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A Clinicopathological and
Molecular Analysis of Sellar/
Suprasellar Neurocytoma Mimicking
Pituitary Adenoma
Lifeng Zhang
1†
, Weiwei Fu
2†
, Limei Zheng
3
, Fangling Song
3
, Yupeng Chen
3
,
Changzhen Jiang
4
, Zhen Xing
5
, Chengcong Hu
3
, Yuhong Ye
3
, Sheng Zhang
3
,
Xiaorong Yan
4
*and Xingfu Wang
3
*
1
Department of Endocrinology, Fujian Provincial Governmental Hospital, Fuzhou, China,
2
Department of Pathology, The
Affiliated Hospital of Qingdao University, Qingdao, China,
3
Department of Pathology, The First Affiliated Hospital of Fujian
Medical University, Fuzhou, China,
4
Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University,
Fuzhou, China,
5
Department of Radiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
Objective: To investigate the clinicopathological characteristics, molecular genetic
characteristics and prognosis of extraventricular neurocytoma located in the sellar/
suprasellar region.
Methods: Seven archived tumor samples derived from 4 patients with neurocytoma in
the sellar/suprasellar region were collected from the First Affiliated Hospital of Fujian
Medical University and the Affiliated Hospital of Qingdao University and retrospectively
analyzed for clinical manifestations, imaging features, and histopathological features.
Neuronal and pituitary biomarkers and molecular features were detected in these tumor
tissues by immunohistochemistry and FISH or Sanger sequencing. The related literature
was reviewed.
Results: Three patients were female, while 1 was male, with an average age of 35.5 years
(range: 27 to 45 years). The initial manifestations were mainly headache and blurred vision
in both eyes. The first MRI examination showed marginally enhancing masses in the
intrasellar or intra- to suprasellar region. The diagnosis of pituitary adenomas was based
on imaging features. The levels of pituitary hormones were normal. Histologically, the
tumor cells were arranged in a sheet-like, monotonous architecture and were uniform in
size and shape with round to oval, exquisite and hyperchromatic nuclei, which densely
packed close to one another and were separated only by a delicate neuropil background.
There was no evident mitosis, necrosis or microvascular proliferation. The three cases of
recurrent tumors were highly cellular and showed increased mitotic activity.
Immunohistochemically, the tumor cells were positive for syn, CR, CgA, and
vasopressin and were focally positive for NeuN, TTF-1, NF, CK8, vimentin, and S100
proteins. Other markers, including IDH1, BRAF VE1, Olig-2, and EMA, were negative.
Pituitary transcription factors and anterior pituitary hormones were negative. Molecular
genetic testing showed that the tumor cells lacked IDH gene mutations, LOH of 1p/19q,
Frontiers in Endocrinology | www.frontiersin.org May 2022 | Volume 13 | Article 8615401
Edited by:
Congxin Dai,
Capital Medical University, China
Reviewed by:
Shun Yao,
Sun Yat-sen University, China
Ting Lei,
Tongji Hospital, China
*Correspondence:
Xingfu Wang
wang_xfu@126.com
Xiaorong Yan
178603351@qq.com
†
These authors have contributed
equally to this work
Specialty section:
This article was submitted to
Pituitary Endocrinology,
a section of the journal
Frontiers in Endocrinology
Received: 24 January 2022
Accepted: 08 April 2022
Published: 18 May 2022
Citation:
Zhang L, Fu W, Zheng L,
Song F, Chen Y, Jiang C, Xing Z,
Hu C, Zhang S, Ye Y, Yan X and
Wang X (2022) A Clinicopathological
and Molecular Analysis of Sellar/
Suprasellar Neurocytoma
Mimicking Pituitary Adenoma.
Front. Endocrinol. 13:861540.
doi: 10.3389/fendo.2022.861540
ORIGINAL RESEARCH
published: 18 May 2022
doi: 10.3389/fendo.2022.861540
MYCN amplification, and EGFR alteration. With a median follow-up of 74.5 months (range
23 to 137 months), 3 patients relapsed at 11, 50, and 118 months after the initial surgery.
Conclusion: The morphological features and immunophenotypes of neurocytoma in the
sellar/suprasellar region are similar to those of classic central neurocytoma. The prognosis
is relatively good. Gross-subtotal resection and atypical subtype may be related to
tumor recurrence.
Keywords: neurocytoma, extraventricular neurocytoma, sellar and suprasellar region, pituitary
tumor, clincopathology
INTRODUCTION
The first case of neurocytoma was reported by Hassoun et al. in
1982, who described two cases of third ventricle tumors with
neuronal differentiation and proposed the term “central
neurocytoma”(CN) (1). Thereafter, tumors with
clinicopathological features similar to central neurocytoma
were found outside the ventricles, including the hemispheric
parenchyma, cerebellum, pons, spinal cord, cauda equina, and
retina, which have been termed “extraventricular neurocytoma”
(EVN) (2). In 2007, EVN was officially recognized by the World
Health Organization (WHO) classification of central nervous
system tumors as a distinct entity among glioneuronal tumors,
making up 10% of all neurocytomas.
The radiological, histopathological, and immunophenotypic
features of EVNs resemble those of CNs. Contrary to CNs,
EVNs have a marked tendency for ganglionic differentiation. In
addition, EVNs have molecular characteristics distinct from those
of CNs (3). The prognosis is generally good for patients with CNs
or EVNs who can undergo complete removal. EVN arising in the
sellar or suprasellar region is an extremely rare tumor proposed to
be within the family of CNS neurocytomas. To the best of our
knowledge, there are only 21 cases of sellar/suprasellar
neurocytoma reported in the English literature. The
neuroimaging features of EVNs arising from the sellar/
suprasellar region are indistinguishable from those seen in
tumors of the pituitary gland. Histopathologically, the
differential diagnosis of sellar/suprasellar EVNs includes
pituitary adenoma/pituitary neuroendocrine tumors that can
also invade the sinuses, paraganglioma, and olfactory
neuroblastoma (4). The biological behavior of sellar/suprasellar
EVNs is unclear because few cases have been reported. Here, we
retrospectively analyzed the clinicopathological and molecular
features of 4 cases of extraventricular neurocytoma arising in the
sellar or suprasellar region and reviewed the related literature.
MATERIALS AND METHODS
Seven tumor samples from 4 patients with sellar/suprasellar EVN
were retrieved from the archives of the Department of Pathology of
the First Affiliated Hospital of Fujian Medical University and the
Affiliated Hospital of Qingdao University between 2000 and 2020
with the approval of the research ethics board. Written informed
consent was obtained from the individual(s) AND/OR minor(s)’
legal guardian/next of kin for the publication of any potentially
identifiable images or data included in this article. Clinical data of
the patients were obtained from their medical records.
All available immunohistochemical stains were reviewed and
documented. If not performed at the time of pathological
diagnosis, immunostaining including pituitary transcription
factors and so on was performed for each tissue sample with the
available formalin-fixed paraffin-embedded tissue blocks. Primary
antibodies used for immunostaining are against the following
proteins: pituitary-specific positive transcription factor 1 (Pit1),
T-box transcription factor 19 (T-Pit), splicing factor 1(SF1),
estrogen receptor alpha (ERa), GATA binding protein 2
(GATA2), thyroid transcription factor 1 (TTF1, SPT24),
synaptophysin(syn), chromogranin A(CgA), cytokeratin 8
(CK8), prolactin, growth hormone (GH), thyroid-stimulating
hormone (TSH), adrenocorticotropic hormone (ACTH), follicle-
stimulating hormone (FSH), luteinizing hormone(LH), S100,
neuron-specific enolase (NSE), neuronal nuclei (NeuN),
calretinin, glial fibrillary acidic protein (GFAP), oligodendrocyte
transcription factor 2(Olig2), neurofilament protein (NF), Ki-67,
GATA3, p53, E-cadherin, and vasopressin. Staining was
performed on a BenchMark ULTRA system (Ventana Medical
Systems, Tucson, AZ). A reticulin stain was also performed.
All 7 samples were tested by fluorescence in situ hybridization
for bHLH transcription factor (MYCN), fibroblast growth factor
receptor 1 (FGFR1), epidermal growth factor receptor (EGFR), 1p/
19q and cyclin dependent kinase inhibitor 2A (CDKN2A) gene
alterations and sequencing by Sanger sequencing for isocitrate
dehydrogenase 1 (IDH1), IDH2, and BRAF V600E mutations. All
probes were obtained from Gene Company Limited (Hong Kong).
RESULTS
Clinical and Radiologic Findings
The study group included 3 women and 1 man whose age at the
onset of symptoms ranged from 27 to 46 years with a median age
of 34 years. Patients presented mainly with worsening visual
disturbances and headaches for 5 months to 2 years. All patients
had no abnormalities of adenohypophyseal hormones on the
preoperative examination. CT scan demonstrated a well-
circumscribed lesion isodense with the brain parenchyma.
Focal calcification in the tumor was present in case 4. Brain
Zhang et al. Sellar/Suprasellar Neurocytoma
Frontiers in Endocrinology | www.frontiersin.org May 2022 | Volume 13 | Article 8615402
magnetic resonance imaging (MRI) revealed a sellar solid mass,
with focal cysts in cases 3 and 4 extending to the suprasellar
region, causing enlargement of the sellar, infiltrating the
cavernous sinus, and encasing the internal carotid artery. The
masses were isointense or hypointense on T1-weighted imaging
and heterogeneously hyperintense on T2-weighted imaging.
Post-contrast T1 images showed moderate enhancement
(Figure 1)(Table 1).
FIGURE 1 | Radiological, histological and immunohistochemical features of sellar/suprasellar neurocytoma (Case 1). MR imaging demonstrated a well-circumscribed
mass located in the sellar and suprasellar regions. The tumor was inhomogeneously hyperintense on coronal T2WI, and the left suprasellar sinus space was involved
(A), while the lesion was hypointense on sagittal T1WI, and the optic chiasma was displaced upwardly (B). The lesion showed significant homogeneous
enhancement on enhanced T1WI (C). Microscopically, the tumor is comprised of solid nests or sheets of noncohesive monotonous small round cells with round to
oval nuclei and fine chromatin. The poorly defined cytoplasm merges with the neuropil. Necrosis and mitotic figures are absent. (D, H&E, ×100; E, H&E, ×200)
Immunohistochemical analysis revealed that the tumor cells had neuronal differentiation and were positive for synaptophysin (F, ×100), NeuN (G, ×200), and
calretinin (H, ×200). TTF1 (I, ×200)and vasopressin (J, ×200)had variable reactivities. The Ki-67 labeling index is approximately 1.5% (K, ×200).
Zhang et al. Sellar/Suprasellar Neurocytoma
Frontiers in Endocrinology | www.frontiersin.org May 2022 | Volume 13 | Article 8615403
Histopathological Features
Histopathological examination revealed a moderately
hypercellular neoplasm comprised of sheets of small- to
medium-sized cells with round-to-oval, monomorphic nuclei
with dispersed chromatin and inconspicuous nucleoli
(Figure 1). The nuclei were surrounded by scant finely
granular eosinophilic cytoplasm or perinuclear halos. Focal
areas of the tumor were less cellular and had anuclear areas
with fine fibrillary neuropil. Rare mitotic figures were present.
Necrosis and vascular proliferation were absent. There was focal
fibrosis and calcification. The recurrent tumor tissues of case 1
(Figure 2) and case 4 showed atypical histologic features,
including focal necrosis, microvascular proliferation, and active
mitoses. In addition, the recurrence of case 1 was comprised of
smaller-sized and partly markedly hypercellular tumor cells.
Classical large gangliocytes were lacking in the tumor tissues of
all 7 samples.
Immunophenotypic Features and
Molecular Genetics Results
Immunohistochemically, the tumor cells were positive for
synaptophysin, chromogranin A, and calretinin and were
focally positive for NeuN, TTF1, NF, CK8, vimentin, and S100
proteins. A few entrapped or reactive astrocytes expressed GFAP,
but the tumor cells were negative. Other markers, including
IDH1, BRAF VE1, Olig-2, EMA, E-cadherin and GATA3, were
negative. All pituitary transcription factors, including Pit-1, T-
pit, SF1, ER
a,
and GATA2, and anterior pituitary hormones,
such as GH, PRL, TSH, FSH, LH and ACTH, were negative.
However, vasopressin expression was identified in all 7 samples.
The Ki-67 labeling index of cases 1-3 was 1% to 2%, and it was
6% in case 4, while those of the recurrent cases 1, 2 and 4 were
5%, 2%, and 10%, respectively.
Sanger sequencing did not detect IDH1, IDH2 or H3F3A
mutations in 5 of 7 FFPE samples (case 1 and its recurrence,
recurrence of case 2 and case 4, and case 3), while loss of ATRX
expression was absent by immunostaining. Fluorescence in situ
hybridization (FISH) detection showed that tumor cells were
intact on chromosomes 1p and 19q, CDKN2A nondeletion, and
EGFR nonamplification. Rearrangement of fibroblast growth
factor receptor 1 (FGFR1) was not found by FGFR1 break-apart
probe FISH. The BRAF V600E mutation and TERT promoter
mutations were negative by tetraprimer amplification refractory
mutation system-polymerase chain reaction (ARMS-PCR), and
the absence of O6-methylguanine-DNA methyltransferase
(MGMT) gene promoter methylation was identified by
pyrosequencing in the 3 cases of recurrence (Table 2).
Treatments and Prognosis
All 4 patients underwent surgical treatment. Case 2 was excised
via a transsphenoidal procedure tumor resection, and
transsphenoidal endoscopic approach resection of the mass
was performed in the other three cases. The tumors in case 1,
case 2 and case 4 were resected subtotally through the nasal sella.
In case 4, only approximately 2/3 of the mass could be removed.
TABLE 1 | Clinicopathological details of the present 4 cases of sellar/suprasellar neurocytoma.
case Sex Age Initial symptoms Serum
vasopressin
Pituitary
hormone
Location Focal infil-
trations
Preoperative
impression
Type Initial
operation
Adjuvant
radiotherapy
Recurrence
(months)
second
operation
Type follow-up
(months)
1 F 28 Visual disturbances; 2-year normal normal S/S yes Pituitary
adenoma
typical STR No Yes (50) STR atypical (live) 63
2 M 46 Visual impairment; 2-year NA NA S/S yes Pituitary
adenoma
typical STR No Yes (118) STR typical (live) 137
3 F 27 Blurred vision; 5-month NA normal S/S yes Pituitary
benign tumor
typical GTR No No No No (live) 65
4 F 40 Bitemporal hemianopsia;
10-month
NA normal S/S yes Pituitary
adenoma
atypical STR No Yes (11) STR atypical (live) 23
NA, Not available; S/S, Sellar/Suprasellar; S, Sellar; PA, Pituitary adenoma; STR, Subtotal resection; GTR, Gross total resection.
Zhang et al. Sellar/Suprasellar Neurocytoma
Frontiers in Endocrinology | www.frontiersin.org May 2022 | Volume 13 | Article 8615404
With a median follow-up of 74.5 months (range 23 to 137
months), all 4 patients survived. Case 1, case 2 and case 4
relapsed at 50, 118 and 11 months after initial surgery, and
they underwent a transsphenoidal endoscopic approach
resection for subtotal removal of the tumor again. Radiation
therapy was performed after the second surgery (Table 1).
DISCUSSION
Sellar/suprasellar neurocytoma is an extraventricular
neurocytoma arising from the hypothalamic-pituitary region.
Only 21 cases of EVNs arising in the sellar/suprasellar region
have ever been reported in the English literature. The clinical,
radiological, and pathological features of the patients are shown
in Table 3. The ages of the patients at first diagnosis ranged from
14 to 70 years, with an average of 44 years, and the female-to-
male ratio was 1:1. The original complaints were reduced visual
acuity with bitemporal or asymmetrical hemianopsia related to
focal compression. Headache and dizziness would also occur.
Radiological examination revealed that the sellar/suprasellar
neurocytomas were generally well-defined, solid, homogeneous,
and with limited or no peritumoral swelling. Small−scattered
calcifications and cystic components occurred in a few cases. The
vast majority of tumors, including the present 4 cases we
reported, presented with invasion of the cavernous sinus. The
CT scans revealed discreetly iso/hyperdense and heterogeneous
enhancing appearances. In general, magnetic resonance imaging
(MRI) showed that the EVNs were iso-signal to gray matter on
T1- and T2-weighted images, with a variable heterogeneous
enhancement pattern (6,9,23).
Histopathologically, EVNs arising in the sellar/suprasellar
region have similar features of central neurocytoma and EVNs
arising from other loci (4,18,19). These tumors are comprised
of sheets of uniform round cells with “salt and pepper”
chromatin and inconspicuous nucleoli. The tumor cells are
usually embedded in a neuropil-like fibrillary background.
Calcifications and ‘chicken wire’-like capillaries are also
common. Ganglion cell differentiation is uncommon in central
neurocytomas but is relatively frequent, up to approximately
50%, in extraventricular neurocytomas (24–26). EVN with
ganglioid differentiation mainly arises from the frontal,
temporal, and parietal lobes. There are only 2 cases of EVN
with ganglioid differentiation occurring in the sellar/suprasellar
region reported in the literature (20). No evidence of ganglioid
differentiation was shown in any of the 7 sample tissues in this
study. Necrosis and microvascular proliferation occur in a few
cases with aggressive growth. In our cases, 2 recurrences showed
anaplastic characteristics and progressed into atypical EVNs.
Immunohistochemistry confirmed that neurocytomas are
positive for neuronal differentiation markers such as
synaptophysin and chromogranin A and variable
neurofilaments, NeuN and calretinin. Hypothalamic hormone
vasopressin and focal TTF-1 expression are seen, and some
FIGURE 2 | Patient 1 relapsed 50 months after the first surgery. The tumor located in the sellar and suprasellar regions demonstrated inhomogeneous
hyperintensity on coronal T2WI, and the bilateral cavernous sinuses were involved (A). On sagittal T1WI images, the lesion exhibited inhomogeneous hypointensity
and irregular margins (B), with significant inhomogeneous enhancement on enhanced T1WI (C). Histologically, there were some atypical or anaplastic features,
including focal necrosis (D, H&E, ×100)and microvascular proliferation (E, H&E,×200), with a high Ki-67 index (F, ×200).
Zhang et al. Sellar/Suprasellar Neurocytoma
Frontiers in Endocrinology | www.frontiersin.org May 2022 | Volume 13 | Article 8615405
researchers have suggested that these tumors may be derived
from the basal hypothalamus, which could provide a useful
diagnostic tool for differential diagnosis. They were all negative
for pituitary transcription factors and hormones, GFAP,
keratins, EMA, IDH1, BRAF VE1, Olig-2 and so on. Most CNs
usually show a Ki-67 labeling index of less than 2%; however, a
small portion of tumors that are termed atypical CNs are
characterized by an increased Ki-67 labeling index of more
than 2% or 3%. Atypical CN was recognized by the WHO in
2016, accounting for approximately 25% of all CNs (27). A strict
definition of “atypical EVN”has not been clarified by the WHO,
and the Ki-67 labeling index for the definition of atypia ranges
from 2% to 5% among different studies (28,29). Generally,
atypical EVNs are characterized by increased mitotic activity or a
higher Ki-67 labeling index and other atypical features, such as
necrosis or microvascular proliferation (29,30). Compared with
atypical CNs, the proportion of atypical EVNs is approximately
30% higher than that of all EVNs. The atypical cases of sellar/
suprasellar EVNs in the literature and this study had a similar
rate, accounting for 32% (8/25).
To date, little is known about the molecular genetic features of
extraventricular neurocytoma. A study from Slevers et al.
revealed that the presence of FGFR1-TACC1 or FGFR3-
TACC3 gene fusions in extraventricular neurocytoma located
in the supratentorial brain is a frequent molecular event,
especially the former, accounting for approximately 60% (3).
However, these gene fusions have not been reported in EVN in
the sellar or parasellar regions. In the present 4 patients, no
FGFR1 gene breakage or rearrangement was found by FISH
detection, suggesting that sellar/suprasellar neurocytomas may
not have the same molecular biological characteristics as those
originating from other parts. A microarray-based comparative
genomic hybridization investigation revealed distinct profiles,
with loss and gain of multiple chromosomal loci, which
concluded that MYCN gene amplification, together with loss of
BIN1 expression, were typical of central neurocytoma (31).
EGFR amplification mutations have been reported in two cases
of atypical EVNs (32,33).Inourcases,therewasno
amplification of MYCN or EGFR, and no alterations in IDH1,
IDH2, BRAF V600E, 1p/19q, H3F3A or CDKN2A were found.
Several cases of sellar/suprasellar EVN reported in the
literature have confirmed that the tumor cells are
immunoreactive for vasopressin (5,21). Through electron
microscopic observation, Maguire et al. found that the
perinuclear cytoplasm of the tumor cells contains
neurosecretory granules, which are also packed in swollen
neuritic processes that resemble Herring bodies (5). They
interpreted the immunohistochemical and ultrastructural
features of this tumor as suggestive of primary hypothalamic
derivation. All samples in this study were positive for
vasopressin, supporting the above view. Asa et al. reported that
3 patients with sellar/suprasellar EVN had a syndrome of
inappropriate antidiuresis, which is associated with excess
vasopressin production by tumors (21). However, serum
vasopressin levels were not investigated preoperatively or
postoperatively in our cases, which is a limitation of this study.
TABLE 2 | Immunohistochemical and molecular features of all 7 samples of 4 cases of sellar/suprasellar neurocytoma.
Case Syn NeuN NF TTF1 vasopressin calretinin MAP2 TFs hormones Ki67
(+,%)
IDH1/2 (Sanger
Sequencing)
1p/19q
(FISH)
EGFR
(FISH)
TERT (Sanger
sequencing)
CDKN2A
(FISH)
FGFR1 (FISH) MGMT (Pyro-
sequencing)
1++f+f+S+ + + +–– 1.5 wildtype intact nonamp wildtype intact nonrearrangement NA
R1 ++ f+ –– +++–– 5 wildtype intact nonamp wildtype intact nonrearrangement unmethylated
2 ++ + f+ S+ + + + –– 1 NA NA NA NA NA nonrearrangement NA
R2 ++ S+ f+ –+++–– 2 wildtype intact nonamp wildtype intact nonrearrangement unmethylated
3 ++ + f+ + + ++ + –– 1.5 wildtype intact nonamp wildtype intact nonrearrangement NA
4++f+f++ + + +–– 6 NA NA nonamp NA intact nonrearrangement NA
R4 ++ f+ f+ S+ + W+ + –– 10 wildtype intact nonamp wildtype intact nonrearrangement unmethylated
+, positive; ++, strongly positive; f, focally; s, scattered; w, weakly; -, negative; TFs, transcr factors of adenohypophysis; NA, not available; FISH, fluorescence in situ hybridization.
Zhang et al. Sellar/Suprasellar Neurocytoma
Frontiers in Endocrinology | www.frontiersin.org May 2022 | Volume 13 | Article 8615406
TABLE 3 | Clinicopathological details of the 21 reported cases of sellar/suprasellar neurocytoma.
Case Reference Sex Age Initial symptoms Serum vaso-
pressin
Pituitary
hormone
Location Focal infil-
trations
Preoperative
impression
Type Resection Adjuvant
radiotherapy
Recurrence
1 Maguire et al. (5) F 55 Visual disturbances; 6 months NA normal S/S no PA typical STR NA NA
2 Yang GF et al. (6) F 46 Visual impairment; 1 year NA normal S/S yes Meningioma typical STR NA NA
3 Chen H et al. (7) M 52 Blurred vision; 6-month NA normal S no NA typical GTR no NA
4 Wang Y et al. (8) F 50 Decreasing vision; 2-month NA normal S/S yes PA or
craniopharyngioma
typical STR yes no
5 Liu K et al. (9) M 40 Visual impairment; NA NA normal S/S yes PA typical NA no no
6 Wang Y et al. (10) F 23 Bitemporal visual deficit and
headache;4-month
NA NA S/S yes NA typical STR yes NA
7 Kawaji H et al. (11) M 48 Visual impairment NA PRL↑S/S yes PA atypical STR yes 6 years
8 Xiong Z et al. (12) NA 56 NA NA NA S NA NA typical NA NA NA
9 Makis W et al. (13) F 64 Bitemporal hemianopsia;30-year history
of recurrent sellar masses
NA NA S/S NA Recurrent PA atypical NA yes 30yrs ago
(typical)
4yrs ago
(atypical)
10 Peng P et al. (14) M 56 Bitemporal hemianopsia NA ACTH↓S/S yes PA typical GTR no no
11 Chen S et al. (15) F 50 Decreasing vision in left eye and
diplopia; 2-month
NA normal S/S yes NA typical STR yes no
12 Chen S et al. (15) M 62 Homonymous hemianopsia, temporal
both eyes; 1 year
NA PRL↓S/S no NA typical,
ganglion
STR yes no
13 Cho et al. (16) M 14 Bitemporal hemianopsia, decreased
visual acuity; 0
NA NA S/S yes Hypothalamic
glioma
typical STR yes 1 year
14 Wang et al. (16) M 25 Worsening vision; 7-month NA normal S/S yes PA or meningioma typical STR yes no
15 Tan CL et al. (17) F 59 Visual disturbances; 2-year; with a
history of osteoporosis and SIADH
NA NA S/S yes PA typical STR yes no
16 Nery B et al. (18) M 27 Progressive bilateral vision loss; 4-year NA normal S/S yes PA typical GTR no no
17 Tish S et al. (19) M 70 Imbalance and dizziness NA normal S/S yes NA atypical,
ganglion
biopsy yes no
18 Asa et al. (21) F 39 5-month history of worsening visual
field loss; idiopathic SIADH; 6-year
vasopressin
excess with
SIAD
normal S/S yes PA atypical STR no NA
19 Asa et al. (21) F 34 Galactorrhea, amenorrhea,
hyponatremia; 18-month
vasopressin
excess with
SIAD
PRL↑S/S NA PA atypical STR yes 30yrs, death
20 Asa et al. (21);
Zhang D et al. (22)
M 17 Progressive abdominal pain, nausea
and emesis; 3-year
vasopressin
excess with
SIAD
low total
testosterone
S yes NA atypical STR no no
21 Asa et al. (21) F 40 Visual disturbance and headache no normal S/S yes PA atypical STR no <1 year
NA, Not available; SIADH, Syndrome of inappropriate antidiuretic hormone secretion; S/S, Sellar/Suprasellar; S, Sellar; PA, Pituitary adenoma; STR, Subtotal resection; GTR, Gross total resection.
Zhang et al. Sellar/Suprasellar Neurocytoma
Frontiers in Endocrinology | www.frontiersin.org May 2022 | Volume 13 | Article 8615407
Therefore, whether the serum level of vasopressin can hint at the
diagnosis of this tumor is unclear, and more case studies
are needed.
Most of the reported cases and the present cases were
diagnosed as giant pituitary adenomas before surgery, and none
of them were suspected to be EVNs based on preoperative
imaging. A large pituitary adenoma suspected to involve the
sellar/suprasellar region with invasion of the venous sinuses and
nonfunctional clinical changes always has the possibility of being a
neurocytoma. Histopathologically, pituitary endocrine tumors are
the first differential diagnosis. In most cases, the histological
characteristics of pituitary endocrine tumors as well as the
pattern of expression of transcription factors and pituitary
hormone markers can easily distinguish them. However, it is
difficult to make a differential diagnosis from null cell adenoma,
a very rare group of pituitary neuroendocrine tumors (PitNETs)
that are negative for all adenohypophyseal hormones and
transcription factors. The main points of differential diagnosis
include the identification of neuropils and the expression of NeuN
and TTF1 in sellar/suprasellar EVNs. In addition, we found that E-
cadherin and P120 are also useful markers for differential
diagnosis (unpublished), which are immune-positive in pituitary
adenomas but immune-negative in neurocytomas. Other
differential diagnoses include paraganglioma and olfactory
neuroblastoma. Immunohistochemical markers are helpful. For
example, paraganglioma generally expresses GATA3 and tyrosine
hydroxylase, while neurocytoma does not (34).
Gross total resection is the preferred treatment for EVN (35,
36). EVN that occurs in the sellar/suprasellar region often
invades the sphenoid sinus and cavernous sinus and usually
compresses the optic nerve and envelops the internal carotid
artery, so gross total resection is quite difficult, and thus subtotal
resection is often performed. Adjuvant radiotherapy, either
conventional or radiosurgery with gamma knife, can improve
both local control and survival in patients who undergo subtotal
resection (37,38). The effect of chemotherapy on EVNs as an
adjuvant management tool remains unclear. The overall
prognosis of EVNs is good, although the recurrence rate is
higher than that of CNs. In addition to incomplete resection
affecting the prognosis, atypical or anaplastic features are
associated with a higher recurrence rate and generally worse
outcomes. In our cases, all 4 patients underwent surgical
treatment radiotherapy or chemotherapy was not performed
postoperatively, and 3 cases underwent subtotal resection have
relapsed after initial surgery.
In summary, neurocytoma of the sellar/suprasellar region is
an extremely rare tumor. The morphological features and
immunophenotypes of a neurocytoma in the sellar/suprasellar
region are similar to classic central neurocytoma. The tumor is
often not completely resected, and adjuvant radiotherapy is
feasible after surgery. Attention should be given to the
differential diagnosis of pituitary endocrine tumors. The overall
prognosis is good. Atypical histological features and subtotal
resection may be related to tumor recurrence. Its biological
behaviors and molecular genetics/epigenetics characteristics
need to be studied further with a larger sample.
DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in
the article/supplementary material. Further inquiries can be
directed to the corresponding authors.
AUTHOR CONTRIBUTIONS
LFZ: Investigation, Data curation, Writing- Original draft
preparation. WF: Investigation, Data curation, Writing-
Original draft preparation. LMZ and YHY: Data curation,
Visualization. FS: Methodology. YC: Methodology. CJ: Data
curation. ZX: Data curation. CH: Data curation. SZ: Project
administration. XY: Data curation,Supervision,Writing-
Reviewing and Editing. XW: Funding acquisition, Supervision,
Writing- Reviewing and Editing. All authors contributed to the
article and approved the submitted version.
FUNDING
This study was supported by Natural Science Foundation of
Fujian Province (2018J01155), Fujian Medical University Startup
Fund for scientific research (2020QH1053) and Fujian Provincial
Health and Family Planning Training Project for Young and
Middle-aged Key Talents (2019-ZQN-61).
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