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Case of oncocytic papilloma with exophytic papillary fronds (A; HE) lined by cells with abundant oncocytic cytoplasm, and showing microcysts containing neutrophils (B; HE), accompanied by p16 immunopositivity (C) and positive HR-HPV mRNA ISH (D)
Source publication
The sinonasal tract is considered a second hotspot for human papillomavirus (HPV)-related tumors in the head and neck, with HPV being identified in up to 62% of squamous cell carcinomas (SCCs) and 38% of papillomas. There is limited data from geographical regions with low prevalence of high-risk (HR)-HPV on the association of HR-HPV in sinonasal ne...
Citations
... A already stated above, there is significant evidence that the presence of HPV in inverted papilloma could be predictive of recurrence and possible subsequent malignant transformation [2,31]. However, the available data from regions with low prevalence of high-risk HPV on the association between HPV infection and sinonasal neoplasms is still somewhat limited [32]. Also, the usefulness of p16 as a surrogate marker of HPV infection and definite prediction of malignant transformation in inverted papilloma cases also needs more investigation [32]. ...
... However, the available data from regions with low prevalence of high-risk HPV on the association between HPV infection and sinonasal neoplasms is still somewhat limited [32]. Also, the usefulness of p16 as a surrogate marker of HPV infection and definite prediction of malignant transformation in inverted papilloma cases also needs more investigation [32]. So despite repeated detection of HPV in inverted papilloma cases, a definitive causal association still remains at best controversial [33]. ...
Inverted sinonasal papilloma is a benign neoplasm that usually affects the intra-nasal cavity and adjacent paranasal sinuses. Inverted papillomas have three unique features that distinguishes them from other sinonasal tumors including; a propensity for local destructive growth, a high rate of recurrence and risk of malignant transformation. The reported yearly incidence is about 0.6 to 1.5 cases per 100,000 people per year and they usually account for 0.5% to 4% of all nasal tumors. They occur at the following locations; both lateral nasal walls, ethmoidal cells, maxillary sinus, the frontal sinus, sphenoid sinuses and the nasal septum in decreasing order. It occurs most commonly in the fifth and sixth decades of life with a male-to-female ratio of 2-3:1. Inverted papilloma can arise from the entire Schneiderian membrane and molecular genetics have confirmed that it is an actual neoplasm that arises from a single progenitor cell. Most cases are diagnosed from clinical history and thorough physical examination. However, complete removal of all affected tissue with thorough histopathological evaluation is recommended to ensure a correct diagnosis. While there is yet no established pathognomonic histopathological feature to predict recurrence with all certainty, there is ongoing investigation for predictive markers of recurrence. Smoking seems to be a recognized risk factor for developing multiple recurrences and there is evidence that the presence of HPV serotypes 16 and 18 could be predictive of malignant transformation. The main aim of treatment is to achieve compete surgical resection and to prevent recurrence and malignant transformation. A period of clinical follow up is recommended after treatment. The aim of this review is to provide a comprehensive and updated overview of the clinical presentation, diagnosis, management and prognosis of this unique lesion.
... Whilst p16 staining has been demonstrated in ocular adnexal SCC, it has also been observed after inflammatory conditions and total body irradiation and with prolonged genomic damage, independent of HPV infection [10,11]. It therefore appears that the specificity and positive predictive value (PPV) of p16 positivity for HR-HPV in ocular adnexal SCC is low, similar to that described at non-oropharyngeal head and neck sites, necessitating direct HPV testing [12][13][14]. ...
... Alternatively, it may be overexpressed by loss of feedback inhibition due to alteration in genes in its downstream pathways, such as loss of heterozygosity of Rb [27,42]. This lack of specificity of p16 for HR-HPV has been demonstrated at non-oropharyngeal head and neck sites [13][14][15], as well as in ocular viz. conjunctival and lacrimal squamous neoplasia [29,43]. ...
... Tumour cells have scant cytoplasm, indistinct cell borders, high N:C ratio, and round to oval hyperchromatic nuclei with inconspicuous nucleoli [44]. In the sinonasal region too, non-keratinizing SCC is more frequently associated with HPV infection than keratinizing SCC [14,45]. HPV-related conjunctival CIN and SCC have been reported to have non-keratinizing or basaloid morphology [46]. ...
Background
High-risk (HR) Human papillomavirus (HPV) has been implicated in pathogenesis of squamous cell carcinomas (SCC) at several sites with mucocutaneous junctions, including the head and neck. SCC is the second most common eyelid malignancy. However, its association with transcriptionally active HR-HPV has not been adequately studied.
Methods
Two index cases of eyelid HPV-associated SCC are described in detail. A retrospective cohort of eyelid SCC was examined for p16 immunoexpression. Cases demonstrating p16 positivity or equivocal staining were subjected to high-risk HPV mRNA in situ hybridization (ISH). Quantitative real-time PCR (qPCR) was performed in mRNA ISH-positive cases for HPV genotyping.
Results
The two index patients were older adult females, with upper eyelid tumours. On histology, both tumours were non-keratinizing SCC with trabecular and nested architecture reminiscent of oropharyngeal HPV-associated non-keratinizing SCC, prompting p16 immunohistochemistry, which was positive. HR-HPV mRNA ISH was positive, and qPCR detected HPV16 in both cases. Three of 20 (15%) archival cases showed p16 immunopositivity and two (10%) showed equivocal staining. However, mRNA ISH was negative. All cases showing p16 immunostaining and lacking HR-HPV were keratinizing SCCs. Thus, 9% of all eyelid SCC examined demonstrated HR-HPV.
Conclusion
The prevalence of HR-HPV in eyelid SCC is low in Indian patients. HPV-associated SCC may mimic commoner eyelid carcinomas as it lacks overt keratinization. In basaloid-appearing eyelid carcinomas, p16 immunopositivity should be followed by reflex HR-HPV mRNA ISH, as p16 immunohistochemistry alone has low specificity. The prognostic role, if any, of HPV association needs further evaluation.
Objectives
Sinonasal inverted papilloma (SNIP) is a noncancerous tumor that develops in the mucous membrane of the nasal sinuses. Many malignancies are tightly linked to autophagy, an intracellular self‐degradation mechanism. HMGB1 has demonstrated its ability to modulate autophagy in many pathological conditions. This work investigates how HMGB1 and other genes involved in autophagy contribute to SNIP.
Material and Methods
The study included 45 patients with SNIP and a control group consisting of 28 individuals. In each group, qPCR was employed to examine the mRNA expression levels of genes correlated with autophagy and HMGB1. HMGB1 and genes associated with autophagy were examined for protein expression levels via Western Blot and immunohistochemical staining assays. At the same time, the association between HMGB1 and genes involved in autophagy was discovered through correlation analysis. Furthermore, Krouse staging was utilized for investigating the expression levels of HMGB1 and other autophagy‐related genes at various stages in clinically staged SNIP patients.
Results
LC3B, ATG5, and Beclin1 autophagy‐related genes and HMGB1 were substantially expressed in SNIP. Additionally, there was a positive correlation between HMGB1 and these genes. During various phases of SNIP, the levels of HMGB1 expression and autophagy‐related genes were notably elevated at stage T4 compared with stage T2.
Conclusion
Clinical staging in SNIP is correlated with HMGB1 expression in conjunction with autophagy‐related genes LC3B, ATG5, and Beclin1, suggesting the possibility of novel prognostic indicators.
Level of Evidence
NA Laryngoscope , 2024
