Papillary Squamous Cell Carcinoma Research Articles

Traversing the Terrain: Potential Pitfalls within the AJCC 8th Edition Staging System for Lip and Oral Cavity Cancers.

In 1977, the American Joint Committee on Cancer (AJCC) introduced the inaugural Cancer Staging Manual, which implemented the T (tumor extent), N (regional lymph node status), and M (presence or absence of distant metastasis) staging system. This systematic approach aimed to convey the extent of disease across various cancer types, providing clinicians with a practical framework to plan treatment strategies, predict prognosis, and assess outcomes. The AJCC 8th edition, effective from January 1, 2018, continues this tradition. However, certain shortcomings persist in the AJCC 8th edition, as identified through clinical experience. Specifically, challenges arise in accurately assessing depth of invasion in unique histological variants of oral squamous cell carcinoma (e.g., Oral verrucous carcinoma, Carcinoma cuniculatum, and Papillary squamous cell carcinoma) and minor salivary gland tumors. Additionally, discrepancies exist in the perception of bone invasion patterns and in reporting practices. There is also a need for staging guidelines for malignant odontogenic tumors and multifocal tumors of the oral cavity, supplemented by diagrammatic representations. Lastly, there is a call for comprehensive staging criteria for carcinomas of the ear, external auditory canal, and temporal bone. We advocate for the inclusion of these considerations in future editions of the AJCC Cancer Staging Manual.

Prevalence and interpretation of AFF immunostain of DEK::AFF2 fusion-associated papillary squamous cell carcinoma in a retrospective cohort of recurrent sinonasal papillomas.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a novel entity characterized by its unique translocation and malignant clinical course. In this study, AFF immunohistochemistry (IHC) was performed in recurrent sinonasal papillomas for reviewing the prevalence of undiagnosed DEK::AFF2 carcinomas and to investigate the performance of AFF IHC in diagnosis of DEK::AFF2 carcinomas. Recurrent sinonasal papillomas after surgical excision in a two-decade period were retrieved. Histologic slides were reviewed for features of DEK::AFF2 carcinoma. AFF IHC was performed, and cases with any (> 1%) nuclear positivity were validated by DEK break apart fluorescence in situ hybridization. Totally 43 cases were included, comprising 28 inverted, 6 exophytic, one oncocytic, and 8 non-specified sinonasal papillomas. Five (11.6%) cases exhibited positivity to AFF IHC. Three cases exhibited patchy weak to moderate staining intensity predominantly in a granular cytoplasmic pattern. Two cases exhibited strong and diffuse (> 90%) nuclear staining. Cases showing weak staining were negative for DEK rearrangement, while those with strong staining were positive. Both cases of DEK::AFF2 carcinoma showed aggressive behavior with extensive local invasion and nodal metastasis. Background stromal plasma cells, when present, consistently showed strong and diffuse staining. AFF IHC was further performed in plasmacytoma samples as control and showed strong and diffuse immunoreactivity. A significant minority of recurrent sinonasal papillomas represent DEK::AFF2 carcinomas. Granular, cytoplasmic, or incomplete AFF staining should be considered as negative. In view of the rarity of DEK::AFF2 carcinomas, plasma cells and plasma cell neoplasms are potential for internal and surrogate external controls.

Papillary Variant of Oral Squamous Cell Carcinoma of Alveolar Mucosa- A Case Report and Review

Papillary Squamous Cell Carcinoma (PSCC) is a less frequent subtype of Squamous Cell Carcinoma (SCC) with a more favorable prognosis compared to conventional oral squamous cell carcinoma. PSCC has a distinctive exophytic and papillary projection. The upper aerodigestive tract is the most commonly affected site with a higher incidence of occurrence in the larynx. The papillary variant of oral squamous cell carcinoma involving gingiva or alveolar ridge is relatively uncommon and less reported. Other differential diagnosis of papillary gingival masses is reactive gingival lesions and fungal infections. An accurate diagnosis is vital for both therapeutic and prognostic purposes. This article describes the case of papillary variant oral squamous cell carcinoma in a 75-year-old male in the maxillary alveolar region depicting histopathological features of exophytic growth with hyperplastic stratified squamous epithelium with basaloid cells invading the underlying connective tissue.

The First Report of Cytology of DEK::AFF2 Fusion-Associated Papillary Squamous Cell Carcinoma on Fine-Needle Aspiration.

DEK::AFF2 fusion-associated papillary squamous cell carcinoma is a recently characterized sinonasal malignancy defined by its unique translocation. DEK::AFF2 carcinomas may be deceptively monotonous and lack keratinization, resembling transitional epithelium. The lack of traditional cytological atypia presents diagnostic challenges. Our case describes the first report of fine-needle aspiration cytology of a lymph node involved by DEK::AFF2 carcinoma in a patient with previously resected sinonasal inverted papilloma with carcinomatous transformation six years prior to presentation. This aspirate consisted of a lymphoid-rich background admixed with a moderate amount of epithelial cells arranged in cohesive structures of variable size, including large sheets. The tumor cells resembled those of the corresponding biopsy, featuring mildly hyperchromatic nuclei with fine to vesicular chromatin. Lesional cells lacked keratinization, mitoses, or hyperchromasia. Our finding suggests that in nodal aspirates of patients with a history of sinonasal-type papillomas, especially those with prior malignant transformation or atypia, there should be consideration for the possibility of DEK::AFF2-related primary. When in doubt, DEK FISH of AFF2 immunohistochemistry should be performed for confirmation.

Case report: Spontaneous mandibular body regeneration following unilateral subtotal mandibulectomy in a 3-month-old French bulldog.

To document a case of spontaneous regeneration of the mandibular body following subtotal mandibulectomy in a juvenile dog. A 3-month-old male intact French bulldog was presented with papillary oral squamous cell carcinoma located at the dorsal aspect of the molar region of the left mandible. Initial biopsy of the mass was performed by the primary care veterinarian. Complete clinical staging revealed no signs of metastasis. Computed tomographic images of the head showed minimal contrast enhancement of the mass with no signs of periosteal or bone involvement. Subtotal mandibulectomy was performed. Histopathology indicated complete excision of the tumor. The patient returned 8-weeks later for follow up and cleft palate surgical repair, at which time bone was noted in the mandibulectomy area on palpation. Repeat computed tomography of the head revealed complete regeneration of the left mandibular body from the level of the ramus to the mandibular symphysis. No treatment for malocclusion was necessary due to the reformation of a functional mandible. The present case demonstrates that spontaneous regeneration of the mandibular body is possible following subtotal mandibulectomy in immature dogs. Subtotal mandibulectomy is a radical procedure that can lead to long term complications including mandibular drift, malocclusion, and oral pain. This case report provides evidence that these sequelae may be mitigated or eliminated in young patients undergoing this procedure.

The Spectrum of HPV-independent Penile Intraepithelial Neoplasia: A Proposal for Subclassification.

Compared with vulva, precursor lesions of human papillomavirus (HPV)-independent invasive squamous cell carcinoma (SCC) of the penis are insufficiently characterized. We analyzed the histologic and immunohistochemical characteristics of 70 peritumoral precursor lesions and correlated them with the histology and mutational profile of the adjacent HPV-negative invasive penile SCC. Atypical basal keratinocyte proliferation with variously elongated epithelial rete with premature squamatiziation, but regular superficial cornification, termed differentiated penile intraepithelial neoplasia (d-PeIN), were identified adjacent to 42/70 (60%) SCC (36/42 keratinizing (P<0.001); 3 papillary, and 1 each verrucous, clear cell, sarcomatoid SCC). d-PeIN were associated with chronic inflammatory dermatoses (32/42; P<0.001), p53 overexpression (26/42; P<0.001), and hotspot mutations in TP53 (32/42; P<0.001), CDKN2A (26/42; P<0.001) or both (21/42; P=0.003) in the adjacent SCC. Cytoplasmic p16ink4a overexpression in 5/42 d-PeIN correlated with CDKN2A missense mutations in the adjacent SCC. In all, 21/70 (30%) cornified verrucous or glycogenated verruciform precursors with minimal atypia and wild-type p53 (18/21; P<0.001) occurred adjacent to verrucous or papillary SCC (17/21; P<0.001) and keratinizing (4/21) SCC, which harbored mutations in HRAS and/or PIK3CA (12/21; P<0.004). Undifferentiated p16ink4a-negative full-thickness precursors were identified in 7/70 (10%) SCC. Four histologically different HPV-independent penile precursor lesions can be assigned to 2 major genetic/biological pathways with characteristic highly differentiated precursors requiring different clinical management decisions. These include d-PeIN in chronic inflammatory dermatoses, with p53 overexpression and TP53/CDKN2A mutations, and the p53 wild-type verrucous and verruciform precursors unassociated with dermatoses, but with mutations in oncogenes PIK3CA and HRAS.

Value of loop electrosurgical excision procedure conization and imaging for the diagnosis of papillary squamous cell carcinoma of the cervix.

Loop electrosurgical excision procedure (LEEP) conization and hysterectomy are performed for some patients with papillary squamous cell carcinoma (PSCC), whereas only hysterectomy is performed for others. We aimed to determine the optimal management for PSCC. Patients diagnosed with PSCC by colposcopy-directed biopsy between June 2008 and January 2020 who underwent LEEP conization and hysterectomy or only hysterectomy at our hospital were enrolled. Results of cervical cytology, high-risk human papillomavirus testing, transvaginal sonography, pelvic magnetic resonance imaging, LEEP, hysterectomy, and pathology testing of colposcopy-directed biopsy samples were analyzed. A total of 379 women were diagnosed with PSCC by colposcopy-directed biopsy; 174 underwent LEEP before hysterectomy and 205 underwent only hysterectomy. Patients underwent and did not undergo LEEP were aged 47 ± 11 years and 52 ± 11 years, respectively. Among women who underwent LEEP, the agreement between LEEP and hysterectomy pathology was 85.1%. For women who underwent only hysterectomy, the agreement between preoperative clinical staging and pathological staging after hysterectomy was 82.4%. For patients with preoperative imaging indicative of malignancy, the accuracy of LEEP for diagnosing and staging PSCC was 88.5%, whereas for the hysterectomy-only group, it was 86.2%. For patients without malignancy detected with imaging, the accuracy of LEEP for diagnosing and staging PSCC was 81.6%; however, for those who did not undergo LEEP, it was 70.0%. For women diagnosed with PSCC by colposcopy-directed biopsy, LEEP conization is necessary for an accurate diagnosis when imaging does not indicate cancer; however, LEEP is not necessary when imaging indicates cancer.

Cornu cutaneum in the maxillofacial region – A case report

Cornu cutaneum are horn-like skin protrusions comprised of dense keratin. They differ from animal horns in a sense that cornu cutaneum do not have a central bone. The lesions may develop in any part of the body, with 30% of the lesions occurring in the head and neck region. Although they are considered benign lesions, they are characteristically associated with pre-malignant or malignant lesions such as squamous cell carcinoma, actinic keratosis, keratoacanthoma, basal cell carcinoma and Kaposi sarcoma. The aim of this clinical case report is to review a case of cornu cutaneum of the face associated with a papillary squamous cell carcinoma in a 72-year-old female We reviewed a case of cornu cutaneum of the left pre auricular area of the face with a 5-year history. The lesion was asymptomatic, measured 6cm in length and was resected under general anaesthetic with wide margins. The histopathological examination showed papillary a squamous cell carcinoma at the base of the lesion. As the lesions are benign and the nearest margin was 9mm, no further adjunct therapy was instituted. Although considered a benign lesion, cornu cutaneum is invariably associated with malignant lesions such as squamous cell carcinoma. Similarly, our case was associated with a papillary squamous cell carcinoma at the base of the lesion. As per current standards, the lesion was resected with wide margins

Treatment trends and prognostic factors related to histology of squamous cell carcinoma of the prostate: A SEER review.

e17120 Background: Excluding skin cancers, prostate cancer is the most common malignancy in males. Over 93% of prostate cancers are adenocarcinomas, and as such, an abundance of literature exists with regards to its screening, treatment, and prognosis. Often overlooked, however, data is lacking with regards to squamous cell carcinoma (SCC) of the prostate, a rare alternative form of prostatic cancer comprising fewer than 1% of malignancies. Given the rarity of SCC of the prostate there are neither accepted treatment guidelines nor consistent characterizations of the disease’s histogenesis and histopathology. This study seeks to improve existing guidelines on the treatment of prostate SCC by supplementing current literature with a novel method of longitudinal data collection in the form of the SEER database. Methods: This was a retrospective cohort study utilizing the Surveillance, Epidemiology and End Results (SEER) database sponsored by the National Cancer Institute (NCI). Investigated variables entailed patient demographics such as race and age, tumor characteristics including grade, tumor type, and histopathologic characteristics. Treatment modalities (surgical resection, radiation therapy, and systemic therapy) as well as disease characteristics were considered in generating Kaplan Meier overall survival (OS) curves compared using log rank test. Results: The most abundantly utilized treatment was surgery (58.6%), either alone or in conjunction with systemic and radiotherapy. Surgery alone was utilized for 24 patients and chemotherapy alone was utilized for 7 patients. Interestingly, only 14% of patients received multimodality treatment. Prostatic squamous cell carcinoma was the ultimate cause of death in 63.8% of cases. Kaplan Meier analysis demonstrated a median OS of 13 months. When stratifying by histopathologic characteristics, our results showed a significant difference in overall survival between patients with papillary carcinoma, with the median survival time of four years, and non-keratinizing squamous cell carcinoma, with a median survival time of one year (p = 0.005). Conclusions: Further studies are warranted regarding this exceedingly rare and understudied malignancy. The current analysis suggests subclassification of SSC of the prostate into papillary versus non-keratinizing squamous cell carcinoma may yield valuable prognostic information. Further research may emphasize this distinction as well as the role of multimodal treatment which appears to be underrepresented in SSC of the prostate when compared to other similar malignancies.

Postoperative Chyle Leak Rate Following Neck Dissection for Squamous Cell Carcinoma Versus Papillary Thyroid Cancer.

Compare the rates of post-operative chyle leak following therapeutic lateral neck dissection during treatment of papillary thyroid carcinoma (PTC) versus squamous cell carcinoma (SCC) of the head and neck. A retrospective analysis of 226 consecutive neck dissections in 201 patients who underwent therapeutic neck dissection involving at least levels II-IV with a final pathologic diagnosis of mucosal SCC of the head and neck or PTC from 2010 to 2020. Specific cases of chyle leak were reviewed. Surgical factors associated with chyle leak were analyzed using logistic regression analysis. Duration of chyle leak was assessed by the Kaplan-Meier curve, and time-to-resolution was analyzed by Cox proportional hazard analysis. Postoperative chyle leak was encountered in 15 (6.6%) neck dissections, eight (12.3%) in PTC, and seven (4.3%) in SCC. High-volume chyle leak and chyle leak requiring operative intervention were only encountered in neck dissections performed for PTC. Chyle leak was significantly associated with PTC on univariable analysis (OR 3.08, p= 0.037), but not on multivariable analysis (OR 1.35, p= 0.711). High-volume chyle leak and the need for operative intervention were associated only with PTC patients (OR 23.6, p= 0.006; OR 18.09, p= 0.023 respectively). Median duration of chyle leak was 12.1 days among patients with SCC, and 20.5 days among patients with PTC (p= 0.089). Among 201 patients undergoing therapeutic neck dissection, chyle leak was associated with PTC pathology on univariable but not multivariable analysis. However, high-volume leaks and leaks requiring operative intervention only occurred among patients with PTC. level III Laryngoscope, 133:2959-2964, 2023.

Cover Image

The cover image is based on the Short Communication Highly recurrent BRAF p.V595E mutation in canine papillary oral squa-mous cell carcinoma by Santiago Peralta et al., https://doi.org/10.1111/vco.12869.image

Early-stage glottic cancer of rare squamous cell carcinoma variants: a population-based study

Background Squamous cell carcinoma (SCC) is the most common histological type of laryngeal cancer. Several variants of SCC have been reported. However, how these variants differ from conventional SCC and how they should be treated remain to be elucidated. Objective To compare the prognosis of early-stage glottic cancer among SCC variants Methods We obtained data from 12471 cases using the Surveillance, Epidemiology, and End Results database. Disease-specific survival (DSS) and overall survival (OS) rates were estimated using the Kaplan–Meier method. A Cox proportional hazard model was used to estimate hazard ratios (HRs) according to the variants. Results HRs for DSS and OS compared with well-differentiated SCC were 3.83 and 3.48 for adenosquamous, 1.42 and 1.42 for basaloid, 1.14 and 1.17 for papillary, 0.85 and 0.94 for spindle, and 0.81 and 1.00 for verrucous SCC. The difference in DSS among the treatment modalities was significant in conventional and papillary SCC (p < .001 and p = .032, respectively). Conclusions The prognosis of SCC variants, except for adenosquamous SCC, is comparable to that of conventional SCC.

Survival comparison of different histological subtypes of oropharyngeal squamous cell carcinoma: A propensity-matched score analysis based on SEER database.

The purpose of this study was to analyze the difference of survival rates in paitents with oropharyngeal keratinizing squamous cell carcinoma (KSCC), nonkeratinizing squamous cell carcinoma (NKSCC), basaloid squamous cell carcinoma (BSCC), and papillary squamous cell carcinoma (PSCC). Patients diagnosed with oropharyngeal squamous cell carcinoma between 2004 and 2015 were collected from the SEER database. Cox proportional hazards models and Kaplan-Meier curves were used for survival analysis. Propensity score matching (PSM) was performed to adjust for the effect of confounding variables. Due to the small sample size of PSCC, this study did not perform PSM between it and other subtypes. The 5-year cancer-specific survival (CSS) rate of PSCC was higher than that of KSCC, NKSCC, and BSCC (0.627 vs. 0.812 vs. 0.789 vs. 0.875, P < 0.05); And the CSS rate of KSCC was lower than that of other subtypes both before and after PSM. In addition, the 5-year and 10-year CSS rates of BSCC were not different from NKSCC (P > 0.05), but not as good as NKSCC in the long term (P = 0.028). After PSM, the 5-year, 10-year, and long-term prognosis of BSCC were significantly worse than those of NKSCC (P < 0.001). The 5-year CSS of PSCC was better than the other three subtypes. The short-term prognosis of BSCC was not significantly different from NKSCC, but the long-term survival was lower than that of NKSCC, and the difference was more obvious after PSM. Meanwhile, the prognosis of KSCC was worst.

Papillary Squamous Cell Carcinoma of the Oropharynx Arising within Cleft Palate Surgical Scar.

Papillary Squamous Cell Carcinoma of the Oropharynx Arising within Cleft Palate Surgical Scar.

Local and Metastatic Relapses in a Young Woman with Papillary Squamous Cell Carcinoma of the Uterine Cervix.

Papillary squamous cell carcinoma (PSCC) is a rare histological type of cervical carcinoma whose biological behavior has not been fully established. A 33-year-old woman with an exophytic cervical mass underwent radical hysterectomy and bilateral pelvic lymph node dissection. Histological examination of the tumor revealed numerous papillary fronds lined by atypical stratified squamous cells, resembling high-grade squamous intraepithelial lesions or urothelium. She was diagnosed with stage IB1 PSCC. Three months postoperatively, a 5.7 cm vaginal stump mass was detected. She received chemoradiotherapy, which helped her achieve a complete response. However, nine months postoperatively, she developed pelvic lymph node metastases. We present a rare case of recurrent cervical PSCC in a young woman. PSCC of the uterine cervix can recur rapidly within just a few months and become aggressive, as in the present case.

Oral carcinoma cuniculatum: an unacquainted entity with diagnostic challenges\u2014a case report

BackgroundOral carcinoma cuniculatum (OCC) is an unacquainted well-differentiated subtype of oral squamous cell carcinoma, which displays unique clinic-pathological features. Up to date, OCC remains rare with about 75 reported cases, and is frequently missed or even misdiagnosed.Case presentationThe aim of the present work was: to report a case of OCC in mandibular gingiva and to highlight its main clinic-pathological diagnostic features: with an exophytic cobble-stone surface and a characteristic endophytic burrowing architecture, as well as to differentiate between it and other closely similar lesions including verrucous carcinoma, papillary squamous cell carcinoma, and well-differentiated conventional oral squamous cell carcinoma.ConclusionsAn accurate diagnosis of OCC entails awareness of the clinicians and pathologists about its entity, proper knowledge of the diagnostic clinical and histopathological evidence, and the ability to differentiate it from closely similar lesions.

Incidence of histopathological variants of oral squamous cell carcinoma: An institutional study

Squamous cell carcinoma is the most important and the most common malignant mucosal neoplasm of the head and neck accounting for over 90% of all malignancies. Conventional oral Squamous cell carcinoma is frequently present in general cancerous conditions. It is bundled up with six different variants. Histomorphologically every variant shows a unique appearance. This raises an opportunity for the different diagnostic consideration with the precise management decision.All cases of OSCC reported at our institution Dentopath Pathologies Amravati in past two months were scrutinized. Representative sections containing the full thickness of the tumor were used for histopathological grading. The structure and identification of carcinomas were done microscopically by two expert dentopathologist.In the present study, we screened 100 slides of a conventional epithelial cell carcinoma. Amonst which 30 Slides showed the verrucous carcinoma. On 5 slides adenoid squamous cell carcinoma were observed. Incidence of Papillary squamous cell carcinoma and basaloid squamous cell carcinoma was only 1 out of 100 slides each. Whereas, the spindle cell/sarcomatoid carcinoma was observed on 2 slides. Adenosquamous carcinoma is the rarest variant and hence no incidence of this carcinoma were observed in our study. The behavior of the OSCC varies amongst due to the presence of different morphological type of tumor. A few studies on OSCC malignancy grading with different clinical parameters were made. In the present study different types of variants are seen according to their histopathological appearances.Histopathological knowledge is very important for the precise diagnosis. Squamous cell carcinoma is the most common neoplasm of oral cavity. However, variants of the same show very less frequency. Hence, it became challenge for the appropriate diagnosis as many times a misdiagnosis affects the course of treatment of the patient

OCT angiography of papillary squamous cell carcinoma in situ

OCT angiography of papillary squamous cell carcinoma in situ

S2108 Progression of Esophageal Lichen Planus to Squamous Papillomatosis and Squamous Cell Carcinoma

Introduction: Esophageal squamous papillomas (ESPs) are typically benign asymptomatic lesions. The pathogenesis is uncertain but has been associated with acid reflux and other mucosal irritants, as well as with HPV. This case presents a patient with a 25-year progression from symptomatic esophageal lichen planus (ELP), through ESPs to papillomatosis, and finally well differentiated papillary squamous cell carcinoma. Case Description/Methods: A 78-year old White female presented to the GI clinic in 2008 for dysphagia. She was 5’0” and 118 lbs with pertinent past medical history of ELP with associated stricture diagnosed in 1996. She was treated with multiple endoscopic dilations of the stricture due to recurrent dysphagia, many with triamcinolone injection. She was also treated with multiple courses of systemic glucocorticoids for months at a time. In 2009, a 10 mm squamous papilloma in the mid esophagus was found at EGD. The lesion was subsequently partially resected by snare polypectomy and completely ablated using argon plasma coagulation (APC). Over the next 6 years she underwent 20 EGDs with bougie dilation, roughly half of which included resection of ESPs and APC fulguration. On EGD in 2016 multiple polypoid ESPs were seen throughout the esophagus; some but not all lesions were resected. Microscopically, the lesions were inflamed squamous papillomas with variable atypia. The patient then moved out of town and was lost to follow-up. She was next seen in 9/2020 for dysphagia to solids with marked weight loss, now down to 76 lbs. EGD at that time revealed extensive squamous papillomatosis extending throughout the entire esophagus, with partial obstruction of the lumen. Dilation and partial resection of ESPs was performed. Subsequent EGD was performed with debulking of the esophageal lumen using hot and cold snares. Histologic examination demonstrated a spectrum of squamous papillomas with atypia to low grade papillary squamous cell carinoma. The patient had subsequent improvement in dysphagia and some weight gain. However she gradually developed recurrent dysphagia and declined further endoscopic intervention or feeding gastrostomy. She died at home in 5/2021. Discussion: ELP and ESPs have both been independently associated with rare malignant transformation. This is the second reported case, to our knowledge, of ELP progression through ESPs to SCC. This case supports a growing body of literature that either entity can harbor malignant potential, and surveillance endoscopy is reasonable.Figure 1.: Left: Origin of the aberrant right subclavian artery Right: Diagonal impression on esophagus from extrinsic compression.

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

A novel DEK-AFF2 fusion has been recently identified in four cases of basaloid to nonkeratinizing squamous cell carcinoma (SCC) in the sinonasal tract and middle ear with high-grade morphology. The exceptional response to immune checkpoint inhibitor in the first reported case highlights the potential clinical importance of identifying tumors with DEK-AFF2 fusions. We herein reported the first series of seven cases of DEK-AFF2 fusion-associated sinonasal SCC with deceptively bland morphology, including four cases of low-grade papillary Schneiderian carcinoma, which is a recently described tumor type with unknown molecular underpinnings. The DEK gene rearrangement was confirmed by DEK break-apart fluorescence in situ hybridization and DEK-AFF2 fusion transcripts were detected by reverse transcription polymerase chain reaction. In contrast to the previously reported DEK-AFF2 fusion-positive high-grade carcinomas, these tumors had a monotonous and bland morphology and were all initially diagnosed as sinonasal papilloma (SP) of various types, with or without dysplasia or carcinoma in situ. The tumor was characterized by mixed exophytic and inverted patterns, broad papillary fronds, acantholytic change, cellular monotony, dense neutrophilic infiltrates, and peripheral palisading. All tumors were diffusely positive for p40 or p63 and negative for NUT and p16. Molecular drivers associated with SP, including EGFR and KRAS mutations and both high and low-risk human papillomavirus infection, were negative in all cases. Although there was no overt stromal invasion or desmoplastic reaction in the initial specimens, these tumors tended to progress locoregionally through a prolonged clinical course and occasionally develop lymph node metastases, high-grade transformation, or extensively local destruction eventually leading to death. These justify more aggressive clinical management. Therefore, we propose the new terminology “DEK-AFF2 fusion-associated papillary SCC of the sinonasal tract” to better describe this clinicopathologically and molecularly distinct entity.