10.14639/0392-100X-suppl.1-41-2021-03
Introduction. The endoscopic endonasal transsphenoidal approach to the sella and parasellar regions is now increasingly used for removal of a variety of lesions localized in the ventral skull base. The advantage of the endoscope is enhanced visualization and improved panoramic view that can result in more complete removal of the tumor. An extensive knowledge of the anatomy is mandatory to approach this region. Materials and methods. From February 2009 to March 2020, the endoscopic endonasal approach was used in 153 patients with sellar and parasellar lesions, at our Institution: 136 pituitary adenomas, 7 craniopharyngiomas, 3 Rathke’s cysts, a tuberculum sellae meningioma, an aneurysm of the internal carotid artery (ICA), a clivus chordoma, a papillary glioneuronal tumor, an histiocytosis, a pituitary metastasis from breast cancer and a chondrosarcoma. Results. The most common surgical complications were cerebral spinal fluid leak (9), bleeding (2), pituitary abscess (2). Among endocrinological complications, the most important were diabete insipidus (23) and panhypopituitarism (3). Two patients complicated with meningitis. There were no visual worsening and no operative mortality. We had persistence of disease in 20 cases. Twelve patients underwent surgical revision for recurrence of the disease. Conclusions. Pre-operative planning and collaboration with several specialists are necessary in order to offer the patient the best treatment, minimizing complications.
application/xml
1827-675X
1684
en
Luca Denaro
https://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
endoscopic endonasal approach
Sellar and parasellar lesions: multidisciplinary management
Text.Serial.Journal
https://www.actaitalica.it/
41
Annual congress report
2021-05-14
2021-05-10
2021-05-14
2021-05-14
30-41
1
Luca Denaro
2021/05/14
10.14639/0392-100X-suppl.1-41-2021-03
30
Department of Neurosciences DNS, Neurosurgery Section, Padua University, Padua, Italy
1827-675X
endoscopic endonasal approach
41
Sellar and parasellar lesions: multidisciplinary management
https://www.actaitalica.it/article/download/1684/557
41
ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41(SUPPL.1):S30-S41; doi: 10.14639/0392-100X-suppl.1-41-2021-03




Sellar and parasellar lesions: multidisciplinary
management
Lesioni della regione sellare e parasellare: gestione multidisciplinare
Enzo Emanuelli1, Claudia Zanotti1, Sara Munari1, Maria Baldovin1, Gloria Schiavo1, Luca Denaro2
1
  Department of Neurosciences DNS, Otolaryngology Section, Padua University, Padua, Italy; 2 Department of Neurosciences DNS,
Neurosurgery Section, Padua University, Padua, Italy


SUMMARY
Introduction. The endoscopic endonasal transsphenoidal approach to the sella and para-
sellar regions is now increasingly used for removal of a variety of lesions localized in the
ventral skull base. The advantage of the endoscope is enhanced visualization and improved
panoramic view that can result in more complete removal of the tumor. An extensive knowl-
edge of the anatomy is mandatory to approach this region.
Materials and methods. From February 2009 to March 2020, the endoscopic endonasal ap-
proach was used in 153 patients with sellar and parasellar lesions, at our Institution: 136 pi-
tuitary adenomas, 7 craniopharyngiomas, 3 Rathke’s cysts, a tuberculum sellae meningioma,
an aneurysm of the internal carotid artery (ICA), a clivus chordoma, a papillary glioneuronal
tumor, an histiocytosis, a pituitary metastasis from breast cancer and a chondrosarcoma.
Results. The most common surgical complications were cerebral spinal fluid leak (9), bleed-
ing (2), pituitary abscess (2). Among endocrinological complications, the most important
were diabete insipidus (23) and panhypopituitarism (3). Two patients complicated with men-
ingitis. There were no visual worsening and no operative mortality. We had persistence of            Received: November 22, 2020
disease in 20 cases. Twelve patients underwent surgical revision for recurrence of the disease.      Accepted: February 18, 2021
Conclusions. Pre-operative planning and collaboration with several specialists are neces-
sary in order to offer the patient the best treatment, minimizing complications.                     Correspondence
KEY WORDS: skull base, sellar and parasellar region, pituitary adenoma, endoscopic                   Enzo Emanuelli
                                                                                                     Department of Neurosciences DNS, Otolaryngo-
endonasal approach
                                                                                                     logy Section, Padua University, Padua, Italy
                                                                                                     E-mail: enzoemanuelli@libero.it
RIASSUNTO
Introduzione. L’approccio endoscopico endonasale trans-naso-sfenoidale alla sella e alla re-         Funding
gione parasellare è a oggi l’approccio più utilizzato per lesioni localizzate nella parte ventrale   None.
della base cranica. Il vantaggio di questa tecnica consiste in una miglior visualizzazione pano-
ramica del sito chirurgico che consente una rimozione quanto più completa del tumore. Un’ap-         Conflict of interest
profondita conoscenza dell’anatomia è d’obbligo per iniziare ad approcciare questa regione.          The Authors declare no conflict of interest.
Materiali e metodi. Da febbraio 2009 a marzo 2020, abbiamo trattato nel nostro Istituto
153 pazienti con lesioni sellari e parassellari mediante approccio endoscopico endonasale;             How to cite this article: Emanuelli E, Zanotti
di questi 136 erano adenomi dell’ipofisi, 7 craniofaringiomi, 3 cisti di Rathke, un menin-             C, Munari S, et al. Sellar and parasellar lesions:
gioma del tubercolo sellae, un aneurisma dell’arteria carotide interna, un cordoma del                 multidisciplinary management. Acta Otorhi-
clivus, un tumore glioneuronale papillare, un’istiocitosi, una metastasi pituitaria da cancro          nolaryngol Ital 2021;41(SUPPL.1):S30-S41.
al seno e un condrosarcoma.                                                                            https://doi.org/10.14639/0392-100X-sup-
Risultati. Le complicanze chirurgiche più comuni sono state la rinoliquorrea (9), il san-              pl.1-41-2021-03
guinamento (2), l’ascesso pituitarico (2). Tra le complicanze endocrinologiche, le più
                                                                                                     © Società Italiana di Otorinolaringoiatria
importanti sono state il diabete insipido (23) e il panipopituitarismo (3). Due pazienti si
                                                                                                     e Chirurgia Cervico-Facciale
sono complicati con meningite. Non ci sono stati deficit visivi né mortalità intraoperatoria.
Abbiamo avuto persistenza di malattia in 20 casi. Dodici pazienti sono stati sottoposti a
                                                                                                                    OPEN ACCESS
reintervento per recidiva.
Conclusioni. Un’adeguata pianificazione preoperatoria e la collaborazione tra diversi                This is an open access article distributed in accordance with
                                                                                                     the CC-BY-NC-ND (Creative Commons Attribution-Non-
specialisti sono necessarie per offrire al paziente il miglior trattamento possibile, riducen-       Commercial-NoDerivatives 4.0 International) license. The
do al minimo le complicanze.                                                                         article can be used by giving appropriate credit and mentio-
                                                                                                     ning the license, but only for non-commercial purposes and
PAROLE CHIAVE: base cranica, regione sellare e parasellare, adenoma ipofisario,                      only in the original version. For further information: https://
approccio endoscopico endonasale                                                                     creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                                                              Endoscopic approach to sella and parasella




Introduction                                                      • suprasellar extension of pituitary adenomas;
                                                                  • craniopharyngiomas;
The sphenoid bone sits at the center of the skull base, rep-      • hypothalamic or optic chiasm gliomas;
resenting the fulcrum of this region and the border point         • hamartomas;
between the anterior and middle cranial fossa. The sella          • germinomas;
turcica is a bone depression included between the anterior        • dermoid and epidermoid tumors.
and posterior clinoid processes of the sphenoid bone. It rep-     The cavernous sinuses, two venous structures that delimit
resents the central portion of the middle cranial fossa and       the pituitary fossa laterally, are in relationship with the fol-
contains the pituitary gland. Laterally to the sella turcica,     lowing cranial nerves: oculomotor (III), trochlear (IV), first
along the fusion line between the body of the sphenoid and        and second branches of the trigeminal nerve (V1 and V2),
greater wings, there is the carotid sulcus for the passage of     and abducent (VI). All the nerves are contained in the lat-
the parasellar portion of the internal carotid artery (ICA).      eral wall of the cavernous sinus, except the abducent nerve
The pituitary gland is composed of two parts: the adeno-          which is located laterally to the carotid artery and medially
hypophysis (anterior lobe), which represents about 70%            to V1. Within the cavernous sinus there is also the cavern-
of the volume of the entire gland and the neurohypophysis         ous carotid artery (with three segments and two genua) and
(posterior lobe).                                                 its branches. The lesions that most affect the cavernous si-
A semitransparent, thin but tight capsule surrounds the           nuses are:
gland’s surface. The pituitary gland is completely sur-           • lateral extension of pituitary adenomas;
rounded by dura mater: its anterior, inferior and posterior       • meningiomas;
walls are surrounded by a double layer and by sellar bone;        • schwannomas;
on the contrary, the upper and lateral walls are covered on-      • aneurysms of the ICA.
ly by dura mater and both offer less resistance to tumour         Clivus is a bony portion behind the dorsum sellae that
growth 1.                                                         slopes obliquely backward to the magnum foramen getting
The upper wall which forms an inextensible diaphragm, is          in touch with the ventral face of the brain stem. The clival
thick at the periphery, thin at the centre, where it is de-       region extends inferiorly to the dorsum sellae and includes
pressed and perforated by the hypothalamus-pituitary stalk.       the sphenoid sinus, the nasopharynx and the clivus. The
Anteriorly the two layers of dura mater continue with the         most common lesions of this region are:
dura mater covering the sphenoidal planum and the ante-           • chordomas;
rior cranial fossa, posteriorly they continue with the dura of    • chondrosarcoma;
dorsum sellae and clivus. Laterally, the two layers separate:     • meningiomas;
the outer periosteal layer continues laterally to form the        • nasopharyngeal carcinomas;
sphenoidal or anterior wall of the cavernous sinus, while         • tumors of the sphenoid sinus;
the inner meningeal layer remains attached to the gland and       • mucoceles;
runs backwards towards the posterior clinoid process and          • juvenile angiofibromas.
the dorsum sellae to form the medial wall of the cavernous        Histology of sellar and parasellar lesions is heterogeneous
sinus. Consequently, both walls (anterior and medial) of the      but the main role is played by the pituitary adenomas; how-
cavernous sinuses are made up of a single layer of dura           ever, in 9% of cases we find different histologies with pecu-
mater 2. The arachnoid is located just above the diaphragm        liar biological features that is essential to know for adequate
and, therefore, there is usually no liquor inside the sella.      surgical treatment (Tab. I). The biological variety does not
The parasellar region includes all the structures surround-       reflect the clinic, since symptoms of sellar and parasellar
ing the sella turcica 3: the suprasellar region at the top, the   neoplasms depend on the sub-site of origin: in this particular
two cavernous sinuses laterally, and the clival region at         district, knowledge of the anatomy is essential not only for
the bottom. It represents a crossroads region where a high        surgical purposes, but also to define the clinical picture.
number of neoplastic, inflammatory, infectious and vascu-         The radiological study plays a key-role in the diagnostic
lar diseases can develop 4.                                       framework of these pathologies. The Magnetic Resonance
The suprasellar region extends above the sellar diaphragm         Imaging (MRI) with gadolinium and the Computer To-
to the floor of the third ventricle and contains the optic chi-   mography (CT) scan are complementary: the first provides
asm, optic nerves, the pituitary stalk and the Willis’ circle.    information about the nature of the lesion and the involve-
It is close to the third ventricle, the hypothalamus, the tuber   ment of vital structures; the second defines in detail the
cinereum and the mammillary bodies. The most common               bone involvement and allows to identify the possible pres-
lesions of this region are:                                       ence of intralesional calcifications.



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Table I. Main lesions of sellar and parasellar region.
 Pathology                     Symptoms            Radiological features         Differential diagnosis             Treatment              Multidisciplinary
                                                                                                                                              approach
 Pituitary adenoma                  Endocrine                 Brain MRI:            Pituitary abscess;          Surgical treatment            Mandatory
                                  dysfunction;   lower density than healthy        pituitary carcinoma;        with trans-sphenoidal
                            visual impairment;      glandular parenchyma          pituitary metastasis;               approach
                             obstruction of the          in T1 sequences;          craniopharyngioma;
                              liquor drainage; heterogeneous increased            hypothalamic glioma;
                                rhinoliquorrea     signal with hyper-intense     parasellar meningioma
                                                    areas in T2 sequences
 Meningioma                 Visual impairment;                Brain MRI:           Pituitary adenoma;         Surgery in symptomatic Strongly recommended
                                    endocrine         same density as the            paraganglioma               or growing mass.
                                  dysfunction;       cerebral parenchyma                                      Adjuvant radiotherapy in
                                cranial nerves          in both T1 and T2                                      macroscopic residual
                                     deficits;     sequences, with marked
                             obstruction of the     contrast-enhancement
                               liquor drainage
 Craniopharyngioma             Hydrocephalus                 - Brain MRI:      Optic glioma; Rathke’s cyst;      Exclusive surgical           Mandatory
                              and endocranial          lower density than           pituitary adenoma          resection (complete/
                                 hypertension    cerebral parenchyma with                                      subtotal) or subtotal
                                 (especially in  hyper-intense cystic areas                                    resection associated
                              children); visual          in T2 sequences.                                        with radiotherapy
                                  impairment;             - Brain CT-scan:
                                    endocrine       calcific components in
                                   dysfunction    adamanthomatous forms
 Glioma                     Visual impairment;                Brain MRI:           Craniopharyngioma            Surgery followed by      Strongly recommended
                               hydrocephalus           lower density than                                     adjuvant radiotherapy in
                              and endocranial cerebral parenchyma with                                           aggressive forms
                                 hypertension    hyper-intense cystic areas
                                                          in T2 sequences
 Chordoma                      Diplopia due to            - Brain CT-scan:      Fibrous dysplasia; Paget’s      The radical surgical     Strongly recommended
                              abducent nerve          hyperintense lesion      disease; pituitary adenoma;    treatment is considered
                            impairment; facial surrounded by reabsorbed             clival meningioma;          the main prognostic
                              nerve paralysis;                   bone;                paraganglioma;             factor in literature
                                   vertigo and     - Brain MRI: hypointense          chondrosarcoma
                            tinnitus; trigeminal         in T1 sequences,
                                  paresthesia          hyperintense in T2
                                                              sequences
 Hemangiopericytoma                 Endocrine             - Brain CT-scan:      Hemangiomas; vascular          Surgery followed by       Strongly recommended
                                  dysfunction;            expansive mass            leiomyomas;               adjuvant radiotherapy
                               hydrocephalus         associated with bone             sarcomas                in case of incomplete
                                                               thinning;                                      removal or recurrence
                                                         - Brain MRI: iso /
                                                   hypointense signal in T2
                                                   sequences, intermediate
                                                  in T1 sequences and avid
                                                    contrast enhancement
CT: Computed Tomography; MRI: Magnetic Resonance Imaging.



Materials and methods                                                               following: 7 craniopharyngiomas, 3 Rathke’s cysts, a tu-
                                                                                    berculum sellae meningioma, an aneurysm of the ICA, a
Since February 2009, a collaboration between our Otorhi-                            clivus chordoma, a papillary glioneuronal tumour, an his-
nolaryngology, Neurosurgery Academy and Endocrinology                               tiocytosis, a pituitary metastasis from breast cancer and a
Units has been started for the management of sellar and                             chondrosarcoma.
parasellar pathologies. From this date to March 2020, a                             Multidisciplinary management is necessary for the correct
total of 153 patients underwent endoscopic trans-sphenoi-                           approach to the patient and pathology. The specialists in-
dal surgery. 136 patients (89%) were affected by pituitary                          volved are Endocrinologist, who often refers the patient for
adenomas, the remaining 17 patients was affected by the                             surgical evaluation and requires complete serum pituitary



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                                                                                                                         Endoscopic approach to sella and parasella




hormone panels both pre and postoperatively, Neuroradi-                               artery. The sphenoidal septum and rostrum must be gen-
ologist for imaging evaluation of the lesion and anatomy,                             tly removed because they can be connected with ICA. The
Neurosurgeon for four-hands technique which we always                                 anatomical landmarks of the lateral wall of the sphenoid
perform, and the Ophthalmologist in case of visual impair-                            sinus are now visible (Fig. 1). The bony irregular edges
ment at diagnosis.                                                                    are then carefully drilled out to obtain a wide access to the
A multidisciplinary skull base conference meets twice a                               sellar floor. When tumours develop into cavernous sinus,
month to discuss the cases. Then, all patients undergo an                             more bone must be removed in the lateral direction towards
endoscopic endonasal approach, which provides the most                                the anterior face of the parasellar carotid artery; when tu-
direct access to the ventral skull base while obviating the                           mours reach the suprasellar region, sellar floor removal is
need for retraction and manipulation of critical neurovas-                            required.
cular structures.                                                                     Sellar phase: once the dura mater is exposed, a cross in-
The trans-sphenoidal approach performed by an expert sur-                             cision is made to avoid damage to the carotid artery and
geon is nowaday a safe procedure, with a remission rate                               the anterior arachnoid cistern. From now on the four-hands
from 42% to 95%, depending on the case studies (with                                  technique with the Neurosurgeon is applied to remove the
most between 70-85%) 5. This surgical technique can be                                tumor. The lesion is detached using ring-shaped curettes:
divided into three phases: nasal, sphenoidal and sellar.                              in case of pituitary adenoma, it can be identified as a grey-
Nasal phase: two endoscopic approaches can be used to                                 ish region in contrast with the pink colour of the gland and
reach the sellar region.                                                              for its soft consistency (Fig. 2). The adenomatous tissue
The paraseptal trans-sphenoidal approach tangent to the                               is carefully separated from the glandular tissue using a
nasal septum removing the upper turbinate body (or su-                                microdissector and removed en bloc. The advantage of a
preme, when present) represents the preferred choice. If the                          dissection along the pituitary pseudo-capsule in order to
anatomy avoids an easy approach to the sphenoid sinus, for                            completely remove the lesion and reduce tumour residue
example in case of nasal septum deviations, the posterior                             has been demonstrated 6-10. Once the lesion is totally ex-
third of the nasal septum can be removed to obtain a wider                            cised, the inspection of the sellar cavity with angled optics
route, to use the four-hand technique.                                                and hydrodissection is mandatory, paying attention to the
The trans-ethmoid-sphenoidal approach is useful when                                  suprasellar and cavernous sinus areas.
more space is necessary or in the laterally extended trans-                           A variety of thoroughly evaluated techniques exist to close
pterygoidal approaches.                                                               the skull base defects, depending on the location and the
Once the sphenoid ostium or anterior sinus wall has been                              size of the defect. We always prefer autologous grafts (bone
identified, the surgical procedure is the same for both ap-                           of the middle turbinate, mucoperiosteum, septal cartilage
proaches.                                                                             and mucopericondrium) or other autologous materials
Sphenoid phase: the anterior wall of the sphenoid sinus                               (such as fascia lata or rarely fat), that allow highly compat-
is opened using a Kerrison’s rongeur to expose the ante-                              ible repair of the dura and can be readily harvested com-
rior margin of the intersphenoidal septum. The mucosa is                              pared to heterologous grafts. The area of the defect must
preserved to save the nasal branch of the sphenopalatine                              be prepared: the mucoperiostium surrounding the defect




Figure 1. Sphenoidal sinuses after drilled out the intersphenoidal septum – asw: anterior sellar wall; ica: internal carotid artery; on: optic nerve; iocr: interoptic-
carotid recess.



                                                                                                                                                                 S33
E. Emanuelli et al.




Figure 2. Removal of the tumour (t) with four hands technique and vision at the end of the procedure with a 0° and 45° telescopes – asw: anterior sellar wall;
psw: posterior sellar wall; fl: frontal lobe; lon :left optic nerve; oa: ophtalmic artery.


is detached with straight and angled dissectors in order to                      Results
expose the bone and locate the dural defect (Fig. 3). When
                                                                                 Of the 153 patients operated, 56 were males and 97 fe-
no cerebrospinal fluid (CSF) leak or dripping is confirmed
                                                                                 males. The mean age at the time of diagnosis was 49 ± 13
by the Valsalva maneuver, we use autologous endonasal tis-                       years. In 35 cases the lesion was a recurrence of previous
sues positioned undelay (intracranially extradurally). When                      surgery performed elsewhere.
moderate or massive CSF leak is present, a multilayer tech-                      Of the 136 patients affected by pituitary adenomas, 43
nique is preferred using fascia lata positioned underlay                         were microadenomas and 93 macroadenomas, divided as
and septal cartilage or bone from the middle turbinate po-                       follows: 50 non-secreting tumours, 43 ACTH-secreting
sitioned immediately above the first layer. A further layer                      adenomas, 27 GH-secreting adenomas, 6 PRL-secreting
of fascia lata is positioned overlay (extracranially extradur-                   adenomas, 4 TSH-secreting adenomas, 1 FSH-secreting
ally), covered by mucoperiosteum or mucopericondrium.                            adenomas and 5 mixed lesions (3 GH-PRL, 1 TSH-GH and
Considering that fascia lata physiologically shrinks, grafts                     1 TSH-FSH).
larger than 30% of the dura defect must be removed. In                           Considering all the patients, endocrinological disorders
case of massive CFS leak or high flow defect, the Hadad                          such as acromegaly, Cushing’s disease, panhypopituita-
                                                                                 rism, hyper- or hypothyroidism, insipidus diabetes, de-
flap vascularized on the nasal branch of the sphenopalatine
                                                                                 creased libido, amenorrhea and galactorrhea were the most
artery can be prepared.
                                                                                 frequent symptoms. In 9 cases the tumour was incidentally
Once repaired the defect, the surgical field is gently filled                    found during a brain imaging performed for other reasons.
with absorbable sponge material that maintains the correct                       Sexteen patients also referred visual impairment such as
positioning of the grafts.                                                       homonymous or bitemporal hemianopsia or decrease in
This study was conducted in compliance with the Declara-                         visual acuity (usually unilateral): in 12 cases the post-sur-
tion of Helsinki. Written informed consent was obtained                          gical visual recovery was complete while in 2 cases it was
from all patients.                                                               partial; in 2 patients there was no improvement.



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                                                                                                                        Endoscopic approach to sella and parasella




Figure 3. Reconstruction of the anterior wall of the sella with a multilayers technique – fl: fascia lata; sb: septal bone.


Based on the extension and histologic type of the tumor,                             bete insipidus in 23 patients (most of which transient) and
we decided to perform a paraseptal approach tangential to                            panhypopituitarism in 3 patients. Two patients complicated
the nasal septum for purely sellar lesions (136 cases), or                           with meningitis.
a transethmoidal approach for lesions extending laterally                            Brain MRI performed 4 months after surgery showed per-
into the cavernous sinus (8 cases). Extended endoscopic                              sistence of disease in 20 patients, 4 of which were ACTH-
transsphenoidal approach was preferred for suprasellar and                           secreting adenomas: in most cases it was intentionally left
clival lesions (9 cases).                                                            during surgery, in order to avoid damage to neuro-vascular
Endoscopic endonasal examination was performed on the                                structures close to the tumour. Twelve patients underwent
15th and 30th postoperative day, then every month during                             surgical revision for recurrence of the disease.
the first six months and every three months during the first
year; every six months for the second year and annually                              Discussion
thereafter. In our case series, the postoperative follow up
period ranged from 9 to 132 months.                                                  The skull base represents the boundary between the intrac-
Follow-up includes endocrinological evaluation with com-                             ranial and facial region and is crossed by important neuro-
plete hormonal assessment at 30 days, within three months                            vascular structures that enter and leave the brain through
and then at 6-months intervals, to assess any persistence or                         bone foramina. For this reason, this anatomical area is one
recurrence of disease.                                                               of the most complex to treat surgically. The pituitary gland,
Neuro-ophthalmologic evaluation was required three                                   enclosed in the sella turcica, is located at the center of the
months after surgery only for those who had visual impair-                           skull base: the extension of any pathology at this level can
ment preoperatively, or at any time for patients who report-                         lead to endocrinological dysfunctions of hyper or hypo-se-
ed alterations of new onset.                                                         cretion. Lateral to the gland there are the cavernous sinuses,
The most common surgical complications were:                                         which contain the III, IV and VI cranial nerves and the first
• epistaxis, which required transfusion in one case and                              and second branches of the trigeminal nerve. Therefore,
   caustication of the sphenopalatine artery in another case;                        the involvement of a cavernous sinus will be reflected in
• cerebrospinal fluid leaks (9 cases) with surgical revision                         the alteration of ocular motility and consequent diplopia.
   of the dural plasty repaired with a multilayer technique                          The VI cranial nerve is the most frequently involved, due
   using autologous fascia lata, cartilage or bone (from tur-                        to its completely intracavernous course. The involvement
   binates or septum) and mucoperiosteum from the infe-                              of intracavernous ICA rarely causes clinical manifesta-
   rior turbinate. Hadad flap was used in 3 cases, when a                            tions. Sometimes, pupillary defects can occur, due to irrita-
   high flow leak was present;                                                       tion or deficit of the pericarotid sympathetic plexus. The
• pituitary abscess (2 cases), the fist successfully treated                         suprasellar region houses many important structures, first
   with surgical drainage, the second quickly complicated                            of all the optic nerves, tracts and chiasm: a neoplasm at
   in a brain abscess leading to coma and subsequent pa-                             this level can appear with visual impairment; moreover, the
   tient’s death.                                                                    hypothalamus, which can lead to various diseases: endo-
Among the endocrinological complications, we had dia-                                crinological dysfunctions such as hypopituitarism due to



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E. Emanuelli et al.




hypo-secretion of the release factors or diabetes insipidus                  four levels of suprasellar extension depending on the rela-
for the interruption of the hypothalamic-pituitary stalk, fur-               tionship between the neoplasm and the optic chiasm 12.
thermore, alterations of thermoregulation and metabolism.                    The lateral development of the adenoma can cause com-
It is also essential to remember the close relationship of                   pression of the cavernous sinus or epilepsy if the temporal
the suprasellar region with the third ventricle: an expanding                lobe is achieved. The classification system used to define
lesion at this level can obstruct the liquor’s circulation in-               the involvement of the cavernous sinus is the Knosp’s clas-
creasing the intracranial pressure 11. Finally, large tumours                sification 13, which recognises four levels of lateral exten-
can grow in the clival region, involving the apex and the                    sion according to the relationships between the tumour and
endocranial surface of the petrosal bone with trigeminal                     the ICA at MRI coronal sections.
nerve compression at the Cavum Meckel, facial and ves-                       In some cases, acute pituitary apoplexy can occur, with
tibulocochlear nerves deficit, compression of the jugular                    sudden blindness and acute hypopituitarism 14.
vein’s bulb or mixed nerves at the level of posterior fora-                  Preoperative brain MRI is essential for diagnostic workup.
men lacerum, even symptoms of nasal obstruction in case                      In T1 sequences, the density of the adenoma is lower than
of massive growth towards the nasopharynx.                                   healthy glandular parenchyma, while it has an increased
Below, are briefly analysed the main lesions that can affect                 signal in the T2 sequences. Macroadenomas often show a
this complex anatomical district.                                            heterogeneous signal, particularly in T2 sequences, with
                                                                             hyper-intense areas corresponding to cystic, necrotic or
Benign tumours                                                               haemorrhagic areas 14. CT scan offers complementary in-
Pituitary adenomas: they are the most frequent neoplasm of                   formation to MRI, since it provides a better definition of
the sellar region, with possible parasellar extension. Signs                 the bone landmarks for the surgical approach. In case of
and symptoms can be determined by tumour hormonal hy-                        suprasellar lesion close to the optic chiasm, a pre-opera-
per-secretion, reduced hormonal secretion (due to the com-                   tory visual examination with Hess screen is necessary.
pression on healthy glandular tissue), compression of the                    Moreover, young patients with family history of pituitary
surrounding structures from an extrasellar adenoma.                          adenomas or other endocrinological pathologies (primary
The expansion can occur in all directions: caudally, the le-                 hyperparathyroidism, neuroendocrine neoplasms) should
sion can cause thinning of the sellar floor and occupy the                   undergo genetic investigations for mutations of the AIP,
sphenoid sinus and the nasal cavities, with nasal obstruc-                   MEN1 and MEN4 genes research.
tion, epistaxis and/or rhinoliquorrea.                                       In the differential diagnosis of a non-typical sellar mass,
Cranial growth can cause symptoms of optic-chiasmatic                        pituitary abscesses, pituitary carcinomas, pituitary metas-
compression (bitemporal or homonymous hemianopsia),                          tases from primitive other tumors (especially breast and
hypothalamic compression (hypersomnia, alterations of                        lung), craniopharyngiomas, hypothalamic gliomas, para-
hydro-electrolytic balance and metabolism), or obstruction                   sellar meningiomas must be considered. In most cases,
of the liquor drainage (hydrocephalus, intracranial hyper-                   differential diagnosis is based on clinical and radiological
tension) (Figs. 4-6). The Hardy’s classification describes                   features 15.




Figure 4. Sagittal and coronal MRI T1 with gadolinium and coronal T2 views showing a macroadenoma stretching upward the optic chiasm.



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                                                                                                         Endoscopic approach to sella and parasella




Figure 5. Brain CT-scan 6 hours after surgery showing complete removal of the tumour.


                                                                              To define a meningioma as atypical, a high mitotic index
                                                                              or cellular atypical features such as an increased nucleus/
                                                                              cytoplasm ratio or high cellularity must be found. Anaplas-
                                                                              tic meningiomas have a clearly malignant appearance and
                                                                              behavior.
                                                                              In sellar and parasellar region, these lesions can originate
                                                                              from the sellar diaphragm, the sellar tuberculum, the an-
                                                                              terior clinoid process and the medial portion of the small
                                                                              wings 19. Symptoms are related to compression of the sur-
                                                                              rounding structures, such as visual impairment, hormonal
                                                                              or cranial nerve deficits. The gold standard for the radiolog-
                                                                              ical study is MRI: the meningioma shows the same density
                                                                              as the cerebral tissue both in T1 and T2 sequences, with
                                                                              an intense contrast-enhancement. Surgery is the therapy of
                                                                              choice in symptomatic or growing lesions. Adjuvant radio-
                                                                              therapy can be used in selected cases of macroscopic re-
                                                                              sidual after surgical resection.
Figure 6. Visual field pre surgery and ten days after surgery.
                                                                              Craniopharyngiomas: they are slow-growing epithelial
                                                                              tumours from ectopic embryonic cells of the pituitary re-
                                                                              cess. Despite benign histology, these lesions have an ag-
Meningiomas: they originate from arachnoid cells located in
                                                                              gressive behaviour since they localize and grow close to
the Pacchioni’s bodies. They represent 13-25% of all primary
                                                                              critical neuro-vascular structures. The incidence is bimodal
intracranial tumours 16, the second most common neoplasm of
                                                                              with a peak between 5 and 14 years and between 50 and 74
the parasellar region, after pituitary adenomas, with an inci-                years 20. Most craniopharyngiomas develop in suprasellar
dence peak between the sixth and the seventh decade of life.                  region, with possible extension in all directions, rarely to-
Meningioma in children is mainly linked to genetic diseases,                  tally intrasellar. In children, craniopharyngiomas represent
especially neurofibromatosis type 2 17. The World Health Or-                  1-4% of all brain tumours and the prevalent histology is
ganization distinguishes 3 categories of meningiomas 18:                      adamanthomatous, typically associated with cystic and cal-
• Grade I: benign meningiomas (92% of cases);                                 cific components at CT-scan imaging. The cystic growth
• Grade II: atypical meningiomas (5-7% of cases);                             inside the third ventricle causes the occlusion of the Mon-
• Grade III: anaplastic meningiomas (1-2% of cases).                          ro’s foramen and consequent hydrocephalus with signs of



                                                                                                                                             S37
E. Emanuelli et al.




endocranial hypertension, that is the more frequent presen-      cal variants are recognized: the classic form, characterized
tation of craniopharyngiomas in pediatric patients. Crani-       by nests of eosinophilic cells in a basophilic/myxoid back-
opharyngiomas represent 1.2-4% of all adult intracranial         ground; the chondroid form, with chondroid differentiation
tumours and the most common histology is papillary, char-        of the matrix; and the dedifferentiated form, which has a
acterized by squamous cells nests surrounded by stromal          malignant fusiform cells component with sarcomatous fea-
tissue 21. In adult patients, the typical symptoms are visual    tures. These tumours are mainly localized in the clivus.
impairment and endocrine dysfunction. The main problem           Symptoms can occur late, in most cases with headache or
of treatment is the need for radical excision avoiding dam-      cranial nerves defects: the most affected is the abducent
age to the surrounding structures. The therapeutic options       nerve with diplopia, but paralysis of the facial nerve, ver-
are exclusive surgical resection (complete or subtotal) or       tigo, tinnitus and paresthesia can also occur due to the close
subtotal resection associated with radiotherapy.                 relation with the posterior cranial fossa. Clival chordomas
According to a review conducted by Clark et al. 22, in           may also present with a spontaneous CSF leak. On CT-scan
pediatric patients the recurrence of craniopharyngiomas          the lesion appears hyperintense expansive, destructive and
amount to 35% after a gross total resection, while in case       lytic, with irregular areas of calcification within the tumour.
of subtotal resection it is 65%, and becomes 50% if surgery      MRI better defines the relationships with surrounding struc-
is combined with adjuvant radiotherapy; furthermore, the         tures. In T1 sequences, the lesion appears hypointense with
two options are not significantly different in terms of 5-year   hyperintense components corresponding to bleeding areas;
disease-free survival. Five-year overall survival is estimat-    while in T2 sequences the lesion is hyperintense. Usually
ed to be 83-96%, but in the review they did not consider         the tumour presents an avid contrast enhancement unless
the long-term morbidity and quality of life after the treat-     the necrotic component is predominant.
ment. Surgery is considered the gold standard for recur-         The differential diagnosis must consider all the benign and
rence, with more surgical risks and greater morbidity due to     malignant bone neoplasms, such as fibrous dysplasia or Pa-
anatomical alterations caused by previous treatments. Post-      get’s disease, or pituitary adenomas with caudal extension,
operative radiotherapy is the choice for residual disease.       clival meningiomas, paragangliomas or chondrosarcomas.
Rathke cleft cyst: it is a congenital lesion from the em-        Because of the high rate of recurrence, surgery must be as
bryonic Rathke’s cleft. Although these lesions are mainly        radical as possible, followed by adjuvant radiation thera-
asymptomatic, they can suddenly grow due to intralesion-         py (conventional or adrotherapy, preferably) 24. In the lit-
al bleeding or infection causing endocrine dysfunctions.         erature, complete resection is considered one of the main
Therapy is surgical excision.                                    prognostic factors.
Schwannomas: they are rare parasellar tumours, usually           Chondrosarcomas: they originate from residual embryonic
from the first and second branches of the trigeminal nerve       mesenchymal tissue of the cranial cartilage at the level of
in the Cavum Meckel, rarely from the nerves of oculo-            the petro-occipital and spheno-petrosal sutures. Often mis-
motion. They are characterized by slow growth with sur-          taken for chordomas, they have a more aggressive behavior
rounding bone thinning. Surgical therapy is preferred for        and a faster growth: this paradoxically involves an earlier
progressive forms.                                               diagnosis and a better prognosis than chordomas 25. Dif-
                                                                 ferentiating between chordomas and chondrosarcomas is
Malignant tumours                                                imperative as they have different behaviors and treatment
Gliomas: they are slow-growing tumours arising from the          response: chordomas tend to be median lesions with an
hypothalamus, the optic chiasm or the optic tract. The most      epicenter at the clivus and spheno-occipital synchondrosis,
common histology is low-grade pilocytic astrocytoma,             whereas chondrosarcomas often have an epicenter at the
considered a benign tumour and related to neurofibroma-          petroclival synchondrosis.
tosis type 1 in one third of cases. The median survival is       Germ cells tumours: the most representative histology is the
7 years 23 and only in advanced stages they present clas-        germinoma, a midline tumour typical of the pineal area, which
sic signs of hypothalamic or optical pathways impairment.        can affect the suprasellar region in 20% of cases 4. The remain-
There is also a small share of high-grade gliomas (multi-        ing histologies are extremely rare at this level and include
form astrocytomas and parasellar glioblastomas) with a           embryonic cell carcinomas, choriocarcinomas and teratomas.
shorter median survival (11.2 months). Therapy is surgery        Chemo-radiotherapy represents the treatment of choice, sur-
followed by adjuvant radiotherapy for aggressive forms.          gery is often necessary to obtain a definitive diagnosis.
Chordomas: they are slow-growing lesions from residues of        Hemangiopericytomas: they are highly vascularized and
the notochord. They have low tendency to distant metasta-        locally invasive lesions. In the parasellar region they are
ses, but a local aggressive behaviour. Three histopathologi-     mostly located above the sellar diaphragm. They originate



S38
                                                                                               Endoscopic approach to sella and parasella




from the pericytes, mesenchymal cells surrounding the en-          significant aesthetic and functional problems. Three years
dothelium of capillaries and blood vessels. Their behaviour        later Hirsch, an otolaryngologist, described for the first time
is borderline, classified as low-grade sarcomas. The preva-        the trans-septal endonasal approach to reach the contents of
lence is slightly higher in women with a peak of incidence         the sella turcica 30. Some years later, Cushing modified this
in the sixth-seventh decade of life. At the CT-scan the le-        access using a sublabial incision, later shifted into a transcra-
sion appears as an expansive mass associated with bone             nial way due to the high risk of rhinoliquorrea, the difficult
thinning, the MRI confirms the solid nature of the lesion          control of bleeding and post-operative cerebral edema. The
with iso/hypointense signal in T2 sequences, intermediate          evolution of the trans-sphenoidal approach to the sellar and
in T1 sequences and avid contrast enhancement 26. Mac-             parasellar region was induced by three factors: first and most
roscopically, hemangiopericytoma appears as non capsu-             important, the persistent efforts of the pioneers of surgery
lated but well-defined subepithelial lesion, with a typical        often against the colleagues’ scepticism; second, the ad-
perivascular growth. Differential diagnosis includes vascu-        vancement of technology; and third, its application to routine
lar lesions, such as hemangiomas or vascular leiomyomas,           surgery. This was the case of endoscopic technique and its
and mesenchymal masses, such as sarcomas or solitary fi-           introduction into skull base surgery. Jho and Carrau reported
brous tumours. Only histology can confirm the diagnosis            the first surgical series of 50 patients affected by sellar le-
and drive the treatment. Nowadays, there is no well-coded          sion operated between September 1993 and June 1996 with
classification system for these lesions; some authors have         an endoscopic approach 31. The use of an endoscopic tech-
proposed the Kadish classification, even if the correlation        nique (pure or assisted with neuronavigator) to access the
between stage and prognosis has not been demonstrated.             sellar and parasellar region is probably the most important
The treatment of choice is surgical, while post-operative          achievement in contemporary skull base surgery.
radiotherapy is indicated in case of incomplete removal            The main advantages of the endoscopic technique are a
or recurrence. The prognosis is excellent with a 5-year            minimally invasive access without aesthetic defects, an ex-
disease-free survival more than 90% in total resection 27.         cellent view of the operating field and the management of
Local recurrence, however, is reported in the literature up        lateral, superior or inferior lesions ensuring a more radical
to 40% of cases and even 5 years or more after surgery 28.         treatment with reduced post-operative complications 32.
Some histopathological features such as size > 5 cm, bone          The involvement of the cavernous sinus is considered one of
invasion, nuclear polymorphism, increased mitotic activity,        the most negative prognostic factors in the surgical treatment
proliferation index > 10% are typical of the more aggres-          of pituitary lesions. Two different trans-sphenoidal corridors
sive forms 29.                                                     can be used to achieve the intracavernous portion of the ICA:
Langherans’ cells histiocytosis: it is a rare systemic disease     the medial side is better reached inserting the endoscope
characterized by the proliferation of dendritic cells of the       through the contralateral nasal fossa; on the contrary, lesions
epithelial immune system. It should be reminded for the pe-        in the lateral side of the cavernous sinus can be approached
culiar tendency of this tumour to involve the hypothalamus         through a trans-ethmoidal trans-pterygoidal access.
and the posterior pituitary lobe, causing diabetes insipidus as    Significant lateral extension, encasement of neurovascular
single manifestation. Therapy is exclusively medical.              structures, and brain invasion in malignant lesions are con-
Lymphomas: large B-cell lymphomas located in the cavern-           sidered some of the contraindications for an endoscopic ap-
ous sinus and in close relation with the pituitary gland are de-   proach. In some cases, a combined approach (transcranial
scribed in the literature. Surgery has only diagnostic purpose.    and endoscopic) is required.
Metastases: in most cases metastases in the pituitary gland        The complication rate of trans-sphenoidal surgery depends on
derive from breast in women and lung in men, while metas-          different factors, such as location, extension, biological behav-
tases in the parasellar region are very rare (less than 1% of      iour of the tumour and the expertise of the surgical team. In
patients undergoing transnasal surgery).                           addition, it is well known that the complication rate in revision
                                                                   surgery is significantly higher than in first surgery. Endocrino-
Treatment                                                          logical and ophthalmic complications can also occur.
Since the 18th century, surgeons from different disciplines ex-    CSF leak is the most common surgical complication in pitui-
perimented with various approaches to the base of the skull.       tary surgery and extended approaches, as confirmed in our
Francesco Durante, general surgeon from Sicily, in 1883            series. When the leak is recognized during surgery, the re-
was the first who successfully removed an anterior cranial         construction of the defect using autologous or heterologous
fossa meningioma with a transoral-transpalatine approach.          grafts is mandatory 33. Sometimes, the defect can remain un-
In 1907, Schloffer treated a pituitary tumour through an           known until complications appear (including meningitis and
open transnasal-transphenoidal approach, with consequent           intracranial abscesses), requiring a revision surgery to repair



                                                                                                                                   S39
E. Emanuelli et al.




the defect. High-flow leaks can involve in cerebral parenchy-       surgery), is generally determined by a trauma at the level
mal herniation through the skull base defect, stretching the        of the lateral wall of the sphenoidal sinus. Other dangerous
intradural or subarachnoid vessels, until break them causing        regions are the posterior ethmoid in case of Onodi’s cell,
an epidural, subdural or parenchymal hematoma. Symptoms             and the optical chiasm in approaches extended to the su-
vary according to the hematoma extension and location, as           prasellar region. Even the abducent nerve can be damaged
well as the treatment that can be conservative or surgical.         along its course in the cavernous sinus, since it is the only
The development of a subdural hematoma represents a rare            structure located inside the sinus.
but potentially fatal event, often the clinical picture is uncer-   At routine 24-hour post-operative brain CT-scan a modest
tain, in some cases it remains asymptomatic.                        pneumocephalus is frequently observed, but in most cases,
Another possible complication is bleeding, generally from           it is reabsorbed spontaneously within a few days. A danger-
the posterior septal branches of the sphenopalatine artery,         ous condition occurs when a defect of the dura mater acts
more frequent in macroadenomas and during extended ap-              as a valve: the air accumulates inside the brain every time
proaches. Arterial bleeding stops spontaneously in most             the pressure of the upper airway increases. The progressive
cases or can be controlled by coagulation with bipolar cau-         increase of intracranic pressure can damage the motor cor-
tery. Venous bleeding mainly originates from the cavernous          tex or cause the development of subdural hematoma, up to
sinus and can be easily solved. Profuse bleeding requires           cardiac arrest due to compression of the brain stem.
immediate suspension of the surgery.                                In experienced hands, endoscopic endonasal removal of
The internal carotid artery damage represents the worst sur-        sellar and parasellar lesions has become increasingly safe
gical complication and can lead to permanent disabilities or        and effective. However, serious complications can occur.
even death. An accurate preoperative radiological study is          Inspection of preoperative MRI and CT scan may predict
mandatory to prevent this complication. The neuronaviga-            surgical challenges as anatomical variations (conchal sphe-
tor and the micro-doppler also provide important support.           noid sinus, vascular anomalies or narrow surgical corridor
The accidental damage of ICA during the trans-sphenoidal            because of reduced distance between the parasellar carot-
approach for pituitary adenomas is reported 0,2-1,4% in lit-        id arteries), or tumour feature (invasion of the cavernous
erature 34,35. In 2016, AlQahtani et al. 36 have distinguished      sinus, vertical extension). Last but not least, an accurate
the risk factors for ICA damage in: anatomical factors              understanding of the anatomy and a multidisciplinary plan-
(thinning or thickening of the ICA bone canal in the lateral        ning are essential to deal with this type of surgery.
wall of the sphenoid sinus, the distance between the two in-
tracavernous tracts, possible presence of aneurysms, pseu-          Conclusions
doaneurysms or arterio-venous malformations, dislocation
of the ICA), factors related to the pathology (tumours in           Sellar and parasellar lesions represent a challenge because of
close contact or invading the artery, previous treatments),         their variable features and because of the importance of un-
surgeon-depending factors (the surgeon’s experience).               derstanding the anatomy of this region, that is essential for
Emergency treatment in case of vascular damage consists             providing improved resections with decreased morbidity.
of blood transfusion and plasma expanders infusion in or-           The evolution of the trans-sphenoidal approach has resulted
der to avoid hypovolemic shock, the use of hemostatic ma-           from technological developments, increasing anatomical un-
terials or vascular clips and, once the bleeding has been           derstanding and collaboration between Otolaryngologist and
controlled, the endovascular treatment.                             Neurosurgeon. Especially in this approach, a treatment plan-
Meningitis is the most frequent intracranial complication           ning involving several specialists (Otolaryngologist, Neuro-
after trans-sphenoidal surgery, especially in patients with         surgeon, Neuroradiologist, Endocrinologist, Ophtalmologist)
cerebrospinal fluid leak. Typical symptoms are fever, head-         is mandatory in order to minimize complications, offering the
ache, photophobia and coma in some cases. The diagnosis             patient the best treatment and a high quality of life.
is performed by the analysis of the CSF; a brain CT scan
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