Small cell neuroendocrine carcinoma of the paranasal sinuses is an extremely rare and aggressive neoplasm. Despite aggressive management, the tumor carries a poor prognosis, with a high risk of local recurrence or distant metastases. The management strategy is based on that for pulmonary small cell cancer and includes platinum-based chemotherapy combined with radiotherapy. We are reporting a case of an 89-year-old female patient diagnosed with small cell carcinoma of right-sided ethmoid and sphenoid sinuses. The tumor was found to have invaded the right orbit and anterior cranial fossa. Metastases to cervical lymph nodes and bone were also found. Due to the extended stage and poor prognosis of the patient, the management plan is palliative chemoradiotherapy.
Small cell carcinoma (SCC) is a poorly differentiated neuroendocrine tumor that most commonly occurs in the lung [
An 89-year-old female with a history of hypertension, hypercholesterolemia, glaucoma, and osteoarthritis presented with a history of headaches and facial pain over the right side of her face for one month. Other symptoms included decreased vision in the right eye, intermittent diplopia, difficulty in closing the right eye, and gait unsteadiness. She described having overall fatigue and lower back pain, worse on walking, for the past 3 months. There was no past history of cigarette smoking. Physical examination was positive for complete right eyelid closure, no overlying skin changes and no cervical lymphadenopathy. Brain CT and MRI scans revealed a large sinonasal mass involving the ethmoid/sphenoid sinuses and extending into the right orbit and anterior cranial fossa (Figures
Axial noncontrast brain CT (bone algorithm image) showing a large sinonasal mass involving the ethmoid/sphenoid minuses (arrows) with right orbital extension (arrowhead).
Axial FLAIR T2-weighted brain MRI showing a sinonasal mass involving the ethmoid/sphenoid sinuses (white arrows) with extension into the right orbit (black arrowhead).
Coronal T2-weighted brain MRI showing a sinonasal mass involving the ethmoid/sphenoid sinuses (white arrows) with extension into the right orbit (white arrow head) and anterior cranial fossa (black arrow).
Hematoxylin and eosin staining showing nasal mass with small cell carcinoma (a), immunohistochemical staining showing tumor positivity for AE1/AE3 in a dot-like pattern (b), synaptophysin (c), and high-risk HPV by in situ hybridization (d). (a) The tumor consisted of a uniform population of small cells with minimal cytoplasm and hyperchromatic, angulated nuclei that demonstrated molding. The tumor exhibited high grade features including a high mitotic rate and necrosis (hematoxylin and eosin, ×400). (b) The neoplasm was positive for cytokeratin on a perinuclear, dot-like pattern (AE1/AE3 immunohistochemistry, ×400). (c) The tumor exhibited neuroendocrine differentiation in the form of diffuse staining for synaptophysin (synaptophysin immunohistochemistry, ×400). (d) HPV studies showed that the tumor harbored high-risk HPV DNA (high-risk HPV in situ hybridization, ×400).
Given the extent of her disease proximal to the orbit, she was started on chemotherapy urgently as inpatient for the first cycle. So far, she has completed 3 cycles of carboplatin/etoposide. Her complications have been mild but include fatigue that peaked with her second cycle of chemotherapy. The fatigue has improved with initiation of packed red blood cell transfusions to treat her chemotherapy induced anemia. Her baseline hemoglobin level was 12 g/dL and decreased to 9 g/dL prior to transfusions. She also developed acute renal insufficiency with a creatinine of 1.6 mg/dL, increased from a baseline of 1.0 mg/dL previously. This developed after the third cycle of chemotherapy. The creatinine returned to baseline with intravenous fluids. Regarding the presenting symptoms of headaches and vision disturbances, these have decreased but not entirely resolved. The headaches are less frequent and now only mildly impaired. A repeated head MRI was done after the third cycle that demonstrates a very good partial response at the site of the primary lesion. The ethmoid lesion has entirely resolved and around 50 percent reduction in the size of the inferior frontal lobe mass. There is still a slight enhancement noted on the orbital nerve but otherwise the lesion in that region has regressed. A restaging PET scan for systemic response is pending at this time.
Carcinoma of the nasal cavity and paranasal sinuses is an uncommon tumor, with an incidence of less than 1 per 100,000 persons per year [
According to the World Health Organization criteria, small cell carcinomas are 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 [
EPSCC of the sinonasal tract has a slight male predominance. It can occur in any age group, and the mean age at presentation is 51–58 years [
Human papilloma virus (HPV) infection is a possible risk factor for small cell carcinoma in the sinonasal tract [
Furthermore, paraneoplastic syndromes, seen in small cell lung cancer, are not common with EPSCC [
Due to the rarity of the disease, clinical trials to identify the optimal management for EPSCC have not been done. Retrospective studies and case reports consistently recommend that EPSCC be managed similar to pulmonary SCC [
In conclusion, the patient in this case was an 89-year-old female who presented with headaches and visual disturbances due to a sinonasal mass with intracranial extension. Biopsy revealed small cell carcinoma of the ethmoid and sphenoid sinuses of the right side, and further investigations demonstrated lymph node and multiple bone metastases. Due to the advanced stage and extensive spread of the tumor, the prognosis in this case is very poor, with an estimated survival of less than 2 years [
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors gratefully acknowledge Dr. Satomi Kawamoto for her expert assistance with the radiological images.