Pathology Aspect of Hypothalamus
and Pituitary Gland
By. Meike Rachmawati,dr
Pathology anatomy Department
Medical Faculty-Unisba
Objective
Pituitary neoplasm :
 Adenomas and hyperpituitarism :
type of adenoma, morphology, and patophysiology
 Hypopituitarism
Craniopharyngioma
morphology
:
histogenesis
and
HYPERPITUITARISM AND PITUITARY
ADENOMAS
 The most common cause of hyperpituitarism is an adenoma arising in the
anterior lobe.
 Pituitary adenomas are classified on the basis of hormone(s) produced by
the neoplastic cells, which are detected by immunohistochemical stains
performed on tissue sections
 rarely, ultrastructural examination may be required to determine
the specific lineage of the neoplastic cell.
 Pituitary adenomas can be functional (i.e., associated with
hormone excess and clinical manifestations thereof) or silent (i.e.,
immunohistochemical and/or ultrastructural demonstration of
hormone production at the tissue level only, without clinical
manifestations of hormone excess).
 Both functional and silent pituitary adenomas are usually
composed of a single cell type and produce a single
predominant hormone, although exceptions are known to
occur.
 Some pituitary adenomas can secrete two hormones (growth
hormone and prolactin being the most common
combination);
 rarely, pituitary adenomas are plurihormonal. Pituitary
adenomas may also be hormone negative, based on absence of
immunohistochemical reactivity and ultrastructural
demonstration of lineage-specific differentiation.
 Clinically diagnosed pituitary adenomas are responsible for
about 10% of intracranial neoplasms.
 They are discovered incidentally in as many as 25% of routine
autopsies.
 In fact, the most recent data using high-resolution computed
tomography or magnetic resonance imaging suggest that
approximately 20% of "normal" adult pituitary glands harbor
an incidental lesion measuring 3 mm or more in diameter,
usually a silent adenoma.
 Pituitary adenomas are usually found in adults, with a peak
incidence from the 30s to the 50s.
The
adenohypophysis
(anterior
pituitary)
releases six hormones that
are, in turn, under the
control
of
various
stimulatory and inhibitory
hypothalamic
releasing
factors:
•ACTH,
adrenocorticotropic
hormone (corticotropin);
•FSH, follicle-stimulating
hormone;
•GH,
growth hormone
(somatotropin);
•LH, luteinizing hormone;
•PRL, prolactin; and
•TSH, thyroid-stimulating
hormone (thyrotropin).
The stimulatory
releasing factors are
:
•CRH (corticotropinreleasing hormone),
•GHRH (growth
hormone-releasing
hormone),
•GnRH (gonadotropinreleasing hormone),
•TRH (thyrotropinreleasing hormone).
The inhibitory
hypothalamic factors
are:
•growth hormone
inhibitory hormone
(GIH, or somatostatin)
•PIF (prolactin
inhibitory factor, or
dopamine
*For each of the
pituitary cell types,
the adenoma may be
functional (producing
symptoms of
hormone excess) or
silent.
The heterogeneous
category of
"nonfunctional"
adenomas includes
silent pituitary
adenomas and true
hormone-negative
adenomas (rare).
ACTH,
adrenocorticotropic
hormone
Classification of Pituitary Adenomas*
 Prolactin cell (lactotroph) adenoma
 Growth hormone cell (somatotroph) adenoma
 Thyroid-stimulating hormone cell (thyrotroph)
adenomas
 ACTH cell (corticotroph) adenomas
 Gonadotroph cell adenomas
 Silent gonadotroph adenomas includes most socalled null cell adenomas
 Mixed (plurihormonal) adenomas Body
 Growth hormone-prolactin mixed adenomas
most common
 Hormone-negative adenomas
 Most pituitary adenomas occur as isolated lesions.
 In about 3% of cases, however, adenomas are associated with
multiple endocrine neoplasia type 1 (MEN-1, discussed later).
 Pituitary adenomas are designated, somewhat arbitrarily,
microadenomas if less than 1 cm in diameter and macroademomas if
they exceed 1 cm in diameter.
 Silent and hormone-negative adenomas are likely to come to
clinical attention at a later stage than those associated with
endocrine abnormalities and are therefore more likely to be
macroadenomas; in addition, these adenomas may cause
hypopituitarism as they encroach on and destroy adjacent anterior
pituitary parenchyma.
Morphology
 The usual pituitary adenoma is a well-circumscribed, soft lesion that
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may, in the case of smaller tumors, be confined by the sella turcica.
Larger lesions typically extend superiorly through the sellar diaphragm
into the suprasellar region, where they often compress the optic chiasm
and adjacent structures
As these adenomas expand, they frequently erode the sella turcica and
anterior clinoid processes. They may also extend locally into the
cavernous and sphenoidal sinuses.
In as many as 30% of cases the adenomas are grossly nonencapsulated
and infiltrate adjacent bone, dura, and (uncommonly) brain.
Such lesions are designated invasive adenomas.
Foci of hemorrhage and/or necrosis are common in larger adenomas.
 Microscopically, pituitary adenomas are composed of relatively uniform,
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polygonal cells arrayed in sheets, cords, or papillae.
Supporting connective tissue, or reticulin, is sparse, accounting for the
soft, gelatinous consistency of many lesions.
The nuclei of the neoplastic cells may be uniform or pleomorphic.
Mitotic activity is usually scanty.
The cytoplasm of the constituent cells may be acidophilic, basophilic, or
chromophobic, depending on the type and amount of secretory product
within the cell, but it is fairly uniform throughout the neoplasm.
This cellular monomorphism and the absence of a significant
reticulin network distinguish pituitary adenomas from nonneoplastic anterior pituitary parenchyma (Fig. 20-4). The
functional status of the adenoma cannot be reliably predicted from its
histologic appearance.
Gross view of a pituitary adenoma
. This massive,
nonfunctional
adenoma has grown
far beyond the
confines of the sella
turcica and has
distorted the
overlying brain.
Nonfunctional
adenomas tend to be
larger at the time of
diagnosis than those
that secrete a
hormone.
Photomicrograph of pituitary
adenoma.
The monomorphism
of these cells
contrasts markedly
to the mixture of
cells seen in the
normal anterior
pituitary in Figure
20-1. Note also the
absence of reticulin
network.
Clinical Manifestations of Pituitary
Adenomas
 Prolactinomas: amenorrhea, galactorrhea, loss of libido, and
infertility
 Growth hormone (somatotroph cell) adenomas: gigantism
(children), acromegaly (adults), impaired glucose tolerance,
and diabetes mellitus
 Corticotroph
cell
adenomas:
Cushing
syndrome,
hyperpigmentation
 All pituitary adenomas, particularly nonfunctioning
adenomas, may be associated with mass effects and
hypopituitarism.
SUMMARY
 The most common cause of hyperpituitarism is an anterior lobe pituitary
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

adenoma.
Pituitary adenomas can be macroadenomas (>1 cm) or microadenomas (<1
cm),
and clinically, they can be functional or silent.
Most adenomas consist of one cell type and produce one hormone, although
there are exceptions.
Mutation of the GNAS1 gene, which results in constitutive activation of a
stimulatory G-protein, is one of the more common genetic alterations.
The two distinctive morphologic features of most adenomas are their cellular
monomorphism and absence of a reticulin network.
HYPOPITUITARISM
 Hypofunction of the anterior pituitary may occur with loss or
absence of 75% or more of the anterior pituitary
parenchyma.
 This may be congenital (exceedingly rare) or may result from
a wide range of acquired abnormalities that are intrinsic to the
pituitary. Less frequently, disorders that interfere with the
delivery of pituitary hormone-releasing factors from the
hypothalamus, such as hypothalamic tumors, may also cause
hypofunction of the anterior pituitary.
 Most cases of anterior pituitary hypofunction are caused by
the following:
 Nonfunctioning pituitary adenomas (see above)Ischemic
necrosis of the anterior pituitary is an important cause of
pituitary insufficiency.
 In general, the anterior pituitary tolerates ischemic insults
fairly well; loss of as much as half of the anterior pituitary
parenchyma causes no clinical consequences.
 However, with destruction of larger amounts of the anterior
pituitary (ε75%), signs and symptoms of hypopituitarism
develop.
 Sheehan syndrome, or postpartum necrosis of the anterior
pituitary, is the most common form of clinically significant
ischemic necrosis of the anterior pituitary.
 During pregnancy the anterior pituitary enlarges
considerably, largely because of an increase in the size and
number of prolactin-secreting cells.
 However, this physiologic enlargement of the gland is not
accompanied by an increase in blood supply from the lowpressure portal venous system. The enlarged gland is thus
vulnerable to ischemic injury, especially in women who
develop significant hemorrhage and hypotension during the
peripartum
 The clinical manifestations of anterior pituitary hypofunction
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depend on the specific hormone(s) that are lacking.
Children can develop growth failure (pituitary dwarfism) as a
result of growth hormone deficiency.
Gonadotropin or gonadotropin-releasing hormone (GnRH)
deficiency leads to amenorrhea and infertility in women and
decreased libido, impotence, and loss of pubic and axillary
hair in men.
TSH and ACTH deficiencies result in symptoms of
hypothyroidism and hypoadrenalism,
Prolactin deficiency results in failure of postpartum lactation.
Craniopharyngioma
 Craniopharyngioma is a slow-growing, extra-axial, epithelial-
squamous, calcified cystic tumor arising from remnants of
the craniopharyngeal duct and/or Rathke cleft and occupying
the (supra)sellar region.
 Two main hypotheses explain the origin of
craniopharyngioma—embryogenetic and metaplastic
 Craniopharyngiomas are dysontogenic tumors with benign
histology and malignant behavior, as they have a tendency to
invade surrounding structures and recur after what was
thought to be total resection.
 Craniopharyngioma usually presents as a single large cyst or
multiple cysts filled with a turbid, proteinaceous material of
brownish-yellow color that glitters and sparkles because of a
high content of floating cholesterol crystals.
 Because of its appearance, it has been compared to machinery
oil.
 It most frequently arises in the pituitary stalk and projects
into the hypothalamus.
 Data from the Central Brain Tumor Registry of the United
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States (CBTRUS), collected between 1990 and 1993,
revealed an average of 338 cases diagnosed annually with 96
occurring in children aged 0-14 years.13
Overall incidence was 0.13 per 100,000 per year.
No variance by gender or race was found.
Craniopharyngioma comprised 4.2% of all childhood tumors
(ages 0-14 years).
Distribution by age was bimodal, with peak incidence in
children aged 5-14 years and older adults aged 65-74 years.
 International
 Incidence is 0.5-2 per 100,000 per year.
 Overall, craniopharyngioma accounts for 1-3% of
intracranial tumors and 13% of suprasellar tumors.
 In children, craniopharyngioma represents 5-10% of all
tumors and 56% of sellar and suprasellar tumors.
 No definite genetic relationship has been found and very few
familial cases have been reported.
 Mortality/Morbidity
 In the United States, data collected during the periods 1985-
1988 and 1990-1992, coinciding with the introduction of CT
scan, for the National Cancer Data Base (NCDB), indicate
that survival rates were 86% at 2 years and 80% at 5 years
after diagnosis.
 Survival rate varied by age group, with excellent rates for
patients younger than 20 years (99% at 5 years).
 Survival rate was poor for those older than 65 years (38% at
5 years).
 Higher frequencies of all intracranial tumors have been
reported from Africa, the Far East, and Japan; they are 18%,
16%, and 10.5%, respectively.
 Slight male predominance exists in all age groups (55%).
 Age of diagnosis varies widely; cases have been reported both
in fetuses and in the elderly (age as high as 70 years).
 Age distribution is bimodal–the first peak is in children aged
5-10 years and a second one is in adults aged 50-
Clinical manifestation
 Craniopharyngioma usually is a slow-growing tumor.
Symptoms frequently develop insidiously and mostly become
obvious only after the tumor attains a diameter of about 3
cm. Time interval between onset of symptoms and diagnosis
ranges from 1-2 years.
 The most common presenting symptoms are headache (5586%), endocrine dysfunction (66-90%), and visual
disturbances (37-68%).
Three major clinical syndromes have been described and relate
to the anatomic location of the craniopharyngioma.
 Prechiasmal localization typically results in associated findings
of optic atrophy (eg, progressive decline of visual acuity and
constriction of visual fields).
 Retrochiasmal location commonly is associated with
hydrocephalus with signs of increased intracranial pressure (eg,
papilledema, horizontal double vision).
 Intrasellar craniopharyngioma usually manifests with headache
and endocrinopathy.
Histopathologic Findings
The histologic spectrum of craniopharyngioma includes 3 main
types—
 adamantinomas,
 papillary,
 and mixed.
Adamantinomatous craniopharyngiomas.
Peripheral
palisading of the
epithelium is a
pronounced
feature
(hematoxylineosin, x100).
Frequently, the
inner epithelium
beneath the
superficial
palisade
undergoes
hydropic
vacuolization
and is referred to
as the stellate
reticulum
(hematoxylineosin, x100).
papillary craniopharyngiomas
papillary
craniopharyngio
mas do not show
complex
heterogeneous
architecture but
rather are
composed of
simple squamous
epithelium and
fibrovascular
islands of
connective tissue
(hematoxylineosin, x40).
[ CLOSE WINDOW
]
, x40).
only
simple
squamous
epithelium is seen
in
a
papillary
craniopharyngioma
. The distinctive
peripheral nuclear
palisading, internal
stellate reticulum,
and nodules of
"wet"
keratin,
which typify the
adamantinomatous
variant, are not
seen
in
the
papillary variant