DEK-AFF2 fusion-associated papillary squamous cell carcinoma of the sinonasal tract: clinicopathologic characterization of seven cases with deceptively bland morphology

Kuo, Ying Ju; Lewis, James S.; Zhai, Changwen; Chen, Yun An; Chernock, Rebecca D.; Hsieh, Min Shu; Lan, Min‐Yu; Lee, Chien Kuan; Weinreb, Ilan; Hang, Jen Fan

doi:10.1038/s41379-021-00846-2

Cited by 45 publications

(56 citation statements)

References 24 publications

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“…These lesions demonstrate pushing invasion, no stromal reaction, and frequent surface papillary growth. They often show minimal cytologic atypia, low mitotic activity, and prominent neutrophilic infiltrate, features that notably overlap with those seen in IP 14,15…”

Section: Discussionmentioning

confidence: 89%

CD163 Immunohistochemical “Circle Sign” Staining Pattern Differentiates Sinonasal Papillomas From Morphologically Similar Non-neoplastic Lesions

Sterling

Mehrad

Ely

et al. 2022

American Journal of Surgical Pathology

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Sinonasal papillomas are a diverse group of benign epithelial neoplasms of the sinonasal tract. Inverted papilloma, in particular, must be distinguished from other lesions with no malignant potential. The aim of this study was to distinguish sinonasal papillomas from morphologically similar lesions using CD163 immunostaining. Cases from a 19-year period were identified. These included 49 inverted, 10 exophytic, and 12 oncocytic papillomas, 21 chronic sinusitides with squamous metaplasia, 27 inflammatory polyps, 5 verrucae vulgares, 5 respiratory epithelial adenomatoid hamartomas, and 6 DEK:: AFF2 carcinomas of the sinonasal tract. A subset of biopsy cases (8 inverted papillomas, 5 inflammatory polyps) was separately analyzed. CD163 immunohistochemistry (IHC) was performed. A unique "circle" staining pattern was identified in the surface epithelium. After locating a hotspot, circles were quantified in 10 consecutive high-power fields. Circles were present in 66/71 (93%) cases of sinonasal papilloma, with a mean of 35 circles/ 10 HPF (range: 0 to 160/10 HPF) and a median of 19 circles/ 10 HPF. Circles were present in 20/58 (34%) non-neoplastic cases, with a mean of 2 circles/10 HPF (range: 0 to 27/10 HPF) and a median of 0. Considering all resection and biopsy cases, performance for distinguishing papillomas from non-neoplastic lesions was best at a cutoff of 10 circles/10 HPF (2-tailed P < 0.0001) with sensitivity, specificity, positive predictive value, and negative predictive value of 66.2%, 93.1%, 92.1%, and 69.2%, respectively. The results were similar in the biopsy subset. One other neoplastic entity, the DEK::AFF2 carcinomas, also showed prominent CD163 circle staining. In summary, si-nonasal papillomas demonstrate extensive CD163 "circle" staining in the epithelium compared with the nonneoplastic lesions studied. As such, the "circle sign" on CD163 IHC may be helpful in distinguishing between diagnoses, particularly on small biopsies or equivocal specimens.

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Section: Discussionmentioning

confidence: 89%

CD163 Immunohistochemical “Circle Sign” Staining Pattern Differentiates Sinonasal Papillomas From Morphologically Similar Non-neoplastic Lesions

Sterling

Mehrad

Ely

et al. 2022

American Journal of Surgical Pathology

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“…Both HPV and EBV testing has been negative. The DEK::AFF2 fusion has been demonstrated by targeted RNA sequencing [56] and confirmed by RT-PCR and by FISH with a DEK break-apart probe [55]. Notably, there has been no evidence of EGFR or KRAS mutations [55,56], indicating that these carcinomas are not related to SP.…”

Section: Squamous Cell Carcinomamentioning

confidence: 97%

“…The DEK::AFF2 fusion has been demonstrated by targeted RNA sequencing [56] and confirmed by RT-PCR and by FISH with a DEK break-apart probe [55]. Notably, there has been no evidence of EGFR or KRAS mutations [55,56], indicating that these carcinomas are not related to SP. Although the number of cases reported so far is small, these carcinomas generally tend to have an aggressive behavior, with occurrence of cervical lymph node metastases and distant metastases [55,56].…”

Section: Squamous Cell Carcinomamentioning

confidence: 97%

“…A recently described molecularly distinct variant of SNSCC is the DEK::AFF2 fusionassociated carcinoma [54][55][56]. These tumors are not limited to the sinonasal region but may also originate in the skull base and temporal bone.…”

Section: Squamous Cell Carcinomamentioning

confidence: 99%

“…Notably, there has been no evidence of EGFR or KRAS mutations [55,56], indicating that these carcinomas are not related to SP. Although the number of cases reported so far is small, these carcinomas generally tend to have an aggressive behavior, with occurrence of cervical lymph node metastases and distant metastases [55,56]. Although one patient presented an excellent response to multimodality treatments including immune checkpoint inhibitors, this result has not been confirmed in other patients [56].…”

Section: Squamous Cell Carcinomamentioning

confidence: 99%

See 2 more Smart Citations

Towards a Molecular Classification of Sinonasal Carcinomas: Clinical Implications and Opportunities

Taverna

Agaimy

Franchi

2022

Cancers

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Sinonasal carcinomas are a heterogeneous group of rare tumors, often with high-grade and/or undifferentiated morphology and aggressive clinical course. In recent years, with increasing molecular testing, unique sinonasal tumor subsets have been identified based on specific genetic alterations, including protein expression, chromosomal translocations, specific gene mutations, or infection by oncogenic viruses. These include, among others, the identification of a subset of sinonasal carcinomas associated with HPV infection, the identification of a subset of squamous cell carcinomas with EGFR alterations, and of rare variants with chromosomal translocations (DEK::AFF2, ETV6::NTRK and others). The group of sinonasal adenocarcinomas remains very heterogeneous at the molecular level, but some recurrent and potentially targetable genetic alterations have been identified. Finally, poorly differentiated and undifferentiated sinonasal carcinomas have undergone a significant refinement of their subtyping, with the identification of several new novel molecular subgroups, such as NUT carcinoma, IDH mutated sinonasal undifferentiated carcinoma and SWI/SNF deficient sinonasal malignancies. Thus, molecular profiling is progressively integrated in the histopathologic classification of sinonasal carcinomas, and it is likely to influence the management of these tumors in the near future. In this review, we summarize the recent developments in the molecular characterization of sinonasal carcinomas and we discuss how these findings are likely to contribute to the classification of this group of rare tumors, with a focus on the potential new opportunities for treatment.

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Precision Medicine in the Treatment of Malignancies Involving the Ventral Skull Base: Present and Future

Ferrari

Taboni

Contro

et al. 2023

Critical Issues in Head and Neck Oncology

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Cancers involving the ventral skull base are rare and exceedingly heterogeneous. The variety of malignant tumors that arise in the nasal cavity, paranasal sinuses, nasopharynx, and adjacent mesenchymal tissues translates into a proportionally vast spectrum of prognoses, with some histologies such as olfactory neuroblastoma being associated with rare disease-specific death to other histologies such as mucosal melanoma for which survival beyond 5 years is considered a fortunate exception. Parallel to prognosis, treatment of sinonasal cancers is complex, controversial, and deeply dependent upon the putative pretreatment diagnosis. Given their heterogeneity, cancers of the ventral skull base are particularly prone to multidisciplinary management, which is indispensable. The therapeutic options available to date for these cancers include surgery, which currently remains the mainstay of treatment in most cases, along with radiotherapy and chemotherapy. Biotherapy and immunotherapy are only anecdotally and compassionately used. For each histology, a careful selection of modalities and their timing is paramount to ensure the best chance of cure. In keeping with the principles of precision medicine, several nuances displayed by malignancies of the ventral skull base are being considered as treatment-driving characteristics. This current trend arose from the observation that a remarkable variability of behavior can be observed even within a single histology. Although evidence is lacking in this field and several potential customizations of treatment are still at a theoretical level, understanding of these cancers is rapidly evolving and practical applications of this increasing knowledge is the much-needed step forward in the management of such rare cancers. This chapter highlights the tumor characteristics that may serve as treatment-driving factors in the most relevant cancers invading the ventral skull base.

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DEK-AFF2 fusion-associated papillary squamous cell carcinoma of the sinonasal tract: clinicopathologic characterization of seven cases with deceptively bland morphology

Cited by 45 publications

References 24 publications

CD163 Immunohistochemical “Circle Sign” Staining Pattern Differentiates Sinonasal Papillomas From Morphologically Similar Non-neoplastic Lesions

CD163 Immunohistochemical “Circle Sign” Staining Pattern Differentiates Sinonasal Papillomas From Morphologically Similar Non-neoplastic Lesions

Towards a Molecular Classification of Sinonasal Carcinomas: Clinical Implications and Opportunities

Precision Medicine in the Treatment of Malignancies Involving the Ventral Skull Base: Present and Future

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