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Non-Eosinophilic Nasal Polyps Shows Increased Epithelial Proliferation and Localized Disease Pattern in the Early Stage.

Kim DK, Jin HR, Eun KM, Mutusamy S, Cho SH, Oh S, Kim DW - PLoS ONE (2015)

Bottom Line: Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs.Histologic, immunologic and clinical data suggest that non-eosinophilic NPs showed enhanced epithelial alteration and more localized maxillary involvement.Combination of cutoff value on IL-5, periostin, IFN-γ, and E/M scores may be one of surrogate markers for non-eosinophil NP subtype.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital and Nano-Bio Regenerative Medical Institute, Hallym University College of Medicine, Chuncheon, Republic of Korea.

ABSTRACT

Background: Non-eosinophilic nasal polyps (NPs) show less inflammatory changes and are less commonly associated with lower airway inflammatory disorders such as asthma, compared with eosinophilic NPs. However, the development of non-eosinophilic NPs which is a predominant subtype in Asian population still remains unclear.

Methods: A total of 81 patients (45 with non-eosinophilic NPs and 36 with eosinophilic NPs) were enrolled. Clinical information and computed tomography (CT), endoscopic, and histological findings were investigated. Tissue samples were analyzed for total IgE levels and for mRNA expression levels of interleukin (IL)-4, IL-5, IL-13, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17A, IL-22, IL-23p19, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, and periostin. Immunostaining assessment of Ki-67 as a proliferation marker was performed.

Results: We found that epithelial in-growing patterns such as pseudocysts were more frequently observed in histological and endoscopic evaluations of non-eosinophilic NPs, which was linked to increase epithelial staining of Ki-67, a proliferating marker. Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs. To investigate the developmental course of each subtype, CT was analyzed according to CT scores and subtypes. Non-eosinophilic NPs showed more localized pattern and maxillary sinus involvement, but lesser olfactory involvement in early stage whereas eosinophilic NPs were characterized by diffuse ethmoidal and olfactory involvement. In addition, high ethmoidal/maxillary (E/M) CT scores, indicating ethmoidal dominant involvement, were one of surrogate markers for eosinophilic NP. E/M CT scores was positively correlated with levels of TH2 inflammatory markers, including IL-4, IL-5, periostin mRNA expression and total IgE levels in NPs, whereas levels of the TH1 cytokine, IFN- γ were inversely correlated. Moreover, if the combinatorial algorithm meet the three of the four markers, including IL-5 (<2.379), periostin (<3.889), IFN-γ (>0.316), and E/M ratio (<2.167), non-eosinophilic CRSwNP are diagnosed with a sensitivity of 84.4% and a specificity of 84.8%.

Conclusion: Histologic, immunologic and clinical data suggest that non-eosinophilic NPs showed enhanced epithelial alteration and more localized maxillary involvement. Combination of cutoff value on IL-5, periostin, IFN-γ, and E/M scores may be one of surrogate markers for non-eosinophil NP subtype.

No MeSH data available.


Related in: MedlinePlus

Distinctive histological features of non-eosinophilic CRSwNP patients.(A) Comparison of the proportion of total NP tissue area occupied by pseudocysts in different endotypes of CRSwNP and representative hematoxylin/eosin staining images of a pseudocyst (red arrow) within the epithelial layer from non-eosinophilic NP tissues (40×) (B) Comparison of a yellowish spot in NP tissue between non-eosinophilic and eosinophilic CRSwNP patients and representative images of a yellowish spot (red arrow) found on endoscopy in a non-eosinophilic CRSwNP patient. (*p<0.05, **p<0.01, and ***p<0.001). Data represent medians. E-NP, eosinophilic nasal polyp; NE-NP, non-eosinophilic nasal polyp.
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pone.0139945.g002: Distinctive histological features of non-eosinophilic CRSwNP patients.(A) Comparison of the proportion of total NP tissue area occupied by pseudocysts in different endotypes of CRSwNP and representative hematoxylin/eosin staining images of a pseudocyst (red arrow) within the epithelial layer from non-eosinophilic NP tissues (40×) (B) Comparison of a yellowish spot in NP tissue between non-eosinophilic and eosinophilic CRSwNP patients and representative images of a yellowish spot (red arrow) found on endoscopy in a non-eosinophilic CRSwNP patient. (*p<0.05, **p<0.01, and ***p<0.001). Data represent medians. E-NP, eosinophilic nasal polyp; NE-NP, non-eosinophilic nasal polyp.

Mentions: Interestingly, pseudocysts were observed in the epithelial layer, primarily in non-eosinophilic CRSwNP. This distinctive histopathological feature of non-eosinophilic NPs was observed in a low-power field (P×) (Fig 2A). This analysis revealed that the pseudocysts occupied a significantly larger area of NPs in non-eosinophilic CRSwNP patients compared with eosinophilic CRSwNP patients (Fig 2A). Furthermore, under endoscopy, we could detect yellowish spots on NPs with the appearance of mucous retention cysts (Fig 2B). These spots were observed at a significantly higher incidence in patients with non-eosinophilic CRSwNP than in patients with eosinophilic CRSwNP (Fig 2B). Similar to the Ki–67 staining results, these epithelial alteration findings also suggest that non-eosinophilic CRSwNP arise from localized lesion, compared with eosinophilic CRSwNP.


Non-Eosinophilic Nasal Polyps Shows Increased Epithelial Proliferation and Localized Disease Pattern in the Early Stage.

Kim DK, Jin HR, Eun KM, Mutusamy S, Cho SH, Oh S, Kim DW - PLoS ONE (2015)

Distinctive histological features of non-eosinophilic CRSwNP patients.(A) Comparison of the proportion of total NP tissue area occupied by pseudocysts in different endotypes of CRSwNP and representative hematoxylin/eosin staining images of a pseudocyst (red arrow) within the epithelial layer from non-eosinophilic NP tissues (40×) (B) Comparison of a yellowish spot in NP tissue between non-eosinophilic and eosinophilic CRSwNP patients and representative images of a yellowish spot (red arrow) found on endoscopy in a non-eosinophilic CRSwNP patient. (*p<0.05, **p<0.01, and ***p<0.001). Data represent medians. E-NP, eosinophilic nasal polyp; NE-NP, non-eosinophilic nasal polyp.
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Related In: Results  -  Collection

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pone.0139945.g002: Distinctive histological features of non-eosinophilic CRSwNP patients.(A) Comparison of the proportion of total NP tissue area occupied by pseudocysts in different endotypes of CRSwNP and representative hematoxylin/eosin staining images of a pseudocyst (red arrow) within the epithelial layer from non-eosinophilic NP tissues (40×) (B) Comparison of a yellowish spot in NP tissue between non-eosinophilic and eosinophilic CRSwNP patients and representative images of a yellowish spot (red arrow) found on endoscopy in a non-eosinophilic CRSwNP patient. (*p<0.05, **p<0.01, and ***p<0.001). Data represent medians. E-NP, eosinophilic nasal polyp; NE-NP, non-eosinophilic nasal polyp.
Mentions: Interestingly, pseudocysts were observed in the epithelial layer, primarily in non-eosinophilic CRSwNP. This distinctive histopathological feature of non-eosinophilic NPs was observed in a low-power field (P×) (Fig 2A). This analysis revealed that the pseudocysts occupied a significantly larger area of NPs in non-eosinophilic CRSwNP patients compared with eosinophilic CRSwNP patients (Fig 2A). Furthermore, under endoscopy, we could detect yellowish spots on NPs with the appearance of mucous retention cysts (Fig 2B). These spots were observed at a significantly higher incidence in patients with non-eosinophilic CRSwNP than in patients with eosinophilic CRSwNP (Fig 2B). Similar to the Ki–67 staining results, these epithelial alteration findings also suggest that non-eosinophilic CRSwNP arise from localized lesion, compared with eosinophilic CRSwNP.

Bottom Line: Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs.Histologic, immunologic and clinical data suggest that non-eosinophilic NPs showed enhanced epithelial alteration and more localized maxillary involvement.Combination of cutoff value on IL-5, periostin, IFN-γ, and E/M scores may be one of surrogate markers for non-eosinophil NP subtype.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital and Nano-Bio Regenerative Medical Institute, Hallym University College of Medicine, Chuncheon, Republic of Korea.

ABSTRACT

Background: Non-eosinophilic nasal polyps (NPs) show less inflammatory changes and are less commonly associated with lower airway inflammatory disorders such as asthma, compared with eosinophilic NPs. However, the development of non-eosinophilic NPs which is a predominant subtype in Asian population still remains unclear.

Methods: A total of 81 patients (45 with non-eosinophilic NPs and 36 with eosinophilic NPs) were enrolled. Clinical information and computed tomography (CT), endoscopic, and histological findings were investigated. Tissue samples were analyzed for total IgE levels and for mRNA expression levels of interleukin (IL)-4, IL-5, IL-13, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-17A, IL-22, IL-23p19, transforming growth factor (TGF)-β1, TGF-β2, TGF-β3, and periostin. Immunostaining assessment of Ki-67 as a proliferation marker was performed.

Results: We found that epithelial in-growing patterns such as pseudocysts were more frequently observed in histological and endoscopic evaluations of non-eosinophilic NPs, which was linked to increase epithelial staining of Ki-67, a proliferating marker. Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs. To investigate the developmental course of each subtype, CT was analyzed according to CT scores and subtypes. Non-eosinophilic NPs showed more localized pattern and maxillary sinus involvement, but lesser olfactory involvement in early stage whereas eosinophilic NPs were characterized by diffuse ethmoidal and olfactory involvement. In addition, high ethmoidal/maxillary (E/M) CT scores, indicating ethmoidal dominant involvement, were one of surrogate markers for eosinophilic NP. E/M CT scores was positively correlated with levels of TH2 inflammatory markers, including IL-4, IL-5, periostin mRNA expression and total IgE levels in NPs, whereas levels of the TH1 cytokine, IFN- γ were inversely correlated. Moreover, if the combinatorial algorithm meet the three of the four markers, including IL-5 (<2.379), periostin (<3.889), IFN-γ (>0.316), and E/M ratio (<2.167), non-eosinophilic CRSwNP are diagnosed with a sensitivity of 84.4% and a specificity of 84.8%.

Conclusion: Histologic, immunologic and clinical data suggest that non-eosinophilic NPs showed enhanced epithelial alteration and more localized maxillary involvement. Combination of cutoff value on IL-5, periostin, IFN-γ, and E/M scores may be one of surrogate markers for non-eosinophil NP subtype.

No MeSH data available.


Related in: MedlinePlus