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Sinonasal undifferentiated carcinoma as a third primary neoplasm: a case report and review of the literature.

Abstract

A 71-year-old man with a history of a pituitary prolactinoma and metastatic pancreatic carcinoma presented with epistaxis, visual changes, bilateral ophthalmoplegia, involuntary closure of the left eye, and ptosis of the right eye. The patient was found to have a soft-tissue mass in the posterior nasal cavity with extension through the floor of the sella turcica, the sphenoid sinuses, cavernous sinuses, and suprasellar region. The patient was subsequently taken to the operating room. Intraoperative frozen section of the sinonasal mass demonstrated carcinoma. The final pathology of the mass revealed sinonasal undifferentiated carcinoma(SNUC)--the patients second skull base lesion and third primary neoplasm. SNUC is a rare neoplasm of the sinonasal cavities that rapidly progresses from symptom onset to mortality in the presence of aggressive multidimensional therapies. Given its poor prognosis and possibly devastating treatments, an open discussion of treatment options between physicians and the patient is of the utmost importance. Although SNUC is rare, it is important that practicing otolaryngologists, neurosurgeons, and skull base surgeons be familiar with this disease process--especially when caring for patients with a history of a benign skull base neoplasm and concern for possible recurrence, as was the case in this report.

Introduction

Sinonasal undifferentiated carcinoma (SNUC) is a rare neoplasm of the nasal cavity and paranasal sinuses. Patients frequently present with extensive local disease involving the superior nasal cavity and ethmoid sinuses. Disease may also invade the anterior skull base and orbits. Presenting complaints include epistaxis, visual changes, nasal obstruction, headache, and facial pain. (1)

Because of its locally aggressive behavior, SNUC carries a poor prognosis. It was first described by Freirson et al in 1986. (2) SNUC can be considered as part of a spectrum of neuroendocrine-type tumors of the sinonasal cavity, ranging from the highly differentiated esthesioneuro blastoma to the poorly differentiated and questionably neuroendocrine SNUC. (3) Although the exact etiology and histopathogenesis are unknown, it has been suggested that the neoplasm may arise within Schneiderian epithelium. (2)

Case report

A 71-year-old man with a history of a pituitary prolactinoma and metastatic pancreatic carcinoma presented with intermittent epistaxis of 2 weeks' duration. The patients pituitary prolactinoma had been diagnosed 3 years earlier. The tumor was approximately 2 cm in diameter with extension into the left cavernous sinus region. Subsequently, the patient underwent a transsphenoidal adenohypophysectomy.

At the current presentation, the patient presented with intermittent epistaxis, visual changes, bilateral ophthalmoplegia, involuntary closure of the left eye, and ptosis of the right eye. Fiberoptic nasopharyngeal examination revealed fleshy polypoid lesions suspicious for tumor in the bilateral posterior nasal cavities. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed the presence of a soft-tissue-density mass with extension through the floor of the sella turcica, the sphenoid sinuses, cavernous sinuses, and suprasellar region (figure 1).

During the 3-year period between the initial pituitary resection and the current presentation of epistaxis, the patient was also found to have pancreatic carcinoma with radiographic suggestion of hepatic metastases. He had refused medical treatment for his pancreatic carcinoma. The patients cancer antigen 19-9 (CA 199) at presentation was 16 U/ml (normal range: 0 to 37 U/ml).

The patient was subsequently taken to the operating room for a second transsphenoidal excision of the presumed recurrence of pituitary prolactinoma. During the endoscopic approach for the transsphenoidal procedure, soft-tissue masses were noted to be obstructing the superior nasal cavities bilaterally. The obstructing masses were biopsied, and intraoperative frozen-section pathology returned as carcinoma. The surgical procedure was then concluded.

The final pathology of the mass was SNUC, the patients second skull base lesion and third primary neoplasm. Histopathologic examination revealed sheets of moderately pleomorphic cells with a high nucleus-to cytoplasm ratio, fine chromatin, high mitotic rate, and single-cell necrosis (figure 2). Immunohistochemical studies revealed that the tumor cells were positive for pancytokeratin and synaptophysin. The cells were negative for myogenic differentiation 1, myogenin, desmin, HMB-45, S-100 protein, and prolactin.

Comparisons were also made with histologic specimens of this patients previously resected pituitary adenoma, which suggested that the two surgical specimens were histopathologically distinct. Additionally, the tumor showed no glandular differentiation, making metastatic pancreatic adenocarcinoma unlikely. The nasal tumor was also morphologically and immunologically distinct from hepatic metastases of the patients pancreatic adenocarcinoma.

Discussion

SNUC is composed of small to medium-sized cells arranged in nests, sheets, and trabeculae, conferring a neuroendocrine appearance. However, apoptosis may sometimes lead to a discohesive lymphomatous appearance. (3) The cells possess a high nucleus-to-cytoplasm ratio with scant eosinophilic cytoplasm. (2,4) Tumor necrosis, vascular invasion, and high mitotic activity are other findings commonly seen in SNUC. (2) Notably, Homer Wright rosettes, fibrillary background, keratinization, and glandular formation are absent in SNUC but are often seen in other neoplasms. (3) SNUC generally stains positively for cytokeratin, with variable staining for the neuroendocrine markers chromogranin, neuron-specific enolase, synaptophysin, and S-100. (3,4)

The differential diagnosis for SNUC spans lymphoma, esthesioneuroblastoma, melanoma, squamous cell carcinoma, rhabdomyosarcoma, and nasopharyngeal-type undifferentiated carcinoma. SNUC can be distinguished from other sinonasal disease via histologic evaluation, immunohistochemical staining and, if necessary, electron microscopy. The histologic appearance of SNUC differs from sinonasal lymphoma, as the latter does not exhibit the nests, sheets, and trabeculae characteristic of neuroendocrine tumors.

SNUC can be distinguished from esthesioneuroblastomas by the histologic occurrence of intercellular fibrils and periodic Homer Wright rosettes in esthesioneuroblastomas. Esthesioneuroblastomas also exhibit a different immunohistochemical profile, which includes the neuroendocrine markers chromogranin, synaptophysin, and S-100.5 While melanoma shares histologic similarities with SNUC, melanoma stains strongly for melanin and S-100.

Squamous cell carcinoma and basaloid carcinoma can be differentiated from SNUC by the absence of keratinization in SNUC. (3) Nonkeratinizing squamous cell carcinomas canbe differentiated by theirtendency toward greater amounts of eosinophilic cytoplasm than seen in SNUC. (6) Rhabdomyosarcomas typically stain positively for desmin, myoglobin, and vimentin, while staining negatively for the epithelial markers (cytokeratin, epithelial membrane antigen) and neuron-specific enolase. (7)

Nasopharyngeal-type undifferentiated carcinoma exhibits histologic characteristics not often seen in SNUC. The presence of an inflammatory lymphocytic infiltrate, large vesicular nuclei, syncytial pattern, and spindle tumor cells and the absence of necrosis are highly suggestive of nasopharyngeal-type undifferentiated carcinoma. (6) Distinguishing SNUC and nasopharyngeal-type undifferentiated carcinoma is critical as the two entities differ in relation to Epstein-Barr virus (EBV), response to radiation therapy, and prognosis. Nasopharyngeal-type undifferentiated carcinoma exhibits a strong association with EBV, good response to radiation therapy, and significantly longer disease-free survival (61 % disease- free survival at a median follow-up of 48 months). (6)

A universally accepted staging system for SNUC does not exist. Historically, the Kadish system has been used to describe the extent of disease. (8) However, patients may also be staged according to the American Joint Committee on Cancer (AJCC) staging system for nasal cavity and ethmoid sinus disease. (9)

While multimodality treatment is universally recommended, there is little evidence in the literature for a universally accepted treatment protocol. Musy et al published a treatment regimen beginning with three cycles of chemotherapy (cyclophosphamide, doxorubicin, and vincristine) and radiotherapy to 5,000 cGy. (1) Then, 1 to 2 months following the completion of radiotherapy, surgery is performed, usually involving a craniofacial resection or medial maxillectomy. (1) Exclusion criteria for surgery include invasion of the cavernous sinus, orbital apex, or brain, or extensive disease of the infratemporal fossa. (1)

Patients with unresectable tumors are treated with definitive radiotherapy and adjuvant chemotherapy. (10) Rischin et al reported the use of a nonsurgical approach to SNUC with comparable outcomes to the published data on SNUC outcomes. (11) This study group implemented chemotherapy and external beam radiotherapy to a median dose of 5,400 cGy. The chemotherapy regimen included induction with three cycles of cisplatin or carboplatin combined with 5-fluorouracil (5-FU). Additionally, two cycles of single- agent platinum were administered during radiation therapy. (11)

With or without the possibility of cure, the primary objective of treatment remains locoregional disease control, as the sinonasal region contains many structures vital to the patient's quality of life.

In spite of aggressive therapies, SNUC carries a poor prognosis, with median survival in reported series of less than 2 years and variable disease-free survival rates with treatment. Given this bleak prognosis, consideration must be made for the patient's quality of life. Furthermore, without a universally accepted treatment strategy, the management of this disease requires open communication between the physician and patient.

While reports of various treatment regimens are present in the literature, the relative infrequency of this disease renders appropriate clinicopathologic characterization difficult. There is a need for more studies to determine the most effective management strategy. Although this disease process is rare, it is important that practicing otolaryngologists, neurosurgeons, and skull base surgeons be familiar with it, especially when caring for patients with a history of a benign skull base neoplasm and concern for possible recurrence, as was the case in this report.

References

(1.) Musy PY, Reibel JF, Levine PA. Sinonasal undifferentiated carcinoma: The search for a better outcome. Laryngoscope 2002;112(8 Pt 1): 1450-5.

(2.) Frierson HF Jr., Mills SE, Fechner RE, et al. Sinonasal undifferentiated carcinoma: An aggressive neoplasm derived from Schneiderian epithelium and distinct from olfactory neuroblastoma. Am J Surg Pathol 1986;10(11):771-9.

(3.) Smith SR, Som P, Fahmy A, et al. A clinicopathological study of sinonasal neuroendocrine carcinoma and sinonasal undifferentiated carcinoma. Laryngoscope 2000; 110(10 Pt l):1617-22.

(4.) Cerilli LA, Holst VA, Brandwein MS, et al. Sinonasal undifferentiated carcionoma: Immunohistochemical profile and lack of EBV association. Am J Surg Pathol 2001;25(2):156-63.

(5.) Hirose T.Scheithaurer BW, Lopes MB, et al. Olfactory neuroblastoma: An immunohistochemical, ultrastructural, and flow cytometric study. Cancer 1995;76(1):4-19.

(6.) Jeng YM, Sung MT, Fang CL, et al. Sinonasal undifferentiated carcinoma and nasopharyngeal-type undifferentiated carcinoma: Two clinically, biologically, and histopathologically distinct entities. Am J Surg Pathol 2002;26(3):371-6.

(7.) Ejaz A, Wenig BM. Sinonasal undifferentiated carcinoma: Clinical and pathologic features and a discussion on classification, cellular differentiation, and differential diagnosis. Adv Anat Pathol 2005; 12(3): 134-43.

(8.) Kadish S, Goodman M, Wang CC. Olfactory neuroblastoma: A clinical analysis of 17 cases. Cancer 1976;37(3):1571-6.

(9.) American Joint Committee on Cancer. Nasal cavity and paranasal sinuses. In: Greene FL, Page DL, Fleming ID, et al (eds). AJCC Cancer Staging Manual, 6th ed. New York: Springer-Verlag; 2002:59-67.

(10.) Mendenhall WM, Mendenhall CM, Riggs CE Jr., et al. Sinonasal undifferentiated carcinoma. Am J Clin Oncol 2006;29(1):27-31.

(11.) Rischin D, Porceddu S, Peters L, et al. Promising results with chemoradiation in patients with sinonasal undifferentiated carcinoma. Head Neck 2004;26(5):435-41.

From the Division of Facial Plastic and Reconstructive Surgery, Washington University, St. Louis (Dr. Chi); and the Department of Pathology and Laboratory Medicine (Dr. Feldman) and the Department of Otorhinolaryngology-Head and Neck Surgery (Dr. Palmer) University of Pennsylvania Health System, Philadelphia. The case described in this article occurred at the University of Pennsylvania Health System.

Corresponding author: John J. Chi, MD, Division of Facial Plastic and Reconstructive Surgery, Washington University, 1020 N. Mason Rd., Suite 205, St. Louis, MO 63141. Email: ChiJ@ent.wustl.edu

Previous presentation: This article has been updated from its presentation as a poster at the North American Skull Base Society Meeting; October 16-18, 2009; New Orleans.
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Title Annotation:ORIGINAL ARTICLE
Author:Chi, John J.; Feldman, Michael D.; Palmer, James N.
Publication:Ear, Nose and Throat Journal
Article Type:Case study
Geographic Code:1USA
Date:Apr 1, 2015
Words:1867
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