Malignancies arising in oncocytic schneiderian papillomas: a report of 2 cases and review of the literature.
REPORT OF CASES
A 71-year-old white man presented to the Dallas Veterans Affairs Medical Center with complaints of left nostril fullness for 2 months. On examination he had proptosis on the left side. A computed tomographic scan of the head revealed a large maxillary sinus mass eroding into the orbital floor and into the nasal cavity. A left medial maxillectomy with removal of the mass was performed. The patient presented 2 months after surgery with adenopathy on the left side of the neck, which showed metastatic SCC on fine needle aspiration. Scattered foci of metastatic SCC were seen in the bone marrow aspirate. Despite chemotherapy, he developed progressive disease involving his liver, spine, and brain and died 9 months after the first biopsy. No postmortem examination was performed.
A 64-year-old African American man presented to the Dallas Veterans Affairs Medical Center with a 4-month history of epistaxis and nasal airway obstruction. Examination revealed a polypoid mass within the left nasal cavity, replacing the left middle turbinate. A computed tomographic scan showed a 3-cm mass in the left nasal cavity, eroding the middle turbinate and abutting the septum. Biopsy of the mass followed by left medial maxillectomy and modified neck dissection was performed. The patient received adjuvant radiotherapy. The patient is in complete clinical remission 14 months after surgery.
The OSP comprised a minor component of the specimen. It was composed of multilayered columnar epithelium that showed both exophytic and inverted growth patterns. The cytoplasm was deeply eosinophilic and granular Numerous mucinous microcysts, some with neutrophils within them, were present in the epithelium. Cytologic atypia or mitotic activity was not seen. The bulk of the specimen, however, was composed of an SCC, with the neoplastic cells having irregular hyperchromatic nuclei, inconspicuous nucleoli, abundant mitotic activity, and single cell necrosis. Nuclear "crush" artifact and molding were present focally. The SCC was intimately associated with the OSP, and in some areas, the epithelium of the OSP was undermined by nests of SCC (Figure, a and b). Immunohistochemical analysis demonstrated diffuse reactivity for cytokeratin AE1/AE3 in the OSP and focal reactivity in the SCC. Focal neuron-specific enolase (NSE) and chromogranin expression was restricted to the SCC, whereas phosphotungstic acid and Luxol fast blue, which stain mitochondria, were positive in the OSP. Ultrastructural examination showed neoplastic cells with prominent nuclear molding and occasional dense core neurosecretory granules, consistent with an SCC.
The initial biopsy specimen showed a tiny focus of classic OSP, with most of the epithelium being composed of markedly dysplastic cells that merged into areas of frank carcinoma in situ. The maxillectomy specimen showed more classic areas of OSP, in conjunction with an invasive SNUC. The SNUC was characterized by sheets of medium-sized polygonal cells with round to oval nuclei and conspicuous nucleoli. Mitotic figures and necrosis were abundant. There was histologic continuity from benign oncocytic epithelium to areas of dysplasia and carcinoma in situ; the latter were intimately associated with intramucosal nests of SNUC (Figure, c and d). Immunohistochemical analysis of the SNUC (see Table 2 for antibody specifications) showed reactivity restricted to cytokeratin CAM 5.2, with lack of expression of cytokeratin AE1/AE3, synaptophysin, chromogranin, NSE, HMB-45, S100, leukocyte common antigen, CD20, and CD3.
Despite their histologic benignity, sinonasal papillomas have a small but definite potential for malignant transformation. Virtually all serious complications of sinonasal papillomas, including progression to local invasion, copresentation with carcinoma, and development of a subsequent malignancy, have been associated with the inverted papilloma. Seven of 83 sinonasal papillomas in the series by Kristensen et al (3) developed either synchronous or metachronous carcinomas, all arising in inverted papillomas. Similarly, Nachtigal et al (4) reported a series of 72 sinonasal papillomas, of which 8 inverted papillomas underwent malignant transformation. Malignancies arising in OSPs are an extremely rare event (Table 1). In the original series of Hyams, (2) 1 of 10 OSPs had an associated malignancy, an invasive squamous cell carcinoma. Subsequently, Barnes and Bedetti (7) reported a coexistent OSP and high-grade mucoepidermoid carcinoma. Ward et al (8) reported 2 cases of invasive carcinomas arising in an OSP, the first a poorly differentiated, nonkeratinizing squamous cell carcinoma and the second a papillary transitional carcinoma. They were the first to document that the surface epithelium in an OSP can be the site of origin for invasive carcinoma. Kapadia et al (9) reported 9 cases of carcinoma ex OSP, the largest series to date. These included 6 cases of squamous cell carcinomas, 2 cases of high-grade mucoepidermoid carcinoma, and 1 case of an SNUC. Most recently, Yang and Abraham (10) have reported the second case of SNUC and the 14th case overall of a malignancy arising in an OSP.
To our knowledge, we describe the first reported association of an SCC and OSP and the third report of an SNUC arising in OSE Sinonasal undifferentiated carcinoma is a recently described highly aggressive neoplasm of the sinonasal tract. (11) It is not uncommon for these tumors to be associated with severe dysplasia of the overlying surface epithelium. Immunohistochemically, these tumors stain for cytokeratin CAM 5.2 and variably for NSE and epithelial membrane antigen. Ultrastructurally, these tumors are composed of cells with high nuclear-cytoplasmic ratios, conspicuous nucleoli, and rare, single, small membrane-bound dense-core granules, compatible with neurosecretory-type vesicles. The morphologic structure of SCC of the sinonasal tract is identical to its pulmonary counterpart. (12) Although there are superficial histologic similarities between SNUC and SCC, the latter is characterized by smaller cells with hyperchromatic nuclei, inconspicuous nucleoli, nuclear molding and nuclear "crush" artifact, and expression of one or more general neuroendocrine markers such as chromogranin or synaptophysin.
Both tumors showed an intimate relationship of the OSP to either SCC (case 1) or SNUC (case 2). This was better demonstrated in case 2, where benign oncocytic epithelium merged into foci of dysplastic epithelium and carcinoma in situ; the latter were admixed with nests of SNUC. As suggested by previous authors, (8-10) this raises the possibility that carcinomas arising in conjunction with OSPs represent malignant transformation of the papilloma, rather than juxtaposed "collision" tumors; however, the unequivocal proof of this requires molecular demonstration of clonality, which was not performed in our cases. An intriguing aspect of case 1 was the coexistence of a neuroendocrine tumor (SCC) with an epithelial neoplasm (OSP). The concept of multipotential neoplastic stem cells with a capacity for divergent differentiation is well established. (13) The coexistence of SCCs with neoplastic glandular or squamous elements has been reported at various anatomic sites, such as the respiratory and gastrointestinal tracts; conversely, neuroendocrine differentiation is frequently found in epithelial malignancies.
In conclusion, we report 2 additional cases of malignancies arising in OSPs, including the first case of a synchronous SCC and the third case of a synchronous SNUC. A small biopsy specimen from an OSP may at times only show foci of dysplastic epithelium or carcinoma in situ, with invasive carcinoma being revealed in the subsequent resection specimen. Therefore, pathologists need to stress the requirement for complete excision and thorough sampling of these benign tumors so as not to miss a coexistent carcinoma.
Table 1. Malignancies Arising in Oncocytic Schneiderian Papillomas Reference, y Cases Histology Hyams, (2) 1971 1 Squamous cell carcinoma Barnes and Bedetti, (7) 1984 1 Mucoepidermoid carcinoma Ward et al, (8) 1990 1 Squamous cell carcinoma (nonkeratinizing) Ward et al, (8) 1990 1 Papillary transitional carcinoma Kapadia et al, (9) 1993 6 Squamous cell carcinoma Kapadia et al, (9) 1993 2 Mucoepidermoid carcinoma Kapadia et al, (9) 1993 1 Sinonasal undifferentiated carcinoma Yang and Abraham, (10) 1997 1 Sinonasal undifferentiated carcinoma Current 1 Sinonasal undifferentiated carcinoma Current 1 Small cell carcinoma Table 2. Immunohistochemical Markers Used in the Study Antigen Dilution Company Cytokeratin AE1/AE3 1:40 BioGenex, San Ramon, Calif Cytokeratin CAM 5.2 Prediluted Becton Dickinson, Franklin Lakes, NJ Neuron-specific 1:4000 Dako Corporation, Carpinteria, enolase Calif Chromogranin A 1:300 Ventana, Tucson, Ariz Synaptophysin Prediluted Zymed, South San Francisco, Calif S100 Prediluted Zymed HMB-45 1:20 Dako Corp Leucocyte common 1:40 BioCare, Walnut Creek, antigen Calif CD20 1:40 BioCare CD3 1:200 Dako Corp
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Accepted for publication March 30, 2001.
From the Department of Pathology, University of Texas Southwestern Medical Center (Drs Maitra, Baskin, and Lee), and Dallas Veterans Affairs Medical Center (Dr Lee), Dallas, Tex.
Reprints: Anirban Maitra, MD, Department of Pathology, Johns Hopkins Medical Institutions, 600 N Wolfe St, Baltimore, MD 21287 (e-mail: firstname.lastname@example.org).
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|Author:||Maitra, Anirban; Baskin, Leland B.; Lee, Edward L.|
|Publication:||Archives of Pathology & Laboratory Medicine|
|Date:||Oct 1, 2001|
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