Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma-An Even Broader Tumor Entity?

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a recently defined tumor subtype with apparent favorable clinical outcome despite aggressive histomorphology. However, in recent years, additional numbers of cases, with more variable features and at locations outside the sinonasal region, have complicated the definition of HMSC. Here, we have performed a systematic review of all cases described so far in order to accumulate more knowledge. We identified 127 articles published between 2013 and 2021, of which 21 presented unique cases. In total, 79 unique patient cases were identified and their clinical and micromorphological nature are herein summarized. In our opinion, better clinical follow-up data and a more detailed tumor characterization are preferably needed before HMSC can finally be justified as its own tumor entity.

[Diagnosis, prognosis and treatment of sinonasal carcinomas (excluding melanomas, sarcomas and lymphomas)]. / Diagnostic, pronostic et traitement des carcinomes nasosinusiens (hors mélanomes, sarcomes et lymphomes).

Sinonasal carcinomas account for 3% of ENT cancers. They are subdivided into squamous cell carcinomas (50%), adenocarcinomas [20%, mostly of intestinal type (ITAC)], and more rarely, adenoid cystic carcinomas, olfactory neuroblastomas (=esthesioneuroblastomas), neuroendocrine carcinomas or undifferentiated sinonasal carcinomas (SNUC). The 5-year survival rates are, in descending order, 72% for neuroblastomas, 63% for adenocarcinomas, 50-60% for large-cell neuroendocrine carcinomas, 53% for squamous cell carcinomas, 25-50% for adenoid cystic, 35% for small-cell neuroendocrine carcinomas and 35% for SNUC and newly discovered histologies. Surgery is the main treatment; endoscopic approaches reduce the morbidity with equivalent tumour control. Intensity-modulated radiation therapy (IMRT) is almost systematic. Nodal involvement is rare in ethmoidal adenocarcinomas and adenoid cystic carcinomas; it is intermediate and may justify prophylactic radiotherapy for N0 necks in SNUC, neuroblastoma, squamous cell carcinomas and sinonasal neuroendocrine carcinomas. IMRT or proton therapy is the mainstay of treatment of unresectable disease. Radiotherapy optimization by carbon ion therapy for adenoid cystic carcinomas, or by chemotherapy for all carcinomas with IMRT or proton therapy, is investigated within clinical trials in France. Neoadjuvant chemotherapy is reserved for rapidly progressive disease or histologies with a high metastatic potential such as neuroendocrine carcinomas or SNUC. Given their histologic and molecular specificities and different relapse patterns, an expertise of the REFCOR network, with REFCORpath review, is likely to correct diagnoses, rectify treatments, with an impact on survival.

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

CONTEXT.­: Sinonasal papillomas and carcinomas are uncommon head and neck neoplasms that comprise a broad clinicopathologic and morphologic spectrum, and thus frequently represent a diagnostic challenge for surgical pathologists. Recent molecular interrogation of these tumors has delineated a number of recurrent alterations that correspond to distinct entities with potential diagnostic and/or therapeutic clinical utility. OBJECTIVE.­: To summarize the salient clinicopathologic, morphologic, and molecular features of sinonasal papillomas and carcinomas. DATA SOURCES.­: Review of pertinent literature regarding sinonasal papillomas and sinonasal carcinomas. CONCLUSIONS.­: Despite their relative rarity in many surgical pathology practices, sinonasal papillomas and carcinomas frequently demonstrate characteristic morphologic features that are important for accurate diagnosis. Given our emerging understanding of the molecular basis for these tumors, judicious use of available ancillary tools-including immunohistochemistry and in situ hybridization-may be helpful in subsets of cases, whereas additional molecular testing may be useful for diagnostically challenging and/or clinically aggressive sinonasal tumors.

Sinonasal undifferentiated carcinoma: clinicopathological spectrums and diagnosis reappraisal.

Sinonasal undifferentiated carcinoma (SNUC) is defined as undifferentiated carcinoma of the sinonasal tract without glandular or squamous features and not otherwise classifiable. SNUC is a rare tumor, with a long list of differential diagnoses, and often poses a considerable diagnostic challenge. In addition, recent advances in molecular and immunohistochemistry techniques have recognized several new entities that were previously included in the SNUC category. These include SMARCB1 (INI-1)-deficient carcinoma, NUT (nuclear protein in testis) carcinoma, adamantinoma-like Ewing sarcoma, and the most recently described and rarer SMARCA4 (BRG)-deficient carcinoma. In this study, we retrospectively reviewed 11 cases with an original diagnosis of SNUC. We found that a significant portion of those cases can be reclassified into specific entities, with potential impact on therapy and prognosis because of misclassification in 2 of these cases.

High-Grade Sinonasal Carcinoma: Classification Through Molecular Profiling.

High-grade sinonasal carcinomas are a cohort of malignant epithelial neoplasms arising in the sinonasal cavities with distinct, ominous morphologic features or lacking well-differentiated features that might otherwise classify them as less biologically worrisome. Recent advances in molecular profiling have led to the identification of several distinct tumor entities previously grouped together. These molecularly distinct lesions include NUT (midline) carcinoma, INI1 (SMARCB1)-deficient carcinoma, SMARCA4-deficient sinonasal carcinoma, and novel IDH-mutant sinonasal undifferentiated carcinoma, in addition to the previously described lymphoepithelial carcinoma that may also be included in the differential diagnosis. The discovery of these distinct molecular tumor profiles may have significant clinical impact as targeted molecular-based therapeutics continue to evolve, and they may offer some respite for patients who have these highly aggressive cancers.

[WHO classification of head and neck tumours 2017: Main novelties and update of diagnostic methods]. / Classification de l'OMS 2017 des tumeurs de la tête et du cou : principales nouveautés et mise à jour des méthodes diagnostiques.

The publication of the new WHO classification of head and neck tumours in 2017 brought major modifications. Especially, a new chapter is dedicated to the oropharynx, focusing on the description of squamous cell carcinoma induced by the virus Human Papilloma Virus (HPV), and new entities of tumors are described in nasal cavities and sinuses. In this article are presented the novelties and main changes of this new classification, as well as the updates of the diagnostic methods (immunohistochemistry, cytogenetics or molecular biology).

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Nasal Cavity, Paranasal Sinuses and Skull Base.

The sinonasal tract remains an epicenter of a diverse array of neoplasia. This paper discusses changes to the WHO classification system of tumors involving this area. In particular, seromucinous hamartoma, NUT carcinoma, biphenotypic sinonasal sarcoma, HPV-related carcinoma with adenoid cystic features, SMARCB1-deficient carcinoma, and renal cell-like adenocarcinoma are discussed.

A simple classification of cranial-nasal-orbital communicating tumors that facilitate choice of surgical approaches: analysis of a series of 32 cases.

Cranial-nasal-orbital communicating tumors involving the anterior and middle skull base are among the most challenging to treat surgically, with high rates of incomplete resection and surgical complications. Currently, there is no recognized classification of tumors with regard to the choice of surgical approaches. From January 2004 to January 2014, we classified 32 cranial-nasal-orbital communicating tumors treated in our center into three types according to the tumor body location, scope of extension and direction of invasion: lateral (type I), central (type II) and extensive (type III). This classification considerably facilitated the choice of surgical routes and significantly influenced the surgical time and amount of hemorrhage during operation. In addition, we emphasized the use of transnasal endoscopy for large and extensive tumors, individualized treatment strategies drafted by a group of multidisciplinary collaborators, and careful reconstruction of the skull base defects. Our treatment strategies achieved good surgical outcomes, with a high ratio of total resection (87.5 %, 28/32, including 16 cases of benign tumors and 12 cases of malignant tumors) and a low percentage of surgical complications (18.8 %, 6/32). Original symptoms were alleviated in 29 patients. The average KPS score improved from 81.25 % preoperatively to 91.25 % at 3 months after surgery. No serious perioperative complications occurred. During the follow-up of 3 years on average, four patients with malignant tumors died, including three who had subtotal resections. The 3-year survival rate of patients with malignant tumors was 78.6 %, and the overall 3-year survival rate was 87.5 %. Our data indicate that the simple classification method has practical significance in guiding the choice of surgical approaches for cranial-nasal-orbital communicating tumors and may be extended to other types of skull base tumors.

Sinonasal Adenocarcinoma: Update on Classification, Immunophenotype and Molecular Features.

Adenocarcinomas of the sinonasal tract may originate from respiratory surface epithelium or the underlying seromucinous glands. These malignancies are divided into salivary-type adenocarcinomas and non-salivary-type adenocarcinomas. The latter are further divided into intestinal-type and nonintestinal-type adenocarcinomas. This review provides an update on tumor classification, differential diagnostic considerations and molecular features, as well as new adenocarcinoma entities in the sinonasal area.

Recently described neoplasms of the sinonasal tract.

Surgical pathology of the sinonasal region (i.e., nasal cavity and the paranasal sinuses) is notoriously difficult, due in part to the remarkable diversity of neoplasms that may be encountered in this area. In addition, a number of neoplasms have been only recently described in the sinonasal tract, further compounding the difficulty for pathologists who are not yet familiar with them. This manuscript will review the clinicopathologic features of some of the recently described sinonasal tumor types: NUT midline carcinoma, HPV-related carcinoma with adenoid cystic-like features, SMARCB1 (INI-1) deficient sinonasal carcinoma, biphenotypic sinonasal sarcoma, and adamantinoma-like Ewing family tumor.

Sinonasal small round blue cell tumors: An approach to diagnosis.

The differential diagnosis for small round cell tumors in the sinonasal tract is diverse and as the body of literature documenting not only uncommon presentations but also availability of ancillary studies grows, so does the need for a reminder to take a conservative and thorough approach before rendering a diagnosis. Small tissue samples are particularly problematic, with limitations that include volume of tumor cells available for studies, lack of architectural context and a non-specific gross description. Incorporation of patient history and presentation, radiologic findings, clinical impression and concurrent studies often guide the course of studies performed by the pathologist. If these are non-specific, the pathologist may need to perform ancillary studies, including a broad panel of immunohistochemical stains and molecular studies. If tissue is limited, a precise classification may not be achievable. Although the expectation to render a definitive diagnosis is high, the pathologist should never feel compelled to go further with a diagnosis than the tissue itself supports.

Human papillomavirus-associated neoplasms of the sinonasal tract and nasopharynx.

It is now well established that human papillomavirus (HPV) is an important causative factor in a subgroup of head and neck cancer. In the head and neck, while HPV is strongly associated with squamous cell carcinoma arising in the oropharynx, there is a growing interest in HPV-associated neoplasms of non-oropharyngeal origin including those which arise within sinonasal and nasopharyngeal mucosa. This article reviews current literature on the association of HPV with Scheiderian papillomas, sinonasal squamous cell carcinoma, sinonasal undifferentiated carcinoma, carcinoma with adenoid cystic-like features, and nasopharyngeal carcinoma. Several clinical implications of HPV detection in sinonasal and nasopharyngeal carcinomas are briefly discussed.

Hematolymphoid lesions of the sinonasal tract.

Various hematolymphoid lesions involve the sinonasal tract, including aggressive B, T, and NK-cell neoplasms; myeloid sarcoma; low-grade lymphomas; indolent T-lymphoblastic proliferations; and Rosai-Dorfman disease. Differentiating aggressive lymphomas from non-hematopoietic neoplasms such as poorly differentiated squamous cell carcinoma, olfactory neuroblastoma, or sinonasal undifferentiated carcinoma may pose diagnostic challenges. In addition, the necrosis, vascular damage, and inflammatory infiltrates that are associated with some hematolymphoid disorders can result in misdiagnosis as infectious, autoimmune, or inflammatory conditions. Here, we review hematolymphoid disorders involving the sinonasal tract including their key clinical and histopathologic features.

Soft tissue tumors of the sinonasal tract.

Primary soft tissue tumors arising in the sinonasal tract are rare. While many mesenchymal neoplasms have been reported in the nasal cavity, sinuses, and nasopharynx, few are distinctive to this anatomic region. Some tumor types are relatively more common in this area, such as schwannoma and rhabdomyosarcoma. Nasopharyngeal angiofibroma and sinonasal hemangiopericytoma are unique entities of the sinonasal tract, as well as the recently characterized biphenotypic sinonasal sarcoma. This review discusses the clinical, morphologic, and immunohistochemical features and currently known molecular data of the more frequently encountered soft tissue tumors of the sinonasal tract.

The Differential Diagnosis of Sinonasal/Nasopharyngeal Neuroendocrine/Neuroectodermally Derived Tumors.

CONTEXT: The differential diagnosis of neuroendocrine neoplasms arising in the sinonasal tract is broad and includes lesions of epithelial, mesenchymal, and neuroectodermal origin. OBJECTIVE: To review the differential diagnosis of sinonasal neuroendocrine and neuroectodermally derived tumors. DATA SOURCES: The current literature was reviewed to provide updated information regarding the differential diagnosis and means for diagnosing neuroendocrine tumors including sinonasal neuroendocrine carcinoma, olfactory neuroblastoma, malignant melanoma, paraganglioma, pituitary adenoma, and Ewing family of tumors. CONCLUSIONS: The differential diagnosis of neoplasms with neuroendocrine differentiation in the sinonasal tract is broad, and diagnosis often includes not only histologic review but also immunohistochemical or molecular analysis.

A Subset of Sinonasal Non-Intestinal Type Adenocarcinomas are Truly Seromucinous Adenocarcinomas: A Morphologic and Immunophenotypic Assessment and Description of a Novel Pitfall.

While sinonasal intestinal type adenocarcinoma (ITAC) is defined by an intestinal phenotype, non-intestinal type adenocarcinoma (non-ITAC) is traditionally viewed as a diagnosis of exclusion, despite previous implication of a seromucinous phenotype and similarity to sinonasal seromucinous hamartomas (SSH). We performed a comparison of clinicopathologic and immunophenotypic features of ITAC, non-ITAC and SSH using traditional discriminatory markers and new markers of seromucinous differentiation. Twenty-three non-ITAC, 17 ITAC, and 5 SSH were retrieved (1987-2014). As expected, ITAC occurred predominantly in the nasal cavity in elderly patients (mean age 65 years) with a striking male predilection (15:2). Regardless of grade/subtype, all ITAC were invariably CK20 and CDX2 positive, and many (11/15) showed some CK7 positivity. Non-ITAC occurred in younger individuals (mean age 51 years) with a slight female predilection (male to female ratio: 10:13) and showed diverse morphologic patterns and grades, some with morphologic similarity to SSH. SSH occurred in younger individuals (mean age 33 years). Non-ITAC and SSH were invariably CK7 positive and CK20 negative, however, 4/22 non-ITAC and 2/5 SSH showed squamoid morular metaplasia that aberrantly expressed CDX2 and co-expressed nuclear ß-catenin. Markers of seromucinous differentiation (S100, DOG1, and SOX10) were essentially absent in ITAC, but present to varying degrees in the majority of non-ITAC and all SSH. Thus, the term 'seromucinous adenocarcinoma' is the more appropriate designation for non-ITAC. Squamoid morules in non-ITAC and SSH may be an immunophenotypic pitfall given the aberrant CDX2 expression.

Recently described sinonasal tract lesions/neoplasms: considerations for the new world health organization book.

Since the publication of the World Health Organization Classification of Head and Neck Tumors (Barnes et al., World Health Organization classification of tumours. Pathology and genetics head and neck tumours, IARC Press, Lyon, pp 10-80, 2001), a number of sinonasal lesions have been more completely described. This manuscript will focus on three such "new" lesions including sero mucinous hamartoma, HPV-related carcinoma with adenoid cystic-like features and low-grade sinonasal sarcoma with neural and myogenic features.

Sinonasal mucosal melanomas: the prognostic value of tumor classifications.

BACKGROUND: The purpose of this study was to assess the prognostic value of the 3 staging systems found in the literature for sinonasal mucosal melanomas tumors: the Ballantyne staging system modified by Prasad (Ballantyne/Prasad staging system), the American Joint Committee on Cancer (AJCC) TNM classification for mucosal melanomas (mmTNM), and the 2009 AJCC TNM classification for carcinomas of the nasal cavity and sinuses (carTNM). METHODS: A retrospective study of 35 patients treated between 1995 and 2010 was conducted for this study. Each patient was retrospectively staged using the Ballantyne/Prasad staging system, mmTNM, and carTNM. RESULTS: There were 20 women (57.1%) and 15 men (42.9%). Only carTNM was significantly correlated with overall survival (p = .012) and disease-free survival (p = .041). The other 2 classifications were not correlated with survival except for metastatic patients whose overall survival was lower (p = .032). CONCLUSION: On the basis of these findings, we believe that carTNM should be the primary staging system for patients with mucosal melanomas of the sinonasal tract