1. No category

CLINICAL MEDICINE / Ê˲Ͳ×ÍÀ ÌÅÄÈÖÈÍÀ
ORIGINAL ARTICLE
UDC 616.432
CLINICAL CASE PRESENTATION OF CRANIOFACIAL
MENINGIOMA WITH ASSOCIATED ACROMEGALY,
DIABETES MELLITUS TYPE 2-A LABYRINTHINE
TUMOUR
Diptajit Basak,
[email protected]
Diptajit Basak, J. Komisarenko, L. Kononenko
Bogomolets National Medical University, Kyiv, Ukraine
Keywords: meningioma, sellaturcica, acromegaly, diabetes mellitus, metastasis.
Introduction. The functional and morphological
peculiarity of craniofacial tumor of meningeal origin in the
sella turcica region of the skull base makes it unique among
neoplastic syndromes. Tumors of this specific type are
exceptionally hard to treat surgically and prone to recurrence
especially ones invaded through the cranial base.
Morphologically, the distinctions between benign and
metastatic tumors of CNS are less well–defined which makes
it a diagnostic challenge. They might present similar
histological structure in terms of cellular differentiation, cell
division and origin which often misleads physicians to
believe that the neoplasm is of benign nature.
Epidemiologically meningiomas constitute almost 20% of all
intracranial tumors and are found in every 10 to 17 people in
100,000 populations. The prevalence increases with age and
sex, predominantly in women, for reasons unknown.
Strikingly, this statistics hold true even for pediatric
neoplastic syndromes where they amount to almost 20% of
all cases and among them 70% tends to occur in the posterior
cranial fossa. Associated complications include invasion
into the surrounding structures of brain, bony structures
and through the skull base. The most commonly occurring
secondary complications are acromegaly, vision loss,
diabetes mellitus type 2, anosmia and panhypopituitarism.
Observations: In our case study, a 28 year old female was
diagnosed with craniofacial meningioma in 2006 located at the
supra sellar region at the anterior skull base. She presented with
insulin dependent diabetes mellitus type II decompensate form
of severe condition and acromegaly at the time of her diagnosis.
22
Anamnesis revealed that the neoplasm supposedly started
forming when she was 15 years of age but her high stature was
misdiagnosed as physiological due her family’s genetic
predisposition. Her laboratory values of high GH/IGF-1 (31,8ng/
mL) suggested hypersecretion of somatotropin and associated
elongated facial features, arthralgia, prognathism, macroglossia
confirmed acromegaly. The blood glycemic index was high
(30mmol/L) and unstable with severe insulin resistance owing
to hypersomatotropism confirmed Diabetes Mellitus type II.
She had numerous episodes of ketoacidosis and coma. She was
treated with 360IU with Actrapide and more than 100IU of
Protophane. The CT-Scans and MRI reports proved that the
meningioma was of en plaque form with involvement of the
pituitary gland, optic chiasma, hypothalamus and greater wing
of the sphenoid bone. Invasiveness of the meningioma led to
bilateral vision loss. The tumour had invaded through the skull
base through the maxillary sinus to the mandible and had
formed fibrous dysplasia of the ramus of the mandible. It had
also invaded the left internal carotid artery and the cavernous
sinus. In 2009 she had undergone highly focused gamma
radiotherapy as an alternative to neurosurgery given her high
glycemic state and inoperable tumor location. The patient also
had to undergo necrectomy for 3rd degree bilateral diabetic
neurogenic ulcers on foot, incisional drainage in maxillary sinus
to drain purulent sinusitis with cefuroxim lavage and
trabulectomy on left eye to manage severe closed angle
glaucoma. It was observed that post radiotherapy her glycemic
level gradually decreased from 25.7mmol/L (29.04.09) to
7.43mmol/l (03.12.2014). Somatotropin level decreased from
Ukrainian Scientific Medical Youth Journal / Óêðà¿íñüêèé íàóêîâî-ìåäè÷íèé ìîëîä³æíèé æóðíàë ¹ 4 (84) • 2014
CLINICAL MEDICINE / Ê˲Ͳ×ÍÀ ÌÅÄÈÖÈÍÀ
31.782mcg/L (15.05.09) to 3.46mcg/L (03.12.2014), Prolactin
decreased from 48.09ng/mL (16.10.09) to 14.8ng/mL (16.05.12)
with much lower insulin resistance. She was treated with Geninsulin according to Basal Bolus Therapy (BTT) in a dose of
18IU medium acting and 8IU short acting in the morning and
16IU medium acting with 8IU short acting in the evening. Along
with insulin she was prescribed with DPP-4 inhibitor Anagliptin
with incretin (GLP-1) Exenatide. The patient is now in a
satisfactory condition.
Conclusion: It can be concluded from this clinical case
presentation that meningioma is a severe form of neoplastic
syndrome which not only clinically significant but also with
immense social and economic implication. This case study is
interesting because of its epidemiological significance,
substantial co-morbidity and potentially aggressive course.
Treating meningioma is a challenge because the associated
complications of radio and chemotherapy is equally
debilitating as the disease itself if not more. The strategic
location of the tumor prevented radical treatment and
conservative treatment is exorbitantly expensive given the
socioeconomic background of our patient. There are many
areas of interest in this research which remains unanswered.
The prevalence of meningiomas in women, alternative
treatment paths to reduce the tumor as opposed to surgery,
the effect of endogenous or exogenous sex hormones
remains obscured in this specific type of tumor regarding
their effect on growth, proliferation or prevention of these
tumors and also the etiology of this neoplastic syndrome. It
is of utmost importance to gain more knowledge about the
development and origin of these tumors to assess the risk
factors and design a preventative protocol.
Introduction. Cranial tumors are generally considered to
be one of the most frequently occurring neoplastic
syndromes in humans. They are not only difficult to treat
owing to their sensitive locations within or near the brain,
but also lead to substantial morbidities and moralities due to
their aggressive nature. Even though craniocerebral tumors
can be broadly classified into 2 main groups of malignant
and benign type, more than often physicians are faced with
the malignant types which tend to be quite aggressive and
fast growing. According to its origin, these tumors may be
primary or secondary, with the former essentially originating
in the brain tissue and the latter formed as a result of distant
metastasis from organs such as the lungs. As of today,
neurosurgery has come a long way since its days of
inception in the Hippocratic era where cranial trepanation
was done to ward off evil spirits yet craniocerebral
neoplastic syndrome still remains as one of the toughest and
most difficult pathology to cure. The difficulty lies in mainly
two different spheres:
1. Location of the tumor which significantly affects the
outcome of the treatment.
2. Type of the tumor which determines its
aggressiveness and its response to treatment
The location of the tumor is often the determining factor
regarding the choice of treatment because it is of utmost
importance to decide whether or not the tumor is surgically
accessible and to what extent of damage might be caused
while accessing it. Following the location, determining the
type of neoplasm is also very important for definite treatment
approach for maximum efficacy. Depending upon whether it
is benign or metastatic the physician must decide the choice
of action between a radical or conservative approach. The
primary concern regarding craniocerebral tumors remains in
the fact that even the most inconspicuous tumors of benign
origin can find itself in the most unfavorable places, thereby
drastically increasing the chances of mortality by simple
compression
of
the
surrounding
structures.
Epidemiologically speaking, the annual occurrence of CNS
tumors can be estimated at about 10 to 17 per 100000
individuals and mostly to the extent of two-thirds of them are
primary and the rest secondary metastatic. This statistics
hold true even for pediatric cases where they amount to
about 20% of all pediatric neoplasm of which 70% occurs in
the posterior cranial fossa whereas in adults a significant
number of tumors arise specifically in the area of cerebral
hemispheres above the tentoriumcerebri.
It is the interesting characters of craniocerebral tumors
which sets them apart from other tumors occurring
elsewhere in the body in many different ways. First, the
European Age-Standardized Incidence Rates per 100,000 Populations, by Sex, UKBrain, Other CNS and Intracranial Tumors (C70-C72,
C75.1-C75.3, D32-D33, D35.2-D35.4, D42-D43, D44.3-D44.5): 1993-2011.
¹ 4 (84) • 2014 Ukrainian Scientific Medical Youth Journal / Óêðà¿íñüêèé íàóêîâî-ìåäè÷íèé ìîëîä³æíèé æóðíàë
23
CLINICAL MEDICINE / Ê˲Ͳ×ÍÀ ÌÅÄÈÖÈÍÀ
morphological distinctions of between benign and
metastatic tumors of CNS are less well-defined than in other
locations. They mightmimic each other in terms of
morphology, cellular structure, differentiation and even rate
of cell division along with cellular uniformity and one might
be mislead to believe that the tumor is of benign nature which
can lead to serious treatment error and signicant clinical
deficits or even death. One of the extraordinary peculiarities
of brain tumors is the lack of metastasis outside the zone of
CNS. The most commonly taken pathway for metastasis
along the brain and spinal cord is the subarachnoid space.
This also provides us with valuable diagnostic prospects
due to presence of anaplastic cells in the CSF or even highly
differentiated metastatic cells. Before delving deeper into the
subject, it is of utmost importance to understand the basic
neoplastic syndromes that are common to occur in the CNS.
The 4 majortypes of craniocerebral tumors are:
• Gliomas
• Neuronal tumors
• Poorly differentiated neoplasm
• Meningiomas
All of these tumors mentioned have their specific
characteristic morphological and histological features, areas
of distribution in the brain, affection in specific age groups
and typical clinical courses. Of these, meningiomas are
known to be predominantly benign in nature, which are
often found in adults. These tumors arise from
meningothelial cells of the arachnoid mater. These cells are
scattered within the arachnoid membranes throughout the
neuro axis with their higher concentrations at the tips of
arachnoid granulations where they are termed as arachnoid
cap cells. Morphologically they are epithelioid to slightly
spindle shaped and are typically seen in small clusters from
10 to 20 cells where they have a tendency to form whorls.
Cells have moderate amounts of eosinophilic cytoplasm and
oval nuclei with dispersed chromatin, often giving the
appearance of central clearing.
Meningiomas usually appear as spherical or round
masses which have a well defined and demarcated dural base
which essentially compresses the immediate neural structure
lying next to it or below but easily separable from it. They
may be found on any external surface of the brain and also
within the ventricles. Meningiomas originate from stromal
arachnoid cells of the choroid plexus. The bunch of
capillaries that form the plexus rests into the telachoroidea
which is a pia mater fold extending into the choroid fissure.
The wall of the ventricle lining the choroid plexus is very thin
and forms the ependymal covering of the plexus.
Meningiomas are often associated with extension or
infiltration in the surrounding bony structure which is
ultimately destroyed due to extensive encroaching and
disintegration by infiltrates. Gross morphologically,
meningiomas are masses generally encapsulated by thin,
fibrous layer of tissue which given it a polyploidy or
bosselated appearance. The clinical and therapeutical
significance of these neoplasms lie in their growth pattern
which is one of their prime characteristic, the en plaque form.
In this case, the neoplasm extends over the surface of the
dura in a sheet like fashion covering the surface which may
also manifest itself even in distant location away from the
primary focus or loci of the tumor. While spreading this
tumor in turn infiltrates into the structures in its path and
gradually destroys them. This presents itself as
hyperostotic reactive changes in the overlying bone. The
lesion formed range from being fibrous and firm to gritty and
fine, on may manifest themselves as extensively calcified
structures with psammoma bodies. Generally speaking,
gross occurrences of necrosis or extensive hemorrhages are
rare if not absent. According to WHO, meningiomas are
ratified are among tumors in the low risk group who are
known to be less aggressive in nature with low risk of
recurrence except the ones that have invaded through the
skull base into the paracranial regions e.g. facial bones,
mandible etc. They are graded according to the standard
WHO specified Overall Stage Grouping System (Grade I/
IV). Meningiomas can be different histomorphological
varieties exhibiting variation in cellular structure,
differentiation andarrangement, namely: Syncytial – a
cluster of neoplastic cells forming a tight forming whorl
without an apparent membranous covering, Fibroblastic –
characterized by abundance in collagenous deposition
between elongated cells, Transitional – they expresses
combined features of both fibroblastic and syncytial types
of meningiomas, Psammomatous – these kind of
meningiomas are characterized by presence of abundant
psammoma bodies in the cellular structure, evidently
originating from calcified syncytial clusters of
meningothelial cells, Secretory – they can be recognized by
presence of PAS-positive cytoplasmic droplets and
intracellular lumen as seen through an electron microscope
and Microcystic – which are evident by their spongy
appearance in a loose formation. With meningiomas the
most often and significant complications are the formation
of osseous metaplasia or dysplasia, xanthomatous
degeneration and nuclear pleomorphism of moderate type.
Another form of these tumors is the Atypicalmeningiomas
(WHO grade II/IV) which are considered to be with higher
recurrent capabilities and of more aggressive nature. These
Systems for Classification of Brain & CNS Tumors
Used by cancer registries generally
ICD-10 codes
ICD-10 groups
C70-C72 and C75.1-C75.3
Malignant (sometimes also
known as invasive, or cancer)
D32-D33, D35.2-D35.4,
Benign, uncertain or
D42-D43, and D44.3-D44.5
unknown behavior
(sometimes also known as
non-invasive)
24
Used by cancer clinicians generally
WHO Grade
Aggressiveness
Few Grade I, most Grade
Moreaggressive
II, almost all Grade III-IV
Almost all Grade I, few
Lessaggressive
grade II, very few Grade
III-IV
Ukrainian Scientific Medical Youth Journal / Óêðà¿íñüêèé íàóêîâî-ìåäè÷íèé ìîëîä³æíèé æóðíàë ¹ 4 (84) • 2014
CLINICAL MEDICINE / Ê˲Ͳ×ÍÀ ÌÅÄÈÖÈÍÀ
require a combined treatment approach that involves both
surgical intervention and pharmacotherapy. The core
diagnostic criteria for these neoplasm is either a high mitotic
index of at least four or more mitosis per 10 high power fields
or presence of three or more atypical features (necrosis, loss
of pattern, prominent nucleus, increased cellularity etc. ) .
Furthermore, Anaplastic (malignant) meningiomasare
classified as Grade III/IV (WHO), owing to their highly
aggressive nature which also has an appearance similar to a
high-grade sarcoma. There are also histological suggestions
that pertain to the fact that they might be of meningothelial
origin as well. They have subtypes like: Papillary
meningioma and Rhabdoid meningioma, both of which are
prone to high recurrence. Malignant meningiomas have very
high mitotic values (>20/10 HPF). It has been noted that it is
easy to separate most meningiomas from the cerebral tissue
even they have compressed or displaced the structure but
with some exceptions where they has been seen to infiltrate
the surrounding brain tissue. This phenomenon is possible
in two plausible situations as either single cells or broad
compressing edges. Even though the infiltration increases
the chance of recurrence significantly, yet they have not
been seemed to alter the grade of the tumor. Genetically, it
has been shown that the loss of long arm of the chromosome
22 is the most commonly observed abnormality for genesis
of meningioma. The 22q12 harbors the NF2 gene whose
deletion leads to at least 40% of all meningiomas.
Clinically speaking, meningiomas are slow growing
neoplasms which are generally associated with late clinical
onset owing to their slow growth and comparatively less
aggressive nature. The symptoms manifested are either vague
or non-localized. The localized and precise focal symptoms
occur only after significant compression of the cerebral
structure lying beneath, above or around it. They lead to
compression symptoms and is progressively degenerating in
nature. The common loci of origin are sellaturcica (sellar
meningioma), large wing of the sphenoid bone, olfactory
groove, foramen magnum, parasagittal sinus, cavernous sinus
and dura over the lateral convexity. The tumors are generally
solitary in nature but present in multiples focuses. These
tumors are highly susceptive towards hormonal changes in
the body and rapid growth spurts have been observed in
pregnant patients. These are due to expression of
progesterone receptors in the tumor and are highly sensitive
towards change in blood progesterone concentration.
Meningiomas found in the region of sellaturcica are often
known to invade the hypophyseal gland by indirect
infiltration or direct compression and causes various
hormonal disbalances by affecting the function of the
pituitary, thereby causing hypo orhypersecretion of various
hormones in the body. One of the hormones whose secretion
is generally affected is the Somatotropin hormone (growth
hormone, GH).This hypersecretion leads to primary and
secondary complications respectively. The primary effect of
growth hormone over secretion is acromegaly, a rare and
potentially life threatening condition usually found in adults.
This pathology is marked by insidious onset which might take
years to develop and manifest. The local effects of this
syndrome can be headache, vision loss, ataxia and other
neurological deficits. Damage to the pituitary stalk may cause
hyperprolactinemia because hypothalamus is responsible for
inhibitory regulation of prolactin secretion. Damage to normal
pituitary tissue can cause deficiencies of glucocorticoids, sex
steroids, and thyroid hormone. Loss of hormones acting on
distant organs like adrenal glands, kidney, ovary, mammary
glands etc. results from diminished anterior pituitary secretion
of corticotropin (i.e., adrenocorticotropic hormone [ACTH]),
gonadotropins (e.g., luteinizing hormone [LH], folliclestimulating hormone [FSH]), and thyrotropin (i.e., thyroidstimulating hormone [TSH]). The secondarycomplication is
caused as a resultof excessive production of GHis Diabetes
Mellitus Type 2. One of the main mechanisms of insulin
functions as a carrier molecule that facilitates the entry of
glucose molecule into the cells to facilitate ATP production as
a means of active transport. Glucose is transported into the
cells by various means but the most effective ones are
achieved through implement of glucose transportersalso
known as contra insular mechanism. These molecules
facilitate glucose transportation down the concentration
gradient by facilitative diffusion. Glucose transporters are
proteins of which 6 are primarily distinguished, GLUT1,
GLUT2, GLUT3, GLUT4, GLUT5 and GLUT7. Structurally
these transporters are alike and they possess a region where
carbohydrates can bind to these proteins. These transporters
exist in intrinsic or extrinsic orientation and act as gateways to
the incoming glucose molecule. Insulin acts as a catalyst to
the reaction by either increasing the number of receptors or
increases the rate of transportation of each transporter.
Chronic GH hypersecretion (acromegaly) increases lipolyis in
the body which leads to higher level of circulating
Brain, Other CNS and Intracranial Tumors, by Morphology, Proportion of Cases, England, 2006-2010
Morphological Group
Astrocytomas
Meningiomas
Pituitary
Gliomas unspecified
Cranial and paraspinal nerve tumours
Oligodendrogliomas
Ependymomas
Embryonal tumours
Other tumour types
Unknown or unspecified type
% of all Brain, other CNS and
intracranial tumor cases
34%
21%
8%
6%
6%
3%
2%
2%
5%
14%
% of the semore
aggressive
95%
8%
1-2%
*
5%
*
75%
100%
*
*
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% of these less
aggressive
5%
92%
98-99%
*
95%
*
25%
0%
*
*
25
CLINICAL MEDICINE / Ê˲Ͳ×ÍÀ ÌÅÄÈÖÈÍÀ
nonesterified fatty acids (NEFA) in the blood. Increased NEFA
availability is an important contributor towards GH-induced
insulin resistance in the body. This triglyceride accumulates in
the skeletal muscles one of the major site of glucose utilization
in the body which reduces sensitivity of the transporter
molecules towards incoming insulin which gradually in turn
decreases the number of transporter receptors in the cell
leading to acute insulin resistance. This phenomenon in turn
precipitates into hyperglycemia due to failure of the GLUT
system to uptake glucose due to lack of receptor activation.
Finally, this chronic hyperglycemic state with high insulin
blocked state leads to Diabetes Mellitus Type II. It has been
noted that glycemic index in patients with GH induced
Diabetes Type II remains at a stable high level even with very
high insulin treatment due to pre-high insulin resistance by
high circulatory GH in blood.
As an added complication to diabetes, degenerative
conditions like diabetic neuropathy leading to trophic ulcers
of distal extremities, diabetic nephropathy pertaining to
proteinuria, elevated urea, creatinine phosphates etc.,
diabetic retinopathy, cardiotrophic disorders leads to long
term morbidity and premature mortality in patients with
craniofacial meningioma especially in the suprasellar region.
Observation. In our patient a 28 year old female from Kyiv,
Ukraine, craniofacial meningioma was diagnosed on 2006 at
the suprasellar region on the anterior skull base in the
parahypophyseal zone. Her history suggested that the
neoplastic syndrome started when she was 15 years of age and
the early manifestations were acromegaly. But phenotypically,
her family is of high stature so her pathological stature was
initially misdiagnosed as physiological. Her facial features and
bone density index confirmed acromegaly. Among the
symptoms she had arthralgia, oily skin, enlarged nose, lips and
tongue, dysmenorrhea and subsequent amenorrhea,
headache and vision loss. She had initial high stable glycemic
index of 30 mmol/L and higher of Insulin Dependent DMII
variant induced by high GH. Numerous episodes of ketoacidic
coma were recorded (at least 10 times) which runs rare in
acromegaly associated DMII. Her somatotropin level was very
high (31,8ng/mL) with classical features of acromegaly and
severe insulin resistance. On subsequent hormonal assays, it
was found that she had elevated TSH, prolactin, cortisol,
ACTH, C-peptide, glucagon, HbA1c and FBG (fasting blood
glucose). On MRI and CT-Scan, the meningioma was assessed
every year from 2006 to 2014 to assess its progress and
26
invasiveness. It was first noted that the meningioma had a
very invasive course and has infiltrated the hypothalamus
anteriorly with the involvement of the optic chiasma by
superior shift and compression. These led to progressive
vision loss and finally complete loss of visual acuity. The
brain images showed that the neoplasm has a heterogeneous
structure without a defined form caused bone infiltration and
destruction in the greater wing of the sphenoid bone on both
right and left with involvement of the orbita. The destruction
of the medial orbital plates by encompassing it inwards led to
the increase of the ocular pressure in the posterior chamber of
the eye, resulting in closed angle glaucoma which further
precipitated in the vision loss. It was also noted during
physical examination the deviation of the pupil to the right
due to medial invasion. The meningioma in this case has
manifested itself in the en plaque form, because x-ray of the
face showed distal fibrous dysplasia of the mandible of the
left side. This dysplastic fibrous structure has spread through
the left cavernous sinus into the facial sinus, subsequently
finding its way into the maxillary sinus ultimately to the left
mandibular ramus where it was found as a fibrotic tumor.
Morphologically, the meningioma had also infiltrated the
internal carotid artery on the left and was a cause of major
concern for rupture and severe hemorrhage. The sheath like
projection of the meningioma with its multiple infiltrations
into the various important structures made it impossible for
surgical intervention. Her uncontrollable high glycemic index
also prevented surgery. Preoperatively, she was treated with
360IU with Actrapide and more than 100IU of Protophane but
her glycemic level did not reduce due to high insulin
resistance due to high somatotropin level. So, on 2009, neurooncologists decided for high-precision radio gamma
therapy. The aim was to reduce the endocrine effect of the
tumor to reduce the high production level of GH/IGF-1. The
gamma therapy proved to be effective in lieu of surgical
resection of the tumor and it was observed that the level of
somatotropin decreased to 3, 46ng/mL with decrease in
glycemic level in blood to 6,6 mmol/L. The level of other
hormones including prolactin, C-peptide, Glucagon and
HbA1c also decreased. The diabetes was more easily
controlled with much less dose of insulin due to reduced
insulin resistance after fall in plasma GH. She was treated with
Gen-insulin according to Basal Bolus Therapy (BTT) in a dose
of 18IU medium acting and 8IU short acting in the morning and
16IU medium acting with 8IU short acting in the evening. Along
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Change in bone width and size as compared to control. Elongated facial features with fibrous dysplasia of mandible
with insulin she was prescribed with DPP-4 inhibitor Anagliptin
with incretin (GLP-1) Exenatide to maximize the hypoglycemic
effort. Due to the tumor invasion and high chronic
uncontrollable DMII, her complications were severe and
needed surgical interventions. The closed angle glaucoma was
managed by trabeculectomy and drainage implant in the left
eye. She had bilateral diabetic neuropathy with 3rd degree
trophic ulcers on her distal extremities which were managed
with surgical debridement. In 2014, she had acute purulent
maxillary sinusitis due to presence of infiltrative process in the
maxillary sinus from the meningioma and required incisional
drainage and antibiotic lavage with cefuroxim. Since, 2009 after
gamma therapy, the growth of the meningioma was observed
every year and no significant changes have been noted ever
since. The patient is now kept under observation for necrotic
ulcerative changes due to diabetes and routine head scans for
changes in the structure and size of the meningioma.
Conclusion. It can be concluded from this clinical case
presentation that meningioma as a neoplastic syndrome is not
only significant as a medical condition but also has immense
economic and social effect. This specific case drew our
attention because it is epidemiologically varied and found
mostly in women, the resulting morbidity and mortality runs
into huge amount of expenses that may or may not be incurred
by many families. Meningiomas are known to be recurring and
treating this pathology sometime causes more morbidity than
the disease itself. Chemotherapy and radiation therapy leads
to permanent disability which increases the social cost of this
disease. Our patient could not bear the expenses of treating
her pathology and therefore denied the option of surgery in
Israel, which also was of doubtful prognostic outcome. She
opted for conservative management which helps management
of the DMII but cannot control further proliferation of the
tumor. Her treatment protocol is expensive enough with
lifelong insulin therapy, DPP-1 and DPP-4 inhibitors along
with frequent ER visits due to complications caused as a result
of either the tumor or diabetes which increases the cost of the
treatment over all. She is categorized in the group of 3rd degree
invalidity and she received pension accordingly. Her
prognosis still remains unfavorable due to presence of the
tumor and high degree of diabetes induced complications like
retinopathy, neuropathy, nephropathy and highly invaded
brain structures by the prolific meningioma. There are many
areas of interest in this research which remains unanswered.
The prevalence of meningiomas in women, alternative
treatment paths to reduce the tumor as opposed to surgery,
the effect of endogenous or exogenous sex hormones remains
obscured in this specific type of tumor regarding their effect
on growth, proliferation or prevention of these tumors and
also the etiology of this neoplastic syndrome. It is of utmost
importance to gain more knowledge about the development
and origin of these tumors to assess the risk factors and
design a preventative protocol.
Reviewer: professor P.M. Bodnar
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types/brain/incidence/uk-brain-and-central-nervous-system-cancerincidence-statistics
12. http://www.medscape.org/viewarticle/438374
13. http://physrev.physiology.org/content/93/2/571
14. Biochemistry 3rd Ed.- U. Satyanarayana, U. Chakrapani
Robbins and Cotran Pathologic Basis of Disease 7th Ed.- Kumar,
Abbas, Fausto
15. Clinical Neuroanatomy for Medical Students 5th Ed.- Richard
S. Snell
16. Concise Histology-Bloom and Fawcett
¹ 4 (84) • 2014 Ukrainian Scientific Medical Youth Journal / Óêðà¿íñüêèé íàóêîâî-ìåäè÷íèé ìîëîä³æíèé æóðíàë
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CLINICAL MEDICINE / Ê˲Ͳ×ÍÀ ÌÅÄÈÖÈÍÀ
œ–≈«≈Õ“¿÷≤fl À≤Õ≤◊ÕŒ√Œ ¬»œ¿ƒ ”
◊≈–≈œÕŒØ Ã≈Õ≤Õ√≤ŒÃ», œŒ¬ífl«¿ÕŒ√Œ «
¿ –ŒÃ≈√¿À≤™fi, ÷” –Œ¬»Ã ƒ≤¿¡≈“ŒÃ II
“»œ” “¿ À¿¡≤–»Õ“ÕŒfi œ”’À»ÕŒfi
œ–≈«≈Õ“¿÷»fl À»Õ»◊≈— Œ√Œ —À”◊¿fl
◊≈–≈œÕŒ… Ã≈Õ»Õ√»ŒÃ¤, —¬fl«¿ÕÕŒ√Œ —
¿ –ŒÃ≈√¿À»≈…, —¿’¿–դà ƒ»¿¡≈“ŒÃ II
“»œ¿ » À¿¡»–»Õ“ÕŒ… Œœ”’ŒÀ‹fi
Áàñàê ijïòàäæ³ò, Êîì³ñàðåíêî Þ.².,
Êîíîíåíêî Ë.Î.
Áàñàê Äèïòàäæèò, Êîìèññàðåíêî Þ.È.,
Êîíîíåíêî Ë.Î.
Íàö³îíàëüíèé ìåäè÷íèé óí³âåðñèòåò
³ìåí³ Î.Î. Áîãîìîëüöÿ, ì. Êè¿â, Óêðà¿íà
Íàöèîíàëüíûé ìåäèöèíñêèé óíèâåðñèòåò
èìåíè À.À. Áîãîìîëüöà, ã. Êèåâ, Óêðàèíà
Ðåçþìå. Êë³í³÷íà îñîáëèâ³ñòü ÷åðåïíî-ëèöüîâî¿ ìåí³íã³îìè â îáëàñò³ òóðåöüêîãî ñ³äëà â îñíîâ³ ÷åðåïà º óí³êàëüíîþ. ³äì³ííîñò³ ì³æ äîáðîÿê³ñíèìè ³ ìåòàñòàòè÷íèìè ïóõëèíàìè öåíòðàëüíî¿ íåðâîâî¿ ñèñòåìè
ìîðôîëîã³÷íî º ðîçïëèâ÷àòèìè òà ñòàþòü ïðîáëåìîþ
äëÿ ä³àãíîñòèêè. Åï³äåì³îëîã³÷íî ìåí³íã³îìè ñòàíîâëÿòü ìàéæå 20% âñ³õ âíóòð³øíüî÷åðåïíèõ ïóõëèí, ³ âèÿâëÿþòüñÿ ó 10-17 íà 100 000 íàñåëåííÿ. Çàõâîðþâàííÿ
á³ëüø ïîøèðåíå ñåðåä ë³òí³õ æ³íîê. Äî óñêëàäíåíü íàëåæàòü: ïðîðîñòàííÿ â ìîçîê, ê³ñòêîâ³ ñòðóêòóðè,
³íô³ëüòðàö³ÿ ÷åðåç îñíîâó ÷åðåïà. Âòîðèííèìè óñêëàäíåííÿìè º àêðîìåãàë³ÿ, ñë³ïîòà ³ öóêðîâèé ä³àáåò II òèïó.
Ó íàøîìó âèïàäêó, ó 2006 ðîö³ áóëà âèÿâëåíà ÷åðåïíà
ìåí³íã³îìà, ùî çíàõîäèòüñÿ íàä òóðåöüêèì ñ³äëîì, ó
ïåðåäí³é îñíîâ³ ÷åðåïà ó 28-ð³÷íî¿ æ³íêè ç ³íñóë³íîçàëåæíèì öóêðîâèì ä³àáåòîì II òèïó äåêîìïåíñîâàíî¿
ôîðìè, ùî õàðàêòåðèçóâàëàñÿ âàæêèì ñòàíîì ³ àêðîìåãà볺þ (30 ììîëü/ë) (GH/IGF-131, 8 íã/ìë ). Âîíà ë³êóâàëàñÿ çà äîïîìîãîþ 360ÌÎ Àêòðàïèäà ³ 100 ÌÎ Ïðîòàôàíà. ÌÐÒ âèÿâèëà, ùî ìåí³íã³îìà ìàëà áëÿøêîâó
ôîðìà òà îõîïëþâàëà ã³ïîô³ç, ë³âó âíóòð³øíþ ñîííó àðòåð³þ, êàâåðíîçíèé ñèíóñ, çîðîâ³ íåðâè, ã³ïîòàëàìóñ,
ìåä³éíó îðá³òà ³ âåëèêå êðèëî êëèíîïîä³áíî¿ ê³ñòêè, âèêëèêàþ÷è äâîñòîðîííþ ñë³ïîòè òà ô³áðîçíó äèñïëàç³þ
íèæíüî¿ ùåëåïè. Ó 2009 ðîö³ ïðîìåíåâà ãàììà-òåðàï³ÿ
áóëà ïðîâåäåíà â ÿêîñò³ àëüòåðíàòèâè íåéðîõ³ðóð㳿. Â
ðåçóëüòàò³ ïðîìåíåâî¿ òåðàﳿ ð³âåíü ãëþêîçè â êðîâ³
çíèçèâñÿ ç 25.7 ììîëü/ë (29.04.09) äî 7.43 ììîëü/ë
(03.12.2014), ñîìàòîòðîï³í ç 31.782 ìêã/ë (15.05.09) äî
3.46 ìêã/ë (03.12.2014) ³ ïðîëàêòèí ç 48.09 íã/ìë
(16.10.09) äî 14.8 íã/ìë (16.05.12). ¯é áóâ ïðèçíà÷åíèé
Gen-³íñóë³í BTT âðàíö³ (18ÌÎ ñåðåäíüî¿ ä³¿, 8ÌÎ êîðîòêî¿ ä³¿) ³ ââå÷åð³ (16ÌÎ ñåðåäíüî¿ ä³¿, 8ÌÎ êîðîòêî÷àñíî¿
䳿) ç ³íã³á³òîðîì ÄÏÏ-4 Anagliptin ç ³íêðåò³íîâèì (ÃÏÏ-1)
åêñåíàòèäîì. Äàíå äîñë³äæåííÿ ö³êàâå çàâäÿêè ñâîºìó
åï³äåì³îëîã³÷íîìó çíà÷åííþ, ñóòòºâ³é ñóïóòí³é ïàòîëî㳿
òà ïîòåíö³éíî àãðåñèâíîìó ïåðåá³ãó. Ðîçòàøóâàííÿ
ïóõëèíè çàïîá³ãëî ðàäèêàëüíîìó ë³êóâàííþ, à êîíñåðâàòèâíå ë³êóâàííÿ âèÿâèëîñÿ äîðîãèì ÷åðåç ñîö³àëüíîåêîíîì³÷íå ñòàíîâèùå ïàö³ºíòà. Íåîáõ³äíî äîñë³äæóâàòè ïîøèðåííÿ ìåí³íã³îìè ñåðåä æ³íîê, àëüòåðíàòèâíå
ë³êóâàííÿ ç ìåòîþ çìåíøåííÿ ïóõëèíè, à òàêîæ åôåêò
åíäîãåííèõ àáî åêçîãåííèõ ñòàòåâèõ ãîðìîí³â. Öå íàäçâè÷àéíî âàæëèâî, ùîá îòðèìàòè á³ëüøå çíàíü ïðî ðîçâèòîê ³ ïîõîäæåííÿ öèõ ïóõëèí, à òàêîæ äëÿ îö³íêè ÷èííèê³â ðèçèêó ³ ðîçðîáêè ïðîô³ëàêòè÷íîãî ïðîòîêîëó.
Êëþ÷îâ³ ñëîâà: ìåí³íã³îìà, òóðåöüêå ñ³äëî, àêðîìåãàë³ÿ, öóêðîâèé ä³àáåò, ìåòàñòàçè.
28
Ðåçþìå. Êëèíè÷åñêàÿ îñîáåííîñòü ÷åðåïíî-ëèöåâîé ìåíèíãèîìû â îáëàñòè òóðåöêîãî ñåäëà â îñíîâàíèÿ
÷åðåïà ÿâëÿåòñÿ óíèêàëüíîé. Ðàçëè÷èÿ ìåæäó äîáðîêà÷åñòâåííûìè è ìåòàñòàòè÷åñêèìè îïóõîëÿìè öåíòðàëüíîé íåðâíîé ñèñòåìû ìîðôîëîãè÷åñêè ÿâëÿþòñÿ
ðàñïëûâ÷àòûìè è ïðåäñòàâëÿþò ïðîáëåìó äëÿ äèàãíîñòèêè. Ýïèäåìèîëîãè÷åñêè ìåíèíãèîìû ñîñòàâëÿþò ïî÷òè 20% âñåõ âíóòðè÷åðåïíûõ îïóõîëåé, è îáíàðóæèâàþòñÿ â êàæäîì 10-17 ÷åëîâåêå íà 100 000 íàñåëåíèÿ.
Çàáîëåâàíèå áîëåå ðàñïðîñòðàíåíî ó ïîæèëûõ æåíùèí. Ê îñëîæíåíèÿì îòíîñÿòñÿ: ïðîðàñòàíèå â ìîçã,
êîñòíûå ñòðóêòóðû, èíôèëüòðàöèÿ ÷åðåç îñíîâàíèå ÷åðåïà. Âòîðè÷íûìè îñëîæíåíèÿìè ÿâëÿþòñÿ àêðîìåãàëèÿ, ñëåïîòà è ñàõàðíûé äèàáåò II òèïà.  íàøåì ñëó÷àå,
â 2006 ãîäó áûëà îáíàðóæåíà ÷åðåïíàÿ ìåíèíãèîìà,
ðàñïîëîæåííàÿ íàä òóðåöêèì ñåäëîì, â ïåðåäíåì îñíîâàíèè ÷åðåïà ó 28-ëåòíåé æåíùèíû ñ èíñóëèíîçàâèñèìûì ñàõàðíûì äèàáåòîì II òèïà äåêîìïåíñèðîâàííîé
ôîðìû, õàðàêòåðèçóþùåéñÿ òÿæåëûì ñîñòîÿíèåì è àêðîìåãàëèåé (30 ììîëü/ë) (GH/IGF-131, 8 íã/ìë). Îíà ëå÷èëàñü ñ ïîìîùüþ 360IU Àêòðàïèä è 100 ÌÅ Ïðîòàôàí.
ÌÐÒ ïîäòâåðäèëà, ÷òî ìåíèíãèîìà èìåëà áëÿøå÷íóþ
ôîðìó è îõâàòûâàëà ãèïîôèç, ëåâóþ âíóòðåííþþ ñîííóþ
àðòåðèþ, êàâåðíîçíûé ñèíóñ, çðèòåëüíûå íåðâû, ãèïîòàëàìóñ, ìåäèàëüíóþ îðáèòó è áîëüøîå êðûëî êëèíîâèäíîé êîñòè, âûçûâàÿ äâóñòîðîííþþ ñëåïîòó è ôèáðîçíóþ
äèñïëàçèþ íèæíåé ÷åëþñòè.  2009 ãîäó ëó÷åâàÿ ãàììàòåðàïèÿ áûëà ïðîâåäåíà â êà÷åñòâå àëüòåðíàòèâû íåéðîõèðóðãèè.  ðåçóëüòàòå ëó÷åâîé òåðàïèè óðîâåíü ãëþêîçû â êðîâè ñíèçèëñÿ ñ 25.7 ììîëü/ë (29.04.09) äî
7.43 ììîëü/ë (03.12.2014), ñîìàòîòðîïèí ñ 31.782 ìêã/ë
(15.05.09) äî 3.46 ìêã/ë (03.12.2014) è ïðîëàêòèí ñ
48.09 íã/ìë (16.10.09) äî 14.8 íã/ìë (16.05.12). Åé áûë íàçíà÷åí Gen-èíñóëèí BTT óòðîì (18 ÌÅ ñðåäíåãî äåéñòâèÿ, 8 ÌÅ êîðîòêîãî äåéñòâèÿ) è âå÷åðîì (16 ÌÅ ñðåäíåãî äåéñòâèÿ, 8 ÌÅ êðàòêîâðåìåííîãî äåéñòâèÿ) ñ
èíãèáèòîðîì ÄÏÏ-4 Anagliptin ñ èíêðåòèíîâûì (ÃÏÏ-1)
ýêñåíàòèäîì. Äàííîå èññëåäîâàíèå èíòåðåñíî áëàãîäàðÿ åãî ýïèäåìèîëîãè÷åñêîìó çíà÷åíèþ, ñóùåñòâåííîé ñîïóòñòâóþùåé ïàòîëîãèè è ïîòåíöèàëüíî àãðåññèâíîìó
òå÷åíèþ. Ðàñïîëîæåíèå îïóõîëè ïðåäîòâðàòèëî ðàäèêàëüíîå ëå÷åíèå, à êîíñåðâàòèâíîå ëå÷åíèå îêàçàëîñü
äîðîãèì â ñèëó ñîöèàëüíî-ýêîíîìè÷åñêîãî ïîëîæåíèÿ
ïàöèåíòà. Íåîáõîäèìî èññëåäîâàòü ðàñïðîñòðàíåíèå
ìåíèíãèîìû ó æåíùèí, àëüòåðíàòèâíîå ëå÷åíèå äëÿ
óìåíüøåíèÿ îïóõîëè, à òàêæå ýôôåêò ýíäîãåííûõ èëè ýêçîãåííûõ ïîëîâûõ ãîðìîíîâ. Ýòî â âûñøåé ñòåïåíè âàæíî
äëÿ òîãî, ÷òîáû ïîëó÷èòü áîëüøå çíàíèé î ðàçâèòèè è ïðîèñõîæäåíèè ýòèõ îïóõîëåé, à òàêæå äëÿ îöåíêè ôàêòîðîâ
ðèñêà è ðàçðàáîòêè ïðîôèëàêòè÷åñêîãî ïðîòîêîëà.
Êëþ÷åâûå ñëîâà: ìåíèíãèîìà, òóðåöêîå ñåäëî, àêðîìåãàëèÿ, ñàõàðíûé äèàáåò, ìåòàñòàçû.
Ukrainian Scientific Medical Youth Journal / Óêðà¿íñüêèé íàóêîâî-ìåäè÷íèé ìîëîä³æíèé æóðíàë ¹ 4 (84) • 2014