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Case Report: Castleman Disease With an Associated Stromal Spindle Cell Proliferation, PDGFRB Mutation and p53 Expression: Clonal Origins of a Rare Disease

Castleman disease (CD) is a rare lymphoproliferative disorder with distinct clinical subtypes. However, our understanding of the underlying pathogenesis of particular subtypes of CD remains unclear. While the characteristic morphologic changes within UCD, including occasional cases of overgrowth of...

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Autores principales: Singh, Kunwar I., Gollapudi, Sumanth, Kumar, Jyoti, Butzmann, Alexandra, Small, Corinn, Kreimer, Sara, Saglam, Emine Arzu, Warnke, Roger, Silva, Oscar, Ohgami, Robert S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043324/
https://www.ncbi.nlm.nih.gov/pubmed/35494027
http://dx.doi.org/10.3389/fonc.2022.857606
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author Singh, Kunwar I.
Gollapudi, Sumanth
Kumar, Jyoti
Butzmann, Alexandra
Small, Corinn
Kreimer, Sara
Saglam, Emine Arzu
Warnke, Roger
Silva, Oscar
Ohgami, Robert S.
author_facet Singh, Kunwar I.
Gollapudi, Sumanth
Kumar, Jyoti
Butzmann, Alexandra
Small, Corinn
Kreimer, Sara
Saglam, Emine Arzu
Warnke, Roger
Silva, Oscar
Ohgami, Robert S.
author_sort Singh, Kunwar I.
collection PubMed
description Castleman disease (CD) is a rare lymphoproliferative disorder with distinct clinical subtypes. However, our understanding of the underlying pathogenesis of particular subtypes of CD remains unclear. While the characteristic morphologic changes within UCD, including occasional cases of overgrowth of spindled stromal and follicular dendritic cells have been described, the nature and origin of these spindle cells remain elusive. Few reports have suggested that underlying stromal cells in UCD are clonally neoplastic and may be of fibroblastic reticular cell (FRC) or follicular dendritic cell (FDC) origins given their close clonal relationship. Although certain histomorphologic features may aid diagnosis, there are no specific biomarkers that can differentiate a reactive process mimicking UCD from true UCD. Hence, we describe an index case with morphology consistent with the hyaline vascular subtype of UCD with concomitant atypical smooth muscle actin (SMA)-positive stromal spindle cell proliferation containing a recurrent PDGFRB N666S mutation and upregulation of p53 expression. Further analysis of 21 additional cases of UCD identified increased p53 expression by digital image analysis and SMA positive stromal cells predominantly within the paracortical and intrafollicular areas further strengthening the hypothesis of the stromal cellular derivation and origins of UCD.
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spelling pubmed-90433242022-04-28 Case Report: Castleman Disease With an Associated Stromal Spindle Cell Proliferation, PDGFRB Mutation and p53 Expression: Clonal Origins of a Rare Disease Singh, Kunwar I. Gollapudi, Sumanth Kumar, Jyoti Butzmann, Alexandra Small, Corinn Kreimer, Sara Saglam, Emine Arzu Warnke, Roger Silva, Oscar Ohgami, Robert S. Front Oncol Oncology Castleman disease (CD) is a rare lymphoproliferative disorder with distinct clinical subtypes. However, our understanding of the underlying pathogenesis of particular subtypes of CD remains unclear. While the characteristic morphologic changes within UCD, including occasional cases of overgrowth of spindled stromal and follicular dendritic cells have been described, the nature and origin of these spindle cells remain elusive. Few reports have suggested that underlying stromal cells in UCD are clonally neoplastic and may be of fibroblastic reticular cell (FRC) or follicular dendritic cell (FDC) origins given their close clonal relationship. Although certain histomorphologic features may aid diagnosis, there are no specific biomarkers that can differentiate a reactive process mimicking UCD from true UCD. Hence, we describe an index case with morphology consistent with the hyaline vascular subtype of UCD with concomitant atypical smooth muscle actin (SMA)-positive stromal spindle cell proliferation containing a recurrent PDGFRB N666S mutation and upregulation of p53 expression. Further analysis of 21 additional cases of UCD identified increased p53 expression by digital image analysis and SMA positive stromal cells predominantly within the paracortical and intrafollicular areas further strengthening the hypothesis of the stromal cellular derivation and origins of UCD. Frontiers Media S.A. 2022-04-13 /pmc/articles/PMC9043324/ /pubmed/35494027 http://dx.doi.org/10.3389/fonc.2022.857606 Text en Copyright © 2022 Singh, Gollapudi, Kumar, Butzmann, Small, Kreimer, Saglam, Warnke, Silva and Ohgami https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Singh, Kunwar I.
Gollapudi, Sumanth
Kumar, Jyoti
Butzmann, Alexandra
Small, Corinn
Kreimer, Sara
Saglam, Emine Arzu
Warnke, Roger
Silva, Oscar
Ohgami, Robert S.
Case Report: Castleman Disease With an Associated Stromal Spindle Cell Proliferation, PDGFRB Mutation and p53 Expression: Clonal Origins of a Rare Disease
title Case Report: Castleman Disease With an Associated Stromal Spindle Cell Proliferation, PDGFRB Mutation and p53 Expression: Clonal Origins of a Rare Disease
title_full Case Report: Castleman Disease With an Associated Stromal Spindle Cell Proliferation, PDGFRB Mutation and p53 Expression: Clonal Origins of a Rare Disease
title_fullStr Case Report: Castleman Disease With an Associated Stromal Spindle Cell Proliferation, PDGFRB Mutation and p53 Expression: Clonal Origins of a Rare Disease
title_full_unstemmed Case Report: Castleman Disease With an Associated Stromal Spindle Cell Proliferation, PDGFRB Mutation and p53 Expression: Clonal Origins of a Rare Disease
title_short Case Report: Castleman Disease With an Associated Stromal Spindle Cell Proliferation, PDGFRB Mutation and p53 Expression: Clonal Origins of a Rare Disease
title_sort case report: castleman disease with an associated stromal spindle cell proliferation, pdgfrb mutation and p53 expression: clonal origins of a rare disease
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043324/
https://www.ncbi.nlm.nih.gov/pubmed/35494027
http://dx.doi.org/10.3389/fonc.2022.857606
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