BLOCK 14

LABORATORY WORK GUIDE

FOR THE PATHOLOGY OF
ENDOCRINOLOGY
I. THYROID GLAND
II. PARATHYROID GLAND
III. ADRENAL GLAND
IV. PITUITARY GLAND
V. ENDOCRINE PANCREAS

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THYROID

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THYROID
Normally weighs between 20 and 30 g.
Follicle is the functional unit of the thyroid
composed of an epithelium-lined sac filled with
colloid stores thyroid hormones in the form of
thyroglobulin T4 (thyroxine) and T3 (triiodothyronine) regulated by TSH
Serum T4 and T3 are bound to thyroid-binding
globulin (TBG)

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Pathology of the thyroid

A.
B.
C.
D.
E.

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HYPOTHYROIDISM
HYPERTHYROIDISM
THYROIDITIS
BENIGN TUMORS (ADENOMAS)
MALIGNANT TUMORS

Colloid Goiter

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Pathology of thyroid

C. HYPOTHYROIDISM

Clinical syndromes
Hypothyroidism is manifest as Myxedema in
adults or as Cretinism in children

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Struma Coloides Macro et

Micro Follicularis

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Non-toxic goiter
Irregular
nodules

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Marked variation in the size of follicles

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Nodular (non-toxic) Goiter

The gland is coarsely nodular and contains areas of fibrosis and cystic change.
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Graves Disease

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Pathology of thyroid

HYPERTHYROIDISM

(THYROTOXICOSIS)

B. Graves Disease
General Charcteristics
1. Hyperthyroidism caused by diffuse toxic goiter
2. Associated with striking exophthalmos autoimmune?
3. More in women
4. incidence increased in HLA-DR3 and HLA-B8 positive individual
Mechanism
1. Thyroid-stimulating-immunoglobulin (TSI) reacts with TSH
receptors stimulates thyroid hormone production
2. Thyroid-growth-immunoglobulin (TGI) stimulates glandular
hyperplasia and enlargement
3. Antimicrosomal and other autoantibodies are characteristic
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Graves disease, hyperthyroidism

Exophthalmos

Thyroid mass
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Major clinical
manifestations
of
Graves disease

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Graves Disease

Diffusely hyperplastic thyroid follicle are lined by tall,

columnar epithelium, and scalloped (moth eaten) appearance of
the edge of the colloid.
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Graves disease, hyperthyroidism

The follicles are lined by hyperplastic, tall columnar cells

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THYROIDITIS
Inflammation of the thyroid gland
(encompasses a heterogenous group of inflammatory disorders of the
thyroid gland, including those that are caused by autoimmune
mechanisms and infectious agents)
A. Acute suppurative thyroiditis: a bacterial infection,
usually occurs in young children or debilitated patients. It is rare
B. Subacute granulomatous thyroiditis (De Quervain thyroiditis)
C. Chronic thyroiditis (Hashimoto thyroiditis, Struma lymphomatosa,
autoimmune thyroiditis)
D. Riedels struma (Riedels disease)
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Chronic autoimmune (Hashimoto)

thyroiditis
Autoimmune disorder that occur more often in women
Common cause of hypothyroidism, may occasionaly
have an early transient hyperthyroid phase
Characterized histologically by massive infiltrates of
lymphocytes with germinal center formation, thyroid
follicles are atrophic, and Hurthle cells are prominent
Associated with various antibodies (antithyroglobulin,
antithyroid peroxidase, anti TSH-receptor, anti-iodine
receptor antobodies)
May be associated with other autoimmune disorders:
pernicious anemia, DM, Sjogren syndrome the
incidence is increased in HLA-DR5 and HLA-B5 positive
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Chronic autoimmune (Hashimoto)

thyroiditis

The thyroid gland is symmetrically enlarged and coarsely nodular.

Coronal section irregular nodules and an intact capsule
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Chronic autoimmune (Hashimoto)

thyroiditis

Atrophic thyroid follicles with conspicuous chronic inflammatory infiltrate

(the inflammatory cells form prominent lymphoid follicles with germinal centers)
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Hashimoto Thyroiditis

Dense lymphocytic infiltrates with germinal centers

Residual thyroid follicle lined by Hurthle cells are also seen
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BENIGN TUMORS
(ADENOMAS)
Are most often solitary
Present clinically as nodules
Can occur in a variety of histologic
pattern (follicular, Hurthle cell)
Are most often nonfunctional but can
occasionally cause hyperthyroidism
Female:male is 7:1
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FOLLICULAR ADENOMA

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Embryonal adenoma
Fetal adenoma
Simple adenoma
Colloid adenoma
Hurthel cell adenoma
Atypical adenoma

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Follicular adenoma

Embryonal adenoma

The tumor features a trabecular pattern with poorly formed follicles

that contain little if any colloid
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Follicular Adenoma

COLLOID ADENOMA
The cut surface of an encapsulated mass reveals:

Hemorrhage

Fibrosis
Cystic change

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Follicular Adenoma

Cystic

A solitary, well-circumscribed nodule is seen.

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Follicular Adenoma

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Well-differentiated follicles resembling

normal thyroid parenchyma.

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Follicular adenoma

FETAL ADENOMA

Regular pattern of small follicles

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Follicular adenoma

Hurthle cell Adenoma

Cells with abundant eosinophilic cytoplasm and small regular nuclei.

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MALIGNANT TUMORS
Papillary Carcinoma
Follicular Carcinoma
Medullary Carcinoma
Anaplastic Carcinoma

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G. MALIGNANT TUMORS

Papillary Thyroid Carcinoma (PTC)

Is the most common thyroid cancer (90%)

Most frequent between ages 20 50 years
Female:male is 3:1
Papillary growth pattern with ground glass nuclei
Better prognosis than other forms of thyroid cancer ,
even when adjacent lymph nodes is involved
Can be long-term consequence of prior radiotherapy to
the neck
Typically invades lymphatics and spreads to regional
lymph nodes
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G. MALIGNANT TUMORS

Papillary Thyroid Carcinoma (PTC)

Macroscopic appearance with

grossly discernible papillary structure
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FNAB

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G. MALIGNANT TUMORS

Papillary
Thyroid
Carcinoma
(PTC)

Cut surface diplays a circumscribed

pale tan mass with foci of
cystic change

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Papillary Thyroid Carcinoma (PTC)

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Well-formed papillae

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Papillary Thyroid Carcinoma (PTC)

Orphan Annie eye, or ground-glass nuclei, or empty appearing nuclei

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Papillary Thyroid Carcinoma (PTC)

the most common thyroid cancer

Branching papillae are lined by neoplastic columnar epithelium with

clear nuclei. A calcospherite (psammoma body) is evident..
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G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma FTC)

Cut surface of follicular carcinoma
with the substantial replacement
of the lobe of the thyroid.
The tumor has a light-tan
appearance and contains small foci
of hemorrage

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G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

Glandular lumen contains recognizable colloid

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G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

ADENOMA

CARCINOMA

Capsular integrity in follicular neoplasm is critical in distinguishing follicular

adenoma from carcinoma.
Follicular adenoma: capsule is usually thin, occasionally more prominent;
no capsular invasion is seen (arrows).
Follicular carcinoma: capsular invasion (arrows)
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G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

A microfollicular tumor has invaded veins in the thyroid parenchyma.

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G. MALIGNANT TUMORS: Medullary Thyroid Carcinoma (MTC)

Clinical Features

Symptoms related to endocrine secretion: carcinoid

syndrome (calcitonin), Cushing syndrome (ACTH)
Watery diarhea in 1/3 cases, caused by secretion
of vasoactive intestinal peptide, pros-taglandin, and
several kinins
Familial MTC: hypertension, episodic hypertension,
symptoms attributable to the secretion of catecholamines and phaeochromocytoma
Therapy: thyroidectomy local recurrencies 1/3
5-year survival rate is 75%
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G. MALIGNANT TUMORS:

Medullary Carcinoma

Solid pattern of growth and do not

have connective tissue capsule.
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Coronal section total (bilateral)

involvement by a firm, pale tumor.
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G. MALIGNANT TUMORS:

Medullary Thyroid Carcinoma

Nest of polygonal cells embedded in a collagenous framework.

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G. MALIGNANT TUMORS:

Medullary Thyroid Carcinoma

Amyloid: Congo red staining polarized light microscope

pale green birefringent
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G. MALIGNANT TUMORS:

Medullary Carcinoma

Typically contain amyloid, visible here as homogenous

extracellular material, derived from calcitonin molecules
secreted by the neoplastic cells
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G. MALIGNANT TUMORS:

Anaplastic Carcinoma of the Thyroid

The tumor in traverse section partially surround the trachea

and extend into the adjecent soft tissue.
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G. MALIGNANT TUMORS:

Anaplastic Carcinoma

The tumor is composed of bizarre spindle and giant cells with numerous mitoses
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PARATHYROID

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PARATHYROID
HYPERPARATHYROIDISM

Primary hyperparathyroidism
Secondary hyperparathyroidism
Tertiary hyperparathyroidism

HYPOPARATHYROIDISM

Surgically induced
Congenital absence of all glands
Pimary (idiopathic) atrophy of the glands
autoimmune disease
Familial hypoparathyroidism

PSEUDOHYPOPARATHYROIDISM

Type 1: Gs deficiency diminished cAMP response

to PTH Albright hereditary osteodystrophy
Type 2: normal PTH-induced cAMP, with blunted
response to the second messenger

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HYPERPARATHYROIDISM
Primary hyperparathyroidism
Adenoma 75 to 80%
Primary hyperplasia (diffuse or nodular) 10 to 15 %
Parathyroid carcinoma less than 5 %

Secondary hyperparathyroidism
Overactivity of parathyroid gland (hyperplastic) due to
chronic depression in Ca serum level (i.e. renal failure
renal osteodystrophy bone abnormality)

Tertiary hyperparathyroidism
Parathyroid activity may become autonomous and
excessive hypercalcemia
Parathyroidectomy is necessary
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PARATHYROID
GLAND

Parathyroid adenoma arising

from the left lower
parathyroid gland

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PARATHYROID GLAND

Gross appearance of two parathyroid adenomas, note the roundish

shape, the homogenous appearance interrupted by a few foci of
fresh hemorrahgic or cystic changes, and the brown to yellowish color
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PARATHYROID ADENOMA

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PARATHYROID

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PARATHYROID

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PARATHYROID

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PARATHYROID

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PARATHYROID CARCINOMA

Sharply outlined fibrous band incompletely dividing tumor into lobules

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PARATHYROID CARCINOMA

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PARATHYROID

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PARATHYROID

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PARATHYROID

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Adrenal glands

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Adrenal glands
CORTEX
- Hypercorticism / Cushing syndrome
- Hyperaldosteronism
- Adrenal virilism
- Hypocorticism
MEDULLA
- Pheochromocytoma
- Medulloblastoma
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Normal adrenal gland

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ADRENOCORTICAL HYPERPLASIA

The adrenal cortex are yellow, thickened and multinodular

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Adrenal virilism
(adrenogenital syndrome)
Causes
a. Congenital enzyme defect result in deminished
corticol production and compensatory increased
ACTH, with resultant adrenal hyperplasia with
androgenic steroid production
(1) 21- hydroxylase deficiency most common
result in salt loss and hypotension
(2) 11- hydroxylase deficiency less common
results in salt retention and hypertension
b. Tumor of the adrenal cortex
Clinical characteristic:
- produces virilism in females and precocious puberty
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Tumors of adrenal medulla

1. Pheochromocytoma

Is derived from chromaffin cells of adrenal medulla (

if derived from extra-adrenal chromaffin cells, called paraganglioma)

Most often benign, only 10% malignant

Is characterized by increased urinary excretion of
catecholamines (epinephrine or norepinephrine) and
their metabolites ( metanephrine, normetanephrine,
and vanillymandelic acid (VMA)

Can also cause hyperglycemia

Can be part of MEN IIa or MEN IIb (III)

Can also be associated with neurofibromatosis or with

von Hippel-Lindau disease
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THE ADRENAL

The three layers of the normal adrenal cortex: A. Zona glomerulosa,

B. Zona fasciculata, C. Zona reticularis
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The Adrenal Cortical Hyperplasia

Adrenal cortical hyperplasia showing multinodular pattern of growth

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The Adrenal Cortical Hyperplasia

Primary pigmented nodular adrenal cortical hyperplasia. Nodules

of eosinophilic cells containing abundant brown pigment are seen,
together with others showing clear cytoplasm and
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nuclear aberations

Adrenal Cortical Adenoma

Gross appearance. Both tumors are well circumscribed, of

homogenous appearance, without hemorrhage or necrosis.
The tumor in A has the typical golden yellow color
associated with aldosterone secretion.
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Adrenal Cortical Carcinoma

Gross appearance. Both tumors are large and exhibit areas of

hemorrhage and necrosis. The tumor shown in A has destroys
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the upper pole of the kidney.

The Adrenal Cortical Adenoma

The tumor showing numerous lipid-laden clear cells similar to

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those of the normal fasciculata layer

Adrenal Cortical Carcinoma

There is nuclear hyperchromasia, diffuse pattern of growth,

and mitotic activity
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Adrenal Cortical Adenoma

Gross appearance of adrenal cortical adenoma with myelolipomatous

component, represented by the small hemorrhagic foci.
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Adrenal Oncocytoma

A. HE staining
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B. Antimitochondrial immnostaining
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Immunohistochemical reactivity of
adrena cortical neoplasia

Inhibin
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Immunohistochemical reactivity of
adrenal cortical neoplasia

Aloz
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Immunohistochemical reactivity of
adrenal cortical neoplasia

Melan-A
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Aldosterone-secreting Adrenal
Cortical Adenoma

Various morphologic pattern

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Aldosterone-secreting Adrenal
Cortical Adenoma

The so-called spironolactone bodies, that appear as concentric

laminated eosinophilic structures
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ADRENAL NEUROBLASTOMA

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Adrenal Neuroblastoma

The tumor shows a variegated appearances

resulted from hemorrhagic and necrosis.
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The tumor shows the typical location

above the upper pole of the kidney,
which is uninvolved
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Adrenal Neuroblastoma

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Adrenal Neuroblastoma

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Adrenal Pheochromocytoma

Variegated appearance
The tumor was fixed with Zenker fluid
and has acquired the typical
dark brown color
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Adrenal Pheochromocytoma

The tumor shows the typical Zellballen configuration

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Adrenal Pheochromocytoma

Evidence of the abundant granular amphophilic cytoplasm

of the tumor cells
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Pituitary Gland

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pituitary gland

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pituitary gland

The normal gross appearance of the pituitary gland removed from

the sella turcica is shown here. The larger portion, the anterior
pituitary (adenohypophysis), is toward the top. The image at the left
shows the superior aspect of the pituitary with the stalk coming from
the hypothalamus entering it. The inferior aspect of the pituitary is
shown at the right. The posterior pituitary (neurohypophysis) is the
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smaller portion at the bottom.

the pituitary gland

The normal microscopic appearance of the pituitary

gland is shown here. The adenohypophysis is at the right
and the neurohypophysis is at the left.
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The neurohypophysis shown here resembles neural tissue, with glial cells,
nerve fibers, nerve endings, and intra-axonal neurosecretory granules.
The hormones vasopressin (antidiuretic hormone, or ADH) and oxytocin made
in the hypothalamus (supraoptic and paraventricular nuclei) are transported into
the intra-axonal neurosecretory granules where they are released.

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the pituitary gland

The normal microscopic appearance of the adenohypophysis is

shown here. The adenohypophysis contains three major cell types:
acidophils, basophils, and chromophobes. The staining is variable,
and to properly identify specific hormone secretion,
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immunohistochemical staining is necessary.

adenohypophysis
A simplistic classification is as follows:
The pink acidophils secrete growth hormone
(GH) and prolactin (PRL)
The dark purple basophils secrete corticotrophin
(ACTH), thyroid stimulating hormone (TSH), and
gonadotrophins follicle stimulating hormoneluteinizing hormone (FSH and LH)
The pale staining chromophobes have few
cytoplasmic granules, but may have secretory
activity.
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Pituitary Neoplasma

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a pituitary adenoma

The circumscribed mass lesion present here in the sella turcica is a

pituitary adenoma. Though pituitary adenomas are benign, they can
produce problems either from a mass effect (usually visual problems
from pressing on the optic chiasm and/or headaches) or from
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production of hormones such as prolactin or ACTH.

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The microscopic appearance of the pituitary

adenoma is shown here. Note the monotonous
appearance of these small round cells.

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A pituitary adenoma

Description : Feinnadelpunktat der Hypophyse: Die hypophysren

Zellen mit erhaltenem Zytoplasma sind alle positiv fr Prolaktin 102
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chromophobe pituitary adenoma

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Endocrine Pancreas

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Secretory Products of Islet Cells and Their Physiologic Actions

Cell

Secretory
Product

Mol.
Wt.

Physiological Action

Glucagon

3500

Catabolic, stimulates glycogenolysis &

gluconeogenesis, raises blood glucose

Beta

Insulin

6000

Anabolic, stimulates glycogenesis, lipogenesis,

protein synthesis, lowers blood glucose. Inhibits
secretion of alpha, beta, D1, acinar cells

Delta
D

Somatostatin

1600

Delta
D1

Vasoactive Intestinal
Polypeptide (VIP)

3800

Same as glucagon, regulates tone & GE tract

motility, activates cAMP of intestinal epithelium

PP

Human pancreatic
polypeptide (ppp)

4300

Stimulates gastric enzyme secretion, inhibits

intestinal motility & bile secretion

EC

Serotonin, substance
P (motilin)

176

Induce vasodilatation, increases vascular

permeability, stimulates motility of gastric
muscle and tone of lower esophageal sphincter

Alpha

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Pancreatic Endocrine Tumors

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Beta cell tumor

Many of the granules have irregular or crystalline content

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Alpha cell tumor

Granules are large and have dense peripheral nucleoid

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G-cell tumor

Granules are similar to those of VIP-producing tumor and

of normal gastrin cells. Most tumors from
Zollinger-Ellison have this appearance
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VIP-producing tumors

This tumor hav larger and more pleomorphic granules

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Alpha cell tumor

Gross appearance shown,
required the performance
of a near total
pancreatectomy.

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Alpha cell tumor (Glucagonoma)

Gross appearance shown,

exhibits foci of
hemorrhage and necrosis.

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Alpha cell tumor

The tumor showing a prominent gyriform arrangement of the

tumor cells. Tumors of this pattern are usually composed of
either alpha or beta cells
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ISLET CELL TUMOR

Gastrinoma
- is often a malignant tumor, sometimes
occuring in extrapancreatic sites
- results in gastrin hypersecretion and hypergastrinemia
- is associated with Zollinger-Ellison syndrome
(marked gastric hypersecretion of HCl),
recurrent peptic ulcer disease and hypergastrinemia

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G-cell tumor

Rosette-like gland formation in G-cell tumor (gastrinoma)

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