Follicular variant of papillary carcinoma

Reproducibility of histologic diagnosis and utility of HBME-1 immunohistochemistry and braf mutational analysis as diagnostic adjuncts

Michelle Wallander, Lester J. Layfield, Elke Jarboe, Lyska Emerson, Ting Liu, Harshwardhan Thaker, Joseph Holden, Sheryl Tripp

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Context: Despite the recognition of the follicular variant of papillary carcinoma of the thyroid (FVPTC) for over 50 years, reproducibility of this diagnostic category has remained poor. Architectural features have been of variable utility as some FVPTC seem encapsulated, whereas others are multifocal and may be confused with nodular hyperplasia. Nuclear features are important for diagnosis of FVPTC, but some authors have discounted the utility of nuclear grooves and inclusions. More recently, BRAF and HBME-1 (Human Bone Marrow Endothelial Cell-1) have been suggested as markers for FVPTC. Objective: To investigate the frequency of BRAF mutations and HBME-1 immunopositivity, in a series of FVPTCs in which the diagnosis was established by 100% consensus among a panel of 6 surgical pathologists. DESIGN: Twenty-eight specimens with an original diagnosis of FVPTC and 10 cases with other diagnoses were obtained from the surgical pathology files of the University of Utah School of Medicine. All specimens were independently reviewed by 6 surgical pathologists. Tissue blocks were analyzed for BRAF exon 15 mutations and HMBE-1 expression. Results: Complete agreement among pathologists for the diagnosis of FVPTC was obtained in 28.6% (8/28) of cases originally diagnosed as FVPTC. Mutations in BRAF exon 15 were found in 25% (2/8) of cases with a 100% consensus diagnosis of FVPTC and 32% (6/19) of cases unanimously diagnosed as a type of papillary carcinoma (classic or follicular variant). HBME-1 was expressed in 87.5% (7/8) of lesions with a 100% consensus diagnosis of FVPTC and 84.2% (16/19) of lesions with a unanimous diagnosis of a type of papillary carcinoma of the thyroid (classic or follicular variant). Conclusions: Interobserver agreement for the diagnosis of FVPTC is poor and testing for the BRAF mutation is only marginally helpful because a minority of FVPTCs possess the mutation. HBME-1 expression when coupled with a BRAF mutation, results in 100% specificity but low sensitivity for the presence of papillary carcinoma of the thyroid including the follicular variant.

Original languageEnglish (US)
Pages (from-to)231-235
Number of pages5
JournalApplied Immunohistochemistry and Molecular Morphology
Volume18
Issue number3
DOIs
StatePublished - May 1 2010
Externally publishedYes

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Carcinoma, Papillary, Follicular
Bone Marrow Cells
Endothelial Cells
Immunohistochemistry
Mutation
Exons
Intranuclear Inclusion Bodies
Surgical Pathology
Papillary Carcinoma
Mutation Rate
Hyperplasia
Medicine

Keywords

  • BRAF
  • Follicular variant papillary carcinoma
  • Thyroid

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology
  • Histology

Cite this

Follicular variant of papillary carcinoma : Reproducibility of histologic diagnosis and utility of HBME-1 immunohistochemistry and braf mutational analysis as diagnostic adjuncts. / Wallander, Michelle; Layfield, Lester J.; Jarboe, Elke; Emerson, Lyska; Liu, Ting; Thaker, Harshwardhan; Holden, Joseph; Tripp, Sheryl.

In: Applied Immunohistochemistry and Molecular Morphology, Vol. 18, No. 3, 01.05.2010, p. 231-235.

Research output: Contribution to journalArticle

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abstract = "Context: Despite the recognition of the follicular variant of papillary carcinoma of the thyroid (FVPTC) for over 50 years, reproducibility of this diagnostic category has remained poor. Architectural features have been of variable utility as some FVPTC seem encapsulated, whereas others are multifocal and may be confused with nodular hyperplasia. Nuclear features are important for diagnosis of FVPTC, but some authors have discounted the utility of nuclear grooves and inclusions. More recently, BRAF and HBME-1 (Human Bone Marrow Endothelial Cell-1) have been suggested as markers for FVPTC. Objective: To investigate the frequency of BRAF mutations and HBME-1 immunopositivity, in a series of FVPTCs in which the diagnosis was established by 100{\%} consensus among a panel of 6 surgical pathologists. DESIGN: Twenty-eight specimens with an original diagnosis of FVPTC and 10 cases with other diagnoses were obtained from the surgical pathology files of the University of Utah School of Medicine. All specimens were independently reviewed by 6 surgical pathologists. Tissue blocks were analyzed for BRAF exon 15 mutations and HMBE-1 expression. Results: Complete agreement among pathologists for the diagnosis of FVPTC was obtained in 28.6{\%} (8/28) of cases originally diagnosed as FVPTC. Mutations in BRAF exon 15 were found in 25{\%} (2/8) of cases with a 100{\%} consensus diagnosis of FVPTC and 32{\%} (6/19) of cases unanimously diagnosed as a type of papillary carcinoma (classic or follicular variant). HBME-1 was expressed in 87.5{\%} (7/8) of lesions with a 100{\%} consensus diagnosis of FVPTC and 84.2{\%} (16/19) of lesions with a unanimous diagnosis of a type of papillary carcinoma of the thyroid (classic or follicular variant). Conclusions: Interobserver agreement for the diagnosis of FVPTC is poor and testing for the BRAF mutation is only marginally helpful because a minority of FVPTCs possess the mutation. HBME-1 expression when coupled with a BRAF mutation, results in 100{\%} specificity but low sensitivity for the presence of papillary carcinoma of the thyroid including the follicular variant.",
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AU - Layfield, Lester J.

AU - Jarboe, Elke

AU - Emerson, Lyska

AU - Liu, Ting

AU - Thaker, Harshwardhan

AU - Holden, Joseph

AU - Tripp, Sheryl

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N2 - Context: Despite the recognition of the follicular variant of papillary carcinoma of the thyroid (FVPTC) for over 50 years, reproducibility of this diagnostic category has remained poor. Architectural features have been of variable utility as some FVPTC seem encapsulated, whereas others are multifocal and may be confused with nodular hyperplasia. Nuclear features are important for diagnosis of FVPTC, but some authors have discounted the utility of nuclear grooves and inclusions. More recently, BRAF and HBME-1 (Human Bone Marrow Endothelial Cell-1) have been suggested as markers for FVPTC. Objective: To investigate the frequency of BRAF mutations and HBME-1 immunopositivity, in a series of FVPTCs in which the diagnosis was established by 100% consensus among a panel of 6 surgical pathologists. DESIGN: Twenty-eight specimens with an original diagnosis of FVPTC and 10 cases with other diagnoses were obtained from the surgical pathology files of the University of Utah School of Medicine. All specimens were independently reviewed by 6 surgical pathologists. Tissue blocks were analyzed for BRAF exon 15 mutations and HMBE-1 expression. Results: Complete agreement among pathologists for the diagnosis of FVPTC was obtained in 28.6% (8/28) of cases originally diagnosed as FVPTC. Mutations in BRAF exon 15 were found in 25% (2/8) of cases with a 100% consensus diagnosis of FVPTC and 32% (6/19) of cases unanimously diagnosed as a type of papillary carcinoma (classic or follicular variant). HBME-1 was expressed in 87.5% (7/8) of lesions with a 100% consensus diagnosis of FVPTC and 84.2% (16/19) of lesions with a unanimous diagnosis of a type of papillary carcinoma of the thyroid (classic or follicular variant). Conclusions: Interobserver agreement for the diagnosis of FVPTC is poor and testing for the BRAF mutation is only marginally helpful because a minority of FVPTCs possess the mutation. HBME-1 expression when coupled with a BRAF mutation, results in 100% specificity but low sensitivity for the presence of papillary carcinoma of the thyroid including the follicular variant.

AB - Context: Despite the recognition of the follicular variant of papillary carcinoma of the thyroid (FVPTC) for over 50 years, reproducibility of this diagnostic category has remained poor. Architectural features have been of variable utility as some FVPTC seem encapsulated, whereas others are multifocal and may be confused with nodular hyperplasia. Nuclear features are important for diagnosis of FVPTC, but some authors have discounted the utility of nuclear grooves and inclusions. More recently, BRAF and HBME-1 (Human Bone Marrow Endothelial Cell-1) have been suggested as markers for FVPTC. Objective: To investigate the frequency of BRAF mutations and HBME-1 immunopositivity, in a series of FVPTCs in which the diagnosis was established by 100% consensus among a panel of 6 surgical pathologists. DESIGN: Twenty-eight specimens with an original diagnosis of FVPTC and 10 cases with other diagnoses were obtained from the surgical pathology files of the University of Utah School of Medicine. All specimens were independently reviewed by 6 surgical pathologists. Tissue blocks were analyzed for BRAF exon 15 mutations and HMBE-1 expression. Results: Complete agreement among pathologists for the diagnosis of FVPTC was obtained in 28.6% (8/28) of cases originally diagnosed as FVPTC. Mutations in BRAF exon 15 were found in 25% (2/8) of cases with a 100% consensus diagnosis of FVPTC and 32% (6/19) of cases unanimously diagnosed as a type of papillary carcinoma (classic or follicular variant). HBME-1 was expressed in 87.5% (7/8) of lesions with a 100% consensus diagnosis of FVPTC and 84.2% (16/19) of lesions with a unanimous diagnosis of a type of papillary carcinoma of the thyroid (classic or follicular variant). Conclusions: Interobserver agreement for the diagnosis of FVPTC is poor and testing for the BRAF mutation is only marginally helpful because a minority of FVPTCs possess the mutation. HBME-1 expression when coupled with a BRAF mutation, results in 100% specificity but low sensitivity for the presence of papillary carcinoma of the thyroid including the follicular variant.

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