Shinshu Med J, 69⑶：121～126, 2021

A Case of Sinonasal Undifferentiated Carcinoma Sucessfully
Responding to Chemoradiotherapy
Hirohide Matsushita1）, Takesumi Ozawa1）, Nodoka Sekiguchi2）, Toshirou Fukushima2）
Takashi Kobayashi2）, Shintaro Kanda2）＊ and Tomonobu Koizumi2）
1） Department of Radiology, Shinshu University School of Medicine
2） 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 determinedbecause 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 bychemoradiotherapy 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

proposed for SNUCs, including surgery, radiothera­

Ⅰ Introduction

py, and chemotherapy, but a standard treatment

Malignant tumors of the sinonasal tract are ex­strategy has not been determined because of its

tremely rare, accounting for only 3 ％ of all head andrarity. We encountered a case of locally advanced

1）

neck cancers . Sinonasal tumors show similar clinical

SNUC treated with cisplatin＋etoposide chemothera­

manifestations, such as nasal obstruction and epistax­

py combined with radiotherapy, which showed a

is, but a wide range of histological features, including

survival period of＞5 years without recurrence. Here,2）histogenesis and differentiation of tumor cells . Sin­

we describe the clinical course of this case along

onasal undifferentiated carcinoma (SNUC), originallywith a brief review of the relevant literature, focus­

3）

described by Frierson et al. in 1986 , is an extremelyrare and high-grade neoplasm arising in the nasal
cavity with highly aggressive clinical behavior andpoor prognosis1）-7）. In a study of 36 cases of SNUC,
8）

ing on diagnosis and treatment.
Ⅱ Case Presentation
A 71-year-old woman had presented with nasal

Jeng et al. reported that 17 ％ and 31 ％ of patientsobstruction and intermittent epistaxis from the leftpresented with cervical lymph node and distant me­

nasal cavity for the previous 3 months. She visited

tastasis, respectively, and had a median survival pe­

another hospital as she also had headache in addition

riod of 10 months. Multimodal therapies have been

to these symptoms. Computed tomography (CT) indi­cated a tumor mass in the left nasal cavity and＊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

No. 3, 2021

the patient was referred to our hospital. On physicalexamination, swelling and hypoesthesia of theleft upper jaw were observed. Cervical lymph nodes
were not palpable. Laboratory findings, including121

Matsushita・Ozawa・Sekiguchi et al.

A

C

B

D

Fig. 1 Magnetic resonance imaging (MRI) at admission. Fat suppressed contrast-enhanced T1weighted (A ; axial, B ; coronal), and T2-weighted (C ; axial, D ; coronal) images showing aheterogenous contrast-enhanced mass occupying the left nasal cavity and infiltrating thebones of the paranasal sinus.

tumor markers (CEA, CA19-9, SCC, NSE, and Pro-

cells were negative for nuclear protein in testis and

GRP), were within normal limits. CT and magnetic

p63 on immunohistochemical examination. Based onresonance imaging (MRI) showed a hypervascularthese histological findings, a diagnosis of SNUC was

mass occupying the left nasal cavity and infiltrating

made. There were no regional lymph nodes andthe bones of the paranasal sinus (Fig. 1). Tumor

distant metastases on systemic radiographic exam­

biopsy was performed, and the histological findings

ination including positron emission tomography withshowed groups of atypical small round cells withfluorodeoxyglucose-computed tomography (FDG-

hyperchromatic nuclei beneath the epithelium (Fig.

PET/CT). However, during the examinations, she

2A, B). The results of immunohistochemical analy­

developed further worsening and painful swelling of

sis indicated that the atypical cells were negative

the left upper jaw. Left exophthalmos and diplopia

for S-100 protein (Fig. 2C), chromogranin A (Fig.

were also present because of tumor growth. Surgical2D), synaptophysin, neuron-specific enolase, mela­

excision was impossible because of the locally ad­noma-associated antigen 45 (Fig. 2E), CD 20, CD 34,

vanced nature of the tumor. Chemotherapy was

CD 56 and α-smooth muscle antigen, and positive for

initiated with cisplatin at 80 mg/m2 intravenously oncytokeratin AE1/AE3, (Fig. 2F). In addition, tumor

day 1 and etoposide at 100 mg/m2 intravenously on

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Sinonasal undifferentiated carcinoma responding to chemoradiotherapy

A

B

C

D

E

F

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) melanomaassociated antigen, and positive for (F) cytokeratin AE1/AE3.

days 1-3 (PE chemotherapy) every 3-4 weeks. Three

plete remission (Fig. 3D, F). Based on the FDG-PET

cycles of PE chemotherapy were effective and resulted

findings, salvage surgery for the residual mass wasin tumor reduction (Fig. 3A, B). Subsequently,

not undertaken and close observation has been per­concurrent radiotherapy at a dose of 60 Gy in 30 frac­

formed. The patient is still alive without recurrence

tions of 2.0 Gy each combined with PE chemotherapy

for over 5 years.

was performed (Fig. 3C, D). Irradiation fields included
primary tumor and bilateral neck as elective neck

Ⅲ

Discussion

treatment. During the chemoradiotherapy, the patient

There are no specific clinical and radiographic

developed febrile neutropenia but recovered withfindings that could be useful for differential diagnosis

appropriate antibiotic therapy. The patient refused aamong nasal malignancies8）9）. Therefore, a histologicalfifth round of PE chemotherapy. FDG-PET/CT re­diagnosis is essential for high-grade malignancies

vealed negative FDG uptake after the chemoradio­

because of the broad and complex histological find­therapy (Fig. 3F) and was considered to show com­

ings in tumors arising from the sinonasal tract1）-6）.

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Matsushita・Ozawa・Sekiguchi et al.

A

B

C

E

F

D

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 combinedwith radiotherapy (60Gy) and (D) 4 years after the chemoradiotherapy. Positron emission tomography withfluorodeoxyglucose-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.

The differential diagnoses of small round cell tumors

for long-term survival. Recently, Faisal et al10）sum­

include squamous cell carcinoma, small cell neuroen­marized clinical data of 255 published patients withdocrine carcinoma, rhabdomyosarcoma, Ewing

SNUCs and reported that the locoregional control

sarcoma, lymphoma, malignant melanoma, etc. Im­

rate was 63.9 ％ undergoing trimodality (surgery

munohistological markers are useful for differential

plus radiotherapy with and without chemotherapy),

4）-6）, and the tumor cells in the present case49.2 ％ in bimodality (chemoradiotherapy), and 31.3 ％were of epithelial origin and lacked any evidence ofin surgery alone. There was no significant difference

neuroendocrine, muscle, melanocyte, or leukocyte

in the locoregional control rate between trimodality

differentiation. The histological findings in our caseand bimodality in their study, however, the data

were consistent with those in other reports of SNUCs.

suggested that surgical resection for residual tumor

Multimodality therapy has been adopted for SNUC,

after chemoradiotherapy could be added for the best

but the optimal treatment has yet to be determinedsuitable management in the present case. However,

because of its rarity. Smith et al.6） reported six pa­

several cases indicated that viable tumor cells in thetients with SNUCs initially treated with surgicalresected specimens were absent after chemoradio­

resection followed by radiation therapy. Only two

therapy and associated with relatively long survival6）-8）.

cases had disease-free survival of 6 and 18 months

In addition, the negative FDG-PET finding after

7）

chemoradiotherapy in our case suggested a complete

reported the clinical outcomes of 20 cases of SNUCs

remission. Several clinical studies suggested that if

initially treated with chemoradiotherapy or radio­

PET scan is negative by FDG-PET, salvage surgery

therapy. Ten cases were followed by craniofacialor subsequent chemotherapy can be omitted safety

resection and the 2-year survival was 64 ％ in thein patients with seminoma11）12）and/or malignant lym­

treatment group. The study suggested that the re­phoma13）. Thus, treatment options in the present casesponse to initial chemoradiotherapy was important

including surveillance or salvage surgery, were em­

diagnosis

at last follow-up. On the other hand, Musy et al.

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Sinonasal undifferentiated carcinoma responding to chemoradiotherapy

ployed and we selected close observation, resulting intine, doxorubicin (CAF), or PE, were used in previous

long-term survival without recurrence over 5 years.

case series4）-8）. However, these studies did not evaluate

Our case suggests that FDG-PET can be a useful

the response. PE combined with concurrent radio­

tool for making a decision regarding optimal treat­

therapy has been widely accepted in limited cases ofment choice for the residual mass in patients withsmall cell lung cancer14）. In addition, radiotherapy

SNUC. We need further clinical experience about the

combined with PE chemotherapy was used in the

FDG-PET information and prognosis in patients withtreatment of other nasal tumors15）-17）. Our experience

SNUC.

suggested that PE is a useful novel chemotherapy
10）

Faisal et al.

also performed a meta-analysis assess­regimen for SNUC. Further clinical studies of SNUC

ing regional (neck) relapse with and without elective

and evaluation of the response to chemoradiotherapy

neck treatments (neck dissection or irradiation) andor chemotherapy are required.

reported that the elective neck treatment was associ­Ⅳ Conclusion

ated with an 80 ％ decreased risk for regional recurrence.
Thus, elective neck treatment should be considered

We described a case of SNUC successfully treatedin patients with SNUC even in initial stage N0, as donewith chemoradiotherapy alone, resulting in completein the present case.

remission and disease-free survival for over 5 years.

In the present case, radiotherapy for all involved

The disease of SNUC should be recognized and dif­tumor lesions would have been difficult because offerential diagnosis of this distinct tumor from otherthe wide fields, especially when including the left

nasal tumors is important. FDG-PET may be a usefulorbit area. Therefore, we selected PE chemotherapy

for making a decision regarding optimal treatment

alone as the initial therapy. The efficacy of this PE

choice in patients with SNUCs.

chemotherapy was remarkable and concurrent

Conflict of Interest

chemoradiotherapy was available after three cyclesof PE chemotherapy. No information is available in

The authors declare no potential conflicts of inter­the literature regarding the usefulness of chemother­

est with respect to the research, authorship, and/or

apy in SNUCs. Various chemotherapeutic regimens,

publication of this article.

including CDDP＋5-FU, cyclophosphamide, vincris­
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