KULIAH PATOLOGI ENDOKRIN 5.

Thyrotrophs: pale basophilic cells

Oleh: Brian Wasita,dr.,Ph.D, Sp.PA
The endocrine system :
 A highly integrated and widely
distributed group of organs that
orchestrate a state of metabolic
equilibrium, or homeostasis, among
the various organs of the body.
 Endocrine signaling, act on target cells
that are distant from their site of
synthesis.
Endocrine diseases:
1. Diseases of underproduction or
overproduction of hormones and their
resulting biochemical and clinical
consequences.
2. Diseases associated with the
development of mass lesions
(nonfunctional or functional).
produce thyroid-stimulating hormone
(TSH).
6. Gonadotrophs: basophilic cells
produce both follicle-stimulating
hormone (FSH) and luteinizing
hormone (LH).
Specific transcription factors have been
identified that regulate the
differentiation of pluripotent stem cells
within the Rathke’s pouch into these
terminally differentiated cell types.
1. Stem cells that express the pituitary
transcription factor, PIT-1 for
somatotrophs, mammosomatotrophs,
and lactotrophs.
2. Steroidogenic factor -1 (SF-1) and
GATA-2 for gonadotroph
differentiation

Pituitary gland cells

ANTERIOR PITUITARY
1. Somatotrophs : acidophilic cells
producing growth hormone (GH)  ACIDOPHILS (growth)

2. Mammosomatotrophs, producing GH  GROWTH HORMONE

and prolactin (PRL)
 PROLACTIN
3. Lactotrophs (mammotrophs):
 BASOPHILS (trophs)
acidophilic cells producing prolactin
 TSH
4. Corticotrophs: basophilic cells
produce adrenocorticotropic  ACTH
hormone (ACTH), pro-
 LH, FSH
opiomelanocortin (POMC),
melanocyte-stimulating hormone
(MSH), endorphins, and lipotropin.

POSTERIOR PITUITARY
1. OXYTOCIN
(contracts uterine smooth muscle and the
smooth muscles surrounding the lactiferous
ducts of the mammary glands).
2. VASOPRESSIN(ADH)
(vasoconstriction, gluconeogenesis, platelet
aggregation, release of Factor-VIII and vWb
factor, concentrates urine, main effects on
kidney and brain).
Clinical Manifestations of Pituitary Disease
A. Hyperpituitarism:
 Arising from excess secretion of
trophic hormones.
 The causes : adenoma, hyperplasia
and carcinomas of the anterior
pituitary, secretion of hormones by
nonpituitary tumors, and certain
hypothalamic disorders.
B. Hypopituitarism:
 Arising from deficiency of trophic
hormones.
 The cause: destructive processes,
including ischemic injury, surgery or
radiation, inflammatory reactions,
and nonfunctional pituitary
adenomas.
C. Local mass effects:
 sellar expansion, bony erosion, and
disruption of the diaphragma sella.
D. Diseases of the posterior pituitary
because of increased or decreased
secretion of ADH
Pituitary Adenomas and Hyperpituitarism
 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
  Pituitary adenomas can be functional
(i.e., associated with hormone excess
and clinical manifestations thereof)
or nonfunctioning (i.e.,
immunohistochemical and/or
ultrastructural demonstration of
hormone production at the tissue
level, without clinical symptoms of
hormone excess).

 Less common causes of

hyperpituitarism include pituitary
carcinomas and some hypothalamic
disorders.

 Large pituitary adenomas, and

particularly nonfunctioning ones,
may cause hypopituitarism as they
encroach on and destroy adjacent
anterior pituitary parenchyma.

Clinical feature:

 Usually found in adults, with a peak

incidence from 35 to 60 years of age.

 Microadenomas <1 cm in diameter

 Macroadenomas >1 cm in diameter.

 The signs and symptoms of pituitary

adenomas include endocrine
abnormalities and mass effects.

 The effects of excessive secretion of

anterior pituitary hormones deppend
on the specific types of pituitary
adenoma.

 Local mass effects may be

encountered in any type of pituitary
tumor include radiographic
abnormalities of the sella turcica,
visual field abnormalities, signs and
symptoms of elevated intracranial
pressure, and occasionally
hypopituitarism, pituitary apoplexy.
Macroscopic
 The typical pituitary adenoma is a
soft, well-circumscribed lesion that
may be confined to the sella turcica.
B. GROWTH HORMONE CELL
(SOMATOTROPH) ADENOMAS
 The second most common type of
functioning pituitary adenoma.

 Larger lesions typically extend  Persistently elevated levels of GH

superiorly through the diaphragm stimulate the hepatic secretion of
sella into the suprasellar region, insulin-like growth factor 1 (IGF-1),
where they often compress the optic which causes many of the clinical
chiasm and adjacent structures, such manifestations
as some of the cranial nerves.
 GH excess is also correlated with a
Microscopic variety of other disturbances,
including gonadal dysfunction,
 Typical pituitary adenomas are
diabetes mellitus, generalized muscle
composed of relatively uniform,
weakness, hypertension, arthritis,
polygonal cells arrayed in sheets or
congestive heart failure, and an
cords.
increased risk of gastrointestinal
 Supporting connective tissue, or cancers.
reticulin, is sparse, accounting for the
GIGANTISM
soft, gelatinous consistency of many
of these lesions.  (excess somatotropin [GH] before
epiphyseal closure)
 Mitotic activity is usually sparse.
ACROMEGALY:
 The cytoplasm of the constituent
cells may be acidophilic, basophilic,  (excess somatotropin [GH] after
or chromophobic, depending on the epiphyseal closure)
type and amount of secretory
product within the cells, but it is
generally uniform throughout the
tumor.

Specific adenoma’s clinical feature

A. Prolactinomas (lactotroph
adenomas)

 the most frequent type of

hyperfunctioning pituitary adenoma,
accounting for about 30% of all
clinically recognized cases.

 Increased serum levels of prolactin,

or prolactinemia, cause amenorrhea,
galactorrhea, loss of libido, and
infertility.
 Pituitary carcinomas
ACTH CELL (CORTICOTROPH) ADENOMAS
Hypopituitarism
 Hypercortisolism (also known as
Cushing syndrome).
 Nelson syndrome
 Hyperpigmentation
Clinical manifestation
Nonfunctioning pituitary adenomas
 Heterogeneous group that
constitutes approximately 25% to 30%
of all pituitary tumors.
 The typical presentation of
nonfunctioning adenomas is mass
effects
 quite rare, < 1% of pituitary tumors.
 The demonstration of craniospinal or
systemic metastases is a sine qua non
of a pituitary carcinoma.
 The majority of pituitary carcinomas
are functional neoplasms, with
prolactin and ACTH being the most
common secreted products.
1. Tumors and other mass lesions.
2. Traumatic brain injury and
subarachnoid hemorrhage.
3. Pituitary surgery or radiation
4. Pituitary apoplexy
5. Ischemic necrosis of the pituitary and
Sheehan syndrome
6. Rathke cleft cyst
7. Empty sella syndrome
8. Genetic defects: POU1F1 mutation
9. Inflammatory disorders and infections
 Pituitary dwarfism due to growth
hormone deficiency.
 Gonadotropin (LH and FSH) 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, respectively.
 Prolactin deficiency results in failure
of postpartum lactation.
 Pallor due to a loss of stimulatory
effects of MSH on melanocytes.
Posterior Pituitary Syndrome  Most are suprasellar, with or
without intrasellar extension.
A. Diabetes insipidus.
 A bimodal age distribution is
 ADH deficiency
observed, with one peak in
 Excessive urination (polyuria) due to childhood (5 to 15 years) and a
an inability of the kidney to resorb second peak in adults 65 years or
water properly from the urine. older.

 Causes: head trauma, tumors, and  Patients usually come to attention

inflammatory disorders of the
hypothalamus and pituitary as well as
surgical procedures involving these
organs
B. Syndrome of inappropriate ADH
(SIADH) secretion.
because of headaches and visual
disturbances, while children
sometimes present with growth
retardation due to pituitary
hypofunction and GH deficiency.

 ADH excess causes resorption of

excessive amounts of free water,
resulting in hyponatremia.

 Causes : the secretion of ectopic ADH

by malignant neoplasms (particularly
small-cell carcinomas of the lung),
drugs that increase ADH secretion,
and a variety of central nervous
system disorders, including infections
and trauma.

 The clinical manifestations of SIADH

are dominated by hyponatremia,
cerebral edema, and resultant
neurologic dysfunction

Hypothalamic Suprasellar Tumors

 Neoplasms in this location may induce

hypofunction or hyperfunction of
the anterior pituitary, diabetes
insipidus, or combinations of these
manifestations.

 The most commonly implicated

tumors are gliomas (sometimes
arising in the chiasm) and
craniopharyngiomas.

 The craniopharyngioma is thought to

arise from vestigial remnants of
Rathke pouch.
Thyroid Pathology
Diseases of the thyroid
A. Excessive release of thyroid
hormones (hyperthyroidism)
B. Thyroid hormone deficiency
(hypothyroidism
C. Mass lesions of the thyroid.
Excessive release of thyroid hormones
(hyperthyroidism)
 Diffuse hyperplasia of the thyroid
associated with Graves disease
(accounts for 85% of cases)
 Hyperfunctional multinodular goiter
 Hyperfunctional adenoma of the
thyroid
Clinical Manifestation
1. Excessive levels of thyroid hormone
result in an increase in the basal
metabolic rate.
 soft, warm, and flushed skin. Heat
intolerance is common.
 Increased sweating.
 weight loss despite increased
appetite.
2. Cardiac manifestations
 Tachycardia, palpitations, arrhythmias
and cardiomegaly
 Hyperthyroid cardiomyopathy.
3. Neuromuscular system
 Tremor, hyperactivity, emotional
lability, anxiety, inability to
concentrate, and insomnia.
 Thyroid myopathy
4. Ocular changes: exopthalmus
5. Gastrointestinal system :
hypermotility, malabsorption, and
diarrhea.
6. Skeletal system : osteoporosis,
atrophy of skeletal muscle.
7. Thyroid storm : febrile and present
with tachycardia out of proportion to
the fever. Thyroid storm is a medical
emergency with a significant number
of untreated patients die of cardiac
arrhythmias
8. Etc

Hypothyroidism
 Causes: any structural or functional
derangement that interferes with the
production of adequate levels of
thyroid hormone.
 Can be congenital, acquired, or
autoimmune.
1. Congenital hypothyroidism is most
often the result of endemic iodine
deficiency in the diet.
2. Acquired hypothyroidism : surgical or
radiation-induced ablation of thyroid
parenchyma.
3. Autoimmune hypothyroidism :
Hashimoto thyroiditis
Clinical manifestations
1. CRETINISM :
 impaired development of the skeletal
system and central nervous system,
manifested by severe mental
retardation, short stature, coarse
facial features, a protruding tongue,
and umbilical hernia.
2. MYXEDEMA
 Clinical features of myxedema are
characterized by a slowing of physical
and mental activity
Thyroiditis
 Thyroiditis, or inflammation of the
thyroid gland, encompasses a diverse
group of disorders characterized by
some form of thyroid inflammation.
1. Acute illness with severe thyroid pain
(e.g., infectious thyroiditis, subacute
granulomatous thyroiditis)
 2. Disorders in which there is relatively
little inflammation and the illness is
manifested primarily by thyroid
dysfunction—subacute lymphocytic
thyroiditis and fibrous (Reidel)
thyroiditis
Common form:
A. Hashimoto thyroiditis
B. Granulomatous (de Quervain)
thyroiditis
C. Subacute lymphocytic thyroiditis :
just like Hashimoto’s but NO fibrosis
and no germinal centers), often post-
partum.
HASHIMOTO THYROIDITIS
 Characterized by gradual thyroid
failure because of autoimmune
destruction of the thyroid gland.
 Caused by a breakdown in self-
tolerance to thyroid auto-antigens
 Most prevalent between 45 and 65
years of age
 More common in women than in
men, with a female predominance of
10 : 1 to 20 : 1.
 Linked with polymorphisms in CTLA4
and PTPN22 gene.
 Clinical feature: painless enlargement
of the thyroid, usually associated with
some degree of hypothyroidism, in a
middle-aged woman. The
enlargement of the gland is usually
symmetric and diffuse
 Macroscopic: The thyroid is often
diffusely enlarged, although more
localized enlargement may be seen in
some cases. The capsule is intact, and
the gland is well demarcated from
adjacent structures. The cut surface is
pale, yellowtan, firm, and somewhat
nodular.
 Microscopic : extensive infiltration of
the parenchyma by a mononuclear
inflammatory infiltrate containing
small lymphocytes, plasma cells, and
well-developed germinal centers. The
thyroid follicles are atrophic and are
lined in many areas by epithelial cells
distinguished by the presence of
abundant eosinophilic, granular
cytoplasm, termed Hürthle cells.
Graves Disease

 Graves disease is characterized by a

breakdown in self-tolerance to
thyroid auto-antigens, most
importantly the TSH receptor.

 Triad of clinical findings: Goiter

1. Hyperthyroidism  The most common manifestation of
2. Exophthalmos thyroid disease.

3. Pretibial myxedema  Diffuse and multinodular goiters

 A peak incidence between 20 and 40  Reflect impaired synthesis of thyroid

years of age. Women are affected as hormone, which is most often caused
much as 10 times more frequently by dietary iodine deficiency.
than men  Iodine deficiency
 Linked with polymorphisms in  Increased TSH
immune-function genes like CTLA4
and PTPN22 and the HLA-DR3 allele  Goitrogens, e.g., cabbage, Brussels
sprouts, cauliflower, turnips, cassava)
 Macroscopic: usually symmetrically
enlarged because of diffuse  Associated with HYPO thyroidism but
hypertrophy and hyperplasia of most patient are euthyroid.
thyroid follicular epithelial .Increases
in weight to over 80 gm are not
uncommon. On cut section, the
parenchyma has a soft, meaty
appearance resembling normal
muscle.

 Microscopic : the follicular epithelial

cells are tall and more crowded than
usual. This crowding often results in
the formation of small papillae, which
project into the follicular lumen and
encroach on the colloid, sometimes
filling the follicles Such papillae lack
fibrovascular cores, in contrast to
those of papillary carcinoma.The
colloid within the follicular lumen is Diffuse Nontoxic (Simple) Goiter
pale, with scalloped margins.
Lymphoid infiltrates, consisting
predominantly of T cells, with fewer B
cells and mature plasma cells, are
present throughout the interstitium;
germinal centers are common.

Multinodular Goiter
Adenoma
Macroscopic:
 The dominant clinical features of
multinodular goiter are those caused
by mass effects. In addition to the
obvious cosmetic effects, goiters may
cause airway obstruction, dysphagia,
and compression of large vessels`
 Most patients are euthyroid or have
subclinical hyperthyroidism (identified
only by reduced TSH levels),
 In a substantial minority of patients
an autonomous nodule may develop
within a long-standing goiter and
produce hyperthyroidism (toxic
multinodular goiter) known as
Plummer syndrome, which is not
accompanied by the infiltrative
ophthalmopathy and dermopathy of
Graves disease.
 A solitary, spherical, encapsulated
lesion that is well demarcated from
the surrounding thyroid parenchyma.
 Follicular adenomas average about 3
cm in diameter, but some are much
larger (≥10 cm in diameter).
 In freshly resected specimens the
adenoma bulges from the cut surface
and compresses the adjacent thyroid.
The color ranges from gray-white to
red-brown, depending on the
cellularity of the adenoma and its
colloid content.
 The neoplastic cells are demarcated
from the adjacent parenchyma by a
well-defined, intact capsule
Adenoma

Macroscopic:

 A solitary, spherical, encapsulated

lesion that is well demarcated from
the surrounding thyroid parenchyma.

 Follicular adenomas average about 3

cm in diameter, but some are much
larger (≥10 cm in diameter).

 In freshly resected specimens the

adenoma bulges from the cut surface
and compresses the adjacent thyroid.
The color ranges from gray-white to
red-brown, depending on the
cellularity of the adenoma and its
colloid content.

 The neoplastic cells are demarcated

from the adjacent parenchyma by a
well-defined, intact capsule

Carcinoma

The major subtypes of thyroid carcinoma :

1. Papillary carcinoma (>85% of cases)

2. Follicular carcinoma (5% to 15% of

cases)

3. Anaplastic (undifferentiated)
carcinoma (<5% of cases)
Microscopic: 4. Medullary carcinoma (5% of cases)
 the constituent cells often form Risk Factors:
uniform-appearing follicles that
 Genetic : (MAP) kinase pathway and
contain colloid
the (PI-3K)/AKT pathway.
 The follicular growth pattern within
 Environment : exposure to ionizing
the adenoma is usually quite distinct
radiation
from the adjacent non-neoplastic
thyroid.

 The epithelial cells composing the

follicular adenoma reveal little
variation in cell and nuclear
morphology, and mitotic figures are
rare
 Medullary Carcinoma
Papillary Carcinoma

BIOLOGIC BEHAVIOR

 Papillary Ca lymph nodes

 Follicular Ca  blood vessels,

bone,liver, lung

Parathyroid

 The function of the parathyroid

glands is to regulate calcium
homeostasis.
Follicular Carcinoma  The four parathyroid glands are
composed of two cell types: chief
cells and oxyphil cells.

Function of PTH

 Increases the renal tubular

reabsorption of calcium, thereby
conserving free calcium

 Increases the conversion of vitamin D

to its active dihydroxy form in the
kidneys
  Increases urinary phosphate
excretion, thereby lowering serum
phosphate levels

 Augments gastrointestinal calcium

absorption

PARATHYROID DISORDERS

 HYPERPARATHYROID

 Primary
hyperparathyroidism: an
autonomous overproduction HYPER-PARATHYROIDISM
of parathyroid hormone  Bone pain, fractures
(PTH), usually resulting from
an adenoma or hyperplasia  Nephrolithiasis
of parathyroid tissue
 Constipation, ulcers, gallstones
 Secondary
 Depression, lethargy
hyperparathyroidism:
compensatory  short QT interval and a widened T
hypersecretion of PTH in wave
response to prolonged
 Weakness, fatigue
hypocalcemia, most
commonly from chronic renal  Calcifications, esp. VALVES
failure
Adenoma
 Tertiary
hyperparathyroidism:
persistent hypersecretion of
PTH even after the cause of
prolonged hypocalcemia is
corrected, for example after
renal transplant

 HYPOPARATHYROID

Surgical, congenital, familial,

idiopathic

 PSEUDO-HYPOPARATHYROID

(end organ resistance)

 Hypoparathyroidism

 Surgically induced
hypoparathyroidism

 Autoimmune hypoparathyroidismis
often associated with chronic
mucocutaneous candidiasis and
primary adrenal insufficiency; this
syndrome is known as autoimmune
polyendocrine syndrome type 1
(APS1) and is caused by mutations in
the autoimmune regulator (AIRE)
gene.

 Autosomal-dominant
hypoparathyroidism is caused by
gain-of-function mutations in the
calcium-sensing receptor (CASR)
gene.

 Familial isolated
Carcinoma hypoparathyroidism(FIH) caused by a
mutation in the gene encoding PTH
precursor peptide, which impairs its
processing to the mature hormone.

 Congenital absence of parathyroid

glands

ADRENAL CORTEX
Diagnosis of carcinoma based on cytologic
detail is unreliable, and invasion of  Glomerulosa (Salt),
surrounding tissues and metastasis are the mineralocorticoids
only reliable criteria  ALDOSTERONE

 Fasciculata (Sugar), glucocorticoids

HYPO-PARATHYROIDISM
 CORTISOL
 Neuromuscular irritability
 Reticularis (Sex), gonadocorticoids
 Mental status change
 ANDROGENS, ESTROGENS
 Parkinsonism like effects

 Lens calcification

 Widened QT interval

 Defective, carious, teeth

  EXOGENOUS STEROIDS (90%)

HYPERADRENALISM

 HYPERALDOSTERONISM (g)

 CUSHING SYNDROME (CORTISOL) (f)

(most common)

 ADRENOGENITAL (VIRILIZING)
SYNDROME (r)

CUSHING SYNDROME

ETIOLOGY:
PRIMARY HYPERALDOSTERONISM
 PITUITARY ACTH INCREASE (Conn’s Syndrome)

 TUMOR ACTH INCREASE  Na+ RETENTION

 HYPERPLASIA OF CORTEX  K+ EXCRETION

 ADENOMA OF CORTEX  HYPERTENSION

 CARCINOMA OF CORTEX
 ADRENAL INSUFFICIENCY

 PRIMARY ACUTE (ADRENAL CRISIS)

 PRIMARY CHRONIC (auto-immune

ADDISON DISEASE)

 SECONDARY (PITUITARY)
PRIMARY HYPERALDOSTERONISM

ETIOLOGY:

 CORTICAL NEOPLASM

 CORTICAL HYPERPLASIA

 FAMILIAL (rare)

SECONDARY HYPERALDOSTERONISM

 DECREASED RENAL PERFUSION

 EDEMA (HEART, LIVER, KIDNEY)

 PREGNANCY

ADRENOGENITAL SYNDROME

 VIRILIZATION/feminization

 CORTICAL NEOPLASM

 CORTICAL HYPERPLASIA
PRIMARY ACUTE
 21-Hydroxylase Deficiency, with
buildup of 17-hydroxy progesterone  RAPID WITHDRAWAL OF STEROIDS

 MASSIVE ADRENAL HEMORRHAGE

(WATERHOUSE-FRIDERICHSEN, if it
follows infection [meningo, staph, H.
flu] and shock)

 Newborns with DIFFICULT

DELIVERY
  ANTICOAGULANT RX

 POSTSURGICAL DIC PATIENTS

PRIMARY CHRONIC

 Most of Addison disease is auto-

immune adrenalitis [ACAs])

 INFECTIONS (fungal diseases, histo-)

 METASTASES (adrenals are an

amazingly preferred site for early
lung carcinoma metastases)

 GENETIC DISORDERS

NEOPLASMS

 ADENOMAS of ADRENAL CORTEX

 CARCINOMAS of ADRENAL CORTEX

Adenoma

ADENOMAS of ADRENAL CORTEX

CARCINOMAS of ADRENAL CORTEX

TWO crucially important points specific for

endocrine tumors:
ADRENAL MEDULLA
 1. FUNCTIONING carcinomas are very
 PHEOCHROMOCYTOMAS (primary RARE in ANY endocrine gland.
tumors of the adrenal medulla)
 2. Benign adenomas may have
 10% arise in an MEN extremely bizarre nuclei, but are
(Multiple Endocrine most usually BENIGN!!!
Neoplasm)
ENDOCRINE
 10% are EXTRA-adrenal
PANCREAS
 10% are bilateral

 10% are malignant

 10% are in childhood

 You can only call them

malignant if they
metastasize.
PATHOGENESIS

 1

 T-Lymphocytes reacting against

poorly defined beta cell antigens

 Inflammatory inflitrate, chronic, i.e.,

“INSULITIS”

 2

 Diet

 Life Style

 Obesity

 INSULIN RESISTANCE

 Beta cells UN-able to adapt to the

“long term demands of insulin
resistance”

How to Diagnose DM:

 A fasting plasma glucose ≥126 mg/dL,

 A random plasma glucose ≥200

mg/dL (in a patient with classic
hyperglycemic signs, as discussed
later),

 2-hour plasma glucose ≥ 200 mg/dL

during an oral glucose tolerance
test (OGTT) with a loading dose of
75 gm

 A glycated hemoglobin (HbA1C)

level ≥ 6.5%
  PANCREAS in DM ATHEROSCLEROSIS

COMPLICATIONS

 Macrovascular disease

 Microvascular disease (kidneys,

retina, nerves)

 Immune related problems,

INFECTIONS, e.g., TB, pneumonia,
pyelonephritis, candida, etc.

ATHEROSCLEROSIS

COMPLICATIONS
MORPHOLOGY

 (MACRO-vascular):

Atherosclerosis

 MICRO-vascular:

 *Retinopathy

 *Nephropathy- glomerular,
vascular

 *Neuropathy (most common

cause of neuropathy)

 Infections
Atherosclerotic plaque

INFECTIONS in DM

 SKIN

 TUBERCULOSIS

 PNEUMONIA

 PYELONEPHRITIS

F: Fibrous cap, projecting into  CANDIDA

L: Lumen, and Pancreatic Neuroendocrine Tumors

C: Necrotic core  Islet cell tumors

RETINOPATHY  Beta cells INSULINOMAS

(NOT rare)
Shows microaneurysms, areas of
hemorrhage, cotton wool spots, hard  Alpha cells
exudates, venousbeading, GLUCAGONOMAS (rare)
neovascularization, retinal detachment,  Delta cells
vitreous detachment, pre retinal SOMATOSTATINOMAS (rare)
hemorrhage
 GASTRINOMAS, producing
ZOLLINGER-ELLISON
SYNDROME, consisting of
increased acid and ulcers

NEPHROPATHY
PINEAL GLAND

 Also called epiphysis, pineal body

 Between superior colliculi at base of

brain; 100-180 mg

 Develops at month 2 of gestation as

diverticulum in diencephalic roof of
third ventricle

 Replaced by connective tissue after

puberty PINEAL GLAND

 Produces melatonin, which helps  PINEALOMAS

regulate circadian rhythms
 Pineoblastoma

 Pineocytomas

Pineoblastoma

 Grade IV of IV

 Second most common pineal gland

tumor after germ cell tumor

 Usually age 20 years or less

 Frequent CNS metastases or spinal

seeding, which is the main cause of
death
Microscopic

 Sheets of densely packed cells with

high grade (anaplastic /
undifferentiated) features including
high N/C ratio with minimal cytoplasm
and large hyperchromatic nuclei

 Also necrosis, frequent mitotic figures

 Focal nuclear molding

 Homer-Wright or Flexner-
Wintersteiner rosettes

Pineocytomas

 Grade I of IV

 Mostly adults age 25-35 years

 Slow growing

Microscopic

 Similar to normal pineal gland’s well

differentiated cells but hypercellular

 Fibrovascular stroma highlights

expansive lobules of tumor cells with
uniform round nuclei

 Pinocytomatous rosettes (large, loose,

Homer-Wright like rosettes with
central fibrillar zones surrounded by
neoplastic cells with round nuclei)

 Non-infiltrative, no/rare mitotic

figures, no necrosis, no/minimal
atypia