Sinonasal Papillomas and Carcinomas: A Contemporary Update With Review of an Emerging Molecular Classification

Weindorf, Steven C.; Brown, Noah A.; McHugh, Jonathan B.; Udager, Aaron M.

doi:10.5858/arpa.2019-0372-ra

Cited by 23 publications

(25 citation statements)

References 49 publications

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“…The sinonasal tract is a unique anatomic subset of the aerodigestive tract, and although the majority of its malignant tumors are squamous cell carcinomas associated with tobacco exposure or high-risk HPV infection, recent morphologic and molecular profiling studies have delineated a number of characteristic tumors with specific molecular alterations (i.e., NUT carcinoma, SMARCB1 (INI-1)-deficient sinonasal carcinoma, IDH2-mutant sinonasal undifferentiated carcinoma, etc.) 21 . The results of this study (and others) clearly indicate that sinonasal papilloma-associated sinonasal carcinomas are similarly molecularly distinct from other aerodigestive tract squamous cell carcinomas, with frequent EGFR and KRAS mutations that are only exceptionally seen at other anatomic sites 11 , 12 .…”

Section: Discussionmentioning

confidence: 99%

“…Sinonasal papillomas are uncommon benign epithelial tumors of the sinonasal tract; however, a small subset of cases are associated with a synchronous or metachronous sinonasal carcinoma – most commonly squamous cell carcinoma or one of its variants (i.e., adenosquamous carcinoma, etc.) 1 , 2 . Over the past several years, our group has utilized a variety of conventional and next-generation sequencing approaches to define the oncogenic events that occur in specific sinonasal papilloma subtypes, including mutually-exclusive EGFR mutations and HPV infection in inverted sinonasal papilloma and KRAS mutations in oncocytic sinonasal papillomas 3 – 5 .…”

Section: Introductionmentioning

confidence: 99%

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TP53 mutations and CDKN2A mutations/deletions are highly recurrent molecular alterations in the malignant progression of sinonasal papillomas

et al. 2021

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Sinonasal papillomas are benign epithelial tumors of the sinonasal tract that are associated with a synchronous or metachronous sinonasal carcinoma in a subset of cases. Our group recently identified mutually exclusive EGFR mutations and human papillomavirus (HPV) infection in inverted sinonasal papillomas and frequent KRAS mutations in oncocytic sinonasal papillomas. We also demonstrated concordant mutational and HPV infection status in sinonasal papilloma-associated sinonasal carcinomas, confirming a clonal relationship between these tumors. Despite our emerging understanding of the oncogenic mechanisms driving formation of sinonasal papillomas, little is currently known about the molecular mechanisms of malignant progression to sinonasal carcinoma. In the present study, we utilized targeted next-generation DNA sequencing to characterize the molecular landscape of a large cohort of sinonasal papilloma-associated sinonasal carcinomas. As expected, EGFR or KRAS mutations were present in the vast majority of tumors. In addition, highly recurrent TP53 mutations, CDKN2A mutations, and/or CDKN2A copy number losses were detected; overall, nearly all tumors ( n = 28/29; 96.6%) harbored at least one TP53 or CDKN2A alteration. TERT copy number gains also occurred frequently (27.6%); however, no TERT promoter mutations were identified. Other recurrent molecular alterations included NFE2L2 and PIK3CA mutations and SOX2 , CCND1 , MYC , FGFR1 , and EGFR copy number gains. Importantly, TP53 mutations and CDKN2A alterations were not detected in matched sinonasal papillomas, suggesting that these molecular events are associated with malignant transformation. Compared to aerodigestive tract squamous cell carcinomas from The Cancer Genome Atlas (TCGA) project, sinonasal papilloma-associated sinonasal carcinomas have a distinct molecular phenotype, including more frequent EGFR , KRAS , and CDKN2A mutations, TERT copy number gains, and low-risk human papillomavirus (HPV) infection. These findings shed light on the molecular mechanisms of malignant progression of sinonasal papillomas and may have important diagnostic and therapeutic implications for patients with advanced sinonasal cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

TP53 mutations and CDKN2A mutations/deletions are highly recurrent molecular alterations in the malignant progression of sinonasal papillomas

et al. 2021

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“…This is in contrast to the other tumors in the differential diagnosis: adenoid cystic carcinoma is characterized by the t(6;9)/MYB-NFIB fusion; non-intestinal-type sinonasal adenocarcinoma has recently been associated with ETV6 gene rearrangements in small cohorts; and basal cell adenocarcinoma has recently been associated with CYLD, PIK3CA, and NFKBIA gene mutations. 19 Of note, low rates of PIK3CA mutations have been described in both ameloblastoma and basal cell adenocarcinoma. 8,20,21 This case exemplifies several uncommonly described features of ameloblastomas in cytology, including an adenoid morphology, and the presence of FGFR2 and SMO mutations.…”

Section: Discussionmentioning

confidence: 99%

Ameloblastoma with adenoid features: Case report with cyto‐histopathologic correlation and molecular findings

Jofré

Roth

Lahouti

et al. 2022

Diagnostic Cytopathology

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Ameloblastomas are benign but locally aggressive odontogenic tumors that commonly present as expansile lesions in the tooth-bearing areas. Fine-needle aspiration (FNA) biopsies of ameloblastomas are rare in clinical practice, and only a handful of case reports and series have described their cytologic features. We present the case of a 70-year-old woman with a large and disfiguring maxillary sinus soft tissue mass sampled via transcutaneous FNA. Aspirate smears were composed of small clusters of cohesive and monotonous basaloid cells. The accompanying cellblock showed similar clusters of basaloid cells in gland-like, or "adenoid," configurations, eliciting a differential diagnosis that included sinonasal and salivary gland neoplasms. Excisional surgery material was consistent with ameloblastoma with adenoid morphology.Next-generation sequencing (NGS) analysis demonstrated FGFR2 and SMO pathogenic variants. This case exemplifies several uncommonly described features of ameloblastomas in cytology, including cyto-histologic correlation, adenoid morphology, and NGS findings. Awareness of the cytologic features of this neoplasm are important for cytopathologists confronted with maxillary sinus lesions.

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“…Although a small number of sinonasal IP are associated with a synchronous or metachronous squamous cell carcinoma, malignant transformation of these lesions leads to longterm morbidity and/or mortality. This necessitates better and novel diagnostic, prognostic, and therapeutic approaches [24]. The oncofetal protein IMP3 has been shown to be expressed in human malignancies but not in nonmalignant lesions, which may serve as a diagnostic marker in such cases.…”

Section: Discussionmentioning

confidence: 99%

IMP3 Immunohistochemical Expression in Inverted Papilloma and Inverted Papilloma-Associated Sinonasal Squamous Cell Carcinoma

Hakim

Raboh

Shash

2021

Analytical Cellular Pathology

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Sinonasal inverted papilloma (IP) has a propensity for malignant transformation. Although the IP-associated squamous cell carcinoma (SCC) is rare, it has a poor prognosis. To the best of our knowledge, this is the first study to assess IMP3 immunohistochemical (IHC) expression in sinonasal tumors and to compare it to the Ki-67 IHC expression and to other established clinicopathological parameters. A retrospective study was conducted on three groups which consisted of 72 cases of sinonasal IP, 20 age-matched samples of normal respiratory epithelium, and 15 cases of sinonasal SCC associated with IP, which were obtained from the archives of the Pathology Lab of Ain Shams University Specialized and Ain Shams University Hospitals during the period from January 2012 to December 2019. An IHC study was performed to evaluate IMP3 and Ki-67 expression in the three groups, with correlation of IMP3 expression to established clinicopathological parameters of sinonasal SCC on top of IP. Both IMP3 and Ki-67 showed a sharp rise in expression in the sinonasal SCC group. In addition, there were statistically significant differences in expression values between the 3 groups ( P = 0.001 ). Receiver Operating Characteristic (ROC) analysis revealed that IMP3 and Ki-67 could be used to discriminate sinonasal SCC from control and IP lesions, with sensitivity and specificity of 100% and 81.5% for IMP3, respectively, and 100% and 62.5% for Ki-67, respectively. Spearman’s rho revealed that both IMP3 and Ki-67 were significantly related to the lymph node and tumor stages but not to the tumor grade. ROC analysis was performed to select cut-off scores for progression and survival for IMP3, and accordingly, Kaplan-Meier analysis showed correlation between IMP3 and overall survival, local recurrence-free survival, and metastasis-free survival in sinonasal SCC cases at the selected cut-off values. Based on our results, IMP3 could serve as a promising diagnostic, prognostic, and therapeutic marker for IP-associated sinonasal SCC.

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Sinonasal Papillomas and Carcinomas: A Contemporary Update With Review of an Emerging Molecular Classification

Cited by 23 publications

References 49 publications

TP53 mutations and CDKN2A mutations/deletions are highly recurrent molecular alterations in the malignant progression of sinonasal papillomas

TP53 mutations and CDKN2A mutations/deletions are highly recurrent molecular alterations in the malignant progression of sinonasal papillomas

Ameloblastoma with adenoid features: Case report with cyto‐histopathologic correlation and molecular findings

IMP3 Immunohistochemical Expression in Inverted Papilloma and Inverted Papilloma-Associated Sinonasal Squamous Cell Carcinoma

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