TUMOR SISTEM ENDOKRIN

BLOCK 21

LABORATORY WORK GUIDE

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

pituitary gland

pituitary gland

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
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.

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.

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,
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.

Pituitary Neoplasma

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
production of hormones such as prolactin or ACTH.

The microscopic appearance of the pituitary

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

pituitary adenoma

Description : Feinnadelpunktat der Hypophyse: Die hypophysren

Zellen mit erhaltenem Zytoplasma sind alle positiv fr Prolaktin

chromophobe pituitary adenoma

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

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

Parathyroid hyperplasia

PARATHYROID

Parathyroid: chief cell hyperplasia

PARATHYROID

PARATHYROID

PARATHYROID
GLAND

Parathyroid adenoma arising

from the left lower
parathyroid gland

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

PARATHYROID

PARATHYROID

PARATHYROID

PARATHYROID

PARATHYROID

PARATHYROID CARCINOMA

Sharply outlined fibrous band incompletely dividing tumor into lobules

PARATHYROID CARCINOMA

THYROID

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)

Pathology of
of the
the thyroid
thyroid
Pathology
A.
B.
C.
D.
E.

HYPOTHYROIDISM
HYPERTHYROIDISM
THYROIDITIS
BENIGN TUMORS (ADENOMAS)
MALIGNANT TUMORS

Colloid Goiter

Pathology of thyroid

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

Non-toxic goiter
Irregular
nodules

Marked variation in the size of follicles

Nodular (non-toxic) Goiter

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

Euthyroid goiter

Graves Disease

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

Graves disease, hyperthyroidism

Exophthalmos

Thyroid mass

Major clinical
manifestations
of
Graves disease

Graves Disease

Diffusely hyperplastic thyroid follicle are lined by tall,

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

Graves disease, hyperthyroidism

The follicles are lined by hyperplastic, tall columnar cells

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)

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

Chronic autoimmune (Hashimoto)

thyroiditis

The thyroid gland is symmetrically enlarged and coarsely nodular.

Coronal section irregular nodules and an intact capsule

Hashimoto thyroiditis

Chronic autoimmune (Hashimoto)

thyroiditis

Atrophic thyroid follicles with conspicuous chronic inflammatory infiltrate

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

Hashimoto Thyroiditis

Dense lymphocytic infiltrates with germinal centers

Residual thyroid follicle lined by Hurthle cells are also seen

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

FOLLICULAR ADENOMA

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

Follicular adenoma

Embryonal adenoma

The tumor features a trabecular pattern with poorly formed follicles

that contain little if any colloid

Follicular Adenoma

COLLOID ADENOMA
The cut surface of an encapsulated mass reveals:

Hemorrhage
Fibrosis
Cystic change

Follicular Adenoma

Cystic

A solitary, well-circumscribed nodule is seen.

Follicular Adenoma

Well-differentiated follicles resembling

normal thyroid parenchyma.

Follicular adenoma

FETAL ADENOMA

Regular pattern of small follicles

Follicular adenoma

Hurthle cell Adenoma

Cells with abundant eosinophilic cytoplasm and small regular nuclei.

MALIGNANT TUMORS
Papillary Carcinoma
Follicular Carcinoma
Medullary Carcinoma
Anaplastic Carcinoma

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

G. MALIGNANT TUMORS

Papillary Thyroid Carcinoma (PTC)

Macroscopic appearance with

grossly discernible papillary structure

FNAB

G. MALIGNANT TUMORS

Papillary
Thyroid
Carcinoma
(PTC)

Cut surface diplays a circumscribed

pale tan mass with foci of
cystic change

Papillary Thyroid Carcinoma (PTC)

Well-formed papillae

Papillary Thyroid Carcinoma (PTC)

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

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..

Papillary Thyroid Carcinoma (PTC)

CYTOLOGY, MMG stain

Frosted glass
nucleus

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

Tumor infiltration (thyroid carcinoma)

G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

Glandular lumen contains recognizable colloid

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)

G. MALIGNANT TUMORS

Follicular Thyroid Carcinoma (FTC)

A microfollicular tumor has invaded veins in the thyroid parenchyma.

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%

G. MALIGNANT TUMORS:

Medullary Carcinoma

Solid pattern of growth and do not

have connective tissue capsule.

Coronal section total (bilateral)

involvement by a firm, pale tumor.

G. MALIGNANT TUMORS:

Medullary Thyroid Carcinoma

Nest of polygonal cells embedded in a collagenous framework.

G. MALIGNANT TUMORS:

Medullary Thyroid Carcinoma

Amyloid: Congo red staining polarized light microscope

pale green birefringent

G. MALIGNANT TUMORS:

Medullary Carcinoma

Typically contain amyloid, visible here as homogenous

extracellular material, derived from calcitonin molecules
secreted by the neoplastic cells

G. MALIGNANT TUMORS:

Anaplastic Carcinoma of the Thyroid

The tumor in traverse section partially surround the trachea

and extend into the adjecent soft tissue.

G. MALIGNANT TUMORS:

Anaplastic Carcinoma

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

Endocrine Pancreas

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

Pancreatic Endocrine Tumors

Beta cell tumor

Many of the granules have irregular or crystalline content

Alpha cell tumor

Granules are large and have dense peripheral nucleoid

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

VIP-producing tumors

This tumor hav larger and more pleomorphic granules

Alpha cell tumor

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

Alpha cell tumor (Glucagonoma)

Gross appearance shown,

exhibits foci of
hemorrhage and necrosis.

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

ISLET CELL TUMOR

Gastrinoma (G-cell tumor)
- 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

G-cell tumor

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