Related Experiment Video
Updated: Sep 22, 2025
An In Vitro Model for the Study of Cellular Pathophysiology in Globoid Cell Leukodystrophy
Published on: October 21, 2014
Cyclin D1 Expression and Molecular Genetic Findings in Periocular Histiocytoses and Neoplasms of Macrophage-Dendritic
Tatyana Milman1, Maya Eiger-Moscovich2, Roger K Henry3
1From the Department of Pathology (T.M., M.E.-M., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Ophthalmology (T.M., C.L.S., S.E.L., R.B.P., M.A.S., J.R.B., C.J.R., M.Ra., R.C.E.), Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania.
Purpose:
Frequent activating mutations in the mitogen-activated protein kinase (MAPK) pathway genes have been identified in histiocytoses. MAPK signaling consistently upregulates cyclin D1. The goal of this study was to determine whether cyclin D1 expression by immunohistochemistry is a useful diagnostic marker for periocular histiocytoses and to further characterize their genetic basis.
Design:
Retrospective observational case series.
Methods:
Pathology records were searched for all patients with histiocytoses diagnosed between 1995 and 2020. Eleven histiocyte-rich inflammatory lesions and 10 xanthelasma served as controls. Cyclin D1 immunohistochemistry was performed on all tissues. A subset of histiocytoses was evaluated by next-generation sequencing (NGS) and droplet digital PCR (ddPCR).
Results:
There were 36 patients, 15 males (42%) and 21 females (58%), with histiocytoses: 9 juvenile xanthogranuloma (25%), 8 adult-onset asthma and periocular xanthogranuloma (22%), 7 Langerhans cell histiocytosis (19%), 5 Rosai-Dorfman disease (14%), 5 xanthogranuloma-not otherwise specified (14%), 1 Erdheim-Chester disease (3%), and 1 histiocytic sarcoma (3%). Moderate to strong nuclear cyclin D1 expression was present in ≥50% of lesional cells in histiocytoses (23/36, 64%), significantly more when compared to histiocyte-rich inflammatory lesions (0/11, 0%, P<.001) and xanthelasma (0/10, 0%, P<.001). Cyclin D1 was expressed in <10% of lesional cells in all 11 histiocyte-rich inflammatory lesions (P<.001) and all 10 xanthelasma lesions (P<.001). MAPK pathway gene mutations were detected in 12 of 14 (86%) histiocytoses successfully assayed by NGS and/or ddPCR.
Conclusions:
Our study confirms that the cyclin D1 immunohistochemical stain is a useful diagnostic marker for periocular histiocytoses, correlating with underlying mutations in MAPK pathway genes.
Related Concept Videos
02:39Positive Regulator Molecules
02:23Abnormal Proliferation
02:34Inhibition of Cdk Activity
02:15M-Cdk Drives Transition Into Mitosis
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
02:11The Cell Cycle Control System