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Journal of Thoracic Oncology : Official... Apr 2012Solitary respiratory papillomas (SRPs) are considered uncommon yet benign neoplasms of the lower respiratory tract. Most of our understanding stems from single case... (Review)
Review
INTRODUCTION
Solitary respiratory papillomas (SRPs) are considered uncommon yet benign neoplasms of the lower respiratory tract. Most of our understanding stems from single case reports or limited case series.
OBJECTIVE
To determine the incidence of solitary SRPs and more accurately describe the localization, distribution of subtypes of solitary SRPs, clinical features, and the risk of malignant transformation. This retrospective report is based on data collected in a busy single-center bronchoscopy practice during a 22-year period.
METHODS
Among 36,780 patients who underwent bronchoscopic procedures between 1986 and 2008, we identified 32 patients with SRPs. This patient group was compared with 69 patients with SRPs described in the English literature as case reports, case series, or diagnostic dilemmas.
RESULTS
Twenty-three patients were men (male/female ratio of 3:1), and 21 patients were former smokers (65.6%). The mean age of initial presentation in men and women was 56.9 ± 14.3 versus 53.3 ± 14.4 years, respectively. The presenting symptoms included cough in 18 patients (40.6%), hemoptysis in 11 (25%), dyspnea in seven (21.8%), and fever in five patients (15.7%). Two patients with papillomas in the subglottic region had wheezing and were on aerosolized bronchodilator therapy. In one patient, the papilloma was incidentally discovered on a chest computed tomography scan. The histologic analysis of lesions revealed squamous papillomas in 65.6%, a glandular subtype in 18.75%, and a mixed subtype in 15.6%. Malignant transformation was observed in five patients (15.7%). The malignancies consisted of squamous cell carcinoma in two patients, and single cases of small cell lung carcinoma, glandular carcinoma, and low-grade carcinoma.
CONCLUSION
In our experience, the estimated incidence of SRPs is 3.95 cases/100,000 patients/yr. SRPs occur more commonly in men (ratio 3:1). Squamous papillomas occur commonly during the fifth decade of life, glandular papillomas predominate in the sixth decade, and the distribution of mixed type papillomas is from the third to the sixth decade of life. Malignant transformation was observed in a minority of patients.
Topics: Adult; Aged; Bronchoscopy; Cell Transformation, Neoplastic; Female; Humans; Incidence; Male; Middle Aged; Papilloma; Respiratory Tract Neoplasms; Retrospective Studies
PubMed: 22425912
DOI: 10.1097/JTO.0b013e3182468d06 -
Journal of Virology Oct 2022Laryngopharynx epithelium neoplasia induced by HPV6/11 infection in juvenile-onset recurrent respiratory papillomatosis (JO-RRP) causes a great health issue...
Restricted Recruitment of NK Cells with Impaired Function Is Caused by HPV-Driven Immunosuppressive Microenvironment of Papillomas in Aggressive Juvenile-Onset Recurrent Respiratory Papillomatosis Patients.
Laryngopharynx epithelium neoplasia induced by HPV6/11 infection in juvenile-onset recurrent respiratory papillomatosis (JO-RRP) causes a great health issue characteristic of frequent relapse and aggressive disease progression. Local cell-mediated immunity shaped by the recruitment and activation of cytotoxic effector cells is critical for viral clearance. In this study, we found that NK cells in the papillomas of aggressive JO-RRP patients, in contrast to massive infiltrated T cells, were scarce in number and impaired in activation and cytotoxicity as they were in peripheral blood. Data from cell infiltration analysis indicated that the migration of NK cell to papilloma was restricted in aggressive JO-RRP patients. Further study showed that the skewed chemokine expression in the papillomas and elevated ICAM-1 expression in hyperplastic epithelia cells favored the T cell but not NK cell recruitment in aggressive JO-RRP patients. In parallel to the increased CD3 T cells, we observed a dramatical increase in Tregs and Treg-promoting cytokines such as IL-4, IL-10 and TGFβ in papillomas of aggressive JO-RRP patients. Our study suggested that likely initialized by the intrinsic change in neoplastic epithelial cells with persistent HPV infection, the aggressive papillomas built an entry barrier for NK cell infiltration and formed an immunosuppressive clump to fend off the immune attack from intra-papillomas NK cells. Frequent relapse and aggressive disease progression of juvenile-onset recurrent respiratory papillomatosis (JO-RRP) pose a great challenge to the complete remission of HPV 6/11 related laryngeal neoplasia. Local immune responses in papillomas are more relevant to the disease control considering the locale infected restriction of HPV virus in epitheliums. In our study, the restricted NK cell number and reduced expression of activating NKp30 receptor suggested one possible mechanism underlying impaired NK cell defense ability in aggressive JO-RRP papillomas. Meanwhile, the negative impact of HPV persistent infection on NK cell number and function represented yet another example of a chronic pathogen subverting NK cell behavior, affirming a potentially important role for NK cells in viral containment. Further, the skewed chemokine/cytokine expression in the papillomas and the elevated adhesion molecules expression in hyperplastic epithelia cells provided important clues for understanding blocked infiltration and antiviral dysfunction of NK cells in papilloma.
Topics: Disease Progression; Human papillomavirus 11; Humans; Intercellular Adhesion Molecule-1; Interleukin-10; Interleukin-4; Killer Cells, Natural; Natural Cytotoxicity Triggering Receptor 3; Neoplasm Recurrence, Local; Papilloma; Papillomavirus Infections; Respiratory Tract Infections; Transforming Growth Factor beta
PubMed: 36154611
DOI: 10.1128/jvi.00946-22 -
Viruses Oct 2023Cutaneous plantar papillomas are a relatively common lesion of wild psittacine birds in Australia. Next-generation sequencing technology was used to investigate the...
Cutaneous plantar papillomas are a relatively common lesion of wild psittacine birds in Australia. Next-generation sequencing technology was used to investigate the potential aetiologic agent(s) for a plantar cutaneous papilloma in a wild rainbow lorikeet (). In the DNA from this lesion, two novel viral sequences were detected. The first was the partial sequence of a herpesvirus with the proposed name, psittacid alphaherpesvirus 6, from the genus of the family alphaherpesviruses. This represents the first mardivirus to be detected in a psittacine bird, the first mardivirus to be detected in a wild bird in Australia, and the second mardivirus to be found in a biopsy of an avian cutaneous papilloma. The second virus sequence was a complete sequence of a hepadnavirus, proposed as parrot hepatitis B genotype H (PHBV-H). PHBV-H is the first hepadnavirus to be detected in a wild psittacine bird in Australia. Whether other similar viruses are circulating in wild birds in Australia and whether either of these viruses play a role in the development of the plantar papilloma will require testing of biopsies from similar lesions and normal skin from other wild psittacine birds.
Topics: Animals; Avihepadnavirus; Parrots; Alphaherpesvirinae; Herpesviridae; Oncogenic Viruses; Papilloma; Polyesters; Bird Diseases
PubMed: 37896884
DOI: 10.3390/v15102106 -
Genetics and Molecular Research : GMR Dec 2015Bovine papillomavirus (BPV) is an oncogenic virus with mucous and epithelial tropism. Possible productive virus infection in other tissues, such as blood, has been...
Bovine papillomavirus (BPV) is an oncogenic virus with mucous and epithelial tropism. Possible productive virus infection in other tissues, such as blood, has been hypothesized. In order to investigate this possibility, three samples of skin papillomas and blood were collected from bovines with BPV infection and five samples of peripheral blood and one sample of normal tissue were collected from a calf without BPV infection. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and examined by reverse transcription-polymerase chain reaction, immunofluorescence, in situ hybridization, and electron microscopy. The tissue samples were examined for histopathological and immunohistochemical features. The skin papillomas showed the presence of DNA sequences of BPV-2, BPV-11, and a putative virus type. The blood samples showed DNA sequences of BPV-1, 2, and 4 simultaneously. Immunohistochemistry showed BPV L1 protein in both epithelium and stroma and BPV E2 protein in koilocytes. In situ hybridization confirmed the presence of BPV DNA in PBMCs and immunofluorescence showed nuclear labeling of E2 and L1 BPV proteins in PBMCs. The transcription analysis revealed transcripts of BPV-1 L1, BPV-2 L2, and BPV-4 E7 in blood and papilloma samples of BPV-infected cattle. The comet assay revealed high levels of host cell DNA damage upon BPV infection. Electron microscopy analysis of PBMCs identified the presence of particles in the cytoplasm that are consistent with papillomavirus in size and shape. The productive infection of PBMCs with BPV has been previously discussed and this study provides evidence indicating that PBMCs are a target of BPV.
Topics: Animals; Bovine papillomavirus 1; Cattle; Epithelium; Monocytes; Papilloma; Skin Neoplasms
PubMed: 26681018
DOI: 10.4238/2015.December.11.19 -
Asian Journal of Surgery Apr 2003A 6-year-review of patients who presented with recurrent respiratory papillomatosis (RRP) to our hospital from January 1996 to December 2001 was carried out. Ten cases...
A 6-year-review of patients who presented with recurrent respiratory papillomatosis (RRP) to our hospital from January 1996 to December 2001 was carried out. Ten cases were identified, of which six were juvenile-onset RRP. Hoarseness was the most common symptom, noted in nine (90%) patients. Other clinical presentations included cough, stridor and aphonia. All patients had glottic papillomas; two had multiple sites of involvement. One patient underwent a tracheostomy that revealed papillomas over the trachea, bronchus and lung parenchyma. Half of the patients were Chinese. Of the six cases of juvenile-onset RRP, three patients were Malay, two Chinese and one Indian. Three Chinese and one German patient had adult-onset RRP. Among the juvenile-onset RRP cases, the mean age at presentation was 2 years, while for adult-onset RRP, it was 42 years. Juvenile-onset RRP was more common in females. There were more papillomas over more sites in patients with juvenile-onset RRP than with adult-onset disease. Subglottic involvement was noted in the juvenile-onset RRP cases. All patients were treated with CO2 laser therapy, but there was complete remission of the papillomas in only two cases.
Topics: Adolescent; Adult; Age of Onset; Aged; Child; Child, Preschool; Female; Humans; Laser Therapy; Male; Middle Aged; Papilloma; Respiratory Tract Neoplasms
PubMed: 12732496
DOI: 10.1016/S1015-9584(09)60231-1 -
Einstein (Sao Paulo, Brazil) May 2019Oral squamous papilloma is a benign tumor whose pathogenesis has been associated with human papillomavirus infection. Thus, it is noteworthy that human papillomavirus...
Oral squamous papilloma is a benign tumor whose pathogenesis has been associated with human papillomavirus infection. Thus, it is noteworthy that human papillomavirus infection is one of the risk factors associated with the development of cervical, anogenital, pharynx, larynx and oral cavity carcinomas. Oral squamous papilloma can affect any region of the oral cavity, and transmission of human papillomavirus can occur by direct contact, sexual intercourse or from mother to child during delivery. The diagnosis is clinical and histopathological, with surgical removal representing the treatment of choice. Recently, widefield optical fluorescence has been used as a complementary examination to the conventional clinical examination in the screening of oral pathological lesions and for the delimitation of surgical margins. We report a case of oral squamous papilloma with its clinical, histopathological features and, in addition, from the perspective of wide field optical fluorescence.
Topics: Fluorescence; Humans; Male; Middle Aged; Mouth Neoplasms; Neoplasms, Squamous Cell; Palate, Hard; Papilloma
PubMed: 31090794
DOI: 10.31744/einstein_journal/2019RC4624 -
Modern Pathology : An Official Journal... Jun 2021Sinonasal papillomas are benign epithelial tumors of the sinonasal tract that are associated with a synchronous or metachronous sinonasal carcinoma in a subset of cases....
Sinonasal papillomas are benign epithelial tumors of the sinonasal tract that are associated with a synchronous or metachronous sinonasal carcinoma in a subset of cases. Our group recently identified mutually exclusive EGFR mutations and human papillomavirus (HPV) infection in inverted sinonasal papillomas and frequent KRAS mutations in oncocytic sinonasal papillomas. We also demonstrated concordant mutational and HPV infection status in sinonasal papilloma-associated sinonasal carcinomas, confirming a clonal relationship between these tumors. Despite our emerging understanding of the oncogenic mechanisms driving formation of sinonasal papillomas, little is currently known about the molecular mechanisms of malignant progression to sinonasal carcinoma. In the present study, we utilized targeted next-generation DNA sequencing to characterize the molecular landscape of a large cohort of sinonasal papilloma-associated sinonasal carcinomas. As expected, EGFR or KRAS mutations were present in the vast majority of tumors. In addition, highly recurrent TP53 mutations, CDKN2A mutations, and/or CDKN2A copy-number losses were detected; overall, nearly all tumors (n = 28/29; 96.6%) harbored at least one TP53 or CDKN2A alteration. TERT copy-number gains also occurred frequently (27.6%); however, no TERT promoter mutations were identified. Other recurrent molecular alterations included NFE2L2 and PIK3CA mutations and SOX2, CCND1, MYC, FGFR1, and EGFR copy-number gains. Importantly, TP53 mutations and CDKN2A alterations were not detected in matched sinonasal papillomas, suggesting that these molecular events are associated with malignant transformation. Compared to aerodigestive tract squamous cell carcinomas from The Cancer Genome Atlas (TCGA) project, sinonasal papilloma-associated sinonasal carcinomas have a distinct molecular phenotype, including more frequent EGFR, KRAS, and CDKN2A mutations, TERT copy-number gains, and low-risk human papillomavirus (HPV) infection. These findings shed light on the molecular mechanisms of malignant progression of sinonasal papillomas and may have important diagnostic and therapeutic implications for patients with advanced sinonasal cancer.
Topics: Cell Transformation, Neoplastic; Cyclin-Dependent Kinase Inhibitor p16; DNA Copy Number Variations; Disease Progression; Humans; Mutation; Papilloma; Paranasal Sinus Neoplasms; Tumor Suppressor Protein p53
PubMed: 33203919
DOI: 10.1038/s41379-020-00716-3 -
The American Journal of Surgical... Nov 2022Sinonasal papillomas are a diverse group of benign epithelial neoplasms of the sinonasal tract. Inverted papilloma, in particular, must be distinguished from other...
Sinonasal papillomas are a diverse group of benign epithelial neoplasms of the sinonasal tract. Inverted papilloma, in particular, must be distinguished from other lesions with no malignant potential. The aim of this study was to distinguish sinonasal papillomas from morphologically similar lesions using CD163 immunostaining. Cases from a 19-year period were identified. These included 49 inverted, 10 exophytic, and 12 oncocytic papillomas, 21 chronic sinusitides with squamous metaplasia, 27 inflammatory polyps, 5 verrucae vulgares, 5 respiratory epithelial adenomatoid hamartomas, and 6 DEK::AFF2 carcinomas of the sinonasal tract. A subset of biopsy cases (8 inverted papillomas, 5 inflammatory polyps) was separately analyzed. CD163 immunohistochemistry (IHC) was performed. A unique "circle" staining pattern was identified in the surface epithelium. After locating a hotspot, circles were quantified in 10 consecutive high-power fields. Circles were present in 66/71 (93%) cases of sinonasal papilloma, with a mean of 35 circles/10 HPF (range: 0 to 160/10 HPF) and a median of 19 circles/10 HPF. Circles were present in 20/58 (34%) non-neoplastic cases, with a mean of 2 circles/10 HPF (range: 0 to 27/10 HPF) and a median of 0. Considering all resection and biopsy cases, performance for distinguishing papillomas from non-neoplastic lesions was best at a cutoff of 10 circles/10 HPF (2-tailed P <0.0001) with sensitivity, specificity, positive predictive value, and negative predictive value of 66.2%, 93.1%, 92.1%, and 69.2%, respectively. The results were similar in the biopsy subset. One other neoplastic entity, the DEK::AFF2 carcinomas, also showed prominent CD163 circle staining. In summary, sinonasal papillomas demonstrate extensive CD163 "circle" staining in the epithelium compared with the non-neoplastic lesions studied. As such, the "circle sign" on CD163 IHC may be helpful in distinguishing between diagnoses, particularly on small biopsies or equivocal specimens.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carcinoma; Chromosomal Proteins, Non-Histone; Humans; Nasopharyngeal Neoplasms; Nose Neoplasms; Oncogene Proteins; Papilloma, Inverted; Paranasal Sinus Neoplasms; Poly-ADP-Ribose Binding Proteins; Receptors, Cell Surface; Staining and Labeling
PubMed: 35993580
DOI: 10.1097/PAS.0000000000001953 -
Viruses Feb 2023Papillomaviruses (PVs) are small, non-enveloped viruses, ubiquitous across the animal kingdom. PVs induce diverse forms of infection, such as cutaneous papillomas,...
Papillomaviruses (PVs) are small, non-enveloped viruses, ubiquitous across the animal kingdom. PVs induce diverse forms of infection, such as cutaneous papillomas, genital papillomatosis, and carcinomas. During a survey on the fertility status of a mare, a novel PV (EcPV) has been identified using Next Generation Sequencing, and it was further confirmed with genome-walking PCR and Sanger sequencing. The complete circular genome 7607 bp long shares 67% average percentage of identity with EcPV9, EcPV2, EcPV1, and EcPV6, justifying a new classification as PV 10 (EcPV10). All EcPV genes are conserved in EcPV10, and phylogenetic analysis indicates that EcPV10 is closely related to EcPV9 and EcPV2, genus Dyoiota 1. A preliminary EcPV10 genoprevalence study, carried out on 216 horses using Real Time PCRs, suggested a low incidence of this isolate (3.7%) compared to EcPVs of the same genus such as EcPV2 and EcPV9 in the same horse population. We hypothesize a transmission mechanism different from the one observed in the closely related EcPV9 and EcPV2 that particularly infect Thoroughbreds. This horse breed is usually submitted to natural mating, thus indicating a possible sexual diffusion. No differences were detected for breeds in terms of susceptibility to EcPV10. Further studies are needed to investigate the molecular mechanisms behind the host and EcPV10 infection to explain the reduced viral spread.
Topics: Horses; Animals; Female; Phylogeny; Horse Diseases; Papillomavirus Infections; Papillomaviridae; Real-Time Polymerase Chain Reaction; Papilloma
PubMed: 36992359
DOI: 10.3390/v15030650 -
Cancer Science Aug 2020CENP-50/U is a component of the CENP-O complex (CENP-O/P/Q/R/U) and localizes to the centromere throughout the cell cycle. Aberrant expression of CENP-50/U has been...
CENP-50/U is a component of the CENP-O complex (CENP-O/P/Q/R/U) and localizes to the centromere throughout the cell cycle. Aberrant expression of CENP-50/U has been reported in many types of cancers. However, as Cenp-50/U-deficient mice die during early embryogenesis, its functions remain poorly understood in vivo. To investigate the role of Cenp-50/U in skin carcinogenesis, we generated Cenp-50/U conditional knockout (K14Cre -Cenp-50/U ) mice and subjected them to the 7,12-dimethylbenz(a)anthracene (DMBA)/terephthalic acid (TPA) chemical carcinogenesis protocol. As a result, early-stage papillomas decreased in Cenp-50/U-deficient mice. In contrast, Cenp-50/U-deficient mice demonstrated almost the same carcinoma incidence as control mice. Furthermore, mRNA expression analysis using DMBA/TPA-induced papillomas and carcinomas revealed that Cenp-50/U expression levels in papillomas were significantly higher than in carcinomas. These results suggest that Cenp-50/U functions mainly in early papilloma development and it has little effect on malignant conversion.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Carcinogens; Cell Cycle Proteins; Humans; Mice; Mice, Knockout; Neoplasms, Experimental; Papilloma; Phthalic Acids; Skin; Skin Neoplasms
PubMed: 32535988
DOI: 10.1111/cas.14533