The Diagnostic Value of microRNA Expression Analysis in Detecting Intraductal Papillomas in Patients with Pathological Nipple Discharge.

Patients with pathological nipple discharge (PND) often undergo local surgical procedures because standard radiologic imaging fails to identify the underlying cause. MicroRNA (MiRNA) expression analysis of nipple fluid holds potential for distinguishing between breast diseases. This study aimed to compare miRNA expression levels between nipple fluids from patients with PND to identify possible relevant miRNAs that could differentiate between intraductal papillomas and no abnormalities in the breast tissue. Nipple fluid samples from patients with PND without radiological and pathological suspicion for malignancy who underwent a ductoscopy procedure were analyzed. We used univariate and multivariate regression analyses to identify nipple fluid miRNAs differing between pathologically confirmed papillomas and breast tissue without abnormalities. A total of 27 nipple fluid samples from patients with PND were included for miRNA expression analysis. Out of the 22 miRNAs examined, only miR-145-5p was significantly differentially expressed (upregulated) in nipple fluid from patients with an intraductal papilloma compared to patients showing no breast abnormalities (OR 4.76, p = 0.046), with a diagnostic accuracy of 92%. miR-145-5p expression in nipple fluid differs for intraductal papillomas and breast tissue without abnormalities and, therefore, has potential as a diagnostic marker to signal presence of papillomas in PND patients. However, further refinement and validation in clinical trials are necessary to establish its clinical applicability.

[Epidemiological features papillomatosis of the larynx in adults: a literature review]. / Epidemiologicheskie osobennosti papillomatoza gortani u vzroslykh (obzor literatury).

The literature review presents current data on the epidemiology, drug, and surgical treatment of laryngeal papillomatosis in adults. Possible prospects for further study of the prevalence and incidence of the disease and provoking factors of recurrence of the disease for the development of possible preventive measures are considered.

Report of a self-resolving corneal viral papilloma in a dog.

A 10-month-old male castrated beagle dog, without prior history of ocular disease, was referred for a corneal mass of the right eye. A non-painful raised mass with frond-like projections originated from the dorsotemporal paraxial cornea of the right eye. In addition, a plaque-like conjunctival lesion and several raised, smooth masses of the eyelid were noted around the right eye. An incisional biopsy of the corneal mass and an excisional biopsy of the conjunctival mass were performed. Histopathology confirmed the clinical diagnosis of viral papilloma. Conservative management with monitoring was elected, and the lesion self-resolved 3 mo after initial appearance. Key clinical message: This case suggests that monitoring is appropriate for corneal lesions definitively diagnosed as viral papillomas, as they may be self-limiting.

Rapport d'un papillome viral cornéen auto-résolutif chez un chien. Un chien beagle mâle castré âgé de 10 mois, sans antécédent de maladie oculaire, a été envoyé pour consultation pour une masse cornéenne de l'oeil droit. Une masse surélevée non douloureuse avec des projections en forme de frondes provenait de la cornée paraxiale dorso-temporale de l'oeil droit. De plus, une lésion conjonctivale en forme de plaque et plusieurs masses surélevées et lisses de la paupière ont été notées autour de l'oeil droit. Une biopsie incisionnelle de la masse cornéenne et une biopsie excisionnelle de la masse conjonctivale ont été réalisées. L'histopathologie a confirmé le diagnostic clinique de papillome viral. Une prise en charge conservatrice avec surveillance a été choisie et la lésion s'est résolue d'elle-même 3 mois après l'apparition initiale.Message clinique clé :Ce cas suggère que la surveillance est appropriée pour les lésions cornéennes définitivement diagnostiquées comme des papillomes viraux, car elles peuvent être spontanément auto-limitantes.(Traduit par Dr Serge Messier).

[Significance of TERT promoter mutation in differential diagnosis of non-invasive inverted urothelial lesions of bladder].

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.

Oral Papillomatosis: Its Relation with Human Papilloma Virus Infection and Local Immunity-An Update.

Oral papilloma lesions may appear as a result of HPV infection, or not, and only special molecular methods could differentiate them. Low-risk and high-risk HPV types could induce oral HPV papillomatosis with different natural evolution, clearance and persistence mechanisms. The pathogenic mechanisms are based on the crosstalk between the oral epithelial and immune cells and this very efficient virus. HPV acts as a direct inducer in the process of transforming a benign lesion into a malignant one, the cancerization process being also debated in this paper. According to the degree of malignity, three types of papillomatous lesions can be described in the oral cavity: benign lesions, potential malign disorders and malignant lesions. The precise molecular diagnostic is important to identify the presence of various virus types and also the virus products responsible for its oncogenicity. An accurate diagnostic of oral papilloma can be established through a good knowledge of etiological and epidemiological factors, clinical examination and laboratory tests. This review intends to update the pathogenic mechanisms driving the macroscopic and histological features of oral papillomatosis having HPV infection as the main etiological factor, focusing on its interreference in the local immunity. In the absence of an accurate molecular diagnostic and knowledge of local immunological conditions, the therapeutic strategy could be difficult to decide.

Pulmonary mixed squamous and glandular papilloma: diagnostic challenges of a rare lesion when the clock is ticking. How to avoid interpretation mistakes.

Pulmonary mixed squamous and glandular papillomas (MSCGPs) are rare, benign neoplasms with peculiar clinical and histological features. However, on occasion, they can present certain characteristics that overlap with other neoplasms including carcinomas. Recognising these features is hence important for treatment purposes. Molecular studies can sometimes help in further characterisation, although they should not guide the diagnosis which ultimately relies on morphology.We report a challenging case of MSCGP with unusual features, received during intraoperative consultation. We highlight the subtle morphological features to help avoid overcalling a benign lesion as malignant.

Clinicopathological analysis of low-grade papillary Schneiderian carcinoma: report of five new cases and review of the literature.

AIMS: Low-grade papillary Schneiderian carcinoma (LGPSC) is a rare and newly described entity of the sinonasal tract. The aim of this study was to evaluate the clinicopathological and molecular characteristics in order to identify typical features for differential diagnosis. METHODS AND RESULTS: Of the 3000 cases of sinonasal tumour studied during a period of 6 years, five cases were reviewed and diagnosed as LGPSC. All five patients were female (mean age, 47.8 years; range, 18-64 years) and had undergone multiple surgeries (3-10 surgeries). Both the sinonasal tract and the middle ear were involved in four patients. Nodal metastasis occurred in two patients, and one patient developed a distant metastasis to the left lung. Histologically, tumours had branched and crowded papillae with pushing boundaries. Tumour epithelia were multilayered and arranged in an orderly pattern without cilia. No malignant cytological features were observed in any of the cases. Immunohistochemical findings revealed a scattered distribution of Ki67-positive cells and positive staining for epithelial membrane antigen, mainly in the outermost-layer cells. Human papillomavirus (HPV) DNA was found in two patients and genotyped as HPV type 16. Sanger sequencing did not reveal any epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene homologue gene mutation in the five cases. CONCLUSIONS: We report on five new cases of LGPSC, and confirm LGPSC as a new sinonasal carcinoma that behaves aggressively with metastatic potential. The combination of clinical behaviour and typical histological features can distinguish LGPSC from sinonasal papilloma and other carcinomas.

Esophageal Squamous Papilloma in Children: A Single-center Case Series.

OBJECTIVES: Esophageal squamous papilloma (ESP) is a rare epithelial lesion most commonly seen in adults, with an unclear etiology and limited pediatric data available. The aim of this study was to provide an estimated prevalence of this lesion in our pediatric population, as well as to identify any demographic, clinical, or pathologic associations-including human papilloma virus (HPV) infection, which has been linked with ESP in adult literature. METHODS: ESP cases at University Hospitals Rainbow Babies & Children's Hospital were identified by conducting a retrospective search through all esophagogastroduodenoscopies (EGDs) performed in children under 18 years old, from January 1, 2000 to December 31, 2014. Histopathology reports were analyzed including Fluorescence In Situ Hybridization (FISH) for HPV, and a comprehensive chart review was performed for demographic data. RESULTS: Of 12,459 children who required an EGD, 10 children were identified with ESP on biopsy, with ages ranging from 2 to 17 years. This provides an estimated prevalence of 0.08% over the entire study period. Seventy percentage of patients underwent endoscopy for abdominal pain, and 40% presented with gastroesophageal reflux. Sixty percentage of lesions were in the proximal esophagus, and 80% of patients had isolated lesions. Notably, none of the lesions tested were positive for HPV on FISH analysis. CONCLUSIONS: ESP is a rare benign lesion found incidentally in the pediatric population. The prevalence at our institution was 0.08%. All samples tested for HPV via FISH analysis were negative. As a result, regular analysis for HPV may not be necessary in pediatric patients with ESP in the future.

A case report of exophytic nasal papilloma with acute dacryocystitis as the first symptom.

BACKGROUND: This study aims to explore a case of exophytic nasal papilloma with acute dacryocystitis as the first symptom. CASE PRESENTATION: A 72-year-old male patient complaining of "a 10-year history of tearing and purulent discharge from the right eye, with subsequent redness and pain in the inner canthus for three days" was initially diagnosed with acute dacryocystitis of the right eye. The patient was treated with anti-inflammatory therapy. However, the redness and swelling of the inner canthus continued to increase. An endoscopic dacryocystorhinostomy of the right eye was performed under general anesthesia. A large amount of purulent secretion was drained during the operation. As a result, the swelling of the inner canthus was significantly reduced. A routine intra-operative biopsy of the wall of the lacrimal sac revealed an exophytic nasal papilloma. A second biopsy, 1 week after the surgery, revealed the same result. The patient was advised to undergo a dacryocystectomy once the swelling had subsided. However, the patient was reluctant to undergo this surgery and remains under clinical observation. CONCLUSION: It is rare for an exophytic nasal papilloma, which is a benign tumor in the lacrimal sac, which has the potential for recurrence and malignant transformation, to manifest with acute dacryocystitis as the first symptom. Therefore, this case report could provide a reference for the future clinical diagnosis of this disease.

Papillomatosis cutis lymphostatica and 'Ski-Jump' nails.

Papillomatosis cutis lymphostatica is an uncommon condition usually associated with lymphedema. "Ski-jump" nails are upward sloping concave nails that can be an important diagnostic sign which may be overlooked in the setting of lymphedema. A diagnosis of papillomatosis cutis lymphostatica should be suspected in patients presenting with persistent, bland papilliform plaques, supported by the additional presence of "ski-jump" nails.

Retrospective review of confluent and reticulated papillomatosis in pediatric patients.

BACKGROUND/OBJECTIVES: Confluent and reticulated papillomatosis is a skin condition with unclear etiology and limited understanding of risk factors, comorbidities, and treatment strategies in the pediatric population. This study aims to describe the varied presentations and outcomes of confluent and reticulated papillomatosis and report associated comorbidities in pediatric patients. METHODS: In this retrospective single-institution case-control study, pediatric patients with a diagnosis of confluent and reticulated papillomatosis seen between 2012 and 2020 were matched approximately 1:5 with an acne vulgaris cohort based on diagnosis, setting, and time period when seen. The primary measures were the clinical features, demographics, comorbidities, treatment, and outcomes of patients with confluent and reticulated papillomatosis. Univariate and multivariable analyses were conducted to describe the association of confluent and reticulated papillomatosis with several potential risk factors and comorbidities. RESULTS: Patients with confluent and reticulated papillomatosis typically presented in adolescence with a median age of 14 years and female predominance. In a multivariable analysis, patients with confluent and reticulated papillomatosis were significantly more likely to identify as Black, be overweight or obese, and have concurrent acanthosis nigricans compared to control patients. Most of the confluent and reticulated papillomatosis patients were treated with oral minocycline or doxycycline. Although all patients who received antibiotics responded to treatment, approximately half presented with recurrence, typically within 1-2 years of first treatment. CONCLUSIONS: Confluent and reticulated papillomatosis is a disorder that presents in adolescence and appears to be more frequent in patients who are Black, obese, or overweight, and also have acanthosis nigricans. Clinicians should assess patients with confluent and reticulated papillomatosis for comorbidities, particularly those associated with insulin resistance, which may help reduce long-term disease burden.

Canine pedal papilloma identification and management: a retrospective series of 44 cases.

BACKGROUND: Papillomavirus infections in dogs have a variety of manifestations and involve multiple viral genera. Canine pedal papillomas have been infrequently studied and reported in the literature. OBJECTIVE: To report the signalment, history, treatment and outcome of biopsy-confirmed cases of canine pedal papillomatosis, collected from veterinarians across the United States and Canada ANIMALS: Medical records from 44 dogs were submitted by North American veterinarians. METHODS AND MATERIALS: Surveys were submitted through the Veterinary Information Network for biopsy-confirmed cases of canine pedal papillomatosis. Submissions included information on patient signalment, history, biopsy report, treatment and outcome. RESULTS: Forty-four cases were reviewed. The median age of presentation was four years old. Dogs most commonly presented with lameness and/or paw licking/chewing. Only one paw was affected in 35 cases, and front paws were more often affected than back paws. Twenty-eight dogs presented with one mass. Histopathological evaluation documented 33 cases of noninverted papillomas and 11 cases of inverted papillomas. Thirty-four papillomas resolved in total; 25 resolved within three weeks after biopsy collection. Twenty-one dogs received no additional treatment and 15 of those cases resolved. Azithromycin was the most commonly reported treatment initiated after biopsy was collected. CONCLUSIONS AND CLINICAL IMPORTANCE: The biological behaviour of canine pedal papillomas in this case series was similar to oral papillomas, and most lesions resolved with or without additional treatment. Further research is needed to better characterise the causative papillomavirus types and genera involved in the development of canine pedal papillomas.

Knuckle pads: an ancient disease frequently misdiagnosed because of minimal modern attention.

Knuckle pads are benign painless papules and nodules that most commonly appear on the extensor surfaces of the proximal interphalangeal joints. Knuckle pads are frequently misdiagnosed due to their location overlying joints, which can lead to costly interventions and patient discomfort for a relatively harmless condition. We describe a 44-year-old woman who presented with mildly painful nodules on multiple bilateral proximal interphalangeal joints. The patient did not have a family history of fibromatosis and the rheumatoid factor was negative. Histology showed mild epidermal hyperkeratosis, papillomatosis, and acanthosis with a deep dermal, poorly circumscribed, proliferative nodule made of spindled myofibroblasts without cytological atypia. The diagnosis of knuckle pads was established based on the clinical and morphological presentation of the nodules. Treatment with intralesional triamcinolone acetonide injection produced significant clinical improvement. Our findings highlight the challenging diagnosis of knuckle pads and the importance of increasing the familiarity of knuckle pads in modern medical practice.

[Esophageal squamous papilloma - a case report]. / Brodawczak plaskonablonkowy przelyku ­ opis przypadku.

Esophageal squamous cell papilloma (ESP) is recognised rarely. Usually it is the finding of diagnostic esophagogastroduodenoscopy (EGD). It is considered as asymptomatic benign lesion, in most cases solitary. Larger papilloma and papillomatous lesions are extremely rare and can cause dysphagia, odynophagia, or bleeding. Squamous cell papilloma of esophagus is the lesion of unknown potential for malignant transformation, which currently has no guidelines for endoscopic surveillance. The aim of the study was to present the patient diagnosed with squamous cell papillomas of oesophagus, method of treatment and endoscopic surveillance. A CASE STUDY: The 65-year-old woman was referred for investigation of epigastric pain and heartburn. The EGG was performed. The normal esophageal mucosa was found with presence of several papillomatous structures from 3 to 8 mm in size within 25-30 cm of incisors line. One 3 mm ESP was completely removed. From the biggest lesion biopsy was obtained. Histopatological examination revealed squamous cell papilloma of oesophagus. However no HPV was detcted. Three months later patient underwent endoscopic resection of ESPs. Two, 8 mm lesions were removed completely by diathermic snare and five 3 mm lesions were removed by biopsy forceps. Histopatological examination of the resected specimen was the same as the previous examination and reveled squamous cell papilloma without HPV presence. After 6 months, no recurrence of papillomas was found in the control EGD, however, it was decided to conduct endoscopic surveillance and perform follow-up EGD in a year's time. Radical removal of squamous cell papillomas of the esophagus was performed using endoscopic resection. After 6 months recurrence of papillomas was not confirmed. CONCLUSIONS: Esophageal squamous papillomas are efficiently removed by endoscopic resection. Esophagogastroduodenoscopy may be used as a method of endoscopic surveillance.

Patients with benign papilloma diagnosed on core biopsies and concordant pathology-radiology findings can be followed: experiences from multi-specialty high-risk breast lesion conferences in an academic center.

BACKGROUND: To determine whether patients with benign papilloma diagnosed on core biopsy can be spared from surgery. METHODS: We prospectively reviewed 150 consecutive core biopsy-diagnosed papilloma cases at a multi-specialty high-risk breast lesion conference to determine whether surgical excision was necessary. Of these 150 cases, 148 had concordant radiologic-pathologic features. Six were excluded due to lack of the first imaging follow-up until analysis. 112 were benign papillomas; 17 were papillomas involved by atypical ductal hyperplasia (atypical papilloma); 6 papillomas had ADH in adjacent tissue but not involving the papilloma; 2 papillomas were involved by atypical lobular hyperplasia (ALH); and 5 papillomas had ALH in adjacent tissue. Two were radiology-pathology (rad-path) discordant. RESULTS: Thirty-nine of the 112 benign papillomas were excised with no upgrade to carcinoma; 73 were followed with no disease progression during follow-up (185-1279 days). Fifteen of 17 atypical papillomas were surgically excised with 4 (26.7%) upgraded to carcinoma. Four of the 6 patients with ADH adjacent to a benign papilloma underwent excision with 2 upgrades to carcinoma. None of the patients with papilloma, which was either involved by ALH or had ALH in adjacent tissue had upgrade or disease progression during follow-up (204-1159 days). Finally, the two cases with discordant path-rad discordant were excised with no upgrade. CONCLUSIONS: Our data confirm that rad-path concordant benign papillomas diagnosed on core biopsy do not require surgery. It also supports the value of a formal multi-specialty review of all benign papilloma cases to create a consensus management plan.

Diagnosis and surgical treatment of pathologic nipple discharge using ultrasound-guided wire localization of focal ductal dilatation.

Nipple discharge is the third breast complaint after pain and lumps. The modern high-resolution ultrasound techniques are becoming more sensitive for the visualization of intraductal changes especially focal ductal dilatation (FDD), hypothesized as a radiographic manifestation of the lesion itself and that ultrasound-guided wire localization of this finding would enable identification and excision of the causative lesion. The aim of this study was to evaluate the safety, feasibility, efficiency and outcome of ultrasound-guided wire localization of FDD as possible cause of pathological nipple discharge (PND). The present study was conducted on 56 patients with PND presented to Surgical Oncology Unit at General Surgery Department, Tanta University Hospital from January 2018 to January 2019. The patients subjected to ultrasound-guided wire localization of FDD on the day of surgery, the involved duct was cannulated with a lacrimal duct probe, the targeted tissue was excised, and the specimen was sent for histopathological examination. The patients' age ranged between 26 and 71 years with a mean age of 48 years. The bloody nipple discharge was the commonest presenting symptom in 44 out of 56 patients (78.5%). The duct dilatation on study ultrasound ranged from 2.1 to 3.7 mm with a mean of 2.6 mm. Preoperative ultrasound-guided wire localization of the site of FDD was successfully performed in all cases. Papilloma alone founded in 40 out of 56 patients (71.4%), papilloma + ductal carcinoma in situ (DCIS) in six patients (10.7%), papilloma + invasive ductal carcinoma in six patients (10.7%), DCIS in two patients (3.6%) and duct ectasia in two patients (3.6%). Ultrasound-guided wire localization of FDD is an easy and safe technique for evaluation, precise localization, and targeted excision of the underlying lesions of PND.

Prognostic factors and risk factors for development and recurrence of sinonasal papillomas: potential role of different HPV subtypes.

PURPOSE AND METHODS: A retrospective study was conducted to identify and assess potential clinical and molecularbiological risk factors for development and recurrence of sinonasal papillomas (i.e. inverted (IP), fungiform (FP), and oncocytic papillomas (OCP)). Investigated risk factors included age, gender, tumor size and localization, tobacco smoking, regular alcohol consumption, essential hypertension, anticoagulant medication, allergies, surgical approach, and HPV infection. Risk factors were evaluated by regression analysis. RESULTS: Apart from age and incomplete tumor resection, the recurrence of Schneiderian papillomas is independent of conventional risk factors. Patients in this study displayed higher HPV infections rates in IP (38.8%) and in FP (100%) than in healthy mucosa, which is reported 0-5.8% in Germany and central Europe. The proportion of HPV-positive IP decreased with advanced tumor stages: 100% HPV positivity of T1 IP (2/2), 40.9% of T2 IP (9/22), and 35.7% of T3 IP (20/56). Most commonly detected HPV types were HPV 6, 11, and 16; however, patients in this study also displayed HPV types that have rarely or not at all been described in sinonasal papillomas before, such as HPV 58, 42, 83, and 91. Recurrent sinonasal papillomas displayed higher rates of HPV infections than non-recurrent tumors. CONCLUSIONS: Young age at initial diagnosis and incomplete tumor resection are risk factors for recurrence of sinonasal papillomas. Our data suggest that HPV infection supports development and/or perpetuation of sinonasal papillomas. Additionally, sinonasal papillomas seem to display a unique subset of HPV genotypes, including genotypes that have not often been described before.

Evaluation of platelet distribution width as a diagnostic and prognostic biomarker in bladder neoplasm.

Aim: To evaluate the role of preoperative platelet distribution width (PDW) as a potential biomarker for distinguishing malignancy and tumor advantage of bladder neoplasm. Methods: The study included 210 subjects with bladder cancer, 76 subjects with urothelial papilloma and 132 healthy control subjects. Preoperative PDW along with other blood indices was evaluated. Results: PDW was higher in urothelial papilloma patients than that in bladder cancer patients (p < 0.001). Bladder cancer patients with advanced-stage disease exhibited lower PDW levels compared with patients with early stage disease. Conclusion: Reduced preoperative PDW level is an indicator of malignancy and advanced bladder cancer stages, suggesting it as a potential biomarker in bladder cancer diagnosis and prognosis.