|Year : 2016 | Volume
| Issue : 2 | Page : 225-228
An extremely rare case report of sinonasal undifferentiated carcinoma of paranasal sinuses
Abhishek Purkayastha, Neelam Sharma, Tejas Pandya, Chhavi Arora
Department of Radiation Oncology, Army Hospital Research and Referral, New Delhi, India
|Date of Web Publication||20-Dec-2016|
Department of Radiation Oncology, Army Hospital Research and Referral, Dhaula Kuan, Delhi Cantonment, New Delhi - 110 010
Source of Support: None, Conflict of Interest: None
Sinonasal undifferentiated carcinoma (SNUC) of the paranasal sinuses represents a very rare and extremely aggressive malignancy posing a diagnostic and therapeutic dilemma for treating physicians due to its location, vast array of differential diagnosis without any definite therapeutic guideline. With only a few cases described in the literature, we hereby report a 34-year-old male with progressive, painless swelling of the left eye and diminution of vision. Radiographic imaging showed a mass lesion in the left anterior ethmoid sinus. Biopsy of nasal mass seen on nasal endoscopy revealed a poorly differentiated malignancy. He underwent craniotomy and excision of tumor. Postoperative histopathology report showed SNUC staining positive for epithelial membrane antigen, neuron-specific enolase, and cytokeratin on immunohistochemistry. He received postoperative radiotherapy (RT) and chemotherapy but developed extensive skeletal metastasis, for which he was treated with palliative RT to which he responded well. At present, he was on close follow-up with a Karnofsky performance status of 60%.
Keywords: Chemotherapy, palliation, paranasal sinuses, radiotherapy, sinonasal undifferentiated carcinoma
|How to cite this article:|
Purkayastha A, Sharma N, Pandya T, Arora C. An extremely rare case report of sinonasal undifferentiated carcinoma of paranasal sinuses. Arch Med Health Sci 2016;4:225-8
|How to cite this URL:|
Purkayastha A, Sharma N, Pandya T, Arora C. An extremely rare case report of sinonasal undifferentiated carcinoma of paranasal sinuses. Arch Med Health Sci [serial online] 2016 [cited 2017 Jul 27];4:225-8. Available from: http://www.amhsjournal.org/text.asp?2016/4/2/225/196203
| Introduction|| |
Sinonasal undifferentiated carcinoma (SNUC) of the paranasal sinuses (PNS) is a rare  and extremely aggressive malignancy with a unique clinicopathological characteristic. The final prognosis and outcome of SNUC have generally been extremely poor despite an aggressive multimodality treatment approach. The aim of reporting this rare malignancy is to highlight the fulminant and highly aggressive nature of this disease and the role of radiotherapy (RT) not only as a definitive treatment modality but also as a palliative option to rehabilitate and improve the quality of life in patients suffering from painful bony metastasis.
| Case Report|| |
A 34-year-old male presented with progressive painless swelling of the left eye [Figure 1] with diminution of vision. Magnetic resonance imaging (MRI) of the face and brain [Figure 2] showed a mass lesion in the left anterior ethmoid sinus filling left nasal cavity and pushing the medial wall of the left orbit causing proptosis with intracranial extension. Biopsy showed poorly differentiated malignancy. Immunohistochemistry (IHC) was positive for epithelial membrane antigen (EMA), cytokeratin (CK), and neuron-specific enolase (NSE). S-100, chromogranin, and synaptophysin stained negative. Positron emission tomography (PET) scan showed a localized disease with no evidence of metastasis.
|Figure 1: Patient on presentation with progressive painless swelling of the left eye.|
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|Figure 2: Magnetic resonance imaging of the face and brain showing a well-defined expansile lobulated mass lesion in the left anterior ethmoid sinus crossing the midline, filling the left nasal cavity, and pushing the medial wall of left orbit causing proptosis with intracranial extension (yellow pointer).|
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The patient underwent bifrontal craniotomy with gross total resection of tumor, left orbital exenteration, and reconstruction of the anterior skull base. However, postoperative MRI showed a residual lesion. Histopathology report revealed undifferentiated sinonasal carcinoma with tumor cells appearing as nests, sheets, and trabecular pattern with high mitotic rate and extensive necrosis [Figure 3]. IHC stained positive for EMA [Figure 4], CK [Figure 5], and NSE while negative for thyroid transcription factor-1 (TTF-1), vimentin, CD-99, CD 20, chromogranin, synaptophysin, leukocyte common antigen (LCA), desmin, S-100, melan A, p63, and terminal deoxynucleotidyl transferase (TdT). In situ hybridization for Epstein–Bar virus (EBV) was negative.
|Figure 3: Histopathology report showing undifferentiated sinonasal carcinoma with tumor cells appearing as nests, sheets, and trabecular pattern with high mitotic rate and extensive necrosis (H and E, ×50).|
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|Figure 4: Immunohistochemistry staining positive for epithelial membrane antigen (×200).|
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|Figure 5: Immunohistochemistry staining positive for cytokeratin (×100).|
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He received adjuvant RT to the brain, face, and neck by three-dimensional conformal RT (3-DCRT) technique to a dose of 50 Gy in 25 fractions at the rate of 200 cGy per fraction, followed by chemotherapy injection docetaxel and cisplatin. However, within 3 months, he developed painful skeletal metastasis to the left humerus, left femur, L2 and L5 vertebra, detected on PET scan [Figure 6]. We treated him with palliative RT to involved sites to a dose of 30 Gy in 10 fractions to which he showed significant symptomatic response. At present, he was on close follow-up with a Karnofsky performance status of 60% over 1 year. His requirement of analgesics has drastically reduced leading to a much better quality of life and is being planned for eye prosthesis.
|Figure 6: Positron emission tomography scan showing increased fluorodeoxyglucose uptake (a) left humerus and (b) left femur suggestive of metastasis (white pointer).|
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| Discussion|| |
SNUC of PNS is extremely rare accounting for <3% of all head and neck  tumors and 0.2–0.8% of all malignancies. It is a rapidly enlarging destructive lesion which tends to present with an orbital and intracranial extension outside the natural anatomical boundaries of the nasal cavity and PNS, resulting in morbid surgery and challenging radiation planning. The term SNUC was first coined by Frierson et al. in 1986 to a group of aggressive undifferentiated or anaplastic round blue cell tumor.
SNUC is known to arise from Schneiderian epithelium which lines the nasal cavity and the PNS. Males are affected more than females in their fourth to sixth decades. SNUC presents with rapid onset of symptoms such as nasal obstruction, nasal discharge, proptosis, diplopia, diminution of vision, epistaxis, and facial pain  resembling any benign lesion, resulting in delay of appropriate treatment. It has a high propensity for early local recurrence and metastasize to lymph nodes, brain, and spine while metastasis to lung, humerus, and femur is quite uncommon. Therefore, it becomes imperative to distinguish it from other sinonasal lesions because of its destructive behavior and dismal clinical outcome. Etiology of SNUC is much debated about, such as prior irradiation for retinoblastoma, smoking, and occupational exposure to coal, nickel, and chrome workers. No association has been found with EBV in contrast to nasopharyngeal carcinoma.,
Radiologic findings show a more anterior involvement of the nasal cavity and ethmoids by SNUC as compared to nasopharyngeal carcinoma. IHC differentiates, prognosticates, and diagnoses SNUC from other pathologies with small round cell tumor appearing at similar head and neck sites , such as sinonasal neuroendocrine carcinoma, nasopharyngeal carcinoma, lymphoma, melanoma, hemangiopericytoma, rhabdomyosarcoma, esthesioneuroblastoma, olfactory neuroblastoma, small cell carcinoma, and metastasis from lung or retinoblastoma. A battery of IHC markers demonstrate positivity for EMA, CK, and NSE while negativity for TTF-1, vimentin, CD-99, CD 20, LCA, chromogranin, synaptophysin, S-100, desmin, melan A, p63, and TdT and in situ hybridization for EBV (EBER-1) thus ruling out other pathologies or metastasis, confirming the diagnosis of SNUC.
Regarding treatment of SNUC, a few authors have proposed upfront surgery followed by RT and chemotherapy; however, they failed to demonstrate any disease-free survival or overall survival. Craniofacial resection with maxillectomy, orbital exenteration, and craniotomy are the most common surgical approaches while chemotherapy drugs such as cisplatin, carboplatin, etoposide,, doxorubicin, cyclophosphamide, docetaxel, vincristine, mitomycin-c, and 5-fluorouracil (5-FU) have been used by different institutes. Different chemotherapeutic agents have been described in published literature and majority have incorporated platinum analogs in combination with taxanes, etoposide, or 5-FU. However, the response to chemotherapy has not been extensively studied. Morphoproteomic-guided targeted therapy  with a combination of metformin, etoposide, doxorubicin, and cisplatin, with melatonin as an adjunct, has shown to produce complete clinical response. On these lines, we used docetaxel and cisplatin in our patient. Morphoproteomics combines morphology using bright field microscopy and IHC probes to identify protein analytes in tumor cells and the microenvironment which might define the unique biology of a tumor and expose potential therapeutic targets. Morphoproteomics can define the biology of a tumor and provides therapeutic options. It interrupts histogenetic and pathogenetic processes in a tumor cell that leads to tumoral growth and chemoradioresistance. The recent concept of using lapatinib against human epidermal growth factor receptor 2 expressed by SNUC cell lines can be a promising approach for treating this disease.
RT remains an integral part of treatment as it reduces local recurrence as definitive modality and improves quality of life in patients with debilitating bony metastasis by providing pain relief, preserving organ function, skeletal integrity, and rehabilitation as palliative therapy. Palliative RT provides symptomatic pain alleviation in approximately 60–85% of cases. Excellent results are obtained using RT to the involved area with appropriate megavoltage devices and time-dose-fractionation schedules. Intensity-modulated RT and 3-DCRT are the commonly employed RT techniques. Boron neutron capture therapy (BNCT) is a novel modality being attempted for optimal management in SNUC patients. BNCT is based on a nuclear capture reaction that occurs when boron captures a low energy neutron of <0.5 eV resulting in production of a high-energy alpha particle and a lithium ion. Intratumor delivery of boron is carried out by 4-dihydroxyboryl-L-phenylalanine which gets bombarded with neutrons. A single fraction of BNCT has shown to cause more significant radiological and clinical response in recurrent or refractory SNUC cases as compared to conventional fractionated RT. The availability of thermal neutron beams only at nuclear research reactors limits the use of BNCT.
Due to lack of randomized trials, optimal treatment algorithm is yet to be determined. The prognosis of SNUC remains extremely poor despite an aggressive multimodality treatment approach involving all three branches of oncology. We recommend that SNUC should be considered whenever any patient presents with proptosis or nasal stuffiness so as to enable a prompt initiation of diagnostic and therapeutic approach. Furthermore, a better understanding and interpretation of the molecular and biological mechanisms may help to devise optimal therapeutic strategies to counter this deadly disease. More sophisticated diagnostic techniques, improved cytogenetic analysis, more novel chemotherapy drugs with optimal RT schedules should be devised to improve the disease-free survival, overall survival, and quality of life of these patients.
We thank the patient for allowing us to publish the case and use the images taken during his stay in the hospital.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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