Etiology of nasal polyps in cystic fibrosis: not a unimodal disease

Abstract

Objectives: The objective was to determine whether the polyp subtypes observed in cystic fibrosis (CF)-related sinusitis were similar to those observed in non-CF-related sinusitis.

Methods: Polyp and mucus samples were collected from CF patients who presented for sinus surgery. The polyps underwent histologic and cytochemical evaluation for the presence of lymphocyte cell populations and their respective cytokine markers. The mucus samples were evaluated for DNA content.

Results: Of the polyps, 42% had an eosinophilic infiltrate, of which 80% had an additional mixed neutrophilic infiltrate. Of the remaining polyp samples, 42% did not have a granulocytic infiltrate, consistent with non-eosinophilic polyps. All samples had CD138-positive plasma cells. The mucus samples from the patients with CF showed higher extracellular DNA concentrations than did the mucus samples from patients with non-CF sinus disease.

Conclusions: Cystic fibrosis-related polyps demonstrated an eosinophil-based dichotomy similar to that of idiopathic non-CF-related polyps. Many also demonstrated neutrophilic infiltrate, indicating that chronic mucus stasis and infection complicate the disease. Agents capable of reducing extracellular DNA may help manage sinusitis in CF patients.

Fig 1

Hematoxylin-eosin (H&E) staining of cystic fibrosis (CF) polyps. Arrows indicate relevant cell types. A) Paucigranulocytic nasal polyp (NP; original ×200). B) Polymorphonuclear cell (PMN) infiltration without eosinophils (original ×200). C) Eosinophilic infiltration without PMNs (original ×200). D) Both eosinophils and PMNs within same field (original ×400).

Fig 2

Trichrome staining of CF polyps (original ×200). A) Marked tissue edema and loose stroma. B) Dense collagenous stalk adjacent to area showing glandular hypertrophy.

Fig 3

Mast cell staining in CF polyp tissue (original ×200). Chloroacetate stain demonstrates numerous mast cells scattered among areas with dense stromal tissue.

Fig 4

Immunohistochemistry of CD138-staining plasma cells.

Fig 5

CD11b (CR3) ImageStream flow cytometry analysis of cells isolated from CF polyp. Dark field (DF) examination reveals cytoplasmic granules, defining these cells as granulocytes. Staining of nucleus with 4’,6-diamidino-2-phenylindole (DAPI) demonstrates multilobed structure of PMNs. BF — bright field.

Fig 6

CD11b (CR3) ImageStream flow cytometry analysis of cells isolated from CF polyp. These cells are larger than those in Fig 5, and dark field examination reveals cytoplasmic granules. DAPI staining of nucleus demonstrates mononuclear structure of macrophages.