The PRKD1 E710D hotspot mutation is highly specific in separating polymorphous adenocarcinoma of the palate from adenoid cystic carcinoma and pleomorphic adenoma on FNA

Simon Andreasen, Linea Cecilie Melchior, Katalin Kiss, Justin Avery Bishop, Estrid Høgdall, Morten Grauslund, Irene Wessel, Preben Homøe, Tina Klitmøller Agander

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Polymorphous adenocarcinoma (PAC) of the palatal minor salivary glands, previously known as polymorphous low-grade adenocarcinoma, is the second most common intraoral malignant salivary gland carcinoma after adenoid cystic carcinoma (ACC) and carries an excellent prognosis. Unfortunately, PAC demonstrates cytological overlap with 2 other salivary gland tumors frequently encountered in the same location, namely ACC and pleomorphic adenoma (PA). Recently, the protein kinase D1 (PRKD1) hotspot mutation E710D was demonstrated to be specific for PAC and to be present in the majority of cases. The objective of the current study was to investigate the value of PRKD1 hotspot sequencing in identifying PAC in paired fine-needle aspiration (FNA) and surgical specimens from cases of PAC, ACC, and PA. METHODS: Paired May-Grunwald-Giemsa-stained FNA and corresponding surgical specimens were collected from 18 PAC cases, 25 ACC cases, and 21 PA cases. Both sets of specimens were subjected to dideoxynucleotide sequencing of PRKD1 exon 15, including the PRKD1 E710D hotspot. RESULTS: Of the PAC cases, approximately 50% demonstrated identical PRKD1 E710D hotspot mutations on the FNA specimen and corresponding surgical specimen. Two ACC specimens had point mutations within the sequenced region in the FNA specimen as well as the surgical specimen, but none were located in the hotspot region. None of the PA cases demonstrated PRKD1 mutations. The specificity of the PRKD1 hotspot mutation for identifying PAC among ACC and PA cases was 100% whereas the sensitivity was 50%. CONCLUSIONS: The PRKD1 E710D hotspot mutation is highly specific for identifying PAC on FNA among cases of ACC and PA, whereas the sensitivity is only modest. Alternative PRKD1 mutations exclude PAC, and are more suggestive of ACC.

Original languageEnglish (US)
JournalCancer cytopathology
DOIs
StateAccepted/In press - Jan 1 2017

Fingerprint

Pleomorphic Adenoma
Adenoid Cystic Carcinoma
Palate
Fine Needle Biopsy
Protein Kinases
Adenocarcinoma
Mutation
Dideoxynucleotides
Minor Salivary Glands
Glandular and Epithelial Neoplasms
Salivary Glands
Point Mutation
Exons

Keywords

  • Adenoid cystic carcinoma (ACC)
  • C.2130
  • E710D
  • Fine-needle aspiration (FNA)
  • Palate
  • Pleomorphic adenoma (PA)
  • Polymorphous adenocarcinoma (PAC)
  • Protein kinase D1 (PRKD1)
  • Salivary gland

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The PRKD1 E710D hotspot mutation is highly specific in separating polymorphous adenocarcinoma of the palate from adenoid cystic carcinoma and pleomorphic adenoma on FNA. / Andreasen, Simon; Melchior, Linea Cecilie; Kiss, Katalin; Bishop, Justin Avery; Høgdall, Estrid; Grauslund, Morten; Wessel, Irene; Homøe, Preben; Agander, Tina Klitmøller.

In: Cancer cytopathology, 01.01.2017.

Research output: Contribution to journalArticle

Andreasen, Simon ; Melchior, Linea Cecilie ; Kiss, Katalin ; Bishop, Justin Avery ; Høgdall, Estrid ; Grauslund, Morten ; Wessel, Irene ; Homøe, Preben ; Agander, Tina Klitmøller. / The PRKD1 E710D hotspot mutation is highly specific in separating polymorphous adenocarcinoma of the palate from adenoid cystic carcinoma and pleomorphic adenoma on FNA. In: Cancer cytopathology. 2017.
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title = "The PRKD1 E710D hotspot mutation is highly specific in separating polymorphous adenocarcinoma of the palate from adenoid cystic carcinoma and pleomorphic adenoma on FNA",
abstract = "BACKGROUND: Polymorphous adenocarcinoma (PAC) of the palatal minor salivary glands, previously known as polymorphous low-grade adenocarcinoma, is the second most common intraoral malignant salivary gland carcinoma after adenoid cystic carcinoma (ACC) and carries an excellent prognosis. Unfortunately, PAC demonstrates cytological overlap with 2 other salivary gland tumors frequently encountered in the same location, namely ACC and pleomorphic adenoma (PA). Recently, the protein kinase D1 (PRKD1) hotspot mutation E710D was demonstrated to be specific for PAC and to be present in the majority of cases. The objective of the current study was to investigate the value of PRKD1 hotspot sequencing in identifying PAC in paired fine-needle aspiration (FNA) and surgical specimens from cases of PAC, ACC, and PA. METHODS: Paired May-Grunwald-Giemsa-stained FNA and corresponding surgical specimens were collected from 18 PAC cases, 25 ACC cases, and 21 PA cases. Both sets of specimens were subjected to dideoxynucleotide sequencing of PRKD1 exon 15, including the PRKD1 E710D hotspot. RESULTS: Of the PAC cases, approximately 50{\%} demonstrated identical PRKD1 E710D hotspot mutations on the FNA specimen and corresponding surgical specimen. Two ACC specimens had point mutations within the sequenced region in the FNA specimen as well as the surgical specimen, but none were located in the hotspot region. None of the PA cases demonstrated PRKD1 mutations. The specificity of the PRKD1 hotspot mutation for identifying PAC among ACC and PA cases was 100{\%} whereas the sensitivity was 50{\%}. CONCLUSIONS: The PRKD1 E710D hotspot mutation is highly specific for identifying PAC on FNA among cases of ACC and PA, whereas the sensitivity is only modest. Alternative PRKD1 mutations exclude PAC, and are more suggestive of ACC.",
keywords = "Adenoid cystic carcinoma (ACC), C.2130, E710D, Fine-needle aspiration (FNA), Palate, Pleomorphic adenoma (PA), Polymorphous adenocarcinoma (PAC), Protein kinase D1 (PRKD1), Salivary gland",
author = "Simon Andreasen and Melchior, {Linea Cecilie} and Katalin Kiss and Bishop, {Justin Avery} and Estrid H{\o}gdall and Morten Grauslund and Irene Wessel and Preben Hom{\o}e and Agander, {Tina Klitm{\o}ller}",
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T1 - The PRKD1 E710D hotspot mutation is highly specific in separating polymorphous adenocarcinoma of the palate from adenoid cystic carcinoma and pleomorphic adenoma on FNA

AU - Andreasen, Simon

AU - Melchior, Linea Cecilie

AU - Kiss, Katalin

AU - Bishop, Justin Avery

AU - Høgdall, Estrid

AU - Grauslund, Morten

AU - Wessel, Irene

AU - Homøe, Preben

AU - Agander, Tina Klitmøller

PY - 2017/1/1

Y1 - 2017/1/1

N2 - BACKGROUND: Polymorphous adenocarcinoma (PAC) of the palatal minor salivary glands, previously known as polymorphous low-grade adenocarcinoma, is the second most common intraoral malignant salivary gland carcinoma after adenoid cystic carcinoma (ACC) and carries an excellent prognosis. Unfortunately, PAC demonstrates cytological overlap with 2 other salivary gland tumors frequently encountered in the same location, namely ACC and pleomorphic adenoma (PA). Recently, the protein kinase D1 (PRKD1) hotspot mutation E710D was demonstrated to be specific for PAC and to be present in the majority of cases. The objective of the current study was to investigate the value of PRKD1 hotspot sequencing in identifying PAC in paired fine-needle aspiration (FNA) and surgical specimens from cases of PAC, ACC, and PA. METHODS: Paired May-Grunwald-Giemsa-stained FNA and corresponding surgical specimens were collected from 18 PAC cases, 25 ACC cases, and 21 PA cases. Both sets of specimens were subjected to dideoxynucleotide sequencing of PRKD1 exon 15, including the PRKD1 E710D hotspot. RESULTS: Of the PAC cases, approximately 50% demonstrated identical PRKD1 E710D hotspot mutations on the FNA specimen and corresponding surgical specimen. Two ACC specimens had point mutations within the sequenced region in the FNA specimen as well as the surgical specimen, but none were located in the hotspot region. None of the PA cases demonstrated PRKD1 mutations. The specificity of the PRKD1 hotspot mutation for identifying PAC among ACC and PA cases was 100% whereas the sensitivity was 50%. CONCLUSIONS: The PRKD1 E710D hotspot mutation is highly specific for identifying PAC on FNA among cases of ACC and PA, whereas the sensitivity is only modest. Alternative PRKD1 mutations exclude PAC, and are more suggestive of ACC.

AB - BACKGROUND: Polymorphous adenocarcinoma (PAC) of the palatal minor salivary glands, previously known as polymorphous low-grade adenocarcinoma, is the second most common intraoral malignant salivary gland carcinoma after adenoid cystic carcinoma (ACC) and carries an excellent prognosis. Unfortunately, PAC demonstrates cytological overlap with 2 other salivary gland tumors frequently encountered in the same location, namely ACC and pleomorphic adenoma (PA). Recently, the protein kinase D1 (PRKD1) hotspot mutation E710D was demonstrated to be specific for PAC and to be present in the majority of cases. The objective of the current study was to investigate the value of PRKD1 hotspot sequencing in identifying PAC in paired fine-needle aspiration (FNA) and surgical specimens from cases of PAC, ACC, and PA. METHODS: Paired May-Grunwald-Giemsa-stained FNA and corresponding surgical specimens were collected from 18 PAC cases, 25 ACC cases, and 21 PA cases. Both sets of specimens were subjected to dideoxynucleotide sequencing of PRKD1 exon 15, including the PRKD1 E710D hotspot. RESULTS: Of the PAC cases, approximately 50% demonstrated identical PRKD1 E710D hotspot mutations on the FNA specimen and corresponding surgical specimen. Two ACC specimens had point mutations within the sequenced region in the FNA specimen as well as the surgical specimen, but none were located in the hotspot region. None of the PA cases demonstrated PRKD1 mutations. The specificity of the PRKD1 hotspot mutation for identifying PAC among ACC and PA cases was 100% whereas the sensitivity was 50%. CONCLUSIONS: The PRKD1 E710D hotspot mutation is highly specific for identifying PAC on FNA among cases of ACC and PA, whereas the sensitivity is only modest. Alternative PRKD1 mutations exclude PAC, and are more suggestive of ACC.

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KW - C.2130

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KW - Fine-needle aspiration (FNA)

KW - Palate

KW - Pleomorphic adenoma (PA)

KW - Polymorphous adenocarcinoma (PAC)

KW - Protein kinase D1 (PRKD1)

KW - Salivary gland

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DO - 10.1002/cncy.21959

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JO - Cancer cytopathology

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