DISCUSSION
Sinonasal tract carcinoma accounts for about 3-5% of total malignancies in the head and neck.6 SMARCB1 is a tumor suppressor gene which is located on chromosome 22q11. It is present in the nucleus of all normal cells and is responsible for the regulation of gene transcription and proliferation.7 SMARCB1 mutation is responsible for the pathogenesis of other malignancies, which include atypical teratoid and malignant rhabdoid tumors, epithelioid sarcoma, renal medullary carcinoma, myoepithelial carcinoma of soft tissue, epithelioid malignant peripheral nerve sheath tumor, and extraskeletal myxoid chondrosarcoma.2,8
SMARCB1-deficient carcinoma commonly arises in the nasal cavity or ethmoid sinus. However, multiple sites are also frequently involved. The most common clinical presentations are nasal obstruction, headache, epistaxis, proptosis, or visual defects owing to the mass effect. Most of the cases present in the late T4 stage with the involvement of the bone, skull base, or periorbital invasion.9 Our patient presented with complaints of right-sided nasal obstruction for several months along with associated occasional nasal bleeding and hyposmia. The carcinoma is involved in the right posterior ethmoid sinus and right frontal sinus reaching up to the nasal cavity along with the erosion of adjacent bones involving right fovea ethmoidalis, lateral lamella, vertical lamella, and middle turbinate. Due to the clinical presentations similar to benign conditions such as allergic rhinitis, nasal polyps, and chronic sinusitis, the cases are identified at a late stage when the carcinoma is already locally aggressive and invasion of the bones owing to challenges in the complete surgical removal.5
Histomorphological examination of the SMARCB1-deficient sinonasal carcinomas shows round tumor cells and anastomosing nests of tumor cells which are separated by bands of fibrous stroma. The tumor cells have enlarged round nuclei with prominent nucleoli. The cytoplasm of tumor cells can be scant to abundant. In the tumor cells with scant cytoplasm, they have basaloid morphology; while other tumor cells have abundant, eccentric, eosinophilic cytoplasm depicting a rhabdoid appearance.2Tumors with the basaloid morphology are characterized by undifferentiated or “blue cell” tumors with high nuclear: cytoplasmic ratios, prominent nucleoli, scant cytoplasm, and sheet-like, nest-like, or palisading arrangements while the rhabdoid tumors are characterized by “pink cell tumors” with abundant eosinophilic cytoplasm and eccentric nuclei.1,2,9,10In our case, tumor cells are arranged in papillary patterns, sheets, and clusters infiltrating into the fibrotic stroma. These tumor cells are basaloid in appearance and exhibit pleomorphism. Cells have a high nucleo-cytoplasmic ratio, hyperchromatic nuclei, few visible nucleoli, and a scant amount of cytoplasm. Mitosis and areas of necrosis seen.
On IHC analysis, tumor cells of SMARCB1 deficient sinonasal carcinoma are diffusely positive for pancytokeratin. Some cases of SMARCB1-deficient sinonasal carcinoma show diffuse p63/40 stains while neuroendocrine markers synaptophysin/chromogranin are positive in around 30% of cases. Tumor cells show loss of SMARCB1 (INI-1) expression while S100, SMA, calponin, CD99/NKX2.2, and NUT1 are usually negative.9,11,12 In our case, on IHC, the tumor cells are positive for CK5/6, EBV, CK, and P40 and negative for S-100 while INI-1 showed loss of expression. Differential diagnoses include Sinonasal undifferentiated carcinoma, NUT carcinoma, Myoepithelial carcinoma, and HPV-related multi-phenotypicsinonasal carcinoma:
The standard recommended treatment of potentially resectable disease for this condition is surgery followed by postoperative adjuvant RT or CCRT. However, some authors recommend that if there is >50% response to induction therapy then it is recommended to continue chemoradation. But if there is < 50% response to induction chemotherapy, then surgery followed by chemoradiation is advised.5,13Also, there have been different ongoing randomized clinical trials regarding the treatment modality of SMARCB1-deficient sinonasal carcinoma. One of the ongoing studies is the phase II clinical trials to investigate a specific EZH2 inhibitor therapy as a target therapy for SMARCB1-deficient cancers.14
Loss of SMARCB1(INI-1) expression has a poor prognosis compared with tumors in which SMARCB1 expression is retained.15 The rate of recurrence and mortality is also high in SMARCB1(INI-1)-deficient tumors. 5-year survival rate of these patients is only 34.9%.16,17 The reported distant metastasis is to the lungs, brain, pleura, bone, and liver.5