Shinshu M ed J, 64⑸ :247〜252, 2016

A Case of Olfactory Neuroblastoma (Esthesioneuroblastoma) Presenting
with Anemia Due to Nasal Bleeding
Daisuke GOMI, Shigeru SASAKI, Nodoka SEKIGUCHI, Takashi KOBAYASHI
Akiyuki SAKAMOTO and Tomonobu KOIZUMIDepartment of Comprehensive Cancer Therapy, Shinshu University School of Medicine

A 69 ‑year‑old man was referred to our hospital because of occasional nosebleeds over a period of 6months. Physical examinations were unremarkable except for anemia. Laboratory ﬁndings on admission
indicated a hemoglobin level of 7.8 g/dL. Magnetic resonance imaging revealed a mass occupying the rightnasal cavity and inﬁltrating the bones of the paranasal sinus.Histological ﬁndings revealed olfactory neuroblastoma (esthesioneuroblastoma)and the disease was diagnosed to be at a locally inoperable advanced stage.
Concurrent chemoradiotherapy (cisplatin plus etoposide and 60 Gy in 30 fractions of 2.0 Gy)was performed.
Chemoradiotherapy failed to show signiﬁcant tumor size reduction, but the nosebleeds stopped. The patient
remains disease‑free over 3 years after treatment. Although olfactory neuroblastoma is an extremely rare
nasal tumor,we should be aware of the disease as a potential cause of nasal bleeding and anemia.Shinshu MedJ 64 : 247 ―252, 2016
(Received for publication March 15, 2016;accepted in revised form M ay 13, 2016)
Key words:epistaxis, chemoradiotherapy, cisplatin, VP‑16, radiotherapy

Introduction
Olfactory neuroblastoma (ONB), or esthesioneuroblastoma, is a rare tumor originating from theolfactoryneuroepithelium,which was ﬁrst describedwith chemoradiotherapy and remains disease-freeover 3 years after treatment.Here,we describe theclinical course and discuss the disease and therapy.
Case Presentation

byBerger et al.in 1924 .ONB accounts for approxi-A 69 ‑year‑old man was referred to our hospitalmately 2%‑3% of all sinonasal tumors with an

because of occasional nosebleeds over a period of 6

incidence of approximately 0.4 cases per million .

months. Physical examinations were unremarkable

Clinically,ONB presents most commonlyas a large,

except for anemia and identiﬁcation of a mass in theunilateral,polypoid,glistening,red-gray mass in theright nasal cavity. There was no superﬁcial lymph

superior nasal cavity. Therefore, the primary clini-node swelling. Laboratory ﬁndings indicated acal symptoms are unilateral nasal obstruction andhemoglobin level of 8.7 g/dL (MCV 83.0 ﬂ, MCH

epistaxis. We encountered a case of ONB with

24.6 pg、MCHC 29.7%). Computed tomographyoccasional epistaxis over a period of 6 months and(CT) and magnetic resonance imaging (MRI)

subsequentlypresenting with persistent nasalbleeding

showed a hypervascular mass occupying the rightafter biopsy examination. The patient was treatednasal cavity and inﬁltrating the bones of the paranasal sinus (Fig. 1, 2). After biopsy of the right

Corresponding author:Tomonobu Koizumi
Department of Comprehensive Cancer Therapy, Shinshu
University School of M edicine, 3‑1‑1 Asahi, M atsumoto,nasal mass,the patient went home.Two days later,
he had a persistent nosebleed and was taken by

Nagano 390‑8621, Japan

ambulance to our hospital where he was admitted.

E-mail:tomonobu＠shinshu‑u.ac.jp.

Gauze packing and intravenous hemostatic drugs

No. 5, 2016

247Gomi.Sasaki.Sekiguchi et al.

Fig. 1 Enhanced computed tomography (CT)showing a contrast‑enhanced hypervascular mass in the right nasal cavity.

ＡＢ

Fig. 2 M agnetic resonance imaging (M RI) A ; axial image, B ; coronal image showed a homogenous
contrast‑enhanced mass occupying the right nasal cavity and inﬁltrating the bones of the paranasal
sinus.

were applied. The bleeding showed marked reduc-chromogranin A and synaptophysin,neuron‑speciﬁction, but his anemia progressed and his hemoglobin

enolase (NSE) (Fig. 5). These observations werelevel decreased to 7.8 g/dL. Histological ﬁndings

consistent with the histological ﬁndings of ONB,

showed groups of atypical small round cells withalthough Flexner‑Wintersteiner and/or Homer

hyperchromatic nuclei under the epithelium (Fig.3).

Wright rosettes were not observed. In addition,

The immunohistochemical ﬁndings revealed thattumor cells were negative for CD 99 and bcl2 in

the atypical cells were negative for cytokeratin

immunohistochemical examination, distinguishing(CK) AE1/AE3, S‑100 protein, and melanoma‑as-them from Ewing sarcoma and primitive neur-sociated antigen (HMB)45 (Fig. 4),and positive foroectodermal tumor.Ki‑67 labeling index was 7% in248

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A case of olfactory neuroblastoma

ＡＢ

Fig. 3 Hematoxylin and eosin staining, low‑(A)and high‑power ﬁelds (B). Groups of atypical small roundcells with hyperchromatic nuclei were observed under the epithelium. Flexner‑Wintersteiner and/orHomer Wright rosettes were not observed in the present case.

ＡＢＣFig. 4 Immunohistochemical ﬁndings indicated that malignant cells were negative for cytokeratin (CK)AE1/AE3 (A)or S‑100 protein in the low‑power ﬁeld (B).S‑100 protein‑positive cells were observed in thehigh‑power ﬁeld (C), but these cells seemed to be sustentacular cells.

No. 5, 2016249

Gomi.Sasaki.Sekiguchi et al.

ＡＢ

Fig. 5 Immunohistochemical ﬁndings indicated that malignant cells were positive for chromogranin A (A)and synaptophysin (B).

the present case.

However, histological diagnosis is essential for

There was no distant metastasis, but surgical

ONB because of the broad and complex histologicalexcision was anyway impossible because of theﬁndings in tumors arising from the sinonasal tract,

locallyadvanced nature ofthetumor.Hewas treatedincluding squamous cell carcinoma, sinonasal

with concurrent chemoradiotherapy,and received aundiﬀerentiated carcinoma, small cell neuroendo

dose of 60 Gy in 30 fractions of 2.0 Gy over 6 weeks.

crine carcinoma,rhabdomyosarcoma,Ewing sarcoma,

Chemotherapy was initiated with cisplatin (CDDP)

lymphoma,malignant melanoma,etc. .In addition,

at 80 mg/m intravenously on days 1 and 29, andthere are no speciﬁc clinical and radiographic

etoposide (VP‑16) at 100 mg/m intravenously on

ﬁndings in patients with ONB that could be usefuldays 1 ‑3 and 29 ‑31.Although chemoradiotherapy

for diﬀerential diagnosis from these nasal tumors.

failed to signiﬁcantly reduce the tumor size, theHistologically, primitive‑appearing ”
small roundtumor remained stable and there were no further

blue cells”with ﬁnely granular chromatin,a distinc-episodes of nasal bleeding after treatment. The

tive lobular and often coalescing architectural

patient has shown progression‑free survival for

growth pattern are remarkable ﬁndings in ONB

over 3 years.

Furthermore, immunohistochemical staining, including neuroendocrine immunophenotype without

Discussion

signiﬁcant cytokeratin expression and positivity for

In general, ONB is a slow‑growing tumor withlong‑standing symptomatology.

. The clinical

S‑100, conﬁrm the diagnosis. These ﬁndings

were consistent with those in the present case.

symptoms are unilateral nasal obstruction and epis

There is no universally accepted staging system

taxis,including pain,excessivelacrimation,rhinorrhea,

for ONB. Kadish et al. proposed a staging system

visual disturbances, and anosmia. In our case,for ONB based on the radiographic extent of therecurrent epistaxis was observed 6 months before

tumor: stage A, disease in only the nasal cavity;

admission. However, the patient presented withstage B, disease conﬁned to the nasal cavity andpersistent nasal bleeding after biopsyand developed

paranasal sinuses;and stage C,lesions with distantfurther anemia, which was a noteworthy clinicalspread from the nasal cavity, usually involving themanifestation in the present case. Thus, extreme

base of the skull, orbit, or intracranial cavity. The

caution should be taken in the approach to thetumor in the present case was considered to bebiopsy,due to thepotentialrisk ofsigniﬁcant bleeding.

Kadish stage C. This staging system has been

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A case of olfactory neuroblastoma

widely utilized and correlates well with prognosis.

chemotherapy regimens in patients with advanced

A study of 311 patients based on the Surveillance,

metastatic ONB to date. Fitzek et al. examined

Epidemiology, and End Results database showed

the usefulness of neoadjuvant CDDP＋VP‑16chemo-that disease‑speciﬁc survival at 10 years was cor-therapy in 19 cases of neuroendocrine tumors in

related with “modiﬁed”Kadish staging (83%,49 %,the sinonasal tract, including nine cases of ONB.

39 %,and 13% for stages A,B,C,and D,respective-

They found that 13 patients showed a signiﬁcantly) .In this analysis,original Kadish C was divided

response to two cycles of CDDP＋VP‑16 with ainto stage C (beyond the sinuses,including the orbit

response rate of 68.4%. In addition, Gupta et al.

or intracranial extension)and D (distant metastasis)

reported a case of ONB with extensive involvementin the “modiﬁed”Kadish staging.

of the nasal cavities, nasopharynx, paranasal

Surgery followed by radiotherapy is generally

sinuses, and orbit that showed a complete response

accepted as the gold standard treatment in ONB

to concurrent chemoradiation with CDDP ＋ VP‑16

regardless of Kadish stage,with the possible excep-chemotherapy. The chemotherapy regimen withtion of disease metastasis. Several caseconcurrent radiotherapy has been widely accepted

series studies demonstrated the longest survivalin limited stage cases of small cell lung cancer ,intimes in patients receiving the modalities,comparedwhich the tumor cells were of neuroendocrine origin

with either surgery or radiation alone.How-

as well as ONB.Therefore,weselected CDDP＋VP‑16

ever, non‑surgically treated or inoperable subjects

combined concurrent radiotherapy in the present

were included among ONB patients with Kadish C,case.Unfortunately,thecombined chemoradiotherapy

as in the present case.Takenaka et al. summarized

failed to reduce the tumor size and the residual

104 Japanese patients with ONB reported from 1990

mass was still inoperable.However,the patient has

to 2013 and found that approximately half of theremained free of symptoms,including epistaxis,forpatients were stage Kadish C. They reported thatover 3 years. Combined chemoradiation might be

40% were non-surgically treated patients and thateﬃcacious for local control of this disease.

survival was signiﬁcantly poorer compared withsurgically treated patients.

In summary, we described a case of olfactory
neuroblastoma that showed occasional epistaxis

Combined modality treatment with chemoradia-

over a period of 6 months, and subsequently devel-tion has been increasingly adopted for these inoper-

oped persistent nose bleeds after obtaining a biopsy

able patients over the last two decades. The

specimen of the primarytumor.We should be aware

eﬃcacy of chemotherapy using CDDP, cyclophos-of the disease as a cause of nasal bleeding, andphamide, vincristine, doxorubicin, or VP‑16, etc.,

further studies regarding therapeutic strategies forwith and without radiotherapy was reported

inoperable olfactory neuroblastoma are warranted.

,although there have been no broad reports of useful
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