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Sinonasal Tumors: a Clinicopathologic Update of Selected Tumors Eur Arch Otorhinolaryngol (2013) 270:5–20 DOI 10.1007/s00405-012-2025-4 REVIEW ARTICLE Sinonasal tumors: a clinicopathologic update of selected tumors Pieter J. Slootweg • Alfio Ferlito • Antonio Cardesa • Lester D. R. Thompson • Jennifer L. Hunt • Primozˇ Strojan • Robert P. Takes • Asterios Triantafyllou • Julia A. Woolgar • Alessandra Rinaldo • Kenneth O. Devaney • Leon Barnes Received: 5 April 2012 / Accepted: 17 April 2012 / Published online: 18 May 2012 Ó Springer-Verlag 2012 Abstract The sinonasal cavities show a wide variety of Keywords Sinonasal tumors Á Pathology Á neoplasms of epithelial, mesenchymal, neural/neuroecto- Immunohistochemistry Á Molecular analysis Á dermal or hematopoietic origin. The differential diagnosis Treatment Á Prognosis for these tumors may be difficult due to overlapping mor- phologies, variable patterns in ancillary studies, and potentially confusing terminology. In this report, an Introduction updated review of the spectrum of neoplasia is provided, using the World Health Organization 2005 classification as Surgical pathology of the sinonasal tract presents consid- a guide. Classic tumors that are generally limited to the erable diagnostic difficulties for the pathologist for several sinonasal tract are described and new information regard- reasons. First, the anatomy of this region is very complex ing molecular pathogenesis is reviewed. Also new entities and while processing specimens care should be paid to that have the sinonasal tract as a site of predilection, such ensure/preserve relationships between structures. Coupled as sinonasal renal cell-like adenocarcinoma and NUT with this, many of the unique lesions that occur in the midline carcinoma are highlighted. sinonasal tract have a predilection for specific sites. Since the anatomic sites are often difficult to reach by standard biopsy approaches, specimens may be compromised in This paper was written by members and invitees of the International terms of integrity (fragmentation, cauterization artifacts, Head and Neck Scientific Group (http://www.IHNSG.com). P. J. Slootweg P. Strojan Department of Pathology, Radboud University Nijmegen Department of Radiation Oncology, Institute of Oncology, Medical Center, Nijmegen, The Netherlands Ljubljana, Slovenia A. Ferlito (&) Á A. Rinaldo R. P. Takes ENT Clinic, University of Udine, Piazzale S. Maria della Department of Otolaryngology-Head and Neck Surgery, Misericordia, 33100 Udine, Italy Radboud University Nijmegen Medical Center, Nijmegen, e-mail: [email protected] The Netherlands A. Cardesa A. Triantafyllou Á J. A. Woolgar Department of Anatomic Pathology, Hospital Clinic, Oral Pathology, School of Dental Sciences and Dental Hospital, University of Barcelona, Barcelona, Spain University of Liverpool, Liverpool, UK L. D. R. Thompson K. O. Devaney Department of Pathology, Woodland Hills Medical Center, Department of Pathology, Allegiance Health, Jackson, MI, USA Woodland Hills, CA, USA L. Barnes J. L. Hunt Department of Pathology, University of Pittsburgh School Department of Pathology, University of Arkansas for Medical of Medicine, Pittsburgh, PA, USA Sciences, Little Rock, AR, USA 123 6 Eur Arch Otorhinolaryngol (2013) 270:5–20 and degradation) and anatomical landmarks may be absent. Secondly, the tumors that arise in these locations may show overlapping histologic features, despite divergent patho- genesis and/or tissues of origin. Since treatment schemes are different for particular tumor types, it is important for the pathologist to sort out the differential diagnosis. Ancillary investigations may also show overlapping and/or aberrant findings, which may increase difficulties in his- tologic diagnosis/classification. Finally, the pertinent lit- erature may be confusing with regard to terminology and traditional classifications have been modified on the basis of immunohistochemical and molecular findings. In this review a wide variety of lesions will be examined with emphasis on current understanding of histologic patterns, ancillary testing and clinical findings. For the discussion, the lesions are grouped into those derived from the mucosal Fig. 1 Inverted papilloma. In spite of its monotonous histologic appearance, the lesion erodes the bony sinus walls surface and those that originate from other tissue types. Inverted papillomas can show areas of cellular/nuclear Tumors of the mucosal surface atypia and increased mitotic activity. If the atypia is extensive, the possibility of malignant transformation Schneiderian papillomas should be considered. Whether the presence of mild or very focal atypia ipso facto has any clinical or prognostic sig- Schneiderian papillomas are epithelial tumors that arise nificance is controversial [2] and minimum criteria for a from the respiratory mucosa (Schneiderian membrane) that diagnosis of frank dysplasia in inverted papilloma have not lines the nasal cavity and the paranasal sinuses. Three been established. histological subtypes are recognized: inverted papilloma, Inverted papilloma can be seen in association with oncocytic papilloma and exophytic papilloma [1]. squamous cell carcinoma (SCC) in about 11 % [3, 4]. If atypia is extensive, and combined with necrosis and Inverted papilloma destructive growth, the possibility of a malignant compo- nent rather than inverted papilloma should be considered. This is the most common variant. It shows a male predi- Two diagnostic possibilities are generally considered in lection and usually occurs in individuals above 40 years of these cases: malignant transformation of an inverted pap- age. The tumor typically arises from the lateral nasal wall illoma (carcinoma ex Schneiderian papilloma) or co-exis- and often extends into one or more adjacent sinuses. The tence of pathogenetically unrelated benign and malignant nasal septum is involved (usually secondarily) in approxi- lesions. Histologically, gradual transition from a typical mately 5 % of cases. inverted papilloma through dysplastic alterations to frankly Histologically, inverted papillomas show endophytic invasive SCC suggests malignant transformation. When growth, though often contain an exophytic or polypoid such a transition is not seen and the histology is charac- component as well. The lesion is characterized by prolifer- terized by two sharply demarcated components, co-exis- ative epithelium invaginating into edematous stroma tence of inverted papilloma and independently arising SCC (Fig. 1). The epithelium is multilayered, often more than ten can be considered. There are no definitive markers indic- layers thick. The invaginations into the underlying stroma ative of malignant transformation, but some studies suggest show medium to large sized nests of cells that typically have that increased, immunohistochemically assessed, prolifer- a rounded, smooth border. The epithelial phenotypes may ation indices and/or the expression of p53 would be of help vary, but they are usually transitional (occasionally referred [5–7]. to as cylindrical). Squamous areas, ciliated cells on surface, The prognosis in inverted papillomas is good provided dispersed mucous cells and superficial keratinization can be they are adequately treated, which usually means complete seen. Within the epithelium, there are also small cystic removal of tumor and surrounding sinonasal mucosa at the spaces that contain cell debris and inflammatory cells. involved site. In incompletely excised/neglected cases, Although there is no significant stromal reaction, neutrophils intracranial extension and death may occur. For lesions transmigrating through the epithelium are usually seen. This associated with SCC, radiotherapy adjuvant to surgical is a useful diagnostic feature. excision is recommended [8]. 123 Eur Arch Otorhinolaryngol (2013) 270:5–20 7 The etiology of inverted papilloma is not completely ‘‘Hybrid’’ oncocytic/inverted papillomas may be seen. This understood and the molecular events that lead to its evo- in conjunction with the various similarities may tempt the lution are not well studied. More extensively investigated, pathologist to adopt a ‘‘lumper’’ rather than ‘‘splitter’’ is the relationship between inverted papilloma and human attitude while reporting on sinonasal papillomas. It may be papilloma virus (HPV). Unfortunately, the data on this prudent, however, to distinguish these various subtypes, as relationship are controversial and whether HPV is causa- not yet further substantiated preliminary data suggest that tive or a bystander is debatable [9]. However, most studies oncocytic papilloma may show a higher rate of recurrence/ using sophisticated and sensitive technologies, have iden- malignant transformation [13]. Importantly, the same tified up to 30 % of inverted papillomas as positive for treatment principles apply for oncocytic papillomas as for HPV [10]. Interestingly, at least one study also examined inverted papilloma [13]. p16ink4a in the same cases, and found that expression was nearly ubiquitous, regardless of HPV status, implying that Exophytic papilloma p16 cannot be used as a surrogate marker in these cases, as it is in HPV-associated SCC of other mucosal sites [11]. Exophytic papilloma (everted papilloma or fungiform papilloma) is mainly seen in men and occurs at a younger Oncocytic papilloma age than inverted/oncocytic papilloma [1, 12]. Exophytic papillomas are usually seen in the vicinity of the lower This lesion is also known as cylindrical cell papilloma or nasal septum and only rarely occur on the lateral nasal wall columnar cell papilloma. It can occur at the
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