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Dab2 is an endocytic adaptor protein involved in various physiological processes and signaling pathways. Dab2 is deregulated in various cancers; however, its role in skin squamous cell carcinoma ( SCC) has not been elucidated yet. In the present study, we used the DMBA/TPA induced murine skin carcinogenesis model to examine the role of Dab2 in skin tumour progression. We generated tamoxifen inducible Dab2 conditional knockout system for our study. Loss of Dab2 led to delayed papilloma initiation and reduced papilloma burden. Delayed papilloma initiation was due to reduce proliferative potential of the papillomas due to Dab2 loss. Furthermore, while the WT papillomas progressed to SCC, the papillomas formed in Dab2 cKO mice failed to undergo malignant conversion to SCC. Dab2 cKO tumours showed reduced expression of K8, a marker for aggressive tumour. Moreover, Dab2 ckO tumours failed to undergo EMT as shown by reduced expression of Vimentin and Twist1. Dab2 cKO tumours also showed reduced expression of Sox2, a stem cell marker. Furthermore, qPCR analysis showed upregulation of Dab2 expression in the human skin cancer cell lines as compared to normal human skin keratinocytes. In patients, TCGA data analysis of skin cancer melanoma (SKCM) showed a trend where high levels of Dab2 correlated with poor overall survival. The present study shows that Dab2 promotes tumour progression in skin SCC., (© 2024 The Author(s). Experimental Dermatology published by John Wiley & Sons Ltd.)

Key Points: Intralesional cidofovir injections in combination with surgery is an effective treatment for recurrent multifocal sinonasal exophytic papilloma. No malignant transformation has been observed in our experience. Anosmia is a potential side effect that patients should be aware of., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Juvenile-onset recurrent respiratory papillomatosis (JORRP) is caused by persistent infection of epithelial cells by low-risk human papillomavirus (HPV) types 6 and 11. While multiple infiltrated immune cells have been reported to mediate disease progress, knowledge of HPV-reactive T-cell subsets in papillomas remains elusive. Through single-cell RNA sequencing and RNA microarray, we found that CD8+ tissue-resident memory T (CD8+ T RM ) cells with strong interferon-gamma (IFN-γ) production expanded, and were negatively correlated to the disease severity in the frequency of surgery. These IFN-γ+ CD8+ memory T cells were readily activated and expanded in vitro by autologous dendritic cells loaded with HPV11 E7 peptide pool. Moreover, T cell receptor (TCR) clonal expansion was observed in JORRP papilloma tissues, indicating a biased TCR repertoire toward HPV-specific recognition. Finally, we identified and characterized HPV11 E7-specific candidate TCR clonotypes from IFN-γ+ CD8+ memory T cells, suggesting their potential application in TCR-engineered T cells (TCR-T) therapy for HPV11-related diseases. Our findings provided insights into the specific local immune response to HPV6/11 infection and highlighted the importance of IFN-γ+ CD8+ T RM cells in anti-HPV6/11 T-cell immunity.IMPORTANCEThe persistent recurrence of human papillomavirus (HPV) 6/11 infection in papillomas underscores the failure of local immune responses in patients with juvenile-onset recurrent respiratory papillomatosis (JORRP). Our previous study demonstrated that T cells constitute the predominant immune cell population in JORRP papilloma tissues. Understanding the T-cell-mediated immune responses within JORRP papilloma tissues is crucial for disease control. In the present study, we characterized CD8+ tissue-resident memory T (CD8+ T RM ) cells as the primary T-cell subset responsible for local anti-HPV6/11 immunity. Moreover, we identified two HPV11 E7-specific candidate T cell receptor (TCR) clonotypes out of IFN-γ+ CD8+ memory T cells. Overall, our findings provided insights into the local immune responses to HPV6/11 infection and offered information for developing more effective immunotherapeutic strategies against JORRP., Competing Interests: The authors declare no conflict of interest.

Fibropapillomatosis (FP) - tumour-associated chelonid alphaherpesvirus 5 (ChHV5; Scutavirus chelonidalpha5) - is a disease that affect marine turtles around the world, and characterized by the formation of cutaneous tumours that can appear anywhere on the body. We carried out a thorough literature search (from 1990 to 2024) in the feeding sites of North-western Mexico, a region that hosts important habitats for feeding, development, and reproduction for five of the seven existing sea turtle species. We found 18 reports recording a total of 32 cases of FP and/or ChHV5/Scutavirus chelonidalpha5 in coastal and insular areas of North-western Mexico. Baja California Sur resulted with the highest number of cases (75%). While the first case of ChHV5/Scutavirus chelonidalpha5 infection was reported in 2004, the presence of FP tumours was reported in 2014 and became more frequent between 2019 and 2024. The affected species were black, Chelonia mydas (50%), olive ridley, Lepidochelys olivacea (46.8%) and loggerhead turtles, Caretta caretta (3.2%). Tumours occurred mainly in anterior flippers (46.1%) and neck (22.5%), and most had a nodular and verrucous appearance with a rough surface. In the study region, there is a potential sign of the emergence of the ChHV5/Scutavirus chelonidalpha5 infections and FP disease during the last 20 years, with a rapid increase during the last 10 years. As long as infections by ChHV5/Scutavirus chelonidalpha5 and the prevalence of the FP disease may be potentially influenced by anthropogenic activities, a One Health approach is needed to understand and improve sea turtles' health., (© 2024. The Author(s).)

Pulmonary mixed squamous cell and glandular papilloma (MSCGP) is a subtype of pulmonary papilloma, which can be classified as central type and peripheral type based on its site of development. The central type is the most common. The clinical manifestations of pulmonary MSCGP are mainly related to the location of the tumor. Surgery is the main treatment for this disease. Bronchoscopic interventional treatment for the MSCGP in the central trachea could receive satisfactory effect. We reported a patient suffered from diffuse tracheal MSCGP who was treated by bronchoscopic interventional treatment in Respiratory Disease Center, Dongzhimen Hospital of Beijing University of Chinese Medicine, aiming to enhance the recognition of the clinical features and provide clinical references for the diagnosis and treatment of such disease.
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Purpose: To report long-term outcomes after surgery for primary benign papillomas of the lacrimal drainage system., Methods: Retrospective review of patients with primary lacrimal drainage system papillomas, first seen between 1984 and 2021, but excluding lesions with sino-nasal origin or malignant histology. Patients were categorized by tumor histology (squamous, transitional, and mixed cell) and growth pattern (exophytic, endophytic, or mixed)., Results: Thirty patients (18 female; 60%) presented at a mean age of 46.1 years (12-79 years). Over an average follow-up of 10.4 years, 30% of patients experienced recurrence, with rates differing slightly by growth pattern: 25% for exophytic tumors and 40% for endophytic and mixed-pattern tumors ( p = 0.431). The overall 5-year recurrence-free survival was 67% (± 9% standard error), this being slightly higher for exophytic lesions (75% ± 10%) as compared to 48% (± 19%) for tumors with an endophytic component ( p = 0.370). No cases of malignant transformation were observed, and the tumor type at recurrence matched the initial diagnosis., Conclusion: Primary benign papillomas of the lacrimal drainage system have a long-term recurrence rate of about one-third, with a higher frequency in those exhibiting an endophytic growth pattern. The study highlights the importance of prolonged surveillance for recurrence, especially for endophytic and mixed growth pattern tumors, and for the potential to undergo malignant transformation. The results support the effectiveness of endoscopic surgical excision or laser thermos-ablation in managing recurrent lacrimal drainage system papillomas after dacryocystorhinostomy., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Background: With advancements in medicine and economy, it would be expected that there will be changes in the clinical characteristics of upper respiratory papillomatosis. The aim of this study was to examine the current clinical characteristics of upper respiratory papillomatosis, as there are no recent data in the literature., Methods: The medical records of 1894 patients with upper respiratory papillomatosis were retrospectively reviewed. Data extracted included clinical features, laryngoscopy images, and surgical procedure data., Results: The upper frequency of upper respiratory papillomatosis in the oropharynx was 69.1 %, and in the larynx was held 28.9 %. The overall postoperative relapse rate was 2.4 %. The relapse rate of laryngeal papillomatosis was 6.5 %. Approximately 2.6 % of cases were in children. All postoperative recurrences in children were laryngeal, and the recurrence rate was 30.4 %., Conclusion: The oropharynx has the highest frequency of upper respiratory papillomatosis. The larynx, however, has the highest rate of postoperative recurrence. Compared to adults, children are more likely to experience a postoperative recurrence., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description., Objectives: To describe the dermatological manifestations of CS; compare them with the literature findings; assess those discriminating CS from other RASopathies, including cardiofaciocutaneous syndrome (CFCS) and the main types of Noonan syndrome (NS); and test for dermatological phenotype-genotype correlations., Methods: We performed a 10-year, large, prospective, multicentric, collaborative dermatological and genetic study., Results: Thirty-one patients were enrolled. Hair abnormalities were ubiquitous, including wavy or curly hair and excessive eyebrows, respectively in 68% and 56%. Acral excessive skin (AES), papillomas and keratotic papules (PKP), acanthosis nigricans (AN), palmoplantar hyperkeratosis (PPHK) and 'cobblestone' papillomatous papules of the upper lip (CPPUL), were noted respectively in 84%, 61%, 65%, 55% and 32%. Excessive eyebrows, PKP, AN, CCPUL and AES best differentiated CS from CFCS and NS. Multiple melanocytic naevi (>50) may constitute a new marker of attenuated CS associated with intragenic duplication in HRAS. Oral acitretin may be highly beneficial for therapeutic management of PPHK. No significant dermatological phenotype-genotype correlation was determined between patients with and without HRAS c.34G>A (p.G12S)., Conclusions and Relevance: This validated phenotypic characterization of a large number of patients with CS will allow future researchers to make a positive diagnosis, and to differentiate CS from CFCS and NS., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Sinonasal papillomas are a group of uncommon benign neoplasms that often represent a diagnostic challenge for surgical pathologists due to their diverse morphologic features. Our understanding of the molecular pathogenesis of these tumors has made significant advances recently that have reinforced the histology-based classification that was introduced over 50 years ago. As some subtypes have features that overlap with other sinonasal tumors, including specific carcinomas such as DEK::AFF2 nonkeratinizing squamous cell carcinoma, being aware of their key diagnostic findings is vital for appropriate classification., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Oral papilloma, a frequently encountered benign lesion, can be managed effectively with various treatments. A unique case of oral mucosal papilloma extending from the buccal fat pad region to the corner of the mouth is presented here. Although papilloma larger than 10 mm 2 are associated with a high risk of becoming cancerous and should be treated promptly, the papilloma in this case would have been difficult to resect due to involvement of the parotid duct opening and the corner of the mouth. Topical external application of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) was employed successfully in this case, with no recurrence at 20 months of follow-up. Therefore, ALA-PDT may represent a promising therapeutic option for challenging cases of multifocal papilloma of the oral mucosal., Competing Interests: Competing interests None., (Copyright © 2024 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study is to describe the incidence and demographics of laryngeal papillomatosis (LP) in Denmark, including sex and age distribution, recurrence rates, and HPV subtypes, using a new method of register identification., Methods: The data were extracted from the Danish Pathology Data Bank using SNOMED codes instead of the usual method using ICD codes from the Danish National Health Register. The derived pathology records were manually verified by three medical doctors. The study period was 1994-2021. Patients were categorized according to age as either juvenile-onset RRP (JoRRP) if <18 years or adult-onset RRP (AoRRP) if 18 years or older., Results: We identified 1819 RRP patients (JoRRP: 56; AoRRP:1763). The overall incidence per 100,000 inhabitants were 0.17 for JoRRP and 1.45 for AoRRP. The vast majority (72%) of the patients were male, but there was no significant difference in age at onset of RRP or recurrence rates between the sexes. Children below 3 years of age had the highest recurrence probability. Extracting data using SNOMED codes resulted in a positive predictive value of 99% regarding total number of biopsies and 98% regarding individuals. The incidence decreased throughout the study period., Conclusion: Comparable incidence and recurrence rates of RRP were found between Denmark and Norway. In this study, the Danish Pathology Register was found to be a highly valuable method for identifying LP patients. The effect of the nationwide HPV vaccination program can be evaluated using this method as the vaccinated cohort is starting to grow older and reproduce., Level of Evidence: Retrospective registry-based national cohort study, 3 Laryngoscope, 134:5047-5053, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: BRCA1-associated protein (BAP1) tumor predisposition syndrome (TPDS) is a cancer genodermatosis associated with high risk of uveal and cutaneous melanoma, basal cell carcinoma, and multiple internal malignant neoplasms, including mesothelioma and renal cell carcinoma. Early detection of the syndrome is important for cancer surveillance and genetic counseling of family members who are at risk., Objective: To determine the prevalence of nail abnormalities in individuals with pathogenic germline variants in BAP1., Design, Setting, and Participants: In this prospective cohort study, individuals who were known carriers of pathogenic BAP1 germline variants were consecutively enrolled between October 10, 2023, and March 15, 2024. Dermatologic evaluation for nail abnormalities was performed, including a history of nail abnormalities and associated symptoms, physical examination, medical photography, and nail biopsy for histopathology. This was a single-center study conducted at the National Institutes of Health Clinical Center., Main Outcomes and Measures: Primary outcomes were the prevalence and spectrum of nail changes and histopathologic characterization., Results: Among 47 participants (30 female [63.8%]; mean [SD] age, 46.4 [15.1] years) ranging in age from 13 to 72 years from 35 families, nail abnormalities were detected in 41 patients (87.2%) and included leukonychia, splinter hemorrhage, onychoschizia, and distal nail hyperkeratosis. Clinical findings consistent with onychopapilloma were detected in 39 patients (83.0%), including 35 of 40 individuals aged 30 years or older (87.5%). Nail bed biopsy was performed in 5 patients and was consistent with onychopapilloma. Polydactylous involvement with onychopapillomas was detected in nearly all patients who had nail involvement (38 of 39 patients [97.4%])., Conclusions and Relevance: This study found that BAP1 TPDS was associated with a high rate of nail abnormalities consistent with onychopapillomas in adult carriers of the disease. Findings suggest that this novel cutaneous sign may facilitate detection of the syndrome in family members who are at risk and patients with cancers associated with BAP1 given that multiple onychopapillomas are uncommon in the general population and may be a distinct clue to the presence of a pathogenic germline variant in the BAP1 gene.

The aim of work is description of new observations related to the participation of demodex in tumor morphogenesis with goal to study the example of eyelid papilloma, imagine the connection between the presence of the demodex mite and certain changes in the typical histomorphological picture of the neoplasm., Materials and Methods: Histomorphological examination covers biopsy and operative material of eye pathology with diagnosis of neoplasm (eyelid papilloma and actinic keratosis (senile keratosis, senile keratoma, solar keratosis)) were selected, with special attention paid to the presence of horn cysts. Agile methodologies were employed to manage the research workflow effectively., Results: As a result of the conducted histomorphological examination, in 24 cases (48%), patterns pathognomonic for demodectic infection were found. Such patterns, which could indicate the presence of a demodex mite, were cystic formations, as well as fragments of a dead parasite. We noted their presence not only in the tumor tissue, but also in the adjacent hair follicles, sebaceous glands, and subepidermal stroma. It is no coincidence that the authors who previously noted the presence of pigmented elements in keratopapillomas or seborrheic keratomas could not explain their origin, resorting to putting forward such fantastic assumptions as the presence of "symbiosis of melanoblasts and epithelial cells, which ensures the transfer of pigment from the first to the second"., Conclusions: Histomorphological study of serial sections allows us to see the successive stages of transformation of cavity intratissue defects created by the activity of the mite into horn cysts. Cavity defects are the main evidence of demodectic infestation. They occur in basal cell and squamous cell carcinomas, xanthomas, sebaceous adenomas, etc. tumors of the eyelids, but only in keratoacanthomas and senile keratomas they can turn into corneal cysts, which can be assumed to be due to the differentiating potential of these neoplasms.

Objectives: To characterize the distribution of immune cell subsets within laryngeal papillomas and to study the function of potentially immunosuppressive neutrophilic and regulatory T cells (Tregs)., Methods: Fresh clinical papilloma specimens were collected at the time of surgery and studied with multiparameter flow cytometry. Papilloma infiltrating neutrophilic cells and Tregs were sorted and studied functionally with ex vivo T cell suppression assays., Results: Flow cytometric analysis of fresh laryngeal papillomas samples from 18 adult patients with recurrent respiratory papillomatosis revealed patterns in immune constituency between patients. Clearly divergent phenotypes based primarily on the degree of neutrophilic and T cell infiltration were identified. Relative neutrophilic cell enrichment and T cell depletion were observed in 50% of samples and neutrophilic cell depletion and T cell enrichment were observed in the others. Greater papilloma neutrophilic cell enrichment was positively associated with the number of clinically indicated interventions required in the 12 months prior to sample collection, linking papilloma neutrophil inflammation to disease severity. Functional assays revealed the ability of both papilloma infiltrating neutrophilic and Tregs to suppress T cell function at roughly equal magnitudes, but substantially increased infiltration of neutrophilic cells compared to Tregs across samples., Conclusion: Neutrophilic cells are an important contributor to immunosuppression within the respiratory papilloma microenvironment. Given these data and the association between greater neutrophilic cell infiltration and lack of clinical response to therapeutic vaccination, additional study of strategies aimed at limiting neutrophilic cell infiltration or function within papillomas is warranted., Level of Evidence: 4 Laryngoscope, 134:3238-3244, 2024., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

This report describes the clinical, onychoscopic, nail clipping, and histopathologic features of a malignant onychopapilloma. A 71-year-old male presented to our outpatient clinic for a stable, asymptomatic lesion on his left middle finger that had been present for 2 years. Prior nail clipping histopathology showed nail plate thinning with subungual abnormal onychocytes. Clinical examination revealed a 2-mm-wide streak of longitudinal xanthonychia extending to the proximal nail fold, with distal hyperkeratosis and onycholysis. Onychoscopy showed irregular longitudinal nail plate ridging with scattered punctate hemorrhagic foci. An excisional nail unit biopsy demonstrated cellular atypia of the nail bed epithelium, matrix metaplasia, longitudinal abnormal onychocytes, increased Ki-67 staining, and negative HPV immunoperoxidase staining, confirming the diagnosis of malignant onychopapilloma., (© 2024 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

Background: Papilloma DNA viruses are one of the viruses that cause skin lesions in ruminants., Objectives: The clinical, histopathological and molecular characteristics of cutaneous papilloma in ruminants in Iran are to be investigated in this study., Methods: Samples were collected from 19 small ruminants (5 sheep and 14 goats) with various papillomatosis lesions. The samples taken were studied with histopathological and molecular techniques., Results: In clinical terms, the lesions appeared in different sizes, ranging from 0.5 to 11 cm, and the cauliflower exophytic masses appeared in other parts of the animal's body. In the limbs, most papilloma lesions have been seen (42.1%). In histopathological examination, perinuclear vacuolation epidermal granule layer with various degrees of hypergranulosis, hyperkeratosis, acanthosis, orthokeratosis and parakeratosis were seen. Moreover, all the suspected samples were positive for papillomavirus using the polymerase chain reaction technique., Conclusions: Although the prevalence of papillomaviruses in Iranian sheep and goats is low, it seems necessary to distinguish them from other viral skin diseases, such as cutaneous contagious ecthyma, using molecular techniques and histopathology., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Introduction: The etiology of esophageal squamous papilloma (ESP) is largely unknown. Previous studies have shown a variable association with human papillomavirus (HPV) with conflicting data. The aim of this study was to further investigate the possible association of HPV in our ESP series using RNA in-situ hybridization (ISH) and compare study groups from the United States of America and China. Methods: Demographic and clinical data of patients with ESP were retrieved from the University of California Los Angeles (UCLA) (1/2016-3/2019) and Peking Union Medical College Hospital (PUMCH) (9/2014-3/2019) pathology databases. Hematoxylin and eosin slides were reexamined. Confirmed cases were examined by high- and low-risk HPV RNA ISH. Results: For the UCLA cohort, 13 429 upper endoscopies were performed and 78 biopsies from 72 patients were identified as ESP (F:M = 45:27, 66.7% > 45 years). Seventy-four (94.9%) biopsies were designated as polyps or nodules and 46.6% were located in the mid-esophagus. Other abnormal findings included gastroesophageal reflux disease (48.6%), hiatal hernia (38.9%), and esophagitis (36.1%). For the PUMCH cohort, 63 754 upper endoscopies were performed and 73 biopsies from 71 patients were identified as ESP (F:M = 48:23, 71.8% > 45 years). Sixty-four (87.7%) biopsies were designated as polyps or nodules and 57.5% were located in the mid-esophagus. Other abnormal findings included esophagitis (19.7%), and hiatal hernia (8.5%). No features of conventional cytologic dysplasia or viral cytopathic change were found. None of the cases was associated with squamous cell carcinoma, and none showed positive HPV RNA ISH results. Conclusions: No association was found between ESP and active HPV infection in our 2 cohorts. Other etiopathogenetic mechanisms, such as aging, might contribute to the development of these innocent lesions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Significance Statement: Neurovascular hamartomas (NVH) is an uncommon tumor-like developmental anomaly. We hereby report the case of a 28-year-old woman presenting with multiple millimetric excrescences in the oral cavity that were clinically interpreted as squamous cell papilloma and histologically consistent with NVHs. Neurovascular hamartomas is rare in the oral cavity. To the best of our knowledge, multiple NVHs have never been reported at this site., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Solitary pulmonary papillomas (SPPs) are rare lung neoplasms. Histologically, SPP is classified into three subtypes, and mixed squamous and glandular papilloma (MP) is the rarest subtype. Although SPPs are considered benign tumors, there have been several reports on the synchronous malignant transformation in SPPs. An 82-year-old asymptomatic man was referred to our hospital for further examination of a 2.2 cm-sized left lung tumor. Pathology of bronchoscopic specimens showed the possibility of pulmonary papilloma but did not reveal any malignancy. The patient complained of bloody sputum during the eighth month after the initial visit. The size of the lesion had increased to 4.3 cm. These data suggested the existence of malignancy, and the patient underwent an operation. Histologically, the tumor was composed of fibrovascular cores and papillomatous fronds lined by pseudostratified columnar cells and mucin-filled goblet cells. Keratinizing squamous epithelium was also observed. Overall, the diagnosis of MP was obtained by fundamental histology. In addition, a solid part beneath mild atypical squamous epithelia, which was composed of malignant-appearing squamous cells and spindle-shaped atypical cells, was observed. The spindle portion was positive for cytokeratin AE1/AE3 and vimentin, and focally positive for alpha-smooth muscle actin (αSMA). The final diagnosis was pulmonary pleomorphic carcinoma (PPC) arising in the MP. Only two cases have been reported for atypical spindle tumor cells that are found in MP or bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT), which has histologically similar features to MP. This is the second case report of PPC arising in MP., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Competing Interests: The authors have no conflicts of interest regarding this article, and have received no funding for this work.

Papilloma of the lung is a rare benign entity and can be solitary or multiple. Solitary papilloma is subclassified into three categories: squamous papilloma, glandular papilloma, and mixed squamous and glandular papilloma. Glandular papilloma is the rarest subtype among them and occurs mostly in the sixth decade without any relation to smoking, syndrome, or infection. Histology is characterized by mixture of pseudostratified, columnar, nonciliated, mucinous epithelium-lined papillary fronds without any mitoses, necrosis, or atypia. The differential diagnosis can be broad depending upon the histologic features present in a particular case and may include both benign and malignant entities. We present here a patient with glandular endobronchial papilloma showing unusual clinical history and atypical histologic features, which required extensive immunohistochemical evaluation to establish a final diagnosis., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Epidemiological data on the distribution of oral and maxillofacial diseases present in early childhood are scarce in the literature. This study analyzed the frequency of lesions biopsied in this region in children aged 0 to 3 years and sent for histopathological analysis in a reference oral pathology laboratory . Histopathological diagnostic data, lesion location, sex, and age were collected. Of the total of 93,950 records, 250 cases (0.27%) belonged to the age group from 0 to 3 years old. The most frequently diagnosed oral alterations were: mucocele (34/250; 13.6%); papilloma (11/250; 4.4%), giant cell fibroma (6/250; 2.4%), pyogenic granuloma (5/250; 2%) and hemangioma (3/250; 1.2%). The lip was the most affected site, followed by the gingiva and the tongue. These results generate information on the lesions most frequently diagnosed in early childhood, which facilitates the process of diagnosis and, consequently, treatment., (© 2023 Wiley Periodicals LLC.)

Rationale: This article presents a challenging case involving an elderly male patient with a misdiagnosed intraductal mammary papilloma initially identified as a sweat adenoma through ultrasound imaging. The study aims to explore the histopathology, clinical presentations, and sonographic features of both conditions, emphasizing the contributing factors to the diagnostic misstep., Patient Concerns: A 61-year-old male reported a persistent left breast mass, along with pain and swelling, spanning a 6-month duration., Diagnoses: Ultrasound examination indicated a deep, square, mixed-echo mass in the left nipple, initially suggestive of a sweat adenoma. However, subsequent pathological analysis following resection under general anesthesia confirmed an intraductal papilloma., Intervention: The patient underwent surgical resection of the left breast mass under general anesthesia., Outcome: Post-surgery, the patient exhibited satisfactory recovery; however, regrettably, he was lost to follow-up., Lessons: This study underscores the challenge in differentiating between clear cell sweat adenoma and male intraductal mammary papilloma solely based on ultrasonic characteristics. It emphasizes the susceptibility of ultrasound-based diagnoses to misinterpretation, highlighting the critical need for a comprehensive pathological examination to establish a definitive diagnosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

A papilloma is a benign tumor arising from an epithelial surface. Mostly a papilloma appears as an asymptomatic intraoral lesion and is often associated with the human papilloma virus (HPV). In this case report two similar, verrucous papules, sessile bilateral on the back of the tongue, were surgically removed in a 65-year-old male patient. Thereby two different methods of treatment were compared. On the right side of the back of the tongue, excision by scalpel, as the gold standard treatment modality, was performed. On the left side a surgical removal by a CO2 laser was performed. In a photothermal procedure, without direct contact to the tissue, the laser beam is cutting through the mucosa. Secondary wound healing can take place. Both methods were compared in relation to their application, wound healing, quality of the biopsy and morbidity. Postoperative less discomfort and a slightly faster wound healing could be seen after scalpel removal. The histopathological examination was comparable for both methods., (Copyright 2024 SWISS DENTAL JOURNAL SSO – Science and Clinical Topics. License: This work is licensed under a Creative Commons Attribution 4.0 International License.)

Introduction: A healthy, 1,5 year old female wild boar (Sus scrofa) was shoot in a hunting district in Switzerland on June 22, 2023. The meat inspection revealed noticeable skin changes on all four distal extremities which were described histologically as multifocal epidermal hyperplasia and moderate orthokeratotic hyperkeratosis. The rest of the animal body, the organs and the lymph nodes were without any obvious lesions. The diagnosis of papilloma virus-associated exophytically growing papillomas was made. The venison was approved as fit for human consumption.

Melanocytic nevus occurring in the external auditory canal (EAC) is uncommon. Therefore, in the absence of sufficient clinical experience, this disease may be challenging to be suspected even with a physical examination. Herein, clinical and demographic features of intradermal nevus in the EAC were investigated. Patients with an intradermal nevus on histopathological examination (n = 15; 2 men and 13 women; P = .005) were included from a pool of patients who underwent surgical resection for EAC tumors between November 2011 and March 2022. Data were retrospectively collected on their sex, appearance of the lesions, surgical method, and outcomes. Nine patients had a dome shape and 6 patients had a papillomatous shape. Ten patients had dark colors and 5 patients had pale colors. All pale colors appeared only in the dome-shaped nevus, and only dark colored papillomatous nevi were observed. A significant difference was noted in terms of the frequency of occurrence by colors (dark or pale) according to shape (dome or papillomatous) (P = .044). No patient showed recurrence or EAC stenosis after circumferential excision. In women, a dome-shaped or papillomatous mass with dark color in the EAC may likely be predicted as the nevus. However, it can also occur in men, and even if it is a pale color, in the case of a dome shape, taking the nevus into account is important. Moreover, successful treatment outcomes were achieved through circumferential excision., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

We conducted a two-year inhalation study of butyraldehyde using F344/DuCrlCrlj rats. The rats were exposed to 0, 300, 1,000 and 3,000 ppm (v/v) for 6 hr/day, 5 days/ week for 104 weeks using whole-body inhalation chambers. The incidence of squamous cell carcinoma of the nasal cavity was increased in the 3,000 ppm groups of both male and female rats, with Fisher's exact test and the Peto test indicating that the incidence was significant. In addition to squamous cell carcinoma in the nasal cavity, in the 3,000 ppm groups one male had an adenosquamous carcinoma, one male had a carcinosarcoma, one male had a sarcoma NOS (Not Otherwise Specified), and one female had a squamous cell papilloma in the nasal cavity. The combined incidence of squamous cell carcinoma, adenosquamous carcinoma and carcinosarcoma was significantly increased in male rats and the combined incidence of squamous cell papilloma and carcinoma was significantly increased in female. Based on these results, we conclude that there is clear evidence of butyraldehyde carcinogenicity in male and female rats.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a novel entity characterized by its unique translocation and malignant clinical course. In this study, AFF immunohistochemistry (IHC) was performed in recurrent sinonasal papillomas for reviewing the prevalence of undiagnosed DEK::AFF2 carcinomas and to investigate the performance of AFF IHC in diagnosis of DEK::AFF2 carcinomas. Recurrent sinonasal papillomas after surgical excision in a two-decade period were retrieved. Histologic slides were reviewed for features of DEK::AFF2 carcinoma. AFF IHC was performed, and cases with any (> 1%) nuclear positivity were validated by DEK break apart fluorescence in situ hybridization. Totally 43 cases were included, comprising 28 inverted, 6 exophytic, one oncocytic, and 8 non-specified sinonasal papillomas. Five (11.6%) cases exhibited positivity to AFF IHC. Three cases exhibited patchy weak to moderate staining intensity predominantly in a granular cytoplasmic pattern. Two cases exhibited strong and diffuse (> 90%) nuclear staining. Cases showing weak staining were negative for DEK rearrangement, while those with strong staining were positive. Both cases of DEK::AFF2 carcinoma showed aggressive behavior with extensive local invasion and nodal metastasis. Background stromal plasma cells, when present, consistently showed strong and diffuse staining. AFF IHC was further performed in plasmacytoma samples as control and showed strong and diffuse immunoreactivity. A significant minority of recurrent sinonasal papillomas represent DEK::AFF2 carcinomas. Granular, cytoplasmic, or incomplete AFF staining should be considered as negative. In view of the rarity of DEK::AFF2 carcinomas, plasma cells and plasma cell neoplasms are potential for internal and surrogate external controls., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Onychopapilloma is a benign tumor presenting as an isolated benign warty distal matrix and bed lesion in association with longitudinal erythronychia for which no underlying cause can be identified. Diagnosis might be challenging due to other, more severe, causes of erythronychia., Objectives: This study aimed to investigate the clinical and sonographic features of onychopapilloma using high-frequency ultrasound., Methods: Between February 2022 and May 2023, a cross-sectional study was conducted, involving 39 patients displaying clinical features suggestive of onychopapilloma. These patients were selected at random and underwent examination using high-frequency ultrasound. High-frequency ultrasound assessments of the nail unit were carried out using 33 MHz and 24 MHz high-frequency linear transducers. An experienced radiologist performed the ultrasound scans while participants assumed an orthostatic seated position. Subsequently, the collected ultrasound images were independently evaluated by two radiologists specializing in nail injuries, ensuring a blinded assessment. This evaluation aimed to provide comprehensive insights into the imaging characteristics of onychopapilloma., Results: High-frequency ultrasound revealed oval or linear hyperechoic masses located in the middle of the nail plate, without vascularity or posterior acoustic shadowing. Nail plate irregularity, thickening, and nail bed indentation were observed in some cases. These findings demonstrate that high-frequency ultrasound can aid in the diagnosis and surgical planning of onychopapilloma, providing detailed visualization of the lesion and surrounding structures., Conclusions: This imaging method could represent a potential tool to differentiate onychopapilloma from other nail conditions, especially malignant neoplasms. However, further research is needed to validate these findings and assess long-term outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: This study aimed to identify the sonographic features of pathologically confirmed onychopapilloma cases., Methods: High-frequency up to 24 MHz and ultra-high frequency-ultrasound up to 71 MHz examinations were performed and correlated with their clinical and pathologic presentations., Results: Twenty-two cases met the criteria. Clinical presentations revealed longitudinal erythronychia in 63.3% of cases. The ultrasound examinations identified a hypoechoic band in the nail bed (86.3%), nail plate abnormalities including upward displacement (68.2%) and thickening (68.1%), focal hyperechoic focal spots on the nail plate (50%) and irregularities of the ventral plate (33.3%). Color Doppler imaging showed no hypervascularity of the nail bed in all studies. These findings correlate with histological characteristics of onychopapilloma, including nail bed acanthosis, papillomatosis, and layered hyperkeratosis. Recurrence occurred in two cases after surgery, with tumors showing proximal extension in the matrix region on ultrasound not evident during clinical examination., Conclusion: High-frequency and ultra-high-frequency can provide anatomical information in onychopapilloma that could enhance understanding and management., (© 2023 American Institute of Ultrasound in Medicine.)

Background: Juvenile papillomatosis (JP) of the breast is a rare and benign proliferative disorder affecting young women. The affected patients tend to have an increased risk of breast cancer development during follow-up., Objective: This article aims to highlight a rare entity of breast disease, that harbor risk of breast cancer., Case Presentation: Here, we present 2 cases of JP in young females; the first case is a 13 year-old presented with spontaneous nipple discharge, while the other patient is a 24 year-old presented with a right breast lump. Both patients had a total excision of the breast lesions, revealing JP at histology. Discussion: Juvenile Papillomatosis is considered a clinicopathological entity and is usually misdiagnosed as fibroadenoma clinically and radiologically, which requires histological correlation. The histologic findings are well-defined (hyperplasia, papillomatosis, and multiple cysts with foamy histiocytes).The controversy in management between surgery and observation is because of insufficient knowledge about the direct relationship between JP and subsequent cancer., Conclusion: Considering the risk of developing breast cancer in JP, enrolling patients and their families in a close follow-up and surveillance program is crucial., Competing Interests: There are no conflicts of interest., (© 2024 Mariam Al-Qurashi, Arwa Ibrahim, Tarek M. ElSharkawy, Areej Al Nemer, Hiyam Alhaddad, Maha Abdel Hadi.)

Nipple adenoma is a rare proliferative lesion that originates from the lactiferous ducts of the nipple. Though it is benign, the typical presentation includes suspicious symptoms-a firm nodule, crusting erosion, and/or discharge from the nipple. These findings can raise concern for malignancy and in particular, Paget's disease. We report two cases of this uncommon entity, highlighting the variable clinical presentation and keys to the diagnostic evaluation and management., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a recently characterized sinonasal malignancy defined by its unique translocation. DEK::AFF2 carcinomas may be deceptively monotonous and lack keratinization, resembling transitional epithelium. The lack of traditional cytological atypia presents diagnostic challenges. Our case describes the first report of fine-needle aspiration cytology of a lymph node involved by DEK::AFF2 carcinoma in a patient with previously resected sinonasal inverted papilloma with carcinomatous transformation six years prior to presentation. This aspirate consisted of a lymphoid-rich background admixed with a moderate amount of epithelial cells arranged in cohesive structures of variable size, including large sheets. The tumor cells resembled those of the corresponding biopsy, featuring mildly hyperchromatic nuclei with fine to vesicular chromatin. Lesional cells lacked keratinization, mitoses, or hyperchromasia. Our finding suggests that in nodal aspirates of patients with a history of sinonasal-type papillomas, especially those with prior malignant transformation or atypia, there should be consideration for the possibility of DEK::AFF2-related primary. When in doubt, DEK FISH of AFF2 immunohistochemistry should be performed for confirmation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Recurrent respiratory papillomatosis (RRP) is a rare, debilitating neoplastic disorder caused by chronic infection with human papillomavirus (HPV) type 6 or 11 and characterized by growth of papillomas in the upper aerodigestive tract. There is no approved medical therapy, and patients require repeated debulking procedures to maintain voice and airway function. PRGN-2012 is a gorilla adenovirus immune-therapeutic capable of enhancing HPV 6/11-specific T cell immunity. This first-in-human, phase 1 study (NCT04724980) of adjuvant PRGN-2012 treatment in adult patients with severe, aggressive RRP demonstrates the overall safety and clinically meaningful benefit observed with PRGN-2012, with a 50% complete response rate in patients treated at the highest dose. Responders demonstrate greater expansion of peripheral HPV-specific T cells compared with nonresponders. Additional correlative studies identify an association between reduced baseline papilloma HPV gene expression, greater interferon responses and expression of CXCL9 and CXCL10 , and greater papilloma T cell infiltration in responders. Conversely, nonresponders were characterized by greater HPV and CXCL8 gene expression, increased neutrophilic cell infiltration, and reduced T cell papilloma infiltration. These results suggest that papilloma HPV gene expression may regulate interferon signaling and chemokine expression profiles within the tumor microenvironment that cooperate to govern clinical response to therapeutic HPV vaccination in patients with respiratory papillomatosis.

Background: Papillary lesions of the breast are a heterogeneous group, encompassing a wide range of lesions. The histologic distinction between papillary breast lesions remains challenging, especially on core biopsy specimens. Aim: This study aimed to determine the rate of upgrade to atypia or malignancy of biopsy-proven papillary lesions on surgical follow-up and to assess for factors associated with an upgrade in Greater Vancouver, BC, Canada. Materials and Methods: This is a retrospective population-based study of all breast papillary lesions diagnosed on core biopsy between 2017 and 2019 in the Fraser Health Authority in Greater Vancouver, Canada. Patients were retrieved from the laboratory information system. Patient demographics, histopathologic, and radiologic findings were analyzed. Results: A total of 269 specimens from 269 patients (mean 61.1 years), including 265 female and 4 male patients, were included in the study. Of the 269 specimens, 129 (48%) were intraductal papillomas and 140 (52%) were atypical papillary lesions. The overall upgrade rate among papillomas was 11.6% (15 of 129) on final excision. The mean age of patients diagnosed with papilloma on core biopsy was significantly younger than those with atypical papillary lesions (55.6 vs 66.1 years, P < .0001). Lesion size in patients with papillomas on core biopsy was significantly smaller than those with atypical papillary lesions (11.1 vs 15.1 mm, P  = .001). The upgrade rates in patients <55 and ≥55 years were 4.9% and 13.2%. Size ( P  = .004) and atypia on core biopsy ( P  = .009) were significantly associated with upgrade. Older age (>55 years) (OR =  5.3, 95% CI: 1.04-27.08) was an independent predictor of upgrade among papillomas. Size, location, and Breast Imaging-Reporting and Data System (BI-RADS) radiologic categories in our study were not associated with predicting the upgrade of papillomas. Conclusion: Our data suggest that the risk of upgrade to atypia or malignancy is sufficient to warrant the excision of benign papillomas of any size in patients aged ≥55 years. In patients younger than 55 years, observation with close clinical and radiological follow-up without surgery may be sufficient. Our findings also support surgical excision of papillomas diagnosed on core biopsy when associated with atypia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To investigate the histopathological and immunohistochemical characteristics of benign apocrine cystic papillary hyperplasia of the breast with loss of myoepithelial cell layer. Methods: The clinical data, histopathological features and immunohistochemical profile of patients with benign apocrine cystic papillary hyperplasia of breast with loss of myoepithelial cell layer from January 2016 to December 2021 were examined, in which six patients were identified. Results: All six patients were female, aged 36-61 years (median 46 years), who presented with a breast mass; three cases were from the left breast and three cases were from the right breast. Microscopic examination of all cases showed breast hyperplasia with apocrine cysts, accompanied by different degrees of micropapillary and papillary hyperplasia of apocrine cells. One case was associated with lobular carcinoma in situ, and one case was associated with apocrine ductal carcinoma in situ with intraductal dissemination in adenosis. Immunohistochemical staining of CK5/6, p63, SMA, SMMHC, Calponin and CD10 showed complete absence of myoepithelial cell layer surrounding ducts in apocrine cystic papillary hyperplasia. Conclusions: The myoepithelial cells of apocrine cystic papillary hyperplasia of the breast may undergo abnormal changes and may even be completely lost. The diagnosis should be comprehensively considered along with cytomorphological and histological features to avoid overdiagnosis.

Endobronchial solitary papillomas are extremely rare lung neoplasms originating from the bronchial surface epithelium. They often present with cough or recurrent hemoptysis. These tumors are benign, but they should be followed closely because they may even have a low probability of malignant transformation features. It should be kept in mind that malignancy may develop especially if the patient is a smoker. Although the etiology is not known for certain, it is thought to be caused by human papillomavirus in some cases. A 43-year-old male patient was admitted with a complaint of chronic cough. Rigid bronchoscopy was performed for diagnostic and therapeutic purposes after imaging techniques revealed a lesion obstructing the lumen of the right main bronchus. The pathology result was reported as mixed bronchial papilloma. We aimed to present our case because of its rarity and to indicate that chronic cough must be further evaluated.

Erosive and oozing lesions of the nipple, especially when unilateral, should raise suspicion about malignant neoplasms. Herein we report a patient with typical clinical and histopathological features of erosive adenomatosis of the nipple (EAN). It is an uncommon, benign proliferative process of lactiferous ducts of the nipple. Clinically, EAN is characterized by erosion, serous discharge, edema, itching, and erythema of one of the nipples. Complete excision of the tumor yields excellent results. Although EAN is a rare disease, clinicians must be aware of this benign neoplasm in patients with erosive lesions of the nipple. The main concern is the need to rule out malignant proliferations in the differential diagnosis. Histology is the gold standard for diagnosis. The coexistence of nipple adenoma and breast cancer is well-reported in the literature. Thus, it is necessary to encourage patients with a history of EAN to maintain regular breast screening.

Purpose: This study aimed to analyze the clinicopathological features of ocular papilloma, a common benign tumor, and the risk factors related to its recurrence and partial deterioration., Methods: We collected and analyzed the clinical information of 298 patients (51.68% males) with mean age of 41.54 ± 21.95 years, in the ophthalmology department of the West China Hospital. Clinical and pathological factors that might be related to papilloma recurrence and partial deterioration were studied., Results: The top three papilloma sites were bulbar conjunctiva, eyelid skin and palpebral conjunctiva. Moreover, 3.59% of lesions presented a malignant transformation, and 16.28% of patients had one or more recurrences after an average follow-up of 4.47 years. The multivariate logistic regression model showed that multiple lesions were a risk factor for recurrence (p = 0.022, OR = 3.088, 95% CI: 1.180-8.079), while cryotherapy decreased the recurrence risk (p = 0.044, OR = 0.364, 95% CI: 0.136-0.972). Additionally, elderly patients and lesions on the corneal limbus or cornea had a higher risk of malignant transformation (p = 0.004 and 0.01, OR = 1.086 and 7.827, 95% CI: 1.027-1.150 and 1.629-37.596, respectively)., Conclusion: Ocular papilloma usually occurs in middle-aged and young patients, with no significant gender differences. Older patients and lesions on the corneal limbus or cornea are risk factors for partial malignant transformation. Finally, multiple lesions were a risk factor for recurrence, and cryotherapy reduced the recurrence rate., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)