

Problems and Controversies in the Histopathology of Thyroid Carcinomas of Follicular Cell Origin

2009 ◽  
Vol 133 (5) ◽  
pp. 683-691
Author(s):  
Ronald Ghossein
Keyword(s):  
Thyroid Carcinoma ◽  
English Language ◽  
Follicular Carcinoma ◽  
Molecular Data ◽  
Follicular Cell ◽  
Clinical Value ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated ◽  
Disease Entities

Abstract Context.—Despite past and recent efforts, many problems and controversies remain in the classification of thyroid carcinomas of follicular cell origin. These controversies have an impact on the prognosis and therapy of patients with thyroid carcinoma as well as on the development of robust cutting-edge research aimed at better outcome and quality of life. Objective.—To focus on 3 contentious areas with significant clinical value: the follicular variant of papillary thyroid carcinoma, the extent of invasion in follicular carcinoma, and the poorly differentiated thyroid carcinomas. Data Sources.—The published English language literature was reviewed. Conclusions.—Recent data show that prognosis and therapy for many disease entities can be better delineated if a meticulous microscopic examination is performed. An accurate assessment of the extent of invasion (especially vascular) is crucial. Proliferative grading (ie, mitosis and necrosis) is of high prognostic value and should be looked for in every specimen. In addition, molecular data gathered to date can help reassess these tumors at the histologic level. Classification proposals based on personal experience rather than adequate and careful clinical follow-up should be discouraged.

Poorly differentiated thyroid carcinomas: application of the Turin proposal provides prognostic results similar to those from the assessment of high-grade features

2013 ◽  
Vol 64 (2) ◽  
pp. 263-273 ◽  
Author(s):  
Viviane Gnemmi ◽  
Florence Renaud ◽  
Christine Do Cao ◽  
Julia Salleron ◽  
Georges Lion ◽  
...  
Keyword(s):  
High Grade ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated

Circulating Cytokeratin 19 Fragments in Patients with benign Nodules and Carcinomas of the Thyroid Gland

2008 ◽  
Vol 23 (1) ◽  
pp. 54-57 ◽  
Author(s):  
L. Giovanella ◽  
L. Ceriani ◽  
A. Ghelfo ◽  
M. Maffioli
Keyword(s):  
Thyroid Carcinoma ◽  
Thyroid Nodules ◽  
Differentiated Thyroid Carcinoma ◽  
Cytokeratin 19 ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated ◽  
Benign Nodules ◽  
Thyroid Malignancies ◽  
Benign Thyroid Nodules ◽  
Benign Thyroid

Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells and is highly expressed by differentiated thyroid carcinomas, mainly of the papillary subtype. The soluble fragments of CK19 (Cyfra 21.1) can be measured by immunometric assays employing specific monoclonal antibodies. The present study was planned to assess the serum expression of Cyfra 21.1 in patients with benign thyroid nodules and thyroid malignancies. We enrolled 135 patients with histologically proven benign thyroid nodules (n=79) and thyroid carcinomas (n=56). No differences were found in serum Cyfra 21.1 levels between patients with benign nodules and patients with carcinomas. When thyroid malignancies were subdivided according to tumor histology, serum Cyfra 21.1 increased significantly from classical differentiated thyroid carcinomas (papillary or follicular) to less differentiated or undifferentiated carcinomas (poorly differentiated or anaplastic). CK19 release into the bloodstream is strongly related to the apoptotic pathway, and particularly to hyperproliferation-related apoptosis. These pathways characterized anaplastic and poorly differentiated thyroid carcinoma but not classical forms of differentiated thyroid carcinoma. Consequently, Cyfra 21.1 may be regarded as a circulating marker of poorly differentiated and anaplastic thyroid carcinoma. Additionally, a role of Cyfra 21.1 as a dedifferentiation marker in patients with classical differentiated thyroid carcinomas may be postulated and should be explored by further focused studies.

Genetic profile of advanced thyroid cancers in relation to distant metastasis

2020 ◽  
Vol 27 (5) ◽  
pp. 285-293 ◽  
Author(s):  
Eyun Song ◽  
Dong Eun Song ◽  
Jonghwa Ahn ◽  
Tae Yong Kim ◽  
Won Bae Kim ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Distant Metastasis ◽  
Distant Metastases ◽  
Thyroid Tumors ◽  
Primary Tumors ◽  
Thyroid Cancers ◽  
Histone Methyltransferases ◽  
Thyroid Carcinomas ◽  
Poorly Differentiated

Major clinical challenges exist with differentiated thyroid cancers with distant metastases or rare but aggressive types, such as poorly differentiated thyroid carcinomas and anaplastic thyroid carcinomas. The precise characterization of the mutational profile in these advanced thyroid cancers is crucial. Samples were collected from primary tumors and distant metastases of 64 patients with distant metastases from differentiated thyroid cancer, poorly differentiated thyroid carcinoma, or anaplastic thyroid carcinoma. Targeted next-generation sequencing was performed with 50 known thyroid-cancer-related genes. Of the 82 tissues, 63 were from primary tumors and 19 from distant metastases. The most prevalent mutation observed from the primary tumors was TERT promoter mutation (56%), followed by BRAF (41%) and RAS (24%) mutations. TP3 was altered by 11%. Mutations in histone methyltransferases, SWI/SNF subunit–related genes, and PI3K/AKT/mTOR pathway-related genes were present in 42%, 12%, and 22%, respectively. When the mutational status was analyzed in 15 matched pairs of thyroid tumors and their matched distant metastases and one pair of distant metastases with two distinct sites, the concordance was high. A similar frequency of mutations in TERT promoter (58%) and BRAF (42%) as well as histone methyltransferases (37%), SWI/SNF subunits (10%), and PI3K/AKT/mTOR pathway (26%) were noted. The same main, early and late mutations were practically always present in individual primary tumor–metastasis pairs. Enrichment of TERT promoter, BRAF, and RAS mutations were detected in highly advanced thyroid cancers with distant metastasis. The genetic profiles of primary thyroid tumors and their corresponding distant metastases showed a high concordance.

Thyroid and Parathyroid Neoplasms with Lipomatous Stroma: Report of Three Cases and Review of the Literature

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S33-S33
Author(s):  
M Toprak ◽  
M Kashi ◽  
J Villanueva ◽  
M Wrzolek ◽  
G Tong ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Thyroid Carcinoma ◽  
Malignant Tumors ◽  
Diagnostic Error ◽  
Needle Aspiration ◽  
Parathyroid Glands ◽  
Fatty Tissue ◽  
Thyroid Carcinomas ◽  
Preoperative Diagnostic ◽  
Poorly Differentiated

Abstract Introduction/Objective Tumors with mixed adipose tissue and epithelial components are rare in thyroid and parathyroid glands. Most of them are benign and referred to as adenolipoma (or lipoadenoma). A handful of malignant tumors of thyroid follicular cell origin have been reported with abundant adipose tissue known as thyroid carcinoma with lipomatous stroma (TCLS). Adenolipomas of thyroid or TCLS are usually manifested as large thyroid nodules and evaluated by fine needle aspiration biopsy (FNAB) which frequently yield low-cellularity samples due to abundant adipose tissue. On FNAB, the adipose tissue usually interpreted as contamination of subcutaneous or perithyroid origin. Similarly, adenolipomas of the parathyroid are not frequently identified because of presence of adipose tissue which is a feature associated with normal parathyroid glands. Therefore, these tumors are not often correctly diagnosed preoperatively. For that reason, pathologist should report additional cases about this rare entity to increase our understanding and to decrease preoperative diagnostic error. Methods We report three cases of thyroid and parathyroid tumors with abundant adipose tissue with sonographic, cytologic and histologic features along with literature review. Results Among the reported cases in the literature and our cases; 10 out of 17 cases of thyroid carcinoma with lipomatous stroma are papillary thyroid carcinomas (58.8%), 3 out of 17 cases are papillary microcarcinomas (17.6%), 2 out of 17 cases are noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) (11.7%), and 2 out of 17 cases are minimally invasive follicular carcinomas (11.7%). No cases of poorly differentiated or anaplastic thyroid carcinomas have been reported. Conclusion Lipomatous stroma in thyroid carcinoma appears to be associated with differentiated carcinomas since no reported cases of poorly differentiated or anaplastic thyroid carcinomas are present to our knowledge. Although the presence of fatty tissue does not appear to alter the prognosis of these lesions, the question of the histogenesis of the adipose component is intriguing. Awareness of this unusual feature and increased utilization of multimodal approaches in the evaluation of this entity may increase preoperative detection and the understanding of the histogenesis and its possible significance.

scholarly journals Etiopathogenesis of Differentiated Thyroid Carcinomas

2016 ◽  
Vol 4 (3) ◽  
pp. 517-522
Author(s):  
Tanja Makazlieva ◽  
Olivija Vaskova ◽  
Venjamin Majstorov
Keyword(s):  
Thyroid Carcinoma ◽  
Epidemiological Studies ◽  
Genetic Alterations ◽  
Anaplastic Thyroid Carcinoma ◽  
Epigenetic Alterations ◽  
Thyroid Carcinomas ◽  
Etiological Factors ◽  
Appropriate Treatment ◽  
Poorly Differentiated ◽  
Thyroid Malignancies

INTRODUCTION: Thyroid malignomas are a heterogeneous group of neoplasm consisting of most frequent differentiated encountered carcinomas, papillary and follicular thyroid carcinoma, then medullary thyroid carcinoma originating from neuroendocrine calcitonin-producing C-cells and rare forms of thyroid lymphomas arising from intrathyroidal lymphatic tissue, thyroid sarcomas and poorly differentiated anaplastic thyroid carcinoma. There are increasing numbers of epidemiological studies and publications that have suggested increased incidence rate of thyroid carcinomas. We have read, analysed and compare available reviews and original articles investigating different etiological factors in the development of thyroid carcinomas through Google Scholar and PubMed Database.DISCUSSION: Aetiology involved in the development of thyroid carcinomas is multifactorial and includes external influences, as well as constitutional predispositions and genetic etiological factors. The actual effect of environmental and constitutional factors is on promoting genetic and epigenetic alterations which result in cell proliferation and oncogenesis. Until now are identified numerous genetic alterations, assumed to have an important role in oncogenesis, with MAPK and PI3K-AKT as crucial signalling networks regulating growth, proliferation, differentiation and cell survival/apoptosis. CONCLUSION: This new molecular insight could have a crucial impact on diagnosis and also on improving and selecting an appropriate treatment to the patients with thyroid malignancies.

Bone Metastases From Thyroid Carcinoma

2000 ◽  
Vol 124 (10) ◽  
pp. 1440-1447
Author(s):  
Satish K. Tickoo ◽  
Anastassios G. Pittas ◽  
Michael Adler ◽  
Melissa Fazzari ◽  
Steven M. Larson ◽  
...  
Keyword(s):  
Bone Metastasis ◽  
Thyroid Carcinoma ◽  
Bone Metastases ◽  
Tumor Type ◽  
Metastatic Tumors ◽  
Thyroid Carcinomas ◽  
Hürthle Cell ◽  
Significant Difference ◽  
Poorly Differentiated ◽  
Worse Prognosis

Abstract Context.—Only limited information exists on the pathologic aspects of thyroid carcinomas with bone metastases, most large studies having concentrated mainly on their clinical features. Objective.—To study in detail the morphologic features of thyroid carcinomas with skeletal metastases. Design.—Seventy-nine cases of thyroid carcinoma with bone metastases treated at Memorial Sloan-Kettering Cancer Center, New York, NY, between 1964 and 1998 were investigated, with emphasis on the pathology of the primary and/or metastatic tumors and comparison of the morphologic features of the tumors at both the sites, wherever possible. The tumors were also compared for various clinical parameters. Results.—The cohort consisted of 22 papillary, 17 follicular, 16 insular, 10 anaplastic, 9 Hürthle cell, and 5 medullary carcinomas. Of these cases, 68% had poorly differentiated or undifferentiated features in the primary and/or metastatic tumors. The metastatic tumors were better differentiated than the primary in one third of the cases (6 of 18). Only one case showed a less differentiated metastasis. The overall 5- and 10-year survival probabilities after the bone metastases were 29% and 13%, respectively (Kaplan-Meier method). Although both the tumor type and differentiation seemed to affect survivals after bone metastasis (P = .007 and .012, respectively) (log-rank test), this was primarily due to the much worse prognosis in the cases of anaplastic and medullary carcinoma. Cases of Hürthle cell carcinoma showed the longest median survival. There was no significant difference in survival among patients up to or older than 45 years at the time of metastases (P = .31). Conclusions.—Most thyroid carcinomas with bone metastases are of papillary type, and most have poorly differentiated or undifferentiated features. The influence of the microscopic tumor type and tumor differentiation on survival after bone metastasis primarily appears to be due to the much worse prognosis among anaplastic and medullary carcinomas. Age at diagnosis of bone metastases does not influence survivals.

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