Evaluation of Some Prognostic Biomarkers in Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma.

Background: Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with high-risk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProExTMC, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics. Methods: Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProExTMC, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method. Results: The expression of VEGF, hTERT, and ProExTMC was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively). Conclusion: HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProExTMC is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC.

Top IHC/ISH Hacks for and Molecular Surrogates of Poorly Differentiated Sinonasal Small Round Cell Tumors.

BACKGROUND: Poorly differentiated sinonasal small round cell tumors (SRCTs) are rare and heterogeneous, posing challenges in diagnosis and treatment. METHODS: Recent advances in molecular findings and diagnostic refinement have promoted better understanding and management of these tumors. RESULTS: The newly defined and emerging sinonasal entities demonstrate diverse morphologies, specific genomic signatures, and clinical behavior from conventional counterparts. In this review of SRCTs, emphasis is placed on the diagnostic approach with the employment of a pertinent panel of immunohistochemistry studies and/or molecular tests, fine-tuned to the latest WHO 5 classification of sinonasal/paranasal tumors and personalized treatment. CONCLUSION: Specifically, this review focuses on tumors with epithelial and neuroectodermal derivation.

[Diagnosis and therapy of sinonasal mucosal melanoma]. / Diagnostik und Therapie von Schleimhautmelanomen der Nase/Nasennebenhöhlen.

Sinonasal mucosal melanoma (SNMM) is a rare and aggressive disease representing only 4% of all sinonasal malignancies and 1.4% of all melanomas. With an incidence of approximately 0.2 to 2 cases per million, the disease represents a very rare cancer type. As a result, there is a lack of data and most of the evidence for this highly aggressive disease is based on retrospective observations and analyses. The standard of care is radical tumor resection followed by an adjuvant radiotherapy. Nevertheless, the rate of local recurrence is high, up to 50%. In addition, the majority of patients (up to 70%) develop distant metastases during the course of their disease. Both contribute to the extremely poor prognosis of the disease. Mucosal melanomas (SM) and cutaneous melanomas (CM) behave differently with respect to biology, clinic presentation and prognosis. Compared to CM, survival rates are significantly lower for SM. The 5-year survival rate is around 25% in SNMM but 39-97% in cutaneous melanoma. Similar to CM, immune checkpoint inhibitors achieve promising results in SM. However, response rates are lower in SM compared to CM. The goal of this CME article is to provide an overview on biology, diagnosis, therapy, and prognosis of SNMM.

[Inverted papilloma of the nose and paranasal sinuses : Diagnosis, treatment, and malignant transformation]. / Invertiertes Papillom der Nase und Nasennebenhöhlen : Diagnostik, Therapie und maligne Transformation.

Inverted papilloma (IP) are benign tumors that show a locally aggressive behavior, a high rate of recurrence, and a potential for malignant transformation. Specific radiological signs such as hyperostosis at the origin of the IP and convoluted cerebriform patterns, as well as the typical endoscopic aspect, can lead to diagnosis and enable preoperative planning of surgical access and the extent of surgery. Endonasal endoscopic techniques are considered the gold standard and the introduction of extended surgical techniques such as the prelacrimal approach, frontal drillout, or orbital transposition facilitate complete subperiosteal resection with preservation of important physiological structures. There is a risk of synchronous and metachronous squamous cell carcinomas (IP-SCC). Research focuses on radiological criteria to differentiate benign IP from IP-SCC, genetic and epigenetic factors in the process of malignant transformation, and estimation of the risk of IP progressing to IP-SCC.

A diagnostic algorithm for sinonasal papillary non-keratinizing squamous cell carcinoma with DEK::AFF2 fusion and mimickers.

Sinonasal carcinomas represent a rare and diverse group of tumors, presenting diagnostic complexities due to their varied histological and molecular features. To ensure accurate differentiation among these malignancies, a systematic and stepwise approach is paramount. Even with the morphological similarities between poorly differentiated (non) keratinizing sinonasal squamous cell carcinoma (SNSCC) and DEK::AFF2 SNSCC, the two lesions are distinguishable using the surrogate immunohistochemical marker AFF2 or molecular testing for DEK::AFF2 mutation. We report a rare case of SMARCB1-retained DEK::AFF2 papillary non-keratinizing SNSCC in a 53-year-old female, who presented with a polypoid mass corresponding to the left middle turbinate. Following the surgical resection of the tumor and locoregional lymph nodes, adjuvant radiotherapy was administered to eradicate any residual cancer cells that may have remained after surgery.

Clinical characteristics analysis of sinonasal diffuse large B-cell lymphoma and extranodal NK/T-cell lymphoma.

KEYPOINTS: Extranodal NK/T-cell lymphoma (ENKL) was the most common sinonasal lymphoma at our hospital. ENKL occurs at a younger age, and is more prevalent in the nasal cavity. ENKL had a lower Ann Arbor stage, and a better prognosis than diffuse large B-cell lymphoma (DLBLC).

[Rare cancers of the head and neck on behalf of the REFCOR, part 1]. / Cancers rares de la tête et du cou sous l'égide du REFCOR, partie 1.

Among the 16,000 new cases of malignant tumors of the head and neck diagnosed in France each year, 10% are not conventional squamous cell carcinomas. These so-called rare cancers are distinguished by their presentation and patterns of failure, which is important to recognize in order to offer specific adapted management and maximize the chances of tumor control. These cancers can be rare by their histology, which determines their local invasiveness, and their hematogenous/nodal spread. Their diagnosis can be difficult and often requires comprehensive immunohistochemistry and genomic techniques. Expert pathology review is recommended in the cases of undifferentiated tumors, sarcomas and at the slightest diagnostic doubt. These rare cancers can also be rare by their anatomical location when arising from the paranasal sinuses, salivary glands and ear. Their location requires knowledge of their specific extension routes, and may call for a specific surgical technique (skull base endoscopic sinus surgery, extended total parotidectomy, etc.) and adapted radiotherapy to spare healthy organs surrounding the tumor. This article (part 1) discusses the diagnostic and therapeutic specificities of these rare cancers, and develops the recommendations of the French ENT Cancer Expertise Network (REFCOR) concerning rare epithelial tumors, i.e., salivary tumors, sinonasal tumors, variants of conventional squamous cell carcinomas, neuroendocrine carcinomas, malignant odontogenic tumors, and ear tumors. A second article (part 2) is focused on non-epithelial tumors (sarcomas, mucosal melanomas, lymphomas, tumors of uncertain or undetermined malignancy) and describes the organization and missions of the REFCOR.

Management of Capillary Hemangioma of the Sphenoid Sinus.

Background and objectives: Capillary hemangiomas are rare, benign vascular tumors that mainly affect the skin and soft tissue, with scarce appearance within the nasal cavities and paranasal sinuses. Materials and methods: We present a case report of capillary hemangioma of the sphenoid sinus and a review of the literature in the last ten years. Results: Clinical and endoscopic examination of the nose, radiologic assessment and particular histologic features contribute to the correct diagnosis of capillary hemangioma of the nose and paranasal sinuses. Conclusions: Transnasal endoscopic resection of capillary hemangioma located in the nose and paranasal sinuses is a valuable treatment method with good outcomes.

SMARCB1 (INI-1) - Deficient sinonasal carcinoma: Report of two cases.

SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare, poorly differentiated carcinoma defined by complete loss of tumor suppressor gene SMARCB1 (INI-1) within the neoplastic cell nuclei demonstrated by the immunohistochemical stain. SMARCB1 (INI-1) gene inactivation has been implicated in the pathogenesis of a diverse group of malignant neoplasms that tend to share "rhabdoid" morphology. SMARCB1 (INI-1)-deficient sinonasal carcinoma was first reported by Agaimy et al. in 2014. These tumors are often basaloid with focal rhabdoid differentiation, prominent necrosis, increased mitotic activity, and aggressive behavior. Other than being INI-1 and NUT negative, they are positive for pancytokeratin and express variable immunoreactivity for squamous markers like p63 and neuroendocrine markers like synaptophysin. Most patients present with locally advanced disease and hence a combination of chemotherapy, radiotherapy, and surgery is usually recommended.

Biphenotypic sinonasal sarcoma-A recently described entity with many mimics: A case report.

Biphenotypic sinonasal sarcoma (BSNS) is a recently described, low-grade, slow-growing sarcoma with neural and myogenic features with exclusive location in sinonasal track and characteristic PAX3- MAML3 gene fusion. Differentiating this tumor from its commoner mimics needs knowledge of this entity to avoid over treatment. This tumor has unique morphology, clinical course, and genetics. We report this in a 47-year-old female who was diagnosed with such a rare, solitary fibrous tumor-hemangiopericytoma (HPC-SFT) on limited initial biopsy. On subsequent excision, typical morphology and immunohistochemistry helped to clinch the diagnosis.

Diagnosis, Treatment and Follow-Up of Sinonasal Leiomyomas: A Systematic Review.

BACKGROUND: Leiomyomas are benign smooth muscle tumors that are rarely diagnosed in the nasal cavity and paranasal sinuses. OBJECTIVE: This systematic review summarizes the histopathologic and clinical tumor characteristics, surgical management, and follow-up of sinonasal leiomyomas. METHODS: A systematic review of the literature on sinonasal leiomyoma was performed by applying the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Studies that met the inclusion criteria were assessed for level of evidence. Patient demographics, clinical and pathological tumor characteristics, primary intervention, and results of follow-up were evaluated. RESULTS: Forty studies including 84 patients with sinonasal leiomyoma were identified. The tumor was most often located in the nasal cavity (47/84, 56%) originating from the inferior turbinate (32/84, 38%). Patients mostly presented with symptoms originating from an intranasal mass, including recurrent epistaxis (41/84, 49%), nasal obstruction (43/84, 51.2%), and localized facial or head pain (25/84, 29.8%). Surgery was performed in all cases. An endoscopic approach was most frequently chosen. Recurrence occurred only twice (2.4%). Morbidity was noted in 2 cases (2.4%) following postoperative bleeding and 1 (1.2%) case following a CSF leak. CONCLUSION: Sinonasal leiomyomas are neoplasms of the smooth muscle manifesting clinically with recurrent epistaxis and nasal obstruction. Management goal is total resection with clear margins to avoid local recurrence.

Challenging differential diagnoses in small biopsies from the sinonasal tract.

Sinonasal biopsy specimens are a challenging area in anatomic pathology. The small, often fragmented or crushed nature of these biopsies can hinder morphologic assessment. Additionally, many of the tumors in this area are rare and share morphologic, and sometime immunophenotypic similarities. In many cases, immunohistochemistry is helpful if not necessary to reach a specific diagnosis. In other cases, a specific diagnosis is not possible and a differential diagnosis must be given on a biopsy specimen despite access to a well-equipped immunohistochemistry laboratory. This review article groups some of the more challenging entities in the sinonasal region based on morphologic patterns. These include low grade squamoid lesions such as sinonasal (Schneiderian) papilloma and DEK::AFF2 rearranged carcinoma, glandular neoplasms such as intestinal and non-intestinal type sinonasal adenocarcinoma, high-grade carcinomas such as HPV-related multiphenotypic sinonasal carcinoma, NUT carcinoma and SWI/SNF deficient carcinomas, small round blue cell tumors such as teratocarcinosarcoma, neuroendocrine carcinoma and olfactory neuroblastoma, and finally, low grade spindle cell neoplasms such as glomangiopericytoma, biphenotypic sinonasal sarcoma and solitary fibrous tumor.

Top 10 Significant Spindled Head and Neck Lesions to Scrutinze.

BACKGROUND: Spindled lesions are a challenging area in head and neck pathology. This is particularly true in the sinonasal tract, where several uncommon entities with both unique and overlapping morphologic, immunophenotypic, and/or molecular features can occur. METHODS: Review. RESULTS: The clinicopathologic characteristics of biphenotypic sinonasal sarcoma and nine important differential diagnostic considerations with one or more overlapping feature are summarized to establish a practical framework for approaching spindled lesions of the sinonasal tract. CONCLUSION: Morphologic evaluation is central to the work up of sinonasal spindle cell lesions-in particular, cellular morphology, tumor architecture and growth pattern, and the presence of admixed epithelial elements - however, focused immunohistochemical analysis of neural, myogenic, rhabdomyoblastic, epithelial, and/or melanocytic marker expression and/or ancillary tests for tumor-specific molecular alterations may be necessary for definitive diagnosis.

Biphenotypic Sinonasal Sarcoma: Case Reports of Diagnostic Findings and Clinical Management of 3 Cases.

BACKGROUND: Biphenotypic sinonasal sarcoma (BSNS) is a rare spindle cell sarcoma distinctly arising in the sinonasal area, with dual myogenic and neural differentiation, and characterised by the presence of PAX3 gene fusion, typically with MAML3. Although the majority may be indolent, up to 25% of cases reported in the literature are locally aggressive, with invasion of adjacent critical structures in the head and neck region. CASE REPORT: We report 3 cases of BSNS reviewed at our institution between 2016-2020 in addition to the current literature. Patient 1 underwent surgery followed by adjuvant radiotherapy but relapsed 24 months later and was not fit for systemic anticancer therapy and managed with palliative care. Due to comorbidities, patient 2 was recommended for active surveillance, with a view to intervening with radiotherapy should there be evidence of clinical progression. At 60 months, the nasal cavity mass remained stable on serial imaging. Patient 3 underwent primary surgical R0 resection and was offered adjuvant post operative radiotherapy 60 Gy/30 fractions/6 weeks but opted for active surveillance and has no clinical or radiological evidence of recurrence 22 months after surgery. CONCLUSION: The primary management for BSNS is surgical resection. We recommend discussing the role of postoperative adjuvant radiotherapy 60 Gy/30 fractions/6 weeks in patients who are fit for treatment. In clinical practice, dose levels will be constrained by surrounding normal tissues. At present, the role of systemic anticancer therapy is undefined. A prospective registry of ultra-rare cases may provide an evidence base with which to select optimal treatment strategies for BSNS in the future.

Biphenotypic Sinonasal Sarcoma: A Genetically Confirmed Case Showing Bone Invasion Accompanying a Non-neoplastic Respiratory Epithelium.

Biphenotypic sinonasal sarcoma is a newly established tumor entity that is associated with distinct clinicopathological findings. Biphenotypic sinonasal sarcoma is a rare, low-grade spindle cell sarcoma that arises in middle-aged females, exclusively in the sinonasal tract. A fusion gene involving PAX3 is detected in most biphenotypic sinonasal sarcomas, which aids in its diagnosis. Here, we report a case of biphenotypic sinonasal sarcoma with its cytological findings. The patient was a 73-year-old woman who presented with purulent nasal discharge and dull pain in the left cheek area. Computed tomography showed a mass extending from the left nasal cavity to the left ethmoid sinus, the left frontal sinus, and the frontal skull base. She underwent a combined transcranial and endoscopic approach for en bloc resection with a safety margin. Histologically, spindle-shaped tumor cells have been thought to proliferate mainly in the subepithelial stroma. Here, nasal mucosal epithelial hyperplasia was noted, and the tumor had invaded the bone tissue accompanying the epithelial cells. Fluorescence in situ hybridization (FISH) analysis showed a PAX3 rearrangement, and next-generation sequencing identified a PAX3::MAML3 fusion. Based on FISH, split signals were observed not in respiratory cells but in stromal cells. This indicated that respiratory cells were non-neoplastic. In the diagnosis of biphenotypic sinonasal sarcoma, the inverted growth of the respiratory epithelium can be a diagnostic pitfall. FISH analysis using a PAX3 break-apart probe is helpful not only for an accurate diagnosis but also for detecting the true neoplastic cells.

Tumors of the Nose and Paranasal Sinuses: Promoting Factors and Molecular Mechanisms-A Systematic Review.

Sinonasal neoplasms are uncommon diseases, characterized by heterogeneous biological behavior, which frequently results in challenges in differential diagnosis and treatment choice. The aim of this review was to examine the pathogenesis and molecular mechanisms underlying the regulation of tumor initiation and growth, in order to better define diagnostic and therapeutic strategies as well as the prognostic impact of these rare neoplasms. A systematic review according to Preferred Reporting Items for Systematic Review and Meta-Analysis criteria was conducted between September and November 2022. The authors considered the three main histological patterns of sinonasal tumors, namely Squamous Cell Carcinoma, Intestinal-Type Adenocarcinoma, and Olfactory Neuroblastoma. In total, 246 articles were eventually included in the analysis. The genetic and epigenetic changes underlying the oncogenic process were discussed, through a qualitative synthesis of the included studies. The identification of a comprehensive model of carcinogenesis for each sinonasal cancer subtype is needed, in order to pave the way toward tailored treatment approaches and improve survival for this rare and challenging group of cancers.

A Low-grade Sinonasal Sarcoma Harboring EWSR1::BEND2: Expanding the Differential Diagnosis of Sinonasal Spindle Cell Neoplasms.

BACKGROUND: Molecular diagnostics has greatly refined sinonasal tumor pathology over the past decade. While much of the attention has focused on carcinomas, it is becoming clear that there are emerging mesenchymal neoplasms which have previously defied classification. METHODS: Here, we present a 33-year-old woman with a multiply recurrent sinonasal spindle cell tumor exhibiting distinctive features, and not easily classifiable into a specific category. RESULTS: The hypercellular tumor was composed of plump spindled cells, with uniform vesicular chromatin arranged as vague fascicles around a prominent hemangiopericytoma-like vasculature. The mitotic rate was brisk at 10 per 10 high power fields. By immunohistochemistry, it was only positive for EMA (focal) and SATB2 (diffuse, weak). Fusion analysis uncovered EWSR1::BEND2, a fusion which is best known for being seen in astroblastoma, but which has not yet been reported in sarcomas. CONCLUSION: This case underscores the utility of fusion analysis when confronted with a sinonasal spindle cell neoplasm which does not neatly fit into any specific category. It remains to be seen if EWSR1::BEND2 sinonasal sarcoma represents a distinct entity.

Small cell neuroendocrine carcinoma with primary orbital involvement - The unseen, and a review of literature.

Neuroendocrine neoplasms are derived from the epithelial lineages mainly of respiratory tract, with predominant neuroendocrine differentiation. There are only a handful of documented cases of paranasal small cell neuroendocrine carcinomas (SNEC) with primary orbital involvement. Here, the authors describe a 33-year-old male patient with rapidly progressive swelling of the right lower lid with proptosis since 4 weeks. On contrast-MRI orbit, an ill-defined multilobulated mass measuring 3.6 × 3.1 cm with intense homogenous enhancement was seen in the right retrobulbar space involving the right ethmoid sinus. On incisional biopsy, a poorly differentiated mass containing numerous small round blue cells and scanty intervening stroma with prominent necrosis and apoptosis was seen. Immunohistochemistry was strongly positive for synaptophysin. He was diagnosed as a case of SNEC and received chemotherapy, with good response till date of 9 months of follow up. The authors present a literature review and describe challenges in management of a primary orbital SNEC.