High Rate Of Malignant Transformation Research Articles

EPID-11. A MULTI-INSTITUTIONAL COMPARATIVE ANALYSIS OF THE CLINICAL, GENOMIC, AND SURVIVAL CHARACTERISTICS OF PEDIATRIC, YOUNG ADULT AND OLDER ADULT PATIENTS WITH IDH-MUTANT GLIOMA

Abstract BACKGROUND Prognostic significance of IDH-mutation in glioma is incompletely understood in children and adolescents/young adults (YAs). We compared the clinico-genomic features, outcomes and prognostic factors observed in IDH-mutant gliomas across age groups. METHODS Clinical, histologic and molecular data of patients with IDH-mutant gliomas from 8 pediatric institutions (spanning twenty years) and adult patients from two institutions (from 2013–2019) were identified. Patients were grouped as pediatric (< 19y), YA (19y to < 40y) or older adult (≥ 40y). Genomic alterations, including somatic mutations and copy number variants, were captured with institutional next generation sequencing. Factors were compared across age categories using Fisher’s exact test or analysis-of-variance. Cox proportional-hazards regression tested factors for association with overall (OS) and progression-free survival (PFS). RESULTS Of 379 patients, 48(13%) were pediatric, 204(54%) YA and 127(33%) older adult. Histological subtype differed significantly by age group (p< 0.0001). YAs had higher rates of malignant transformation (p=0.01) and shorter time-from-diagnosis-to-malignant transformation (p=0.01) compared to other age groups. Analysis of genomic alterations revealed an age-related difference in distribution in ATRX mutations only (p=0.0018). Median PFS and OS for the entire cohort were 4.62 and 17.19 years. In univariate models, PFS differed by age group (p=0.0012), with YAs having the worst outcomes. Lack of MGMT methylation (p=0.024) predicted poorer OS. Upfront observant management was predictive of poorer PFS. Gene mutations were not associated with PFS. In multi-variable models, YAs had shorter PFS compared to pediatric (hazard ratio [HR]=2.03, p=0.01) and older adults (HR=1.59, p=0.003) after adjusting for histology, extent of resection, and initial therapy. Age at diagnosis was not associated with OS in multi-variable analysis. CONCLUSIONS Within our cohort, YA with IDH-mutant tumors progressed more quickly compared to their pediatric counterparts. Further study of YA patients with IDH-mutant glioma is critical to better define best practices for this group.

Carcinogenesis of Male Oral Submucous Fibrosis Alters Salivary Microbiomes

Most oral squamous cell carcinoma (OSCC) tumors arise from oral premalignant lesions. Oral submucous fibrosis (OSF), usually occurring in male chewers of betel quid, is a premalignant stromal disease characterized by a high malignant transformation rate and high prevalence. Although a relationship between the inhabited microbiome and carcinogenesis has been proposed, no detailed information regarding the oral microbiome of patients with OSF exists; the changes of the salivary microbiome during cancer formation remain unclear. This study compared the salivary microbiomes of male patients with OSCC and a predisposing OSF background (OSCC-OSF group) and those with OSF only (OSF group). The results of high-throughput sequencing of the bacterial 16S rRNA gene indicated that OSF-related carcinogenesis and smoking status significantly contributed to phylogenetic composition variations in the salivary microbiome, leading to considerable reductions in species richness and phylogenetic diversity. The microbiome profile of OSF-related malignancy was associated with increased microbial stochastic fluctuation, which dominated the salivary microbiome assembly and caused species co-occurrence network collapse. Artificial intelligence selection algorithms consistently identified 5 key species in the OSCC-OSF group: Porphyromonas catoniae, Prevotella multisaccharivorax, Prevotella sp. HMT-300, Mitsuokella sp. HMT-131, and Treponema sp. HMT-927. Robust accuracy in predicting oral carcinogenesis was obtained with our exploratory and validation data sets. In functional analysis, the microbiome of the OSCC-OSF group had greater potential for S-adenosyl-l-methionine and norspermidine synthesis but lower potential for l-ornithine and pyrimidine deoxyribonucleotide synthesis and formaldehyde metabolism. These findings indicated that the salivary microbiome plays important roles in modulating microbial metabolites during oral carcinogenesis. In conclusion, our results provided new insights into salivary microbiome alterations during the malignant transformation of OSF.

Gastrointestinal stromal tumor in perforated Meckel\u2019s diverticulum: a case report and literature review

IntroductionGastrointestinal stromal tumor (GIST) is rare neoplasms of the gastrointestinal tract associated with high rates of malignant transformation. GIST has been found largely in the stomach, small bowel, colon and rectum, and esophagus, but about 5% are found in other locations. We herein report a 56-year-old woman with a GIST in perforated Meckel's diverticulum. After encountering this patient, a review of the literature found reports of 18 similar patients.Case presentationA 56-year-old woman diagnosed with galactosialidosis (β-galactosidase-neuraminidase deficiency) presented with vomiting. On contrast-enhanced computed tomography, peritonitis due to perforation of the intestine was diagnosed based on the free air and dilated loop of the small bowel. Laparotomy revealed perforation of Meckel’s diverticulitis located 50 cm from the ileocecal valve. Partial resection of the ileum, including the diverticulum, and end-to-end anastomosis of the small intestine were performed. Regarding the pathological findings, the edge of the diverticulum wall consisted of a solid mass measuring 1.0 cm in size, and the tumor cells were spindle-shaped with 1 mitosis present per 50 high-power fields. The diagnosis was established as GIST of the Meckel's diverticulum. The postoperative period was uneventful. Follow-up at two years revealed no evidence of recurrence.ConclusionGIST in perforated Meckel's diverticulum is very rare. The potential for the coexistence of GIST or other tumor should be considered in the treatment of perforated Meckel's diverticulum.

Standardized Surgical Management for Cystic Dilation of the Bile Ducts Based on Clinical and Pathological Studies: A Narrative Review.

The surgical method of complete/radical cyst excision plus Roux-en-Y hepaticojejunostomy remains the primary therapy and the only effective treatment for cystic dilation of the bile ducts (CDBDs). However, the incidence of long-term postoperative complications is still high, as is the reoperation rate, and the potential for postoperative malignant transformation still exists. In recent years, significant progress has been made in understanding the pathogenic mechanism and pathological changes of adult CDBDs. Based on which, the surgical procedures for CDBDs have been revised to further improve their effectiveness. The purpose of this review is to systematically summarize the latest concepts of the etiology and pathogenic mechanism and the pathological changes of adult CDBDs. Based on the findings of these clinical and pathological studies, a comprehensive theoretical system in the surgical treatment of CDBDs has been established, which corrects many previous theoretical misunderstandings. The specific surgical method for each type of CDBDs and the key technical notes are also described in detail. Using these principles, treatment outcomes for CDBDs can be significantly improved, and the current high complication rate, reoperation rate, and rate of postoperative malignant transformation can be reduced.

Immune expression profile identification in a group of proliferative verrucous leukoplakia patients: a pre-cancer niche for oral squamous cell carcinoma development.

To explore the pathophysiology of proliferative verrucous leukoplakia, a rare oral disorder that exhibits high rates of recurrence and malignant transformation, through a RNAseq case-control study. We obtained oral biopsies from 10 patients with verrucous leukoplakia lesions and from the mucosa of 5 healthy individuals for sequencing using RNAseq technology. Using bioinformatic methods, we investigated gene expression and enrichment differences between patients both with and without the disorder. We applied network biology methods to investigate functional relations among those genes that were differentially deregulated. We detected 140 differentially expressed genes with distinct roles in immune surveillance, tissue and organ morphogenesis, development, and organization. Of these 140 genes, 111 have been previously described as cancer expression biomarkers, being oral squamous cell carcinoma the most represented type of cancer among them. Of these 140 genes, 26 were prioritized for further investigation as biomarkers using larger sample sizes. The gene expression patterns of healthy and unhealthy patients differed in 140 genes whose deregulation has a functional impact on normal functioning of the immune system. This immune expression profile provides a plausible hypothesis to explain the transformation to oral squamous cell carcinoma observed in 6 of the 10 assayed cases. By determining the molecular bases of the proliferative verrucous leukoplakia disorder and identifying early biomarkers of malignancy, this can allow us to develop new treatment strategies.

NUCLEAR FACTOR KAPPA B PATHWAY MAY BE IMPORTANT IN THE MALIGNANT TRANSFORMATION OF PROLIFERATIVE VERRUCOUS LEUKOPLAKIA IN PATIENTS

The nuclear factor kappa B (NFkB) may promote tumor cell proliferation, tumor angiogenesis, and inhibition of apoptosis in oral squamous cell carcinoma through the activation of the pathway by tumor necrosis factor-alpha (TNFα). A previous study from our group identified an increase of TNFα using a multiplex immunoassay in samples of proliferative verrucous leukoplakia (PVL), a rare and particular disorder with high rates of malignant transformation and recurrence. Our aim was to evaluate the expression of NFkB through an immunofluorescence assay in paraffin, tissue samples from PVL (n = 12), and oral squamous cell carcinoma derived from PVL (OSCC-PVL; n = 12). At least 5 fields (×400) per sample were registered, and the average percentage of positive cells were statistically accessed. We found that NFkB is statistically increased in the group OSCC-PVL. These findings suggest that the NFkB pathway may be activated by TNFα in OSCC-PVL, and this activation may be important in the malignant transformation of PVL in patients. Apoio financeiro FAPESP (Nº Processo 2017/01798-7), CAPES (Nº Processo 88881.187412/2018-01) University of Michigan. The nuclear factor kappa B (NFkB) may promote tumor cell proliferation, tumor angiogenesis, and inhibition of apoptosis in oral squamous cell carcinoma through the activation of the pathway by tumor necrosis factor-alpha (TNFα). A previous study from our group identified an increase of TNFα using a multiplex immunoassay in samples of proliferative verrucous leukoplakia (PVL), a rare and particular disorder with high rates of malignant transformation and recurrence. Our aim was to evaluate the expression of NFkB through an immunofluorescence assay in paraffin, tissue samples from PVL (n = 12), and oral squamous cell carcinoma derived from PVL (OSCC-PVL; n = 12). At least 5 fields (×400) per sample were registered, and the average percentage of positive cells were statistically accessed. We found that NFkB is statistically increased in the group OSCC-PVL. These findings suggest that the NFkB pathway may be activated by TNFα in OSCC-PVL, and this activation may be important in the malignant transformation of PVL in patients. Apoio financeiro FAPESP (Nº Processo 2017/01798-7), CAPES (Nº Processo 88881.187412/2018-01) University of Michigan.

PROLIFERATIVE VERRUCOUS LEUKOPLAKIA: A CASE REPORT

Proliferative verrucous leukoplakia (LVP) is a rare type of oral leukoplakia with slow growth and high potential for malignancy, with female predilection in the sixth decade of life. The aim of this report is to describe the clinical and histopathologic findings of a case of LVP. A 52-year-old male patient, an alcoholic since 12 years old, sought the health service because of an asymptomatic lesion with a 1-year evolution. The intraoral examination revealed multiple bilateral whitish plates with clear borders and verrucous surface located in jugal mucosa and labial commissure. The initial diagnostic hypothesis was verrucous carcinoma. An incisional biopsy was performed, and the histologic slices revealed fragments of mucosa coated by hyperkeratinized squamous epithelium with a verrucous surface corresponding to LVP. The patient is stable and under follow-up. The importance of early diagnosis and routine follow-up of patients because of the high rates of malignant transformation is emphasized.

Medicinal management of oral submucous fibrosis in the past decade- A systematic review

IntroductionOral submucous fibrosis (OSMF) is a potentially malignant disorder with a high rate of malignant transformation. It is associated with chewing of areca nut and tobacco products with a high global prevalence, particularly in the southeast Asian countries. A wide range of treatment modalities are available, ranging from corticosteroids, antioxidants, nutritional supplements to herbal medicines but lacks a reliable treatment regimen. AimThis systematic review will comprehensively analyze the medicinal treatment for OSMF from 2011 to 2020, apprise the literature with new clinical studies, and initiate a discussion about other potential medicines. Material and methodsA comprehensive electronic search was conducted in Pubmed, Scopus, and other databases from January 2011 to June 2020 according to the PRISMA guidelines, to identify all the clinical studies for the medicinal management of OSMF with definite keywords and defined criteria. ResultsAmong the thirty-two included clinical studies 23 were randomized controlled studies and 9 were case-control studies. The treatment outcomes were diverse, and the majority of the studies showed improvement in the subjective signs and symptoms of OSMF. Only a few studies noticed the side effects. ConclusionNo single treatment modality is effective in the management of OSMF. The concurrent use of triple therapy is efficacious. The naturally occurring herbal medicines have an immense potential in the management of OSMF. Therefore, high-quality, longitudinal, multi-center randomized controlled trials with larger samples need to be conducted to further assess the efficacy of various medicinal formulations in conjunction with physiotherapy in the management of OSMF.

Avapritinib: novel hope for patients with metastatic gist with PDGFRA exon 18 mutation

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms of the gastrointestinal tract associated with high rates of malignant transformation. The activating mutations in platelet-derived growth factor receptor A (PDGFRA) have been linked to the development of GISTs, and up to approximately 10% of GIST cases involve mutations of this gene. Current treatment options for metastatic GIST are minimal, mainly trusting on tyrosine kinase inhibitors (TKIs) such as Imatinib, Sunitinib and Regorafenib. However, eventually, most patients develop resistance to TKIs, usually due to the acquisition of secondary mutations. Moreover, 5-6% of patients with unresectable of metastatic GIST have the primary PDGFRA D842V mutation, which makes it resistant to all approved treatment options. Avapritinib, a potent and selective TKI of KIT and PDGFRA activation loop mutants. The drug demonstrates anti-tumor activity by inhibiting the autophosphorylation of KIT D816V and PDGFRA D842V, thereby terminating the downstream signalling. The drug is available in oral formulation with a recommended dosage of 300 mg once daily. The onset of Avapritinib is fast, shows rapid absorption and linear pharmacokinetics. Most common adverse reactions seen are edema, fatigue, abdominal pain, and neurocognitive defects. Clinical trials for Avapritinib have been positive, and results suggest that the drug may be a new safe and effective option for metastatic GIST treatment. With Blueprint Medicines having already received US FDA approval in January 2020, Avapritinib may soon be an addition to the mounting armoury of drugs against metastatic GIST harbouring PDGFRA exon 18 mutation.

Malignant transformation of oral proliferative verrucous leukoplakia: a series of 48 patients with suggestions for management

Proliferative verrucous leukoplakia (PVL) is a rare and refractory form of oral mucosal leukoplakia of unknown origin, characterized by high rates of malignant transformation. Different diagnostic criteria, terminologies, and therapeutic approaches have been proposed since the first report in 1985. There remains no general agreement regarding the clinical and histological diagnosis, prevention, and correct management of this disease. This retrospective study investigated 48 patients affected by PVL showing at least one malignant transformation and followed up at 2-month intervals. Twenty-five were female (52.1%) and 23 (47.9%) were male; their median age was 67 years (range 40–93 years). Follow-up ranged from 18 to 240 months. Clinical examination included the use of Lugol’s solution to prevent clinical underestimation of the margins and toluidine blue for suspicious areas. Surgical excision by scalpel was the preferred treatment for suspicious lesions, with only five carcinomas surgically removed by diode laser and two by CO2 laser. All specimens were accurately mapped after formalin fixation. Fifteen patients (31.3%; 10 female, five male) developed one oral carcinoma, while 33 (68.7%) developed two or more primary tumours (range 3–12). Only four patients (8.3%), who developed between 2 and 8 oral squamous cell carcinomas (OSCCs), died of tumour-related causes. The pre-surgical clinical workup, subsequent surgical treatment, and follow-up are key to success for patients affected by PVL with malignant transformation into stage 1 OSCC and/or verrucous carcinoma, leading to a high overall survival rate.

Research progress of oral erythroplakia

Oral erythroplakia is an rare oral disorder with relatively high potential of becoming malignant. It has a lower prevalence but a higher malignant transformation rate than oral leukoplakia. The etiology and pathogenesis of the disease is so far not clear, but several studies have pointed to tobacco chewing, tobacco smoking, and betel quid chewing with or without tobacco and alcohol usage as etiologic factors.The treatment methods are mainly surgical excision operations as well as laser treatment. However, the recurrence rate and the malignant transformation rate of oral erythroplakiaare high, thus long-term close follow-up is needed. In the present article, the definition, epidemiological characteristics, clinical manifestations, histopathological characteristics, etiology and pathogenesis, diagnosis, treatment and prognosis of oral erythroplakiaare reviewed.

Bilateral pre cancerous lesions: A case report

Oral precancerous lesions are potentially malignant disorders, consisting of a group of diseases, which should be diagnosed in the early stage. Oral leukoplakia, oral submucous fibrosis, oral erythroplakia and lichen planus are the most common oral mucosal diseases that have a very high malignant transformation rate. There are various etiological factors amongst which consumption of tobacco or alcohol, chewing betel nut are the predominant factors. Early diagnosis is very important and can be lifesaving, because in late stages, they may be progressed to severe dysplasia and even carcinoma in situ and/or squamous cell carcinoma. The following case report highlights the treatment outcome using retinoids and antioxidants in treating erythroplakia and leukoplakia in a 55 year old male patient. Key Words: Leukoplakia, erythroplakia, pre-cancerous lesions, pre-malignant lesions, malignant transformation

Orabase-Formulated Benzalkonium Chloride Effectively Suppressed Oral Potentially Malignant Disorder In Vitro and In Vivo.

Oral potentially malignant disorder (OPMD) is associated with an increased risk of progression to oral cancer. Patients with dysplastic changes of the precancerous lesions have a higher malignant transformation rate than those without dysplastic changes. Radiotherapy and surgery are the traditionally preferred choices for OPMD treatment. However, side effects caused by radiotherapy and surgery may reduce the willingness of patients to accept therapy. Therefore, developing an Orabase-formulated drug, which can be non-invasively administered, may provide an alternative treatment choice. To find, verify, and develop a new anti-cancer drug cost a lot of time and money, while drug repurposing can shorten both time and cost. In this study, we utilized high-throughput screening library to identify clinical drugs, which may have new bioactivities. Herein, we report that benzalkonium chloride (BAK), an antimicrobial preservative for pharmaceutical products, significantly induced reactive oxygen species production and cell death in oral precancerous cells. Additionally, our results showed that phosphorylation of STAT3 (Tyr705) and Akt (Ser473) were involved in cell death caused by BAK in DOK cells. According to animal studies, the development of DMBA-induced oral precancerous lesions was inhibited by 2% BAK. In conclusion, Orabase-formulated BAK may be a potential treatment for OPMD in the future.

Does placental invasiveness lead to higher rates of malignant transformation in mammals?: Response to: 'Available data suggests positive relationship between placental invasion an malignancy'.

Does placental invasiveness lead to higher rates of malignant transformation in mammals?: Response to: 'Available data suggests positive relationship between placental invasion an malignancy'.

Prevalence of oral cancer and oral epithelial dysplasia among North Indian population: A retrospective institutional study.

Background:Despite our sincere and serious efforts, oral cancer (particularly oral squamous cell carcinoma [OSCC]) is the major cause of morbidity and mortality in the Indian population. Oral precancerous lesions show quite high malignant transformation rate. Epidemiological data of oral epithelial dysplasia (OED) and OSCC could help in early diagnosis and thus may improve the prognosis. The current study aims to retrospectively analyze the epidemiological profile of patients with different grades of OED and OSCCs.Materials and Methods:The current study is a retrospective analysis of OED and OSCC reported in 5 years in our institution from 2014 to 2018. Data for the analysis were attained from the case sheets from the patients diagnosed with OED and OSCC.Results:The mean prevalence of OED and OSCC was 5.71% and 9.85%, respectively. Among the dysplastic lesions, severe dysplasia was more common, while well-differentiated squamous cell carcinoma was more common among the carcinomatous lesions. The peak age prevalence of both the lesions was third to fifth decade. Males were more frequently affected than females, with buccal mucosa being the most common site.Conclusion:The data attained from this study highlight the need for community-based screening and awareness programs for general population and thus obtain a healthier society.

ORAL PROLIFERATIVE VERRUCOUS LEUKOPLAKIA: A LONG-TERM CLINICAL, CYTOPATHOLOGIC, AND HISTOPATHOLOGIC FOLLOW-UP

Proliferative verrucous leukoplakia (PVL) is an aggressive form of leukoplakia, which affects multiple oral sites, with high probability of recurrence and a high rate of malignant transformation. Clinically it may present as a homogeneous white plaque or leukoeritroplakia, with an exophytic or verrucous surface. We report a case with 8 years of follow-up of an 85-year-old woman with white plaques on the left buccal mucosa, inferior alveolar mucosa, floor of the mouth, and lateral border of the tongue. Combined cytopathologic and histopathologic examination was performed over 6 years, showing initially mild dysplasia and keratosis, which progressed to moderate and severe dysplasia. After 6 years of follow-up evaluation, an upper alveolar mucosa lesion was diagnosed as an in situ carcinoma. The patient was referred for treatment, and a surgical resection was performed. The patient is currently being monitored and evaluated with periodic cytopathologic exams.

THREE CASE REPORTS OF PROLIFERATIVE VERRUCOUS LEUKOPLAKIA MISDIAGNOSED AS LICHEN PLANUS

Proliferative verrucous leukoplakia (PVL) is a potentially malignant disorder of unknown etiology and has a progressive and multifocal behavior. Characteristically, PVL presents with high rates of recurrence and malignant transformation to squamous cell carcinoma or verrucous carcinoma. We reported 3 cases that initially presented as oral lichenoid lesions spread by the oral mucosa and the microscopic analysis in all cases revealed epithelial hyperplasia and lymphohistiocytic infiltrate in a subepithelial pattern, compatible with a lichen planus diagnosis. However, some years after, some lichenoid areas evolved into dysplastic white lesions and 2 of the patients developed squamous cell carcinoma. We have concluded these to be cases of PVL. Thus, we emphasize that diffuse white lesions of the oral mucosa with a verrucous aspect can present, in the initial phases, clinical pathologic features similar to lichen planus, leading to initial failure to correctly diagnose and treat PVL.

Orabase-formulated gentian violet effectively improved oral potentially malignant disorder in vitro and in vivo

Oral cancer is a prevalent cancer in male worldwide. Oral potentially malignant disorders (OMPDs) are the oral mucosa lesions that have high malignant transformation rate to oral cancer. The mainstay for OMPDs treatment includes carbon dioxide (CO2) laser and surgery, which may lead to the side effects of scarring and impaired function of oral cavity in the patients and reduced their willingness to receive curative therapy. Therefore, developing a non-invasive and function-preserving therapy is clinically important. Since development of a novel chemotherapeutic drug requires a lot of time and cost, we applied the high-throughput screening (HTS) approach to identify new bioactivities for FDA-approved drugs, known as drug repurposing. Through this drug repurposing approach, we discovered that gentian violet (GV), which is well known for its antibacterial, antifungal, antihelminthic, antitrypanosomal and antiviral activities, was able to induce significant cell death in DOK oral precancerous cells through ROS production. Moreover, decreased phosphorylation of p53(Ser15) and NFκB(Ser536) was required for GV-induced cell death. In vivo, 3% GV orabase effectively suppressed the progression of DMBA-induced oral precancerous lesions. In conclusion, this new formulation of GV through drug repurposing has the potential to be further developed as a therapeutic drug for OPMD clinically.

Transient induction of telomerase expression mediates senescence and reduces tumorigenesis in primary fibroblasts

Telomerase is an enzymatic ribonucleoprotein complex that acts as a reverse transcriptase in the elongation of telomeres. Telomerase activity is well documented in embryonic stem cells and the vast majority of tumor cells, but its role in somatic cells remains to be understood. Here, we report an unexpected function of telomerase during cellular senescence and tumorigenesis. We crossed Tert heterozygous knockout mice (mTert+/- ) for 26 generations, during which time there was progressive shortening of telomeres, and obtained primary skin fibroblasts from mTert+/+ and mTert-/- progeny of the 26th cross. As a consequence of insufficient telomerase activities in prior generations, both mTert+/+ and mTert-/- fibroblasts showed comparable and extremely short telomere length. However, mTert-/- cells approached cellular senescence faster and exhibited a significantly higher rate of malignant transformation than mTert+/+ cells. Furthermore, an evident up-regulation of telomerase reverse-transcriptase (TERT) expression was detected in mTert+/+ cells at the presenescence stage. Moreover, removal or down-regulation of TERT expression in mTert+/+ and human primary fibroblast cells via CRISPR/Cas9 or shRNA recapitulated mTert-/- phenotypes of accelerated senescence and transformation, and overexpression of TERT in mTert-/- cells rescued these phenotypes. Taking these data together, this study suggests that TERT has a previously underappreciated, protective role in buffering senescence stresses due to short, dysfunctional telomeres, and preventing malignant transformation.

Sinonasal inverted papilloma: rate of recurrence and malignant transformation in 44 operated patients

IntroductionAlthough sinonasal inverted papillomas are benign lesions, they are locally aggressive and have a potential malignant transformation ranging from 5% to 15%, with a high recurrence rate. ObjectiveThe aim of this article is to describe the rate of recurrence and malignant transformation in patients with a diagnosis of inverted papilloma who underwent surgery in a tertiary hospital in São Paulo. MethodsWe performed a retrospective analysis of patients diagnosed with sinonasal papilloma who had undergone surgery in a tertiary hospital in São Paulo, between August 1998 and August 2017. A patient chart review was conducted to assess data of patients’ demographics, tumors characteristics, follow-up appointments, recurrence and malignancy. Inverted papillomas were analyzed and classified under the Krouse staging system. ResultsA total of 69 surgeries were performed in patients with diagnosis of sinonasal papilloma. Inverted papilloma was the most prevalent subtype (49 cases ‒ 80.33%), followed by exophytic papilloma (6 cases ‒ 9.84%) and by oncocytic papilloma (6 cases – 9.84%). The recurrence rate was 34.09% for inverted papilloma (15/44) and the mean time of recurrence was 24.6 months. Malignant transformation occurred in 6 patients (13.64%). Three of these patients presented carcinoma in the first surgery and three patients developed carcinoma during the follow-up. ConclusionThe high recurrence rate and malignancy potential allow us to consider inverted papillomas as aggressive tumors. In a tertiary hospital in São Paulo the recurrence rate the mean time to recurrence is 24.6 months. The recurrence after 10 years implies was 34.09% and the need for long-term follow up. It is possible that the high recurrence rate and the high malignant transformation rate we found are due to the large number of tumors discovered at an advanced stage (most of them staged T3 and T4), secondary to poor access to health system, in developing countries.