ⅠIntroduction
Malignant tumors of the sinonasal tract are ex­
tremely rare, accounting for only 3 ％ of all head and 
neck cancers1）. Sinonasal tumors show similar clinical 
manifestations, such as nasal obstruction and epistax­
is, but a wide range of histological features, including 
histogenesis and differentiation of tumor cells2）. Sin­
onasal undifferentiated carcinoma (SNUC), originally 
described by Frierson et al. in 19863）, is an extremely 
rare and high-grade neoplasm arising in the nasal 
cavity with highly aggressive clinical behavior and 
poor prognosis1）-7）. In a study of 36 cases of SNUC, 
Jeng et al.8） reported that 17 ％ and 31 ％ of patients 
presented with cervical lymph node and distant me­
tastasis, respectively, and had a median survival pe­
riod of 10 months. Multimodal therapies have been 
proposed for SNUCs, including surgery, radiothera­
py, and chemotherapy, but a standard treatment 
strategy has not been determined because of its 
rarity. We encountered a case of locally advanced 
SNUC treated with cisplatin＋etoposide chemothera­
py combined with radiotherapy, which showed a 
survival period of＞5 years without recurrence. Here, 
we describe the clinical course of this case along 
with a brief review of the relevant literature, focus­
ing on diagnosis and treatment. 
ⅡCase Presentation
A 71-year-old woman had presented with nasal 
obstruction and intermittent epistaxis from the left 
nasal cavity for the previous 3 months. She visited 
another hospital as she also had headache in addition 
to these symptoms. Computed tomography (CT) indi­
cated a tumor mass in the left nasal cavity and 
the patient was referred to our hospital. On physical 
examination, swelling and hypoesthesia of the 
left upper jaw were observed. Cervical lymph nodes 
were not palpable. Laboratory findings, including 
A Case of Sinonasal Undifferentiated Carcinoma Sucessfully Responding to Chemoradiotherapy
Hirohide Matsushita
1）, Takesumi Ozawa
1）, Nodoka Sekiguchi
2）, Toshirou Fukushima
2） Takashi Kobayashi
2）, Shintaro Kanda
2）＊ and Tomonobu Koizumi
1） Department of Radiology, Shinshu University School of Medicine2） Department of Comprehensive Cancer Therapy, Shinshu University School of Medicine
Sinonasal undifferentiated carcinoma is an extremely rare and high-grade neoplasm arising in the nasal 
cavity, with highly aggressive clinical behavior and poor prognosis. Multimodal therapies have been proposed, 
including surgery, radiotherapy, and chemotherapy, but a standard treatment strategy has not been determined 
because of its rarity. Here, we present a case of sinonasal undifferentiated carcinoma treated with cisplatin＋
etoposide chemotherapy combined with radiotherapy (2 Gy×30 fractions, total 60 Gy). The patient achieved 
complete remission and is still alive without recurrence for over 5 years. A beneficial therapeutic outcome by 
chemoradiotherapy alone is extremely rare in patients with sinonasal undifferentiated carcinoma.  Shinshu Med J 
69 : 121―126, 2021
(Received for publication June 16, 2020 ; accepted in revised form January 5, 2021)
Key words : undifferentiated carcinoma, FDG-PET, cisplatin VP-16, nasal cavity, complete remission
＊ Corresponding author : Shintaro Kanda
 Department of Comprehensive Cancer Therapy, 
 Shinshu University School of Medicine, 
 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
 E-mail : skanda@shinshu-u.ac.jp
121No. 3, 2021
Shinshu Med J, 69⑶：121～126, 2021
tumor markers (CEA, CA19-9, SCC, NSE, and Pro-
GRP), were within normal limits. CT and magnetic 
resonance imaging (MRI) showed a hypervascular 
mass occupying the left nasal cavity and infiltrating 
the bones of the paranasal sinus (Fig. 1). Tumor 
biopsy was performed, and the histological findings 
showed groups of atypical small round cells with 
hyperchromatic nuclei beneath the epithelium (Fig. 
2A, B). The results of immunohistochemical analy­
sis indicated that the atypical cells were negative 
for S-100 protein (Fig. 2C), chromogranin A (Fig. 
2D), synaptophysin, neuron-specific enolase, mela­
noma-associated antigen 45 (Fig. 2E), CD 20, CD 34, 
CD 56 and α-smooth muscle antigen, and positive for 
cytokeratin AE1/AE3, (Fig. 2F). In addition, tumor 
cells were negative for nuclear protein in testis and 
p63 on immunohistochemical examination. Based on 
these histological findings, a diagnosis of SNUC was 
made. There were no regional lymph nodes and 
distant metastases on systemic radiographic exam­
ination including positron emission tomography with 
fluorodeoxyglucose-computed tomography (FDG-
PET/CT). However, during the examinations, she 
developed further worsening and painful swelling of 
the left upper jaw. Left exophthalmos and diplopia 
were also present because of tumor growth. Surgical 
excision was impossible because of the locally ad­
vanced nature of the tumor. Chemotherapy was 
initiated with cisplatin at 80 mg/m2 intravenously on 
day 1 and etoposide at 100 mg/m2 intravenously on 
Fig. 1 Magnetic resonance imaging (MRI) at admission. Fat suppressed contrast-enhanced T1- 
weighted (A ; axial, B ; coronal), and T2-weighted (C ; axial, D ; coronal) images showing a 
heterogenous contrast-enhanced mass occupying the left nasal cavity and infiltrating the bones of the paranasal sinus.
122Shinshu Med JVol. 69
Matsushita・Ozawa・Sekiguchi et al.
days 1-3 (PE chemotherapy) every 3-4 weeks. Three 
cycles of PE chemotherapy were effective and resulted 
in tumor reduction (Fig. 3A, B). Subsequently, 
concurrent radiotherapy at a dose of 60 Gy in 30 frac­
tions of 2.0 Gy each combined with PE chemotherapy 
was performed (Fig. 3C, D). Irradiation fields included 
primary tumor and bilateral neck as elective neck 
treatment. During the chemoradiotherapy, the patient 
developed febrile neutropenia but recovered with 
appropriate antibiotic therapy. The patient refused a 
fifth round of PE chemotherapy. FDG-PET/CT re­
vealed negative FDG uptake after the chemoradio­
therapy (Fig. 3F) and was considered to show com­
plete remission (Fig. 3D, F). Based on the FDG-PET 
findings, salvage surgery for the residual mass was 
not undertaken and close observation has been per­
formed. The patient is still alive without recurrence 
for over 5 years. 
ⅢDiscussion
There are no specific clinical and radiographic 
findings that could be useful for differential diagnosis 
among nasal malignancies8）9）. Therefore, a histological 
diagnosis is essential for high-grade malignancies 
because of the broad and complex histological find­
ings in tumors arising from the sinonasal tract1）-6）. 
Fig. 2 Hematoxylin and eosin staining ; (A) low-power (x 2) and (B) high-power fields (×40). Immunohistochemical 
findings indicated that malignant cells were negative for (C) S-100, (D) chromogranin A and (E) melanoma-
associated antigen, and positive for (F) cytokeratin AE1/AE3.
Sinonasal undifferentiated carcinoma responding to chemoradiotherapy
No. 3, 2021
The differential diagnoses of small round cell tumors 
include squamous cell carcinoma, small cell neuroen­
docrine carcinoma, rhabdomyosarcoma, Ewing 
sarcoma, lymphoma, malignant melanoma, etc. Im­
munohistological markers are useful for differential 
diagnosis4）-6）, and the tumor cells in the present case 
were of epithelial origin and lacked any evidence of 
neuroendocrine, muscle, melanocyte, or leukocyte 
differentiation. The histological findings in our case 
were consistent with those in other reports of SNUCs. 
Multimodality therapy has been adopted for SNUC, 
but the optimal treatment has yet to be determined 
because of its rarity. Smith et al.6） reported six pa­
tients with SNUCs initially treated with surgical 
resection followed by radiation therapy. Only two 
cases had disease-free survival of 6 and 18 months 
at last follow-up. On the other hand, Musy et al.7） 
reported the clinical outcomes of 20 cases of SNUCs 
initially treated with chemoradiotherapy or radio­
therapy. Ten cases were followed by craniofacial 
resection and the 2-year survival was 64 ％ in the 
treatment group. The study suggested that the re­
sponse to initial chemoradiotherapy was important 
for long-term survival. Recently, Faisal et al10） sum­
marized clinical data of 255 published patients with 
SNUCs and reported that the locoregional control 
rate was 63.9 ％ undergoing trimodality (surgery 
plus radiotherapy with and without chemotherapy), 
49.2 ％ in bimodality (chemoradiotherapy), and 31.3 ％ 
in surgery alone. There was no significant difference 
in the locoregional control rate between trimodality 
and bimodality in their study, however, the data 
suggested that surgical resection for residual tumor 
after chemoradiotherapy could be added for the best 
suitable management in the present case. However, 
several cases indicated that viable tumor cells in the 
resected specimens were absent after chemoradio­
therapy and associated with relatively long survival6）-8）. 
In addition, the negative FDG-PET finding after 
chemoradiotherapy in our case suggested a complete 
remission. Several clinical studies suggested that if 
PET scan is negative by FDG-PET, salvage surgery 
or subsequent chemotherapy can be omitted safety 
in patients with seminoma11）12） and/or malignant lym­
phoma13）. Thus, treatment options in the present case 
including surveillance or salvage surgery, were em­
Fig. 3 Serial contrast-enhanced computed tomographies are shown, (A) before, (B) after three cycles of cisplatin 
plus etoposide chemotherapy, (C) after chemoradiotherapy by 4th cycle cisplatin plus etoposide combined 
with radiotherapy (60Gy) and (D) 4 years after the chemoradiotherapy. Positron emission tomography with 
fluorodeoxyglucose-computed tomography (FDG-PET/CT) (E) before and (F) after chemoradiotherapy. 
Positive FDG uptake in the nasal mass was completely diminished after the chemoradiotherapy, suggested 
complete remission after chemoradiotherapy.
124Shinshu Med JVol. 69
Matsushita・Ozawa・Sekiguchi et al.
ployed and we selected close observation, resulting in 
long-term survival without recurrence over 5 years. 
Our case suggests that FDG-PET can be a useful 
tool for making a decision regarding optimal treat­
ment choice for the residual mass in patients with 
SNUC. We need further clinical experience about the 
FDG-PET information and prognosis in patients with 
Faisal et al.10） also performed a meta-analysis assess­
ing regional (neck) relapse with and without elective 
neck treatments (neck dissection or irradiation) and 
reported that the elective neck treatment was associ­
ated with an 80 ％ decreased risk for regional recurrence. 
Thus, elective neck treatment should be considered 
in patients with SNUC even in initial stage N0, as done 
in the present case. 
In the present case, radiotherapy for all involved 
tumor lesions would have been difficult because of 
the wide fields, especially when including the left 
orbit area. Therefore, we selected PE chemotherapy 
alone as the initial therapy. The efficacy of this PE 
chemotherapy was remarkable and concurrent 
chemoradiotherapy was available after three cycles 
of PE chemotherapy. No information is available in 
the literature regarding the usefulness of chemother­
apy in SNUCs. Various chemotherapeutic regimens, 
including CDDP＋5-FU, cyclophosphamide, vincris­
tine, doxorubicin (CAF), or PE, were used in previous 
case series4）-8）. However, these studies did not evaluate 
the response. PE combined with concurrent radio­
therapy has been widely accepted in limited cases of 
small cell lung cancer14）. In addition, radiotherapy 
combined with PE chemotherapy was used in the 
treatment of other nasal tumors15）-17）. Our experience 
suggested that PE is a useful novel chemotherapy 
regimen for SNUC. Further clinical studies of SNUC 
and evaluation of the response to chemoradiotherapy 
or chemotherapy are required.
ⅣConclusion
We described a case of SNUC successfully treated 
with chemoradiotherapy alone, resulting in complete 
remission and disease-free survival for over 5 years. 
The disease of SNUC should be recognized and dif­
ferential diagnosis of this distinct tumor from other 
nasal tumors is important. FDG-PET may be a useful 
for making a decision regarding optimal treatment 
choice in patients with SNUCs.
Conflict of Interest
The authors declare no potential conflicts of inter­
est with respect to the research, authorship, and/or 
publication of this article.
References
 1） Goel R, Ramalingam K, Ramani P, Chandrasekar T : Sino nasal undifferentiated carcinoma : A rare entity. J Nat Sci 
Biol Med 3 : 101-104, 2012
 2） Devi CP, Devi KM, Kumar P, Amrutha Sindhu RV : Diagnostic challenges in malignant tumors of nasal cavity and 
paranasal sinuses. J Oral Maxillofac Pathol 23 : 378-382, 2019
 3） Frierson HF Jr, Mills SE, Fechner RE, Taxy JB, Levine PA : Sinonasal undifferentiated carcinoma. An aggressive 
neoplasm derived from schneiderian epithelium and distinct from olfactory neuroblastoma. Am J Surg Pathol 10 :  
771-779, 1986
 4） Ejaz A, Wenig BM : Sinonasal undifferentiated carcinoma : clinical and pathologic features and a discussion on 
classification, cellular differentiation, and differential diagnosis. Adv Anat Pathol 12 : 134-143, 2005
 5） Enepekides DJ : Sinonasal undifferentiated carcinoma : an update. Curr Opin Otolaryngol Head Neck Surg 13 : 222-
225, 2005
 6） Smith SR, Som P, Fahmy A, Lawson W, Sacks S, Brandwein M : A clinicopathological study of sinonasal neuro­
endocrine carcinoma and sinonasal undifferentiated carcinoma. Laryngoscope 110(10 Pt 1) : 1617-1622, 2000
 7） Musy PY, Reibel JF, Levine PA : Sinonasal undifferentiated carcinoma : the search for a better outcome. Laryngoscope 
112(8 Pt 1) : 1450-1455, 2002
Sinonasal undifferentiated carcinoma responding to chemoradiotherapy
No. 3, 2021
 8） Jeng YM, Sung MT, Fang CL, et al : Sinonasal undifferentiated carcinoma and nasopharyngeal-type undifferentiated 
carcinoma : two clinically, biologically, and histopathologically distinct entities. Am J Surg Pathol 26 : 371-376, 2002
 9） Phillips CD, Futterer SF, Lipper MH, Levine PA : Sinonasal undifferentiated carcinoma : CT and MR imaging of an 
uncommon neoplasm of the nasal cavity. Radiology 202 : 477-480, 1997 
10） Faisal M, Seemann R, Lill C, et al : Elective neck treatment in sinonasal undifferentiated carcinoma : Systematic 
review and meta-analysis. Head Neck 42 : 1057-1066, 2020
11）  Bachner M, Loriot Y, Gross-Goupil M, et al : 2-18fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) 
for postchemotherapy seminoma residual lesions : a retrospective validation of the SEMPET trial. Ann Oncol 23 : 59-
64, 2012
12） Sakaguchi Y, Isowa N : Successful resection of mediastinal seminoma evaluated the response to induction chemo­
therapy with fluorodeoxyglucose-positron emission tomography. Ann Thorac Cardiovasc Surg 18 : 45-47, 2012
13） Johnson P, Federico M, Kirkwood A, et al : Adapted Treatment Guided by Interim PET-CT Scan in Advanced 
Hodgkin’s Lymphoma. N Engl J Med 374 : 2419-2429, 2016 
14） Stinchcombe TE, Gore EM : Limited-stage small cell lung cancer : current chemoradiotherapy treatment paradigms. 
Oncologist 15 : 187-195, 2010
15） Gomi D, Sasaki S, Sekiguchi N, Kobayashi T, Sakamoto A, Koizumi T : A case of olfactory neuroblastoma (esthesio­
neuroblastoma) presenting with anemia due to nasal bleeding. Shinshu Med J 64 : 247-252, 2016
16） Lucas JT Jr, Ladra MM, MacDonald SM, et al : Proton therapy for pediatric and adolescent esthesioneuroblastoma. 
Pediatr Blood Cancer 62 : 1523-1528, 2015 
17） Nakamura Y, Suzuki M, Ozaki S, et al : Sinonasal inverted papilloma associated with small cell neuroendocrine 
carcinoma : A case report and literature review of rare malignancies associated with inverted papilloma. Auris 
Nasus Larynx 46 : 641-650, 2019 
（2020. 6. 16 received ; 2021. 1. 5 accepted）
126Shinshu Med JVol. 69
Matsushita・Ozawa・Sekiguchi et al.