Histological evidence of MAPK pathway activation across subtypes of adult orbital xanthogranulomatous disease irrespective of the detection of oncogenic mutations

Sanne Emilie Detiger; A D A Paridaens; P G  Kemps; A G S  van Halteren; P Martin  van Hagen; Jan van Laar; Robert M Verdijk

Histological evidence of MAPK pathway activation across subtypes of adult orbital xanthogranulomatous disease irrespective of the detection of oncogenic mutations

Sanne Emilie Detiger, A D A Paridaens, P G Kemps, A G S van Halteren, P Martin van Hagen, Jan van Laar, Robert M Verdijk

Research output: Contribution to journal › Article › Research › peer-review

Abstract

Adult orbital xanthogranulomatous disease (AOXGD) is a spectrum of histiocytoses with four subtypes. Mitogen-activated protein kinase (MAPK) pathway mutations have been detected in various histiocytic neoplasms, little is known about this in AOXGD. Targeted regions of cancer- and histiocytosis-related genes were analyzed and immunohistochemical staining of phosphorylated ERK (pERK), cyclin D1 and PU.1 was performed in 28 AOXGD and 10 control xanthelasma biopsies to assess MAPK pathway activation.

Mutations were detected in 7/28 (25%) patients. Positive staining for pERK and/or cyclin D1 was found across all subtypes in 17/27 (63%) patients of whom 12/17 (71%) did not harbour a mutation. Xanthelasma tissue stained negative for pERK and cyclin D1. Relapse occurred in 5/7 (71%) patients with a MAPK pathway mutation compared to 8/21 (38%) patients in whom no mutation could be detected.

Molecular analysis and evaluation for systemic disease is warranted to identify patients at risk of recurrent xanthomatous disease.

Original language	English
Article number	110299
Journal	Clinical Immunology
Volume	265
Publication status	Published - 1 Aug 2024

Keywords

Adult orbital xanthogranuloma
Adult-onset asthma and periocular xanthogranuloma
Erdheim-Chester disease
Histiocytic neoplasms
MAPK pathway
Necrobiotic xanthogranuloma

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https://doi.org/10.1016/j.clim.2024.110299

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Detiger, S. E., Paridaens, A. D. A., Kemps, P. G., van Halteren, A. G. S., van Hagen, P. M., van Laar, J., & Verdijk, R. M. (2024). Histological evidence of MAPK pathway activation across subtypes of adult orbital xanthogranulomatous disease irrespective of the detection of oncogenic mutations. Clinical Immunology, 265, Article 110299. https://doi.org/10.1016/j.clim.2024.110299

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title = "Histological evidence of MAPK pathway activation across subtypes of adult orbital xanthogranulomatous disease irrespective of the detection of oncogenic mutations",

abstract = "Adult orbital xanthogranulomatous disease (AOXGD) is a spectrum of histiocytoses with four subtypes. Mitogen-activated protein kinase (MAPK) pathway mutations have been detected in various histiocytic neoplasms, little is known about this in AOXGD. Targeted regions of cancer- and histiocytosis-related genes were analyzed and immunohistochemical staining of phosphorylated ERK (pERK), cyclin D1 and PU.1 was performed in 28 AOXGD and 10 control xanthelasma biopsies to assess MAPK pathway activation.Mutations were detected in 7/28 (25%) patients. Positive staining for pERK and/or cyclin D1 was found across all subtypes in 17/27 (63%) patients of whom 12/17 (71%) did not harbour a mutation. Xanthelasma tissue stained negative for pERK and cyclin D1. Relapse occurred in 5/7 (71%) patients with a MAPK pathway mutation compared to 8/21 (38%) patients in whom no mutation could be detected.Molecular analysis and evaluation for systemic disease is warranted to identify patients at risk of recurrent xanthomatous disease.",

keywords = "Adult orbital xanthogranuloma, Adult-onset asthma and periocular xanthogranuloma, Erdheim-Chester disease, Histiocytic neoplasms, MAPK pathway, Necrobiotic xanthogranuloma",

author = "Detiger, {Sanne Emilie} and Paridaens, {A D A} and Kemps, {P G} and {van Halteren}, {A G S} and {van Hagen}, {P Martin} and {van Laar}, Jan and Verdijk, {Robert M}",

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language = "English",

volume = "265",

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T1 - Histological evidence of MAPK pathway activation across subtypes of adult orbital xanthogranulomatous disease irrespective of the detection of oncogenic mutations

AU - Detiger, Sanne Emilie

AU - Paridaens, A D A

AU - Kemps, P G

AU - van Halteren, A G S

AU - van Hagen, P Martin

AU - van Laar, Jan

AU - Verdijk, Robert M

PY - 2024/8/1

Y1 - 2024/8/1

N2 - Adult orbital xanthogranulomatous disease (AOXGD) is a spectrum of histiocytoses with four subtypes. Mitogen-activated protein kinase (MAPK) pathway mutations have been detected in various histiocytic neoplasms, little is known about this in AOXGD. Targeted regions of cancer- and histiocytosis-related genes were analyzed and immunohistochemical staining of phosphorylated ERK (pERK), cyclin D1 and PU.1 was performed in 28 AOXGD and 10 control xanthelasma biopsies to assess MAPK pathway activation.Mutations were detected in 7/28 (25%) patients. Positive staining for pERK and/or cyclin D1 was found across all subtypes in 17/27 (63%) patients of whom 12/17 (71%) did not harbour a mutation. Xanthelasma tissue stained negative for pERK and cyclin D1. Relapse occurred in 5/7 (71%) patients with a MAPK pathway mutation compared to 8/21 (38%) patients in whom no mutation could be detected.Molecular analysis and evaluation for systemic disease is warranted to identify patients at risk of recurrent xanthomatous disease.

AB - Adult orbital xanthogranulomatous disease (AOXGD) is a spectrum of histiocytoses with four subtypes. Mitogen-activated protein kinase (MAPK) pathway mutations have been detected in various histiocytic neoplasms, little is known about this in AOXGD. Targeted regions of cancer- and histiocytosis-related genes were analyzed and immunohistochemical staining of phosphorylated ERK (pERK), cyclin D1 and PU.1 was performed in 28 AOXGD and 10 control xanthelasma biopsies to assess MAPK pathway activation.Mutations were detected in 7/28 (25%) patients. Positive staining for pERK and/or cyclin D1 was found across all subtypes in 17/27 (63%) patients of whom 12/17 (71%) did not harbour a mutation. Xanthelasma tissue stained negative for pERK and cyclin D1. Relapse occurred in 5/7 (71%) patients with a MAPK pathway mutation compared to 8/21 (38%) patients in whom no mutation could be detected.Molecular analysis and evaluation for systemic disease is warranted to identify patients at risk of recurrent xanthomatous disease.

KW - Adult orbital xanthogranuloma

KW - Adult-onset asthma and periocular xanthogranuloma

KW - Erdheim-Chester disease

KW - Histiocytic neoplasms

KW - MAPK pathway

KW - Necrobiotic xanthogranuloma

M3 - Article

C2 - 38936524

SN - 1521-6616

VL - 265

JO - Clinical Immunology

JF - Clinical Immunology

M1 - 110299

ER -

Histological evidence of MAPK pathway activation across subtypes of adult orbital xanthogranulomatous disease irrespective of the detection of oncogenic mutations

Abstract

Keywords

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