A Detailed Histologic and Molecular Assessment of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma

Angela Chou¹, Min Ru Qiu², Henry Crayton³, Bin Wang⁴, Mahsa S Ahadi⁵, John Turchini⁶, Adele Clarkson⁷, Loretta Sioson⁸, Amy Sheen⁸, Nisha Singh⁹, Roderick J Clifton-Bligh¹⁰, Bruce G Robinson¹⁰, Matti L Gild¹⁰, Venessa Tsang¹⁰, David Leong¹¹, Stanley B Sidhu¹², Mark Sywak¹², Leigh Delbridge¹², Ahmad Aniss¹², Dale Wright¹³, Nicole Graf¹⁴, Amit Kumar¹⁵, Vivek Rathi¹⁶, Paul Benitez-Aguirre¹⁷, Anthony R Glover¹⁸, Anthony J Gill¹⁹

Affiliations

¹ NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia. Electronic address: AngelaShihYuan.Chou@health.nsw.gov.au.
² Department of Anatomical Pathology, SydPATH, St Vincent's Hospital, Darlinghurst, New South Wales, Australia; University of NSW, Randwick, New South Wales, Australia.
³ Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia.
⁴ Department of Anatomical Pathology, SydPATH, St Vincent's Hospital, Darlinghurst, New South Wales, Australia.
⁵ NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia.
⁶ Department of Anatomical Pathology, Douglass Hanly Moir Pathology (A Sonic Healthcare Practice), Macquarie Park, New South Wales, Australia; Discipline of Pathology, Macquarie Medical School, Macquarie University, New South Wales, Australia.
⁷ NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia.
⁸ Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia.
⁹ NSW Health Pathology, Cytogenetics Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
¹⁰ Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Department of Endocrinology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
¹¹ Endocrine Surgical Unit, Royal North Shore Hospital, St Leonards, University of Sydney, New South Wales, Australia.
¹² Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Endocrine Surgical Unit, Royal North Shore Hospital, St Leonards, University of Sydney, New South Wales, Australia.
¹³ Cytogenetics Department, Sydney Genome Diagnostics, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; Specialty of Genome Medicine, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
¹⁴ Histopathology Department, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
¹⁵ Diagnostic Genomics, Monash Health Pathology, Monash Health, Clayton, Victoria, Australia.
¹⁶ LifeStrands Genomics, Mount Waverley, Victoria, Australia.
¹⁷ Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
¹⁸ Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Endocrine Surgical Unit, Royal North Shore Hospital, St Leonards, University of Sydney, New South Wales, Australia; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, New South Wales, Australia. Electronic address: Anthony.Glover@sydney.edu.au.
¹⁹ NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia. Electronic address: affgill@med.usyd.edu.au.

PMID: 37716505
DOI: 10.1016/j.modpat.2023.100329

Free article

A Detailed Histologic and Molecular Assessment of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma

Angela Chou et al. Mod Pathol. 2023 Dec.

Free article

. 2023 Dec;36(12):100329.

doi: 10.1016/j.modpat.2023.100329. Epub 2023 Sep 15.

Authors

Affiliations

¹ NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia. Electronic address: AngelaShihYuan.Chou@health.nsw.gov.au.
² Department of Anatomical Pathology, SydPATH, St Vincent's Hospital, Darlinghurst, New South Wales, Australia; University of NSW, Randwick, New South Wales, Australia.
³ Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia.
⁴ Department of Anatomical Pathology, SydPATH, St Vincent's Hospital, Darlinghurst, New South Wales, Australia.
⁵ NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia.
⁶ Department of Anatomical Pathology, Douglass Hanly Moir Pathology (A Sonic Healthcare Practice), Macquarie Park, New South Wales, Australia; Discipline of Pathology, Macquarie Medical School, Macquarie University, New South Wales, Australia.
⁷ NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia.
⁸ Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia.
⁹ NSW Health Pathology, Cytogenetics Department, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
¹⁰ Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Department of Endocrinology, Royal North Shore Hospital, St Leonards, New South Wales, Australia.
¹¹ Endocrine Surgical Unit, Royal North Shore Hospital, St Leonards, University of Sydney, New South Wales, Australia.
¹² Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Endocrine Surgical Unit, Royal North Shore Hospital, St Leonards, University of Sydney, New South Wales, Australia.
¹³ Cytogenetics Department, Sydney Genome Diagnostics, The Children's Hospital at Westmead, Westmead, New South Wales, Australia; Specialty of Genome Medicine, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
¹⁴ Histopathology Department, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
¹⁵ Diagnostic Genomics, Monash Health Pathology, Monash Health, Clayton, Victoria, Australia.
¹⁶ LifeStrands Genomics, Mount Waverley, Victoria, Australia.
¹⁷ Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
¹⁸ Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Endocrine Surgical Unit, Royal North Shore Hospital, St Leonards, University of Sydney, New South Wales, Australia; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, New South Wales, Australia. Electronic address: Anthony.Glover@sydney.edu.au.
¹⁹ NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, New South Wales, Australia; Faculty of Medicine and Health Sciences and Northern Clinical School, University of Sydney, Sydney, New South Wales, Australia; Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, New South Wales, Australia. Electronic address: affgill@med.usyd.edu.au.

PMID: 37716505
DOI: 10.1016/j.modpat.2023.100329

Abstract

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 BRAF^V600E 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 BRAF^V600E mutations. All 10 pediatric cases were all gene rearranged (P = .02). Compared with BRAF^V600E-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 BRAF^V600E-negative tumors (1.5% of papillary thyroid carcinomas) are driven by potentially actionable oncogenic fusions.

Keywords: ALK; BRAF; NTRK; RET; diffuse sclerosing; gene fusions; papillary thyroid carcinoma.

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A Detailed Histologic and Molecular Assessment of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma

Affiliations

A Detailed Histologic and Molecular Assessment of the Diffuse Sclerosing Variant of Papillary Thyroid Carcinoma

Authors

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Abstract

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Medical

Research Materials