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

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).

CDX2 Is a Useful Marker of Intestinal-Type Differentiation: A Tissue Microarray–Based Study of 629 Tumors From Various Sites

2005 ◽  
Vol 129 (9) ◽  
pp. 1100-1105 ◽  
Author(s):  
Lindsey B. De Lott ◽  
Carl Morrison ◽  
Saul Suster ◽  
David E. Cohn ◽  
Wendy L. Frankel
Keyword(s):  
Squamous Cell ◽  
Signet Ring Cell ◽  
Squamous Cell Carcinomas ◽  
Intestinal Type ◽  
High Grade ◽  
Poorly Differentiated Neuroendocrine Carcinoma ◽  
Poorly Differentiated ◽  
Lung Adenocarcinomas ◽  
Colorectal Adenocarcinomas ◽  
Neuroendocrine Carcinomas

Abstract Context.—CDX2, a critical nuclear transcription factor for intestinal development, is expressed in intestinal epithelium and adenocarcinomas. Objectives.—To determine if CDX2 is a useful marker for intestinal-type differentiation and to correlate tumor histology with CDX2 staining in colorectal adenocarcinomas. Design.—Tissue microarrays from 71 colorectal adenocarcinomas, 31 hepatocellular carcinomas, 47 lung adenocarcinomas, 55 squamous cell carcinomas of the lung, 69 neuroendocrine carcinomas of the lung and 43 of the pancreas, 57 pancreatic adenocarcinomas, and 256 endometrial adenocarcinomas were stained with antibody against CDX2. Results.—CDX2 staining was positive in 51 (71.8%) of 71 colorectal cancers, including 38 (74.5%) of 51 well- or moderately differentiated tumors and 13 (65.0%) of 20 high-grade tumors. Of the high-grade tumors, 5 (71.4%) of 7 mucinous, 3 (100%) of 3 signet ring cell, and 5 (50.0%) of 10 poorly differentiated tumors were positive. Other tumors showing occasional CDX2 staining included 1 of 30 well- or moderately differentiated neuroendocrine carcinomas of the lung and 2 of 43 from the pancreas, 1 of 47 lung adenocarcinomas, 3 of 57 pancreatic adenocarcinomas, and 15 of 256 endometrial carcinomas. Hepatocellular, poorly differentiated neuroendocrine carcinoma of the lung and squamous cell carcinomas of the lung were not immunoreactive for CDX2. Conclusions.—CDX2 is a useful marker for intestinal-type differentiation, is rarely seen in tumors from the other sites evaluated, and may be useful in determining the site of origin for some metastatic tumors. However, CDX2 is not a sensitive marker for poorly differentiated colorectal carcinoma.

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.

scholarly journals Pannus Is the New Prepuce? Penile Cancer in a Buried Phallus

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Jared Manwaring ◽  
Srinivas Vourganti ◽  
Dmitriy Nikolavsky ◽  
Alfredo L. Valente ◽  
Timothy Byler
Keyword(s):  
Squamous Cell Carcinoma ◽  
Early Detection ◽  
Cell Carcinoma ◽  
Chronic Inflammation ◽  
Penile Cancer ◽  
High Grade ◽  
Fat Pad ◽  
Poorly Differentiated ◽  
Suspicious Lesions ◽  
Buried Penis

Two males presented to our urology department with complaints of bleeding and malodor from buried phallus within a suprapubic fat pad. Although both men had neonatal circumcisions, advanced penile carcinoma was found in both men. Formal penectomies showed high grade, poorly differentiated squamous cell carcinoma invading the corporal bodies and urethra. Buried penis represents a difficulty in early detection of suspicious lesions but may also provide an environment susceptible to poor hygiene and subsequent chronic inflammation. Patients with buried penis may be at a higher risk for development of invasive penile cancer and may benefit from regular and thorough genital exams.

Diagnostic and Prognostic Role of HBME-1, Galectin-3, and β-Catenin in Poorly Differentiated and Anaplastic Thyroid Carcinomas

2013 ◽  
Vol 21 (3) ◽  
pp. 237-241 ◽  
Author(s):  
Esther D. Rossi ◽  
Patrizia Straccia ◽  
Marianna Palumbo ◽  
Egidio Stigliano ◽  
Luca Revelli ◽  
...  
Keyword(s):  
Prognostic Role ◽  
Thyroid Carcinomas ◽  
Galectin 3 ◽  
Poorly Differentiated

scholarly journals RAS Mutations Are the Predominant Molecular Alteration in Poorly Differentiated Thyroid Carcinomas and Bear Prognostic Impact

2009 ◽  
Vol 23 (10) ◽  
pp. 1715-1715
Author(s):  
Marco Volante ◽  
Ida Rapa ◽  
Manoj Gandhi ◽  
Gianni Bussolati ◽  
Daniela Giachino ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Diagnostic Criteria ◽  
Molecular Data ◽  
Genetic Alteration ◽  
Prognostic Impact ◽  
Genetic Event ◽  
Thyroid Carcinomas ◽  
Ras Mutations ◽  
Poorly Differentiated Carcinoma ◽  
Poorly Differentiated

ABSTRACT Context Poorly differentiated carcinomas represent an aggressive group of thyroid tumors with controversial classification placement and poorly understood pathogenesis. Molecular data in this group of tumors are extremely heterogeneous, possibly reflecting different inclusion criteria. Recently homogeneous diagnostic criteria have been proposed by our group (Turin proposal) that need to be complemented by detailed molecular characterization. Objective The objective of the study was to define a comprehensive molecular typing of poorly differentiated thyroid carcinomas classified following homogeneous diagnostic criteria. Design Sixty-five cases of poorly differentiated carcinoma selected following the Turin proposal have been screened for N-, K-, H-RAS, BRAF, RET/PTC1 and 3, and PAX8/PPARγ mutations-rearrangements using alternative techniques and in two different laboratories. Molecular data were compared with clinical pathological parameters and survival by univariate and multivariate analysis. Results RAS mutations in codon 61 were by far the most common genetic alteration in poorly differentiated carcinomas (23% of cases), with all mutation in NRAS except one in the HRAS gene. A single BRAF mutation was found in a poorly differentiated carcinoma with a residual component of a tall cell variant of papillary carcinoma. No KRAS, RET/PTC, or PAX8/PPARγ genetic alteration was detected. In this series, the presence of RAS mutations was a unique negative prognostic parameter at multivariate analysis. Conclusions The present study demonstrates that strictly classified poorly differentiated carcinomas are genetically homogeneous, RAS mutations being the almost exclusive genetic event. Moreover, the detection of RAS mutations might be clinically relevant for the prognostic stratification of these tumors.

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