Primary Sinonasal Mucosal Melanoma with Aberrant Diffuse and Strong Desmin Reactivity: A Potential Diagnostic Pitfall!

The broad morphologic spectrum, inherent immunophenotypic heterogeneity of malignant melanoma and its rarity in the sinonasal tract are major challenges in eliciting the correct diagnosis, which may lead to misclassification and inadequate medical management. Herein, we describe a single case of a 70 year-old male with sinonasal mucosal melanoma, exhibiting varying histologic phenotypes including small round blue cell morphology, epithelioid and focal rhabdoid morphology and strong, diffuse desmin immunoreactivity. These constellation of features initially prompted the diagnosis of rhabdomyosarcoma. The differential diagnosis in this anatomic area includes other malignant small round blue cell tumors of the sinonasal mucosa such as rhabdomyosarcoma, olfactory neuroblastoma, sinonasal undifferentiated carcinoma, and lymphoma. We reviewed precedent literature and further discuss the potential pitfalls to which pathologists may be prone.     

Sinonasal Squamous Cell Carcinoma: A Review with Emphasis on Emerging Histologic Subtypes and the Role of Human Papillomavirus

The sinonasal tract is one of the least frequent sites for squamous cell carcinoma in the head and neck. However, it is still a complex tumor type for pathologists because there are numerous histologic variants with unusual morphologic features, several non-squamous carcinomas in the differential diagnosis that can have similar morphology and even squamous differentiation, and because of the increasing recognition of human papillomavirus (HPV) in a subset of the tumors. In addition, the unique and complex anatomy of the sinonasal tract can make proper staging and management of patients’ tumors quite challenging. This article reviews sinonasal tract squamous cell carcinoma in depth and provides the latest data on Schneiderian papillomas and HPV in their pathogenesis.     

Neuroendocrine Neoplasms of the Sinonasal Tract: Neuroendocrine Carcinomas and Olfactory Neuroblastoma

Neuroendocrine neoplasms (NENs) can occur in organs or tissues that do not contain neuroendocrine cells normally and do not necessarily imply embryologic derivation from the neuroectoderm; but rather reflect a shared phenotype characterized by the expression of multiple genes encoding both endocrine and neuronal features. NENs are rare in the sinonasal tract and are subdivided into epithelial and neural subtypes based on the presence of keratins or neurofilaments, respectively. Although relatively rare, neuroendocrine carcinomas (NECs) and olfactory neuroblastoma (ONB) are the most common neuroendocrine neoplasms of the sinonasal tract. The focus of this review is to highlight recent developments in the pathology of sinonasal NECs and ONB in light of the upcoming update of the World Health Organization (WHO) 2005 classification of tumors of the head and neck.     

Neuroendocrine neoplasms of the sinonasal region

Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small‐cell and large‐cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high‐grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined. © 2015 Wiley Periodicals, Inc. Head Neck 38 : E2259–E2266, 2016     

Inflammatory and Infectious Lesions of the Sinonasal Tract

The sinonasal tract is frequently affected by nonneoplastic inflammatory diseases. Inflammatory lesions of the sinonasal tract can be divided into 3 main categories: chronic rhinosinusitis, which encompasses a heterogeneous group of entities, all of which result in mucosal inflammation with or without polyps-eosinophils; infectious diseases; and autoimmune diseases and vasculitides, which can result in midline necrosis and facial deformities. This article reviews the common inflammatory lesions of the sinonasal tract with emphasis on infectious diseases, vasculitis, iatrogenic, and diseases of unknown cause. Many of these lesions can result in midline destruction and result in facial deformity.     

Among Sinonasal Tumors,CDX-2 Immunoexpression is not Restricted to Intestinal-Type Adenocarcinomas

Intestinal-type adenocarcinoma (ITAC) is a rare form of sinonasal cancer characterized by an association with exposure to industrial dusts, aggressive clinical behavior, and histologic/immunophenotypic similarity to tumors of the gastrointestinal tract. ITAC is sometimes very poorly differentiated and difficult to distinguish from other sinonasal neoplasms, particularly in a limited biopsy. CDX-2 and cytokeratin 20 are consistently immunoreactive in ITAC and as a result, these immunostains are often used to support the diagnosis. However, CDX-2 and cytokeratin 20 have not been tested on a broad range of sinonasal tumors, so their specificities remain unknown. Immunohistochemistry for CDX-2 and cytokeratin 20 was performed on 6 sinonasal ITACs as well as 176 non-intestinal-type sinonasal neoplasms. CDX-2 and cytokeratin 20 were positive in all 6 cases of ITAC. CDX-2 immunoexpression was also observed in 17 of 176 (10 %) non-intestinal-type tumors including 6 of 16 (38 %) sinonasal undifferentiated carcinomas, 8 of 81 (10 %) squamous cell carcinomas (including 5 of 39 non-keratinizing variants), 2 of 20 (10 %) salivary-type adenocarcinomas, and 1 of 2 (50 %) small cell carcinomas. In contrast, among non-intestinal types of sinonasal tumors, cytokeratin 20 was only focally observed in 1 of 176 non-intestinal tumors (a non-keratinizing squamous cell carcinoma). All cases of non-intestinal surface-derived adenocarcinoma and esthesioneuroblastoma were negative for both markers. Both CDX-2 and cytokeratin 20 are highly sensitive for the diagnosis of sinonasal ITAC, but cytokeratin 20 is more specific. CDX-2 staining may be observed in other high grade tumor types, especially sinonasal undifferentiated carcinoma and non-keratinizing squamous cell carcinoma. As a result, in the setting of a poorly differentiated sinonasal carcinoma the diagnosis of ITAC should not be based on CDX-2 immunoexpression alone. Clear-cut glandular differentiation and cytokeratin 20 immunoexpression are more reliable features.     

Radiologic Features of Sinonasal Tumors

Imaging evaluation of sinonasal tumors is most often conducted with computed tomography, which excels at identifying the effects of these masses on adjacent osseous structures, and magnetic resonance imaging that is ideal for distinguishing pathologic masses from mucosal thickening and fluid that are common in the sinonasal spaces and depicting extension into the surrounding soft tissues, orbits, and intracranial compartment. Accordingly, the two studies are complementary exams and both are commonly utilized in the assessment of these masses. Less commonly, positron emission tomography can provide additional metabolic evaluation of potential metastatic disease in patients with malignant disease. While these imaging modalities are excellent for the portrayal of an abnormality, there is considerable overlap in the imaging appearance of these tumors and specific imaging manifestations linked to a particular tumor are frequently lacking. Therefore, while the mass may be readily identified, narrowing the differential diagnosis to a single specific entity is rare. Nevertheless, cross-sectional imaging plays an essential role in patient management and valuable guidance for successful biopsy or surgical resection in virtually all cases. This review emphasizes essential imaging manifestations that correlate with sinonasal tumors in general and highlight certain features that may implicate a specific disease process.     

Update on Select Benign Mesenchymal and Meningothelial Sinonasal Tract Lesions

Several benign and malignant mesenchymal and meningothelial lesions may preferentially affect or extend into the sinonasal tract. Glomangiopericytoma (GPC, formerly sinonasal-type hemangiopericytoma) is a specific tumor with a predilection to the sinonasal tract. Sinonasal tract polyps with stromal atypia (antrochoanal polyp) demonstrate unique histologic findings in the sinonasal tract. Juvenile nasopharyngeal angiofibroma (JNA) arises from specialized tissue in this location. Meningioma may develop as direct extension from its intracranial counterpart or as an ectopic tumor. Selected benign mesenchymal tumors may arise in the sinonasal tract and pose a unique differential diagnostic consideration, such as solitary fibrous tumor and GPC or lobular capillary hemangioma and JNA. Although benign and malignant vascular, fibrous, fatty, skeletal muscle, and nerve sheath tumors may occur in this location, this paper focuses on a highly select group of rare benign sinonasal tract tumors with their clinicopathological and molecular findings, and differential diagnosis.     

Endonasal Endoscopic Surgery in the Management of Sinonasal and Anterior Skull Base Malignancies

Sinonasal malignancies represent a rare subset of tumors with a wide variety of histopathologic diagnoses and overall poor prognosis. These tumors tend to have an insidious onset with non-specific symptoms which often leads to delayed diagnosis and advanced local disease at presentation. The principal goal of surgery is to obtain a negative margin resection. Open craniofacial techniques are well established in the management of sinonasal malignancies and remain the treatment of choice for many advanced tumors. Over the past couple of decades, there has been tremendous application of endoscopic techniques to skull base pathologies including sinonasal malignancies. For selected cases, endonasal endoscopic techniques can be performed with curative intent and reduced surgical morbidity and mortality. Here we discuss principles of surgical management of sinonasal malignancies, review the techniques of endonasal endoscopic resection of sinonasal malignancies, and highlight the importance of pathology in the multi-disciplinary management of patients with these complex lesions.     

Low Grade Glandular Lesions of the Sinonasal Tract: A Focused Review

The sinonasal tract is a complex anatomic site with an exhaustive list of possible diagnoses. While most biopsies or resections encountered routinely consist of common diagnoses such as inflammatory polyps and papillomas, occasional cases are more difficult, and separating reactive or benign from malignancy can be challenging. One of the most poorly understood and daunting categories is low grade glandular or tubular proliferations, particularly on small biopsies. Possible diagnoses such as reactive lesions, respiratory epithelial adenomatoid hamartoma (REAH), seromucinous (glandular) hamartoma (SH) and low grade sinonasal adenocarcinomas (LGSNAC) must be entertained. REAH is composed of respiratory epithelial lined submucosal glands with variable connection to the surface and periglandular hyalinization. SH is a tubular proliferation reminiscent of normal serous glands which may be associated with REAH. LGSNAC is a diverse group of bland tubular and/or papillary tumors, which have a recurrence potential but an as yet uncertain potential for metastasis or mortality. The management for these lesions can be vastly different and conservative management is preferable, making this distinction more than academic. However, complicating this category are controversies surrounding their nature as reactive lesions versus neoplasms, the histologic and immunohistochemical overlap, and possible precursor relationships between some of them.     

Ganglioneuroblastic Transformation in Olfactory Neuroblastoma

Ganglioneuroblastic transformation in olfactory neuroblastoma (ONB) is an exceptionally rare phenomenon. We document the case of a patient with a poorly differentiated sinonasal malignancy that recurred following treatment with chemoradiotherapy and showed ganglioneuroblastic transformation. Although the index tumour showed neuroendocrine differentiation, it did not have the typical clinico-pathological features associated with ONB. We highlight the diagnostic difficulties in establishing an accurate diagnosis for undifferentiated sinonasal tumours and present evidence that the index tumour was an ONB. The current report is only the third case of ONB showing complete ganglioneuroblastic transformation.     

Hereditary Paraganglioma of the Nasopharynx

Head and neck paragangliomas are rare neuroendocrine tumors derived from neural crest cells of parasympathetic ganglia or the widely dispersed neuroendocrine cells of the head and neck region. Paragangliomas of the sinonasal tract and nasopharynx are rare. The clinicopathologic features of this unique example of a hereditary, nasopharyngeal paraganglioma, and selective entities that are included in its differential diagnosis are presented.     

Sinonasal Small Round Blue Cell Tumors: An Immunohistochemical Approach

Although clinical history and morphologic appearance should be the initial considerations when evaluating small round blue cell tumors of the sinonasal tract, the final diagnosis often hinges on immunohistochemical findings. Unfortunately, interpretation of stains in these tumors is fraught with numerous pitfalls and limitations. This article presents an approach to sinonasal small round blue cell tumors based on four common immunohistochemical patterns: cytokeratin positivity, squamous marker positivity, neuroendocrine marker positivity, and cytokeratin negativity.     

Primary and Secondary/ Metastatic Salivary Duct Carcinoma Presenting within the Sinonasal Tract

Traditionally, sinonasal adenocarcinomas have been subdivided into intestinal (ITAC) and non-intestinal (non-ITAC) categories. The latter encompasses salivary-type adenocarcinomas originating from the seromucinous glands of the sinonasal mucosa and non-salivary adenocarcinomas. The non-salivary adenocarcinoma category is further subdivided into low-and high-grade variants. Among salivary-type sinonasal adenocarcinomas, tumors recapitulating salivary duct carcinoma (SDC) are exceedingly rare, but some might have been lumped into the high-grade non-ITAC category. To date, only three primary SDCs originating in the sinonasal tract have been reported. We herein describe 7 cases of SDC including one previously reported case (4 primary sinonasal, 3 metastatic/ extension from parotid gland SDC). The primary tumors affected 3 males and one female aged 60 – 75. Different sites were involved by the primary tumors while the secondary tumors affected the sphenoidal (2) and the frontal + maxillary (1) sinuses. Three primary tumors were de novo high-grade SDC and one was confined to contours of a pre-existing pleomorphic adenoma. All 3 secondary tumors were SDC ex pleomorphic adenoma of the parotid with a long history of recurrences, ultimately involving the sinonasal tract. Androgen receptor was positive in 7/7 cases. Four of 6 cases were strongly HER2/neu + (either score 3 + or with verified amplification). This small case series adds to the delineation of primary sinonasal SDC highlighting that almost half of invasive SDC presenting within sinonasal tract indeed represents extension or metastasis from a parotid gland primary. There is a tendency towards overrepresentation of HER2/neu-positive cases in both categories (primary and metastatic), but this needs clarification in larger studies.     

Endoscopic treatment of esthesioneuroblastoma: a minimally invasive approach combined with radiation therapy.

OBJECTIVE: In a retrospective analysis we discuss our experience in the treatment of olfactory neuroblastoma (ON), a rare tumor of the sinonasal tract. STUDY DESIGN AND SETTING: Nine patients with olfactory neuroblastoma were treated at the Bolognini Hospital of Seriate and at the Department of Otolaryngology of "La Sapienza" University of Rome combining endoscopic surgery and postoperative radiation therapy. All patients were staged according to Kadish criteria. No chemotherapy was administered in any cases. Local radiation therapy was started postoperatively in all the cases. RESULTS: All patients, over an average follow-up which ranged from 26 through 60 months, are actually alive with non evidence of disease (NED). CONCLUSIONS: Despite the short follow-up in this small series of patients, we suggest endoscopic surgery combined with postoperative radiation therapy as an alternative to the conventional modalities of treatment for esthesioneuroblastoma in selected cases.     

Glandular Neoplasia of the Sinonasal Tract

Glandular lesions that cannot be diagnosed readily as salivary gland tumors occur uncommonly in the upper aerodigestive tract. They occur only with some frequency within the sinonasal tract. Well-characterized lesions at this site include the respiratory epithelial adenomatoid hamartoma, seromucinous hamartoma, and intestinal and non–intestinal-type adenocarcinomas. This article reviews the clinicopathologic features of these fascinating lesions.     

Sinonasal Tract Angiosarcoma: A Clinicopathologic and Immunophenotypic Study of 10 Cases with a Review of the Literature

Background    Primary sinonasal tract angiosarcoma are rare tumors that are frequently misclassified, resulting in inappropriate clinical management. There are only a few reported cases in the English literature. Materials and Methods    Ten patients with sinonasal tract angiosarcoma were retrospectively retrieved from the Otorhinolaryngic Registry of the Armed Forces Institute of Pathology. Results    Six males and four females, aged 13 to 81 years (mean, 46.7 years), presented with epistaxis and bloody discharge. Females were on average younger than their male counterparts (37.8 vs. 52.7 years, respectively). The tumors involved the nasal cavity alone (n = 8) or the maxillary sinus (n = 2), with a mean size of 4.3 cm; the average size was different between the genders: males: 2.8 cm; females: 6.4 cm. Histologically, all tumors had anastomosing vascular channels lined by remarkably atypical endothelial cells protruding into the lumen, neolumen formation, frequent atypical mitotic figures, necrosis, and hemorrhage. All cases tested (n = 6) demonstrated immunoreactivity with antibodies to Factor VIII-RA, CD34, CD31, and smooth muscle actin, while non-reactive with keratin and S-100 protein. The principle differential diagnosis includes granulation tissue, lobular capillary hemangioma (pyogenic granuloma), and Kaposi’s sarcoma. All patients had surgery followed by post-operative radiation (n = 4 patients). Follow-up was available in all patients: Six patients died with disease (mean, 28.8 months); two patients had died without evidence of disease (mean, 267 months); and two are alive with no evidence of disease at last follow-up (mean, 254 months). Conclusions    Sinonasal tract angiosarcoma is a rare tumor, frequently presenting in middle-aged patients as a large mass usually involving the nasal cavity with characteristic histomorphologic and immunophenotypic features. Sinonasal tract angiosarcoma will often have a poor prognosis making appropriate separation from other conditions important.