Primary Sinonasal Small Cell Neuroendocrine Carcinoma: A Case Report and Literature Review

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Primary Sinonasal Small Cell Neuroendocrine Carcinoma: A Case Report and Literature Review

Mayand Vakil1, Marc J. Gibber1*

1Department of Otorhinolaryngology – Head and Neck Surgery, Albert Einstein College of Medicine, Bronx, NY 10467

*Corresponding author: Dr. Marc J. Gibber, Department of Otorhinolaryngology – Head and Neck Surgery, Albert Einstein College of Medicine, 3400 Bainbridge Avenue, Medical Arts Pavilion, 3rd Floor, Bronx, NY 10467, Tel: (718) 920-8471; Fax: (718) 405-9014; Email: mgibber@montefiore.org

Abstract

Sinonasal small cell neuroendocrine carcinoma is a very rare, but aggressive cancer. It has a high rate of early metastases and local recurrence. Even with aggressive management, the prognosis is poor. Treatment is often based on cytotoxic chemotherapy and radiation. This case report details a case of a 68-year-old man diagnosed with small cell carcinoma of the right nares extending into the ethmoid sinuses with dehiscence of the cribrifrom plate and intracranial extension of disease. No distant metastases were found. His prognosis is poor based off grading and stage, but definitive therapy is currently being pursued with chemo radiotherapy.

Keywords

Extra pulmonary Small Cell Carcinoma; Sinonasal; Neuroendocrine Carcinoma

Introduction

Small cell neuroendocrine carcinomas are high grade epithelial neoplasms with predominant neuroendocrine differentiation. There are various types, depending on epithelial origin, but small cell carcinoma of the lung is the most common. [1] Extra pulmonary small cell neuroendocrine carcinomas (EPSCC) are exceptionally rare, but are very aggressive tumors with rapid expansion, and early hematogenous spread. They are also frequently associated with local recurrence and new distant metastases. Overall the prognosis for these tumors in poor. [2] In this article we report the case of a patient diagnosed with EPSCC of the right sino-nasal cavity with locally advanced disease with intracranial extension.

Case Report

A 68-year-old man with a history of hypertension, hyperlipidemia, benign prostatic hyperplasia, and adenomatous polyps of the gastrointestinal tract presented to outpatient otolaryngology clinic complaining of 3 weeks of recurrent heavy epistaxis from the right side of his nose approximately 2 times a day lasting about 1 hour each time. Additionally, he complained of right sided nasal congestion and dizziness. At the time of presentation, he denied any history of nasal or sinus problems, no history of facial trauma, pain, or unexplained weight loss. During the office visit, the patient was sent to the emergency department (ED) due to the persistence and severity of his bleeding as well as a visualized mass on exam. In the ED stay the bleeding was controlled with surgical packing, and a CT and MRI were done. CT of the sinuses revealed a soft tissue opacification within the right nasal cavity and dehiscence of the medial and lateral lamella of the right cribriform plate as well as complete opacification of the right ethmoid and sphenoid sinuses and deviation of the nasal septum to the left. (Figure 1) MRI furthered revealed the mass to be a large heterogeneously enhancing lobulated and spectated mass with a small area of intracranial extension through the cribriform plate. (Figures 2 and 3) A PET scan was also done, but revealed no distant metastasis or cervical lymphadenopathy. After interventional radiology embolization of the vascular supply to the mass, a biopsy was taken and immunohistochemically studies demonstrated tumor positivity for AE1/3, CAM5.2, synaptophysin, chromogranin, and CD56. Staining was negative for S100, and p40. Ki-67 showed a proliferative index of about 80-90%. The patient was diagnosed with high grade, locally invasive EPSCC, stage IVa, cT4aN0M0.

Figure 1: Coronal CT imaging showing soft tissue mass in right nasal cavity, maxillary sinus, and opacification of ethmoid sinuses with superior dehiscence of cribriform plate.

Figure 2: T1 weighted sagittal view showing right nasal mass with intracranial invasion and complete obstruction of sphenoid drainage

Figure 3: T1 weighted axial view showing septated heterogeneous mass in right nasal cavity and complete obstruction of sphenoid sinus

In conjunction between otolaryngology, medical oncology, and radiation oncology, the patient was started on chemotherapy and radiation treatment. So far, he has completed 4 cycles of carboplatin/etoposide, and 70 gray in 33 fractions. He has tolerated therapy fairly well with a few treatments related side effects including grade 2 mucositis, weight loss, nausea, and constipation. The mucositis on palate, nasal cavity, and tongue surfaces, is improving with mucositis cocktail. Weight loss is also improving from nadir of 15-pound loss. Tumor size has reduced with improvement in nasal congestion symptoms and reduced epistaxis. Most recent complete blood count reveals elevated white blood cells at 21 thousand per microliter from 7.7 at the start of therapy. He is hyponatremia to 130 mEq/L, down from 139 mEq/L. Otherwise creatinine and blood urea nitrogen have been within normal limits and stable.

Discussion

Sinonasal carcinoma is a very rare cancer, with an incidence rate of less than 1 per 100,000 per year. [3] EPSCC is incredibly rare as well. Approximately 2.5% of all small cell carcinomas present in extra pulmonary sites, these account for 0.1% to 0.4% of all malignancies. [4] In the past 45 years there have only been 77 reported cases of small cell neuroendocrine carcinomas of the paranasal region in the medical literature. [5] Diagnosis of this malignancy is made by histopathological appearance. According to the World Health Organization small cell neuroendocrine carcinoma defined as malignant epithelial tumors consisting of small cells with scant cytoplasm, ill-defined borders, granular nuclear chromatin, absent nucleoli with extensive necrosis and high mitotic count. The tumor often also stains positive for synaptophysin, CD56, and chromogranin A. [6] Grading is broken into 4 levels from lowest to highest: carcinoid (grade 1), atypical carcinoid (grade 2), large cell neuroendocrine (grade 3 large cell), and small cell neuroendocrine (grade 3 small cell). [7] Grading is determined by Ki-67 index (a marker for mitosis and cell proliferation), and mitotic figures per high power field. Higher grading connotes a more aggressive tumor and is an important prognostic factor for neuroendocrine tumors. [8]

A retrospective study by Wong and colleagues demonstrated that EPSCC has a slight male predilection with an incidence rate of 0.45 per 100,000 in males and 0.37 per 100,000 in females. Compared to pulmonary small cell carcinoma, EPSCC is approximately 15 times rarer. [9] The most common site of EPSCC is the gastrointestinal tract at 33%, next is genitourinary at 20%.  Head and neck EPSCCs made up 11% of the cancers found in this study. [9] Several other studies by other groups have found similar incidences and location distributions. [10,11] Overall these cancers have a poor prognosis and a prone to metastasis and recurrence. [2] Survival varies based on location of disease gastrointestinal and chest malignances have the worst 3-year survival rates, 8% and 7% respectively. While head and neck lesions have a 16% survival rate at 3 years. [9] Other poor prognostic factors include extensive disease (defined by any indication of spread beyond local boundaries), medical comorbidities, and hyponatremia. Although, the hyponatremia may not be an independent prognostic factor due to its association with high staging. Interestingly however, age, smoking status or history, and white blood cell count was not associated with worse prognosis. [12] Due to the rarity of paranasal EPSCC, there are no evidence based specific recommendations. [13] However, a large retrospective review head and neck using the national cancer database of 851 cases found that the most common therapy for locally advanced disease was chemotherapy and radiation. They didn’t find any improvement in survival rates with multimodal therapy verses single modality therapy. [14]

EPSCC is quite different from other tumors of that more often occur in the Sinonasal tract. Treatment options are more align with pulmonary small cell carcinoma. For limited disease curative treatment is certainly possible using the same therapies utilized for pulmonary small cell carcinoma. For extensive disease however, EPSCC has an incredibly poor prognosis with a median survival of 0.7 years. [15] As far as head and neck EPSCC goes, nasal cavity neoplasms had the best overall survival with 53% surviving at the 3-year mark. [14]

Conclusion

The patient was found to have stage IVa locally spread small cell carcinoma of the right nasal cavity and extending into the ethmoid sinuses and intracranially. Prognosis is poor based off grading and stage, but definitive therapy is currently being pursued.

References

 

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