Case Reports

Journal of International Medical Research

2023, Vol. 51(9) 1–16
Neuroendocrine neoplasms ! The Author(s) 2023
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of the orbit: report of three sagepub.com/journals-permissions
DOI: 10.1177/03000605231199762
cases and a literature review journals.sagepub.com/home/imr

JunYi Qiao , Yujiao Wang and Weimin He

Abstract
Neuroendocrine neoplasms (NENs) originate from neuroendocrine cells, and mainly occur in the
gastrointestinal tract and lungs, rarely occurring in the orbit. Here, the clinicopathologic factors,
treatments and prognosis of three cases of orbital NENs are described. The mean age of the
three patients (two females and one male) was 59 years. Two cases exhibited ocular symptoms,
including unilateral proptosis and eyelid mass, while the third case presented systemic symptoms
exhibited as Cushing’s syndrome. The tumours were surgically resected in all three patients.
Immunohistochemistry assays revealed positive expression for pan cytokeratin and epithelial
membrane antigen in all cases. Additionally, neural cell adhesion molecule 1 (also known as
CD56) and synaptophysin were positive in two cases. The pathological diagnosis for case 1
and 2 was ‘neuroendocrine carcinoma’ and both patients died three months after diagnosis.
Case 3 was diagnosed with a neuroendocrine tumour and the symptoms of Cushing’s syndrome
gradually improved following surgery. In addition, no recurrence was observed during the four-
year follow-up period. These cases demonstrate that orbital neuroendocrine tumours show
different clinical manifestations due to the different types. Pathology may clarify the diagnosis,
classification and grading, and provide a reference value for treatment and prognosis.

Keywords
Neuroendocrine carcinoma, neuroendocrine tumour, orbital tumour, histopathology, case
report, unilateral proptosis
Date received: 12 May 2023; accepted: 21 August 2023

Introduction Department of Ophthalmology, West China Hospital of

Neuroendocrine neoplasms (NENs) are a
rare group of neoplasms that arise from
neuroendocrine cells and account for less
than 1% of all malignant tumours.1 NENs
may occur in various organs and tissues,
Sichuan University, Chengdu, Sichuan, China
Corresponding author:
Weimin He, Department of Ophthalmology, West China
Hospital of Sichuan University, 37 Guoxue Lane, Wuhou
District, Chengdu 610041, Sichuan, China.
Email: hewm888@hotmail.com

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2 Journal of International Medical Research
including the gastrointestinal tract, lungs,
pancreas and bronchus.2 Orbital NENs
are rare and exhibit atypical clinical and
imaging manifestations,3 which pose chal-
lenges in their diagnosis. Therefore, it is
crucial for ophthalmologists and patholo-
gists to be well-versed in the clinicopatho-
logical features of orbital NENs to facilitate
early and accurate treatment interventions.
In the present study, three cases of orbital
NENs with unknown primary origin are
reported, highlighting their diverse clinical
profiles. Additionally, the PubMed and
Web of Science databases were searched
to identify and review previously published
cases of orbital NENs.
Case reports
Three cases of orbital NENs, diagnosed
between 2016 and 2021, were retrospective-
ly identified by reviewing databases of
the Departments of Ophthalmology and
Pathology of the West China Hospital of
Sichuan University, China. The clinical his-
tories, manifestations and pathological
findings of these patients were carefully
evaluated. Written informed consent for
publication was obtained from the patients
or their next of kin, and all patient details
have been de-identified. Prior to hospital
admission, all patients provided written
informed consent for treatment. Due to
the case report study design, institutional
review board approval was waived. The
study adhered to the tenets of the
Declaration of Helsinki, and the reporting
of the three cases conforms to CARE
guidelines.4
Case 1
In February 2018, a 48-year-old Chinese
male patient presented at the Department
of Ophthalmology, West China Hospital
of Sichuan University, with a 2-month
history of progressive right eye proptosis.
No history of ocular discharge or thyroid
eye disease was recorded. Best-corrected
visual acuity was assessed using logarithm
of the minimum angle of resolution
(LogMAR) and was found to be 2.47 cm
in the right eye and 0.1 in the left eye.
Clinical examinations revealed proptosis
(Hertel’s exophthalmometry was asymmet-
ric at 19 mm for the right eye and 14 mm for
the left eye), conjunctival oedema with pro-
trusion beyond the eyelid fissure (Figure 1a
and 1b), sluggish pupillary reactions, and
mild optic disc pallor observed through indi-
rect ophthalmoscopy. Computed tomogra-
phy (CT) imaging revealed a well-defined
and heterogeneous density retrobulbar
nodule measuring 3.3
3.0
2.8 cm in the
posterior part of the right orbit, which sur-
rounded the optic nerve and compressed
extraocular muscles (Figure 1c). Eye surgery
was performed through a lateral orbitotomy
approach, during which a brittle red neo-
plasm was found in the intraconal space
and lateral rectus muscle (Figure 1d).
Histological examination of the tumour
showed positive staining for pan cytokeratin,
thyroid transcription factor-1, neural cell
adhesion molecule 1 (also known as CD56),
epithelial membrane antigen (EMA), chro-
mogranin A, and a MIB-1 rate of 80%
(Figure 1e–k). According to the 2015 World
Health Organization (WHO) classification,
the lesion was identified as a poorly differen-
tiated neuroendocrine carcinoma. The patient
was then referred for extensive systemic exam-
ination, including chest and abdominal CT,
and bone marrow evaluation, which yielded
unremarkable results. Due to financial con-
straints, the patient declined a treatment rec-
ommendation of chemotherapy, and no
further therapy was administered. After a
follow-up of 3 months, the patient died due
to tumour recurrence.
Case 2
In June 2021, an 82-year-old Chinese
female patient presented at the
Qiao et al. 3

Figure 1. Images from a 48-year-old male patient who presented with a 2-month history of progressive
right eye proptosis: (a) right eye proptosis; (b) conjunctival congestion and oedema of the right eye; (c)
preoperative axial computed tomography image showing the neoplasm surrounding the optic nerve and
squeezed extraocular muscles; (d) gross image of resected specimen showing the red and brittle tumour
mass. Histology findings: (e) tumour cells were closely arranged with a round or oval nucleus and no
nucleolus, and no apparent cytoplasm (haematoxylin and eosin); (f) positive cytoplasmic pan cytokeratin
immunostaining of tumour cells; (g) neural cell adhesion molecule 1 (CD56) immunostaining of tumour cells
showing diffuse cytoplasmic immunoreactivity; (h) thyroid transcription factor-1 staining of tumour cells
showing nuclear immunoreactivity; (i) positive cytoplasmic epithelial membrane antigen immunostaining of
tumour cells; (j) positive cytoplasmic chromogranin immunostaining of tumour cells and (k) MIB-1 positive
staining demonstrating strong nuclear immunoreactivity in about 80% of tumour cells. (All photomicro-
graphs: original magnification,
200).
4 Journal of International Medical Research
Figure 1. Continued.
Department of Ophthalmology, West
China Hospital of Sichuan University, due
to a progressively increasing lower eyelid
mass that had been noted 1 month previ-
ously. Best-corrected visual acuity was
assessed using LogMAR and found to be
1.4 and 2.77 in the right and left eyes,
respectively. Clinical examination revealed
a red mass on the nasal side of the left
lower eyelid (Figure 2a). Apart from lens
opacity, no definite abnormalities were
observed in the anterior and posterior seg-
ments of the left eye. In May 2021, a CT
scan showed a well-defined peribulbar
nodule measuring 2.2
1.9
2.1 cm in the
area of the orbital muscle cone and nasola-
crimal duct (Figure 2b and 2c). One month
later, a magnetic resonance imaging (MRI)
scan revealed a maximum cross-section of
the lesion measuring 4.0
3.2 cm (Figure 2e
[1–4]). The mass was surgically resected
through a transcutaneous orbitotomy
Qiao et al. 5

Figure 2. Images from an 82-year-old female patient who presented with an increasing lower eyelid mass
from 1 month previously. In May 2021: (a) left lower eyelid red mass; (b) axial computed tomography (CT)
Continued.
6 Journal of International Medical Research

approach, revealing a large grey-white purple striae on the abdomen, scattered

neoplasm with hard and brittle character-
istics in the left orbit (Figure 2f).
Immunohistochemistry results demonstrat-
ed positive pan cytokeratin, EMA, CD56,
and synaptophysin staining, along with
a Ki-67 proliferation index of 90%
(Figure 2g–m), confirming a diagnosis of
poorly differentiated neuroendocrine carci-
noma. A subsequent comprehensive work-
up, including total body CT and bone
marrow evaluation, ruled out any occult
internal malignancy. Despite the diagnosis,
the patient declined further therapy due to
her advanced age. During regular follow-up
intervals, the patient’s condition deteriorat-
ed, and she eventually died due to cachexia
associated with the tumour after 3 months
of follow-up.
Case 3
In July 2016, a 48-year-old female patient
was admitted to the Endocrinology
Department of West China Hospital of
Sichuan University, with fatigue, anasarca
for 1 year, alopecia, and skin pigmentation
for the previous 5 months. Physical exami-
nation revealed mildly elevated blood
pressure (150/79 mmHg), moon face
(Figure 3a), central obesity, multiple
bruises, and proximal muscle weakness.
The patient had a history of an orbital
mass 20 years ago, which was previously
considered an inflammatory pseudotumor,
and she was discharged without surgery as
she was asymptomatic at that time.
Laboratory tests showed abnormally elevat-
ed cortisol levels, and the 1-mg overnight
dexamethasone suppression test confirmed
Cushing’s syndrome. Subsequent adrenocor-
ticotropic hormone (ACTH) measurement
revealed a significant elevation in ACTH
levels, but the failure to suppress plasma
total cortisol with a high-dose dexametha-
sone suppression test suggested possible
ectopic Cushing’s syndrome. Despite nega-
tive findings in the pituitary enhanced
MRI, an enhancement was incidentally dis-
covered in the lateral rectus muscle of the
patient’s left orbit. Subsequently, an orbital
enhanced MRI was performed, and an
enhanced orbital mass was found encom-
passing the left orbital lateral rectus muscle
(Figure 3b [1–4]). Surgery was then per-
formed through a lateral orbitotomy
approach. After complete excision of the
mass (Figure 3c), histopathological analysis
confirmed a typical orbital carcinoid tumour.
Immunohistochemistry showed positive
staining for pan cytokeratin, EMA, CD56,

Figure 2. Continued
image showing a well‑defined peribulbar nodule in the orbital muscle cone; (c) coronal CT image showing
that the muscle and the eyeball were squeezed by the neoplasm. In June 2021: (d) the left lower eyelid mass
was found to be rapidly growing; (e [1–4]) magnetic resonance imaging scans showing T1, fat-suppressed,
post-contrast, axial T2, T1 and coronal images with a well‑defined mass squeezing the eyeball and muscle.
A moderately hypointense region on T1 and mildly hyperintense region on T2 with heterogeneous contrast
enhancement of fat suppression were also detected; (f) gross image of resected specimen showing hard,
brittle and grey-white masses. Histology images, showing: (g) closely arranged tumour cells with dense
chromatin staining, and fusiform or oval nucleus with no nucleolus (haematoxylin and eosin [H&E]; original
magnification,
200); (h) tumour cells invading the muscle (H&E; original magnification,
200); (i) positive
cytoplasmic epithelial membrane antigen immunostaining of tumour cells (original magnification,
400);
(j) positive cytoplasmic pan cytokeratin immunostaining of tumour cells (original magnification,
400);
(k) neural cell adhesion molecule 1 (CD56) immunostaining of tumour cells showing diffuse cytoplasmic
immunoreactivity (original magnification,
400); (l) positive cytoplasmic synaptophysin immunostaining of
tumour cells (original magnification,
400); and (m) Ki67 immunostaining demonstrating strong nuclear
immunoreactivity in approximately 90% of tumour cells (original magnification,
400).
Qiao et al. 7

Figure 2. Continued.
8 Journal of International Medical Research

Figure 3. Images from a 48-year-old female patient who presented with fatigue, anasarca for 1 year,
alopecia, and skin pigmentation for 5 months: (a) patient’s moon face appearance; (b1–4) preoperative
orbital magnetic resonance images (MRIs) showing T1, fat-suppressed, post-contrast, axial T2, T1 and
coronal images. A 1.5
2.6 cm lesion was detected and presented slightly high T1 and equal T2 signals.
Continued.
Qiao et al. 9

and synaptophysin (Figure 3d–i). The patient
underwent extensive systemic examination,
with a normal chest CT and hyperplastic
adrenal glands noted on abdominal CT.
The patient appeared stable and her ACTH
levels gradually returned to normal during
follow-up. Subsequent MRIs showed no
signs of recurrence (Figure 3j [1–4]).
Notably, the patient’s clinical manifestations,
including moon face, purple striate and cen-
tral obesity, disappeared (Figure 3k). Up to
the latest follow-up (in July 2023), no recur-
rence had been observed.
Discussion
Neuroendocrine neoplasms of the orbit are
extremely rare, with most cases being
metastases from a distant primary NEN.5
The current study describes three cases of
orbital NENs with unknown primary, as no
primary lesion was detected upon thorough
whole-body examination. A review of the
published literature regarding studies on pri-
mary orbital NENs, or orbital NENs with
unknown primary, identified a total of 12
previously reported cases (Table 1).6–14
The 12 patients in the previously pub-
lished cases demonstrated an equal distribu-
tion of sexes, with a mean age of 60 years.
The present cases comprised two female
and one male patient, with a mean age of
59 years. Among all 15 patients with avail-
able clinical information, the most com-
monly observed signs of orbital NENs
were proptosis and visual disturbances,
including blurry vision, diplopia, and
ocular motility disturbances (Table 1).
A minority of orbital NENs were found to
secrete hormones, leading to the manifesta-
tion of typical carcinoid syndromes,6,12
which was consistent with the present case 3.
Typical radiographic findings play a cru-
cial role in diagnosing NENs. Orbital
NENs often present as heterogeneous,
well-circumscribed, and contrast-
enhancing lesions on CT.3 The masses are
mostly confined to the extraocular muscles,
with some cases extending into the adjacent
orbital or lacrimal gland tissues. On MRIs,
these lesions typically appear moderately
hypointense or isointense on T1-weighted
imaging, and isointense or mildly hyperin-
tense on T2-weighted imaging.15 In instan-
ces where the primary NENs are unknown,
further systemic investigation is always
warranted. Whole-body contrast-enhanced
CT and MRI scans have been employed
as the initial approach to localize the pri-
mary site and identify any metastatic dis-
ease.3 Additionally, functional imaging
modalities, such as metaiodobenzylguani-
dine (MIBG scan), somatostatin receptor
scintigraphy (octreotide scan) and

Figure 3. Continued
A well-circumscribed lesion in the orbit was detected with homogeneous contrast enhancement that
surrounded the external rectus muscle and pushed the optic nerve; (c) gross image of resected specimen
(2.5 cm, ovoid, well-circumscribed, glistening mass). Histology images, showing: (d) fusiform or round
tumour cells with rare nucleolus and mitotic appearance, and punctate or dense chromatin detected in the
nucleus (haematoxylin and eosin [H&E]; original magnification,
200); (e) tumour cells invading the muscle
(H&E; original magnification,
200); (f) positive cytoplasmic pan cytokeratin immunostaining of tumour cells
(original magnification,
400); (g) positive cytoplasmic epithelial membrane antigen immunostaining of
tumour cells (original magnification,
400); (h) neural cell adhesion molecule 1 (CD56) immunostaining of
tumour cells showing diffuse cytoplasmic immunoreactivity (original magnification,
400); (i) positive
cytoplasmic synaptophysin immunostaining of tumour cells (original magnification,
400); (j1–4) postoper-
ative orbital MRIs showing T1, fat-suppressed, post-contrast, axial T2, T1 and coronal images, respectively.
The left extraocular rectus muscle was thickened with a blurred edge and the orbital fat was swollen; and
(k) symptoms of Cushing’s syndrome disappeared after the operation, including moon face appearance.
10
Figure 3. Continued.
fluorine-18-fluorodeoxyglucose positron
emission tomography (FDG-PET scan)
have proven to be useful in detecting an
occult primary tumour, uncovering unsus-
pected metastatic disease, and monitoring
the response to treatment.16
Histopathological analysis of tissue sam-
ples serves as the gold standard for diagnos-
ing NENs. According to the 5th edition of
the WHO classification in 2021, NENs are
categorized into well-differentiated epitheli-
al neuroendocrine neoplasms (termed
Journal of International Medical Research
neuroendocrine tumour, NET) and poorly
differentiated neuroendocrine neoplasms
(termed neuroendocrine carcinoma, NEC).17
This classification emphasizes the importance
of diagnostic immunohistochemical bio-
markers to confirm the neuroendocrine
nature of a neoplasm. Positive immunohisto-
chemical staining for epithelial markers
(EMA and cytokeratin) and neuroendocrine
markers, including chromogranin A, synap-
tophysin, neuron-specific enolase and neural
cell adhesion molecule 1 (CD56), is used.18
Qiao et al.
Figure 3. Continued.
Mitotic count and Ki-67 proliferation index/
MIB1 staining are employed to assess cell
proliferation activity.19 NETs are graded as
G1 NET (no necrosis and < 2 mitoses per
2 mm2; Ki67 < 20%), G2 NET (necrosis or
2–10 mitoses per 2 mm2, and Ki67 < 20%),
and G3 NET (> 10 mitoses per 2 mm2 or
Ki67 > 20%, and absence of poorly
11
differentiated cytomorphology). NEC (>10
mitoses per 2 mm2, Ki67 > 20%, and often
associated with a Ki67 > 55%) are further
subtyped, based on cytomorphological char-
acteristics, as small cell and large cell neuro-
endocrine carcinomas. The distinction
between G3 NET and NEC is often challeng-
ing in clinical practice, despite potential
Table 1. Summary of previously published cases and the present case of primary neuroendocrine tumour.
12

Patient
Author age
(publication year) (years) Sex Presentation CT/MRI scan Immunohist Classification Treatment Survival Follow-up Metastasis

Riddle (1982)14 NM M Proptosis NM NM Carcinoid S Alive 4 months No

NM F Proptosis NM NM Carcinoid S Alive 4 months No
Yang (2011)13 54 M Proptosis and A soft tissue mass in the supe- Syn Carcinoid S Alive NM NM
decreased vision rior orbit situated behind
the globe
59 M Proptosis A mass in the right inferior Syn Carcinoid S þ RA Alive 5 years No
rectus muscle
78 F Proptosis and upper A multi-lobulated mass in the NM Carcinoid S Alive 3.5 years Yes
lidptosis right superior orbit measur-
ing involving the superior
rectus and levator palpebrae
superioris complex
Zimmerman 71 F Proptosis, A large mass in the right orbit NM Carcinoid S Alive 3 years No
(1983)12 decreased vision,
carcinoid
syndrome
Di Maria (2000)11 84 M Nodular mass Mass in the whole left upper lid EMA, CK, Carcinoma S þ RA Alive 2.5 years Yes
and the orbital soft tissues CgA, NSE
around the eyeball, involve-
ment at recurrence
79 F Proptosis – EMA, CK, CgA, Carcinoma S Alive 1 year No
NSE
Thyparampil 64 F Proptosis, pain, A 2-cm intraconal lesion in the CgA, Syn, CDX2, Carcinoid S Alive 3 years No
(2018)10 swelling right orbit Ki-67 (3–5%)
Mititelu (2008)9 60 M Diplopia, decreased A 17
9-mm fusiform lesion CK, Syn Carcinoma S þ ChT Dead 4 years Yes
vision along the expected course of
the left supraorbital nerve
Atik (2013)8 35 F Pain Inflammatory mass in the right Syn , CgA, CD56 Carcinoma S þ ChT Dead 2 years Yes
orbit, ethmoid, and right
frontal bone
Mittal (2019)7 25 F Proptosis, orbital Large mass in left orbit, Syn, NSE, CD56, Carcinoma S þ ChT Dead 2 years Yes
abscess ethmoid, frontal sinus Ki-67 (90%)
involvement at recurrence
Journal of International Medical Research

(continued)
 Qiao et al. 13

differences in pathological features and che-

CT, computed tomography; EMA, epithelial membrane antigen; Immunohist, immunohistochemistry; MRI, magnetic resonance imaging; NM, not mentioned; NSE, neuronal-
Classification Treatment Survival Follow-up Metastasis

M, male; F, female; CgA, chromogranin A; ChT, chemotherapy; CD56, neural cell adhesion molecule 1; CDX2, caudal type homeobox transcription factor 2; CK, cytokeratin;
motherapy response.20 Additional immuno-

3 months Yes

3 months Yes

No
histochemistry, including protein 53 (p53),
retinoblastoma-associated protein (RB1),
transcriptional regulator ATRX, delta-like

4 years
protein 3 (DLL3) and outer dense fibre pro-
tein 1 (ODF1), may be helpful in differenti-
ating the two conditions.17
Dead

Dead

Alive Treatment options for orbital NENs

include surgery, chemotherapy and radio-
therapy, either alone or in combination.
Among these, surgery is the most common
S

intervention.21 Depending on the specific

Carcinoma

Carcinoma

location of the tumour within the orbit, dif-

Carcinoid

ferent surgical approaches are chosen to

achieve the most radical resection of the
mass,22 aiming for curative intent.
CgA, MIB-1 (80%)

However, for the treatment of NEC,23

Syn, Ki-67 (90%)
A mass in the right orbit, sur- PCK, CD56, EMA,

PCK, EMA, CD56,

PCK, EMA, CD56,

orbital surgery is mainly reserved for

diagnostic purposes, and subsequent che-
Syn, CgA
Immunohist

motherapy (platinum–etoposide-based regi-

mens), or radiotherapy (external beam
radiotherapy) plays a crucial role.24
specific enolase; PCK, pan cytokeratin; RA, radiotherapy; S, surgery; Syn, synaptophysin.
rounded the optic nerve and

Somatostatin analogues (SSAs) are the pri-

squeezed the extraocular

mary treatment for functional tumours,

lateral rectus muscle of
A mass in the left orbit,

A mass surrounded the

aiming to control symptoms related to hor-

squeezed the eyeball

mone excess. Additionally, SSAs are

considered a first-line therapy for the low-
the left eye
CT/MRI scan

grade NETs with a Ki-67 tumour index of

muscles

10% or less, or for unresectable locally

advanced or metastatic NETs.25 Peptide
receptor radionuclide therapy with radiola-
belled SSAs has emerged as a promising
systemic treatment modality for patients
with inoperable or metastatic NETs.26 In
syndrome
(publication year) (years) Sex Presentation

Carcinoid
Proptosis

Proptosis

the present review of the literature, all

cases underwent surgical intervention, and
patients with orbital NEC received a
combination of radiotherapy and/or
M

chemotherapy.
Patient

The prognosis of orbital NENs is

Table 1. Continued

age

48

82

48

reported to be better than other systemic

metastatic diseases. In a study of orbital
metastatic NETs,27 the median survival
Present study

was found to be 11.3 years and the

Author

10-year survival was estimated at 71%.21

Among cases included in the present
14
review, five patients with NEC died during
a follow-up of 3 months to 4 years, whereas
seven patients with confirmed diagnosis of
carcinoids were reported to be alive with no
metastasis during follow-up of between 4
months and 5 years (Table 1).6–14
Discussion surrounding the primary ori-
gins of the three cases in the present case
series is intriguing. The patients in case 1
and case 2 deteriorated and died within 3
months without further treatment. This
raises the question of whether the orbital
lesions were metastases from occult primary
tumours elsewhere, or if they originated as
primary lesions in the orbit. NECs are
known to exhibit a high propensity for
metastasis.16 In particular, small cell neuro-
endocrine carcinomas (SNECs) are charac-
terized by rapid local invasion, metastasis
and a median survival time for untreated
patients of only 2–3 months. In the head
and neck region, the prognosis of SNECs
is even poorer than that of lung NEC,
with a survival rate of only about 13
months.28 If the present two cases indeed
represent metastatic tumours, there may
be a greater inclination towards head and
neck NECs, particularly paranasal small
cell neuroendocrine carcinomas, due to
their closer anatomical proximity.
Moreover, there have been a few docu-
mented cases of paranasal SNECs with pri-
mary orbital involvement.20 To date, the
patient in case 3 has been followed-up for
4 years without identification of the prima-
ry site. However, it is essential to consider
that even in cases where well-differentiated
NETs demonstrate distant metastases,
patients may still achieve longer survival,
as reported in cases with survival rates of
5 years or even 10 years after radical resec-
tion. In a review of 102 cases of orbital
NENs conducted by Mustak et al.,21
among the remaining five cases without an
identified primary tumour, only orbital dis-
ease was observed. Within this subgroup,
one death from the disease occurred
Journal of International Medical Research
during a 105-month follow-up period.
Therefore, extended follow-up is required
for the patient in the present case 3.
In conclusion, orbital NENs may mani-
fest as increased eye proptosis or rapid-
onset orbital masses. Therefore, it is crucial
to conduct imaging examinations and seek
histopathological evaluation of all orbital
lesions. Additionally, it should be noted that
some patients may not initially present to the
ophthalmology department, due to systemic
symptoms. Hence, proactive efforts are
required to identify potential primary lesions.
Surgical intervention remains the optimal
treatment approach for orbital NENs, either
as a standalone option or in combination
with radiotherapy and chemotherapy. The
selection of treatment strategy depends on
the tumour classification and grading, and
the patient’s overall condition. Regular re-
examination is necessary to monitor and
detect any potential tumour metastasis.
Author contributions
Conceptualisation of the study: WMH. Data
acquisition: QJY and WYJ. Manuscript prepa-
ration: QJY and WYJ. Manuscript revision:
WMH and QJY. All authors have read and
approved the final manuscript.
Data availability statement
The datasets used and analysed during the cur-
rent study are available from the corresponding
author upon reasonable request.
Declaration of conflicting interest
The Authors declare that there is no conflict of
interest.
Funding
This research received no specific grant from any
funding agency in the public, commercial, or
not-for-profit sectors.
ORCID iD
JunYi Qiao https://orcid.org/0000-0003-
3968-8765
Qiao et al.
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