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