Presence of Tertiary Lymphoid Organ in Nasal Inverted Papilloma Is Correlated with Eosinophil Infiltration and Local Immunoglobulin Production.

INTRODUCTION: Nasal inverted papilloma (NIP) is a benign tumour with multiple inflammatory cell infiltration. Tertiary lymphoid organs (TLOs) support local antibody production and play important roles in airway inflammation. However, the evidence of TLOs and local immunoglobulins in NIP has not been reported yet. We investigated the presence of TLOs and immunoglobulins in NIP tissues and their association with the clinical-pathological characteristics of NIPs. METHODS: We analyzed the occurrence and composition of TLOs and local immunoglobulins by immunohistochemistry and evaluated the lymph organogenesis associated genes and cytokines by quantitative qPCR and Luminex assays, respectively, in papilloma tissues from 84 NIP cases. RESULTS: TLOs were present in 54% (45/84) of the NIP patients but not in control subjects. TLOs were composed of T cells, B cells, follicular dendritic cells, macrophages, and natural killer cells. Compared to NIP tissues without TLOs, tissues with TLOs showed significantly higher eosinophil infiltration levels (3.5-fold), elevation of lymphorganogenic genes (CXCL12, CXCL13, CCL20, CCL21, CD21L, and lymphotoxin alpha and beta), and increased Th17 (IL-21, IL-22, and GM-CSF) and Th2 (IL-5 and IL-13) cytokine production. Moreover, NIP with TLOs demonstrated a higher number of follicular T helper cells and immunoglobulin-producing plasma cells (CD138+ IgA+, CD138+ IgM+, CD138+ IgE+, and CD138+ IgG+) than those without TLOs, and these antibody-producing cells were positively correlated with the eosinophil number. CONCLUSION: The high frequency of TLOs and excess local immunoglobulin production are associated with an eosinophilic and Th2 skew microenvironment in the NIP mucosa, which would contribute to an important immunopathogenic response during NIP pathogenesis.

Human papillomavirus and infiltration of CD8- and Foxp3-positive immune cells in sinonasal inverted papillomas.

Background: Sinonasal inverted papilloma (IP) is a benign tumor with a high risk of local recurrence and a potential to malignify and Human papillomavirus (HPV) has been suggested an etiological factor. p16INK4a (p16) overexpression is considered a surrogate marker for HPV, but whether p16 and HPV correlate to IP is uncertain. Besides, a prognostic role of tumor infiltrating lymphocytes (TILs) are observed in many tumors, however their role in IP is sparsely studied. Aims/objectives: We hence analyzed IPs for the presence and the prognostic role of HPV and p16 overexpression together with CD8+ and FoxP3+ TILs in a population-based study. Material and methods: 98 IP patients diagnosed 2001-2010 were identified from the Swedish Cancer Registry and analyzed for HPV by PCR and p16, CD8 and FoxP3 was by immunohistochemistry. Results: In total, 12.2% of the IPs were HPV-positive (nine HPV-11, two HPV-6 and one HPV-45). Patients with HPV-positive lesions were younger (p = .003) and tended to present with more dysplasia. No correlation was observed between TILs and prognosis. Conclusions and significance: Our data suggests that patients with HPV-positive IPs present with different clinical characteristics, suggesting possibly different disease entities. Moreover, recurrences may occur >5 years, which should be considered in the follow-up.

[Different methods of antigen retrieval impact on Pan of sinonasal inverted papilloma].

OBJECTIVE: To explore different conditions and buffers of antigen retrieval which affect the CK of SNIP on immunohistochemical staining results. METHOD: Dividing paraffin tissue sections of 11 patients into four groups. Using the Image-Pro Plus Image analyzer and taking five horizons for each section to calculate an average of 200 areas, measured standard optical density of the positive reaction areas. RESULT: It is divided into four groups: high temperature and high pressure citrate buffer retrieval, microwave EDTA buffer retrieval, microwave citrate retrieval, high temperature and high pressure EDTA buffer retrieval. The standard optical density of positive reaction areas respectively express: 0.324 ± 0.051, 0.325 ± 0.056, 0.303 ± 0.061, 0.365 ± 0.023. The rates of CK positive expression with high temperature and high pressure EDTA buffer retrieval is batter than other repairing groups in the same paraffin tissue sections (P < 0.05). CONCLUSION: For the Pan of Sinonasal inverted papilloma, the method of high temperature and high pressure EDTA buffer antigen retrieval can achieve the ideal staining results? which is worth while to promote and maybe as a bet? ter guide of clinic work.

Increased frequencies of CD4+ CD25+ FOXP3+ regulatory T cells in human nasal inverted papilloma.

BACKGROUND: The purpose of this study was to investigate the presence of CD4(+) CD25(+) FOXP3(+) regulatory T (Treg) cells both in peripheral blood and local tumors in patients with nasal inverted papilloma (NIP). METHODS: By using flow cytometry, the frequencies of CD4(+) CD25(+) FOXP3(+) Treg cells in both peripheral blood and tissues from 18 patients with NIP and 8 control subjects were determined. CCL22 and CCL17 proteins in NIP tumors were analyzed by using enzyme-linked immunosorbent assay. The suppressive capacity of Treg cells was estimated by WST-8 and enzyme-linked immunosorbent assay (ELISA; interferon-gamma [IFN-γ] and interleukin-4 [IL-4]) analysis. RESULTS: Patients with NIP showed increased CD4(+) CD25(+) FOXP3(+) Treg cell frequencies in tumor tissues and CD4(+) T cell fraction rather than in peripheral blood. CCL22 increased in NIP tumors. Phytohemagglutinin (PHA)-induced proliferation and cytokine production of CD4(+) CD25(-) T cells were suppressed equally well by CD4(+) CD25(high) cells from both patients with NIP and controls. CONCLUSION: Our study demonstrated the increased frequencies of CD4(+) CD25(+) FOXP3(+) Treg cells in NIP tumors, which might be influenced by CCL22.

Pulmonary inverted Schneiderian papilloma causing high serum levels of carcinoembryonic antigen and squamous cell carcinoma-associated antigen: report of a case.

We report a rare case of inverted Schneiderian papilloma causing exceedingly high serum levels of carcinoembryonic antigen (CEA) and squamous cell carcinoma-associated antigen (SCC). A 74-year-old man presented with a 6-month history of a productive cough, bloody sputa, and dyspnea. Chest computed tomography showed massive infiltration in the lower lobe with multiple focal soft tissue densities. Blood biochemical analysis revealed a serum CEA level of 107.0 ng/ml (normal <5.0 ng/ml), and an SCC level of 373.0 ng/ml (normal <1.5 ng/ml). Squamous papilloma was diagnosed by histological examination of a bronchoscopic biopsy specimen. To alleviate the patient's symptoms and refine the diagnosis, we performed a right lower lobectomy. The lower lobe of the lung was filled with mucinous sputa and very fragile papillary tumors of various sizes. Microscopic examination revealed papillary growth of stratified epithelial cells with massive mucin production. No nuclear abnormality or invasion of the basal membrane of the tumor cells was observed. Postoperatively, the patient's symptoms resolved quickly, and the serum levels of CEA and SCC decreased to 6.4 ng/ml and 1.7 ng/ml, respectively, within 3 months.

[Immunohistological study of dendritic cells and macrophages in sino-nasal lesions--distributions in metaplastic squamous epithelium and squamous cell carcinoma].

Dendritic cells, macrophages and lymphocytes infiltrating the epithelia of sino-nasal lesions were investigated immunohistochemically using antibody S-100 protein for dendritic cells, Ki-M1P for macrophages, MT1 for T-cells and L26 for B-cells, respectively. Seventy-five specimens of sino-nasal mucosae involving 51 cases of metaplastic squamous epithelium (MSE), 12 of inverted papilloma, 1 of atypical hyperplasia and 11 of squamous cell carcinoma (SCC) were studied. Dendritic cells were observed in 12 cases of MSE (23.5%), in 4 of inverted papilloma (33.3%), and in 6 of SCC (54.5%). More dendritic cells were found infiltrating MSE of the infective and fibrotic types than of the mild and edematous types, histopathologically. Furthermore, infiltration correlated with the degree of squamous differentiation in MSE, but not in SCC. The number of macrophages was significantly smaller in MSE than in columnar ciliated epithelium, while that in SCC was significantly greater than that in MSE. With dendritic cell infiltration macrophages in MSE as well as SCC and T-cells in and around the carcinoma were often increased. These findings suggest that dendritic cells may be attracted to maturative squamous epithelium, and may play an important role in the immunologic defence mechanisms of MSE. Dendritic cells, in contrast, may play a role in the cellular immune response of T-cells against the carcinoma.