A Detailed Histologic and Molecular Assessment of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma
Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved..
Diffuse sclerosing variant papillary thyroid carcinoma (DS-PTC) is characterized clinically by a predilection for children and young adults, bulky neck nodes, and pulmonary metastases. Previous studies have suggested infrequent BRAFV600E mutation but common RET gene rearrangements. Using strict criteria, we studied 43 DS-PTCs (1.9% of unselected PTCs in our unit). Seventy-nine percent harbored pathogenic gene rearrangements involving RET, NTRK3, NTRK1, ALK, or BRAF; with the remainder driven by BRAFV600E mutations. All 10 pediatric cases were all gene rearranged (P = .02). Compared with BRAFV600E-mutated tumors, gene rearrangement was characterized by psammoma bodies involving the entire lobe (P = .038), follicular predominant or mixed follicular architecture (P = .003), pulmonary metastases (24% vs none, P = .04), and absent classical, so-called "BRAF-like" atypia (P = .014). There was no correlation between the presence of gene rearrangement and recurrence-free survival. Features associated with persistent/recurrent disease included pediatric population (P = .030), gene-rearranged tumors (P = .020), microscopic extrathyroidal extension (P = .009), metastases at presentation (P = .007), and stage II disease (P = .015). We conclude that DS-PTC represents 1.9% of papillary thyroid carcinomas and that actionable gene rearrangements are extremely common in DS-PTC. DS-PTC can be divided into 2 distinct molecular subtypes and all BRAFV600E-negative tumors (1.5% of papillary thyroid carcinomas) are driven by potentially actionable oncogenic fusions.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
|---|---|
| Enthalten in: |
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc - 36(2023), 12 vom: 01. Dez., Seite 100329 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Chou, Angela [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
ALK |
|---|
| Anmerkungen: |
Date Completed 25.12.2023 Date Revised 25.12.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.modpat.2023.100329 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM362135975 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM362135975 | ||
| 003 | DE-627 | ||
| 005 | 20231227140858.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.modpat.2023.100329 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1238.xml |
| 035 | |a (DE-627)NLM362135975 | ||
| 035 | |a (NLM)37716505 | ||
| 035 | |a (PII)S0893-3952(23)00234-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Chou, Angela |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Detailed Histologic and Molecular Assessment of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 25.12.2023 | ||
| 500 | |a Date Revised 25.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Diffuse sclerosing variant papillary thyroid carcinoma (DS-PTC) is characterized clinically by a predilection for children and young adults, bulky neck nodes, and pulmonary metastases. Previous studies have suggested infrequent BRAFV600E mutation but common RET gene rearrangements. Using strict criteria, we studied 43 DS-PTCs (1.9% of unselected PTCs in our unit). Seventy-nine percent harbored pathogenic gene rearrangements involving RET, NTRK3, NTRK1, ALK, or BRAF; with the remainder driven by BRAFV600E mutations. All 10 pediatric cases were all gene rearranged (P = .02). Compared with BRAFV600E-mutated tumors, gene rearrangement was characterized by psammoma bodies involving the entire lobe (P = .038), follicular predominant or mixed follicular architecture (P = .003), pulmonary metastases (24% vs none, P = .04), and absent classical, so-called "BRAF-like" atypia (P = .014). There was no correlation between the presence of gene rearrangement and recurrence-free survival. Features associated with persistent/recurrent disease included pediatric population (P = .030), gene-rearranged tumors (P = .020), microscopic extrathyroidal extension (P = .009), metastases at presentation (P = .007), and stage II disease (P = .015). We conclude that DS-PTC represents 1.9% of papillary thyroid carcinomas and that actionable gene rearrangements are extremely common in DS-PTC. DS-PTC can be divided into 2 distinct molecular subtypes and all BRAFV600E-negative tumors (1.5% of papillary thyroid carcinomas) are driven by potentially actionable oncogenic fusions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ALK | |
| 650 | 4 | |a BRAF | |
| 650 | 4 | |a NTRK | |
| 650 | 4 | |a RET | |
| 650 | 4 | |a diffuse sclerosing | |
| 650 | 4 | |a gene fusions | |
| 650 | 4 | |a papillary thyroid carcinoma | |
| 650 | 7 | |a Proto-Oncogene Proteins B-raf |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Receptor Protein-Tyrosine Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 700 | 1 | |a Qiu, Min Ru |e verfasserin |4 aut | |
| 700 | 1 | |a Crayton, Henry |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Ahadi, Mahsa S |e verfasserin |4 aut | |
| 700 | 1 | |a Turchini, John |e verfasserin |4 aut | |
| 700 | 1 | |a Clarkson, Adele |e verfasserin |4 aut | |
| 700 | 1 | |a Sioson, Loretta |e verfasserin |4 aut | |
| 700 | 1 | |a Sheen, Amy |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Nisha |e verfasserin |4 aut | |
| 700 | 1 | |a Clifton-Bligh, Roderick J |e verfasserin |4 aut | |
| 700 | 1 | |a Robinson, Bruce G |e verfasserin |4 aut | |
| 700 | 1 | |a Gild, Matti L |e verfasserin |4 aut | |
| 700 | 1 | |a Tsang, Venessa |e verfasserin |4 aut | |
| 700 | 1 | |a Leong, David |e verfasserin |4 aut | |
| 700 | 1 | |a Sidhu, Stanley B |e verfasserin |4 aut | |
| 700 | 1 | |a Sywak, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Delbridge, Leigh |e verfasserin |4 aut | |
| 700 | 1 | |a Aniss, Ahmad |e verfasserin |4 aut | |
| 700 | 1 | |a Wright, Dale |e verfasserin |4 aut | |
| 700 | 1 | |a Graf, Nicole |e verfasserin |4 aut | |
| 700 | 1 | |a Kumar, Amit |e verfasserin |4 aut | |
| 700 | 1 | |a Rathi, Vivek |e verfasserin |4 aut | |
| 700 | 1 | |a Benitez-Aguirre, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Glover, Anthony R |e verfasserin |4 aut | |
| 700 | 1 | |a Gill, Anthony J |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc |d 1992 |g 36(2023), 12 vom: 01. Dez., Seite 100329 |w (DE-627)NLM012660051 |x 1530-0285 |7 nnns |
| 773 | 1 | 8 | |g volume:36 |g year:2023 |g number:12 |g day:01 |g month:12 |g pages:100329 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.modpat.2023.100329 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 36 |j 2023 |e 12 |b 01 |c 12 |h 100329 | ||